Publications by authors named "Ann E Clarke"

177 Publications

The value of hackathons in integrated knowledge translation (iKT) research: Waterlupus.

Health Res Policy Syst 2021 Nov 24;19(1):138. Epub 2021 Nov 24.

Division of Rheumatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Background: Despite a growing movement toward a knowledge-user-driven research process, our understanding of the generation, implementation and evaluation of specific approaches in the integrated knowledge translation (iKT) toolbox that aim to engage health and healthcare knowledge users is limited. Health hackathons offer an innovative approach with potential to generate direct and indirect health-related outcomes benefitting participants, knowledge users and the broader population. In May 2019, our research team hosted Waterlupus, a health hackathon to improve the economic lives of individuals with systemic lupus erythematosus (SLE) in Canada. Waterlupus was held with a multi-stakeholder group of 50 participants that included advocacy organization representatives, policy-makers, researchers, physicians, individuals with lived experience and students. While the hackathon generated viable solutions with the potential to positively impact the lives of individuals with SLE, understanding how participants perceived the hackathon as an iKT tool is critical in the planning and implementation of future iKT research.

Methods: Semi-structured in-depth telephone interviews were conducted with Waterlupus participants (n = 13) between August and November 2019 to (1) explore participant experiences of the hackathon; (2) investigate participant-identified hackathon outcomes; and (3) elicit recommendations for future iKT research using health hackathons.

Results: Participants provided feedback on the format and organization of Waterlupus, and identified direct and indirect outcomes to knowledge users, students and researchers beyond the innovations generated at the event. While the majority (n = 11) had never participated in a hackathon prior to Waterlupus, all 13 stated they would participate in future hackathons. Positive outcomes identified include connecting with students and other SLE stakeholders, the formation of professional and support networks, increased awareness of SLE, as well as the innovations generated. Participant recommendations for future health hackathons include the addition of stakeholders from industry or technology, and the need for clear and designated roles for stakeholders to ensure efficient use of resources.

Conclusions: This work contributes to a limited literature regarding the use of health hackathons for social innovation, and offers knowledge-user suggestions relevant to the implementation of future iKT events, and hackathons specifically.
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http://dx.doi.org/10.1186/s12961-021-00785-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611392PMC
November 2021

Elevated cow's milk-specific IgE levels prior to oral immunotherapy decreases the likelihood of reaching the maintenance dose.

J Allergy Clin Immunol Pract 2021 Nov 15. Epub 2021 Nov 15.

Division of Allergy and Clinical Immunology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, QC, Canada.

Background: Food desensitization via oral immunotherapy (OIT) is gaining higher acceptance in clinical practice. Due to adverse reactions, the duration of the build-up phase until a maintenance dose is achieved may be prolonged, and in a minority of cases, OIT is stopped.

Objective: We aimed to assess factors associated with the probability of reaching the maintenance dose in cow's milk (CM) OIT.

Methods: Data was collected from patients undergoing CM OIT at the Montreal Children's Hospital, BC Children's Hospital, and Hospital for Sick Children. We compared uni- and multivariable Cox regressions to evaluate sociodemographic factors, co-morbidities, clinical characteristics and biomarkers at study entry associated with the likelihood of reaching a maintenance dose of 200 mL of CM.

Results: Among 69 children who reached 4 mL of milk, the median age was 12 years (Interquartile Range [IQR] 9-15) and 59% were male. The median duration of build-up phase from 4 mL to 200 mL was 24.0 weeks (IQR 17.7-33.4). After adjusting for age and sex, higher baseline levels of specific IgE (sIgE) antibodies for α-lactalbumin (ALA, hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.67-0.95), β-lactoglobulin (BLG, HR 0.86, 95% CI 0.76-0.98), casein (HR 0.82, 95% CI 0.72-0.94), and total CM (HR 0.79, 95% CI 0.65-0.97), were associated with a decreased probability of reaching maintenance. Additionally, for every increase of 10 mL CM tolerated at entry challenge, the probability of reaching maintenance increased by 10%.

Conclusion: The data suggest that higher levels of CM-sIgE decreased the likelihood of reaching maintenance, while an increased cumulative CM dose at entry challenge increased the likelihood. Assessing these factors prior to therapy may assist in predicting the success of CM OIT.
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http://dx.doi.org/10.1016/j.jaip.2021.11.005DOI Listing
November 2021

Risk of malignancy in patients with systemic lupus erythematosus: Systematic review and meta-analysis.

Semin Arthritis Rheum 2021 Sep 30;51(6):1230-1241. Epub 2021 Sep 30.

Formerly of BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA.

Background: Malignancy is a potential comorbidity in patients with systemic lupus erythematosus (SLE). However, risk by malignancy type remains to be fully elucidated. We evaluated the risk of malignancy type in SLE patients in a systematic review and meta-analysis.

Methods: MEDLINE and EMBASE were searched from inception to July 2018 to identify observational studies that evaluated malignancy risk in adult SLE patients compared with the general population. Random-effects models were used to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Heterogeneity was quantified using the I test.

Findings: Forty-one studies reporting on 40 malignancies (one overall, 39 site-specific) were included in the meta-analysis. The pooled RR for all malignancies from 3694 events across 80 833 patients was 1.18 (95% CI: 1.00-1.38). The risk of 24 site-specific malignancies (62%) was increased in SLE patients. For malignancies with ≥6 studies, non-Hodgkin lymphoma and Hodgkin lymphoma risk was increased >3-fold; myeloma and liver >2-fold; cervical, lung, bladder, and thyroid ≥1.5-fold; stomach and brain >1.3-fold. The risk of four malignancies (breast, uterine, melanoma, prostate) was decreased, whereas risk of 11 other malignancies did not differ between SLE patients and the general population. Heterogeneity ranged between 0% and 96%, and 63% were non-significant.

