Health Care Utilization and Direct Costs Prior to Subspecialty Care in Children with Chronic Pain Compared with Other Chronic Childhood Diseases: A Cohort Study.

OBJECTIVES: To understand the burden associated with pediatric chronic pain (CP) on the health care system compared with other costly chronic diseases prior to subspecialty care. STUDY DESIGN: In this retrospective cohort study, we assessed all-cause health care utilization and direct health care costs associated with pediatric CP (n = 91) compared with juvenile arthritis (n = 135), inflammatory bowel disease (n = 90), type 1 diabetes (n = 475) or type 2 diabetes (n = 289), anxiety (n = 7193), and controls (n = 273) 2 and 5 years prior to patients entering subspecialty care in Manitoba, Canada. Linked data from physician encounters, emergency department visits, hospitalizations, and prescriptions were extracted from administrative databases. Differences in health care utilization and direct health care costs associated with CP vs the other conditions were tested using negative binomial and zero-inflated negative binomial regression models, respectively. RESULTS: After adjustment for age at diagnosis, sex, location of residence, and socioeconomic status, CP continued to be associated with the highest number of consulted physicians and subspecialists and the highest number of physician billings compared with all other conditions (P < .01, respectively). CP was significantly associated with higher physician costs than juvenile arthritis, inflammatory bowel disease, type 1 diabetes, type 2 diabetes, or controls (P < .01, respectively); anxiety was associated with the highest physician and prescription costs among all cohorts (P < .01, respectively). CONCLUSION: Compared with chronic inflammatory and endocrinologic conditions, pediatric CP and anxiety were associated with substantial burden on the health care system prior to subspecialty care, suggesting a need to assess gaps and resources in the management of CP and mental health conditions in the primary care setting.

A decade of progress in juvenile idiopathic athritis treatments and outcomes in Canada: results from ReACCh-Out and the CAPRI registry.

OBJECTIVE: To assess changes in juvenile idiopathic arthritis (JIA) treatments and outcomes in Canada, comparing a 2005-2010 and a 2017-2021 inception cohorts. METHODS: Patients enrolled within three months of diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) and the Canadian Alliance of Pediatric Rheumatology Investigators Registry (CAPRI) cohorts were included. Cumulative incidences of drug starts and outcome attainment within 70 weeks of diagnosis were compared with Kaplan Meier survival analysis and multivariable Cox regression. RESULTS: The 2005-2010 and 2017-2021 cohorts included 1128 and 721 patients, respectively. JIA category distribution and baseline clinical juvenile idiopathic arthritis disease activity (cJADAS10) scores at enrolment were comparable. By 70 weeks, 6% of patients (95% CI 5, 7) in the 2005-2010 and 26% (23, 30) in the 2017-2021 cohort had started a biologic DMARD (bDMARD), and 43% (40, 47) and 60% (56, 64) had started a conventional DMARD (cDMARD), respectively. Outcome attainment was 64% (61, 67) and 83% (80, 86) for Inactive disease (Wallace criteria), 69% (66, 72) and 84% (81, 87) for minimally active disease (cJADAS10 criteria), 57% (54, 61) and 63% (59, 68) for pain control (<1/10), and 52% (47, 56) and 54% (48, 60) for a good health-related quality of life. CONCLUSION: Although baseline disease characteristics were comparable in the 2005-2010 and 2017-2021 cohorts, cDMARD and bDMARD use increased with a concurrent increase in minimally active and inactive disease. Improvements in parent and patient reported outcomes were smaller than improvements in disease activity.

Framing Slogans for Responsible Gambling Campaigns: A Tale of Two Models.

This study investigates the persuasive mechanism of slogans employed in responsible gambling campaigns. We analyse slogans from official posters in the U.S., Singapore, and Macau, focusing on two domains. First, the Theory of Planned Behaviour is applied to examine the intention to gamble expressed in the slogans to reveal how gambling is positioned in social contexts. Second, two framing devices-i.e., conceptual metaphors and the frame of gains/losses-are examined to understand how these framing devices reinforce the persuasive message while interacting with each other. Two models of persuasion emerge from our data-one encouraged 'grounded games' for enjoyment, while the other discouraged gambling due to its potentially 'harmful' consequences. We advocate for a gestalt view on the theoretical constructs that contribute to the overall effectiveness of persuasive messaging. These constructs should be integrated into an analytical framework, with particular attention given to the framing effect of conceptual metaphors and the gain/loss frame, and their interplay.

