Osteoarthritis year in review 2021: epidemiology & therapy

This "Year in review" presents a selection of research themes and individual studies from the clinical osteoarthritis (OA) field (epidemiology and therapy) and includes noteworthy descriptive, analytical-observational, and intervention studies. The electronic database search for the review was conducted in Medline, Embase and medRxiv (15th April 2020 to 1st April 2021). Following study screening, the following OA-related themes emerged: COVID-19; disease burden; occupational risk; prediction models; cartilage loss and pain; stem cell treatments; novel pharmacotherapy trials; therapy for less well researched OA phenotypes; benefits and challenges of Individual Participant Data (IPD) meta-analyses; patient choice-balancing benefits and harms; OA and comorbidity; and inequalities in OA. Headline study findings included: a longitudinal cohort study demonstrating no evidence for a harmful effect of non-steroidal anti-inflammatory drugs (NSAIDs) in terms of COVID-19 related deaths; a Global Burden of Disease study reporting a 102% increase in crude incidence rate of OA in 2017 compared to 1990; a longitudinal study reporting cartilage thickness loss was associated with only a very small degree of worsening in pain over 2 years; an exploratory analysis of a non-OA randomised controlled trial (RCT) finding reduced risk of total joint replacement with an Interleukin -1ß inhibitor (canakinumab); a significant relationship between cumulative disadvantage and clinical outcomes of pain and depression mediated by perceived discrimination in a secondary analysis from a RCT; worsening socioeconomic circumstances were associated with future arthritis diagnosis in an innovative natural experiment (with implications for unique research possibilities arising from the COVID-19 pandemic context)

Risk of gastrointestinal bleeding with direct oral anticoagulants: a systematic review and network meta-analysis

Background: Direct oral anticoagulants are increasingly used for a wide range of indications. However, data are conflicting about the risk of major gastrointestinal bleeding with these drugs. We compared the risk of gastrointestinal bleeding with direct oral anticoagulants, warfarin, and low-molecular-weight heparin. Methods: For this systematic review and meta-analysis, we searched MEDLINE and Embase from database inception to April 1, 2016, for prospective and retrospective studies that reported the risk of gastrointestinal bleeding with use of a direct oral anticoagulant compared with warfarin or low-molecular-weight heparin for all indications. We also searched the Cochrane Library for systematic reviews and assessment evaluations, the National Health Service (UK) Economic Evaluation Database, and ISI Web of Science for conference abstracts and proceedings (up to April 1, 2016). The primary outcome was the incidence of major gastrointestinal bleeding, with all gastrointestinal bleeding as a secondary outcome. We did a Bayesian network meta-analysis to produce incidence rate ratios (IRRs) with 95% credible intervals (CrIs). Findings: We identified 38 eligible articles, of which 31 were included in the primary analysis, including 287 692 patients exposed to 230 090 years of anticoagulant drugs. The risk of major gastrointestinal bleeding with direct oral anticoagulants did not differ from that with warfarin or low-molecular-weight heparin (factor Xa vs warfarin IRR 0·78 [95% CrI 0·47−1·08]; warfarin vs dabigatran 0·88 [0·59−1·36]; factor Xa vs low-molecular-weight heparin 1·02 [0·42−2·70]; and low-molecular-weight heparin vs dabigatran 0·67 [0·20−1·82]). In the secondary analysis, factor Xa inhibitors were associated with a reduced risk of all severities of gastrointestinal bleeding compared with warfarin (0·25 [0.07–0.76]) or dabigatran (0.24 [0.07–0.77]). Interpretation: Our findings show no increase in risk of major gastrointestinal bleeding with direct oral anticoagulants compared with warfarin or low-molecular-weight heparin. These findings support the continued use of direct oral anticoagulants. Funding: Leeds Teaching Hospitals Charitable Foundation

Interventions to identify and manage depression delivered by 'nontraditional' providers to community-dwelling older adults: A realist review.