Interpretation: The risk of overall and some site-specific malignancies is increased in SLE compared with the general population. However, the risk for some site-specific malignancies is decreased or did not differ. Further examination of risk profiles and SLE patient phenotypes may support guidelines aimed at reducing malignancy risk.

Funding: AstraZeneca.

Systematic Review Registration: PROSPERO number: CRD42018110433.
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http://dx.doi.org/10.1016/j.semarthrit.2021.09.009DOI Listing
September 2021

Canadian workplace experiences of systemic lupus erythematosus (SLE).

Lupus Sci Med 2021 09;8(1)

Geography and Environmental Management, University of Waterloo, Waterloo, Ontario, Canada.

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http://dx.doi.org/10.1136/lupus-2021-000536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458365PMC
September 2021

Publisher Correction: Global epidemiology of systemic lupus erythematosus.

Nat Rev Rheumatol 2021 Oct;17(10):642

Department of Medicine, Rheumatology Division, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

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http://dx.doi.org/10.1038/s41584-021-00690-3DOI Listing
October 2021

Global epidemiology of systemic lupus erythematosus.

Nat Rev Rheumatol 2021 09 3;17(9):515-532. Epub 2021 Aug 3.

Department of Medicine, Rheumatology Division, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Systemic lupus erythematosus (SLE) is an autoimmune disease with protean manifestations that predominantly affects young women. Certain ethnic groups are more vulnerable than others to developing SLE and experience increased morbidity and mortality. Reports of the global incidence and prevalence of SLE vary widely, owing to inherent variation in population demographics, environmental exposures and socioeconomic factors. Differences in study design and case definitions also contribute to inconsistent reporting. Very little is known about the incidence of SLE in Africa and Australasia. Identifying and remediating such gaps in epidemiology is critical to understanding the global burden of SLE and improving patient outcomes. Mortality from SLE is still two to three times higher than that of the general population. Internationally, the frequent causes of death for patients with SLE include infection and cardiovascular disease. Even without new therapies, mortality can potentially be mitigated with enhanced quality of care. This Review focuses primarily on the past 5 years of global epidemiological studies and discusses the regional incidence and prevalence of SLE and top causes of mortality.
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http://dx.doi.org/10.1038/s41584-021-00668-1DOI Listing
September 2021

Demographic characteristics associated with food allergy in a Nationwide Canadian Study.

Allergy Asthma Clin Immunol 2021 Jul 17;17(1):72. Epub 2021 Jul 17.

Division of Allergy and Clinical Immunology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, QC, Canada.

Introduction: We conducted a nationwide Canadian telephone survey on food allergy prevalence between February 2016 and January 2017, targeting vulnerable populations (New, Indigenous, and lower-income Canadians).

Objective: To examine the independent effect of demographic characteristics on food allergy.

Methods: Canadian households with vulnerable populations were targeted using Canadian Census data and the household respondent reported whether each household member had a perceived (self-reported) or probable (self-report of a convincing history or physician diagnosis) food allergy. The association between perceived and probable food allergy and demographic characteristics was assessed through weighted multivariable random effects logistic regressions.

Results: Children, females, Canadian-born participants, adults with post-secondary education, and those residing in smaller households were more likely to report perceived or probable food allergy. Although immigrant parents self-reported less food allergy, Canadian-born children of Southeast/East Asian immigrant versus other immigrant or Canadian-born parents reported more food allergy.

Conclusion: We have demonstrated clear associations between demographic characteristics and food allergy, which may provide important clues to the environmental determinants of food allergy.
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http://dx.doi.org/10.1186/s13223-021-00572-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285771PMC
July 2021

Neuropsychiatric Events in Systemic Lupus Erythematosus: Predictors of Occurrence and Resolution in a Longitudinal Analysis of an International Inception Cohort.

Arthritis Rheumatol 2021 May 27. Epub 2021 May 27.

Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Objective: To determine predictors of change in neuropsychiatric (NP) event status in a large, prospective, international inception cohort of patients with systemic lupus erythematosus (SLE).

Methods: Upon enrollment and annually thereafter, NP events attributed to SLE and non-SLE causes and physician-determined resolution were documented. Factors potentially associated with the onset and resolution of NP events were determined by time-to-event analysis using a multistate modeling structure.

Results: NP events occurred in 955 (52.3%) of 1,827 patients, and 593 (31.0%) of 1,910 unique events were attributed to SLE. For SLE-associated NP (SLE NP) events, multivariate analysis revealed a positive association with male sex (P = 0.028), concurrent non-SLE NP events excluding headache (P < 0.001), active SLE (P = 0.012), and glucocorticoid use (P = 0.008). There was a negative association with Asian race (P = 0.002), postsecondary education (P = 0.001), and treatment with immunosuppressive drugs (P = 0.019) or antimalarial drugs (P = 0.056). For non-SLE NP events excluding headache, there was a positive association with concurrent SLE NP events (P < 0.001) and a negative association with African race (P = 0.012) and Asian race (P < 0.001). NP events attributed to SLE had a higher resolution rate than non-SLE NP events, with the exception of headache, which had comparable resolution rates. For SLE NP events, multivariate analysis revealed that resolution was more common in patients of Asian race (P = 0.006) and for central/focal NP events (P < 0.001). For non-SLE NP events, resolution was more common in patients of African race (P = 0.017) and less common in patients who were older at SLE diagnosis (P < 0.001).