Do Patterns of Early Disease Severity Predict Grade 12 Academic Achievement in Youths With Childhood-Onset Chronic Rheumatic Diseases?

OBJECTIVE: To test the association of early disease severity with grade 12 standards test performance in individuals with childhood-onset chronic rheumatic diseases (ChildCRDs), including juvenile arthritis and systemic autoimmune rheumatic diseases. METHODS: We used linked provincial administrative data to identify patients with ChildCRDs born between 1979 and 1998 in Manitoba, Canada. Primary outcomes were Language and Arts Achievement Index (LAI) scores and Math Achievement Index (MAI) scores from grade 12 standards test results as well as enrollment data. The secondary outcome was enrollment in grade 12 by 17 years of age. Latent class trajectory analysis identified disease severity groups using physician visits following diagnosis. Multivariable linear regression tested the association of disease severity groups with LAI and MAI scores, and logistic regression tested the association of disease severity with age-appropriate enrollment, after adjusting for sociodemographic factors and psychiatric morbidities. RESULTS: The study cohort included 541 patients, 70.1% of whom were female. A 3-class trajectory model provided the best fit; it classified 9.7% of patients as having severe disease, 54.5% as having moderate disease, and 35.8% as having mild disease. After covariate adjustment, severe disease was associated with poorer LAI and MAI scores but not with age-appropriate enrollment. CONCLUSION: Among patients with ChildCRDs, those with severe disease performed more poorly on grade 12 standards tests, independent of sociodemographic and psychiatric risk factors. Clinicians should work with educators and policy makers to advocate for supports to improve educational outcomes of patients with ChildCRDs.

Probability of Response in the First Sixteen Weeks After Starting Biologics: An Analysis of Juvenile Idiopathic Arthritis Biologics Trials.

OBJECTIVES: Most juvenile idiopathic arthritis (JIA) biologic disease-modifying antirheumatic drugs (bDMARDs) trials used an open-label run-in period followed by randomized medication withdrawal. We used data from the run-in period of 4 bDMARD trials to 1) delineate early response trajectory to bDMARDs and 2) identify predictors of early response. METHODS: Data from the first 16 weeks of 4 bDMARD trials were used. The primary outcome was the American College of Rheumatology (ACR) Pediatric 50 (Pedi 50) response criteria: clinically significant response defined as ACR Pedi 50 or greater. The secondary outcome was the clinical Juvenile Arthritis Disease Activity Score in 10 joints (cJADAS10) minimal disease activity state. Response transition rates and predictors were modeled using an inhomogeneous Markov multistate model. RESULTS: Five hundred thirty-two participants (70% receiving methotrexate, 41% prednisone) were included. By month 4, the probability of attaining ACR Pedi 50 or greater was 0.698. If ACR Pedi 50 or more was not achieved by month 1, the probability of achieving it by month 4 was 0.60. If ACR Pedi 50 or more was not achieved by month 3, the probability of achieving this by month 4 was 0.31. Age at diagnosis, disease duration, baseline rheumatoid factor, and active joint counts predicted ACR and cJADAS state transitions, adjusted for concomitant treatment. CONCLUSIONS: No response ACR Pedi 50 or more by month 1 after treatment was associated with a 0.60 probability of responding by month 4, but not responding by month 3 was associated with a 0.31 probability of response by month 4. Baseline disease duration, rheumatoid factor, and active joint counts predicted early treatment response (ACR and cJADAS10 states).

A Rare Case of Candida glabrata Cervical Spondylodiscitis.

Introduction: Invasive candidiasis can lead to numerous life-threatening sequelae. Candida glabrata is the second-most common causative species of invasive candidiasis. This species possesses a high risk for persistent infection and candidemia. An uncommon complication of invasive candidiasis is spondylodiscitis and can rarely affect the cervical spine. Case Presentation: The patient is a female in her late 50s with a complex medical history inclusive of chronic obstructive pulmonary disease, chronic pain, multiple abdominal surgeries, prolonged intensive care unit admission, and administration of total parenteral nutrition and broad-spectrum antibiotics who presented with complaints of worsening neck pain. She was last hospitalized 3 months prior and found to have C glabrata fungemia but was nonadherent to antifungal therapy.She was found to have advanced C5-6 spondylodiscitis and an epidural abscess. Her surgical cultures grew C glabrata. Despite surgical intervention and antimicrobial therapy, she clinically deteriorated and acquired septic shock with multiorgan failure. Conclusion: This is a rare case of cervical spondylodiscitis caused by a deep-seated C glabrata infection.

