Topical agents or dressings for pain in venous leg ulcers.

Venous leg ulcers affect up to 1% of people at some time in their lives and are often painful. The main treatments are compression bandages and dressings. Topical treatments to reduce pain during and between dressing changes are sometimes used

Methods for a rapid systematic review and meta-analysis in evaluating selective serotonin reuptake inhibitors for premature ejaculation

The aim of this study was to evaluate a rapid systematic review method in which randomised controlled trial (RCT) data was extracted from existing reviews and subsequent RCTs. The method enabled: identification of RCTs not included by existing reviews; cross-checking RCT data for consistency where there was more than one review; double data extraction due to time saved by extracting data from existing reviews; correction of data synthesis errors in existing reviews; and pooling data across all RCTs to produce contemporary effect estimates. When subsequently compared to extracting data directly from all RCT original publications, the findings and conclusions concurred

Rapid diagnostic test for antenatal syphilis screening in low-income and middle-income countries: a systematic review and meta-analysis

OBJECTIVES: To undertake a systematic review and meta-analysis to evaluate the test performance including sensitivity and specificity of rapid immunochromatographic syphilis (ICS) point-of-care (POC) tests at antenatal clinics compared with reference standard tests (non-treponemal (TP) and TP tests) for active syphilis in pregnant women. METHODS: Five electronic databases were searched (PubMed, EMBASE, CRD, Cochrane Library and LILACS) to March 2016 for diagnostic accuracy studies of ICS test and standard reference tests for syphilis in pregnant women. Methodological quality was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies). A bivariate meta-analysis was undertaken to generate pooled estimates of diagnostic parameters. Results were presented using a coupled forest plot of sensitivity and specificity and a scatter plot. RESULTS: The methodological quality of the five included studies with regards to risk of bias and applicability concern judgements was either low or unclear. One study was judged as high risk of bias for patient selection due to exclusion of pregnant women with a previous history of syphilis, and one study was judged at high risk of bias for study flow and timing as not all patients were included in the analysis. Five studies contributed to the meta-analysis, providing a pooled sensitivity and specificity for ICS of 0.85 (95% CrI: 0.73 to 0.92) and 0.98 (95% CrI: 0.95 to 0.99), respectively. CONCLUSIONS: This review and meta-analysis observed that rapid ICS POC tests have a high sensitivity and specificity when performed in pregnant women at antenatal clinics. However, the methodological quality of the existing evidence base should be taken into consideration when interpreting these results. PROSPERO REGISTRATION NUMBER: CRD42016036335

Evidence for the impact of interventions and medicines reconciliation on problematic polypharmacy in the UK: A rapid review of systematic reviews

This was a rapid review of systematic reviews (SRs) on problematic polypharmacy (PP) in the UK. The commissioner-defined topics were burden of PP, interventions to reduce PP, implementation activities to increase uptake of interventions, and efficient handover between primary and secondary care to reduce PP. Databases including Medline were searched to June 2019, SR quality was assessed using AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews) and a narrative synthesis was undertaken. Except for burden of PP (SRs had to include UK studies), there were no restrictions on country, location of care or outcomes. Nine SRs were included. On burden, three SRs (including six UK studies) found a high prevalence of polypharmacy in long term care. PP was associated with mortality, although unclear if causal, with no information on costs or health consequences. On interventions, six reviews (27 UK studies) found that interventions can reduce PP, but no effects on health outcomes. On handover between primary and secondary care, one review (two UK studies) found medicine reconciliation activities to reduce medication discrepancies at care transitions reduce PP, although the evidence is low quality. No SRs on implementation activities to increase uptake of interventions were found. SR quality was variable, with some concerns regarding meta-analysis methods. Evidence of the extent of PP in the UK, and what interventions to address it are effective in the UK, is limited. Future UK research is needed on the prevalence and consequences of PP, the effectiveness and cost-effectiveness of interventions to reduce PP, and barriers and activities to ensure uptake

