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Objectives To explore current management practices for PMR by general practitioners (GPs) and rheumatologists including implications for clinical trial recruitment. Methods An English language questionnaire was constructed by a working group of rheumatologists and GPs from six countries. The questionnaire focused on: 1: Respondent characteristics; 2: Referral practices; 3: Treatment with glucocorticoids; 4: Diagnostics; 5: Comorbidities; and 6: Barriers to research. The questionnaire was distributed to rheumatologists and GPs worldwide via members of the International PMR/Giant Cell Arteritis Study Group. Results In total, 394 GPs and 937 rheumatologists responded to the survey. GPs referred a median of 25% of their suspected PMR patients for diagnosis and 50% of these were returned to their GP for management. In general, 39% of rheumatologists evaluated patients with suspected PMR >2 weeks after referral, and a median of 50% of patients had started prednisolone before rheumatologist evaluation. Direct comparison of initial treatment showed that the percentage prescribing >25 mg prednisolone daily for patients was 30% for GPs and 12% for rheumatologists. Diagnostic imaging was rarely used. More than half (56%) of rheumatologists experienced difficulties recruiting people with PMR to clinical trials. Conclusion This large international survey indicates that a large proportion of people with PMR are not referred for diagnosis, and that the proportion of treatment-naive patients declined with increasing time from referral to assessment. Strategies are needed to change referral and management of people with PMR, to improve clinical practice and facilitate recruitment to clinical trials.

BackgroundThe Valneva COVID-19 vaccine (VLA2001; Valneva Austria, Vienna, Austria) is an inactivated whole-virus, adjuvanted SARS-CoV-2 vaccine. We aimed to assess the safety and immunogenicity of primary vaccination with VLA2001 versus the ChAdOx1-S (Oxford-AstraZeneca) adenoviral-vectored vaccine.MethodsIn this immunobridging phase 3 trial (COV-COMPARE), participants aged 18 years and older who were medically stable (as determined by an investigator) were enrolled at 26 sites in the UK. In the double-blind, randomised, controlled arm of the trial, participants aged 30 years and older were randomly assigned (2:1) to receive two doses of VLA2001 (0·5 mL; with 33 antigen units [AU] per dose) or ChAdOx1-S (0·5 mL; with 2·5 × 108 infectious units per dose) on days 1 and 29. In another arm, participants aged 18–29 years received two doses of VLA2001 (same dose) open label on days 1 and 29. The primary immunogenicity outcome was the immune response of a two-dose schedule of VLA2001 on day 43, in adults aged 30 years and older, versus two doses of ChAdOx1-S via superiority of geometric mean titres (GMTs) of neutralising antibodies (GMT ratio of >1 at a two-sided significance level of 5%) and non-inferiority of the seroconversion rate (non-inferiority margin of –10% for the lower limit of the 95% CI for the difference between groups). The primary safety outcome was the frequency and severity of any adverse events in all participants up to day 43. Safety was assessed in all participants who received at least one dose of vaccine. GMTs were assessed in a subset of participants aged 30 years and older who were seronegative at baseline, had at least one evaluable antibody titre measurement after vaccination, and had no confirmed COVID-19 during the study (immunogenicity population); and seroconversion was assessed in the per-protocol population, which comprised the immunogenicity population but excluding any participants with major protocol violations. For each timepoint, only participants with available data were included in the analysis. This study is registered with ClinicalTrials.gov, NCT04864561, and is ongoing.FindingsBetween April 28 and June 3, 2021, 4181 individuals were screened and 4017 enrolled, of whom 2975 (74%) were aged 30 years or older and randomly assigned to receive VLA2001 (n=1978) or ChAdOx1-S (n=997), and 1042 (26%) were aged 18–29 years (all received open-label VLA2001). 4012 participants received at least one dose of vaccine (1040 in the open-label VLA2001 group, 1977 in the randomised VLA2001 group, and 995 in the ChAdOx1-S group). The immunogenicity population comprised 492 participants in the randomised VLA2001 group and 498 in the ChAdOx1-S group; three participants in the VLA2001 group were excluded from the per-protocol population. VLA2001 induced higher neutralising GMTs than did ChAdOx1-S (803·5 [95% CI 748·5–862·6] vs 576·6 [543·6–611·7]; GMT ratio 1·39 [95% CI 1·25–1·56]; pInterpretationVLA2001 has a favourable tolerability profile and met superiority criteria for neutralising antibodies and non-inferiority criterion for seroconversion rates compared with ChAdOx1-S. The data presented here formed the basis of successful marketing approval for use of VLA2001 in primary vaccination in the EU, the UK, Bahrain, and United Arab Emirates.

