GEM/cochrane-simplification huggingface dataset:
Abstract: We included 77 studies with 5619 randomised participants. There was potential bias in most studies, with small size being the most common; individual treatment groups had fewer than 50 participants in 60 studies. Participants were relatively young, with mean age in the studies typically between 50 and 70 years. Multiple major problems with adverse event reporting were found, including failing to report adverse events in all participants who received medication, all adverse events experienced, how adverse events were collected, and not defining adverse event terminology or whether a reporting system was used. Direct measures of patient consciousness, patient appetite, or thirst were not apparent. For opioids used to treat cancer pain adverse event incidence rates were 25% for constipation, 23% for somnolence, 21% for nausea, 17% for dry mouth, and 13% for vomiting, anorexia, and dizziness. Asthenia, diarrhoea, insomnia, mood change, hallucinations and dehydration occurred at incidence rates of 5% and below. We found no direct evidence that opioids affected patient consciousness, appetite or thirst when used to treat cancer pain. However, somnolence, dry mouth, and anorexia were common adverse events in people with cancer pain treated with morphine, fentanyl, oxycodone, or codeine. We are aware that there is an important literature concerning the problems that exist with adverse event measurement, reporting, and attribution. Together with the known complications concerning concomitant medication, data collection and reporting, and nomenclature, this means that these adverse events cannot always be attributed unequivocally to the use of opioids, and so they provide only a broad picture of adverse events with opioids in cancer pain. The research agenda includes developing definitions for adverse events that have a spectrum of severity or importance, and the development of appropriate measurement tools for recording such events to aid clinical practice and clinical research.

Plain-language summary: This review identified 77 studies with over 5,000 people who received various treatments. The population in these trials was mainly aged between 50 and 70 years. Trial quality was generally poor; particular problems included small study size, and not reporting adverse events in all patients, or all recorded adverse events. Known problems with adverse event measurement, recording, and reporting made assessment even more difficult. For all four opioids together, 1 in 4 people experienced constipation and somnolence (sleepiness, drowsiness), 1 in 5 experienced nausea and dry mouth, and 1 in 8 experienced vomiting, loss of appetite, and dizziness. Weakness, diarrhoea, insomnia (difficulty in sleeping), mood change, hallucinations and dehydration occurred at rates of 1 in 20 people and below. These results may contribute to understanding the effects of opioids on consciousness, appetite, and thirst in end-of-life care in all patients deemed to be people who are dying.
Abstract: One RCT and two non-randomised studies that allowed for multivariate analyses met the inclusion criteria and included a total of 141 women. One RCT found that neoadjuvant chemoradiation did not appear to offer longer survival compared to primary surgery in advanced vulval tumours (RR = 1.29, 95% confidence interval (CI) 0.87 to 1.91). There was also no statistically significant difference in survival between primary chemoradiation and primary surgery in a study that included 63 women (pooled adjusted HR= 1.09, 95% CI 0.37 to 3.17) and in another study that only included 12 eligible women and compared the same interventions (HR was non-informative when statistical adjustment was made). Adverse events were extensively reported in only one study, which found no statistically significant difference in risk of adverse events between primary chemoradiation and primary surgery due to the very small numbers in each group. In the RCT there was no observed statistically significant difference between neoadjuvant chemoradiation and primary surgery. Adverse events were not reported in the largest study of 63 women. Quality of life (QoL) was not reported in any of the included studies. All studies were at high risk of bias. Women with advanced vulval tumours showed no significant difference in overall survival or treatment-related adverse events when chemoradiation (primary or neoadjuvant) was compared with primary surgery. The retrospective studies had a high risk of bias as the entry criteria for primary chemoradiation was based on inoperability or tumour requiring exenteration.The radiochemotherapy regimens varied widely. There was no data on QoL. There is no standard terminology for 'operable and inoperable vulval cancer', and for 'primary and neoadjuvant chemoradiation'. Stratification according to unresectability of the primary tumour and/or lymph nodes is needed, for good quality comparison.

