GEM/cochrane-simplification huggingface dataset:
Abstract: One randomised trial was identified and included in the review. It was of low methodological quality. The trial compared D-penicillamine versus placebo in 70 patients with primary sclerosing cholangitis. Compared with placebo, D-penicillamine therapy had no significant effect on mortality (RR 1.14, 95% CI 0.49 to 2.64), liver transplantation (RR 1.11, 95% CI 0.39 to 3.17), hepatic histologic progression (RR 1.17, 95% CI 0.79 to 1.74), or cholangiographic deterioration (RR 0.87, 95% CI 0.43 to 1.79). D-penicillamine led to a significant improvement in the serum aspartate aminotransferase (WMD -23.00 U/L; 95% CI -30.66 to -15.34), but not in serum bilirubin level (WMD 0.40 mg/L; 95% CI -0.19 to 0.99) and serum alkaline phosphatases activity (WMD 44.00 U/L; 95% CI -37.89 to 125.89). There were significantly more adverse events in patients receiving D-penicillamine (P = 0.013). There is not sufficient evidence to support or refute the use of D-penicillamine for patients with primary sclerosing cholangitis. We do not recommend the use of D-penicillamine for patients with primary sclerosing cholangitis outside randomised trials.

Plain-language summary: The only identified randomised clinical trial did not demonstrate any beneficial effect of D-penicillamine on the course, complications, and survival of patients with primary sclerosing cholangitis. In addition, its use was associated with a number of adverse events. Therefore, we cannot recommend the use of D-penicillamine outside randomised trials.
Abstract: Forty-one RCTs with a total of 2732 participants (1564 cell therapy, 1168 controls) were eligible for inclusion. Cell treatment was not associated with any changes in the risk of all-cause mortality (34/538 versus 32/458; RR 0.93, 95% CI 0.58 to 1.50; 996 participants; 14 studies; moderate quality evidence), cardiovascular mortality (23/277 versus 18/250; RR 1.04, 95% CI 0.54 to 1.99; 527 participants; nine studies; moderate quality evidence) or a composite measure of mortality, reinfarction and re-hospitalisation for heart failure (24/262 versus 33/235; RR 0.63, 95% CI 0.36 to 1.10; 497 participants; six studies; moderate quality evidence) at long-term follow-up. Statistical heterogeneity was low (I2  = 0% to 12%). Serious periprocedural adverse events were rare and were generally unlikely to be related to cell therapy. Additionally, cell therapy had no effect on morbidity, quality of life/performance or LVEF measured by magnetic resonance imaging. Meta-analyses of LVEF measured by echocardiography, single photon emission computed tomography and left ventricular angiography showed evidence of differences in mean LVEF between treatment groups although the mean differences ranged between 2% and 5%, which are accepted not to be clinically relevant. Results were robust to the risk of selection, performance and attrition bias from individual studies. The results of this review suggest that there is insufficient evidence for a beneficial effect of cell therapy for AMI patients. However, most of the evidence comes from small trials that showed no difference in clinically relevant outcomes. Further adequately powered trials are needed and until then the efficacy of this intervention remains unproven.

Plain-language summary: Randomised trials comparing bone marrow-derived cells with no cells in patients diagnosed with acute myocardial infarction were eligible for this review. We searched databases to March 2015. This review was supported by the National Institute of Health Research (NIHR) through its Cochrane Incentive Award programme. In this updated systematic review we analysed data from a total of 41 trials with over 2700 patients. Evaluation of the currently available evidence indicates that this treatment may not lead to improvement when compared to standard treatment, as measured by the frequency of deaths, heart attacks and/or heart failure requiring re-hospitalisation following treatment, as well as tests of heart function, in the short and long term. The evidence in this review is of moderate quality due to the small number of events.
Abstract: Only one trial, involving 256 children, met the inclusion criteria for this review. This study was assessed as having high risk of bias because of non-random allocation, incomplete outcome data and insufficient control of confounding factors. Results from this study suggest that centre-based day care may have a positive effect on child cognitive ability compared with no treatment (care at home) (assessed using a modified version of the British Ability Scale-II (BAS-II) (standardised mean difference (SMD) 0.74, 95% confidence interval (CI) 0.48 to 1.00, 256 participants, 1 study, very low-quality evidence). This study did not measure other variables relevant to this review. The single study included in this review provides limited evidence on the effects of centre-based day care for children younger than five years of age in low- and middle-income countries. This study was at high risk of bias and may have limited generalisability to other low- and middle-income countries. Many of the studies excluded from this review paired day care attendance with co-interventions that are unlikely to be provided in normal day care centres. Effectiveness studies on centre-based day care without these co-interventions are few, and the need for such studies is significant. In future studies, comparisons might include home visits or alternative day care arrangements.

