Association of stigma, diabetes distress and self-efficacy with quality of life in adolescents with type 1 diabetes preparing to transition to adult care.

AIMS: In type 1 diabetes (T1D), psychosocial factors may impact quality of life (QOL) and clinical outcomes, but remain understudied, particularly during late adolescence. Our aim was to determine whether stigma, diabetes distress and self-efficacy are associated with QOL in adolescents with T1D as they are preparing to transition to adult care. METHODS: We conducted a cross-sectional study of adolescents (ages 16-17 years) with T1D participating in the Group Education Trial to Improve Transition (GET-IT) in Montreal, Canada. Participants completed validated questionnaires on stigma using the Barriers to Diabetes Adherence (BDA) stigma subscale, self-efficacy (Self-Efficacy for Diabetes Self-Management Measure [SEDM], score 1-10), diabetes distress (Diabetes Distress Scale for Adults with type 1 diabetes) and QOL (Pediatric Quality of Life Inventory [PedsQL] 4.0 Generic Core Scale and PedsQL 3.2 Diabetes Module). We examined associations of stigma, diabetes distress and self-efficacy with QOL using multivariate linear regression models adjusted for sex, diabetes duration, socioeconomic status and HbA1c. RESULTS: Of 128 adolescents with T1D, 76 (59%) self-reported having the diabetes-related stigma and 29 (22.7%) reported experiencing diabetes distress. Those with stigma had lower diabetes-specific and general QOL scores compared with those without stigma, and stigma and diabetes distress were both associated with lower diabetes-specific QOL and lower general QOL. Self-efficacy was associated with higher diabetes-specific and general QOL. CONCLUSIONS: Stigma and diabetes distress are associated with lower QOL, whereas self-efficacy is associated with higher QOL in adolescents with T1D preparing to transfer to adult care.

Diabetes duration, perceived comfort with self-management and glycaemic control in adolescents with type 1 diabetes: A cross-sectional study.

AIMS: Evidence is lacking on whether diabetes duration is associated with type 1 diabetes (T1D) self-management during late adolescence before transfer from paediatric to adult care. We examined associations of diabetes duration with dimensions of perceived comfort with diabetes self-management (self-efficacy, transition readiness, diabetes distress) and glycaemic control in late adolescence. METHODS: Using a cross-sectional design, we conducted a secondary analysis of baseline data of adolescents (ages 16-17 years) with T1D followed at paediatric diabetes academic hospitals in Montreal and enrolled in the Group Education Trial to Improve Transition (GET-IT-T1D). Participants completed validated questionnaires on self-efficacy (Self-Efficacy for Diabetes Self-Management Measure [SEDM], score 1 to 10), diabetes distress and transition readiness, as well as a haemoglobin (HbA1c) capillary blood test. Our primary outcome was self-efficacy. We examined associations of diabetes duration with self-efficacy, diabetes distress, transition readiness and HbA1c using linear and logistic regression models adjusted for sex, socioeconomic status, insulin pump use, glucose sensor use and psychiatric comorbidity. RESULTS: Of 203 adolescents with T1D, mean diabetes duration (SD) was 7.57 (4.44) years. Mean SEDM score was 6.83 (SD 1.62). Diabetes duration was not associated with self-efficacy, diabetes distress or transition readiness. Each additional year of diabetes duration was associated with 0.11% (95% CI, 0.05 to 0.16) higher HbA1c. CONCLUSIONS: Although diabetes duration is not associated with dimensions of perceived comfort with diabetes self-management, adolescents with longer diabetes duration are at risk for higher HbA1c and may need additional support to improve glycaemic control before transition to adult care.

Clinical Accuracy of Serum Neurofilament Light to Differentiate Frontotemporal Dementia from Primary Psychiatric Disorders is Age-Dependent.

