Andrea Benedetti

Objective: Health literacy reflects the ability to find, understand, evaluate, and use information to make health-related decisions. We evaluated sociodemographic and disease factors associated with health literacy among people with SSc. Methods: Participants with SSc in the Scleroderma Patient-centred Intervention Network Cohort completed the Health Literacy Scale19 − 12 Item Questionnaire from February to November 2025. Multivariable linear regression was used to assess associations of sociodemographic and disease characteristics with health literacy. Results: The 1019 participants were mainly female (N = 898, 88%) and White (N = 850, 84%). Mean (SD) years of education was 15.5 (3.9). Most had limited cutaneous SSc (N = 669, 66%). Mean health literacy total score was 69.7; 438 (43%) participants had excellent or sufficient and 581 (57%) had problematic or inadequate health literacy. Education (1.63 points per 5 years, 95% CI 0.25–3.01) was significantly associated with higher health literacy scores. Compared with the United States, participants from Canada (−4.98 points, 95% CI −7.99 to −1.97), the United Kingdom (−7.79 points, 95% CI −12.03 to −3.55), France (−6.05 points, 95% CI −8.84 to −3.27), and Australia, Mexico or Spain (−7.02 points, 95% CI −12.39 to −1.66) had significantly lower health literacy scores. Age, gender, race or ethnicity, marital status, time since first non-Raynaud symptom onset and disease subtype were not associated with health literacy. Conclusion: The association between health literacy and education was small. Differences between countries may reflect self-evaluation tendencies. More work is needed to better understand health literacy measurement.

BACKGROUND Cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) are leading causes of death in lung cancer screening (LCS) populations but remain underdiagnosed and undertreated. Low-dose computed tomography (LDCT) for lung cancer screening can identify untreated COPD and CVD. Treating these comorbidities may increase the value of screening programs. OBJECTIVE to determine whether a dual-target intervention directed to the participants and their primary care providers (PCP) improves guideline-recommended pharmacotherapy for CVD and COPD. METHODS Quebec Lung Cancer Screening Plus (QLC Plus) is a 12-month, open-label, randomized controlled trial with 2 arms (CVD and COPD) embedded within the Quebec LCS program. Adults aged 55–74 years in the Quebec Lung Cancer Screening Program are eligible if they have coronary artery calcification without lipid-lowering therapy and/or symptomatic COPD (radiographic emphysema with modified Medical Research Council dyspnea score ≥1 and/or COPD Assessment Test score ≥10) without long-acting bronchodilator therapy. Patients with suspected lung cancer are excluded. The one-time multimodal intervention combines patient activation materials with clinician decision support delivered electronically and by mail to participants, family doctors, and pharmacists. Controls receive usual care (LDCT report alone). Primary outcomes are initiation and adherence to guideline-recommended pharmacotherapy within 12 months post-intervention: statin for the CVD arm and long-acting inhaler for the COPD arm. A total of 330 participants will be enrolled, 180 participants for the CVD arm and 150 participants for the COPD arm. Randomization will be stratified by access to a family doctor at baseline. Participants are followed up electronically at 3, 6, and 12 months. RESULTS Analyses will follow the intention-to-treat principle. Between-groups difference in primary outcomes will be examined with absolute risk difference (ARD), 95%CI, and number needed to treat (NNT). Generalized linear mixed models (GLMM) will compare the initiation of guideline-recommended pharmacotherapies between intervention and control groups. Subgroup analyses will examine outcomes by arm, sex, access to a family doctor, and baseline COPD treatment. Findings will be disseminated through conference presentations and peer-reviewed publications in 2026-2027. Timeline: Participant recruitment began in April 2023 and ended in December 2024. Prospective follow-up ended in December 2025. Extraction of primary outcomes ended in May 2026 with results expected in 2026. CONCLUSIONS QLC plus dual-target intervention by activating patients and cueing clinicians to address untreated CVD and symptomatic COPD may improve guideline-concordant pharmacotherapy and extend the clinical benefit of lung cancer screening beyond nodule detection. CLINICALTRIAL ClinicalTrials.gov: NCT05444062

