Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for the treatment of rheumatoid arthritis not previously treated with disease-modifying antirheumatic drugs and after the failure of conventional disease-modifying antirheumatic drugs only: systematic review and economic evaluation.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increasing disability, reduced quality of life and substantial costs (as a result of both intervention acquisition and hospitalisation). The objective was to assess the clinical effectiveness and cost-effectiveness of seven biologic disease-modifying antirheumatic drugs (bDMARDs) compared with each other and conventional disease-modifying antirheumatic drugs (cDMARDs). The decision problem was divided into those patients who were cDMARD naive and those who were cDMARD experienced; whether a patient had severe or moderate to severe disease; and whether or not an individual could tolerate methotrexate (MTX). DATA SOURCES: The following databases were searched: MEDLINE from 1948 to July 2013; EMBASE from 1980 to July 2013; Cochrane Database of Systematic Reviews from 1996 to May 2013; Cochrane Central Register of Controlled Trials from 1898 to May 2013; Health Technology Assessment Database from 1995 to May 2013; Database of Abstracts of Reviews of Effects from 1995 to May 2013; Cumulative Index to Nursing and Allied Health Literature from 1982 to April 2013; and TOXLINE from 1840 to July 2013. Studies were eligible for inclusion if they evaluated the impact of a bDMARD used within licensed indications on an outcome of interest compared against an appropriate comparator in one of the stated population subgroups within a randomised controlled trial (RCT). Outcomes of interest included American College of Rheumatology (ACR) scores and European League Against Rheumatism (EULAR) response. Interrogation of Early Rheumatoid Arthritis Study (ERAS) data was undertaken to assess the Health Assessment Questionnaire (HAQ) progression while on cDMARDs. METHODS: Network meta-analyses (NMAs) were undertaken for patients who were cDMARD naive and for those who were cDMARD experienced. These were undertaken separately for EULAR and ACR data. Sensitivity analyses were undertaken to explore the impact of including RCTs with a small proportion of bDMARD experienced patients and where MTX exposure was deemed insufficient. A mathematical model was constructed to simulate the experiences of hypothetical patients. The model was based on EULAR response as this is commonly used in clinical practice in England. Observational databases, published literature and NMA results were used to populate the model. The outcome measure was cost per quality-adjusted life-year (QALY) gained. RESULTS: Sixty RCTs met the review inclusion criteria for clinical effectiveness, 38 of these trials provided ACR and/or EULAR response data for the NMA. Fourteen additional trials contributed data to sensitivity analyses. There was uncertainty in the relative effectiveness of the interventions. It was not clear whether or not formal ranking of interventions would result in clinically meaningful differences. Results from the analysis of ERAS data indicated that historical assumptions regarding HAQ progression had been pessimistic. The typical incremental cost per QALY of bDMARDs compared with cDMARDs alone for those with severe RA is > £40,000. This increases for those who cannot tolerate MTX (£50,000) and is > £60,000 per QALY when bDMARDs were used prior to cDMARDs. Values for individuals with moderate to severe RA were higher than those with severe RA. Results produced using EULAR and ACR data were similar. The key parameter that affected the results is the assumed HAQ progression while on cDMARDs. When historic assumptions were used typical incremental cost per QALY values fell to £38,000 for those with severe disease who could tolerate MTX. CONCLUSIONS: bDMARDs appear to have cost per QALY values greater than the thresholds stated by the National Institute for Health and Care Excellence for interventions to be cost-effective. Future research priorities include: the evaluation of the long-term HAQ trajectory while on cDMARDs; the relationship between HAQ direct medical costs; and whether or not bDMARDs could be stopped once a patient has achieved a stated target (e.g. remission). STUDY REGISTRATION: This study is registered as PROSPERO CRD42012003386. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

LGBT+ Networks, 2017-2020

The LGBT+ Networks data consists of 9 case studies of LGBT+ employee networks in the NHS (located in England, Scotland and Wales) and 118 short video clips from LGBT+ people and their allies. Qualitative data form the case studies was collected from September 2017 to October 2019. Each case study comprises transcripts from network meetings (38) and transcripts from interviews (65) with network chairs, network members, allies, EDI/HR representatives and chief executive officers in organisations. The short video clips (118) were recorded in a custom-made video booth located in 8 different organisations during LGBT+ history month in February 2020.This research aims to offer better understanding of how lesbian, gay, bisexual and transgender (LGBT+) employee networks are run and what they can do to improve relationships between colleagues, and ultimately, improve the wellbeing of LGBT+ employees. In doing so, the research focuses on LGBT+ employee networks within the NHS in nine different institutions by administering surveys, interviewing network members and taking part in network activities. To achieve our research aims, the following objectives have been set: 1) Establish baseline understanding of how LGBT+ employee networks operate; 2) Map network membership and explore ways of addressing insufficient representation of different groups with the networks; 3) Explore what support is in place to archive networks' vision and what barriers exists to realise this vision; 4) Examine ways of using LGBT+ employee networks to address negativity towards gender and sexual minorities more effectively.</p

