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1.
Mult Scler ; : 1352458519876038, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31517571

RESUMO

BACKGROUND: Although multiple sclerosis (MS) confers an elevated risk of acute myocardial infarction (AMI), little is known about how it influences management of AMI. METHODS: Using population-based administrative (health) data from two Canadian provinces, we conducted a retrospective matched cohort study. We identified people with MS who had an incident AMI, and up to five AMI controls without MS matched on age, sex, and region. We compared the likelihood of undergoing cardiac catheterization within 30 days of AMI, time to revascularization, use of recommended pharmacotherapy post-AMI, and mortality at 30 and 365 days post-AMI using multivariable regression models adjusting for potential confounders. We pooled findings across provinces using meta-analysis. RESULTS: We identified 559 MS cases and 2523 matched controls. In the matched cohort, the MS cohort was less likely to undergo cardiac catheterization within 30 days of admission (odds ratio (OR) = 0.61; 95% confidence interval (CI) = 0.49-0.77), revascularization (hazard ratio (HR) = 0.78; 95% CI = 0.69-0.88), or to fill a prescription for recommended therapy. Mortality risk was higher in the MS cohort than in the matched cohort at 30 and 365 days post-AMI. CONCLUSION: Rates of diagnostic and therapeutic care, and survival after AMI were lower in the MS population than in a matched population.

2.
Mult Scler Relat Disord ; 36: 101387, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31539739

RESUMO

BACKGROUND: Thinning of the retinal nerve fiber layer (RNFL) and ganglion cell/inner plexiform layer (GCIPL) occur in the chronic phase after optic neuritis (ON) in children and reflect neuroaxonal injury. The objective of this study was to describe changes in RNFL and GCIPL thickness in the acute phase following pediatric ON. METHODS: Data were collected prospectively from consecutive children presenting with ON as part of an incident acquired demyelinating event. Children with a final diagnosis of multiple sclerosis (n = 9, 10 ON-affected eyes) or monophasic demyelination (n = 16, 25 ON-affected eyes) who underwent spectral-domain optical coherence tomography (OCT) testing within 30 days of symptom onset were included. Standardized visual assessment was performed at presentation and 6-18 months follow-up. OCT measures were compared to those of healthy controls (n = 25, 50 eyes). RESULTS: Median (interquartile range [IQR]) global RNFL thickness was increased in ON-affected eyes (155 µm [114-199 µm]) compared to control eyes (104 µm [98.5-107.5 µm]; p < 0.0001). Compared to controls, fellow eyes demonstrated a reduced temporal quadrant RNFL thickness (59 µm [53-72 µm] versus 71.5 µm [65-81 µm]; p = 0.013) and lower GCIPL thickness (80.5 µm [74-88 µm] versus 87 µm [85-89 µm]; p = 0.003). The ON-affected eyes of children with monophasic demyelination demonstrated a greater global RNFL thickness (183.5 µm [146.5-206 µm]) compared to the ON-affected eyes of children with multiple sclerosis (108.5 µm [95-124 µm]; p = 0.01). OCT measures at presentation did not predict low-contrast visual acuity nor color vision at 6-18 months follow-up. CONCLUSION: Children with multiple sclerosis show less RNFL swelling in their ON-affected eyes at onset compared to children with monophasic demyelination. Lower GCIPL and temporal RNFL thickness in the clinically unaffected eyes of those children with unilateral ON suggests the presence of pre-existing neuroaxonal injury in children presenting with a first episode of ON. This finding may be driven by the subset of children with multiple sclerosis.