BACKGROUND: Symptoms of behavioral variant frontotemporal dementia (bvFTD) overlap with primary psychiatric disorders (PPD) making diagnosis challenging. Serum neurofilament light (sNfL) is a candidate biomarker to distinguish bvFTD from PPD, but large-scale studies in PPD are lacking. OBJECTIVE: Determine factors that influence sNfL from a large database of PPD patients, and test its diagnostic accuracy. DESIGN, SETTINGS, SUBJECTS, MEASUREMENTS: Clinical data of people aged 40-81 were obtained from healthy subjects (n = 69), and patients with PPD (n = 848) or bvFTD (n = 82). sNfL was measured using Simoa technology on an HD-X instrument. Data were analyzed using general linear models, and Receiver Operating Characteristic (ROC) curve analyses to determine global and age-specific sNfL cutoffs to distinguish bvFTD from PPD, using the Youden Index. RESULTS: sNfL increased with age, while sex, BMI and diabetes status were modestly associated with sNfL. sNfL was slightly higher in PPD than healthy subjects (14.1 versus 11.7 pg/mL), when controlling for covariates. sNfL was markedly lower in PPD than bvFTD (14.1 versus 44.1 pg/mL). sNfL could differentiate PPD from bvFTD with an AUC = 0.868, but the effect was driven by the younger subjects between age 40-60 years at a cutoff of 16.0 pg/mL. No valid cutoff was detected over age 60, however, values of sNfL above 38.5 pg/mL, or below 13.9 pg/mL, provided 90% diagnostic certainty of bvFTD or PPD, respectively. CONCLUSION: PPD have mildly elevated sNfL compared to healthy subjects but much lower than bvFTD. Results support the use of sNfL as a biomarker to differentiate PPD from bvFTD at age 60 or below, but accuracy decreases in older ages.

Multimorbidity prevalence and health outcome prediction: assessing the impact of lookback periods, disease count, and definition criteria in health administrative data at the population-based level.

BACKGROUND: Health administrative databases play a crucial role in population-level multimorbidity surveillance. Determining the appropriate retrospective or lookback period (LP) for observing prevalent and newly diagnosed diseases in administrative data presents challenge in estimating multimorbidity prevalence and predicting health outcome. The aim of this population-based study was to assess the impact of LP on multimorbidity prevalence and health outcomes prediction across three multimorbidity definitions, three lists of diseases used for multimorbidity assessment, and six health outcomes. METHODS: We conducted a population-based study including all individuals ages > 65 years on April 1st, 2019, in Québec, Canada. We considered three lists of diseases labeled according to the number of chronic conditions it considered: (1) L60 included 60 chronic conditions from the International Classification of Diseases (ICD); (2) L20 included a core of 20 chronic conditions; and (3) L31 included 31 chronic conditions from the Charlson and Elixhauser indices. For each list, we: (1) measured multimorbidity prevalence for three multimorbidity definitions (at least two [MM2+], three [MM3+] or four (MM4+) chronic conditions); and (2) evaluated capacity (c-statistic) to predict 1-year outcomes (mortality, hospitalisation, polypharmacy, and general practitioner, specialist, or emergency department visits) using LPs ranging from 1 to 20 years. RESULTS: Increase in multimorbidity prevalence decelerated after 5-10 years (e.g., MM2+, L31: LP = 1y: 14%, LP = 10y: 58%, LP = 20y: 69%). Within the 5-10 years LP range, predictive performance was better for L20 than L60 (e.g., LP = 7y, mortality, MM3+: L20 [0.798;95%CI:0.797-0.800] vs. L60 [0.779; 95%CI:0.777-0.781]) and typically better for MM3 + and MM4 + definitions (e.g., LP = 7y, mortality, L60: MM4+ [0.788;95%CI:0.786-0.790] vs. MM2+ [0.768;95%CI:0.766-0.770]). CONCLUSIONS: In our databases, ten years of data was required for stable estimation of multimorbidity prevalence. Within that range, the L20 and multimorbidity definitions MM3 + or MM4 + reached maximal predictive performance.

Prevalence of omalizumab resistant chronic urticaria and real world effectiveness of dupilumab in omalizumab refractory chronic urticaria patients: a single center experience.

Chronic urticaria (CU) is characterized by wheals, angioedema, or both lasting for ≥ 6 weeks with chronic spontaneous urticaria (CSU) being the most common subtype. Omalizumab-resistant CSU cases represent an unmet clinical need. In this study, we aimed to assess the prevalence and predictors of omalizumab failure in a large cohort of CU patients and assess the effectiveness of dupilumab for omalizumab-recalcitrant CU. Of 338 CU patients, 33 received omalizumab. 69.7% (23 patients) were responders and 30.3% (10 patients) non-responders. Bivariate regression demonstrated that female sex (adjusted OR [aOR] = 1.53; 95%CI = 1.14-2.06), higher baseline UAS7 (aOR = 1.05; 95%CI = 1.01-1.09) and older age (controlling for sex) (aOR = 1.00; 95%CI = 1.00, 1.01) were associated with omalizumab failure. Of 10 omalizumab-refractory patients, three were well controlled with cyclosporine (all children), whereas the seven adults failed on average 5.6 ± 2.6 therapies including cyclosporine. All 7 achieved a complete response with dupilumab with time to response varying between 1 to 6 months. While our results suggest a favourable efficacy of dupilumab omalizumab-resistant cases, future confirmatory studies are required.

