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Patients with heart failure (HF) and a reduced ejection fraction (HFrEF) who experience worsening HF (WHF) events are at increased risk of adverse outcomes and experience significant morbidity and mortality. We herein describe the epidemiology of these patients and identify those potentially eligible for vericiguat therapy in this population-based study.This retrospective cohort study included hospitalized or emergency department patients with a primary diagnosis of HF and a left ventricular ejection fraction (LVEF) of less than 45% diagnosed between April 1, 2009, and March 31, 2019 in Alberta, Canada, with follow-up to March 31, 2020. Inclusion criteria from the VerICiguaT Global Study in Subjects with Heart Failure with Reduced Ejection (VICTORIA) trial were applied to explore eligibility for vericiguat. Among 25,629 patients with HF and LVEF data, 9948 (38.8%) had HFrEF, of which 5259 (52.8%) experienced WHF at some point during a median 5.8 years of follow-up, and 38.3% of those met the vericiguat trial eligibility criteria. Compared with patients with HFrEF without WHF, those with WHF were older, with more comorbidities, worse renal function, and similar LVEF status, but greater use of HF medications at baseline. At the time of WHF, 27% of those with HFrEF and WHF were on triple therapy, 50.6% were on dual therapy, and 15.4% were on monotherapy. All-cause mortality and the composite outcome of all-cause mortality or cardiovascular hospitalization at 1-year of follow-up were higher in the HFrEF with WHF cohort compared with HFrEF without WHF (adjusted hazard ratios of 1.92 and 1.51, respectively, both P.0001).Approximately one-half of patients with HFrEF experienced WHF over the long-term follow-up. Most were not on triple therapy, highlighting the underuse of the existing standard-of-care treatments and opportunities for application of newer therapies; more than one-third of patients with HFrEF may be eligible for vericiguat.Among patients with heart failure (HF), those who experience worsening HF (WHF) are at increased risk of adverse outcomes. A few new therapies, including vericiguat, have emerged recently for patients with HF and reduced ejection fraction. However, the epidemiology, treatment patterns, and outcomes of patients with WHF in large representative populations is unclear. In the current study, approximately one-half of the patients with HF and reduced ejection fraction experienced WHF and 38.3% were potentially eligible for vericiguat therapy. The guideline-recommended therapies were under-utilized among patients with WHF, which highlights the need for initiatives to address this care gap.

Short-term outcomes are worse for patients with acute coronary syndrome (ACS) with a history of nonvalvular atrial fibrillation (NVAF). However, long-term prognosis remains unclear. We linked administrative health databases to identify patients hospitalized with ACS (ST-elevation myocardial infarction [STEMI], non-STEMI [NSTEMI], and unstable angina) between 2008 and 2019 in Alberta, Canada. Patients were stratified according to history of NVAF before hospitalization. The primary outcome was a composite of all-cause mortality, hospitalization for myocardial infarction, or stroke at 3 years. Cox models were constructed to estimate the association between ACS, NVAF, and outcomes. Of 54,309 ACS hospitalizations, 6,351 patients (11.7%) had a history of NVAF. Compared with patients without NVAF, patients with previous NVAF were older (75.6 ± 11.6 vs 64.9 ± 13.4 years), women (35.1% vs 30.0%), had higher comorbid burden (Charlson co-morbidity index 3.0 vs 1.0), and more often presented with NSTEMI (57.5% vs 49.0%). The primary outcome occurred in 37.0% of patients with previous NVAF and 17.4% without (p0.001). In the multivariable analysis, there was a 1.14-fold (95% confidence interval [CI] 1.09 to 1.20) higher risk of the primary outcome in patients with previous NVAF. There was a significant association with STEMI (adjusted harazard ratio [aHR] 1.24, 95% CI 1.12 to 1.36) and NSTEMI (aHR 1.12, 95% CI 1.06 to 1.19) but not with unstable angina (aHR 1.04, 95% CI 0.90 to 1.22). In conclusion, in this population-based study, we identified that a history of NVAF at ACS presentation is associated with worse long-term prognosis, particularly for STEMI and NSTEMI.