Conclusion: In a large and long-term study of the occurrence and resolution of NP events in SLE, we identified subgroups with better and worse prognosis. The course of NP events differs greatly depending on their nature and attribution.
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http://dx.doi.org/10.1002/art.41876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626529PMC
May 2021

Anti-beta 2 glycoprotein I IgA in the SLICC classification criteria dataset.

Lupus 2021 Jul 6;30(8):1283-1288. Epub 2021 May 6.

Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, Netherlands.

Objective: Anti-beta 2 glycoprotein I IgA is a common isotype of anti-beta 2 glycoprotein I in SLE. Anti-beta 2 glycoprotein I was not included in the American College of Rheumatology (ACR) SLE classification criteria, but was included in the Systemic Lupus International Collaborating Clinics (SLICC) criteria. We aimed to evaluate the prevalence of anti-beta 2-glycoprotein I IgA in SLE versus other rheumatic diseases. In addition, we examined the association between anti-beta 2 glycoprotein I IgA and disease manifestations in SLE.

Methods: The dataset consisted of 1384 patients, 657 with a consensus physician diagnosis of SLE and 727 controls with other rheumatic diseases. Anti-beta 2 glycoprotein I isotypes were measured by ELISA. Patients with a consensus diagnosis of SLE were compared to controls with respect to presence of anti-beta 2 glycoprotein I. Among patients with SLE, we assessed the association between anti-beta 2 glycoprotein I IgA and clinical manifestations.

Results: The prevalence of anti-beta 2 glycoprotein I IgA was 14% in SLE patients and 7% in rheumatic disease controls (odds ratio, OR 2.3, 95% CI: 1.6, 3.3). It was more common in SLE patients who were younger patients and of African descent (p = 0.019). Eleven percent of SLE patients had anti-beta 2 glycoprotein I IgA alone (no anti-beta 2 glycoprotein I IgG or IgM). There was a significant association between anti-beta 2 glycoprotein I IgA and anti-dsDNA (p = 0.001) and the other antiphospholipid antibodies (p = 0.0004). There was no significant correlation of anti-beta 2 glycoprotein I IgA with any of the other ACR or SLICC clinical criteria for SLE. Those with anti-beta 2 glycoprotein I IgA tended to have a history of thrombosis (12% vs 6%, p = 0.071), but the difference was not statistically significant.

Conclusion: We found the anti-beta 2 glycoprotein I IgA isotype to be more common in patients with SLE and in particular, with African descent. It could occur alone without other isotypes.
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http://dx.doi.org/10.1177/09612033211014248DOI Listing
July 2021

Author Correction: Evolving concepts in systemic lupus erythematosus damage assessment.

Nat Rev Rheumatol 2021 Jun;17(6):375

Manchester University Hospitals NHS Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester, UK.

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http://dx.doi.org/10.1038/s41584-021-00620-3DOI Listing
June 2021

Evolving concepts in systemic lupus erythematosus damage assessment.

Nat Rev Rheumatol 2021 06;17(6):307-308

Manchester University Hospitals NHS Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester, UK.

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http://dx.doi.org/10.1038/s41584-021-00611-4DOI Listing
June 2021

Fruit-Induced Anaphylaxis: Clinical Presentation and Management.

J Allergy Clin Immunol Pract 2021 07 13;9(7):2825-2830.e2. Epub 2021 Mar 13.

Division of Allergy and Clinical Immunology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, QC, Canada.

Background: Data are sparse regarding the clinical characteristics and management of fruit-induced anaphylaxis.

Objective: To assess clinical characteristics and management of patients with fruit-induced anaphylaxis and determine factors associated with severe reactions and epinephrine use.

Methods: Over 9 years, children and adults presenting with anaphylaxis to seven emergency departments in four Canadian provinces and patients requiring emergency medical services in Outaouais, Quebec were recruited as part of the Cross-Canada Anaphylaxis Registry. A standardized form documenting symptoms, triggers, and management was collected. Multivariate logistic regression was used to identify factors associated with severe reactions and epinephrine treatment in the pre-hospital setting.

Results: We recruited 250 patients with fruit-induced anaphylaxis, median age 10.2 years (interquartile range, 3.6-23.4 years); 48.8% were male. The most common fruit triggers were kiwi (15.6%), banana (10.8%), and mango (9.2%). Twenty-three patients reported having eczema (9.3%). Epinephrine use was low in both the pre-hospital setting and the emergency department (28.4% and 40.8%, respectively). Severe reactions to fruit were more likely to occur in spring and among those with eczema (adjusted odds ratio [aOR] = 1.12, 95% confidence interval [CI], 1.03-1.23; and 1.17, 95% CI, 1.03-1.34, respectively). Patients with moderate and severe reactions (aOR = 1.23; 95% CI, 1.06-1.43) and those with a known food allergy (aOR = 1.38; 95% CI, 1.24-1.54) were more likely to be treated with epinephrine in the pre-hospital setting.

Conclusions: Severe anaphylaxis to fruit is more frequent in spring. Cross-reactivity to pollens is a potential explanation that should be evaluated further.
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http://dx.doi.org/10.1016/j.jaip.2021.02.055DOI Listing
July 2021

Lower vitamin D is associated with metabolic syndrome and insulin resistance in systemic lupus: data from an international inception cohort.

Rheumatology (Oxford) 2021 Oct;60(10):4737-4747

Department of Rheumatology, Kantonsspital Schaffhausen, Schaffhausen, Schaffhausen, Switzerland.

