GEM/cochrane-simplification huggingface dataset:
Abstract: Twenty-four RCTs were identified. The overall quality of the trials was low. Five drugs were evaluated; dexamphetamine, methylphenidate, methylamphetamine, pemoline and modafinil. Modafinil was evaluated separately as its pharmacology is different to that of the other PS. PS were administered as a monotherapy, adjunct therapy, in oral or intravenous preparation and in comparison with a placebo or an active therapy. Most effects were measured in the short term (up to four weeks). Thirteen trials had some usable data for meta-analyses. Three trials (62 participants) demonstrated that oral PS, as a monotherapy, significantly reduced short term depressive symptoms in comparison with placebo (SMD -0.87, 95% CI -1.40, -0.33, with non-significant heterogeneity. A similar effect was found for fatigue. In the short term PS were acceptable and well tolerated. Tolerance and dependence were under evaluated. No statistically significant difference in depression symptoms was found between modafinil and placebo. There is some evidence that in the short-term, PS reduce symptoms of depression. Whilst this reduction is statistically significant, the clinical significance is less clear. Larger high quality trials with longer follow-up and evaluation of tolerance and dependence are needed to test the robustness of these findings and, furthermore, to explore which PS may be more beneficial and in which clinical situations they are optimal.

Plain-language summary: This review evaluated the evidence from randomised controlled trials (RCTs) evaluating the effectiveness of psychostimulants (PS) in the treatment of depression. Twenty-four RCTs were identified, of which 14 had data for meta-analysis. Five drugs were evaluated, including dexamphetamine, methylphenidate, methylamphetamine, pemoline and modafinil. Modafinil was evaluated separately as its pharmacology differs from other PS. Three small trials of PS involving a total of 62 participants indicated that oral treatment with PS in the short term (up to four weeks) significantly reduced depressive symptoms when compared with placebo, however, the overall quality of the trials was poor, limiting confidence in the findings. Two trials involving 411 participants compared modafinil against placebo when combined with antidepressant treatment at 6-8 weeks, and showed a non-significant difference in reducing depression symptoms. One small trial of 50 participants compared oral modafinil against placebo after 12 weeks of treatment, and also showed a non-significant difference in reducing depression symptoms. No trials examined the longer-term effect of PS. Further well conducted trials with long term follow-up are required to find out which PS may be more effective in the treatment of depression, and whether PS are more effective in certain subgroups of depressed patients.
Abstract: Three studies totalling 147 participants (107 adults and 40 adolescents) met the inclusion criteria. Seventy-four participants took part in DMT treatment, while 73 comprised the control groups. Two studies included male and female adults with depression. One of these studies included outpatient participants; the other study was conducted with inpatients at an urban hospital. The third study reported findings with female adolescents in a middle-school setting. All included studies collected continuous data using two different depression measures: the clinician-completed Hamilton Depression Rating Scale (HAM-D); and the Symptom Checklist-90-R (SCL-90-R) (self-rating scale). Statistical heterogeneity was identified between the three studies. There was no reliable effect of DMT on depression (SMD -0.67 95% CI -1.40 to 0.05; very low quality evidence). A planned subgroup analysis indicated a positive effect in adults, across two studies, 107 participants, but this failed to meet clinical significance (SMD -7.33 95% CI -9.92 to -4.73). One adult study reported drop-out rates, found to be non-significant with an odds ratio of 1.82 [95% CI 0.35 to 9.45]; low quality evidence. One study measured social functioning, demonstrating a large positive effect (MD -6.80 95 % CI -11.44 to -2.16; very low quality evidence), but this result was imprecise. One study showed no effect in either direction for quality of life (0.30 95% CI -0.60 to 1.20; low quality evidence) or self esteem (1.70 95% CI -2.36 to 5.76; low quality evidence). The low-quality evidence from three small trials with 147 participants does not allow any firm conclusions to be drawn regarding the effectiveness of DMT for depression. Larger trials of high methodological quality are needed to assess DMT for depression, with economic analyses and acceptability measures and for all age groups.

