Explore the vast range of titles available.

AbstractObjectiveTo compare the efficacy, safety, and cost effectiveness of direct acting oral anticoagulants (DOACs) for patients with atrial fibrillation.DesignSystematic review, network meta-analysis, and cost effectiveness analysis.Data sourcesMedline, PreMedline, Embase, and The Cochrane Library.Eligibility criteria for selecting studiesPublished randomised trials evaluating the use of a DOAC, vitamin K antagonist, or antiplatelet drug for prevention of stroke in patients with atrial fibrillation.Results23 randomised trials involving 94 656 patients were analysed: 13 compared a DOAC with warfarin dosed to achieve a target INR of 2.0-3.0. Apixaban 5 mg twice daily (odds ratio 0.79, 95% confidence interval 0.66 to 0.94), dabigatran 150 mg twice daily (0.65, 0.52 to 0.81), edoxaban 60 mg once daily (0.86, 0.74 to 1.01), and rivaroxaban 20 mg once daily (0.88, 0.74 to 1.03) reduced the risk of stroke or systemic embolism compared with warfarin. The risk of stroke or systemic embolism was higher with edoxaban 60 mg once daily (1.33, 1.02 to 1.75) and rivaroxaban 20 mg once daily (1.35, 1.03 to 1.78) than with dabigatran 150 mg twice daily. The risk of all-cause mortality was lower with all DOACs than with warfarin. Apixaban 5 mg twice daily (0.71, 0.61 to 0.81), dabigatran 110 mg twice daily (0.80, 0.69 to 0.93), edoxaban 30 mg once daily (0.46, 0.40 to 0.54), and edoxaban 60 mg once daily (0.78, 0.69 to 0.90) reduced the risk of major bleeding compared with warfarin. The risk of major bleeding was higher with dabigatran 150 mg twice daily than apixaban 5 mg twice daily (1.33, 1.09 to 1.62), rivaroxaban 20 mg twice daily than apixaban 5 mg twice daily (1.45, 1.19 to 1.78), and rivaroxaban 20 mg twice daily than edoxaban 60 mg once daily (1.31, 1.07 to 1.59). The risk of intracranial bleeding was substantially lower for most DOACs compared with warfarin, whereas the risk of gastrointestinal bleeding was higher with some DOACs than warfarin. Apixaban 5 mg twice daily was ranked the highest for most outcomes, and was cost effective compared with warfarin.ConclusionsThe network meta-analysis informs the choice of DOACs for prevention of stroke in patients with atrial fibrillation. Several DOACs are of net benefit compared with warfarin. A trial directly comparing DOACs would overcome the need for indirect comparisons to be made through network meta-analysis.Systematic review registrationPROSPERO CRD 42013005324.

To develop ROBIS, a new tool for assessing the risk of bias in systematic reviews (rather than in primary studies). We used four-stage approach to develop ROBIS: define the scope, review the evidence base, hold a face-to-face meeting, and refine the tool through piloting. ROBIS is currently aimed at four broad categories of reviews mainly within health care settings: interventions, diagnosis, prognosis, and etiology. The target audience of ROBIS is primarily guideline developers, authors of overviews of systematic reviews (“reviews of reviews”), and review authors who might want to assess or avoid risk of bias in their reviews. The tool is completed in three phases: (1) assess relevance (optional), (2) identify concerns with the review process, and (3) judge risk of bias. Phase 2 covers four domains through which bias may be introduced into a systematic review: study eligibility criteria; identification and selection of studies; data collection and study appraisal; and synthesis and findings. Phase 3 assesses the overall risk of bias in the interpretation of review findings and whether this considered limitations identified in any of the phase 2 domains. Signaling questions are included to help judge concerns with the review process (phase 2) and the overall risk of bias in the review (phase 3); these questions flag aspects of review design related to the potential for bias and aim to help assessors judge risk of bias in the review process, results, and conclusions. ROBIS is the first rigorously developed tool designed specifically to assess the risk of bias in systematic reviews.

