GEM/cochrane-simplification huggingface dataset:
Abstract: We included 12 studies (in 13 publications) in this review, but interpretability and generalizability of these studies is difficult and the study designs used were at high risk of bias. The additional yield (calculated by dividing the additional 'unique' yield identified by checking reference lists by the total number of studies found to be eligible within the study) of relevant studies identified through checking reference lists ranged from 2.5% to 42.7%. Only two studies reported yield information by publication type (dissertations and systematic reviews). No cost data were reported although one study commented that it was impossible to isolate the time spent on reference tracking since this was done in parallel with the critical appraisal of each paper, and for that particular study costs were not specifically estimated. There is some evidence to support the use of checking reference lists for locating studies in systematic reviews. However, this evidence is derived from weak study designs. In situations where the identification of all relevant studies through handsearching and database searching is difficult, it would seem prudent that authors of reviews check reference lists to supplement their searching. The challenge, therefore, is for review authors to recognize those situations.

Plain-language summary: We found 12 studies that explored whether or not checking reference lists was useful for systematic reviews. These studies reported a range of results, from identifying only a few additional studies (2.5%: 2 of 79 included studies) to identifying many additional studies (42.7%: 111 of 260 included studies) through checking reference lists. Unfortunately, none of the studies looked at how much time or money were spent on the process of checking reference lists, and it was suggested this would be almost impossible to estimate. Unfortunately our findings are based on weak information. The data do suggest that in situations where researchers may have difficulty locating information, checking through the reference lists may be an important way to reduce the risk of missing relevant information.
Abstract: No RCTs of interventions were identified. Eleven observational studies were included - two medical records reviews, one matched pair study, one clinician interview study, two studies documenting clinicians' decisions and five postal surveys. Three measures of recruitment were used, invitation to participate, entry into RCT and reported entry to RCT. Five studies explored the effect of patient characteristics. The effect of age and prognosis varied between trials. Six studies considered the association between clinicians' views and recruitment. Clinicians who agreed to participate because they were acquainted with the researchers were less likely to participate than those otherwise motivated (1 study, 2-sided p = 0.04 Fisher's exact test) and (Odds Ratio [OR] 0.4, 95% Confidence Interval [CI] 0.2 to 0.9, 1 study). Clinicians who had recruited were more likely to report some difficulties including "trials involve extra work" (OR 92.94, 95% CI 4.54 - 1902.11; p ≤ 0.01, 1 study) and "inviting patients to participate is embarrassing" (chi-square 15.55, df = 1, p < 0.0001, 1 study). The effect of the need to discuss clinical uncertainty was unclear but concern that the doctor-patient relationship would be adversely affected by participation was a deterrent (chi-square = 7.25, df = 1, p = 0.007, 1 study). The impact of factors varied across studies. Researchers need to be aware that aspects of the design and conduct of trials can affect clinicians' willingness to invite patients to participate. Further research is needed.

Plain-language summary: Randomised controlled trials (RCTs) are needed to provide robust evidence of the relative efficacy and safety of treatments. In many RCTs, clinicians (i.e. healthcare professionals inviting patients to take part in an RCT in which they provide at least one of the interventions) only invite a small proportion of the people who are eligible for trials to take part. Observational studies have been conducted to explore reasons for this but the results do not identify any factors that appear to have a consistent impact on recruitment.
Abstract: Ten trials involving 11,795 women met the inclusion criteria. We found no trials of freestanding birth centres or Snoezelen rooms. Allocation to an alternative setting increased the likelihood of: no intrapartum analgesia/anesthesia (six trials, n = 8953; RR 1.18, 95% CI 1.05 to 1.33); spontaneous vaginal birth (eight trials; n = 11,202; RR 1.03, 95% CI 1.01 to 1.05); breastfeeding at six to eight weeks (one trial, n = 1147; RR 1.04, 95% CI 1.02 to 1.06); and very positive views of care (two trials, n = 1207; RR 1.96, 95% CI 1.78 to 2.15). Allocation to an alternative setting decreased the likelihood of epidural analgesia (eight trials, n = 10.931; RR 0.80, 95% CI 0.74 to 0.87); oxytocin augmentation of labour (eight trials, n = 11,131; RR 0.77, 95% CI 0.67 to 0.88); instrumental vaginal birth (eight trials, n = 11,202; RR 0.89, 95% CI 0.79 to 0.99), and episiotomy (eight trials, n = 11,055; RR 0.83, 95% CI 0.77 to 0.90). There was no apparent effect on other adverse maternal or neonatal outcomes. Care by the same or separate staff had no apparent effects. No conclusions could be drawn regarding the effects of continuity of caregiver or architectural characteristics. In several of the trials included in this review, the design features of the alternative setting were confounded by important differences in the organizational models for care (separate staff for the alternative setting, offering more continuity of caregiver), and thus it is difficult to draw inferences about the independent effects of the physical birth environment. Hospital birth centres are associated with lower rates of medical interventions during labour and birth and higher levels of satisfaction, without increasing risk to mothers or babies.

