Impact of lung function decline on time to hospitalisation events in systemic sclerosis-associated interstitial lung disease (SSc-ILD): a joint model analysis

Background Interstitial lung disease (ILD) is a common organ manifestation in systemic sclerosis (SSc) and is the leading cause of death in patients with SSc. A decline in forced vital capacity (FVC) is an indicator of ILD progression and is associated with mortality in patients with SSc-associated ILD (SSc-ILD). However, the relationship between FVC decline and hospitalisation events in patients with SSc-ILD is largely unknown. The objective of this post hoc analysis was to investigate the relationship between FVC decline and clinically important hospitalisation endpoints. Methods We used data from SENSCIS®, a phase III trial investigating the efficacy and safety of nintedanib in patients with SSc-ILD. Joint models for longitudinal and time-to-event data were used to assess the association between rate of decline in FVC% predicted and hospitalisation-related endpoints (including time to first all-cause hospitalisation or death; time to first SSc-related hospitalisation or death; and time to first admission to an emergency room [ER] or admission to hospital followed by admission to intensive care unit [ICU] or death) during the treatment period, over 52 weeks in patients with SSc-ILD. Results There was a statistically significant association between FVC decline and the risk of all-cause (n = 78) and SSc-related (n = 42) hospitalisations or death (both P < 0.0001). A decrease of 3% in FVC corresponded to a 1.43-fold increase in risk of all-cause hospitalisation or death (95% confidence interval [CI] 1.24, 1.65) and a 1.48-fold increase in risk of SSc-related hospitalisation or death (95% CI 1.23, 1.77). No statistically significant association was observed between FVC decline and admission to ER or to hospital followed by admission to ICU or death (n = 75; P = 0.15). The estimated slope difference for nintedanib versus placebo in the longitudinal sub-model was consistent with the primary analysis in SENSCIS®. Conclusions The association of lung function decline with an increased risk of hospitalisation suggests that slowing FVC decline in patients with SSc-ILD may prevent hospitalisations. Our findings also provide evidence that FVC decline may serve as a surrogate endpoint for clinically relevant hospitalisation-associated endpoints. Trial registration ClinicalTrials.govNCT02597933. Registered on 8 October 2015.

Comparative effectiveness of the BNT162b2 vs ChAdOx1 vaccine against Covid-19

Although pivotal trials with varying populations and study methods suggest higher efficacy for mRNA than adenoviral Covid-19 vaccines, no direct evidence is available. Here, we conducted a head-to-head comparison of BNT162b2 versus ChAdOx1 against Covid-19. We analysed 235,181 UK Biobank participants aged 50 years or older and vaccinated with one or two doses of BNT162b2 or ChAdOx1. People were followed from the vaccination date until 18/10/2021. Inverse probability weighting was used to minimise confounding and the Cox models to derive hazard ratio. We found that, compared with two doses of ChAdOx1, vaccination with BNT162b2 was associated with 30% lower risks of both SARS-CoV-2 infection and related hospitalisation during the period dominated by the delta variant. Also, this comparative effectiveness was consistent across several subgroups and persisted for at least six months, suggesting no differential waning between the two vaccines. Our findings can inform evidence-based Covid-19 vaccination campaigns and booster strategies.

Feasibility of using real-world data in the evaluation of cardiac ablation catheters: a test-case of the National Evaluation System for Health Technology Coordinating Center

ObjectivesTo determine the feasibility of using real-world data to assess the safety and effectiveness of two cardiac ablation catheters for the treatment of persistent atrial fibrillation and ischaemic ventricular tachycardia.DesignRetrospective cohort.SettingThree health systems in the USA.ParticipantsPatients receiving ablation with the two ablation catheters of interest at any of the three health systems.Main outcome measuresFeasibility of identifying the medical devices and participant populations of interest as well as the duration of follow-up and positive predictive values (PPVs) for serious safety (ischaemic stroke, acute heart failure and cardiac tamponade) and effectiveness (arrhythmia-related hospitalisation) clinical outcomes of interest compared with manual chart validation by clinicians.ResultsOverall, the catheter of interest for treatment of persistent atrial fibrillation was used for 4280 ablations and the catheter of interest for ischaemic ventricular tachycardia was used 1516 times across the data available within the three health systems. The duration of patient follow-up in the three health systems ranged from 91% to 97% at ≥7 days, 89% to 96% at ≥30 days, 77% to 90% at ≥6 months and 66% to 84% at ≥1 year. PPVs were 63.4% for ischaemic stroke, 96.4% for acute heart failure, 100% at one health system for cardiac tamponade and 55.7% for arrhythmia-related hospitalisation.ConclusionsIt is feasible to use real-world health system data to evaluate the safety and effectiveness of cardiac ablation catheters, though evaluations must consider the implications of variation in follow-up and endpoint ascertainment among health systems.