3.
JAMA Neurol ; 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31545352

RESUMO

Importance: Identifying the course of demyelinating disease associated with myelin oligodendrocyte glycoprotein (MOG) autoantibodies is critical to guide appropriate treatment choices. Objective: To characterize serial anti-MOG antibody serologies and clinical and imaging features at presentation and during follow-up in an inception cohort of prospectively monitored children with acquired demyelination. Design, Setting, and Participants: In this prospective cohort study, study participants were recruited from July 2004 to February 2017 through the multicenter Canadian Pediatric Demyelinating Disease Study. Inclusion criteria included (1) incident central nervous system demyelination, (2) at least 1 serum sample obtained within 45 days from onset, and (3) complete clinical information. Of 430 participants with acquired demyelinating syndrome recruited, 274 were included in analyses. Of 156 excluded participants, 154 were excluded owing to missing baseline samples and 2 owing to incomplete clinical information. Data were analyzed from May to October 2018. Main Outcomes and Measures: Presence of anti-MOG antibodies was blindly assessed in serial samples collected over a median of 4 years. Clinical, magnetic resonance imaging, and cerebrospinal fluid features were characterized at presentation, and subsequent disease course was assessed by development of new brain magnetic resonance imaging lesions, total lesion volume at last evaluation, annualized relapse rates, Expanded Disability Status Scale score and visual functional score at 4 years, and any disease-modifying treatment exposure. Results: Of the 274 included participants, 140 (51.1%) were female, and the median (interquartile range) age of all participants was 10.8 (6.2-13.9) years. One-third of children were positive for anti-MOG antibodies at the time of incident demyelination. Clinical presentations included a combination of optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis for 81 of 84 anti-MOG antibody-positive children (96%). Brain lesions were present in 51 of 76 anti-MOG antibody-positive participants (67%), but magnetic resonance imaging characteristics differed with age at presentation. Complete resolution of baseline lesions was observed in 26 of 49 anti-MOG antibody-positive participants (53%). On serial serum analysis, 38 of 67 participants (57%) who were seropositive at onset became seronegative (median time to conversion, 1 year). Among all participants who were positive for anti-MOG antibodies at presentation, clinical relapses occurred in 9 of 24 children (38%) who remained persistently seropositive and in 5 of 38 children (13%) who converted to seronegative status. Conclusions and Relevance: Myelin oligodendrocyte glycoprotein antibodies are common in children with acquired demyelinating syndrome and are transient in approximatively half of cases. Even when persistently positive, most anti-MOG antibody-positive children experience a monophasic disease. The presence of anti-MOG antibodies at the time of incident demyelination should not immediately prompt the initiation of long-term immunomodulatory therapy.

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5.
Mult Scler Relat Disord ; 35: 42-49, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31319354

RESUMO

BACKGROUND: To establish whether a unique multiple sclerosis (MS) prodrome exists by comparing health care utilization in the five-year period before initial presentation with optic neuritis (ON) or transverse myelitis (TM) among those who were and were not subsequently diagnosed with MS. METHODS: Using population-based administrative health data we conducted a retrospective cohort study in three Canadian provinces. We identified individuals with a clinically isolated syndrome (ON or TM), who were eventually diagnosed with MS (CIS-MS) or not (CIS-non MS), and a control cohort matched on age, sex and region without a CIS. We compared rates of hospitalization, physician services use and prescription drug use in the five years before the first ON or TM claim (labeled years -1,-2,-3,-4,-5) using negative binomial regression models adjusted for age, sex, socioeconomic status and index year. RESULTS: We identified 1,155 CIS-MS cases, 20,638 CIS-non MS cases, and 108,726 matched controls. Compared to matched controls, the CIS-MS cohort had a higher hospitalization rate (years -5 and -1), physician visits (all years) and prescription drug use (years -4 and -1). Compared to matched controls, the CIS-non MS cohort had a higher rate of hospitalizations (all years), physician visits (all years) and prescription drug use (all years). CONCLUSION: Health care use was higher in individuals with a CIS than without a CIS in the five years before an incident demyelinating event, regardless of whether they were subsequently diagnosed with MS. This suggests that there is a prodromal period before CIS which is not unique to MS.

6.
Addiction ; 114(10): 1791-1799, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31240747

RESUMO

BACKGROUND AND AIMS: To estimate prevalence of continuous use (persistence) of prescribed cannabinoid medications for up to 1 year from initial prescription in Manitoba, Canada and predictors of duration of use. DESIGN AND SETTING: A retrospective, population-based, cohort study using administrative data from the Manitoba Population Research Data Repository located at the Manitoba Centre for Health Policy, Canada. PARTICIPANTS: People without a record of a previous prescription who were prescribed a cannabinoid medication from 1 April 2004 to 1 April 2016 followed for 1 year from the date of first prescription. MEASUREMENTS: Continuous prescribed cannabinoid medication use was defined as use without a gap exceeding 60 days between prescriptions. The primary outcome was prevalence of continuous prescribed cannabinoid medication use for up to 1 year. A secondary outcome was duration of continuous use. Predictors were socio-demographic characteristics, medical diagnoses and type of cannabinoid medication. FINDINGS: Among 5452 new users, 18.1% [95% confidence interval (CI) = 17.08-19.12] were still using cannabinoids at 1 year. Median duration of use was 31 days [interquartile range (IQR) = 25-193]. This was highest for nabilone (33 days, IQR = 25-199) and lowest for nabiximols (20 days, IQR = 7-30). Use was longest among 19-45- and 46-64-year-old users and those with the highest socio-economic status. Fibromyalgia [hazard ratio (HR) = 0.89, 95% CI = 0.84-0.95], osteoarthritis (HR = 0.91, 95% CI = 0.82-0.97) and substance use disorder (HR = 0.85, 95% CI = 0.76-0.94) diagnoses were associated with longer use (HR for discontinuation-HR < 1 less discontinuation and longer use). A diagnosis of cancer was associated with shorter use (HR = 2.73, 95% CI = 2.02-3.67). CONCLUSIONS: In Manitoba, Canada approximately 18% of people prescribed cannabinoid medication continue using for at least 1 year. Duration of use varies with type of cannabinoid medication, age, socio-economic status and dagnosis.

