GEM/cochrane-simplification huggingface dataset:
Abstract: A total of 43 randomised controlled trials (4,364 participants) were included in this review. Very few trials provided data suitable for inclusion in a meta-analysis. Among the five trials that yielded data assessing the daily frequency of hot flushes suitable for pooling, no significant difference overall was noted in the incidence of hot flushes between participants taking Promensil (a red clover extract) and those given placebo (mean difference (MD) -0.93, 95% confidence interval (CI) -1.95 to 0.10, I2 = 31%). No evidence indicated a difference in percentage reduction in hot flushes in two trials between Promensil and placebo (MD 20.15, 95% CI -12.08 to 52.38, I2 = 82%). Four trials that were not combined in meta-analyses suggested that extracts with high (> 30 mg/d) levels of genistein consistently reduced the frequency of hot flushes. Individual results from the remaining trials were compared in broad subgroups such as dietary soy, soy extracts and other types of phytoestrogens that could not be combined. Some of these trials found that phytoestrogen treatments alleviated the frequency and severity of hot flushes and night sweats when compared with placebo, but many trials were small and were determined to be at high risk of bias. A strong placebo effect was noted in most trials, with a reduction in frequency ranging from 1% to 59% with placebo. No indication suggested that discrepant results were due to the amount of isoflavone in the active treatment arm, the severity of vasomotor symptoms or trial quality factors. Also, no evidence indicated that these treatments caused oestrogenic stimulation of the endometrium or the vagina or other adverse effects when used for up to two years. No conclusive evidence shows that phytoestrogen supplements effectively reduce the frequency or severity of hot flushes and night sweats in perimenopausal or postmenopausal women, although benefits derived from concentrates of genistein should be further investigated.

Plain-language summary: This review found 43 RCTs conducted up to July 2013 that included 4,084 participants with hot flushes who were close to the menopause or were menopausal. Evidence obtained is current to July 2013. Some trials reported a slight reduction in hot flushes and night sweats with phytoestrogen-based treatment. Extracts containing high levels of genistein (a substance derived from soy) appeared to reduce the number of daily hot flushes and need to be investigated further. Overall no indication suggested that other types of phytoestrogens work any better than no treatment. No evidence was found of harmful effects on the lining of the womb, stimulation of the vagina or other adverse effects with short-term use. Many of the trials in this review were small, of short duration and of poor quality, and the types of phytoestrogens used varied substantially.
Abstract: Ten randomised controlled trials were available for analysis. The quality of included studies was adequate, though in some trials the numbers were small and they were inadequately powered for equivalence or to detect significant differences. Comparisons were made between various modalities of treatments. There were no significant difference in recurrence rates or incontinence rates in any of the studied comparisons except in the case of advancement flaps. There were more recurrences in the glue plus flap group, a significant difference that favoured the flap only technique. It was also noted that Fibrin glue and advancement flap procedures report low incontinence rates.In the review of literature of non-randomised trials, most trials on fibrin glue indicate good healing in simple fistulae with low incontinence rates. There are very few randomized controlled trials comparing the various modalities of surgery for fistula in ano. While post operative pain, time to healing and discharge from hospital affect quality of life, recurrence and incontinence are the most important. As it turns out, there seems to be no major difference between the various techniques used as far as recurrence rates are concerned. The use of Fibrin glue and advancement flaps are associated with low incontinence rates. There is a crying need for well powered, well conducted randomised controlled trials comparing various modes of treatment of fistula in ano. Newer operations like the anal fistula plug and the LIFT procedure need to be evaluated by randomised clinical trials.

