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Objective: The aim was to determine the impact of PMR on intimate and sexual relationships over time. Methods: The PMR Cohort study is a longitudinal study of patients with incident PMR in English primary care. Participants were sent questionnaires about their PMR symptoms, treatments and overall health, including an item about how their PMR symptoms affected intimate and sexual relationships. The proportions 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: The baseline survey was completed by 652 of 739 patients (response 90.1%), with 446 of 576 (78.0%) responding at 2 years. The mean age of respondents was 72.4 years, and 62.2% were female. At baseline, 363 of 640 (56.7%) respondents reported that intimate and sexual relationships were not relevant to them. One hundred and thirteen of 277 (40.8%) respondents 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 recognized as important for healthy ageing, and health professionals should consider this as part of a holistic approach to the management of PMR. Study registration: UKCRN ID16477. 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 and makes 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 was not relevant for them. For those people to whom it mattered, 4 in 10 said that PMR had a large effect on their relationships. Men, people who were younger, those with worse PMR symptoms and those with 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 their PMR symptoms improved. We suggest that doctors should consider people's intimate and sexual relationships as part of their care for people with PMR. Keywords: PMR, primary health care, cohort study, sexual relationships

The theoretical telescopic image of a star is for all practical purposes that predicted by diffraction theory for a point source at an infinite distance. The fact that the image does not behave according to prediction is well known. The image is in general much larger than predicted and shows changes in shape, position and brightness which cannot be explained in terms of the telescopic optics.

The release of eosinophil granule proteins in the lungs of patients with asthma has been dogmatically linked with lung remodeling and airway hyperresponsiveness. However, the demonstrated inability of established mouse models to display the eosinophil degranulation occurring in human subjects has prevented a definitive in vivo test of this hypothesis. To demonstrate in vivo causative links between induced pulmonary histopathologies/lung dysfunction and eosinophil degranulation. A transgenic mouse model of chronic T-helper cell type 2-driven inflammation overexpressing IL-5 from T cells and human eotaxin 2 in the lung (I5/hE2) was used to test the hypothesis that chronic histopathologies and the development of airway hyperresponsiveness occur as a consequence of extensive eosinophil degranulation in the lung parenchyma. Studies targeting specific inflammatory pathways in I5/hE2 mice surprisingly showed that eosinophil-dependent immunoregulative events and not the release of individual secondary granule proteins are the central contributors to T-helper cell type 2-induced pulmonary remodeling and lung dysfunction. Specifically, our studies highlighted a significant role for eosinophil-dependent IL-13 expression. In contrast, extensive degranulation leading to the release of major basic protein-1 or eosinophil peroxidase was not causatively linked to many of the induced pulmonary histopathologies. However, these studies did define a previously unappreciated link between the release of eosinophil peroxidase (but not major basic protein-1) and observed levels of induced airway mucin. These data suggest that improvements observed in patients with asthma responding to therapeutic strategies ablating eosinophils may occur as a consequence of targeting immunoregulatory mechanisms and not by simply eliminating the destructive activities of these purportedly end-stage effector cells.

ObjectiveIgA vasculitis (IgAV) is the most frequently experienced subtype of vasculitis seen in children. Most children fully recover, however, complications including chronic kidney disease are recognised. The aim of this project was to use a best available evidence, group agreement, based approach to develop national recommendations for the initial management of IgAV and its associated complications.MethodsA fully representative multiprofessional guideline development group (GDG), consisting of 28 members, was formed and met monthly. Graded recommendations were generated using nationally accredited methods, which included a predefined scope, open consultation, systematic literature review, evidence appraisal, review of national or international guidelines and a period of open consultation. Audit measures and research priorities were incorporated.ResultsThe IgAV GDG met over a 14-month period. A total of 82 papers were relevant for evidence synthesis. For the initial management, four topic areas were identified with five key questions generating six graded recommendations related to classification, specialist referral and musculoskeletal involvement. For the associated complications, five topic areas with 12 key questions generated 15 graded recommendations covering nephritis, gastrointestinal and testicular involvement, atypical disease and follow-up. Open consultation feedback was incorporated. The guidelines were endorsed by the UK Kidney Association and Royal College of Paediatrics and Child Health and are available online.ConclusionDespite IgAV being a rare disease with limited evidence, a national standardised approach to the clinical management for children and young people has been achieved. This should unite approaches to care and act as a foundation for improvement.

