GEM/cochrane-simplification huggingface dataset:
Abstract: Seven studies enrolling a total of 669 participants were eligible for inclusion in this review. Moderately early steroid treatment (vs placebo or nothing) reduced mortality by 28 days, chronic lung disease at 28 days and 36 weeks, and death or chronic lung disease at 28 days or 36 weeks. Earlier extubation was facilitated. There was no significant effect on the rates of pneumothorax, severe ROP, or NEC. Adverse effects included hypertension, hyperglycaemia, gastrointestinal bleeding, hypertrophic cardiomyopathy and infection. Steroid-treated infants were less likely to need late rescue with dexamethasone. There were limited data from four studies of long term follow-up; these did not show evidence of an increase in adverse neurological outcomes. Moderately early corticosteroid therapy (started at 7-14 days) reduces neonatal mortality and CLD, but at the cost of important short term adverse effects. Limited evidence concerning long term effects is provided by the trials included in this review. The methodological quality of the studies determining the long-term outcome is limited in some cases, the children have been assessed predominantly before school age, and no study has been sufficiently powered to detect important adverse long-term neurosensory outcomes. Therefore, given the risk:benefit ratio of short-term effects and the limited long-term follow-up data, it seems appropriate to reserve moderately early corticosteroid treatment to infants who cannot be weaned from mechanical ventilation and to minimise the dose and duration of any course of therapy. More research is urgently needed, including long term follow-up of survivors included in previous and any future trials, before the benefits and risks of postnatal steroid treatment, including initiation at 7-14 days, can be reliably assessed (See DART study; Doyle 2000a).

Plain-language summary: Steroid drugs have been effective in improving lung function but early use is associated with an increase in adverse effects (see Early Review). The review of trials found that moderately early use of corticosteroids (started at 7-14 days) reduces the risk of developing CLD. There is limited evidence about possible long term harmful effects. Short term adverse effects include high blood pressure, infection and an excess of glucose in the blood of these preterm babies. More research is needed. Steroid use should be limited until more information is available.
Abstract: We identified 15 eligible trials enrolling a total of 1690 infants. Ten trials (1371 infants) compared systemic antifungal prophylaxis versus placebo or no drug. These trials were generally of good methodological quality. Meta-analysis found a statistically significant reduction in the incidence of invasive fungal infection (typical risk ratio (RR) 0.43, 95% confidence interval (CI) 0.31 to 0.59; risk difference (RD) −0.09, 95% CI −0.12 to −0.06). The average incidence of invasive fungal infection in the control groups of the trials (16%) was much higher than that generally reported from large cohort studies. Meta-analysis did not find a statistically significant difference in the risk of death prior to hospital discharge (typical RR 0.79, 95% CI 0.61 to 1.02; typical RD −0.04, 95% CI −0.07 to 0.00). Very limited data on long-term neurodevelopmental outcomes were available. Three trials that compared systemic versus oral or topical non-absorbed antifungal prophylaxis did not detect any statistically significant effects on invasive fungal infection or mortality. Two trials that compared different dose regimens of prophylactic intravenous fluconazole did not detect any significant differences in infection rates or mortality. Prophylactic systemic antifungal therapy reduces the incidence of invasive fungal infection in very preterm or very low birth weight infants. This finding should be interpreted and applied cautiously since the incidence of invasive fungal infection was very high in the control groups of many of the included trials. Meta-analysis does not demonstrate a statistically significant effect on mortality. There are currently only limited data on the long-term neurodevelopmental consequences for infants exposed to this intervention. In addition, there is a need for further data on the effect of the intervention on the emergence of organisms with antifungal resistance.