Cutaneous Melanoma Mortality-to-Incidence Ratio and Its Association With Socioeconomic and Healthcare Factors in Canada: A National Ecological Study.

INTRODUCTION: The mortality-to-incidence ratio (MIR) can be used to approximate healthcare inequities and is helpful to understand/compare cancer survival between geographic regions/jurisdictions. We investigated cutaneous melanoma (CM) outcomes through MIR analysis in Canadian jurisdictions and census divisions (CDs) between 1992 and 2016. METHODS: Data were obtained from the national databases from 1992 to 2016 for all Canadian jurisdictions, except Quebec. Age-standardized overall and median MIRs were calculated per province per year, while crude MIRs were calculated for CDs. Generalized linear regression models were conducted to study the effect of province and year on MIR, while a mixed effect regression model was used to determine how healthcare and socioeconomic factors affect MIR, while accounting for possible clustering effects (eg, year and province). RESULTS: We identified 106,015 CM cases and 20,570 CM deaths between 1992 and 2016. National MIR from 1992 to 2016 demonstrated a significant linear decrease (P value < .0001). The national median MIR was 15.4 (ie, 0.154 × 100), whereby Manitoba (19.9), Ontario (19.5), Saskatchewan (18.5), British Columbia (16.1), and Newfoundland and Labrador (15.9) demonstrated higher MIRs than the Canadian average. CDs with the highest MIRs were commonly identified in the southern regions of provinces. No healthcare or socioeconomic factors were found to be significantly associated with higher MIR at the provincial level. CONCLUSION: MIRs have decreased at the national and provincial levels in recent decades, which is reassuring. Higher MIRs were noted in select rural CDs and in the Canadian territories, reinforcing the importance of proper dermatological care in all parts of the country.

Profiles of quality of outpatient care among individuals with mental disorders based on survey and administrative data.

RATIONALE: Though it is crucial to contribute to patient recovery through access, diversity, continuity and regularity of outpatient care, still today most of these are deemed nonoptimal. Identifying patient profiles based on outpatient service use and quality of care indicators might help formulate more personalized interventions and reduce adverse outcomes. AIMS AND OBJECTIVES: This study aimed to identify profiles of individuals with mental disorders (MDs) patterned after their outpatient care use and quality of care received, and to link those profiles to individual characteristics and subsequent outcomes. METHODS: A cohort of 5669 individuals with MDs was considered based on data from the 2013-2014 and 2015-2016 Canadian Community Health Survey, which were linked to administrative data from the Quebec health insurance registry. Latent class analysis generated profiles based on service use over the 12 months preceding each respondent's interview, and comparative analyses were used to associate profiles with sociodemographic and clinical characteristics, and health outcomes over the three following months. RESULTS: Four profiles were identified. Profile 1 (P-1) was labelled 'Low service use'; P-2 'Moderate general practitioner (GP) care and continuity and regularity of care'; P-3 'High GP care, continuity and regularity of care, and low psychiatrist care'; and P-4 'High psychiatrist care and regularity of care, and low GP care'. Profiles 3 and 4 (~50% of the cohort) were provided with better care, but showed worse outcomes, mainly acute care use due to more complex conditions and unmet needs. Profiles 1 and 2 had better outcomes as they showed fewer risk factors such as being younger and having better social conditions. CONCLUSION: Intensity, diversity and regularity of care were higher in profiles with more complex MDs, chronic physical illnesses, and worse perceived health conditions. Adapting specific interventions for each profile, such as assertive community treatment or intensive case management for Profile 4, is recommended.

Patterns of Gestational Hypertension or Preeclampsia Across 2 Pregnancies in Relationship to Chronic Hypertension Development: A Retrospective Cohort Study.

