GEM/cochrane-simplification huggingface dataset:
Abstract: Eight randomized controlled trials fulfilled the inclusion criteria for this review. Four trials enrolled healthy older people, and four recruited participants with mild to moderate cognitive impairment or dementia with or without diagnosed folate deficiency. Pooling the data was not possible owing to heterogeneity in sample selections, outcomes, trial duration, and dosage. Two studies involved a combination of folic acid and vitamin B12. There is no adequate evidence of benefit from folic acid supplemententation with or without vitamin B12 on cognitive function and mood of unselected healthy elderly people. However, in one trial enrolling a selected group of healthy elderly people with high homocysteine levels, 800 mcg/day folic acid supplementation over three years was associated with significant benefit in terms of global functioning (WMD 0.05, 95% CI 0.004 to 0.096, P = 0.033); memory storage (WMD 0.14, 95% CI 0.04 to 0.24, P = 0.006) and information-processing speed (WMD 0.09, 95% CI 0.02 to 0.16, P = 0.016). Four trials involved people with cognitive impairment. In one pilot trial enrolling people with Alzheimer's disease, the overall response to cholinesterase inhibitors significantly improved with folic acid at a dose of 1mg/day (odds ratio: 4.06, 95% CI 1.22 to 13.53; P = 0.02) and there was a significant improvement in scores on the Instrumental Activities of Daily Living and the Social Behaviour subscale of the Nurse's Observation Scale for Geriatric Patients (WMD 4.01, 95% CI 0.50 to 7.52, P = 0.02). Other trials involving people with cognitive impairment did not show any benefit in measures of cognitive function from folic acid, with or without vitamin B12. Folic acid plus vitamin B12 was effective in reducing serum homocysteine concentrations (WMD -5.90, 95% CI -8.43 to -3.37, P < 0.00001). Folic acid was well tolerated and no adverse effects were reported. The small number of studies which have been done provide no consistent evidence either way that folic acid, with or without vitamin B12, has a beneficial effect on cognitive function of unselected healthy or cognitively impaired older people. In a preliminary study, folic acid was associated with improvement in the response of people with Alzheimer's disease to cholinesterase inhibitors. In another, long-term use appeared to improve the cognitive function of healthy older people with high homocysteine levels.  More studies are needed on this important issue.

Plain-language summary: Eight trials met the criteria for inclusion. It was not possible to pool the data because the trials studied different populations, tested folic acid in different doses, and used different outcome measures. There were two trials of folic acid in conjunction with B12. The analysis showed significant benefit of folic acid over placebo in some measures of cognition in a long-term trial recruiting elderly people with high homocysteine levels from a general population. In one pilot trial, 1 mg/day of folic acid was associated with significant improvement in behavioural response to cholinesterase inhibitors in people with Alzheimer's disease.
Abstract: Outcomes were evaluated separately for unopposed oestrogen and oestrogen combined with progestogen regimens. No statistically significant difference was found in mean weight gain between those using unopposed oestrogen and non-HRT users (0.03kg, 95% CI -0.61 to 0.67) and those using oestrogen with progestogen therapy and non-HRT users (0.04 kg, 95% CI -0.42 to 0.50). There was no significant difference in body mass index (BMI) between women using unopposed oestrogen and non-HRT users (-0.14, 95% CI -0.40 to 0.12) or oestrogen combined with progestogen and non-HRT users (-0.10, 95% CI -0.27 to 0.07). Insufficient data were available to enable meta-analysis of the effect of HRT on waist to hip ratio, fat mass or skinfold thickness. There is no evidence of an effect of unopposed oestrogen or combined oestrogen with progestogen on body weight and on the BMI increase normally experienced at the time of menopause. Insufficient evidence currently exists to enable examination of the effect of HRT on waist-hip ratio, fat mass or skinfold thickness.

Plain-language summary: The review of trials found no evidence that unopposed oestrogen and combined oestrogen and progestogen have an effect on body weight additional to that usually gained at the time of menopause. The review did not find any evidence that HRT prevents weight gain experienced at menopause.
Abstract: Two trials were included; one comparing the McRobert's manoeuvre and suprapubic pressure with no prophylactic manoeuvres in 185 women likely to give birth to a large baby and one trial comparing the use of the McRobert's manoeuvre versus lithotomy positioning in 40 women. We decided not to pool the results of the two trials. One study reported 15 cases of shoulder dystocia in the therapeutic (control) group compared to five in the prophylactic group (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.17 to 1.14) and the other study reported one episode of shoulder dystocia in both prophylactic and lithotomy groups. In the first study, there were significantly more caesarean sections in the prophylactic group and when these were included in the results, significantly fewer instances of shoulder dystocia were seen in the prophylactic group (RR 0.33, 95% CI 0.12 to 0.86). In this study, 13 women in the control group required therapeutic manoeuvres after delivery of the fetal head compared to three in the treatment group (RR 0.31, 95% CI 0.09 to 1.02). One study reported no birth injuries or low Apgar scores recorded. In the other study, one infant in the control group had a brachial plexus injury (RR 0.44, 95% CI 0.02 to 10.61), and one infant had a five-minute Apgar score less than seven (RR 0.44, 95% CI 0.02 to 10.61). There are no clear findings to support or refute the use of prophylactic manoeuvres to prevent shoulder dystocia, although one study showed an increased rate of caesareans in the prophylactic group. Both included studies failed to address important maternal outcomes such as maternal injury, psychological outcomes and satisfaction with birth. Due to the low incidence of shoulder dystocia, trials with larger sample sizes investigating the use of such manoeuvres are required.