Objectives To determine the impact of polymyalgia rheumatica (PMR) on intimate and sexual relationships over time. Methods The PMR Cohort study (UKCRN ID16477) is a longitudinal study of patients with incident PMR in English primary care. Participants were sent questions about their PMR symptoms, treatments and overall health, including an item about how their PMR symptoms affected intimate and sexual relationships. The proportion reporting the relevance of intimate and sexual relationships, the effect of PMR on these relationships and the associations with PMR symptoms and general health were explored. Results 652/739 patients (response 90.1%) completed the baseline survey, with 446/576 (78.0%) responding at two years. Mean age of responders was 72.4 years. 62.2% were female. 363/640 (56.7%) participants reported that intimate and sexual relationships were not relevant to them at baseline. 113/277 (40.8%) reported that PMR had a large effect on intimate relationships. This proportion decreased over time in those responding to 12- and 24-month surveys, but continued to be associated with younger age, male gender, worse PMR symptoms, poorer physical function and worse mental health. Conclusion Intimate and sexual relationships are increasingly recognised as important for healthy ageing and health professionals should consider this as part of a holistic approach to the management of PMR. Lay summary What does this mean for patients? Polymyalgia rheumatica (PMR) is a condition that affects older people. It causes pain and stiffness in the hips and shoulders, as well as making people feel very tired. It can stop people from doing routine things that they previously did with no problem (e.g. walking upstairs, getting out of a car). We know very little about how PMR affects people’s personal lives. Therefore, we sent a questionnaire to 652 people in England with newly diagnosed PMR. One question asked people whether their PMR affected their “intimate and sexual relationships”. We asked the same question again 1 and 2 years later. Just over half of people said this wasn’t relevant for them. For people where it mattered to them, 4 in 10 said PMR had a large effect on their relationships. Men, people who were younger, those with worse PMR symptoms and worse mental health were more likely to report a negative effect of PMR on their relationships. The proportion of people reporting a problem reduced over time, as people’s PMR symptoms improved. We suggest that doctors should consider people’s intimate and sexual relationships as part of their care for people with PMR.

Summary The COVID-19 pandemic signalled a radical shift in health and social care services globally. In UK, many of the people with existing social care needs were identified as ‘clinically vulnerable’ to COVID-19. Those at greatest risk were encouraged to adhere to additional public health measures that inadvertently exacerbated social disadvantages. Social workers were challenged to ‘dig deep’ to continue to provide services as usual. However, problems implementing new ways of working were reported but not examined in-depth through research. Our study explored experiences and perceptions of social workers responding to the first wave (April–July 2020) of COVID-19, in England, UK. Interviews with thirteen social workers, all working in the West Midlands region, were conducted via telephone or online video. Transcripts were analysed using reflexive thematic analysis. We use ‘managing uncertainty’ as a central concept underpinning the four themes identified after analysis: (1) providing social care at a physical distance, (2) negotiating home/work boundaries, (3) managing emerging risks and (4) long-term implications for social work. We discuss our findings in the context of resilience and organisational adaptation. Social workers in our study demonstrated resilience in action and rapid adaptation to new practices, but equally expressed concern about short-term efficiencies being prioritised over individual service user needs., The COVID-19 pandemic signalled a dramatic shift in how health and social care services were delivered to members of the public. Social workers reported challenges implementing new ways of working during the first wave of COVID-19. However, such challenges received little coverage in the media or in research. This article explores the views and experiences of social workers responding to the first COVID-19 wave in England, UK (April–July 2020). Telephone and online interviews were carried out with thirteen social workers active in the West Midlands region. Social workers shared experiences of how they managed uncertainty—a core theme in the study. Interviewees described managing the uncertainty of: (1) providing social care at a physical distance, (2) negotiating home/work boundaries, (3) managing emerging risks and (4) contemplating the future of social work practice. Our study demonstrates how social work professionals adapted rapidly to new practices during the first wave. However, social workers raised concerns about the impact of short-term solutions on long-term needs of service users. Implications for research and practice are discussed with reference to key literature.

