Satisfaction, adherence and health-related quality of life with transdermal buprenorphine compared with oral opioid medications in the usual care of osteoarthritis pain

Background Osteoarthritis (OA) causes substantial pain and reduced health-related quality of life (HRQL). Although opioid analgesics are commonly used, the relative benefits of different opioids are poorly studied. Transdermal buprenorphine (TDB) offers an alternative to oral opioids for the treatment of moderate-to-severe chronic pain. This observational study of people with OA pain assessed satisfaction, HRQL and medication adherence. Methods Patients in the UK with self-reported knee and/or hip OA who had been receiving one or more of TDB, co-codamol (an oral paracetamol/codeine combination) and tramadol for at least 1 month completed an online or telephone questionnaire. Medication satisfaction scores, HRQL scores (Short-Form 36 [SF-36]), medication adherence (Morisky Medication Adherence Scale [MMAS™]), adverse events and treatment discontinuations were recorded. Linear and logistic regression models were used to compare the treatment effect of TDB with co-codamol or tramadol. Results Overall, 966 patients met the inclusion criteria; 701 were taking only one of the target medications (TDB: 85; co-codamol: 373; tramadol: 243). The largest age group was 50–59 years and 76.0 % of patients were female. The TDB group was younger, with more male patients, therefore the statistical models were adjusted for age and sex. Medication satisfaction scores were significantly higher in the TDB group than the other two groups (TDB vs. co-codamol: 3.56, 95 % confidence interval [CI] 1.90–6.68, p < 0.0001; TDB vs. tramadol: 3.22, 95 % CI 1.67–6.20, p = 0.0005). Physical Component Summary scores for HRQL and mean adherence were also higher in the TDB group, while Mental Component Summary HRQL scores were similar across the three groups. Conclusions Patients with knee and/or hip OA pain treated with TDB were more satisfied and more adherent with their medication, and reported higher Physical Component Summary HRQL scores than those treated with co-codamol or tramadol, although demographic differences were observed between groups

Ultrasound-detected pathologies cluster into groups with different clinical outcomes: data from 3000 community referrals for shoulder pain

Background Ultrasound is increasingly used to evaluate shoulder pain but the benefits of this are unclear. This study examined whether ultrasound-defined pathologies have implications for clinical outcomes. Methods We extracted reported pathologies from 3000 ultrasound scans of people with shoulder pain referred from primary care. Latent class analysis (LCA) identified whether individual pathologies clustered in groups. Optimal group number was determined by the minimum Bayesian information criterion. A questionnaire was sent to all patients scanned over a 12-month period (n=2322). Data collected included demographics, treatments received, current pain and function. The relationship between pathology-defined groups and clinical outcomes was examined. Results LCA revealed four groups: 1. bursitis with limited inflammation elsewhere (n=1280); 2. bursitis with extensive inflammation (n=595); 3. rotator cuff tears (n=558); 4. limited pathology (n=567). 777 (33%) completed questionnaires; median (IQR) duration post-ultrasound scan was 25 (22, 29) months. Subsequent injections were most common in groups 1 & 2 (groups 1-4: 76%; 67%; 48%; 61%); surgery was most common in group 3 (23%; 21%; 28%; 16%). Shoulder Pain and Disability Index scores were highest in group 3 (median 48 and 30 respectively) and lowest in group 4 (32 and 9). Patients in group 4 who had surgery reported poor outcomes. Conclusion In a community-based population, ultrasound identified clusters of pathologies. Our retrospective data suggests these groups have different treatment pathways and outcomes. This requires replication in a prospective study to determine the value of a pathology-based classification in people with shoulder pain

Association of FCGR3A and FCGR3B haplotypes with rheumatoid arthritis and primary Sjögren's syndrome [POSTER PRESENTATION]