Introduction: Lung cancer screening (LCS) with low-dose computed tomography (LDCT) is a unique opportunity to improve diagnosis and treatment of chronic obstructive pulmonary disease (COPD) in high-risk individuals. Gender differences have been reported in the management of COPD, though inconsistently. We examined the factors associated with pharmacological treatment of COPD among LCS participants with radiologic visual emphysema and the gender-differences in treatment and symptoms of COPD. Methods: Participants were recruited from the Quebec LCS program (smokers or ex-smokers aged 55–74 years with a PLCOm2012 ≥2%) between April 2023 and July 2024. An LCS cohort was constituted from LCS participants with any level of visual emphysema on their LDCT scans and defined as having probable COPD. Primary outcome was pharmacological treatment for probable COPD defined as self-reported use of long-acting bronchodilators. Participants were screened for respiratory symptoms with the modified Medical Research Council (mMRC) and the COPD Assessment Test (CAT) scales. Probable symptomatic COPD was defined as visual emphysema on LDCT scan with mMRC score ≥1 and/or CAT score ≥10. Logistic regression was used to identify factors associated with the likelihood of pharmacological treatment for probable COPD, including gender, sociodemographic variables, radiologic emphysema severity, smoking, and body mass index. Gender-based differences in pharmacotherapy and symptoms were further examined using stratified analyses in males and females. Results: Among 1,026 participants undergoing LCS, 801 (78%) had visual emphysema of any level on LDCT, with 75% (603/801) of these lacking pharmacological treatment for probable COPD. Males were more likely to lack pharmacological treatment compared to females (58% vs. 42%). In multivariable analysis, the factors associated with treatment for probable COPD were female gender (OR 1.58; 95% CI: 1.11–2.24) and moderate-to-severe emphysema (OR 2.36; 95% CI: 1.64–3.41). Among participants screened for respiratory symptoms (397/603), 56% (221/397) were symptomatic (mean CAT score = 12.6 and mMRC score = 0.91). Females (111/174; 64%) reported more symptoms than males (110/223; 49%), particularly for minimal-to-mild emphysema: mean CAT = 10.3 and mMRC = 0.62 vs. mean CAT = 8.2 and mMRC = 0.41, respectively. Conclusion: The lack of pharmacological treatment was frequent among LCS participants with symptomatic radiologic emphysema. The lack of treatment was associated with male gender and a lesser degree of radiologic emphysema. Females reported more symptoms for milder emphysema. Integrating respiratory diagnosis within LCS programs is an important opportunity to leverage the LDCT results and raise clinical suspicion of individuals with COPD. Raising awareness on the gender differences in pharmacological treatments is essential to close the treatment gap in COPD.

Participants who continue across the full duration of longitudinal studies often differ from those lost to attrition, defined as discontinuing participation for any reason, and some participants may sporadically miss assessments. Complex participation patterns, such as in multicenter chronic disease cohorts, have not been studied. We aimed to implement an approach to identify participation subgroups and factors associated with these. We applied our approach in the Scleroderma Patient-centered Intervention Network Cohort, a multicenter, longitudinal systemic sclerosis cohort, because it is an example of an open-ended cohort with no planned end date and complex participation patterns. We used group-based trajectory modeling to identify participation subgroups and multinomial logistic regression to identify predictors of subgroup membership. Data were obtained for 2883 participants from 54 sites in 7 countries. We identified 5 participation subgroups: Ongoing Participation (29%), Immediate Attrition (29%), Mid-Term Attrition (19%), Long-Term Attrition (12%), and Ongoing Sporadic (11%) participation. Older age and sites outside the United States were associated with lower odds of belonging to all subgroups other than Ongoing Participation. Compared to Ongoing Participation, several sociodemographic variables were associated with higher odds of being in the Immediate Attrition group. Our method can be applied to other cohorts with complex participation patterns.