Additional file 2 of Co-production practice and future research priorities in United Kingdom-funded applied health research: a scoping review

Additional file 2: Conceptualization and implementation of co-production in the included papers

Additional file 1 of Co-production practice and future research priorities in United Kingdom-funded applied health research: a scoping review

Additional file 1: Example search strategy for MEDLINE (adapted for other databases)

Co-production practice and future research priorities in United Kingdom-funded applied health research: a scoping review

Abstract Background Interest in and use of co-production in healthcare services and research is growing. Previous reviews have summarized co-production approaches in use, collated outcomes and effects of co-production, and focused on replicability and reporting, but none have critically reflected on how co-production in applied health research might be evolving and the implications of this for future research. We conducted this scoping review to systematically map recent literature on co-production in applied health research in the United Kingdom to inform co-production practice and guide future methodological research. Methods This scoping review was performed using established methods. We created an evidence map to show the extent and nature of the literature on co-production and applied health research, based on which we described the characteristics of the articles and scope of the literature and summarized conceptualizations of co-production and how it was implemented. We extracted implications for co-production practice or future research and conducted a content analysis of this information to identify lessons for the practice of co-production and themes for future methodological research. Results Nineteen articles reporting co-produced complex interventions and 64 reporting co-production in applied health research met the inclusion criteria. Lessons for the practice of co-production and requirements for co-production to become more embedded in organizational structures included (1) the capacity to implement co-produced interventions, (2) the skill set needed for co-production, (3) multiple levels of engagement and negotiation, and (4) funding and institutional arrangements for meaningful co-production. Themes for future research on co-production included (1) who to involve in co-production and how, (2) evaluating outcomes of co-production, (3) the language and practice of co-production, (4) documenting costs and challenges, and (5) vital components or best practice for co-production. Conclusion Researchers are operationalizing co-production in various ways, often without the necessary financial and organizational support required and the right conditions for success. We argue for accepting the diversity in approaches to co-production, call on researchers to be clearer in their reporting of these approaches, and make suggestions for what researchers should record. To support co-production of research, changes to entrenched academic and scientific practices are needed. Protocol registration details: The protocol for the scoping review was registered with protocols.io on 19 October 2021: https://dx.doi.org/10.17504/protocols.io.by7epzje

Additional file 3 of Characterisation of ethnic differences in DNA methylation between UK-resident South Asians and Europeans

Additional file 3. Table S1. EWAS results

Additional file 4 of Characterisation of ethnic differences in DNA methylation between UK-resident South Asians and Europeans

Additional file 4. Table S2. DMR results. Table S3. Epigenetic age acceleration results. Table S4. Cell count differences. Table S5. Effects of adjustment for mQTL and allele frequency differences. Table S6. Effects of adjustment for mQTL and allele frequency differences. Table S7. ANNOVAR enrichment. Table S8. GO term enrichment. Table S9. LOLA enrichment

Additional files of Polypharmacy during pregnancy and associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019

Additional files. Proportions of pregnancies with a prescribed medication – sensitivity analysis

Additional file 1 of Investigating causal relations between sleep duration and risks of adverse pregnancy and perinatal outcomes: linear and nonlinear Mendelian randomization analyses

Additional file 1: Table S1. Results extracted from recent systematic reviews. Table S2. Key characteristics of GWAS of self-report sleep duration. Table S3. SNP list and female-specific effect estimates of sleep duration SNPs identified in UK Biobank. Table S4. Definitions of outcomes. Table S5. Details of UKB women by sleep duration groups in one-sample MR. Table S6. Characteristics of the women in MoBa by sleep duration categories. Table S7. Associations of 78 SNPs with sleep duration and with outcomes in UKB, ALSPAC, BiB, and MoBa. Table S8. Two-sample MR estimates for causal effects of sleep duration on the outcomes. Table S9. MVreg associations of self-reported sleep duration categories with the outcomes in MoBa