GEM/cochrane-simplification huggingface dataset:
Abstract: Of the 27,865 records identified, 39 clinical trials and 14 observational studies, including a total of 945,240 participants, were eligible for inclusion. Five studies are awaiting classification. Overall, we found 114 adverse events in 33 studies (30 RCTs and three observational studies), and mortality was reported in 41 studies (32 RCTs and nine observational studies). Most studies were at low to moderate risk of bias for harms outcomes. However, overall harm assessment and reporting were of moderate to low quality in the RCTs, and of low quality in the observational studies. We downgraded the GRADE quality of evidence for venous thromboembolism and mortality to very low and low, respectively, because of risk of bias, high inconsistency, imprecision and limitations of study design. It is unclear whether there is an increase in the risk of any adverse events (Bayesian risk ratio (RR) 1.05, 95% confidence interval (CI) 0.93 to 1.21; 3099 participants; 9 studies; low-quality evidence) or venous thromboembolism (Bayesian RR 1.04, 95% CI 0.70 to 1.41; 18,917 participants; 18 studies; very low-quality evidence). There was a decreased risk of mortality with off-label use of ESAs in critically-ill people (Bayesian RR 0.76, 95% CI 0.61 to 0.92; 930,470 participants; 34 studies; low-quality evidence). Low quality of evidence suggests that off-label use of ESAs may reduce mortality in a critical care setting. There was a lack of high-quality evidence about the harm of ESAs in critically-ill people. The information for biosimilar ESAs is less conclusive. Most studies neither evaluated ESAs' harm as a primary outcome nor predefined adverse events. Any further studies of ESA should address the quality of evaluating, recording and reporting of adverse events.

Plain-language summary: We searched 10 databases for studies where ESAs were used to treat critically-ill people. The evidence is current to February 2017. We found 53 studies, involving 945,240 participants treated with epoetin-alfa, epoetin-beta, and darbepoetin-alfa or placebo. Five studies are awaiting classification. Based on mainly low-quality evidence, we were unable to exclude relevant harms in terms of adverse effects of ESAs. 'Adverse effects' included any adverse events and problems from blood clotting in the veins. However, we found low-quality evidence for protective effects on the overall risk of dying in critically-ill people.
Abstract: We included eight studies involving 646 participants, most of which were of poor methodological quality. The urinary biomarkers were evaluated either in a specific phase of menstrual cycle or irrespective of the cycle phase. Five studies evaluated the diagnostic performance of four urinary biomarkers for endometriosis, including three biomarkers distinguishing women with and without endometriosis (enolase 1 (NNE); vitamin D binding protein (VDBP); and urinary peptide profiling); and one biomarker (cytokeratin 19 (CK 19)) showing no significant difference between the two groups. All of these biomarkers were assessed in small individual studies and could not be statistically evaluated in a meaningful way. None of the biomarkers met the criteria for a replacement test or a triage test. Three studies evaluated three biomarkers that did not differentiate women with endometriosis from disease-free controls. There was insufficient evidence to recommend any urinary biomarker for use as a replacement or triage test in clinical practice for the diagnosis of endometriosis. Several urinary biomarkers may have diagnostic potential, but require further evaluation before being introduced into routine clinical practice. Laparoscopy remains the gold standard for the diagnosis of endometriosis, and diagnosis of endometriosis using urinary biomarkers should only be undertaken in a research setting.