Background: Data are limited data on the prevalence of cardiovascular disease (CVD) and multimorbidity in contemporary cohorts of high-cost users (HCUs) in Canada.We examined the following: (i) the prevalence of CVD, with a comparison of total healthcare costs among HCUs with vs without CVD; (ii) the contribution of other comorbidities to costs among HCUs with CVD; and (iii) the trajectory of healthcare costs in the years before and after becoming an HCU. Methods: The study included adult Alberta patients in the Canadian Institutes of Health Research/Canadian Institute for Health Information Dynamic Cohort of Complex, High System Users from 2011-2012 through 2014-2015. We examined total healthcare costs, including hospital, ambulatory care, physician services, and drugs. Results: Among 88,536 HCUs, 23.4% had no CVD, 28.9% were hospitalized with a primary diagnosis of CVD, and 47.7% were hospitalized with a secondary diagnosis of CVD. Total healthcare costs were $2.0 billion (20.4% non-hospital costs), $2.8 billion (24.1% non-hospital costs), and $4.9 billion (19.8% non-hospital costs), respectively, in the 3 groups. Many HCUs with CVD were frail (74.2%) and many had diabetes (33.8%) or chronic obstructive pulmonary disease (27.9%), which contributed to higher costs and mortality. Healthcare expenditures in HCUs with CVD were several times higher than per capita health expenditures in the years prior to, and following, their inclusion in the dynamic HCU cohort. Conclusions: CVD is very common in HCUs of healthcare. HCUs with CVD have high rates of frailty and multimorbidity. Further research is needed to identify and intervene earlier, in order to flatten the cost curve in these complex patients. Résumé: Introduction: Les données sur la prévalence des maladies cardiovasculaires (MCV) et de la multimorbidité au sein des cohortes contemporaines de grands utilisateurs (GU) du Canada sont limitées. Nous avons examiné ce qui suit : (i) la prévalence des MCV en comparant les coûts totaux des soins de santé entre les GU atteints de MCV et les GU non atteints de MCV; (ii) la contribution des autres comorbidités aux coûts liés aux GU atteints de MCV; (iii) la trajectoire des coûts des soins de santé dans les années avant et après avoir été considérés comme un GU. Méthodes: L’étude portait sur des patients adultes de l’Alberta de la Cohorte dynamique de grands utilisateurs du système de santé aux besoins complexes de 2011-2012 à 2014-2015 des Instituts de recherche en santé du Canada et de l’Institut canadien d’information sur la santé. Nous avons examiné les coûts totaux des soins de santé, notamment les coûts hospitaliers, les coûts des soins ambulatoires, des services médicaux et des médicaments. Résultats: Parmi les 88 536 GU, 23,4 % n’avaient pas de MCV, 28,9 % étaient hospitalisés et avaient un diagnostic principal de MCV, et 47,7 % étaient hospitalisés et avaient un diagnostic secondaire de MCV. Les coûts totaux des soins de santé des 3 groupes étaient respectivement de 2,0 G$ (20,4 % de coûts non hospitaliers), 2,8 G$ (24,1 % de coûts non hospitaliers) et 4,9 G$ (19,8 % de coûts non hospitaliers). Plusieurs GU atteints de MCV étaient fragiles (74,2 %) et beaucoup avaient le diabète (33,8 %) ou une maladie pulmonaire obstructive chronique (27,9 %), qui contribuaient à des coûts et à une mortalité plus élevés. Les dépenses de santé par personne liées aux GU atteints de MCV étaient beaucoup plus élevées que les dépenses de santé par personne dans les années qui précédaient ou suivaient leur inclusion dans la cohorte dynamique de GU atteints de MCV. Conclusions: Les GU de soins de santé sont très fréquemment atteints de MCV. Les GU atteints de MCV présentent des taux de fragilité et de multimorbidité élevés. D’autres recherches sont nécessaires pour cerner et intervenir plus tôt afin d’aplatir la courbe des coûts chez ces patients aux besoins complexes.

The extent to which the introduction of direct oral anticoagulants (DOACs) influenced treatment patterns in frail and nonfrail patients with nonvalvular atrial fibrillation (NVAF) is unclear.This was a retrospective cohort study of all Albertans 20 years or older who were discharged from an emergency department or hospital with a new diagnosis of NVAF between April 1, 2009, and March 31, 2019. The Hospital Frailty Risk Score was used to define frailty and the CHAAmong 75,796 patients (median age, 75 years; 45% female) with a new diagnosis of NVAF, 17,143 (22.6%) were frail. Although guideline criteria for anticoagulation were more commonly met by frail patients than nonfrail patients (92.1% vs 74.2%, for CHAAlthough they stand to potentially derive greater benefits from anticoagulation, frail patients were less likely to receive an anticoagulant and, if anticoagulated, they were more likely to receive warfarin than a DOAC. The introduction of DOACs has increased anticoagulation rates but not resolved treatment gaps for frail patients with NVAF.

Aims The incidence of respiratory failure and use of invasive or non-invasive mechanical ventilation (MV) in the cardiac intensive care units (CICUs) is increasing. While institutional MV volumes are associated with reduced mortality in medical and surgical ICUs, this volume–mortality relationship has not been characterized in the CICU. Methods and results National population-based data were used to identify patients admitted to CICUs (2005–2015) requiring MV in Canada. CICUs were categorized into low (≤100), intermediate (101–300), and high (>300) volume centres based on spline knots identified in the association between annual MV volume and mortality. Outcomes of interest included all-cause in-hospital mortality, the proportion of patients requiring prolonged MV (>96 h) and CICU length of stay (LOS). Among 47 173 CICU admissions requiring MV, 89.5% (42 200) required invasive MV. The median annual CICU MV volume was 43 (inter-hospital range 1–490). Compared to low-volume centres (35.9%), in-hospital mortality was lower in intermediate [29.2%, adjusted odds ratio (aOR) 0.84, 95% confidence interval (CI) 0.72–0.97, P = 0.019] and high-volume (18.2%; aOR 0.82, 95% CI 0.66–1.02, P = 0.076) centres. Prolonged MV was higher in low-volume (29.2%) compared to high-volume (14.8%, aOR 0.70, 95% CI 0.55–0.89, P = 0.003) and intermediate-volume (23.0%, aOR 0.85, 95% CI 0.68–1.06, P = 0.14] centres. Mortality and prolonged MV were lower in percutaneous coronary intervention (PCI)-capable and academic centres, but a shorter CICU LOS was observed only in subgroup of PCI-capable intermediate- and high-volume hospitals. Conclusions In a national dataset, we observed that higher CICU MV volumes were associated with lower incidence of in-hospital mortality, prolonged MV, and CICU LOS. Our data highlight the need for minimum MV volume benchmarks for CICUs caring for patients with respiratory failure.