7.
PLoS One ; 14(6): e0218215, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31185042

RESUMO

We aimed to compare health care utilization of children with pediatric-onset multiple sclerosis to that of age, sex and geographically-matched children without multiple sclerosis. Using population-based administrative data from Ontario, Canada for the period 2003-2014, we applied a validated case definition to identify persons aged ≤18 years with multiple sclerosis. We identified up to 5 children without multiple sclerosis matched on sex, age, and region of residence. In each cohort, we determined annual rates of any hospitalization and physician services use. Using general linear models we compared utilization rates adjusting for age, sex, region, socioeconomic status and year. Subsequently, we limited the analysis to incident cases of multiple sclerosis and their matches, and compared rates of utilization in the year of multiple sclerosis diagnosis, and the three years thereafter. We identified 659 youth with multiple sclerosis (428 incident cases), and 3,294 matched controls. Two-thirds of both cohorts were female. After adjustment for sociodemographic factors and year, the multiple sclerosis cohort was more likely to be hospitalized than the matched cohort (odds ratio 15.2; 95%CI: 12.0, 19.1), and had higher rates of ambulatory physician visits (rate ratio 4.58; 95%CI: 4.26, 4.92). The odds of hospitalization (odds ratio 40.1; 95%CI: 27.1, 59.5) and physician visits (rate ratio 5.14; 95%CI: 4.63, 5.71) were markedly elevated in the year of MS diagnosis, declining thereafter but remaining elevated versus the matched cohort. Children with multiple sclerosis have substantially elevated rates of health care utilization as compared to matched children without multiple sclerosis, over calendar time and throughout the early disease course.

8.
Mult Scler ; : 1352458519852722, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31161917

RESUMO

BACKGROUND: Researchers studying health-related quality of life (HRQOL) in multiple sclerosis (MS) can choose from many instruments, but findings from studies which use different instruments cannot be easily combined. We aimed to develop a crosswalk that associates scores from the RAND-12 to scores on the Health Utilities Index-Mark III (HUI3) in persons with MS. METHODS: In 2018, participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) registry completed the RAND-12 and the HUI3 to assess HRQOL. We used item-response theory (IRT) and equipercentile linking approaches to develop a crosswalk between instruments. We compared predicted scores for the HUI3 from each crosswalk to observed scores using Pearson correlations, intraclass correlation coefficients (ICCs), and Bland-Altman plots. RESULTS: Of 11,389 invited participants, 7129 (62.6%) responded. Predicted and observed values of the HUI3 from the IRT-linking method were moderately correlated (Pearson r = 0.76) with good concordance (ICC = 0.72). However, the Bland-Altman plots suggested biased prediction. Predicted and observed values from the equipercentile linking method were also moderately correlated (Pearson r = 0.78, ICC = 0.78). The Bland-Altman plots suggested no bias. CONCLUSION: We developed a crosswalk between the RAND-12 and the HUI3 in the MS population which will facilitate data harmonization efforts.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31199570

