GEM/cochrane-simplification huggingface dataset:
Abstract: Eight studies met the inclusion criteria. Three papers compared the effects of anticholinergic drugs with placebo, and a meta-analysis of these results demonstrated no statistically significant benefit of the use of anticholinergic drugs over placebo in any of the outcome measures used. The results of one of these trials could not be included in the meta-analysis but the authors did report significantly lower symptom scores with inhaled anticholinergics compared with placebo. However, there was no significant difference between ipratropium bromide and placebo in the percentage of symptom-free nights or days. Two trials studied the effects of anticholinergics on bronchial hyper responsiveness to histamine, by measuring the provocation dose of histamine needed to cause a fall of 20 % in FEV1 (PD 20). One study (comparing anticholinergics with placebo) reported a statistically significant increase in PD 20 but this was not found in another study (comparing anticholinergics with a beta-2 agonist). Both trials also examined the effect of anticholinergic drugs on diurnal variation in peak expiratory flow rate (PEFR) and reported no significant effect. Two studies compared the addition of an anticholinergic drug to a beta-2 agonist with the beta-2 agonist alone. Both trials failed to show any significant benefit from the long term use of combined anticholinergics with beta-2 agonists compared with beta-2 agonists alone. One trial compared the effects of oral and inhaled anticholinergic drugs with placebo. No statistically significant differences were found in any of the outcome measures except for a higher FEV1 / VC ratio and RV / TLC ratio with oral anticholinergic therapy when compared with placebo. The present review summarises the best evidence available to date. Although there were some small beneficial findings in favour of anticholinergic therapy, there is insufficient data to support the use of anticholinergic drugs in the maintenance treatment of chronic asthma in children.

Plain-language summary: This study undertook a comprehensive search of the literature unrestricted by country of publication or language. Unfortunately small numbers of relevant trials were found and these were of variable quality. This review found that although anticholinergic drugs are well tolerated, in children over two years of age, there is not enough data to be sure if they are better than placebo in terms of effects on lung function or symptoms.
Abstract: Based on a total of 50 RCTs with 7793 patients, naltrexone reduced the risk of heavy drinking to 83% of the risk in the placebo group RR 0.83 (95% CI 0.76 to 0.90) and decreased drinking days by about 4%, MD -3.89 (95% CI -5.75 to -2.04). Significant effects were also demonstrated for the secondary outcomes of the review including heavy drinking days, MD - 3.25 (95% CI -5.51 to -0.99), consumed amount of alcohol, MD - 10.83 (95% CI -19.69 to -1.97) and gamma-glutamyltransferase, MD - 10.37 (95% CI -18.99 to -1.75), while effects on return to any drinking, RR 0.96 (95 CI 0.92 to 1.00) missed statistical significance. Side effects of naltrexone were mainly gastrointestinal problems (e.g. nausea: RD 0.10; 95% CI 0.07 to 0.13) and sedative effects (e.g. daytime sleepiness: RD 0.09; 95% CI 0.05 to 0.14). Based on a limited study sample, effects of injectable naltrexone and nalmefene missed statistical significance. Effects of industry-sponsored studies, RR 0.90 (95% CI 0.78 to 1.05) did not significantly differ from those of non-profit funded trials, RR 0.84 (95% CI 0.77 to 0.91) and the linear regression test did not indicate publication bias (P = 0.765). Naltrexone appears to be an effective and safe strategy in alcoholism treatment. Even though the sizes of treatment effects might appear moderate in their magnitudes, these should be valued against the background of the relapsing nature of alcoholism and the limited therapeutic options currently available for its treatment.

