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CochranePLS3200

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Forty-nine RCTs were included of which 33 trials investigated smoking cessation interventions with specific mood management components for depression. In smokers with current depression, meta-analysis showed a significant positive effect for adding psychosocial mood management to a standard smoking cessation intervention when compared with standard smoking cessation intervention alone (11 trials, N = 1844, RR 1.47, 95% CI 1.13 to 1.92). In smokers with past depression we found a similar effect (13 trials, N = 1496, RR 1.41, 95% CI 1.13 to 1.77). Meta-analysis resulted in a positive effect, although not significant, for adding bupropion compared with placebo in smokers with current depression (5 trials, N = 410, RR 1.37, 95% CI 0.83 to 2.27). There were not enough trial data to evaluate the effectiveness of fluoxetine and paroxetine for smokers with current depression. Bupropion (4 trials, N = 404, RR 2.04, 95% CI 1.31 to 3.18) might significantly increase long-term cessation among smokers with past depression when compared with placebo, but the evidence for bupropion is relatively weak due to the small number of studies and the post hoc subgroups for all the studies. There were not enough trial data to evaluate the effectiveness of fluoxetine, nortriptyline, paroxetine, selegiline, and sertraline in smokers with past depression. Twenty-three of the 49 trials investigated smoking cessation interventions without specific components for depression. There was heterogeneity between the trials which compared psychosocial interventions with standard smoking cessation counselling for both smokers with current and past depression. Therefore, we did not estimate a pooled effect. One trial compared nicotine replacement therapy (NRT) versus placebo in smokers with current depression and found a positive, although not significant, effect (N = 196, RR 2.64, 95% CI 0.93 to 7.45). Meta-analysis also found a positive, although not significant, effect for NRT versus placebo in smokers with past depression (3 trials, N = 432, RR 1.17, 95% CI 0.85 to 1.60). Three trials compared other pharmacotherapy versus placebo and six trials compared other interventions in smokers with current or past depression. Due to heterogeneity between the interventions of the included trials we did not estimate pooled effects. Evidence suggests that adding a psychosocial mood management component to a standard smoking cessation intervention increases long-term cessation rates in smokers with both current and past depression when compared with the standard intervention alone. Pooled results from four trials suggest that use of bupropion may increase long-term cessation in smokers with past depression. There was no evidence found for the use of bupropion in smokers with current depression. There was not enough evidence to evaluate the effectiveness of the other antidepressants in smokers with current or past depression. There was also not enough evidence to evaluate the group of trials that investigated interventions without specific mood management components for depression, including NRT and psychosocial interventions. Output:

In this review, treatments were divided into those with or without specific attention to handling depression. We found that smoking cessation treatments with specific attention to handling depression helped smokers who suffered from depression to quit. Psychosocial 'mood management' interventions, where participants learn how to handle depressive symptoms with psychological techniques, were effective in those with current depression and with a history of it. Bupropion, an antidepressant medication to help quit smoking, has been shown to be effective for smoking cessation in healthy smokers. Our findings show that bupropion may benefit smokers with a history of depression as well. However, this was not found for those with current depression. There was a lack of evidence for the effectiveness of other antidepressants to help smokers with a history of depression to quit. There was also not enough evidence for the use of antidepressants in smokers with current depression. Although treatments without specific attention to handling depression, such as nicotine replacement therapy and standard psychosocial smoking cessation interventions, have been shown to help other groups of people to quit smoking, there was not enough evidence to show that they were helpful in people with a history of or with current depression.

CochranePLS3201

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: The 13 included trials involved 2498 older, usually female, patients who had undergone hip fracture surgery. Though generally well conducted, some trials were at risk of bias such as from imbalances in key baseline characteristics. There was substantial clinical heterogeneity in the trial interventions and populations. Multidisciplinary rehabilitation was provided primarily in an inpatient setting in 11 trials. Pooled results showed no statistically significant difference between intervention and control groups for poor outcome (risk ratio 0.89; 95% confidence interval 0.78 to 1.01), mortality (risk ratio 0.90, 95% confidence interval 0.76 to 1.07) or hospital readmission. Individual trials found better results, often short-term only, in the intervention group for activities of daily living and mobility. There was considerable heterogeneity in length of stay and cost data. Three trials reporting carer burden showed no evidence of detrimental effect from the intervention. Overall, the evidence indicates that multidisciplinary rehabilitation is not harmful. The trial comparing primarily home-based multidisciplinary rehabilitation with usual inpatient care found marginally improved function and a clinically significantly lower burden for carers in the intervention group. Participants of this group had shorter hospital stays, but longer periods of rehabilitation. One trial found no significant effect from doubling the number of weekly contacts at the patient's home from a multidisciplinary rehabilitation team. While there was a tendency to a better overall result in patients receiving multidisciplinary inpatient rehabilitation, these results were not statistically significant. Future trials of multidisciplinary rehabilitation should aim to establish both effectiveness and cost effectiveness of multidisciplinary rehabilitation overall, rather than evaluate its components. Output:

This review included 13 trials, which involved a total of 2498 older, usually female, patients who had undergone surgery for hip fracture. Generally the trials appeared well conducted, although some were at risk of bias that could affect the reliability of their results. For example, despite randomisation, in five trials there were some important differences in patient characteristics, such as age, at the start of the trial that could have influenced trial findings. The trial interventions were very varied but all compared multidisciplinary rehabilitation with usual care. In 11 trials, care was provided either totally or mainly in an inpatient or hospital setting. While there was a tendency for a better outcome after multidisciplinary rehabilitation, the results were not statistically significant and thus cannot be considered conclusive. However, the overall evidence indicates that multidisciplinary rehabilitation is not harmful. Additionally, there was some inconclusive evidence that multidisciplinary rehabilitation did not add to the burden of carers. In one trial that compared home-based multidisciplinary rehabilitation with usual inpatient care, carers reported significantly lower burden in the long term after multidisciplinary rehabilitation. Participants in the home-based rehabilitation group of this trial had shorter hospital stays, but longer periods of rehabilitation. One other trial found no significant effect from doubling the number of weekly contacts at the patient's home by a multidisciplinary rehabilitation team. Overall, the results of this review suggest that multidisciplinary rehabilitation may help more older people recover after a hip fracture. However, the results are not conclusive and more research is needed.

CochranePLS3202

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: This review included only one trial (21 participants), which compared fish oil-derived (n-3) fatty acid-based lipid emulsion (50 mL per infusion (1.05 g eicosapentaenoic and 10.5 g docosahexaenoic acid)) (10 participants) to soya oil-derived (n-6) fatty acid-based lipid emulsion (50 mL per infusion (1.05 g eicosapentaenoic and 10.5 g docosahexaenoic acid)) (11 participants) administered intravenously twice daily for 10 days, with a total follow-up of 40 days. The study was conducted in a single centre in Germany in 18 men and three women, aged between 21 and 65 years, who were in hospital with acute guttate psoriasis and had mean total body surface involvement of 25.7% ± 20.4% (range 10 to 90). The study was funded by a company that produces the oil emulsions. We found no other evidence regarding non-antistreptococcal interventions used in clinical practice for guttate psoriasis, such as topical treatments (corticosteroids, vitamin D₃ analogues), systemic drugs, biological therapy, and phototherapy. The primary outcomes of the review were not measured, and only one of our secondary outcomes was measured: improvement in participant satisfaction measures and quality of life assessment measures. However, the study authors did report that there was rare skin irritation at the site of peripheral intravenous route, but the number of affected participants was not provided. Improvement between baseline and day 10, using a non-validated score assessed by participants themselves daily based on five items (appearance of lesions, impairment of daily life, pruritus, burning, and pain), was greater in the group that received the fish oil-derived (n-3) fatty acid-based lipid emulsion (75%) than in the group receiving the soya oil-derived (n-6) fatty acid-based lipid emulsion (18%) (one trial, 21 participants). However, these results are uncertain as they are based on very low-quality evidence. There is no evidence regarding topical and systemic drugs, biotherapy, or phototherapy in guttate psoriasis (we did not consider drugs that aimed to eradicate streptococcal infection because these are assessed in another Cochrane Review). We are uncertain of the effect of intravenously administered lipid emulsion on guttate psoriasis because the quality of the evidence is very low, due to risk of bias (unclear risk of bias for all domains), indirectness (the trial only included adults, and the follow-up from baseline was only 10 days), and imprecision (small number of participants). This review highlights the need for trials assessing the efficacy and safety of phototherapy and topical and systemic drugs for guttate psoriasis. There is also a need for studies that clearly distinguish the specific population with guttate psoriasis from the larger group of people with chronic plaque psoriasis, and children and young adults should be assessed as a distinct group. Output:

We found one relevant study that compared the effects of giving injections into the vein of two different lipid (fat) emulsions twice daily for 10 days: one emulsion (two or more liquids that are often unmixable) was derived from fish oil, and the other was derived from soya oil. Participants were followed for a total of 40 days. The study was conducted in Germany in 21 adults (18 men and 3 women) aged 21 to 65 years, with a mean of involved skin surface of 25%, who were in hospital with acute guttate psoriasis. The study was funded by the company that produces the oil emulsions. Treatments for which we found no evidence include phototherapy and topical, oral, and biological medicines. The only study identified did not measure our two primary outcomes: percentage of people treated whose skin became clear (or almost clear) of lesions; and the side effects, or harms, of the treatments. Most of our secondary outcomes were also not measured, including worsening of guttate psoriasis or recurrence within a period of six months after the treatment has finished; and percentage of participants achieving a Psoriasis Area Severity Index 75 or Physician's Global Assessment of 1 or 2. The included study did not report measuring any harms of the treatments; however, the study authors did report rare skin irritation at site of injection, but did not provide the number of affected participants. The study participants rated some outcomes themselves, including the appearance of the skin lesions, the effects on their daily life, itching, burning, and pain. After 10 days of treatment, study participants who received the fish oil-derived lipid emulsion (75% of people in this group) rated greater improvements than those receiving the soya oil-derived lipid emulsion (18% of people in this group). However, these results are uncertain as they are based on very low-quality evidence. The evidence is current to June 2018. We rated the quality of the available evidence as very low. We considered that the study may be at risk of bias due to limitations in its design, and only a small number of people were included in the study. In addition, the study only enrolled adults, although guttate psoriasis is more common in children.

CochranePLS3203

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 11 studies that randomised 343 people. Overall, the risk of bias in the included studies was unclear, mainly due to poor reporting; allocation concealment was not described, generation of the sequence was not explicit, participants and outcome assessors were not clearly blinded. For some studies we were unsure if data were complete, and data were often poorly or selectively reported. Data from six trials showed that there may be a clinically important improvement in TD symptoms after GABA agonist treatment compared with placebo at six to eight weeks follow-up (6 RCTs, n = 258, RR 0.83, CI 0.74 to 0.92; low-quality evidence). Data from five studies showed no difference between GABA agonist treatment and placebo for deterioration of TD symptoms (5 RCTs, n = 136, RR 1.90, CI 0.70 to 5.16; very low-quality evidence). Studies reporting adverse events found a significant effect favouring placebo compared with baclofen, sodium valproate or progabide for dizziness/confusion (3 RCTs, n = 62 RR 4.54, CI 1.14 to 18.11; very low-quality evidence) and sedation/drowsiness (4 RCTS, n = 144, RR 2.29, CI 1.08 to 4.86; very low-quality evidence). Studies reporting on akathisia (RR 1.05, CI 0.32 to 3.49, 2 RCTs, 80 participants), ataxia (RR 3.25, CI 0.36 to 29.73, 2 RCTs, 95 participants), nausea/vomiting (RR 2.61, CI 0.79 to 8.67, 2 RCTs, 64 participants), loss of muscle tone (RR 3.00, CI 0.15 to 59.89, 1 RCT, 10 participants), seizures (RR 3.00, CI 0.24 to 37.67, 1 RCT, 2 participants), hypotension (RR 3.04, CI 0.33 to 28.31, 2 RCTs, 119 participants) found no significant difference between GABA drug and placebo (very low-quality evidence). Evidence on mental state also showed no effect between treatment groups (6 RCTS, n = 121, RR 2.65, CI 0.71 to 9.86; very low-quality evidence) as did data for leaving the study early (around 10% in both groups, 6 RCTS, n = 218, RR 1.47, CI 0.69 to 3.15; very low-quality evidence). No study reported on social confidence, social inclusion, social networks, or personalised quality of life, a group of outcomes selected as being of particular importance to patients. We are uncertain about the evidence of the effects of baclofen, progabide, sodium valproate or tetrahydroisoxazolopyridinol (THIP) for people with antipsychotic-induced TD. Evidence is inconclusive and unconvincing. The quality of data available for main outcomes ranges from very low to low. Any possible benefits are likely to be outweighed by the adverse effects associated with their use. Output:

. The review includes 11 studies investigating the use of GABA agonist drugs compared with placebo. All studies involved small numbers of participants (2 to 80 people) with schizophrenia or other chronic mental illnesses who had also developed antipsychotic-induced tardive dyskinesia. . Evidence of the effects of GABA agonist drugs in the treatment of tardive dyskinesia is not conclusive and not convincing. Any possible benefits of GABA agonist drugs are likely to be outweighed by the adverse effects associated with their use. . Evidence is weak, short term, small scale and poorly reported. It is not possible to recommend these drugs as a treatment for tardive dyskinesia. This plain language summary was adapted by the review authors from a summary originally written by Ben Gray, Senior Peer Researcher, McPin Foundation (http://mcpin.org/).

CochranePLS3204

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Thirty-two RCTs and two cluster-RCTs that randomised 3554 people satisfied criteria for inclusion. Only one study examined the effects of early warning signs interventions without additional psychological interventions, and many of the outcomes for this review were not reported or poorly-reported. Significantly fewer people relapsed with early warning signs interventions than with usual care (23% versus 43%; RR 0.53, 95% CI 0.36 to 0.79; 15 RCTs, 1502 participants; very low quality evidence). Time to relapse did not significantly differ between intervention groups (6 RCTs, 550 participants; very low quality evidence). Risk of re-hospitalisation was significantly lower with early warning signs interventions compared to usual care (19% versus 39%; RR 0.48, 95% CI 0.35 to 0.66; 15 RCTS, 1457 participants; very low quality evidence). Time to re-hospitalisation did not significantly differ between intervention groups (6 RCTs; 1149 participants; very low quality evidence). Participants' satisfaction with care and economic costs were inconclusive because of a lack of evidence. This review indicates that early warning signs interventions may have a positive effect on the proportions of people re-hospitalised and on rates of relapse, but not on time to recurrence. However, the overall quality of the evidence was very low, indicating that we do not know if early warning signs interventions will have similar effects outside trials and that it is very likely that further research will alter these estimates. Moreover, the early warning signs interventions were used along side other psychological interventions, and we do not know if they would be effective on their own. They may be cost-effective due to reduced hospitalisation and relapse rates, but before mental health services consider routinely providing psychological interventions involving the early recognition and prompt management of early warning signs to adults with schizophrenia, further research is required to provide evidence of high or moderate quality regarding the efficacy of early warning signs interventions added to usual care without additional psychological interventions, or to clarify the kinds of additional psychological interventions that might aid its efficacy. Future RCTs should be adequately-powered, and designed to minimise the risk of bias and be transparently reported. They should also systematically evaluate resource costs and resource use, alongside efficacy outcomes and other outcomes that are important to people with serious mental illness and their carers. Output:

Many people with schizophrenia experience periods of illness followed by relatively stable periods (although symptoms of illness such as hearing voices and seeing things often remain in the background). This means that many people with schizophrenia may become unwell again and need to go back into hospital. Training in early warning signs techniques encourages people to learn, detect and recognise the early warning signs of future illness. Studies indicate that noticing even small changes in signs and symptoms of schizophrenia can often predict future illness and relapse two to 10 weeks later. Early warning training may help to prevent or delay relapse, so reducing the chances of going into hospital. Recognition of early warning signs requires detailed history taking, sometimes with additional techniques such as diary keeping, completion of questionnaires and a plan of action based on anticipated early warning signs. Training can be undertaken by the individual or be group-based, involving health professionals, family members or carers. Successful training seems to require around 12 sessions and involves therapists of high competency. This review includes a total of 34 studies. It found that there are positive benefits of training in early warning signs. It reduces rates of relapse and re-hospitalisation (but not on time to recurrence). It should be noted that training in early warning signs was mainly used alongside other psychological therapies, so it is not entirely clear what proportion of the positive effect is due to training in early warning signs alone. Moreover, the overall quality of the evidence from these studies was judged to be very low. This means that we do not know if interventions using early warning signs, with or without additional psychological treatments, will have the same beneficial effects outside clinical trials. Further research is required to decide whether training in early warning signs is effective on its own. Effects on quality of life, satisfaction with care, money spent, and burden of care for carers are unclear, so ideally should be known before training programmes are put into wider use. At this time, there is not enough evidence to support training in early warning signs alone. This plain language summary was written by consumer, Ben Gray of RETHINK.

CochranePLS3205

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We found three eligible randomized controlled trials, with a total of 2081 participants. One of the three included studies did not mention the amount of participants and presented no outcome data. The 'Risk of bias' assessment indicated that there was a high risk of detection bias owing to lack of blinding of outcomes assessors, but we assessed all other domains to be at low risk of bias. Trial design and conduct were generally adequate, with the most common areas of weakness in blinding. The majority of participants were included in centres across North America. The mean age of participants ranged from 61 to 64 years, and the mean duration of intubation was between 3.2 and 7.7 days. One trial comparing silver-coated ETTs versus non-coated ETTs showed a statistically significant decrease in VAP in favour of the silver-coated ETT (1 RCT, 1509 participants; 4.8% versus 7.5%, risk ratio (RR) 0.64, 95% confidence interval (CI) 0.43 to 0.96; number needed to treat for an additional beneficial outcome (NNTB) = 37; low-quality evidence). The risk of VAP within 10 days of intubation was significantly lower with the silver-coated ETTs compared with non-coated ETTs (1 RCT, 1509 participants; 3.5% versus 6.7%, RR 0.51, 95% CI 0.31 to 0.82; NNTB = 32; low-quality evidence). Silver-coated ETT was associated with delayed time to VAP occurrence compared with non-coated ETT (1 RCT, 1509 participants; hazard ratio 0.55, 95% CI 0.37 to 0.84). The confidence intervals for the results of the following outcomes did not exclude potentially important differences with either treatment. There were no statistically significant differences between groups in hospital mortality (1 RCT, 1509 participants; 30.4% versus 26.6%, RR 1.09, 95% CI 0.93 to 1.29; low-quality evidence); device-related adverse events (2 RCTs, 2081 participants; RR 0.65, 95% CI 0.37 to 1.16; low-quality evidence); duration of intubation; and length of hospital and ICU stay. We found no clinical studies evaluating the cost-effectiveness of silver-coated ETTs. This review provides limited evidence that silver-coated ETT reduces the risk of VAP, especially during the first 10 days of mechanical ventilation. Output:

We found three randomized controlled trials involving 2081 participants. No outcome data were available for one included study. The design of the other two RCTs was generally good, although there were some weaknesses. The majority of participants were included in centres around North America. The evidence is current to October 2014. Both RCTs were funded but stated that the sponsors contributed only to the study design and did not participate in the conduct of the study. We found that silver-coated ETT reduced the risk for developing VAP from 6.7% to 3.5% within 10 days of intubation compared with non-coated ETT in people who required mechanical ventilation for 24 hours of longer, although the quality of evidence for this outcome was low. One study showed that an initial VAP occurrence appeared much later in time in people who had a silver-coated ETT compared with a non-coated ETT, although again the evidence was low quality. We could not draw conclusions about hospital mortality, device-related complications, duration of intubation, and length of hospital and intensive care unit stay owing to uncertainty of the effects. We found no clinical studies evaluating the cost-effectiveness of silver-coated ETTs. The overall quality of evidence was low for all interested outcomes mentioned. Limited evidence suggests that silver-coated ETT seems to be an effective device in reducing the risk of VAP, although data for our other key outcome of hospital mortality were inconclusive. Larger studies with more participants who are at risk for VAP and who require mechanical ventilation for a longer period of time are needed.

CochranePLS3206

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Randomised evidence was sparse. Only four trials were eligible for inclusion, one comparing the efficacy of real ECT versus simulated ECT, two comparing the efficacy of unilateral versus bilateral ECT and the other comparing the efficacy of ECT once a week with ECT three times weekly. All trials had major methodological shortcomings; reports were mostly lacking essential information to perform a quantitative analysis. Although the findings from one study (35 participants) concluded that real ECT was superior to simulated ECT, these conclusions need to be interpreted cautiously. Only results from one of the trials (29 participants) comparing unilateral versus bilateral ECT could be analysed, and did not show convincing efficacy of unilateral ECT over bilateral ECT, WMD 6.06 (CI -5.20 to 17.32). Randomised evidence on the efficacy and safety of ECT in depressed elderly with concomitant dementia, cerebrovascular disorders or Parkinson's disease was lacking completely. Possible side-effects could not be adequately examined because of the lack of randomised evidence and methodological shortcomings. None of the objectives of this review could be adequately tested because of the lack of firm, randomised evidence. Given the specific problems in the treatment of depressed elderly, a well designed randomised controlled trial should be conducted in which the efficacy of ECT is compared to one or more antidepressants. Output:

This review involved searching the literature for well-conducted (randomised) studies that compared ECT to both simulated ECT and to antidepressants. The review found only four studies, all of which had serious problems in their methods. At present, therefore, it is not possible to draw firm conclusions on whether ECT is more effective than antidepressants,.or on the safety or side effects of ECT in elderly people with depression.

CochranePLS3207

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Seven RCTs were included in the review, involving a total of 393 participants. All of the included studies assessed psychoeducational methods, and one study also assessed a type of systems psychotherapy. In all trials, participants continued to receive pharmacotherapy treatment. Due to the diversity of interventions, outcome measures and endpoints used across studies, it was not possible to perform meta-analyses for primary outcomes. Five studies compared a variety of family interventions, involving carers, families or spouses, against no intervention, with individual findings indicating no significant added effect for family interventions. Three studies compared one type or modality of family intervention against another family intervention, with inconsistent findings. To date there is only a small and heterogeneous body of evidence on the effectiveness of family oriented approaches for bipolar disorder, and it is not yet possible to draw any definite conclusions to support their use as an adjunctive treatment for bipolar disorder. Further well designed RCTs should be a research priority. Output:

Studies on psychosocial interventions for mental disorders such as schizophrenia and anxiety show that they are effective treatments. Reports in the literature suggest that they may be useful for people with bipolar disorder as well. The role of the family is important in the care of people with bipolar disorder, with effective family functioning helping to maintain a person's psychological balance. This systematic review investigated the effectiveness of any psychosocial family intervention for people with bipolar disorder and/or their families and carers. Seven randomised controlled trials (393 participants) were included in the review, all of which evaluated psychoeducational interventions. Five studies compared family interventions against no treatment, and three studies compared one type or delivery of family intervention against another family intervention. Differences in the interventions, outcome measures and end points used in the trials did not allow us to perform a meta-analysis. Whilst results from individual studies did not suggest a significant effect for family interventions when added to drug therapy, the studies provide insufficient evidence to draw conclusions which can be generalised to everyday practice. Further research using appropriate randomised controlled trial methodology and evaluating family interventions other than psychoeducation is called for in this under-researched and important topic.

CochranePLS3208

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We found six RCTs that met the inclusion criteria after independent and duplicate review of the search results. These RCTs included 937 participants and compared outcomes at six months to sham injection for four anti-VEGF agents: aflibercept (VEGF Trap-Eye, Eylea), bevacizumab (Avastin), pegaptanib sodium (Macugen) and ranibizumab (Lucentis). Three trials were conducted in Norway, Sweden and the USA, and three trials were multicentre, one including centres in the USA, Canada, India, Israel, Argentina and Columbia, a second including centres in the USA, Australia, France, Germany, Israel, and Spain, and a third including centres in Austria, France, Germany, Hungary, Italy, Latvia, Australia, Japan, Singapore and South Korea. We performed meta-analysis on three key visual outcomes, using data from up to six trials. High-quality evidence from six trials revealed that participants receiving intravitreal anti-VEGF treatment were 2.71 times more likely to gain at least 15 letters of visual acuity at six months compared to participants treated with sham injections (risk ratio (RR) 2.71; 95% confidence intervals (CI) 2.10 to 3.49). High-quality evidence from five trials suggested anti-VEGF treatment was associated with an 80% lower risk of losing at least 15 letters of visual acuity at six months compared to sham injection (RR 0.20; 95% CI 0.12 to 0.34). Moderate-quality evidence from three trials (481 participants) revealed that the mean reduction from baseline to six months in central retinal thickness was 267.4 µm (95% CI 211.4 µm to 323.4 µm) greater in participants treated with anti-VEGF than in participants treated with sham. The meta-analyses demonstrate that treatment with anti-VEGF is associated with a clinically meaningful gain in vision at six months. One trial demonstrated sustained benefit at 12 months compared to sham. No significant ocular or systemic safety concerns were identified in this time period. Compared to no treatment, repeated intravitreal injection of anti-VEGF agents in eyes with CRVO macular oedema improved visual outcomes at six months. All agents were relatively well tolerated with a low incidence of adverse effects in the short term. Future trials should address the relative efficacy and safety of the anti-VEGF agents and other treatments, including intravitreal corticosteroids, for longer-term outcomes. Output:

This systematic review identified six trials which included 937 participants with macular oedema secondary to CRVO (as of 29 October 2013). The trials compared sham injections with one of four types of anti-VEGF agents: aflibercept (VEGF Trap-Eye, Eylea), bevacizumab (Avastin), pegaptanib sodium (Macugen) and ranibizumab (Lucentis). All trials treated participants for at least six months. Three trials were multicentre, international trials and three were conducted in Norway, Sweden or the USA. Overall, treatment with anti-VEGF agents increased the chance of a significant gain in vision (at least 3 lines on the vision chart) at six months by more than two and a half times, compared to no treatment. Furthermore, the risk of losing significant vision (at least 3 lines on the vision chart) was reduced by 80% in those receiving anti-VEGF therapy compared to those receiving no treatment. No significant safety concerns were identified at six or 12 months, but the available studies do not allow a conclusion about their long-term effectiveness and safety to be drawn. Nevertheless, the availability of anti-VEGF treatment for CRVO macular oedema represents an important advance in the clinical management options for this sight-threatening disease. The six trials included in this review were high quality and consistently demonstrated visual benefit from anti-VEGF injections.

CochranePLS3209

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included six trials (n = 698; most participants were women approximately 40 years of age). All studies evaluated psychotherapy plus usual care (with antidepressants) versus usual care (with antidepressants). Three studies addressed the addition of cognitive-behavioural therapy (CBT) to usual care (n = 522), and one each evaluated intensive short-term dynamic psychotherapy (ISTDP) (n = 60), interpersonal therapy (IPT) (n = 34), or group dialectical behavioural therapy (DBT) (n = 19) as the intervention. Most studies were small (except one trial of CBT was large), and all studies were at high risk of detection bias for the main outcome of self-reported depressive symptoms. A random-effects meta-analysis of five trials (n = 575) showed that psychotherapy given in addition to usual care (vs usual care alone) produced improvement in self-reported depressive symptoms (MD -4.07 points, 95% confidence interval (CI) -7.07 to -1.07 on the Beck Depression Inventory (BDI) scale) over the short term (up to six months). Effects were similar when data from all six studies were combined for self-reported depressive symptoms (SMD -0.40, 95% CI -0.65 to -0.14; n = 635). The quality of this evidence was moderate. Similar moderate-quality evidence of benefit was seen on the Patient Health Questionnaire-9 Scale (PHQ-9) from two studies (MD -4.66, 95% CI 8.72 to -0.59; n = 482) and on the Hamilton Depression Rating Scale (HAMD) from four studies (MD -3.28, 95% CI -5.71 to -0.85; n = 193). High-quality evidence shows no differential dropout (a measure of acceptability) between intervention and comparator groups over the short term (RR 0.85, 95% CI 0.58 to 1.24; six studies; n = 698). Moderate-quality evidence for remission from six studies (RR 1.92, 95% CI 1.46 to 2.52; n = 635) and low-quality evidence for response from four studies (RR 1.80, 95% CI 1.2 to 2.7; n = 556) indicate that psychotherapy was beneficial as an adjunct to usual care over the short term. With the addition of CBT, low-quality evidence suggests lower depression scores on the BDI scale over the medium term (12 months) (RR -3.40, 95% CI -7.21 to 0.40; two studies; n = 475) and over the long term (46 months) (RR -1.90, 95% CI -3.22 to -0.58; one study; n = 248). Moderate-quality evidence for adjunctive CBT suggests no difference in acceptability (dropout) over the medium term (RR 0.98, 95% CI 0.66 to 1.47; two studies; n = 549) and lower dropout over long term (RR 0.80, 95% CI 0.66 to 0.97; one study; n = 248). Two studies reported serious adverse events (one suicide, two hospitalisations, and two exacerbations of depression) in 4.2% of the total sample, which occurred only in the usual care group (no events in the intervention group). An economic analysis (conducted as part of an included study) from the UK healthcare perspective (National Health Service (NHS)) revealed that adjunctive CBT was cost-effective over nearly four years. Moderate-quality evidence shows that psychotherapy added to usual care (with antidepressants) is beneficial for depressive symptoms and for response and remission rates over the short term for patients with TRD. Medium- and long-term effects seem similarly beneficial, although most evidence was derived from a single large trial. Psychotherapy added to usual care seems as acceptable as usual care alone. Further evidence is needed on the effectiveness of different types of psychotherapies for patients with TRD. No evidence currently shows whether switching to a psychotherapy is more beneficial for this patient group than continuing an antidepressant medication regimen. Addressing this evidence gap is an important goal for researchers. Output:

We included six randomised trials (studies in which participants are allocated at random (by chance) to receive one of the treatments being compared). These trials included 698 people and tested three different types of psychotherapy. All studies looked at whether adding psychotherapy to current medical treatment leads to improvement in depression. All studies were funded by public research grants. We found that patients who receive psychotherapy as well as usual care with antidepressants had fewer depressive symptoms and were more often depression-free six months later compared with patients who continued with usual care alone. We are moderately confident of these findings, which means that the true effect of adding CBT may be different from what we found, although findings are likely to be close. We also found that added psychotherapy was as acceptable to patients as usual care alone. Two studies noted similar beneficial effects after 12 months, and one study at 46 months. Two studies reported harmful effects in people receiving usual care alone (one suicide, two people hospitalised) but none in people receiving psychotherapy in addition to usual care. Because participants were aware of the treatment they had received, and because we identified only a small number of studies, we graded the evidence as moderate in quality for findings at six months and low in quality for long-term results. This assessment might change in the future, if higher-quality research results become available.

CochranePLS3210

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We could not identify any studies in which the only difference between the treatment groups was the use of intracystic bleomycin. We did identify a RCT comparing intracystic bleomycin with intracystic phosphorus32 (32P) (seven children). In this update we identified no additional studies. The included study had a high risk of bias. Survival could not be evaluated. There was no clear evidence of a difference between the treatment groups in cyst reduction (MD -0.15, 95% confidence interval (CI) -0.69 to 0.39, P value = 0.59, very low quality of evidence), neurological status (Fisher's exact P value = 0.429, very low quality of evidence), third nerve paralysis (Fischer's exact P value = 1.00, very low quality of evidence), fever (RR 2.92, 95% CI 0.73 to 11.70, P value = 0.13, very low quality of evidence) or total adverse effects (RR 1.75, 95% CI 0.68 to 4.53, P value = 0.25, very low quality of evidence). There was a significant difference in favour of the 32P group for the occurrence of headache and vomiting (Fischer's exact P value = 0.029, very low quality of evidence for both outcomes). Since we identified no RCTs, quasi-randomised trials or CCTs of the treatment of cystic craniopharyngiomas in children in which only the use of intracystic bleomycin differed between the treatment groups, no definitive conclusions could be made about the effects of intracystic bleomycin in these patients. Only one low-power RCT comparing intracystic bleomycin with intracystic 32P treatment was available, but no definitive conclusions can be made about the effectiveness of these agents in children with cystic craniopharyngiomas. Based on the currently available evidence, we are not able to give recommendations for the use of intracystic bleomycin in the treatment of cystic craniopharyngiomas in children. High-quality RCTs are needed. Output:

This systematic review focused on (randomised) controlled studies. We could not identify any randomised controlled trials (RCTs), quasi-randomised trials or controlled clinical trials (CCTs) in which the only difference between the intervention and control group was the use of intracystic bleomycin. However, we did identify one RCT comparing intracystic bleomycin with intracystic phosphorus32 (32P), which is a radioactive isotope of phosphorous used for intracystic irradiation. Only seven children were included in this study. The study has a high risk of bias and the sample size is too small to detect a difference in outcomes. The therapeutic use of intracystic bleomycin in children with cystic craniopharyngiomas currently remains uncertain. Although there was no significant difference in total adverse effects between the two treatment groups, there was a significant difference in both headache and vomiting in favour of the 32P group. The quality of the evidence is, however, very low. More high-quality studies are needed but will be difficult as so few children get these tumours.

CochranePLS3211

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: The methodological quality of primary studies was generally unsatisfying and the results were reported inadequately in many aspects. Additional information was not available from primary trialists. The meta-analysis results showed that patients who had been given G. lucidum alongside with chemo/radiotherapy were more likely to respond positively compared to chemo/radiotherapy alone (RR 1.50; 95% CI 0.90 to 2.51, P = 0.02). G. lucidum treatment alone did not demonstrate the same regression rate as that seen in combined therapy. The results for host immune function indicators suggested that G. lucidum simultaneously increases the percentage of CD3, CD4 and CD8 by 3.91% (95% CI 1.92% to 5.90%, P < 0.01), 3.05% (95% CI 1.00% to 5.11%, P < 0.01) and 2.02% (95% CI 0.21% to 3.84%, P = 0.03), respectively. In addition, leukocyte, NK-cell activity and CD4/CD8 ratio were marginally elevated. Four studies showed that patients in the G. lucidum group had relatively improved quality of life in comparison to controls. One study recorded minimal side effects, including nausea and insomnia. No significant haematological or hepatological toxicity was reported. Our review did not find sufficient evidence to justify the use of G. lucidum as a first-line treatment for cancer. It remains uncertain whether G. lucidum helps prolong long-term cancer survival. However, G. lucidum could be administered as an alternative adjunct to conventional treatment in consideration of its potential of enhancing tumour response and stimulating host immunity. G. lucidum was generally well tolerated by most participants with only a scattered number of minor adverse events. No major toxicity was observed across the studies. Although there were few reports of harmful effect of G. lucidum, the use of its extract should be judicious, especially after thorough consideration of cost-benefit and patient preference. Future studies should put emphasis on the improvement in methodological quality and further clinical research on the effect of G. lucidum on cancer long-term survival are needed. An update to this review will be performed every two years. Output:

Our review identified and subsequently included five relevant randomised controlled trials. A total of 373 subjects were analysed. A meta-analysis was performed to pool available data from individual trials. Our results found that patients with G. lucidum extract in their anticancer regimen were 1.27 times more likely to respond to chemotherapy or radiotherapy than those without. However, the data failed to demonstrate significant effect on tumour shrinkage when it was used alone. In addition, G. lucidum could stimulate host immune functions by considerably increasing CD3, CD4 and CD8 lymphocyte percentages. Nevertheless, natural killer (NK)-cell activity, which has been suggested to be an indicator of self-defence against tumour cell, was marginally elevated. Patients in the G. lucidum group were found to have a relatively better quality of life after treatment than those in the control group. A few cases of minor side effect associated with G. lucidum treatment including nausea and insomnia were reported. There are limitations of the results from this systematic review. First, most included studies were small and there were concerns on the methodological quality of individual trials. Second, all participants in the individual trials were recruited from the Chinese population. Together, the robustness and applicability of the results were largely affected.

