IntroductionHand osteoarthritis is more common in women, and its risk increases around the time of the menopause. We set out to describe the timing between menopause and the onset of symptomatic hand osteoarthritis (OA), and associations with the use of hormone replacement therapy (HRT) or its discontinuation, describing any identifiable subgroups of women.MethodsRetrospective healthcare-records study of sequential women referred to a specialist hand OA clinic, 2007–2015. Confirmation of hand OA diagnosis was by clinican, by accepted criteria. Demographics and clinical variables were from healthcare-records, recorded by standardised proforma. Outcomes of interest were reported age of onset of hand symptoms, reported age at final menstrual period (FMP), time from FMP to reported onset of hand symptoms and time from cessation of HRT to reported onset of hand symptoms. Exposure categories for systemic HRT use were never users, current users, previous users. Analysis of Variance compared groups; linear regression analysed associations of exposure with outcome.Results82/92(89%) of eligible women were post-menopausal, mean age at FMP 49.9 years (SD5.4). In these post-menopausal women, median time from FMP to hand symptom onset was 3 years. 48/82 (59%) developed hand symptoms within the defined peri-menopausal period (FMP ± 4 years), whilst some women developed their symptoms before or after (range −25, 30 years). In women who discontinued HRT prior to symptom onset, the median time from HRT cessation to onset of hand symptoms was 6 months. Past HRT users were older at hand symptom onset than women who had not taken HRT [coeff.4.7 years (0.92, 8.39); P = 0.015].ConclusionsThis study adds to evidence associating the menopause/sex hormone deficiency with hand OA symptom onset in a sizeable subgroup of women (but not all). HRT use/cessation appears to influence the timing of onset of hand OA symptoms. It is not possible to interpret from this type of study whether sex hormone deficiency is causative of disease or modulates its symptoms. It is also not possible to judge whether painful hand osteoarthritis in post-menopausal women is a subtype of disease. Further investigation is indicated of sex-specific subtypes and potential for personalised medicine for post-menopausal women with hand osteoarthritis, as a clearly definable high-risk subgroup.

The association of female sex with certain rheumatic symptoms and diseases is now indisputable. Some of the most striking examples of this association occur in individuals with musculoskeletal pain and osteoarthritis, in whom sex-dependent changes in incidence and prevalence of disease are seen throughout the lifecourse. Joint and muscle pain are some of the most common symptoms of menopause, and there is increasingly compelling evidence that changes in or loss of sex hormones (be it natural, autoimmune, pharmacological, or surgical) influence musculoskeletal pain propensity and perhaps disease. However, the effects of modulation or replacement of sex hormones in this context are far less established, particularly whether these approaches could represent a preventative or therapeutic opportunity once symptoms have developed. In this Review, we present evidence for the association of changes in sex hormones with musculoskeletal pain and painful osteoarthritis, discussing data from diverse natural, therapeutic, and experimental settings in humans and relevant animal models relating to hormone loss or replacement and the consequent effects on health, pain, and disease. We also postulate mechanisms by which sex hormones could mediate these effects. Further research is needed; however, increased scientific understanding of this complex area could lead to real benefits in musculoskeletal and women's health.

