Trends in chronic disease incidence rates from the Canadian Chronic Disease Surveillance System. / Tendances des taux d'incidence des maladies chroniques d'après le Système canadien de surveillance des maladies chroniques.

INTRODUCTION: The Public Health Agency of Canada's Canadian Chronic Disease Surveillance System (CCDSS) produces population-based estimates of chronic disease prevalence and incidence using administrative health data. Our aim was to assess trends in incidence rates over time, trends are essential to understand changes in population risk and to inform policy development. METHODS: Incident cases of diagnosed asthma, chronic obstructive pulmonary disease (COPD), diabetes, hypertension, ischemic heart disease (IHD), and stroke were obtained from the CCDSS online infobase for 1999 to 2012. Trends in national and regional incidence estimates were tested using a negative binomial regression model with year as a linear predictor. Subsequently, models with year as a restricted cubic spline were used to test for departures from linearity using the likelihood ratio test. Age and sex were covariates in all models. RESULTS: Based on the models with year as a linear predictor, national incidence rates were estimated to have decreased over time for all diseases, except diabetes; regional incidence rates for most diseases and regions were also estimated to have decreased. However, likelihood ratio tests revealed statistically significant departures from a linear year effect for many diseases and regions, particularly for hypertension. CONCLUSION: Chronic disease incidence estimates based on CCDSS data are decreasing over time, but not at a constant rate. Further investigations are needed to assess if this decrease is associated with changes in health status, data quality, or physician practices. As well, population characteristics that may influence changing incidence trends also require exploration.

National public health system responses to diabetes and other important noncommunicable diseases : Background, goals, and results of an international workshop at the Robert Koch Institute.

Diabetes mellitus and other noncommunicable diseases (NCDs) represent an emerging global public health challenge. In Germany, about 6.7 million adults are affected by diabetes according to national health surveys, including 1.3 million with undiagnosed diabetes. Complications of diabetes result in an increasing burden for individuals and society as well as enormous costs for the health care system. In response, the Federal Ministry of Health commissioned the Robert Koch Institute (RKI) to implement a diabetes surveillance system and the Federal Center for Health Education (BZgA) to develop a diabetes prevention strategy. In a two-day workshop jointly organized by the RKI and the BZgA, representatives from public health institutes in seven countries shared their expertise and knowledge on diabetes prevention and surveillance. Day one focused on NCD surveillance systems and emphasized both the strengthening of sustainable data sources and the timely and targeted dissemination of results using innovative formats. The second day focused on diabetes prevention strategies and highlighted the importance of involving all relevant stakeholders in the development process to facilitate its acceptance and implementation. Furthermore, the effective translation of prevention measures into real-world settings requires data from surveillance systems to identify high-risk groups and evaluate the effect of measures at the population level based on analyses of time trends in risk factors and disease outcomes. Overall, the workshop highlighted the close link between diabetes prevention strategies and surveillance systems. It was generally stated that only robust data enables effective prevention measures to encounter the increasing burden from diabetes and other NCDs.

The Canadian Chronic Disease Surveillance System: A model for collaborative surveillance.

Chronic diseases have a major impact on populations and healthcare systems worldwide. Administrative health data are an ideal resource for chronic disease surveillance because they are population-based and routinely collected. For multi-jurisdictional surveillance, a distributed model is advantageous because it does not require individual-level data to be shared across jurisdictional boundaries. Our objective is to describe the process, structure, benefits, and challenges of a distributed model for chronic disease surveillance across all Canadian provinces and territories (P/Ts) using linked administrative data. The Public Health Agency of Canada (PHAC) established the Canadian Chronic Disease Surveillance System (CCDSS) in 2009 to facilitate standardized, national estimates of chronic disease prevalence, incidence, and outcomes. The CCDSS primarily relies on linked health insurance registration files, physician billing claims, and hospital discharge abstracts. Standardized case definitions and common analytic protocols are applied to the data for each P/T; aggregate data are shared with PHAC and summarized for reports and open access data initiatives. Advantages of this distributed model include: it uses the rich data resources available in all P/Ts; it supports chronic disease surveillance capacity building in all P/Ts; and changes in surveillance methodology can be easily developed by PHAC and implemented by the P/Ts. However, there are challenges: heterogeneity in administrative databases across jurisdictions and changes in data quality over time threaten the production of standardized disease estimates; a limited set of databases are common to all P/Ts, which hinders potential CCDSS expansion; and there is a need to balance comprehensive reporting with P/T disclosure requirements to protect privacy. The CCDSS distributed model for chronic disease surveillance has been successfully implemented and sustained by PHAC and its P/T partners. Many lessons have been learned about national surveillance involving jurisdictions that are heterogeneous with respect to healthcare databases, expertise and analytical capacity, population characteristics, and priorities.