CochranePLS3212

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Seven studies enrolling a total of 669 participants were eligible for inclusion in this review. Moderately early steroid treatment (vs placebo or nothing) reduced mortality by 28 days, chronic lung disease at 28 days and 36 weeks, and death or chronic lung disease at 28 days or 36 weeks. Earlier extubation was facilitated. There was no significant effect on the rates of pneumothorax, severe ROP, or NEC. Adverse effects included hypertension, hyperglycaemia, gastrointestinal bleeding, hypertrophic cardiomyopathy and infection. Steroid-treated infants were less likely to need late rescue with dexamethasone. There were limited data from four studies of long term follow-up; these did not show evidence of an increase in adverse neurological outcomes. Moderately early corticosteroid therapy (started at 7-14 days) reduces neonatal mortality and CLD, but at the cost of important short term adverse effects. Limited evidence concerning long term effects is provided by the trials included in this review. The methodological quality of the studies determining the long-term outcome is limited in some cases, the children have been assessed predominantly before school age, and no study has been sufficiently powered to detect important adverse long-term neurosensory outcomes. Therefore, given the risk:benefit ratio of short-term effects and the limited long-term follow-up data, it seems appropriate to reserve moderately early corticosteroid treatment to infants who cannot be weaned from mechanical ventilation and to minimise the dose and duration of any course of therapy. More research is urgently needed, including long term follow-up of survivors included in previous and any future trials, before the benefits and risks of postnatal steroid treatment, including initiation at 7-14 days, can be reliably assessed (See DART study; Doyle 2000a). Output:

Steroid drugs have been effective in improving lung function but early use is associated with an increase in adverse effects (see Early Review). The review of trials found that moderately early use of corticosteroids (started at 7-14 days) reduces the risk of developing CLD. There is limited evidence about possible long term harmful effects. Short term adverse effects include high blood pressure, infection and an excess of glucose in the blood of these preterm babies. More research is needed. Steroid use should be limited until more information is available.

CochranePLS3213

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We found 14 studies that included siblings amongst other family members in receipt of psychoeducational interventions. However, we were only able to include one small trial with relevant and available data (n = 9 siblings out of n = 84 family member/carer-participants) comparing psychoeducational intervention with standard care in a community care setting, over a duration of 21 months. There was insufficient evidence to determine the effects of psychoeducational interventions compared with standard care on 'siblings' quality of life' (n = 9, MD score 3.80 95% CI -0.26 to 7.86, low quality of evidence), coping with (family) burden (n = 9, MD -8.80 95% CI -15.22 to -2.34, low quality of evidence). No sibling left the study early by one year (n = 9, RD 0.00 CI -0.34 to 0.34, low quality of evidence). Low quality and insufficient evidence meant we were unable to determine the effects of psychoeducational interventions compared with standard care on service users' global mental state (n = 9, MD -0.60 CI -3.54 to 2.38, low quality of evidence), their frequency of re-hospitalisation (n = 9, MD -0.70 CI -2.46 to 1.06, low quality of evidence) or duration of inpatient stay (n = 9, MD -2.60 CI -6.34 to 1.14, low quality of evidence), whether their siblings received psychoeducation or not. No study data were available to address the other primary outcomes: 'siblings' psychosocial wellbeing', 'siblings' distress' and adverse effects. Most studies evaluating psychoeducational interventions recruited siblings along with other family members. However, the proportion of siblings in these studies was low and outcomes for siblings were not reported independently from those of other types of family members. Indeed, only data from one study with nine siblings were available for the review. The limited study data we obtained provides no clear good quality evidence to indicate psychoeducation is beneficial for siblings' wellbeing or for clinical outcomes of people affected by SMI. More randomised studies are justified and needed to understand the role of psychoeducation in addressing siblings' needs for information and support. Output:

. A search for randomised trials investigating psychoeducation for the siblings of people with severe mental illness was run in 2013. Results of the search suggest that brothers and sisters form a small proportion of family members participating in studies of this kind. Only one study meeting the review criteria was found. This study included nine siblings and compared a psychoeducational intervention with standard care in a community care setting, over a period of 21 months. . Better outcomes in terms of coping were identified for those siblings who received psychoeducation. However, the number of participants was small and the quality of evidence low, and there is no conclusive evidence that psychoeducation is of benefit for brothers/sisters in this and other important areas (such as wellbeing, quality of life) or for the outcomes of people with mental illness (such as mental state, hospital admission or length of hospital stay). . Further studies are needed to understand the role of psychoeducation in specifically helping brothers and/or sisters to cope with providing care for their mentally ill siblings. The scarcity of good quality studies means that it is not possible to assess which type of psychoeducation is the most effective, although interventions using a group format that brings many family members together to receive education and share their experiences seem well-received by the participants. This plain language summary has been written by a consumer: Ben Gray, Senior Peer Researcher, McPin Foundation.http://mcpin.org/

CochranePLS3214

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We found four double-blind, double-dummy trials comparing LAMA to placebo, including 1197 people with asthma taking combination LABA/ICS. One of the trials was designed to study glycopyrronium bromide but was withdrawn prior to enrolment, and the other three all studied tiotropium bromide (mostly 5 µg once daily via Respimat) over 48 to 52 weeks. People in the trials had a mean forced expiratory volume in one second (FEV1) of 55% of their predicted value, indicating severe asthma. People randomised to take tiotropium add-on had fewer exacerbations requiring oral corticosteroids than those continuing to take LABA/ICS alone, but the confidence intervals did not rule out no difference (OR 0.76, 95% CI 0.57 to 1.02; moderate quality evidence). Over 48 weeks, 328 out of 1000 people taking their usual LABA/ICS would have to take oral corticosteroids for an exacerbation compared with 271 if they took tiotropium as well (95% CI 218 to 333 per 1000). Analyses comparing the number of exacerbations per patient in each group (rate ratio) and the time until first exacerbation (hazard ratio) were in keeping with the main result. Quality of life, as measured by the Asthma Quality of Life Questionnaire (AQLQ) was no better for those taking tiotropium add-on than for those taking LABA/ICS alone when considered in light of the 0.5 minimal clinically important difference on the scale (MD 0.09, 95% CI − 0.03 to 0.20), and evidence for whether tiotropium increased or decreased serious adverse events in this population was inconsistent (OR 0.60, 95% CI 0.24 to 1.47; I2 = 76%). Within the secondary outcomes, exacerbations requiring hospital admission were too rare to tell whether tiotropium was beneficial over LABA/ICS alone. There was high quality evidence showing benefits to lung function (trough FEV1 and forced vital capacity (FVC)) and potentially small benefits to asthma control. People taking tiotropium add-on were less likely to experience non-serious adverse events. Tiotropium add-on may have additional benefits over LABA/ICS alone in reducing the need for rescue oral steroids in people with severe asthma. The effect was imprecise, and there was no evidence for other LAMA preparations. Possible benefits on quality of life were negligible, and evidence for the effect on serious adverse events was inconsistent. There are likely to be small added benefits for tiotropium Respimat 5 µg daily on lung function and asthma control over LABA/ICS alone and fewer non-serious adverse events. The benefit of tiotropium add-on on the frequency of hospital admission is still unknown, despite year-long trials. Ongoing and future trials should clearly describe participants' background medications to help clinicians judge how the findings relate to stepwise care. If studies test LAMAs other than tiotropium Respimat for asthma, they should be at least six months long and use accepted and validated outcomes to allow comparisons of the safety and effectiveness between different preparations. Output:

We found four relevant studies, but one was withdrawn before anyone was signed up. The other three compared a LAMA called tiotropium Respimat to placebo for around a year, with participants in both groups continuing to take their usual LABA/ICS inhaler. People generally had quite poor lung function when they entered the studies, suggesting their asthma was not well controlled - in respiratory medicine, this is known as 'severe asthma'. Over 48 weeks, 328 out of 1000 people taking their usual LABA/ICS had to take a course of oral steroids compared with 271 if they took tiotropium as well. However, uncertainty in the results meant that rather than there being 271 people taking oral steroids, there could be anywhere from 218 to 333 people per 1000 who would have to take oral steroids, so we couldn't be sure of the benefit. Quality of life scores were not that different between those who took tiotropium and those who didn't. The studies showed different results for whether people taking tiotropium were more likely to suffer a serious side effect, but fewer people had non-serious side effects if they took tiotropium. We couldn't tell whether taking tiotropium on top of LABA/ICS reduced the number of people who had to go to hospital for an asthma attack because it didn't happen often enough for us to have confidence in the result. There was high quality evidence that showed benefits to lung function and probably small benefits on measures of asthma control.

CochranePLS3215

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Fourteen trials (590 participants) were included. No overall difference was found for the primary outcome of response to treatment compared with placebo (risk ratio (RR) 1.07, 95% confidence interval (CI) 0.91 to 1.26; 9 trials, N = 454). There was a small reduction in depression symptoms (standardised mean difference (SMD) -0.32, 95% CI -0.59 to -0.04; 13 trials, N = 533), but the evidence was of low quality. Subgroup analyses suggested a small reduction in depression symptoms among adolescents (SMD -0.45, 95% CI -0.83 to -0.007), and negligible change among children (SMD 0.15, 95% CI -0.34 to 0.64). Treatment with a tricyclic antidepressant caused more vertigo (RR 2.76, 95% CI 1.73 to 4.43; 5 trials, N = 324), orthostatic hypotension (RR 4.86, 95% CI 1.69 to 13.97; 5 trials, N = 324), tremor (RR 5.43, 95% CI 1.64 to 17.98; 4 trials, N = 308) and dry mouth (RR 3.35, 95% CI 1.98 to 5.64; 5 trials, N = 324) than did placebo, but no differences were found for other possible adverse effects. Wide CIs and the probability of selective reporting mean that there was very low-quality evidence for adverse events. There was heterogeneity across the studies in the age of participants, treatment setting, tricyclic drug administered and outcome measures. Statistical heterogeneity was identified for reduction in depressive symptoms, but not for rates of remission or response. As such, the findings from analyses of pooled data should be interpreted with caution. We judged none of these trials to be at low risk of bias, with limited information about many aspects of risk of bias, high dropout rates, and issues regarding measurement instruments and the clinical usefulness of outcomes, which were often variously defined across trials. Data suggest tricyclic drugs are not useful in treating depression in children. There is marginal evidence to support the use of tricyclic drugs in the treatment of depression in adolescents. Output:

This review contained 14 trials (with 590 participants) and tested the effectiveness of tricyclic drugs against placebo. Trial data were available for amitriptyline, desipramine, imipramine and nortriptyline. Based on nine trials (454 participants), there was no evidence that tricyclic drugs lead to higher rates of remission or response than placebo. Based on 13 of the trials (533 participants), there was evidence that people treated with a tricyclic drug had lower depression severity scores than those on placebo, however, the size of this difference was small. Consistent with their known mechanism of action, tricyclic drugs were more likely than placebo to cause vertigo, symptoms of lowered blood pressure, tremor and dry mouth. Subgroup analyses of six trials involving only adolescents (239 participants) and two trials involving only children (77 participants) found no evidence of differential rates of remission or response between the age groups. In contrast, there was lowering of depression scores in eight trials involving only adolescents (414 participants) and no lowering of depression scores in three trials involving only children (64 participants). Most of the included studies were conducted in the era before standard methods for conducting treatment trials for depression in children and adolescents came about. There were considerable differences between the studies with regards to the clinical tools and methods used in assessment of improvement. Most trials were small. Only two trials produced a definitive result for depressive symptoms, and no trial produced a definitive result for response or remission. There was typically insufficient information to judge the quality of the trials accurately. With these limitations, it is difficult to answer questions about the effectiveness and safety of tricyclic drugs for treating depression in children and adolescents. Current evidence suggests that the situation is much the same for newer-generation antidepressants. Clinicians need to provide accurate information to children and adolescents, and their families, about the uncertainties regarding the benefits and risks of antidepressants as a treatment option for depression. Tricyclic drugs do not seem useful for treating children before puberty, and are, at most, of moderate benefit for adolescents.

CochranePLS3216

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We identified 15 eligible trials enrolling a total of 1690 infants. Ten trials (1371 infants) compared systemic antifungal prophylaxis versus placebo or no drug. These trials were generally of good methodological quality. Meta-analysis found a statistically significant reduction in the incidence of invasive fungal infection (typical risk ratio (RR) 0.43, 95% confidence interval (CI) 0.31 to 0.59; risk difference (RD) −0.09, 95% CI −0.12 to −0.06). The average incidence of invasive fungal infection in the control groups of the trials (16%) was much higher than that generally reported from large cohort studies. Meta-analysis did not find a statistically significant difference in the risk of death prior to hospital discharge (typical RR 0.79, 95% CI 0.61 to 1.02; typical RD −0.04, 95% CI −0.07 to 0.00). Very limited data on long-term neurodevelopmental outcomes were available. Three trials that compared systemic versus oral or topical non-absorbed antifungal prophylaxis did not detect any statistically significant effects on invasive fungal infection or mortality. Two trials that compared different dose regimens of prophylactic intravenous fluconazole did not detect any significant differences in infection rates or mortality. Prophylactic systemic antifungal therapy reduces the incidence of invasive fungal infection in very preterm or very low birth weight infants. This finding should be interpreted and applied cautiously since the incidence of invasive fungal infection was very high in the control groups of many of the included trials. Meta-analysis does not demonstrate a statistically significant effect on mortality. There are currently only limited data on the long-term neurodevelopmental consequences for infants exposed to this intervention. In addition, there is a need for further data on the effect of the intervention on the emergence of organisms with antifungal resistance. Output:

Study characteristics: We identified 15 eligible trials enrolling a total of 1690 infants. These trials were generally of good quality. Key findings: The overall analysis showed a reduction in the risk of severe fungal infection in infants who received systemic antifungal prophylaxis but did not show a difference in the risk of death. The trials did not assess the risk of long-term problems, including disabilities. Conclusions: There is evidence from some good-quality trials that giving infants an antifungal drug regularly for the first four to six weeks after birth reduces the number of infants who develop severe infection. There is not yet any convincing evidence that death or disability rates are affected.

CochranePLS3217

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Forty RCTs and two QRCTs were identified, including 17 new trials since the first edition of this review in 1999. Many of the early trials were of some form of chemonucleolysis, whereas the majority of the later studies either compared different techniques of discectomy or the use of some form of membrane to reduce epidural scarring. Despite the critical importance of knowing whether surgery is beneficial for disc prolapse, only four trials have directly compared discectomy with conservative management and these give suggestive rather than conclusive results. However, other trials show that discectomy produces better clinical outcomes than chemonucleolysis and that in turn is better than placebo. Microdiscectomy gives broadly comparable results to standard discectomy. Recent trials of an inter-position gel covering the dura (five trials) and of fat (four trials) show that they can reduce scar formation, though there is limited evidence about the effect on clinical outcomes. There is insufficient evidence on other percutaneous discectomy techniques to draw firm conclusions. Three small RCTs of laser discectomy do not provide conclusive evidence on its efficacy, There are no published RCTs of coblation therapy or trans-foraminal endoscopic discectomy. Surgical discectomy for carefully selected patients with sciatica due to lumbar disc prolapse provides faster relief from the acute attack than conservative management, although any positive or negative effects on the lifetime natural history of the underlying disc disease are still unclear. Microdiscectomy gives broadly comparable results to open discectomy. The evidence on other minimally invasive techniques remains unclear (with the exception of chemonucleolysis using chymopapain, which is no longer widely available). Output:

Despite the critical importance of knowing whether surgery is beneficial, only three trials directly compared discectomy with non-surgical approaches. These provide suggestive rather than conclusive results. Overall, surgical discectomy for carefully selected patients with sciatica due to a prolapsed lumbar disc appears to provide faster relief from the acute attack than non-surgical management. However, any positive or negative effects on the lifetime natural history of the underlying disc disease are unclear. Microdiscectomy gives broadly comparable results to standard discectomy. There is insufficient evidence on other surgical techniques to draw firm conclusions. Trials showed that discectomy produced better outcomes than chemonucleolysis, which in turn was better than placebo. For various reasons including concerns about safety, chemonucleolysis is not commonly used today to treat prolapsed disc. Many trials provided limited information on complications, but generally included recurrence of symptoms, need for additional surgery and allergic reactions (chemonucleolysis). Many of the trials had major design weaknesses that introduced considerable potential for bias. Therefore, the conclusions of this review should be read with caution. Future trials should be designed to reduce potential bias. Future research should explore the optimal timing of surgery, patient-centred outcomes, costs and cost-effectiveness of treatment options, and longer-term results over a lifetime perspective.

CochranePLS3218

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Two new trials reporting three comparisons were found in the update. Nineteen trials are included in the review, reporting 22 oral versus intra-vaginal anti-fungal comparisons. No statistically significant differences were shown between oral and intra-vaginal anti-fungal treatment for clinical cure at short term (OR 0.94, 95% CI, 0.75 to 1.17) and long term (OR 1.07, 95% CI, 0.82 to 1.41) follow-up. No statistically significant differences for mycological cure were observed between oral and intra-vaginal treatment at short term (OR 1.15, 95% CI, 0.94 to 1.42). There was a statistically significant difference for long term follow-up (OR 1.29, 95% CI, 1.05 to 1.60) in favour of oral treatment, however the clinical significance of this result is uncertain. Two trials each reported one withdrawal from treatment due to an adverse reaction. Treatment preference data were poorly reported. No statistically significant differences were observed in clinical cure rates of anti-fungals administered by the oral and intra-vaginal routes for the treatment of uncomplicated vaginal candidiasis. No definitive conclusion can be made regarding the relative safety of oral and intra-vaginal anti-fungals for uncomplicated vaginal candidiasis. The decision to prescribe or recommend the purchase of an anti-fungal for oral or intra-vaginal administration should take into consideration: safety, cost and treatment preference. Unless there is a previous history of adverse reaction to one route of administration or contraindications, women who are purchasing their own treatment should be given full information about the characteristics and costs of treatment to make their own decision. If health services are paying the treatment cost, decision-makers should consider whether the higher cost of some oral anti-fungals is worth the gain in convenience, if this is the patient's preference. Output:

The primary objective of this review was to assess the relative effectiveness of oral versus intra-vaginal anti-fungals for the treatment of uncomplicated vulvovaginal candidiasis. The secondary objectives of the review were to assess the cost-effectiveness, safety and patient preference of oral versus intra-vaginal anti-fungals. No statistically significant differences were observed in clinical cure rates of anti-fungals administered by the oral and intra-vaginal routes for the treatment of uncomplicated vaginal candidiasis. No definitive conclusion can be made regarding the relative safety of oral and intra-vaginal anti-fungals for uncomplicated vaginal candidiasis. The decision to prescribe or recommend the purchase of an anti-fungal for oral or intra-vaginal administration should take into consideration: safety, cost and treatment preference. Unless there is a previous history of adverse reaction to one route of administration or contraindications, women who are purchasing their own treatment should be given full information about the characteristics and costs of treatment to make their own decision. If health services are paying the treatment cost, decision-makers should consider whether the higher cost of some oral anti-fungals is worth the gain in convenience, if this is the patient's preference.

CochranePLS3219

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Fifty-six studies, with a total of 4076 participants, met the inclusion criteria. Comparing anticonvulsants with placebo, no statistically significant differences for the six outcomes considered. Comparing anticonvulsant versus other drug, 19 outcomes considered, results favour anticonvulsants only in the comparison carbamazepine versus benzodiazepine (oxazepam and lorazepam) for  alcohol withdrawal symptoms (CIWA-Ar score): 3 studies, 262 participants, MD -1.04 (-1.89 to -0.20),  none of the other comparisons reached statistical significance. Comparing different anticonvulsants no statistically significant differences in the two outcomes considered. Comparing anticonvulsants plus other drugs versus other drugs (3 outcomes considered), results from one study, 72 participants, favour paraldehyde plus chloral hydrate versus chlordiazepoxide, for the severe-life threatening side effects, RR 0.12 (0.03 to 0.44). Results of this review do not provide sufficient evidence in favour of anticonvulsants for the treatment of AWS. There are some suggestions that carbamazepine may actually be more effective in treating some aspects of alcohol withdrawal when compared to benzodiazepines, the current first-line regimen for alcohol withdrawal syndrome. Anticonvulsants seem to have limited side effects, although adverse effects are not rigorously reported in the analysed trials. Output:

This Cochrane review summarizes evidence from forty-eight randomised controlled trials evaluating the effectiveness and safety of anticonvulsants in the treatment of alcohol withdrawal symptoms. There are limited data comparing anticonvulsants versus placebo and no clear differences between anticonvulsants and other drugs in the rates of therapeutic success. Data on safety outcomes are sparse and fragmented. There is a need for larger, well-designed studies in this field.

CochranePLS3220

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included four studies with 1684 participants. Three parallel-group placebo comparisons were in painful diabetic neuropathy (1643 participants), and one cross-over study with diphenhydramine as an active placebo (41 participants) was in lumbar radiculopathy. Doses of topiramate were titrated up to 200 mg/day or 400 mg/day. All studies had one or more sources of potential major bias, as they either used LOCF imputation or were of small size. No study provided first tier evidence for an efficacy outcome. There was no convincing evidence for efficacy of topiramate at 200 to 400 mg/day over placebo. Eighty-two per cent of participants taking topiramate 200 to 400 mg/day experienced at least one adverse event, as did 71% with placebo, and the number needed to treat for an additional harmful effect (NNTH) was 8.6 (95% confidence interval (CI) 4.9 to 35). There was no difference in serious adverse events recorded (6.6% versus 7.5%). Adverse event withdrawals with 400 mg daily were much more common with topiramate (27%) than with placebo (8%), with an NNTH of 5.4 (95% CI 4.3 to 7.1). Lack of efficacy withdrawal was less frequent with topiramate (12%) than placebo (18%). Weight loss was a common event in most studies. No deaths attributable to treatment were reported. Topiramate is without evidence of efficacy in diabetic neuropathic pain, the only neuropathic condition in which it has been adequately tested. The data we have includes the likelihood of major bias due to LOCF imputation, where adverse event withdrawals are much higher with active treatment than placebo control. Despite the strong potential for bias, no difference in efficacy between topiramate and placebo was apparent. Output:

On 8 May 2013, we performed searches to look for clinical trials on the use of topiramate to treat neuropathic pain or fibromyalgia. We found four studies of reasonable quality that tested topiramate against placebo for a number of weeks. Almost all of the 1684 people in the studies had painful limbs because of damaged nerves caused by diabetes. Topiramate did not help the pain and was no different from placebo except in causing more side-effects, which made many more people withdraw from the studies early. About 3 people in 10 withdrew because of side-effects with topiramate compared with 1 in 10 with placebo. Topiramate has not been shown to work as a pain medicine in diabetic neuropathy.

CochranePLS3221

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Two trials were included in the review, totaling 104 participants. One trial assessed additional (four times a day) versus once daily stretching and the other assessed exercise for movement dysfunction versus stretching and strengthening. The first trial, involving 80 elite athletes, suggested additional stretching could reduce time to return to full activity (mean difference (MD) -1.8 days, 95% confidence interval (CI) -2.1 to -1.5, P < 0.001). The second trial, involving 24 participants from a diverse sporting background, did not find conclusive evidence of a difference (MD -14.5 days, 95% CI -30.64 to 1.64, P = 0.08). It did, however, report reduced re-injury rates using exercise for movement dysfunction of 8% versus 64% (odds ratio (OR) 0.05, 95% CI 0.00 to 0.52, P = 0.01). No other outcomes relevant to this review were reported by either study: most notably pain and participant satisfaction. Most proposed physiotherapy techniques for rehabilitation of hamstring injuries have not been assessed using randomised trials. Those that have only have single studies with a limited range of participants and outcomes. There is limited evidence to suggest that time to recovery for elite athletes can be reduced with an increased daily frequency of hamstring stretching exercises. There is preliminary evidence from another small study of mixed ability athletes to suggest that exercise to correct movement dysfunction could reduce time to return to full activity and the risk of re-injury. Further studies are required to check these findings. Until further evidence is available, current practice and widely published rehabilitation protocols cannot either be supported or refuted. Output:

Only two randomised studies, totaling 104 participants, were found that compared rehabilitation programmes for this condition. This means that many proposed techniques have not been subjected to proper scrutiny. There is limited evidence from one study to suggest that rate of recovery can be increased with an increased daily frequency of hamstring stretching exercises. There is preliminary evidence from another small study of mixed ability athletes to suggest that exercise to correct movement dysfunction could reduce time to return to full activity and the risk of re-injury. Further studies are required to check these findings and to inform on current practice and the widely published rehabilitation protocols for these injuries.

CochranePLS3222

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: In this update, review authors added one study to the study from the original review. The first relevant study involved 62 adults with recent-onset dilated cardiomyopathy randomly assigned to receive IVIG or an equivalent volume of 0.1% albumin in a blinded fashion. The overall risk of bias was unclear. The incidence of death or the requirement for cardiac transplant or placement of a left ventricular assist device was low in both groups (odds ratio (OR) for event-free survival 0.52, 95% confidence interval (CI) 0.12 to 2.30). Follow-up at six months and at 12 months showed equivalent improvement in LVEF (mean difference (MD) 0.00, 95% CI -0.07 to 0.07 at six months; MD 0.01, 95% CI -0.06 to 0.08 at 12 months). Functional capacity as assessed by peak oxygen consumption was equivalent in the two groups at 12 months (MD -0.80, 95% CI -4.57 to 2.97). Infusion-related side effects were more common in the treated group, but all were reported to be mild (OR 30.16, 95% CI 1.69 to 539.42). The second study added at this update included 83 children in India with suspected viral encephalitis and myocarditis. The overall risk of bias was high. The odds ratio for event-free survival was 7.39 (95% CI 0.91 to 59.86). Follow-up occurred only until hospital discharge, and LVEF was 49.5% in the treated group versus 35.9% in the placebo group (risk difference 13.6%, 95% CI 5.1 to 22.1%; P value = 0.001). Evidence from one trial does not support the use of IVIG for the treatment of adults with presumed viral myocarditis. The only paediatric trial had high risk of bias but suggested that benefit may be seen in the select group of children beyond the neonatal period who have viral encephalitis with myocarditis. Until higher-quality studies have demonstrated benefit in a particular group of patients, IVIG for presumed viral myocarditis should not be provided as routine practice in any situation. Further studies of the pathophysiology of myocarditis would lead to improved diagnostic criteria, which would facilitate future research. Output:

This is an update of a previous review, which found only one randomised trial of 62 adults, suggesting that IVIG is not useful in myocarditis. A second trial was added with this update. This trial evaluated 83 children who had the relatively rare combination of myocarditis and encephalitis (inflammation of the brain). Investigators found a lower death rate among children receiving IVIG than in those who did not, but this study had high risk of bias. More study is required before IVIG can be routinely recommended for adults or children with myocarditis.

CochranePLS3223

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We identified 10 completed RCTs, most of which were relatively recent (2007 or later) and were conducted with at least some involvement from the intervention developer or the FAST organisation. Nine of the 10 trials were from the USA; the other was from the UK. Children were young (five to nine years old; mean age approximately six years), and therefore, whilst not so named in the reports, evaluations consisted of what is sometimes referred to as 'Kids FAST' and sometimes 'Elementary Level FAST'). Among the USA-based studies, at least 62% of participants were members of a racial/ethnic minority group (most commonly, African American or Latino). FAST was usually delivered in schools after the school day. Trials lasted about eight weeks and usually examined the effects of FAST relative to no additional intervention. Most studies were funded by agencies in the US federal government. We judged the certainty of evidence in the included studies to be moderate or low for the main review outcomes. Failure to include all families in outcome analyses (attrition) and possible bias in recruitment of families into the trials were the main limitations in the evidence. We included over 9000 children and their families in at least one meta-analysis. The follow results relate to meta-analyses of data at long-term follow-up. Primary outcomes Four studies (approximately 6276 children) assessed child school performance at long-term follow-up. The effect size was very small, and the CI did not include effects that, if real, suggest possibly important positive or negative effects if viewed from an individual perspective (SMD -0.02, 95% CI -0.11 to 0.08). We assessed the certainty of evidence for this outcome as moderate. No studies assessed child adverse events, parental substance use, or parental stress. Secondary outcomes Parent reports of child internalising behaviour (SMD -0.03, 95% CI -0.11 to 0.17; 4 RCTs, approximately 908 children; low-certainty evidence) and family relationships (SMD 0.08, 95% CI -0.03 to 0.19; 4 RCTs, approximately 2569 children; moderate-certainty evidence) also yielded CIs that did not include effects that, if real, suggest possibly important positive or negative effects. The CI for parent reports of child externalising behaviour, however, did include effects that, if real, were possibly large enough to be important (SMD -0.19, 95% CI -0.32 to -0.05; 4 RCTs, approximately 754 children; low-certainty evidence). Given these results, it is hard to support the assertion that assignment to FAST is associated with important positive outcomes for children and their parents. Output:

We found 10 randomised controlled studies (studies where schools were assigned to receive FAST or to continue as usual, by a procedure similar to tossing a coin), with a total of more than 9000 children and their families. Nine of the studies took place in the USA and were funded by agencies in the US federal government. One study took place in the UK. Children's ages ranged from five to nine years, and most of the USA-based children were members of a racial or ethnic minority group. Boys and girls were represented at approximately equal rates. In most studies, FAST was delivered at children's schools after the end of the school day, although in some studies it was delivered outside of school (e.g. at a community centre). The trials lasted about eight weeks and usually examined the effects of FAST compared to no additional intervention. The evidence is current as of December 2018. A meta-analysis is a statistical method of combining data from several studies to reach a single, more robust conclusion. We were able to use data from nine studies in a meta-analysis measuring the impact of FAST for children aged between five and eight years. Although individual studies reported some positive findings, there was little evidence to suggest that being involved in a FAST programme results in important improvements in the primary outcomes of child school performance, parental substance abuse, or parental stress. No study measured child adverse outcomes. Furthermore, there was little evidence to suggest that FAST leads to important improvements in child behaviour or family relations. We judged the certainty of evidence in the included studies for the main review outcomes to be moderate or low risk. Failure to include all families in outcome analyses (attrition) and possible bias in recruitment of families into the trials were the main limitations in the evidence. Evidence on the effectiveness of being assigned to FAST is of moderate to low certainty and does not suggest that being assigned to FAST confers important benefits for students and their families.

CochranePLS3224

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: For this update, we identified three new studies and therefore included in the Review four studies with a total of 459 participants who received subcutaneous injections of LMWH into the abdomen. Only one trial reported the injected drug volume (0.4 mL). Owing to the nature of the intervention, it was not possible to blind participants and care givers (personnel) in any included study. Two studies described blinding of outcome assessors; therefore overall, the methodological quality of included studies was moderate. The duration of the fast injection was 10 seconds and the duration of the slow injection was 30 seconds in all included studies. Three studies reported site pain intensity after each injection at different time points. Two studies assessed site pain intensity immediately after each injection, and meta-analysis on 140 participants showed no clear difference in site pain intensity immediately post slow injection when compared to fast injection (low-quality evidence; P = 0.15). In contrast, meta-analysis of two studies with 59 participants showed that 48 hours after the heparin injection, slow injection was associated with less pain intensity compared to fast injection (low-quality evidence; P = 0.007). One study (40 participants) reported pain intensity at 60 and 72 hours after injection. This study described no clear difference in site pain intensity at 60 and 72 hours post slow injection compared to fast injection. All four included studies assessed bruise size at 48 hours after each injection. Meta-analysis on 459 participants showed no difference in bruise size after slow injection compared to fast injection (low-quality evidence; P = 0.07). None of the included studies measured the incidence of haematoma as an outcome. We found four RCTs that evaluated the effect of subcutaneous heparin injection duration on pain intensity and bruise size. Owing to the small numbers of participants, we found insufficient evidence to determine any effect on pain intensity immediately after injection or at 60 and 72 hours post injection. However, slow injection may reduce site pain intensity 48 hours after injection (low-quality evidence). We observed no clear difference in bruise size after slow injection compared to fast injection (low-quality evidence). We judged this evidence to be of low quality owing to imprecision and inconsistency. Output:

We searched for studies that investigated the effects of speed of injection on the amount of pain and bruising where the injection is given (current to March 2017) and found four studies that fitted our review criteria. These studies took place in Turkey, Italy, and China. They enrolled a total of 459 people including 287 female and 172 male participants. All patients received LMWH, and none of the studies used UFH. Participants were treated in hospital, in neurology, orthopaedic, and cardiology units. Investigators injected heparin slow or fast into the abdomen (stomach) of participants. Participants could watch the injection being given and knew whether it was fast (10 seconds long) or slow (30 seconds long). Participants given injections said that pain was less with the slow injection after 48 hours. Owing to the small numbers of participants, we found insufficient evidence to determine any effect on pain intensity immediately after injection or at 60 hours and 72 hours after injection. The bruise was not smaller with the slow injection. None of the included studies reported if participants had a swelling with blood inside (haematoma). We graded the quality of evidence as low because we found only a small number of published studies that reported on this question. These studies were small and had contradictory results. The fact that participants knew whether they received a fast or a slow injection may have affected the results.

CochranePLS3225

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: The original review was based on nineteen trials (17 published and two unpublished) including 4580 patients. This update includes twenty four trials (21 published, 3 unpublished) and 4921 patients, although due to patient exclusion and differential reporting 61% to 75% were available for the analyses. The review strongly suggests chemoradiation improves overall survival and progression free survival, whether or not platinum was used with absolute benefits of 10% and 13% respectively. There was, however, statistical heterogeneity for these outcomes. There was some evidence that the effect was greater in trials including a high proportion of stage I and II patients. Chemoradiation also showed significant benefit for local recurrence and a suggestion of a benefit for distant recurrence. Acute haematological and gastrointestinal toxicity was significantly greater in the concomitant chemoradiation group. Late effects of treatment were not well reported and so the impact of chemoradiation on these effects could not be determined adequately. Treatment-related deaths were rare. Concomitant chemoradiation appears to improve overall survival and progression-free survival in locally advanced cervical cancer. It also appears to reduce local and distant recurrence suggesting concomitant chemotherapy may afford radiosensitisation and systemic cytotoxic effects. Some acute toxicity is increased, but the long-term side effects are still not clear. Output:

The effect appeared to be greater in trials including a high proportion of patients with early stage disease. Combined chemotherapy/radiotherapy also delayed tumour recurrence and reduced the risk of re-growth near the original cancer site as well as in other parts of the body. There was an increase in side-effects, principally affecting the blood and bowel, but these generally only lasted a short time. Long-term effects were poorly reported.

