GEM/cochrane-simplification huggingface dataset:
Abstract: Twenty-three trials with a total of 1821 children and young people were included. Generally, the trials were small, and only one was assessed to have a low risk of bias. Thirteen trials compared exercise alone with no intervention. Eight were included in the meta-analysis, and overall the results were heteregeneous. One study with a low risk of bias showed a standardised mean difference (SMD) of 1.33 (95% CI 0.43 to 2.23), while the SMD's for the three studies with a moderate risk of bias and the four studies with a high risk of bias was 0.21 (95% CI -0.17 to 0.59) and 0.57 (95% CI 0.11 to 1.04), respectively. Twelve trials compared exercise as part of a comprehensive programme with no intervention. Only four provided data sufficient to calculate overall effects, and the results indicate a moderate short-term difference in self-esteem in favour of the intervention [SMD 0.51 (95% CI 0.15 to 0.88)]. The results indicate that exercise has positive short-term effects on self-esteem in children and young people. Since there are no known negative effects of exercise and many positive effects on physical health, exercise may be an important measure in improving children's self-esteem.  These conclusions are based on several small low-quality trials.

Plain-language summary: This review of trials suggests that exercise has positive short-term effects on self-esteem in children and young people, and concludes that exercise may be an important measure in improving children's self-esteem. However, the reviewers note that the trials included in the review were small-scale, and recognise the need for further well-designed research in this area.
Abstract: We found no RCTs comparing pre-admission antibiotics versus no pre-admission antibiotics or placebo. We included one open-label, non-inferiority RCT with 510 participants, conducted during an epidemic in Niger, evaluating a single dose of intramuscular ceftriaxone versus a single dose of intramuscular long-acting (oily) chloramphenicol. Ceftriaxone was not inferior to chloramphenicol in reducing mortality (RR 1.21, 95% CI 0.57 to 2.56; N = 503; 308 confirmed meningococcal meningitis; 26 deaths; moderate-quality evidence), clinical failures (RR 0.83, 95% CI 0.32 to 2.15; N = 477; 18 clinical failures; moderate-quality evidence), or neurological sequelae (RR 1.29, 95% CI 0.63 to 2.62; N = 477; 29 with sequelae; low-quality evidence). No adverse effects of treatment were reported. Estimated treatment costs were similar. No data were available on disease burden due to sequelae. We found no reliable evidence to support the use pre-admission antibiotics for suspected cases of non-severe meningococcal disease. Moderate-quality evidence from one RCT indicated that single intramuscular injections of ceftriaxone and long-acting chloramphenicol were equally effective, safe, and economical in reducing serious outcomes. The choice between these antibiotics should be based on affordability, availability, and patterns of antibiotic resistance. Further RCTs comparing different pre-admission antibiotics, accompanied by intensive supportive measures, are ethically justified in people with less severe illness, and are needed to provide reliable evidence in different clinical settings.

Plain-language summary: We searched for studies comparing giving versus not giving empiric antibiotics or comparing different antibiotics in those with suspected meningococcal disease. We found one randomised trial comparing single intramuscular doses of two different long-acting antibiotics. The evidence is current to January 2017. The included study was conducted in nine primary care facilities in Niger during an outbreak of meningococcal disease in 2003. Of 510 adults and children studied, 251 received ceftriaxone and 259 received chloramphenicol. The study was funded by Médecins Sans Frontières. There was no difference in the number of people who died, did not respond to treatment, or with neurological disabilities with either antibiotic empirically. The results were similar in whom the diagnosis was subsequently confirmed. Neither antibiotic had significant adverse effects. Although the study was well conducted, the overall quality of the evidence was only moderate for death and treatment failures because the study excluded children less than two months old, pregnant women, and the severely ill. The quality of evidence was lower for neurological disabilities because of the shortness of follow-up. Since meningococcal disease has serious consequences, not giving antibiotics empirically would be unethical. However, future research comparing different antibiotics in people of all ages and illness severity is required to provide reliable evidence in different clinical settings.
Abstract: We included seven studies, which involved 723 participants. We assessed four of the seven studies as being at high risk of bias and three had an unclear risk of bias; the quality of the evidence was difficult to assess as there was often insufficient detail reported to enable any conclusions to be drawn about the methodological rigour of the studies. Four trials involving 285 participants measured cognitive development and we synthesised these data in a meta-analysis. Compared to the control group, there was no statistically significant impact of the intervention on cognitive development (standardised mean difference (SMD) 0.30; 95% confidence interval -0.18 to 0.78). Only three studies reported socioemotional outcomes and there was insufficient data to combine into a meta-analysis. No study reported on adverse effects. This review does not provide evidence of the effectiveness of home-based interventions that are specifically targeted at improving developmental outcomes for preschool children from socially disadvantaged families. Future studies should endeavour to better document and report their methodological processes.