Plain-language summary: The evidence included in this review is current to July 2015. We included eight studies involving 646 participants. All studies evaluated reproductive-aged women who were undertaking diagnostic surgery to investigate symptoms of endometriosis or for other indications. Five studies evaluated the diagnostic accuracy of four urinary biomarkers, including four biomarkers that were expressed differently in women with and without endometriosis and one showing no difference between the two groups. Three other studies just identified three biomarkers that did not distinguish the two groups. None of the assessed biomarkers, including cytokeratin 19 (CK 19), enolase 1 (NNE), vitamin D binding protein (VDBP) and urinary peptide profiling have been evaluated by enough studies to provide a meaningful assessment of test accuracy. None of the tests were accurate enough to replace diagnostic surgery. Several studies identified biomarkers that might be of value in diagnosing endometriosis, but there are too few reports to be sure of their diagnostic benefit. There is not enough evidence to recommend any urinary biomarker for use in clinical practice for the diagnosis of endometriosis. Generally, the reports were of low methodological quality and urine tests were only assessed in small individual studies. More high quality research trials are needed to accurately assess the diagnostic potential of urinary biomarkers identified in small numbers of studies as having value in detecting endometriosis.
Abstract: The 2010 search strategy identified 1664 abstracts (and 827 duplicates) of which we obtained 23 studies in full as potentially meeting the inclusion criteria. On review of the full papers, we identified no studies that met the inclusion criteria. The updated searches carried out in November 2013 identified 304 abstracts (261 excluding duplicates) of which we obtained 18 references in full as potentially meeting the inclusion criteria. On review of the full papers, we identified no studies that met the inclusion criteria, therefore there were no included studies in this review. We found no registered trials of droperidol for the management of nausea or vomiting in palliative care. Since first publication of this review, no new studies were found. There is insufficient evidence to advise on the use of droperidol for the management of nausea and vomiting in palliative care. Studies of antiemetics in palliative care settings are needed to identify which agents are most effective, with minimum side effects.

Plain-language summary: In our search updated in November 2013 we found no randomised studies of droperidol for the treatment of nausea or vomiting for people receiving palliative care or suffering from an incurable progressive medical condition. Several studies reported on the use of droperidol for the prevention of nausea and vomiting associated with chemotherapy. Further studies are needed to find out which medications are most suitable to treat nausea and vomiting in palliative care.
Abstract: Six randomized controlled clinical trials met selection criteria and were included in this review. In these studies of infants with signs and symptoms of RDS, intubation and early surfactant therapy followed by extubation to nasal CPAP (NCPAP) compared with later selective surfactant administration was associated with a lower incidence of mechanical ventilation [typical RR 0.67, 95% CI 0.57, 0.79], air leak syndromes [typical RR 0.52, 95% CI 0.28, 0.96] and BPD [typical RR 0.51, 95% CI 0.26, 0.99]. A larger proportion of infants in the early surfactant group received surfactant than in the selective surfactant group [typical RR 1.62, 95% CI 1.41, 1.86]. The number of surfactant doses per patient was significantly greater among patients randomized to the early surfactant group [WMD 0.57 doses per patient, 95% CI 0.44, 0.69]. In stratified analysis by FIO2 at study entry, a lower threshold for treatment (FIO2< 0.45) resulted in lower incidence of airleak [typical RR 0.46 and 95% CI 0.23, 0.93] and BPD [typical RR 0.43, 95% CI 0.20, 0.92]. A higher treatment threshold (FIO2 > 0.45) at study entry was associated with a higher incidence of patent ductus arteriosus requiring treatment [typical RR 2.15, 95% CI 1.09, 4.13]. Early surfactant replacement therapy with extubation to NCPAP compared with later selective surfactant replacement and continued mechanical ventilation with extubation from low ventilator support is associated with less need mechanical ventilation, lower incidence of BPD and fewer air leak syndromes. A lower treatment threshold (FIO2< 0.45) confers greater advantage in reducing the incidences of airleak syndromes and BPD; moreover a higher treatment threshold (FIO2 at study > 0.45) was associated with increased risk of PDA. These data suggest that treatment with surfactant by transient intubation using a low treatment threshold (FIO2< 0.45) is preferable to later, selective surfactant therapy by transient intubation using a higher threshold for study entry (FIO2 > 0.45) or at the time of respiratory failure and initiation of mechanical ventilation.