Plain-language summary: The reviewers identified 10 trials that compare various fistula treatments against one another. There are various parameters that these procedures can be compared on, but we looked at the two most important ones, recurrence (the numbers who got the disease again) and incontinence (a worsening in the ability to control rectal content). In the trials that were compared, there was no significant difference between the various comparisons for the disease to recur. However the trials on fibrin glue, as well as data from non randomised trials show that incontinence is less, probably as there is no surgical disruption of the anal muscle. There is a paucity of good quality data that compares various types of operative treatment for anorectal fistula and there is scope for further trials in the area.
Abstract: A total of 24 studies met our inclusion criteria. Seventeen studies provided data for the primary analysis: six studies (434 children) included data on procalcitonin, 13 studies (1638 children) included data on CRP, and six studies (1737 children) included data on ESR (some studies had data on more than one test). The summary sensitivity estimates (95% CI) for the procalcitonin, CRP, ESR tests at the aforementioned cutoffs were 0.86 (0.72 to 0.93), 0.94 (0.85 to 0.97), and 0.87 (0.77 to 0.93), respectively. The summary specificity values for procalcitonin, CRP, and ESR tests at these cutoffs were 0.74 (0.55 to 0.87), 0.39 (0.23 to 0.58), and 0.48 (0.33 to 0.64), respectively. The ESR test does not appear to be sufficiently accurate to be helpful in differentiating children with cystitis from children with pyelonephritis. A low CRP value (< 20 mg/L) appears to be somewhat useful in ruling out pyelonephritis (decreasing the probability of pyelonephritis to < 20%), but unexplained heterogeneity in the data prevents us from making recommendations at this time. The procalcitonin test seems better suited for ruling in pyelonephritis, but the limited number of studies and the marked heterogeneity between studies prevents us from reaching definitive conclusions. Thus, at present, we do not find any compelling evidence to recommend the routine use of any of these tests in clinical practice.

Plain-language summary: We found 24 relevant studies of which 17 provided data for our primary outcome. Six studies (434 children) provided data for the procalcitonin test; 13 studies (1638 children) provided data for the C-reactive protein test, and six studies (1737 children) provided data for the erythrocyte sedimentation rate test. We found all three tests to be sensitive (summary sensitivity values ranged from 86% to 95%), but not very specific (summary specificity values ranged from 38% to 71%). None of the tests were accurate enough to allow clinicians to confidently differentiate upper from lower urinary tract disease.
Abstract: Twelve double-blind RCTs (n=700) met the inclusion criteria. The meta-analysis was done on seven studies using the total score on the Hamilton Anxiety (HAM-A) scale as a common outcome measure. The result suggests a significant effect towards a reduction of the HAM-A total score in patients receiving kava extract compared with patients receiving placebo (weighted mean difference: 3.9, 95% confidence interval: 0.1 to 7.7; p = 0.05; n = 380). The results of the five studies that were not submitted to meta-analysis largely support these findings. Adverse events as reported in the reviewed trials were mild, transient and infrequent. Compared with placebo, kava extract is an effective symptomatic treatment for anxiety although, at present, the size of the effect seems small. The effect lacks robustness and is based on a relatively small sample. The data available from the reviewed studies suggest that kava is relatively safe for short-term treatment (1 to 24 weeks), although more information is required. Rigorous trials with large sample sizes are needed to clarify the existing uncertainties. Also, long-term safety studies of kava are required.

Plain-language summary: Twelve trials met the inclusion criteria. The meta-analysis of seven trials suggests a significant treatment effect for the total score on the Hamilton Anxiety Scale in favour of kava extract. Few adverse events were reported in the reviewed trials, which were all mild, transient and infrequent. These data imply that, compared with placebo, kava extract might be an effective symptomatic treatment for anxiety although, at present, the size of the effect seems to be small. Rigorous trials with large sample sizes are needed to clarify the existing uncertainties. Particularly long-term safety studies of kava are needed.
Abstract: We included 12 controlled trials that recruited 982 infants. There was heterogeneity between trials for the outcome IVH, with three trials finding a significant decrease in IVH and one trial finding an increase in IVH in the group receiving phenobarbital. Meta-analysis showed no difference between the phenobarbital-treated group and the control group in either all IVH (typical risk ratio (RR) 0.91; 95% CI 0.77 to 1.08), severe IVH (typical RR 0.77; 95% CI 0.58 to 1.04), posthaemorrhagic ventricular dilation (typical RR 0.89; 95% CI 0.38 to 2.08), severe neurodevelopmental impairment (typical RR 1.44; 95% CI 0.41 to 5.04) or death before hospital discharge (typical RR 0.88; 95% CI 0.64 to 1.21). There was a consistent trend in the trials towards increased use of mechanical ventilation in the phenobarbital-treated group, which was supported by the meta-analysis (typical RR 1.18; 95% CI 1.06 to 1.32; typical risk difference 0.129; 95% CI 0.04 to 0.21), but there was no significant difference in pneumothorax, acidosis or hypercapnia. Postnatal administration of phenobarbital cannot be recommended as prophylaxis to prevent IVH in preterm infants and is associated with an increased need for mechanical ventilation.