Plain-language summary: 50 studies with 7793 participants were included in the review, in most studies treatment was provided over a period of three months. The review shows that more patients who took naltrexone were able to reduce the amount and frequency of drinking than those who took an identical appearing, but inert substance (placebo). On average, one out of nine patients was helped by naltrexone. Naltrexone does not have serious side effects, but gastrointestinal symptoms like nausea, stomach pain and loss of appetite are common. Some patients also get tired from naltrexone. For injectable formulations of naltrexone, which can be advantageous for patients who have problems with taking their medication on schedule, and the second opioid antagonist nalmefene, the database is still too sparse to allow final conclusions. Nevertheless, the available studies indicate that these drugs might have comparable effects on drinking than oral naltrexone has. Naltrexone does not cause dependency and unlike disulfiram, another medicine that is sometimes used to treat alcohol dependence, it does not make patients feel sick if they drink alcohol while taking it.
Abstract: Two studies met the inclusion criteria. Method of generation of allocation sequence, concealment of allocation and blinding were unclear in both studies. A total of 134 children were allocated to three treatment groups comprising diazepam alone, phenobarbitone and chlorpromazine, or phenobarbitone and chlorpromazine and diazepam.   Meta-analysis of in-hospital deaths indicates that children treated with diazepam alone had a better chance of survival than those treated with combination of phenobarbitone and chlorpromazine (Relative Risk for death 0.36; 95% confidence interval 0.15 to 0.86; Risk Difference -0.22; 95% CI -0.38 to -0.06). Giving diazepam alone, or supplementing conventional anticonvulsants (phenobarbitone and chlorpromazine) with diazepam, was reported in one study to be associated with a statistically significantly milder clinical course and shorter duration of hospitalization. Although this review suggests that diazepam alone compared with combination of phenobarbitone and chlorpromazine may be more effective in treating tetanus, the small size, methodological limitations and lack of data on drug safety from available trials preclude definite conclusions to support change in current clinical practice. The application of this observation should be moderated by local needs and circumstances, pending the availability of better evidence. We recommend a reinforcement of preventive measures against tetanus infection and it is hoped that in the light of clear evidence about the preventive efficacy of tetanus toxoid immunization, concerted efforts should be made towards preventive interventions and ultimate eradication such that there will not be enough case materials for a trial. In the event of a need for a trial, a large prospective, multicenter, randomized controlled trial, which compares diazepam alone with combinations of other drugs (excluding diazepam) will be ideal.

Plain-language summary: The review authors searched the medical literature and identified two randomised controlled trials with a total of 134 hospitalized neonates and older children who had tetanus from Nigeria (19 neonates, seven children aged between one month and 10 years of age) and Indonesia (74 neonates, 34 children aged between three days and 12 years). All drugs were given orally as medications and feeds are usually given via nasogastric tube in the settings where the disease burden is high. Neither study provided information on the safety of the interventions or followed up survivors beyond discharge from hospital.
Abstract: It was not possible to extract the results from the first phases of the two crossover studies and therefore the meta-analyses are based on the two parallel group 6-month studies. There was no indication of a positive effect favouring D-cycloserine for the numbers showing improvement at 6 months as assessed by the Clinical Global Impression for any dose. The number of withdrawals for any reason before end of treatment at 6 months was significantly in favour of placebo (fewer withdrawals) compared with D-cycloserine for dose levels of 30 mg/day (OR 2.94, 95% CI 1.52, 5.70) and 100 mg/day (OR 3.23, 95% CI 1.67, 6.25). There was no significant difference between treatment, (2, 10, 30, 100, or 200 mg/day) and placebo for the number of withdrawals due to adverse events by six months. The lack of a positive effect of D-cycloserine on cognitive outcomes in controlled clinical trials with statistical power high enough to detect a clinically meaningful effect means that D-cycloserine has no place in the treatment of patients with Alzheimer's disease.