CochranePLS3226

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: A total of 40 randomised or quasi-randomised controlled trials (10 new in this update) met the inclusion criteria, with a total of 1780 out of 2440 children who enrolled receiving an active drug other than desmopressin or a tricyclic. In all, 31 different drugs or classes of drugs were tested. The trials were generally small or of poor methodological quality. There was an overall paucity of data regarding outcomes after treatment was withdrawn. For drugs versus placebo, when compared to placebo indomethacin (risk ratio [RR] 0.36, 95% CI 0.16 to 0.79), diazepam (RR 0.22, 95% CI 0.11 to 0.46), mestorelone (RR 0.32, 95% CI 0.17 to 0.62) and atomoxetine (RR 0.81, 95% CI 0.70 to 0.94) appeared to reduce the number of children failing to have 14 consecutive dry nights. Although indomethacin and diclofenac were better than placebo during treatment, they were not as effective as desmopressin and there was a higher chance of adverse effects. None of the medications were effective in reducing relapse rates, although this was only reported in five placebo controlled trials. For drugs versus drugs, combination therapy with imipramine and oxybutynin was more effective than imipramine monotherapy (RR 0.68, 95% CI 0.50 to 0.94) and also had significantly lower relapse rates than imipramine monotherapy (RR 0.35, 95% CI 0.16 to 0.77). There was an overall paucity of data regarding outcomes after treatment was withdrawn. For drugs versus behavioural therapy, bedwetting alarms were found to be better than amphetamine (RR 2.2, 95% CI 1.12 to 4.29), oxybutynin (RR 3.25, 95% CI 1.77 to 5.98), and oxybutynin plus holding exercises (RR 3.3, 95% CI 1.84 to 6.18) in reducing the number of children failing to achieve 14 consecutive dry nights. Adverse effects of drugs were seen in 19 trials while 17 trials did not adequately report the occurrence of side effects. There was not enough evidence to judge whether or not the included drugs cured bedwetting when used alone. There was limited evidence to suggest that desmopressin, imipramine and enuresis alarms therapy were better than the included drugs to which they were compared. In other reviews, desmopressin, tricyclics and alarm interventions have been shown to be effective during treatment. There was also evidence to suggest that combination therapy with anticholinergic therapy increased the efficacy of other established therapies such as imipramine, desmopressin and enuresis alarms by reducing the relapse rates, by about 20%, although it was not possible to identify the characteristics of children who would benefit from combination therapy. Future studies should evaluate the role of combination therapy against established treatments in rigorous and adequately powered trials. Output:

In other Cochrane reviews, alarms triggered by wetting, desmopressin and tricyclic drugs have been shown to work during treatment. However, alarms have a more sustained effect than desmopressin and tricyclics after treatment has finished. The adverse effects of alarm therapy (tiredness and waking other members of the family) are relatively benign and self limiting compared with the adverse effects of drugs. One class of drugs (anticholinergic drugs) appears to improve the efficacy of other established treatments such as tricyclics, bedwetting alarms and desmopressin. The cost of treating children with bedwetting with alarm therapy or drugs may vary in different countries.

CochranePLS3227

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included eight studies in the review involving a total of 1338 low-risk women in the first stage of spontaneous labour at term. Two comparisons were made; 1) the use of oxytocin versus placebo or no treatment (three trials); 2) the early use of oxytocin versus its delayed use (five trials). There were no significant differences in the rates of caesarean section or instrumental vaginal delivery in either comparison. Early use of oxytocin resulted in an increase in uterine hyperstimulation associated with fetal heart changes. However, the early use of oxytocin versus its delayed use resulted in no significant differences in a range of neonatal and maternal outcomes. Use of early oxytocin resulted in a statistically significant reduction in the mean duration in labour of approximately two hours but did not increase the normal delivery rate. There was significant heterogeneity for this analysis and we carried out a random-effects meta-analysis; however, all of the trials are strongly in the same direction so it is reasonable to conclude that this is the true effect. We also performed a random-effects meta-analysis for the four other analyses which showed substantial heterogeneity in the review. For women making slow progress in spontaneous labour, treatment with oxytocin as compared with no treatment or delayed oxytocin treatment did not result in any discernable difference in the number of caesarean sections performed. In addition there were no detectable adverse effects for mother or baby. The use of oxytocin was associated with a reduction in the time to delivery of approximately two hours which might be important to some women. However, if the primary goal of this treatment is to reduce caesarean section rates, then doctors and midwives may have to look for alternative options. Output:

This review of eight studies, involving 1338 low-risk women in the first stage of spontaneous labour at term, showed that oxytocin did not reduce the need for caesarean sections. Neither did it reduce the need for forceps deliveries or increase the number of normal deliveries when compared with no treatment or delayed oxytocin treatment. Oxytocin seemed to shorten labour by nearly two hours on average. The uptake of epidurals was no different. It does not seem to cause harm to the mother or baby, but the sample size was too small to determine if its use has an effect on the death rates of babies. The decision whether to undergo this treatment is one that can reasonably be left to women to decide in the context of a reduction in the length of labour. The included trials used different doses of oxytocin, and different criteria for starting treatment in the delayed oxytocin arm.

CochranePLS3228

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We found one eligible trial. Participants were 210 newborn infants with birth weight less than 1251 grams. The trial was unblinded but otherwise of good methodological quality. This trial compared removal of an umbilical venous catheter within 10 days after insertion (and replacement with a peripheral cannula or a percutaneously inserted central catheter as required) versus expectant management (UVC in place up to 28 days). More infants in the early planned removal group than in the expectant management group (83 vs 33) required percutaneous insertion of a central catheter (PICC). Trial results showed no difference in the incidence of catheter-related bloodstream infection (RR 0.65, 95% CI 0.35 to 1.22), in hospital mortality (RR 1.12, 95% CI 0.42 to 2.98), in catheter-associated thrombus necessitating removal (RR 0.33, 95% confidence interval 0.01 to 7.94), or in other morbidity. GRADE assessment indicated that the quality of evidence was "low" at outcome level principally as the result of imprecision and risk of surveillance bias due to lack of blinding in the included trial. Currently available trial data are insufficient to show whether early planned removal of umbilical venous catheters reduces risk of infection, mortality, or other morbidity in newborn infants. A large, simple, and pragmatic randomised controlled trial is needed to resolve this ongoing uncertainty. Output:

We found only one small randomised controlled trial (including 210 very low birth weight newborn infants) that addressed this question. This trial did not show that early planned removal of UVCs from infants could reduce their chance of developing a bloodstream infection. However, because the trial was small, this finding is not certain. The trial did not provide sufficient evidence to inform policy or practice; larger trials are needed to resolve this question fully.

CochranePLS3229

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Forty-three randomized trials met the inclusion criteria, of which 29 are new in this update. In most of the studies, training interventions were directed at primary care physicians (general practitioners, internists, paediatricians or family doctors) or nurses practising in community or hospital outpatient settings. Some studies trained specialists. Patients were predominantly adults with general medical problems, though two studies included children with asthma. Descriptive and pooled analyses showed generally positive effects on consultation processes on a range of measures relating to clarifying patients' concerns and beliefs; communicating about treatment options; levels of empathy; and patients' perception of providers' attentiveness to them and their concerns as well as their diseases. A new finding for this update is that short-term training (less than 10 hours) is as successful as longer training. The analyses showed mixed results on satisfaction, behaviour and health status. Studies using complex interventions that focused on providers and patients with condition-specific materials generally showed benefit in health behaviour and satisfaction, as well as consultation processes, with mixed effects on health status. Pooled analysis of the fewer than half of included studies with adequate data suggests moderate beneficial effects from interventions on the consultation process; and mixed effects on behaviour and patient satisfaction, with small positive effects on health status. Risk of bias varied across studies. Studies that focused only on provider behaviour frequently did not collect data on patient outcomes, limiting the conclusions that can be drawn about the relative effect of intervention focus on providers compared with providers and patients. Interventions to promote patient-centred care within clinical consultations are effective across studies in transferring patient-centred skills to providers. However the effects on patient satisfaction, health behaviour and health status are mixed. There is some indication that complex interventions directed at providers and patients that include condition-specific educational materials have beneficial effects on health behaviour and health status, outcomes not assessed in studies reviewed previously. The latter conclusion is tentative at this time and requires more data. The heterogeneity of outcomes, and the use of single item consultation and health behaviour measures limit the strength of the conclusions. Output:

We found 29 new randomized trials (up to June 2010), bringing the total of studies included in the review to 43. In most of the studies, training interventions were directed at primary care physicians (general practitioners, internists, paediatricians or family doctors) or nurses practising in community or hospital outpatient settings. Some studies trained specialists. Patients were predominantly adults with general medical problems, though two studies included children with asthma. These studies showed that training providers to improve their ability to share control with patients about topics and decisions addressed in consultations are largely successful in teaching providers new skills. Short-term training (less than 10 hours) is as successful in this regard as longer training. Results are mixed about whether patients are more satisfied when providers practice these skills. The impact on general health is also mixed, although the limited data that could be pooled showed small positive effects on health status. Patients' specific health behaviours show improvement in the small number of studies where interventions use provider training combined with condition-specific educational materials and/or training for patients, such as teaching question-asking during the consultation or medication-taking after the consultation. However, the number of studies is too small to determine which elements of these multi-faceted studies are essential in helping patients change their healthcare behaviours.

CochranePLS3230

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included eight trials (1563 patients). The drug was IFN alfa-2b in six trials and alfa-2a in two. Trials were heterogeneous in terms of diagnosis of FL, using several classification systems. IFN had been compared with placebo/no intervention in five trials and other chemotherapy in three. The effect of IFN was similar to that of placebo on overall survival (hazard ratio (HR) 0.90, 95% CI 0.61 to 1.34) whereas IFN was more effective when added to chemotherapy (HR 0.68, 95% confidence interval (CI) 0.52 to 0.90). Considering IFN versus all comparators, IFN was effective in prolonging progression-free survival (HR 0.66, 95% CI 0.57 to 0.77) and overall survival (fixed effects HR 0.79, 95% CI 0.67 to 0.94, I2 = 52%). After adjustment for heterogeneity this statistically significance disappeared (random effects HR 0.82, 95% CI 0.63 to 1.08). Toxicity and patients lost to follow up were significantly higher in the IFN groups. There is evidence that addition of IFN as maintenance therapy for FL improves progression-free survival. A net benefit for overall survival is less evident. In the included studies, IFN was associated with significant toxicities that may have a major impact on a patient's quality of life. Output:

The aim of this systematic review is to outline the possible benefits (i.e. prolonging survival) and also the disadvantages (adverse events) of therapy with interferon-alpha, administered alone or in combination with other proven drug regimens (otherwise known as chemotherapy) to patients affected by follicular non-Hodgkin's lymphoma. Interferons are proteins secreted by vertebrate cells that exhibit various biological actions. They confer resistance against many different viruses, inhibit proliferation of normal and malignant cells, augment natural killer cell activity, and show several other immunomodulatory functions. Interferons, types alfa-2a or alfa-2b, are usually administered in combination with other drugs to treat a variety of infective and neoplastic diseases. The results showed a significant benefit in progression-free survival in patients treated with interferon-alpha alone or combined with chemotherapy as compared with comparator therapies. There was, however, less evidence that interferon-alpha supported any benefit on overall survival. Furthermore, the presence of relevant drug-related adverse events suggested that a careful analysis of the risks and benefits has to be performed when making a specific clinical decision about this therapy.

CochranePLS3231

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Twelve trials reporting on nine treatment comparisons (2317 patients randomised) were identified. The majority of trials (10 trials) had an unclear or high risk of bias. Time-to-event data were collected for nine trials for overall survival and eight trials for progression-free survival. All 12 trials reported results for tumour response. In the 12 trials there were 1023 deaths in 2317 women randomised. There was no difference in overall survival, with an overall HR of 1.04 (95% confidence interval (CI) 0.93 to 1.16; P = 0.45), and no significant heterogeneity. This result was consistent in the four subgroups analysed (risk of bias, line of chemotherapy, type of schema of chemotherapy, and relative dose intensity). In particular, there was no difference in survival according to the type of schema of chemotherapy, that is whether chemotherapy was given on disease progression or after a set number of cycles. In the seven trials that reported progression-free survival (time to first progression in the sequential arm), 637 women progressed out of the 846 women randomised. There was weak evidence of a higher risk of progression in the combination arm (HR 1.11; 95% CI 0.99 to 1.25; P = 0.08) with no significant heterogeneity. This result was consistent in all subgroups. Overall tumour response rates were higher in the combination arm (RR 1.16; 95% CI 1.06 to 1.28; P = 0.001) but there was significant heterogeneity for this outcome across the trials. In the seven trials that reported treatment-related deaths, there was no significant difference between the two arms, although the CIs were very wide due to the small number of events (RR 1.53; 95% CI 0.71 to 3.29; P = 0.28). The risk of febrile neutropenia was higher in the combination arm (RR 1.32; 95% CI 1.06 to 1.65; P = 0.01). There was no statistically significant difference in the risk of neutropenia, nausea and vomiting, or treatment-related deaths. Overall quality of life showed no difference between the two groups, but only three trials reported this outcome. There is weak evidence that sequential single agent chemotherapy has a positive effect on progression-free survival, whereas combination chemotherapy has a higher response rate and a higher risk of febrile neutropenia in metastatic breast cancer. There is no difference in overall survival time between these treatment strategies, both overall and in the subgroups analysed. In particular, there was no difference in survival according to the schema of chemotherapy (giving chemotherapy on disease progression or after a set number of cycles) or according to the line of chemotherapy (first-line versus second- or third-line). Generally this review supports the recommendations by international guidelines to use sequential monotherapy unless there is rapid disease progression. Output:

A literature search conducted in October 2013 resulted in 12 randomised controlled studies with 2317 patients that could be included in the analysis. The patients had metastatic breast cancer and either they had not been treated or had received one or two treatments after their diagnosis of metastatic breast cancer. The primary outcomes were overall survival and progression-free survival (time from randomisation to the time of disease progression). Secondarily, we compared the degree the tumour shrunk in response to chemotherapy (overall response rate), toxicity and quality of life. There was no difference in overall survival between the two groups but we found that when drugs were given one at a time there maybe more time before the tumours grew back again (longer progression-free survival). However, combination chemotherapy caused tumours to shrink more, although this did not result in longer survival than when using sequential chemotherapy. Rates of febrile neutropenia (infection) were higher in the combination arm but there was no difference in the rates of neutropenia (low white blood cells). There was no difference in quality of life between the two groups but there were only three trials that reported this information. Quality of life should be included as an outcome in future trials addressing this question. Overall, the studies did not consistently report the way patients were randomised and this may be a source of bias in the results. Generally this review supports the recommendations by international guidelines to use sequential monotherapy unless there is rapid disease progression.

CochranePLS3232

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Three RCTs (1713 participants) fulfilled the selection criteria and we included them in the review. All three trials compared alemtuzumab versus subcutaneous interferon beta-1a for patients with relapsing–remitting MS. Patients were treatment-naive in the CARE-MS and CAMMS223 studies. The CARE-MS II study included patients with at least one relapse while being treated with interferon beta or glatiramer acetate. Alemtuzumab was given for 12 or 24 months; for some outcomes, the follow-up period reached 36 months. The regimens were (a) 12 mg or 24 mg per day administered intravenously, once a day for five consecutive days at month 0 and 12 or (b) 24 mg per day, intravenously, once a day for three consecutive days at month 12 and 24. The patients in the other arm of the trials received interferon beta-1a 44 μg subcutaneously three times weekly after dose titration. At 24 months, alemtuzumab 12 mg was associated with: (a) higher relapse-free survival (hazard ratio (HR) 0.50, 95% CI 0.41 to 0.60; 1248 participants, two studies, moderate quality evidence); (b) higher sustained disease progression-free survival (HR 0.62, 95% CI 0.44 to 0.87; 1191 participants; two studies; moderate quality evidence); (c) a slightly higher number of participants with at least one adverse event (RR 1.04, 95% CI 1.01 to 1.06; 1248 participants; two studies; moderate quality evidence); (d) a lower number of participants with new or enlarging T2-hyperintense lesions on magnetic resonance imaging (MRI) (RR 0.74, 95% CI 0.59 to 0.91; 1238 participants; two studies; I2 = 80%); and (e) a lower number of dropouts (RR 0.31, 95% CI 0.23 to 0.41; 1248 participants; two studies, I2 = 29%; low quality evidence). At 36 months, alemtuzumab 24 mg was associated with: (a) higher relapse-free survival (45 versus 17; HR 0.21, 95% CI 0.11 to 0.40; one study; 221 participants); (b) a higher sustained disease progression-free survival (HR 0.33, 95% CI 0.16 to 0.69; one study; 221 participants); and (c) no statistical difference in the rate of participants with at least one adverse event. We did not find any study that reported any of the following outcomes: rate of participants free of clinical disease activity, quality of life, fatigue or change in the numbers of MRI T2- and T1-weighted lesions after treatment. It was not possible to perform subgroup analyses according to disease type and disability at baseline due to lack of data. In patients with relapsing-remitting MS, alemtuzumab 12 mg was better than subcutaneous interferon beta-1a for the following outcomes assessed at 24 months: relapse-free survival, sustained disease progression-free survival, number of participants with at least one adverse event and number of participants with new or enlarging T2-hyperintense lesions on MRI. The quality of the evidence for these results was low to moderate. Alemtuzumab 24 mg seemed to be better than subcutaneous interferon beta-1a for relapse-free survival and sustained disease progression-free survival, at 36 months. More randomised clinical trials are needed to evaluate the effects of alemtuzumab on other forms of MS and compared with other therapeutic options. These new studies should assess additional relevant outcomes such as the rate of participants free of clinical disease activity, quality of life, fatigue and adverse events (individual rates, serious adverse events and long-term adverse events). Moreover, these new studies should evaluate other doses and durations of alemtuzumab course. Output:

We found three studies (including 1713 participants) that fulfilled the review selection criteria. All studies compared alemtuzumab versus subcutaneous interferon beta-1a for people with relapsing–remitting MS. In two of the studies (CARE-MS and CAMMS223) the participants were being treated for the first time (treatment-naive). The third study (CARE-MS II) included participants with at least one relapse while being treated with interferon beta or glatiramer acetate for at least six months. The review of these comparative studies found that, compared to subcutaneous interferon beta-1a, alemtuzumab reduces the risk of relapse, improves function and seems not to increase the overall risk of adverse events. Additionally, alemtuzumab reduces the risk of new or enlarging lesions of MS detected using magnetic resonance imaging (MRI). However, there is a lack of information about the effects of alemtuzumab on several patient-related outcomes such as (a) quality of life, (b) the rate of each adverse events (separately) and (c) the frequency of long-term adverse events and serious adverse events. The overall methodological quality of the included studies was moderate to high. However, because of the small number of included studies and the low rate of events, we judged the overall quality of the evidence for the main outcomes as very low to moderate. This means that new studies are likely to have an important impact on our confidence in the estimate of effect and may change the estimate or that we are very uncertain about the estimate.

CochranePLS3233

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 24 trials involving 7099 participants. Using the Cochrane 'Risk of bias' tool, we assessed no study as being at low risk of bias for all domains. Many studies were poorly reported, so the risk of selection and detection biases were often unclear. Most studies reported important outcomes incompletely, and we judged them to be at high risk of reporting bias. All but one study enrolled oral poisoning patients in an emergency department; the remaining study was conducted in a pre-hospital setting. Fourteen studies included multiple toxic syndromes or did not specify, while the other studies specifically investigated paracetamol (2 studies), carbamazepine (2 studies), tricyclic antidepressant (2 studies), yellow oleander (2 studies), benzodiazepine (1 study), or toxic berry intoxication (1 study). Twenty-one trials investigated the effects of activated charcoal (AC), administered as a single dose (SDAC) or in multiple doses (MDAC), alone or in combination with other first aid interventions (a cathartic) and/or hospital treatments. Six studies investigated syrup of ipecac plus other first aid interventions (SDAC + cathartic) versus ipecac alone. The collected evidence was mostly of low to very low certainty, often downgraded for indirectness, risk of bias or imprecision due to low numbers of events. First aid interventions that limit or delay the absorption of the poison in the body We are uncertain about the effect of SDAC compared to no intervention on the incidence of adverse events in general (zero events in both treatment groups; 1 study, 451 participants) or vomiting specifically (Peto odds ratio (OR) 4.17, 95% confidence interval (CI) 0.30 to 57.26, 1 study, 25 participants), ICU admission (Peto OR 7.77, 95% CI 0.15 to 391.93, 1 study, 451 participants) and clinical deterioration (zero events in both treatment groups; 1 study, 451 participants) in participants with mixed types or paracetamol poisoning, as all evidence for these outcomes was of very low certainty. No studies assessed SDAC for mortality, duration of symptoms, drug absorption or hospitalization. Only one study compared SDAC to syrup of ipecac in participants with mixed types of poisoning, providing very low-certainty evidence. Therefore we are uncertain about the effects on Glasgow Coma Scale scores (mean difference (MD) −0.15, 95% CI −0.43 to 0.13, 1 study, 34 participants) or incidence of adverse events (risk ratio (RR) 1.24, 95% CI 0.26 to 5.83, 1 study, 34 participants). No information was available concerning mortality, duration of symptoms, drug absorption, hospitalization or ICU admission. This review also considered the added value of SDAC or MDAC to hospital interventions, which mostly included gastric lavage. No included studies investigated the use of body positioning in oral poisoning patients. First aid interventions that evacuate the poison from the gastrointestinal tract We found one study comparing ipecac versus no intervention in toxic berry ingestion in a pre-hospital setting. Low-certainty evidence suggests there may be an increase in the incidence of adverse events, but the study did not report incidence of mortality, incidence or duration of symptoms of poisoning, drug absorption, hospitalization or ICU admission (103 participants). In addition, we also considered the added value of syrup of ipecac to SDAC plus a cathartic and the added value of a cathartic to SDAC. No studies used cathartics as an individual intervention. First aid interventions that neutralize or dilute the poison No included studies investigated the neutralization or dilution of the poison in oral poisoning patients. The studies included in this review provided mostly low- or very low-certainty evidence about the use of first aid interventions for acute oral poisoning. A key limitation was the fact that only one included study actually took place in a pre-hospital setting, which undermines our confidence in the applicability of these results to this setting. Thus, the amount of evidence collected was insufficient to draw any conclusions. Output:

In December 2018 we searched for high-quality studies (randomly dividing participants into different treatment groups) investigating treatments for poisoning that laypeople can perform. We found 24 studies with 7099 participants. All but one study took place in hospitals; the remaining one was in a home setting. Fourteen studies either did not specify the type of poison or studied different kinds. The others investigated overdoses of specific medicines (paracetamol, carbamazepine, antidepressant, benzodiazepine) or poisonous plants (yellow oleander or poisonous berries). Twenty-one trials studied different treatments with activated charcoal: as a single dose or multiple doses, with or without other first aid treatments (a substance to speed up bowel transit), and with or without hospital treatments. Six studies compared syrup of ipecac, with or without other first aid treatments (single-dose activated charcoal plus bowel transit enhancing substance) versus no treatment. We found no studies that investigated the neutralization or dilution of the poison or the use of certain body positions. Two studies compared a single dose of activated charcoal to no treatment following poisoning with paracetamol or different kinds of poisoning. We are uncertain about the treatment's side effects, admission to intensive care or worsening of the patient, and there was no information about effects on death, symptom duration, poison uptake or hospitalization. One study compared a single dose of activated charcoal to ipecac in mixed types of poisoning. We are uncertain about the effect of activated charcoal compared to ipecac, on the patient's level of coma or the number of unwanted effects. There was no information about effects on death, symptom duration, poison uptake, hospitalization or intensive care admission. One study compared ipecac to no treatment in children who ate poisonous berries at home. There may be an increase in the number of unwanted effects for ipecac. There was no information about effects on death, poisoning symptoms, symptoms duration, poison uptake, hospitalization or intensive care admission. We also investigated the use of single-dose or multi-dose activated charcoal, with or without hospital treatment, compared to each other or no treatment. Furthermore, we investigated the added value of ipecac to single-dose activated charcoal and the added value of adding bowel transit enhancing substances to AC. All but one study took place in a hospital setting, which means that the results cannot be directly applied to the lay setting. Because studies did not always report the methods they used, we are uncertain about the quality of the research conduct for many. Outcomes important to patients and pre-specified by us as important outcomes for this review were often absent or incompletely reported. Our certainty about the results of this review is mostly low to very low. Therefore future research is highly likely to change the findings. Based on the identified evidence, we cannot draw any conclusions about the effects of any of the investigated first aid treatments in a lay setting.

CochranePLS3234

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Nine trials in which a total of 754 very preterm or very low birth weight infants participated were eligible for inclusion. Few participants were extremely preterm (< 28 weeks) or extremely low birth weight (< 1000 grams) or growth restricted. These trials did not provide any evidence that early trophic feeding affected feed tolerance or growth rates. Meta-analysis did not detect a statistically significant effect on the incidence of necrotising enterocolitis: typical risk ratio 1.07 (95% confidence interval 0.67 to 1.70); risk difference 0.01 (-0.03 to 0.05). The available trial data do not provide evidence of important beneficial or harmful effects of early trophic feeding for very preterm or very low birth weight infants. The applicability of these findings to extremely preterm, extremely low birth weight or growth restricted infants is limited. Further randomised controlled trials would be needed to determine how trophic feeding compared with enteral fasting affects important outcomes in this population. Output:

Analysis of nine trials does not suggest that this practice increases the risk of a severe bowel disorder called 'necrotising enterocolitis'. Further trials could provide more robust evidence to inform this key area of care.

CochranePLS3235

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: The searches identified 9900 titles and, after excluding duplicates, 6433 titles were initially screened. After the initial title screen, 6266 were excluded. Abstracts were screened for 167 studies and 33 articles were identified as meeting the inclusion criteria, of which 13 were included in the review after an assessment of the complete manuscripts. Seven trials evaluating IE nutrition were included in the review, of which 6 were combined in a meta-analysis. These studies showed a low to moderate level of heterogeneity and significantly reduced total post-operative complications (risk ratio (RR) 0.67 CI 0.53 to 0.84). Three trials evaluating PN were included in a meta-analysis and a significant reduction in post-operative complications was demonstrated (RR 0.64 95% CI 0.46 to 0.87) with low heterogeneity, in predominantly malnourished participants. Two trials evaluating enteral nutrition (RR 0.79, 95% CI 0.56 to 1.10) and 3 trials evaluating standard oral supplements (RR 1.01 95% CI 0.56 to 1.10) were included, neither of which showed any difference in the primary outcomes. There have been significant benefits demonstrated with pre-operative administration of IE nutrition in some high quality trials. However, bias was identified which may limit the generalizability of these results to all GI surgical candidates and the data needs to be placed in context with other recent innovations in surgical management (eg-ERAS). Some unwanted effects have also been reported with components of IE nutrition in critical care patients and it is unknown whether there would be detrimental effects by administering IE nutrition to patients who could require critical care support after their surgery. The studies evaluating PN demonstrated that the provision of PN to predominantly malnourished surgical candidates reduced post-operative complications; however, these data may not be applicable to current clinical practice, not least because they have involved a high degree of 'hyperalimentation'. Trials evaluating enteral or oral nutrition were inconclusive and further studies are required to select GI surgical patients for these nutritional interventions. Output:

Results showed that studies evaluating oral drinks with added nutrients to assist fighting infections ('immune enhancing') given before an operation could reduce total complications from 42% in the control group to 27% in those who received the drinks, while infections were reduced from 27% in the control group to 14% in the group given the drinks. Parenteral nutrition reduced total complications from 45% in the control group to 28% in the group receiving parenteral nutrition. There were no benefits demonstrated for either enteral or standard supplement drinks. Thus, some benefits have been demonstrated from giving nutritional support to patients before an operation with immune enhancing drinks and with parenteral nutrition. However, studies on parenteral nutrition were over 20 years old and during that time there have been many changes to surgical practice. Quality assessment of studies on PN was generally low. Immune enhancing drinks have only been tested with selected surgical patients and some unwanted effects have also been reported using these drinks in critical care patients; it is therefore unknown whether there would be detrimental effects by giving these drinks to patients who could potentially require critical care support after their surgery. No benefit of standard oral or enteral feeding was demonstrated and more research is required in these areas with malnourished patients.

CochranePLS3236

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 51 studies that analysed a total of 5345 participants. One study was assessed as being at unclear risk of bias, with the remaining 50 being at high risk of bias, however, this did not affect the quality assessments for gingivitis and plaque as we believe that further research is very unlikely to change our confidence in the estimate of effect. Gingivitis After 4 to 6 weeks of use, chlorhexidine mouthrinse reduced gingivitis (Gingival Index (GI) 0 to 3 scale) by 0.21 (95% CI 0.11 to 0.31) compared to placebo, control or no mouthrinse (10 trials, 805 participants with mild gingival inflammation (mean score 1 on the GI scale) analysed, high-quality evidence). A similar effect size was found for reducing gingivitis at 6 months. There were insufficient data to determine the reduction in gingivitis associated with chlorhexidine mouthrinse use in individuals with mean GI scores of 1.1 to 3 (moderate or severe levels of gingival inflammation). Plaque Plaque was measured by different indices and the SMD at 4 to 6 weeks was 1.45 (95% CI 1.00 to 1.90) standard deviations lower in the chlorhexidine group (12 trials, 950 participants analysed, high-quality evidence), indicating a large reduction in plaque. A similar large reduction was found for chlorhexidine mouthrinse use at 6 months. Extrinsic tooth staining There was a large increase in extrinsic tooth staining in participants using chlorhexidine mouthrinse at 4 to 6 weeks. The SMD was 1.07 (95% CI 0.80 to 1.34) standard deviations higher (eight trials, 415 participants analysed, moderate-quality evidence) in the chlorhexidine mouthrinse group. There was also a large increase in extrinsic tooth staining in participants using chlorhexidine mouthrinse at 7 to 12 weeks and 6 months. Calculus Results for the effect of chlorhexidine mouthrinse on calculus formation were inconclusive. Effect of concentration and frequency of rinsing There were insufficient data to determine whether there was a difference in effect for either chlorhexidine concentration or frequency of rinsing. Other adverse effects The adverse effects most commonly reported in the included studies were taste disturbance/alteration (reported in 11 studies), effects on the oral mucosa including soreness, irritation, mild desquamation and mucosal ulceration/erosions (reported in 13 studies) and a general burning sensation or a burning tongue or both (reported in nine studies). There is high-quality evidence from studies that reported the Löe and Silness Gingival Index of a reduction in gingivitis in individuals with mild gingival inflammation on average (mean score of 1 on the 0 to 3 GI scale) that was not considered to be clinically relevant. There is high-quality evidence of a large reduction in dental plaque with chlorhexidine mouthrinse used as an adjunct to mechanical oral hygiene procedures for 4 to 6 weeks and 6 months. There is no evidence that one concentration of chlorhexidine rinse is more effective than another. There is insufficient evidence to determine the reduction in gingivitis associated with chlorhexidine mouthrinse use in individuals with mean GI scores of 1.1 to 3 indicating moderate or severe levels of gingival inflammation. Rinsing with chlorhexidine mouthrinse for 4 weeks or longer causes extrinsic tooth staining. In addition, other adverse effects such as calculus build up, transient taste disturbance and effects on the oral mucosa were reported in the included studies. Output:

We included 51 studies that analysed a total of 5345 participants. The evidence in this review is up to date as of 28 September 2016. Generally study participants were children and adults who had gingivitis or periodontitis, were able to use usual tooth cleaning methods and were healthy. We did not exclude studies where some or all participants had medical conditions or special care needs as we considered the use of mouthrinses with chlorhexidine to be particularly relevant to them. The included studies assessed the effects of chlorhexidine mouthrinse used for at least 4 weeks in addition to conventional tooth cleaning on gingivitis in children and adults. There is high-quality evidence that the use of mouthrinses containing chlorhexidine in addition to usual toothbrushing and cleaning for 4 to 6 weeks or 6 months leads to a large reduction in the build-up of plaque. There is also high-quality evidence of a moderate reduction in gingivitis in people with a mild level of it, although because the level of disease was already low this is not considered clinically important. The nature of the available evidence does not allow us to determine the level of reduction of gingivitis in people with moderate to severe levels of it. There was no evidence that one concentration or strength of chlorhexidine rinse was more effective than another. Rinsing for 4 weeks or longer causes tooth staining, which requires scaling and polishing carried out by a dental professional. Other side effects have been reported, including build-up of calculus (tartar), temporary taste disturbance and temporary shedding of/damage to the lining of the mouth. One study was assessed as being at unclear risk of bias, with the remaining 50 being at high risk of bias, however this did not affect the quality assessments for gingivitis and plaque as we believe that further research is very unlikely to change our confidence in the estimate of effect.

CochranePLS3237

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Two RCTs were included, involving 2667 adult patients with RRMS to evaluate the efficacy and safety of two dosages of dimethyl fumarate (240 mg orally three times daily or twice daily) by direct comparison with placebo for two years. Among them, a subsample of 1221 (45.8%) patients were selected to participate in MRI evaluations by each study site with MRI capabilities itself. No powered head-to-head study with an active treatment comparator has been found. Meta-analyses showed that dimethyl fumarate both three times daily and twice daily reduced the number of patients with a relapse (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.50 to 0.66, P < 0.00001 and 0.64, 95% CI 0.54 to 0.77, P < 0.00001, respectively) or disability worsening (RR 0.70, 95% CI 0.57 to 0.87, P = 0.0009 and 0.65, 95% CI 0.53 to 0.81, P = 0.0001, respectively) over two years, compared to placebo. The treatment effects were decreased in the likely-case scenario analyses taking the effect of dropouts into consideration. Both dosages also reduced the annualised relapse rate. Data of active lesions on MRI scans were not combined because there was a high risk of selection bias for MRI outcomes and imprecision of MRI data in both studies, as well as an obvious heterogeneity between the studies. In terms of safety profile, both dosages increased the risk for adverse events and the risk for drug discontinuation due to adverse events. The most common adverse events included flushing and gastrointestinal events (upper abdominal pain, nausea and diarrhoea). Uncommon adverse events included lymphopenia and leukopenia, but they were more likely to happen with dimethyl fumarate than with placebo (high dosage: RR 5.25, 95% CI 2.20 to 12.51, P = 0.0002 and 5.23, 95% CI 2.47 to 11.07, P < 0.0001, respectively; low dosage: RR 5.69, 95% CI 2.40 to 13.46, P < 0.0001 and 6.53, 95% CI 3.13 to 13.64, P < 0.00001, respectively). Both studies had a high attrition bias resulting from the unbalanced reasons for dropouts among groups. Quality of evidence for relapse outcome was moderate, but for disability worsening was low. There is moderate-quality evidence to support that dimethyl fumarate at a dose of 240 mg orally three times daily or twice daily reduces both the number of patients with a relapse and the annualised relapse rate over two years of treatment in comparison with placebo. However, the quality of the evidence to support the benefit in reducing the number of patients with disability worsening is low. There is no high-quality data available to evaluate the benefit on MRI outcomes. The common adverse effects such as flushing and gastrointestinal events are mild-to-moderate for most patients. Lymphopenia and leukopenia are uncommon adverse events but significantly associated with dimethyl fumarate. Both dosages of dimethyl fumarate have similar benefit and safety profile, which supports the option of low-dose administration. New studies of high quality and long-term follow-up are needed to evaluate the benefit of dimethyl fumarate on prevention of disability worsening and to observe the long-term adverse effects including progressive multifocal leukoencephalopathy. Output:

We searched medical databases for studies in which participants were randomly assigned to dimethyl fumarate or a control drug (randomised controlled trials). The efficacy of this therapy was considered in terms of occurrence of relapses and progression of the disease. We found moderate quality evidence that both dosages of dimethyl fumarate reduce the number of people with RRMS having relapse after two years of treatment, while there is low quality evidence showing that the medicine reduces the number of people who experience worsening disability at the end of two years. Common adverse effects such as flushing and gastrointestinal events (diarrhoea, nausea and upper abdominal pain) are mild to moderate for most of patients. Dimethyl fumarate can have an effect on the body's immune system by causing a drop in the number of the white blood cells which help to fight infection. More people in the groups treated with dimethyl fumarate experienced this than they did with placebo. We found moderate quality that people were more likely to leave the study early because of adverse events if they were treated with dimethyl fumarate than with placebo.

