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Objective: Up to one in five patients with axial spondyloarthritis (AxSpA) or psoriatic arthritis (PsA) newly initiated on opioids transition to long-term use within the first year. This study aimed to investigate individual factors associated with long-term opioid use among opioid new users with AxSpA/PsA., Methods: Adult patients with AxSpA/PsA and without prior cancer who initiated opioids between 2006-2021 were included from Clinical Practice Research Datalink Gold, a national UK primary care database. Long-term opioid use was defined as having ≥3 opioid prescriptions issued within 90 days, or ≥ 90 days of opioid supply, in the first year of follow-up. Individual factors assessed included sociodemographic, lifestyle factors, medication use and comorbidities. A mixed-effects logistic regression model with patient-level random intercept was used to examine the association of individual characteristics with the odds of long-term opioid use., Results: In total 10 300 opioid initiations were identified from 8,212 patients (3037 AxSpA; 5175 PsA). The following factors were associated with long-term opioid use: being a current smoker (OR : 1.62; 95%CI : 1.38,1.90), substance use disorder (OR : 2.34, 95%CI : 1.05,5.21), history of suicide/self-harm (OR : 1.84; 95%CI : 1.13,2.99), co-existing fibromyalgia (OR : 1.62; 95%CI : 1.11,2.37), higher Charlson Comorbidity Index (OR : 3.61; 95%CI : 1.69,7.71 for high scores), high MME/day at initiation (OR : 1.03; 95%CI : 1.02,1.03) and gabapentinoid (OR : 2.35; 95%CI : 1.75,3.16) and antidepressant use (OR : 1.69; 95%CI : 1.45,1.98)., Conclusions: In AxSpA/PsA patients requiring pain relief, awareness of lifestyle, sociodemographic and prescribing characteristics associated with higher risk of long-term opioid use can prompt timely interventions such as structured medication reviews and smoking cessation to promote safer prescribing and better patient outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Digital technologies, such as wearable devices and smartphone applications (apps), can enable the decentralisation of clinical trials by measuring endpoints in people's chosen locations rather than in traditional clinical settings. Digital endpoints can allow high-frequency and sensitive measurements of health outcomes compared to visit-based endpoints which provide an episodic snapshot of a person's health. However, there are underexplored challenges in this emerging space that require interdisciplinary and cross-sector collaboration. A multi-stakeholder Knowledge Exchange event was organised to facilitate conversations across silos within this research ecosystem., Methods: A survey was sent to an initial list of stakeholders to identify potential discussion topics. Additional stakeholders were identified through iterative discussions on perspectives that needed representation. Co-design meetings with attendees were held to discuss the scope, format and ethos of the event. The event itself featured a cross-disciplinary selection of talks, a panel discussion, small-group discussions facilitated via a rolling seating plan and audience participation via Slido. A transcript was generated from the day, which, together with the output from Slido, provided a record of the day's discussions. Finally, meetings were held following the event to identify the key challenges for digital endpoints which emerged and reflections and recommendations for dissemination., Results: Several challenges for digital endpoints were identified in the following areas: patient adherence and acceptability; algorithms and software for devices; design, analysis and conduct of clinical trials with digital endpoints; the environmental impact of digital endpoints; and the need for ongoing ethical support. Learnings taken for next generation events include the need to include additional stakeholder perspectives, such as those of funders and regulators, and the need for additional resources and facilitation to allow patient and public contributors to engage meaningfully during the event., Conclusions: The event emphasised the importance of consortium building and highlighted the critical role that collaborative, multi-disciplinary, and cross-sector efforts play in driving innovation in research design and strategic partnership building moving forward. This necessitates enhanced recognition by funders to support multi-stakeholder projects with patient involvement, standardised terminology, and the utilisation of open-source software., (© 2024. The Author(s).)