BACKGROUND: Gestational hypertension (GHTN) and preeclampsia are established risk indicators for chronic hypertension. While recurrence is associated with a greater risk, it is unclear whether there are differences in risk when these gestational complications occur for the first time in an earlier pregnancy versus first occurrence in a subsequent one. We hypothesized that the absence of recurrence reflects a transition toward a lower hypertension risk trajectory, whereas a new occurrence in a later pregnancy indicates a transition toward elevated risk. METHODS AND RESULTS: We analyzed linked data in Quebec, Canada, from public health care insurance administrative databases and birth, stillbirth, and death registries. Our retrospective cohort study included mothers with 2 singleton deliveries between April 1990 and December 2012. The primary exposure was patterns of GHTN or preeclampsia across 2 pregnancies (GHTN/preeclampsia in neither, first only, second only, or both). The outcome was incident chronic hypertension. We performed an adjusted multivariable Cox regression analysis. Among 431 980 women with 2 singleton pregnancies, 27 755 developed hypertension during the follow-up period. Compared with those without GHTN/preeclampsia, those with GHTN/preeclampsia only in the first pregnancy had a 2.7-fold increase in hazards (95% CI, 2.6-2.8), those with GHTN/preeclampsia only in the second had a 4.9-fold increase (95% CI, 4.6-5.1), and those with GHTN/preeclampsia in both pregnancies experienced a 7.3-fold increase (95% CI, 6.9-7.6). Patterns and estimates were similar when we considered GHTN and preeclampsia separately. CONCLUSIONS: The magnitude of hypertension risk is associated with the number and sequence of GHTN/preeclampsia-affected pregnancies. Considering both allows more personalized risk estimates.

Incident Diabetes in Women With Patterns of Gestational Diabetes Occurrences Across 2 Pregnancies.

Importance: Gestational diabetes is a type 2 diabetes risk indicator, and recurrence further augments risk. In women with a single occurrence across 2 pregnancies, it is unclear whether first- vs second-pregnancy gestational diabetes differ in terms of risk. Objective: To compare the hazards of incident diabetes among those with gestational diabetes in the first, in the second, and in both pregnancies with women without gestational diabetes in either. Design, Setting, and Participants: This was a retrospective cohort study with cohort inception from April 1, 1990, to December 31, 2012. Follow-up was April 1, 1990, to April 1, 2019. Participants were mothers with 2 singleton deliveries between April 1, 1990, and December 31, 2012, without diabetes before or between pregnancies, who were listed in public health care insurance administrative databases and birth, stillbirth, and death registries in Quebec, Canada. Data were analyzed from July to December 2023. Exposure: Gestational diabetes occurrence(s) across 2 pregnancies. Main outcomes and measures: Incident diabetes from the second delivery until a third pregnancy, death, or the end of the follow-up period, whichever occurred first. Results: The 431 980 women with 2 singleton deliveries studied had a mean (SD) age of 30.1 (4.5) years at second delivery, with a mean (SD) of 2.8 (1.5) years elapsed between deliveries; 373 415 (86.4%) were of European background, and 78 770 (18.2%) were at the highest quintile of material deprivation. Overall, 10 920 women (2.5%) had gestational diabetes in their first pregnancy, 16 145 (3.7%) in their second, and 8255 (1.9%) in both (12 205 incident diabetes events; median [IQR] follow-up 11.5 [5.3-19.4] years). First pregnancy-only gestational diabetes increased hazards 4.35-fold (95% CI, 4.06-4.67), second pregnancy-only increased hazards 7.68-fold (95% CI, 7.31-8.07), and gestational diabetes in both pregnancies increased hazards 15.8-fold (95% CI, 15.0-16.6). Compared with first pregnancy-only gestational diabetes, second pregnancy-only gestational diabetes increased hazards by 76% (95% CI, 1.63-1.91), while gestational diabetes in both pregnancies increased it 3.63-fold (95% CI, 3.36-3.93). Conclusions and relevance: In this retrospective cohort study of nearly half a million women with 2 singleton pregnancies, both the number and ordinal pregnancy of any gestational diabetes occurrence increased diabetes risk. These considerations offer greater nuance than an ever or never gestational diabetes dichotomy.

Epidemiology of systemic sclerosis in Quebec, Canada: a population-based study.