CochranePLS3238

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included eight studies that reported on 916 infants. One of these studies compared paracetamol to both ibuprofen and indomethacin. Five studies compared treatment of PDA with paracetamol versus ibuprofen and enrolled 559 infants. There was no significant difference between paracetamol and ibuprofen for failure of ductal closure after the first course of drug administration (typical risk ratio (RR) 0.95, 95% confidence interval (CI) 0.75 to 1.21; typical risk difference (RD) −0.02, 95% CI −0.09 to 0.09); I² = 0% for RR and RD; moderate quality of evidence. Four studies (n = 537) reported on gastrointestinal bleed which was lower in the paracetamol group versus the ibuprofen group (typical RR 0.28, 95% CI 0.12 to 0.69; typical RD −0.06, 95% CI −0.09 to −0.02); I² = 0% for RR and RD; number needed to treat for an additional beneficial outcome (NNTB) 17 (95% CI 11 to 50); moderate quality of evidence. The serum levels of creatinine were lower in the paracetamol group compared with the ibuprofen group in four studies (moderate quality of evidence), as were serum bilirubin levels following treatment in two studies (n = 290). Platelet counts and daily urine output were higher in the paracetamol group compared with the ibuprofen group. One study reported on long-term follow-up to 18 to 24 months of age following treatment with paracetamol versus ibuprofen. There were no significant differences in the neurological outcomes at 18 to 24 months (n = 61); (low quality of evidence). Two studies compared prophylactic administration of paracetamol for a PDA with placebo or no intervention in 80 infants. Paracetamol resulted in a lower rate of failure of ductal closure after 4 to 5 days of treatment compared to placebo or no intervention which was of borderline significance for typical RR 0.49 (95% CI 0.24 to 1.00; P = 0.05); but significant for typical RD −0.21 (95% CI −0.41 to −0.02); I² = 0 % for RR and RD; NNTB 5 (95% CI 2 to 50); (low quality of evidence). Two studies (n = 277) compared paracetamol with indomethacin. There was no significant difference in the failure to close a PDA (typical RR 0.96, 95% CI 0.55 to 1.65; I² = 11%; typical RD −0.01, 95% CI −0.09 to 0.08; I² = 17%) (low quality of evidence). Serum creatinine levels were significantly lower in the paracetamol group compared with the indomethacin group and platelet counts and daily urine output were significantly higher in the paracetamol group. Moderate-quality evidence according to GRADE suggests that paracetamol is as effective as ibuprofen; low-quality evidence suggests paracetamol to be more effective than placebo or no intervention; and low-quality evidence suggests paracetamol as effective as indomethacin in closing a PDA. There was no difference in neurodevelopmental outcome in children exposed to paracetamol compared to ibuprofen; however the quality of evidence is low and comes from only one study. In view of concerns raised regarding neurodevelopmental outcomes following prenatal and postnatal exposure to paracetamol, long-term follow-up to at least 18 to 24 months' postnatal age must be incorporated in any studies of paracetamol in the newborn population. At least 19 ongoing trials have been registered. Such trials are required before any recommendations for the possible routine use of paracetamol in the newborn population can be made. Output:

We identified a total of eight studies that enrolled 916 preterm infants and compared the effectiveness and safety of paracetamol versus ibuprofen, indomethacin or placebo in the treatment of a PDA in early life. When the results of the included studies were combined, the success rate for paracetamol to close a PDA was higher than that of placebo and similar to that of ibuprofen and indomethacin. Paracetamol appears to have fewer adverse effects on kidney and liver functions. In one small study that followed children to 18 to 24 months of age there was no difference in neurodevelopmental impairment. The evidence is up to date as of November 2017. Paracetamol appears to be a promising alternative to indomethacin and ibuprofen for the closure of a PDA with possibly fewer adverse effects. Additional studies testing this intervention and including longer-term follow-up are needed before paracetamol can be recommended as standard treatment for a PDA in preterm infants. Several studies are ongoing that will eventually provide additional information. Because of reports of a possible association between prenatal paracetamol and the development of autism or autism spectrum disorder in childhood and language delay in girls, long-term follow-up to at least 18 to 24 months' postnatal age must be incorporated in any studies of paracetamol in the newborn population. Although the healthcare providers were not always 'blinded' (unaware of which drug the infants received) we judged the quality of the evidence to be moderate.

CochranePLS3239

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included nine RCTs involving 2888 participants without occupational irritant hand dermatitis (OIHD) at baseline. Six studies, including 1533 participants, investigated the effects of barrier creams, moisturisers, or both. Three studies, including 1355 participants, assessed the effectiveness of skin protection education on the prevention of OIHD. No studies were eligible that investigated the effects of protective gloves. Among each type of intervention, there was heterogeneity concerning the criteria for assessing signs and symptoms of OIHD, the products, and the occupations. Selection bias, performance bias, and reporting bias were generally unclear across all studies. The risk of detection bias was low in five studies and high in one study. The risk of other biases was low in four studies and high in two studies. The eligible trials involved a variety of participants, including: metal workers exposed to cutting fluids, dye and print factory workers, gut cleaners in swine slaughterhouses, cleaners and kitchen workers, nurse apprentices, hospital employees handling irritants, and hairdressing apprentices. All studies were undertaken at the respective work places. Study duration ranged from four weeks to three years. The participants' ages ranged from 16 to 67 years. Meta-analyses for barrier creams, moisturisers, a combination of both barrier creams and moisturisers, or skin protection education showed imprecise effects favouring the intervention. Twenty-nine per cent of participants who applied barrier creams developed signs of OIHD, compared to 33% of the controls, so the risk may be slightly reduced with this measure (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.72 to 1.06; 999 participants; 4 studies; low-quality evidence). However, this risk reduction may not be clinically important. There may be a clinically important protective effect with the use of moisturisers: in the intervention groups, 13% of participants developed symptoms of OIHD compared to 19% of the controls (RR 0.71, 95% CI 0.46 to 1.09; 507 participants; 3 studies; low-quality evidence). Likewise, there may be a clinically important protective effect from using a combination of barrier creams and moisturisers: 8% of participants in the intervention group developed signs of OIHD, compared to 13% of the controls (RR 0.68, 95% CI 0.33 to 1.42; 474 participants; 2 studies; low-quality evidence). We are uncertain whether skin protection education reduces the risk of developing signs of OIHD (RR 0.76, 95% CI 0.54 to 1.08; 1355 participants; 3 studies; very low-quality evidence). Twenty-one per cent of participants who received skin protection education developed signs of OIHD, compared to 28% of the controls. None of the studies addressed the frequency of treatment discontinuation due to adverse effects of the products directly. However, in three studies of barrier creams, the reasons for withdrawal from the studies were unrelated to adverse effects. Likewise, in one study of moisturisers plus barrier creams, and in one study of skin protection education, reasons for dropout were unrelated to adverse effects. The remaining studies (one to two in each comparison) reported dropouts without stating how many of them may have been due to adverse reactions to the interventions. We judged the quality of this evidence as moderate, due to the indirectness of the results. The investigated interventions to prevent OIHD probably cause few or no serious adverse effects. Moisturisers used alone or in combination with barrier creams may result in a clinically important protective effect, either in the long- or short-term, for the primary prevention of OIHD. Barrier creams alone may have slight protective effect, but this does not appear to be clinically important. The results for all of these comparisons were imprecise, and the low quality of the evidence means that our confidence in the effect estimates is limited. For skin protection education, the results varied substantially across the trials, the effect was imprecise, and the pooled risk reduction was not large enough to be clinically important. The very low quality of the evidence means that we are unsure as to whether skin protection education reduces the risk of developing OIHD. The interventions probably cause few or no serious adverse effects. We conclude that at present there is insufficient evidence to confidently assess the effectiveness of interventions used in the primary prevention of OIHD. This does not necessarily mean that current measures are ineffective. Even though the update of this review included larger studies of reasonable quality, there is still a need for trials which apply standardised measures for the detection of OIHD in order to determine the effectiveness of the different prevention strategies. Output:

We included nine studies in this review, involving 2888 male and female workers aged between 16 and 67. The studies included several types of workers: metal workers, dye and print factory workers, gut cleaners in swine slaughterhouses, cleaners and kitchen workers, hospital employees, and hairdressing apprentices. We were unable to find out whether or not the preventive measures were equally effective in all these professions because there were too few trials. The studies lasted from four weeks up to three years. Some of the preventive measures may reduce the risk of hand skin irritations. However, there were too few studies to be sure of this. The studies were too different from each other to combine in a meaningful way, and the results were too imprecise. Our results are therefore still debatable. Various barrier creams, moisturisers, and skin protection education programs were investigated. It is possible that barrier creams may slightly reduce the risk of developing OIHD. This result was based on four studies. In these studies, 29% of people who applied barrier creams developed hand skin irritations. In the control group, who did not apply barrier creams, 33% developed hand skin irritations. The results of three studies showed that moisturisers may reduce the risk of developing OIHD by a useful amount. Thirteen per cent of the people who used moisturisers developed hand skin irritations, compared to 19% of those who did not use moisturisers. Two studies showed that using a combination of barrier creams and moisturisers may reduce the risk of developing OIHD by a useful amount. Eight per cent of the people who used moisturisers and barrier creams developed hand skin irritations, compared to 13% of the control group. Based on three studies, we are uncertain whether skin protection education reduces the risk of developing OIHD. In these studies, 21% of the people who received skin protection education developed hand skin irritations, compared to 28% of the people in the control group. The safety and tolerability of these measures were not systematically addressed in these studies. However, no serious reactions to the treatments were reported. Mild reactions like itching or reddening of the skin were reported for only few people who applied the barrier creams or moisturisers. The measures to prevent hand skin irritations probably cause only few or no serious adverse effects. For barrier creams, moisturisers, or a combination of both, the quality of the evidence was low concerning the prevention of OIHD. There was not enough information and hand dermatitis was assessed differently across the studies. For educational programmes, the quality of the evidence was very low concerning the prevention of hand skin irritation. There was not enough information, hand dermatitis was assessed differently across the studies, and the studies were poorly conducted in some important respects. For the other key outcome, safety and tolerability of the treatments, the quality of the evidence was moderate because only indirect results were available.

CochranePLS3240

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Nine randomised (Banner 2000; Baum 2000; Goldman 1990; Kilmann 1987; Kockott 1975; Melnik 2005; Munjack 1984; Price 1981; Wylie 2003) and two quasi-randomised trials (Ansari 1976; Van Der Windt 2002), involving 398 men with ED (141 in psychotherapy group, 109 received medication, 68 psychotherapy plus medication, 20 vacuum devices and 59 control group) met the inclusion criteria. In data pooled from five randomised trials (Kockott 1975; Ansari 1976; Price 1981; Munjack 1984; Kilmann 1987), group psychotherapy was more likely than the control group (waiting list - a group of participants who did not receive any active intervention) to reduce the number of men with "persistence of erectile dysfunction" at post-treatment (RR 0.40, 95% CI 0.17 to 0.98, N = 100; NNT 1.61, 95% CI 0.97 to 4.76). At six months follow up there was continued maintenance of reduction of men with "persistence of ED" in favour of group psychotherapy (RR 0.43, 95% CI 0.26 to 0.72, N = 37; NNT 1.58, 95% CI 1.17 to 2.43). In data pooled from two randomised trials (Price 1981; Kilmann 1987), sex-group psychotherapy reduced the number of men with "persistence of erectile dysfunction" in post-treatment (RR 0.13, 95% CI 0.04 to 0.43, N = 37), with a 95% response rate for sex therapy and 0% for the control group (waiting list - no treatment) (NNT 1.07, 95% CI 0.86 to 1.44). Treatment response appeared to vary between patient subgroups, although there was no significant difference in improvement in erectile function according to mean group age, type of relationship, and severity of ED. In two trials (Melnik 2005; Banner 2000) that compared group therapy plus sildenafil citrate versus sildenafil, men randomised to receive group therapy plus sildenafil showed significant reduction of "persistence of ED" (RR 0.46, 95% CI 0.24 to 0.88; NNT 3.57, 95% CI 2 to 16.7, N = 71), and were less likely than those receiving only sildenafil to drop out (RR 0.29, 95% CI 0.09 to 0.93). One small trial (Melnik 2005) directly compared group therapy and sildenafil citrate. It found a significant difference favouring group therapy versus sildenafil in the mean difference of the IIEF (WMD -12.40, 95% CI -20.81 to -3.99, N = 20). No differences in effectiveness were found between psychosocial interventions versus local injection and vacuum devices. There was evidence that group psychotherapy may improve erectile function. Treatment response varied between patient subgroups, but focused sex-group therapy showed greater efficacy than control group (no treatment). In a meta-analysis that compared group therapy plus sildenafil citrate versus sildenafil, men randomised to receive group therapy plus sildenafil showed significant improvement of successful intercourse, and were less likely than those receiving only sildenafil to drop out. Group psychotherapy also significantly improved ED compared to sildenafil citrate alone. Regarding the effectiveness of psychosocial interventions for the treatment of ED compared to local injection, vacuum devices and other psychosocial techniques, no differences were found. Output:

Distinct sources of randomised clinical trials (RCTs) were searched, such as electronic databases (between 1966 and 2007). We also crosschecked references and contacted scientific societies. Eleven trials involving 398 men met the inclusion criteria. Conclusions: there is evidence that group therapy (GT) improves ED in selected patients. Focused sex GT showed greater efficacy than control group. Men who received GT plus sildenafil showed significant improvement of ED and were less likely than those receiving only sildenafil to drop out. In comparing the effectiveness of psychological interventions for the treatment of ED versus local injection and vacuum devices, no difference was found.

CochranePLS3241

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Seven trials with a total of 2144 participants were included. Four studies (1959 participants) addressed subjective change in severity of rhinorrhoea. All studies were consistent in reporting statistically significant changes in favour of IB. Nasal congestion was reported in four studies and was found to have no significant change between the two groups. Two studies found a positive response in the IB group for the global assessment of overall improvement. Side effects were more frequent in the IB group, odds ratio (OR) 2.09 (95% confidence interval (CI) 1.40 to 3.11). Commonly encountered side effects included nasal dryness, blood tinged mucus and epistaxis. The overall risk of bias in the included studies was moderate. For people with the common cold, the existing evidence, which has some limitations, suggests that IB is likely to be effective in ameliorating rhinorrhoea. IB had no effect on nasal congestion and its use was associated with more side effects compared to placebo or no treatment although these appeared to be well tolerated and self limiting. There is a need for larger, high-quality trials to determine the effectiveness of IB in relieving common cold symptoms. Output:

We identified seven trials that included 2144 participants. There were more side effects with IB, such as dryness of the nose, mucus with streaks of blood and bleeding from the nose. Limitations in this review included two studies with missing participants and four studies with unclear blinding of the participants, personnel or outcome assessors. These limitations resulted in the majority of studies having an unclear risk of bias, which raises the concern of overestimation of the overall effect of IB. We concluded from this review that IB may be effective in improving the runny nose with some side effects that are well tolerated. There is a need for more high-quality studies to determine the effectiveness of IB in relieving common cold symptoms.

CochranePLS3242

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Psychological interventions as a group The SMD for symptom score improvement at 2 and 3 months was 0.97 (95% CI 0.29 to 1.65) and 0.62 (95% CI 0.45 to 0.79) respectively compared to usual care. Against placebo, the SMDs were 0.71 (95% CI 0.08 to 1.33) and -0.17 (95% CI -0.45 to 0.11) respectively. For improvement of abdominal pain, the SMDs at 2 and 3 months were 0.54 (95%CI 0.10 to 0.98) and 0.26 (95% CI 0.07 to 0.45) compared to usual care. The SMD from placebo at 3 months was 0.31 (95% CI -0.16 to 0.79). For improvement in quality of life, the SMD from usual care at 2 and 3 months was 0.47 (95%CI 0.11 to 0.84) and 0.31 (95%CI -0.16 to 0.77) respectively. Cognitive behavioural therapy The SMD for symptom score improvement at 2 and 3 months was 0.75 (95% CI -0.20 to 1.70) and 0.58 (95% CI 0.36 to 0.79) respectively compared to usual care. Against placebo, the SMDs were 0.68 (95% CI -0.01 to 1.36) and -0.17 (95% CI -0.45 to 0.11) respectively. For improvement of abdominal pain, the SMDs at 2 and 3 months were 0.45 (95% CI 0.00 to 0.91) and 0.22 (95% CI -0.04 to -0.49) compared to usual care. Against placebo the SMD at 3 months was 0.33 (95% CI -0.16 to 0.82). For improvement in quality of life, the SMDs at 2 and 3 months compared to usual care were 0.44 (95% CI 0.04 to 0.85) and 0.92 (95% CI 0.07 to 1.77) respectively. Interpersonal psychotherapy The RR for adequate relief of symptoms was 2.02 (95% CI 1.13 to 3.62), RD 0.30 (95% CI 0.13 to 0.46), NNT 4 for comparison with care as usual. The SMD for improvement of symptom score was 0.35 (95% CI -0.75 to 0.05) compared with usual care. Relaxation/Stress management The SMD in symptom score improvement at 2 months was 0.50 (95%CI 0.02 to 0.98) compared with usual care. The SMD in improvement of abdominal pain at 3 months was 0.02 (95%CI -0.56 to 0.61) compared with usual care. Long term results Very few long term follow-up results were available. There was no convincing evidence that treatment effects were sustained following completion of treatment for any treatment modality. Psychological interventions may be slightly superior to usual care or waiting list control conditions at the end of treatment although the clinical significance of this is debatable. Except for a single study, these therapies are not superior to placebo and the sustainability of their effect is questionable. The meta-analysis was significantly limited by issues of validity, heterogeneity, small sample size and outcome definition. Future research should adhere to current recommendations for IBS treatment trials and should focus on the long-term effects of treatment. Output:

In this review, the effectiveness of psychological therapies for adult patients with irritable bowel syndrome was evaluated. Studies involving cognitive behavioural therapy, interpersonal psychotherapy and relaxation therapy or stress management were reviewed. Although it is difficult to draw conclusions because of differences between studies and quality issues, the results suggest that cognitive behavioural therapy and interpersonal psychotherapy may be effective immediately after finishing treatment. It is unclear whether the effects of these therapies are sustained thereafter. These results have to be interpreted with caution as the quality of the studies was sub-optimal. Physicians should be aware of the limitations of these therapies and should choose an appropriate therapy based on the individual patient's characteristics.

CochranePLS3243

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Twenty-six studies, with 2295 participants, were included comparing paracetamol plus codeine with placebo. Significant dose response was seen for the outcome of at least 50% pain relief over four-to-six hours, with NNTs of 2.2 (95% CI 1.8 to 2.9) for 800 to 1000 mg paracetamol plus 60 mg codeine, 3.9 (2.9 to 4.5) for 600 to 650 mg paracetamol plus 60 mg codeine, and 6.9 (4.8 to 12) for 300 mg paracetamol plus 30 mg codeine. Time to use of rescue medication was over four hours with paracetamol plus codeine and two hours with placebo. The NNT to prevent remedication was 5.6 (4.0 to 9.0) for 600 mg paracetamol plus 60 mg codeine over four to six hours. Adverse events increased of mainly mild to moderate severity with paracetamol plus codeine than placebo. Fourteen studies, with 926 participants, were included in the comparison of paracetamol plus codeine with the same dose of paracetamol alone. Addition of codeine increased proportion of participants achieving at least 50% pain relief over four-to-six hours by 10 to 15%, increased time to use of rescue medication by about one hour, and reduced proportion of participants needing rescue medication by about 15% (NNT to prevent remedication 6.9 (4.2 to 19). Adverse events were mainly mild to moderate in severity and incidence did not differ between groups. This update confirms previous findings that combining paracetamol with codeine provided clinically useful levels of pain relief in about 50% of patients with moderate to severe postoperative pain, compared with under 20% with placebo. New information for remedication shows that the combination extended the duration of analgesia by about one hour compared to treatment with the same dose of paracetamol alone. At higher doses, more participants experienced adequate pain relief, but the amount of information available for the 1000 mg paracetamol plus 60 mg codeine dose was small, and based on limited information. Output:

This review assessed data from twenty-six studies comparing paracetamol plus codeine with placebo, and fourteen studies comparing paracetamol plus codeine with the same dose of paracetamol alone. The combination provided effective pain relief for about 40% of participants experiencing moderate to severe pain after an operation with 600 to 650 mg paracetamol plus 60 mg codeine, the dose most commonly used in these studies, and about 50% of participants with 800 to 1000 mg paracetamol plus 60 mg codeine, the dose most commonly used in clinical practice. The addition of codeine provided effective pain relief to about 10% more participants than the same dose of paracetamol alone. These single dose studies did not associate paracetamol plus codeine with any serious side effects.

CochranePLS3244

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Twenty studies (986 participants; 966 MS participants and 20 healthy controls) fulfilled the inclusion criteria. The mean age of the participants was 44.6 years, mean length of education was 12.3 years and 70% of the participants were women. Most of the participants had a relapsing-remitting course of disease. The mean Expanded Disability Status Scale score was 3.2 and the mean duration of disease was 14.0 years. On the basis of these studies, we found low-level evidence that neuropsychological rehabilitation reduces cognitive symptoms in MS. Cognitive training was found to improve memory span (standardised mean difference (SMD) 0.54, 95% confidence interval (CI) 0.20 to 0.88, P = 0.002) and working memory (SMD 0.33, 95% CI 0.09 to 0.57, P = 0.006). Cognitive training combined with other neuropsychological rehabilitation methods was found to improve attention (SMD 0.15, 95% CI 0.01 to 0.28, P = 0.03), immediate verbal memory (SMD 0.31, 95% CI 0.08 to 0.54, P = 0.008) and delayed memory (SMD 0.22, 95% CI 0.02 to 0.42, P = 0.03). There was no evidence of an effect of neuropsychological rehabilitation on emotional functions. The overall quality, as well as the comparability of the included studies, was relatively low due to methodological limitations and heterogeneity of interventions and outcome measures. Although most of the pooled results in the meta-analyses yielded no significant findings, 18 of the 20 studies showed some evidence of positive effects when the studies were individually analysed. This review found low-level evidence for positive effects of neuropsychological rehabilitation in MS. The interventions and outcome measures included in the review were heterogeneous, which limited the comparability of the studies. New trials may therefore change the strength and direction of the evidence. Output:

Twenty relevant studies comprising a total of 986 participants (966 MS participants and 20 healthy controls) were identified and included in this review. Low-level evidence was found that neuropsychological rehabilitation reduces cognitive symptoms in MS. However, when analysed individually, 18 out of the 20 studies showed positive effects. Cognitive training was found to improve memory span and working memory. Cognitive training combined with other neuropsychological rehabilitation methods was found to improve attention, immediate verbal memory and delayed memory. It is worth noting that the small numbers of patients in the studies and some methodological weaknesses reduce the level of the evidence. To further strengthen the evidence well-designed, high-quality studies are needed.

CochranePLS3245

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Five randomised or quasi-randomised double-blind trials fulfilled the selection criteria, but were not sufficiently comparable to undertake a meta-analysis. The drugs studied were verapamil (8 participants), diltiazem (56 participants), nifedipine (105 participants) and flunarizine (27 participants). There were limitations in the description of blinding and randomisation, and definition of outcome measures. One trial, using verapamil, showed a difference between groups in muscle force measured by ergometry, but also revealed cardiac side effects. The numbers of people included in the trials were low, and so the studies may not have included enough people for sufficient power to detect small differences in muscle force or function between placebo and control groups. In addition, calcium antagonists were in an early stage of development and some of the second generation drugs that have a better side effect profile, such as amlodipine, have not been studied. There is no evidence to show a significant beneficial effect of calcium antagonists on muscle function in DMD. Output:

This is an updated review. In the original review original eight studies were identified and five were high enough quality to be included. In this update no new trials were identified and so five were still included in the review. These studies were of different types of calcium channel blocking drugs and measured a variety of outcomes such as muscle strength, scales of muscle function, biochemical changes in muscle and electrocardiographic findings. Only one study showed a beneficial effect, which was an increase in muscle strength, but in this study the drug used was also associated with cardiac side effects. Adverse effects noted were mostly known side effects of calcium channel blockers. Limitations of the review were that a meta-analysis could not be done as the trials used different calcium channel blockers and measured different outcomes, and all but one of the trials included a low number of patients. In conclusion, the review did not find calcium antagonists to have a useful effect.

CochranePLS3246

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Nine Cochrane reviews were selected for this overview. Their scores on the Overview Quality Assessment Questionnaire varied from four to six of a maximal possible score of seven. Compared with general anaesthesia, neuraxial blockade reduced the zero to 30-day mortality (risk ratio [RR] 0.71, 95% confidence interval [CI] 0.53 to 0.94; I2 = 0%) based on 20 studies that included 3006 participants. Neuraxial blockade also decreased the risk of pneumonia (RR 0.45, 95% CI 0.26 to 0.79; I2 = 0%) based on five studies that included 400 participants. No difference was detected in the risk of myocardial infarction between the two techniques (RR 1.17, 95% CI 0.57 to 2.37; I2 = 0%) based on six studies with 849 participants. Compared with general anaesthesia alone, the addition of a neuraxial block to general anaesthesia did not affect the zero to 30-day mortality (RR 1.07, 95% CI 0.76 to 1.51; I2 = 0%) based on 18 studies with 3228 participants. No difference was detected in the risk of myocardial infarction between combined neuraxial blockade-general anaesthesia and general anaesthesia alone (RR 0.69, 95% CI 0.44 to 1.09; I2 = 0%) based on eight studies that included 1580 participants. The addition of a neuraxial block to general anaesthesia reduced the risk of pneumonia (RR 0.69, 95% CI 0.49 to 0.98; I2 = 9%) after adjustment for publication bias and based on nine studies that included 2433 participants. The quality of the evidence was judged as moderate for all six comparisons. No serious adverse events (seizure or cardiac arrest related to local anaesthetic toxicity, prolonged central or peripheral neurological injury lasting longer than one month or infection secondary to neuraxial blockade) were reported. The quality of the reporting score of complications related to neuraxial blocks was nine (four to 12 (median range)) of a possible maximum score of 14. Compared with general anaesthesia, a central neuraxial block may reduce the zero to 30-day mortality for patients undergoing surgery with intermediate to high cardiac risk (level of evidence, moderate). Further research is required. Output:

When epidurals or spinals were used to replace general anaesthesia, the risk of dying during the surgery or within the following 30 days was reduced by approximately 29% (from 20 studies with 3006 participants). Also, the risk of developing pneumonia (chest infection) was reduced by 55% (from five studies with 400 participants). However, the risk of developing a myocardial infarction (heart attack) was the same for both anaesthetic techniques (from six studies with 849 participants). When epidurals (and less frequently spinals) were used to reduce the quantity of other drugs required while general anaesthesia was used, the risk of dying during the surgery or within 30 days was the same for both anaesthetic techniques (from 18 studies with 3228 participants). Also, a difference was not detected for the risk of developing myocardial infarction (from eight studies with 1580 participants). The risk of developing pneumonia was reduced by approximately 30% when a correction was made for possible missing studies (from nine studies with 2433 participants). No serious side effects (seizures, cardiac arrest, nerve damage lasting longer than one month or infection) were reported from the use of epidurals or spinals in these studies. The quality of the evidence for all six comparisons was rated as moderate because of some imperfections in how the studies were carried out. Therefore further research is likely to have an important impact on our confidence in these results and may even change the results. .

CochranePLS3247

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Six RCTs with 456 participants and variable treatment and follow-up periods were included. From the limited data, the live birth rate per couple randomly assigned (27% vs 0%; Peto odds ratio (OR) 9.31, 95% confidence interval (CI) 1.17 to 73.75, one study, 30 participants, very low-quality evidence) and the spontaneous pregnancy rate per couple randomly assigned (16% vs 7%; Peto OR 4.94, 95% CI 2.13 to 11.44, five studies, 412 participants, I2 = 0%, moderate-quality evidence) were significantly higher in men receiving gonadotrophin treatment than in men receiving placebo or no treatment. No significant difference between groups was noted when intracytoplasmic sperm injection (ICSI) or intrauterine insemination (IUI) was performed. None of the included studies reported miscarriage rates, and adverse events data were sparse. Encouraging preliminary data suggest a beneficial effect on live birth and pregnancy of gonadotrophin treatment for men with idiopathic male factor subfertility, but because the numbers of trials and participants are small, evidence is insufficient to allow final conclusions. Large multi-centre trials with adequate numbers of participants are needed. Output:

There was a trend towards an increase in live birth and pregnancy rates during and within three months of gonadotrophin treatment. The quality of the evidence was very low. We did not find enough studies to allow final conclusions about the use of gonadotrophins in the treatment of men with idiopathic male factor subfertility. The quality of the evidence was very low. More studies on this subject are needed. The evidence is current to January 2013.

CochranePLS3248

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: One trial (46 participants) was eligible for inclusion. After randomization eight participants were withdrawn, mainly because they declined to participate in the trial. Data were analysed for 38 participants at the end of the trial. After a mean follow-up of three years, hip core decompression and physical therapy did not show clinical improvement when compared with physical therapy alone using the score from the original trial (an improvement of 18.1 points for those treated with intervention therapy versus an improvement of 15.7 points with control therapy). We are very uncertain whether there is any difference between groups regarding major complications (hip pain, risk ratio 0.95 (95% confidence interval 0.56 to 1.60; vaso-occlusive crises, risk ratio 1.14 (95% confidence interval 0.72 to 1.80; very low quality of evidence); and acute chest syndrome, risk ratio 1.06 (95% confidence interval 0.44 to 2.56; very low quality of evidence)). This trial did not report results on mortality or quality of life. We found no evidence that adding hip core decompression to physical therapy achieves clinical improvement in people with sickle cell disease with avascular necrosis of bone compared to physical therapy alone. However, we highlight that our conclusion is based on one trial with high attrition rates. Further randomized controlled trials are necessary to evaluate the role of hip-core depression for this clinical condition. Endpoints should focus on participants' subjective experience (e.g. quality of life and pain) as well as more objective 'time-to-event' measures (e.g. mortality, survival, hip longevity). The availability of participants to allow adequate trial power will be a key consideration for endpoint choice. Output:

We found one eligible trial, published in 2006, which analysed data from 38 people from 32 different treatment centers from the USA. The trial compared a treatment of surgery and physical therapy with physical therapy on its own. This trial did not show that the addition of surgery to a physical therapy regimen could improve the outcome for people with sickle cell disease and avascular necrosis. After a mean follow-up of three years, the combination of surgery and physical therapies did not show clinical improvement when compared with physical therapy alone. Given that the results are imprecise, we are uncertain as to whether surgery and physical therapies in combination has an important effect on hip pain, vaso-occlusive crises and acute chest syndrome. Trial authors did not report information on mortality and quality of life. The limited number of participants included in the study led to imprecise results, therefore, the confidence in the results is very low.

CochranePLS3249

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included in the analysis one small sham-controlled randomised trial of 173 women performed in the United States. Participants enrolled in this study had been diagnosed with stress UI and were randomly assigned to transurethral radiofrequency collagen denaturation (treatment) or a sham surgery using a non-functioning catheter (no treatment). Mean age of participants in the 12-month multi-centre trial was 50 years (range 22 to 76 years). Of three patient-important primary outcomes selected for this systematic review, the number of women reporting UI symptoms after intervention was not reported. No serious adverse events were reported for the transurethral radiofrequency collagen denaturation arm or the sham treatment arm during the 12-month trial. Owing to high risk of bias and imprecision, we downgraded the quality of evidence for this outcome to low. The effect of transurethral radiofrequency collagen denaturation on the number of women with an incontinence quality of life (I-QOL) score improvement ≥ 10 points at 12 months was as follows: RR 1.11, 95% CI 0.77 to 1.62; participants = 142, but the confidence interval was wide. For this outcome, the quality of evidence was also low as the result of high risk of bias and imprecision. We found no evidence on the number of women undergoing repeat continence surgery. The risk of other adverse events (pain/dysuria (RR 5.73, 95% CI 0.75 to 43.70; participants = 173); new detrusor overactivity (RR 1.36, 95% CI 0.63 to 2.93; participants = 173); and urinary tract infection (RR 0.95, 95% CI 0.24 to 3.86; participants = 173) could not be established reliably as the trial was small. Evidence was insufficient for assessment of whether use of transurethral radiofrequency collagen denaturation was associated with an increased rate of urinary retention, haematuria and hesitancy compared with sham treatment in 173 participants. The GRADE quality of evidence for all other adverse events with available evidence was low as the result of high risk of bias and imprecision. We found no evidence to inform comparisons of transurethral radiofrequency collagen denaturation with conservative physical treatment, mechanical devices, drug treatment, injectable treatment for UI or other surgery for UI. It is not known whether transurethral radiofrequency collagen denaturation, as compared with sham treatment, improves patient-reported symptoms of UI. Evidence is insufficient to show whether the procedure improves disease-specific quality of life. Evidence is also insufficient to show whether the procedure causes serious adverse events or other adverse events in comparison with sham treatment, and no evidence was found for comparison with any other method of treatment for UI. Output:

We searched for all randomised controlled trials that studied this form of treatment up to December 2014. We found only one trial of 173 women who were troubled by urinary leakage. On average, these women were 50 years of age. Through random assignment, two-thirds of them were treated with low-temperature heat via the urethra; the others did not receive this treatment. Researchers followed these women for 12 months. The makers of this treatment paid for the study. No information revealed whether more or fewer women complained of urinary leakage at 12 months, or whether there was a difference in the number of women having repeat surgery. The study did not show that quality of life was improved. Evidence was insufficient to show whether there was a difference in serious or minor side effects. Using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, we found no evidence for the question of whether low-temperature heat via the urethra changed the number of women who leaked. We found low-quality evidence related to serious side effects, minor side effects and quality of life when compared with no treatment because data were limited and the study was poorly conducted. We found no evidence on whether this treatment changed the number of women who underwent another surgery. Because we did not find studies that compared this treatment with other treatments, we do not know whether this treatment results in better or worse outcomes.

CochranePLS3250

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Only two eligible trials were included (593 patients), both of reasonable quality although one was unblinded. Both trials compared selegiline with a dopamine agonist, whilst one also compared selegiline with levodopa. MAO-B inhibitors were not associated with a significant increase or decrease in deaths compared with levodopa (odds ratio (OR) 0.96; 95% confidence interval (CI) 0.52 to 1.76) or dopamine agonists (OR 1.30; 95% CI 0.69 to 2.45). Those receiving MAO-B inhibitors were more likely to require add-on therapy during follow-up than those receiving levodopa (OR 12.02; 95% CI 6.78 to 21.31) or dopamine agonist (OR 2.00; 95% CI 1.05 to 3.81). There was a reduction in motor fluctuations with MAO-B inhibitors compared with levodopa (OR 0.55; 95% CI 0.32 to 0.94) but not dopamine agonists (OR 1.15; 95% CI 0.65 to 2.05). Withdrawals due to adverse events were less common with MAO-B inhibitors than with dopamine agonists (OR 0.11; 95% CI 0.01 to 0.99). MAO-B inhibitors are one option for the early treatment of PD although they have weaker symptomatic effects than levodopa and dopamine agonists. They may reduce the rate of motor fluctuations compared with initial levodopa therapy and may have fewer significant adverse effects than the older agonists but data are too few to provide reliable conclusions. Output:

We reviewed the trials that compared giving MAO-B inhibitors with other types of medication in people with early Parkinson's to see if there was good evidence that MAO-B inhibitors were the best treatment to offer. However, unfortunately we only identified two trials (593 patients) so there was only limited evidence. The results showed that MAO-B inhibitors were less good at improving the symptoms of Parkinson's than either levodopa or dopamine agonists but that they may reduce motor fluctuations compared with levodopa, though not compared with dopamine agonists. MAO-B inhibitors did, however, have fewer major side effects than some dopamine agonists.