Background There is growing interest in the use of cognitive, behavioural, and organisational theories in implementation research. However, the extent of use of theory in implementation research is uncertain. Methods We conducted a systematic review of use of theory in 235 rigorous evaluations of guideline dissemination and implementation studies published between 1966 and 1998. Use of theory was classified according to type of use (explicitly theory based, some conceptual basis, and theoretical construct used) and stage of use (choice/design of intervention, process/mediators/moderators, and post hoc/explanation). Results Fifty-three of 235 studies (22.5%) were judged to have employed theories, including 14 studies that explicitly used theory. The majority of studies (n = 42) used only one theory; the maximum number of theories employed by any study was three. Twenty-five different theories were used. A small number of theories accounted for the majority of theory use including PRECEDE (Predisposing, Reinforcing, and Enabling Constructs in Educational Diagnosis and Evaluation), diffusion of innovations, information overload and social marketing (academic detailing). Conclusions There was poor justification of choice of intervention and use of theory in implementation research in the identified studies until at least 1998. Future research should explicitly identify the justification for the interventions. Greater use of explicit theory to understand barriers, design interventions, and explore mediating pathways and moderators is needed to advance the science of implementation research.

Researchers are increasingly encouraged to co-produce research, involving members of the public, service users, policy makers and practitioners in more equal relationships throughout a research project. The sharing of power is often highlighted as a key principle when co-producing research. However, health and social care research, as with many other academic disciplines, is carried out within embedded hierarchies and structural inequalities in universities, public service institutions, and research funding systems—as well as in society more broadly. This poses significant challenges to ambitions for co-production. This article explores the difficulties that are faced when trying to put ideal co-production principles into practice. A reflective account is provided of an interdisciplinary project that aimed to better understand how to reduce power differentials within co-produced research. The project facilitated five workshops, involving researchers from different disciplines, health, social care and community development staff and public contributors, who all had experience in co-production within research. In the workshops, people discussed how they had attempted to enable more equal relationships and shared ideas that supported more effective and equitable co-produced research. Shared interdisciplinary learning helped the project team to iteratively develop a training course, a map of resources and reflective questions to support co-produced research. The gap between co-production principles and practice is challenging. The article examines the constraints that exist when trying to share power, informed by multidisciplinary theories of power. To bring co-production principles into practice, changes are needed within research practices, cultures and structures; in understandings of what knowledge is and how different forms of knowledge are valued. The article outlines challenges and tensions when co-producing research and describes potential ideas and resources that may help to put co-production principles into practice. We highlight that trying to maintain all principles of co-production within the real-world of structural inequalities and uneven distribution of resources is a constant challenge, often remaining for now in the realm of aspiration.

ObjectivesThis qualitative study aimed to investigate: (1) priorities of patients and healthcare professionals during recovery from a burn injury, (2) how priorities change over time and (3) how priorities map to outcomes currently reported in burns research.DesignSemi-structured interviews were conducted. Interviews were audio recorded, transcribed and analysed thematically.Setting, participantsA total of 53 patients and healthcare professionals were recruited from four National Health Service (NHS) burn services across England and Wales across England and Wales. Patient participants (n=32) included adults, adolescents and parents of paediatric patients, with a variety of burn injuries in terms of severity and cause of burn injury. Healthcare professionals (n=21) were NHS staff members involved in burn care and included professionals with a range of clinical experience and roles (eg, nurses, surgeons, occupational therapists, physiotherapist, administration).ResultsTen themes relating to priorities (outcomes) during recovery from a burn injury were identified for patients and professionals. Of those, six were identified for patients and professionals (‘pain and discomfort’, ‘psychological well-being’, ‘healing’, ‘scarring’, ‘function’, ‘infection’), three were unique to professionals (‘patient knowledge, understanding and support’, ‘sense of control’, ’survival’) and one was unique to patients (‘uncertainty’). Results highlighted that importance of these priorities changes over time (eg, ‘survival’ was only a concern in the short term). Likewise, priorities differed between patients and professionals (eg, ‘pain’ was important to patients throughout their recovery, but not for professionals). Seven out of 10 themes overlapped with outcomes commonly assessed in burn research.ConclusionProfessionals’ and patients’ priorities (important outcomes) change over time after burn injury and differ between those groups. Burn care research should consider measuring outcomes at different time points during the recovery from a burn injury to accurately reflect complexity of burn recovery.