Self-management of mood and/or anxiety disorders through physical activity/exercise. / Autogestion des troubles de l'humeur et/ou d'anxiété par l'activité physique et l'exercice.

INTRODUCTION: Physical activity/exercise is regarded as an important self-management strategy for individuals with mental illness. The purpose of this study was to describe individuals with mood and/or anxiety disorders who were exercising or engaging in physical activity to help manage their disorders versus those who were not, and the facilitators for and barriers to engaging in physical activity/exercise. METHODS: For this study, we used data from the 2014 Survey on Living with Chronic Diseases in Canada-Mood and Anxiety Disorders Component. Selected respondents (n = 2678) were classified according to the frequency with which they exercised: (1) did not exercise; (2) exercised 1 to 3 times a week; or (3) exercised 4 or more times a week. We performed descriptive and multinomial multiple logistic regression analyses. Estimates were weighted to represent the Canadian adult household population living in the 10 provinces with diagnosed mood and/or anxiety disorders. RESULTS: While 51.0% of the Canadians affected were not exercising to help manage their mood and/or anxiety disorders, 23.8% were exercising from 1 to 3 times a week, and 25.3% were exercising 4 or more times a week. Increasing age and decreasing levels of education and household income adequacy were associated with increasing prevalence of physical inactivity. Individuals with a mood disorder (with or without anxiety) and those with physical comorbidities were less likely to exercise regularly. The most important factor associated with engaging in physical activity/exercise was to have received advice to do so by a physician or other health professional. The most frequently cited barriers for not exercising at least once a week were as follows: prevented by physical condition (27.3%), time constraints/too busy (24.1%) and lack of will power/self-discipline (15.8%). CONCLUSION: Even though physical activity/exercise has been shown beneficial for depression and anxiety symptoms, a large proportion of those with mood and/or anxiety disorders did not exercise regularly, particularly those affected by mood disorders and those with physical comorbidities. It is essential that health professionals recommend physical activity/exercise to their patients, discuss barriers and support their engagement.

INTRODUCTION: L'activité physique et l'exercice constituent une stratégie d'autogestion importante pour les personnes vivant avec une maladie mentale. Cette étude visait à caractériser à la fois les personnes atteintes d'un trouble de l'humeur et/ou d'anxiété qui faisaient de l'exercice ou de l'activité physique pour aider à gérer leur trouble et celles qui n'en faisaient pas, ainsi qu'à identifier les facteurs facilitant l'activité physique et l'exercice et ceux constituant un obstacle. MÉTHODOLOGIE: L'Enquête sur les personnes ayant une maladie chronique au Canada ­ Composante des troubles de l'humeur et/ou d'anxiété de 2014 a été utilisée pour cette étude. Les répondants (n = 2 678) ont été classés en fonction de la fréquence à laquelle ils faisaient de l'exercice : (1) aucun exercice, (2) exercice une à trois fois par semaine et (3) exercice quatre fois ou plus par semaine. Nous avons pondéré toutes les estimations afin que les données soient représentatives de la population canadienne adulte vivant en logement privé dans l'une des 10 provinces et ayant déclaré avoir reçu un diagnostic de troubles de l'humeur et/ou d'anxiété. RÉSULTATS: Sur l'ensemble des Canadiens affectés, 51,0 % ne faisaient aucun exercice pour aider à gérer leur trouble de l'humeur et/ou d'anxiété, 23,8 % en faisaient d'une à trois fois par semaine et 25,3 % en faisaient quatre fois ou plus par semaine. On a établi un lien entre, d'une part, un âge plus avancé, des niveaux de scolarité plus bas et une suffisance de revenu du ménage plus faible et, d'autre part, une fréquence plus importante de l'inactivité. Les individus vivant avec un trouble de l'humeur (avec ou sans anxiété) et ceux avec des comorbidités physiques étaient moins susceptibles de faire régulièrement de l'exercice. Les recommandations d'un médecin ou d'un autre professionnel de la santé constituaient le facteur le plus important associé à la décision de faire de l'exercice. Les obstacles mentionnés le plus souvent à de l'exercice au moins une fois par semaine étaient un problème physique (27,3 %), un manque de temps ou un horaire trop chargé (24,1 %) et un manque de volonté ou d'autodiscipline (15,8 %). CONCLUSION: Malgré les bénéfices de l'activité physique et de l'exercice pour contrer les symptômes de dépression et d'anxiété, un pourcentage important de personnes atteintes d'un trouble de l'humeur et/ou d'anxiété ne fait aucun exercice sur une base régulière, particulièrement celles atteintes de trouble de l'humeur et celles présentant des comorbidités physiques. Il est essentiel que les professionnels de la santé recommandent à leurs patients de faire une activité physique ou de l'exercice, discutent avec eux des obstacles rencontrés et les encouragent à persévérer.