Latent classes of early response trajectories to biologics initiation in juvenile idiopathic arthritis: an analysis of four trials.

AIMS: 1) To delineate latent classes of treatment response to biologics in juvenile idiopathic arthritis (JIA) patients in the first 16 weeks after initiation. 2) To identify predictors of early disease response. METHODS: The study population was drawn from four biologics trials in polyarticular course JIA: Etanercept 2000, Abatacept 2008, TRial of Early Aggressive Therapy (TREAT) 2012 and Tocilizumab 2014. The outcome was active joint counts (AJC). Semiparametric latent class trajectory analysis was applied to identify latent classes of response to treatment; AJC was transformed for this modelling. We tested baseline disease and treatment characteristics for their abilities to predict class membership of response. RESULTS: There were 480 participants, 74% females. At baseline, 26% were rheumatoid factor positive. 67% were on methotrexate at enrollment. Three latent class solution provided the best fit. Baseline AJC was the sole best predictor of class membership. Participants classified by their highest membership probabilities into high baseline AJC (> 30) and slow response (26.5%), low baseline AJC (< 10), early and sustained response (29.7%), and moderate baseline AJC progressive response (43.8%). Participants were classified into the latent classes with a mean class membership posterior probability of 0.97. Those on methotrexate at baseline were less likely to belong to high baseline AJC class. CONCLUSIONS: Three latent classes of responses were detectable in the first 16 weeks of biologics therapy. Those with the highest baseline AJC demonstrated very slow response in this window and were less likely to be on concomitant methotrexate. TRIALS REGISTRATION: TREAT 2012 (NCT NCT00443430 ) (Wallace et. al, Arthritis Rheum 64:2012-21, 2012), tocilizumab trial 2014 ( NCT00988221 ), abatacept trial 2008 ( NCT00095173 ). Etanercept 2000 from Amgen does not have a trial registration number.

A Population-based Study of Grade 12 Academic Performance in Adolescents With Childhood-onset Chronic Rheumatic Diseases.

OBJECTIVE: The aims of this study were (1) to compare grade 12 standardized test results of patients diagnosed with childhood-onset chronic rheumatic diseases (ChildCRD) and unaffected peers; and (2) to identify factors associated with test results of patients with ChildCRD and unaffected peers. METHODS: This was a population-based retrospective cohort study. All patients with ChildCRD (juvenile arthritis and systemic autoimmune rheumatic diseases) from the only pediatric rheumatology center in Manitoba for birth cohorts January 1979 to December 1998 were linked to the provincial administrative databases containing records of healthcare use and education outcomes. Patients were matched by age, sex, and postal codes to their peers who did not have ChildCRD. The primary outcomes were the grade 12 Language Arts Achievement Index (LAI) and the Math Achievement Index (MAI) scores. ChildCRD, sociodemographic, and mental health factors were tested for their associations with LAI and MAI scores using multivariable linear regression. RESULTS: Five hundred and forty-one patients with ChildCRD were matched to 2713 unaffected peers. Patients with ChildCRD had lower LAI and MAI scores compared to their peers. More patients with ChildCRD failed or did not take the language arts (51% vs 41%, P < 0.001) and math (61% vs 55%, P = 0.02) tests. On multivariable analysis, ChildCRD, lower socioeconomic status, younger maternal age at first childbirth, family income assistance, involvement with child welfare services, and mental health morbidities (between ChildCRD diagnosis and standardized testing), were associated with worse LAI and MAI results. CONCLUSION: This population-based study showed that patients with ChildCRD performed less well than their peers on grade 12 standardized testing, independent of sociodemographic and mental health comorbidities.

A population-based study to develop juvenile arthritis case definitions for administrative health data using model-based dynamic classification.