Background Rheumatoid arthritis (RA) is an autoimmune disease that is thought to arise from a complex interaction between multiple genetic factors and environmental triggers. We have previously demonstrated an association between a Fc gamma receptor (FcγR) haplotype and RA in a cross-sectional cohort of RA patients. We have sought to confirm this association in an inception cohort of RA patients and matched controls. We also extended our study to investigate a second autoanti-body associated rheumatic disease, primary Sjögren's syndrome (PSS). Methods The FCGR3A-158F/V and FCGR3B-NA1/NA2 functional polymorphisms were examined for association in an inception cohort of RA patients (n = 448), and a well-characterised PSS cohort (n = 83) from the United Kingdom. Pairwise disequilibrium coefficients (D') were calculated in 267 Blood Service healthy controls. The EHPlus program was used to estimate haplotype frequencies for patients and controls and to determine whether significant linkage disequilibrium was present. A likelihood ratio test is performed to test for differences between the haplotype frequencies in cases and controls. A permutation procedure implemented in this program enabled 1000 permutations to be performed on all haplotype associations to assess significance. Results There was significant linkage disequilibrium between FCGR3A and FCGR3B (D' = -0.445, P = 0.001). There was no significant difference in the FCGR3A or FCGR3B allele or genotype frequencies in the RA or PSS patients compared with controls. However, there was a significant difference in the FCGR3A-FCGR3B haplotype distributions with increased homozygosity for the FCGR3A-FCGR3B 158V-NA2 haplotype in both our inception RA cohort (odds ratio = 2.15, 95% confidence interval = 1.1–4.2 P = 0.027) and PSS (odds ratio = 2.83, 95% confidence interval = 1.0–8.2, P = 0.047) compared with controls. The reference group for these analyses comprised individuals who did not possess a copy of the FCGR3A-FCGR3B 158V-NA2 haplotype. Conclusions We have confirmed our original findings of association between the FCGR3A-FCGR3B 158V-NA2 haplotype and RA in a new inception cohort of RA patients. This suggests that there may be an RA-susceptibility gene at this locus. The significant increased frequency of an identical haplotype in PSS suggests the FcγR genetic locus may contribute to the pathogenesis of diverse autoantibody-mediated rheumatic diseases

Order enables efficient electron-hole separation at an organic heterojunction with a small energy loss.

Donor-acceptor organic solar cells often show low open-circuit voltages (V OC) relative to their optical energy gap (E g) that limit power conversion efficiencies to ~12%. This energy loss is partly attributed to the offset between E g and that of intermolecular charge transfer (CT) states at the donor-acceptor interface. Here we study charge generation occurring in PIPCP:PC61BM, a system with a very low driving energy for initial charge separation (E g-E CT ~ 50 meV) and a high internal quantum efficiency (η IQE ~ 80%). We track the strength of the electric field generated between the separating electron-hole pair by following the transient electroabsorption optical response, and find that while localised CT states are formed rapidly (<100 fs) after photoexcitation, free charges are not generated until 5 ps after photogeneration. In PIPCP:PC61BM, electronic disorder is low (Urbach energy <27 meV) and we consider that free charge separation is able to outcompete trap-assisted non-radiative recombination of the CT state

Motivating Questions and Partial Answers:A Response to Prosecuting Domestic Violence by Michelle Madden Dempse

Michelle Madden Dempsey’s compelling book sets out a normative feminist argument as to why and when prosecutors should continue to pursue prosecutions in domestic violence cases where the victim refuses to participate in or has withdrawn their support for the prosecution. This paper will explore two of the key aspects of her argument—the centrality and definition of the concept of patriarchy, and the definition of domestic violence—before concluding with some final thoughts as to the appropriate parameters of feminist prosecutorial decision-making. The paper argues that Madden Dempsey could offer a more detailed and nuanced argument about the role that patriarchy plays, particularly its relevance in marking out appropriate cases for pursuit; and that her thesis requires a more convincing exposition of the precise reasons for offering such a narrow account of domestic violence

The ability of synovitis to predict structural damage in rheumatoid arthritis: A comparative study between clinical examination and ultrasound

Objectives: To evaluate synovitis (clinical vs ultrasound (US)) to predict structural progression in rheumatoid arthritis (RA). Methods: Patients with RA. Study design: Prospective, 2-year follow-up. Data collected: Synovitis (32 joints (2 wrists, 10 metacarpophalangeal, 10 proximal interphalangeal, 10 metatarsophalangeal)) at baseline and after 4 months of therapy by clinical, US grey scale (GS-US) and power doppler (PD-US); x-rays at baseline and at year 2. Analysis: Measures of association (OR) were tested between structural deterioration and the presence of baseline synovitis, or its persistence, after 4 months of therapy using generalised estimating equation analysis. Results: Structural deterioration was observed in 9% of the 1888 evaluated joints in 59 patients. Baseline synovitis increased the risk of structural progression: OR=2.01 (1.36-2.98) p<0.001 versus 1.61 (1.06-2.45) p=0.026 versus 1.75 (1.18-2.58) p=0.005 for the clinical versus US-GS versus US-PD evaluation, respectively. In the joints with normal baseline examination (clinical or US), an increased probability for structural progression in the presence of synovitis for the other modality was also observed (OR=2.16 (1.16-4.02) p=0.015 and 3.50 (1.77-6.95) p<0.001 for US-GS and US-PD and 2.79 (1.35-5.76) p=0.002) for clinical examination. Persistent (vs disappearance) synovitis after 4 months of therapy was also predictive of subsequent structural progression. Conclusions: This study confi rms the validity of synovitis for predicting subsequent structural deterioration irrespective of the modality of examination of joints, but also suggests that both clinical and ultrasonographic examinations may be relevant to optimally evaluate the risk of subsequent structural deterioration