Plain-language summary: Study characteristics: We identified 15 eligible trials enrolling a total of 1690 infants. These trials were generally of good quality. Key findings: The overall analysis showed a reduction in the risk of severe fungal infection in infants who received systemic antifungal prophylaxis but did not show a difference in the risk of death. The trials did not assess the risk of long-term problems, including disabilities. Conclusions: There is evidence from some good-quality trials that giving infants an antifungal drug regularly for the first four to six weeks after birth reduces the number of infants who develop severe infection. There is not yet any convincing evidence that death or disability rates are affected.
Abstract: Fifty-six studies, with a total of 4076 participants, met the inclusion criteria. Comparing anticonvulsants with placebo, no statistically significant differences for the six outcomes considered. Comparing anticonvulsant versus other drug, 19 outcomes considered, results favour anticonvulsants only in the comparison carbamazepine versus benzodiazepine (oxazepam and lorazepam) for  alcohol withdrawal symptoms (CIWA-Ar score): 3 studies, 262 participants, MD -1.04 (-1.89 to -0.20),  none of the other comparisons reached statistical significance. Comparing different anticonvulsants no statistically significant differences in the two outcomes considered. Comparing anticonvulsants plus other drugs versus other drugs (3 outcomes considered), results from one study, 72 participants, favour paraldehyde plus chloral hydrate versus chlordiazepoxide, for the severe-life threatening side effects, RR 0.12 (0.03 to 0.44). Results of this review do not provide sufficient evidence in favour of anticonvulsants for the treatment of AWS. There are some suggestions that carbamazepine may actually be more effective in treating some aspects of alcohol withdrawal when compared to benzodiazepines, the current first-line regimen for alcohol withdrawal syndrome. Anticonvulsants seem to have limited side effects, although adverse effects are not rigorously reported in the analysed trials.

Plain-language summary: This Cochrane review summarizes evidence from forty-eight randomised controlled trials evaluating the effectiveness and safety of anticonvulsants in the treatment of alcohol withdrawal symptoms. There are limited data comparing anticonvulsants versus placebo and no clear differences between anticonvulsants and other drugs in the rates of therapeutic success. Data on safety outcomes are sparse and fragmented. There is a need for larger, well-designed studies in this field.
Abstract: We included four studies with 1684 participants. Three parallel-group placebo comparisons were in painful diabetic neuropathy (1643 participants), and one cross-over study with diphenhydramine as an active placebo (41 participants) was in lumbar radiculopathy. Doses of topiramate were titrated up to 200 mg/day or 400 mg/day. All studies had one or more sources of potential major bias, as they either used LOCF imputation or were of small size. No study provided first tier evidence for an efficacy outcome. There was no convincing evidence for efficacy of topiramate at 200 to 400 mg/day over placebo. Eighty-two per cent of participants taking topiramate 200 to 400 mg/day experienced at least one adverse event, as did 71% with placebo, and the number needed to treat for an additional harmful effect (NNTH) was 8.6 (95% confidence interval (CI) 4.9 to 35). There was no difference in serious adverse events recorded (6.6% versus 7.5%). Adverse event withdrawals with 400 mg daily were much more common with topiramate (27%) than with placebo (8%), with an NNTH of 5.4 (95% CI 4.3 to 7.1). Lack of efficacy withdrawal was less frequent with topiramate (12%) than placebo (18%). Weight loss was a common event in most studies. No deaths attributable to treatment were reported. Topiramate is without evidence of efficacy in diabetic neuropathic pain, the only neuropathic condition in which it has been adequately tested. The data we have includes the likelihood of major bias due to LOCF imputation, where adverse event withdrawals are much higher with active treatment than placebo control. Despite the strong potential for bias, no difference in efficacy between topiramate and placebo was apparent.

