GEM/cochrane-simplification huggingface dataset:
Abstract: The review currently includes two short-term low-quality randomised trials (total n=508) both comparing sertindole with risperidone. One third of participants left the studies early (2 RCTs, n=504, RR 1.23 CI 0.94 to 1.60). There was no difference in efficacy (2 RCTs, n=493, WMD PANSS total change from baseline 1.98 CI -8.24 to 12.20). Compared with relatively high doses of risperidone (between 4 and 12 mg/day), sertindole produced significantly less akathisia and parkinsonism (1 RCT, n=321, RR 0.24 CI 0.09 to 0.69, NNT 14, CI 8 to 100). Sertindole produced more cardiac effects (2 RCTs, n=508, RR QTc prolongation 4.86 CI 1.94 to 12.18), weight change (2 RCTs, n=328, WMD 0.99 CI 0.12 to 1.86) and male sexual dysfunction (2 RCTs, n=437, RR 2.90 CI 1.32 to 6.35, NNH 13 CI 8 to 33). Sertindole may induce fewer movement disorders, but more cardiac effects, weight change and male sexual dysfunction than risperidone. However these data are based on only two studies and are too limited to allow firm conclusions. Nothing can be said about the effects of sertindole compared with second generation antipsychotics other than risperidone. There are several relevant trials underway or completed and about to report.

Plain-language summary: This review aims to compare sertindole to the other newer second generation (atypical) antipsychotics in people who have schizophrenia. Two studies were identified which included 508 people. Both compared sertindole to risperidone, were short (12 weeks) and the participants were either at least moderately ill or treatment resistant. There was no overall significant difference between these two medications in terms of improvement in people’s general well-being or their mental state. Also while people on risperidone showed more movement side-effects, those on sertindole were more likely to put on weight, have changes in their heart rhythm and the men were more likely to suffer from sexual dysfunction. The data from these trials are limited and a considerable number of the participants left the study early. In addition, sertindole has only been compared to one second generation antipsychotic and the trials are relatively short. A larger and longer trial comparing sertindole to other second generation antipsychotics, with the outcomes including mental state, general functioning, adverse effects and quality of life, would enhance our knowledge in this area considerably. (Plain language summary prepared for this review by Janey Antoniou of RETHINK, UK www.rethink.org).
Abstract: We included one study involving 15 participants from the UK. The included participants were diagnosed with delirium based on the Confusion Assessment Method (CAM) criteria. Eight males and seven females were included, with a mean age of 82.5 years. Seven of the 15 participants had comorbid dementia at baseline. The risk of bias was low in all domains. The study compared rivastigmine with placebo. We did not find any clear differences between the two groups in terms of duration of delirium (MD -3.6, 95% CI -15.6 to 8.4), adverse events (nausea, RR 0.30, 95% CI 0.01 to 6.29), use of rescue medications (RR 0.13, 95% CI 0.01 to 2.1), mortality (RR 0.10, 95% CI 0.01 to 1.56), and leaving the study early (RR 0.88, 95% CI 0.07 to 11.54). Evidence was not available regarding the severity of delirium, persistent cognitive impairment, length of hospitalisation, cost of intervention, or other predefined secondary outcomes. The quality of evidence is low due to the very small sample size. There is insufficient evidence to support or refute the use of cholinesterase inhibitors for the treatment of delirium in non-ICU settings. No clear benefits or harms associated with cholinesterase inhibitors were observed when compared with placebo due to the lack of data. More trials are required.

Plain-language summary: We found one trial from the UK, which included 15 participants with delirium. The average age of the participants was 82.5 years; eight participants were male and seven were female. Seven participants also had a history of dementia. This trial compared rivastigmine (a type of cholinesterase inhibitor used in the treatment of dementia) with an inactive treatment (placebo). The trial did not show any difference in effect between those participants given rivastigmine and those given placebo. The study was conducted and reported appropriately, but the small number of participants limits any conclusions that could be made about rivastigmine as a treatment for delirium.
Abstract: Four trials including a total of 1447 young offenders were included in the review. Results failed to find a significant effect for restorative justice conferencing over normal court procedures for any of the main analyses, including number re-arrested (odds ratio (OR) 1.00, 95% confidence interval (CI) 0.59 to 1.71; P = 0.99), monthly rate of reoffending (standardised mean difference (SMD) -0.06, 95% CI -0.28 to 0.16; P = 0.61), young person’s remorse following conference (OR 1.73, 95% CI 0.97 to 3.10; P = 0.06), young person's recognition of wrongdoing following conference (OR 1.97, 95% CI 0.81 to 4.80; P = 0.14), young person's self-perception following conference (OR 0.95, 95% CI 0.55 to 1.63; P = 0.85), young person's satisfaction following conference (OR 0.42, 95% CI 0.04 to 4.07; P = 0.45) and victim's satisfaction following conference (OR 4.05, 95% CI 0.56 to 29.04; P = 0.16). A small number of sensitivity analyses did indicate significant effects, although all are to be interpreted with caution. There is currently a lack of high quality evidence regarding the effectiveness of restorative justice conferencing for young offenders. Caution is urged in interpreting the results of this review considering the small number of included studies, subsequent low power and high risk of bias. The effects may potentially be more evident for victims than offenders. The need for further research in this area is highlighted.