RESUMO

OBJECTIVE: To test the validity and reliability of screening instruments for depression and anxiety in rheumatoid arthritis (RA). METHODS: Participants with RA completed the Patient Health Questionnaire (PHQ-2, PHQ-9), Patient Reported Outcomes Measurement Information System Depression Short Form-8a (PROMIS Depression) and Anxiety Short Form-8a (PROMIS Anxiety), Hospital Anxiety and Depression Scale anxiety score (HADS-A) and depression score (HADS-D), Overall Anxiety Severity and Impairment Scale (OASIS), Generalized Anxiety Disorder-2 and 7 item scales (GAD-2, GAD-7) and Kessler-6 scale. Clinical depression and anxiety disorders were confirmed using the Structured Clinical Interview for DSM-IV-TR Axis I Disorders-Research version (SCID). We reported sensitivity (SENS), specificity (SPEC), positive predictive value (PPV) and negative predictive value (NPV) using SCID diagnoses as the criterion standard. Test-retest reliability was assessed with the intra-class correlation coefficient (ICC). RESULTS: Of 150 participants, 11.3% had SCID-diagnosed depression, 7.3% SCID-diagnosed generalized anxiety disorder and 19.3% any SCID-diagnosed anxiety disorder. For depression, SENS ranged from HADS-D (cut-point 11: 35%) to PHQ-2 (88%) and PHQ-9 (87%). SPEC ranged from PHQ-9 (77%), PHQ-2 (84%) to HADS-D (cut-point 11: 94%). PPV ranged from 30% to 43%. NPV ranged from 92% to 98%. For generalized anxiety disorder, SENS ranged from HADS-A (cut-point 11: 45%) to HADS-A (cut-point 8: 91%). SPEC ranged from 81% to 89% for all measures except the HADS-A (cut-point 8: 63%). ICC estimates ranging from 0.69 to 0.88 confirmed good test-retest reliability. CONCLUSIONS: Depression screening instruments had good diagnostic performance; anxiety instruments were more variable. Identified depression and anxiety require clinical confirmation. This article is protected by copyright. All rights reserved.

10.
Mult Scler ; 25(11): 1425-1426, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31134835
11.
Stat Med ; 38(19): 3669-3681, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31115088

RESUMO

In epidemiological studies of secondary data sources, lack of accurate disease classifications often requires investigators to rely on diagnostic codes generated by physicians or hospital systems to identify case and control groups, resulting in a less-than-perfect assessment of the disease under investigation. Moreover, because of differences in coding practices by physicians, it is hard to determine the factors that affect the chance of an incorrectly assigned disease status. What results is a dilemma where assumptions of non-differential misclassification are questionable but, at the same time, necessary to proceed with statistical analyses. This paper develops an approach to adjust exposure-disease association estimates for disease misclassification, without the need of simplifying non-differentiality assumptions, or prior information about a complicated classification mechanism. We propose to leverage rich temporal information on disease-specific healthcare utilization to estimate each participant's probability of being a true case and to use these estimates as weights in a Bayesian analysis of matched case-control data. The approach is applied to data from a recent observational study into the early symptoms of multiple sclerosis (MS), where MS cases were identified from Canadian health administrative databases and matched to population controls that are assumed to be correctly classified. A comparison of our results with those from non-differentially adjusted analyses reveals conflicting inferences and highlights that ill-suited assumptions of non-differential misclassification can exacerbate biases in association estimates.

12.
Mult Scler ; : 1352458519845836, 2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31079537

RESUMO

BACKGROUND: Metabolic comorbidity is overrepresented in people with multiple sclerosis (MS) and is associated with adverse MS outcomes. Excess visceral adiposity, approximated using waist circumference (WC), is a risk factor for metabolic comorbidity and predicts poorer outcomes in other neurologic diseases. OBJECTIVE: To evaluate the association between WC and clinical and disease characteristics in people with MS. METHODS: North American Research Committee on MS (NARCOMS) registry participants reported height and weight (used to calculate body mass index (BMI)) and were mailed a tape measure with instructions to measure WC. We considered WC continuously and used cut-points derived from the abdominal obesity criteria for the metabolic syndrome (men: WC ⩾ 40 in; women: WC ⩾ 35 in). We assessed the association between WC and disability (Patient-Determined Disease Steps) and symptom severity (validated scales) using multivariable-adjusted multinomial models. RESULTS: Of 6367 responders with MS, we included 5832 (92%). Of these, 3181 (55%) reported WC meeting criteria for the abdominal obesity component of metabolic syndrome. In multivariable models adjusting for overall obesity status, WC was associated with 47% increased odds of severe versus mild disability (odds ratio (OR): 1.47; 95% confidence interval (CI): 1.22-1.78). CONCLUSIONS: Increased WC is associated with more severe disability, even after adjusting for overall obesity in this large cross-sectional survey.