Evidence from the Global Burden of Disease studies suggests that osteoarthritis (OA) is a significant cause of disability globally; however, it is less clear how much of this burden exists in low-income and lower middle-income countries. This study aims to determine the prevalence of OA in people living in low-income and lower middle-income countries. Four electronic databases (MEDLINE, EMBASE, CINAHL and Web of Science) were systematically searched from inception to October 2018 for population-based studies. We included studies reporting the prevalence of OA among people aged 15 years and over in low-income and lower middle-income countries. The prevalence estimates were pooled across studies using random effects meta-analysis. Our study was registered with PROSPERO, number CRD42018112870.The search identified 7414 articles, of which 356 articles were selected for full text assessment. 34 studies were eligible and included in the systematic review and meta-analysis. The pooled prevalence of OA was 16·05% (95% confidence interval (CI) 12·55–19·89), with studies demonstrating a substantial degree of heterogeneity (I2 = 99·50%). The pooled prevalence of OA was 16.4% (CI 11·60–21.78%) in South Asia, 15.7% (CI 5·31–30·25%) in East Asia and Pacific, and 14.2% (CI 7·95–21·89%) in Sub Saharan Africa. The meta-regression analysis showed that publication year, study sample size, risk of bias score and country-income categories were significantly associated with the variations in the prevalence estimates. The prevalence of OA is high in low-income and lower middle-income countries, with almost one in six of the study participants reported to have OA. With the changing population demographics and the shift to the emergence of non-communicable diseases, targeted public health strategies are urgently needed to address this growing epidemic in the aging population. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-021-04838-y.

Objectives: To determine the burden of comorbidities, including glucocorticoid (GC) related adverse effects, in patients with polymyalgia rheumatica (PMR) before and after diagnosis.\ud \ud Methods: We extracted anonymised electronic medical records of patients over the age of 40 years from the Clinical Practice Research Datalink from 1990-2016. Patients with PMR were individually matched on age, sex and registered General Practice to between three and five controls. The prevalence, cumulative probability and likelihood of a range of comorbidities was estimated. Odds ratios (ORs) and hazard ratios (HRs) were calculated using conditional logistic regression and Cox proportional hazards regression respectively, adjusted for a wide range of covariates.\ud \ud Results: 31,984 patients with PMR were matched to 149,436 controls. PMR was prospectively associated with vascular disease (adjusted HR 1.23 [95% confidence interval (CI) 1.19, 1.28]), as well as respiratory (HR 1.25 [1.18, 1.32]), renal (HR 1.34 [1.30, 1.39]), and autoimmune diseases (HR 4.68 [4.35, 5.03]). Conversely, before PMR diagnosis, the risk of cancer (adjusted OR [OR] 0.89 [0.86, 0.93]) and neurological disease (OR 0.36 [0.33, 0.40]) was significantly lower. Patients with PMR had an increased risk of comorbidities associated with glucocorticoid (GC) use.\ud \ud Conclusions\ud Patients with PMR have a high comorbidity burden, both before and after diagnosis. Whilst further work is needed to more fully understand these associations, clinicians should be aware of the high prevalence of comorbid conditions in this group and the impact that treatment with glucocorticoids may have on comorbidity.

Objectives To investigate potential subgroups of primary care–diagnosed patients with PMR based on self-reported pain and stiffness severity over time. Methods A total of 652 people with an incident PMR diagnosis were recruited from English general practices and completed a baseline postal questionnaire. They were followed up with a further six questionnaires over a 2 year period. A total of 446 people completed the 2 year follow-up. Pain and stiffness were reported on a 0–10 numerical rating scale. Latent class growth analysis was used to estimate the joint trajectories of pain and stiffness over time. A combination of statistical and clinical considerations was used to choose the number of clusters. Characteristics of the classes were described. Results Five clusters were identified. One cluster represented the profile of ‘classical’ PMR symptoms and one represented sustained symptoms that may not be PMR. The other three clusters displayed a partial recovery, a recovery followed by worsening and a slow, but sustained recovery. Those displaying classical PMR symptoms were in better overall health at diagnosis than the other groups. Conclusion PMR is a heterogeneous condition, with a number of phenotypes. The spectrum of presentation, as well as varying responses to treatment, may be related to underlying health status at diagnosis. Future research should seek to stratify patients at diagnosis to identify those likely to have a poor recovery and in need of an alternative treatment pathway. Clinicians should be aware of the different experiences of patients and monitor symptoms closely, even where there is initial improvement.