Objectives: Vitamin D (25(OH)D) deficiency and metabolic syndrome (MetS) may both contribute to increased cardiovascular risk in SLE. We aimed to examine the association of demographic factors, SLE phenotype, therapy and vitamin D levels with MetS and insulin resistance.

Methods: The Systemic Lupus International Collaborating Clinics (SLICC) enrolled patients recently diagnosed with SLE (<15 months) from 33 centres across 11 countries from 2000. Clinical, laboratory and therapeutic data were collected. Vitamin D level was defined according to tertiles based on distribution across this cohort, which were set at T1 (10-36 nmol/l), T2 (37-60 nmol/l) and T3 (61-174 nmol/l). MetS was defined according to the 2009 consensus statement from the International Diabetes Federation. Insulin resistance was determined using the HOMA-IR model. Linear and logistic regressions were used to assess the association of variables with vitamin D levels.

Results: Of the 1847 patients, 1163 (63%) had vitamin D measured and 398 (34.2%) subjects were in the lowest 25(OH)D tertile. MetS was present in 286 of 860 (33%) patients whose status could be determined. Patients with lower 25(OH)D were more likely to have MetS and higher HOMA-IR. The MetS components, hypertension, hypertriglyceridemia and decreased high-density lipoprotein (HDL) were all significantly associated with lower 25(OH)D. Increased average glucocorticoid exposure was associated with higher insulin resistance.

Conclusions: MetS and insulin resistance are associated with lower vitamin D in patients with SLE. Further studies could determine whether vitamin D repletion confers better control of these cardiovascular risk factors and improve long-term outcomes in SLE.
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http://dx.doi.org/10.1093/rheumatology/keab090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487307PMC
October 2021

Do anti-DFS70 antibodies temper disease activity and progression in SLE?

Lupus 2021 04 2;30(5):852-853. Epub 2021 Feb 2.

Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

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http://dx.doi.org/10.1177/0961203321990439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020300PMC
April 2021

Myositis in systemic lupus erythematosus.

Lupus 2021 Apr 18;30(4):615-619. Epub 2021 Jan 18.

Department of Medicine, McGill University, Montreal, Canada.

Objectives: Myositis is an infrequent feature of SLE and may often be overlooked. We aimed to estimate the incidence of myositis in SLE, and to determine demographic and clinical factors associated with it.

Methods: Within our lupus cohort, we identified potential myositis cases using the SLICC Damage Index for muscle atrophy or weakness, the SLEDAI-2K item for myositis, and annually measured serum creatinine kinase. Cases were confirmed through chart review. We performed descriptive analyses of prevalent myositis cases as of January 2000. From that point onward, we studies patients without myositis to determine risk of incident myositis, using cohort analyses adjusted for demographic variables (age, sex, race/ethnicity).

Results: As of January 2000, there were 5 prevalent myositis cases in our SLE cohort. Among 560 SLE patients with a study visit from January 2000 onward, with no history of myositis at baseline, 5 new cases (4 females, 1 male) were identified over an average follow-up of 8.5 years (incidence 1.05 cases per 1000 person-years). There was a higher proportion of Caucasians in the non-myositis group versus myositis group, with a trend for fewer females in the myositis cases. Arthritis, Raynaud's phenomenon, and anti-Smith antibodies were common pre-existing features, occurring in all incident myositis cases. In Cox regression analyses adjusting for age, race/ethnicity and sex, non-Caucasian patients had a markedly increased risk of developing myositis.

Conclusion: We found a low incidence of myositis in our SLE cohort. A cluster of variables, particularly non-Caucasian race/ethnicity, arthritis, Raynaud's phenomenon, and anti-Smith antibodies were associated with risk of developing myositis in SLE. These variables may aid clinicians in identifying SLE patients at highest risk for this important complication.
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http://dx.doi.org/10.1177/0961203320988587DOI Listing
April 2021

Predictors of unsuccessful hydroxychloroquine tapering and discontinuation: Can we personalize decision-making in systemic lupus treatment?

Arthritis Care Res (Hoboken) 2020 Dec 26. Epub 2020 Dec 26.

Department of Medicine, Division of Rheumatology and Division of Clinical Epidemiology and Centre for Outcomes Research and Evaluation, Research Institute, McGill University Health Centre, Quebec, Canada.

Objective: Hydroxychloroquine (HCQ) is a key systemic lupus (SLE) drug, making concerns of drug shortages grave. We evaluated factors associated with poor outcomes after HCQ taper or discontinuation in SLE.

Methods: We studied five Canadian SLE cohorts between 1999-2019, following patients from date of HCQ tapering (cohort 1) or discontinuation (cohort 2). A composite outcome was defined as any of the following: need for therapy augmentation, increase (of at least 4 points) in SLEDAI-2K, or hospitalization for SLE. In each cohort, multivariable Cox regression was used to identify demographic and clinical factors associated with time to the earliest of these events. A third cohort remaining on HCQ was also studied, to assess if the same factors influenced the outcome even when HCQ dose was unchanged.

Results: The poor outcome rate, per 100 person-years, was 35.7 (95% CI 31.6, 40.3) in the HCQ taper cohort (N=398), 29.0 (95% CI 25.5, 33.0) in the discontinuation cohort (N=395), and 16.1 (95%CI 13.2, 19.6) in the maintenance cohort (N=395). In patients tapering HCQ, baseline prednisone use was independently associated with greater risk of poor outcomes. In the discontinuation cohort, risk of poor outcomes was greater for blacks and those diagnosed with SLE at age ≤25 years. Among those maintaining HCQ, baseline immunosuppressive use and First Nation ethnicity were associated with poor outcomes.