Plain-language summary: Various manoeuvres are used to assist the passage of the baby through the birth canal by manipulating the fetal shoulders and increasing the functional size of the pelvis. These manoeuvres can also be used before the baby's head appears to prevent the fetal shoulders becoming trapped in the maternal pelvis (shoulder dystocia). In this review, the two studies involving 25 women were not large enough to show if manoeuvres such as manipulating the mother's pelvis can prevent instances of shoulder dystocia. Rates of birth injury did not appear to be affected by carrying out the manoeuvres early. Neither study addressed important maternal outcomes such as maternal injury, psychological outcomes and satisfaction with birth. Because shoulder dystocia is a rare occurrence, more studies involving larger groups of women are required to properly assess the benefits and adverse outcomes associated with such interventions.
Abstract: Eleven studies were included in the review (791 participants). Studied psychostimulants included dexamphetamine, bupropion, methylphenidate and modafinil. No significant differences were found between psychostimulants and placebo for any of the studied efficacy outcomes. Overall retention in studies was low (50.4%). Psychostimulants did not reduce amphetamine use (mean difference (MD) -0.26, 95% confidence interval (CI) -0.85 to 0.33) or amphetamine craving (MD 0.07, 95% CI -0.44 to 0.59) and did not increase sustained abstinence (relative risk (RR) 1.12, 95% CI 0.84 to 1.49). The proportion of adverse events inducing dropout was similar for psychostimulants and placebo (risk difference (RD) 0.01, 95% CI -0.03 to 0.04). The main findings did not change in any subgroup analysis. Results of this review do not support the use of psychostimulant medications at the tested doses as a replacement therapy for amphetamine abuse or dependence. Future research could change this conclusion, as the numbers of included studies and participants are limited and information on relevant outcomes, such as efficacy according to the severity of dependence or craving, is still missing.

Plain-language summary: In this review, the efficacy and safety of psychostimulants for amphetamine abuse or dependence were studied. We found eleven studies enrolling 791 amphetamine-dependent participants and assessing the effects of four different psychostimulants: dexamphetamine, bupropion, methylphenidate and modafinil. Psychosocial interventions were additionally provided to all participants. The studies were conducted in the USA, Australia or Northern Europe, and study length ranged from 8 to 20 weeks. Psychostimulants did not reduce amphetamine use or amphetamine craving and also did not increase sustained abstinence in comparison with placebo. Retention in treatment was similar and low with both treatments. Psychostimulants also did not increase the risk of adverse events that were intense enough to induce dropouts. Research with larger and longer trials is needed to determine whether psychostimulants can be a useful replacement therapy for patients with amphetamine abuse or dependence. The design of future trials should consider the level of dependence at study entry, the potency and the dose of the psychostimulant administered, the length of the trial and the representativeness of included participants.
Abstract: We included three trials (353 participants). Two trials compared intranasal corticosteroids to placebo and one trial compared intranasal corticosteroids to usual care; no trials studied oral corticosteroids. In the two placebo-controlled trials, no benefit of intranasal corticosteroids was demonstrated for duration or severity of symptoms. The risk of bias overall was low or unclear in these two trials. In a trial of 54 participants, the mean number of symptomatic days was 10.3 in the placebo group, compared to 10.7 in those using intranasal corticosteroids (P value = 0.72). A second trial of 199 participants reported no significant differences in the duration of symptoms. The single-blind trial in children aged two to 14 years, who were also receiving oral antibiotics, had inadequate reporting of outcome measures regarding symptom resolution. The overall risk of bias was high for this trial. Mean symptom severity scores were significantly lower in the group receiving intranasal steroids in addition to oral amoxicillin. One placebo-controlled trial reported the presence of rhinovirus in nasal aspirates and found no differences. Only one of the three trials reported on adverse events; no differences were found. Two trials reported secondary bacterial infections (one case of sinusitis, one case of acute otitis media; both in the corticosteroid groups). A lack of comparable outcome measures meant that we were unable to combine the data. Current evidence does not support the use of intranasal corticosteroids for symptomatic relief from the common cold. However, there were only three trials, one of which was very poor quality, and there was limited statistical power overall. Further large, randomised, double-blind, placebo-controlled trials in adults and children are required to answer this question.