BACKGROUND: Mental health problems experienced by older adults (60+ years of age) may remain hidden due to individual and system-level barriers. Opportunities to support early identification and management are therefore crucial. The National Health Service recommends wider public services that are embedded within local communities, but are not traditionally part of the healthcare landscape (i.e., 'nontraditional'), could facilitate engagement with healthcare by members of the public. Evidence for interventions involving Fire and Rescue, Police, Library services and postal workers, as nontraditional providers of mental health services, has not been synthesized previously. This review aims to understand how, why and in what contexts mental health interventions delivered by these nontraditional providers, to older adults, work. METHODS: A realist review of interventions to identify and/or manage mental health problems (depression with or without anxiety) experienced by older adults. Systematic, cluster and iterative literature searches were conducted. Intervention evidence was appraised for rigour and explanatory relevance and then coded to inform context-mechanism-outcome configurations (CMOCs). A public advisory group supported our initial evidence search strategy and definition of key terms. This review is registered with PROSPERO (CRD42020212498). RESULTS: Systematic searches revealed a dearth of evidence reporting mental health interventions delivered by nontraditional providers. Our scope was adjusted to consider interventions delivered by Fire and Police services only and for wider health and wellbeing concerns (e.g., dementia, falls prevention, mental health crises). Forty-three pieces of evidence were synthesized. Key themes included: legitimizing expanded roles, focusing on risk, intervention flexibility and organization integration; further subthemes are described. Themes map onto CMOCs and inform a preliminary programme theory. Findings were transposed to mental health contexts. CONCLUSIONS: Findings highlight challenges and opportunities for Fire and Police services, as nontraditional providers, to deliver interventions that identify and/or manage mental health problems among older adults. Our programme theory explains what could work, how, for whom and also by whom (i.e., which public services). Further empirical evidence is needed to test interventions, understand acceptability and inform implementation. PATIENT OR PUBLIC CONTRIBUTION: A public advisory group comprising older adults with lived experience of mental health problems and informal caregivers contributed to the original application, reviewed the scope and informed the approach to dissemination

Perceptions of gay men’s masculinity are associated with sexual self-label, voice quality and physique

Like all other men, gay men may utilise stereotypically masculine attributes and behaviours in an attempt to accrue ‘masculine capital’, a term referring to the social power afforded by the display of traits and behaviours associated with orthodox, ‘hegemonic’ masculinity. Previous research findings suggest that gay sexual self-labels – conveying position preferences in anal intercourse between men – voice quality and muscularity may contribute to gay men’s masculine capital. This study examined the relative contribution to gay men’s masculine capital made by sexual self-labels, voice quality (deep/high-pitched) and physique (muscularity/thinness). It also assessed the beliefs gay men and straight people hold regarding the gendered nature of gay sexual self-labels in anal intercourse. Results from a survey of 538 participants showed that gay and straight people perceived the anally insertive sexual self-label as the most masculine and the anally receptive self-label the least masculine. The findings also revealed that voice quality and physique were more strongly associated with perceptions of gay men’s masculinity than their sexual self-label, although gay men who had masculine attributes and were anally receptive were perceived as less masculine than those who had the same attributes and were anally insertive

Correction to: The association between anxiety and disease activity and quality of life in rheumatoid arthritis: a systematic review and meta-analysis.

The authors of the published original version of the above article wanted to correct the below text in the Abstract section

Postglacial colonization history reflects in the genetic structure of natural populations of Festuca rubra in Europe

We conducted a large-scale population genetic survey of genetic diversity of the host grass Festuca rubra s.l., which fitness can be highly dependent on its symbiotic fungus Epichloe festucae, to evaluate genetic variation and population structure across the European range. The 27 studied populations have previously been found to differ in frequencies of occurrence of the symbiotic fungus E. festucae and ploidy levels. As predicted, we found decreased genetic diversity in previously glaciated areas in comparison with nonglaciated regions and discovered three major maternal genetic groups: southern, northeastern, and northwestern Europe. Interestingly, host populations from Greenland were genetically similar to those from the Faroe Islands and Iceland, suggesting gene flow also between those areas. The level of variation among populations within regions is evidently highly dependent on the postglacial colonization history, in particular on the number of independent long-distance seed colonization events. Yet, also anthropogenic effects may have affected the population structure in F. rubra. We did not observe higher fungal infection rates in grass populations with lower levels of genetic variability. In fact, the fungal infection rates of E. festucae in relation to genetic variability of the host populations varied widely among geographical areas, which indicate differences in population histories due to colonization events and possible costs of systemic fungi in harsh environmental conditions. We found that the plants of different ploidy levels are genetically closely related within geographic areas indicating independent formation of polyploids in different maternal lineages.Peer reviewe