Conclusions: We identified demographic and clinical factors associated with poor outcomes after HCQ taper/discontinuation. This information is critical in the current setting of potential shortages, but long-term, this could inform personalized therapies.
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http://dx.doi.org/10.1002/acr.24548DOI Listing
December 2020

The Challenges of Perceived Self-Management in Lupus.

Arthritis Care Res (Hoboken) 2020 Dec 20. Epub 2020 Dec 20.

Jack Digital Productions, Inc, Montreal, Quebec and Toronto, Ontario, Canada.

Objective: Systemic lupus erythematosus is a chronic autoimmune disease with varied and unpredictable levels of disease activity. The ability to self-manage lupus is important in controlling disease activity. Our objective was to determine levels of patient activation toward self-management in lupus.

Methods: We used baseline results from the MyLupusGuide study that had recruited 541 lupus patients from ten centers. We used the Patient Activation Measure (PAM), a validated self-reported tool designed to measure activation towards self-management ability, as our primary variable and examined its association with demographic, disease-related, patient-provider communication and psychosocial variables captured in our study protocol. Univariable and multivariable linear regressions were performed using linear mixed models, with a random effect for centers.

Results: The average age was 50±14 years, 93% were female, 74% were Caucasian and the average disease duration was 17±12 years. The mean PAM score was 61.2±13.5 with 36% of participants scoring in the two lower levels, indicating low activation. Variables associated with low activation included being single, lower physical health status, lower self-reported disease activity, lower self-efficacy, use of more emotional coping and less distraction and instrumental coping strategies, and perceived lack of clarity in patient-doctor communication.

Conclusion: Low patient activation was observed in more than one third of lupus patients indicating a large proportion of patients perceived that they are lacking in lupus self-management skills. These results highlight a modifiable gap in perceived self-management ability among patients with lupus.
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http://dx.doi.org/10.1002/acr.24542DOI Listing
December 2020

Specific IgE antibody levels during and after food-induced anaphylaxis.

Clin Exp Allergy 2021 02 9;51(2):364-368. Epub 2020 Dec 9.

Division of Pediatric Allergy and Clinical Immunology, Department of Pediatrics, McGill University, Montreal, QC, Canada.

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http://dx.doi.org/10.1111/cea.13796DOI Listing
February 2021

Prediction of hospitalizations in systemic lupus erythematosus using the Systemic Lupus International Collaborating Clinics Frailty Index (SLICC-FI).

Arthritis Care Res (Hoboken) 2020 Nov 5. Epub 2020 Nov 5.

Emory University School of Medicine, Division of Rheumatology, Atlanta, Georgia, USA.

Objective: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) predicts mortality and damage accrual in SLE, but its association with hospitalizations has not been described. We estimated the association of baseline SLICC-FI values with future hospitalizations in the SLICC inception cohort.

Methods: Baseline SLICC-FI scores were calculated. The number and duration of inpatient hospitalizations during follow-up were recorded. Negative binomial regression was used to estimate the association between baseline SLICC-FI values and the rate of hospitalizations per patient-year of follow-up. Linear regression was used to estimate the association of baseline SLICC-FI scores with the proportion of follow-up time spent in hospital. Multivariable models were adjusted for relevant baseline characteristics.

Results: The 1549 SLE patients eligible for this analysis were mostly female (88.7%) with mean (SD) age 35.7 (13.3) years and median (IQR) disease duration 1.2 (0.9-1.5) years at baseline. Mean (SD) baseline SLICC-FI was 0.17 (0.08). During mean (SD) follow-up of 7.2 (3.7) years, 614 patients (39.6%) experienced 1570 hospitalizations. Higher baseline SLICC-FI values (per 0.05 increment) were associated with more frequent hospitalizations during follow-up (Incidence Rate Ratio 1.21; 95%CI 1.13-1.30), adjusting for baseline age, sex, corticosteroid use, immunosuppressive use, ethnicity/location, SLE disease activity index 2000 (SLEDAI-2K), SLICC/ACR damage index (SDI), and disease duration. Among patients with ≥1 hospitalization, higher baseline SLICC-FI values predicted a greater proportion of follow-up time spent hospitalized (Relative Rate 1.09; 95%CI 1.02-1.16).

Conclusion: The SLICC-FI predicts future hospitalizations among incident SLE patients, further supporting the SLICC-FI as a valid health measure in SLE.
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http://dx.doi.org/10.1002/acr.24504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096857PMC
November 2020

Relationship Between Genetic Risk and Age of Diagnosis in Systemic Lupus Erythematosus.

J Rheumatol 2021 06 15;48(6):852-858. Epub 2020 Oct 15.

E. Rich, MD, Division of Rheumatology, Centre Hospitalier de l'Université de Montreal, Department of Medicine, University of Montreal School of Medicine, Montreal, Quebec.

Objective: Specific risk alleles for childhood-onset systemic lupus erythematosus SLE (cSLE) vs adult-onset SLE (aSLE) patients have not been identified. The aims of this study were to determine if there is an association (1) between non-HLA-related genetic risk score (GRS) and age of SLE diagnosis, and (2) between HLA-related GRS and age of SLE diagnosis.

Methods: Genomic DNA was obtained from 2001 multiethnic patients and genotyped using the Immunochip. Following quality control, genetic risk counting (GRCS), weighted (GRWS), standardized counting (GRSCS), and standardized weighted (GRSWS) scores were calculated based on independent single-nucleotide polymorphisms from validated SLE loci. Scores were analyzed in a regression model and adjusted by sex and ancestral population.