Plain-language summary: Due to the low number of studies and low quality of evidence, it was not possible to draw firm conclusions about the effectiveness of DMT for depression. It was not possible to compare DMT with medication, talking therapies, physical treatments or to compare types of DMT due to lack of available evidence. Key findings were: Overall, there is no evidence for or against DMT as a treatment for depression. There is some evidence to suggest DMT is more effective than standard care for adults, but this was not clinically significant. DMT is no more effective than standard care for young people. Evidence from just one study of low methodological quality suggested that drop-out rates from the DMT group were not significant, and there is no reliable effect in either direction for quality of life or self esteem. A large positive effect was observed for social functioning, but since this was from one study of low methodological quality the result is imprecise. Future studies should be of high methodological quality, comparing DMT with other treatments for depression, and include economic analyses.
Abstract: We reviewed 23 studies: three randomised trials, two non-randomised trials, 14 cohort studies and four case-control studies. Five examined mandatory pre-licence training, 14 assessed non-mandatory training, three of the case-control studies assessed ‘any’ type of rider training, and one case-control study assessed mandatory pre-licence training and non-mandatory training. The types of assessed rider training varied in duration and content. Most studies suffered from serious methodological weaknesses. Most studies were non-randomised and controlled poorly for confounders. Most studies also suffered from detection bias due to the poor use of outcome measurement tools such as the sole reliance upon police records or self-reported data. Small sample sizes and short follow-up time after training were also common. Due to the poor quality of studies identified, we were unable to draw any conclusions about the effectiveness of rider training on crash, injury, or offence rates. The findings suggest that mandatory pre-licence training may be an impediment to completing a motorcycle licensing process, possibly indirectly reducing crashes through a reduction in exposure. It is not clear if training (or what type) reduces the risk of crashes, injuries or offences in motorcyclists, and a best rider training practice can therefore not be recommended. As some type of rider training is likely to be necessary to teach motorcyclists to ride a motorcycle safely, rigorous research is needed.

Plain-language summary: The authors of this review examined all research studies that report an evaluation of the effectiveness of motorcycle rider courses in reducing the number of traffic offences, motorcycle rider crashes, injuries and deaths. This review included 23 research studies, including three randomised trials, two non-randomised trials, 14 cohort studies and four case-control studies. The types of rider training that were evaluated varied in content and duration. The findings suggest that mandatory pre-licence training may present a barrier to completing a motorcycle licensing process, thus possibly indirectly reducing crash, injury, death and offence rates through a reduction in exposure to riding a motorcycle. However, on the basis of the existing evidence, it is not clear if (or what type of) training reduces the risk of crashes, injuries, deaths or offences in motorcyclists and the selection of the best rider training practice can therefore not be recommended. It is likely that some type of rider training is necessary to teach motorcyclists basic motorcycle handling techniques and to ride a motorcycle safely. It is therefore important that further research work be conducted to rigorously evaluate motorcycle rider training courses, particularly in low income countries where the main burden of motorcycle injuries and deaths occur.
Abstract: Eleven studies (794 participants) were included. Overall quality of studies was moderate with nine studies being placebo-controlled but only five double-blinded. Compared to control, ESA treatment significantly improved exercise duration by 96.8 seconds (95% CI 5.2 to 188.4, p=0.04) and 6-minute walk distance by 69.3 metres (95% CI 17.0 to 121.7, p=0.009). Benefit was also noted in terms of peak VO2 (+2.29 mL/kg/min, p=0.007), NYHA class (-0.73, p<0.001), ejection fraction (+5.8%, p<0.001), B-type natriuretic peptide (-226.99 pg/mL, p<0.001) and quality-of-life indicators, with a mean increase in haemoglobin of 1.98 g/dL (p<0.0001). There was also a significantly lower rate of heart failure related hospitalisations (RR 0.62, 95% CI 0.44 to 0.87) and lower all-cause mortality (RR 0.61, 95% CI 0.37 to 0.99). No increase in adverse events with ESA therapy was observed, however studies were of small sample sizes and limited duration. Meta-analysis of small RCTs suggests that ESA treatment in patients with symptomatic CHF and mild anaemia (haemoglobin more than 10g/dL) can improve anaemia and exercise tolerance, reduce symptoms and have benefits on clinical outcomes. Confirmation requires well-designed studies with careful attention to dose, haemoglobin treatment target and associated iron therapy.