The historical vanishing of the Blazhko effect of RR Lyr from GEOS and Kepler surveys

RR Lyr is one of the most studied variable stars. Its light curve has been regularly monitored since the discovery of the periodic variability in 1899. Analysis of all observed maxima allows us to identify two primary pulsation states defined as pulsation over a long (P0 longer than 0.56684 d) and a short (P0 shorter than 0.56682 d) primary pulsation period. These states alternate with intervals of 13-16 yr, and are well defined after 1943. The 40.8 d periodical modulations of the amplitude and the period (i.e. Blazhko effect) were noticed in 1916. We provide homogeneous determinations of the Blazhko period in the different primary pulsation states. The Blazhko period does not follow the variations of P0 and suddenly diminished from 40.8 d to around 39.0 d in 1975. The monitoring of these periodicities deserved and deserves a continuous and intensive observational effort. For this purpose we have built dedicated, transportable and autonomous small instruments, Very Tiny Telescopes (VTTs), to observe the times of maximum brightness of RR Lyr. As immediate results the VTTs recorded the last change of P0 state in mid-2009 and extended the time coverage of the Kepler observations, thus recording a maximum O-C amplitude of the Blazhko effect at the end of 2008, followed by the historically smallest O-C amplitude in late 2013. This decrease is still ongoing and VTT instruments are ready to monitor the expected increase in the next few years.Comment: 10 pages, 6 figures. Accepted for publication in MNRAS. Contents of appendix B may be requested to first autho

Acceptability of bisphosphonates among patients, clinicians and managers: a systematic review and framework synthesis

Objective: To explore the acceptability of different bisphosphonate regimens for the treatment of osteoporosis among patients, clinicians and managers, payers and academics. Design: A systematic review of primary qualitative studies. Seven databases were searched from inception to July 2019. Screening, data extraction and quality assessment of full-articles selected for inclusion were performed independently by two authors. A framework synthesis was applied to extracted data based on the theoretical framework of acceptability (TFA). The TFA includes seven domains relating to sense-making, emotions, opportunity costs, burden, perceived effectiveness, ethicality and self-efficacy. Confidence in synthesis findings was assessed. Setting: Any developed country healthcare setting. Participants: Patients, healthcare professionals, managers, payers and academics. Intervention: Experiences and views of oral and intravenous bisphosphonates. Results: Twenty-five studies were included, mostly describing perceptions of oral bisphosphonates. We identified, with high confidence, how patients and healthcare professionals make sense (coherence) of bisphosphonates by balancing perceptions of need against concerns, how uncertainty prevails about bisphosphonate perceived effectiveness and a number of individual and service factors that have potential to increase self-efficacy in recommending and adhering to bisphosphonates. We identified, with moderate confidence, that bisphosphonate taking induces concern, but has the potential to engender reassurance, and that both side effects and special instructions for taking oral bisphosphonates can result in treatment burden. Finally, we identified with low confidence that multimorbidity plays a role in people’s perception of bisphosphonate acceptability. Conclusion: By using the lens of acceptability, our findings demonstrate with high confidence that a theoretically informed, whole-system approach is necessary to both understand and improve adherence. Clinicians and patients need supporting to understand the need for bisphosphonates, and clinicians need to clarify to patients what constitutes bisphosphonate treatment success. Further research is needed to explore perspectives of male patients and those with multimorbidity receiving bisphosphonates, and patients receiving intravenous treatment