CochranePLS3251

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included seven trials involving a total of 75 people with mild to moderate asthma. The studies were all of cross-over design. Six trials involving 55 people showed that in comparison with placebo, caffeine, even at a 'low dose' (less than 5 mg/kg body weight), appears to improve lung function for up to two hours after consumption. Forced expiratory volume in one second (FEV1) showed a small improvement up to two hours after caffeine ingestion (standardised mean difference 0.72; 95% confidence interval 0.25 to 1.20), which translates into a 5% mean difference in FEV1. However in two studies the mean differences in FEV1 were 12% and 18% after caffeine. Mid-expiratory flow rates also showed a small improvement with caffeine and this was sustained up to four hours. One trial involving 20 people examined the effect of drinking coffee versus a decaffeinated variety on the exhaled nitric oxide levels in patients with asthma and concluded that there was no significant effect on this outcome. Caffeine appears to improve airways function modestly, for up to four hours, in people with asthma. People may need to avoid caffeine for at least four hours prior to lung function testing, as caffeine ingestion could cause misinterpretation of the results. Drinking caffeinated coffee before taking exhaled nitric oxide measurements does not appear to affect the results of the test, but more studies are needed to confirm this. Output:

This review carefully examines all the available high-quality clinical trials on caffeine in asthma. This review was conducted to discover if people should avoid consuming caffeine before taking lung function tests. This review found that even small amounts of caffeine can improve lung function for up to four hours. Therefore caffeine can affect the result of a lung function test (e.g. spirometry) and so caffeine should be avoided before taking a lung function test if possible, and previous caffeine consumption should be recorded. It is not known if taking caffeine leads to improvements in symptoms. It may be that in order to improve the symptoms of asthma, caffeine is needed in such large amounts that the drug's adverse effects would become a problem, so more research is needed. Another clinical trial looked at the effect of caffeine on exhaled nitric oxide levels and found that there is no significant effect, so it appears unlikely that patients would need to avoid caffeine before taking this type of test. However, this is the result of just a single study so more research is needed to clarify this.

CochranePLS3252

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Six studies (reported in 50 publications) were included with a total of 784 participants. Duration of treatment in the included studies ranged from 12 days to six months, with open-label treatment for an additional six months in two of the studies. Five studies compared mannitol with control (a very low dose of mannitol or non-respirable mannitol) and the final study compared mannitol to dornase alfa alone and to mannitol plus dornase alfa. Two large studies had a similar parallel design and provided data for 600 participants, which could be pooled where data for a particular outcome and time point were available. The remaining studies had much smaller sample sizes (ranging from 22 to 95) and data could not be pooled due to differences in design, interventions and population. Pooled evidence from the two large parallel studies was judged to be of low to moderate quality and from the smaller studies was judged to be of low to very low quality. In all studies, there was an initial test to see if participants tolerated mannitol, with only those who could tolerate the drug being randomised; therefore, the study results are not applicable to the cystic fibrosis population as a whole. While the published papers did not provide all the data required for our analysis, additional unpublished data were provided by the drug's manufacturer and the author of one of the studies. Pooling the large parallel studies comparing mannitol to control, up to and including six months, lung function (forced expiratory volume at one second) measured in both mL and % predicted was significantly improved in the mannitol group compared to the control group (moderate-quality evidence). Beneficial results were observed in these studies in adults and in both concomitant dornase alfa users and non-users in these studies. In the smaller studies, statistically significant improvements in lung function were also observed in the mannitol groups compared to the non-respirable mannitol groups; however, we judged this evidence to be of low to very low quality. For the comparisons of mannitol and control, we found no consistent differences in health-related quality of life in any of the domains except for burden of treatment, which was less for mannitol up to four months in the two pooled studies of a similar design; this difference was not maintained at six months. It should be noted that the tool used to measure health-related quality of life was not designed to assess mucolytics and pooling of the age-appropriate tools (as done in some of the included studies) may not be valid so results were judged to be low to very low quality and should be interpreted with caution. Cough, haemoptysis, bronchospasm, pharyngolaryngeal pain and post-tussive vomiting were the most commonly reported side effects in both treatment groups. Where rates of adverse events could be compared, statistically no significant differences were found between mannitol and control groups; although some of these events may have clinical relevance for people with CF. For the comparisons of mannitol to dornase alfa alone and to mannitol plus dornase alfa, very low-quality evidence from a 12-week cross-over study of 28 participants showed no statistically significant differences in the recorded domains of health-related quality of life or measures of lung function. Cough was the most common side effect in the mannitol alone arm but there was no occurrence of cough in the dornase alfa alone arm and the most commonly reported reason of withdrawal from the mannitol plus dornase alfa arm was pulmonary exacerbations. In terms of secondary outcomes of the review (pulmonary exacerbations, hospitalisations, symptoms, sputum microbiology), evidence provided by the included studies was more limited. For all comparisons, no consistent statistically significant and clinically meaningful differences were observed between mannitol and control treatments (including dornase alfa). There is moderate-quality evidence to show that treatment with mannitol over a six-month period is associated with an improvement in some measures of lung function in people with cystic fibrosis compared to control. There is low to very low-quality evidence suggesting no difference in quality of life for participants taking mannitol compared to control. This review provides very low-quality evidence suggesting no difference in lung function or quality of life comparing mannitol to dornase alfa alone and to mannitol plus dornase alfa. The clinical implications from this review suggest that mannitol could be considered as a treatment in cystic fibrosis; but further research is required in order to establish who may benefit most and whether this benefit is sustained in the longer term. Furthermore, studies comparing its efficacy against other (established) mucolytic therapies need to be undertaken before it can be considered for mainstream practice. Output:

We included six studies (with a total of 784 adults and children) in this review. Five studies compared a standard dose of mannitol with control (a very low dose of mannitol or a version of mannitol which did not allow the active drug to reach the lungs) and the sixth study compared mannitol with nebulised recombinant human deoxyribonuclease (dornase alfa), both alone and taken together. Participants could continue using dornase alfa and other standard therapies, but were excluded from the five of the six studies if they were using hypertonic saline. Treatment in these studies lasted from 12 days to six months. Five studies provided the treatments to people as outpatients and in one study, the children treated were in hospital due to pulmonary exacerbations (flare ups of disease). It was difficult to combine evidence from the studies in this review due to differences in the designs of the studies, treatments examined and the settings (hospital or outpatients). Some additional information was obtained from the drug manufacturer and one study author to aid the review. The review found low- to very low-quality evidence that there is no difference between mannitol and control treatments or mannitol given either with or without additional dornase alfa in terms of quality of life. There was moderate-quality evidence of improvements in some measures of lung function across the larger studies comparing mannitol to control. Beneficial effects were also seen in the subgroup of adults and in both those who were using dornase alfa and those who were not. Cough (including coughing up blood), contraction of the airways, pain in the pharynx or larynx and post-treatment vomiting were the most commonly reported side effects on both treatments, but there was no evidence to suggest that these side effects occurred more on mannitol than on control treatments or on dornase alfa. None of the studies compared mannitol to nebulised hypertonic saline and so we can not comment on which agent is better for airway clearance. More research is needed to answer this question. We judged the quality of the evidence from this review to be of very low to moderate quality, depending on the outcome measured. We do not think that the way the studies were designed affected the results. We judged that everyone taking part had equal chances of being in either of the treatment groups and would not have known in advance or during the study which treatment they were receiving. However, the numbers of people who dropped out of the studies might affect how the results are interpreted, as well as how many people were recruited into the studies and how they were selected from all people with cystic fibrosis who could have been included. Although some of these issues were resolved when the drug's manufacturer (who also sponsored the studies) provided some additional information. It is important to realise that before people started the study, they took a test to see if they could tolerate mannitol and only those who did could carry on. This means that the results of the studies only apply to those people with cystic fibrosis who can tolerate mannitol.

CochranePLS3253

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Forty seven randomised controlled trials involving 3448 children (of whom 2210 received desmopressin) met the inclusion criteria. The quality of many of the trials was poor. Desmopressin was effective in reducing bed-wetting during treatment, compared with placebo (e.g. 20 µg: 1.34 fewer wet nights per week; 95% confidence interval (CI) 1.11 to 1.57), and children were more likely to become dry (e.g. 118/146, 81% versus 140/142, 98% still wet; relative risk (RR) for failure to achieve 14 dry nights with 20 µg was 0.84; 95% CI 0.79 to 0.91). However, there was no difference between the two patient groups after treatment was finished. There was no clear dose-related effect of desmopressin, but the evidence was limited. Data which compared oral and nasal administration were too few to be conclusive. In four small trials, there were no significant differences between desmopressin and alarms during treatment when these were used separately, but the chance of failure or relapse after treatment stopped was lower after an alarm in two small trials (40/62, 65% versus 26/57, 46%; RR 1.42, 95% CI 1.05 to 1.91). Although children had fewer wet nights during treatment when they used desmopressin combined with alarm treatment compared with alarms alone (WMD -0.83, 95% CI -1.11 to -0.55), there were no significant differences either in failure rates during treatment (RR 0.88; 95% CI 0.73 to 1.05) or for relapse after treatment stopped (105/213, 49% versus 118/214, 55%: RR 0.91, 95% CI 0.76 to 1.08). Comparison with some tricyclic drugs (e.g. amitriptyline) suggested that they might be as effective as desmopressin, although in two trials children were less likely to achieve 14 dry nights with imipramine than desmopressin (RR 0.44, 95% CI 0.27 to 0.73) but there was not enough information about subsequent relapse. There were more side effects with the tricyclics. Desmopressin may be better than diclofenac or indomethacin. There was not enough information to evaluate the relative effects of behavioural or complementary treatments against desmopressin. Desmopressin rapidly reduced the number of wet nights per week experienced by children, but the limited evidence available suggested that this was not sustained after treatment stopped. Comparison with alternative treatments suggested that desmopressin and tricyclics had similar clinical effects during treatment, but that alarms may produce more sustained benefits. However, based on the available limited evidence, these conclusions are only tentative. Children should be advised not to drink more than 240 ml (8 ounces) of fluid during the evening before desmopressin treatment in order to avoid the possible risk of water intoxication. Output:

When desmopressin is used, most of the children have fewer wet nights (one night less on average per week) and more become dry (19% compared with only 2% using dummy treatment in five trials involving 288 children). However, many children start wetting again when treatment stops. On the other hand, more children remain dry when alarm treatment is finished (54% after alarm compared with 35% after desmopressin in two trials involving 119 children). Adding desmopressin to alarm treatment did not result in better cure rates after the end of treatment (51% remained dry after combination treatment compared with 45% after alarm alone). Those using desmopressin (or their parents) should be warned that over-drinking before bedtime should be avoided as this may lead to serious, but rare, adverse effects. Drugs called tricyclic antidepressants have a similar effect to desmopressin and are cheaper, but have more adverse effects. There are few adverse effects with alarms, other than short-term disruption for the family. In summary, alarms take longer to reduce bed-wetting, but their effect may persist longer than desmopressin.

CochranePLS3254

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Three RCTs were identified, comprising a total of 847 participants. One trial compared silver-containing foam (Contreet®) with hydrocellular foam (Allevyn®) in patients with leg ulcers. The second trial compared a silver-containing alginate (Silvercel®) with an alginate alone (Algosteril®). The third trial compared a silver-containing foam dressing (Contreet®)) with best local practice in patients with chronic wounds. The data from these trials show that silver-containing foam dressings did not significantly increase complete ulcer healing as compared with standard foam dressings or best local practice after up to four weeks of follow-up, although a greater reduction of ulcer size was observed with the silver-containing foam. The use of antibiotics was assessed in two trials, but no significant differences were found. Data on pain, patient satisfaction, length of hospital stay, and costs were limited and showed no differences. Leakage occurred significantly less frequently in patients with leg ulcers and chronic wounds treated with a silver dressing than with a standard foam dressing or best local practice in one trial. Only three trials with a short follow-up duration were found. There is insufficient evidence to recommend the use of silver-containing dressings or topical agents for treatment of infected or contaminated chronic wounds. Output:

Three studies looking at people with chronic wounds were included in the review and found that silver-containing foam dressings did not result in faster wound healing after up to four weeks of follow-up. One study did find that the overall size of the ulcer reduced more quickly when dressed with a silver-containing foam. There is no enough evidence to recommend the use of silver-containing dressings or topical agents for treating infected or contaminated chronic wounds.

CochranePLS3255

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Eleven studies involving 496 participants met some of the inclusion criteria stated in the protocol. One hundred and eighty patients in five studies had peripheral interventions, 229 patients in five studies had percutaneous interventions applied to the Gasserian ganglion, and 87 patients in one study underwent two modalities of stereotactic radiosurgery (Gamma Knife) treatment. No studies addressing microvascular decompression (which is the only non-ablative procedure) met the inclusion criteria. All but two of the identified studies had a high to medium risk of bias because of either missing data or methodological inconsistency. It was not possible to undertake meta-analysis because of differences in the intervention modalities and variable outcome measures. Three studies had sufficient outcome data for analysis. One trial, which involved 40 participants, compared two techniques of radiofrequency thermocoagulation (RFT) of the Gasserian ganglion at six months. Pulsed RFT resulted in return of pain in all participants by three months. When this group were converted to conventional (continuous) treatment these participants achieved pain control comparable to the group that had received conventional treatment from the outset. Sensory changes were common in the continuous treatment group. In another trial, of 87 participants, investigators compared radiation treatment to the trigeminal nerve at one or two isocentres in the posterior fossa. There were insufficient data to determine if one technique was superior to another. Two isocentres increased the incidence of sensory loss. Increased age and prior surgery were predictors for poorer pain relief. Relapses were nonsignificantly reduced with two isocentres (risk ratio (RR) 0.72, 95% confidence intervaI (CI) 0.30 to 1.71). A third study compared two techniques for RFT in 54 participants for 10 to 54 months. Both techniques produced pain relief (not significantly in favour of neuronavigation (RR 0.70, 95% CI 0.46 to 1.04) but relief was more sustained and side effects fewer if a neuronavigation system was used. The remaining eight studies did not report outcomes as predetermined in our protocol. There is very low quality evidence for the efficacy of most neurosurgical procedures for trigeminal neuralgia because of the poor quality of the trials. All procedures produced variable pain relief, but many resulted in sensory side effects. There were no studies of microvascular decompression which observational data suggests gives the longest pain relief. There is little evidence to help comparative decision making about the best surgical procedure. Well designed studies are urgently needed. Output:

For this review, we searched for all of the surgical procedures for trigeminal neuralgia. We found 11 studies, which included 496 patients, but only three had sufficient outcome data to report. These three studies, which involved a total of 181 participants, fulfilled the inclusion criteria and form the basis of this review. The primary aim of all three studies was to determine if one technique was better than the other. All three included studies evaluated destructive techniques. None of the three studies evaluated the non-destructive procedure of microvascular decompression and this is a major drawback in the literature. One study compared two different techniques of radiofrequency thermocoagulation, in 40 participants six months after the procedure. This technique involves heating the nerve by passing an electrical current through the tip of a special needle which has been introduced through the skin into a hole in the base of the skull and into the ganglion from which the three divisions of the trigeminal nerve branch out (Gasserian ganglion). If the radiofrequency was given as pulsed treatment (which causes the tip of the needle to heat up intermittently and not continuously) the original pain in all participants returned by three months. The continuous radiofrequency treatment then had to be applied, and these participants then achieved pain control comparable to those who had received continuous radiofrequency throughout. Changes in sensation ranging from mild to severe numbness were common in the conventional (continuous) radiofrequency treatment group. A second trial, in 87 participants, looked at using one or two isocentres (specific points in the nerve) to deliver radiation to the trigeminal nerve just as it leaves the brainstem inside the skull. Use of medication afterwards was considered a surrogate measure for pain. Use of two isocentres increased the occurrence of sensory loss as a complication. Increased age and prior surgery were predictors for poorer pain relief. There were insufficient data given to judge the effectiveness of one procedure better than the other. A third study compared two techniques for performing radiofrequency thermocoagulation of the Gasserian ganglion in 54 participants. The study compared two ways of introducing the needle and guiding it, using either X-rays or a special neuronavigation system. Pain relief was measured by a questionnaire at three months. Both techniques provided pain relief (which did not differ significantly between the two arms) but it was more sustained if a neuronavigation system was used and this system also decreased side effects. All the reviewed procedures resulted in pain relief and some participants were then able to stop taking medications. However, many procedures tended to result in sensory side effects. All the studies in this review had flaws in their methods and all but two showed considerable risk of bias. There is little evidence from these trials to guide the person with trigeminal neuralgia as to the most effective surgical procedure. There is now an urgent need to evaluate the surgical interventions used in trigeminal neuralgia and to design robust studies; either randomised controlled trials or long-term prospective independently assessed cohort studies.

CochranePLS3256

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Seven evaluable studies randomised 404 patients. There was no statistically significant effect on reduction of mortality with therapy: 8.4% versus controls 14.4%, and infected pancreatic necrosis rates: 19.7% versus controls 24.4%. Non-pancreatic infection rates and the incidence of overall infections were not significantly reduced with antibiotics: 23.7% versus 36%; 37.5% versus 51.9% respectively. Operative treatment and fungal infections were not significantly different. Insufficient data were provided concerning antibiotic resistance. With beta-lactam antibiotic prophylaxis there was less mortality (9.4% treatment, 15% controls), and less infected pancreatic necrosis (16.8% treatment group, 24.2% controls) but this was not statistically significant. The incidence of non-pancreatic infections was non-significantly different (21% versus 32.5%), as was the incidence of overall infections (34.4% versus 52.8%), and operative treatment rates. No significant differences were seen with quinolone plus imidazole in any of the end points measured. Imipenem on its own showed no difference in the incidence of mortality, but there was a significant reduction in the rate of pancreatic infection (p=0.02; RR 0.34, 95% CI 0.13 to 0.84). No benefit of antibiotics in preventing infection of pancreatic necrosis or mortality was found, except for when imipenem (a beta-lactam) was considered on its own, where a significantly decrease in pancreatic infection was found. None of the studies included in this review were adequately powered. Further better designed studies are needed if the use of antibiotic prophylaxis is to be recommended. Output:

In the current review, data were found and analysed from 7 trials involving 404 patients randomly allocated to receive antibiotics or placebo. Although death occurred less after antibiotics (8.4%) than placebo (14.4%), as did infected pancreatic necrosis (19.7% versus 24.4%) and other infections (23.7% versus 36%), the differences were not statistically significant and so genuine benefit cannot be confirmed. There were no major problems with antibiotic resistance, and fungal infections were similar (3.9% versus 5%). The quality of studies was variable and only two were ‘blinded’, whereby investigators and patients were unaware of which treatment patients received. Many different regimens were used, and of the two main types of antibiotics used, a beta-lactam appeared to work better. Only one type of antibiotic (imipenem) was considered on its own, showing a significant decrease in infection of the pancreatic necrosis. Although we cannot confirm benefit from the use of prophylactic antibiotics in this condition, consistent trends towards a beneficial effect nevertheless remain. Further, better designed studies, ideally with beta-lactam antibiotics, are required.

CochranePLS3257

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Searches identified 23 trials; nine trials (255 participants) are included, of these seven trials are more than 10 years old. Three trials of nebulized thiol derivatives were identified (one compared 20% N-acetylcysteine to 2% N-acetylcysteine; another compared sodium-2-mercaptoethane sulphonate to 7% hypertonic saline; and another compared glutathione to 4% hypertonic saline). Although generally well-tolerated with no significant adverse effects, there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments. Six trials of oral thiol derivatives were identified. Three trials compared N-acetylcysteine to placebo; one compared N-acetylcysteine, ambroxol and placebo; one compared carbocysteine to ambroxol; and one compared low and high-dose N-acetylcysteine. Oral thiol derivatives were generally well-tolerated with no significant adverse effects, however there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments. We found no evidence to recommend the use of either nebulized or oral thiol derivatives in people with cystic fibrosis. There are very few good quality trials investigating the effect of these medications in cystic fibrosis, and further research is required to investigate the potential role of these medications in improving the outcomes of people with cystic fibrosis. Output:

Six included trials assessed the effects of oral thiol derivatives.Three of these trials compared oral N-acetylcysteine to placebo; one compared oral N-acetylcysteine, oral ambroxol and placebo; and one compared oral carbocysteine and oral ambroxol (no placebo). None of the trials showed an overall significant benefit in any of the outcome measures of this review. Oral thiol derivatives were generally well-tolerated with no major adverse effects. In summary, the trials included in the review did not provide any evidence that nebulized or oral thiol derivatives were either beneficial or harmful to people with cystic fibrosis. Further research investigating the effects of thiol derivatives in people with cystic fibrosis is required before their use can be recommended.

CochranePLS3258

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: No new studies were identified for this 2018 update. In total, four studies with 1644 participants are included. Two studies assessed the effect of extensive tests including computed tomography (CT) scanning versus tests at the physician's discretion, while the other two studies assessed the effect of standard testing plus positron emission tomography (PET)/CT scanning versus standard testing alone. For extensive tests including CT versus tests at the physician's discretion, the quality of the evidence, as assessed according to GRADE, was low due to risk of bias (early termination of the studies). When comparing standard testing plus PET/CT scanning versus standard testing alone, the quality of evidence was moderate due to a risk of detection bias. The quality of the evidence was downgraded further as detection bias was present in one study with a low number of events. When comparing extensive tests including CT versus tests at the physician's discretion, pooled analysis on two studies showed that testing for cancer was consistent with either benefit or no benefit on cancer-related mortality (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.15 to 1.67; 396 participants; 2 studies; P = 0.26; low-quality evidence). One study (201 participants) showed that, overall, malignancies were less advanced at diagnosis in extensively tested participants than in participants in the control group. In total, 9/13 participants diagnosed with cancer in the extensively tested group had a T1 or T2 stage malignancy compared to 2/10 participants diagnosed with cancer in the control group (OR 5.00, 95% CI 1.05 to 23.76; P = 0.04; low-quality evidence). There was no clear difference in detection of advanced stages between extensive tests versus tests at the physician's discretion: one participant in the extensively tested group had stage T3 compared with four participants in the control group (OR 0.25, 95% CI 0.03 to 2.28; P = 0.22; low-quality evidence). In addition, extensively tested participants were diagnosed earlier than control group (mean: 1 month with extensive tests versus 11.6 months with tests at physician's discretion to cancer diagnosis from the time of diagnosis of VTE). Extensive testing did not increase the frequency of an underlying cancer diagnosis (OR 1.32, 95% CI 0.59 to 2.93; 396 participants; 2 studies; P = 0.50; low-quality evidence). Neither study measured all-cause mortality, VTE-related morbidity and mortality, complications of anticoagulation, adverse effects of cancer tests, participant satisfaction or quality of life. When comparing standard testing plus PET/CT screening versus standard testing alone, standard testing plus PET/CT screening was consistent with either benefit or no benefit on all-cause mortality (OR 1.22, 95% CI 0.49 to 3.04; 1248 participants; 2 studies; P = 0.66; moderate-quality evidence), cancer-related mortality (OR 0.55, 95% CI 0.20 to 1.52; 1248 participants; 2 studies; P = 0.25; moderate-quality evidence) or VTE-related morbidity (OR 1.02, 95% CI 0.48 to 2.17; 854 participants; 1 study; P = 0.96; moderate-quality evidence). Regarding stage of cancer, there was no clear difference for detection of early (OR 1.78, 95% 0.51 to 6.17; 394 participants; 1 study; P = 0.37; low-quality evidence) or advanced (OR 1.00, 95% CI 0.14 to 7.17; 394 participants; 1 study; P = 1.00; low-quality evidence) stages of cancer. There was also no clear difference in the frequency of an underlying cancer diagnosis (OR 1.71, 95% CI 0.91 to 3.20; 1248 participants; 2 studies; P = 0.09; moderate-quality evidence). Time to cancer diagnosis was 4.2 months in the standard testing group and 4.0 months in the standard testing plus PET/CT group (P = 0.88). Neither study measured VTE-related mortality, complications of anticoagulation, adverse effects of cancer tests, participant satisfaction or quality of life. Specific testing for cancer in people with unprovoked VTE may lead to earlier diagnosis of cancer at an earlier stage of the disease. However, there is currently insufficient evidence to draw definitive conclusions concerning the effectiveness of testing for undiagnosed cancer in people with a first episode of unprovoked VTE (DVT or PE) in reducing cancer- or VTE-related morbidity and mortality. The results could be consistent with either benefit or no benefit. Further good-quality large-scale randomised controlled trials are required before firm conclusions can be made. Output:

This review assessed whether testing for undiagnosed cancer in people with a first unprovoked VTE (DVT or PE) was effective in reducing cancer and VTE-related illness and death. We found four studies with 1644 participants (current to July 2018). Two studies compared extensive cancer tests with tests carried out at the physician's discretion and two studies compared cancer tests plus scanning with cancer tests alone. Combining the results of the two studies showed that extensive testing had no effect on the number of cancer-related deaths. Additionally, extensive testing did not identify more people with cancer. However, extensive testing did identify cancers at an earlier stage (approximately 10 months earlier) and cancers were less advanced in people in the extensive testing group than in people in the group with tests carried out at the physician's discretion. Neither study looked at the number of deaths due to any cause, deaths and illness associated with VTE, side effects of cancer tests, side effects of VTE treatment or participant satisfaction. Two studies that compared tests plus scanning with tests alone showed that adding computed tomography scanning had little or no effect on the number of deaths, cancer-related deaths, illness associated with VTE; nor did it identify more people with cancer, or show a clear difference in time to diagnosis or stages of cancer diagnosed. Neither study looked at deaths associated with VTE, side effects of cancer tests, side effects of VTE treatment, participant satisfaction or quality of life. When comparing extensive tests versus tests at the physician's discretion, the quality of the evidence was low due to bias caused by two of the studies stopping early. When comparing tests plus PET/CT scanning with tests alone, the quality of the evidence ranged from low to moderate due to imprecision caused by a low number of events and bias due to lack of blinding of people assessing the effects. This review found that there are too few trials to determine whether testing for undiagnosed cancer in people with a first unprovoked VTE (DVT or PE) is effective in reducing cancer and VTE-related deaths and illness. Further good-quality and large-scale studies are required.

CochranePLS3259

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Seventeen potentially eligible RCTs were identified but only six trials with 138 patients in total could be included. One study was at low risk of bias, two studies were judged to be at unclear risk of bias and three at high risk of bias. Two trials (56 patients) compared flapless placement of dental implants with conventional flap elevation, one trial (10 patients) compared crestal versus vestibular incisions, one trial (20 patients) Erbium:YAG laser versus flap elevation at the second-stage surgery for implant exposure, one split-mouth trial (10 patients) evaluated whether connective tissue graft at implant placement could be effective in augmenting peri-implant tissues, and one trial (40 patients) compared autograft with an animal-derived collagen matrix to increase the height of the keratinised mucosa. On a patient, rather than per implant basis, implants placed with a flapless technique and implant exposures performed with laser induced statistically significantly less postoperative pain than flap elevation. Sites augmented with soft tissues connective grafts showed a better aesthetic and thicker tissues. Both palatal autografts or the use of a porcine-derived collagen matrix are effective in increasing the height of keratinised mucosa at the price of a 0.5 mm recession of peri-implant soft tissues. There were no other statistically significant differences for any of the remaining analyses. There is limited weak evidence suggesting that flapless implant placement is feasible and has been shown to reduce patient postoperative discomfort in adequately selected patients, that augmentation at implant sites with soft tissue grafts is effective in increasing soft tissue thickness improving aesthetics and that one technique to increase the height of keratinised mucosa using autografts or an animal-derived collagen matrix was able to achieve its goal but at the price of a worsened aesthetic outcome (0.5 mm of recession). There is insufficient reliable evidence to provide recommendations on which is the ideal flap design, the best soft tissue augmentation technique, whether techniques to increase the width of keratinised/attached mucosa are beneficial to patients or not, and which are the best incision/suture techniques/materials. Properly designed and conducted RCTs, with at least 6 months of follow-up, are needed to provide reliable answers to these questions. Output:

The review found some weak evidence from only two studies with 56 patients that flapless placement of dental implants reduces postoperative discomfort (pain and swelling), without jeopardising implant success in selected patients. There is insufficient evidence to recommend any specific flap or suturing technique. There is only a small study (10 patients) suggesting that soft tissue grafts from the palate improve gum thickness and aesthetics. There are no studies evaluating whether there is a benefit in increasing the amount of firm gum surrounding dental implants but there is a small trial suggesting that it is possible to increase the amount of firm gum surrounding dental implants using either tissue taken from the palate or a porcine-derived collagen matrix at the price of considerable postoperative pain/discomfort and aesthetic deterioration (there were several cases where the gum receded exposing the metal of the implant).

CochranePLS3260

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included four studies that compared SDM versus control and included a total of 1342 participants. Three studies recruited children with asthma and their care-givers, and one recruited adults with asthma. Three studies took place in the United States, and one in the Netherlands. Trial duration was between 6 and 24 months. One trial delivered the SDM intervention to the medical practitioner, and three trials delivered the SDM intervention directly to the participant. Two paediatric studies involved use of an online portal, followed by face-to-face consultations. One study delivered an SDM intervention or a clinical decision-making intervention through a mixture of face-to-face consultations and telephone calls. The final study randomised paediatric general practice physicians to receive a seminar programme promoting application of SDM principles. All trials were open-label, although one study, which delivered the intervention to physicians, stated that participants were unaware of their physicians' involvement in the trial. We had concerns about selection and attrition bias and selective reporting, and we noted that one study substantially under-recruited participants. The four included studies used different approaches to measure fidelity/intervention adherence and to report study findings. One study involving adults with poorly controlled asthma reported improved quality of life (QOL) for the SDM group compared with the control group, using the Asthma Quality of Life Questionnaire (AQLQ) for assessment (mean difference (MD) 1.90, 95% confidence interval (CI) 1.24 to 2.91), but two other trials did not identify a benefit. Patient/parent satisfaction with the performance of paediatricians was greater in the SDM group in one trial involving children. Medication adherence was better in the SDM group in two studies - one involving adults and one involving children (all medication adherence: MD 0.21, 95% CI 0.11 to 0.31; mean number of controlled medication prescriptions over 26 weeks: 1.1 in the SDM group (n = 26) and 0.7 in the control group (n = 27)). In one study, asthma-related visit rates were lower in the SDM group than in the usual care group (1.0/y vs 1.4/y; P = 0.016), but two other studies did not report a difference in exacerbations nor in prescriptions for short courses of oral steroids. Finally, one study described better odds of reporting no asthma problems in the SDM group than in the usual care group (odds ratio (OR) 1.90, 95% CI 1.26 to 2.87), although two other studies reporting asthma control did not identify a benefit with SDM. We found no information about acceptability of the intervention to the healthcare professional and no information on adverse events. Overall, our confidence in study results ranged from very low to moderate, and we downgraded outcomes owing to risk of bias, imprecision, and indirectness. Substantial differences between the four included randomised controlled trials (RCTs) indicate that we cannot provide meaningful overall conclusions. Individual studies demonstrated some benefits of SDM over control, in terms of quality of life; patient and parent satisfaction; adherence to prescribed medication; reduction in asthma-related healthcare visits; and improved asthma control. Our confidence in the findings of these individual studies ranges from moderate to very low, and it is important to note that studies did not measure or report adverse events. Future trials should be adequately powered and of sufficient duration to detect differences in patient-important outcomes such as exacerbations and hospitalisations. Use of core asthma outcomes and validated scales when possible would facilitate future meta-analysis. Studies conducted in lower-income settings and including an economic evaluation would be of interest. Investigators should systematically record adverse events, even if none are anticipated. Studies identified to date have not included adolescents; future trials should consider their inclusion. Measuring and reporting of intervention fidelity is also recommended. Output:

We reviewed the evidence up to November 2016. We found four studies, including 1342 people, that attempted to answer this question. All participants had asthma; participants in three studies were children and those in one study were adults. Three studies took place in the United States and one in the Netherlands; studies lasted from six months to two years. Different studies used different methods of shared decision-making, including face-to-face discussions, telephone calls, and online messages. Because these studies were conducted in different ways, we were unable to combine their findings. We found evidence from individual studies indicating that shared decision-making may improve quality of life and asthma control and may reduce healthcare visits for asthma. Shared decision-making may also help people to take their asthma inhaler(s) more regularly owing to better understanding of why they need to do that. Going through this process may make people feel more satisfied with their care, as they may feel empowered about making choices. However, all of these findings were reported by different studies, and some studies showed benefit of shared decision-making, while others did not. It is important to mention that none of these studies looked into whether shared decision-making causes unwanted side effects. All four studies measured how well the shared decision-making intervention had been delivered or received but did this in different ways. We were not very confident in the quality of the evidence presented in this review. We were concerned about the small number of studies and about differences in the way included studies were designed. Also, participants knew which group they were in (i.e. shared decision-making or standard care), and this may have affected how they answered questions about their asthma during the trial. Some evidence suggests that shared decision-making might help people with asthma, but we are not sure whether it is helpful. In the future, larger studies that include adolescents while looking out for side effects, harms, and benefits should prove useful in answering this question.

CochranePLS3261

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included one trial comparing oral dextrose gel versus placebo in 416 infants at risk of hypoglycaemia. We judged this trial to be at low risk of bias. Using the GRADE method, we determined that evidence ranged from high quality to moderate quality. For outcomes selected for the GRADE analysis, we found the following. • Oral dextrose gel prophylaxis (any dose) is associated with reduced risk of neonatal hypoglycaemia compared with placebo (risk ratio (RR) 0.76, 95% confidence interval (CI) 0.62 to 0.94; one RCT; n = 415 infants; high-quality evidence). The risk difference (RD) is -0.13 (95% CI -0.23 to -0.03), and on average, 8.3 infants would have to receive prophylactic dextrose gel to prevent one additional case of neonatal hypoglycaemia. • Investigators found no statistically significant differences between dextrose gel and placebo groups in the number of adverse events (RR 1.09, 95% CI 0.55 to 2.17; one RCT; n = 413 infants; moderate-quality evidence); separation from mother for treatment of hypoglycaemia (RR 0.46, 95% CI 0.21 to 1.01; one RCT, n = 415 infants; moderate-quality evidence); exclusive breastfeeding at discharge (RR 1.00, 95% CI 0.86 to 1.15; one RCT; n = 415 women; moderate-quality evidence); or breastfeeding at six weeks postpartum (RR 1.06, 95% CI 0.88 to 1.29; one RCT; n = 386 women; moderate-quality evidence). • Researchers provided no data for the other prespecified GRADE outcomes for this review (major neurological disability at two years of age or older; receipt of treatment for hypoglycaemia during initial hospital stay; receipt of intravenous treatment for hypoglycaemia). Oral dextrose gel reduced the risk of neonatal hypoglycaemia in at-risk infants in a single trial. Results showed no statistically significant differences in the number of adverse events or in risk of separation of infant from mother for treatment of hypoglycaemia between babies who received oral dextrose gel and those given placebo. Caution is suggested in interpreting data for the latter two outcomes owing to low event rates. Available evidence is limited to a cohort of at-risk infants, most of whom were infants of diabetic mothers and were treated on the postnatal ward. Minimal data available for many of the prespecified outcomes of this review showed no long-term neurodevelopmental and disability outcomes. Additional evidence is needed to assess the efficacy and safety of dextrose gel for prevention of neonatal hypoglycaemia. Output:

During searches updated to January 2017, we found one study (with low risk of bias) that compared oral dextrose gel versus placebo for prevention of low blood glucose levels in 415 at-risk babies. Evidence from this single study suggests that in babies at risk, oral dextrose gel followed by a feed is associated with reduced risk of low blood glucose levels when compared with placebo (high-quality evidence). Results showed no statistically significant differences between oral dextrose gel and placebo in terms of the number of adverse events (moderate-quality evidence), risk of separation of baby from mother for treatment of low glucose levels (moderate-quality evidence), exclusive breastfeeding at discharge (moderate-quality evidence), or continued breastfeeding at six weeks of age (moderate-quality evidence). We must be careful when interpreting the evidence for adverse events and separation of mother and baby, as a small number of events have been reported for these outcomes. Researchers provided no data on long-term outcomes including developmental and disability outcomes. Available evidence came from only one study, and no long-term outcome data have been reported. Additionally, this study considers only oral dextrose gel compared with placebo and does not consider other measures that could potentially prevent hypoglycaemia. Therefore, not enough evidence is available at this time to support the routine use of oral dextrose gel for prevention of hypoglycaemia in newborn babies at risk. Childhood follow-up of the single study included here is under way, and an additional ongoing study is seeking to determine the effect of oral dextrose gel on preventing admission to the neonatal intensive care unit (NICU). We advise waiting for data on outcomes of these additional studies to assess the longer-term safety and efficacy of oral dextrose gel for prevention of neonatal hypoglycaemia.