Background: Most trials in long COVID rehabilitation included only previously hospitalized patients and omitted outcome measures such as mobility, an important outcome for assessing life impact. Primary objective: to investigate whether an 8-week tele-rehabilitation program for individuals with long COVID improves functional mobility compared to usual care. Methods and Findings: Randomized controlled trial involving individuals with long COVID and persistent symptoms of reduced mobility, muscle weakness, dyspnea, or fatigue. Participants were randomized to either an individualized 8-week tele-rehabilitation program plus usual care or usual care. In both groups, usual care was supplemented with generic guidance on physical activity and symptom management. Primary outcome: Activity Measure for Post-Acute Care (AM-PAC) mobility. Secondary outcomes: dyspnea, fatigue, quality of life, physical function, mental health, acceptability, and adverse events. 132 participants were randomized (65 intervention; 67 control; 48±11.8 years; 75% female), with 78% not previously hospitalized. Adherence was high (96%), though 39% of intervention participants were unable to progress their exercises. No significant between-group differences were found in AM-PAC mobility (mean difference (MD): 0.61; 95% CI −0.91 to 2.13). The intervention group showed greater improvements in EQ-5D-5L pain (MD: −0.36; 95% CI −0.70 to −0.03), health status (MD: 7.74; 95% CI 1.05 to 14.43), fatigue (MD: −0.90; 95% CI −1.78 to −0.02), and dyspnea (MD: 1.24; 95% CI 0.10 to 2.37). No serious adverse events occurred. Conclusions: In the context of limited evidence around exercise in non-hospitalized individuals with long COVID, our study offers important insights into feasibility, safety and clinical relevance.

KEY POINTS: Question: Did changes in mental health symptoms from pre-COVID-19 to during the pandemic differ by sex or gender? Findings: In this systematic review and meta-analysis study of findings from 27 unique cohorts, changes from before to during the COVID-19 pandemic in mental health symptoms, including general mental health, anxiety, depression, and stress, were not statistically significantly different by sex or gender. Meaning: There were not likely substantial sex and gender differences in mental health symptom changes during the COVID-19 pandemic. Importance: Concerns remain about whether COVID-19 affected mental health differently across sex or gender groups. We previously reported that changes in general mental health and anxiety symptoms, but not depression or stress, worsened more for females or women than males or men, but that was based on 12 studies published up to August 2021. Objective: To investigate the sex or gender differences in mental health symptoms before and during the COVID-19 pandemic with updated evidence. Data Sources: MEDLINE, PsycINFO, CINAHL, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang, medRxiv, Open Science Framework Preprints searched to August 31, 2023. Study Selection: Eligible studies included change data for general mental health, anxiety symptoms, depression symptoms, or stress from pre-to during COVID-19 by sex or gender. Two independent reviewers reviewed citations for eligibility. Data Extraction and Synthesis: Standardized mean differences (SMDs) were extracted for changes of continuous outcomes and proportions for dichotomous outcomes. Two independent reviewers completed data extraction and risk of bias assessment with an adapted Joanna Briggs Institute Checklist for Prevalence Studies. Data were pooled by random-effects models. Main Outcomes and Measures: Difference in change of SMDs and proportions between sex or gender groups pre-COVID-19 to COVID-19. Results: We included data from 27 unique cohorts (N = 102 to 18,127). Change differences by sex or gender were minimal and not statistically significant: general mental health (SMD change _women-men = 0.01, 95% confidence interval [CI]:-0.07 to 0.10; proportion change _women-men = −0.03, 95% CI: −0.08 to 0.03), anxiety (SMD change _women-men = 0.09, 95% CI −0.04 to 0.22; proportion change _women-men = −0.05, 95% CI: −0.20 to 0.11), depression (SMD change _women-men = 0.10, 95% CI: −0.00 to 0.20; proportion change _women-men = −0.13, 95% CI: −0.81 to 0.55), and stress (SMD change _women-men = −0.08, 95% CI −0.16 to 0.01, proportion change _women-men = 0.04, 95% CI −0.10 to 0.17). No studies reported eligible mental health outcomes for gender minorities. Conclusion and Relevance: We found no significant sex or gender differences in mental health changes. Future research should report outcomes for gender minority groups, even if small numbers, to support evidence synthesis. Registration: PROSPERO (CRD42020179703)