Plain-language summary: An early surfactant therapy strategy results in a greater number of infants receiving surfactant and so more infants being exposed to the potential risks of intubation and surfactant administration. Although no complications of surfactant administration were reported in the studies reviewed, infants treated with an early surfactant therapy strategy tended to have a higher prevalence of patent ductus arteriosus (PDA). Two trials were terminated prior to achieving the targeted enrollment when the need for mechanical ventilation was found to be significantly different between groups at a scheduled interim analysis. Two other trials experienced slow enrollment leading to reduced numbers.
Abstract: We found and included three unblinded randomised trials in 8221 older adults (mean age 74.8 years), in which higher BP targets of less than 150/90 mmHg (two trials) and less than 160/90 mmHg (one trial) were compared to a lower target of less than 140/90 mmHg. Treatment to the two different BP targets over two to four years failed to produce a difference in any of our primary outcomes, including all-cause mortality (RR 1.24 95% CI 0.99 to 1.54), stroke (RR 1.25 95% CI 0.94 to 1.67) and total cardiovascular serious adverse events (RR 1.19 95% CI 0.98 to 1.45). However, the 95% confidence intervals of these outcomes suggest the lower BP target is probably not worse, and might offer a clinically important benefit. We judged all comparisons to be based on low-quality evidence. Data on adverse effects were not available from all trials and not different, including total serious adverse events, total minor adverse events, and withdrawals due to adverse effects. At the present time there is insufficient evidence to know whether a higher BP target (less than150 to 160/95 to 105 mmHg) or a lower BP target (less than 140/90 mmHg) is better for older adults with high BP. Additional good-quality trials assessing BP targets in this population are needed.

Plain-language summary: We systematically retrieved all randomised trials that compared the effect of a higher BP target (upper BP number less than 150 to 160 mmHg) with a conventional lower BP target (upper BP number less than140 mmHg) in people over the age of 65 years. The evidence is current to February 2017. We found three randomised trials (the 'gold standard' of medical evidence) that investigated this question in a total of 8221 older adults (average age 75 years, 59% female). We did not find a difference between the higher BP target and the conventional lower BP target, however an important difference favoring the lower BP target could not be ruled out. We judged the pooled evidence to be of low-quality and not able to adequately answer the question as to which target BP was better. More good-quality trials addressing this question are needed.
Abstract: The five eligible trials reported on a total of 359 infants with RDS. Overall the risk of any reported mortality was less frequent in the MV group (summary RR 0.86, 95% CI 0.74, 1.00; RD -0.10, 95% CI -0.20, -0.01; NNT 10, 95% CI 5, 100). In infants with a birth weight of 1 to 2 kg, no significant difference in mortality was found (summary RR 0.86, 95% CI 0.70, 1.07). In infants with a birth weight of more than 2 kg there was a significant reduction in mortality with MV (summary RR 0.67, 95%CI 0.52, 0.87). Any IVH at autopsy was not significantly different between the groups in any study or overall in four studies reporting on 202 infants who had an autopsy. Pneumothorax was reported in two studies of 275 infants and there is a non-significant trend towards an increase in the mechanical ventilation group (summary RR 2.75, 95% CI 0.72, 10.45). When MV was introduced in the 1960s to treat infants with severe respiratory failure due to pulmonary disease, trials showed an overall reduction in mortality which was most marked in infants born with a birthweight of more than 2 kg. This review does not provide information to evaluate the relative benefits or harms of MV in the setting of modern perinatal care.