Use of medication and psychological counselling among Canadians with mood and/or anxiety disorders. / Recours aux médicaments et aux consultations psychologiques chez les Canadiens atteints d'un trouble de l'humeur et/ou d'anxiété.

INTRODUCTION: This study describes the use of prescription medications and psychological counselling in the past 12 months among Canadian adults with a self-reported mood and/or anxiety disorder diagnosis; the sociodemographic and clinical characteristics associated with their use; and reasons for not using them. METHODS: We used data from the 2014 Survey on Living with Chronic Diseases in Canada-Mood and Anxiety Disorders Component. The study sample (n = 2916) was divided into four treatment subgroups: (1) taking medication only; (2) having received counselling only; (3) both; or (4) neither. We combined the first three subgroups and carried out descriptive and multivariate logistic regression analyses comparing those who are taking medication and/or have received counselling in the past 12 months, versus those doing neither. Estimates were weighted to represent the Canadian adult household population living in the 10 provinces with diagnosed mood and/or anxiety disorders. RESULTS: The majority (81.8%) of Canadians with a mood and/or an anxiety disorder diagnosis reported they are taking medications and/or have received counselling (47.6% taking medications only; 6.9% received counselling only; and 27.3% taking/having received both). Upon controlling for individual characteristics, taking medications and/or having received counselling was significantly associated with older age; higher household income; living in the Atlantic region or Quebec versus Ontario; and having concurrent disorders or mood disorders only. Symptoms controlled without medication was the most common reason for not taking medications, while preferring to manage on their own and taking medications were among the common reasons for not having received counselling. CONCLUSION: The majority of Canadian adults with a mood and/or an anxiety disorder diagnosis are taking medications, while few have received counselling. Insights gained regarding the factors associated with these treatments, and reasons for not using them, emphasize the importance of discussing treatment options and perceived barriers with patients to ensure they receive the best treatment according to their needs and preference.

INTRODUCTION: L'étude décrit le recours aux médicaments sur ordonnance et aux consultations psychologiques au cours des 12 derniers mois chez les Canadiens adultes ayant déclaré avoir reçu un diagnostic de trouble de l'humeur et/ou d'anxiété, les caractéristiques sociodémographiques et cliniques associées à ce recours et les raisons invoquées pour ne pas y recourir. MÉTHODOLOGIE: L'Enquête sur les personnes ayant une maladie chronique au Canada ­ Composante sur les troubles de l'humeur et d'anxiété de 2014 a été utilisée. L'échantillon de l'étude (n = 2 916) a été divisé en quatre sous-groupes de traitement : (1) prend des médicaments seulement; (2) a reçu des consultations psychologiques seulement; (3) prend des médicaments et a reçu des consultations psychologiques; ou (4) n'a eu recours à aucun de ces deux traitements. Nous avons combiné les trois premiers sous-groupes et effectué des analyses descriptives et de régression logistique multivariée pour comparer ceux qui prenaient des médicaments et/ou avaient reçu des consultations psychologiques par rapport à ceux n'ayant pas eu recours à ces deux traitements. Nous avons pondéré toutes les estimations afin que les données soient représentatives de la population canadienne adulte vivant en logement privé dans l'une des 10 provinces et ayant déclaré avoir reçu un diagnostic de troubles de l'humeur et/ou d'anxiété. RÉSULTATS: La majorité (81,8 %) des Canadiens adultes ayant déclaré avoir reçu un diagnostic de trouble de l'humeur et/ou d'anxiété ont indiqué prendre des médicaments et/ou avoir reçu des consultations psychologiques (47,6 % prenaient des médicaments seulement, 6,9 % avaient reçu des consultations psychologiques seulement et 27,3 % avaient eu recours aux deux modalités de traitement). Après ajustement des caractéristiques individuelles, le recours aux médicaments et/ou aux consultations psychologiques était significativement associé à un âge plus avancé, à un revenu du ménage plus élevé, à une résidence dans la région de l'Atlantique ou au Québec et à un trouble de l'humeur et d'anxiété concomitants ou à un trouble de l'humeur seulement. Le contrôle des symptômes sans l'utilisation de médicaments était la raison le plus souvent invoquée pour ne pas prendre de médicaments, et le désir de se débrouiller seul et la prise de médicaments figuraient parmi les raisons le plus souvent citées pour ne pas avoir bénéficié de consultations psychologiques. CONCLUSION: La majorité des Canadiens adultes atteints d'un trouble de l'humeur et/ou d'anxiété diagnostiqué prenaient des médicaments, mais une moins grande proportion d'entre eux avaient reçu des consultations psychologiques. En dégageant les facteurs associés au recours à ces traitements et les raisons invoquées pour ne pas y recourir, cette étude met en lumière l'importance de discuter avec les patients des options de traitement et des obstacles perçus afin d'offrir un traitement adapté à leurs besoins et leurs préférences.