Permanent vision loss is one of the most serious complications of giant cell arteritis (GCA) and therefore prompt diagnosis is paramount. However, diagnosis of GCA remains challenging due to its frequently non-specific presentation. Our aim was to identify differences in the characteristics of GCA patients with, and without, current visual symptoms. A cross-sectional survey was mailed to patients with a GCA Read code entered in their GP electronic medical record. Responders were categorised as those currently reporting a visual symptom or not. We compared general and GCA-specific characteristics in these two groups. The association of diagnostic delay with subsequent experience of visual symptoms was examined using unadjusted and adjusted linear regression analysis. 318 GCA patients responded to the survey (59.6%). Responders were predominantly female (69.8%), with a mean age of 73.7 years (SD 8.2). 28% reported current visual symptoms. There was no statistically significant difference in the general characteristics between those with and without visual symptoms. Of GCA-specific characteristics, pre-GCA diagnosis of diplopia (p = 0.018), temporary (p ≤ 0.001) or permanent visual problems (p = 0.001) and hoarseness (p = 0.004) were more common among those reporting current visual symptoms. There was no association between the extent of diagnostic delay and reporting of current visual symptoms. Though we found few characteristics to distinguish between GCA patients with or without current visual symptoms, diagnostic delay was not associated with current visual symptoms. Our findings highlighted the continued difficulty for clinicians to identify GCA patients at the highest risk of visual complications.

Background Antibiotic-induced disturbances of the human microbiota have been implicated in the development of chronic autoimmune conditions. This study aimed to assess whether antibiotic use is associated with the onset of rheumatoid arthritis (RA). Methods A nested case-control study was conducted utilising data from the primary care Clinical Practice Research Datalink (CPRD). Patients with an incident diagnosis of RA were identified (1995–2017). Each case was matched on age, gender, and general practice to ≥ 5 controls without RA. Conditional logistic regression was used to examine previous antibiotic prescriptions and RA onset after controlling for confounding factors. Results We identified 22,677 cases of RA, matched to 90,013 controls, with a median follow-up of 10 years before RA diagnosis. The odds of developing RA were 60% higher in those exposed to antibiotics than in those not exposed (OR 1.60; 95% CI 1.51–1.68). A dose- or frequency-dependent association was observed between the number of previous antibiotic prescriptions and RA. All classes of antibiotics were associated with higher odds of RA, with bactericidal antibiotics carrying higher risk than bacteriostatic (45% vs. 31%). Those with antibiotic-treated upper respiratory tract (URT) infections were more likely to be RA cases. However, this was not observed for URT infections not treated with antibiotics. Antifungal (OR = 1.27; 95% CI 1.20–1.35) and antiviral (OR = 1.19; 95% CI 1.14–1.24) prescriptions were also associated with increased odds of RA. Conclusion Antibiotic prescriptions are associated with a higher risk of RA. This may be due to microbiota disturbances or underlying infections driving risk. Further research is needed to explore these mechanisms. Electronic supplementary material The online version of this article (10.1186/s12916-019-1394-6) contains supplementary material, which is available to authorized users.

Background and aim Comorbidities are known to exist in many rheumatological conditions. Polymyalgia rheumatica (PMR) is a common inflammatory rheumatological condition affecting older people which, prior to effective treatment, causes severe disability. Our understanding of associated comorbidities in PMR is based only on case reports or series and small cohort studies. The objective of this study is to review systematically the existing literature on the comorbidities associated with PMR. Methods MEDLINE, EMBASE, PsycINFO and CINAHL databases were searched for original observational research from inception to November 2016. Papers containing the words ‘Polymyalgia Rheumatica’ OR ‘Giant Cell Arteritis’ OR the terms ‘PMR’ OR ‘GCA’ were included. Article titles were reviewed based on pre-defined criteria by two reviewers. Following selection for inclusion, studies were quality assessed using the Newcastle–Ottawa tool and data were extracted. Results A total of 17,329 papers were reviewed and 41 were incorporated in this review, including three published after the search took place. Wide variations were found in study design, comorbidities reported and populations studied. Positive associations were found between PMR diagnosis and stroke, cardiovascular disease, peripheral arterial disease, diverticular disease and hypothyroidism. Two studies reported a positive association between PMR and overall malignancy rate. Seven studies reported an association between PMR and specific types of cancer, such as leukaemia, lymphoma, myeloproliferative disease and specified solid tumours, although nine studies found either no or negative association between cancer and PMR. Conclusion Quantification of the prevalence of comorbidities in PMR is important to accurately plan service provision and enable identification of cases of PMR which may be more difficult to treat. This review highlights that research into comorbidities in PMR is, overall, methodologically inadequate and does not comprehensively cover all comorbidities. Future studies should consider a range of comorbidities in patients with a validated diagnosis of PMR in representative populations. Electronic supplementary material The online version of this article (10.1186/s13075-018-1757-y) contains supplementary material, which is available to authorized users.

