Okechukwu Ekuma

Health-care use before a first demyelinating event suggestive of a multiple sclerosis prodrome: a matched cohort study

BACKGROUND Degenerative processes in neurodegenerative diseases can start years before clinical manifestation. We aimed to establish whether a multiple sclerosis prodromal period exists by examining patterns of health-care use before a first demyelinating event. METHODS In this matched cohort study, we used data from linked health administrative and clinical databases from four Canadian provinces (British Columbia, Saskatchewan, Manitoba, and Nova Scotia) to compare hospital, physician, and prescription use data from people with multiple sclerosis and matched general population controls in the 5 years before the first demyelinating disease claim (health administrative index date) or clinically reported symptom onset (clinical index date). Rate ratios (RRs) were estimated using negative binomial regression and combined across provinces using random effect models. The primary outcome was all-cause use of health care during each of the 5 years before the health administrative or clinical index date. FINDINGS The health administrative cohort included 14 428 multiple sclerosis cases and 72 059 matched controls for whom data were available between April, 1984, and April, 2014. Annual health-care use increased steadily between 5 years and 1 year before the first demyelinating disease claim in people with multiple sclerosis compared with controls (from RR 1·26 [95% CI 1·16-1·36] to 1·78 [1·50-2·10] for hospital admissions; from 1·24 [1·16-1·32] to 1·88 [1·72-2·07] for physician claims; and from 1·23 [1·06-1·41] to 1·49 [1·41-1·59] for prescriptions, assessed as drug classes). Similar patterns for physician claims and prescriptions were observed in the cohort with available clinical symptom onset (3202 individuals with multiple sclerosis and 16 006 controls), although the differences in use in each of the 5 years mostly did not reach statistical significance. INTERPRETATION More frequent use of health care in patients with multiple sclerosis than in controls in the 5 years before a first demyelinating event, according to health administrative data, suggests the existence of a measurable multiple sclerosis prodrome. These findings have clinical and research implications, including the establishment of an earlier window of opportunity to identify and potentially treat multiple sclerosis. FUNDING National Multiple Sclerosis Society.

The impact of opioid prescription dose and duration during a Workers Compensation claim, on post‐claim continued opioid use: A retrospective population‐based study

BACKGROUND Workers Compensation Board (WCB) recipients are a group commonly prescribed opioids. METHODS We explored factors influencing post-claim opioid dose and duration by linking data from 22,451 claims with the Manitoba Center for Population Health registry. RESULTS On average, the WCB paid for 94.55% of opioids prescribed during a claim. The amount paid for by the WCB varied significantly by total opioids prescribed. The main predictors of high opioid dosage (120 + morphine equivalents (ME)/day) during the first year post-claim (logistic regression), and of longer post-claim opioid usage (survival analysis), included opioid dosage during the final month of the claim both paid for and not paid for by the WCB. CONCLUSIONS Amongst low dose opioid claims, the WCB covers most opioids prescribed. Higher opioid dose WCB recipients are often prescribed opioids not covered by the WCB. Both opioids paid for and not paid for by the WCB are associated with post-claim opioid use.

Drinking pattern as a predictor of cardiovascular harm: A longitudinal study using alternative drinking pattern measures

Background: This study compared measures of drinking pattern at baseline, and subsequent cardiovascular harm in a longitudinal study. Method: In Winnipeg, Manitoba, Canada, a community sample of 1154 adult men and women was interviewed at baseline in 1990 and 1991, then followed with all‐cause surveillance. Cox proportional hazards regressions were used to assess the “time to event” for morbidity or mortality from coronary heart disease (CHD), hypertension, or other cardiovascular disease. Surveillance was through a 10‐year series of documented physician visits, hospital discharges and deaths, classified by diagnosis. Drinking pattern was defined as either ⩾8 drinks (80–120 g of alcohol or more) at a sitting in the past 12 months, a report of feeling the effects, or ⩾5 usual drinks/day. Results: There were 104 individuals with CHD events in the data. When ⩾8 drinks at a sitting was the predictor, there were significant hazards for CHD among both men and women [hazard ratio (HR) = 2.32 and 1.07; p = 0.004 and 0.04], and marginally significant hazards for hypertension among men (HR = 1.40; p = 0.08). When feeling the effects or ⩾5 usual drinks/day were the predictors, there were no significant hazards of drinking pattern. Conclusion: Eight or more drinks was a stronger predictor of cardiovascular harm in these data than were feeling the effects or ⩾5 usual drinks.