Plain-language summary: Women requiring extensive surgery (urinary and or feacal stoma formation) or with inoperable tumour were predominantly given primary chemoradiation in the two retrospective studies identified, making the available evidence weak (although we only included studies that used statistical adjustment). There was no data on quality of life. There is a great need for good quality studies comparing various primary treatments in locally advanced vulval cancer which are either inoperable at presentation or operable but would require extensive surgery.
Abstract: Eighteen trials which randomised 3888 people to rosiglitazone treatment were identified. Longest duration of therapy was four years with a median of 26 weeks. Published studies of at least 24 weeks rosiglitazone treatment in people with type 2 diabetes mellitus did not provide evidence that patient-oriented outcomes like mortality, morbidity, adverse effects, costs and health-related quality of life are positively influenced by this compound. Metabolic control measured by glycosylated haemoglobin A1c (HbA1c) as a surrogate endpoint did not demonstrate clinically relevant differences to other oral antidiabetic drugs. Occurrence of oedema was significantly raised (OR 2.27, 95% confidence interval (CI) 1.83 to 2.81). The single large RCT (ADOPT - A Diabetes Outcomes Progression Trial) indicated increased cardiovascular risk. New data on raised fracture rates in women reveal extensive action of rosiglitazone in various body tissues. New studies should focus on patient-oriented outcomes to clarify the benefit-risk ratio of rosiglitazone therapy. Safety data and adverse events of all investigations (published and unpublished) should be made available to the public.

Plain-language summary: Eighteen trials randomised 3888 people to rosiglitazone therapy. The longest duration of rosiglitazone treatment was four years, most trials lasted around half a year. Unfortunately, the published studies of at least 24 weeks rosiglitazone treatment in people with type 2 diabetes mellitus did not provide relevant evidence that patient-oriented outcomes are positively influenced by this agent. The chance of developing oedema was approximately doubled, the risk of cardiovascular diseases increased. The single large randomised controlled trial showed evidence of raised cardiovascular risk after rosiglitazone treatment. Moreover, new safety data show increased numbers of broken bones in women. This finding was published years after approval of this agent by drug regulatory authorities. New ways of exploring drug effects, for example by early long-term studies in many people, as well as public access to all safety data of published and unpublished investigations have to be established.
Abstract: We found two studies involving 4993 participants. The methodological quality of the trials was good. Both studies included women at low risk for hypertensive disorders, with Doppler ultrasound of the uterine arteries performed in the second trimester of pregnancy. In both studies, pathological finding of uterine arteries was followed by low-dose aspirin administration. We identified no difference in short-term maternal and fetal clinical outcomes. We identified no randomised studies assessing the utero-placental vessels in the first trimester or in women at high risk for hypertensive disorders. Present evidence failed to show any benefit to either the baby or the mother when utero-placental Doppler ultrasound was used in the second trimester of pregnancy in women at low risk for hypertensive disorders. Nevertheless, this evidence cannot be considered conclusive with only two studies included. There were no randomised studies in the first trimester, or in women at high risk. More research is needed to investigate whether the use of utero-placental Doppler ultrasound may improve pregnancy outcome.

Plain-language summary: It is used in pregnancy to study blood circulation in the baby, the mother's uterus and the placenta. If abnormal blood circulation is identified, then it is possible that medical interventions might improve outcomes. We set out to assess the value of using Doppler ultrasound of the mother's uterus or placenta (utero-placental Doppler ultrasound) as a screening tool. Other reviews have looked at the use of Doppler ultrasound on the babies' vessels (fetal and umbilical Doppler ultrasound). We also choose to look at women with low-risk and high-risk pregnancies, and in their first or second trimesters. This screening offers a potential for benefit, but also a possibility of unnecessary interventions and adverse effects. The review of randomised controlled trials of routine Doppler ultrasound of the uterus or placenta identified two studies involving 4993 women. All the women were in the second trimester of pregnancy and at low risk for hypertensive disorders. The studies were of good quality but small in size. We identified no improvements for the baby or the mother. However, more data would be needed to show whether maternal Doppler is effective, or not, for improving outcomes. We did not find any studies in the first trimester of pregnancy or in women at risk of high blood pressure disorders. More research is needed on this important aspect of care.
Abstract: A total of four studies (one randomized controlled trial, three non- randomized studies) involving 8488 people living with HIV/AIDS were included. The main findings of this review demonstrated a trend to improved outcomes when treated by a provider with more training/expertise in HIV/AIDS care in the outpatient (clinic) setting. Due to the heterogeneity of the included studies, we could not perform a meta-analysis. We present a descriptive review of the results. The results demonstrate improved medical outcomes when treated by a provider with more training/expertise in HIV/AIDS care in the outpatient (clinic) setting. Since all of these studies were conducted in North America, this does not address any issues regarding the level of training/expertise required by providers working in countries with more limited resources. Practitioners who do not consider themselves 'experts' in HIV/AIDS care and care for few of these patients need to seriously consider this review which demonstrates a trend towards worse patient outcomes when receiving care by those with low caseloads/training in HIV/AIDS care.