Plain-language summary: The primary aim of this review is to evaluate the effects, on labour and birth outcomes, of care in an alternative institutional birth setting compared with care in a conventional hospital labour ward. We included ten trials involving 11,795 women. We found no trials of freestanding birth centres. When compared to conventional institutional settings, alternative settings were associated with reduced likelihood of medical interventions, increased likelihood of spontaneous vaginal birth, increased maternal satisfaction, and greater likelihood of continued breastfeeding at one to two months postpartum, with no apparent risks to mother or baby. Unfortunately, in several trials, the design features of the alternative setting were confounded by differences in the organizational models of care (including separate staff and more continuity of caregiver in the alternative setting), and thus it is not possible to draw conclusions about the independent effects of the design of the birth environment. We conclude that women and policy makers should be informed about the benefits of institutional settings which focus on supporting normal labour and birth.
Abstract: Nine RCTs (N = 341 participants, 301 included in analyses) investigated various types and intensities of non pharmacological interventions for treating spasticity in adults with MS. These interventions included: physical activity programmes (such as physiotherapy, structured exercise programme, sports climbing); transcranial magnetic stimulation (Intermittent Theta Burst Stimulation (iTBS), Repetitive Transcranial Magnetic Stimulation (rTMS)); electromagnetic therapy (pulsed electromagnetic therapy; magnetic pulsing device), Transcutaneous Electrical Nerve Stimulation (TENS); and Whole Body Vibration (WBV). All studies scored 'low' on the methodological quality assessment implying high risk of bias. There is 'low level' evidence for physical activity programmes used in isolation or in combination with other interventions (pharmacological or non pharmacological), and for repetitive magnetic stimulation (iTBS/rTMS) with or without adjuvant exercise therapy in improving spasticity in adults with MS. No evidence of benefit exists to support the use of TENS, sports climbing and vibration therapy for treating spasticity in this population. There is 'low level' evidence for non pharmacological interventions such as physical activities given in conjunction with other interventions, and for magnetic stimulation and electromagnetic therapies for beneficial effects on spasticity outcomes in people with MS. A wide range of non pharmacological interventions are used for the treatment of spasticity in MS, but more robust trials are needed to build evidence about these interventions.

Plain-language summary: In this review, nine studies evaluating various non drug treatments to treat spasticity in adult with MS were included, comprising a total of 341 participants. Results from these studies suggest that all included non pharmacological therapies have low level of evidence or no evidence in improving spasticity in people with MS. However, caution should be used in the interpretation of the results, due to the poor methodological quality of all the included studies. More research is needed to determine the usefulness of these interventions before they can be recommended as routine treatments.
Abstract: Eleven studies (n = 927 participants) met our inclusion criteria. Eight studies compared CTA with IADSA (n = 526) and three studies compared MRA with IADSA (n = 401). Methodological quality varied considerably among studies, with partial verification bias in 7/11 (64%) and retrospective designs in 5/10 (50%). In studies of CTA, the pooled estimate of sensitivity was 0.95 (95% confidence interval (CI) 0.90 to 0.97) and specificity was 0.99 (95% CI 0.95 to 1.00). The results remained robust in a sensitivity analysis in which only studies evaluating adult patients (≥ 16 years of age) were included. In studies of MRA, the pooled estimate of sensitivity was 0.98 (95% CI 0.80 to 1.00) and specificity was 0.99 (95% CI 0.97 to 1.00). An indirect comparison of CTA and MRA using a bivariate model incorporating test type as one of the parameters failed to reveal a statistically significant difference in sensitivity or specificity between the two imaging modalities (P value = 0.6). CTA and MRA appear to have good sensitivity and specificity following ICH for the detection of intracranial vascular malformations, although several of the included studies had methodological shortcomings (retrospective designs and partial verification bias in particular) that may have increased apparent test accuracy.