Objective: To investigate opioid prescribing trends and assess the impact of the COVID-19 pandemic on opioid prescribing in rheumatic and musculoskeletal diseases (RMDs)., Methods: Adult patients with RA, PsA, axial spondyloarthritis (AxSpA), SLE, OA and FM with opioid prescriptions between 1 January 2006 and 31 August 2021 without cancer in UK primary care were included. Age- and gender-standardized yearly rates of new and prevalent opioid users were calculated between 2006 and 2021. For prevalent users, monthly measures of mean morphine milligram equivalents (MME)/day were calculated between 2006 and 2021. To assess the impact of the pandemic, we fitted regression models to the monthly number of prevalent opioid users between January 2015 and August 2021. The time coefficient reflects the trend pre-pandemic and the interaction term coefficient represents the change in the trend during the pandemic., Results: The study included 1 313 519 RMD patients. New opioid users for RA, PsA and FM increased from 2.6, 1.0 and 3.4/10 000 persons in 2006 to 4.5, 1.8 and 8.7, respectively, in 2018 or 2019. This was followed by a fall to 2.4, 1.2 and 5.9, respectively, in 2021. Prevalent opioid users for all RMDs increased from 2006 but plateaued or dropped beyond 2018, with a 4.5-fold increase in FM between 2006 and 2021. In this period, MME/day increased for all RMDs, with the highest for FM (≥35). During COVID-19 lockdowns, RA, PsA and FM showed significant changes in the trend of prevalent opioid users. The trend for FM increased pre-pandemic and started decreasing during the pandemic., Conclusion: The plateauing or decreasing trend of opioid users for RMDs after 2018 may reflect the efforts to tackle rising opioid prescribing in the UK. The pandemic led to fewer people on opioids for most RMDs, providing reassurance that there was no sudden increase in opioid prescribing during the pandemic., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: Epidemiological estimates of psoriatic arthritis (PsA) underpin the provision of healthcare, research, and the work of government, charities and patient organizations. Methodological problems impacting prior estimates include small sample sizes, incomplete case ascertainment, and representativeness. We developed a statistical modelling strategy to provide contemporary prevalence and incidence estimates of PsA from 1991 to 2020 in the UK., Methods: Data from Clinical Practice Research Datalink (CPRD) were used to identify cases of PsA between 1st January 1991 and 31st December 2020. To optimize ascertainment, we identified cases of Definite PsA (≥1 Read code for PsA) and Probable PsA (satisfied a bespoke algorithm). Standardized annual rates were calculated using Bayesian multilevel regression with post-stratification to account for systematic differences between CPRD data and the UK population, based on age, sex, socioeconomic status and region of residence., Results: A total of 26293 recorded PsA cases (all definitions) were identified within the study window (77.9% Definite PsA). Between 1991 and 2020 the standardized prevalence of PsA increased twelve-fold from 0.03 to 0.37. The standardized incidence of PsA per 100,000 person years increased from 8.97 in 1991 to 15.08 in 2020, an almost 2-fold increase. Over time, rates were similar between the sexes, and across socioeconomic status. Rates were strongly associated with age, and consistently highest in Northern Ireland., Conclusion: The prevalence and incidence of PsA recorded in primary care has increased over the last three decades. The modelling strategy presented can be used to provide contemporary prevalence estimates for musculoskeletal disease using routinely collected primary care data., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: The past decade has seen an explosion of research in causal mediation analysis. However, most analytic tools developed so far rely on frequentist methods which may not be robust in the case of small sample sizes. In this paper, we propose a Bayesian approach for causal mediation analysis based on Bayesian g-formula, which will overcome the limitations of the frequentist methods., Methods: We created BayesGmed, an R-package for fitting Bayesian mediation models in R. The application of the methodology (and software tool) is demonstrated by a secondary analysis of data collected as part of the MUSICIAN study, a randomised controlled trial of remotely delivered cognitive behavioural therapy (tCBT) for people with chronic pain. We tested the hypothesis that the effect of tCBT would be mediated by improvements in active coping, passive coping, fear of movement and