Plain-language summary: The purpose of this review was to look at whether young people who are part of a restorative justice conference are less likely to reoffend than those who go through normal court proceedings. Four randomised controlled trials were included in this review. Findings indicate that there was no difference between those who are part of restorative justice conferences and those in normal court proceedings in terms of the rate of reoffending after the intervention. There was also no difference between these two groups in terms of a change in their self-esteem or their satisfaction with the process. Results may indicate that victims who are part of a restorative conference are more satisfied than those who are part of court proceedings. The quality of the included studies was low. More high quality research using a design where participants are randomly allocated to an intervention or control group is needed.
Abstract: We identified one RCT, with 18 participants, that fulfilled the predetermined inclusion criteria. The trial compared plasma exchange to sham plasma exchange in participants with IgG or IgA paraproteinaemic neuropathy over a three-week follow-up period. We identified four other studies but these were not RCTs or quasi-RCTs. The included RCT did not report our predefined primary outcome measure, change in disability six months after randomisation. The trial revealed a modest benefit of plasma exchange in the weakness component of the Neuropathy Disability Score (NDS, now the Neuropathy Impairment Score); the mean improvement with plasma exchange was 17 points (95% confidence interval (CI) 5.2 to 28.8 points) versus 1 point (95% CI -7.7 to 9.7 points) in the sham exchange group at three weeks' follow-up (mean difference (MD) 16.00; 95% CI 1.37 to 30.63, low quality evidence). There was no statistically significant difference in the overall NDS (MD 18.00; 95% CI -2.03 to 38.03, low quality evidence), vibration thresholds or neurophysiological indices. Adverse events were not reported. The trial was at low risk of bias overall, although limitations of trial size and duration reduce the quality of the evidence in support of its conclusions. The evidence from RCTs for the treatment of IgG or IgA paraproteinaemic neuropathy is currently inadequate. More RCTs of treatments are required. These should have adequate follow-up periods and contain larger numbers of participants, perhaps through multicentre collaboration, considering the relative infrequency of this condition. Observational or open trial data provide limited support for the use of treatments such as plasma exchange, cyclophosphamide combined with prednisolone, intravenous immunoglobulin, and corticosteroids. These interventions show potential therapeutic promise but the potential benefits must be weighed against adverse effects. Their optimal use and the long-term benefits need to be considered and validated with well-designed RCTs.

Plain-language summary: We identified only one randomised controlled trial (RCT), which compared plasma exchange with sham exchange, in 18 participants with either IgA or IgG paraproteinaemic neuropathy. The results were reported after three weeks of treatment. The trial did not report our primary outcome measure, which was improvement in disability measured by a validated scale six months after randomisation, or our other specified outcomes at six months. The trial demonstrated a modest benefit in improvement of weakness and overall disability as measured by the neuropathy disability score (NDS) over a period of three weeks. There was no improvement in this timescale in measures of sensory disturbance or electrical studies of the nerves. Adverse events were not reported. Further RCTs of this and other treatments with larger numbers of participants are needed. This is an update of a review first published in 2007. We found no additional trials for inclusion. The evidence is current to January 2014.
Abstract: The review includes 22 studies (8032 participants) comparing regular formoterol to placebo and salbutamol. Non-fatal serious adverse event data could be obtained for all participants from published studies comparing formoterol and placebo but only 80% of those comparing formoterol with salbutamol or terbutaline. Three deaths occurred on regular formoterol and none on placebo; this difference was not statistically significant. It was not possible to assess disease-specific mortality in view of the small number of deaths. Non-fatal serious adverse events were significantly increased when regular formoterol was compared with placebo (Peto odds ratio (OR) 1.57; 95% CI 1.06 to 2.31). One extra serious adverse event occurred over 16 weeks for every 149 people treated with regular formoterol (95% CI 66 to 1407 people). The increase was larger in children than in adults, but the impact of age was not statistically significant. Data submitted to the FDA indicate that the increase in asthma-related serious adverse events remained significant in patients taking regular formoterol who were also on inhaled corticosteroids. No significant increase in fatal or non-fatal serious adverse events was found when regular formoterol was compared with regular salbutamol or terbutaline. In comparison with placebo, we have found an increased risk of serious adverse events with regular formoterol, and this does not appear to be abolished in patients taking inhaled corticosteroids. The effect on serious adverse events of regular formoterol in children was greater than the effect in adults, but the difference between age groups was not significant. Data on all-cause serious adverse events should be more fully reported in journal articles, and not combined with all severities of adverse events or limited to those events that are thought by the investigator to be drug-related.

