Lawrence Elliott

Correlates of severe disease in patients with 2009 pandemic influenza (H1N1) virus infection

Background: In the context of 2009 pandemic influenza (H1N1) virus infection (pandemic H1N1 influenza), identifying correlates of the severity of disease is critical to guiding the implementation of antiviral strategies, prioritization of vaccination efforts and planning of health infrastructure. The objective of this study was to identify factors correlated with severity of disease in confirmed cases of pandemic H1N1 influenza. Methods: This cumulative case–control study included all laboratory-confirmed cases of pandemic H1N1 influenza among residents of the province of Manitoba, Canada, for whom the final location of treatment was known. Severe cases were defined by admission to a provincial intensive care unit (ICU). Factors associated with severe disease necessitating admission to the ICU were determined by comparing ICU cases with two control groups: patients who were admitted to hospital but not to an ICU and those who remained in the community. Results: As of Sept. 5, 2009, there had been 795 confirmed cases of pandemic H1N1 influenza in Manitoba for which the final treatment location could be determined. The mean age of individuals with laboratory-confirmed infection was 25.3 (standard deviation 18.8) years. More than half of the patients (417 or 52%) were female, and 215 (37%) of 588 confirmed infections for which ethnicity was known occurred in First Nations residents. The proportion of First Nations residents increased with increasing severity of disease (116 [28%] of 410 community cases, 74 [54%] of 136 admitted to hospital and 25 [60%] of 42 admitted to an ICU; p < 0.001), as did the presence of an underlying comorbidity (201 [35%] of 569 community cases, 103 [57%] of 181 admitted to hospital and 34 [76%] of 45 admitted to an ICU; p < 0.001). The median interval from onset of symptoms to initiation of antiviral therapy was 2 days (interquartile range, IQR 1–3) for community cases, 4 days (IQR 2–6) for patients admitted to hospital and 6 days (IQR 4–9) for those admitted to an ICU (p < 0.001). In a multivariable logistic model, the interval from onset of symptoms to initiation of antiviral therapy (odds ratio [OR] 8.24, 95% confidence interval [CI] 2.82–24.1), First Nations ethnicity (OR 6.52, 95% CI 2.04–20.8) and presence of an underlying comorbidity (OR 3.19, 95% CI 1.07–9.52) were associated with increased odds of admission to the ICU (i.e., severe disease) relative to community cases. In an analysis of ICU cases compared with patients admitted to hospital, First Nations ethnicity (OR 3.23, 95% CI 1.04–10.1) was associated with increased severity of disease. Interpretation: Severe pandemic H1N1 influenza necessitating admission to the ICU was associated with a longer interval from onset of symptoms to treatment with antiviral therapy and with the presence of an underlying comorbidity. First Nations ethnicity appeared to be an independent determinant of severe infection. Despite these associations, the cause and outcomes of pandemic HINI influenza may involve many complex and interrelated factors, all of which require further research and analysis.

The rising prevalence and changing age distribution of multiple sclerosis in Manitoba

Objective: Several studies suggest an increasing prevalence of multiple sclerosis (MS) in Canada. We aimed to validate a case definition for MS using administrative health insurance data, and to describe the incidence and prevalence of MS in Manitoba, Canada. Methods: We used provincial administrative claims data to identify persons with demyelinating disease using International Classification of Diseases 9/10 codes and prescription claims. To validate the case definition, questionnaires were mailed to 2,000 randomly selected persons with an encounter for demyelinating disease, requesting permission for medical records review. We used diagnoses abstracted from medical records as the gold standard to evaluate candidate case definitions using administrative data. Results: From 1984 to 1997, cases of MS using claims data were defined as persons with ≥7 medical contacts for MS. From 1998 onward, cases were defined as persons with ≥3 medical contacts. As compared to medical records, this definition had a positive predictive value of 80.5% and negative predictive value of 75.5%. From 1998 to 2006, the average age- and sex-adjusted annual incidence of MS per 100,000 population was 11.4 (95% confidence interval [CI] 10.7–12.0). The age-adjusted prevalence of MS per 100,000 population increased from 32.6 (95% CI 29.4–35.8) in 1984 to 226.7 (95% CI 218.1–235.3) in 2006, with the peak prevalence shifting to older age groups. Conclusion: The prevalence of multiple sclerosis (MS) in Manitoba is among the highest in the world. The rising prevalence with minimally changing incidence suggests improving survival. This study supports the use of administrative data to develop case definitions and further define the epidemiology of MS.