Plain-language summary: The review of trials found that there was not enough evidence that postnatal phenobarbital is effective in preventing IVH. Furthermore, phenobarbital suppresses breathing in infants who are breathing spontaneously, causing a need for mechanical ventilation.
Abstract: Eighteen trials (reporting 20 study comparisons) met the review entry criteria. We report findings from 18 group comparisons where data were available (6343 participants, of whom 1692 were children). Ciclesonide versus placebo: The short duration of the included studies means that there is a lack of data with respect to the impact of ciclesonide on asthma exacerbations. At doses of 100 mcg/d or less up to 400 mcg/d in mild to moderate asthma, ciclesonide improved lung function, asthma symptoms and rescue inhaler use, compared with placebo. Dose response outcomes: Comparisons of 100 versus 200 mcg/d, 100 versus 400 mcg/d and 400 versus 800 mcg/d did not yield significant differences in lung function outcomes.  Adverse event data were not available in sufficient detail to permit assessment of the safety profile of this drug. Ciclesonide was more effective than placebo, in the short term, in improving lung function in patients with mild to moderate asthma previously treated with inhaled corticosteroids. There remain questions as to dose response, and the lack of data on the longer term impact on exacerbations and safety profile should be addressed in future studies.

Plain-language summary: The results from this review indicate that CIC at low to moderate doses improves lung function and reduces asthma symptoms compared to placebo, but the short duration of the studies means that there is a lack of information about the impact on asthma exacerbations. Thus the currently recommended doses of CIC of 100-200 mcg daily would seem appropriate. However, the number of studies in the higher dose range are low and further studies are therefore required in adults and children to determine whether higher CIC doses will give significant benefit without increasing adverse events. It will also be important to determine in clinical studies how CIC compares to the other currently available ICS in terms of efficacy and safety in asthmatic adults and children in order to determine the precise role of CIC therapy in asthma. The published data are insufficient to assess the reputed safety advantage of ciclesonide, and better assessment and reporting in studies is required to address this important question.
Abstract: Over 900 children were recruited for the secretin trials. Twenty-five established standardised outcome measures were reported to assess core features of ASD, communication, behaviour, visuospatial skills, affect and adverse events. One standardised measure of global impression was also used. No more than four studies used any one outcome measure similarly. When duration from the start of the intervention to outcome assessment was known, outcomes were reported at between three and six weeks. Meta-analysis of data was not possible but there is now consistency of findings, with RCTs of the efficacy of secretin in autism not showing improvements for core features of ASD. There is no evidence that single or multiple dose intravenous secretin is effective and as such currently it should not be recommended or administered as a treatment for ASD. Further experimental assessment of secretin's effectiveness for ASD can only be justified if there is new high-quality and replicated scientific evidence that either finds that secretin has a role in neurotransmission in a way that could benefit all children with ASD or identifies important subgroups of children with ASD who could benefit from secretin because of a proven link between the action of secretin and the known cause of their ASD, or the type of problems they are experiencing.