Plain-language summary: This review looked at different tests used to identify blood vessel abnormalities in the brain. Intra-arterial digital subtraction angiography (IADSA) is the standard test used and involves positioning a tube, introduced through a blood vessel in the groin, into blood vessels near the brain. Dye is directly injected into the brain's blood vessels using this tube. Computed tomographic angiography (CTA) and magnetic resonance angiography (MRA) are newer tests that may be done without any injections (MRA) or only through an injection into the arm (CTA and MRA). This review investigated the accuracy of CTA or MRA, or both, compared with IADSA after intracerebral haemorrhage. We found eight studies (involving 526 participants) that compared CTA with IADSA and three studies (involving 401 participants) that compared MRA with IADSA. Both CTA and MRA appear to have good accuracy when compared with IADSA. However, the studies were small and were limited in many cases by their design. Further research that looks at accuracy, practicality, and costs is needed.
Abstract: We identified one randomised controlled trial that included 226 people with high-risk neuroblastoma who were pre-treated with autologous HSCT. The study randomised 113 participants to receive immunotherapy including isotretinoin, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2, and ch14.18, a type of anti-GD2 antibody also known as dinutuximab. The study randomised another 113 participants to receive standard therapy including isotretinoin. The results on overall survival favoured the dinutuximab-containing immunotherapy group (hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31 to 0.80; P = 0.004). The results on event-free survival also favoured the dinutuximab-containing immunotherapy group (HR 0.61, 95% CI 0.41 to 0.92; P = 0.020). Randomised data on adverse events were not reported separately. The study did not report progression-free survival, late non-haematological toxicity, and health-related quality of life as separate endpoints. We graded the quality of the evidence as moderate. The evidence base favours dinutuximab-containing immunotherapy compared to standard therapy concerning overall survival and event-free survival in people with high-risk neuroblastoma pre-treated with autologous HSCT. Randomised data on adverse events are lacking, therefore more research is needed before definitive conclusions can be made regarding this outcome.

Plain-language summary: The evidence is current to 20 September 2018. We included a single randomised trial (a type of study in which participants are assigned to one of two or more treatment groups using a random method) with 113 people allocated to immunotherapy including isotretinoin, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2, and ch14.18, a distinct type of anti-GD2 antibody also known as dinutuximab. Another 113 people were allocated to receive standard therapy including isotretinoin. The results on overall survival and event-free survival favoured the dinutuximab-containing immunotherapy group. Other outcomes including those on adverse events were not adequately reported; more research is needed before definitive conclusions can be made regarding these outcomes. We assessed the quality of the evidence as moderate.
Abstract: We included seven trials involving 1,020 participants. Mean time to cessation of vomiting in one study was 0.34 days less with dimenhydrinate suppository compared to placebo (P value = 0.036). Pooled data from three studies comparing oral ondansetron with placebo showed: a reduction in the immediate hospital admission rate (RR 0.40, NNT 17, 95% CI 10 to 100) but no difference between the hospitalization rates at 72 hours after discharge from the Emergency Department (ED); a reduction in IV rehydration rates both during the ED stay (RR 0.41, NNT 5, 95% CI 4 to 8), and in follow-up to 72 hours after discharge from the ED stay (worst-best scenario for ondansetron RR 0.57, NNT 6, 95% CI 4 to 13) and an increase in the proportion of patients with cessation of vomiting (RR 1.34, NNT 5, 95% CI 3 to 7)). No significant difference was noted in the revisit rates or adverse events, although diarrhea was reported as a side effect in four of the five ondansetron studies. In one study the proportion of patients with cessation of vomiting in 24 hours was (58%) with IV ondansetron, (17%) placebo and (33%) in the metoclopramide group (P value = 0.039). Oral ondansetron increased the proportion of patients who had ceased vomiting and reduced the number needing intravenous rehydration and immediate hospital admission. Intravenous ondansetron and metoclopramide reduced the number of episodes of vomiting and hospital admission, and dimenhydrinate as a suppository reduced the duration of vomiting.