Plain-language summary: It was not possible to extract the results from the first phases of two included crossover studies of D-cycloserine for Alzheimer's disease and therefore the meta-analyses are based on the included two parallel group 6-month studies. The lack of a positive effect of D-cycloserine on cognitive outcomes in controlled clinical trials with statistical power high enough to detect a clinically meaningful effect means that D-cycloserine has no place in the treatment of patients with Alzheimer's disease.
Abstract: We identified two new studies for inclusion in the review update; the review now includes seven trials with 622 participants who presented to an emergency department with SVT. All included studies were RCTs, but only three described the randomisation process, and none had blinded participants, personnel, or outcome assessors to the intervention given. Moderate-quality evidence shows no differences in the number of people reverting to sinus rhythm who were treated with adenosine or CCA (89.7% vs 92.9%; OR 1.51, 95% confidence interval (CI) 0.85 to 2.68; participants = 622; studies = 7; I2 = 36%). Low-quality evidence suggests no appreciable differences in major adverse event rates between CCAs and adenosine. Researchers reported only one case of hypotension in the CCA group and none in the adenosine group (0.66% vs 0%; OR 3.09, 95% CI 0.12 to 76.71; participants = 306; studies = 3; I2 = 0%). Included trials did not report length of stay in hospital nor patient satisfaction. Moderate-quality evidence shows no differences in effects of adenosine and calcium channel antagonists for treatment of SVT on reverting to sinus rhythm, and low-quality evidence suggests no appreciable differences in the incidence of hypotension. A study comparing patient experiences and prospectively studied adverse events would provide evidence on which treatment is preferable for management of SVT.

Plain-language summary: This review compares effectiveness and side effects of adenosine and CCAs in terminating SVT episodes. We included in the review seven trials involving 622 patients. Evidence is current to July 2017. Combined analysis of these trials showed no differences between adenosine and CCAs in successfully treating SVT. This finding is based on moderate-quality evidence. A temporary drop in blood pressure that did not require treatment was reported in only one of 152 study participants treated with CCAs, and low-quality evidence suggests that no patients treated with adenosine experienced low blood pressure. We have no data on length of stay in hospital nor on patient satisfaction. Moderate-quality evidence shows no differences in effects of adenosine and calcium channel antagonists for treatment of SVT on reverting to sinus rhythm, and low-quality evidence suggests no differences in cases of hypotension. None of these trials examined patient preferences, which is an important factor in deciding which drug is the 'best' treatment.
Abstract: Three RCTs randomising 853 women, of whom 781 were evaluated, met the inclusion criteria. Meta-analysis of three trials for overall survival (OS) found no statistically significant difference between IDS and chemotherapy alone (hazard ratio (HR) = 0.80, 95% confidence interval (CI) 0.61 to 1.06, I² = 58%). Subgroup analysis for OS in two trials, where the primary surgery was not performed by gynaecologic oncologists or was less extensive, showed a benefit of IDS (HR = 0.68, 95% CI 0.53 to 0.87, I² = 0%). Meta-analysis of two trials for PFS found no statistically significant difference between IDS and chemotherapy alone (HR = 0.88, 95% CI 0.57 to 1.33, I² = 83%). Rates of toxic reactions to chemotherapy were similar in both arms (risk ratio = 1.19, 95% CI 0.53 to 2.66, I² = 0%), but little information was available for other adverse events or quality or life (QoL). We found no conclusive evidence to determine whether IDS between cycles of chemotherapy would improve or decrease the survival rates of women with advanced ovarian cancer, compared with conventional treatment of primary surgery followed by adjuvant chemotherapy. IDS appeared to yield benefit only in women whose primary surgery was not performed by gynaecologic oncologists or was less extensive. Data on QoL and adverse events were inconclusive.

