Incidence and prevalence of paediatric-onset multiple sclerosis in two Canadian provinces: a population-based study representing over half of Canada's population.

BACKGROUND: Population-based studies estimating the epidemiology of paediatric-onset multiple sclerosis (PoMS) are scarce. METHODS: We accessed population-based health administrative data from two provinces in Canada, Ontario and British Columbia (BC). Individuals with PoMS were identified via a validated case definition. The index date ('MS onset') was the first demyelinating or MS specific claim recorded ≤18 years of age. We estimated the age-standardised annual incidence and prevalence of PoMS, and 95% CIs between 2003 and 2019. We used negative binomial regression models to assess the temporal changes in the annual crude incidence and prevalence of PoMS, and the ratios comparing sex groups. RESULTS: From 2003 to 2019, a total of 148 incident PoMS cases were identified in BC, and 672 in Ontario. The age-standardised annual incidence of PoMS was stable in both provinces, averaging 0.95 (95% CI 0.79 to 1.13) in BC and 0.98 (95%CI 0.84 to 1.12) in Ontario per 100 000 person-years. The incidence ratio by sex (female vs male) was also stable over the study period, averaging 1.5:1 (95% CI 1.06 to 2.08, BC) and 2.0:1 (95% CI 1.61 to 2.59, Ontario). The age-standardised prevalence per 100 000 people rose from 4.75 (2003) to 5.52 (2019) in BC and from 2.93 (2003) to 4.07 (2019) in Ontario, and the increase was statistically significant in Ontario (p=0.002). There were more female prevalent PoMS cases than males in both provinces. CONCLUSIONS: Canada has one of the highest rates of PoMS globally, and the prevalence, but not incidence, has increased over time. Allocation of resources to support the growing youth population with MS should be a priority.

Gastrointestinal conditions in the multiple sclerosis prodrome.

OBJECTIVE: To investigate gastrointestinal (GI)-related physician visits and drug dispensations in the 5 years preceding a first recorded demyelinating event or multiple sclerosis (MS) onset. METHODS: Using linked administrative and clinical data from British Columbia (1996-2013), Canada, we identified an administrative cohort via a validated algorithm (n = 6863), a clinical cohort diagnosed at a MS clinic (n = 966), and matched controls (administrative cohort: n = 31,865; clinical cohort: n = 4534). In each cohort, the 5 years before a first demyelinating event or MS symptom onset (i.e., index date) were examined. We compared rates of GI-related physician visits and risk of ≥1 GI-related dispensation between MS cases and controls using negative binomial and robust Poisson models. Sex differences were tested using interaction terms. RESULTS: The administrative cohort MS cases had higher rates of physician visits related to gastritis and duodenitis (adjusted rate/risk ratio (aRR):1.42, 95% CI: 1.10-1.83) and diseases of the esophagus (aRR: 1.46, 95% CI: 1.06-2.02) prior to the index date. MS cases also had greater risk of at least one dispensation for several drug classes, including constipation-related (aRR: 1.82, 95% CI: 1.50-2.22), antiemetics/antinauseants (aRR: 1.64, 95% CI: 1.43-1.89), and propulsives (promotility drugs; aRR: 1.62, 95% CI: 1.47-1.79). Men had a disproportionally higher relative risk for propulsives than women (aRR: men = 2.32, 95% CI: 1.79-3.00; women = 1.54, 95% CI: 1.36-1.72). Several findings were similar in the smaller clinical cohort though none reached statistical significance. INTERPRETATION: GI-related physician visits and drug dispensations were more common in the 5 years before the first demyelinating event versus matched controls. GI symptoms are a measurable feature of the prodromal or early phase of MS, with a sex difference evident.