Introduction Tuberculosis (TB) is a major global cause of morbidity and mortality. Emerging evidence in high-burden settings suggests significant long-term sequelae among people surviving TB; however, evidence from high-income, low-TB burden settings like Canada is lacking. In a person with TB infection, provision of TB preventive treatment (TPT) can prevent TB disease and its sequelae, but remains underused. We propose the Functional Outcomes, Lung health and Livelihood Outcomes among people With Tuberculosis study, a multicentre, prospective cohort study in Canada to help improve our understanding of the impacts of TPT and TB disease on individuals. Methods and analysis This is a prospective cohort study taking place in Montreal and Vancouver, Canada. We aim to recruit and retain at least 120 people with microbiologically confirmed TB disease, 340 people treated for TB infection and 120 without TB disease or infection who will be considered our unexposed group. All participants must be ≥6 years of age. Participants with TB disease or infection will be recruited within 2 weeks of treatment initiation. We will follow-up unexposed participants and participants with TB disease for 24 months, and participants with TB infection for 12 months. Throughout follow-up, participants will complete assessments measuring lung health and function, quality of life, disability, dyspnoea, psychological distress, as well as changes in employment and direct and indirect costs incurred because of treatment. Among participants with TB disease, our primary outcome is the difference in quality-adjusted life years between participants with TB disease and those unexposed at 24 months. For participants with TB infection, our primary outcome is the identification of non-patient characteristics (eg, patient cost, quality of life) associated with participant decision to discontinue treatment. Patient partners have contributed to the design of the study and will be involved with the study through to its dissemination. Ethics and dissemination This study has been approved by institutional ethics review boards at The Research Institute of the McGill University Health Centre (2025–10344) and The University of British Columbia (H24-02071). All participants will provide informed consent (and assent, if required) prior to participating in the study. We will disseminate study results to participants, national and international organisations, and through open-access peer-reviewed academic journals and conferences.

Objective: We (1) compared anxiety symptom levels in a multinational SSc cohort to a general population normative sample and (2) evaluated sociodemographic, lifestyle and SSc disease factors associated with symptoms. Methods: Scleroderma Patient-centered Intervention Network Cohort participants completed the Patient-Reported Outcomes Measurement Information System (PROMIS) Version 2 4a Anxiety domain upon enrolment. PROMIS domain scores use T-scores (mean = 50, S.D. = 10) calibrated to a United States normative sample. We compared T-scores to the PROMIS United States normative sample and, in SSc, assessed associations of sociodemographic, lifestyle and physician-reported disease-related variables with multivariable linear regression. Results: Among 2463 participants with SSc, mean anxiety symptom T-score (52.6, S.D. = 10.0, 95% CI 52.2, 53.0) was ∼1/3 S.D. higher than the United States general population mean of 50 (S.D. = 10), though within normal limits. Higher T-scores were associated with younger age (1.07 T-score points per 10 years, 95% CI 0.74, 1.40), female sex (1.81, 95% CI 0.63, 3.00), non-married status (0.99, 95% CI 0.14, 1.84), race or ethnicity other than White (1.79, 95% CI 0.72, 2.85), living in Canada (1.70, 95% CI 0.61, 2.79), the United Kingdom (1.53, 95% CI 0.06, 2.99) or France (2.01, 95% CI 0.98, 3.03) (vs the United States), higher BMI (0.11, 95% CI 0.03, 0.17), less time since non-Raynaud’s symptom onset (0.82 per 10 years, 95% CI 0.40, 1.30), gastrointestinal involvement (2.70, 95% CI 1.52, 3.88), moderate small joint contractures (1.24, 95% CI 0.10, 2.38), the absence of interstitial lung disease (0.93, 95% CI −1.79, −0.07) and Sjögren disease (1.67, 95% CI 0.17, 3.17). Interstitial lung disease was not statistically significant when accounting for an interaction with country. Anxiety was also associated with pruritus and pain intensity in a sensitivity analysis that included variables with possible bi-directional pathways with anxiety. Conclusion: Anxiety symptoms were somewhat elevated among individuals with SSc and associated with multiple sociodemographic and disease factors.