Background: Systemic sclerosis (SSc) is a systemic life-threatening autoimmune rheumatic disease. We aimed to assess the incidence, prevalence, mortality and spatiotemporal trends of SSc in Quebec, Canada with stratification by sex and age. Methods: SSc cases were identified from Quebec populational databases from 1989 to 2019. Negative Binomial (NB) Generalized Linear Models were used for age-standardized incidence rates (ASIR) analyses and NB random walk for prevalence and mortality. A Poisson Besag-York-Mollié regression model was used for spatial analysis. Findings: 8180 incident SSc cases were identified between 1996 and 2019 with an average age of 57.3 ± 16.3 years. The overall ASIR was 4.14/100,000 person-years (95%, Confidence Interval (CI) 4.05-4.24) with a 4:1 female predominance. ASIR increased steadily over time with an Average Annual Percent Change (AAPC) of 3.94% (95% CI 3.49-4.38). While the highest incidence rates were in those aged 60-79 years old among females and >80 years old among males, the highest AAPC (∼10%) was seen in children. Standarized incidence ratios varied geographically between 0.52 to 1.64. The average prevalence was 28.96/100,000 persons (95% CI 28.72-29.20). The Standardized Mortality Ratio (SMR) decreased from 4.18 (95% CI 3.64-4.76) in 1996 to 2.69 (95% CI 2.42-2.98) in 2019. Females had a greater SMR until 2007 and males thereafter. The highest SMR was in children and young adults [31.2 (95% CI 8.39-79.82) in the 0-19-year age group]. Interpretation: We showed an increasing trend in SSc incidence and prevalence and a decline in SMR over a 25-year period in Quebec. An uneven geographic distribution of SSc incidence was demonstrated. Funding: National Scleroderma Foundation, Canadian Dermatology Foundation/Canadian Institutes of Health Research.

10-Year Multimorbidity Trajectories in Older People Have Limited Benefit in Predicting Short-Term Health Outcomes in Comparison to Standard Multimorbidity Thresholds: A Population-Based Study.

Purpose: To identify multimorbidity trajectories among older adults and to compare their health outcome predictive performance with that of cross-sectional multimorbidity thresholds (eg, ≥2 chronic conditions (CCs)). Patients and Methods: We performed a population-based longitudinal study with a random sample of 99,411 individuals aged >65 years on April 1, 2019. Using health administrative data, we calculated for each individual the yearly CCs number from 2010 to 2019 and constructed the trajectories with latent class growth analysis. We used logistic regression to determine the increase in predictive capacity (c-statistic) of multimorbidity trajectories and traditional cross-sectional indicators (≥2, ≥3, or ≥4 CCs, assessed in April 2019) over that of a baseline model (including age, sex, and deprivation). We predicted 1-year mortality, hospitalization, polypharmacy, and frequent general practitioner, specialist, or emergency department visits. Results: We identified eight multimorbidity trajectories, each representing between 3% and 25% of the population. These trajectories exhibited trends of increasing, stable, or decreasing number of CCs. When predicting mortality, the 95% CI for the increase in the c-statistic for multimorbidity trajectories [0.032-0.044] overlapped with that of the ≥3 indicator [0.037-0.050]. Similar results were observed when predicting other health outcomes and with other cross-sectional indicators. Conclusion: Multimorbidity trajectories displayed comparable health outcome predictive capacity to those of traditional cross-sectional multimorbidity indicators. Given its ease of calculation, continued use of traditional multimorbidity thresholds remains relevant for population-based multimorbidity surveillance and clinical practice.

ADHD medications use and risk of mortality and unintentional injuries: a population-based cohort study.

We assessed the association between the use of medications for attention-deficit/hyperactivity disorder (ADHD) and the risk of all-cause mortality and unintentional injuries leading to emergency department (ED) or hospital admission in individuals aged ≤24 years with ADHD. We conducted a population-based retrospective cohort study between 2000 and 2021 using Quebec health administrative data. Individuals were followed from the first ADHD diagnosis or ADHD medication claim until turning 25, death, or study end. Exposure was defined as mutually exclusive episodes of ADHD medication use and/or coverage under the public provincial drug plan (PDP): 1) covered and not treated with ADHD medication; 2) covered and treated with ADHD medication; and 3) not covered under the PDP. The risk of all-cause mortality and unintentional injuries associated with exposure episodes was estimated using multivariable survival analyses. The cohort included n = 217 192 individuals aged 1-24 years with a male to female ratio of close to 2:1. Compared to non-medication use, episodes of ADHD medication use, overall, were associated with reduced all-cause mortality (adjusted hazard ratio, aHR 0.61, 95% CI 0.48-0.76) and unintentional injury leading to ED (0.75, 0.74-0.77) or hospitalisation (0.71, 0.68-0.75). Episodes of stimulants were associated with a lower risk of all-cause mortality and reduced risk of unintentional injuries, while episodes with non-stimulants and with both stimulants and non-stimulants concomitantly were associated with reduced risk of unintentional injuries, but not of all-cause mortality. Although residual confounding cannot be excluded, stimulants may have a protective effect in terms of risk of all-cause mortality and both stimulants and non-stimulants for ADHD may reduce the risk of unintentional injuries. The findings of the current study should inform clinical decision making on the choice of starting a pharmacological treatment for ADHD, when a balance needs to be struck between expected benefits and possible risks.