sure definition and immortal time bias, we would like to clarify our approach to this study design and the necessity of “peeking into the future.” The main problem in our study was confounding by indication; namely, there were reasons why some patients were prescribed bDMARDs and others were not (e.g., severity of disease, relative unavailability of biologics in the past, good response to systemic treatments). Those not prescribed bDMARDs thus formed our control group, which was made up of patients treated with 2 systemic medications, as required by local regulations before approval for bDMARDs, and we measured the follow-up time from the psoriasis diagnosis, as time from psoriasis diagnosis is one of the major factors for PsA development. As mentioned by Mutlu and Tascilar, this splitting of a cohort at baseline according to future exposure to bDMARDs implemented an immortality time interval; that is, a time interval passed between the initiation of systemic treatment and the start of bDMARD treatment, but only for the bDMARD treatment group. The authors of the letter suggested that immortal person-time should have been also classified for non-bDMARD (systemic) treatments, which would have reduced the incidence of PsA reported in the nonbDMARD treatment group. To estimate the influence of this bias, we performed additional analysis in which, as noted by Mutlu and Tascilar, the time axis for the primary analysis started at the point when specific treatment (bDMARD or non-bDMARD) was started. By doing so, patients who developed PsA after initiation of systemic treatment but before initiation of bDMARDs were relocated to the control group, and no immortal time interval existed. Multivariable Cox regression analysis was performed, with adjustment for age, sex, and time to systemic treatment initiation. Under these conditions, our preliminary analysis demonstrated that the adjusted hazard ratio (HRadj) for PsA was lower than originally reported (HRadj 1.28 versus 1.39), as was noted by Mutlu and Tascilar. Nonetheless, the finding of higher risk in the non-bDMARD group is still clinically and statistically significant, and therefore the conclusion of our study is valid. Although immortal time bias can occur in cohort studies and can overestimate the outcome rate in the unexposed group (1), sound efforts at minimizing the influence of more common biases should not be sacrificed to that of immortal time bias (2). In general, retrospective studies such as ours have inherent limitations, as recently mentioned in a review of retrospective studies on PsA development (3). Therefore larger, multinational studies are needed to clarify this important clinical issue. Author disclosures are available at https://onlinelibrary.wiley.com/ action/downloadSupplement?doi=10.1002%2Fart.42123&file=art42123sup-0001-Disclosureform.pdf. Yael Shalev Rosenthal, MPH Tel Aviv University Tel Aviv, Israel Naama Schwartz, PhD University of Haifa Haifa, Israel Iftach Sagy, MD, MPA, PhD Soroka University Medical Center and Ben-Gurion University of the Negev Beer Sheva, Israel Lev Pavlovsky, MD, PhD levp@clalit.org.il Tel Aviv University and Rabin Medical Center Petah Tikva, Israel

Background Symptomatic hand osteoarthritis is more common in women than in men, and its incidence increases around the age of menopause, implicating oestrogen deficiency. No randomised controlled trials of honnone replacement therapy (HRT) have been done in people with hand osteoarthritis. We aimed to determine the feasibility and acceptability of a form of HRT (conjugated oestrogens plus bazedoxifene) in post-menopausal women with painful hand osteoarthritis. Methods The HOPE-e feasibility study was a randomised, double-blind, placebo-controlled trial, for which we recruited women aged 40-65 years, for whom 1-10 years had passed after their final menstrual period, with definite hand osteoarthritis and at least two painful hand joints. Participants were recruited across three primary or secondary care sites and from the community and were randomly assigned (1:1) to receive conjugated oestrogens plus bazedoxifene or placebo, orally once every day for 24 weeks, before weaning for 4 weeks until the end of the study. The primary feasibility outcomes were rates of identification, recruitment, randomisation, retention, and compliance of eligible participants, and the likelihood of unmasking. The secondary objective was to generate proof-of-concept quantitative and qualitative data on the acceptability of proposed clinical outcomes for a full trial and adverse events. We used an intention-to-treat analysis, and criteria for progression to a full trial were pre-defined as recruitment of at least 30 participants across all sites in 18 months; a dropout rate of less than or equal to 30% of randomised individuals; and acceptability to the majority of participants, including acceptable rates of adverse events. Due to the COVID-19 pandemic, the recruitment window was reduced to 12-15 months. A proportionately reduced minimum sample size of 22 was judged to be sufficient to test feasibility. This trial was registered at ISRCTN, ISRCTN12196200. Findings From May 9, 2019 to Dec 31, 2020, 434 enquiries or referrals were received. We did 96 telephone pre-screens; of the 35 eligible participants, seven were excluded as ineligible at the telephone or face-to-face screening and 28 (80% [95% CI 63-92]) were randomly assigned. Of the 406 who were not randomly assigned, 250 (62%) were ineligible (with contraindicated medications accounting for 50 [20%] of these), 101 (25%) did not respond to further enquiries, and 55 (14%) chose not to proceed (with the most common reason being not wanting to take a hormone-based drug). All 28 randomised participants completed all follow-up assessments with high compliance and outcome measure completeness. All three adverse event-related treatment withdrawals were in the placebo group. No serious adverse events were reported. Participants and investigators were successfully masked (participant Bang's blinding index placebo group 0.50 [95% CI 0.25-0.75]). The trial met the prespecified criteria for progression to a full trial. Interpretation This first-ever feasibility study of a randomised controlled trial of HRT for post-menopausal women with painful hand osteoarthritis met its progression criteria, although it was not powered to detect a clinical effect. This outcome indicates that a full trial of an HRT in this population is feasible and acceptable and identifies potential refinements with regard to the design of such a trial. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.