Plain-language summary: This systematic review examined studies from 1980-2009 that identified both provider experience/qualifications as well as a volumes indicator (number of HIV/AIDS patients). Only four studies met the inclusion criteria for the final review. Given the varied methods of each study, a meta-analysis was not possible.
Abstract: We identified nine studies. We excluded eight of these as they did not restrict participation to people with high fatigue. The single eligible trial investigated the use of modafinil compared to placebo. Although this study found a significant improvement over time in the primary outcome of fatigue, the improvement occurred after both modafinil and placebo with no significant difference in response between the two groups. The included trial did not reach its planned recruitment target and therefore may not, in practice, have been adequately powered to detect a difference. The trial was at a low risk of bias across most areas. There was an unclear risk of bias related to the use of mean imputation because the investigators did not analyse the impact of imputation on the results. There was insufficient evidence to draw reliable and generalisable conclusions regarding potential effectiveness or harm of any pharmacological or non-pharmacological treatments for fatigue in people with PBT. More research is needed on how best to treat people with brain tumours with high fatigue.

Plain-language summary: In March 2016, we searched five medical databases. We found one clinical trial that was eligible for inclusion; the trial investigated the medicine modafinil in 37 adults with PBT and high levels of fatigue. People in the study received six weeks of modafinil followed by a one-week washout period and six further weeks of placebo, or vice versa. The washout period aims to allow time for any effects of the first treatment to wear off before the new one gets started. The one included trial found no evidence of a difference between modafinil and placebo in treating fatigue. It is possible that this could be due to the trial not reaching its planned number of participants. Several other studies investigated the management of fatigue too, but in these studies high fatigue was not essential for participation. We do not currently know whether any treatments are effective in the management of people with PBT and high fatigue. With only one included trial, the overall quality of evidence was low. More high-quality studies are needed that enrol adults with BPT and high fatigue.
Abstract: We included 56 studies (2838 participants). Antihypertensive agents were the most beneficial non-immunosuppressive intervention for IgAN. The antihypertensives examined were predominantly angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB) or combinations of both, versus other antihypertensives and other agents. The benefits of antihypertensive agents, particularly inhibitors of the renin angiotensin system, appear to potentially outweigh the harms in patients with IgAN. The benefits are largely manifest as a reduction in proteinuria, a surrogate outcome. There is no evidence that treatment with any of the antihypertensive agents evaluated affect major renal and/or cardiovascular endpoints or long-term mortality risk beyond the benefit that arises from controlling hypertension in patients with IgAN. The RCT evidence is insufficiently robust to demonstrate efficacy for any of the other non-immunosuppressive therapies evaluated here. IgAN remains a disease in search of adequately powered RCTs to reliably inform clinical practice. More and better evidence is needed to understand the magnitude of benefit and the possible risks of anti-hypertensive or more specifically of ACEi/ARB therapy alone or in combination and which specific types of patients with the IgAN might have the greatest potential for benefit. For other non-immunosuppressive therapies, where neither benefit nor significant harm has yet to be demonstrated, there remains some justification for further exploration of the potential benefits.