COVID-19 Immunologic Antiviral Therapy With Omalizumab (CIAO)-a Randomized Controlled Clinical Trial.

Background: Omalizumab is an anti-immunoglobulin E monoclonal antibody used to treat moderate to severe chronic idiopathic urticaria, asthma, and nasal polyps. Recent research suggested that omalizumab may enhance the innate antiviral response and have anti-inflammatory properties. Objective: We aimed to investigate the efficacy and safety of omalizumab in adults hospitalized for coronavirus disease 2019 (COVID-19) pneumonia. Methods: This was a phase II randomized, double blind, placebo-controlled trial comparing omalizumab with placebo (in addition to standard of care) in hospitalized patients with COVID-19. The primary endpoint was the composite of mechanical ventilation and/or death at day 14. Secondary endpoints included all-cause mortality at day 28, time to clinical improvement, and duration of hospitalization. Results: Of 41 patients recruited, 40 were randomized (20 received the study drug and 20 placebo). The median age of the patients was 74 years and 55.0% were male. Omalizumab was associated with a 92.6% posterior probability of a reduction in mechanical ventilation and death on day 14 with an adjusted odds ratio of 0.11 (95% credible interval 0.002-2.05). Omalizumab was also associated with a 75.9% posterior probability of reduced all-cause mortality on day 28 with an adjusted odds ratio of 0.49 (95% credible interval, 0.06-3.90). No statistically significant differences were found for the time to clinical improvement and duration of hospitalization. Numerically fewer adverse events were reported in the omalizumab group and there were no drug-related serious adverse events. Conclusions: These results suggest that omalizumab could prove protective against death and mechanical ventilation in hospitalized patients with COVID-19. This study could also support the development of a phase III trial program investigating the antiviral and anti-inflammatory effect of omalizumab for severe respiratory viral illnesses requiring hospital admission. ClinicalTrials.gov ID: NCT04720612.

Tree-Based Machine Learning to Identify Predictors of Psoriasis Incidence at the Neighborhood Level: A Populational Study from Quebec, Canada.

BACKGROUND: Psoriasis is a major global health burden affecting ~ 60 million people worldwide. Existing studies on psoriasis focused on individual-level health behaviors (e.g. diet, alcohol consumption, smoking, exercise) and characteristics as drivers of psoriasis risk. However, it is increasingly recognized that health behavior arises in the context of larger social, cultural, economic and environmental determinants of health. We aimed to identify the top risk factors that significantly impact the incidence of psoriasis at the neighborhood level using populational data from the province of Quebec (Canada) and advanced tree-based machine learning (ML) techniques. METHODS: Adult psoriasis patients were identified using International Classification of Disease (ICD)-9/10 codes from Quebec (Canada) populational databases for years 1997-2015. Data on environmental and socioeconomic factors 1 year prior to psoriasis onset were obtained from the Canadian Urban Environment Health Consortium (CANUE) and Statistics Canada (StatCan) and were input as predictors into the gradient boosting ML. Model performance was evaluated using the area under the curve (AUC). Parsimonious models and partial dependence plots were determined to assess directionality of the relationship. RESULTS: The incidence of psoriasis varied geographically from 1.6 to 325.6/100,000 person-years in Quebec. The parsimonious model (top 9 predictors) had an AUC of 0.77 to predict high psoriasis incidence. Amongst top predictors, ultraviolet (UV) radiation, maximum daily temperature, proportion of females, soil moisture, urbanization, and distance to expressways had a negative association with psoriasis incidence. Nighttime light brightness had a positive association, whereas social and material deprivation indices suggested a higher psoriasis incidence in the middle socioeconomic class neighborhoods. CONCLUSION: This is the first study to highlight highly variable psoriasis incidence rates on a jurisdictional level and suggests that living environment, notably climate, vegetation, urbanization and neighborhood socioeconomic characteristics may have an association with psoriasis incidence.