Plain-language summary: We included studies that assessed the effects of centre-based day care for children younger than five years of age in low- and middle-countries. To isolate the effects of day care, we excluded interventions that involved medical, psychological or non–child-focused co-interventions. Of the 34,902 citations identified through electronic searches, we found only one study that met our inclusion criteria. This study was based in Kenya, Uganda and Tanzania/Zanzibar and included 256 children. Evidence is current to April 2014. The one included study reported positive effects of centre-based day care on the cognitive development of children. It did not report the effects of centre-based day care on children's psychosocial development, the incidence or prevalence of infectious diseases, parental employment or household income. This review includes only one trial. This study did not assign participants to the intervention by chance, so the comparison groups may have differed in important ways. Therefore results must be interpreted with caution. Although current studies do not now allow for conclusive judgements regarding the effects of centre-based day care on the development of children and the economic situation of parents, this does not imply that these services are not important in low- and middle-income countries. Effectiveness studies of centre-based day care without co-interventions are few, and the need for such studies is significant. This review is one of a pair of reviews; researchers and practitioners may find evidence from the high-income country review to be informative also (Van Urk 2014).
Abstract: We included five RCTs (with 264 women) comparing gonadotrophins plus metformin versus gonadotrophins. The gonadotrophin used was recombinant FSH in four studies and highly purified FSH in one study. Evidence was of low quality: The main limitations were serious risk of bias due to poor reporting of study methods and blinding of participants and outcome assessors. Live birth Metformin plus FSH was associated with a higher cumulative live birth rate when compared with FSH (odds ratio (OR) 2.31, 95% confidence interval (CI) 1.23 to 4.34; two RCTs, n = 180; I2 = 0%; low-quality evidence). This suggests that if the chance of live birth after FSH is assumed to be 27%, then the chance after addition of metformin would be between 32% and 60%. Other pregnancy outcomes Metformin use was associated with a higher ongoing pregnancy rate (OR 2.46, 95% CI 1.36 to 4.46; four RCTs, n = 232; I2 = 0%; low-quality evidence) and a higher clinical pregnancy rate (OR 2.51, 95% CI 1.46 to 4.31; five RCTs, n = 264; I2 = 0%; low-quality evidence). Multiple pregnancy Results showed no evidence of a difference in multiple pregnancy rates between metformin plus FSH and FSH (OR 0.55, 95% CI 0.15 to 1.95; four RCTs, n = 232; I2 = 0%; low-quality evidence) and no evidence of a difference in rates of miscarriage or OHSS. Other adverse effects Evidence was inadequate as the result of limited available data on adverse events after metformin compared with after no metformin (OR 1.78, 95% CI 0.39 to 8.09; two RCTs, n = 91; I2 = 0%; very low-quality evidence). Preliminary evidence suggests that metformin may increase the live birth rate among women undergoing ovulation induction with gonadotrophins. At this moment, evidence is insufficient to show an effect of metformin on multiple pregnancy rates and adverse events. Additional trials are necessary before we can provide further conclusions that may affect clinical practice.

Plain-language summary: We included five randomised controlled trials of women with PCOS undergoing gonadotrophin treatment for ovulation induction. This review of trials compared metformin or placebo added to gonadotrophins for ovulation induction. Evidence is current to July 2016. We were able to include only five trials with a total of 264 women. We graded the quality of the evidence as low. We found no evidence of a difference in risk of multiple pregnancy between metformin and placebo, but we noted higher rates of live birth, ongoing pregnancy and clinical pregnancy with metformin. Evidence was of low quality for live birth, ongoing pregnancy, clinical pregnancy and multiple pregnancy. Limitations of the evidence included inadequate reporting of study methods and blinding of participants and outcome assessors.
Abstract: We included four studies in this review (251 participants), and found few significant differences between treatment and comparison groups for the outcomes of interest. Blood phenylalanine levels were significantly lower in participants with phenylketonuria following a low-phenylalanine diet compared to those on a less restricted diet, mean difference (MD) at three months -698.67 (95% confidence interval (CI) -869.44 to -527.89). Intelligence quotient was significantly higher in participants who continued the diet than in those who stopped the diet, MD after 12 months 5.00 (95% CI 0.40 to 9.60). However, these results came from a single study. The results of non-randomised studies have concluded that a low-phenylalanine diet is effective in reducing blood phenylalanine levels and improving intelligence quotient and neuropsychological outcomes. We were unable to find any randomised controlled studies that have assessed the effect of a low-phenylalanine diet versus no diet from diagnosis. In view of evidence from non-randomised studies, such a study would be unethical and it is recommended that low-phenylalanine diet should be commenced at the time of diagnosis. There is uncertainty about the precise level of phenylalanine restriction and when, if ever, the diet should be relaxed. This should be addressed by randomised controlled studies.

