Responders to Exercise Therapy in Patients with Osteoarthritis of the Hip: A Systematic Review and Meta-Analysis.

The Outcome Measures in Rheumatology workgroup (OMERACT), together with the Osteoarthritis Research Society International (OARSI) developed the OMERACT-OARSI responder criteria. These criteria are used to determine if a patient with osteoarthritis (OA) 'responds' to therapy, meaning experiences a clinically relevant effect of therapy. Recently, more clinical OA trials report on this outcome and most OA trials have data to calculate the number of responders according to these criteria. A systematic review and meta-analysis were performed on the response to exercise therapy, compared to no or minimal intervention in patients with hip OA using the OMERACT-OARSI responder criteria. The literature was searched for relevant randomized trials. If a trial fit the inclusion criteria, but number of responders was not reported, the first author was contacted. This way the numbers of responders of 14 trials were collected and a meta-analysis on short term (directly after treatment, 12 trials n = 1178) and long term (6-8 months after treatment, six trials n = 519) outcomes was performed. At short term, the risk difference (RD) was 0.14 (95% confidence interval (CI) 0.06-0.22) and number needed to treat (NNT) 7.1 (95% CI 4.5-17); at long term RD was 0.14 (95% CI 0.07-0.20) and NNT 7.1 (95% CI 5.0-14.3). Quality of evidence was moderate for the short term and high for the long term. In conclusion, 14% more hip OA patients responded to exercise therapy than to no therapy

Do we need another trial on exercise in patients with knee osteoarthritis?: No new trials on exercise in knee OA

© 2019 Osteoarthritis Research Society International Objective: We aim to investigate if we need additional trials on exercise in knee osteoarthritis (OA) to accept a certain effect size to be a ‘true’ effect size, and new studies are not needed anymore. Design: We performed a secondary analyses of a meta-analysis of studies on patients with knee osteoarthritis, on pain immediately post treatment. We performed five different analysis: a) we evaluated publication bias, b) we performed subgroup analysis, c) a sensitivity analysis based on the overall risk of bias (RoB) score, d) a cumulative meta-analysis and e) we developed an extended funnel plot to explore the potential impact of a new study on the summary effect estimate. Results: We included 42 studies with in total 6863 patients. The analyses showed that a) there is no clear publication bias, b) subgrouping did not affect the overall effect estimate, c) the effect estimate of exercise is more consistent (no heterogeneity) in the studies of low RoB, d) the benefit of exercise was clear since 2010 and e) the extended funnel plot suggests that an additional study has a none or very limited impact to change the current effect estimate. Conclusion: Exercise is effective and clinically worthwhile in reducing pain immediately post treatment compared to no or minimal interventions in patients with knee OA and adding new data will unlikely change this conclusion

Subgrouping and TargetEd Exercise pRogrammes for knee and hip OsteoArthritis (STEER OA): a systematic review update and individual participant data meta-analysis protocol.

Knee and hip osteoarthritis (OA) is a leading cause of disability worldwide. Therapeutic exercise is a recommended core treatment for people with knee and hip OA, however, the observed effect sizes for reducing pain and improving physical function are small to moderate. This may be due to insufficient targeting of exercise to subgroups of people who are most likely to respond and/or suboptimal content of exercise programmes. This study aims to identify: (1) subgroups of people with knee and hip OA that do/do not respond to therapeutic exercise and to different types of exercise and (2) mediators of the effect of therapeutic exercise for reducing pain and improving physical function. This will enable optimal targeting and refining the content of future exercise interventions.Systematic review and individual participant data meta-analyses. A previous comprehensive systematic review will be updated to identify randomised controlled trials that compare the effects of therapeutic exercise for people with knee and hip OA on pain and physical function to a non-exercise control. Lead authors of eligible trials will be invited to share individual participant data. Trial-level and participant-level characteristics (for baseline variables and outcomes) of included studies will be summarised. Meta-analyses will use a two-stage approach, where effect estimates are obtained for each trial and then synthesised using a random effects model (to account for heterogeneity). All analyses will be on an intention-to-treat principle and all summary meta-analysis estimates will be reported as standardised mean differences with 95% CI.Research ethical or governance approval is exempt as no new data are being collected and no identifiable participant information will be shared. Findings will be disseminated via national and international conferences, publication in peer-reviewed journals and summaries posted on websites accessed by the public and clinicians.CRD42017054049