Results: The analyzed cohort consisted of 1540 patients: 1351 females and 189 males (675 cSLE and 865 aSLE). There were significant negative associations between all non-HLA GRS and age of SLE diagnosis: = 0.011 and r = 0.175 for GRWS; = 0.008 and r = 0.178 for GRSCS; = 0.002 and r = 0.176 for GRSWS (higher GRS correlated with lower age of diagnosis.) All HLA GRS showed significant positive associations with age of diagnosis: = 0.049 and r = 0.176 for GRCS; = 0.022 and r = 0.176 for GRWS; = 0.022 and r = 0.176 for GRSCS; = 0.011 and r = 0.177 for GRSWS (higher GRS correlated with higher age of diagnosis).

Conclusion: Our data suggest that there is a linear relationship between genetic risk and age of SLE diagnosis and that HLA and non-HLA GRS are associated with age of diagnosis in opposite directions.
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http://dx.doi.org/10.3899/jrheum.200002DOI Listing
June 2021

Evaluation of the Economic Benefit of Earlier Systemic Lupus Erythematosus (SLE) Diagnosis Using a Multivariate Assay Panel (MAP).

ACR Open Rheumatol 2020 Nov 12;2(11):629-639. Epub 2020 Oct 12.

Exagen Inc, Vista, California.

Objective: Diagnosis of systemic lupus erythematosus (SLE) made by standard diagnostic laboratory tests (SDLTs) has sensitivity and specificity of 83% and 76%, respectively. A multivariate assay panel (MAP) combining complement C4d activation products on erythrocytes and B cells with SDLTs yields a sensitivity and specificity of 80% and 86%, respectively, presumably enabling earlier SLE diagnosis at lower severity, with associated lower health care costs compared with SDLT diagnoses. We compared the payer budget impact of diagnosing SLE using MAP (incremental cost of $108) versus SDLTs.

Methods: We modeled a health plan of 1 million enrollees. SLE diagnosis among suspected patients was 9.2%. The MAP arm assumed 80%/20% of patients were tested with MAP/SDLTs, versus 100% tested with SDLTs in the SDLT arm. Prediagnosis direct costs were estimated from claims data, and postdiagnosis costs were obtained from the literature. Based on improved MAP performance, the assumed hazard ratio for diagnosis rate compared with SDLTs was 1.74 (71%, 87%, 90%, and 91% of patients who develop SLE are diagnosed in years 1 to 4 compared with 53%, 75%, 84%, and 88% of patients diagnosed with SDLTs).

Results: Total 4-year pre- and postdiagnosis direct costs for patients with suspected SLE tested with MAP were $59 183 666 compared with $61 174 818 tested by SDLTs, with lower costs in the MAP arm due primarily to prediagnosis savings related to reduced hospital admissions.

Conclusion: Incorporating MAP into SLE diagnosis results in estimated 4-year direct cost savings of $1 991 152 ($0.04 per member per month). By facilitating earlier diagnosis of SLE, MAP may enhance patient outcomes.
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http://dx.doi.org/10.1002/acr2.11177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672303PMC
November 2020

Risk of peanut- and tree-nut-induced anaphylaxis during Halloween, Easter and other cultural holidays in Canadian children.

CMAJ 2020 Sep;192(38):E1084-E1092

Division of Allergy and Clinical Immunology (Leung, Gabrielli, Ben-Shoshan), Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montréal, Que.; Division of Rheumatology (Clarke, Shand), Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alta.; Department of Emergency Medicine (Morris), Hôpital Sacré-Coeur; Division of Pediatric Emergency Medicine (Gravel), Department of Pediatrics, Centre hospitalier universitaire Sainte-Justine, Montréal, Que.; Division of Pediatric Emergency Medicine (Lim), Department of Pediatrics, Children's Hospital at London Health Sciences Centre, London, Ont.; Divisions of Allergy and Immunology (Chan) and Emergency Medicine (Goldman, Enarson), Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC; Department of Pediatrics (O'Keefe), Faculty of Medicine, Memorial University, St. John's, NL; Food Allergy Canada (Gerdts), Toronto, Ont.; Division of Clinical Immunology & Allergy (Chu), Department of Medicine, and Department of Health Research Methods, Evidence, and Impact (Chu), McMaster University, Hamilton, Ont.; Division of Immunology and Allergy (Upton), Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ont.; Centre for Outcomes Research and Evaluation (Zhang), Research Institute of McGill University Health Centre, Montréal, Que.

Background: It is not established whether the risk of anaphylaxis induced by peanuts or tree nuts in children increases at specific times of the year. We aimed to evaluate the risk of peanut-and tree-nut-induced anaphylaxis during certain cultural holidays in Canadian children.

Methods: We collected data on confirmed pediatric cases of anaphylaxis presenting to emergency departments in 4 Canadian provinces as part of the Cross-Canada Anaphylaxis Registry. We assessed the mean number of cases per day and incidence rate ratio (IRR) of anaphylaxis induced by unknown nuts, peanuts and tree nuts presenting during each of 6 holidays (Halloween, Christmas, Easter, Diwali, Chinese New Year and Eid al-Adha) versus the rest of the year. We estimated IRRs and 95% confidence intervals (CIs) using Poisson regression.

Results: Data were collected for 1390 pediatric cases of anaphylaxis between 2011 and 2020. Their median age was 5.4 years, and 864 (62.2%) of the children were boys. During Halloween and Easter, there were higher rates of anaphylaxis to unknown nuts (IRR 1.66, 95% CI 1.13-2.43 and IRR 1.71, 95% CI 1.21-2.42, respectively) and peanuts (IRR 1.86, 95% CI 1.12-3.11 and IRR 1.57, 95% CI 0.94-2.63, respectively) compared to the rest of the year. No increased risk of peanut- or tree-nut-induced anaphylaxis was observed during Christmas, Diwali, Chinese New Year or Eid al-Adha. Anaphylaxis induced by unknown nuts, peanuts and tree nuts was more likely in children aged 6 years or older than in younger children.