Psychiatric Comorbidity During the Prodromal Period in Patients With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Psychiatric morbidity is common after a multiple sclerosis (MS) diagnosis. However, little is known about psychiatric comorbidity during the prodromal phase (before MS onset). To compare the prevalence and relative burden of psychiatric morbidity in individuals with MS with matched controls before MS onset. METHODS: Using linked administrative and clinical data from British Columbia, Canada, we identified cases with MS through a validated algorithm or from neurologist-diagnosed MS clinic attendees. Cases were matched by age, sex, and geographical location with up to 5 general population controls. We identified psychiatric morbidity through a validated definition and determined its prevalence in cases/controls in the 5 years before the first demyelinating claim of cases with MS ("administrative cohort") or symptom onset ("clinical cohort") and estimated case/control prevalence ratios with 95% CIs. We also compared the yearly number of physician visits for psychiatric morbidity, visits to psychiatrists, psychiatric-related admissions, and psychotropic dispensations pre-MS onset in cases/controls regardless of whether psychiatric morbidity algorithm was fulfilled using negative binomial regression fitted through generalized estimating equations; results were reported as adjusted rate ratios with 95% CIs. We assessed yearly trends through interaction terms between cases/controls and each year pre-MS onset. RESULTS: The administrative cohort comprised 6,863/31,865 cases/controls; the clinical cohort comprised 966/4,534 cases/controls. Over the entire 5-year period pre-MS onset, 28.0% (1,920/6,863) of cases and 14.9% (4,738/31,865) of controls (administrative cohort) had psychiatric morbidity, as did 22.0% (213/966) of clinical cases and 14.1% (638/4,534) controls. Psychiatric morbidity prevalence ratios ranged from 1.58; 95% CI 1.38-1.81 (clinical cohort) to 1.91; 95% CI 1.83-2.00 (administrative cohort). In the administrative cohort, health care use was higher for cases in each year pre-MS onset (all 95% CIs >1); physician visits were 78% higher in year 5 pre-MS onset and 124% 1 year before; visits to psychiatrists were 132% higher in year 5 and 146% in year 1; hospitalizations were 129% higher in year 5 and 197% in year 1; and prescription dispensations were 72% higher in year 5 and 100% in year 1. Results were not significant in the clinical cohort. DISCUSSION: Psychiatric morbidity represents a significant burden before MS onset and may be a feature of the MS prodrome.

Sex and age differences in the Multiple Sclerosis prodrome.

Background and objectives: Little is known of the potential sex and age differences in the MS prodrome. We investigated sex and age differences in healthcare utilization during the MS prodrome. Methods: This was a population-based matched cohort study linking administrative and clinical data from British Columbia, Canada (population = 5 million). MS cases in the 5 years preceding a first demyelinating event ("administrative cohort;" n = 6,863) or MS symptom onset ("clinical cohort;" n = 966) were compared to age-, sex- and geographically-matched controls (n = 31,865/4,534). Negative binomial and modified Poisson models were used to compare the rates of physician visits and hospitalizations per international classification of diseases chapter, and prescriptions filled per drug class, between MS cases and controls across sex and age-groups (< 30, 30-49, ≥50 years). Results: In the administrative cohort, males with MS had a higher relative rate for genitourinary-related visits (males: adjusted Rate Ratio (aRR) = 1.65, females: aRR = 1.19, likelihood ratio test P = 0.02) and antivertigo prescriptions (males: aRR = 4.72, females: aRR = 3.01 P < 0.01). Injury and infection-related hospitalizations were relatively more frequent for ≥50-year-olds (injuries < 30/30-49/≥50: aRR = 1.16/1.39/2.12, P < 0.01; infections 30-49/≥50: aRR = 1.43/2.72, P = 0.03), while sensory-related visits and cardiovascular prescriptions were relatively more common in younger persons (sensory 30-49/≥50: aRR = 1.67/1.45, P = 0.03; cardiovascular < 30/30-49/≥50: aRR = 1.56/1.39/1.18, P < 0.01). General practitioner visits were relatively more frequent in males (males: aRR = 1.63, females: aRR = 1.40, P < 0.01) and ≥50-year-olds (< 30/≥50: aRR = 1.32/1.55, P = 0.02), while differences in ophthalmologist visits were disproportionally larger among younger persons, < 50-years-old (< 30/30-49/≥50: aRR = 2.25/2.20/1.55, P < 0.01). None of the sex and age-related differences in the smaller clinical cohort reached significance (P ≥ 0.05). Discussion: Sex and age-specific differences in healthcare use were observed in the 5 years before MS onset. Findings demonstrate fundamental heterogeneity in the MS prodromal presentation.

The association between diabetes and excessive daytime sleepiness among American adults aged 20-79 years: findings from the 2015-2018 National Health and Nutrition Examination Surveys.