Plain-language summary: The purpose of this review was to look at whether home-based parenting programmes, which aim to improve child development by showing parents how to provide a better quality home environment for their child, are effective in doing so. Seven randomised controlled trials (RCTs) met the inclusion criteria for this review. It was possible to combine the results from four of the seven studies, which showed that children who received the programme did not have better cognitive development than a control group. Socioemotional development was measured in three studies but we could not combine this data to help reach a conclusion about effectiveness. None of the studies measured adverse effects. The quality of the evidence in the studies was difficult to assess due to poor reporting. More high quality research is needed.
Abstract: Eight studies (225 participants) were included. In general, children included in the studies were young (average age less than two years in the majority of included studies). Severity of croup was described as moderate to severe in all included studies. Six studies took place in the inpatient setting, one in the ED and one setting was not specified. Six of the eight studies were deemed to have a low risk of bias and the risk of bias was unclear in the remaining two studies. Nebulized epinephrine was associated with croup score improvement 30 minutes post-treatment (three RCTs, standardized mean difference (SMD) -0.94; 95% confidence interval (CI) -1.37 to -0.51; I2 statistic = 0%). This effect was not significant two and six hours post-treatment. Nebulized epinephrine was associated with significantly shorter hospital stay than placebo (one RCT, MD -32.0 hours; 95% CI -59.1 to -4.9). Comparing racemic and L-epinephrine, no difference in croup score was found after 30 minutes (SMD 0.33; 95% CI -0.42 to 1.08). After two hours, L-epinephrine showed significant reduction compared with racemic epinephrine (one RCT, SMD 0.87; 95% CI 0.09 to 1.65). There was no significant difference in croup score between administration of nebulized epinephrine via IPPB versus nebulization alone at 30 minutes (one RCT, SMD -0.14; 95% CI -1.24 to 0.95) or two hours (SMD -0.72; 95% CI -1.86 to 0.42). None of the studies sought or reported data on adverse effects. Nebulized epinephrine is associated with clinically and statistically significant transient reduction of symptoms of croup 30 minutes post-treatment. Evidence does not favor racemic epinephrine or L-epinephrine, or IPPB over simple nebulization. The authors note that data and analyses were limited by the small number of relevant studies and total number of participants and thus most outcomes contained data from very few or even single studies.