Inadequate prenatal care and its association with adverse pregnancy outcomes: A comparison of indices

BackgroundThe objectives of this study were to determine rates of prenatal care utilization in Winnipeg, Manitoba, Canada from 1991 to 2000; to compare two indices of prenatal care utilization in identifying the proportion of the population receiving inadequate prenatal care; to determine the association between inadequate prenatal care and adverse pregnancy outcomes (preterm birth, low birth weight [LBW], and small-for-gestational age [SGA]), using each of the indices; and, to assess whether or not, and to what extent, gestational age modifies this association.MethodsWe conducted a population-based study of women having a hospital-based singleton live birth from 1991 to 2000 (N = 80,989). Data sources consisted of a linked mother-baby database and a physician claims file maintained by Manitoba Health. Rates of inadequate prenatal care were calculated using two indices, the R-GINDEX and the APNCU. Logistic regression analysis was used to determine the association between inadequate prenatal care and adverse pregnancy outcomes. Stratified analysis was then used to determine whether the association between inadequate prenatal care and LBW or SGA differed by gestational age.ResultsRates of inadequate/no prenatal care ranged from 8.3% using APNCU to 8.9% using R-GINDEX. The association between inadequate prenatal care and preterm birth and LBW varied depending on the index used, with adjusted odds ratios (AOR) ranging from 1.0 to 1.3. In contrast, both indices revealed the same strength of association of inadequate prenatal care with SGA (AOR 1.4). Both indices demonstrated heterogeneity (non-uniformity) across gestational age strata, indicating the presence of effect modification by gestational age.ConclusionSelection of a prenatal care utilization index requires careful consideration of its methodological underpinnings and limitations. The two indices compared in this study revealed different patterns of utilization of prenatal care, and should not be used interchangeably. Use of these indices to study the association between utilization of prenatal care and pregnancy outcomes affected by the duration of pregnancy should be approached cautiously.

Post-traveler's diarrhea irritable bowel syndrome: a prospective study.

Abstract Objective Anecdotal evidence suggests that irritable bowel syndrome (IBS) can develop after an episode of traveler’s diarrhea (TD). This observation supports a contemporary paradigm proposed for the etiology of IBS and may have important implications for public health strategies aimed at preventing TD. This study aimed to determine the incidence of IBS in people experiencing TD. Methods A total of 109 healthy adults traveling outside of Canada or the United States were identified and enrolled in a prospective, cohort field study. GI symptoms before and after travel were assessed using the Rome I criteria. Travel diaries and questionnaires were used to assess for TD. Results The incidence of TD in the study cohort was 44%. Among those experiencing TD, the incidence of IBS was 4.2%. In those not experiencing TD, the incidence of IBS posttravel was 1.6% (relative risk = 2.5, 95% CI = 0.2–27.2, p = 0.41, ns). There was no significant difference in the incidence of IBS between the exposed and nonexposed groups. Conclusions This study does not support a large association between TD and an increased risk of developing IBS. A small increase in relative risk may have been undetected because of the size of the study.