PURPOSE: To examine the association between diabetes and excessive daytime sleepiness (EDS). METHODS: Using the 2015-2018 cycles of the National Health and Nutrition Examination Survey, we applied survey-featured modified Poisson regression to estimate the association between diabetes and EDS among American adults aged 20-79 years, adjusting for confounding demographic, clinical and lifestyle variables. Effect modification by age, sex, race, education, income, sleep apnea and inadequate sleep was assessed. We performed sensitivity analyses using propensity score matched (PS) data and applied ordinal logistic regression using multiple levels of daytime sleepiness. Among people with diabetes, we assessed the association between EDS and diabetes care variables. RESULTS: Of the 6289 participants, 895 (10%) had diabetes. The estimated prevalence of EDS was higher among adults with diabetes (30.6%) than counterparts without diabetes (26.3%). After adjusting for confounding variables, diabetes remained associated with EDS (aPR:1.20; 95%CI:1.06 1.36). There was no statistically significant effect modification. Sensitivity analyses confirmed our main results. Among people with diabetes, there was limited evidence that the diabetes care variables were related to EDS. CONCLUSIONS: Among American adults, diabetes is associated with EDS after controlling for confounding variables. Although the cross-sectional design is a limitation, our findings support further exploration of the role of diabetes in EDS.

Fatigue, sleep disorders, anaemia and pain in the multiple sclerosis prodrome.

BACKGROUND: There is increasing evidence of prodromal multiple sclerosis (MS). OBJECTIVE: The aim of this study was to determine whether fatigue, sleep disorders, anaemia or pain form part of the MS prodrome. METHODS: This population-based matched cohort study used linked administrative and clinical databases in British Columbia, Canada. The odds of fatigue, sleep disorders, anaemia and pain in the 5 years preceding the MS cases' first demyelinating claim or MS symptom onset were compared with general population controls. The frequencies of physician visits for these conditions were also compared. Modifying effects of age and sex were evaluated. RESULTS: MS cases/controls were assessed before the first demyelinating event (6863/31,865) or MS symptom onset (966/4534). Fatigue (adj.OR: 3.37; 95% CI: 2.76-4.10), sleep disorders (adj.OR: 2.61; 95% CI: 2.34-2.91), anaemia (adj.OR: 1.53; 95% CI: 1.32-1.78) and pain (adj.OR: 2.15; 95% CI: 2.03-2.27) during the 5 years preceding the first demyelinating event were more frequent among cases, and physician visits increased for cases relative to controls. The association between MS and anaemia was greater for men; that between MS and pain increased with age. Pre-MS symptom onset, sleep disorders (adj.OR: 1.72; 95% CI: 1.12-2.56) and pain (adj.OR: 1.53; 95% CI: 1.32-1.76) were more prevalent among cases. CONCLUSION: Fatigue, sleep disorders, anaemia and pain were elevated before the recognition of MS. The relative anaemia burden was higher in men and pain more evident among older adults.

A systematic review of morbidities suggestive of the multiple sclerosis prodrome.

INTRODUCTION: The identification of a prodromal phase in multiple sclerosis (MS) could have major implications for earlier recognition and management of MS. The authors conducted a systematic review assessing studies of morbidities before, or at, MS onset or diagnosis.Areas covered: Two independent reviewers searched Medline, Embase, Psycinfo and CINAHL from inception to February 8th, 2019. To be eligible, studies had to be published in English and report the relative occurrence of at least one morbidity or symptom before, or at, MS onset or diagnosis among MS cases in comparison to a control group not known to have MS. Findings were narratively synthesized. Study quality was assessed using the Newcastle-Ottawa scale (NOS, maximum score 9).Expert opinion: Twenty-nine studies were included, which comprised 83,590 MS cases and 396,343 controls. Most were case-control studies (25/29), 8/29 were of high quality (NOS≥8) and 19/29 examined the period before MS symptom onset. Most studies assessing anxiety, depression, migraine and lower cognitive performance found these conditions to be more prevalent before MS onset or diagnosis relative to controls. There was limited evidence to implicate other conditions. Thus, there is evidence that anxiety, depression, migraine and lower cognitive performance form part of the MS prodrome.

