Outcome Measures in Rheumatology - Interventions for medication Adherence (OMERACT-Adherence) Core Domain Set for Trials of Interventions for Medication Adherence in Rheumatology: 5 Phase Study Protocol

Background: Over the last 20 years, there have been marked improvements in the availability of effective medications for rheumatic conditions such as gout, osteoporosis and rheumatoid arthritis (RA), which have led to a reduction in disease flares and the risk of re-fracture in osteoporosis, and the slowing of disease progression in RA. However, medication adherence remains suboptimal, as treatment regimens can be complex and difficult to continue long term. Many trials have been conducted to improve adherence to medication. Core domains, which are the outcomes of most relevance to patients and clinicians, are a pivotal component of any trial. These core domains should be measured consistently, so that all relevant trials can be combined in systematic reviews and meta-analyses to reach conclusions that are more valid. Failure to do this severely limits the potential for trial-based evidence to inform decisions on how to support medication adherence. The Outcome Measures in Rheumatology (OMERACT) - Interventions for Medication Adherence study by the OMERACT-Adherence Group aims to develop a core domain set for interventions that aim to support medication adherence in rheumatology. Methods/design: This OMERACT-Adherence study has five phases: (1) a systematic review to identify outcome domains that have been reported in interventions focused on supporting medication adherence in rheumatology; (2) semi-structured stakeholder interviews with patients and caregivers to determine their views on the core domains; (3) focus groups using the nominal group technique with patients and caregivers to identify and rank domains that are relevant to them, including the reasons for their choices; (4) an international three-round modified Delphi survey involving patients with diverse rheumatic conditions, caregivers, health professionals, researchers and other stakeholders to develop a preliminary core domain set; and (5) a stakeholder workshop with OMERACT members to review, vote on and reach a consensus on the core domain set for interventions to support medication adherence in rheumatology. Discussion: Establishing a core domain set to be reported in all intervention studies undertaken to support patients with medication adherence will enhance the relevance and the impact of these results and improve the lives of people with rheumatic conditions.The OMERACT-Adherence Group receives funding from OMERACT, which will be used to support a patient research partner in the OMERACT-Adherence Group to attend the OMERACT conference. OMERACT (http://www.omeract.org, contact: secretariat [email protected]) is the primary sponsor responsible for approving the initiation and overviewing the ongoing progress and management of the study. OMERACT mentors overview the design and conduct of the studies, including the interpretation of data and preparation, and review and approval of manuscripts. The following funding organisations had no role in the design and conduct of the studies; collection, management, analysis and interpretation of the data; or preparation, review or approval of manuscripts. AK is supported by the Arthritis Australia Scholarship funded by the Allan and Beryl Stephens Grant from the Estate of the Late Beryl Stephens. AT is supported by a National Health and Medical Research Council Fellowship (1037162). RC’s employer, the Parker Institute, Bispebjerg, and Frederiksberg Hospital, is supported by a core grant (OCAY-13-309) from the Oak Foundation. Phases 1–3 of the OMERACT-Adherence study were funded by a 2018 Arthritis Australia project grant (major funder), and a private research grant provided by Professor Stephen Hall

Patient and parent perspectives on transition from paediatric to adult healthcare in rheumatic diseases: an interview study.

OBJECTIVES: To describe the experiences, priorities, and needs of patients with rheumatic disease and their parents during transition from paediatric to adult healthcare. SETTING: Face-to-face and telephone semistructured interviews were conducted from December 2018 to September 2019 recruited from five hospital centres in Australia. PARTICIPANTS: Fourteen young people and 16 parents were interviewed. Young people were included if they were English speaking, aged 14-25 years, diagnosed with an inflammatory rheumatic disease (eg, juvenile idiopathic arthritis, juvenile dermatomyositis, systemic lupus erythematosus, panniculitis, familial Mediterranean fever) before 18 years of age. Young people were not included if they were diagnosed in the adult setting. RESULTS: We identified four themes with respective subthemes: avoid repeat of past disruption (maintain disease stability, preserve adjusted personal goals, protect social inclusion); encounter a daunting adult environment (serious and sombre mood, discredited and isolated identity, fear of a rigid system); establish therapeutic alliances with adult rheumatology providers (relinquish a trusting relationship, seek person-focused care, redefine personal-professional boundaries, reassurance of alternative medical supports, transferred trust to adult doctor) and negotiate patient autonomy (confidence in formerly gained independence, alleviate burden on patients, mediate parental anxiety). CONCLUSIONS: During transition, patients want to maintain disease stability, develop a relationship with their adult provider centralised on personal goals and access support networks. Strategies to comprehensively communicate information between providers, support self-management, and negotiate individualised goals for independence during transition planning may improve satisfaction, and health and treatment outcomes

Epistatic Roles for Pseudomonas aeruginosa MutS and DinB (DNA Pol IV) in Coping with Reactive Oxygen Species-Induced DNA Damage