BACKGROUND: Previous research has shown that chronic disease case definitions constructed using population-based administrative health data may have low accuracy for ascertaining cases of episodic diseases such as rheumatoid arthritis, which are characterized by periods of good health followed by periods of illness. No studies have considered a dynamic approach that uses statistical (i.e., probability) models for repeated measures data to classify individuals into disease, non-disease, and indeterminate categories as an alternative to deterministic (i.e., non-probability) methods that use summary data for case ascertainment. The research objectives were to validate a model-based dynamic classification approach for ascertaining cases of juvenile arthritis (JA) from administrative data, and compare its performance with a deterministic approach for case ascertainment. METHODS: The study cohort was comprised of JA cases and non-JA controls 16 years or younger identified from a pediatric clinical registry in the Canadian province of Manitoba and born between 1980 and 2002. Registry data were linked to hospital records and physician billing claims up to 2018. Longitudinal discriminant analysis (LoDA) models and dynamic classification were applied to annual healthcare utilization measures. The deterministic case definition was based on JA diagnoses in healthcare use data anytime between birth and age 16 years; it required one hospitalization ever or two physician visits. Case definitions based on model-based dynamic classification and deterministic approaches were assessed on sensitivity, specificity, and positive and negative predictive values (PPV, NPV). Mean time to classification was also measured for the former. RESULTS: The cohort included 797 individuals; 386 (48.4 %) were JA cases. A model-based dynamic classification approach using an annual measure of any JA-related healthcare contact had sensitivity = 0.70 and PPV = 0.82. Mean classification time was 9.21 years. The deterministic case definition had sensitivity = 0.91 and PPV = 0.92. CONCLUSIONS: A model-based dynamic classification approach had lower accuracy for ascertaining JA cases than a deterministic approach. However, the dynamic approach required a shorter duration of time to produce a case definition with acceptable PPV. The choice of methods to construct case definitions and their performance may depend on the characteristics of the chronic disease under investigation.

Summarizing the extent of visit irregularity in longitudinal data.

BACKGROUND: Observational longitudinal data often feature irregular, informative visit times. We propose descriptive measures to quantify the extent of irregularity to select an appropriate analytic outcome approach. METHODS: We divided the study period into bins and calculated the mean proportions of individuals with 0, 1, and > 1 visits per bin. Perfect repeated measures features everyone with 1 visit per bin. Missingness leads to individuals with 0 visits per bin while irregularity leads to individuals with > 1 visit per bin. We applied these methods to: 1) the TARGet Kids! study, which invites participation at ages 2, 4, 6, 9, 12, 15, 18, 24 months, and 2) the childhood-onset Systemic Lupus Erythematosus (cSLE) study which recommended at least 1 visit every 6 months. RESULTS: The mean proportions of 0 and > 1 visits per bin were above 0.67 and below 0.03 respectively in the TARGet Kids! study, suggesting repeated measures with missingness. For the cSLE study, bin widths of 6 months yielded mean proportions of 1 and > 1 visits per bin of 0.39, suggesting irregular visits. CONCLUSIONS: Our methods describe the extent of irregularity and help distinguish between protocol-driven visits and irregular visits. This is an important step in choosing an analytic strategy for the outcome.

Joint trajectories of disease activity, and physical and mental health-related quality of life in an inception lupus cohort.

OBJECTIVES: To examine for latent patterns of SLE disease activity trajectories that associate with specific latent patterns of health-related quality of life (HRQoL; Medical Outcomes Study Short Form-36), and to determine baseline predictors of class membership. METHODS: In this retrospective longitudinal inception cohort of 222 SLE adults over 10 years, trajectories of three outcomes were studied jointly: Short Form-36 physical (PCS) and mental (MCS) component summaries and adjusted mean SLEDAI-2000 (AMS). Group-based joint trajectory modelling was used to model latent classes; univariable and multivariable analyses were used to identify predictors of class membership. RESULTS: Four latent classes were identified: Class 1 (C1) (24%) had moderate AMS, and persistently low PCS and MCS; C2 (26%) had low AMS, moderate PCS and improved then worsened MCS; C3 (38%) had moderate AMS, and persistently high PCS and MCS; and C4 (11%) had high AMS, moderate-low PCS and improving MCS. Baseline older age was associated with lower HRQoL trajectories. Higher AMS trajectories did not associate with a particular pattern of HRQoL trajectory. A higher prevalence of fibromyalgia (44% in C1) was associated with worse HRQoL trajectories. Disease manifestations, organ damage and cumulative glucocorticoid were not differentially distributed across the latent classes. CONCLUSION: High disease activity did not necessarily associate with low HRQoL. More patients with worse HRQoL trajectories had fibromyalgia. Older age at diagnosis increased the probability of belonging to a class with low HRQoL trajectories. The care of SLE patients may be improved through addressing fibromyalgia in addition to disease activity.