Plain-language summary: There was no statistically significant difference in the number of people who died during treatment with formoterol compared with placebo or salbutamol. Because so few people die of asthma, huge trials or observational studies are normally required to detect a difference in death rates from asthma. There were more non-fatal serious adverse events in people taking formoterol compared to those on placebo; for every 149 people treated with formoterol for 16 weeks, one extra non-fatal event occurred in comparison with placebo. There was no significant difference in serious adverse events in people on formoterol compared to regular salbutamol. We conclude that regular formoterol should not be taken by people who are not taking regular inhaled steroids due to the increased risk of serious adverse events. Formoterol should not be used as a substitute for inhaled corticosteroids, and adherence with inhaled steroids should be kept under review if separate inhalers are used when formoterol is added to inhaled corticosteroids.
Abstract: Cognitive training was not associated with positive or negative effects in relation to any reported outcomes. The overall quality of the trials was low to moderate. The single RCT of cognitive rehabilitation found promising results in relation to a number of participant and caregiver outcomes, and was generally of high quality. Available evidence regarding cognitive training remains limited, and the quality of the evidence needs to improve. However, there is still no indication of any significant benefit derived from cognitive training. Trial reports indicate that some gains resulting from intervention may not be captured adequately by available standardised outcome measures. The results of the single RCT of cognitive rehabilitation show promise but are preliminary in nature. Further, well-designed studies of cognitive training and cognitive rehabilitation are required to obtain more definitive evidence. Researchers should describe and classify their interventions appropriately using available terminology.

Plain-language summary: This review included 11 trials of cognitive training and a single trial of cognitive rehabilitation. We found no evidence for the efficacy of cognitive training in improving cognitive functioning, mood or activities of daily living in people with mild to moderate Alzheimer's disease or vascular dementia; however the quality of the studies was generally not high. The single trial of cognitive rehabilitation provided preliminary indications of the potential benefits of individual cognitive rehabilitation in improving activities of daily living in people with mild Alzheimer's disease. More high-quality trials of both cognitive training and cognitive rehabilitation are needed to establish their efficacy for people with early-stage dementia.
Abstract: One study with a total of 24 participants was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE receiving either propofol or thiopental sodium for the control of seizure activity. This study was terminated early due to recruitment problems. For our primary outcome of total control of seizures after the first course of study drug, there were 6/14 patients versus 2/7 patients in the propofol and thiopental sodium groups, respectively (risk ratio (RR) 1.50, 95% confidence interval (CI) 0.40 to 5.61, low quality evidence). Mortality was seen in 3/14 patients versus 1/7 patients in the propofol and thiopental sodium groups, respectively (RR 1.50, 95% CI 0.19 to 11.93, low quality evidence). Our third primary outcome of length of ICU stay was not reported. For our secondary outcomes of adverse events, infection was seen in 7/14 patients versus 5/7 patients in the propofol and thiopental sodium groups, respectively (RR 0.70; 95% CI 0.35 to 1.41). Hypotension during administration of study drugs and requiring use of vasopressors was seen in 7/14 patients versus 4/7 patients in the propofol and thiopental sodium groups, respectively (RR 0.87; 95% CI 0.38 to 2.00). The other severe complication noted was non-fatal propofol infusion syndrome in one patient. Patients receiving thiopental sodium required more days of mechanical ventilation when compared with patients receiving propofol: (median (range) 17 days (5 to 70 days) with thiopental sodium versus four days (2 to 28 days) with propofol). At three months there was no evidence of a difference between the drugs with respect to outcome measures such as control of seizure activity and functional outcome. Since the last version of this review we have found no new studies. There is a lack of robust, randomised, controlled evidence to clarify the efficacy of propofol and thiopental sodium compared to each other in the treatment of RSE. There is a need for large RCTs for this serious condition.