The burden of generalized anxiety disorder in Canada. / Le fardeau du trouble d'anxiété généralisée au Canada.

INTRODUCTION: Although generalized anxiety disorder (GAD) is common and disabling, there are few Canadian studies on this mental illness. We compared the characteristics, health status, health services use and health care needs of Canadians with GAD to those with depression. METHODS: Data are from the 2012 Canadian Community Health Survey-Mental Health, which surveyed a nationally representative sample of Canadians aged 15 years and older (n = 23 709; response rate of 68.9%). The respondents we studied had selfreported symptoms compatible with GAD and/or major depressive episode (MDE) in the preceding 12 months (n = 1598). Estimates were weighted to represent the Canadian household population. We performed descriptive and multinomial multivariate logistic regression analyses. RESULTS: In 2012, an estimated 700 000 (2.5%) Canadians aged 15 years and older reported symptoms compatible with GAD in the previous 12 months. MDE symptoms co-occurred in 50% of these individuals. Those with GAD only reported fair/poor perceived health (29.7%), moderate to severe psychological distress (81.2%) and moderate to severe disability (28.1%) comparable to (or even slightly worse) than those with MDE only (24.7%, 78.8% and 24.8% respectively). Those with comorbid GAD and MDE demonstrated the worst health outcomes; 47.3% of them reported fair/poor perceived health, 94.0% reported moderate to severe psychological distress and 52.4% reported moderate to severe disability. Nearly 50% of those with comorbid GAD and MDE reported that their need for health care was not met or only partially met, compared to about 30% of those with GAD or MDE only. CONCLUSION: While GAD is associated with levels of distress and disability comparable to (or slightly worse) than those affected by MDE only, the health status of those with comorbid disease is significantly worse than those with GAD or MDE only. Improved diagnosis, screening for comorbidity and management are essential to minimize the impacts of this mental illness.