Plain-language summary: On 8 May 2013, we performed searches to look for clinical trials on the use of topiramate to treat neuropathic pain or fibromyalgia. We found four studies of reasonable quality that tested topiramate against placebo for a number of weeks. Almost all of the 1684 people in the studies had painful limbs because of damaged nerves caused by diabetes. Topiramate did not help the pain and was no different from placebo except in causing more side-effects, which made many more people withdraw from the studies early. About 3 people in 10 withdrew because of side-effects with topiramate compared with 1 in 10 with placebo. Topiramate has not been shown to work as a pain medicine in diabetic neuropathy.
Abstract: Two trials were included in the review, totaling 104 participants. One trial assessed additional (four times a day) versus once daily stretching and the other assessed exercise for movement dysfunction versus stretching and strengthening. The first trial, involving 80 elite athletes, suggested additional stretching could reduce time to return to full activity (mean difference (MD) -1.8 days, 95% confidence interval (CI) -2.1 to -1.5, P < 0.001). The second trial, involving 24 participants from a diverse sporting background, did not find conclusive evidence of a difference (MD -14.5 days, 95% CI -30.64 to 1.64, P = 0.08). It did, however, report reduced re-injury rates using exercise for movement dysfunction of 8% versus 64% (odds ratio (OR) 0.05, 95% CI 0.00 to 0.52, P = 0.01). No other outcomes relevant to this review were reported by either study: most notably pain and participant satisfaction. Most proposed physiotherapy techniques for rehabilitation of hamstring injuries have not been assessed using randomised trials. Those that have only have single studies with a limited range of participants and outcomes. There is limited evidence to suggest that time to recovery for elite athletes can be reduced with an increased daily frequency of hamstring stretching exercises. There is preliminary evidence from another small study of mixed ability athletes to suggest that exercise to correct movement dysfunction could reduce time to return to full activity and the risk of re-injury. Further studies are required to check these findings. Until further evidence is available, current practice and widely published rehabilitation protocols cannot either be supported or refuted.

Plain-language summary: Only two randomised studies, totaling 104 participants, were found that compared rehabilitation programmes for this condition. This means that many proposed techniques have not been subjected to proper scrutiny. There is limited evidence from one study to suggest that rate of recovery can be increased with an increased daily frequency of hamstring stretching exercises. There is preliminary evidence from another small study of mixed ability athletes to suggest that exercise to correct movement dysfunction could reduce time to return to full activity and the risk of re-injury. Further studies are required to check these findings and to inform on current practice and the widely published rehabilitation protocols for these injuries.
Abstract: In this update, review authors added one study to the study from the original review. The first relevant study involved 62 adults with recent-onset dilated cardiomyopathy randomly assigned to receive IVIG or an equivalent volume of 0.1% albumin in a blinded fashion. The overall risk of bias was unclear. The incidence of death or the requirement for cardiac transplant or placement of a left ventricular assist device was low in both groups (odds ratio (OR) for event-free survival 0.52, 95% confidence interval (CI) 0.12 to 2.30). Follow-up at six months and at 12 months showed equivalent improvement in LVEF (mean difference (MD) 0.00, 95% CI -0.07 to 0.07 at six months; MD 0.01, 95% CI -0.06 to 0.08 at 12 months). Functional capacity as assessed by peak oxygen consumption was equivalent in the two groups at 12 months (MD -0.80, 95% CI -4.57 to 2.97). Infusion-related side effects were more common in the treated group, but all were reported to be mild (OR 30.16, 95% CI 1.69 to 539.42). The second study added at this update included 83 children in India with suspected viral encephalitis and myocarditis. The overall risk of bias was high. The odds ratio for event-free survival was 7.39 (95% CI 0.91 to 59.86). Follow-up occurred only until hospital discharge, and LVEF was 49.5% in the treated group versus 35.9% in the placebo group (risk difference 13.6%, 95% CI 5.1 to 22.1%; P value = 0.001). Evidence from one trial does not support the use of IVIG for the treatment of adults with presumed viral myocarditis. The only paediatric trial had high risk of bias but suggested that benefit may be seen in the select group of children beyond the neonatal period who have viral encephalitis with myocarditis. Until higher-quality studies have demonstrated benefit in a particular group of patients, IVIG for presumed viral myocarditis should not be provided as routine practice in any situation. Further studies of the pathophysiology of myocarditis would lead to improved diagnostic criteria, which would facilitate future research.