13.
Mult Scler Relat Disord ; 31: 165-172, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31063935

RESUMO

INTRODUCTION: Fatigue is an important aspect of health-related quality of life and a commonly reported symptom by many persons with multiple sclerosis (MS). There are multiple validated instruments available to assess fatigue in MS with differing benefits for each instrument. OBJECTIVE: We aimed to assess the relationship between the PROMIS Fatigue instrument and the Fatigue Performance Scale (FPS) in the NARCOMS registry. Additionally, we aimed to examine the association of fatigue with social participation. METHODS: The NARCOMS registry is a voluntary, self-report registry, which has enrolled participants with MS who provide semi-annual updates regarding their MS. The Fall 2016 semi-annual survey included the PROMIS Fatigue and Ability to Participate in Social Roles and Activities questionnaires, in addition to demographic and clinical information. We examined the association between instruments using Spearman correlations. Linear and ordinal regression models were used to evaluate associations with fatigue using the PROMIS Fatigue and the FPS. RESULTS: Of the 7,006 Fall 2016 respondents, 6,883 (98.2%) completed the PROMIS instruments. Respondents were mostly female (79.5%) and Caucasian (87.4%), had a mean (SD) age of 59.9 (10.2) years and moderate disability level (median Patient Determined Disease Steps [PDDS] 4 [early cane]). The mean (SD) PROMIS Fatigue T-score was 56.8 (11.0) and median (25th, 75th) FPS was 3 [moderate] (1 [minimal], 4 [severe]). Fatigue measures were strongly correlated (r = 0.83, 95% CI: [0.827, 0.842]). Factors consistently associated with fatigue were PDDS level, depression and pain functionality scales, and symptoms worsening. The ability to participate in social roles and activities was strongly associated with fatigue and had an independent effect on fatigue after adjusting for PDDS, depression and pain levels. CONCLUSION: A high proportion of respondents experience some level of fatigue and it is independently associated with reduced social participation.

14.
Patient Educ Couns ; 102(9): 1722-1729, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30982700

RESUMO

OBJECTIVE: We assessed the information needs of persons with any of three immune-mediated inflammatory diseases (multiple sclerosis [MS], inflammatory bowel disease [IBD] and rheumatoid arthritis [RA]) regarding depression, as a first step toward developing patient-relevant information resources, ultimately to facilitate self-management and appropriate care. We also compared information needs across genders. METHODS: We surveyed participants with MS, IBD and RA regarding depression-related information needs including types of treatments, effectiveness, risks, benefits, and perceived helpfulness of treatments. We compared responses between groups using multivariate regression. RESULTS: 328 participants provided complete responses (MS: 141, IBD: 114, RA: 73). Most of the topics queried were perceived as very important, and similarly important for all groups. Women placed higher importance than men on most topics. The most popular formats for receiving information were discussion with a counselor (very preferred: 67.4%) and written information (very preferred: 65.5%); this did not differ between groups. CONCLUSIONS: Persons affected by MS, IBD and RA are interested in receiving information about multiple topics related to depression treatment, from multiple sources. Women desire more information than men. PRACTICE IMPLICATIONS: These findings can be used to design information resources to meet information needs regarding depression in MS, IBD and RA.

15.
Neurology ; 92(14): e1624-e1633, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30842298

RESUMO

OBJECTIVE: To compare the risk of incident acute myocardial infarction (AMI) in the multiple sclerosis (MS) population and a matched population without MS, controlling for traditional vascular risk factors. METHODS: We conducted a retrospective matched cohort study using population-based administrative (health claims) data in 2 Canadian provinces, British Columbia and Manitoba. We identified incident MS cases using a validated case definition. For each case, we identified up to 5 controls without MS matched on age, sex, and region. We compared the incidence of AMI between cohorts using incidence rate ratios (IRR). We used Cox proportional hazards regression to compare the hazard of AMI between cohorts adjusting for sociodemographic factors, diabetes, hypertension, and hyperlipidemia. We pooled the provincial findings using meta-analysis. RESULTS: We identified 14,565 persons with MS and 72,825 matched controls. The crude incidence of AMI per 100,000 population was 146.2 (95% confidence interval [CI] 129.0-163.5) in the MS population and 128.8 (95% CI 121.8-135.8) in the matched population. After age standardization, the incidence of AMI was higher in the MS population than in the matched population (IRR 1.18; 95% CI 1.03-1.36). After adjustment, the hazard of AMI was 60% higher in the MS population than in the matched population (hazard ratio 1.63; 95% CI 1.43-1.87). CONCLUSION: The risk of AMI is elevated in MS, and this risk may not be accounted for by traditional vascular risk factors.