Plain-language summary: The small number of included trials provided evidence which appeared to favour the use of antiemetics over placebo to reduce the number of episodes of vomiting due to gastroenteritis in children. A single oral dose of ondansetron given to children with mild to moderate dehydration can control vomiting, avoid hospitalization and intravenous fluid administration which would otherwise be needed. There were no major side effects other than a few reports of increased frequency of diarrhea.
Abstract: Only one trial met the inclusion criteria for this review which was a small, open-label, unblinded, randomised trial of the safety and feasibility of switching from phenytoin to levetiracetam monotherapy or continuing phenytoin for glioma-related seizure control following craniotomy (Lim 2009). Levetiracetam (a non enzyme-inducing antiepileptic drug) appears to have been at least as well tolerated and as effective as phenytoin (an enzyme-inducing antiepileptic drug) for the treatment of seizures in people with brain tumours. Eighty-seven per cent of participants treated with levetiracetam were free of seizures at six months compared with 75% of participants treated with phenytoin.   There is one ongoing study of levetiracetam versus pregabalin for the treatment of seizures in adults undergoing chemotherapy, radiotherapy,or both for primary brain tumours. No data from this study were available at the time of preparing this review. There is a lack of robust, randomised, controlled evidence to support the choice of antiepileptic drug for the treatment of seizures in adults with brain tumours. While some authors support the use of non enzyme-inducing antiepileptic drugs, reliable, comparative evidence to provide clinical justification for this is limited. There is a need for further large, randomised, controlled trials in this area.

Plain-language summary: There is a lack of good quality evidence to support the choice of any particular antiepileptic drug for the treatment of seizures in adults with brain tumours. Our searches identified one small randomised trial directly comparing two different antiepileptic drugs (phenytoin and levetiracetam) for the treatment of seizures in adults with brain tumours. No significant difference was identified between the effectiveness of these two drugs. This small study was intended as a feasibility study for a larger trial that was not carried out. We also identified one ongoing study of levetiracetam versus pregabalin for the treatment of seizures in adults undergoing chemotherapy, radiotherapy,or both for primary brain tumours although no data from this study were available at the time of preparing this review. We identified a number of other small studies but we excluded them from the review as they were not randomised controlled trials. There is a clear need for larger randomised controlled trials to study the effectiveness of different antiepileptic drugs in the treatment of seizures in adults with brain tumours.
Abstract: Fifteen trials were included which tested two treatment regimes, 90 and 180 mg/day of nimodipine for 12, 24 weeks and 52 weeks. Two trials included only patients with Alzheimer's disease (AD), 10 trials included only patients with cerebrovascular dementia (CVD), and three trials included patients with AD, CVD and mixed disease. Available outcome data from nine trials (2492 patients) cover the domains of cognitive function, activities of daily living, global clinical state, safety and tolerability. By pooling available data from all trials, whatever the diagnosis of the patients included, this review found benefit associated with nimodipine (90 mg/day at 12 weeks) compared with placebo on the SCAG scale (WMD -7.59, 95% CI -9.87 to -5.31, P<0.00001), on clinical global impression (WMD -0.87, 95% CI -1.07 to -0.67, P<0.00001) and cognitive function (SMD 0.61, 95% CI 0.42 to 0.81, P<0.00001) but not on scales assessing activities of daily living. When the AD trials and the VD trials were pooled separately, similar significant results were found for the 90 mg/day dose of nimodipine at 12 weeks. Drop-out rates were low in the trials, affecting similar proportions of treatment and placebo groups. Nimodipine is well tolerated with a low rate of adverse effects similar to that associated with placebo. There were slightly more adverse cerebrovascular events, and adverse events due to blood problems, associated with placebo than with nimodipine, and adverse autonomic events were slightly more common with nimodipine than with placebo. Nimodipine can be of some benefit in the treatment of patients with features of dementia due to unclassified disease or to Alzheimer's disease, cerebrovascular disease, or mixed Alzheimer's and cerebrovascular disease. It appears to be well tolerated with few side effects. Data were not available from several trials, a total of more than 500 patients. A meta-analysis of individual patient data from all trials is desirable. Dementia is a chronic disorder and the short-term benefits of nimodipine demonstrated in the trials reviewed do not justify its use as a long-term anti-dementia drug. New research must focus on longer term outcomes.