Pseudomonas aeruginosa is especially adept at colonizing the airways of individuals afflicted with the autosomal recessive disease cystic fibrosis (CF). CF patients suffer from chronic airway inflammation, which contributes to lung deterioration. Once established in the airways, P. aeruginosa continuously adapts to the changing environment, in part through acquisition of beneficial mutations via a process termed pathoadaptation. MutS and DinB are proposed to play opposing roles in P. aeruginosa pathoadaptation: MutS acts in replication-coupled mismatch repair, which acts to limit spontaneous mutations; in contrast, DinB (DNA polymerase IV) catalyzes error-prone bypass of DNA lesions, contributing to mutations. As part of an ongoing effort to understand mechanisms underlying P. aeruginosa pathoadaptation, we characterized hydrogen peroxide (H2O2)-induced phenotypes of isogenic P. aeruginosa strains bearing different combinations of mutS and dinB alleles. Our results demonstrate an unexpected epistatic relationship between mutS and dinB with respect to H2O2-induced cell killing involving error-prone repair and/or tolerance of oxidized DNA lesions. In striking contrast to these error-prone roles, both MutS and DinB played largely accurate roles in coping with DNA lesions induced by ultraviolet light, mitomycin C, or 4-nitroquinilone 1-oxide. Models discussing roles for MutS and DinB functionality in DNA damage-induced mutagenesis, particularly during CF airway colonization and subsequent P. aeruginosa pathoadaptation are discussed

Patient and caregiver priorities for medication adherence in gout, osteoporosis and rheumatoid arthritis: nominal group technique

Objectives: This study aimed to identify and prioritize factors important to patients and caregivers with regard to medication adherence in gout, osteoporosis (OP) and rheumatoid arthritis (RA), and to describe the reasons for their decisions. Methods: Patients with gout, OP and RA, and their caregivers purposively sampled from five rheumatology clinics in Australia, identified and ranked factors considered important for medication adherence using nominal group technique and discussed their decisions. An importance score (scale 0-1) was calculated, and qualitative data were analysed thematically. Results: From 14 focus groups, 82 participants (67 patients, 15 caregivers) identified 49 factors. The top five factors based on the ranking of all participants were trust in doctor (importance score 0.46), medication effectiveness (0.31), doctor's knowledge (0.25), side effects (0.23), medication taking routine (0.13). The order of the ranking varied by participant groupings with patients ranking trust in doctor the highest whilst caregivers ranked side effects the highest. Five themes reflecting the reasons for factors influencing adherence were: motivation and certainty in supportive individualised care; living well and restoring function; fear of toxicity and cumulative harm; seeking control and involvement; and unnecessarily difficult and inaccessible. Conclusions: Factors related to the doctor, medication properties and patients' medication knowledge and routine were important for adherence. Strengthening doctor-patient trust and partnership, managing side effects, and empowering patients with knowledge and skills for medicine-taking could enhance medication adherence in patients with rheumatic conditions

Implementing an osteoporosis refracture prevention (ORP) service for South Western Sydney

Aim: To implement a patient centred re-fracture prevention service in Liverpool Hospital. This includes identification, assessment and treatment of all patients >50 years old presenting to Liverpool Hospital with a minimal trauma fracture. Method: Prior to the implementation, the Fracture Liaison Coordinator (FLC) conducted site visits across NSW and attended several FLC Network Meetings. By collaborating with the Emergency Department, we developed a system enabling a weekly report to be generated listing all patients aged >50 years who have sustained a fracture. We initially found the proportion of patients who had completed bone mineral density (BMD) testing prior to medical review was very low (20%). Various factors were identified including the culturally diverse population (25% of patients required interpreters) and long waiting times for booking radiology appointments in the public hospital. A public/private partnership was established with a local private rheumatology service to provide quick access to bone mineral density testing. The private BMD provider proactively contacted patients where necessary and offered an appointment within 1 week, including offering interpreter services. Results: To date, 246 patients have been seen by the FLC and rheumatologist. 88% of patients were prescribed pharmacotherapy to reduce fracture risk. Reasons for not starting treatment included medical contraindications and patient preference. The development of a public/private partnership with a local Liverpool Rheumatology clinic improved our BMD completion rates at the initial medical officer review appointment from 20% to 75%. Conclusions: The Liverpool Hospital ORP service has grown significantly over the last 12 months. We provide holistic patient-centred care with a multidisciplinary treating team. Initiating a private/public partnership significantly improved access to bone mineral density testing. Future work will focus on expanding the service to capture all minimal trauma fractures in South-West Sydney

The Scope and Consistency of Outcomes Reported in Trials in Patients with Systemic Sclerosis