Plain-language summary: This review compares the survival of women with advanced epithelial ovarian cancer, who had IDS performed between cycles of chemotherapy after primary surgery, with survival of women who had conventional treatment (primary debulking surgery and adjuvant chemotherapy). It found similar survival rates in women who did and did not receive IDS. Not enough information about adverse effects was available. Information on quality of life of the women was also inconclusive.
Abstract: Twelve trials (seven with duration of at least three months) met the inclusion criteria, with 19,715 participants randomised. The two largest trials that were conducted in the USA (SELECT and NPC) reported clinical events. There were no statistically significant effects of selenium supplementation on all cause mortality (RR 0.97, 95% CI 0.88 to 1.08), CVD mortality (RR 0.97, 95% CI 0.79 to 1.2), non-fatal CVD events (RR 0.96, 95% CI 0.89 to 1.04) or all CVD events (fatal and non-fatal) (RR 1.03, 95% CI 0.95 to 1.11). There was a small increased risk of type 2 diabetes with selenium supplementation but this did not reach statistical significance (RR 1.06, 95% CI 0.97 to 1.15). Other adverse effects that increased with selenium supplementation, as reported in the SELECT trial, included alopecia (RR 1.28, 95% CI 1.01 to 1.62) and dermatitis grade 1 to 2 (RR 1.17, 95% CI 1.0 to 1.35). Selenium supplementation reduced total cholesterol but this did not reach statistical significance (WMD - 0.11 mmol/L, 95% CI - 0.3 to 0.07). Mean high density lipoprotein (HDL) levels were unchanged. There was a statistically significant reduction in non-HDL cholesterol (WMD - 0.2 mmol/L, 95% CI - 0.41 to 0.00) in one trial of varying selenium dosage. None of the longer term trials examined effects on blood pressure. Overall, the included studies were regarded as at low risk of bias. The limited trial evidence that is available to date does not support the use of selenium supplements in the primary prevention of CVD.

Plain-language summary: This review assessed the effects of providing selenium supplements to healthy adults in order to prevent the occurrence of cardiovascular disease. Whether selenium supplements would reduce the risk factors associated with heart disease was also examined. We found 12 trials in which 19,715 healthy adults were randomly assigned to receive selenium supplements or placebo. The vast majority of participants involved in these trials were male individuals from the US, where people are already well nourished and take large amounts of selenium from natural foods. Overall, the included studies were regarded as at low risk of bias. In our review, providing selenium supplements to healthy adults did not prevent the occurrence of major cardiovascular disease. The increased risk of developing type 2 diabetes when taking selenium supplements, as suggested in some previous studies, could not definitely be ruled out in our review. In summary, this review of the available evidence to date suggests that taking selenium supplements is neither beneficial nor harmful for cardiovascular disease, but it is probably unnecessary for those who are already well nourished and who take large amounts of selenium from natural foods.
Abstract: Fifteen studies (8 parallel, 7 crossover; 352 patients) were included. Only one study enrolled women. Studies evaluated the effects of phosphodiesterase-5 inhibitors (PDE5i), zinc, vitamin E, vitamin D or bromocriptine compared to placebo. PDE5i significantly increased the overall International Index of Erectile Function-5 (IIEF-5) score (2 studies, 101 patients, MD 10.65, 95% CI 5.34 to 15.96), all its individual domains and the complete 15-item IIEF tool (1 study, 41 patients, MD 2.64, 95% CI 1.32 to 3.96). End of treatment testosterone levels were not significantly increased by addition of zinc to dialysate (2 studies, 22 patients, MD 0.21 ng/mL, 95% CI -2.14 to 2.55) but oral zinc improved end of treatment testosterone levels (1 study, 20 patients, SMD 1.62, 95% CI 0.58 to 2.66). There was no difference in plasma luteinizing and follicle-stimulating hormone levels at the end of the study period with zinc therapy. Only sparse data were available for vitamin E, bromocriptine and dihydroxycholecalciferol in CKD patients and there were no studies of intracavernous injections, transurethral injections, mechanical devices or psychosexual therapies in people with CKD. PDE5i and zinc are promising interventions for treating sexual dysfunction in men with CKD. Evidence supporting their routine use in CKD patients is limited. There is an unmet need for studying interventions for both male and female sexual dysfunction in CKD, considering the significant disease burden.

