GEM/cochrane-simplification huggingface dataset:
Abstract: Only one randomised controlled trial of treatment was identified. This trial compared the effectiveness of thalidomide with placebo and included 22 patients, 12 in the treatment group and 10 in the placebo group. Patients on the treatment arm received thalidomide 200 mg twice daily for 5 days. The main end point was the measurement of the progression of skin detachment after seven days. Other end points were the overall mortality and severity of the disease evaluated with the simplified acute physiology score. The study was terminated as the mortality on the treatment arm was 83% compared to 30% on the control arm (relative risk 2.78, 95% confidence interval 1.04 to 7.40). No randomised controlled trials of the most commonly used current treatments i.e. systemic steroids, cyclosporin A and intravenous immunoglobulins were found. Treatment with thalidomide was not shown to be effective and was associated with significantly higher mortality than placebo. There is no reliable evidence on which to base treatment for toxic epidermal necrolysis, a disease commonly associated with mortality rates of around 30%. More research is required to understand the mechanisms of toxic epidermal necrolysis. International multi-centre studies are needed in the form of randomised controlled trials, to evaluate treatments for toxic epidermal necrolysis, especially those using high doses of steroid and intravenous immunoglobulins.

Plain-language summary: This review of trials did not find any reliable evidence for the treatment of TEN. The only trial available used thalidomide, but this trial did not show any benefit from treatment compared against placebo but highlighted increased chances of dying from the treatment. Thalidomide is not safe or effective for the skin condition toxic epidermal necrolysis, but there is not enough evidence to show which treatments are effective.
Abstract: Five trials involving 187 women with an age range of 15 to 40 years were included. Oral isoxsuprine was compared with placebo in two trials; terbutaline oral spray, ritodrine chloride and oral hydroxyphenyl-orciprenalin were compared with placebo in a further three trials. Clinical diversity in the studies in terms of the interventions being evaluated, assessments at different time points and the use of different assessment tools mitigated against pooling of outcome data across studies in order to provide a summary estimate of effect for any of the comparisons. Only one study, with unclear risk of bias, reported pain relief with a combination of isoxsuprine, acetaminophen and caffeine. None of the other studies reported any significant clinical difference in effectiveness between the intervention and placebo. Adverse effects were reported with all of these medications in up to a quarter of the total number of participants. They included nausea, vomiting, dizziness, quivering, tremor and palpitations. The evidence presented in this review was based on a few relatively small-sized studies that were categorised to have unclear to high risk of bias, which does not allow confident decision-making at present about the use of beta2-adrenoceptor agonists for dysmenorrhoea. The benefits as reported in one study should be balanced against the wide array of unacceptable side effects documented with this class of medication. We have emphasised the lack of precision and limitations in the reported data where appropriate.

Plain-language summary: Five studies involving 187 females with an age range of 15 to 40 years were included in this review. Oral isoxsuprine was examined in two studies; terbutaline oral spray, ritodrine chloride and oral hydroxyphenyl-orciprenalin were compared with placebo in a further three studies. All of the studies were conducted over 30 years ago and none were of high quality. None of these medications, other than isoxsuprine combined with acetaminophen and caffeine, were reported to have any beneficial effect. Side effects with these medications were reported in up to a quarter of the participants and included nausea, vomiting, dizziness, quivering, tremor and palpitations. At present there is insufficient evidence to allow confident decision-making about the use of beta2-adrenoceptor agonists for dysmenorrhoea.
Abstract: We included nine trials involving 3137 participants. We did not identify any new trials for inclusion in this updated review. None of the studies reported data on the primary outcome in sufficient detail to enable analysis for the review. Overall, there was a moderate risk of bias in the included studies. Compared with UFH, there was no evidence of an effect of LMWH or heparinoids on death from all causes during the treatment period (96/1616 allocated LMWH/heparinoid versus 78/1486 allocated UFH; odds ratio (OR) 1.06, 95% CI 0.78 to 1.47; 8 trials, 3102 participants, low quality evidence). LMWH or heparinoid were associated with a significant reduction in deep vein thrombosis (DVT) compared with UFH (OR 0.55, 95% CI 0.44 to 0.70, 7 trials, 2585 participants, low quality evidence). However, the number of the major clinical events such as pulmonary embolism (PE) and intracranial haemorrhage was too small to provide a reliable estimate of the effects. Treatment with a LMWH or heparinoid after acute ischaemic stroke appears to decrease the occurrence of DVT compared with standard UFH, but there are too few data to provide reliable information on their effects on other important outcomes, including functional outcome, death and intracranial haemorrhage.