International audienceOBJECTIVE: The core outcome set for trials in systemic sclerosis (SSc) was developed in 2008 and comprises eleven domains and thirty-one measures, leading to the development of a composite index (CRISS). We aimed to assess the scope, and consistency of outcomes reported in trials of SSc, and the uptake of this core set and CRISS. METHODS: MEDLINE, Cochrane CENTRAL, Embase and clinicaltrials gov were searched to identify randomized trials published from 2000 to 29 April 2018 in adults with limited or diffuse SSc. Outcomes and measures were recorded for each trial, classified into domains and the frequency of outcomes before after publication of the publication of the core set calculated. RESULTS: From 152 trials, 4193 outcomes were classified into 84 domains. The three most common domains were health-related quality of life and function (59%, 130 measures), skin (47%, 59 measures) and pulmonary (45%, 168 measures). After the publication of the core outcome set, no trial reported the complete core set with adherence to each of the eleven domains ranging from 6.1% to 54.4% and adherence to each of the thirty-one measures ranging from 0 to 48.1%. The five measures required for CRISS were reported completely in 11% of trials. CONCLUSION: Despite recognition that uniform acquisition and reporting of outcomes would enable a better evaluation of proposed SSc therapeutics, the outcome domains and measures reported in randomized trials in systemic sclerosis remain very inconsistent, with little impact of the core outcome set. This article is protected by copyright. All rights reserved

Frailty and risk of subsequent fracture among older adults presenting to hospital with a minimal trauma fracture

Summary: We investigated frailty and refracture risk among older adults with a minimal trauma fracture. After adjusting for age, sex, and site of initial fracture, increasing frailty was associated with an increased risk subsequent fracture. These results indicate the need to routinely screen for frailty following an initial fracture among older adults. Introduction: Minimal trauma fractures are common among older adults, and frailty increases risk of an initial minimal trauma fracture. This study was undertaken to estimate the risk of subsequent fracture based on frailty status at the time of an initial fracture. Methods: The study population was older adults presenting to hospital, aged 60 years or more, with a minimal trauma fracture. Frailty was estimated using a cumulative deficit approach. The risk of subsequent fracture based on increasing cumulative frailty deficit item group, adjusted for sex, age, and site of initial fracture, was estimated using Cox’s proportional hazard model. Results: Between January 2014 and December 2020, 12,115 older adults presented to hospital (8371 women [69%]), with an initial minimal trauma fracture. The average age was 80 years (SD 9.5). Subsequent fractures identified during the follow-up period occurred in 1137 (9.4%) of study participants. The incidence of subsequent fracture ranged from 25.0 per 1000 older adults (95% confidence interval (CI) 22.4 to 27.8) among the lowest frailty deficit group (1 deficit item) to 31.8 per 1000 (95% CI 28.0 to 35.8) among the highest frailty deficit group (4 to 12 deficit items). After adjusting for age, sex, and site of initial fracture, an increasing number of frailty deficit items was associated with increased risk subsequent fracture (p-value for trend = 0.008). Conclusion: Our results indicate that following an initial minimal trauma fracture, frailty independently increases the risk of a subsequent fracture. Therefore, it is important at the time of an initial fracture that older women and men are screened for the presence of frailty, and models of care are implemented to reduce the risk of subsequent fracture among this vulnerable group of older adults

The feasibility of implementing a cultural mentoring program alongside pain management and physical rehabilitation for chronic musculoskeletal conditions: results of a controlled before-and-after pilot study

Abstract Background Culturally diverse communities face barriers managing chronic musculoskeletal pain conditions including navigation challenges, sub-optimal healthcare provider engagement and difficulty adopting self-management behaviours. Objectives To explore the feasibility and trends of effectiveness of implementing a cultural mentoring program alongside clinical service delivery. Methods This quasi-experimental controlled before-and-after multiple case study was conducted in three hospital-based services that provide treatment for patients with musculoskeletal pain. Two prospective cohorts, a pre-implementation and a post-implementation cohort, of adults with chronic musculoskeletal pain who attended during the 6-month recruitment phase, were eligible if they self-identified with one of the cultures prioritised for mentoring by the clinic. The pre-implementation cohort received routine care for up to 3-months, while the post-implementation cohort received up to 3-months of cultural mentoring integrated into routine care (3 to 10 sessions), provided by a consumer (n = 6) with lived experience. Feasibility measures (recruitment and completion rates, attendance, satisfaction), and trends of effectiveness (Patient Activation Measure and Health Literacy Questionnaire items one and six) were collated over 3-months for both cohorts. Outcomes were presented descriptively and analysed using Mann-Whitney U-tests for between-group comparisons. Translation and transcription of post-treatment semi-structured interviews allowed both cohorts’ perspectives of treatment to be analysed using a Rapid Assessment Process. Results The cultural mentor program was feasible to implement in clinical services with comparable recruitment rates (66% pre-implementation; 61% post-implementation), adequate treatment attendance (75% pre-implementation; 89% post-implementation), high treatment satisfaction (97% pre-implementation; 96% post-implementation), and minimal participant drop-out (< 5%). Compared to routine care (n = 71), patients receiving mentoring (n = 55) achieved significantly higher Patient Activation Measure scores (median change 0 vs 10.3 points, p < 0.01) at 3-months, while Health Literacy Questionnaire items did not change for either cohort over time. Three themes underpinned participant experiences and acceptability of the mentoring intervention: ‘expectational priming’, ‘lived expertise’ and ‘collectivist orientation’ to understand shared participant experiences and explore the potential differential effect of the mentoring intervention. Conclusion Participant experiences and observations of improved patient activation provide support for the acceptability of the mentoring intervention integrated into routine care. These results support the feasibility of conducting a definitive trial, while also exploring issues of scalability and sustainability