16.
Clin Invest Med ; 42(1): E5-E12, 2019 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-30904030

RESUMO

PURPOSE: Multiple sclerosis (MS) is an inflammatory and degenerative condition affecting the central nervous system. Like many neurologic diseases, it is chronic and incurable, and confers a substantial burden on affected individuals, their families and society. Although many individuals suffering from a serious chronic disease also suffer from comorbid conditions, the important consequences of their interaction often receive little attention. This was particularly true for MS two decades ago. Broadening our perspective by better understanding the effects of comorbidity on an individual with a particular chronic disease offers us an opportunity to improve understanding of prognosis, personalize disease management, develop new therapeutic approaches and illuminate the pathophysiology of disease. SOURCE: Studies examining the incidence, prevalence and outcomes related to comorbidity in MS will be discussed, along with areas requiring further investigation. CONCLUSION: Comorbidity is highly prevalent in MS throughout the disease course. Comorbid conditions, including depression, anxiety, hypertension, hyperlipidemia, diabetes and chronic lung disease, adversely affect a broad range of outcomes. Less is known about the effects of MS on outcomes related to these comorbid conditions. These findings highlight an urgent need to determine how to best prevent and treat comorbidity in MS.

17.
Inflamm Bowel Dis ; 2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30888037

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is associated with a high prevalence of comorbid depressive and anxiety disorders. A significant proportion of IBD patients with comorbid psychiatric disorders remain undiagnosed and untreated, but factors associated with diagnosis are unknown. We evaluated the prevalence of undiagnosed depression and anxiety in an IBD cohort, along with the associated demographic and clinical characteristics. METHODS: We obtained data from the enrollment visit of a cohort study of psychiatric comorbidity in immune-mediated diseases including IBD. Each participant underwent a Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID) to identify participants who met lifetime criteria for a diagnosis of depression or anxiety. Those with a SCID-based diagnosis were classified as diagnosed or undiagnosed based on participant report of a physician diagnosis. RESULTS: Of 242 eligible participants, 97 (40.1%) met SCID criteria for depression, and 74 (30.6%) met criteria for anxiety. One-third of participants with depression and two-thirds with anxiety were undiagnosed. Males were more likely to have an undiagnosed depressive disorder (odds ratio [OR], 3.36; 95% confidence interval [CI], 1.28-8.85). Nonwhite participants were less likely to have an undiagnosed anxiety disorder (OR, 0.17; 95% CI, 0.042-0.72). CONCLUSION: Our findings highlight the importance of screening for depression and anxiety in patients with IBD, with particular attention to those of male sex and with a lower education level.

18.
Neurology ; 92(10): e1016-e1028, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30770432

RESUMO

OBJECTIVE: To develop a valid algorithm for identifying multiple sclerosis (MS) cases in administrative health claims (AHC) datasets. METHODS: We used 4 AHC datasets from the Veterans Administration (VA), Kaiser Permanente Southern California (KPSC), Manitoba (Canada), and Saskatchewan (Canada). In the VA, KPSC, and Manitoba, we tested the performance of candidate algorithms based on inpatient, outpatient, and disease-modifying therapy (DMT) claims compared to medical records review using sensitivity, specificity, positive and negative predictive values, and interrater reliability (Youden J statistic) both overall and stratified by sex and age. In Saskatchewan, we tested the algorithms in a cohort randomly selected from the general population. RESULTS: The preferred algorithm required ≥3 MS-related claims from any combination of inpatient, outpatient, or DMT claims within a 1-year time period; a 2-year time period provided little gain in performance. Algorithms including DMT claims performed better than those that did not. Sensitivity (86.6%-96.0%), specificity (66.7%-99.0%), positive predictive value (95.4%-99.0%), and interrater reliability (Youden J = 0.60-0.92) were generally stable across datasets and across strata. Some variation in performance in the stratified analyses was observed but largely reflected changes in the composition of the strata. In Saskatchewan, the preferred algorithm had a sensitivity of 96%, specificity of 99%, positive predictive value of 99%, and negative predictive value of 96%. CONCLUSIONS: The performance of each algorithm was remarkably consistent across datasets. The preferred algorithm required ≥3 MS-related claims from any combination of inpatient, outpatient, or DMT use within 1 year. We recommend this algorithm as the standard AHC case definition for MS.