Delphi consensus reached to produce a decision tool for SelecTing Approaches forRapid Reviews (STARR)

OBJECTIVES: There are many rapid review methods; however, there is little pragmatic guidance on which methods to select. This study aimed to reach consensus among international rapid review experts outlining areas to consider when selecting approaches for rapid reviews. STUDY DESIGN AND SETTING: A two-round modified online Delphi survey was conducted between May and July 2018. Participants were asked to rank the importance of a predefined list of 19 items. A consensus definition of at least 70% agreement for each item was decided a priori. RESULTS: Thirty experts from ten countries participated in Round 1 and 24 in Round 2. During Round 1, consensus was reached on all items. One additional item on quality assessment was suggested by respondents and comments suggested wording changes to improve clarity and understanding of the tool. Respondents in the second round indicated a high level of importance and all 20 items achieved consensus. These items addressed interaction with commissioners, scoping and searching the evidence-base, data extraction and synthesis methods, and reporting of rapid review methods. CONCLUSIONS: International consensus was reached to produce the STARR decision tool for planning rapid reviews and will lead to improved shared understanding between review teams and review commissioners

Improving sleep quality leads to better mental health: A meta-analysis of randomised controlled trials.

The extent to which sleep is causally related to mental health is unclear. One way to test the causal link is to evaluate the extent to which interventions that improve sleep quality also improve mental health. We conducted a meta-analysis of randomised controlled trials that reported the effects of an intervention that improved sleep on composite mental health, as well as on seven specific mental health difficulties. 65 trials comprising 72 interventions and N = 8608 participants were included. Improving sleep led to a significant medium-sized effect on composite mental health (g+ = −0.53), depression (g+ = −0.63), anxiety (g+ = −0.51), and rumination (g+ = −0.49), as well as significant small-to-medium sized effects on stress (g+ = −0.42), and finally small significant effects on positive psychosis symptoms (g+ = −0.26). We also found a dose response relationship, in that greater improvements in sleep quality led to greater improvements in mental health. Our findings suggest that sleep is causally related to the experience of mental health difficulties. Future research might consider how interventions that improve sleep could be incorporated into mental health services, as well as the mechanisms of action that explain how sleep exerts an effect on mental health

The impact of different forms of exercise on endothelial progenitor cells in healthy populations

Circulating endothelial progenitor cells (EPCs) contribute to vascular healing and neovascularisation, while exercise is an effective means to mobilise EPCs into the circulation. Objectives: to systematically examine the acute and chronic effects of different forms of exercise on circulating EPCs in healthy populations. Methods: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. Results: Thirty-one articles met the inclusion criteria including 747 participants aged 19 to 76 years. All included trials used flow cytometry for identification of circulating EPCs. Eight and five different EPC phenotypes were identified in the acute and chronic trials respectively. In the acute trials, moderate intensity continuous (MICON), maximal, prolonged endurance, resistance and high intensity interval training (HIIT) exercise protocols were utilised. Prolonged endurance and resistance exercise had the most profound effect on circulating EPCs followed by maximal exercise. In the chronic trials, MICON exercise, HIIT, HIIT compared to MICON and MICON compared to exergame (exercise modality based on an interactive video game) were identified. MICON exercise had a positive effect on circulating EPCs in older sedentary individuals which was accompanied by improvements in endothelial function and arterial stiffness. Long-stage HIIT (4min bouts) appears to be an effective means and superior than MICON exercise in mobilising circulating EPCs. In conclusion, both in acute and chronic trials the degree of exercise-induced EPC mobilisation depends upon the exercise regime applied. In future, more research is warranted to examine the dose-response relationship of different exercise forms on circulating EPCs using standardised methodology and EPC phenotype

A novel accelerometer-based method to describe day-to-day exposure to potentially osteogenic vertical impacts in older adults: findings from a multi-cohort study

