Quantification and dosimetric impact of intra‐fractional bladder changes during CBCT‐guided online adaptive radiotherapy for pelvic cancer treatments

Abstract Purpose This study quantitatively evaluates bladder changes and their dosimetric impact during the on‐couch adaptive process on a commercial CBCT‐based online adaptive radiotherapy (CT‐gART) platform. Methods Data from 183 fractions of ten patients receiving online ART for pelvic cancers were analyzed retrospectively. Bladder contours were automatically generated and revised by an expert for each pair of planning and verification CBCTs. Bladder shape changes were assessed using geometric and boundary distance metrics. A deformable image registration (DIR) workflow was implemented to obtain spatial motion characteristics, validated by the dice similarity coefficient between bladder contours. Dosimetric parameters were quantified by warping ’intended’ dose distributions to the verification CBCT anatomy using DIR to evaluate coverage and OAR objectives. Results Bladder volume changed noticeably during the on‐couch adaptation process (19.7 ± 3.3 min). Day‐to‐day bladder expansion showed an average increase of 3.4 cc/min ± 1.5 cc/min for the full bladder and 0.8 cc/min ± 0.3 cc/min for empty bladder protocols. Deformation occurred mainly in the superior region and was more pronounced for the full bladder protocol. Displacements over 5 mm in cranial‐caudal and anterior‐posterior directions averaged 16% and 5% of the volume for full bladders and 5% and 4% for empty bladders, respectively. CTV coverage (V100%) was maintained when the bladder was the target, but PTV V95% was reduced by an average of 7%. For non‐bladder treatments, bladder constraints increased slightly for supine subjects (0.5 Gy/fx), with prone subjects almost unaffected. Conclusions A framework using auto‐segmentation and DIR was developed to evaluate the intra‐fractional motion of the bladder during CTgART. Results suggest that reducing the isotropic PTV margin to less than 7 mm may be feasible for oART, allowing patient‐specific anisotropic margins while maintaining the quality of the adaptive plan.

Psoriasis and dementia: A population‐based matched cohort study of adults in England

Abstract Objective Evidence for an association between psoriasis and dementia is limited and conflicting. We aimed to investigate the association using large and representative population‐based data and describe risk by dementia subtype and over time. Methods We compared dementia risk between people with and without psoriasis using an age‐, sex‐ and primary care practice‐matched cohort of adults aged ≥40 years from the Clinical Practice Research Datalink Aurum in England (1997–2021) linked to hospital admissions data, analysed with stratified Cox regression. Results Among 360,014 individuals with psoriasis and 1,799,617 without, psoriasis was associated with a small increased risk of all‐cause dementia (adjusted hazard ratio [aHR] 1.06, 95% CI 1.04–1.08; absolute rate difference 24 per 100,000 person‐years). Strength of association increased with time since psoriasis diagnosis (e.g. aHR 0.99, 0.96–1.03 within 0 to 5 years; 1.20, 1.05–1.37 within 20 to 25 years). The association was stronger for vascular dementia (aHR 1.10, 1.06–1.14) than Alzheimer's dementia (aHR 1.03, 1.00–1.06). Hazard ratios were larger for severe psoriasis (all‐cause aHR 1.32, 1.25–1.39; vascular aHR 1.58, 1.44–1.74; Alzheimer's aHR 1.11, 1.02–1.21). Interpretation Long‐term risk of all‐cause dementia and vascular dementia, but not Alzheimer's dementia, was slightly higher in people with psoriasis, but absolute risk differences were small. Risks were more substantially raised with time since psoriasis diagnosis and in severe psoriasis compared to mild to moderate psoriasis, suggesting a potential dose–response relationship.