The risk of fall-related hospitalisations at entry into permanent residential aged care

Background Entering permanent residential aged care (PRAC) is a vulnerable time for individuals. While falls risk assessment tools exist, these have not leveraged routinely collected and integrated information from the Australian aged and health care sectors. Our study examined individual, system, medication, and health care related factors at PRAC entry that are predictors of fall-related hospitalisations and developed a risk assessment tool using integrated aged and health care data. Methods A retrospective cohort study was conducted on N = 32,316 individuals ≥65 years old who entered a PRAC facility (01/01/2009-31/12/2016). Fall-related hospitalisations within 90 or 365 days were the outcomes of interest. Individual, system, medication, and health care-related factors were examined as predictors. Risk prediction models were developed using elastic nets penalised regression and Fine and Gray models. Area under the receiver operating characteristics curve (AUC) assessed model discrimination. Results 64.2% (N = 20,757) of the cohort were women and the median age was 85 years old (interquartile range 80-89). After PRAC entry, 3.7% (N = 1209) had a fall-related hospitalisation within 90 days and 9.8% (N = 3156) within 365 days. Twenty variables contributed to fall-related hospitalisation prediction within 90 days and the strongest predictors included fracture history (sub-distribution hazard ratio (sHR) = 1.87, 95% confidence interval (CI) 1.63-2.15), falls history (sHR = 1.41, 95%CI 1.21-2.15), and dementia (sHR = 1.39, 95%CI 1.22-1.57). Twenty-seven predictors of fall-related hospitalisation within 365 days were identified, the strongest predictors included dementia (sHR = 1.36, 95%CI 1.24-1.50), history of falls (sHR = 1.30, 95%CI 1.20-1.42) and fractures (sHR = 1.28, 95%CI 1.15-1.41). The risk prediction models had an AUC of 0.71 (95%CI 0.68-0.74) for fall-related hospitalisations within 90 days and 0.64 (95%CI 0.62-0.67) for within 365 days. Conclusion Routinely collected aged and health care data, when integrated at a clear point of action such as entry into PRAC, can identify residents at risk of fall-related hospitalisations, providing an opportunity for better targeting risk mitigation strategies.

Role of targeted therapies in rheumatic patients on COVID-19 outcomes: results from the COVIDSER study

ObjectivesTo analyse the effect of targeted therapies, either biological (b) disease-modifying antirheumatic drugs (DMARDs), targeted synthetic (ts) DMARDs and other factors (demographics, comorbidities or COVID-19 symptoms) on the risk of COVID-19 related hospitalisation in patients with inflammatory rheumatic diseases.MethodsThe COVIDSER study is an observational cohort including 7782 patients with inflammatory rheumatic diseases. Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation. Antirheumatic medication taken immediately prior to infection, demographic characteristics, rheumatic disease diagnosis, comorbidities and COVID-19 symptoms were analysed.ResultsA total of 426 cases of symptomatic COVID-19 from 1 March 2020 to 13 April 2021 were included in the analyses: 106 (24.9%) were hospitalised and 19 (4.4%) died. In multivariate-adjusted models, bDMARDs and tsDMARDs in combination were not associated with hospitalisation compared with conventional synthetic DMARDs (OR 0.55, 95% CI 0.24 to 1.25 of b/tsDMARDs, p=0.15). Tumour necrosis factor inhibitors (TNF-i) were associated with a reduced likelihood of hospitalisation (OR 0.32, 95% CI 0.12 to 0.82, p=0.018), whereas rituximab showed a tendency to an increased risk of hospitalisation (OR 4.85, 95% CI 0.86 to 27.2). Glucocorticoid use was not associated with hospitalisation (OR 1.69, 95% CI 0.81 to 3.55). A mix of sociodemographic factors, comorbidities and COVID-19 symptoms contribute to patients’ hospitalisation.ConclusionsThe use of targeted therapies as a group is not associated with COVID-19 severity, except for rituximab, which shows a trend towards an increased risk of hospitalisation, while TNF-i was associated with decreased odds of hospitalisation in patients with rheumatic disease. Other factors like age, male gender, comorbidities and COVID-19 symptoms do play a role.