Recently, we introduced a novel measure of “average life span shortened” (ALSS) to improve comparability of premature mortality over time. In this study, we applied this novel measure to examine trends in premature mortality caused by hematological cancers in Canada from 1980 to 2015. Mortality data for Hodgkin lymphoma, non-Hodgkin lymphoma, multiple myeloma, and leukemia were obtained from the World Health Organization mortality database. Years of life lost was calculated according to Canadian life tables. ALSS was defined as the ratio between years of life lost and expected life span. Over the study period, age-standardized rates of mortality decreased for all types of hematological cancers. Our new ALSS measure showed favorable trends in premature mortality for all types of hematological cancers among both sexes. For instance, men with non-Hodgkin lymphoma lost an average of 23.7% of their life span in 1980 versus 16.1% in 2015, while women with non-Hodgkin lymphoma lost an average of 21.7% of their life span in 1980 versus 15.5% in 2015. Results from this study showed that patients with hematological cancers experienced prolonged survival over a 35-year period although the magnitude of these life span gains varied by types of hematological cancers.

To examine sex differences in oral anticoagulation management and outcomes among patients with incident nonvalvular atrial fibrillation presenting to the emergency department (ED).We identified patients older than 20 years presenting to the ED with incident nonvalvular atrial fibrillation between April 1, 2012, and March 30, 2019, using linked administrative databases in Alberta, Canada. We assessed the use of and adherence to oral anticoagulants at 1 year using the proportion of days covered for direct oral anticoagulants and time in therapeutic range for warfarin. Outcomes included stroke, heart failure, and all-cause mortality at 1 year.Of the 28,886 patients with nonvalvular atrial fibrillation presenting to ED, 44% were females. After adjustment, the rate of oral anticoagulant use was 5% lower in females with a guideline indication than that in males (adjusted hazard ratio 0.95, 95% confidence interval [CI] 0.91 to 0.99) discharged home, and there was no difference among admitted patients (adjusted hazard ratio 1.00, 95% CI 0.96 to 1.05). Females had high adherence to direct oral anticoagulants (≥80% proportion of days covered) compared to males (discharged: 77.7% versus 74.0%; admitted: 80.0% versus 76.7%; adjusted odds ratio for females: 1.15, 95% CI 1.02 to 1.29). More than half of the females and males had poor warfarin control (time in therapeutic range65%) regardless of discharge status. In multivariable analyses, there was no sex difference in outcomes except a 1.48-fold (95% CI 1.14 to 1.92) higher risk of stroke in females.Females with incident nonvalvular atrial fibrillation discharged from the ED are less likely to receive oral anticoagulants than males. When oral anticoagulant treatment is initiated, females have high adherence to direct oral anticoagulants, and both the sexes have poor warfarin control. At 1 year, females were at a significantly higher risk of developing stroke.

Funding Acknowledgements Type of funding sources: None. Background The incidence of respiratory failure and the provision of invasive and non-invasive mechanical ventilation (MV) in patients admitted to cardiac intensive care units (CICU) are increasing. While institutional MV volumes are associated with reduced mortality in medical and surgical ICUs, this relationship has not been characterized in the CICU population. Purpose By describing the relationship between institutional MV volume and outcomes in the CICUs, we hope to shed light on minimum volume benchmarks for providing MV. Methods National Canadian population-based data from 2005 to 2015 was used to identify patients admitted to CICUs requiring MV. CICUs were categorized into low (≤100), intermediate (101-300), and high (>300) volume centers based on spline knots identified in the association between annual MV volume and mortality (Figure). Outcomes of interests included all-cause in-hospital mortality, the proportion of patients requiring prolonged MV (>96 hours) and CICU length of stay (LOS). Results Among the 47,173 CICU admissions that required MV, 89.5% (42,200) required invasive mechanical ventilation. The median annual CICU MV volume was 127 (range 1-490). In-hospital mortality was lower in intermediate (29.2%, adjusted odds ratio [aOR] 0.84, 95% CI 0.72-0.97, p = 0.019) and high-volume (18.2%; aOR 0.82, 95% CI 0.66-1.02, p = 0.076) centers, compared to low volume centers (35.9%). The proportion of patients requiring prolonged MV was higher in low-volume (29.2%) compared to high-volume (14.8%, OR 0.70, 95% 0.55-0.89, p = 0.003) centers. Point estimates for mortality and prolonged MV were lower in PCI-capable and academic centers (Table). Significantly (p Conclusions In a national dataset, we observed that higher CICU MV hospital volumes were associated with lower in-hospital mortality, CICU LOS, and fewer episodes of prolonged MV. Pending further validation, these data suggest minimum MV volume benchmarks for CICUs caring for patients with respiratory failure. Further research is warranted to explore these associations in more detail. Unadjusted volume-outcome relationshipsOutcomesGroup 1 Annual Volume ≤100Group 2 Annual Volume 101-300Group 3 Annual Volume >300Totalp-valueTotal N1770224351512047173In-hospital mortality6357 (35.0%)7122 (29.2%)933 (18.2%)14412 (30.6%)p