Plain-language summary: We looked for randomised controlled trials in people with recent onset of stroke symptoms that compared LMWH or heparinoids with UFH. We found nine trials involving 3137 participants; overall these trials had a moderate risk of bias (this means that the results are likely to be less credible than if the risk of bias was low). No new trials were included in this updated review. None of the studies reported reliable information on disability or recovery after stroke. Compared with UFH, there was no evidence of an effect of LMWH or heparinoids on death from all causes during the treatment period (quality of the evidence was low). Although LMWH or heparinoid were associated with significantly fewer clots in leg veins (DVT) than UFH, the number of major events such as when a blood clot becomes lodged in an artery in the lung (pulmonary embolism) and bleeding inside the skull (intracranial haemorrhages) was too small to know whether the harms outweighed the benefits. For people with ischaemic stroke who need immediate treatment with anticoagulants, evidence from the included clinical trials did not provide reliable evidence on the balance of risk and benefit for each type of heparin. Additional large scale research would be needed to resolve this uncertainty. Overall, there was a moderate risk of bias in the included studies. Using GRADE criteria we found that evidence quality was low overall.
Abstract: We included 17 studies. Methodological quality of included studies was poor. Of these 17, only seven studies specifically addressed the discharge question; none found any delay in premedicated patients. Two other studies used clinical criteria to assess fitness for discharge, though times were not given. Again, there was no difference from placebo. Eleven studies used tests of psychomotor function with or without clinical measures as indicators of recovery from anaesthesia. In none of these studies did the premedication appear to delay discharge, although performance on tests of psychomotor function was sometimes still impaired. Three studies showed no impairment in psychomotor function, six showed some impairment which had resolved by three hours or time of discharge and two showed significant impairment. We found no evidence of a difference in time to discharge from hospital, assessed by clinical criteria, in patients who received anxiolytic premedication. However, in view of the age and variety of anaesthetic techniques used and clinical heterogeneity between studies, inferences for current day case practice should be made with caution.

Plain-language summary: We identified 17 studies which compared premedication with a placebo prior to day case surgery. Twelve studies involved benzodiazepines (sedatives), two involved opioids (painkillers), two involved beta-blockers, one compared a benzodiazepine with a beta-blocker and one involved a herbal medication. In general, the studies were of poor quality and many used anaesthetic techniques which are no longer common. Only seven studies directly measured time to ambulation or discharge and found that this was not affected by the use of premedication. Some studies used specific tests to assess for residual effects of the premedication. Although these were often impaired after surgery, this did not appear to delay discharge.
Abstract: We included 32 RCTs (approximately 54,000 participants) and data from 25 cohorts. There is consistent evidence from RCTs in adults of a small weight-reducing effect of eating a smaller proportion of energy from fat; this was seen in almost all included studies and was highly resistant to sensitivity analyses. The effect of eating less fat (compared with usual diet) is a mean weight reduction of 1.5 kg (95% confidence interval (CI) -2.0 to -1.1 kg), but greater weight loss results from greater fat reductions. The size of the effect on weight does not alter over time and is mirrored by reductions in body mass index (BMI) (-0.5 kg/m2, 95% CI -0.7 to -0.3) and waist circumference (-0.3 cm, 95% CI -0.6 to -0.02). Included cohort studies in children and adults most often do not suggest any relationship between total fat intake and later measures of weight, body fatness or change in body fatness. However, there was a suggestion that lower fat intake was associated with smaller increases in weight in middle-aged but not elderly adults, and in change in BMI in the highest validity child cohort. Trials where participants were randomised to a lower fat intake versus usual or moderate fat intake, but with no intention to reduce weight, showed a consistent, stable but small effect of low fat intake on body fatness: slightly lower weight, BMI and waist circumference compared with controls. Greater fat reduction and lower baseline fat intake were both associated with greater reductions in weight. This effect of reducing total fat was not consistently reflected in cohort studies assessing the relationship between total fat intake and later measures of body fatness or change in body fatness in studies of children, young people or adults.