Plain-language summary: This review shows that ESAs improves anaemia, exercise tolerance, quality of life and reduces symptoms in heart failure patients with a mild anaemia. ESAs may also reduce hospital admission and improve survival. There was no increase in major side effects in those receiving ESA therapy compared to control over the 2-12 month study period (maximum 12 months) although the effects of treatment over a longer period are not known. More research is needed to clarify the full effects and safety of ESAs as a treatment for anaemia in these patients.
Abstract: We found one eligible trial that included 64 infants. This trial was not blinded. Analysis showed a higher rate of weight gain in the high-volume feeds group: mean difference 6.20 g/kg/d (95% confidence interval 2.71 to 9.69). There was no increase in the risk of feed intolerance or necrotising enterocolitis with high-volume feeds, but 95% confidence intervals around these estimates were wide. We assessed the quality of evidence for these outcomes as 'low' or 'very low' because of imprecision of the estimates of effect and concern about risk of bias due to lack of blinding in the included trial. Trial authors provided no data on other outcomes, including gastro-oesophageal reflux, aspiration pneumonia, necrotising enterocolitis, patent ductus arteriosus, bronchopulmonary dysplasia, or long-term growth and neurodevelopment. We found only very limited data from one small unblinded trial on the effects of high-volume feeds on important outcomes for preterm or low birth weight infants. The quality of evidence is low to very low. Hence, available evidence is insufficient to support or refute high-volume enteral feeds in preterm or low birth weight infants. A large, pragmatic randomised controlled trial is needed to provide data of sufficient quality and precision to inform policy and practice.

Plain-language summary: Through literature searches up-to-date until Novebember 2016, we found only one small randomised controlled trial (with 64 very low birth weight infant participants) that addressed this question. Very low birth weight infants who receive more milk than standard volumes gain weight more quickly during their hospital stay. We found no evidence suggesting that giving infants high volumes of milk causes feeding or gut problems, but this finding is not certain. Available evidence is insufficient to support or refute the use of high-volume feeds in preterm or low birth weight infants. High-volume feeds might increase the rate of weight gain, but more trials are needed to confirm this finding and to examine whether high-volume feeds cause any problems for preterm or low birth weight infants.
Abstract: Eight studies, with a total of 702 participants, met the inclusion criteria. Overall, the studies were predominantly assessed as being at low or unclear risk of bias; unclear risk was mainly due lack of information. There was no evidence of selective reporting. Pooled estimates favoured the intervention, but did not show a significant effect on tympanometry (type C2 and B) at less than one month, nor at more than one month. Similarly, there were no significant changes for discrete pure-tone audiometry and non-discrete audiometry. Pooled estimates favoured, but not significantly, the intervention for the composite measure of tympanogram or audiometry at less than one month; at more than one month the result became significant (RRI 1.74, 95% CI 1.22 to 2.50). Subgroup analysis based on the type of intervention showed a significant effect using a Politzer device under one month (RRI 7.07, 95% CI 3.70 to 13.51) and over one month (RRI 2.25, 95% CI 1.67 to 3.04). None of the studies demonstrated a significant difference in the incidence of side effects between interventions. All of the studies were small, of limited treatment duration and had short follow-up. However, because of the low cost and absence of adverse effects it is reasonable to consider autoinflation whilst awaiting natural resolution of otitis media with effusion. Primary care could prove a beneficial place to evaluate such interventions and there is ongoing research in this area. Further research should also consider the duration of treatment, the long-term impact on developmental outcomes in children and additional quality of life outcome measures for children and families.