Plain-language summary: The evidence is current to August 2016. We could only identify one trial, which was terminated early due to recruitment problems. This study enrolled only 24 participants of the required 150. This study was a small, single-blind, multicentre trial studying adults with RSE receiving either propofol or thiopental sodium for the control of seizure activity. There was no difference between the two drugs in their ability to control seizure activity. The only difference noted was the requirement for prolonged mechanical ventilation for patients in the thiopental sodium group. This could be due to the prolonged presence of the drug in the body due to its slow removal. We judged the quality of the evidence for our primary outcomes of total control of seizures and in-hospital mortality to be low. There is a clear need for a large randomised controlled trial to study the efficacy of anaesthetic agents in the treatment of RSE.
Abstract: A total of four studies were included that involved 823 participants, 412 in the exercise group and 411 in the control group. Follow-up of participants ranged from 16 weeks to 6 months. Overall, the included studies had a high risk of selection, detection, and attrition bias. Meta-analysis was not possible because the interventions (setting, type and intensity of exercise) and outcome measurements were not comparable, and the risk of bias in the identified studies was high. No study assessed cardiovascular or all‑cause mortality or cardiovascular events as individual outcomes. One or more of the studies reported on total cardiovascular risk, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, blood pressure, body mass index, exercise capacity, and health-related quality of life but the available evidence was not sufficient to determine the effectiveness of exercise. Adverse events and smoking cessation were not assessed in the included studies. Evidence to date is entirely limited to small studies with regard to sample size, short-term follow-up, and high risk of methodological bias, which makes it difficult to derive any conclusions on the efficacy or safety of aerobic or resistance exercise on groups with increased cardiovascular risk or in individuals with two or more coexisting risk factors. Further randomized clinical trials assessing controlled exercise programmes on total cardiovascular risk in individuals are warranted.

Plain-language summary: We included four studies, with 823 participants in total, comparing exercise for increased-risk individuals against control or no treatment. Follow-up of patients ranged from 16 weeks to six months. No study assessed cardiovascular or all-cause mortality, or cardiovascular events as individual outcomes. One or more of the studies reported on total cardiovascular risk, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, blood pressure, body mass index, exercise capacity, and health-related quality of life, but the results did not provide conclusive evidence of the effects of exercise in this population. The included studies did not assess smoking cessation or any adverse effects of the exercise intervention. We conclude that the evidence to date is entirely limited to small studies in terms of sample size, short-term follow-up, and high-risk of methodological bias, which makes it difficult to derive any conclusions on the efficacy or safety of the exercise carried out in the included trials on total cardiovascular risk, mortality, or cardiovascular events. It is necessary to conduct high-quality clinical trials that evaluate the effect of exercise on people with increased cardiovascular risk.
Abstract: We included 19 studies (2256 participants). Epinephrine versus placebo among outpatients showed a significant reduction in admissions at Day 1 (risk ratio (RR) 0.67; 95% confidence interval (CI) 0.50 to 0.89) but not at Day 7 post-emergency department visit. There was no difference in LOS for inpatients. Epinephrine versus salbutamol showed no differences among outpatients for admissions at Day 1 or 7. Inpatients receiving epinephrine had a significantly shorter LOS compared to salbutamol (mean difference -0.28; 95% CI -0.46 to -0.09). One large RCT showed a significantly shorter admission rate at Day 7 for epinephrine and steroid combined versus placebo (RR 0.65; 95% CI 0.44 to 0.95). There were no important differences in adverse events. This review demonstrates the superiority of epinephrine compared to placebo for short-term outcomes for outpatients, particularly in the first 24 hours of care. Exploratory evidence from a single study suggests benefits of epinephrine and steroid combined for later time points. More research is required to confirm the benefits of combined epinephrine and steroids among outpatients. There is no evidence of effectiveness for repeated dose or prolonged use of epinephrine or epinephrine and dexamethasone combined among inpatients.

Plain-language summary: Our systematic review found 19 studies involving 2256 children that use epinephrine for the treatment of bronchiolitis in acute care settings. When comparing epinephrine with placebo, no differences were found for length of hospital stay but there is some indication that epinephrine is effective for reducing hospital admissions. Exploratory results from one large, high-quality trial suggest that combined treatment with systemic glucocorticoids (dexamethasone) and epinephrine may significantly reduce admissions. There is insufficient evidence to support the use of epinephrine for the treatment of bronchiolitis among children admitted to the hospital. The evidence shows no important differences in adverse effects with epinephrine over the short-term with long-term safety not being assessed. Some limitations of this review include the quality of the included studies and inconsistent timing of measurement across studies which limited the number of children included in some meta-analyses. Further research is needed to confirm the efficacy, applicability and long-term safety of epinephrine as a treatment for bronchiolitis. In summary, our systematic review provides evidence that epinephrine is more effective than placebo for bronchiolitis in outpatients. Recent research suggests combined epinephrine and steroids may be effective for outpatients. There is no evidence to support the use of epinephrine for inpatients.