Plain-language summary: It was compared with standard treatment in five trials for infants with very severe lung disease and resulted in a reduction in mortality. This effect was observed principally in infants with birth weights over two kilograms. Mechanical ventilation has become standard therapy for severe respiratory failure. There have been no trials in modern neonatal intensive care units so the magnitude of the benefits and harms in current practice are not known.
Abstract: We included nine trials with 645 participants. Six trials assessed TACE versus control and three trials assessed TAE versus control. Seven trials had low risk of selection bias based on adequate generation of allocation sequence and concealment - but all these trials had other risks of bias. Three trials were stopped early due to interim inspections and one due to slow accrual. For all-cause mortality, statistical heterogeneity between trials was low to moderate (I2= 30%). Meta-analysis of trials with low risk of selection bias showed that TACE or TAE versus control does not significantly increase survival (HR 0.88; 95% CI 0.71 to 1.10). Two trials with low risk of selection bias, no early stopping, and no co-intervention did not establish any significant effect of TACE or TAE on overall survival (hazard ratio 1.22, 95% confidence interval 0.82 to 1.83; P = 0.33). Trial sequential analysis confirmed the absence of evidence for a beneficial effect of TACE or TAE on survival indicating the need for future randomisation of up to 383 additional participants. Substantial differences in criteria for assessing tumour response did not allow quantitative analyses. One trial investigated quality of life but did not detect any significant differences between the intervention groups. A range of adverse events including post-embolisation syndrome and serious complications were reported. There is no firm evidence to support or refute TACE or TAE for patients with unresectable HCC. More adequately powered and bias-protected trials are needed.

Plain-language summary: The review included nine trials with 645 participants. Six trials assessed TACE versus control and three trials assessed TAE versus control. All trials had risks of systematic errors ('bias'). Contrary to current practice in many hospitals, we could not demonstrate any beneficial effect of TACE or TAE on either survival or tumour growth in patients with primary liver cancer not suitable for surgical resection. Furthermore, we calculated that more clinical trials involving a further 383 trial participants may be needed before firm evidence may become available. Importantly, TACE or TAE is associated with a wide range of adverse events, some being potentially serious. Accordingly, we recommend that TACE or TAE should not be used as standard treatment for liver cancer until firmer evidence is available from randomised clinical trials.
Abstract: The search identified 102 potentially eligible studies. Judged from the information in the title and abstract six of these concerning the percutaneous block, involving 358 participants, fulfilled the inclusion criteria and were included in the review. All were RCTs in which the participants were followed for at least four weeks. We excluded studies published only as abstracts. We identified one RCT comparing EUS-guided or computed tomography (CT) -guided CPB but its aim was to assess efficacy in controlling chronic abdominal pain associated with chronic pancreatitis rather than pancreatic cancer, so it was excluded. For pain (VAS) at four weeks the mean difference was -0.42 in favour of CPB (95% confidence interval (CI) -0.70 to - 0.13, P = 0.004, fixed-effect model). At eight weeks the mean difference was -0.44 (95% CI -0.89 to - 0.01, random-effects model). At eight weeks there was significant heterogeneity (I2 = 89%). Opioid consumption was significantly lower in the CPB group than the control group (P < 0.00001). Although statistical evidence is minimal for the superiority of pain relief over analgesic therapy, the fact that CPB causes fewer adverse effects than opioids is important for patients. Further studies and RCTs are recommended to demonstrate the potential efficacy of a less invasive technique under EUS guidance.