Plain-language summary: This review looked at trials of inhaled epinephrine for the treatment of children with croup and is comprised of only eight studies with 225 participants. Of the eight included studies, six were assessed as having low risk of bias and two as unclear risk of bias (based upon assessment of adequate random sequence generation, allocations concealment, blinding of participants and personnel, blinding of outcome assessment, completeness of outcome data, and selective reporting). Studies assessed a variety of outcome measures and few studies examined the same outcomes; therefore, most outcomes contained data from a maximum of three studies, and in some cases only single studies. Compared to no medication, inhaled epinephrine improved croup symptoms in children at 30 minutes following treatment (three studies, 94 children). This treatment effect disappeared two hours after treatment (one study, 20 children). However, children's symptoms did not become worse than prior to treatment. No study measured adverse events. The evidence is current to July 2013.
Abstract: Eighteen RCTs enrolling a total of 10,499 participants were eligible for the review. The results from 17 of 18 of these RCTs, published between 1995 and 2011, were suitable for meta-analysis and allowed us to quantify the therapeutic efficacy of interferon in terms of disease-free survival (17 trials) and overall survival (15 trials). Adjuvant interferon was associated with significantly improved disease-free survival (HR (hazard ratio) = 0.83; 95% CI (confidence interval) 0.78 to 0.87, P value < 0.00001) and overall survival (HR = 0.91; 95% CI 0.85 to 0.97; P value = 0.003). We detected no significant between-study heterogeneity (disease-free survival: I² statistic = 16%, Q-test P value = 0.27; overall survival: I² statistic = 6%; Q-test P value = 0.38). Considering that the 5-year overall survival rate for TNM stage II–III cutaneous melanoma is 60%, the number needed to treat (NNT) is 35 participants (95% CI = 21 to 108 participants) in order to prevent 1 death. The results of subgroup analysis failed to answer the question of whether some treatment features (i.e. dosage, duration) might have an impact on interferon efficacy or whether some participant subgroups (i.e. with or without lymph node positivity) might benefit differently from interferon adjuvant treatment. Grade 3 and 4 toxicity was observed in a minority of participants: In some trials, no-one had fever or fatigue of Grade 3 severity, but in other trials, up to 8% had fever and up to 23% had fatigue of Grade 3 severity. Less than 1% of participants had fever and fatigue of Grade 4 severity. Although it impaired quality of life, toxicity disappeared after treatment discontinuation. The results of this meta-analysis support the therapeutic efficacy of adjuvant interferon alpha for the treatment of people with high-risk (AJCC TNM stage II-III) cutaneous melanoma in terms of both disease-free survival and, though to a lower extent, overall survival. Interferon is also valid as a reference treatment in RCTs investigating new therapeutic agents for the adjuvant treatment of this participant population. Further investigation is required to select people who are most likely to benefit from this treatment.

Plain-language summary: Whereas not all single studies demonstrated a survival benefit for patients treated with interferon, combining the available evidence, we found that the use of postoperative interferon improves the survival of those with high-risk melanoma. On average, the toxicity associated with interferon administration (such as fever and fatigue) is limited; moreover, it is reversible when the treatment is stopped. Since interferon alpha is the only approved drug after surgery for those with high-risk melanoma, efforts to identify those who might benefit most from this treatment are very important in order to avoid unnecessary toxicity for those who would not benefit from interferon alpha treatment. Combination of interferon with novel drugs is another field of ongoing research to improve the life expectancy of people with high-risk melanoma.
Abstract: We included 73 RCTs, with 12,212 participants, comparing GnRH antagonist to long-course GnRH agonist protocols. The quality of the evidence was moderate: limitations were poor reporting of study methods. Live birth There was no evidence of a difference in live birth rate between GnRH antagonist and long course GnRH agonist (OR 1.02, 95% CI 0.85 to 1.23; 12 RCTs, n = 2303, I2= 27%, moderate quality evidence). The evidence suggested that if the chance of live birth following GnRH agonist is assumed to be 29%, the chance following GnRH antagonist would be between 25% and 33%. OHSS GnRH antagonist was associated with lower incidence of any grade of OHSS than GnRH agonist (OR 0.61, 95% C 0.51 to 0.72; 36 RCTs, n = 7944, I2 = 31%, moderate quality evidence). The evidence suggested that if the risk of OHSS following GnRH agonist is assumed to be 11%, the risk following GnRH antagonist would be between 6% and 9%. Other adverse effects There was no evidence of a difference in miscarriage rate per woman randomised between GnRH antagonist group and GnRH agonist group (OR 1.03, 95% CI 0.82 to 1.29; 34 RCTs, n = 7082, I2 = 0%, moderate quality evidence). With respect to cycle cancellation, GnRH antagonist was associated with a lower incidence of cycle cancellation due to high risk of OHSS (OR 0.47, 95% CI 0.32 to 0.69; 19 RCTs, n = 4256, I2 = 0%). However cycle cancellation due to poor ovarian response was higher in women who received GnRH antagonist than those who were treated with GnRH agonist (OR 1.32, 95% CI 1.06 to 1.65; 25 RCTs, n = 5230, I2 = 68%; moderate quality evidence). There is moderate quality evidence that the use of GnRH antagonist compared with long-course GnRH agonist protocols is associated with a substantial reduction in OHSS without reducing the likelihood of achieving live birth.