Summary: This observational study assessed vertical impacts experienced in older adults as part of their day-to-day physical activity using accelerometry and questionnaire data. Population-based older adults experienced very limited high-impact activity. The accelerometry method utilised appeared to be valid based on comparisons between different cohorts and with self-reported activity. Introduction: We aimed to validate a novel method for evaluating day-to-day higher impact weight-bearing physical activity (PA) in older adults, thought to be important in protecting against osteoporosis, by comparing results between four cohorts varying in age and activity levels, and with self-reported PA levels. Methods: Participants were from three population-based cohorts, MRC National Survey of Health and Development (NSHD), Hertfordshire Cohort Study (HCS) and Cohort for Skeletal Health in Bristol and Avon (COSHIBA), and the Master Athlete Cohort (MAC). Y-axis peaks (reflecting the vertical when an individual is upright) from a triaxial accelerometer (sampling frequency 50 Hz, range 0–16 g) worn at the waist for 7 days were classified as low (0.5–1.0 g), medium (1.0–1.5 g) or higher (≥1.5 g) impacts. Results: There were a median of 90, 41 and 39 higher impacts/week in NSHD (age 69.5), COSHIBA (age 76.8) and HCS (age 78.5) participants, respectively (total n = 1512). In contrast, MAC participants (age 68.5) had a median of 14,322 higher impacts/week. In the three population cohorts combined, based on comparison of beta coefficients, moderate-high-impact activities as assessed by PA questionnaire were suggestive of stronger association with higher impacts from accelerometers (0.25 [0.17, 0.34]), compared with medium (0.18 [0.09, 0.27]) and low impacts (0.13 [0.07,0.19]) (beta coefficient, with 95 % CI). Likewise in MAC, reported moderate-high-impact activities showed a stronger association with higher impacts (0.26 [0.14, 0.37]), compared with medium (0.14 [0.05, 0.22]) and low impacts (0.03 [−0.02, 0.08]). Conclusions: Our new accelerometer method appears to provide valid measures of higher vertical impacts in older adults. Results obtained from the three population-based cohorts indicate that older adults generally experience very limited higher impact weight-bearing PA

Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy (including a review of TA140 and TA262): clinical effectiveness systematic review and economic model.

BACKGROUND: Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the UK. UC can have a considerable impact on patients' quality of life. The burden for the NHS is substantial. OBJECTIVES: To evaluate the clinical effectiveness and safety of interventions, to evaluate the incremental cost-effectiveness of all interventions and comparators (including medical and surgical options), to estimate the expected net budget impact of each intervention, and to identify key research priorities. DATA SOURCES: Peer-reviewed publications, European Public Assessment Reports and manufacturers' submissions. The following databases were searched from inception to December 2013 for clinical effectiveness searches and from inception to January 2014 for cost-effectiveness searches for published and unpublished research evidence: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library including the Cochrane Systematic Reviews Database, Cochrane Controlled Trials Register, Database of Abstracts of Reviews of Effects, the Health Technology Assessment database and NHS Economic Evaluation Database; ISI Web of Science, including Science Citation Index, and the Conference Proceedings Citation Index-Science and Bioscience Information Service Previews. The US Food and Drug Administration website and the European Medicines Agency website were also searched, as were research registers, conference proceedings and key journals. REVIEW METHODS: A systematic review [including network meta-analysis (NMA)] was conducted to evaluate the clinical effectiveness and safety of named interventions. The health economic analysis included a review of published economic evaluations and the development of a de novo model. RESULTS: Ten randomised controlled trials were included in the systematic review. The trials suggest that adult patients receiving infliximab (IFX) [Remicade(®), Merck Sharp & Dohme Ltd (MSD)], adalimumab (ADA) (Humira(®), AbbVie) or golimumab (GOL) (Simponi(®), MSD) were more likely to achieve clinical response and remission than those receiving placebo (PBO). Hospitalisation data were limited, but suggested more favourable outcomes for ADA- and IFX-treated patients. Data on the use of surgical intervention were sparse, with a potential benefit for intervention-treated patients. Data were available from one trial to support the use of IFX in paediatric patients. Safety issues identified included serious infections, malignancies and administration site reactions. Based on the NMA, in the induction phase, all biological treatments were associated with statistically significant beneficial effects relative to PBO, with the greatest effect associated with IFX. For patients in response following induction, all treatments except ADA and GOL 100 mg at 32-52 weeks were associated with beneficial effects when compared with PBO, although these were not significant. The greatest effects at 8-32 and 32-52 weeks were associated with 100 mg of GOL and 5 mg/kg of IFX, respectively. For patients in remission following induction, all treatments except ADA at 8-32 weeks and GOL 50 mg at 32-52 weeks were associated with beneficial effects when compared with PBO, although only the effect of ADA at 32-52 weeks was significant. The greatest effects were associated with GOL (at 8-32 weeks) and ADA (at 32-52 weeks). The economic analysis suggests that colectomy is expected to dominate drug therapies, but for some patients, colectomy may not be considered acceptable. In circumstances in which only drug options are considered, IFX and GOL are expected to be ruled out because of dominance, while the incremental cost-effectiveness ratio for ADA versus conventional treatment is approximately £50,300 per QALY gained. LIMITATIONS: The health economic model is subject to several limitations: uncertainty associated with extrapolating trial data over a lifetime horizon, the model does not consider explicit sequential pathways of non-biological treatments, and evidence relating to complications of colectomy was identified through consideration of approaches used within previous models rather than a full systematic review. CONCLUSIONS: Adult patients receiving IFX, ADA or GOL were more likely to achieve clinical response and remission than those receiving PBO. Further data are required to conclusively demonstrate the effect of interventions on hospitalisation and surgical outcomes. The economic analysis indicates that colectomy is expected to dominate medical treatments for moderate to severe UC. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013006883. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Clinical effectiveness of denosumab, raloxifene, romosozumab, and teriparatide for the prevention of osteoporotic fragility fractures : a systematic review and network meta-analysis