CochranePLS3262

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We screened a total of 3667 records, identifying 16 relevant RCTs involving 5626 patients and included 12 trials in the meta-analyses. All trials were randomised and open-label studies. Two trials were published in abstract form and therefore we were unable to assess potential risk of bias in full. There is moderate-quality evidence that bortezomib prolongs OS (four studies, 1586 patients; Peto OR 0.77, 95% CI 0.65 to 0.92) and PFS (five studies, 1855 patients; Peto OR 0.65, 95% CI 0.57 to 0.74) from analysing trials of bortezomib versus no bortezomib with the same background therapy in each arm. There is high-quality evidence that bortezomib prolongs OS (five studies, 2532 patients; Peto OR 0.76, 95% CI 0.67 to 0.88) but low-quality evidence for PFS (four studies, 2489 patients; Peto OR 0.67, 95% CI 0.61 to 0.75) from analysing trials of bortezomib versus no bortezomib with different background therapy in each arm or compared to other agent(s). Four trials (N = 716) examined different doses, methods of administrations and treatment schedules and were reviewed qualitatively only. We identified four trials in the meta-analysis that measured time to progression (TTP) and were able to extract and analyse PFS data for three of the studies, while in the case of one study, we included TTP data as PFS data were not available. We therefore did not analyse TTP separately in this review. Patients treated with bortezomib have increased risk of thrombocytopenia, neutropenia, gastro-intestinal toxicities, peripheral neuropathy, infection and fatigue with the quality of evidence highly variable. There is high-quality evidence for increased risk of cardiac disorders from analysing trials of bortezomib versus no bortezomib with different background therapy in each arm or versus other agents. The risk of TRD in either comparison group analysed is uncertain due to the low quality of the evidence. Only four trials analysed HRQoL and the data could not be meta-analysed. Subgroup analyses by disease setting revealed improvements in all outcomes, whereas for therapy setting, an improved benefit for bortezomib was observed in all outcomes and subgroups except for OS following consolidation therapy. This meta-analysis found that myeloma patients receiving bortezomib benefited in terms of OS, PFS and response rate compared to those who did not receive bortezomib. This benefit was observed in trials of bortezomib versus no bortezomib with the same background therapy and in trials of bortezomib versus no bortezomib with different background therapy in each arm or compared to other agent(s). Further evaluation of newer proteasome inhibitors is required to ascertain whether these agents offer an improved risk-benefit profile, while more studies of HRQoL are also required. Output:

We wanted to know the benefits and harms from bortezomib treatment for myeloma. We searched medical databases and trial registries until January 2016. We included studies of bortezomib compared to no bortezomib, with either the same or different background therapy or compared to other drugs. Studies of newly diagnosed and relapsed myeloma were included as well as those that compared different doses, ways of administering bortezomib and treatment schedules. We found 16 studies involving 5626 myeloma patients. The results of this review suggest that bortezomib can lead to better survival, a longer time without progression and better response rates compared to those not receiving bortezomib. Treatment with bortezomib causes a number of side effects including: low levels of some blood cells; gastro-intestinal effects such as constipation, diarrhoea, nausea and vomiting; nerve pain and tingling in hands and feet, as well as infection. A greater risk of heart problems was seen in one of the comparison groups studied. Risk of death from bortezomib treatment was uncertain in either group analysed. Only four studies assessed quality of life and could not be analysed together. We judged quality of the evidence as high to moderate for mortality or number of deaths, whereas it was considered low-quality evidence for progression-free survival. the quality of evidence for adverse events was highly variable (low to high). For assessment of treatment-related death, there was no evidence of a difference, with low-quality evidence in one comparison (bortezomib compared to no bortezomib with the same background therapy) and very low-quality evidence in comparison two (bortezomib compared to no bortezomib with different background therapy or compared to other drugs). Patients receiving bortezomib had better response rates, longer time without progression and appeared to live longer compared to those not receiving bortezomib, however patients receiving bortezomib experienced more side effects. Other proteasome inhibitor drugs have also been developed, therefore further research should focus on whether these newer drugs provide additional benefits and fewer side effects than bortezomib. More studies on health-related quality of life are also needed.

CochranePLS3263

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Eight trials involving around 1100 people were included but data were only available for 1036 women in seven trials, of whom 526 received urodynamics. There was some evidence of risk of bias. The four deaths and 12 dropouts in the control arm of one trial were unexplained. There was significant evidence that the tests did change clinical decision making. Women in the urodynamic arms of three trials were more likely to have their management changed (proportion with change in management compared with the control arm 17% versus 3%, risk ratio (RR) 5.07, 95% CI 1.87 to 13.74), although there was statistical heterogeneity. There was evidence from two trials that women treated after urodynamic investigations were more likely to receive drugs (RR 2.09, 95% CI 1.32 to 3.31). On the other hand, in five trials women undergoing treatment following urodynamic investigation were not more likely to undergo surgery (RR 0.99, 95% CI 0.88 to 1.12). There was no statistically significant difference however in the number of women with urinary incontinence if they received treatment guided by urodynamics (37%) compared with those whose treatment was based on history and clinical findings alone (36%) (for example, RR for the number with incontinence after the first year 1.02, 95% CI 0.86 to 1.21). It was calculated that the number of women needed to treat was 100 women (95% CI 86 to 114 women) undergoing urodynamics to prevent one extra individual being incontinent at one year. One trial reported adverse effects and no significant difference was found (RR 1.10, 95% CI 0.81 to 1.50). While urodynamic tests did change clinical decision making, there was some evidence that this did not result in better outcomes in terms of a difference in urinary incontinence rates after treatment. There was no evidence about their use in men, children, or people with neurological diseases. Larger definitive trials are needed in which people are randomly allocated to management according to urodynamic findings or to management based on history and clinical examination to determine if performance of urodynamics results in higher continence rates after treatment. Output:

Eight trials were found, which included around 1100 people, although information was only available for 1036 women. There was not enough evidence to determine whether the urodynamic tests led to better outcomes. There was some evidence that urodynamic testing increased the number of people given drugs but not the number of people undergoing surgery. This did not result in any difference in the number of people who leaked urine, and it was not known whether they had a better quality of life. More research is needed in which people are randomised to having treatment decisions based on either their symptoms and examination alone or after taking into account the extra information provided by urodynamic tests.

CochranePLS3264

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We found 14 relevant studies, mostly of short duration, poorly reported and conducted in the 1970s (total n=794 participants). Nine of these compared oral formulations of both compounds, and five compared intramuscular formulations. Haloperidol was associated with significantly fewer people leaving the studies early (13 RCTs, n=476, RR 0.26 CI 0.08 to 0.82). The efficacy outcome 'no significant improvement' tended to favour haloperidol, but this difference was not statistically significant (9 RCTs, n=400, RR 0.81 CI 0.64 to 1.04). Movement disorders were more frequent in the haloperidol groups ('at least one extrapyramidal side effect': 6 RCTs, n=37, RR 2.2 CI 1.1 to 4.4, NNH 5 CI 3 to 33), while chlorpromazine was associated with more frequent hypotension (5 RCTs, n=175, RR 0.31 CI 0.11 to 0.88, NNH 7 CI 4 to 25). Similar trends were found when studies comparing intramuscular formulations and studies comparing oral formulations were analysed separately. Given that haloperidol and chlorpromazine are global standard antipsychotic treatments for schizophrenia, it is surprising that less than 800 people have been randomised to a comparison and that incomplete reporting still makes it difficult for anyone to draw clear conclusions on the comparative effects of these drugs. However, it seems that haloperidol causes more movement disorders than chlorpromazine, while chlorpromazine is significantly more likely to lead to hypotonia. We are surprised to have to say that we feel further, large, well designed, conducted and reported studies are required. Output:

Overall the mental health and general functioning of people taking chlorpromazine or haloperidol improved. Compared to nowadays fewer people in both arms of the trial left the study early but those taking chlorpromazine were statistically more likely to do so. This was also the case when the oral medications were analysed on their own, but not in the case of the injected form. There was a suggestion that people may leave the study because of either adverse events or because the treatment did not work well. Haloperidol had statistically more movement side effects while chlorpromazine was statistically more likely to cause low blood pressure (hypotension). Although these trials show both haloperidol and chlorpromazine to be effective drugs for schizophrenia, a lot of data were not able to be used because some measures were not reported. Therefore the area would benefit from a new trial with a large number of people and lasting at least a year. (Plain language summary prepared for this review by Janey Antoniou of RETHINK, UK www.rethink.org).

CochranePLS3265

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: The searches identified 17 trials; four are included (287 participants aged five to 39 years; maximum follow-up of four years) and one is currently awaiting classification pending publication of the full trial report and two are ongoing. Three trials compared ibuprofen to placebo (two from the same center with some of the same participants); one trial assessed piroxicam versus placebo. The three ibuprofen trials were deemed to have good or adequate methodological quality, but used various outcomes and summary measures. Reviewers considered measures of lung function, nutritional status, radiological assessment of pulmonary involvement, intravenous antibiotic usage, hospital admissions, survival and adverse effects. Combined data from the two largest ibuprofen trials showed a lower annual rate of decline for lung function, % predicted forced expiratory volume in one second (FEV1), mean difference (MD) 1.32 (95% confidence interval (CI) 0.21 to 2.42) (moderate-quality evidence); forced vital capacity (FVC), MD 1.27 (95% CI 0.26 to 2.28) (moderate-quality evidence); forced expiratory flow (FEF25%-75%), MD 1.80 (95% CI 0.15 to 3.45). The post hoc analysis of data from two trials split by age showed a slower rate of annual decline of FEV1 % predicted and FVC in the ibuprofen group in younger children, MD 1.41% (95% CI 0.03 to 2.80) (moderate-quality evidence) and MD 1.32% (95% CI 0.04 to 2.60) (moderate-quality evidence) respectively. Data from four trials demonstrated the proportion of participants with at least one hospitalization may be slightly lower in the ibuprofen group compared to placebo, Peto odds ratio 0.61 (95% CI 0.37 to 1.01) (moderate-quality evidence). In one trial, long-term use of high-dose ibuprofen was associated with reduced intravenous antibiotic usage, improved nutritional and radiological pulmonary status. No major adverse effects were reported, but the power of the trials to identify clinically important differences in the incidence of adverse effects was low. We did not have any concerns with regards to risk of bias for the trial comparing piroxicam to placebo. However, the trial did not report many data in a form that we could analyze in this review. No data were available for the review's primary outcome of lung function; available data for hospital admissions showed no difference between the groups. No analyzable data were available for any other review outcome. High-dose ibuprofen can slow the progression of lung disease in people with cystic fibrosis, especially in children, which suggests that strategies to modulate lung inflammation can be beneficial for people with cystic fibrosis. Output:

We looked for trials comparing oral non-steroidal anti-inflammatory drugs to a a placebo (a tablet that contained no active medicine). We looked for any dose level. but the trial had to run for at least two months in people with cystic fibrosis. We found 17 trials and included four of these with a total of 287 people aged five to 39 years; one further trial has not yet been published in full and two are still ongoing; we will assess these when we have more information. Three of the four included trials compared ibuprofen to a placebo; two of these trials were run in the same center and used some of the same people. One trial compared a drug called piroxicam to placebo. The longest trial lasted four years. We aimed to report on lung function, nutritional status, lung x-rays, how often intravenous antibiotics were needed, details about hospital admissions, survival and side effects. We combined results from the two largest ibuprofen trials and showed that those taking ibuprofen had a lower annual rate of decline in lung function which was consistent across three lung function measurements. We then looked at these results split by age (even though we did not originally plan to do this) and found that two of the measurements showed a slower rate of annual decline in lung function in younger children. Results from four trials showed that fewer participants in the ibuprofen group were admitted to hospital at least once compared to placebo, although it was not clear if the difference was just chance or not. In one trial, people taking a long-term high dose of ibuprofen were less likely to need intravenous antibiotics, had better nutritional status and healthier lungs as seen by X-ray. No major side effects were reported in the trials, but they had not been designed to show differences in the rates of side effects. To summarize, we found evidence showing that a high dose of a non-steroidal anti-inflammatory drug, most notably ibuprofen, may slow the progression of lung damage in people with cystic fibrosis, especially in younger people. The long-term safety results are limited but we feel that there is enough evidence to suggest that non-steroidal anti-inflammatory drugs be temporarily stopped when people with cystic fibrosis are receiving intravenous aminoglycosides or other drugs that may badly damage the kidneys. The trial of the drug piroxicam did not report many results in a form that we could analyse in the review. We did not have any results for our main outcome of lung function. The only results we had reported no difference between the piroxicam group and the placebo group for the number of hospital admissions. We judged the evidence to be of moderate quality overall. We thought the three ibuprofen trials had a good or adequate level of methodological quality with little risk of bias to the results, but used a range of different outcomes and summary measures. We did not have any concerns with regards to risks of bias for the trial comparing piroxicam to placebo.

CochranePLS3266

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Seventy-eight studies met the inclusion criteria, and we assessed all evidence to be of low or very low quality based on GRADE assessment. We judged nine studies to be at low risk of bias, 35 to have unclear overall risk of bias, and 34 to have high risk of bias. Twenty-one interventions targeted populations or community settings, 27 studies were conducted in the well-child healthcare setting and 26 in the ill-child healthcare setting. Two further studies conducted in paediatric clinics did not make clear whether visits were made to well- or ill-children, and another included visits to both well- and ill-children. Forty-five studies were reported from North America, 22 from other high-income countries, and 11 from low- or middle-income countries. Only 26 of the 78 studies reported a beneficial intervention effect for reduction of child ETS exposure, 24 of which were statistically significant. Of these 24 studies, 13 used objective measures of children's ETS exposure. We were unable to pinpoint what made these programmes effective. Studies showing a significant effect used a range of interventions: nine used in-person counselling or motivational interviewing; another study used telephone counselling, and one used a combination of in-person and telephone counselling; three used multi-component counselling-based interventions; two used multi-component education-based interventions; one used a school-based strategy; four used educational interventions, including one that used picture books; one used a smoking cessation intervention; one used a brief intervention; and another did not describe the intervention. Of the 52 studies that did not show a significant reduction in child ETS exposure, 19 used more intensive counselling approaches, including motivational interviewing, education, coaching, and smoking cessation brief advice. Other interventions consisted of brief advice or counselling (10 studies), feedback of a biological measure of children's ETS exposure (six studies), nicotine replacement therapy (two studies), feedback of maternal cotinine (one study), computerised risk assessment (one study), telephone smoking cessation support (two studies), educational home visits (eight studies), group sessions (one study), educational materials (three studies), and school-based policy and health promotion (one study). Some studies employed more than one intervention. 35 of the 78 studies reported a reduction in ETS exposure for children, irrespective of assignment to intervention and comparison groups. One study did not aim to reduce children's tobacco smoke exposure but rather sought to reduce symptoms of asthma, and found a significant reduction in symptoms among the group exposed to motivational interviewing. We found little evidence of difference in effectiveness of interventions between the well infant, child respiratory illness, and other child illness settings as contexts for parental smoking cessation interventions. A minority of interventions have been shown to reduce children's exposure to environmental tobacco smoke and improve children's health, but the features that differentiate the effective interventions from those without clear evidence of effectiveness remain unclear. The evidence was judged to be of low or very low quality, as many of the trials are at a high risk of bias, are small and inadequately powered, with heterogeneous interventions and populations. Output:

We searched six databases for relevant research. This is an update of a previously published review, and the date of the most recent search was February 2017. We found 78 studies on the effects of interventions aimed at family and carers with the goal of reducing children’s exposure to tobacco smoke. These studies included parents and other family members, child care workers, and teachers involved in the care and education of infants and young children (from birth to 12 years of age), and used a variety of interventions, including different kinds of counselling, brief advice, and educational materials. Only 26 studies reported that an intervention was successful in reducing children’s exposure to tobacco smoke. These studies used a range of interventions. Nine studies used more intensive counselling methods or motivational interviewing, but in other studies, these types of interventions were not effective. Of the 52 studies that did not show a significant reduction in child tobacco smoke exposure, 19 used intensive counselling methods or motivational interviewing. One study successfully reduced children's asthma symptoms by using motivational interviewing. This review does not show whether any particular interventions reduced parental smoking and child smoke exposure more effectively than others. The quality of evidence ranged from low to very low. Future studies should aim to provide evidence of higher quality by addressing study design problems, including more participants, and describing interventions in more detail.

CochranePLS3267

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Twenty one trials involving 7243 participants were included. Equal daily doses of ciclesonide and beclomethasone (BDP) or budesonide (BUD) gave similar results for peak expiratory flow rates (PEF), although forced vital capacity (FVC) was higher with ciclesonide. Data on forced expired volume in one second (FEV1) were inconsistent. Withdrawal data and symptoms were similar between treatments. Compared with the same dose of fluticasone (FP), data on lung function parameters (FEV1, FVC and PEF) did not differ significantly. Paediatric quality of life score favoured ciclesonide. Candidiasis was less frequent with ciclesonide, although other side-effect outcomes did not give significant differences in favour of either treatment. When lower doses of ciclesonide were compared to BDP or BUD, the difference in FEV1 did not reach significance but we cannot exclude a significant effect in favour of BDP/BUD. Other lung function outcomes did not give significant differences between treatments. Paediatric quality of life scores did not differ between treatments. Adverse events occurred with similar frequency between ciclesonide and BDP/BUD. Comparison with FP at half the nominal dose was undertaken in three studies, which indicated that FEV1 was not significantly different, but was not equivalent between the treatments (per protocol: -0.05 L 95% confidence intervals -0.11 to 0.01). The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority. Output:

This findings of this review of 21 trials (7243 participants) do not allow certainty about the relative efficacy of ciclesonide compared to older inhaled corticosteroids, especially at higher doses. The results of the review to date do not indicate whether ciclesonide provides a significantly more useful safety profile that other inhaled corticosteroids at similar equivalent doses. However, the finding of lower oral candidiasis in patients treated with ciclesonide compared to fluticasone may be important for those patients who experience oral thrush with their current ICS. In addition, further studies in children are required to obtain data on the side-effect profile of ciclesonide in this population.

CochranePLS3268

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: For this update, 12 trials (1557 women and 1661 infants) were included. Dexamethasone was associated with a reduced risk of intraventricular haemorrhage (IVH) compared with betamethasone (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.21 to 0.92; four trials, 549 infants). No statistically significant differences were seen for other primary outcomes: respiratory distress syndrome (RDS) (RR 1.06, 95% CI 0.88 to 1.27; five trials, 753 infants) and perinatal death (neonatal death RR 1.41, 95% CI 0.54 to 3.67; four trials, 596 infants). Similarly, very few differences were seen for secondary outcomes such as rate of admission to the neonatal intensive care unit (NICU) although in one trial, those infants exposed to dexamethasone, compared with betamethasone, had a significantly shorter length of NICU admission (mean difference (MD) -0.91 days, 95% CI -1.77 to -0.05; 70 infants). Results for biophysical parameters were inconsistent, but mostly no clinically important differences were seen. Compared with intramuscular dexamethasone, oral dexamethasone significantly increased the incidence of neonatal sepsis (RR 8.48, 95% CI 1.11 to 64.93) in one trial of 183 infants. No statistically significant differences were seen for other outcomes reported. Apart from a reduced maternal postpartum length of stay for women who received betamethasone at 12-hourly intervals compared to 24-hourly intervals in one trial (MD -0.73 days, 95% CI -1.28 to -0.18; 215 women), no differences in maternal or neonatal outcomes were seen between the different betamethasone dosing intervals assessed. Similarly, no significant differences in outcomes were seen when betamethasone acetate and phosphate was compared with betamethasone phosphate in one trial. It remains unclear whether one corticosteroid (or one particular regimen) has advantages over another. Dexamethasone may have some benefits compared with betamethasone such as less IVH, and a shorter length of stay in the NICU. The intramuscular route may have advantages over the oral route for dexamethasone, as identified in one small trial. Apart from the suggestion that 12-hour dosing may be as effective as 24-hour dosing of betamethasone based on one small trial, few other conclusions about optimal antenatal corticosteroid regimens were able to be made. No long-term results were available except for a small subgroup of 18 month old children in one trial. Trials comparing the commonly used corticosteroids are most urgently needed, as are trials of dosages and other variations in treatment regimens. Output:

Most trials have compared the two most commonly used corticosteroids before early birth, dexamethasone and betamethasone. In this review of 12 trials (involving 1557 women and 1661 infants) of moderate quality, 10 trials compared dexamethasone and betamethasone; one trial compared two different ways of giving dexamethasone and one trial compared two different ways of giving betamethasone. We found that dexamethasone and betamethasone showed similar results, although there was less bleeding of the brain and a shorter length of neonatal intensive care unit hospital stay for dexamethasone compared with betamethasone. On the basis of one trial, giving dexamethasone by injection (intramuscularly) may be better than giving the drug to the mother by mouth (orally). Usually the drug is given in two doses 24 hours apart and one trial showed that this interval could perhaps be reduced to 12 hours if required. We need more studies to establish which is the best drug and what is the best way to give it, and babies in these trials need to be followed up over a long period to monitor any effects on child and adult development.

CochranePLS3269

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Administration of dexamethasone prior to extubation significantly reduced the need for reintubation of the trachea. This result applies to both the high-risk group and to the total population of infants enrolled. However, the incidence of extubation failure was zero in the trial that attempted to exclude infants at high risk of airway edema. The side effects of higher blood sugar levels and glycosuria were found in the two trials where these were sought. Implications for practice Dexamethasone reduces the need for endotracheal reintubation of neonates after a period of IPPV. In view of the lack of effect in low-risk infants and the documented and potential side effects, it appears reasonable to restrict its use to infants at increased risk for airway edema and obstruction, such as those who have received repeated or prolonged intubations. Implications for research Issues of dosage and applicability to the extremely low birthweight population could be addressed in future trials. Outcomes such as chronic lung disease, duration of assisted ventilation and length of hospital stay as well as long-term neurodevelopment should also be examined. Output:

This review found that giving dexamethasone (a corticosteroid drug) around the time of extubation can help prevent swelling in the baby's throat that might require reinsertion of the tube. However, the review found that there are adverse effects of dexamethasone. The benefits only outweigh the risks for babies at high risk of complication (such as those who have received several, or prolonged, intubations).

CochranePLS3270

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 12 new RCTs for this update, giving a total of 39 RCTs (6013 participants). These additional 12 RCTs have not changed the original conclusions about the clinical efficacy of minocycline. The identified RCTs were generally small and poor quality. Meta-analysis was rarely possible because of the lack of data and different outcome measures and trial durations. Although minocycline was shown to be an effective treatment for moderate to moderately-severe acne vulgaris, there was no evidence that it is better than any of the other commonly-used acne treatments. One company-sponsored RCT found minocycline to be less effective than combination treatment with topical erythromycin and zinc. No trials have been conducted using minocycline in those participants whose acne is resistant to other therapies. Also, there is no evidence to guide what dose should be used. The adverse effects studies must be interpreted with caution. The evidence suggests that minocycline is associated with more severe adverse effects than doxycycline. Minocycline, but not other tetracyclines, is associated with lupus erythematosus, but the risk is small: 8.8 cases per 100,000 person-years. The risk of autoimmune reactions increases with duration of use. The evidence does not support the conclusion that the more expensive extended-release preparation is safer than standard minocycline preparations. Minocycline is an effective treatment for moderate to moderately-severe inflammatory acne vulgaris, but there is still no evidence that it is superior to other commonly-used therapies. This review found no reliable evidence to justify the reinstatement of its first-line use, even though the price-differential is less than it was 10 years ago. Concerns remain about its safety compared to other tetracyclines. Output:

In summary, there is no evidence to support the first-line use of minocycline in the treatment of acne. All of the trials showed that, on average, people treated with minocycline experienced an improvement in their acne. However, no study conclusively showed any important clinical difference between minocycline or other commonly-used therapies. The analysis found that minocycline may act more quickly than oxytetracycline or tetracycline, but there is no overall difference in the end. There is no evidence that it is more effective in acne that is resistant to other therapies, or that the effects last longer. Although it is often claimed that the more expensive once-daily slow-release preparation is a more attractive option to teenagers with acne, the evidence in this review does not show it to be any better or safer compared to other oral antibiotics that have to be taken more frequently. Despite a thorough search for evidence, it is still not known which of the tetracyclines are the safest to take overall as they are all associated with side-effects. The only conclusion that we could make was that people treated with minocycline for acne are at a significantly greater risk of developing an autoimmune (lupus-like) syndrome than those given tetracycline or no treatment.

CochranePLS3271

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 15 trials with 6515 patients. The median follow up was six years. Tumour sites were mostly oropharynx and larynx; 5221 (74%) patients had stage III-IV disease (UICC 2002). There was a significant survival benefit with altered fractionation radiotherapy, corresponding to an absolute benefit of 3.4% at five years (hazard ratio (HR) 0.92, 95% CI 0.86 to 0.97; P = 0.003). The benefit was significantly higher with hyperfractionated radiotherapy (8% at five years) than with accelerated radiotherapy (2% with accelerated fractionation without total dose reduction and 1.7% with total dose reduction at five years, P = 0.02). There was a benefit in locoregional control in favour of altered fractionation versus conventional radiotherapy (6.4% at five years; P < 0.0001), which was particularly efficient in reducing local failure, whereas the benefit on nodal control was less pronounced. The benefit was significantly higher in the youngest patients (under 50 year old) (HR 0.78, 95% CI 0.65 to 0.94), 0.95 (95% CI 0.83 to 1.09) for 51 to 60 year olds, 0.92 (95% CI 0.81 to 1.06) for 61 to 70 year olds, and 1.08 (95% CI 0.89 to 1.30) for those over 70 years old; test for trends P = 0.007). Altered fractionation radiotherapy improves survival in patients with head and neck squamous cell carcinoma. Comparison of the different types of altered radiotherapy suggests that hyperfractionation provides the greatest benefit. An update of this IPD meta-analysis (MARCH 2), which will increase the power of this analysis and allow for other comparisons, is currently in progress. Output:

This Cochrane Review is an individual patient data based meta-analysis and the aim was to assess whether this type of radiotherapy could improve survival. We identified randomised trials comparing conventional radiotherapy with hyperfractionated or accelerated radiotherapy, or both, in patients with non-metastatic head and neck cancers and grouped trials into three pre-specified categories: hyperfractionated, accelerated without total dose reduction and accelerated with total dose reduction. The results of this meta-analysis suggest that altered fractionation radiotherapy improves survival in patients with head and neck cancer. Comparison of the different types of altered fractionation radiotherapy suggests that hyperfractionation provides the greatest benefit. Individual patient data meta-analysis is a long process and this review included all eligible trials which had completed recruiting patients by 1998. A major update of the analysis, including data from more recent trials, is currently underway.

CochranePLS3272

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Five primary studies that collectively researched a total of 725 women living with HIV were analysed. When compared to standard care or minimal HIV support intervention, meta-analysis showed that behavioral interventions had no effect on increasing condom use among HIV-positive women. This finding was consistent at 3 (OR= 0.72; 95% CI 0.43-1.20; p=0.21), 6 (OR= 0.96; 95% CI 0.66-1.40; p=0.83) and 12-months follow-up meetings (OR= 0.75; 95% CI 0.51-1.11; p=0.15). Only one study presented adequate data to analyze the relationship between behavioral interventions and STI incidence. Studies included in this analysis demonstrated low risk of bias based on the risk of bias criteria. However, sample size was considered inadequate across all studies. Meta-analysis shows that behavioral interventions have little effect on increasing condom use among HIV-positive women. However, these findings should be used with caution since results were based on a few small trials that were targeted specifically towards HIV-positive women. To decrease sexual transmission of HIV among this population, we recommend interventions that combine condom promotion, family planning provision and counselling, and efforts to reduce viral loads among HIV-positive women and their partners (e.g., HAART treatment provision). New research is needed to address the needs of HIV-positive women, including an assessment of the impact of interventions that combine safer sexual behavior and harm reduction approaches. Output:

This systematic review of randomized controlled trials assessed the effects of behavioral interventions on promoting condom use among women living with HIV, a population at higher risk to other sexually transmitted infections (STIs). Based on five eligible studies, we found that behavioral interventions promoting consistent condom use in HIV-positive women did not have a significant impact on outcomes, when compared to standard care or minimal HIV-related support. However, these findings should be used with caution since they are based on a few small trials that were targeted specifically towards HIV-positive women. New research is needed to assess the potential personal and public health gains that could arise from a combination of interventions that promote safe sexual behavior and adopt a harm reduction approach, particularly in developing countries, where HIV infection rates among women remain high.

CochranePLS3273

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Eight randomised controlled trials with 856 patients were included. Three studies used a mixed intervention (including either aerobic exercises or breathing exercises); five studies used inspiratory muscle training. Only one study used sham training in the controls. Patients that received preoperative physical therapy had a reduced risk of postoperative atelectasis (four studies including 379 participants, relative risk (RR) 0.52; 95% CI 0.32 to 0.87; P = 0.01) and pneumonia (five studies including 448 participants, RR 0.45; 95% CI 0.24 to 0.83; P = 0.01) but not of pneumothorax (one study with 45 participants, RR 0.12; 95% CI 0.01 to 2.11; P = 0.15) or mechanical ventilation for > 48 hours after surgery (two studies with 306 participants, RR 0.55; 95% CI 0.03 to 9.20; P = 0.68). Postoperative death from all causes did not differ between groups (three studies with 552 participants, RR 0.66; 95% CI 0.02 to 18.48; P = 0.81). Adverse events were not detected in the three studies that reported on them. The length of postoperative hospital stay was significantly shorter in experimental patients versus controls (three studies with 347 participants, mean difference -3.21 days; 95% CI -5.73 to -0.69; P = 0.01). One study reported an increased physical function measure on the six-minute walking test in experimental patients compared to controls. One other study reported a better health-related quality of life in experimental patients compared to controls. Postoperative death from respiratory causes did not differ between groups (one study with 276 participants, RR 0.14; 95% CI 0.01 to 2.70; P = 0.19). Cost data were not reported on. Evidence derived from small trials suggests that preoperative physical therapy reduces postoperative pulmonary complications (atelectasis and pneumonia) and length of hospital stay in patients undergoing elective cardiac surgery. There is a lack of evidence that preoperative physical therapy reduces postoperative pneumothorax, prolonged mechanical ventilation or all-cause deaths. Output:

The authors of this review evaluated the efficacy and safety of preoperative physical therapy with an exercise component in cardiac surgery patients. From the pertinent literature, eight studies met the inclusion criteria, comprising a total of 856 participants. The results showed that preoperative physical therapy reduced the number of patients who experienced atelectasis or pneumonia but not the number of patients who experienced pneumothorax, prolonged ventilation or postoperative death. Patients who had preoperative physical therapy had an earlier (on average by more than three days) discharge from the hospital. Information on adverse events was limited but those studies that did report on adverse events reported none. None of the studies reported on the costs of preoperative physical therapy. The authors concluded that preoperative physical therapy, especially inspiratory muscle training, prevents some postoperative complications including atelectasis, pneumonia, and length of hospital stay.

CochranePLS3274

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: A total of 3309 records were identified, examined and the trials subjected to selection criteria; 30 trials were included in the review. No significant effects were observed for QoL at 6-month follow up (in 9 studies, SMD 0.11; 95% CI -0.00 to 0.22); however, a small improvement in QoL was observed when QoL was measured using cancer-specific measures (in 6 studies, SMD 0.16; 95% CI 0.02 to 0.30). General psychological distress as assessed by 'mood measures' improved also (in 8 studies, SMD - 0.81; 95% CI -1.44 to - 0.18), but no significant effect was observed when measures of depression or anxiety were used to assess distress (in 6 studies, depression SMD 0.12; 95% CI -0.07 to 0.31; in 4 studies, anxiety SMD 0.05; 95% CI -0.13 to 0.22). Psychoeducational and nurse-delivered interventions that were administered face to face and by telephone with breast cancer patients produced small positive significant effects on QoL (in 2 studies, SMD 0.23; 95% CI 0.04 to 0.43). The significant variation that was observed across participants, mode of delivery, discipline of 'trained helper' and intervention content makes it difficult to arrive at a firm conclusion regarding the effectiveness of psychosocial interventions for cancer patients. It can be tentatively concluded that nurse-delivered interventions comprising information combined with supportive attention may have a beneficial impact on mood in an undifferentiated population of newly diagnosed cancer patients. Output:

This review examines the effectiveness of individual psychosocial interventions in the first 12 months after diagnosis. The psychosocial interventions involve a 'trained helper' providing therapeutic dialogue, sometimes referred to as talking therapy, with an individual diagnosed with cancer with the aim of improving quality of life and emotional wellbeing. The review combines research data from 1249 people who took part in clinical trials to test psychosocial interventions. The results are inconclusive. No improvement in general quality of life was found, but small improvements in 'illness related' quality of life were observed. No improvements in anxiety or depression were found, but small improvements in mood were detected. Nurse-led interventions using telephone and face-to-face delivery appear to show some promise. Future research should test assessment methods designed to identify patients who may benefit from psychosocial interventions, such as patients who are at risk of emotional problems; evaluate which type of 'trained helper' is the most appropriate professional to deliver psychosocial interventions for cancer patients; and conduct economic appraisals of the cost-effectiveness of interventions.

CochranePLS3275

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We identified one new trial from the updated searches. Seven trials (347 participants) met the selection criteria. The interventions varied but had common components: interventions that increased the intensity and frequency of service delivery (4 trials, 200 participants), community-based specialist behaviour therapy (1 trial, 63 participants), and outreach treatment (1 trial, 50 participants). Another trial compared two active arms (traditional counselling and integrated intervention for bereavement, 34 participants). The included studies investigated interventions dealing with the mental health problems of persons with an intellectual disability; none focused on physical health problems. Four studies assessed the effect of organisational interventions on behavioural problems for persons with an intellectual disability, three assessed care giver burden, and three assessed the costs associated with the interventions. None of the included studies reported data on the effect of organisational interventions on adverse events. Most studies were assessed as having low risk of bias. It is uncertain whether interventions that increase the frequency and intensity of delivery or outreach treatment decrease behavioural problems for persons with an intellectual disability (two and one trials respectively, very low certainty evidence). Behavioural problems were slightly decreased by community-based specialist behavioural therapy (one trial, low certainty evidence). Increasing the frequency and intensity of service delivery probably makes little or no difference to care giver burden (MD 0.03, 95% CI -3.48 to 3.54, two trials, moderate certainty evidence). It is uncertain whether outreach treatment makes any difference for care giver burden (one trial, very low certainty evidence). There was very limited evidence regarding costs, with low to very low certainty evidence for the different interventions. There is very limited evidence on the organisation of healthcare services for persons with an intellectual disability. There are currently no well-designed studies focusing on organising the health services of persons with an intellectual disability and concurrent physical problems. There are very few studies of organisational interventions targeting mental health needs and the results of those that were found need corroboration. There is an urgent need for high-quality health services research to identify optimal health services for persons with an intellectual disability and concurrent physical problem. Output:

We searched for all relevant studies until 4 September 2015. We found seven studies, six of which we identified previously and one retrieved for this update. All of the studies assessed the impact of the intervention on the mental health of persons with an intellectual disability; none considered the physical health. Those studies used different interventions, including giving persons with an intellectual disability more health services, psychological support, and treating them at home, instead of at the hospital. Studies mainly looked at how the interventions helped the behavioural problems of those with an intellectual disability, how much burden they caused the care givers, and how much they cost. No study assessed adverse events. Community-based behaviour therapy might decrease behavioural problems. We are uncertain whether other interventions make any difference in reducing behavioural problems. There was limited evidence about how those interventions helped care givers to deal with the burden of caring for their relatives with an intellectual disability, or how much they might cost compared with the usual care already provided. uthors' conclusions There is little information on different ways to organise services for people with intellectual disabilities. Most studies focused on people who had intellectual disabilities and mental health problems. There were no studies on people who had intellectual disabilities and physical problems.