Polytomous regression models generalize logistic models for the case of a categorical outcome variable with more than two distinct categories. These models are currently used in clinical research, and it is essential to measure their abilities to distinguish between the categories of the outcome. In 2012, van Calster et al proposed the polytomous discrimination index (PDI) as an extension of the binary discrimination c-statistic to unordered polytomous regression. The PDI is a summary of the simultaneous discrimination between all outcome categories. Previous implementations of the PDI are not capable of running on "big data." This article shows that the PDI formula can be manipulated to depend only on the distributions of the predicted probabilities evaluated for each outcome category and within each observed level of the outcome, which substantially improves the computation time. We present a SAS macro and R function that can rapidly evaluate the PDI and its components. The routines are evaluated on several simulated datasets after varying the number of categories of the outcome and size of the data and two real-world large administrative health datasets. We compare PDI with two other discrimination indices: M-index and hypervolume under the manifold (HUM) on simulated examples. We describe situations where the PDI and HUM, indices based on multiple comparisons, are superior to the M-index, an index based on pairwise comparisons, to detect predictions that are no different than random selection or erroneous due to incorrect ranking.

Aim To determine the concurrent use of P-glycoprotein (P-gp) or Cytochrome (CYP) 3A4 drugs and non-vitamin K antagonist oral anticoagulants (NOACs) among non-valvular AF (NVAF) patients in clinical practice. Methods and results Administrative databases identified all adults (≥18 years) with incident or prevalent NVAF who initiated a NOAC in an outpatient or inpatient setting, between July 2012 and March 2019 in Alberta, Canada. Concurrent use was defined as a P-gp or CYP3A4 dispensation in the 100 days prior to and overlapping NOAC dispensation. The P-gp and CYP3A4 drugs were categorized into three groups and drug-drug interactions classified according to the 2018 European Heart Rhythm Association practical guide. Time-varying Cox models calculated the crude hazard ratio (HR) of outcomes at 1-year. A total of 642 255 NOAC dispensations occurred for 36 566 NVAF patients. Of these, 71 643 (11.2%) had a concurrent dispensation of an interacting P-gp or CYP3A4 drug. Overall, the drug–drug interaction was defined as contraindicated in 2.5%, avoid/caution in 2.3%, and for another 6.7% should require a dose adjustment. When all drug–drug interactions were considered, inappropriate NOAC prescribing occurred in 63% (n = 45 080) of dispensations. There was a significantly higher risk of death (HR 1.58, 1.47–1.70) for a drug–drug interaction but not for stroke (P = 0.89) or major bleeding risk (P = 0.13). Conclusions The concurrent use of P-gp or CYP3A4 drugs and NOACs was uncommon but important since almost two-thirds of patients with drug–drug interactions had inappropriate NOAC dosing and a higher risk of death. More attention to this issue is needed.

The epidemiological trends of malignant melanoma have been well described in the literature. However, there remains a paucity of population-based studies assessing melanoma epidemiology in our younger patients (20 years of age or less). Other studies indicate that melanoma incidence has risen in pediatric populations over the last several decades and that these tumors may display different clinical characteristics from those arising in adult populations. We conducted a retrospective, population-based analysis of all incident cases of melanoma occurring in young patients aged ≤20 years in Alberta from 1992 to 2011. Information, including patient age, sex, anatomical location, date of diagnosis, histological subtype (if available), level of invasion, and date of death (if applicable), was obtained from the Alberta Cancer Registry. All cases occurring during a 10-year period from 1993 to 2011 have been reviewed. A total of 71 cases were diagnosed during this time (63% female and 37% male). Age range was 0-20 years (mean of 17.5 years). Truncal melanomas made up 36% of cases, while 28% occurred on the lower limbs, 17% on the upper limbs, and 18% in the head and neck region. Average Breslow thickness was 1.97 mm; 67% of tumors were less than 1 mm thick. Unfortunately, 8 of 71 patients died from their disease. Overall, the incidence of melanoma in patients aged ≤20 years appeared to decrease in Alberta in the past 20 years; however, there has been an increase in the thickness of melanoma at diagnosis, which needs to be addressed.

Background and purpose: Varicella disease is a risk factor for pediatric Arterial Ischemic Stroke (AIS). Isolated case reports have emerged suggesting that varicella vaccination may also pose a risk for AIS. Methods: This retrospective population-based cohort study assessed the risk of AIS in children who received a varicella-containing vaccine, as compared to those who did not. The study cohort consisted of children born between January 1, 2006 and December 31, 2013, in the Canadian province of Alberta, where all routine childhood vaccinations are publicly-funded, and recorded in a central immunization repository. These data were linked with hospital discharge abstract data to identify children diagnosed with AIS. A Cox proportional hazard model assessed the risk of AIS in the 12 months following vaccination for children receiving a varicella vaccine between 11 and 23 months of age, as compared to non-vaccinated children. Results: Of the 368,992 children in the cohort, 325,729 were vaccinated with a varicella-containing vaccine between 11 and 23 months of age. The rate of AIS was 7.8 (95% CI 4.8–10.9) per 100,000 person years at risk in the 12 months following varicella vaccination, as compared to 6.8 (95% CI 1.3–12.2) for children who did not receive a varicella vaccine. The adjusted Hazard Ratio for the risk of AIS, controlling for other AIS risk factors, in vaccinated children as compared to non-vaccinated children was 1.6 (95% CI 0.7–3.7) in the 12 months following vaccination and 1.7 (95% CI 0.5–4.9) in the 30 days following vaccination. Conclusions: Our study found no evidence of an increased risk of AIS following varicella vaccination. This population-based cohort study provides reassurance to parents and clinicians regarding the safety of varicella vaccination.