Interpretation: We found an increased risk of anaphylaxis induced by unknown nuts and peanuts during Halloween and Easter among Canadian children. Educational tools are needed to increase awareness and vigilance in order to decrease the risk of anaphylaxis induced by peanuts and tree nuts in children during these holidays.
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http://dx.doi.org/10.1503/cmaj.200034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532006PMC
September 2020

Cancer Risk in a Large Inception Systemic Lupus Erythematosus Cohort: Effects of Demographic Characteristics, Smoking, and Medications.

Arthritis Care Res (Hoboken) 2020 Aug 19. Epub 2020 Aug 19.

Fossvogur Landspitali University Hospital, Reykjavik, Iceland.

Objective: To assess cancer risk factors in incident systemic lupus erythematosus (SLE).

Methods: Clinical variables and cancer outcomes were assessed annually among incident SLE patients. Multivariate hazard regression models (overall risk and most common cancers) included demographic characteristics and time-dependent medications (corticosteroids, antimalarial drugs, immunosuppressants), smoking, and the adjusted mean Systemic Lupus Erythematosus Disease Activity Index 2000 score.

Results: Among 1,668 patients (average 9 years follow-up), 65 cancers occurred: 15 breast, 10 nonmelanoma skin, 7 lung, 6 hematologic, 6 prostate, 5 melanoma, 3 cervical, 3 renal, 2 each gastric, head and neck, and thyroid, and 1 each rectal, sarcoma, thymoma, and uterine cancers. Half of the cancers (including all lung cancers) occurred in past/current smokers, versus one-third of patients without cancer. Multivariate analyses indicated that overall cancer risk was related primarily to male sex and older age at SLE diagnosis. In addition, smoking was associated with lung cancer. For breast cancer risk, age was positively associated and antimalarial drugs were negatively associated. Antimalarial drugs and higher disease activity were also negatively associated with nonmelanoma skin cancer risk, whereas age and cyclophosphamide were positively associated. Disease activity was associated positively with hematologic and negatively with nonmelanoma skin cancer risk.

Conclusion: Smoking is a key modifiable risk factor, especially for lung cancer, in SLE. Immunosuppressive medications were not clearly associated with higher risk except for cyclophosphamide and nonmelanoma skin cancer. Antimalarials were negatively associated with breast cancer and nonmelanoma skin cancer risk. SLE activity was associated positively with hematologic cancer and negatively with nonmelanoma skin cancer. Since the absolute number of cancers was small, additional follow-up will help consolidate these findings.
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http://dx.doi.org/10.1002/acr.24425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892637PMC
August 2020

Hacking systemic lupus erythematosus (SLE): outcomes of the Waterlupus hackathon.

Health Promot Chronic Dis Prev Can 2020 Aug;40(7-8):235-244

Department of Geography and Environmental Management, University of Waterloo, Waterloo, Ontario, Canada.

Introduction: There is a growing literature demonstrating the benefits of engaging knowledge-users throughout the research process. We engaged a multi-stakeholder team to undertake a hackathon as part of an integrated knowledge translation (iKT) process to develop nonpharmacological interventions to enhance the economic lives of people with systemic lupus erythematosus (SLE). The aims of this research were to (1) increase understanding of the economic challenges of living with SLE through stakeholder engagement at a research hackathon; (2) investigate possible interventions to improve the economic lives of individuals affected by SLE in Canada; and (3) document the outcomes of the Waterlupus hackathon.

Methods: Waterlupus was held at the University of Waterloo in May 2019, attended by lupus advocacy organization representatives, researchers, physicians, individuals with lived experience and students. We conducted participant observation with participants' understanding and consent; notes from the hackathon were qualitatively analyzed to document hackathon outcomes.

Results: At the conclusion of the 28-hour hackathon event, five teams pitched nonpharmacological interventions to address the economic challenges of living with SLE. The winning team's pitch focussed on increasing accessibility of affordable sun-protective clothing. Other Waterlupus outcomes include increased awareness of SLE among participants, and professional and informal networking opportunities.

Conclusion: This paper contributes to a limited literature on health hackathons. The successful outcomes of Waterlupus emphasize the value of hackathons as an iKT tool. Research about how knowledge-users perceive hackathons is an important next step.
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http://dx.doi.org/10.24095/hpcdp.40.7/8.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450907PMC
August 2020

Cancer and Systemic Lupus Erythematosus.

Rheum Dis Clin North Am 2020 Aug 10;46(3):533-550. Epub 2020 Jun 10.

Department of Medicine, McGill University, 1001 Decarie Boulevard, Suite D05-2212, Montreal, Quebec H4A 3J1, Canada; Division of Clinical Epidemiology, Research Institute of McGill University Health Centre, 5252 de Maisonneuve West, 3rd Floor, Montreal, Quebec H4A 3S5, Canada. Electronic address:

Systemic lupus erythematosus is associated with a small overall increased cancer risk compared with the general population. This risk includes a 4-fold increased risk of non-Hodgkin lymphoma, but a decreased risk of other cancers (such as breast cancer). The pathophysiology underlying the increased risk of hematologic cancer is not fully understood, but many potential mechanisms have been proposed, including dysfunction of the tumor necrosis factor and other pathways. A decreased risk of breast, ovarian, and endometrial cancer might be driven by hormonal factors or lupus-related antibodies, but these links have not been proved.
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http://dx.doi.org/10.1016/j.rdc.2020.05.005DOI Listing
August 2020

The economic burden of systemic lupus erythematosus in commercially- and medicaid-insured populations in the United States.

