GEM/cochrane-simplification huggingface dataset:
Abstract: Only one study met the criteria of inclusion in the review. This study compared oral zinc with placebo. Oral zinc was administered in a dose of 5 mL twice daily from day 2 to day 7 postpartum. The drug was administered into the mouth of the infant by the plastic measure provided with the bottle or with a spoon. Incidence of hyperbilirubinaemia, defined as serum total bilirubin (STB) ≥ 15 mg/dL, was similar between groups (N = 286; risk ratio (RR) 0.94, 95% confidence interval (CI) 0.58 to 1.52). Mean STB levels, mg/dL, at 72 ± 12 hours were comparable in both the groups (N = 286; mean difference (MD) -0.20; 95% CI -1.03 to 0.63). Although the duration of phototherapy in the zinc group was significantly shorter compared to the placebo group (N = 286; MD -12.80, 95% CI -16.93 to -8.67), the incidence of need for phototherapy was comparable across both the groups (N = 286; RR 1.20; 95% CI 0.66 to 2.18). Incidences of side effects like vomiting (N = 286; RR 0.65, 95% CI 0.19 to 2.25), diarrhoea (N = 286; RR 2.92, 95% CI 0.31 to 27.71), and rash (N = 286; RR 2.92, 95% CI 0.12 to 71.03) were found to be rare and statistically comparable between groups. The limited evidence available has not shown that oral zinc supplementation given to infants up to one week old reduces the incidence of hyperbilirubinaemia or need for phototherapy.

Plain-language summary: Researchers from Cochrane searched for all available literature up to 30 November 2014. One randomised controlled trial met our inclusion criteria. In this review, the efficacy of oral zinc salt was compared with placebo. One study enrolling 294 infants was identified. This study evaluated oral zinc salt, given in a dose of 5 mg twice daily to infants between 25 and 168 hours old. The administration of oral zinc salt did not affect the incidence of jaundice (hyperbilirubinaemia) in these infants.
Abstract: There were no new included studies for this update. Eight studies (3118 participants) were included in this review. We found no evidence for difference in overall mortality between the groups treated with heparin and placebo (risk ratio (RR) = 0.84, 95% confidence interval (CI) 0.36 to 1.98). Heparins compared with placebo, reduced the occurrence of myocardial infarction in patients with unstable angina and NSTEMI (RR = 0.40, 95% CI 0.25 to 0.63, number needed to benefit (NNTB) = 33). There was a trend towards more major bleeds in the heparin studies compared to control studies (RR = 2.05, 95% CI 0.91 to 4.60). From a limited data set, there appeared to be no difference between patients treated with heparins compared to control in the occurrence of thrombocytopenia (RR = 0.20, 95% CI 0.01 to 4.24). Assessment of overall risk of bias in these studies was limited as most of the studies did not give sufficient detail to allow assessment of potential risk of bias. Compared with placebo, patients treated with heparins had a similar risk of mortality, revascularization, recurrent angina, and thrombocytopenia. However, those treated with heparins had a decreased risk of myocardial infarction and a higher incidence of minor bleeding. Overall, the evidence assessed in this review was classified as low quality according to the GRADE approach. The results presented in this review must therefore be interpreted with caution.

Plain-language summary: This review of trials found that UFH and LMWH when given to patients with high-risk unstable angina or NSTEMI in the acute phase of treatment, in addition to standard therapy with aspirin, prevent more heart attacks than placebo but do not reduce mortality, the need for revascularization procedures or recurrent angina. Although there was limited reporting of side-effects, heparins caused more cases of minor bleeding.
Abstract: This review includes 15 trials with a total of 791 participants that have evaluated Pycnogenol® for the treatment of seven different chronic disorders. These included asthma (two studies; N = 86), attention deficit hyperactivity disorder (one study; N = 61), chronic venous insufficiency (two studies; N = 60), diabetes mellitus (four studies; N = 201), erectile dysfunction (one study; N = 21), hypertension (two studies; N = 69) and osteoarthritis (three studies; N = 293). Two of the studies were conducted exclusively in children; the others involved adults. Due to small sample size, limited numbers of trials per condition, variation in outcomes evaluated and outcome measures used, as well as the risk of bias in the included studies, no definitive conclusions regarding the efficacy or safety of Pycnogenol® are possible. Current evidence is insufficient to support Pycnogenol® use for the treatment of any chronic disorder. Well-designed, adequately powered trials are needed to establish the value of this treatment.