Maternal depression and anxiety disorders (MDAD) and child development: A Manitoba population-based study

Objective To examine the association between maternal depression and anxiety disorders (MDAD) and child development assessed during the kindergarten year. Methods Administrative data from several health and social databases in Manitoba, Canada, were used to study 18,331 mother-child pairs. MDAD over the period from one year prior to the childs birth to the kindergarten year was defined using physician diagnoses and filled prescriptions. Child development was assessed during the kindergarten year using the Early Development Instrument (EDI) which measures vulnerability across five domains of development. Structural equation modeling was used to examine associations between timing, recurrence and severity of MDAD and child outcomes. Health at Birth (preterm, low birth weight, neonatal intensive care stay and long birth hospitalization), Family Context (teen mother, lone parent, socio-economic status (SES)), child age and child sex were covariates. Results MDAD had a modest negative association with child EDI scores across all models tested, particularly for social, emotional and physical development. Prenatal MDAD had a stronger negative association with outcomes than other time periods; however, recurrent MDAD had a stronger negative association with outcomes than any specific time period or MDAD severity. The influence of MDAD was mediated by Family Context, which had a strong, negative association with outcomes, particularly language and cognitive development. Conclusion The number of time periods a child was exposed to MDAD in early childhood was more negatively associated with five areas of child development than timing or severity. Prenatal exposure may be more sensitive to MDAD than other time periods. The familial context (teen mother, lone parenthood and low SES) had a stronger influence on child outcomes than MDAD. Findings can be used to inform interventions which address maternal mental health from the prenatal period onward, and to support disadvantaged families to encourage healthy birth outcomes, early childhood development and school readiness.

Predictors of Childhood Anxiety: A Population-Based Cohort Study

Background Few studies have explored predictors of early childhood anxiety. Objective To determine the prenatal, postnatal, and early life predictors of childhood anxiety by age 5. Methods Population-based, provincial administrative data (N = 19,316) from Manitoba, Canada were used to determine the association between demographic, obstetrical, psychosocial, medical, behavioral, and infant factors on childhood anxiety. Results Risk factors for childhood anxiety by age 5 included maternal psychological distress from birth to 12 months and 13 months to 5 years post-delivery and an infant 5-minute Apgar score of ≤7. Factors associated with decreased risk included maternal age < 20 years, multiparity, and preterm birth. Conclusion Identifying predictors of childhood anxiety is a key step to early detection and prevention. Maternal psychological distress is an early, modifiable risk factor. Future research should aim to disentangle early life influences on childhood anxiety occurring in the prenatal, postnatal, and early childhood periods.

A comparison of opioid use between WCB recipients and other Manitobans for knee, shoulder, back and carpal tunnel release procedures

Background This studys objectives were to evaluate whether WCB claimants with conditions requiring certain surgical procedures are more likely to be prescribed outpatient opioids than other Manitobans and whether those prescribed opioids are more likely to still be on opioid medications 6 months post procedure. Methods We compared 7,246 WCB claims for a number of surgical procedures to 65,032 similar procedures performed in other Manitobans. Logistic regression was used to explore the association between being a WCB claimant and being prescribed opioids, while controlling for type of surgical procedure and other potential confounders. Results WCB claimants were more likely than other Manitobans to be prescribed opioids (adjusted OR 1.38; 95%CI 1.30–1.47). Amongst those prescribed opioids, the odds of being still on opioids 6 months post‐procedure were not significantly elevated for WCB claimants (adjusted OR 1.09 95%CI 0.97–1.23). Conclusions WCB claimants are prescribed opioids more often than non‐claimants for similar procedures. Am. J. Ind. Med. 59:257–263, 2016.