Plain-language summary: This review included eight randomised controlled trials of autoinflation for glue ear. All of the studies were small, of limited treatment duration and had short follow-up. The review authors used a combined outcome measure which included any outcome signifying improvement (as defined in the individual studies) and measured outcomes at the time points 'up to one month' and 'more than one month'. Improvement was demonstrated only in 'more than one month' analyses. Subgroup analysis based on the type of intervention showed a significant effect using a Politzer device at both under one month and over one month. None of the studies demonstrated a significant difference in the incidence of side effects between interventions. The authors conclude that the evidence for the use of autoinflation in the short term appears favourable. Given the small number of studies and the lack of long-term follow-up, the long-term effects associated with the use of these devices cannot be determined.
Abstract: Ten published RCTs were included (involving 1825 women). Comparisons were local cooling treatments (ice packs, cold gel pads (with or without compression) or cold/iced baths) with no treatment, gel pads with compression, hamamelis water (witch hazel), pulsed electromagnetic energy (PET), hydrocortisone/pramoxine foam (Epifoam), oral paracetamol or warm baths. Ice packs provided improved pain relief 24 to 72 hours after birth compared with no treatment (risk ratio (RR) 0.61; 95% confidence interval (CI) 0.41 to 0.91; one study, n = 208). Women preferred the utility of the gel pads compared with ice packs or no treatment (RR 0.82; 95% CI 0.73, 0.92). Differences detected in a composite of perineal oedema and bruising and overall wound healing were noted in one small study, favouring cold gel pads (n = 37) over ice (n = 35, mean difference (MD) 0.63 on a scale of 0 to 15; 95% CI 0.20 to 1.06) or no treatment (n = 39, MD -2.10; 95% CI -3.80 to -0.40) three to 14 days after giving birth. Women reported more pain (RR 5.60; 95% CI 2.35 to 13.33; one study, 100 women) and used more additional analgesia (RR 4.00; 95% CI 1.44 to 11.13; one study, 100 women) following the application of ice packs compared with PET. There is only limited evidence to support the effectiveness of local cooling treatments (ice packs, cold gel pads, cold/iced baths) applied to the perineum following childbirth to relieve pain.

Plain-language summary: This review looked to see if local cooling for a short period of time helped to relieve perineal pain for women and helped with healing. We found 10 studies including 1825 women that compared cooling treatments such as ice, cold gel pads, or cold bath with no treatment, or other treatments. One study found that women reported less pain 24 to 72 hours after giving birth when they used the ice packs for 10 to 20 minutes, rather than when they had no treatment. No effect on healing was identified. There is only a small amount of evidence of how safe and effective cooling treatments are to relieve perineal pain.
Abstract: Three studies met the criteria. Four other studies were excluded, as they did not compare double versus single wall incubators. Double wall incubators have the advantage of decreasing heat loss, decreasing heat production and decreasing radiant heat loss when compared to single wall incubators. There is also the advantage of reduced oxygen consumption. A minimal increase in conductive heat loss was noted when compared to single wall incubators. All of these effects are small and do not support the proposition that double wall incubators have a beneficial effect on long-term outcomes including mortality or the duration of hospitalization. Although it appears that caring for extremely small infants in double wall incubators may theoretically result in shorter hospitalization and may have metabolic advantages, this review was unable to find any data in the literature to support or refute this hypothesis. The studies do not provide any evidence that the small decrease in heat loss improves clinical outcome. Therefore, the available data is insufficient to directly guide clinical practice.