Plain-language summary: We identified 15 studies enrolling 352 patients with only one study enrolling both men and women. Studies evaluated the effects of phosphodiesterase-5 inhibitors (PDE5i), zinc, vitamin E, vitamin D or bromocriptine compared to placebo. In two studies (101 patients) PDE5i significantly increased the individual domains and the overall International Index of Erectile Function-5 (IIEF-5) score and the complete 15-item IIEF tool (1 study, 41 patients). End of treatment testosterone levels were not significantly increased by addition of zinc to dialysate (2 studies, 22 patients) but oral zinc improved end of treatment testosterone levels (1 study, 20 patients). There was no difference in plasma luteinizing and follicle-stimulating hormone levels at the end of the study period with zinc therapy. Little data were available for vitamin E, bromocriptine and dihydroxycholecalciferol in CKD patients and there were no studies of intracavernous injections, transurethral injections, mechanical devices or behavioural therapy in people with CKD. PDE5i and zinc are promising interventions for treating sexual dysfunction in men with CKD however evidence supporting their routine use in CKD patients is limited. There is an unmet need for studying interventions for both male and female sexual dysfunction in CKD, considering the significant disease burden.
Abstract: Seven studies with a total of 2422 participants were included in this systematic review. Meta-analysis could be performed with the data of four included studies, with a total of 1382 participants. The methodological quality of the included trials was relatively low. Evidence of a beneficial effect of culturing in low oxygen concentration was found for live birth rate (OR 1.39; 95% CI 1.11 to 1.76; P = 0.005; I2 = 0%); this would mean that a typical clinic could improve a 30% live birth rate using atmospheric oxygen concentration to somewhere between 32% and 43% by using a low oxygen concentration. The results were very similar for ongoing and clinical pregnancy rates. There was no evidence that culturing embryos under low oxygen concentrations resulted in higher numbers of adverse events such as multiple pregnancies, miscarriages or congenital abnormalities. The results of this systematic review and meta-analysis suggest that culturing embryos under conditions with low oxygen concentrations improves the success rates of IVF and ICSI, resulting in the birth of more healthy newborns.

Plain-language summary: The results of clinical studies that have been undertaken to study the effect on the outcomes of IVF and ICSI procedures of culturing embryos under low oxygen concentrations have been conflicting. Therefore, we performed a systematic review and meta-analysis of the literature to find the best available evidence. It has shown that culturing embryos under low oxygen concentrations does indeed improve clinical outcomes after IVF and ICSI, such as number of deliveries (live birth rate) and ongoing and clinical pregnancy rates. Furthermore, no evidence was found of an increased risk of adverse events such as multiple pregnancies, miscarriages and congenital abnormalities. We concluded that culturing embryos under low oxygen concentrations seems beneficial with an increase in the number of newborns, but more studies are needed to strongly prove this effect.
Abstract: Sixteen trials were included in the review and fourteen contained data in a suitable form for quantitative analysis. Most comparisons did not show differences between rTMS and other interventions. No difference was seen between rTMS and sham TMS using the Beck Depression Inventory or the Hamilton Depression Rating Scale, except for one time period (after two weeks of treatment) for left dorsolateral prefrontal cortex and high frequency; and also for right dorsolateral prefrontal cortex and low frequency, both in favour of rTMS and both using the Hamilton scale. Comparison of rTMS (left dorsolateral prefrontal cortex and high frequency) with electroconvulsive therapy showed no difference except for psychotic patients after two weeks treatment, using the Hamilton scale, which indicated that electroconvulsive therapy was more effective than rTMS. The information in this review suggests that there is no strong evidence for benefit from using transcranial magnetic stimulation to treat depression, although the small sample sizes do not exclude the possibility of benefit.

Plain-language summary: It has been used for physiological studies and it has also been proposed as a treatment for depression. Sixteen trials were included in the review and fourteen contained data in a suitable form for quantitative analysis. Most comparisons did not show differences between repetitive (rTMS) and other interventions. No difference was seen between rTMS and sham TMS using the Beck Depression Inventory or the Hamilton Depression Rating Scale, except for one time period (after two weeks of treatment) for left dorsolateral prefrontal cortex and high frequency; and also for right dorsolateral prefrontal cortex and low frequency, both in favour of rTMS and both using the Hamilton scale. Comparison of rTMS (left dorsolateral prefrontal cortex and high frequency) with electroconvulsive therapy showed no difference except for psychotic patients after two weeks treatment, using the Hamilton scale, which indicated that electroconvulsive therapy was more effective than rTMS.