Plain-language summary: Other studies suggest that a low-phenylalanine diet can reduce blood phenylalanine levels. The review includes four studies, but we were not able to combine many results. Results from one study showed that blood phenylalanine levels were lower and intelligent quotient higher for people on a special diet. We recommend that a low-phenylalanine diet should be followed from the time of diagnosis. More research is needed to show if it is safe to relax this diet later on.
Abstract: Four trials, enrolling a total of 614 infants, compared low (restrictive) to high (liberal) haemoglobin thresholds. Restrictive thresholds tended to be similar, but one trial used liberal thresholds much higher than the other three. There were no statistically significant differences in the combined outcomes of death or serious morbidity at first hospital discharge (typical risk ratio (RR) 1.19; 95% confidence interval (CI) 0.95 to 1.49) or in component outcomes. Only the largest trial reported follow-up at 18 to 21 months corrected gestational age; in this study there was no statistically significant difference in a composite of death or adverse neurodevelopmental outcome (RR 1.06; 95% CI 0.95 to 1.19). One additional trial comparing transfusion for clinical signs of anaemia versus transfusion at a set level of haemoglobin or haematocrit, reported no deaths and did not address disability. The use of restrictive as compared to liberal haemoglobin thresholds in infants of very low birth weight results in modest reductions in exposure to transfusion and in haemoglobin levels. Restrictive practice does not appear to have a significant impact on death or major morbidities at first hospital discharge or at follow-up. However, given the uncertainties of these conclusions, it would be prudent to avoid haemoglobin levels below the lower limits tested here. Further trials are required to clarify the impact of transfusion practice on long term outcome.

Plain-language summary: This review of five studies compares the effects of blood transfusion at low levels of haemoglobin to transfusion at high levels. Within the levels tested, there were no differences seen in survival, in the serious complications of prematurity, or in longer term development as measured at 18 to 21 months past the baby's due date. Allowing the baby to become a little more anaemic did not affect the baby's weight gain or breathing patterns. These conclusions are not firm, because too few babies have been studied. Our overall recommendation is not to exceed the higher levels of haemoglobin used in these trials, and thus diminish the risks of over-transfusion, but not to allow the level of haemoglobin to fall below the lower limits tested in these studies until further studies are completed.
Abstract: Thirty randomized controlled studies (21 blinded, four open and five active control) with a total of 3682 subjects were included. For each outcome, there were few studies with available data. For the proportion of patients with pain relief (eight studies) pooled data showed benefits for the treatment group, with an NNT at 4 weeks of 11[95% CI 6-36] and at 12 weeks of 7 [95% CI 5-12]. In terms of adverse drug reactions, the NNH was 16 [95% CI 12-27] for discontinuation of therapy. Nausea and vomiting were reported in 24 studies with a non-significant trend for greater risk in the treatment group. One study showed a small improvement in quality of life for the treatment group at 4 weeks. The small number of studies in each subgroup with relevant data limited our ability to explore the most effective bisphosphonates and their relative effectiveness for different primary neoplasms. There is evidence to support the effectiveness of bisphosphonates in providing some pain relief for bone metastases. There is insufficient evidence to recommend bisphosphonates for immediate effect; as first line therapy; to define the most effective bisphosphonates or their relative effectiveness for different primary neoplasms. Bisphosphonates should be considered where analgesics and/or radiotherapy are inadequate for the management of painful bone metastases.

Plain-language summary: This review looked at the effect of bisphosphonates on pain caused by bone metastases. Bisphosphonates do have some effect but are not as useful as either strong analgesics (such as morphine) or radiotherapy. However, where other methods of pain relief are inadequate, the addition of bisphosphonates can be beneficial. Bisphosphonates can cause nausea and vomiting.
Abstract: A total of 16,558 patients from four trials contributed to the analyses. The methodological quality was high in all four trials. The anticoagulants tested were unfractionated heparin (UFH) and low molecular-weight heparin. Aspirin was used as control in all trials. Overall, there was no evidence that anticoagulants were superior to aspirin in reducing 'death or dependency' at long-term follow-up (odds ratio (OR) 1.07, 95% confidence interval (CI) 0.98 to 1.15). Compared with aspirin, anticoagulants were associated with a small but significant increase in the number of deaths at the end of follow-up (OR 1.10, 95% CI 1.01 to 1.29), equivalent to 20 more deaths (95% CI 0 to 30) per 1000 patients treated; a significant increased risk of symptomatic intracranial haemorrhage (OR 2.35, 95% CI 1.49 to 3.46); and a non-significant increased risk of 'any recurrent stroke' during treatment (OR 1.20, 95% CI 0.99 to 1.46). These neutral or adverse effects outweighed a small, but significant effect on symptomatic deep vein thrombosis (OR 1.20, 95% CI 0.07 to 0.58), equivalent to 10 fewer (95% CI 0 to 30) DVTs by 14 days per 1000 patients treated with anticoagulants instead of aspirin. Subgroup analysis could not identify any type, dose, or route of administration of anticoagulants associated with net benefit, or any benefit in patients with atrial fibrillation. Overall, the combination of UFH and aspirin did not appear to be associated with a net advantage over aspirin alone. A subgroup analysis showed that, compared with aspirin, the combination of low-dose UFH and aspirin was associated with a marginally significant reduced risk of 'any recurrent stroke' (OR 0.75, 95% CI 0.56 to 1.03) and a marginally significant reduced risk of death at 14 days (OR 0.84, 95% CI 0.69 to 1.01), and with no clear adverse effect on death at end of follow-up (OR 0.98, 95% CI 0.85 to 1.12). Anticoagulants offered no net advantages over antiplatelet agents in acute ischaemic stroke. The combination of low-dose UFH and aspirin appeared in a subgroup analysis to be associated with net benefits compared with aspirin alone, and this merits further research.