EEG Response to Sedation Interruption Complements Behavioral Assessment After Severe Brain Injury

ABSTRACT Objective Accurate assessment of the level of consciousness and potential to recover in patients with severe brain injury underpins crucial decisions in the intensive care unit but remains a major challenge for the clinical team. The neurological wake‐up test is a widely used assessment tool. However, many patients' behavioral responses during a short interruption of sedation are ambiguous or absent, yielding little prognostic value. This study assesses the brain's electroencephalogram response during an interruption of propofol sedation to complement behavioral assessment during the neurological wake‐up test to predict survival, recovery of consciousness, and long‐term functional outcomes in patients with acute severe brain injury. Methods We recorded 128‐channel EEG from 41 severely brain‐injured patients during a clinically indicated neurological wake‐up test. Behavioral assessment was performed before and after interruption of propofol sedation, using the Glasgow Coma Scale. Brain response to sedation interruption was quantified using EEG power, spatial ratios, and the spectral exponent. Results Recovery of responsiveness during the neurological wake‐up test is reflected in participants' brain response to sedation interruption. Electrophysiological patterns can be decoupled from participant behavioral response, with some individuals demonstrating neurophysiological signs of waking up despite an absent behavioral response. Using the brain response to complement behavioral assessment improved prognostic value, distinguished patients according to survival and outperformed outcome predictions of the patients' attending physician. Interpretation EEG can complement behavioral assessment during the neurological wake‐up test to improve prognostication, inform clinicians, family members, and caregivers, and to set realistic goals for treatment and therapy.

Association of Foot Symptoms With Decreased Time to All‐Cause Mortality: The Johnston County Osteoarthritis Project

Objective Adults with foot symptoms (ie, pain, aching, or stiffness) may be at increased risk of reduced time to all‐cause mortality. The purpose of this study was to evaluate whether foot symptoms are independently associated with all‐cause mortality in older adults. Methods We analyzed longitudinal data from 2613 participants from the Johnston County Osteoarthritis Project, a longitudinal population‐based cohort of adults 45 years of age and older. Participants completed questionnaires at baseline to determine presence of foot symptoms and covariable status. Baseline walking speed was measured via an 8‐foot walk test. To examine the association of foot symptoms with time to mortality, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression models, adjusted for potential confounders. Results We observed 813 deaths over 4 to 14.5 years of follow‐up. At baseline, 37% of participants had foot symptoms, mean age was 63 years, mean body mass index was approximately 31 kg/m 2 , 65% were women, and 33% were Black. Moderate to severe foot symptoms were associated with reduced time to mortality after adjustment for demographics, comorbidities, physical activity, and knee and hip symptoms (HR = 1.30, 95% CI 1.09–1.54). Importantly, this association was not modified by walking speed or diabetes. Conclusion Individuals with foot symptoms had an increased hazard of all‐cause mortality compared with those with no foot symptoms. These effects were independent of key confounders and were not moderated by walking speed. Effective interventions to identify and manage at least moderate foot symptoms may reduce the risk of decreased time to mortality.

Measurable Outcomes of an Ophthalmology and Rheumatology Coordinated Care Clinic

Objective We evaluated the impact of an Ophthalmology/Rheumatology multidisciplinary clinic for patients with anterior uveitis by comparing outcomes between those who received traditional care (TC) versus coordinated care (CC). Methods We conducted a retrospective cohort study of children with anterior uveitis from a pediatric tertiary care center between 2013 and 2022. Standard descriptive statistics were used; survival analyses explored differences in cohort disease activity and biologic disease‐modifying antirheumatic drug (DMARD) treatment. Steroid treatment by cohort was compared using generalized estimating equation model with Poisson distribution and log link. Complications were compared using logistic regression. Number of visits in each cohort were assessed using Poisson generalized estimating equation model adjusted for complications. Results We studied 215 patients with anterior uveitis; 66% were female, 53% had juvenile idiopathic arthritis, and 23% were idiopathic, with a median age at diagnosis of 8 years old (interquartile range 5–12). CC was associated with a 60% higher hazard of reaching disease control (hazard ratio 1.6; P < 0.01) when controlling for time since diagnosis and anterior chamber cell counts at the beginning of disease activity. CC was associated with starting biologic DMARDs earlier than TC ( P < 0.01). Compared with the group who received TC, the group who received CC had a 96% lower rate of glucocorticoid reception per appointment within the first year ( P < 0.01). The visit rate was 64% lower for the group who received CC when controlling for total complications per patient. Conclusion Patients who received multidisciplinary care had better outcomes than patients who received TC. Limitations include different cohort start times and absence of defined criteria for CC referral.