Plain-language summary: We found 73 randomised controlled trials comparing GnRH antagonist with GnRH agonist in a total of 12,212 women undergoing ART. The evidence is current to May 2015 There was no evidence of a difference between the groups in live birth rates (i.e. rates at conclusion of a course of treatment). The evidence suggested that if the chance of live birth following GnRH agonist is assumed to be 29%, the chance following GnRH antagonist would be between 25% and 33%. However, the OHSS rates were much higher after GnRH agonist. The evidence suggested that if the risk of OHSS following GnRH agonist is assumed to be 11%, the risk following GnRH antagonist would be between 6% and 9%. The evidence was of moderate quality for both live birth and OHSS. The main limitations of the evidence were the possibility of publication bias for live birth (with small studies likely to report favourable outcomes for GnRH antagonist) and poor reporting of study methods for OHSS.
Abstract: We included 15 studies with 498 participants. Ten studies compared physical activity to minimal dietary and behavioural intervention or no intervention. Five studies compared combined dietary, exercise and behavioural intervention to minimal intervention. One study compared behavioural intervention to minimal intervention. Risk of bias varied: eight studies had adequate sequence generation, seven had adequate clinician or outcome assessor blinding, seven had adequate allocation concealment, six had complete outcome data and six were free of selective reporting. No studies assessed the fertility primary outcomes of live birth or miscarriage. No studies reported the secondary reproductive outcome of menstrual regularity, as defined in this review. Lifestyle intervention may improve a secondary (endocrine) reproductive outcome, the free androgen index (FAI) (MD -1.11, 95% confidence interval (CI) -1.96 to -0.26, 6 RCTs, N = 204, I2 = 71%, low-quality evidence). Lifestyle intervention may reduce weight (kg) (MD -1.68 kg, 95% CI -2.66 to -0.70, 9 RCTs, N = 353, I2 = 47%, low-quality evidence). Lifestyle intervention may reduce body mass index (BMI) (kg/m2) (-0.34 kg/m2, 95% CI -0.68 to -0.01, 12 RCTs, N = 434, I2= 0%, low-quality evidence). We are uncertain of the effect of lifestyle intervention on glucose tolerance (glucose outcomes in oral glucose tolerance test) (mmol/L/minute) (SMD -0.02, 95% CI -0.38 to 0.33, 3 RCTs, N = 121, I2 = 0%, low-quality evidence). Lifestyle intervention may improve the free androgen index (FAI), weight and BMI in women with PCOS. We are uncertain of the effect of lifestyle intervention on glucose tolerance. There were no studies that looked at the effect of lifestyle intervention on live birth, miscarriage or menstrual regularity. Most studies in this review were of low quality mainly due to high or unclear risk of bias across most domains and high heterogeneity for the FAI outcome.

Plain-language summary: We found 15 studies that included 498 participants. Ten studies compared physical activity to minimal dietary and behavioural intervention or no intervention. Five studies compared combined dietary, exercise and behavioural intervention to minimal intervention. One study compared behavioural intervention to minimal intervention. The risk of bias in the studies varied and was generally unclear. The evidence is current to March 2018. There were no studies that investigated the effect of a healthy lifestyle on live birth, miscarriage or regularity of menstrual cycles. Adopting a healthy lifestyle may result in weight loss or reduction in male hormone levels in some individuals. Diet and exercise may not have an effect on the body's ability to maintain normal blood glucose levels. The evidence was of low quality. The main limitations in the evidence were inconsistent and imprecise findings, and poor reporting of the methods used in the studies.
Abstract: We found17 studies involving 3212 patients. The methods of 15 studies were at high risk of bias. In only two studies was the risk of bias low. Trials used "positive drugs", of which the efficacy was not known, as controls. Different Chinese herbal preparations were tested in nearly all trials. In only one trial was a Chinese herbal preparation tested twice. In seven trials, six herbal preparations were found to be more effective at enhancing recovery than the control preparations. In the other 10 studies, seven herbal preparations were not shown to be significantly different from the control. One study did not describe the difference between the intervention and control groups. Chinese herbal medicines may shorten the symptomatic phase in patients with the common cold. However, the lack of trials of low enough risk of bias, or using a placebo or a drug clearly identified as a control, means that we are uncertain enough to be unable to recommend any kind of Chinese medicinal herbs for the common cold.