Plain-language summary: This review aimed to test whether any anticoagulant regimen offers net advantages over antiplatelet agents, overall, or in specific categories of patients. There was no evidence that anticoagulants are superior to antiplatelet agents (in fact, anticoagulants caused a small increase in the number of deaths at long-term follow-up). However, the combination of low-dose anticoagulant and aspirin seemed to offer benefits over aspirin alone, and the combination should be investigated further.
Abstract: Twelve trials on artificial or bioartificial support systems versus standard medical therapy (483 patients) and two trials comparing different artificial support systems (105 patients) were included. Most trials had unclear methodological quality. Compared to standard medical therapy, support systems had no significant effect on mortality (RR 0.86; 95% CI 0.65 to 1.12) or bridging to liver transplantation (RR 0.87; 95% CI 0.73 to 1.05), but a significant beneficial effect on hepatic encephalopathy (RR 0.67; 95% CI 0.52 to 0.86). Meta-regression indicated that the effect of support systems depended on the type of liver failure (P = 0.03). In subgroup analyses, artificial support systems appeared to reduce mortality by 33% in acute-on-chronic liver failure (RR 0.67; 95% CI 0.51 to 0.90), but not in acute liver failure (RR 0.95; 95% CI 0.71 to 1.29). Two trials comparing artificial support systems showed significant mortality reductions with intermittent versus continuous haemofiltration (RR 0.58; 95% CI 0.36 to 0.94) and no significant difference between five versus ten hours of charcoal haemoperfusion (RR 1.03; 95% CI 0.65 to 1.62). The incidence of adverse events was inconsistently reported. This Review indicates that artificial support systems may reduce mortality in acute-on-chronic liver failure. Artificial and bioartificial support systems did not appear to affect mortality in acute liver failure. However, considering the strength of the evidence additional randomised clinical trials are needed before any support system can be recommended for routine use.

Plain-language summary: Evidence from twelve small randomised trials were combined. Most trials had unclear methodologic quality. Overall, support systems did not appear to affect mortality or bridging to transplantation, but had a beneficial effect on hepatic encephalopathy. The risk of adverse events could not be established. Further evidence is needed before support systems can be recommended for routine use.
Abstract: Seven RCTs (1205 patients) were included in the review. Stone-free rates were lower in patients who underwent ESWL (7 studies, 1205 participants: RR 0.84, 95% CI 0.73 to 0.96) but re-treatment rates were lower in ureteroscopy patients (6 studies, 1049 participants: RR 6.18, 95% CI 3.68 to 10.38. ESWL-treated patients had less need for auxiliary treatment (5 studies, 751 participants: RR 0.43, 95% CI 0.25 to 0.74; fewer complications (7 studies, 1205 participants: RR 0.54, 95% CI 0.33 to 0.88); and shorter length of hospital stay (2 studies, 198 participants: MD -2.55 days, 95% CI -3.24 to -1.86). Three studies adequately described the randomisation sequence, three studies were unclear on how they randomised, while one study had a high risk of selection bias. All the studies had an unclear risk of performance bias and detection bias, while all had a low risk of attrition bias, reporting bias, or other sources of bias identified. Compared with ESWL, ureteroscopic removal of ureteral stones achieves a greater stone-free state, but with a higher complication rate and longer hospital stay.

Plain-language summary: We analysed reports from seven randomised controlled trials of 1205 patients and found that ureteroscopy provided a better stone-free rate after treatment, but patients had to stay in hospital longer, and there was a higher risk of complications. We found that there were many variations among the seven studies in their design, duration, and data collected which made comparison and evaluation challenging. We recommend that further evaluation and research is conducted to ensure that new and improved treatments and studies are considered to inform clinical practice.