INTRODUCTION: Bien que le trouble d'anxiété généralisée (TAG) soit une affection courante et incapacitante, peu d'études ont été menées à son sujet au Canada. Nous avons comparé les Canadiens atteints du TAG avec ceux atteints de dépression sur le plan de leurs caractéristiques, de leur état de santé, de leur utilisation des services de santé et de leurs besoins en matière de santé. MÉTHODOLOGIE: : Les données sont tirées de l'Enquête sur la santé dans les collectivités canadiennes ­ Santé mentale de 2012, qui portait sur un échantillon représentatif de la population canadienne de 15 ans et plus (n = 23 709; taux de réponse de 68,9 %). Nous avons sélectionné les répondants ayant fait état de symptômes compatibles avec un TAG ou un épisode dépressif majeur (EDM) dans les 12 mois précédant l'enquête (n = 1 598). Les estimations ont été pondérées afin de représenter la population des ménages au Canada. Nous avons mené des analyses de régression logistiques multidimensionnelles multinomiales et descriptives. RÉSULTATS: En 2012, environ 700 000 (2,5 %) Canadiens de 15 ans et plus ont fait état de symptômes compatibles avec un TAG dans les 12 derniers mois. La moitié d'entre eux ont également mentionné des symptômes d'EDM. La fréquence des perceptions d'une santé passable ou mauvaise (29,7 %), de détresse psychologique modérée et sévère (81,2 %) et d'incapacité modérée et sévère (28,1 %) était comparable (voire légèrement supérieure) chez les personnes présentant un TAG seulement par rapport aux personnes présentant un EDM seulement (respectivement 24,7 %, 78,8 % et 24,8 %). Les pires résultats de santé ont été observés chez les personnes souffrant d'un TAG et d'un EDM en comorbidité : 47,3 % ont fait état d'une santé passable ou mauvaise, 94,0 % d'une détresse psychologique modérée ou sévère et 52,4 % d'une incapacité modérée ou sévère. Près de 50 % des personnes souffrant d'un TAG et d'un EDM en comorbidité ont déclaré que leurs besoins en matière de santé n'avaient pas été satisfaits ou avaient été partiellement satisfaits, contre environ 30 % des personnes souffrant d'un TAG ou d'un EDM seulement. CONCLUSION: Bien que le TAG soit associé à des degrés de détresse et d'incapacité comparables (ou légèrement supérieurs) à l'EDM, l'état de santé des personnes présentant ces deux affections en même temps est nettement moins bon que celui des personnes présentant uniquement l'un ou l'autre. Il est essentiel d'améliorer le diagnostic, le dépistage des comorbidités et la prise en charge pour réduire les impacts de ce trouble mental.

Risk factors for severe outcomes following 2009 influenza A (H1N1) infection: a global pooled analysis.

BACKGROUND: Since the start of the 2009 influenza A pandemic (H1N1pdm), the World Health Organization and its member states have gathered information to characterize the clinical severity of H1N1pdm infection and to assist policy makers to determine risk groups for targeted control measures. METHODS AND FINDINGS: Data were collected on approximately 70,000 laboratory-confirmed hospitalized H1N1pdm patients, 9,700 patients admitted to intensive care units (ICUs), and 2,500 deaths reported between 1 April 2009 and 1 January 2010 from 19 countries or administrative regions--Argentina, Australia, Canada, Chile, China, France, Germany, Hong Kong SAR, Japan, Madagascar, Mexico, The Netherlands, New Zealand, Singapore, South Africa, Spain, Thailand, the United States, and the United Kingdom--to characterize and compare the distribution of risk factors among H1N1pdm patients at three levels of severity: hospitalizations, ICU admissions, and deaths. The median age of patients increased with severity of disease. The highest per capita risk of hospitalization was among patients <5 y and 5-14 y (relative risk [RR] = 3.3 and 3.2, respectively, compared to the general population), whereas the highest risk of death per capita was in the age groups 50-64 y and ≥65 y (RR = 1.5 and 1.6, respectively, compared to the general population). Similarly, the ratio of H1N1pdm deaths to hospitalizations increased with age and was the highest in the ≥65-y-old age group, indicating that while infection rates have been observed to be very low in the oldest age group, risk of death in those over the age of 64 y who became infected was higher than in younger groups. The proportion of H1N1pdm patients with one or more reported chronic conditions increased with severity (median = 31.1%, 52.3%, and 61.8% of hospitalized, ICU-admitted, and fatal H1N1pdm cases, respectively). With the exception of the risk factors asthma, pregnancy, and obesity, the proportion of patients with each risk factor increased with severity level. For all levels of severity, pregnant women in their third trimester consistently accounted for the majority of the total of pregnant women. Our findings suggest that morbid obesity might be a risk factor for ICU admission and fatal outcome (RR = 36.3). CONCLUSIONS: Our results demonstrate that risk factors for severe H1N1pdm infection are similar to those for seasonal influenza, with some notable differences, such as younger age groups and obesity, and reinforce the need to identify and protect groups at highest risk of severe outcomes. Please see later in the article for the Editors' Summary.

Age-specific differences in influenza A epidemic curves: do children drive the spread of influenza epidemics?