To compare the views of participants from different income-status countries on outcome selection for a burn care Core Outcome Set (COS). A retrospective analysis of data collected during a two round Delphi survey to prioritise the most important outcomes in burn care research. There was considerable agreement between participants from low- and middle-income countries (LMICs) and high-income countries (HICs) across outcomes. The groups agreed on 91% of 88 outcomes in round 1 and 92% of 100 in round 2. In cases of discordance, the consensus of participants from LMICs was to include the outcome and for participants from HICs to exclude. There was also considerable agreement between the groups for the top-ten ranking outcomes. Discordance in outcome prioritisation gives an insight into the different values clinicians from LMICs place on outcomes compared to those from HICs. Limitations of the study were that outcome rankings from international patients were not available. Healthcare professionals from LMICs were not involved in the final consensus meeting. COS developers should consider the need for a COS to be global at protocol stage. Global COS should include equal representation from both LMICs and HICs at all stages of development.

Background Infantile colic is a distressing condition characterised by excessive crying in the first few months of life. The aim of this research was to update the synthesis of evidence of complementary and alternative medicine (CAM) research literature on infantile colic and establish what evidence is currently available. Methods Medline, Embase and AMED (via Ovid), Web of Science and Central via Cochrane library were searched from their inception to September 2018. Google Scholar and OpenGrey were searched for grey literature and PROSPERO for ongoing reviews. Published systematic reviews that included randomised controlled trials (RCTs) of infants aged up to 1 year, diagnosed with infantile colic using standard diagnostic criteria, were eligible. Reviews of RCTs that assessed the effectiveness of any individual CAM therapy were included. Three reviewers were involved in data extraction and quality assessment using the AMSTAR-2 scale and risk of bias using the ROBIS tool. Results Sixteen systematic reviews were identified. Probiotics, fennel extract and spinal manipulation show promise to alleviate symptoms of colic, although some concerns remain. Acupuncture and soy are currently not recommended. The majority of the reviews were assessed as having high or unclear risk of bias and low confidence in the findings. Conclusion There is clearly a need for larger and more methodologically sound RCTs to be conducted on the effectiveness of some CAM therapies for IC. Particular focus on probiotics in non-breastfed infants is pertinent. Systematic review registration PROSPERO: CRD42018092966.

Background Fibromyalgia (FM) is a chronic, debilitating pain disorder. Dissatisfaction with conventional medicine can lead people with FM to turn to complementary and alternative medicine (CAM). Two previous overviews of systematic reviews of CAM for FM have been published, but they did not assessed for risk of bias in the review process. Methods Five databases Medline, Embase, AMED (via OVID), Web of Science and Central were searched from their inception to December 2015. Reference lists were hand-searched. We had two aims: the first was to provide an up-to-date and rigorously conducted synthesis of systematic reviews of CAM literature on FM; the second was to evaluate the quality of the available systematic review evidence using two different tools: AMSTAR (Shea et al. BMC Med Res Methodol 15; 7:10, 2007) and a more recently developed tool ROBIS (Whiting et al. J Clin Epidemiol 69:225-34, 2016) specifically designed to assess risk of bias in systematic reviews. Any review that assessed one of eight CAM therapies for participants diagnosed with FM was considered. The individual studies had to be randomised controlled trials where the intervention was compared to placebo, treatment as usual or waitlist controls to be included. The primary outcome measure was pain, and the secondary outcome measure was adverse events. Results We identified 15 reviews that met inclusion criteria. There was low-quality evidence that acupuncture improves pain compared to no treatment or standard treatment, but good evidence that it is no better than sham acupuncture. The evidence for homoeopathy, spinal manipulation and herbal medicine was limited. Conclusions Overall, five reviews scored 6 or above using the AMSTAR scale and the inter-rater agreement was good (83.6%), whereas seven reviews achieved a low risk of bias rating using ROBIS and the inter-rater agreement was fair (60.0%). No firm conclusions were drawn for efficacy of either spinal manipulation or homoeopathy for FM. There is limited evidence for topical Capsicum , but further research is required. There is some evidence to support the effectiveness of acupuncture for FM, but further high-quality trials are needed to investigate its benefits, harms and mechanisms of action, compared with no or standard treatment. Systematic review registration PROSPERO CRD42016035846 .