sleep problems. We then demonstrate the use of informative priors to conduct probabilistic sensitivity analysis around violations of causal identification assumptions., Result: The analysis of MUSICIAN data shows that tCBT has better-improved patients' self-perceived change in health status compared to treatment as usual (TAU). The adjusted log-odds of tCBT compared to TAU range from 1.491 (95% CI: 0.452-2.612) when adjusted for sleep problems to 2.264 (95% CI: 1.063-3.610) when adjusted for fear of movement. Higher scores of fear of movement (log-odds, -0.141 [95% CI: -0.245, -0.048]), passive coping (log-odds, -0.217 [95% CI: -0.351, -0.104]), and sleep problem (log-odds, -0.179 [95% CI: -0.291, -0.078]) leads to lower odds of a positive self-perceived change in health status. The result of BayesGmed, however, shows that none of the mediated effects are statistically significant. We compared BayesGmed with the mediation R- package, and the results were comparable. Finally, our sensitivity analysis using the BayesGmed tool shows that the direct and total effect of tCBT persists even for a large departure in the assumption of no unmeasured confounding., Conclusion: This paper comprehensively overviews causal mediation analysis and provides an open-source software package to fit Bayesian causal mediation models., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Yimer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Routinely collected prescription data provides drug exposure information for pharmacoepidemiology, informing start/stop dates and dosage. Prescribing information includes structured data and unstructured free-text instructions, which can include inherent variability, such as "one to two tablets up to four times a day". Preparing drug exposure data from raw prescriptions to a research ready dataset is rarely fully reported, yet assumptions have considerable implications for pharmacoepidemiology. This may have bigger consequences for "pro re nata" (PRN) drugs. Our aim was, using a worked example of opioids and fracture risk, to examine the impact of incorporating narrative prescribing instructions and subsequent drug preparation assumptions on adverse event rates., Methods: R-packages for extracting free-text medication prescription instructions in a structured form (doseminer) and an algorithm for transparently processing drug exposure information (drugprepr) were developed. Clinical Practice Research Datalink GOLD was used to define a cohort of adult new opioid users without prior cancer. A retrospective cohort study was performed using data between January 1, 2017 and July 31, 2018. We tested the impact of varying drug preparation assumptions by estimating the risk of opioids on fracture risk using Cox proportional hazards models., Results: During the study window, 60 394 patients were identified with 190 754 opioid prescriptions. Free-text prescribing instruction variability, where there was flexibility in the number of tablets to be administered, was present in 42% prescriptions. Variations in the decisions made during preparing raw data for analysis led to marked differences impacting the event number (n = 303-415) and person years of drug exposure (5619-9832). The distribution of hazard ratios as a function of the decisions ranged from 2.71 (95% CI: 2.31, 3.18) to 3.24 (2.76, 3.82)., Conclusions: Assumptions made during the drug preparation process, especially for those with variability in prescription instructions, can impact results of subsequent risk estimates. The developed R packages can improve transparency related to drug preparation assumptions, in line with best practice advocated by international pharmacoepidemiology guidelines., (© 2023 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

It is well-known that mood and pain interact with each other, however individual-level variability in this relationship has been less well quantified than overall associations between low mood and pain. Here, we leverage the possibilities presented by mobile health data, in particular the "Cloudy with a Chance of Pain" study, which collected longitudinal data from the residents of the UK with chronic pain conditions. Participants used an App to record self-reported measures of factors including mood, pain and sleep quality. The richness of these data allows us to perform model-based clustering of the data as a mixture of Markov processes. Through this analysis we discover four endotypes with distinct patterns of co-evolution of mood and pain over time. The differences between endotypes are sufficiently large to play a role in clinical hypothesis generation for personalised