Plain-language summary: Although we included 17 trials, involving 3212 patients, in this review, the risk of bias was so high that the evidence did not support using any Chinese herbal preparation(s) for the common cold. Well-designed clinical trials are required.
Abstract: Five studies provided results from adequate parallel-group data. Barnhart 1999 and Dayal 2006 enrolled perimenopausal women with complaints of decreased well being and, using three cognitive measures, found no significant effect of DHEA compared with placebo at 3 months. Wolf 1998b enrolled 75 healthy volunteers (37 women and 38 men aged 59-81) in a study of the effect of DHEA supplements on cognitive impairment induced by stress; after two weeks of treatment, placebo group performance deteriorated significantly on a test of selective attention following a psychosocial stressor (p<0.05), while deterioration was not evident in the DHEA group (p=0.85). However, when compared with placebo, DHEA was associated with significant impairment on a visual memory recall test (p<0.01) following the stressor. No significant effects were found on a third cognitive task. Effects were not found on tasks when administered in the absence of a stressor. van Niekerk 2001 found no effect on cognitive function in 46 men aged 62-76 from three months of DHEA supplementation. Nair 2006, enrolled 57 women and 87 men with low level of sulphated DHEA in a 24-month study, no significant changes in quality of life measures for either sex were found. In Von Muhlen 2008 DHEA for one year showed no benefit on cognition performance in 225 healthy older people. Reduced performance in a visual memory recall test observed in one trial and a significant drop-out rate in favour of placebo emerged in another trial. What little evidence there is from controlled trials does not support a beneficial effect of DHEA supplementation on cognitive function of non-demented middle-aged or elderly people. There is inconsistent evidence from the controlled trials about adverse effects of DHEA. In view of growing public enthusiasm for DHEA supplementation, particularly in the USA, and the theoretical possibility of long-term neuroprotective effects of DHEA there is a need for further high quality trials in which the duration of DHEA treatment is longer than one year, and the number of participants is large enough to provide adequate statistical power. Cognitive outcomes should be assessed in all trials.

Plain-language summary: In the USA there is growing public enthusiasm for DHEA supplementation as a means of retarding ageing and age-associated cognitive impairment but there is very little evidence from controlled trials. In two trials DHEA was associated with a deleterious effect on visual memory after a psychosocial stressor and quality of life measures, but there is inconsistent systematic evidence of adverse effects from DHEA. Longer-term randomized placebo controlled trials are needed for low and high doses.
Abstract: Data on 2281 participants from eight RCTs were available from reports of single-agent doxorubicin versus doxorubicin-based combination chemotherapy. Meta-analysis using the fixed effect model detected a higher tumour response rate with combination chemotherapy compared with single-agent chemotherapy (odds ratio [OR= 1.29; 95% confidence interval [CI], 1.03 to 1.60; p = 0.03), but the OR from a pooled analysis using the random effects model and the same data did not achieve statistical significance (OR= 1.26; 95% CI, 0.96 to 1.67; p = 0.10). No significant difference between the two regimens was detected in the pooled one-year mortality rate (OR = 0.87; 95% CI, 0.73 to 1.05; p=0.14) or two-year mortality rate (OR = 0.84; 95% CI, 0.67 to 1.06; p=0.13) (N=2097). Although reporting of adverse effects was limited and inconsistent among trials (making pooling of data for this outcome impossible), adverse effects such as nausea/vomiting and hematologic toxic effects were consistently reported as being worse with combination chemotherapy across the eight eligible studies. Compared to single-agent doxorubicin, the combination chemotherapy regimens evaluated, given in conventional doses, produced only marginal increases in response rates, at the expense of increased toxic effects and with no improvements in overall survival.

Plain-language summary: This review was conducted to find out if combining doxorubicin with other drugs is more effective than doxorubicin alone. Eight studies were considered together, which showed if combination chemotherapy is given: (1) tumour shrinkage was marginally better than in patients treated with doxorubicin alone; (2) survival was no different; and (3) side effects were worse than for patients treated with doxorubicin alone