Scoring ultrasound synovitis in Rheumatoid Arthritis: a EULAR-OMERACT Ultrasound Taskforce–Part 1: definition and development of a standardized, consensus-based scoring system

Objectives: To develop a consensus-based ultrasound (US) definition and quantification system for synovitis in rheumatoid arthritis (RA). Methods: A multistep, iterative approach was used to: (1) evaluate the baseline agreement on defining and scoring synovitis according to the usual practice of different sonographers, using both grey-scale (GS) (synovial hypertrophy (SH) and effusion) and power Doppler (PD), by reading static images and scanning patients with RA and (2) evaluate the influence of both the definition and acquisition technique on reliability followed by a Delphi exercise to obtain consensus definitions for synovitis, elementary components and scoring system. Results: Baseline reliability was highly variable but better for static than dynamic images that were directly acquired and immediately scored. Using static images, intrareader and inter-reader reliability for scoring PD were excellent for both binary and semiquantitative (SQ) grading but GS showed greater variability for both scoring systems (κ ranges: −0.05 to 1 and 0.59 to 0.92, respectively). In patient-based exercise, both intraobserver and interobserver reliability were variable and the mean κ coefficients did not reach 0.50 for any of the components. The second step resulted in refinement of the preliminary Outcome Measures in Rheumatology synovitis definition by including the presence of both hypoechoic SH and PD signal and the development of a SQ severity score, depending on both the amount of PD and the volume and appearance of SH. Conclusion: A multistep consensus-based process has produced a standardised US definition and quantification system for RA synovitis including combined and individual SH and PD components. Further evaluation is required to understand its performance before application in clinical trials

Synovitis in osteoarthritis: current understanding with therapeutic implications

Modern concepts of osteoarthritis (OA) have been forever changed by modern imaging phenotypes demonstrating complex and multi-tissue pathologies involving cartilage, subchondral bone and (increasingly recognized) inflammation of the synovium. The synovium may show significant changes, even before visible cartilage degeneration has occurred, with infiltration of mononuclear cells, thickening of the synovial lining layer and production of inflammatory cytokines. The combination of sensitive imaging modalities and tissue examination has confirmed a high prevalence of synovial inflammation in all stages of OA, with a number of studies demonstrating that synovitis is related to pain, poor function and may even be an independent driver of radiographic OA onset and structural progression. Treating key aspects of synovial inflammation therefore holds great promise for analgesia and also for structure modification. This article will review current knowledge on the prevalence of synovitis in OA and its role in symptoms and structural progression, and explore lessons learnt from targeting synovitis therapeutically

Successful Stepwise Development of Patient Research Partnership:14 Years' Experience of Actions and Consequences in Outcome Measures in Rheumatology (OMERACT)

There is increasing interest in making patient participation an integral component of medical research. However, practical guidance on optimizing this engagement in healthcare is scarce. Since 2002, patient involvement has been one of the key features of the Outcome Measures in Rheumatology (OMERACT) international consensus effort. Based on a review of cumulative data from qualitative studies and internal surveys among OMERACT participants, we explored the potential benefits and challenges of involving patient research partners in conferences and working group activities. We supplemented our review with personal experiences and reflections regarding patient participation in the OMERACT process. We found that between 2002 and 2016, 67 patients have attended OMERACT conferences, of whom 28 had sustained involvement; many other patients contributed to OMERACT working groups. Their participation provided face validity to the OMERACT process and expanded the research agenda. Essential facilitators have been the financial commitment to guarantee sustainable involvement of patients at these conferences, procedures for recruitment, selection and support, and dedicated time allocated in the program for patient issues. Current challenges include the representativeness of the patient panel, risk of pseudo-professionalization, and disparity in patients' and researchers' perception of involvement. In conclusion, OMERACT has embedded long-term patient involvement in the consensus-building process on the measurement of core health outcomes. This integrative process continues to evolve iteratively. We believe that the practical points raised here can improve participatory research implementation.</p