Immunogenicity and safety of high-dose versus standard-dose inactivated influenza vaccine in rheumatoid arthritis patients: a randomised, double-blind, active-comparator trial.

BACKGROUND: Patients with rheumatoid arthritis have increased risk of seasonal influenza and influenza-related complications but have reduced vaccine immunogenicity. It is unknown whether patients with rheumatoid arthritis would benefit from more immunogenic vaccine formulations. This study investigated the immunogenicity and safety of a high-dose trivalent inactivated influenza vaccine (HD-TIV) in patients with rheumatoid arthritis compared to a standard-dose quadrivalent influenza vaccine (SD-QIV). METHODS: This study was a treatment-stratified, randomised, double-blind trial to compare the immunogenicity and safety of SD-QIV (15 µg of haemagglutinin [HA] per strain) versus HD-TIV (60 µg of HA per strain) in adults with rheumatoid arthritis who are positive for rheumatoid factor or anti-cyclic citrullinated peptide, or both, recruited during the 2016-17 and 2017-18 influenza seasons at three hospitals affiliated with McGill University (Montreal, QC, Canada). Participants had received treatment for rheumatoid arthritis with conventional or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) or biological DMARDs, or combinations of them, were still on treatment at the time of enrolment, and their treatment had not been modified during the 3 months before enrolment. They were stratified into one of three groups according to treatment. Patients who, at enrolment, were taking conventional or targeted synthetic DMARDs (methotrexate, hydroxychloroquine, and sulfasalazine) as monotherapy or in combination were stratified to group 1; those who were taking a biological DMARD (anti-tumour necrosis factor or anti-interleukin 6), with or without methotrexate, hydroxychloroquine, or sulfasalazine (or a combination thereof) were stratified to group 2; and those who were taking abatacept, tofacitinib, or rituximab, with or without methotrexate, hydroxychloroquine, or sulfasalazine (or a combination thereof) were stratified to group 3. Participants were randomly allocated (1:1) to receive the SD-QIV or HD-TIV vaccine. Randomisation was based on a computer-generated allocation sequence, and participants, investigators, and research nurses responsible for safety assessments were masked to vaccine assignment. The primary outcome was the seroconversion rate (as measured by haemagglutination-inhibition assay) per strain at day 28. Analysis was done in the modified intention-to-treat population, which included all randomly assigned participants for whom seroconversion status was available. Safety was assessed throughout the surveillance period (day 0-186). This trial is registered at ClinicalTrials.gov, number NCT02936180. FINDINGS: Between Oct 24, 2016, and Dec 6, 2017, 696 patients with rheumatoid arthritis were invited to participate in the study and 279 were randomly assigned and vaccinated (140 [50%] received SD-QIV and 139 [50%] HD-TIV). 136 patients who received SD-QIV and 138 who received HD-TIV were included in the modified intention-to-treat anaysis. Patients who received HD-TIV were more likely to seroconvert than those who received SD-QIV: the odds ratio was 2·99 (95% CI 1·46-6·11) for seroconversion to strain A/H3N2, 1·95 (1·19-3·22) for seroconversion to strain B/Bris, 3·21 (1·57-6·56) for seroconversion to strain A/H1N1 (in 2016-2017), and 2·44 (1·18-5·06) for seroconversion to strain A/H1N1 (in 2017-2018). Similar results were observed in patients from groups 1 and 2; the number of individuals in group 3 was insufficient to draw conclusions. Local and systemic adverse events were similar in both vaccine groups, no serious adverse events were reported between days 0 and 28 in any group, and neither vaccine increased rheumatoid arthritis disease activity. INTERPRETATION: Our data suggest that in patients with seropositive rheumatoid arthritis, HD-TIV is safe and more immunogenic than SD-QIV. These results are the first evidence to support the use of the HD-TIV in these patients. FUNDING: The Arthritis Society-Canada.