IntroductionUsing a surrogate endpoint as a substitute for a primary patient-relevant outcome enables randomised controlled trials (RCTs) to be conducted more efficiently, that is, with shorter time, smaller sample size and lower cost. However, there is currently no consensus-driven guideline for the reporting of RCTs using a surrogate endpoint as a primary outcome; therefore, we seek to develop SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) and CONSORT (Consolidated Standards of Reporting Trials) extensions to improve the design and reporting of these trials. As an initial step, scoping and targeted reviews will identify potential items for inclusion in the extensions and participants to contribute to a Delphi consensus process.Methods and analysisThe scoping review will search and include literature reporting on the current understanding, limitations and guidance on using surrogate endpoints in trials. Relevant literature will be identified through: (1) bibliographic databases; (2) grey literature; (3) handsearching of reference lists and (4) solicitation from experts. Data from eligible records will be thematically analysed into potential items for inclusion in extensions. The targeted review will search for RCT reports and protocols published from 2017 to 2021 in six high impact general medical journals. Trial corresponding author contacts will be listed as potential participants for the Delphi exercise.Ethics and disseminationEthical approval is not required. The reviews will support the development of SPIRIT and CONSORT extensions for reporting surrogate primary endpoints (surrogate endpoint as the primary outcome). The findings will be published in open-access publications.This review has been prospectively registered in the OSF Registration DOI: 10.17605/OSF.IO/WP3QH.

Background To help resolve high suicide rates in Bristol, North Somerset and South Gloucestershire, the charity Second Step was commissioned to roll-out the Hope service offering a psychosocial intervention for men, supporting them through acute distress and addressing financial difficulties. This study evaluated the impact of the Hope service on men at risk of suicide experiencing financial and other difficulties. Methods Mixed methods study using: (i) a prospective cohort study design to compare depression, suicidal ideation and financial self-efficacy scores of men aged 30–64, referred to the service between October 2018 and July 2020, at baseline and 6 months follow-up and between low and moderate to high-intensity service users; and (ii) a qualitative interview study to evaluate the acceptability and impact of the Hope service to Hope service users. Results There was a 49% reduction in depression score (mean reduction − 10.0, 95% CI − 11.7 to − 8.3) and in the proportion of service users with suicidal ideation (percent reduction − 52.5, 95% CI − 64.1% to − 40.9%) at 6 months follow-up compared to baseline. Financial self-efficacy scores increased by 26% (mean increase 2.9, 95% CI 1.8 to 3.9). Qualitative accounts illustrated how ‘Hope saved my life’ for several men interviewed; most respondents described being able to move forward and tackle challenges with more confidence following the Hope intervention. Professional advice to tackle financial and other difficulties such as housing helped to relieve anxiety and stress and enable practical issues to be resolved. Conclusions The Hope service offered practical and emotional support to men who have experienced suicidal feelings, redundancy, homelessness and poverty and occupies an important space between mental health and social care provision. Hope demonstrates the value of an intervention which cuts across traditional boundaries between psychiatric care and social advice agencies to provide, what is, in effect, an integrated care service.