Plain-language summary: This review looked at the effect of cutting down the proportion of energy from fat in our food on body weight and fatness in both adults and children who are not aiming to lose weight. The review found that cutting down on the proportion of fat in our food leads to a small but noticeable decrease in body weight, body mass index and waist circumference. This effect was found both in adults and children. The effect did not change over time.
Abstract: We found six prospective controlled trials relating to our question. Four of these were described as randomised controlled trials, one was a prospective controlled trial that did not specify allocation to comparison groups, and one was a repeated cross-sectional study comparing different interventions. Comparison interventions included non-iodised salt, iodised water, iodised oil, and salt iodisation with potassium iodide versus potassium iodate. Numbers of participants in the trials ranged from 35 to 334; over 20,000 people were included in the cross-sectional study. Three studies were in children only, two investigated both groups of children and adults and one investigated pregnant women. There was a tendency towards goitre reduction with iodised salt, although this was not significant in all studies. There was also an improved iodine status in most studies (except in small children in one of the studies), although urinary iodine excretion did not always reach the levels recommended by the WHO. None of the studies observed any adverse effects of iodised salt. The results suggest that iodised salt is an effective means of improving iodine status. No conclusions can be made about improvements in other, more patient-oriented outcomes, such as physical and mental development in children and mortality. None of the studies specifically investigated development of iodine-induced hyperthyroidism, which can be easily overlooked if just assessed on the basis of symptoms. High quality controlled studies investigating relevant long term outcome measures are needed to address questions of dosage and best means of iodine supplementation in different population groups and settings.

Plain-language summary: This review looked at studies of iodised salt in the diet that included a comparison group. Six studies, most of them in children but some also in adults, were included. Iodine in the urine increased in all but one studies, but there was some concern that small children did not eat enough salt to achieve adequate iodine status. Some studies, but not all, also showed a reduction in the enlargement of the thyroid gland (goitre) that can accompany lack of iodine in the diet. Adverse effects were not reported, but these may not have been studied adequately. More high quality long term studies measuring outcomes related to child development, to deaths associated with iodine-deficiency and to adverse effects are needed.
Abstract: Eleven studies met the inclusion criteria. All were small, and randomised fewer than 30 people to each group. Most included people after the most acute phase of psychosis and investigated a wide range of antidepressants. The quality of reporting varied a great deal. For the outcome of 'no important clinical response' antidepressants were significantly better than placebo (n=209, 5 RCTs, summary risk difference fixed effects -0.26, 95% CI -0.39 to -0.13, NNT 4 95% CI 3 to 8). The depression score at the end of the trial, as assessed by the Hamilton Rating Scale (HAM-D), seemed to suggest that using antidepressants was beneficial, but this was only statistically significant when a fixed effects model was used (n=261, 6 RCTs, WMD fixed effects -2.2 95% CI -3.8 to -0.6; WMD random effects -2.1 95% CI -5.04 to 0.84). There was no evidence that antidepressant treatment led to a deterioration of psychotic symptoms in the included trials. Heterogeneous data on 'any adverse effect' are equivocal (n=110, 2 RCTs, RD fixed 0.11 CI -0.03 to 0.25, Chi square 7.5, df=1, p=0.0062). In one small study extrapyramidal adverse effects were reported less often by those allocated to antidepressant (n=52, 1 RCT, RD fixed -0.28 CI -0.5 to -0.04). Only about 10% of people left these studies by 12 weeks. There was no apparent difference between those allocated placebo and those given an antidepressant (n=426, 10 RCTs, RD fixed 0.04 CI -0.02 to 0.1). Overall, the literature was of poor quality, and only a small number of trials made useful contributions. Though our results provide some evidence to indicate that antidepressants may be beneficial for people with depression and schizophrenia, the results, at best, are likely to overestimate the treatment effect, and, at worst, could merely reflect selective reporting of statistically significant results and publication bias. At present, there is no convincing evidence to support or refute the use of antidepressants in treating depression in people with schizophrenia. We need further well-designed, conducted and reported research to determine the best approach towards treating depression in people with schizophrenia. Note: the 71 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.

Plain-language summary: This review identified eleven randomised controlled trials that compared antidepressants with a placebo in people with schizophrenia who also had depression. There was some evidence that antidepressants did lead to an improvement in global outcome, but the small number of studies providing usable data and their poor quality, suggest that this evidence should be interpreted with caution. At present, there is no convincing evidence either to support or refute the use of antidepressants in treating depression in people with schizophrenia. Further well-designed, conducted and reported research is needed in this area.
Abstract: Ten randomised trials randomising 1709 patients were included. Tamoxifen versus placebo/no intervention had no significant effect on overall survival (hazard ratio 1.05; 95% CI 0.94 to 1.16; P = 0.4). This comparison showed no statistical heterogeneity (P = 0.2 and I2 = 25.9%). Subgroup analysis showed that tamoxifen tended to increase mortality in trials with three adequate/three methodological components (hazard ratio 1.15; 95% CI 0.99 to 1.34; P = 0.06), showed no significant effect in trials with two adequate/three methodological components (hazard ratio 1.00; 95% CI 0.84 to 1.18; P = 0.98), and tended to reduce mortality in trials with one or less adequate/three methodological components (hazard ratio 0.82; 95% CI 0.60 to 1.12; P = 0.2), although this may have been confounded by the use of higher doses of tamoxifen in the better quality trials. Tamoxifen was associated with adverse effects. One trial measured patient quality of life, but the results were not reported in detail. These data do not support the use of tamoxifen for patients with hepatocellular carcinoma. Further research on the effects of tamoxifen in hepatocellular carcinoma does not seem warranted.