Purpose We assessed the effectiveness of shingles vaccine in preventing incident shingles among Alberta residents aged 50 years or older over the period 2009 – 2015, using administrative health data. Methods The cohort comprised of Albertans from the Alberta Health Care Insurance Plan Registry (AHCIP) as of June 30, 2009 and aged 50 years or older. Those who received shingles vaccine were identified from the provincial pharmaceutical information network. The occurrence of incident shingles was identified through both inpatient and outpatients/community care data. Incident shingles was defined as the earliest dated record of ICD 9-CM 053 or ICD-10-CA B02. Starting on November 1, 2009, individuals with no history of shingles or shingles vaccination were followed until Nov 1, 2015 (6 years), or until shingles incidence, death, or AHCIP cancellation (including leaving Alberta). Vaccine effectiveness (VE) was estimated as the inverse of the relative risk of developing incident shingles in each year following vaccination compared to time at risk without vaccination, while adjusting for age, sex, income quintile, and immune compromising conditions (identified from physician claims, inpatient, and cancer registry data). Results There were 1,094,236 individuals in the cohort, with 85,439 (7.80%) vaccinated individuals. The shingles incidence rate was 9.03 [95% CI: 8.95, 9.11] cases per 1,000 person years (49,243 cases). Adjusted VE in the first year following immunization was 50.02% [95% CI: 44.71%, 54.83%] against incident shingles, decreasing to no effect by the fifth year (VE = 14.00% [95% CI: −20.99%, 38.88%]). Conclusions Our findings are consistent with observations from other population based studies and provide population level data for policy-makers to review when making decisions related to public funding of shingles vaccine.

Background Studies in non-Emergency Department (ED) settings have shown women with non-valvular atrial fibrillation (NVAF) differ in presentation, treatment, and outcomes compared to men. Despite AF being a common reason for ED visit, little is known regarding sex differences in patients presenting to ED. Purpose We sought to determine whether sex differences exist in rates of admission among NVAF patients presenting to the ED and if oral anticoagulant (OAC) use and outcomes differ by ED discharge status. Methods Patients≥18 years old, presenting to the ED with incident NVAF in two western Canadian provinces (Alberta and British Columbia) from April 2012 to March 2015 were included. ED records were linked to hospital records to identify patients admitted to hospital versus discharged from the ED. Outcomes of interest were 30-day mortality and 1-year stroke, heart failure (HF) and mortality. Pharmaceutical claims were queried for OAC use within 90 days following NVAF ED event. Results Of 16,991 ED NVAF patients, 7,770 (46%) were women and 9,221 (54%) were men (p Outcomes by Sex and ED Discharge Status Outcome Discharged Admitted Women (N=4,560) Men (N=5,780) p-value Women (N=3,210) Men (N=3,441) p-value 30 Day Mortality, n (%) 63 (1.4) 50 (0.9) 0.01 261 (8.1) 228 (6.6) 0.019 1 Year Mortality, n (%) 270 (5.9) 248 (4.7) Conclusions In this population-based study of patients presenting to ED with NVAF, we found women were more likely to be admitted to hospital than men. Women had a worse prognosis than men, irrespective of ED discharge status. Use of OAC was suboptimal, regardless of patient sex. Acknowledgement/Funding Heart and Stroke Foundation of Canada, UBC Cardiology, Servier Alberta Innovation Health Fund

OBJECTIVE: In June of 2013, southern Alberta underwent flooding that affected approximately 100,000 people. We describe the process put in place for public health surveillance and assessment of the impacts on health. METHODS: Public health surveillance was implemented for the six-week period after the flood to detect anticipated health events, including injuries, mental health problems and infectious diseases. Data sources were emergency departments (EDs) for presenting complaints, public health data on the post-exposure administration of tetanus vaccine/immunoglobulin, administrative data on prescription drugs, and reportable diseases. RESULTS: An increase in injuries was detected through ED visits among Calgary residents (rate ratio [RR] 1.28, 95% confidence interval [CI]: 1.14–1.43) and was supported by a 75% increase in the average weekly administration of post-exposure prophylaxis against tetanus. Mental health impacts in High River residents were observed among females through a 1.64-fold (95% CI: 1.11–2.43) and 2.32-fold (95% CI: 1.45–3.70) increase in new prescriptions for anti-anxiety medication and sleep aids respectively. An increase in sexual assaults presenting to EDs (RR 3.18, 95% CI: 1.29–7.84) was observed among Calgary residents. No increases in infectious gastrointestinal disease or respiratory illness were identified. Timely identification and communication of surveillance alerts allowed for messaging around the use of personal protective equipment and precautions for personal safety. CONCLUSION: Existing data sources were used for surveillance following an emergency situation. The information produced, though limited, was sufficiently timely to inform public health decision-making.