treatments of comorbid pain and low mood., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Das et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: People with rheumatic diseases experience troublesome fluctuations in fatigue. Debated causes include pain, mood and inflammation. To determine the relationships between these potential causes, serial assessments are required but are methodologically challenging. This mobile health (mHealth) study explored the viability of using a smartphone app to collect patient-reported symptoms with contemporaneous Dried Blood Spot Sampling (DBSS) for inflammation., Methods: Over 30 days, thirty-eight participants (12 RA, 13 OA, and 13 FM) used uMotif, a smartphone app, to report fatigue, pain and mood, on 5-point ordinal scales, twice daily. Daily DBSS, from which C-reactive Protein (CRP) values were extracted, were completed on days 1-7, 14 and 30. Participant engagement was determined based on frequency of data entry and ability to calculate within- and between-day symptom changes. DBSS feasibility and engagement was determined based on the proportion of samples returned and usable for extraction, and the number of days between which between-day changes in CRP which could be calculated (days 1-7)., Results: Fatigue was reported at least once on 1085/1140 days (95.2%). Approximately 65% of within- and between-day fatigue changes could be calculated. Rates were similar for pain and mood. A total of 287/342 (83.9%) DBSS, were returned, and all samples were viable for CRP extraction. Fatigue, pain and mood varied considerably, but clinically meaningful (≥ 5 mg/L) CRP changes were uncommon., Conclusions: Embedding DBSS in mHealth studies will enable researchers to obtain serial symptom assessments with matched biological samples. This provides exciting opportunities to address hitherto unanswerable questions, such as elucidating the mechanisms of fatigue fluctuations., (© 2022. The Author(s).)

Background: Sleep disturbances and poor health-related quality of life (HRQoL) are common in people with rheumatoid arthritis (RA). Sleep disturbances, such as less total sleep time, more waking periods after sleep onset, and higher levels of nonrestorative sleep, may be a driver of HRQoL. However, understanding whether these sleep disturbances reduce HRQoL has, to date, been challenging because of the need to collect complex time-varying data at high resolution. Such data collection is now made possible by the widespread availability and use of mobile health (mHealth) technologies., Objective: This mHealth study aimed to test whether sleep disturbance (both absolute values and variability) causes poor HRQoL., Methods: The quality of life, sleep, and RA study was a prospective mHealth study of adults with RA. Participants completed a baseline questionnaire, wore a triaxial accelerometer for 30 days to objectively assess sleep, and provided daily reports via a smartphone app that assessed sleep (Consensus Sleep Diary), pain, fatigue, mood, and other symptoms. Participants completed the World Health Organization Quality of Life-Brief (WHOQoL-BREF) questionnaire every 10 days. Multilevel modeling tested the relationship between sleep variables and the WHOQoL-BREF domains (physical, psychological, environmental, and social)., Results: Of the 268 recruited participants, 254 were included in the analysis. Across all WHOQoL-BREF domains, participants' scores were lower than the population average. Consensus Sleep Diary sleep parameters predicted the WHOQoL-BREF domain scores. For example, for each hour increase in the total time asleep physical domain scores increased by 1.11 points (β=1.11, 95% CI 0.07-2.15) and social domain scores increased by 1.65 points. These associations were not explained by sociodemographic and lifestyle factors, disease activity, medication use, anxiety levels, sleep quality, or clinical sleep disorders. However, these changes were attenuated and no longer significant when pain, fatigue, and mood were included in the model. Increased variability in total time asleep was associated with poorer physical and psychological domain scores, independent of all covariates. There was no association between actigraphy-measured sleep and WHOQoL-BREF., Conclusions: Optimizing total sleep time, increasing sleep efficiency, decreasing sleep onset latency, and reducing variability in total sleep time could improve HRQoL in people with RA., (©John McBeth, William G Dixon, Susan Mary Moore, Bruce Hellman, Ben James, Simon D Kyle, Mark Lunt, Lis Cordingley, Belay Birlie Yimer, Katie L Druce. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 22.04.2022.)