Plain-language summary: This is an update of a previous review, which found only one randomised trial of 62 adults, suggesting that IVIG is not useful in myocarditis. A second trial was added with this update. This trial evaluated 83 children who had the relatively rare combination of myocarditis and encephalitis (inflammation of the brain). Investigators found a lower death rate among children receiving IVIG than in those who did not, but this study had high risk of bias. More study is required before IVIG can be routinely recommended for adults or children with myocarditis.
Abstract: The original review was based on nineteen trials (17 published and two unpublished) including 4580 patients. This update includes twenty four trials (21 published, 3 unpublished) and 4921 patients, although due to patient exclusion and differential reporting 61% to 75% were available for the analyses. The review strongly suggests chemoradiation improves overall survival and progression free survival, whether or not platinum was used with absolute benefits of 10% and 13% respectively. There was, however, statistical heterogeneity for these outcomes. There was some evidence that the effect was greater in trials including a high proportion of stage I and II patients. Chemoradiation also showed significant benefit for local recurrence and a suggestion of a benefit for distant recurrence. Acute haematological and gastrointestinal toxicity was significantly greater in the concomitant chemoradiation group. Late effects of treatment were not well reported and so the impact of chemoradiation on these effects could not be determined adequately. Treatment-related deaths were rare. Concomitant chemoradiation appears to improve overall survival and progression-free survival in locally advanced cervical cancer. It also appears to reduce local and distant recurrence suggesting concomitant chemotherapy may afford radiosensitisation and systemic cytotoxic effects. Some acute toxicity is increased, but the long-term side effects are still not clear.

Plain-language summary: The effect appeared to be greater in trials including a high proportion of patients with early stage disease. Combined chemotherapy/radiotherapy also delayed tumour recurrence and reduced the risk of re-growth near the original cancer site as well as in other parts of the body. There was an increase in side-effects, principally affecting the blood and bowel, but these generally only lasted a short time. Long-term effects were poorly reported.
Abstract: We included eight studies in the review involving a total of 1338 low-risk women in the first stage of spontaneous labour at term. Two comparisons were made; 1) the use of oxytocin versus placebo or no treatment (three trials); 2) the early use of oxytocin versus its delayed use (five trials). There were no significant differences in the rates of caesarean section or instrumental vaginal delivery in either comparison. Early use of oxytocin resulted in an increase in uterine hyperstimulation associated with fetal heart changes. However, the early use of oxytocin versus its delayed use resulted in no significant differences in a range of neonatal and maternal outcomes. Use of early oxytocin resulted in a statistically significant reduction in the mean duration in labour of approximately two hours but did not increase the normal delivery rate. There was significant heterogeneity for this analysis and we carried out a random-effects meta-analysis; however, all of the trials are strongly in the same direction so it is reasonable to conclude that this is the true effect. We also performed a random-effects meta-analysis for the four other analyses which showed substantial heterogeneity in the review. For women making slow progress in spontaneous labour, treatment with oxytocin as compared with no treatment or delayed oxytocin treatment did not result in any discernable difference in the number of caesarean sections performed. In addition there were no detectable adverse effects for mother or baby. The use of oxytocin was associated with a reduction in the time to delivery of approximately two hours which might be important to some women. However, if the primary goal of this treatment is to reduce caesarean section rates, then doctors and midwives may have to look for alternative options.