Background STAMPEDE previously reported adding upfront docetaxel improved overall survival for prostate cancer patients starting long-term androgen deprivation therapy. We report long-term results for non-metastatic patients using, as primary outcome, metastatic progression-free survival (mPFS), an externally demonstrated surrogate for overall survival. Methods Standard of care (SOC) was androgen deprivation therapy with or without radical prostate radiotherapy. A total of 460 SOC and 230 SOC plus docetaxel were randomly assigned 2:1. Standard survival methods and intention to treat were used. Treatment effect estimates were summarized from adjusted Cox regression models, switching to restricted mean survival time if non-proportional hazards. mPFS (new metastases, skeletal-related events, or prostate cancer death) had 70% power (α = 0.05) for a hazard ratio (HR) of 0.70. Secondary outcome measures included overall survival, failure-free survival (FFS), and progression-free survival (PFS: mPFS, locoregional progression). Results Median follow-up was 6.5 years with 142 mPFS events on SOC (3 year and 54% increases over previous report). There was no good evidence of an advantage to SOC plus docetaxel on mPFS (HR = 0.89, 95% confidence interval [CI] = 0.66 to 1.19; P = .43); with 5-year mPFS 82% (95% CI = 78% to 87%) SOC plus docetaxel vs 77% (95% CI = 73% to 81%) SOC. Secondary outcomes showed evidence SOC plus docetaxel improved FFS (HR = 0.70, 95% CI = 0.55 to 0.88; P = .002) and PFS (nonproportional P = .03, restricted mean survival time difference = 5.8 months, 95% CI = 0.5 to 11.2; P = .03) but no good evidence of overall survival benefit (125 SOC deaths; HR = 0.88, 95% CI = 0.64 to 1.21; P = .44). There was no evidence SOC plus docetaxel increased late toxicity: post 1 year, 29% SOC and 30% SOC plus docetaxel grade 3-5 toxicity. Conclusions There is robust evidence that SOC plus docetaxel improved FFS and PFS (previously shown to increase quality-adjusted life-years), without excess late toxicity, which did not translate into benefit for longer-term outcomes. This may influence patient management in individual cases.

Background Musculoskeletal problems are common, accounting for up to 30 % of general practitioner (GP) consultations and are a major cause of chronic disability worldwide. Demand for health care for musculoskeletal conditions is likely to continue to rise given the ageing population and the increasing impact of these common painful conditions. Physiotherapists are well equipped to deliver evidence-based management for these conditions. Direct access allows patients to access physiotherapy without seeing their GP or another referring practitioner first; however, for most patients in the UK, access to National Health Service physiotherapy is controlled through GP referral. Methods/Design The aim of this pilot, pragmatic, cluster trial is to assess the feasibility of a future large trial to compare the clinical and cost-effectiveness of the additional offer of direct access to physiotherapy versus continuing with usual GP-led primary care alone for adults with common musculoskeletal problems. The pilot will focus on process outcomes to assess feasibility, although performance of the likely outcomes of a main trial will also be assessed. This is a two-arm parallel, cluster RCT where GP practices are the units of randomisation (the clusters), yet data are collected from individual patients with musculoskeletal problems (the participants). A direct access service will be set up in the participating physiotherapy service to provide the option of direct access to patients of the intervention arm practices. Inclusion criteria are broad to reflect the ‘real-world’ operation of an NHS physiotherapy direct access service for patients with musculoskeletal pain. Data collection will be through patient self-reported questionnaires at baseline, 2, 6 and 12 months and medical record review. Discussion No previous trials have been conducted into direct access to physiotherapy for patients with musculoskeletal problems. The strengths of the STEMS pilot trial are its size, the length of follow-up, and collection of process, clinical and cost outcomes to fully inform a future main trial to meet calls to provide robust trial evidence of the impact on clinical outcomes, work loss and costs to provide clinicians and service funders with the high quality trial data they need to guide decisions on the best models of care. Trial registration The STEMS pilot trial is registered at Current Controlled Trials: ISRCTN23378642