Plain-language summary: We chose to focus on Pycnogenol® as this supplement is a standardised product, many trials have been conducted, and it is extensively marketed internationally. Our review aimed to assess the efficacy and safety of Pycnogenol® as a treatment for chronic disorders. We identified 15 eligible randomised controlled trials with a total of 791 participants which addressed seven different chronic conditions: asthma (two studies); attention deficit hyperactivity disorder (one study), chronic venous insufficiency (two studies), diabetes (four studies), erectile dysfunction (one study), hypertension (two studies) and osteoarthritis (three studies). Due to small sample size, limited number of trials per condition, variation in outcomes evaluated and outcome measures used, as well as the risk of bias in the included studies, no definite conclusions regarding the efficacy and safety of Pycnogenol® are possible.
Abstract: We included three trials, involving 496 participants, and defined four trials as waiting assessment. All three included trials were of edaravone plus another treatment compared with the other treatment alone. The dose of edaravone injections in the three trials was the same at 60 mg per day. The course of treatment in all three trials is 14 days. None of the included trials reported the pre-specified primary outcome of death or dependency defined using the modified Rankin scale during the follow-up period. The three trials evaluated the effect of edaravone at different times and using different methods. All three trials reported adverse events; there were no differences between the treatment group and the control group. Overall, edaravone appeared to increase the proportion of participants with marked neurological improvement compared with the control group, and the difference was significant (risk ratio (RR) 1.99, 95% confidence interval (CI) 1.60 to 2.49). The risk of bias in the included trials was moderate and the sample was small. Hence, although the data in this review show an effective treatment trend of edaravone for acute ischaemic stroke, further large, high-quality trials are required to confirm this trend.

Plain-language summary: Data from some experimental and human studies have suggested that edaravone, a neuroprotective agent, may be beneficial for people with acute ischaemic stroke. It has been widely used in China to treat stroke. To obtain a reliable assessment of the effects of edaravone in acute ischaemic stroke, we reviewed data from three studies involving 496 participants. The quality of the trials was moderate. It would appear that edaravone is an effective treatment for acute ischaemic stroke. However, more high-quality and bigger sample trials are needed to confirm this result.
Abstract: Five trials that randomly assigned 144 participants with overt hepatic encephalopathy that were published during 1979 to 1982 were included. Three trials assessed levodopa, and two trials assessed bromocriptine. The mean daily dose was 4 grams for levodopa and 15 grams for bromocriptine. The median duration of treatment was 14 days (range seven to 56 days). None of the trials followed participants after the end of treatment. Only one trial reported adequate bias control; the remaining four trials were considered to have high risk of bias. Random-effects model meta-analyses showed that dopamine agents had no beneficial or detrimental effect on hepatic encephalopathy in the primary analyses (15/80 (19%) versus 14/80 (18%); odds ratio (OR) 2.99, 95% confidence interval (CI) 0.09 to 100.55; two trials) or when paired data from cross-over trials were included (OR 1.04, 95% CI 0.75 to 1.43). Clear evidence of intertrial heterogeneity was identified both in the primary analysis (I2 = 65%) and when paired data from cross-over trials were included (I2 = 40%). Dopamine agents had no beneficial or harmful effect on mortality (42/144 (29%) versus 38/144 (26%); OR 1.11, 95% CI 0.35 to 3.54; five trials). Trial sequential analyses demonstrated that we lacked information to refute or recommend the interventions for all outcomes. Dopamine agonists did not seem to increase the risk of adverse events. This review found no evidence to recommend or refute the use of dopamine agents for hepatic encephalopathy. More randomised placebo-controlled clinical trials without risks of systematic errors and risks of random errors seem necessary to permit firm decisions on dopamine agents for patients with hepatic encephalopathy.