Exploring the boundary between health protective and hazardous drinking in a community cohort

We sought to identify a level of alcohol consumption representing the boundary between health protective and hazardous drinking. The Winnipeg Health and Drinking Survey began in 1990-91 (n = 1257). Seven years later, a third wave of interviews (n = 785) expanded questions on heavy episodic drinking (HED) and assessed the consumption of > or = 3, > or = 5, > or = 8, and > or = 12 drinks at a sitting for each of wine, beer and liquor (equivalent to about 40 g, 65 g, 105 g and 155 g of ethanol). Cox proportional hazards models were based on seven years of illness and mortality data following the Wave 3 interview, and were stratified by gender and HED definition. For HED of > or = 40 g, > or = 65 g, > or = 105 g, or > or = 155 g per occasion, the hazard ratios for morbidity and mortality from all causes were 1.06, 1.09, 1.17, and 1.16 respectively in women, and 1.00, 0.98, 1.02, and 1.02 in men. Most of these hazard ratios were significant in women, whereas none was significant in men. This study did not provide support for a definition of HED that could divide protective from hazardous alcohol consumption.

Identifying optic neuritis and transverse myelitis using administrative data

OBJECTIVE We aimed to validate administrative case definitions to identify individuals with optic neuritis (ON) or transverse myelitis (TM), and to distinguish which of these individuals had a monophasic presentation versus multiple sclerosis (MS). METHODS Using population-based administrative (health claims) data from Manitoba, Canada, we developed case definitions for ON and TM, and distinguished individuals who had monophasic presentations (ON-nonMS, TM-nonMS) versus those later diagnosed with MS (ON-MS, TM-MS). We compared performance of these case definitions to diagnoses based on medical records review in a reference cohort (n = 1251) using sensitivity, specificity, positive predictive value and negative predictive value. We estimated the annual incidence of these conditions for a three-year period (2011-2013). RESULTS When compared to medical records, using ≥1 physician visit, the case definition for ON had good sensitivity (88.5%), and specificity (82.7%) whereas the case definition for TM had low sensitivity (25.9%) and higher specificity (89.0%). Findings for the other case definitions tested were: ON-MS (sensitivity: 84.1%, specificity: 83.9%), ON-nonMS (sensitivity: 66.7%, specificity 98.5%), TM-MS (sensitivity: 22.2%, specificity: 90.4%), and TM-nonMS (sensitivity: 3.7%, specificity: 99.7%). After applying the ON and TM case definitions to administrative data, the average annual incidence of ON over the period 2011-2013 was 75.9 per 100,000 person-years (95%CI: 72.8, 79.1) and of TM was 18.3 per 100,000 person-years (95%CI: 16.8, 19.8). CONCLUSION Administrative data can be used to identify individuals with incident ON and TM, and to distinguish those with monophasic syndromes from those with an incident presentation of MS.

Five years before multiple sclerosis onset: Phenotyping the prodrome:

Background: The multiple sclerosis (MS) prodrome is poorly characterized. Objective: To phenotype the MS prodrome via health care encounters. Methods: Using data from a population-based cohort study linking administrative and clinical data in four Canadian provinces, we compared physician and hospital encounters and prescriptions filled (via International Classification of Diseases chapters, physician specialty or drug classes) for MS subjects in the 5 years before the first demyelinating claim in an administrative cohort or the clinical symptom onset in an MS clinic-derived cohort, to age-, sex- and geographically matched controls. Rate ratios (RRs), 95% confidence intervals (95% CIs) and proportions were estimated. Results: The administrative and clinical cohorts included 13,951/66,940 and 3202/16,006 people with and without MS (cases/controls). Compared to controls, in the 5 years before the first demyelinating claim or symptom onset, cases had more physician and hospital encounters for the nervous (RR (range) = 2.31; 95% CI: 1.05–5.10 to 4.75; 95% CI: 3.11–7.25), sensory (RR (range) = 1.40; 95% CI: 1.34–1.46 to 2.28; 95% CI: 1.72–3.02), musculoskeletal (RR (range) = 1.19; 95% CI: 1.07–1.33 to 1.70; 95% CI: 1.57–1.85) and genito-urinary systems (RR (range) = 1.17; 95% CI: 1.05–1.30 to 1.59; 95% CI: 1.48–1.70). Cases had more psychiatrist and urologist encounters (RR (range) = 1.48; 95% CI: 1.36–1.62 to 1.80; 95% CI: 1.61–2.01), and higher proportions of musculoskeletal, genito-urinary or hormonal-related prescriptions (1.1–1.5 times higher, all p < 0.02). However, cases had fewer pregnancy-related encounters than controls (RR = 0.78; 95% CI: 0.71–0.86 to 0.88; 95% CI: 0.84–0.92). Conclusion: Phenotyping the prodrome 5 years before clinical recognition of MS is feasible.