Plain-language summary: Our evidence is current to May 2015. We found three trials in total. Two trials recruited adults from the general population or from among hospital staff in Finland. These trials (total 253 adults) compared intranasal steroid sprays, which allow steroids to be puffed into the nostrils, to sprays containing placebo only. We found a third trial, which recruited 100 children referred to outpatient clinics in an Iranian paediatric hospital. This trial compared intranasal steroid spray to no spray and gave oral antibiotics to all participants. Neither of the two trials comparing steroid spray to placebo spray in adults showed a benefit of steroids across a range of different measures. The trial comparing steroid spray to no spray in children did find some evidence of benefit but we rated the quality of the evidence from this trial as very poor and the results were unclear. We could not combine the results of the trials to assess this question further. There were no reports of adverse events. The available evidence suggests that we should not use intranasal steroids for the common cold. However, as we found only three small trials, we cannot be sure that there is no effect without performing larger, well-designed trials.
Abstract: Five studies (316 adult patients) were included. Four compared thiazides with standard treatment (periodic clinical follow-up and increased water intake) or specific dietary recommendations and one analysed the effect of thiazide plus a neutral potassium salt. There was a significant decrease in the number of new stone recurrences in those treated with thiazides (RR 1.61, 95% CI 1.33 to 1.96), although the follow-up periods varied. The stone formation rate also showed a statistically significant decrease in the patients treated with diuretics (MD -0.18, 95% CI -0.30 to -0.06). Thiazides plus potassium salts significantly decreased calciuria and vitamin D levels. There is some evidence that in patients with idiopathic hypercalciuria and recurrent stones, the addition of thiazides to a normal or modified diet for short to long periods (five months to three years) reduced the number of stone recurrences and decreased the stone formation rate. Thiazides and neutral potassium phosphate decreased calciuria in symptomatic patients with idiopathic hypercalciuria. There were no studies investigating the effect of pharmacological treatment on other clinical complications or asymptomatic idiopathic hypercalciuria.

Plain-language summary: The aim of this review was to evaluate the benefits and harms of drug treatments for preventing the complications of idiopathic hypercalciuria. We identified four studies comparing thiazides (diuretics) with either standard treatment of clinical follow-up and increased water intake or specific dietary recommendations and one study comparing thiazides plus a potassium salt. There was a decrease in the number of new stones in the group receiving thiazides as well as an increase in the time taken for new stone formation. The addition of potassium salts to thiazide treatment significantly reduced the amount of calcium excreted in the urine. No studies in children were identified and there were no studies investigating the use of drug treatment for those with hypercalciuria but were symptom free.
Abstract: Nine studies (3519 patients) were included. Four RCTs included patients with multiple vessel disease, five focused on single vessel disease. Four studies reported beyond 1 year. No statistical differences were observed between CABG and stenting for meta-analysis of mortality or AMI, but there was heterogeneity. Composite cardiac event and revascularisation rates were lower for CABG than for stents. Odds ratios resulting from meta-analysis of event rate data at 1 year were, odds ratio 0.43 (95% CI 0.35 to 0.54) and at 3 years, odds ratio 0.37 (95% CI 0.29 to 0.48). Odds ratios for revascularisation at 1 year were, odds ratio 0.18 (95% CI 0.13 to 0.25) and at 3 years, odds ratio 0.09 (95% CI 0.02 to 0.34). Binary restenosis at 6 months (single vessel trials) favoured CABG, odds ratio 0.29 (95% CI 0.17 to 0.51). CABG is associated with reduced rates of major adverse cardiac events, mostly driven by reduced repeat revascularisation. However, the RCT data are limited by follow-up, unrepresentative samples and rapid development of both surgical techniques and stenting. Research on real-world patient population or patient level data meta-analyses may identify risk factors and groupings who may benefit most from one strategy over the other.