Background Despite the wealth of frameworks on social determinants of health (SDOH), two current limitations include the relative superficial description of factors affecting health and a lack of focus on measuring health equity. The Health Equity Measurement Framework (HEMF) addresses these gaps by providing a more encompassing view of the multitude of SDOH and drivers of health service utilisation and by guiding quantitative analysis for public health surveillance and policy development. The objective of this paper is to present the HEMF, which was specifically designed to measure the direct and indirect effects of SDOH to support improved statistical modelling and measurement of health equity. Methods Based on a framework synthesis, the HEMF development involved initially integrating theoretical components from existing SDOH and health system utilisation frameworks. To further develop the framework, relevant publications on SDOH and health equity were identified through a literature review in major electronic databases. White and grey literatures were critically reviewed to identify strengths and gaps in the existing frameworks in order to inform the development of a unique health equity measurement framework. Finally, over a two-year period of consultation, scholars, health practitioners, and local policy influencers from municipal and provincial governments provided critical feedback on the framework regarding its components and causal relationships. Results This unified framework includes the socioeconomic, cultural, and political context, health policy context, social stratification, social location, material and social circumstances, environment, biological factors, health-related behaviours and beliefs, stress, quality of care, and healthcare utilisation. Alongside the HEMF’s self-exploratory diagram showing the causal pathways in-depth, a number of examples are provided to illustrate the framework’s usefulness in measuring and monitoring health equity as well as informing policy-making. Conclusions The HEMF highlights intervention areas to be influenced by strategic public policy for any organisation whose purview has an effect on health, including helping non-health sectors (such as education and labour) to better understand how their policies influence population health and perceive their role in health equity promotion. The HEMF recognises the complexity surrounding the SDOH and provides a clear, overarching direction for empirical work on health equity. Electronic supplementary material The online version of this article (10.1186/s12939-019-0935-0) contains supplementary material, which is available to authorized users.

Purpose: A universal publicly funded chickenpox vaccination program was implemented in Alberta in 2002. We examine the epidemiology of medically attended shingles in Alberta from 1994 to 2010. Methods: Incident shingles cases (earliest health service utilizations for ICD-9 053 or ICD-10-CA B02) and their co-morbid conditions for the 12 months prior to shingles diagnosis were identified from the records of Alberta's universal, publicly funded health-care insurance system for 1994–2010. Shingles diagnostic codes at least 180 days after the first were classified as recurrent episodes. Denominators for rates were estimated using mid-year population estimates from the Alberta Health Care Insurance Plan Registry. Annual age- and sex-specific rates were estimated. We estimated the proportion of all cases that were hospitalized. We explored the pattern of rates for sex, age-group co-morbidity and year effects and their interactions. Results: Crude rates of shingles increased over the interval 1994–2010. Most persons had only a single episode of shingles; 4% of cases were hospitalized. Shingles rates were higher among females than males. While only 2% of shingles cases had one or more co-morbidities, this proportion was also higher for females than males. Prior to 2002, all age groups of both sexes experienced increasing annual rates of shingles. However, there was a sharp decline in the rate of shingles for both females and males under the age of 10 years for 2002–2010, the period in which there was publicly funded chickenpox vaccination. Conclusion: The declining rates of shingles among persons under the age of 10 years are consistent with an impact of the chickenpox vaccination program. The trend of increasing rates of shingles among older persons began prior to implementation of vaccination.

Background Herpes zoster (shingles) is a reactivation of latent varicella virus. Shingles is uncommon in children and children vaccinated against varicella may be at a reduced risk of shingles. Alberta has a publicly funded healthcare system and added publicly funded varicella vaccine to the routine childhood vaccination schedule in 2001. Methods We used provincially held administrative health databases to examine the epidemiology of incident shingles cases in children under the age of 19. Incident shingles cases were defined as the earliest record of ICD-9-CM 053 OR ICD-10-CA B02 coded physician claims, hospital, or emergency room visits between 1985 and 2016, with incident cases in this cohort occurring between January 1, 2016 and December 31, 2016. Varicella immunization was identified through Alberta’s immunization repository and immunosuppressive comorbid conditions (neoplasms, HIV/AIDS, cystic fibrosis, and immune system disorders) were identified using ICD diagnostic codes from physician claims, hospital, or emergency room visits and Alberta’s Communicable Disease Control databases. Results 1,003 incident shingles cases were identified in children under the age of 19 in 2016, a crude rate of 0.98/1,000 persons. Females comprised 54% of cases. The largest proportion of cases occurred among those aged 15–19 years. About 39% of cases were prescribed antiviral medication, most commonly those aged 15–19 years. The crude rate per 1,000 population increased with age: 0.5 for children under the age of 1, 1.2 for those 1–4 years, 1.25 for children 5–9 years, 2.19 for children 10–14 years, and 3.7 for children aged 15–19 years. Crude rates were similar among both males and females. Less than 3% of the cases had ever been immunized against varicella. Shingles diagnostic codes were not validated, which likely led to an overestimation of the true rates of disease. Conclusion Additional studies are needed on pediatric shingles cases and factors that influence shingles in this group, as well as validation studies of ICD diagnostic coding in administrative data. Disclosures M. L. Russell, Novartis Pharmaceuticals Canada Inc.: Grant Investigator and Unconditional Research Grant, Grant recipient. Merck Frosst Canada Inc.: Grant Investigator and Unconditional Research Grant, Grant recipient.