There is accumulating evidence suggesting that children may drive the spread of influenza epidemics. The objective of this study was to quantify the lead time by age using laboratory-confirmed cases of influenza A for the 1995/1996-2005/2006 seasons from Canadian communities and laboratory-confirmed hospital admissions for the H1N1/2009 pandemic strain. With alignment of the epidemic curves locally before aggregation of cases, slight age-specific differences in the timing of infection became apparent. For seasonal influenza, both the 10-19- and 20-29-year age groups peaked 1 week earlier than other age groups, while during the fall wave of the 2009 pandemic, infections peaked earlier among only the 10-19-year age group. In the H3N2 seasons, infections occurred an average of 3.9 (95% confidence interval: 1.7, 6.1) days earlier in the 20-29-year age group than for youth aged 10-19 years, while during the fall pandemic wave, the 10-19-year age group had a statistically significant lead of 3 days compared with both younger children aged 4-9 years and adults aged 20-29 years (P < 0.0001). This analysis casts doubt on the hypothesis that younger school-age children actually lead influenza epidemic waves.

Pandemic (H1N1) 2009 outbreak at Canadian Forces cadet camp.

We conducted a case-control study to describe the clinical and epidemiologic characteristics of an outbreak of pandemic (H1N1) 2009 at a Canadian military cadet training center. We found that asthma and obesity confer greater risk for infection. Viral shedding was detected by PCR up to 18 days after symptom onset.

Incidence of hospital admissions and severe outcomes during the first and second waves of pandemic (H1N1) 2009.

BACKGROUND: Canada experienced two distinct waves of pandemic (H1N1) influenza during the 2009 pandemic, one in the spring and the second in early fall 2009. We compared the incidence of hospital admissions and severe outcomes (admission to intensive care unit [ICU] and death) during the two waves. METHODS: We reviewed data on all laboratory-confirmed cases of pandemic (H1N1) influenza that resulted in hospital admission, ICU admission or death reported to the Public Health Agency of Canada by all provinces and territories from Apr. 18, 2009, to Apr. 3, 2010. RESULTS: A total of 8678 hospital admissions (including 1473 ICU admissions) and 428 deaths related to pandemic (H1N1) influenza were reported during the pandemic and post-peak period. There were 4.8 times more hospital admissions, 4.0 times more ICU admissions and 4.6 times more deaths in the second pandemic wave than in the first wave. ICU admissions and deaths as a proportion of hospital admissions declined in the second wave; there was a 16% proportional decline in ICU admissions and a 6% proportional decline in deaths compared with the first wave. Compared with patients admitted to hospital in the first wave, those admitted in the second wave were older (median age 30 v. 23 years) and more had underlying conditions (59.7% v. 47.5%). Pregnant women and Aboriginal people accounted for proportionally fewer patients who were admitted to hospital or who died in the second wave than in the first. INTERPRETATION: The epidemiologic features of the first and second waves of the 2009 pandemic differed. The second wave was substantially larger and, although the patients admitted to hospital were older and more of them had underlying conditions, a smaller proportion had a severe outcome.

Pandemic influenza in Canadian children: a summary of hospitalized pediatric cases.

A total of 324 pandemic H1N1 cases were reported to the Immunization Monitoring Program, Active from May 1, 2009 to August 31, 2009. As of August 31, 2009, case details were available for 73% (n=235) of these cases. The median age was 4.8 years and 69% of children were older than 2 years of age. In total, 95 (40%) of children were previously healthy. The proportion with an underlying health condition increased with age. Close to 50% of children received antiviral medication. Two children died from the infection. The pediatric risk groups affected and course of disease caused by pandemic H1N1 appear similar to seasonal influenza.

Risk of severe outcomes among patients admitted to hospital with pandemic (H1N1) influenza.

BACKGROUND: We describe the disease characteristics and outcomes, including risk factors for admission to intensive care unit (ICU) and death, of all patients in Canada admitted to hospital with pandemic (H1N1) influenza during the first five months of the pandemic. METHODS: We obtained data for all patients admitted to hospital with laboratory-confirmed pandemic (H1N1) influenza reported to the Public Health Agency of Canada from Apr. 26 to Sept. 26, 2009. We compared inpatients who had nonsevere disease with those who had severe disease, as indicated by admission to ICU or death. RESULTS: A total of 1479 patients were admitted to hospital with confirmed pandemic (H1N1) influenza during the study period. Of these, 1171 (79.2%) did not have a severe outcome, 236 (16.0%) were admitted to ICU and survived, and 72 (4.9%) died. The median age was 23 years for all of the patients, 18 years for those with a nonsevere outcome, 34 years for those admitted to ICU who survived and 51 years for those who died. The risk of a severe outcome was elevated among those who had an underlying medical condition and those 20 years of age and older. A delay of one day in the median time between the onset of symptoms and admission to hospital increased the risk of death by 5.5%. The risk of a severe outcome remained relatively constant over the five-month period. INTERPRETATION: The population-based incidence of admission to hospital with laboratory-confirmed pandemic (H1N1) influenza was low in the first five months of the pandemic in Canada. The risk of a severe outcome was associated with the presence of one or more underlying medical conditions, age of 20 years or more and a delay in hospital admission.