Rheumatoid arthritis (RA) is a multiorgan chronic inflammatory condition that affects 0.84% of the UK population. The cardinal clinical feature is a symmetrical polyarthritis that predominantly affects the small joints. RA can affect other components of the musculoskeletal system (bursitis, tendinopathy, muscle atrophy, osteoporosis) and almost every organ in the body. Extra-articular manifestations of RA can be cutaneous, haematological, neurological, pulmonary, cardiac, renal and ocular. A better understanding of the varied clinical aspects of RA is vital to instigating appropriate management. This review provides a detailed description of the clinical manifestations of RA, both musculoskeletal and extra-articular.

Involving research users in setting priorities for research is essential to ensure the outcomes are patient-centred and maximise its value and impact. The Musculoskeletal Disorders Research Advisory Group Versus Arthritis led a research priority setting exercise across musculoskeletal disorders. The Child Health and Nutrition Research Initiative (CHNRI) method of setting research priorities with a range of stakeholders was used, involving four stages and two surveys, to: (1) gather research uncertainties, (2) consolidate these, (3) score uncertainties against importance and impact, and (4) analyse scoring for prioritisation. 213 people responded to the first survey and 285 people to the second, representing clinicians, researchers, and people with musculoskeletal disorders. Key priorities included developing and testing new treatments, better treatment targeting, early diagnosis, prevention, and better understanding and management of pain, with an emphasis on understanding underpinning mechanisms. We present a call to action to researchers and funders to target these priorities.