BACKGROUND: Previous studies that quantified the risk of fracture among patients with gout and assessed the potential effect of urate-lowering therapy have provided conflicting results. Our study aims to provide better estimates of risk by minimizing the effect of selection bias and confounding on the observed association. METHODS: We used data from the Clinical Practice Research Datalink, which records primary care consultations of patients from across the United Kingdom. We identified patients with incident gout from 1990 to 2004 and followed them up until 2015. Each patient with gout was individually matched to 4 controls on age, sex and general practice. We calculated absolute rate of fracture and hazard ratios (HRs) using Cox regression models. Among patients with gout, we assessed the impact of urate-lowering therapy on fracture, and used landmark analysis and propensity score matching to account for immortal time bias and confounding by indication. RESULTS: We identified 31 781 patients with incident gout matched to 122 961 controls. The absolute rate of fracture was similar in both cases and controls (absolute rate = 53 and 55 per 10 000 person-years, respectively) corresponding to an HR of 0.97 (95% confidence interval 0.92–1.02). Our finding remained unchanged when we stratified our analysis by age and sex. We did not observe statistically significant differences in the risk of fracture among those prescribed urate-lowering therapy within 1 and 3 years after gout diagnosis. INTERPRETATION: Overall, gout was not associated with an increased risk of fracture. Urate-lowering drugs prescribed early during the course of disease had neither adverse nor beneficial effect on the long-term risk of fracture.

This paper aims to examine the relationship between different characteristics of pain and stiffness and the functional status of patients with newly diagnosed polymyalgia rheumatica (PMR). Baseline analysis of an inception cohort study was conducted. Patients aged ≥18 years, with a new diagnosis of PMR were recruited from 382 English general practices. Participants were mailed a baseline questionnaire, including separate pain and stiffness manikins and numerical rating scales (NRS), a question on their ability to raise their arms above their head and the modified Health Assessment Questionnaire (mHAQ) to examine participants’ functional status. Linear regression analysis, reported as regression co-efficients (95% confidence intervals (95% CI)), was used to assess the association of pain and stiffness with function, initially unadjusted and then adjusted for age, gender, deprivation status, smoking status, BMI, anxiety and depression. Six hundred fifty two patients responded to the baseline survey (88.5%). The majority (88.2%) reported no, or mild impairment in their functional status. Adjusted linear regression analysis demonstrated that high (NRS ≥8) pain (0.20 (95% CI 0.10–0.28)) or stiffness (0.18 (0.09–0.26)) ratings, an increasing number of sites of pain (0.18 (0.06–0.29)) or stiffness (0.19 (0.08–0.31)) and shoulder pain (0.18 (0.05–0.31)), stiffness (0.10 (0.01–0.20)) and difficulty raising arms above one’s head (0.19 (0.10–0.28)) were all associated with increased functional impairment. The majority of newly diagnosed PMR patients reported no or minimal functional difficulty. However, those who experience severe or widespread pain or stiffness often have significant functional limitation in performing their daily activities and may be a subset worthy of additional focus in primary care.

BackgroundIn the UK, general practitioners (GPs) are usually the first medical contact for patients with suspected giant cell arteritis (GCA). While rare, it is critical not to miss, as delayed treatment can lead to significant complications including permanent visual loss. To date, little is known about the approach and challenges to diagnosis and management of GCA by GPs.ObjectiveTo investigate the diagnosis and management of patients with suspected GCA in UK general practice.Design and participantsA multimethods approach was taken, comprising a postal survey of 5000 randomly selected UK GPs and semistructured telephone interviews of 24 GPs from across the UK.SettingUK general practice.Results1249 questionnaires were returned. 879 responders (70%) indicated that they had diagnosed and managed a patient with GCA. A variety of clinical features were used to identify GCA. 21.9% suggested that they would exclude GCA as a diagnosis if headache was absent and around one-third do not routinely initiate glucocorticoid treatment prior to referral. Significant regional variations in referral pathways were reported. Thematic analysis of interview transcripts highlighted fears relating to a missed diagnosis of GCA and the non-specific nature of early GCA presentation. Accessing specialist care was highlighted as challenging by many GPs and that a national standard fast-track pathway is lacking to support this patient group. Additionally there were significant concerns regarding potential adverse effects relating to long-term treatment with glucocorticoids.ConclusionGPs appear to over-rely on headache to identify GCA and marked geographical differences in management, with conflicting referral pathways and difficulties in accessing appropriate services exist in the UK. A national standard for fast-tracking patients with suspected GCA to relevant specialists would be beneficial to improve care and outcomes for patients with GCA.