Plain-language summary: This review of eight studies, involving 1338 low-risk women in the first stage of spontaneous labour at term, showed that oxytocin did not reduce the need for caesarean sections. Neither did it reduce the need for forceps deliveries or increase the number of normal deliveries when compared with no treatment or delayed oxytocin treatment. Oxytocin seemed to shorten labour by nearly two hours on average. The uptake of epidurals was no different. It does not seem to cause harm to the mother or baby, but the sample size was too small to determine if its use has an effect on the death rates of babies. The decision whether to undergo this treatment is one that can reasonably be left to women to decide in the context of a reduction in the length of labour. The included trials used different doses of oxytocin, and different criteria for starting treatment in the delayed oxytocin arm.
Abstract: We found one eligible trial. Participants were 210 newborn infants with birth weight less than 1251 grams. The trial was unblinded but otherwise of good methodological quality. This trial compared removal of an umbilical venous catheter within 10 days after insertion (and replacement with a peripheral cannula or a percutaneously inserted central catheter as required) versus expectant management (UVC in place up to 28 days). More infants in the early planned removal group than in the expectant management group (83 vs 33) required percutaneous insertion of a central catheter (PICC). Trial results showed no difference in the incidence of catheter-related bloodstream infection (RR 0.65, 95% CI 0.35 to 1.22), in hospital mortality (RR 1.12, 95% CI 0.42 to 2.98), in catheter-associated thrombus necessitating removal (RR 0.33, 95% confidence interval 0.01 to 7.94), or in other morbidity. GRADE assessment indicated that the quality of evidence was "low" at outcome level principally as the result of imprecision and risk of surveillance bias due to lack of blinding in the included trial. Currently available trial data are insufficient to show whether early planned removal of umbilical venous catheters reduces risk of infection, mortality, or other morbidity in newborn infants. A large, simple, and pragmatic randomised controlled trial is needed to resolve this ongoing uncertainty.

Plain-language summary: We found only one small randomised controlled trial (including 210 very low birth weight newborn infants) that addressed this question. This trial did not show that early planned removal of UVCs from infants could reduce their chance of developing a bloodstream infection. However, because the trial was small, this finding is not certain. The trial did not provide sufficient evidence to inform policy or practice; larger trials are needed to resolve this question fully.
Abstract: We included eight trials (1563 patients). The drug was IFN alfa-2b in six trials and alfa-2a in two. Trials were heterogeneous in terms of diagnosis of FL, using several classification systems. IFN had been compared with placebo/no intervention in five trials and other chemotherapy in three. The effect of IFN was similar to that of placebo on overall survival (hazard ratio (HR) 0.90, 95% CI 0.61 to 1.34) whereas IFN was more effective when added to chemotherapy (HR 0.68, 95% confidence interval (CI) 0.52 to 0.90). Considering IFN versus all comparators, IFN was effective in prolonging progression-free survival (HR 0.66, 95% CI 0.57 to 0.77) and overall survival (fixed effects HR 0.79, 95% CI 0.67 to 0.94, I2 = 52%). After adjustment for heterogeneity this statistically significance disappeared (random effects HR 0.82, 95% CI 0.63 to 1.08). Toxicity and patients lost to follow up were significantly higher in the IFN groups. There is evidence that addition of IFN as maintenance therapy for FL improves progression-free survival. A net benefit for overall survival is less evident. In the included studies, IFN was associated with significant toxicities that may have a major impact on a patient's quality of life.

Plain-language summary: The aim of this systematic review is to outline the possible benefits (i.e. prolonging survival) and also the disadvantages (adverse events) of therapy with interferon-alpha, administered alone or in combination with other proven drug regimens (otherwise known as chemotherapy) to patients affected by follicular non-Hodgkin's lymphoma. Interferons are proteins secreted by vertebrate cells that exhibit various biological actions. They confer resistance against many different viruses, inhibit proliferation of normal and malignant cells, augment natural killer cell activity, and show several other immunomodulatory functions. Interferons, types alfa-2a or alfa-2b, are usually administered in combination with other drugs to treat a variety of infective and neoplastic diseases. The results showed a significant benefit in progression-free survival in patients treated with interferon-alpha alone or combined with chemotherapy as compared with comparator therapies. There was, however, less evidence that interferon-alpha supported any benefit on overall survival. Furthermore, the presence of relevant drug-related adverse events suggested that a careful analysis of the risks and benefits has to be performed when making a specific clinical decision about this therapy.