Involving research users in setting priorities for musculoskeletal research is essential to raise awareness of the unmet needs for MSK research, to ensure research outcomes are patient-centred and relevant, have a high likelihood of resulting in patient benefit, reduce research waste and increase research value and impact. In 2018, Versus Arthritis convened an MSK Disorders Research Advisory Group (RAG) which included people with arthritis, health care professionals and researchers in MSK, in order to identify and prioritise research areas with a long-term aim of improving quality and impact of MSK research. On further review, there were few previous prioritisation approaches in this area looking across discovery science to more clinical research, at important research questions which might be common to a range of disorders or approaches incorporating input at all stages of the process by a range of stakeholders including people with arthritis. The group identified that more work to define research priorities in these areas was justified and designed a research priority setting process for MSK disorders. This manuscript documents the methodology that was developed by the group for this process. Methods Following a review, the Child Health and Nutrition Research Initiative (CHNRI) method for research prioritisation was selected as best aligning with the needs of this process. The group agreed on adaptations to the CHNRI approach, context, purpose and remit of the exercise and identified through consensus four priority research Domains: Mechanisms of disease; Diagnosis (including early diagnosis) and measuring the impact of these disorders; Living well with MSK disorders and Successful Translation. From all published CHNRI scoring criteria for generated research avenues or themes of research, the group identified six which were most relevant to this process. To ensure accessibility of the survey and scoring, these were refined to three: Equity (considered cross cutting, not scored but considered throughout the process), Importance (Will research in this area have potential to lead to important new knowledge) and Impact (Might research in this area make a difference). Importance and Impact were to be scored on a scale of 1-10 for each research avenue with equal weighting of these two criteria in the subsequent generation of a total score. Data collection Following ethical approval, an electronic first survey asking for important research uncertainties in the four research domains and any other areas will be distributed to all stakeholders (people with arthritis, researchers in all stages of MSK disorders research, healthcare professionals, industry e.g. pharmaceutical and medical technology companies, research funders, healthcare providers, government policy makers and charities). The next step is to consolidate all the gathered research uncertainties from the first survey into finalised research domains and avenues. Uncertainties will be summarised using deductive thematic analysis and organised into possible themes which will then be considered and refined by each of four appointed subgroups within the RAG. Following group and lay review and refinement of the wording including tests of readability, the second survey including this full list of research avenues will be submitted for ethical approval. The second survey will be completed by the same range of stakeholders as the first survey, both those who previously completed and new respondents. Respondents will be invited to rate each research avenue using the two scoring criteria, with the avenues presented in a random sequence to avoid bias. Analysis Plan All available data will be analysed, from all respondents completing the survey in full and all partial respondents. For each research avenue, a mean criterion score will be calculated for each of the two criteria from all available survey responses (considering the number of respondents in each case), and then the two mean criterion scores will be summed to create a total score. Response rates and missing data for scoring of avenues will be reported. The primary prioritisation output of this exercise will be to produce a single ranked list of these total scores of research avenues, from highest to lowest. The most highly ranked avenues will be highlighted, for example the top five to top ten overall and from each research domain, with the exact number and nature of this depending on the distribution of the data. Respondent characteristics will be summarised including self-identified stakeholder group, age group, gender and ethnic background, to describe the diversity and representation within the survey respondents as far as possible. Dissemination plan Findings will be communicated in a number of formats, both written and spoken, to ensure accessibility to all stakeholders, and will also be used by the charity in internal strategy development. Dissemination will include the submission of a manuscript to a peer-reviewed journal.

Wandering spleen is a rare condition in which the spleen is hypermobile due to laxity or lack of its supporting ligaments. It can be located anywhere in the abdomen besides its usual position. The other terms that are used to describe this condition are splenic ptosis, displaced spleen, dislocated spleen and ectopic spleen. Splenic torsion is a dreaded complication and the usual cause of symptoms. There is a high chance of missing the diagnosis as it remains asymptomatic or may be incidentally discovered on radio-imaging done for a different purpose. An acute abdomen is the most common presentation. Here we describe an unusual case presenting with torsion of the wandering spleen that was adherent to the right ovary.

Chronically discharging ear is a common cause of morbidity in developing countries, and it is also associated with intratemporal and intracranial complications. The surgeon is often able to detect the disease. However, cholesteatoma in the "hidden areas" like anterior epitympanic recess and sinus tympani can be missed. Facial nerve involvement and cholesteatomatous erosion of the bony labyrinth are dreaded complications, the extent of which cannot be assessed completely on clinical examination. Adding to the complexity are the various variations in anatomy like high riding jugular bulb and aberrant internal carotid artery which could lead to catastrophic complications during surgery if left undetected preoperatively. HRCT temporal bone is useful to detect the extent of the disease, various complications, and guide the surgeon for pre-operative planning. In this review, we go through the various HRCT imaging features of acquired cholesteatoma, a reporting template, and a few words about imaging of the post-operative ear.

Osteoarthritis (OA) is the most common form of arthritis, yet has historically lagged far behind rheumatoid arthritis in terms of drug development. Despite the many challenges presented by clinical trials in OA, improvements in our understanding of disease pathogenesis and a move to treat pain, as well as underlying disease process, mean there are now many new pharmacological therapies currently in various stages of clinical trials. The medical need for these therapies and the evidence for recent tissue and molecular targets are reviewed. Current therapeutic examples in each area are discussed, including both novel therapeutics and existing agents which may be repurposed from other disease areas. Some challenges remain, but opportunities for improving symptoms and disease process in OA in the clinic with new pharmacological agents would appear to be on the close horizon.