Prognostic factors for progression of osteoarthritis of the hip: a systematic review

Background: Predicting which patients with hip osteoarthritis are more likely to show disease progression is important for healthcare professionals. Therefore, the aim of this review was to assess which factors are predictive of progression in patients with hip osteoarthritis. Methods: A literature search was made up until 14 March 2019. Included were cohort and case-control studies evaluating the association between factors and progression (either clinical, radiological, or THR). Excluded were studies with a follow-up < 1 year or specific underlying pathologies of osteoarthritis. Risk of bias was assessed using the QUIPS tool. A best-evidence synthesis was conducted. Results: We included 57 articles describing 154 different factors. Of these, a best-evidence synthesis was

Estimating transmission parameters for respiratory syncytial virus and predicting the impact of maternal and pediatric vaccination

Background Respiratory syncytial virus (RSV) is a leading cause of respiratory tract illness in young children and a major cause of hospital admissions globally. Methods Here we fit age-structured transmission models with immunity propagation to data from the Netherlands (2012–2017). Data included nationwide hospitalizations with confirmed RSV, general practitioner (GP) data on attendance for care from acute respiratory infection, and virological testing of acute respiratory infections at the GP. The transmission models, equipped with key parameter estimates, were used to predict the impact of maternal and pediatric vaccination. Results Estimates of the basic reproduction number were generally high (R0 > 10 in scenarios with high statistical support), while susceptibility was estimated to be low in nonelderly adults (<10% in persons 20–64 years) and was higher in older adults (≥65 years). Scenario analyses predicted that maternal vaccination reduces the incidence of infection in vulnerable infants (<1 year) and shifts the age of first infection from infants to young children. Conclusions Pediatric vaccination is expected to reduce the incidence of infection in infants and young children (0–5 years), slightly increase incidence in 5 to 9-year-old children, and have minor indirect benefits

Synergistic effect of IL-12 and IL-18 induces TIM3 regulation of γδ T cell function and decreases the risk of clinical malaria in children living in Papua New Guinea

BACKGROUND: γδ T cells are important for both protective immunity and immunopathogenesis during malaria infection. However, the immunological processes determining beneficial or detrimental effects on disease outcome remain elusive. The aim of this study was to examine expression and regulatory effect of the inhibitory receptor T-cell immunoglobulin domain and mucin domain 3 (TIM3) on γδ T cells. While TIM3 expression and function on conventional αβ T cells have been clearly defined, the equivalent characterization on γδ T cells and associations with disease outcomes is limited. This study investigated the functional capacity of TIM3+ γδ T cells and the underlying mechanisms contributing to TIM3 upregulation and established an association with malaria disease outcomes. METHODS: We analyzed TIM3 expression on γδ T cells in 132 children aged 5-10 years living in malaria endemic areas of Papua New Guinea. TIM3 upregulation and effector functions of TIM3+ γδ T cells were assessed following in vitro stimulation with parasite-infected erythrocytes, phosphoantigen and/or cytokines. Associations between the proportion of TIM3-expressing cells and the molecular force of infection were tested using negative binomial regression and in a Cox proportional hazards model for time to first clinical episode. Multivariable analyses to determine the association of TIM3 and IL-18 levels were conducted using general linear models. Malaria infection mouse models were utilized to experimentally investigate the relationship between repeated exposure and TIM3 upregulation. RESULTS: This study demonstrates that even in the absence of an active malaria infection, children of malaria endemic areas have an atypical population of TIM3-expressing γδ T cells (mean frequency TIM3+ of total γδ T cells 15.2% ± 12). Crucial factors required for γδ T cell TIM3 upregulation include IL-12/IL-18, and plasma IL-18 was associated with TIM3 expression (P = 0.002). Additionally, we show a relationship between TIM3 expression and infection with distinct parasite clones during repeated exposure. TIM3+ γδ T cells were functionally impaired and were associated with asymptomatic malaria infection (hazard ratio 0.54, P = 0.032). CONCLUSIONS: Collectively our data demonstrate a novel role for IL-12/IL-18 in shaping the innate immune response and provide fundamental insight into aspects of γδ T cell immunoregulation. Furthermore, we show that TIM3 represents an important γδ T cell regulatory component involved in minimizing malaria symptoms