Introduction: Previous studies on the association between weather and pain severity among patients with chronic pain have produced mixed results. In part, this inconsistency may be due to differences in individual pain responses to the weather., Methods: To test the hypothesis that there might be subgroups of participants with different pain responses to different weather conditions, we examined data from a longitudinal smartphone-based study, Cloudy with a Chance of Pain, conducted between January 2016 and April 2017. The study recruited more than 13,000 participants and recorded daily pain severity on a 5-point scale (range: no pain to very severe pain) along with hourly local weather data for up to 15 months. We used a Bayesian multilevel model to examine the weather-pain association., Results: We found 1 in 10 patients with chronic pain were sensitive to the temperature, 1 in 25 to relative humidity, 1 in 50 to pressure, and 3 in 100 to wind speed, after adjusting for age, sex, belief in the weather-pain association, mood, and activity level. The direction of the weather-pain association differed between people. Although participants seem to be differentially sensitive to weather conditions, there is no definite indication that participants' underlying pain conditions play a role in weather sensitivity., Conclusion: This study demonstrated that weather sensitivity among patients with chronic pain is more apparent in some subgroups of participants. In addition, among those sensitive to the weather, the direction of the weather-pain association can differ., Competing Interests: W.G. Dixon has received consultancy fees from Google and AbbVie unrelated to this study.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

Background: Smartphone location data can be used for observational health studies (to determine participant exposure or behavior) or to deliver a location-based health intervention. However, missing location data are more common when using smartphones compared to when using research-grade location trackers. Missing location data can affect study validity and intervention safety., Objective: The objective of this study was to investigate the distribution of missing location data and its predictors to inform design, analysis, and interpretation of future smartphone (observational and interventional) studies., Methods: We analyzed hourly smartphone location data collected from 9665 research participants on 488,400 participant days in a national smartphone study investigating the association between weather conditions and chronic pain in the United Kingdom. We used a generalized mixed-effects linear model with logistic regression to identify whether a successfully recorded geolocation was associated with the time of day, participants' time in study, operating system, time since previous survey completion, participant age, sex, and weather sensitivity., Results: For most participants, the app collected a median of 2 out of a maximum of 24 locations (1760/9665, 18.2% of participants), no location data (1664/9665, 17.2%), or complete location data (1575/9665, 16.3%). The median locations per day differed by the operating system: participants with an Android phone most often had complete data (a median of 24/24 locations) whereas iPhone users most often had a median of 2 out of 24 locations. The odds of a successfully recorded location for Android phones were 22.91 times higher than those for iPhones (95% CI 19.53-26.87). The odds of a successfully recorded location were lower during weekends (odds ratio [OR] 0.94, 95% CI 0.94-0.95) and nights (OR 0.37, 95% CI 0.37-0.38), if time in study was longer (OR 0.99 per additional day in study, 95% CI 0.99-1.00), and if a participant had not used the app recently (OR 0.96 per additional day since last survey entry, 95% CI 0.96-0.96). Participant age and sex did not predict missing location data., Conclusions: The predictors of missing location data reported in our study could inform app settings and user instructions for future smartphone (observational and interventional) studies. These predictors have implications for analysis methods to deal with missing location data, such as imputation of missing values or case-only analysis. Health studies using smartphones for data collection should assess context-specific consequences of high missing data, especially among iPhone users, during the night and for disengaged participants., (©Anna L Beukenhorst, Jamie C Sergeant, David M Schultz, John McBeth, Belay B Yimer, Will G Dixon. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 16.11.2021.)