Plain-language summary: The reviewers identified 10 trials assessing the effect of tamoxifen on survival, quality of life, tumour size, and treatment side effects in advanced hepatocellular carcinoma. Tamoxifen had no significant effect on survival or tumour size. Tamoxifen did not improve quality of life.
Abstract: We included 69 studies involving more than 15,000 health professionals. Twenty-eight studies (34 comparisons) contributed to the calculation of the median and interquartile range for the main comparison. The median adjusted risk difference (RD) in compliance with desired practice was 5.6% (interquartile range 3.0% to 9.0%). The adjusted RDs were highly consistent for prescribing (median 4.8%, interquartile range 3.0% to 6.5% for 17 comparisons), but varied for other types of professional performance (median 6.0%, interquartile range 3.6% to 16.0% for 17 comparisons). Meta-regression was limited by the large number of potential explanatory factors (eight) with only 31 comparisons, and did not provide any compelling explanations for the observed variation in adjusted RDs. There were 18 comparisons with continuous outcomes, with a median adjusted relative improvement of 21% (interquartile range 11% to 41%). There were eight trials (12 comparisons) in which the intervention included an EOV and was compared to another type of intervention, usually audit and feedback. Interventions that included EOVs appeared to be slightly superior to audit and feedback. Only six studies evaluated different types of visits in head-to-head comparisons. When individual visits were compared to group visits (three trials), the results were mixed. EOVs alone or when combined with other interventions have effects on prescribing that are relatively consistent and small, but potentially important. Their effects on other types of professional performance vary from small to modest improvements, and it is not possible from this review to explain that variation.

Plain-language summary: This review found 69 studies that evaluated educational outreach visits. Educational outreach visits appear to improve the care delivered to patients. When trying to change how health care professionals prescribe medications, outreach visits consistently provide small changes in prescribing, which might be potentially important when hundreds of patients are affected. For other types of professional practice, such as providing screening tests, outreach visits provide small to moderate changes in practice. But the effects really varied and why it varied could not be explained.
Abstract: Only one study was included. This time series study assessed the migration of Philippine nurses to the United States of America (USA) from 1954 to 1990. We re-analysed it as an interrupted time series study. The intervention was a modification of migratory law in the US, called the 'Act of October 1965', which decreased the restrictions on Eastern hemisphere immigrants to the USA. The analysis showed a significant immediate increase of 807.6 (95% confidence interval (CI) 480.9 to 1134.3) in the number of nurses migrating to the USA annually after the intervention. This represents a relative increase of 5000% over the underlying pre-intervention trend. There were no significant differences in the slopes of the underlying trends for the number of nurses migrating between the pre- and postintervention periods. There is an important gap in knowledge about the effectiveness of policy interventions in either HICs or LMICs that could regulate positively the movement of health professionals from LMICs. The only evidence found was from an intervention in a HIC that increased the movement of health professionals from a LMIC. New initiatives to improve records on the migration of health professionals from LMICs should be implemented, as a prerequisite to conducting more rigorous research in the field. This research should focus on whether the range of interventions outlined in the literature could be effective in retaining health professionals in LMICs. Such interventions include financial rewards, career development and continuing education, improving hospital infrastructure, resource availability, better hospital management and improved recognition of health professionals.

Plain-language summary: In most cases, efforts to regulate health worker migration have not been properly evaluated. The review authors found only one study that met their stated requirements for types of study designs. This study looked at the impact of United States (US) immigration law on the number of nurses emigrating from the Philippines to the USA. US government immigration laws were changed in the 1960s, giving equal access to European and non-European immigrants. The study measured the number of nurses migrating from the Philippines to the USA in the years before and after the law had changed. The study showed that: - The change in US immigration laws probably increased the number of nurses migrating from the Philippines to the USA. The quality of this evidence is moderate. The review shows that there is a huge gap in our knowledge about the effectiveness of policy interventions that attempt to regulate the movement of health professionals from low- and middle-income countries.