Plain-language summary: Three studies were found that met our criteria. The double wall incubators had advantages as far as decreasing heat loss and decreasing heat production. These infants seemed to be in the best temperature range, as their need to burn energy was less. However, these effects were small and did not provide any evidence of any long-term improvement regarding duration of hospitalization or survival. Although it appears that caring for extremely small infants in double wall incubators may result in certain metabolic advantages, this review was unable to find any data in the literature to support or refute this theory. Available data is insufficient to directly guide clinical practice.
Abstract: We included 23 studies involving 188,934 young people, conducted in the USA, Canada and Australia between 1991 and 2012. Twelve studies were randomised controlled trials (RCT), two were prospective cohort studies (PCS), one study was both a RCT and a PCS, six were interrupted time series and two were controlled before and after (CBA) studies. The RCTs had an overall low risk of bias, along with the ITS (apart from the dimension 'formal test of trend'), and the PCS had overall good quality, apart from the description of loss to follow-up by exposure. Self reported or biomarker-assessed illicit drug use was measured with an array of published and unpublished scales making comparisons difficult. Pooled results of five RCTs (N = 5470) show no effect of media campaign intervention (standardised mean difference (SMD) -0.02; 95% confidence interval (CI) -0.15 to 0.12). We also pooled five ITS studies (N = 26,405) focusing specifically on methamphetamine use. Out of four pooled estimates (two endpoints measured in two age groups), there was evidence of a reduction only in past-year prevalence of methamphetamine use among 12 to 17 years old. A further five studies (designs = one RCT with PCS, two PCS, two ITS, one CBA, N = 151,508), which could not be included in meta-analyses, reported a drug use outcome with varied results including a clear iatrogenic effect in one case and reduction of use in another. Overall the available evidence does not allow conclusions about the effect of media campaigns on illicit drug use among young people. We conclude that further studies are needed.

Plain-language summary: We reviewed 23 studies of different designs involving 188,934 young people and conducted in the United States, Canada and Australia. The studies tested different interventions and used several questionnaires to interview the young people about the effects of having participated in the studies brought to them. As a result it was very difficult to reach conclusions and for this reason we are highlighting the need for further studies.
Abstract: We included four RCTs of moderate risk of bias involving 362 women. In one trial of 115 women, levothyroxine therapy to treat pregnant euthyroid (normal thyroid function) women with thyroid peroxidase antibodies was not shown to reduce pre-eclampsia significantly (risk ratio (RR) 0.61; 95% confidence interval (CI) 0.11 to 3.48) but did significantly reduce preterm birth by 72% (RR 0.28; 95% CI 0.10 to 0.80). Two trials of 30 and 48 hypothyroid women respectively compared levothyroxine doses, but both trials reported only biochemical outcomes. A trial of 169 women compared the trace element selenomethionine (selenium) with placebo and no significant differences were seen for either pre-eclampsia (RR 1.44; 95% CI 0.25 to 8.38) or preterm birth (RR 0.96; 95% CI 0.20 to 4.61). None of the four trials reported on childhood neurodevelopmental delay. There was a non-significant trend towards fewer miscarriages with levothyroxine, and selenium showed some favourable impact on postpartum thyroid function and a decreased incidence of moderate to advanced postpartum thyroiditis. This review found no difference between levothyroxine therapy and a control for treating pregnant euthyroid women with thyroid peroxidase antibodies for the outcome of pre-eclampsia, however a reduction in preterm birth and a trend towards reduced miscarriage with levothyroxine was shown. This review also showed no difference for pre-eclampsia or preterm birth when selenium was compared with placebo, however a promising reduction in postpartum thyroiditis was shown. Childhood neurodevelopmental delay was not assessed by any trial included in the review. Given that this review is based on four trials of moderate risk of bias, with only two trials contributing data (n = 284), there is insufficient evidence to recommend the use of one intervention for clinical or subclinical hypothyroidism pre-pregnancy or during pregnancy over another, for improving maternal, fetal, neonatal and childhood outcomes.

Plain-language summary: We identified four randomised studies involving only 362 women with hypothyroidism. In one trial of 115 women with thyroid autoantibodies but normal thyroid hormone levels, levothyroxine clearly reduced the risk of preterm birth by 72% compared with no treatment. The risk of women developing pre-eclampsia was not reduced, but there was a trend toward a reduction in miscarriage. In a study of 169 women with autoimmune hypothyroidism, supplementation with selenium did not decrease preterm birth rates or pre-eclampsia, but appeared to reduce moderate to severe inflammation of the thyroid gland and thyroid dysfunction after the birth. The third and fourth studies looked at different doses of levothyroxine on thyroid hormone levels. Levothyroxine is an established treatment for women with symptomatic hypothyroidism, but it may also benefit women with low thyroid levels who do not have symptoms. Selenium also shows promise for women with hypothyroidism but needs further testing.