Plain-language summary: This review included 16 randomised trials with a placebo control group, with over 900 children involved. The review found no evidence that single or multiple dose intravenous secretin is effective in improving the main problems seen in ASD, namely a lack of social interaction and communication and restrictive, repetitive behaviours and routines. As such, currently it should not be recommended or administered as a treatment for ASD. Further experimental assessment of secretin's effectiveness for ASD can only be justified if there is convincing new evidence that finds that secretin can influence brain function in a way that could benefit children with ASD or a link is proven between secretin and the known cause of ASD for some or all children.
Abstract: Forty-four trials were included. The antibiotics assessed were cefepime, ceftazidime, piperacillin-tazobactam, imipenem and meropenem. Adequate allocation concealment and generation were reported in about half of the trials and only two trials were double-blinded. The risk for all-cause mortality was significantly higher with cefepime compared to other beta-lactams (RR 1.39, 95% CI 1.04 to 1.86, 21 trials, 3471 participants), without heterogeneity and with higher RRs in trials at low risk for bias. There were no differences in secondary outcomes but for a non-significantly higher rate of bacterial superinfections with cefepime. Mortality was significantly lower with piperacillin-tazobactam compared to other antibiotics (RR 0.56, 95% CI 0.34 to 0.92, 8 trials, 1314 participants), without heterogeneity. Carbapenems resulted in similar all-cause mortality and a lower rate of clinical failure and antibiotic modifications as compared to other antibiotics, but a higher rate of diarrhea caused by Clostridium difficile. Current evidence supports the use of piperacillin-tazobactam in locations where antibiotic resistance profiles do not mandate empirical use of carbapenems. Carbapenems result in a higher rate of antibiotic-associated and Clostridium difficile-associated diarrhea. There is a high level of evidence that all-cause mortality is higher with cefepime compared to other beta-lactams and it should not be used as monotherapy for patients with febrile neutropenia.

Plain-language summary: We identified 44 studies comparing different antibiotics. Cefepime resulted in significantly higher mortality compared to all other antibiotics combined, at the end of patients' hospital stay or 30 days after entry into the study. The risk was 39% higher with cefepime, ranging from 4 to 86% increased risk. We did not find an explanation for this when looking into other outcomes reported in the primary studies. Piperacillin-tazobactam resulted in lower mortality than other antibiotics. The other antibiotics (ceftazidime, imipenem and meropenem) showed comparable efficacy, with a lower rate of antibiotic changes for imipenem or meropenem and a higher rate of severe diarrhea with these two antibiotics. We conclude that piperacillin-tazobactam might be the preferred antibiotic for the treatment of cancer patients with fever and neutropenia and that cefepime should not be used. Antibiotic selection (other than cefepime) depends on the individual patient and the type of bacteria prevalent in the specific hospital.
Abstract: 1162 people from 13 studies were randomised to trifluoperazine or placebo. For global improvement, small short-term studies favoured trifluoperazine (n=95, 3 RCTs, RR 0.62 CI 0.49 to 0.78 NNT 3 CI 2 to 4). Loss to follow up was about 12% in both groups (n=280, 7 RCTs, RR 0.99 CI 0.62 to 1.57) and more people allocated trifluoperazine used antiparkinson drugs to alleviate movements disorders compared with placebo (n=195, 4 RCTs, RR 5.06 CI 2.49 to 10.27, NNH 4 CI 2 to 9). 2230 people from 49 studies were randomised to trifluoperazine or another older generation antipsychotic. Trifluoperazine was not clearly different in terms of 'no substantial improvement' (n=1016, 27 RCTs, RR 1.06 CI 0.98 to 1.14) or leaving the study early (n=930, 22 RCTs, RR 1.15 CI 0.83 to 1.58). Almost identical numbers of people reported at least one adverse event (˜60%) in each group (n=585, 14 RCTs, RR 0.99 CI 0.87 to 1.13), although trifluoperazine was more likely to cause extrapyramidal adverse effects overall when compared to low potency antipsychotics such as chlorpromazine (n=130, 3 RCTs, RR 1.66 CI 1.03 to 2.67, NNH 6 CI 3 to 121). One small study (n=38) found no clear differences between trifluoperazine and the atypical drug, sulpiride. Although there are shortcomings and gaps in the data, there appears to be enough consistency over different outcomes and periods to confirm that trifluoperazine is an antipsychotic of similar efficacy to other commonly used neuroleptics for people with schizophrenia. Its adverse events profile is similar to that of other drugs. It has been claimed that trifluoperazine is effective at low doses for patients with schizophrenia but this does not appear to be based on good quality trial based evidence.