Plain-language summary: We performed the present systematic review to determine the beneficial and harmful effects of dopamine agents for patients with hepatic encephalopathy. Our analyses included five small trials published in 1982 or earlier. All trials but one had high risks of bias (i.e., risks of systematic errors or risks of overestimation of beneficial effects or risks of underestimation of harmful effects). Only 144 patients were included in the five trials, and accordingly risks of random errors (i.e., play of chance) are present. Our analyses showed no significant differences regarding symptoms of hepatic encephalopathy or mortality in patients treated with dopamine agents compared with patients who received an inactive placebo or no intervention. The number of patients with adverse events seemed comparable in the two intervention groups. Based on the available evidence, we conclude that no evidence can be found to recommend or refute the use of dopamine agents for hepatic encephalopathy. More randomised placebo-controlled clinical trials without risks of systematic errors and risks of random errors seem necessary to obtain firm evidence on dopamine agents for patients with hepatic encephalopathy.
Abstract: We identified a single cross-over RCT (enrolling 9 participants) that compared home haemodialysis (long hours: 6 to 8 hours, 3 times/week) with in-centre haemodialysis (short hours: 3.5 to 4.5 hours, 3 times/weeks) for 8 weeks in prevalent home haemodialysis patients. Outcome data were limited and not available for the end of the first phase of treatment in this cross-over study which was at risk of bias due to differences in dialysate composition between the two treatment comparisons. Overall, home haemodialysis reduced 24 hour ambulatory blood pressure and improved uraemic symptoms, but increased treatment-related burden of disease and interference in social activities. Insufficient data were available for mortality, hospitalisation or dialysis vascular access complications or treatment durability. Insufficient randomised data were available to determine the effects of home haemodialysis on survival, hospitalisation, and quality of life compared with in-centre haemodialysis. Given the consistently observed benefits of home haemodialysis on quality of life and survival in uncontrolled studies, and the low prevalence of home haemodialysis globally, randomised studies evaluating home haemodialysis would help inform clinical practice and policy.

Plain-language summary: We found that only one study that involved nine patients had compared home haemodialysis with in-centre haemodialysis. There was insufficient information to understand the effects of home haemodialysis on survival or need for hospital admission in this study. Home haemodialysis may improve blood pressure and physical symptoms, but may increase the burden of care for families and patients. Given the potential benefits of home haemodialysis in non-randomised studies, larger randomised trials of home haemodialysis could help inform clinical care and policy.
Abstract: Ten RCTs were included. One trial reported near final height in girls and found that girls treated with GH were 7.5 cm taller than untreated controls (GH group, 155.3 cm ± 6.4; control, 147.8 cm ± 2.6; P = 0.003); another trial which reported adult height standard deviation score found that children treated with GH were 3.7 cm taller than children in a placebo-treated group (95% confidence intervals 0.03 to 1.10; P < 0.04). The other trials reported short term outcomes. Results suggest that short-term height gains can range from none to approximately 0.7 SD over one year. One study reported health related quality of life and showed no significant improvement in GH treated children compared with those in the control group, whilst another found no significant evidence that GH treatment impacts psychological adaptation or self-perception in children with ISS. No serious adverse effects of treatment were reported. GH therapy can increase short-term growth and improve (near) final height. Increases in height are such that treated individuals remain relatively short when compared with peers of normal stature. Large, multicentre RCTs are required which should focus on final height and address quality of life and cost issues.