Effects of the COVID-19 pandemic on patients with inflammatory joint diseases in Sweden: from infection severity to impact on care provision

ObjectivesTo compare risks for COVID-19-related outcomes in inflammatory joint diseases (IJDs) and across disease-modifying antirheumatic drugs (DMARDs) during the first two waves of the pandemic and to assess effects of the pandemic on rheumatology care provision.MethodsThrough nationwide multiregister linkages and cohort study design, we defined IJD and DMARD use annually in 2015–2020. We assessed absolute and relative risks of hospitalisation or death listing COVID-19. We also assessed the incidence of IJD and among individuals with IJD, rheumatologist visits, DMARD use and incidence of selected comorbidities.ResultsBased on 115 317 patients with IJD in 2020, crude risks of hospitalisation and death listing COVID-19 (0.94% and 0.33% across both waves, respectively) were similar during both waves (adjusted HR versus the general population 1.33, 95% CI 1.23 to 1.43, for hospitalisation listing COVID-19; 1.23, 95% CI 1.08 to 1.40 for death listing COVID-19). Overall, biological disease-modifying antirheumatic drugs (bDMARDs)/targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) did not increase risks of COVID-19 related hospitalisation (with the exception of a potential signal for JAK inhibitors) or death. During the pandemic, decreases were observed for IJD incidence (−7%), visits to rheumatology units (−16%), DMARD dispensations (+6.5% for bDMARD/tsDMARDs and −8.5% for conventional synthetic DMARDs compared with previous years) and for new comorbid conditions, but several of these changes were part of underlying secular trends.ConclusionsPatients with IJD are at increased risk of serious COVID-19 outcomes, which may partially be explained by medical conditions other than IJD per se. The SARS-CoV-2 pandemic has exerted measurable effects on aspects of rheumatology care provision demonstrated, the future impact of which will need to be assessed.

Factors affecting adherence to disease-modifying therapies in multiple sclerosis: systematic review

People with multiple sclerosis (MS) face challenges adhering to disease-modifying drug (DMD) treatment. Poor adherence to treatment reduces its clinical effectiveness which can adversely impact disease progression, MS-related hospitalisation, and mortality rates. Understanding the barriers to adherence is essential to addressing these issues in clinical practice and a consolidation of the literature had not yet been carried out. A systematic search was carried out using the electronic databases PsycINFO, and PubMed (Medline) using the search terms treatment compliance or treatment adherence and multiple sclerosis or MS. Studies included adults, with a diagnosis of relapsing–remitting MS (RRMS) (sample > 80% RRMS), taking a DMD. The studies used an adequate measurement of treatment adherence and analysed possible factors associated with adherence. A total of 349 studies were retrieved, of which 24 were considered eligible for inclusion. Overall adherence rates of the included studies ranged from 52 to 92.8%. Narrative synthesis revealed the most prevalent factors associated with adherence were age, gender, depression, cognition, treatment satisfaction, injection-site reactions, and injection anxiety. There was contradictory evidence for disability in association with treatment adherence. The findings should be used to inform the development of targeted patient support programs which improve treatment compliance. The review also highlights the opportunities for advancing research into treatment adherence in MS.

Occupational risk of COVID-19 in the first versus second epidemic wave in Norway, 2020

Background The occupational risk of COVID-19 may be different in the first versus second epidemic wave. Aim To study whether employees in occupations that typically entail close contact with others were at higher risk of SARS-CoV-2 infection and COVID-19-related hospitalisation during the first and second epidemic wave before and after 18 July 2020, in Norway. Methods We included individuals in occupations working with patients, children, students, or customers using Standard Classification of Occupations (ISCO-08) codes. We compared residents (3,559,694 on 1 January 2020) in such occupations aged 20–70 years (mean: 44.1; standard deviation: 14.3 years; 51% men) to age-matched individuals in other professions using logistic regression adjusted for age, sex, birth country and marital status. Results Nurses, physicians, dentists and physiotherapists had 2–3.5 times the odds of COVID-19 during the first wave when compared with others of working age. In the second wave, bartenders, waiters, food counter attendants, transport conductors, travel stewards, childcare workers, preschool and primary school teachers had ca 1.25–2 times the odds of infection. Bus, tram and taxi drivers had an increased odds of infection in both waves (odds ratio: 1.2–2.1). Occupation was of limited relevance for the odds of severe infection, here studied as hospitalisation with the disease. Conclusion Our findings from the entire Norwegian population may be of relevance to national and regional authorities in handling the epidemic. Also, we provide a knowledge foundation for more targeted future studies of lockdowns and disease control measures.