Area‐Level Socioeconomic Status Impacts Health Care Visit Frequency by Australian Patients With Inflammatory Arthritis: Results From the Australian Rheumatology Association Database

Objective Individuals with inflammatory arthritis require long‐term rheumatologist care for optimal outcomes. We sought to determine if socioeconomic status (SES) influences general practitioner (GP) and specialist physician visit frequency and out‐of‐pocket (OOP) visit costs. Methods We linked data from Australian Rheumatology Association Database (ARAD) participants with rheumatoid arthritis or psoriatic arthritis to the Pharmaceutical Benefits (PBS) and Medicare Benefits Schedule from 2011 to 2018. Small‐area SES was approximated as quintiles of the Index of Relative Socioeconomic Advantage and Disadvantage. A comorbidity index (Rx‐Risk) was determined from PBS data. Analysis was performed using panel regression methods. Results We included 1,916 ARAD participants (76.3% rheumatoid arthritis, 71.1% women, mean ± SD age 54 ± 12 years and disease duration 6 ± 4 years). Participants averaged 9.0 (95% confidence interval [CI] 8.6–9.4) annual GP visits and 3.9 (95% CI 3.8–4.1) annual specialist physician visits. After adjustment for sex, age, education, remoteness, and comorbidity, there was an inverse relationship between annual GP visit frequency and higher SES quintile (–0.6, 95% CI –0.9 to –0.3 visits per quintile) and a direct relationship between more frequent specialist visits and higher SES (linear slope 0.3, 95% CI 0.2–0.5 visits per quintile). Average OOP costs/visit were higher for specialist physician (AUD$38.43; 95% CI 37.34–39.53) versus GP visits (AUD$7.86; 95% CI 7.42–8.31), and higher SES was associated with greater OOP cost. Conclusion Patients with higher SES have relatively fewer GP visits and more specialist physician visits compared with patients with lower SES, suggesting individuals with lower SES may receive suboptimal specialist physician care. OOP costs may be a contributing factor.

Recommendations for the Use of Disease‐Modifying Antirheumatic Drugs in Pregnancy and Reproductive Health for Patients With Rheumatic Disease: A Scoping Review

Objective Autoimmune rheumatic diseases commonly affect individuals of childbearing age, with historically increased adverse pregnancy outcomes in this group. The advent of disease‐modifying antirheumatic drugs (DMARDs) has fostered more suitable conditions for pregnancy; however, this is accompanied by challenges in ensuring safe use in reproductive health. The aim of this review is to compare existing guideline recommendations for the use of DMARDs in pregnancy and reproductive health for patients with rheumatic disease. Methods A scoping review was performed with Medline and Embase, in addition to a hand search, to identify guidelines published since 2014 by academic societies in rheumatology that addressed the management of DMARDs in pregnancy in any of rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and systemic lupus erythematosus. Conventional synthetic DMARDs (csDMARDs) (methotrexate, sulfasalazine, leflunomide, and hydroxychloroquine), biologic DMARDs (bDMARDs) (adalimumab, etanercept, infliximab, golimumab, certolizumab, abatacept, tocilizumab, rituximab, and anakinra), and targeted synthetic DMARDs (tsDMARDs) (tofacitinib, baricitinib, and upadacitinib) were targeted. Two authors performed data extraction in duplicate (AC, AT). Results A total of 18 guidelines were included. Recommendations for DMARD use in preconception were present in 10 guidelines (56%), lactation in 12 guidelines (67%), and male fertility in 6 guidelines (33%). A total of 13 guidelines (72%) included recommendations for csDMARDs, 13 guidelines (72%) included recommendations for bDMARDs, and 5 guidelines (28%) included recommendations for tsDMARDs. There was moderate evidence supporting relatively uniform csDMARD recommendations, compared to minimal evidence for bDMARD and tsDMARD use with variable recommendations. Conclusion There is heterogeneity in the formulation of guidelines on the use of DMARDs in pregnancy. Recommendations for csDMARDs were similar between guidelines. There was significant variability in recommendations for bDMARD and tsDMARD use, reflecting current minimal literature in this area.