Translation, Adaptation, and Validation of the Malay Version of the Cardiac Rehabilitation Barriers Scale.

BACKGROUND: The rate of cardiac rehabilitation attendance at the Sarawak Heart Centre was identified as very low, and the reason has not been investigated. A scale is needed to identify barriers to participation in cardiac rehabilitation among patients with heart disease in Sarawak, Malaysia. PURPOSE: The purposes of this study were to translate, adapt, and evaluate the Malay-language version of the Cardiac Rehabilitation Barriers Scale (CRBS) and to measure the psychometric properties of the Malay-version CRBS to justify its use in Sarawak. METHODS: A forward and back-translation method was used. Content validity was assessed by three experts. Psychometric testing was conducted on a sample of 283 patients who were eligible to participate in cardiac rehabilitation. A construct validity test was performed using factor analysis. Cronbach's alpha was used to examine the internal consistency. The test-retest reliability was calculated using the intraclass correlation coefficient on 22 participants. Independent-samples t test and analysis of variance were conducted to assess the criterion validity. Mean scores for total barriers of the scale and each individual factor were compared among the different patient characteristics. RESULTS: The Malay-version CRBS showed an item level of content validity index of 1.00 for all of the items after improvements were made based on the experts' suggestions. The factor analysis, using principal component analysis with direct oblimin rotation, extracted four factors that differed from the original study. These four factors explained 52.50% of the cumulative percentage of variance. The Cronbach's alphas ranged from .74 to .81 for the obtained factors. Test-retest reliability was established using the intraclass correlation coefficient value of .78. Criterion validity was supported using the significant differences in the mean score for total barriers among educational level, driving distance, travel time to the hospital, and cardiac rehabilitation attendance. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This study found the Malay-version CRBS to be a valid and reliable instrument. It may be used with inpatients to identify barriers to participation in cardiac rehabilitation to promote rehabilitation attendance and improve patient care.

Real-World Effectiveness of Common Treatment Strategies for Juvenile Idiopathic Arthritis: Results From a Canadian Cohort.

OBJECTIVE: Undervaluing the effectiveness of conventional treatments may lead to overtreatment with biologic medications in children with juvenile idiopathic arthritis (JIA). Using data from a nationwide inception cohort and strict methods to control bias, the aim of our study was to estimate the real-world effectiveness of simple JIA treatment strategies recommended in current guidelines. METHODS: Children with JIA who were recruited at 16 Canadian centers from 2005 to 2010 were followed for up to 5 years. For each child, all observed treatment changes over time were assessed by independent physicians using prospectively collected data and published response criteria. Success was defined as attainment of inactive disease or maintenance of this state when stepping down treatment; minimally active disease was deemed acceptable for children with polyarticular JIA. Success rates were calculated for treatments tried ≥25 times, and logistic regression analysis identified features associated with success. RESULTS: A total of 4,429 treatment episodes were observed in 1,352 children. Nonsteroidal antiinflammatory drug (NSAID) monotherapy was attempted 697 times, mostly as initial treatment when <5 joints were involved, with a 54.4% success rate (95% confidence interval [95% CI] 50.3-58.6). NSAIDs plus joint injections had a 64.7% success rate (95% CI 59.8-69.7). Adding methotrexate to NSAIDs and/or joint injections (attempted 566 times) had a 60.5% success rate (95% CI 55.7-65.3). In adjusted analyses, each additional active joint reduced chances of success for treatment with NSAIDs (odds ratio [OR] 0.90 [95% CI 0.85-0.94]) and for methotrexate combinations (OR 0.96 [95% CI 0.94-0.99]). Each additional year after disease onset reduced chances of success for treatment with methotrexate combinations (OR 0.83 [95% CI 0.72-0.95]). CONCLUSION: These real-world effectiveness estimates show that conventional nonbiologic treatment strategies that are recommended in current guidelines are effective in achieving treatment targets in many children with JIA.

Using Registry Data to Understand Disease Evolution in Inflammatory Myositis and Other Rheumatic Diseases.