Mutational analysis of the FXNPXY motif within LDL receptor-related protein 1 (LRP1) reveals the functional importance of the tyrosine residues in cell growth regulation and signal transduction.

LRP1 [LDL (low-density lipoprotein) receptor-related protein 1]-null CHO cells (Chinese-hamster ovary cells) (13-5-1 cells) exhibited accelerated cell growth and severe tumour progression after they were xenografted into nude mice. Reconstitution of LRP1 expression in these cells, either with the full-length protein or with a minireceptor, reduced growth rate as well as suppressed tumour development. We tested the role of the tyrosine residue in the FXNPXY63 motif within the LRP1 cytoplasmic domain in signal transduction and cell growth inhibition by site-specific mutagenesis. The LRP1 minireceptors harbouring Tyr63 to alanine or Tyr63 to phenylalanine substitution had diametrically opposite effects on cell growth, cell morphology and tumour development in mice. The Y63F-expressing cells showed suppressed cell growth and tumour development, which were associated with decreased beta-catenin and cadherin concentrations in the cells. On the other hand, the Y63A-expressing cells lacked inhibition on cell growth and tumour development, which were associated with hyperactivation of ERKs (extracellular-signal-regulated kinases), FAK (focal adhesion kinase) and cyclin D1 in the cells. The mutant Y63A minireceptor also exhibited reduced capacity in binding to the Dab2 (disabled 2) adaptor protein. In addition, the Y63A mutant showed increased caveolar localization, and cells expressing Y63A had altered caveolae architecture. However, tyrosine to alanine substitution at the other NPXY29 motif had no effect on cell growth or tumorigenesis. These results suggest that the FXNPXY63 motif of LRP1 not only governs cellular localization of the receptor but also exerts multiple functional effects on signalling pathways involved in cell growth regulation.

Distribution of neuronal apoptosis inhibitory protein in human tissues.

The neuronal apoptosis inhibitory protein (NAIP) gene, also known as the baculovirus inhibitor of apoptosis repeat-containing protein 1 (BIRC1) gene, is a member of the inhibitors of apoptosis (IAP) family and was first characterized as a candidate gene for spinal muscular atrophy (SMA). The expression of NAIP has been thoroughly studied in the central nervous system and overlaps the pattern of neurodegeneration in SMA. Recent studies have pointed to a role for NAIP in non-neuronal cells. We report here the production of a specific anti-NAIP antibody and the profile of NAIP expression in human adult tissues by Western blot and immunohistochemical detection methods. NAIP was detected in a number of tissues by Western blot analysis, but immunohistochemistry revealed that NAIP's presence in certain tissues, such as liver, lung, and spleen, is most likely due to macrophage infiltration. In the small intestine, the expression of NAIP coincides with the expression of p21(WAF1). This observation, coupled with findings from other groups, suggests a role for NAIP in increasing the survival of cells undergoing terminal differentiation as well as the possibility that the protein serves as an intestinal pathogen recognition protein. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.

Mouse dystrophin enhancer preferentially targets lacZ expression in skeletal and cardiac muscle.

Duchenne muscular dystrophy is a muscle wasting disease that results from a dystrophin deficiency in skeletal and cardiac muscle. Studies concerning the regulatory elements that govern dystrophin gene expression in skeletal and/or cardiac muscle in both mouse and human have identified a promoter and an enhancer located in intron 1. In transgenic mice, the muscle promoter alone targets the expression of a lacZ reporter gene only to the right ventricle of the heart, suggesting the need for other regulatory elements to target skeletal muscle and the rest of the heart. Here we report that the mouse dystrophin enhancer from intron 1 can target the expression of a lacZ reporter gene in skeletal muscle as well as in other heart compartments of transgenic mice. Our results also suggest that sequences surrounding the mouse dystrophin enhancer may affect its function throughout mouse development.