Plain-language summary: Ten studies included altogether 741 children and lasted between six months and 6.2 years. Results showed that individuals treated with growth hormone remain relatively short when compared with peers of normal stature. Girls treated with growth hormone were 7.5 cm taller than untreated controls (growth hormone treated group 155.3 cm and control group 147.8 cm); another trial found that children treated with growth hormone were 3.7 cm taller than children in a placebo-treated group. No serious adverse effects were reported in the included studies. Although serious adverse effects (there has been concern that growth hormone would induce new tumours or increase the likelihood of tumour relapse) may be rare, their possibility must also be taken into consideration.
Abstract: There was one trial with 20 participants (16 females) included in the review. The mean age of participants was 13.1 years. The trial was a double-blinded, randomised cross-over trial which had a duration of 12 months in total and compared high-dose and low-dose pancreatic enzyme therapy. As only the abstract of the trial was available, the overall risk of bias was judged to be unclear. The trial did not address either of our primary outcomes (time until resolution of DIOS and treatment failure rate), but reported episodes of acute DIOS, presence of abdominal mass and abdominal pain. There were no numerical data available for these outcomes, but the authors stated that there was no difference between treatment with high-dose or low-dose pancreatic enzymes. The overall quality of the evidence was found to be very low. There is a clear lack of evidence for the treatment of DIOS in people with cystic fibrosis. The included abstract did not address our primary outcome measures and did not provide numerical data for the two secondary outcomes it did address. Therefore, we cannot justify the use of high-dose pancreatic enzymes for treating DIOS, nor can we comment on the efficacy and safety of other laxative agents. From our findings, it is clear that more randomised controlled trials need to be conducted in this area.

Plain-language summary: We found the overall quality of the evidence to be very low. The trial itself was only published as an abstract from a conference which did not include numerical data and it was not published as a full report. This meant that we do not know many details about the trial. We thought that the overall risk of bias was unclear, as the trial authors did not describe how participants were put into the treatment groups, whether any participants dropped out or whether the planned outcomes were the same as the reported outcomes. The trial also had a very small number of participants and a limited age range, making it difficult to draw conclusions about the relevance of the treatment for all people with cystic fibrosis.
Abstract: We included one study that met our selection criteria; a double-masked, placebo-controlled, randomised trial of high dose intravenous steroids in patients with indirect TON diagnosed within seven days of the initial injury. A total of 31 eligible participants were randomised to receive either high dose intravenous steroids (n = 16) or placebo (n = 15), and they were all followed-up for three months. Mean final best corrected visual acuity (BCVA) was 1.78±1.23 Logarithm of the Minimum Angle of Resolution (LogMAR) in the placebo group, and 1.11±1.14 LogMAR in the steroid group. The mean difference in BCVA between the placebo and steroid groups was 0.67 LogMAR (95% confidence interval -1.54 to 0.20), and this difference was not statistically significant (P = 0.13). At three months follow-up, an improvement in BCVA of 0.40 LogMAR occurred in eight eyes (8/15, 53.3%) in the placebo group, and in 11 eyes (11/16, 68.8%) in the treatment group. This difference was not statistically significant (P = 0.38). There is a relatively high rate of spontaneous visual recovery in TON and there is no convincing data that steroids provide any additional visual benefit over observation alone. Recent evidence also suggests a possible detrimental effect of steroids in TON and further studies are urgently needed to clarify this important issue. Each case therefore needs to be assessed on an individual basis and proper informed consent is paramount.