PURPOSE OF REVIEW: While rheumatic disease registries collect longitudinal patient information, longitudinal analytic methods are usually not applied to these data. This review will showcase advances in longitudinal designs/analyses, and ways to leverage digital technologies to recruit and retain more registry participants. RECENT FINDINGS: We will show how the accelerated cohort and longitudinal multiform methods are more efficient than traditional longitudinal designs. We illustrate how a smartphone app is used to recruit participants for a new rheumatic disease registry in the USA. Examples of newer longitudinal techniques applied in myositis and childhood-onset lupus are also presented. Applying high-efficiency longitudinal design and analysis let investigators leverage the rich registry information collected over time. They allow more sophisticated and precise questions to be asked about the disease course of myositis and other rheumatic diseases, which in turn will inform the practice of clinicians and important decisions made by stakeholders.

Canadian Rheumatology Association Recommendations for the Assessment and Monitoring of Systemic Lupus Erythematosus.

OBJECTIVE: To develop recommendations for the assessment of people with systemic lupus erythematosus (SLE) in Canada. METHODS: Recommendations were developed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. The Canadian SLE Working Group (panel of Canadian rheumatologists and a patient representative from Canadian Arthritis Patient Alliance) was created. Questions for recommendation development were identified based on the results of a previous survey of SLE practice patterns of members of the Canadian Rheumatology Association. Systematic literature reviews of randomized trials and observational studies were conducted. Evidence to Decision tables were prepared and presented to the panel at 2 face-to-face meetings and online. RESULTS: There are 15 recommendations for assessing and monitoring SLE, with varying applicability to adult and pediatric patients. Three recommendations focus on diagnosis, disease activity, and damage assessment, suggesting the use of a validated disease activity score per visit and annual damage score. Strong recommendations were made for cardiovascular risk assessment and measuring anti-Ro and anti-La antibodies in the peripartum period and conditional recommendations for osteoporosis and osteonecrosis. Two conditional recommendations were made for peripartum assessments, 1 for cervical cancer screening and 2 for hepatitis B and C screening. A strong recommendation was made for annual influenza vaccination. CONCLUSION: These are considered the first guidelines using the GRADE method for the monitoring of SLE. Existing evidence is largely of low to moderate quality, resulting in more conditional than strong recommendations. Additional rigorous studies and special attention to pediatric SLE populations and patient preferences are needed.

Purification and characterization of a novel GH1 beta-glucosidase from Jeotgalibacillus malaysiensis.

Beta-glucosidase (BGL) is an important industrial enzyme for food, waste and biofuel processing. Jeotgalibacillus is an understudied halophilic genus, and no beta-glucosidase from this genus has been reported. A novel beta-glucosidase gene (1344 bp) from J. malaysiensis DSM 28777T was cloned and expressed in E. coli. The recombinant protein, referred to as BglD5, consists of a total 447 amino acids. BglD5 purified using a Ni-NTA column has an apparent molecular mass of 52 kDa. It achieved the highest activity at pH 7 and 65 °C. The activity and stability were increased when CaCl2 was supplemented to the enzyme. The enzyme efficiently hydrolyzed salicin and (1 → 4)-beta-glycosidic linkages such as in cellobiose, cellotriose, cellotetraose, cellopentose, and cellohexanose. Similar to many BGLs, BglD5 was not active towards polysaccharides such as Avicel, carboxymethyl cellulose, Sigmacell cellulose 101, alpha-cellulose and xylan. When BglD5 blended with Cellic® Ctec2, the total sugars saccharified from oil palm empty fruit bunches (OPEFB) was enhanced by 4.5%. Based on sequence signatures and tree analyses, BglD5 belongs to the Glycoside Hydrolase family 1. This enzyme is a novel beta-glucosidase attributable to its relatively low sequence similarity with currently known beta-glucosidases, where the closest characterized enzyme is the DT-Bgl from Anoxybacillus sp. DT3-1.

Alternative Design and Analytical Techniques for Longitudinal Rheumatology Studies: Improved Understanding of Outcomes.

Longitudinal cohort designs (with three or more measurement occasions) are invaluable to investigate between- and within-individual variation in outcomes. However, traditional longitudinal designs require a lengthy implementation and data collection period and impose a substantial burden on participants and investigators. We discuss alternative longitudinal designs, including planned missing data designs and retrospective cohort studies with secondary data, which require a shorter period for data accrual and reduce participant burden while maintaining statistical power. We also discuss analysis strategies to maximize data use and produce unbiased estimates of treatment effectiveness, including models for recurrent or multistate events and time-varying covariates.