Treatment persistence in patients with rheumatoid arthritis and ankylosing spondylitis / Persistência do tratamento em pacientes com artrite reumatoide e espondilite anquilosante

ABSTRACT OBJECTIVE To evaluate treatment persistence in patients with rheumatoid arthritis and ankylosing spondylitis who started therapies with disease-modifying antirheumatic drugs (DMARD) and tumor necrosis factor blockers (anti-TNF drugs). METHODS This retrospective cohort study from July 2008 to September 2013 evaluated therapy persistence, which is defined as the period between the start of treatment until it is discontinued, allowing for an interval of up to 30 days between the prescription end and the start of the next prescription. Odds ratio (OR) with 95% confidence intervals (95%CI) were calculated by logistic regression models to estimate the patients' chances of persisting in their therapies after the first and after the two first years of follow-up. RESULTS The study included 11,642 patients with rheumatoid arthritis - 2,241 of these started on anti-TNF drugs (+/-DMARD) and 9,401 patients started on DMARD - and 1,251 patients with ankylosing spondylitis - 976 of them were started on anti-TNF drugs (+/-DMARD) and 275 were started on DMARD. In the first year of follow-up, 63.5% of the patients persisted in their therapies with anti-TNF drugs (+/-DMARD) and 54.1% remained using DMARD in the group with rheumatoid arthritis. In regards to ankylosing spondylitis, 79.0% of the subjects in anti-TNF (+/-DMARD) group and 41.1% of the subjects in the DMARD group persisted with their treatments. The OR (95%CI) for therapy persistence was 1.50 (1.34-1.67) for the anti-TNF (+/-DMARD) group as compared with the DMARD group in the first year for the patients with rheumatoid arthritis, and 2.33 (1.74-3.11) for the patients with ankylosing spondylitis. A similar trend was observed at the end of the second year. CONCLUSIONS A general trend of higher rates of therapy persistence with anti-TNF drugs (+/-DMARD) was observed as compared to DMARD in the study period. We observed higher persistence rates for anti-TNF drugs (+/-DMARD) in patients with ankylosing spondylitis as compared to rheumatoid arthritis; and a higher persistence for DMARD in patients with rheumatoid arthritis as compared to ankylosing spondylitis.

RESUMO OBJETIVO Avaliar a persistência do tratamento em pacientes com artrite reumatoide e espondilite anquilosante que iniciaram terapia com medicamentos modificadores do curso da doença (MMCD) e agentes bloqueadores do fator de necrose tumoral (anti-TNF). MÉTODOS Este estudo de coorte retrospectiva de julho de 2008 a setembro de 2013 avaliou a persistência na terapia, definida como o tempo do início até a descontinuação, permitindo-se um intervalo de até 30 dias entre o fim da prescrição e o início da prescrição seguinte. Odds ratio (OR) com intervalos de confiança de 95% (IC95%) foram calculados por meio de modelos de regressão logística para estimar a chance de apresentar persistência na terapia após o primeiro e os dois primeiros anos de seguimento. RESULTADOS Foram incluídos 11.642 pacientes com artrite reumatoide - 2.241 iniciaram uso de agentes anti-TNF (+/-MMCD) e 9.401 iniciaram MMCD - e 1.251 pacientes com espondilite anquilosante - 976 iniciaram uso de agentes anti-TNF (+/-MMCD) e 275 iniciaram MMCD. No primeiro ano de acompanhamento, 63,5% persistiram em terapia com anti-TNF (+/-MMCD) e 54,1% em uso de MMCD do grupo com artrite reumatoide. Em relação à espondilite anquilosante, 79,0% do grupo anti-TNF (+/-MMCD) e 41,1% do grupo MMCD persistiram no tratamento. O OR (IC95%) para persistência na terapia foi de 1,50 (1,34-1,67) para o grupo anti-TNF (+/-MMCD) comparado com MMCD no primeiro ano em pacientes com artrite reumatoide, e de 2,33 (1,74-3,11) em pacientes com espondilite anquilosante. Foi observada tendência semelhante ao final do segundo ano. CONCLUSÕES Observou-se uma tendência geral de taxas mais elevadas de persistência na terapia com anti-TNF (+/-MMCD) em relação a MMCD no período estudado. Foram observadas taxas de persistência mais elevadas para os usuários de anti-TNF (+/-MMCD) em pacientes com espondilite anquilosante em relação a artrite reumatoide, e maior persistência para MMCD em pacientes com artrite reumatoide em relação à espondilite anquilosante.