Plain-language summary: Risk of death or heart attack following either treatment appeared the same, but this may be because too few trial participants were collected together in the review and variation between trials (heterogeneity) may be masking true differences. Further trials of new techniques in a greater variety of patients with subsequent systematic review are needed.
Abstract: Eight studies involving 2007 patients met the inclusion criteria. Five studies compared supervised injected heroin plus flexible dosages of methadone treatment to oral methadone only and showed that heroin helps patients to remain in treatment (valid data from 4 studies, N=1388 Risk Ratio 1.44 (95%CI 1.19-1.75) heterogeneity P=0.03), and to reduce use of illicit drugs. Maintenance with supervised injected heroin has a not statistically significant protective effect on mortality (4 studies, N=1477 Risk Ratio 0.65 (95% CI 0.25-1.69) heterogeneity P=0.89), but it exposes at a greater risk of adverse events related to study medication (3 studies N=373 Risk Ratio 13.50 (95% CI 2.55-71.53) heterogeneity P=0.52). Results on criminal activity and incarceration were not possible to be pooled but where the outcome were measured results of single studies do provide evidence that heroin provision can reduce criminal activity and incarceration/imprisonment. Social functioning improved in all the intervention groups with heroin groups having slightly better results. If all the studies comparing heroin provision in any conditions vs any other treatment are pooled the direction of effect remain in favour of heroin. The available evidence suggests an added value of heroin prescribed alongside flexible doses of methadone for long-term, treatment refractory, opioid users, to reach a decrease in the use of illicit substances, involvement in criminal activity and incarceration, a possible reduction in mortaliity; and an increase in retention in treatment. Due to the higher rate of serious adverse events, heroin prescription should remain a treatment for people who are currently or have in the past failed maintenance treatment, and it should be provided in clinical settings where proper follow-up is ensured.

Plain-language summary: The authors of the review identified eight randomised studies involving 2007 adult patients with a history of previous treatment failures in outpatient settings. The heroin users on the programs were requested to attend the clinic to receive and inject prescribed heroin from two to three times a day. Adverse events were consistently more frequent in the heroin groups. The trialists recommend that the treatment should be properly established so that necessary intensive care can be provided in an emergency. According with the current evidence, heroin prescription should be indicated to people who is currently or have previously failed maintenance treatment, and it should be provided in clinical settings where proper follow-up is ensured.
Abstract: Only one trial satisfying the selection criteria could be identified. In this trial, comparing the effect of the benzodiazepine, lorazepam, with dexmedetomidine, a selective alpha-2-adrenergic receptor agonist, on delirium among mechanically ventilated intensive care unit patients, dexmedetomidine treatment was associated with an increased number of delirium- and coma-free days compared with lorazepam treated patients (dexmedetomidine patients, average seven days; lorazepam patients, average three days; P = 0.01). One partially controlled study showed no advantage of a benzodiazepine (alprazolam) compared with neuroleptics in treating agitation associated with delirium, and another partially controlled study showed decreased effectiveness of a benzodiazepine (lorazepam), and increased adverse effects, compared with neuroleptics (haloperidol, chlorpromazine) for the treatment of acute confusion. No adequately controlled trials could be found to support the use of benzodiazepines in the treatment of non-alcohol withdrawal related delirium among hospitalised patients, and at this time benzodiazepines cannot be recommended for the control of this condition. Because of the scarcity of trials with randomization of patients, placebo control, and adequate concealment of allocation of subjects, it is clear that further research is required to determine the role of benzodiazepines in the treatment of non-alcohol withdrawal related delirium.

Plain-language summary: A systematic review of benzodiazepine treatment of non-alcohol related delirium discovered very few trials (one randomized, controlled study of mechanically ventilated patients, and thus poorly reflective of delirious patients as a whole; and two partially controlled studies), the results of which indicate that at this time there is no evidence to support the use of benzodiazepines in the treatment of non-alcohol withdrawal related delirium among hospitalised patients.
Abstract: We included three trials in this review (n = 197 participants). Study sample sizes ranged from 33 to 123 participants. Low-quality evidence indicates no clinically important differences between MCE and spinal manipulative therapy for pain at short term and for disability at short term and long term. Low-quality evidence also suggests no clinically important differences between MCE and other forms of exercise for pain at short or intermediate term and for disability at intermediate term or long term follow-up. Moderate-quality evidence shows no clinically important differences between MCE and other forms of exercise for disability at short term follow-up. Finally, very low-quality evidence indicates that addition of MCE to medical management does not provide clinically important improvement for pain or disability at short term follow-up. For recurrence at one year, very low-quality evidence suggests that MCE and medical management decrease the risk of recurrence by 64% compared with medical management alone. We identified only three small trials that also evaluated different comparisons; therefore, no firm conclusions can be drawn on the effectiveness of MCE for acute LBP. Evidence of very low to moderate quality indicates that MCE showed no benefit over spinal manipulative therapy, other forms of exercise or medical treatment in decreasing pain and disability among patients with acute and subacute low back pain. Whether MCE can prevent recurrences of LBP remains uncertain.

Plain-language summary: We included in this review three trials evaluating acute or subacute pain in patients with LBP (n = 197 participants). Most participants were middle-aged and were recruited from primary or tertiary care centres. Duration of treatment programmes ranged from four weeks to six weeks. MCE showed no benefit over spinal manipulative therapy, other forms of exercise or medical treatment for reducing pain or disability among patients with acute and subacute LBP. Whether MCE can prevent recurrences of LBP remains unclear. Results of this review include evidence of very low to moderate quality. We downgraded all comparisons for imprecision due to small study sample sizes.