CochranePLS3276

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: One randomised controlled trial (91 participants) was included in this review. We judged the trial to have a low risk of bias for method of randomisation and outcome reporting, and an unclear risk of bias for other criteria. No non-randomised controlled trials meeting our inclusion criteria were identified. The included study measured change in tinnitus severity (primary measure of interest) using a tinnitus questionnaire measure, and change in tinnitus loudness (secondary measure of interest) on a visual analogue scale. Other secondary outcome measures of interest, namely change in the psychoacoustic characteristics of tinnitus, change in self reported anxiety, depression and quality of life, and change in neurophysiological measures, were not investigated in this study. The included study compared hearing aid use to sound generator use. The estimated effect on change in tinnitus loudness or severity as measured by the Tinnitus Handicap Inventory score was compatible with benefits for both hearing aids or sound generators but no difference was found between the two alternative treatments (MD -0.90, 95% confidence interval (CI) -7.92 to 6.12) (100-point scale); moderate quality evidence. No negative or adverse events were reported. The current evidence base for hearing aid prescription for tinnitus is limited. To be useful, future studies should make appropriate use of blinding and be consistent in their use of outcome measures. Whilst hearing aids are sometimes prescribed as part of tinnitus management, there is currently no evidence to support or refute their use as a more routine intervention for tinnitus. Output:

Our search identified just one randomised controlled trial which evaluated 91 participants who had tinnitus for at least six months and some degree of hearing loss. It compared those receiving hearing aids to those receiving sound generators. The average age of the patients was 38 and there were 40 women and 51 men. The study took place in two centres in Italy and the USA. The result from the single study we reviewed was not definitive and was compatible with only small differences between the effect of hearing aids and sound generators. We also found another relevant study which has not yet been completed. We believe further high-quality trials are needed. The quality of this evidence is moderate to low. This review is up to date to August 2013.

CochranePLS3277

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Only three trials tested the efficacy of interferon (IFN) beta including a total of 1160 participants (639 treatment, 521 placebo); no trial tested the efficacy of glatiramer acetate (GA). The metanalyses showed that the proportion of patients converting to CDMS was significantly lower in IFN beta-treated than in placebo-treated patients both after one year (pooled OR 0.53; 95% CI, 0.40 to 0.71; p <0.0001) as well as after two years of follow-up (pooled OR 0.52; 95% CI, 0.38 to 0.70; p <0.0001). Early treatment with IFN beta was associated with the side effect profile reported by the randomised controlled trials with this drug. Since side effects were reported with some heterogeneity in the three studies the metanalysis was possible only for the frequency of serious adverse events, not significantly different in IFN beta-treated or placebo-treated patients. The efficacy of IFN beta treatment on preventing the conversion from CIS to CDMS was confirmed over two years of follow-up. Since patients had some clinical heterogeneity (length of follow-up, clinical findings of initial attack), it could be useful for the clinical practice to further analyse the efficacy of IFN beta treatment in different patient subgroups. Output:

IFN and GA demonstrated only partial efficacy that could be ascribed to the fact that in the studies that lead to their approval they have been initiated in patients with a disease history of several years. The objective of this review was to assess IFN beta and GA efficacy in preventing the conversion to clinically defined multiple sclerosis in patients after the first demyelinating events. Among the pertinent literature, only three studies were found to test the efficacy of IFN beta including a total of 1160 participants (639 under treatment, 521 under placebo); while no published study testing the efficacy of GA was found. The review found that early interferon beta-1a treatment is effective in preventing the conversion of the first isolated demyelinating episodes into clinically definite MS both after one year and two years of follow-up. Side effects and adverse events occurrence was the same as reported by the many studies on IFN beta treatments in MS patients with different levels of the disease. More research is however needed to evaluate the long term preventing efficacy of these drugs and dosages.

CochranePLS3278

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: For the original version of the review, 17 studies met the inclusion criteria and examined either brachytherapy, laser or photodynamic therapy (eight studies) or a variety of pharmacological therapies (nine studies). Overall, there was an absence of credible evidence and the majority of studies were of low methodological quality and at high risk of bias. Brachytherapy in a variety of doses seemed to improve cough in selected participants, suggesting that possibly the lowest effective dose should be used to minimise side effects. Photodynamic therapy was examined in one study and, while improvements in cough were observed, its role in relationship to other therapies for cough was unclear. Some indication of positive effect was observed with morphine, codeine, dihydrocodeine, levodropropizine, sodium cromoglycate and butamirate citrate linctus (cough syrup), although all studies had significant risk of bias. For this update, we did not identify any additional trials for inclusion. Two ongoing trials were identified but no study results were available. No new trials were included since the publication of the original version of this review, while 11 new studies that were identified were eventually excluded from this review. Therefore, our conclusions remain unchanged. No practice recommendations could be drawn from this review. There is an urgent need to increase the number and quality of studies evaluating the effects of interventions for the management of cough in cancer. Output:

Hence, the aim of this review was to assess and synthesise the available literature on the management of cough in cancer patients in order to improve practice recommendations. Studies with chemotherapy or radiotherapy were excluded. An extensive literature search yielded 17 studies for evaluation. For this update, we did not identify any additional studies for inclusion. Eight of the studies were about the use of brachytherapy (a technique where a radiation source is placed inside the bronchus in the lung for lung cancer or next to the area requiring treatment), use of laser resection or photodynamic therapy (a treatment that uses a drug plus a special type of light to kill cancer cells). Nine studies assessed the effects of a number of different medications, including codeine and morphine. Overall, the research was of poor quality with significant methodological problems, hence no credible evidence was available in the literature to guide practice. Acknowledging these limitations, brachytherapy in a variety of radiation doses was found to be helpful in selected patients. Some pharmacological treatments were found to be helpful, in particular morphine, codeine, dihydrocodeine, levodropropizine, sodium cromoglycate and butamirate citrate linctus (a cough syrup), although all studies had significant risk of bias and some reported side effects. No practice recommendations could be drawn from this review. There is an urgent need to increase the number and quality of studies evaluating the effects of interventions for the management of cough in cancer.

CochranePLS3279

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included four trials (two cluster-randomised trials reported in three articles and two non-randomised cluster trials). Three trials assessed retail sector ACT subsidies combined with supportive interventions (retail outlet provider training, community awareness and mass media campaigns). One trial assessed vouchers provided to households to purchase subsidised ACTs. Price subsidies ranged from 80% to 95%. One trial enrolled children under five years of age; the other three trials studied people of all age groups. The studies were done in rural districts in East Africa (Kenya, Uganda and Tanzania). In this East Africa setting, these ACT subsidy programmes increased the percentage of children under five years of age receiving ACTs on the day, or following day, of fever onset by 25 percentage points (95% confidence interval (CI) 14.1 to 35.9 percentage points; 1 study, high certainty evidence). This suggests that in practice, among febrile children under five years of age with an ACT usage rate of 5% without a subsidy, subsidy programmes would increase usage by between 19% and 41% over a one year period. The ACT subsidy programmes increased the percentage of retail outlets stocking ACTs for children under five years of age by 31.9 percentage points (95% CI 26.3 to 37.5 percentage points; 1 study, high certainty evidence). Effects on ACT stocking for patients of any age is unknown because the certainty of evidence was very low. The ACT subsidy programmes decreased the median cost of ACTs for children under five years of age by US$ 0.84 (median cost per ACT course without subsidy: US$ 1.08 versus with subsidy: US$ 0.24; 1 study, high certainty evidence). The ACT subsidy programmes increased the market share of ACTs for children under five years of age by between 23.6 and 63.0 percentage points (1 study, high certainty evidence). The ACT subsidy programmes decreased the use of older antimalarial drugs (such as amodiaquine and sulphadoxine-pyrimethamine) among children under five years of age by 10.4 percentage points (95% CI 3.9 to 16.9 percentage points; 1 study, high certainty evidence). None of the three studies of ACT subsidies reported the number of patients treated who had confirmed malaria. Vouchers increased the likelihood that an illness is treated with an ACT by 16 to 23 percentage points; however, vouchers were associated with a high rate of over-treatment of malaria (only 56% of patients taking ACTs from the drug shop tested positive for malaria under the 92% subsidy; 1 study, high certainty evidence). Programmes that include substantive subsidies for private sector retailers combined with training of providers and social marketing improved use and availability of ACTs for children under five years of age with suspected malaria in research studies from three countries in East Africa. These programmes also reduced prices of ACTs, improved market share of ACTs and reduced the use of older antimalarial drugs among febrile children under five years of age. The research evaluates drug delivery but does not assess whether the patients had confirmed (parasite-diagnosed) malaria. None of the included studies assessed patient outcomes; it is therefore not known whether the effects seen in the studies would translate to an impact on health. Output:

We included four studies. One study looked at the effect of subsidising ACT drugs for children under five years of age and three studies looked at subsidising ACT drugs for people of all ages. All studies were from rural districts in East Africa (Kenya, Uganda and Tanzania). ACT price subsidies were accompanied with activities (such as staff training at shops and pharmacies, community awareness and mass media campaigns) to promote appropriate use of antimalarial drugs in all except one study. In all four studies, the effect of subsidising the drugs was compared to not subsidising the drugs. Price subsidies ranged from 80% to 95% of the actual price; vouchers to households were used in one study. The findings from these studies indicate that ACT subsidy programmes: (i) lead to a substantial increase in the number of children under five years of age who used ACTs when they had a fever (high certainty evidence); (ii) lead to a substantial increase in the number of shops that stocked ACTs for children under five years of age (high certainty evidence); we could not draw any conclusion on the effect on the number of shops that stocked ACTs for patients of any age because the quality of evidence was very low; (iii) lead to a substantial decrease in the price of ACTs for children under five years of age (high certainty evidence); (iv) lead to a substantial increase in the market share of ACTs for children under five years of age (high certainty evidence); and (v) lead to a decrease in the use of older, less effective antimalarials among children under five years of age (high certainty evidence). None of the studies measured whether the subsidy programmes led to any harmful effects (such as the inappropriate use of ACTs, in other words people who receive ACTs but do not actually have malaria). The review findings also showed that subsidising ACT prices using vouchers lead to an increase in the likelihood that an illness was treated with an ACT among people seeking treatment for fever or suspected malaria. However, vouchers also lead to an increase in inappropriate use of ACTs (high certainty evidence).

CochranePLS3280

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 13 trials in this review and IPD were available for 836 individuals out of 1455 eligible individuals from six trials, 57% of the potential data. For remission outcomes, a HR of less than 1 indicates an advantage for phenobarbitone and for first seizure and treatment failure outcomes a HR of less than 1 indicates an advantage for carbamazepine. Results for the primary outcome of the review were: time to treatment failure for any reason related to treatment (pooled HR adjusted for seizure type for 676 participants: 0.66, 95% CI 0.50 to 0.86, moderate-quality evidence), time to treatment failure due to adverse events (pooled HR adjusted for seizure type for 619 participants: 0.69, 95% CI 0.49 to 0.97, low-quality evidence), time to treatment failure due to lack of efficacy (pooled HR adjusted for seizure type for 487 participants: 0.54, 95% CI 0.38 to 0.78, moderate-quality evidence), showing a statistically significant advantage for carbamazepine compared to phenobarbitone. For our secondary outcomes, we did not find any statistically significant differences between carbamazepine and phenobarbitone: time to first seizure post-randomisation (pooled HR adjusted for seizure type for 822 participants: 1.13, 95% CI 0.93 to 1.38, moderate-quality evidence), time to 12-month remission (pooled HR adjusted for seizure type for 683 participants: 1.09, 95% CI 0.84 to 1.40, low-quality evidence), and time to six-month remission pooled HR adjusted for seizure type for 683 participants: 1.01, 95% CI 0.81 to 1.24, low-quality evidence). Results of these secondary outcomes suggest that there may be an association between treatment effect in terms of efficacy and seizure type; that is, that participants with focal onset seizures experience seizure recurrence later and hence remission of seizures earlier on phenobarbitone than carbamazepine, and vice versa for individuals with generalised seizures. It is likely that the analyses of these outcomes were confounded by several methodological issues and misclassification of seizure type, which could have introduced the heterogeneity and bias into the results of this review. Limited information was available regarding adverse events in the trials and we could not compare the rates of adverse events between carbamazepine and phenobarbitone. Some adverse events reported on both drugs were abdominal pain, nausea, and vomiting, drowsiness, motor and cognitive disturbances, dysmorphic side effects (such as rash), and behavioural side effects in three paediatric trials. Moderate-quality evidence from this review suggests that carbamazepine is likely to be a more effective drug than phenobarbitone in terms of treatment retention (treatment failures due to lack of efficacy or adverse events or both). Moderate- to low-quality evidence from this review also suggests an association between treatment efficacy and seizure type in terms of seizure recurrence and seizure remission, with an advantage for phenobarbitone for focal onset seizures and an advantage for carbamazepine for generalised onset seizures. However, some of the trials contributing to the analyses had methodological inadequacies and inconsistencies that may have impacted upon the results of this review. Therefore, we do not suggest that results of this review alone should form the basis of a treatment choice for a patient with newly onset seizures. We recommend that future trials should be designed to the highest quality possible with consideration of masking, choice of population, classification of seizure type, duration of follow-up, choice of outcomes and analysis, and presentation of results. Output:

The last search for trials was in May 2018. We assessed the evidence from 13 clinical trials in which people received either carbamazepine or phenobarbitone and their treatment was decided randomly. We were able to combine data for 836 people from six of the 13 trials; for the remaining 619 people from seven trials, data were not available to use in this review. Key results Results of the review suggest that people are likely to stop taking phenobarbitone treatment earlier than carbamazepine treatment, because of seizure recurrence, side-effects of the drug, or both. Results also suggest that recurrence of seizures after starting treatment with phenobarbitone may happen later than treatment with carbamazepine (and therefore a seizure free period of 6 months or 12 months may occur earlier with phenobarbitone than with carbamazepine) for people with focal onset seizures, and vice-versa for people with generalised onset seizures. Some side effects reported by people taking carbamazepine and people taking phenobarbitone were abdominal pain, nausea, vomiting, tiredness, motor problems (such as poor co-ordination), cognitive problems (poor memory), rashes and other skin problems. Behavioural side effects such as aggression were reported on both drugs in three trials in children. Quality of the evidence Some of the trials contributing data to the review had methodological problems, which may have introduced bias and inconsistent results into this review, and some individuals over the age of 30 with newly diagnosed generalised onset seizures may have had their seizure type wrongly diagnosed. These problems may have affected the results of this review and we judged the quality of the evidence provided by this review to be moderate to low quality. We do not suggest using the results of this review alone for making a choice between carbamazepine or phenobarbitone for the treatment of epilepsy. We recommend that all future trials comparing these drugs or any other antiepileptic drugs should be designed using high-quality methods to ensure results are also of high quality.

CochranePLS3281

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 25 RCTs (1688 participants) in this review (23 trials combined within meta-analyses). In 18 studies, participants underwent total knee arthroplasty (TKA), whereas seven trials investigated patients undergoing arthroscopic knee surgery. We identified 11 studies awaiting classification and 11 ongoing studies. We investigated the following comparisons. ACB versus sham treatment We included eight trials for this comparison. We found no significant differences in postoperative pain intensity at rest (2 hours: standardized mean difference (SMD) -0.56, 95% confidence interval (CI) -1.20 to 0.07, 4 trials, 208 participants, low-quality evidence; 24 hours: SMD -0.49, 95% CI -1.05 to 0.07, 6 trials, 272 participants, low-quality evidence) or during movement (2 hours: SMD -0.59, 95% CI -1.5 to 0.33; 3 trials, 160 participants, very low-quality evidence; 24 hours: SMD 0.03, 95% CI -0.26 to 0.32, 4 trials, 184 participants, low-quality evidence). Furthermore, they noted no evidence of a difference in postoperative nausea between groups (24 hours: risk ratio (RR) 1.91, 95% CI 0.48 to 7.58, 3 trials, 121 participants, low-quality evidence). One trial reported that no accidental falls occurred 24 hours postoperatively (low-quality evidence). ACB versus femoral nerve block We included 15 RCTs for this comparison. We found no evidence of a difference in postoperative pain intensity at rest (2 hours: SMD -0.74, 95% CI -1.76 to 0.28, 5 trials, 298 participants, low-quality evidence; 24 hours: SMD 0.04, 95% CI -0.09 to 0.18, 12 trials, 868 participants, high-quality evidence) or during movement (2 hours: SMD -0.47, 95% CI -1.86 to 0.93, 2 trials, 88 participants, very low-quality evidence; 24 hours: SMD 0.56, 95% CI -0.00 to 1.12, 9 trials, 576 participants, very low-quality evidence). They noted no evidence of a difference in postoperative nausea (24 hours: RR 1.22, 95% CI 0.42 to 3.54, 2 trials, 138 participants, low-quality evidence) and no evidence that the rate of accidental falls during postoperative care was significantly different between groups (24 hours: RR 0.20, 95% CI 0.04 to 1.15, 3 trials, 172 participants, low-quality evidence). We are currently uncertain whether patients treated with ACB suffer from lower pain intensity at rest and during movement, fewer opioid-related adverse events, and fewer accidental falls during postoperative care compared to patients receiving sham treatment. The same holds true for the comparison of ACB versus femoral nerve block focusing on postoperative pain intensity. The overall evidence level was mostly low or very low, so further research might change the conclusion. The 11 studies awaiting classification and the 11 ongoing studies, once assessed, may alter the conclusions of this review. Output:

We included 25 clinical studies in which people are randomly put into one of two or more treatment groups (called 'randomized controlled trials'), with results reported from a total of 1688 participants (929 females, 759 males). Participants were 29 to 72 years old. Eight trials compared participants receiving adductor canal block against patients receiving saline. A total of 15 RCTs compared adductor canal block versus femoral nerve block. The evidence is current to October 2018. No trial was funded by industry. We are uncertain whether patients treated with adductor canal block have lower pain intensity at rest or during movement (e.g. walking) compared with those who received only saline. It is unclear whether rates of adverse events after taking opioids (e.g. nausea) or after accidental falls during postoperative care are lower. It is also uncertain whether patients receiving adductor canal block show different postoperative pain intensity at rest and during movement compared to those treated with femoral nerve block. We noted no differences in adverse events after taking opioids and after accidental falls. We rated the quality of evidence for many outcomes as low or very low. In contrast, we rated pain at rest (at 24 hours) as high-quality evidence.

CochranePLS3282

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We identified five high quality studies with a total of 366 participants. All measured pain or disability levels at six months, and four measured the proportion of participants reporting a greater than 50% reduction in pain or disability scores. Three randomised controlled trials (206 participants) found that prolotherapy injections alone are no more effective than control injection for chronic low-back pain and disability. At six months, there was no difference between groups in mean pain or disability scores (2 RCTs; 184 participants) and no difference in proportions who reported over 50% improvement in pain or disability (3 RCTs; 206 participants). These trials could not be pooled due to clinical heterogeneity. Two RCTs (160 participants) found that prolotherapy injections, given with spinal manipulation, exercise, and other therapies, are more effective than control injections for chronic low-back pain and disability. At six months, one study reported a significant difference between groups in mean pain and disability scores, whereas the other study did not. Both studies reported a significant difference in the proportion of individuals who reported over 50% reduction in disability or pain. Co-interventions confounded interpretation of results and clinical heterogeneity in the trials prevented pooling. There is conflicting evidence regarding the efficacy of prolotherapy injections for patients with chronic low-back pain. When used alone, prolotherapy is not an effective treatment for chronic low-back pain. When combined with spinal manipulation, exercise, and other co-interventions, prolotherapy may improve chronic low-back pain and disability. Conclusions are confounded by clinical heterogeneity amongst studies and by the presence of co-interventions. Output:

This review included five studies that examined the effects of prolotherapy injections on 366 patients with low-back pain that had lasted for longer than three months. Because these studies used different types of prolotherapy injections and different treatment protocols, their results could not be combined. The five studies we examined were therefore divided according to whether they used prolotherapy injections alone or combined prolotherapy injections with spinal manipulation, exercise, and other treatments. Of the five studies we reviewed, three found that prolotherapy injections alone were not an effective treatment for chronic low-back pain and two found that a combination of prolotherapy injections, spinal manipulation, exercises, and other treatments can help chronic low-back pain and disability. Minor side effects such as increased back pain and stiffness were common but short-lived. Based on these five studies, the role of prolotherapy injections for chronic low-back pain is still not clear.

CochranePLS3283

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: The review included four trials (186 women) that hugely differed in terms of the diversity of the intervention modalities and outcomes measured. Most trials assessed the effects of electromyographic biofeedback in women who were pregnant for the first time. The trials were judged to be at a high risk of bias due to the lack of data describing the sources of bias assessed. There was no significant evidence of a difference between biofeedback and control groups in terms of assisted vaginal birth, caesarean section, augmentation of labour and the use of pharmacological pain relief. The results of the included trials showed that the use of biofeedback to reduce the pain in women during labour is unproven. Electromyographic biofeedback may have some positive effects early in labour, but as labour progresses there is a need for additional pharmacological analgesia. Despite some positive results shown in the included trials, there is insufficient evidence that biofeedback is effective for the management of pain during labour. Output:

The purpose of the review was to see whether biofeedback, taught in prenatal classes, would have an effect in relieving pain during labour. The review includes four studies (involving 186 women who were pregnant for the first time). The randomised controlled studies were very different, and of poor quality, making it difficult to draw any firm conclusions. Most studies assessed the effects of electromyographic biofeedback, which measures muscle tone. There was no significant evidence of a difference between biofeedback and control groups in terms of assisted vaginal birth, caesarean section, augmentation of labour and the use of pharmacological pain relief. There was not enough information on electromyographic to assess its effect on pain during labour. This review is one in a series of Cochrane reviews examining pain relief in labour, which will contribute to an overview of systematic reviews of pain relief for women in labour (in preparation).

CochranePLS3284

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Three new studies were added in this update, resulting in a total of six included studies (five in adults and one involving children/adolescents). These six studies were clinically and methodologically heterogeneous (use of medications, cut-off for percentage of sputum eosinophils and definition of asthma exacerbation). Of 374 participants randomised, 333 completed the trials. In the meta-analysis, there was a significant reduction in the occurrence of any exacerbations when treatment was based on sputum eosinophil counts, compared to that based on clinical symptoms with or without lung function; pooled odds ratio (OR) was 0.57 (95% confidence interval (CI) 0.38 to 0.86). The risk of having one or more exacerbations over 16 months was 82% in the control arm and 62% (95% CI 49% to 74%) in the sputum strategy arm, resulting in a number needed to treat to benefit (NNTB) of 6 (95% CI 4 to 13). There were also differences between the groups in the rate of exacerbation (any exacerbation per year) and severity of exacerbations defined by requirement for use of oral corticosteroids and hospitalisations: the risk of one or more hospitalisations over 16 months was 24% in controls compared to 8% (95% CI 3% to 21%) in the sputum arm. Data for clinical symptoms, quality of life and spirometry were not significantly different between groups. The mean dose of inhaled corticosteroids per day was also similar in both groups. However sputum induction was not always possible. The included studies did not record any adverse events. One study was not blinded and thus was considered to have a high risk of bias. However, when this study was removed in a sensitivity analysis, the difference between the groups for the primary outcome (exacerbations) remained statistically significant between groups. The GRADE quality of the evidence ranged from moderate (for the outcomes 'Occurrence of any exacerbation' and 'Hospitalisation' ) to low (for the outcome 'Mean dose of inhaled corticosteroids per person per day') due to the inconsistency in defining exacerbations and the small number of hospital admissions. In this updated review, tailoring asthma interventions based on sputum eosinophils is beneficial in reducing the frequency of asthma exacerbations in adults with asthma. Adults with frequent exacerbations and severe asthma may derive the greatest benefit from this additional monitoring test, although we were unable to confirm this through subgroup analysis. There is insufficient data available to assess tailoring asthma medications based on sputum eosinophilia in children. Further robust RCTs need to be undertaken and these should include participants with different underlying asthma severities and endotypes. Output:

We included studies that compared adjustment of asthma medicines by counting sputum eosinophils versus usual care. To be included, the studies has to decide who would be in which group by chance. The participants all had asthma, diagnosed according to asthma guidelines. The most recent search for studies was undertaken in February 2017. This updated review includes six studies involving 382 people with asthma (55 children/adolescents, 327 adults). The studies varied in several ways including study duration and follow-up, sputum eosinophil counts used for adjusting medication and the way the asthma attacks were defined. Studies were between 6 and 24 months long. The age spread of participants in the studies was 12 to 48 years. We found that guiding asthma medicines based on sputum eosinophil counts (compared to a control group) reduced the number and severity of asthma attacks in adults. In the control group where treatment was guided according to clinical symptoms, 82 participants out of 100 had at least one attack. This was reduced to 62 out of 100 in participants who had their medications guided by sputum eosinophil count. We are not certain about the effect on other measures, such as quality of life or dose of inhaled steroids needed. There is not enough data in children to assess whether using sputum eosinophil is useful. We are moderately confident in the evidence for any asthma attack and hospital admissions. We were concerned about the different ways the studies defined asthma attacks and the small number of hospital admissions overall, which makes it harder to detect a difference. We are less confident in the evidence about the dose of inhaled steroids. This is because the studies used very different doses. Also, we cannot tell if the eosinophil-guided treatment reduced or increased the steroid dose overall.

CochranePLS3285

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included eight RCTs (with a total of 559 participants) in this review. The studies recruited outpatients aged between 17 and 76 years who were referred to endoscopy centres in several different countries. The certainty of evidence was reduced for most outcomes due to the poor methodological quality of included studies; issues mainly related to the generation of allocation sequence, allocation concealment, and blinding (this last domain related specifically to adverse outcomes). We are uncertain whether the addition of NAC to antibiotics improves H pylori eradication rates, compared with the addition of placebo or no NAC (38.8% versus 49.1%, risk ratio (RR) 0.74, 95% confidence interval (CI) 0.51 to 1.08; participants = 559; studies = eight; very low-certainty evidence). A post-hoc sensitivity analysis, in which we removed studies that tested antibiotic regimens no longer recommended in clinical practice, showed that the addition of NAC may improve eradication rates compared to control (27.2% versus 37.6%, RR 0.71, 95% CI 0.53 to 0.94; participants = 397; published studies = five). We are uncertain whether NAC is associated with a higher risk of gastrointestinal adverse events compared to control (23.9% versus 18.9%, RR 1.25, 95% CI 0.85 to 1.85; participants = 336; studies = five; very low-certaintyevidence), or allergic adverse events (2% versus 0%, RR 2.98, 95% CI 0.32 to 27.74; participants = 336; studies = five; very low-certainty evidence). There were no reports of toxic adverse events amongst included studies. We are uncertain whether the addition of NAC to antibiotics improves H pylori eradication rates compared with the addition of placebo or no NAC. Due to the clinical, statistical and methodological heterogeneity found in included studies, and the uncertainty observed when analysing therapy subgroups, any possible beneficial effect of NAC should be regarded cautiously. We are uncertain whether NAC is associated with a higher risk of gastrointestinal or allergic adverse events compared with placebo or no NAC. There were no reports of toxic adverse events amongst the included studies. Further large, well-designed, randomised clinical studies should be conducted, with good reporting standards and appropriate collection of efficacy and safety outcomes, especially for current recommended antibiotic regimens. Output:

We included eight studies (specifically, randomised controlled trials (RCTs)) with a total of 559 people aged between 17 and 76 years old. The evidence is current to April 2018. All studies recruited outpatients from endoscopy centres (centres that specialise in an examination done with a flexible tube with a camera that is inserted into stomach) in several countries. The antibiotic combinations tested were very different in the included studies, as were the doses of NAC (600 mg to 1800 mg per day). NAC was compared with placebo (dummy pill) or nothing. We are uncertain whether the addition of NAC to antibiotics improves H pylori cure rates compared with the addition of placebo or no NAC. Any possible beneficial effect of NAC should be regarded cautiously because the included studies were very different and of low certainty, with some flaws that could have compromised their results and consequently, the results of this review. We are uncertain whether NAC is associated with a higher risk of gastrointestinal or allergic adverse events compared with placebo or no NAC. There were no reports of toxic adverse events amongst the included studies. Further large, well-designed randomised clinical studies, with good reporting standards and appropriate collection of effectiveness and safety outcomes should be done, especially for current recommended antibiotic combinations. The overall certainty of the evidence for eradication rates ranged from very low to low. Five studies provided information on adverse events (side effects), and the certainy of evidence was very low. The included studies were poorly conducted and this reduced our confidence in the results.

CochranePLS3286

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included four randomised clinical trials analysing a total of 1892 women comparing a freeze-all strategy with a conventional IVF/ICSI strategy. The evidence was of moderate to low quality due to serious risk of bias and (for some outcomes) serious imprecision. Risk of bias was associated with unclear blinding of investigators for preliminary outcomes of the study, unit of analysis error, and absence of adequate study termination rules. There was no clear evidence of a difference in cumulative live birth rate between the freeze-all strategy and the conventional IVF/ICSI strategy (odds ratio (OR) 1.09, 95% confidence interval (CI) 0.91 to 1.31; 4 trials; 1892 women; I2 = 0%; moderate-quality evidence). This suggests that if the cumulative live birth rate is 58% following a conventional IVF/ICSI strategy, the rate following a freeze-all strategy would be between 56% and 65%. The prevalence of OHSS was lower after the freeze-all strategy compared to the conventional IVF/ICSI strategy (OR 0.24, 95% CI 0.15 to 0.38; 2 trials; 1633 women; I2 = 0%; low-quality evidence). This suggests that if the OHSS rate is 7% following a conventional IVF/ICSI strategy, the rate following a freeze-all strategy would be between 1% and 3%. The freeze-all strategy was associated with fewer miscarriages (OR 0.67, 95% CI 0.52 to 0.86; 4 trials; 1892 women; I2 = 0%; low-quality evidence) and a higher rate of pregnancy complications (OR 1.44, 95% CI 1.08 to 1.92; 2 trials; 1633 women; low-quality evidence). There was no difference in multiple pregnancies per woman after the first transfer (OR 1.11, 95% CI 0.85 to 1.44; 2 trials; 1630 women; low-quality evidence), and no data were reported for time to pregnancy. We found moderate-quality evidence showing that one strategy is not superior to the other in terms of cumulative live birth rates. Time to pregnancy was not reported, but it can be assumed to be shorter using a conventional IVF/ICSI strategy in the case of similar cumulative live birth rates, as embryo transfer is delayed in a freeze-all strategy. Low-quality evidence suggests that not performing a fresh transfer lowers the OHSS risk for women at risk of OHSS. Output:

We included four studies comparing a freeze-all strategy with a conventional IVF/ICSI strategy in a total of 1892 women undergoing assisted reproductive technology. The evidence is current to November 2016. We found evidence showing seemingly no difference between the strategies in cumulative live birth rate per woman. Our findings suggest that if the cumulative live birth rate is 58% following a conventional IVF/ICSI strategy, the rate following a freeze-all strategy would be between 56% and 65%. Time to pregnancy was not reported as an outcome in in the included studies, but it can be assumed to be shorter using a conventional IVF/ICSI strategy including fresh transfer in the case of similar cumulative live birth rates, as embryo transfer is delayed in a freeze-all strategy. Not performing a fresh transfer (freeze-all strategy) lowers the OHSS risk for women at risk of OHSS. Our findings suggest that if the OHSS rate is 7% following a conventional IVF/ICSI strategy, the rate following a freeze-all strategy would be between 1% and 3%. The evidence was of moderate to low quality due to serious risk of bias and (for some outcomes) serious imprecision. Risk of bias was associated with unclear blinding of investigators for preliminary outcomes of the study, unit of analysis error, and absence of adequate study termination rules.

CochranePLS3287

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: One RCT was identified that compared different platelet transfusion thresholds prior to insertion of a CVC in people with chronic liver disease. This study is still recruiting participants (expected recruitment: up to 165 participants) and is due to be completed in December 2017. There were no completed studies. There were no studies that compared no platelet transfusions to a platelet transfusion threshold. There is no evidence from RCTs to determine whether platelet transfusions are required prior to central line insertion in patients with thrombocytopenia, and, if a platelet transfusion is required, what is the correct platelet transfusion threshold. Further randomised trials with robust methodology are required to develop the optimal transfusion strategy for such patients. The one ongoing RCT involving people with cirrhosis will not be able to answer this review's questions, because it is a small study that assesses one patient group and does not address all of the comparisons included in this review. To detect an increase in the proportion of participants who had major bleeding from 1 in 100 to 2 in 100 would require a study containing at least 4634 participants (80% power, 5% significance). Output:

The evidence is current to February 2015. In this review one randomised controlled trial was identified that compared giving platelet transfusions at a low platelet count (25 x 109/l) versus giving platelet transfusions at a higher platelet count (50 x 109/l) prior to insertion of a central line to prevent bleeding. This trial is still recruiting and is due to complete recruitment in December 2017. There were no trials that compared no platelet transfusions versus giving platelet transfusions at a prespecified platelet count. There are no results from the one eligible study because it is still recruiting participants. This ongoing study (expected to recruit 165 participants) will be unable to provide sufficient data for this review's primary outcomes because major bleeding and mortality are uncommon. We would need to design a study with at least 4634 participants to be able to detect an increase in the number of people who had major bleeding from 1 in 100 to 2 in 100. There is no evidence from randomised controlled trials to answer our review questions.

CochranePLS3288

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Fourteen studies were included in this review. Some of the included studies did not present numerical data suitable for analysis. Description of participants varied over the years and by type of disorders and severity, and ranged from aged individuals with subjective memory disorders to patients with Vascular Cognitive Impairment (mild to moderate), Vascular Dementia or Senile Dementia (mild to moderate). Seven of the included studies observed the subjects for a period between 20 to 30 days, one study was of 6 weeks duration, four studies used periods extending over 2 and 3 months, one study observed continuous administration over 3 months and one study was prolonged, with 12 months of observation. The studies were heterogeneous in dose, modalities of administration, inclusion criteria for subjects, and outcome measures. Results were reported for the domains of attention, memory testing, behavioural rating scales, global clinical impression and tolerability. There was no evidence of a beneficial effect of CDP-choline on attention. There was evidence of benefit of CDP-choline on memory function and behaviour. The drug was well tolerated. There was some evidence that CDP-choline has a positive effect on memory and behaviour in at least the short to medium term. The evidence of benefit from global impression was stronger, but is still limited by the duration of the studies. Further research with CDP-choline should focus on longer term studies in subjects who have been diagnosed with currently accepted standardised criteria, especially Vascular Mild Cognitive Impairment (VaMCI) or vascular dementia. Output:

These findings, however, are limited by the relatively short-term of clinical controlled observations which in all studies but one lasted for no more than three months. Subjective evaluations of these patients as given by their doctors were consistently positive and no noticeable side effects were evidenced in the various studies over the years.