Plain-language summary: We included 56 studies enrolling 2838 participants. Antihypertensive agents were the most beneficial non-immunosuppressive intervention for IgAN. The antihypertensives examined here were predominantly angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB) or combinations of both, compared with other antihypertensives and other agents. The benefits of antihypertensive agents appear to potentially outweigh the harms in patients with IgAN. The benefits were mostly reported as a reduction in 24 hour proteinuria. There is no evidence that treatment with any of the antihypertensive agents evaluated to date affect major renal and/or cardiovascular endpoints or long-term mortality risk beyond the benefit that arises from controlling hypertension in patients with IgAN. The RCT evidence is insufficiently robust to demonstrate efficacy for any of the other non-immunosuppressive therapies evaluated here. IgAN remains a disease in search of adequately powered RCTs to reliably inform clinical practice. More and better evidence is needed to understand the magnitude of benefit and the possible risks of anti-hypertensive or more specifically of ACEi/ARB therapy alone or in combination and which specific types of patients with the IgAN might have the greatest potential for benefit. For other non-immunosuppressive therapies, where benefit nor significant harm has yet to be demonstrated, there remains some justification for further exploration of the potential benefits.
Abstract: Twelve RCTs (n=545) with eight to 26 weeks follow-up met our inclusion criteria. The results of the individual trials were heterogeneous. Combining all trials, participants receiving magnesium supplements as compared to control did not significantly reduce SBP (mean difference: -1.3 mmHg, 95% CI: -4.0 to 1.5, I2=67%), but did statistically significantly reduce DBP (mean difference: -2.2 mmHg, 95% CI: -3.4 to -0.9, I2=47%). Sensitivity analyses excluding poor quality trials yielded similar results. Sub-group analyses and meta-regression indicated that heterogeneity between trials could not be explained by dose of magnesium, baseline blood pressure or the proportion of males among the participants. In view of the poor quality of included trials and the heterogeneity between trials, the evidence in favour of a causal association between magnesium supplementation and blood pressure reduction is weak and is probably due to bias. This is because poor quality studies generally tend to over-estimate the effects of treatment. Larger, longer duration and better quality double-blind placebo controlled trials are needed to assess the effect of magnesium supplementation on blood pressure and cardiovascular outcomes.

Plain-language summary: This review examined whether taking magnesium supplements could be recommended for treating adults with high blood pressure from no known cause. It reviewed 12 trials enrolling 545 people, which compared magnesium supplementation with a dummy drug (placebo) or no treatment, and measured blood pressure 8 weeks to 6 months later. The results of trials varied a lot: some trials found magnesium lowered blood pressure much more than placebo, while others found little difference between magnesium and placebo. On average, people receiving extra magnesium achieved slightly lower diastolic blood pressure at the end of trials. None of the studies reported any serious side effects of taking magnesium supplements. However, most included trials were of poor quality, so their results may not be reliable. The trials were not long enough or large enough to measure whether extra magnesium can reduce possible consequences of high blood pressure: death, heart attack or stroke. The review did not find robust evidence that oral magnesium supplementation reduces high blood pressure in adults. Larger, longer duration, better quality trials are needed to clarify whether magnesium supplementation can lower high blood pressure.
Abstract: Data for the primary outcome (prevention of disease) were lacking. We performed a meta-analysis to pool the results of 20 studies with 5874 participants in an immunogenicity analysis and 5232 participants in the reactogenicity analysis. There were no data on clinical outcomes for the primary outcome (prevention of disease) and all studies used immunogenicity and reactogenicity (adverse events). The number of vaccine doses differed significantly between the studies. Heterogeneous interventions, study location, healthcare environment and combining research across disparate geographical locations, may have lead to bias. The risk of bias was unclear across most of the included studies. Comparisons found little heterogeneity. In two immunological responses the combined vaccine achieved lower responses than the separate vaccines for HIB and tetanus. No significant differences in immunogenicity were found for pertussis, diphtheria, polio and hepatitis B. Serious adverse events were comparable with mainly hospitalisation and acute bronchiolitis cases. Minor adverse events such as pain and redness were more common in children given the combined vaccine. Overall, the direction shown by the results is in favour of the DTPw (diptheria-tetanus-whole cell pertussis)-HBV-HIB vaccine rather than the DTPa (diptheria-tetanus-acellular pertussis)-HBV-HIB vaccine when compared to the separate vaccines (size of effect: risk ratio (RR) 1.43; 95% confidence interval (CI) 0.98 to 2.10, for 5269 participants). We could not conclude that the immune responses elicited by the combined vaccine were different from or equivalent to the separate vaccines. There was significantly less immunological response for HIB and tetanus and more local reactions in the combined injections. However, these differences rely mostly on one study each. Studies did not use an intention-to-treat (ITT) analysis and we were uncertain about the risk of bias in many of the studies. These results are therefore inconclusive. Studies addressing clinical end points whenever possible, using correct methodology and a large enough sample size should be conducted.

Plain-language summary: We included 20 studies with 5874 participants in the immunogenicity analysis and 5232 in the reactogenicity analysis. In two immunological responses, the combined vaccine achieved lower responses than the separate vaccines for HIB and tetanus. We did not find any significant differences in immunogenicity for pertussis-diphtheria-polio and hepatitis B. Serious adverse events were comparable. Minor adverse events were more common with the combined vaccine. Overall, the level of evidence provided by the studies was low and we could not conclude that the immune responses with the combined vaccine were equivalent to the separate injections.