Objectives: To determine the clinical effectiveness of denosumab (DEN), raloxifene (RLX), romosozumab (ROMO) and teriparatide (TPTD), within their licensed (or anticipated licensed) indications, for the treatment of osteoporosis. Methods: A systematic review was conducted. Nine electronic databases and trial registries were searched up to the end of July 2018. Studies were eligible for inclusion if they were randomised controlled trials (RCT) in a population at risk of osteoporotic fracture, comparing these four non-bisphosphonates DEN, RLX, ROMO, or TPTD with each other, a non-active treatment, or the bisphosphonates alendronate (ALN), risedronate (RIS), ibandronate (IBN) and zoledronic acid (ZOL). Quality of included studies was assessed using the Cochrane Risk of Bias tool. Network metaanalyses (NMA) were used to determine the relative effectiveness of treatments. Results: The systematic review identified 7,898 citations. Forty-six RCTs of non-bisphosphonates met the inclusion criteria for the review and provided data for analyses. Additionally 49 RCTs of bisphosphonates were used in the NMAs. Forty-six RCTs were included in the NMA of vertebral fracture data, 23 RCTs for hip fractures and 73 RCTs in the NMA of femoral neck bone mineral density (FN BMD). For vertebral fractures, all four non-bisphosphonates showed statistically significant benefit relative to placebo: TPTD HR 0.23 (95% credible internal (CrI) 0.16, 0.32); ROMO followed by ALN 0.25 (95% CrI 0.15, 0.43); DEN HR 0.30 (95% CrI 0.21, 0.43); RLX HR 0.61 (95% CrI 0.44, 0.80). The four non-bisphosphonates interventions studied also showed statistically significant benefit relative to placebo for FN BMD, and for hip fractures TPTD, ROMO followed by ALN, and DEN showed statistically significant benefit relative to placebo. Conclusions: The four non-bisphosphonate interventions studied were all statistically significantly clinically effective for reducing vertebral fractures when compared to placebo, and were beneficial for change in FN BMD compared to placebo. All reduced hip fractures, and this was statistically significant for TPTD, ROMO followed by ALN, and DEN