From Childhood to Adulthood: Disease Activity Trajectories in Childhood-Onset Systemic Lupus Erythematosus.

OBJECTIVE: No previous study has studied the longitudinal disease course of childhood-onset systemic lupus erythematosus (cSLE). Our objectives are to assess distinguishable differences in disease activity trajectories in cSLE patients, determine baseline factors predictive of disease trajectory membership, and assess if the different disease activity trajectories are associated with different damage trajectories. METHODS: This is a retrospective, longitudinal inception cohort of cSLE patients. Patients were followed from diagnosis as children, until they were adults. SLE disease activity was modeled as a latent characteristic, jointly using the Systemic Lupus Erythematosus Disease Activity Index 2000 and prednisone in a Bayesian growth mixture model. Baseline factors were tested for membership prediction of the latent classes of disease trajectories. Differences in damage trajectories by disease activity classes were tested using a mixed model. RESULTS: A total of 473 patients (82% females), with median age at diagnosis of 14.1 years, were studied. We studied 11,992 visits (2,666 patient-years). We identified 5 classes of disease activity trajectories. Baseline major organ involvement, number of American College of Rheumatology criteria, and age at diagnosis predicted memberships into different classes. A higher proportion of Asians was in class 2 compared to class 5. Class 1 was associated with the most accrual of damage, while class 5 was associated with no significant damage accrual, even after 10 years. CONCLUSION: There are 5 distinct latent classes of disease trajectory in patients with cSLE. Membership within disease trajectories is predicted by baseline clinical and demographic factors. Membership in different disease activity trajectory classes is associated with different damage trajectories.

Methods for analyzing observational longitudinal prognosis studies for rheumatic diseases: a review & worked example using a clinic-based cohort of juvenile dermatomyositis patients.

Most outcome studies of rheumatic diseases report outcomes ascertained on a single occasion. While single assessments are sufficient for terminal or irreversible outcomes, they may not be sufficiently informative if outcomes change or fluctuate over time. Consequently, longitudinal studies that measure non-terminal outcomes repeatedly afford a better understanding of disease evolution.Longitudinal studies require special analytic methods. Newer longitudinal analytic methods have evolved tremendously to deal with common challenges in longitudinal observational studies. In recent years, an increasing number of studies have used longitudinal design. This review aims to help readers understand and apply the findings from longitudinal studies. Using a cohort of children with juvenile dermatomyositis (JDM), we illustrate how to study evolution of disease activity in JDM using longitudinal methods.

From Childhood to Adulthood: The Trajectory of Damage in Patients With Juvenile-Onset Systemic Lupus Erythematosus.

OBJECTIVE: To determine the longitudinal damage trajectory of patients with juvenile-onset systemic lupus erythematosus (SLE), and to identify baseline and disease course predictors of damage trajectory. METHODS: This is a retrospective inception cohort. Longitudinal pediatric-age data were obtained from a juvenile-onset SLE research database, while adult-age data were obtained from either a research database or patients' charts. Baseline factors were tested as predictors. Time-varying factors were lagged 6-24 months before a visit for testing their predictive effects. The longitudinal damage trajectory was modeled using a weighted generalized estimating equation. RESULTS: This study cohort consisted of 473 subjects, with followup to 26 years. A total of 65% of patients were ages >18 years at last followup. Cataracts (14%), avascular necrosis (10%), and osteoporosis (5%) were the most common items of damage. Two patients had myocardial infarctions. Baseline features, self-reported ethnicity (Afro-Caribbean), earlier time periods of diagnosis, and the presence of a life-threatening major organ manifestation (lupus nephritis class III-V, cerebrovascular accidents, major organ vasculitis, pulmonary hemorrhage, or myocarditis), were associated with greater damage. Throughout the disease course, an acute confusional state, lupus headache, and fever predicted subsequent increases in the damage trajectory. A higher prednisone dose and exposure to cyclophosphamide also predicted subsequent increases in the damage trajectory. Antimalarial exposure was protective against an increase in damage trajectory. CONCLUSION: Patients with juvenile-onset SLE accrue damage steadily into adulthood. Baseline factors predict greater damage and/or influence the evolution of the damage trajectory. Additionally, SLE clinical features and therapies during the course of disease predict additional changes in the damage trajectory.