Development and Pilot Testing of a Patient‐Centered Reproductive Decision Aid for Pregnancy‐Capable People With Rheumatic Diseases

Prevalence of Frailty and Associated Factors in a US ‐Wide Cohort of Rheumatic Diseases

Objective We quantified the prevalence of self‐reported frailty and identified associated factors in a US‐wide cohort of people with rheumatic and musculoskeletal diseases (RMDs). Methods Frailty was measured using the FRAIL scale, a patient‐reported frailty instrument, in FORWARD, The US‐based National Databank for Rheumatic Diseases. Frailty prevalence was determined overall and by individual RMD, which included rheumatoid arthritis, connective tissue diseases (CTDs), osteoarthritis (OA), fibromyalgia, spondyloarthritis (SpA), and vasculitis. Multivariable logistic regression models evaluated the cross‐sectional associations between RMDs and frailty, as well as factors associated with frailty within each RMD. Results Among 4,345 individuals, 1,422 were frail (33%). Participants were on average 67.1 ± 11.6 years of age, 82% were female, and 89% self‐identified as White. Difficulty with ambulation was the most common frailty feature. With OA as referent, those with CTD had a higher odds of frailty (odds ratio [OR] 1.44, 95% confidence interval [CI] 1.01–2.04), and those with SpA had a lower odds (OR 0.45, 95% CI 0.31–0.67). Age, female sex, pain, disease severity, disease duration, and elevated body mass index categories were all associated with frailty. In the RMD‐stratified analyses, disease severity remained associated with frailty in all RMDs except vasculitis. Conclusion Frailty was present in 1 in 3 participants with RMDs, a higher prevalence than estimates from the general population, and primarily manifests as difficulty with mobility. Disease severity was consistently associated with an increased odds of frailty across RMDs. Future interventions to improve physical activity and prevent disease damage may improve frailty status in people with RMDs.

Agreement Between Self‐Reported Antirheumatic Medications and Pharmaceutical Claims in an Australian Inflammatory Arthritis Cohort

Objective To assess agreement between prescription claims data and self‐reported medication use via longitudinal questionnaires in the Australian Rheumatology Association Database inflammatory arthritis cohort and to identify predictors of discordant self‐reports. Methods Agreement was determined between longitudinal questionnaire self‐reports (2012–2023) of disease‐modifying antirheumatic drug (DMARD), glucocorticoid, anti‐inflammatory, and analgesic use and Australian reference standard prescription medication dispensing data (Pharmaceutical Benefits Scheme) using Cohen's kappa, sensitivity, positive predictive value (PPV), and negative predictive value (NPV). Analyses were repeated using four look‐back windows of dispensing data (1, 3, 6, and 12 months) before each questionnaire to characterize variations in agreement metrics at the individual medication level. Predictors of discordant self‐reports were explored using multivariable logistic regression. Results In our study population (N = 3,407, 67% female, 93.7% White, 64.4% with rheumatoid arthritis, 18.5% with psoriatic arthritis, 14.6% with ankylosing spondylitis, 2.6% with juvenile idiopathic arthritis), agreement with prescription claims data was substantial to high for DMARDs (κ 0.67–0.95, sensitivity 0.69–0.96, PPV 0.64–0.96, NPV 0.9–1), substantial for prescription‐only nonopioid analgesics and oral prednisolone/prednisone (κ 0.66–0.80, sensitivity 0.65–0.88, PPV 0.68–0.77, NPV 0.93–1), and moderate to substantial for prescription‐only opioid analgesics (κ 0.48–0.7, sensitivity 0.57–0.74, PPV 0.36–0.69, NPV 0.94–1). A 3‐month look‐back window optimized agreement for most medications, whereas 6‐ and 12‐month windows further improved agreement for specific drugs. No consistent predictors of discordant self‐reports were identified, though greater self‐rated disability severity and poorer overall health showed the most consistent associations with discordance. Conclusion Agreement between self‐reported and pharmaceutical claims data was moderate to high. Poorer overall health and disability may impact accuracy of medication self‐report.