19.
Brain ; 142(3): 617-632, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30759186

RESUMO

Elucidation of distinct T-cell subsets involved in multiple sclerosis immune-pathophysiology continues to be of considerable interest since an ultimate goal is to more selectively target the aberrant immune response operating in individual patients. While abnormalities of both effector (Teff) and regulatory (Treg) T cells have been reported in patients with multiple sclerosis, prior studies have mostly assessed average abnormalities in either limb of the immune response, rather than both at the same time, which limits the ability to evaluate the balance between effectors and regulators operating in the same patient. Assessing both phenotypic and functional responses of Teffs and Tregs has also proven important. In studies of adults with multiple sclerosis, in whom biological disease onset likely started many years prior to the immune assessments, an added challenge for any reported abnormality is whether the abnormality indeed contributes to the disease (and hence of interest to target therapeutically) or merely develops consequent to inflammatory injury (in which case efforts to develop targeted therapies are unlikely to be beneficial). Paediatric-onset multiple sclerosis, though rare, offers a unique window into early disease mechanisms. Here, we carried out a comprehensive integrated study, simultaneously assessing phenotype and functional responses of both effector and regulatory T cells in the same children with multiple sclerosis, monophasic inflammatory CNS disorders, and healthy controls, recruited as part of the multicentre prospective Canadian Pediatric Demyelinating Disease Study (CPDDS). Stringent standard operating procedures were developed and uniformly applied to procure, process and subsequently analyse peripheral blood cells using rigorously applied multi-parametric flow cytometry panels and miniaturized functional assays validated for use with cryopreserved cells. We found abnormally increased frequencies and exaggerated pro-inflammatory responses of CD8+CD161highTCR-Vα7.2+ MAIT T cells and CD4+CCR2+CCR5+ Teffs in paediatric-onset multiple sclerosis, compared to both control groups. CD4+CD25hiCD127lowFOXP3+ Tregs of children with multiple sclerosis exhibited deficient suppressive capacity, including diminished capacity to suppress disease-implicated Teffs. In turn, the implicated Teffs of multiple sclerosis patients were relatively resistant to suppression by normal Tregs. An abnormal Teff/Treg ratio at the individual child level best distinguished multiple sclerosis children from controls. We implicate abnormalities in both frequencies and functional responses of distinct pro-inflammatory CD4 and CD8 T cell subsets, as well as Treg function, in paediatric-onset multiple sclerosis, and suggest that mechanisms contributing to early multiple sclerosis development differ across individuals, reflecting an excess abnormality in either Teff or Treg limbs of the T cell response, or a combination of lesser abnormalities in both limbs.

20.
Ann Neurol ; 85(3): 340-351, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30719730

RESUMO

OBJECTIVE: Central nervous system pathology in multiple sclerosis includes both focal inflammatory perivascular injury and injury to superficial structures, including the subpial region of the cortex, which reportedly exhibits a gradient of damage from the surface inward. We assessed how early in the multiple sclerosis course a "surface-in" process of injury suggesting progressive biology may begin. METHODS: We focused on the thalamus, which notably has both a cerebrospinal fluid (CSF) interface and a white matter interface. Thalamic volume trajectories were assessed in a prospectively followed cohort of children from initial presentation with either multiple sclerosis or monophasic acquired demyelination, and healthy controls. Voxelwise volume changes were calculated using deformation-based morphometry, and analyzed in relation to distance from the CSF interface by mixed effects modeling and semiparametric smoothing methods. RESULTS: Twenty-seven children with multiple sclerosis and 73 children with monophasic demyelination were prospectively followed with yearly brain scans (mean follow-up = 4.6 years, standard deviation = 1.9). A total of 282 healthy children with serial scans were included as controls. Relative to healthy controls, children with multiple sclerosis and children with monophasic demyelination demonstrated volume loss in thalamic regions adjacent to the white matter. However, only children with multiple sclerosis exhibited an additional surface-in gradient of thalamic injury on the ventricular side, which was already notable in the first year of clinical disease (asymptote estimate = 3.01, 95% confidence interval [CI] = 1.44-4.58, p = 0.0002) and worsened over time (asymptote:time estimate = 0.33, 95% CI = 0.12-0.54, p = 0.0021). INTERPRETATION: Our results suggest that a multiple sclerosis disease-specific surface-in process of damage can manifest at the earliest stages of the disease. ANN NEUROL 2019;85:340-351.

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