Background: Inflammatory aortitis is a rare condition that can occur in the context of primary systemic vasculitis, systemic autoimmune disease or in isolation.We describe the clinical spectrum of the disease and outcomes in patients with inflammatory aortitis treated in a large UK tertiary centre.Methods: We retrospectively reviewed all case records of patients with a diagnosis of Aortitis who attended our Vasculitis clinic at Louise Coote Lupus Unit at Guys and St Thomas' Hospital from 2005 till 2016.Data for patient demographics, clinical characteristics, serological status, histology and imaging findings, including FDG-PET scans were collected from the patient records.Results: 18 patients (45% women) were identified; mean age was 59 (Range 21-82 years).Most were Caucasians (83%) and the rest were Afro-Caribbean.Median follow up was 16 months (1 month-10 years).The clinical subgroups were idiopathic aortitis (8), Giant cell arteritis (4), Takayasu's arteritis (3), Granulomatosis with Polyangiitis (1), isolated thoracic aortitis (1) and retroperitoneal fibrosis (1).There was a diagnostic delay of 0-24 months (median 2m) from initial onset of symptoms to diagnosis, two patients were diagnosed incidentally on imaging.At initial presentation, the median CRP was 50 (5-255) and the median ESR was 56 (range 5-106).ANCA positivity was observed in 3 patients, negative in 14 and ANCA was not measured in 1 patient.Mean creatinine at presentation was 76 umol/L.Histology reports were available for 5 patients (28%) which showed IgG4 positive plasma cells in 1 case (aortic tissue), granulomatous changes on subglottic tissue in 1 patient with known GPA, 1 positive and 2 negative temporal artery biopsies.FDG-PET scans in 16 patients (89%) showed pan-aortitis in 5 patients, thoracic and subclavien artery uptake in 4, ascending aorta and arch involvement in 3 patients, infrarenal aortitis in 1 and 2 had negative FDG-PET scans.Mean initial treatment dose Prednisolone dose was 30mg (7.5-80); 9 patients received DMARD therapy (6 on Methotrexate, 3 on Azathioprine), while 2 had cyclophosphamide, 1 had rituximab and 1 had FEC-T chemotherapy for associated Lymphoma.Significant disease related complications included 2 patients needing thoracic stents and aortic root repair, 1 each with abdominal and thoracic artery dissection and one developed cardiac amyloidosis.3 deaths were reported: 1 due to treatment noncompliance and 2 unrelated deaths.Conclusion: Inflammatory Aortitis has a varied clinical spectrum with underlying disease subgroups which can lead to diagnostic delay.Early diagnosis and treatment is needed to prevent potentially life threatening complications.

Background: Demonstration of monosodium urate (MSU) crystals remains the gold standard for diagnosing gout.In clinical practice, this is not always possible.This creates a diagnostic challenge when clinical features could support alternative diagnoses.In such cases, dual-energy CT (DECT) can be used reliably to visualize urate deposits.In a recent study, all false-negative and false-positive DECT results

Conclusion: At these centres, the number of patients referred, and especially the number with inflammatory polyarthritis continues to increase.The great majority of follow-up appointments are for inflammatory arthritis.The overall follow-up to new ratio is a poor measure in rheumatology and should be interpreted in relation to case mix.Centres have adopted two strategies for follow-up appointments-direct access and long appointment times-to help manage long term care of inflammatory arthritis.Rheumatology services need to adapt and seek innovative sustainable ideas which improve productivity and efficiency while reducing inequality and dependency.These changes need to be specific to local circumstances and address the whole patient journey and long-term follow-up.