Mental comorbidity and multiple sclerosis: validating administrative data to support population-based surveillance

BackgroundWhile mental comorbidity is considered common in multiple sclerosis (MS), its impact is poorly defined; methods are needed to support studies of mental comorbidity. We validated and applied administrative case definitions for any mental comorbidities in MS.MethodsUsing administrative health data we identified persons with MS and a matched general population cohort. Administrative case definitions for any mental comorbidity, any mood disorder, depression, anxiety, bipolar disorder and schizophrenia were developed and validated against medical records using a a kappa statistic (k). Using these definitions we estimated the prevalence of these comorbidities in the study populations.ResultsCompared to medical records, administrative definitions showed moderate agreement for any mental comorbidity, mood disorders and depression (all k ≥ 0.49), fair agreement for anxiety (k = 0.23) and bipolar disorder (k = 0.30), and near perfect agreement for schizophrenia (k = 1.0). The age-standardized prevalence of all mental comorbidities was higher in the MS than in the general populations: depression (31.7% vs. 20.5%), anxiety (35.6% vs. 29.6%), and bipolar disorder (5.83% vs. 3.45%), except for schizophrenia (0.93% vs. 0.93%).ConclusionsAdministrative data are a valid means of surveillance of mental comorbidity in MS. The prevalence of mental comorbidities, except schizophrenia, is increased in MS compared to the general population.

Rising prevalence of vascular comorbidities in multiple sclerosis: validation of administrative definitions for diabetes, hypertension, and hyperlipidemia.

Background: Despite the importance of comorbidity in multiple sclerosis (MS), methods for comorbidity assessment in MS are poorly developed. Objective: We validated and applied administrative case definitions for diabetes, hypertension, and hyperlipidemia in MS. Methods: Using provincial administrative data we identified persons with MS and a matched general population cohort. Case definitions for diabetes, hypertension, and hyperlipidemia were derived using hospital, physician, and prescription claims, and validated in 430 persons with MS. We examined temporal trends in the age-adjusted prevalence of these conditions from 1984–2006. Results: Agreement between various case definitions and medical records ranged from kappa (κ) =0.51–0.69 for diabetes, κ =0.21–0.71 for hyperlipidemia, and κ =0.52–0.75 for hypertension. The 2005 age-adjusted prevalence of diabetes was similar in the MS (7.62%) and general populations (8.31%; prevalence ratio [PR] 0.91; 0.81–1.03). The age-adjusted prevalence did not differ for hypertension (MS: 20.8% versus general: 22.5% [PR 0.91; 0.78–1.06]), or hyperlipidemia (MS: 13.8% versus general: 15.2% [PR 0.90; 0.67–1.22]). The prevalence of all conditions rose in both populations over the study period. Conclusion: Administrative data are a valid means of tracking diabetes, hypertension, and hyperlipidemia in MS. The prevalence of these comorbidities is similar in the MS and general populations.

Social inequalities in use of prenatal care in Manitoba.

OBJECTIVEnAnalysis of regional variations in use of prenatal care to identify individual-level and neighbourhood-level determinants of inadequate prenatal care among women giving birth in the province of Manitoba.nnnMETHODSnData were obtained from Manitoba Health administrative databases and the 1996 Canadian Census. An index of prenatal care use was calculated for each singleton live birth from 1991 to 2000 (N = 149,291). Births were geocoded into 498 geographic districts, and a spatial analysis was conducted, consisting of data visualization, spatial clustering, and data modelling using Poisson regression.nnnRESULTSnWe found wide variation in rates of inadequate prenatal care across geographic areas, ranging from 1.1% to 21.5%. Higher rates of inadequate care were found in the inner-city of Winnipeg and in northern Manitoba. After adjusting for individual characteristics, the highest rates of inadequate prenatal care were among women living in neighbourhoods with the lowest average family income, the highest proportion of the population who were unemployed, the highest rates of recent immigrants, the highest percentage of the population reporting Aboriginal status, the highest percentage of single parent families, the highest percentage of the population with fewer than nine years of education, and the highest rates of women who smoked during pregnancy.nnnCONCLUSIONnSocial inequalities exist in the use of prenatal care among Manitoba women, despite there being a universally funded health care system. Regional disparities in rates of inadequate prenatal care emphasize the need for further research to determine specific risk factors for inadequate prenatal care in socioeconomically disadvantaged neighbourhoods, followed by provision of effective targeted services.