Background Despite widespread use of a universal rubella standard, variability in rubella antibody titre can be observed between assays, particularly at the low end of the linear range. Objectives Here, we investigate the impact of a methodology change for rubella IgG from the Abbott AXSYM to the Abbott Architect in a comprehensive prenatal screening program in the Canadian province of Alberta. Study design 51,815 specimens (21,399 tested by AxSYM and 30,416 tested by Architect) submitted for routine prenatal screening between January 2006 and December 2012 from women who lived in Alberta after the universal childhood immunization programme for rubella was implemented, and whose immunization records were available, were included in the study. Results Prenatal samples tested by AxSYM for rubella IgG were approximately 30% higher than those reported by Architect. Among individuals who had tests across multiple pregnancies, the change in test platform led to an additional 7% of women who initially tested positive, becoming non-positive (i.e. negative or indeterminate) in their subsequent tests. The tendency of the Architect IgG assay to report lower quantitative values was demonstrated across all birth cohorts and vaccination status, and resulted in an additional 2800 women requiring vaccination between 2010 and 2012 with an estimated cost of $38,500. Conclusion The change in rubella IgG screening assay resulted in a significant increase in the number of women who required post partum vaccination and Public Health follow-up.

The ability to determine an individual's susceptibility to infection relies heavily on the assay used, and the ability to correlate results of the assay to a clinical interpretation. Current rubella immunity screening methods identify total rubella IgG antibodies circulating in the serum, however both humoral and cell mediated immune responses have been shown to contribute to protection from infection. Therefore, antibody screening assays may under-estimate immunity in some populations. In fact, waning antibody titers over time in a large prenatal population were recently documented in North America, and the trend has been echoed in other countries that have achieved elimination through universal rubella vaccination. Despite decreasing antibody titers, the number of acute rubella cases has not increased in these populations, suggesting that the lower antibody levels may still be protective. Based on the changing epidemiology in universally vaccinated populations, it may be time to reassess the level of antibody that indicates immunity to rubella infection.

Background: The epidemiology of sebaceous carcinoma (SC) has not previously been examined in a Canadian population. Objective: To determine the epidemiologic trends of SC in Alberta, Canada, from 1988 to 2007. Methods: This study was a population-based, retrospective, epidemiologic analysis of SC in Alberta over a 20-year span. Results: Over the study period, the age-standardized SC incidence increased from 0.22 per 100,000 to 0.65 per 100,000. Sebaceous carcinoma is a cancer that predominantly affects the elderly (over 85% of cases were in persons 60 years or older). Interestingly, the face (37.7% of cases), not the eyelids (26.2% of cases), was the most frequently affected site overall. Gender-specific trends reflected a slight male predominance (1.4:1) and significant differences in anatomic distribution between the sexes. Conclusion: For unexplained reasons, there has been a threefold increase in SC incidence in Alberta over the last two decades. In addition, there are significant gender-specific differences in the anatomic distribution of SC. Contexte: L'épidémiologie du carcinome sébacé (CS) n'a jamais fait l'objet d'étude au Canada. Objectif: L'étude visait à déterminer les tendances épidémiologiques du CS en Alberta, au Canada, de 1988 à 2007. Méthodes: Il s'agit d'une analyse épidémiologique, rétrospective, fondée sur la population, du CS, en Alberta, sur une période de 20 ans. Résultats: Au cours de la période à l'étude, l'incidence du CS normalisée selon l'âge est passée de 0.22 pour 100,000 à 0.65 pour 100,000. Le carcinome sébacé est un cancer qui touche surtout les personnes âgées (plus de 85% des cas se comptaient parmi les personnes de 60 ans et plus). Point intéressant, la région le plus souvent touchée, dans l'ensemble, était la face (37.7% des cas), et non les paupières (26.2% des cas). Les tendances propres à chaque sexe ont révélé une fréquence légèrement plus élevée chez les hommes que chez les femmes (1.4/1) et des différences importantes entre les sexes quant à la répartition anatomique du siège des lésions. Conclusion: Pour des raisons inconnues, l'incidence du CS a triplé en Alberta au cours des deux dernières décennies. De plus, il existe des différences importantes entre les sexes quant à la répartition anatomique du CS.

Summary Background Nonmelanoma skin cancer (NMSC) is the most common malignancy affecting caucasian populations and has been seeing global increases in incidence for decades. Objectives The objective of this study was to determine trends in incidence of NMSC in Alberta, Canada from 1988 to 2007. Methods A retrospective analysis of patients from Alberta diagnosed with NMSC from 1988 to 2007 inclusive was conducted with data retrieved from the Alberta Cancer Registry (ACR). Sex-, age- and anatomical location-specific incidence rates and trends were examined. Results From 1988 to 2007, there were 66 192 basal cell carcinomas, 19 959 invasive squamous cell carcinomas (SCC) and 12 494 in situ SCC. ACR coding for the 2007 data was not completed at the time of this study; hence, data from this year were not included in the trend analyses. Incidence of NMSC in women has been stable since 2000 [annual percentage change (APC) 0·08, P = 0·88] and has declined in men since 2001 (APC −1·28, P = 0·026). BCC incidence has been stable since 2000 (APC −0·80, P = 0·09). In situ and invasive SCC also showed a trend towards stabilization in 2000 (APC 0·36, P = 0·77) and 1995 (APC 0·01, P = 0·98), respectively. NMSC primarily affects the elderly and is rarely seen in individuals before the age of 40 years. Although the head and neck region was the location most often involved with NMSC (71·1%), it revealed a stabilizing trend, whereas most other anatomical regions demonstrated an increasing NMSC incidence rate. Conclusions NMSC incidence in Alberta has stabilized in women and declined in men. As 95–99% of NMSC occurs in patients aged 40 years or older, and with its increased frequency in traditionally clothed areas, the authors recommend regular complete skin examinations starting at 40 years of age.