CochranePLS3289

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 67 trials with 5438 participants that comprised 79 comparisons. Forty-five RCTs compared ABSW versus control, whereas 18 compared two different types of ABSW, and 10 compared two different techniques to administer the same type of ABSW. Forced-air warming (FAW) was by far the most studied intervention. Trials varied widely regarding whether the interventions were applied alone or in combination with other active (based on a different mechanism of heat transfer) and/or passive methods of maintaining normothermia. The type of participants and surgical interventions, as well as anaesthesia management, co-interventions and the timing of outcome measurement, also varied widely. The risk of bias of included studies was largely unclear due to limitations in the reports. Most studies were open-label, due to the nature of the intervention and the fact that temperature was usually the principal outcome. Nevertheless, given that outcome measurement could have been conducted in a blinded manner, we rated the risk of detection and performance bias as high. The comparison of ABSW versus control showed a reduction in the rate of surgical site infection (risk ratio (RR) 0.36, 95% confidence interval (CI) 0.20 to 0.66; 3 RCTs, 589 participants, low-quality evidence). Only one study at low risk of bias observed a beneficial effect with forced-air warming on major cardiovascular complications (RR 0.22, 95% CI 0.05 to 1.00; 1 RCT with 12 events, 300 participants, low-quality evidence) in people at high cardiovascular risk. We found no beneficial effect for mortality. ABSW also reduced blood loss during surgery but the magnitude of this effect seems to be irrelevant (MD -46.17 mL, 95% CI -82.74 to -9.59; I² = 78%; 20 studies, 1372 participants). The same conclusion applies to total fluids infused during surgery (MD -144.49 mL, 95% CI -221.57 to -67.40; I² = 73%; 24 studies, 1491 participants). These effects did not translate into a significant reduction in the number of participants being transfused or the average amount of blood transfused. ABSW was associated with a reduction in shivering (RR 0.39, 95% CI 0.28 to 0.54; 29 studies, 1922 participants) and in thermal comfort (standardized mean difference (SMD) 0.76, 95% CI 0.29 to 1.24; I² = 77%, 4 trials, 364 participants). For the comparison between different types of ABSW system or modes of administration of a particular type of ABSW, we found no evidence for the superiority of any system in terms of clinical outcomes, except for extending systemic warming to the preoperative period in participants undergoing major abdominal surgery (one study at low risk of bias). There were limited data on adverse effects (the most relevant being thermal burns). While some trials included a narrative report mentioning that no adverse effects were observed, the majority made no reference to it. Nothing so far suggests that ABSW involves a significant risk to patients. Forced-air warming seems to have a beneficial effect in terms of a lower rate of surgical site infection and complications, at least in those undergoing abdominal surgery, compared to not applying any active warming system. It also has a beneficial effect on major cardiovascular complications in people with substantial cardiovascular disease, although the evidence is limited to one study. It also improves patient's comfort, although we found high heterogeneity among trials. While the effect on blood loss is statistically significant, this difference does not translate to a significant reduction in transfusions. Again, we noted high heterogeneity among trials for this outcome. The clinical relevance of blood loss reduction is therefore questionable. The evidence for other types of ABSW is scant, although there is some evidence of a beneficial effect in the same direction on chills/shivering with electric or resistive-based heating systems. Some evidence suggests that extending systemic warming to the preoperative period could be more beneficial than limiting it only to during surgery. Nothing suggests that ABSW systems pose a significant risk to patients. The difficulty in observing a clinically-relevant beneficial effect with ABSW in outcomes other than temperature may be explained by the fact that many studies applied concomitant procedures that are routinely in place as co-interventions to prevent hypothermia, whether passive or active warming systems based in other physiological mechanisms (e.g. irrigation fluid or gas warming), as well as a stricter control of temperature in the context of the study compared with usual practice. These may have had a beneficial effect on the participants in the control group, leading to an underestimation of the net benefit of ABSW. Output:

The review includes 67 randomized controlled trials (5438 people). The trials included patients of all ages and both genders undergoing all types of surgery. The evidence was from studies available to October 2015. Forty-five trials compared a warming system to a control intervention, 18 compared different types of warming systems, and 10 compared different modalities of the same warming system. Forced-air warming was the most studied system. Active warming had some beneficial clinical effects on the patient. It reduced the risk of a major complication of heart and circulation in one trial in people with substantial disease of that system, but the evidence remains inconclusive. Active warming reduced the rate of infection and complications of surgical wounds.. This effect was shown in two quite large trials in people undergoing abdominal surgery; forced-air warming was applied exclusively before the operation in one study, while in the other it was applied during the operation. Patients receiving active warming systems had about one-third the risk of postsurgical chills or shivering compared to those receiving control treatment (29 trials, 1922 people). Thermal comfort was increased for the patient compared with the control intervention (10 trials involving 700 people). On the other hand, warming made little or no difference to the risk of death, blood loss or the need for a blood transfusion. We found no differences in the number of non-fatal heart attacks, in anxiety or in pain, compared with people in the control groups. The trials in the review did not allow us to identify which warming system was better. However, there was an indication from one trial at low risk of bias that results were better when systemic warming was extended to the period before the operation in people undergoing major abdominal surgery. We could only get limited information from the study reports regarding adverse effects. In some cases the trials reported that there had been no adverse effects. The quality of the evidence was low for surgical site infections and complications of the heart and circulation. This is because very few trials with few events reported on these outcomes, although they were at low risk of bias. Patients differed in the types of surgery, with different complexities and duration, the type of anaesthesia, patient age, the severity of the condition and other illnesses. The trials did not last long, which made it difficult to detect clinical effects. These outcomes are also strongly influenced by other management components during the operation that we did not evaluate in this review. While some studies applied a single intervention, others used two or more interventions in combination, and/or included other methods of passive warming. The control group did not always consist of a 'pure control' without active heating, and sometimes patients also received another intervention as part of usual care. All these reasons may explain the diversity that we observed for some outcomes among the studies. The temperature of the control group may also have been more strictly controlled, as there is now widespread awareness of the risk of hypothermia.

CochranePLS3290

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Three studies, with a combined total of 496 patients, matched the inclusion criteria for this review. All three included studies evaluated the role of KL and TL in thromboprophylaxis among a group of postoperative patients. These studies showed no significant difference in the ability of the two modalities of leg compression to reduce the incidence of deep vein thrombosis in postoperative patients. In both the fixed-effect model (odds ratio (OR) 1.55, 95% confidence interval (CI) 0.78 to 3.07, P = 0.21) and random-effects model (OR 1.32, 95% CI 0.43 to 4.06, P = 0.63) KL graduated compression stockings were as effective as TL stockings in thromboprophylaxis. However, there was significant heterogeneity (Tau2 = 0.50; Chi2 = 4.12, df = 2 (P = 0.13); I2 = 51%) among trials. Results of this review may be considered weak because there was significant heterogeneity among included trials resulting from inadequate randomisation techniques, allocation concealment, power calculations and the absence of intention-to-treat analysis. This review found that there is insufficient high quality evidence to determine whether or not KL and TL GCS differ in their effectiveness in terms of reducing the incidence of deep vein thrombosis (DVT) in hospitalised patients.  A major multicentre RCT is required to address this issue. In the meantime, the decision on which type of stocking to use in clinical practice is likely to be influenced by factors such as patient compliance, ease of use and cost implications. Output:

Due to the limited number of patients and trials, and significant differences between the included trials, the conclusion may be weak. There was insufficient high quality evidence to determine whether or not knee length and thigh length graduated compression stockings differed in their effectiveness in terms of reducing the incidence of DVT in hospitalised patients. The majority of patients analysed in this review also received heparin and physiotherapy, along with the use of either knee length or thigh length stockings. A major multicentre RCT is required. In the meantime, the decision on which type of stocking to use in clinical practice is likely to be influenced by factors such as patient compliance, ease of use and cost implications.

CochranePLS3291

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included three trials randomising 295 participants: 147 to T-tube drainage versus 148 to primary closure. All trials had a high risk of bias. No one died during the follow-up period. There was no significant difference in the proportion of patients with serious morbidity (17/147 (weighted percentage 11.3%) in the T-tube drainage versus 9/148 (6.1%) in the primary closure group; RR 1.86; 95% CI 0.87 to 3.96; three trials), and no significant difference was found in the serious morbidity rates (weighted serious morbidity rate = 97 events per 1000 patients) in participants randomised to T-tube drainage versus serious morbidity rate = 61 events per 1000 patients in the primary closure group; RR 1.59; 95% CI 0.66 to 3.83; three trials). Quality of life was not reported in any of the trials. The operating time was significantly longer in the T-tube drainage group compared with the primary closure group (MD 21.22 minutes; 95% CI 12.44 minutes to 30.00 minutes; three trials). The hospital stay was significantly longer in the T-tube drainage group compared with the primary closure group (MD 3.26 days; 95% CI 2.49 days to 4.04 days; three trials). According to one trial, the participants randomised to T-tube drainage returned to work approximately eight days later than the participants randomised to the primary closure group (P < 0.005). T-tube drainage appears to result in significantly longer operating time and hospital stay as compared with primary closure without any evidence of benefit after laparoscopic common bile duct exploration. Based on currently available evidence, there is no justification for the routine use of T-tube drainage after laparoscopic common bile duct exploration in patients with common bile duct stones. More randomised trials comparing the effects of T-tube drainage versus primary closure after laparoscopic common bile duct exploration may be needed. Such trials should be conducted with low risk of bias, assessing the long-term beneficial and harmful effects including long-term complications such as bile stricture and recurrence of common bile duct stones. Output:

We identified a total of three trials including 295 participants, of whom 148 were randomly chosen to receive primary closure and the remaining patients had T-tube drainage after laparoscopic exploration of common bile duct. All three trials were at high risk of bias (risk of underestimating or overestimating the benefits and harms of the intervention). There were no deaths in either group. There was no significant difference in the serious complication rate (approximately 97 complications per 1000 patients in the T-tube group versus 61 complications per 1000 participants in the primary closure group) or in the proportion of participants who developed serious complications (11.3% in the T-tube group versus 6.2% in the primary closure group). Although the complication rates in the T-tube group appear to be twice as high as those in the primary closure group, there is a possibility that this was not a true observation but rather a difference that occurred by chance (similar to there being one chance in eight of flipping a coin and having it come up heads or tails four times in a row). For this reason, we cannot be sufficiently confident scientifically that these differences were not just due to chance and that is the reason why we have stated that there was no 'significant' difference. Of course, if such a difference truly exists, it would be clinically important. None of the trials reported the quality of life of the participants. The average operating time was significantly longer in the T-tube group than in the primary closure group (by about 20 minutes). The average hospital stay was significantly longer in the T-tube group than in the primary closure group (by about three days). Participants returned to work significantly later in the T-tube group than primary closure group (by about eight days). Use of T-tube appears to increase the cost without providing any benefit to the patients. Further randomised trials with low risk of bias (low chance of arriving at wrong conclusions because of prejudice by healthcare providers, researchers, or patients) with longer follow-up period are necessary. Until the results from such trials are available, we discourage the routine use of T-tube after laparoscopic common bile duct exploration.

CochranePLS3292

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We identified two studies with a total of 100 participants for inclusion in the review. We found the overall risk of bias to be unclear in a number of domains. Neither study reported the time taken to the first INR in range. Only one study (70 participants) reported the mean time in therapeutic range as a percentage. This study found that in the group of participants deemed to have poor INR control, the addition of 150 micrograms (mcg) oral vitamin K significantly improved anticoagulation control in those with unexplained instability of response to warfarin. The second study (30 participants) reported the effect of 175 mcg oral vitamin K versus placebo on participants with high variability in their INR levels. The study concluded that vitamin K supplementation did not significantly improve the stability of anticoagulation for participants on chronic anticoagulation therapy. However, the study was only available in abstract form, and communication with the lead author confirmed that there were no further publications. Therefore, we interpreted this conclusion with caution. Neither study reported any thromboembolic events, haemorrhage, or death from the addition of vitamin K supplementation. Two included studies in this review compared whether the addition of a low dose (150 to 175 mcg) of vitamin K given to participants with a high-variability response to warfarin improved their INR control. One study demonstrated a significant improvement, while another smaller study (published in abstract only) suggested no overall benefit. Currently, there are insufficient data to suggest an overall benefit. Larger, higher quality trials are needed to examine if low-dose vitamin K improves INR control in those starting or already taking warfarin. Output:

In this review, our primary outcomes were to assess if the addition of low-dose vitamin K to warfarin had an effect on the time taken to the first INR in range; the mean within the therapeutic range; or any adverse events, such as thromboembolic events, haemorrhage, or mortality. We found two studies that met our inclusion criteria. Neither study reported the time taken to the first INR in range. One study was only available in an abbreviated format, so we were unable to interpret the results fully. Nonetheless, it was suggested that the addition of vitamin K had no benefit. A second six-month study gave a small dose of vitamin K (150 mcg daily) or placebo to participants taking warfarin with existing poor INR control. This study reported the mean time in therapeutic range as a percentage and found that in the group of participants deemed to have poor INR control, the addition of 150 mcg oral vitamin K significantly improved their anticoagulation control. However, the study was relatively small. Neither study reported any adverse events, such as thromboembolism, haemorrhage, or death. We conclude that further larger, higher quality studies are needed to conclude whether adding vitamin K to warfarin for patients starting or already on warfarin improves their anticoagulation control.

CochranePLS3293

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 26 trials with 2435 randomised participants aged between 2 and 16 years. Studies were carried out between 2002 and 2019 in dental clinics in the UK, USA, the Netherlands, Iran, India, France, Egypt, Saudi Arabia, Syria, Mexico, and Korea. Studies included equipment interventions (using several LA delivery devices for injection or audiovisual aids used immediately prior to or during LA delivery or both) and dentist interventions (psychological behaviour interventions delivered in advance of LA (video modelling), or immediately prior to or during delivery of LA or both (hypnosis, counter-stimulation). We judged one study to be at low risk and the rest at high risk of bias. Clinical heterogeneity of the included studies rendered it impossible to pool data into meta-analyses. None of the studies reported on our primary outcome of acceptance of LA. No studies reported on the following secondary outcomes: completion of dental treatment, successful LA/painless treatment, patient satisfaction, parent satisfaction, and adverse events. Audiovisual distraction compared to conventional treatment: the evidence was uncertain for the outcome pain-related behaviour during delivery of LA with a reduction in negative behaviour when 3D video glasses where used in the audiovisual distraction group (risk ratio (RR) 0.13, 95% confidence interval (CI) 0.03 to 0.50; 1 trial, 60 participants; very low-certainty evidence). The wand versus conventional treatment: the evidence was uncertain regarding the effect of the wand on pain-related behaviour during delivery of LA. Four studies reported a benefit in using the wand while the remaining studies results suggested no difference between the two methods of delivering LA (six trials, 704 participants; very low-certainty evidence). Counter-stimulation/distraction versus conventional treatment: the evidence was uncertain for the outcome pain experience during delivery of LA with children experiencing less pain when counter-stimulation was used (RR 0.12, 95% CI 0.04 to 0.34; 1 trial, 134 participants; very low-certainty evidence). Hypnosis versus conventional treatment: the evidence was uncertain for the outcome pain experience during delivery of LA with participants in the hypnosis group experiencing less pain (mean difference (MD) -1.79, 95% CI -3.01 to -0.57; 1 trial, 29 participants; very low-certainty evidence). Other comparisons considered included pre-cooling of the injection site, the wand versus Sleeper One, the use of a camouflage syringe, use of an electrical counter-stimulation device, and video modelling acclimatisation, and had a single study each. The findings from these other comparisons were insufficient to draw any affirmative conclusions about their effectiveness, and were considered to be very low-certainty evidence. We did not find sufficient evidence to draw firm conclusions as to the best interventions to increase acceptance of LA in children due to variation in methodology and nature/timing of outcome measures. We recommend further parallel RCTs, reported in line with the CONSORT Statement. Care should be taken when choosing outcome measures. Output:

This review is up-to-date as of 24 May 2019. We included 26 studies with a total of 2435 children aged between 2 and 16 years. The studies were carried out between 2002 and 2019 in dental clinics in the UK, USA, the Netherlands, Iran, India, France, Egypt, Saudi Arabia, Syria, Mexico, and Korea. We included studies comparing the use of different equipment like audiovisual glasses or a computerised device for injection called the wand, or dentist interventions like hypnosis, counter-stimulation/distraction, video modelling, to increase the acceptance of delivery of local anaesthetic. These interventions were compared against delivery of local anaesthetic using a conventional syringe (usual care), or any other dental equipment or dentist intervention. Interventions were given just before the injection and others were given just before, during the injection, and continued during the dental treatment. The evidence was uncertain for audiovisual distraction (using 3D video glasses as distraction) compared to conventional treatment. The evidence was uncertain when comparing the wand to conventional treatment. The evidence was also uncertain for counter-stimulation/distraction compared to conventional treatment and for hypnosis compared to conventional treatment. Other comparisons considered included pre-cooling of the injection site, the wand versus another electronic system called Sleeper One, the use of a camouflage syringe, use of an electrical counter-stimulation device, and video modelling. They had a single study each. The findings from these other comparisons were not enough to be able to decide on their effectiveness. The included studies did not mention if there were any harmful effects of the different interventions. The level of belief we have in these findings is very low. This was due to high risk of bias and the small number of people studied in the included trials. We do not have enough evidence to say which intervention works better to increase acceptance of local anaesthetic in children and adolescents. We suggest that more well-conducted studies should be done in this area.

CochranePLS3294

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We identified 14 studies (16 reports) that met inclusion criteria for this review and involved 3077 randomised participants in total. Most of these studies included a mixed sample of participants; we obtained data for the subset of interest for this review (diagnosis of incurable cancer and receiving cancer treatment) from the study investigators of 12 studies, for which we included 535 participants in the subset meta-analysis for fatigue post intervention. Researchers investigated a broad range of psychosocial interventions with different intervention aims and durations. We identified sources of potential bias, including lack of description of methods of blinding and allocation concealment and inclusion of small study populations. Findings from our meta-analysis do not support the effectiveness of psychosocial interventions for reducing fatigue post intervention (standardised mean difference (SMD) -0.25, 95% confidence interval (CI) -0.50 to 0.00; not significant; 535 participants, 12 studies; very low-quality evidence). First follow-up findings on fatigue suggested benefit for participants assigned to the psychosocial intervention compared with control (SMD -0.66, 95% CI -1.00 to -0.32; 147 participants, four studies; very low-quality evidence), which was not sustained at second follow-up (SMD -0.41, 95% CI -1.12 to 0.30; not significant; very low-quality evidence). Results for our secondary outcomes revealed very low-quality evidence for the efficacy of psychosocial interventions in improving physical functioning post intervention (SMD 0.32, 95% CI 0.01 to 0.63; 307 participants, seven studies). These findings were not sustained at first follow-up (SMD 0.37, 95% CI -0.20 to 0.94; not significant; 122 participants, two studies; very low-quality evidence). Findings do not support the effectiveness of psychosocial interventions for improving social functioning (mean difference (MD) 4.16, 95% CI -11.20 to 19.53; not significant; 141 participants, four studies), role functioning (MD 3.49, 95% CI -12.78 to 19.76; not significant; 143 participants, four studies), emotional functioning (SMD -0.11, 95% CI -0.56 to 0.35; not significant; 115 participants, three studies), or cognitive functioning (MD -2.23, 95% CI -12.52 to 8.06; not significant; 86 participants, two studies) post intervention. Only three studies evaluated adverse events. These studies found no difference between the number of adverse events among participants in the intervention versus control group. Using GRADE, we considered the overall quality of evidence for our primary and secondary outcomes to be very low. Therefore, we have very little confidence in the effect estimate, and the true effect is likely to be substantially different from the estimate of effect. Limitations in study quality and imprecision due to sparse data resulted in downgrading of the quality of data. Additionally, most studies were at high risk of bias owing to their small sample size for the subset of patients with incurable cancer (fewer than 50 participants per arm), leading to uncertainty about effect estimates. We found little evidence around the benefits of psychosocial interventions provided to reduce fatigue in adult patients with incurable cancer receiving cancer treatment with palliative intent. Additional studies with larger samples are required to assess whether psychosocial interventions are beneficial for addressing fatigue in patients with incurable cancer. Output:

In November 2016, we searched for clinical trials looking at psychological therapies in patients with incurable cancer receiving cancer treatment. We found 14 small studies of very low quality reporting data on tiredness outcomes, 12 of which provided data for analyses. A limited number (three studies) reported results about side effects; these studies investigated a psychological therapy combined with medication. Review authors found no support for the effectiveness of psychological therapies in reducing tiredness when assessed directly following the intervention. Very low-quality evidence suggests that psychological therapies may improve physical functioning directly after the intervention and may improve tiredness at first follow-up. Evidence shows no support for the effectiveness of psychosocial therapies in improving other domains of functioning. Limited evaluation of potential harm suggests no differences in side effects between patients receiving psychological therapy and those given usual care. Limited good quality evidence allows no conclusions on the use of psychological therapies in people with incurable cancer. Larger, high-quality trials are needed to find out whether psychological therapies help reduce tiredness for people with incurable cancer during cancer treatment. We rated the quality of study evidence using four levels: very low, low, moderate, and high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. Included studies had design problems and included a very small number of participants. Therefore, the quality of the evidence in this review is very low, and results of this review should be interpreted with caution.

CochranePLS3295

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 22 studies (total of 2761 participants). Of those 22 studies, 12 were included in the original published review and 10 were newly identified. Eleven trials compared the use of fluconazole to placebo or no antifungal treatment. Three trials compared ketoconazole versus placebo. One trial compared anidulafungin with placebo. One trial compared caspofungin to placebo. Two trials compared micafungin to placebo. One trial compared amphotericin B to placebo. Two trials compared nystatin to placebo and one trial compared the effect of clotrimazole, ketoconazole, nystatin and no treatment. We found two new ongoing studies and four new studies awaiting classification. The RCTs included participants of both genders with wide age range, severity of critical illness and clinical characteristics. Funding sources from pharmaceutical companies were reported in 11 trials and one trial reported funding from a government agency. Most of the studies had an overall unclear risk of bias for key domains of this review (random sequence generation, allocation concealment, incomplete outcome data). Two studies had a high risk of bias for key domains. Regarding the other domains (blinding of participants and personnel, outcome assessment, selective reporting, other bias), most of the studies had a low or unclear risk but four studies had a high risk of bias. There was moderate grade evidence that untargeted antifungal treatment did not significantly reduce or increase total (all-cause) mortality (RR 0.93, 95% CI 0.79 to 1.09, P value = 0.36; participants = 2374; studies = 19). With regard to the outcome of proven invasive fungal infection, there was low grade evidence that untargeted antifungal treatment significantly reduced the risk (RR 0.57, 95% CI 0.39 to 0.83, P value = 0.0001; participants = 2024; studies = 17). The risk of fungal colonization was significantly reduced (RR 0.71, 95% CI 0.52 to 0.97, P value = 0.03; participants = 1030; studies = 12) but the quality of evidence was low. There was no difference in the risk of developing superficial fungal infection (RR 0.69, 95% CI 0.37 to 1.29, P value = 0.24; participants = 662; studies = 5; low grade of evidence) or in adverse events requiring cessation of treatment between the untargeted treatment group and the other group (RR 0.89, 95% CI 0.62 to 1.27, P value = 0.51; participants = 1691; studies = 11; low quality of evidence). The quality of evidence for the outcome of total (all-cause) mortality was moderate due to limitations in study design. The quality of evidence for the outcome of invasive fungal infection, superficial fungal infection, fungal colonization and adverse events requiring cessation of therapy was low due to limitations in study design, non-optimal total population size, risk of publication bias, and heterogeneity across studies. There is moderate quality evidence that the use of untargeted antifungal treatment is not associated with a significant reduction in total (all-cause) mortality among critically ill, non-neutropenic adults and children compared to no antifungal treatment or placebo. The untargeted antifungal treatment may be associated with a reduction of invasive fungal infections but the quality of evidence is low, and both the heterogeneity and risk of publication bias is high. Further high-quality RCTs are needed to improve the strength of the evidence, especially for more recent and less studied drugs (e.g. echinocandins). Future trials should adopt standardized definitions for microbiological outcomes (e.g. invasive fungal infection, colonization) to reduce heterogeneity. Emergence of resistance to antifungal drugs should be considered as outcome in studies investigating the effects of untargeted antifungal treatment to balance risks and benefit. Output:

We included 22 randomized controlled trials (RCTs) (total of 2761 participants). Eleven trials compared the use of fluconazole to placebo or no antifungal treatment. Three trials compared ketoconazole versus placebo. One trial compared anidulafungin with placebo. One trial compared caspofungin to placebo. Two trials compared micafungin to placebo. One trial compared amphotericin B to placebo. Two trials compared nystatin to placebo and one trial compared the effect of clotrimazole, ketoconazole, nystatin and no treatment. The RCTs included participants of both genders with a wide age range and severity of critical illness. The evidence is current as of February 2015. Funding sources from drug manufacturers were reported in 11 out of 22 studies. Another study was funded by a government agency. Results of 19 from 22 randomized trials involved 2374 participants and showed that antifungal medications given before definitive diagnosis of fungal infection did not reduce mortality from all causes. None of the studied drugs were associated with a significant reduction of mortality from all causes. However, results from 17 randomized studies involving 2024 participants showed that antifungal drugs significantly reduced the risk of developing invasive fungal infections. We also reviewed the evidence from five trials (662 participants) about the effect of antifungal treatment on the development of superficial fungal infections but we did not find any significant difference. However, we found evidence from 12 trials (1020 participants) of a significant reduction of fungi in body sites (excluding blood) not causing an infection. Eleven trials (1691 participants) reported serious adverse events requiring cessation of therapy. We found no evidence of differences in serious adverse events requiring interruption of antifungal medications between people who received and those who did not receive them. The quality of evidence for the outcome of mortality (all-cause) was moderate due to limitations in study design. The quality of evidence for the outcome of invasive fungal infection, superficial fungal infection, fungal colonization and adverse events requiring cessation of therapy was low due to limitations in study design, non-optimal total number of patients studied and results inconsistent across studies. There is moderate quality evidence that the use of antifungal treatment given before definitive diagnosis of fungal infection is not associated with a significant reduction in mortality from all causes among critically ill adults and children with a normal number of neutrophils in the blood. This type of antifungal treatment may be associated with a reduction of invasive fungal infections but the quality of evidence on this point is low. Further studies with high-quality design are needed to improve the evidence.

CochranePLS3296

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Six RCTs with 1162 participants were included: three trials compared 2 g of preoperative amoxicillin versus placebo (927 participants), one compared 3 g of preoperative amoxicillin versus placebo (55 participants), one compared 1 g of preoperative amoxicillin plus 500 mg four times a day for two days versus no antibiotics (80 participants), and one compared four groups: (1) 2 g of preoperative amoxicillin; (2) 2 g of preoperative amoxicillin plus 1 g twice a day for seven days; (3) 1 g of postoperative amoxicillin twice a day for seven days, and (4) no antibiotics (100 participants). The overall body of evidence was considered to be of moderate quality. The meta-analyses of the six trials showed a statistically significant higher number of participants experiencing implant failures in the group not receiving antibiotics (RR 0.33; 95% CI 0.16 to 0.67, P value 0.002, heterogeneity: Tau2 0.00; Chi2 2.87, df = 5 (P value 0.57); I2 0%). The number needed to treat for one additional beneficial outcome (NNTB) to prevent one person having an implant failure is 25 (95% CI 14 to 100), based on an implant failure rate of 6% in participants not receiving antibiotics. There was borderline statistical significance for prosthesis failures (RR 0.44; 95% CI 0.19 to 1.00), with no statistically significant differences for infections (RR 0.69; 95% CI 0.36 to 1.35), or adverse events (RR 1; 95% CI 0.06 to 15.85) (only two minor adverse events were recorded, one in the placebo group). No conclusive information can be derived from the only trial that compared three different durations of antibiotic prophylaxis since no event (implant/prosthesis failures, infections or adverse events) occurred in any of the 25 participants included in each study group. There were no trials that evaluated different antibiotics or different antibiotic dosages. Scientific evidence suggests that, in general, antibiotics are beneficial for reducing failure of dental implants placed in ordinary conditions. Specifically 2 g or 3 g of amoxicillin given orally, as a single administration, one hour preoperatively significantly reduces failure of dental implants. No significant adverse events were reported. It might be sensible to suggest the use of a single dose of 2 g prophylactic amoxicillin prior to dental implant placement. It is still unknown whether postoperative antibiotics are beneficial, and which antibiotic is the most effective. Output:

The evidence on which this review is based was up to date as of 17 June 2013. Six trials were included with a total of 1162 participants. All six of these trials compared the use of antibiotics to prevent infection (failures and complications) with no treatment or treatment with a placebo (a fake medicine with no active ingredient). The antibiotic used in all the trials was amoxicillin; doses and timing of doses varied, although most used a single dose taken just before the implant was placed. One of the trials, with 100 participants, also looked at different doses of amoxicillin taken at different times. There were no trials that looked at alternative antibiotics. Participants were people over 18 years of age who were able to give consent to taking part in a medical trial. Potential participants were excluded for a variety of reasons that included: if they were at risk of heart disease, had artificial joints, had problems with their immune system, were affected by diabetes, had received radiotherapy in the head and neck area, had need of additional procedures at the time of implant placement, were allergic to penicillin, had chronic/acute infections near the planned implant site, were already receiving antibiotic treatment for any other reasons (or had taken them up to six months previously), had been treated with or were receiving intravenous amino-bisphosphonates, were pregnant or breast feeding, were receiving long-term nonsteroidal anti-inflammatory drug therapy, or had blood clotting problems. The follow-up period in all the trials was at least three months. It appears that the oral administration of two grams of amoxicillin one hour before placement of dental implants is effective in reducing implant failures. More specifically, giving antibiotics to 25 people will avoid one person experiencing early implant losses. It is still unclear whether postoperative antibiotics are beneficial, or which antibiotics work best. The evidence from the six trials (1162 participants) that compared the use of antibiotics with placebo or no treatment was considered to be of moderate quality. However, the one trial (100 participants) that investigated antibiotics given for different lengths of time was found to be at high risk of bias.

CochranePLS3297

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included eight studies, with a total of 1308 women randomised. The pooled data from these studies show a statistically significant and clinically meaningful reduction in non-cephalic presentation at birth (average risk ratio (RR) 0.42, 95% confidence interval (CI) 0.29 to 0.61, eight trials, 1305 women); vaginal cephalic birth not achieved (average RR 0.46, 95% CI 0.33 to 0.62, seven trials, 1253 women, evidence graded very low); and caesarean section (average RR 0.57, 95% CI 0.40 to 0.82, eight trials, 1305 women, evidence graded very low) when ECV was attempted in comparison to no ECV attempted. There were no significant differences in the incidence of Apgar score ratings below seven at one minute (average RR 0.67, 95% CI 0.32 to 1.37, three trials, 168 infants) or five minutes (RR 0.63, 95% CI 0.29 to 1.36, five trials, 428 infants, evidence graded very low), low umbilical vein pH levels (RR 0.65, 95% CI 0.17 to 2.44, one trial, 52 infants, evidence graded very low), neonatal admission (RR 0.80, 95% CI 0.48 to 1.34, four trials, 368 infants, evidence graded very low), perinatal death (RR 0.39, 95% CI 0.09 to 1.64, eight trials, 1305 infants, evidence graded low), nor time from enrolment to delivery (mean difference -0.25 days, 95% CI -2.81 to 2.31, two trials, 256 women). All of the trials included in this review had design limitations, and the level of evidence was graded low or very low. No studies attempted to blind the intervention, and the process of random allocation was suboptimal in several studies. Three of the eight trials had serious design limitations, however excluding these studies in a sensitivity analysis for outcomes with substantial heterogeneity did not alter the results. Attempting cephalic version at term reduces the chance of non-cephalic presentation at birth, vaginal cephalic birth not achieved and caesarean section. There is not enough evidence from randomised trials to assess complications of ECV at term. Large observational studies suggest that complications are rare. A visual summary of some of the results from this review can be found here. Output:

We found 8 studies involving 1308 women. (We included studies up to 28 February 2015.) All the studies were randomised and involved women with low-risk pregnancies. Using ECV around 36 weeks or more increased the chance that babies were born head-first and reduced the risk of having a caesarean section. There were no clear differences in other outcomes such as the risk of babies dying. The quality of the studies and therefore the strength of the evidence was varied. If an unborn baby is lying bottom-down, turning it by ECV just before birth can reduce some of the problems this position can cause. These studies are too small to show if ECV is safe to use in women with low-risk pregnancies, however other types of studies suggest that it is safe. We also do not know if it should be used in high-risk cases, such as mothers who have already had a caesarean section, or who are expecting twins. A visual summary of some of the results from this review can be found here.

CochranePLS3298

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 11 trials with a total of 828 oncology patients (adults and children). We assessed most included studies to be at a low or unclear risk of bias. Five trials compared the use of antibiotics (vancomycin, teicoplanin or ceftazidime) given before the insertion of the long-term CVC with no antibiotics, and six trials compared antibiotics (vancomycin, amikacin or taurolidine) and heparin with a heparin-only solution for flushing or locking the long-term CVC after use. Administering an antibiotic prior to insertion of the CVC did not significantly reduce Gram positive catheter-related sepsis (CRS) (five trials, 360 adults; risk ratio (RR) 0.72, 95% confidence interval (CI) 0.33 to 1.58; I² = 5 2%; P = 0.41). Flushing and locking long-term CVCs with a combined antibiotic and heparin solution significantly reduced the risk of Gram positive catheter-related sepsis compared with a heparin-only solution (468 participants, mostly children; RR 0.47, 95% CI 0.28 to 0.80; I² = 0%; P = 0.005). For a baseline infection rate of 15%, this reduction translated into a number needed to treat (NNT) of 12 (95% CI 9 to 33) to prevent one catheter-related infection. We considered this evidence to be of a moderate quality. There was no benefit to administering antibiotics before the insertion of long-term CVCs to prevent Gram positive catheter-related infections. Flushing or locking long-term CVCs with a combined antibiotic and heparin solution appeared to reduce Gram positive catheter-related sepsis experienced in people at risk of neutropenia through chemotherapy or disease. Due to insufficient data it was not clear whether this applied equally to TCVCs and totally implanted devices (TIDs), or equally to adults and children. The use of a combined antibiotic and heparin solution may increase microbial antibiotic resistance, therefore it should be reserved for high risk people or where baseline CVC infection rates are high (> 15%). Further research is needed to identify high risk groups most likely to benefit. Output:

We searched the literature from 1966 to 2013 for relevant studies (randomised controlled trials only). We included five studies (involving 360 children and adults) that compared antibiotics given before the insertion of the CVC with no antibiotics before insertion. We found that giving an antibiotic before inserting a tunnelled CVC did not prevent Gram positive catheter-related infections. We included six studies (involving 468 people, mainly children) that tested flushing or locking the newly inserted CVC with a combination of an antibiotic and heparin compared with heparin only. We found that flushing the catheter with a solution containing an antibiotic and heparin reduced the number of catheter-related infections. This practice is most likely to be of value where the risk of such infections is high. We considered this evidence to be of a moderate quality.

CochranePLS3299

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included six studies (375 participants) in this review; these compared alginate dressings with basic wound contact dressings, foam dressings and a silver-containing, fibrous-hydrocolloid dressing. Meta analysis of two studies found no statistically significant difference between alginate dressings and basic wound contact dressings: risk ratio (RR) 1.09 (95% CI 0.66 to 1.80). Pooled data from two studies comparing alginate dressings with foam dressings found no statistically significant difference in ulcer healing (RR 0.67, 95% CI 0.41 to 1.08). There was no statistically significant difference in the number of diabetic foot ulcers healed when an anti-microbial (silver) hydrocolloid dressing was compared with a standard alginate dressing (RR 1.40, 95% CI 0.79 to 2.47). All studies had short follow-up times (six to 12 weeks), and small sample sizes. Currently there is no research evidence to suggest that alginate wound dressings are more effective in healing foot ulcers in people with diabetes than other types of dressing however many trials in this field are very small. Decision makers may wish to consider aspects such as dressing cost and the wound management properties offered by each dressing type e.g. exudate management. Output:

This review (six studies involving a total of 375 participants) identified no research evidence to suggest that alginate wound dressings are more effective in healing diabetic foot ulcers than other types of dressing. More, better quality research is needed.