Plain-language summary: Thousands of people with schizophrenia have participated in studies and therefore we are reasonably sure that it is a potent antipsychotic drug and as good as similar older drugs. Most people taking it do experience adverse effects, but this also applies to other older drugs. Not enough comparisons with newer generations of drugs have been undertaken to be sure of how trifluoperazine compares to them.
Abstract: We included 16 trials involving 4759 participants. Analysis did not show a significant overall difference for subjective health status (standardised mean difference (SMD) -0.03, 95% confidence interval (CI) -0.11 to 0.04, P = 0.34) or extended activities of daily living (SMD 0.04, 95% CI -0.03 to 0.11, P = 0.22). There was no overall significant effect for the outcome of carer subjective health status (SMD 0.04, 95% CI -0.05 to 0.14, P = 0.37). Patients with mild to moderate disability (Barthel 15 to 19) had a significant reduction in dependence (odds ratio (OR) 0.62, 95% CI 0.44 to 0.87, P = 0.006). This would equate to 10 fewer dependent patients (95% CI 17 fewer to 4 fewer) for every 100 patients seen by the stroke liaison worker. Similar results were seen for the outcome of death or dependence for the subgroup with Barthel 15 to 19 (OR 0.55, 95% CI 0.38 to 0.81, P = 0.002). This risk difference equates to 11 fewer dead or dependent patients (95% CI 17 fewer to 4 fewer) for every 100 patients seen by the stroke liaison worker. There is no evidence for the effectiveness of this multifaceted intervention in improving outcomes for all groups of patients or carers. Patients with mild to moderate disability benefit from a reduction in death and disability. Patients and carers do report improved satisfaction with some aspects of service provision.

Plain-language summary: In this review, we evaluated 16 studies (involving 4759 participants) of healthcare workers or volunteers (a 'stroke liaison worker') providing education and social support (including counselling) and liaison with services. Overall, there do not appear to be any significant benefits for patients in terms of their perceived health, mood, activities or participation. Patients appeared to be more satisfied that someone had really listened to them, and carers appeared to be more satisfied with aspects of the care provided. It also appears that patients with mild to moderate disability may benefit from a reduction in disability and death as a result of the input from the stroke liaison worker. The reason for this is not yet clear and further research is required.
Abstract: Four trials are now included in the review, with 753 participants. They were different in many ways including the intervention, duration, outcomes and control group so pooling of data was not possible. Overall, the quality of the evidence was rated as very low. Re-analysis of outcomes using data from the published studies found no significant effects of respite care compared to no respite care on any caregiver variable. When respite care was compared to polarity therapy a significant effect was found in favour of polarity therapy for caregiver perceived stress (n = 38, MD 5.80, 95% CI 1.43 to 10.17), but not for other measures of psychological health and other caregiver outcomes. No studies reported evaluable data on outcomes related to the people with dementia. Current evidence does not demonstrate any benefits or adverse effects from the use of respite care for people with dementia or their caregivers. These results should be treated with caution, however, as they may reflect the lack of high quality research in this area rather than an actual lack of benefit. Given the frequency with which respite care is advocated and provided, well-designed trials are needed in this area.

Plain-language summary: Four studies with 753 participants were included in this review. Three compared respite care to no respite care and one compared respite care to polarity therapy, a type of touch therapy. All studies included people with dementia and their caregivers. We were not able to pool the results of the studies as there were so few studies and they measured the outcomes in different ways. All the studies reported outcomes for the caregiver, but only one reported outcomes for the person with dementia. The three studies that compared respite care to no respite care found no evidence of any benefit of respite care for people with dementia or for their caregivers for any outcome, including rates of institutionalisation and caregiver burden. The study that compared respite care to polarity therapy found that polarity therapy decreased caregiver perceived stress but that there was no difference between polarity therapy and respite care for other measures of psychological health and other caregiver outcomes. A host of methodological problems were identified in the available trials. One study did not report data that could be analysed, the remaining three studies were very small and had a very short duration. Further methodologically sound research is needed before any firm conclusions can be drawn.