Plain-language summary: The efficacy of nimodipine, a calcium channel blocker, has been tested in randomized controlled trials for the treatment of dementia, particularly Alzheimer's disease and multi-infarct dementia, the commonest forms of dementia in older people. The rationale for its use is to restrict the influx of calcium ions into neurons, and, by vasodilatation, to improve blood flow to the brain. This review found evidence of some short-term benefit attributable to nimodipine, mainly in measures of cognitive function and global impression, but not in activities on daily living, for patients with degenerative and multi-infarct dementia, and mixed dementia. Nimodipine is well tolerated with a low rate of adverse effects similar to that associated with placebo.
Abstract: The review now includes 13 poorly reported randomised trials (total 478 people), all participants were adults with chronic psychiatric disorders, mostly schizophrenia, and antipsychotic-induced TD. There was no clear difference between vitamin E and placebo for the outcome of TD: not improved to a clinically important extent (6 RCTs, N = 264, RR 0.95, 95% CI 0.89 to 1.01, low-quality evidence). However, people allocated to placebo may show more deterioration of their symptoms compared with those given vitamin E (5 RCTs, N = 85, RR 0.23, 95% CI 0.07 to 0.76, low-quality evidence). There was no evidence of a difference in the incidence of any adverse effects (9 RCTs, N = 205, RR 1.21, 95% CI 0.35 to 4.15, very low-quality evidence), extrapyramidal adverse effects (1 RCT, N = 104, MD 1.10, 95% CI -1.02 to 3.22, very low-quality evidence), or acceptability of treatment (measured by participants leaving the study early) (medium term, 8 RCTs, N = 232, RR 1.07, 95% CI 0.64 to 1.80, very low-quality evidence). No trials reported on social confidence, social inclusion, social networks, or personalised quality of life, outcomes designated important to patients. There is no trial-based information regarding the effect of vitamin E for those with early onset of TD. Small trials of limited quality suggest that vitamin E may protect against deterioration of TD. There is no evidence that vitamin E improves symptoms of this problematic and disfiguring condition once established. New and better trials are indicated in this under-researched area, and, of the many adjunctive treatments that have been given for TD, vitamin E would be a good choice for further evaluation.

Plain-language summary: We searched for trials, July 2015 and April 2017, using the Cochrane Schizophrenia Group's register of trials. The review includes 13 poorly reported randomised trials investigating the effects of vitamin E for people with schizophrenia or other chronic mental illnesses who also developed TD as a result of taking antipsychotics. The trials randomised a total of 478 participants who had been ill for a long time. Vitamin E may protect against tardive dyskinesia. However, there is no clear evidence that vitamin E improves this problematic and disfiguring condition. Available evidence is weak, limited and poor and we are unable to make any conclusions regarding the use of Vitamin E for antipsychotic-induced tardive dyskinesia. Well-designed trials involving a large number of participants investigating the effects of vitamin E over long periods of time are needed to determine whether this vitamin provides an effective treatment option 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/).