Objectives: Patients with RA are frequently treated with glucocorticoids (GCs), but evidence is conflicting about whether GCs are associated with hypertension. The aim of this study was to determine whether GCs are associated with incident hypertension in patients with RA., Methods: A retrospective cohort of patients with incident RA and without hypertension was identified from UK primary care electronic medical records (Clinical Practice Research Datalink). GC prescriptions were used to determine time-varying GC use, dose and cumulative dose, with a 3 month attribution window. Hypertension was identified through either: blood pressure measurements >140/90 mmHg, or antihypertensive prescriptions and a Read code for hypertension. Unadjusted and adjusted Cox proportional hazards regression models were fitted to determine whether there was an association between GC use and incident hypertension., Results: There were 17 760 patients in the cohort. A total of 7421 (42%) were prescribed GCs during follow-up. The incident rate of hypertension was 64.1 per 1000 person years (95% CI: 62.5, 65.7). The Cox proportional hazards model indicated that recent GC use was associated with a 17% increased hazard of hypertension (hazard ratio 1.17; 95% CI: 1.10, 1.24). When categorized by dose, only doses above 7.5 mg were significantly associated with hypertension. Cumulative dose did not indicate a clear pattern., Conclusion: Recent GC use was associated with incident hypertension in patients with RA, in particular doses ≥7.5 mg were associated with hypertension. Clinicians need to consider cardiovascular risk when prescribing GCs, and ensure blood pressure is regularly monitored and treated where necessary., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Comorbid conditions appear to be common among individuals hospitalised with coronavirus disease 2019 (COVID-19) but estimates of prevalence vary and little is known about the prior medication use of patients. Here, we describe the characteristics of adults hospitalised with COVID-19 and compare them with influenza patients. We include 34,128 (US: 8362, South Korea: 7341, Spain: 18,425) COVID-19 patients, summarising between 4811 and 11,643 unique aggregate characteristics. COVID-19 patients have been majority male in the US and Spain, but predominantly female in South Korea. Age profiles vary across data sources. Compared to 84,585 individuals hospitalised with influenza in 2014-19, COVID-19 patients have more typically been male, younger, and with fewer comorbidities and lower medication use. While protecting groups vulnerable to influenza is likely a useful starting point in the response to COVID-19, strategies will likely need to be broadened to reflect the particular characteristics of individuals being hospitalised with COVID-19.

Patients with chronic pain commonly believe their pain is related to the weather. Scientific evidence to support their beliefs is inconclusive, in part due to difficulties in getting a large dataset of patients frequently recording their pain symptoms during a variety of weather conditions. Smartphones allow the opportunity to collect data to overcome these difficulties. Our study Cloudy with a Chance of Pain analysed daily data from 2658 patients collected over a 15-month period. The analysis demonstrated significant yet modest relationships between pain and relative humidity, pressure and wind speed, with correlations remaining even when accounting for mood and physical activity. This research highlights how citizen-science experiments can collect large datasets on real-world populations to address long-standing health questions. These results will act as a starting point for a future system for patients to better manage their health through pain forecasts., Competing Interests: Competing interestsW.G.D. has received consultancy fees from Bayer Pharmaceuticals and Google, unrelated to this study. B.J. and B.H. are co-founders of uMotif. All other authors declare no competing interests., (© The Author(s) 2019.)

Background: At the diabetic clinic of Jimma University Specialized Hospital, health professionals provide regular follow-up to help people with diabetes live long and relatively healthy lives. Based on patient condition, they also provide interventions in the form of counselling to promote a healthy diet and physical activity and prescribing medicines. The main purpose of this study is to estimate the rate of change of fasting blood sugar (FBS) profile experienced by patients over time. The change may help to assess the effectiveness of interventions taken by the clinic to regulate FBS level, where rates of change close to zero over time may indicate the interventions are good regulating the level., Methods: In the analysis of longitudinal data, the mean profile is often estimated by parametric linear mixed effects model. However, the individual and mean profile plots of FBS level for diabetic patients are nonlinear and imposing parametric models may be too restrictive and yield unsatisfactory results. We propose a semi-parametric mixed model, in particular using spline smoothing to efficiently analyze a longitudinal measured fasting blood sugar level of adult diabetic patients accounting for correlation between observations through random effects., Results: The semi-parametric mixed models had better fit than the linear mixed models for various variance structures of subject-specific random effects. The study revealed that the rate of change in FBS level in diabetic patients, due to the clinic interventions, does not continue as a steady pace but changes with time and weight of patients., Conclusions: The proposed method can help a physician in clinical monitoring of diabetic patients and to assess the effect of intervention packages, such as healthy diet, physical activity and prescribed medicines, because individualized curve may be obtained to follow patient-specific FBS level trends.