Semin Arthritis Rheum 2020 08 23;50(4):759-768. Epub 2020 May 23.

Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Objective: To estimate the economic burden of systematic lupus erythematous (SLE), stratified by disease severity, in commercially- and Medicaid-insured US populations.

Methods: Adults (≥18 years) with SLE treated with antimalarials, selected biologics, immunosuppressants, and systemic glucocorticoids (2010-2014) were identified within the commercial and Medicaid insurance IBM MarketScan® databases (index date = first SLE medication claim). Both cohorts were stratified into mild (receiving antimalarial or glucocorticoid monotherapy ≤5 mg/day) versus moderate/severe SLE (receiving glucocorticoids >5 mg/day, biologic, immunosuppressant, or combination therapy) during a 6-month exposure period. All-cause healthcare utilization and costs were evaluated during the 12 months following the exposure period.

Results: Among 8231 commercially-insured patients, 32.6% had mild and 67.4% had moderate/severe SLE by our definition. Among 802 Medicaid-insured patients, 25.2% had mild and 74.8% had moderate/severe SLE. Adjusted mean total healthcare costs, excluding pharmacy, for moderate/severe SLE patients were higher than for mild SLE patients in the commercially-insured ($39,021 versus $23,519; p < 0.0001) and Medicaid-insured populations ($56,050 versus $44,932; p = 0.06). In both SLE severity populations total unadjusted costs were significantly higher among Medicaid-insured than commercially-insured patients.

Conclusion: Commercially-insured patients with treatment suggesting moderate/severe SLE incurred significantly higher adjusted mean healthcare costs, excluding pharmacy, compared with mild SLE patients. While not reaching statistical significance, moderate/severe Medicaid-insured patients had higher costs then mild SLE patients. Total unadjusted healthcare costs were significantly higher among Medicaid-insured than commercially-insured patients. These differential costs are important to consider and monitor when implementing interventions to improve health and reduce healthcare spending for SLE.
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http://dx.doi.org/10.1016/j.semarthrit.2020.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857313PMC
August 2020

Systemic lupus erythematosus and risk of infection.

Expert Rev Clin Immunol 2020 05 1;16(5):527-538. Epub 2020 Jun 1.

Division of Rheumatology, University of Calgary , Calgary, Alberta, Canada.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects almost every organ system and it is treated with immunomodulation and immunosuppression. SLE patients have an intrinsically dysfunctional immune system which is exacerbated by disease activity and leaves them vulnerable to infection. Treatment with immunosuppression increases susceptibility to infection, while hydroxychloroquine use decreases this risk. Infectious diseases are a leading cause of hospitalization and death.

Areas Covered: This narrative review provides an overview of recent epidemiology and predictors of infections in SLE, delineates the risk of infection by therapeutic agent, and provides suggestions for risk mitigation. Articles were selected from Pubmed searches conducted between September 2019 and January 2020.

Expert Opinion: Despite the large burden of infection, effective and safe preventative care such as universal hydroxychloroquine use and vaccination are underutilized. Future efforts should be directed to quality improvement, glucocorticoid reduction, and validation of risk indices that identify patients at the highest risk of infection.
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http://dx.doi.org/10.1080/1744666X.2020.1763793DOI Listing
May 2020

Comparison of the 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology Systemic Lupus Erythematosus Classification Criteria With Two Sets of Earlier Systemic Lupus Erythematosus Classification Criteria.

Arthritis Care Res (Hoboken) 2021 09 14;73(9):1231-1235. Epub 2021 Jul 14.

Kantonsspital, Schaffhausen, Switzerland.

Objective: The Systemic Lupus International Collaborating Clinics (SLICC) 2012 systemic lupus erythematosus (SLE) classification criteria and the revised American College of Rheumatology (ACR) 1997 criteria are list based, counting each SLE manifestation equally. We derived a classification rule based on giving variable weights to the SLICC criteria and compared its performance to the revised ACR 1997, the unweighted SLICC 2012, and the newly reported European Alliance of Associations for Rheumatology (EULAR)/ACR 2019 criteria sets.

Methods: The physician-rated patient scenarios used to develop the SLICC 2012 classification criteria were reemployed to devise a new weighted classification rule using multiple linear regression. The performance of the rule was evaluated on an independent set of expert-diagnosed patient scenarios and compared to the performance of the previously reported classification rules.

Results: The weighted SLICC criteria and the EULAR/ACR 2019 criteria had less sensitivity but better specificity compared to the list-based revised ACR 1997 and SLICC 2012 classification criteria. There were no statistically significant differences between any pair of rules with respect to overall agreement with the physician diagnosis.

Conclusion: The 2 new weighted classification rules did not perform better than the existing list-based rules in terms of overall agreement on a data set originally generated to assess the SLICC criteria. Given the added complexity of summing weights, researchers may prefer the unweighted SLICC criteria. However, the performance of a classification rule will always depend on the populations from which the cases and non-cases are derived and whether the goal is to prioritize sensitivity or specificity.
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http://dx.doi.org/10.1002/acr.24263DOI Listing
September 2021

Anaphylaxis as a presenting symptom of food allergy in children with no known food allergy.

J Allergy Clin Immunol Pract 2020 09 26;8(8):2811-2813.e2. Epub 2020 Apr 26.

Division of Allergy and Clinical Immunology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, QC, Canada.

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http://dx.doi.org/10.1016/j.jaip.2020.04.033DOI Listing
September 2020
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