Role of Postoperative Patient-Reported Outcomes to Predict Ankle Arthroplasty and Arthrodesis Revision.

BACKGROUND: Patient-reported outcomes are becoming common for measuring patient-centric outcomes in surgery. However, there is little known about the relationship between postoperatively collected patient-reported outcomes and objective clinical outcomes. The objective of this study was to measure whether postoperative Ankle Osteoarthritis Scale (AOS) values were associated with risk of revision among patients having ankle arthrodesis or total ankle arthroplasty for treatment of symptomatic end-stage ankle arthritis. METHODS: This is a retrospective analysis of a longitudinal cohort of ankle arthrodesis and total ankle arthroplasty patients. A single center recruited patients between 2003 and 2013 and follow-up was at least 4 years. Patients completed the AOS preoperatively and annually following surgery. An extended Cox regression model incorporating time-varying AOS values was used to model risk of failure. A total of 336 patients and 348 ankles were included, representing 139 ankle arthrodesis procedures and 209 total ankle arthroplasties. RESULTS: The median follow-up time for revisions was 8.2 years and 46 patients had a revision. Higher values of patients' AOS scores in the postoperative period were associated with a higher likelihood of revision (hazard ratio, 1.04 per 1-point increase; 95% confidence interval, 1.03-1.05). Ankle arthrodesis was associated with a reduced risk of revision compared with ankle fusion (hazard ratio, 0.12; 95% confidence interval, 0.03-0.49). CONCLUSION: This study showed that persistent pain and poor function after fusion or replacement surgery, as measured by elevated values of the AOS, were associated with higher risk of further surgery. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Validating the Foot and Ankle Outcome score for measuring foot dysfunction among hallux valgus surgery patients using item response theory.

BACKGROUND: There is an absence of high quality research validating instruments that measure foot and ankle related quality of life among hallux valgus (bunion) patients' perspectives. The Foot and Ankle Outcome Scale is a patient-reported outcome instrument, that when administered to patients with symptomatic hallux valgus, provides a patient-centric perspective of their foot function. The aim of this study is to assess the psychometric properties of the instrument's five subscales among preoperative bunion surgery patients. METHODS: The Foot and Ankle Outcome Scale instrument measures Pain, Symptoms, Activities of Daily Living, Sport and Recreational Activities and Foot/Ankle Related Quality of Life. Preoperative data is collected from a sample of patients scheduled for surgical treatment of their condition in Vancouver, Canada. Classical and item response theory methods are used to report on reliability, validity and differential item functioning among subgroups. RESULTS: This study included 249 surveys, representing an overall response rate of 44.1% among 564 eligible patients. The instrument demonstrated high reliability for all subscales, though 18 items across subscales, exhibited poor discrimination between item levels. Four items score differently according to patients' sex and one item scored differently by age. CONCLUSIONS: The instrument measures five domains of health important to bunion patients. These findings suggest that the current instrument can be used with an understanding of its limitations, including redundant questions and sex-based differences. Future research should revise a number of items. The results highlight the importance of the psychometric analyses of instruments in specific patient populations.

Assessing quality of life in diabetes: II - Deconstructing measures into a simple framework.

A growing number of instruments measuring diabetes-specific health-related quality of life (HRQOL) have been identified in previous systematic reviews, the most recent being published in 2008. The purpose of this paper is report on an updated systematic review of diabetes-specific HRQOL measures highlighting the time period 2006-2016; to deconstruct existing diabetes-specific HRQOL measures into a simple framework for evaluating the goodness-of-fit between specific research needs and instrument characteristics; and to present core characteristics of measures not yet reported in other reviews to further facilitate scale selection. Using the databases Medline, Pubmed, CINAHL, OVID Embase, and PsycINFO, we identified 20 diabetes-specific HRQOL measures that met our inclusion criteria. For each measure, we extracted eight core characteristics for our measurement selection framework. These characteristics include target population (type 1 vs. type 2), number and type of HRQOL dimensions measured and scored, type of score and calculation algorithm, sensitivity to change data reported in subsequent studies, number of survey items, approximate time length to complete, number of studies using the instrument in the past 10years, and specific languages instruments is translated. This report provides a way to compare and contrast existing diabetes-specific HRQOL measures to aid in appropriate scale selection and utilization.