Plain-language summary: We searched for studies comparing CPB with standard analgesic therapy in patients with inoperable pancreatic cancer. We were interested in the primary outcome of pain, measured on a visual analogue scale (VAS). We also looked at the amount of opioid (morphine-like drugs) patients took (opioid consumption) and adverse effects of the treatment. Six studies (358 participants) comparing CPB with standard therapy (painkillers) met our inclusion criteria. At four weeks pain scores were significantly lower in the CPB group. Opioid consumption was also significantly lower than in the control group. The main adverse effects were diarrhoea or constipation (this symptom was significantly more likely in the control group, where opioid consumption was higher). Endoscopic ultrasonography (EUS)-guided CPB is becoming popular as a minimally invasive technique that has fewer risks, but we were not able to find any RCTs assessing this method (current medical literature on this subject is limited to studies without control groups). Although the data on EUS-guided CPB and pain control are promising, we await rigorously designed RCTs that may validate these findings. We conclude that, although statistical evidence is minimal for the superiority of pain relief over analgesic therapy, the fact that CPB causes fewer adverse effects than opioids is important for patients.
Abstract: Thirty-nine RCTs met the inclusion criteria contributing a total of 4615 participants. Most trials enrolled a small number of patients and showed moderate to poor (reporting of) methodological quality, in particular regarding allocation concealment and intention-to-treat analysis. Fifteen systemic acting prokinetic drugs were investigated and ten comparisons could be summarized. Six RCTs support the effect of Alvimopan, a novel peripheral mu receptor antagonist. However, the trials do not meet reporting guidelines and the drug is still in an investigational stage. Erythromycin showed homogenous and consistent absence of effect across all included trials and outcomes. The evidence is insufficient to recommend the use of cholecystokinin-like drugs, cisapride, dopamine-antagonists, propranolol or vasopressin. Effects are either inconsistent across outcomes, or trials are too small and often of poor methodological quality. Cisapride has been withdrawn from the market due to adverse cardiac events in many countries. Intravenous lidocaine and neostigmine might show a potential effect, but more evidence on clinically relevant outcomes is needed. Heterogeneity among included trials was seen in 10 comparisons. No major adverse drug effects were evident. Alvimopan may prove to be beneficial but proper judgement needs adherence to reporting standards. Further trials are needed on intravenous lidocaine and neostigmine. The remaining drugs can not be recommended due to lack of evidence or absence of effect.

Plain-language summary: Many of the 39 studies assessed in this review enrolled only a small number of patients and date back to before 1990. The novel drug alvimopan shortened bowel recovery, but many studies failed to report methodology according to current guidelines. Erythromycin, cholecystokinin, cisapride, dopamine-antagonists, propranolol or vasopressin are not supported due to lack of evidence or absence of effect. Intravenous lidocaine and neostigmine might show to be beneficial, but more evidence is needed.
Abstract: Twenty-five studies met our inclusion criteria (18 RCTs involving 64,852 participants and seven non-RCTs involving 62,294 participants). Meta-analysis of the RCTs found strong evidence of PPV efficacy against IPD with no statistical heterogeneity (OR 0.26, 95% CI 0.14 to 0.45; random-effects model, I2 statistic = 0%). There was efficacy against all-cause pneumonia in low-income (OR 0.54, 95% CI 0.43 to 0.67, I2 statistic = 19%) but not high-income countries in either the general population (OR 0.71, 95% CI 0.45 to 1.12, I2 statistic = 93%) or in adults with chronic illness (OR 0.93, 95% CI 0.73 to 1.19, I2 statistic = 10%). PPV was not associated with substantial reductions in all-cause mortality (OR 0.90, 95% CI 0.74 to 1.09; random-effects model, I2 statistic = 69%). Vaccine efficacy against primary outcomes appeared poorer in adults with chronic illness. Non-RCTs provided evidence for protection against IPD in populations for whom the vaccine is currently utilised (OR 0.48, 95% CI 0.37 to 0.61; random-effects model, I2 statistic = 31%). This review did not consider adverse events as it was outside the scope of the review. This meta-analysis provides evidence supporting the recommendation for PPV to prevent IPD in adults. The evidence from RCTs is less clear with respect to adults with chronic illness. This might be because of lack of effect or lack of power in the studies. The meta-analysis does not provide evidence to support the routine use of PPV to prevent all-cause pneumonia or mortality.

Plain-language summary: We found consistently strong evidence that the vaccine is effective in preventing the rarer outcome of invasive pneumococcal disease. Evidence from the included studies indicates vaccination might not afford as much protection in adults with chronic illness as it does for healthy adults. The available evidence does not demonstrate that pneumococcal polysaccharide vaccines prevent pneumonia (of all causes) or mortality in adults. This review did not consider adverse events as it was outside the scope of the study.