Effect of comorbidity on mortality in multiple sclerosis

Objective: We aimed to compare survival in the multiple sclerosis (MS) population with a matched cohort from the general population, and to evaluate the association of comorbidity with survival in both populations. Methods: Using population-based administrative data, we identified 5,797 persons with MS and 28,807 controls matched on sex, year of birth, and region. We estimated annual mortality rates. Using Cox proportional hazards regression, we evaluated the association between comorbidity status and mortality, stratifying by birth cohort, and adjusting for sex, socioeconomic status, and region. We compared causes of death between populations. Results: Median survival from birth in the MS population was 75.9 years vs 83.4 years in the matched population. MS was associated with a 2-fold increased risk of death (adjusted hazard ratio 2.40; 95% confidence interval: 2.24–2.58). Several comorbidities were associated with increased hazard of death in both populations, including diabetes, ischemic heart disease, depression, anxiety, and chronic lung disease. The magnitude of the associations of mortality with chronic lung disease, diabetes, hypertension, and ischemic heart disease was lower in the MS population than the matched population. The most common causes of death in the MS population were diseases of the nervous system and diseases of the circulatory system. Mortality rates due to infectious diseases and diseases of the respiratory system were higher in the MS population. Conclusion: In the MS population, survival remained shorter than expected. Within the MS population, comorbidity was associated with increased mortality risk. However, comorbidity did not preferentially increase mortality risk in the MS population as compared with controls.

The utility of administrative data for surveillance of comorbidity in multiple sclerosis: a validation study.

Background: Although comorbidity is important in multiple sclerosis (MS), few validated methods for its assessment exist. We validated and applied administrative case definitions for several comorbidities in MS. Methods: Using provincial administrative data we identified persons with MS and a matched general population cohort. Case definitions for chronic lung disease (CLD), epilepsy, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and migraine were developed using administrative data, and validated against medical records. We applied these definitions to estimate the age-standardized prevalence of these comorbidities in the MS and matched cohorts. Results: Versus medical records, administrative case definitions showed moderate agreement for CLD (ĸ = 0.41), migraine (ĸ = 0.51), and epilepsy (ĸ = 0.44), fair agreement for IBS (ĸ = 0.36) and could not be calculated for IBD (small sample size). The 2005 prevalence of CLD was similar in the MS (15.6%) and general populations (14.4%). The prevalence of the remaining comorbidities was higher in the MS than the general populations: epilepsy (4.12 vs. 1.12%), IBD (0.78 vs. 0.65%), IBS (12.2 vs. 6.80%) and migraine (23.0 vs. 16.5%). Conclusions: Administrative data are valid for tracking CLD, epilepsy, and migraine in MS. The prevalence of epilepsy, IBD, IBS and migraine is increased in MS versus the general population.

Twenty-year trends in the incidence and prevalence of diagnosed anogenital warts in Canada.

Background: A vaccine has recently been licensed in many countries that protects against the human papillomavirus types 6, 11, 16, and 18. Types 6 and 11 account for approximately 90% of anogenital warts (AGWs). We describe the 20-year trends in the incidence and prevalence of AGWs in Manitoba, Canada. Methods: We used linked population-based hospital and physician databases for Manitoba for 1984 to 2004. Cases were identified using tariff (billing) and ICD codes. A case was considered to be incident if it was preceded by a 12-month interval free period of AGWs care. Otherwise, it was deemed to be prevalent. An episode was considered over once a 12-month interval had elapsed without an AGW claim. Results: Approximately 25,000 Manitobans were diagnosed with AGWs between 1985 and 2004. The annual age-standardized incidence rates peaked in 1992 (men, 149.9/100,000; women 170.8/100,000). In recent years, the rates have been increasing again, particularly for men. The male:female incidence rate ratio increased from 0.76 in 1985 to 1.25 in 2004. The highest incidence rate tended to be in those aged 20 to 24 years. Trends in prevalence were similar. Prevalence in 2004 was 165.2/100,000 for men and 128.4/100,000 for women. Conclusions: These population-based findings suggest that AGWs are a substantial burden to Manitobans and that their pattern has changed over time, with incidence and prevalence becoming higher in men than women. Monitoring the future trends in AGWs will provide an early marker of the effectiveness and duration of protection of human papillomavirus vaccination at a population level.