Plain-language summary: The recommendations in this review are based on a critical analysis of the available evidence in the medical literature. We found only one, relatively small, randomised controlled trial of steroids in TON, which included 31 participants within seven days of their initial injury. These participants received either high dose intravenous steroids (n = 16) or placebo (n = 15). At three months follow-up, no significant difference in best corrected visual acuity was found between these two groups. There is a relatively high rate of spontaneous visual recovery in TON and no convincing data that steroids provide any additional benefit over observation alone. Each case needs to be assessed on an individual basis and the patient needs to be made fully aware of the possibility of a serious adverse reaction, although rare, to steroids. Furthermore, recent studies have highlighted possible detrimental effects of steroids when used in brain and spinal cord injuries and these new lines of evidence need to be considered seriously.
Abstract: Fifty-three double-blind RCTs evaluating a thiazide in 15129 hypertensive patients (baseline BP of 156/101 mmHg) were included. Hydrochlorothiazide was the thiazide used in 49/53 (92%) of the included studies. The additional BP reduction caused by the thiazide as a second drug was estimated by comparing the difference in BP reduction between the combination and monotherapy groups. Thiazides as a second-line drug reduced BP by 6/3 and 8/4 mmHg at doses of 1 and 2 times the manufacturer's recommended starting dose respectively. The BP lowering effect was dose related. The effect was similar to that obtained when thiazides are used as a single agent. Only 3 double-blind RCTs evaluating loop diuretics were identified. These RCTs showed a BP lowering effect of a starting dose of about 6/3 mmHg. Thiazides when given as a second-line drug have a dose related effect to lower blood pressure that is similar to when they are added as a first-line drug. This means that the BP lowering effect of thiazides is additive. Loop diuretics appear to have a similar blood pressure lowering effect as thiazides at 1 times the recommended starting dose. Because of the short duration of the trials and lack of reporting of adverse events, this review does not provide a good estimate of the incidence of adverse effects of diuretics given as a second-line drug.

Plain-language summary: We performed a search of the available scientific literature to find all trial evidence to assess this question. Fifty-six trials were found. Fifty-three trials involved thiazide diuretics (92% with the drug hydrochlorothiazide) and included a total of 15310 participants. Adding a thiazide to another anti-hypertensive drug further reduces the BP by an additional 6/3 mmHg when given at the starting dose and reduces BP by 8/4 mmHg at 2 times the starting dose. This is approximately the same effect as when the drugs are used alone. A good estimate of the harms associated with diuretics cannot be estimated in this review because of the lack of reporting and the short duration of the trials.
Abstract: This review included three studies. However, data for progestogen-releasing intrauterine systems were available from only one study that compared 29 women with a levonorgestrel (LNG)-IUS versus 29 women with a combined oral contraceptive (COC) for treating uterine fibroids. There was a significant reduction of menstrual blood loss (MBL) in women receiving the LNG-IUS compared to the COC using the alkaline hematin test (mean difference (MD) 77.5%, 95% CI 71.3% to 83.67%, 58 women) and a pictorial assessment chart (PBAC) (MD 34.5%, 95% CI 14.9% to 54.1%, 58 women). The reduction in uterine fibroid size was significantly greater in the leuprorelin group at 16 weeks compared to the progestogen lynestrenol group (MD -15.93 mm, 95% CI -18.02 to -13.84 mm, 46 women). There was no RCT evaluating the effect of DMPA on uterine fibroids. Progestogen-releasing intrauterine systems appear to reduce menstrual blood loss in premenopausal women with uterine fibroids. Oral progestogens did not reduce fibroid size or fibroid- related symptoms. However, there was a methodological limitation and the one included study with data had a small sample size. This evidence is insufficient to support the use of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids.

Plain-language summary: The progestogen-releasing (levonorgestrel) intrauterine system (LNG-IUS) is a device placed inside the uterus that releases the hormone progesterone and can cause endometrial suppression. In this review, three randomised controlled studies were included. Two randomised controlled studies included 131 women and evaluated the beneficial and harmful effects of the LNG-IUS compared with hysterectomy or a low dose combined oral contraceptive (COC). However, the results were from only one study that compared 29 women with an LNG-IUS versus 29 women with COC for treating uterine fibroids. The LNG-IUS appeared to reduce menstrual blood loss and increase haemoglobin levels in premenopausal women with uterine fibroids. Reduction of fibroid size was not significant. In one study that included 56 women treated with preoperative oral progestogens (lynestrenol) compared with gonadotropin-releasing hormone (GnRH) agonist, the uterine fibroid size was not different. There was no randomised controlled study of DMPA to treat uterine fibroids. The included studies were of poor quality and had small numbers of participants. Indeed, the authors did not recommend the use of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids. More high quality randomized controlled studies evaluating progestogens or progestogen-releasing intrauterine systems for treating uterine fibroids that have an adequate sample size are needed.