Background There is evidence to suggest that melanoma incidence rates continue to rise in Canada and the United States. Objective Our objective was to determine cutaneous melanoma trends from 1993 to 2002 in the province of Alberta and to compare the results to previously published provincial analyses for the decade of 1967-1976. Methods A retrospective study of 3479 patients with cutaneous melanoma diagnosed in Alberta between 1993 and 2002 was conducted. Estimates of relative survival compared the survival of melanoma patients with the Alberta population to derive the likelihood of surviving melanoma in the absence of other causes of death. Further comparison to published Canadian data was also conducted. Results For the period 1993-2002, the annual melanoma age-standardized incidence rates per 100,000 person-years ranged between 11.1 and 15.9 and between 9.8 and 14.1 among men and women, respectively. These rates are considerably higher than the previously reported (1976) highest Alberta incidence rates of 4.1 and 4.8 in men and women, respectively. The rates increased slightly for the period 1993-1999 with an average annual percentage change of +3.5%, but appeared to decrease for the interval 1999-2002 with an average annual percentage change of −6.4%. The majority of the tumors were less than 1.0 mm in thickness for both genders. On univariate analysis the following parameters were associated with decreasing patient survival: male gender, increasing age, head and neck tumors, Clark level of invasion, and Breslow tumor thickness. Multivariate analysis demonstrated that the strongest determinant of survival was Breslow tumor thickness. Limitations Melanomas in-situ were not included in this study. Conclusions Although melanoma incidence rates in Alberta are higher than previously reported, the incidence rates over the study period of 1993 to 2002 appear to have leveled and may in fact be declining over the past several years.

Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for late effects of cancer therapy. Five-year ALL survivors (< 21 years at diagnosis; n = 5760 eligible, 4151 participants), diagnosed from 1970 to 1986 were compared with the general population and a sibling cohort (n = 3899). Cumulative mortality of 5760 5-year survivors was 13% at 25 years from diagnosis. Recurrent ALL (n = 483) and second neoplasms (SNs; n = 89) were the major causes of death. Among 185 survivors, 199 SNs occurred, 53% in the CNS. Survivors reported more multiple chronic medical conditions (CMCs; odds ratio [OR], 2.8; 95% CI, 2.4-3.2) and severe or life-threatening CMCs (OR, 3.6; 95% CI, 3.0-4.5) than siblings. Cumulative incidence of severe CMCs, including death, 25 years from diagnosis was 21.3% (95% CI, 18.2-24.4; 23.3% [95% CI, 19.4-27.2] and 13.4% [95% CI, 8.4-18.4] for irradiated and nonirradiated survivors, respectively). Survivors reported more adverse general and mental health, functional impairment, and activity limitations compared with siblings (P < .001). Rates of marriage, college graduation, employment, and health insurance were all lower compared with sibling controls (P < .001). Long-term survivors of childhood ALL exhibit excess mortality and morbidity. Survivors who received radiation therapy as part of their treatment or had a leukemia relapse are at greatest risk for adverse outcomes.

BACKGROUND Limited data exist on the comprehensive assessment of late medical and social effects experienced by survivors of childhood and young adult acute myeloid leukemia (AML). METHODS This analysis included 272 5-year AML survivors who participated in the Childhood Cancer Survivor Study (CCSS). All patients were diagnosed at age ≤21 years between the years 1970 and 1986, and none underwent stem cell transplantation. Rates of survival, relapse, and late outcomes were analyzed. RESULTS The average follow-up was 20.5 years (range, 5–33 years). The overall survival rate was 97% at 10 years (95% confidence interval [95%CI], 94%–98%) and 94% at 20 years (95% CI, 90%–96%). Six survivors reported 8 recurrences. The cumulative incidence of recurrent AML was 6.6% at 10 years (95% CI, 3.7%–9.6%) and 8.6% at 20 years (95% CI, 5.1%–12.1%). Ten subsequent malignant neoplasms (SMN) were reported, including 4 with a history of radiation therapy, for a 20-year cumulative incidence of 1.7% (95% CI, 0.02%–3.4%). Six cardiac events were reported, for a 20-year cumulative incidence 4.7% (95% CI, 2.1%–7.3%). Half of the survivors reported a chronic medical condition and, compared with siblings, were at increased risk for severe or life-threatening chronic medical conditions (16% vs 5.8%; P < .001). Among those aged ≥25 years, the age-adjusted marriage rates were similar among survivors and the general United States population (57% for both) and lower compared with siblings (67%; P < .01). Survivors' college graduation rates were lower compared with siblings but higher than the general population (40% vs 52% vs 34%, respectively; P < .01). Employment rates were similar between survivors, siblings, and the general population (93%, 97.6%, and 95.8%, respectively). CONCLUSIONS Long-term survival from childhood AML ≥5-years after diagnosis was favorable. Late-occurring medical events remained a concern with socioeconomic achievement lower than expected within the individual family unit, although it was not different from the general United States population. Cancer 2008. © 2008 American Cancer Society.

OBJECTIVE: To describe the trends over calendar period and birth cohort in lung cancer incidence by histopathology and sex, in Alberta. METHODS: Lung cancer data were extracted from the Alberta Cancer Registry for the years 1979 to 1998. Trends in age-standardized rates over calendar period and trends of age-specific rates over birth cohorts are presented. These trends are discussed in relation to historic smoking patterns. RESULTS: Lung cancer incidence is increasing over calendar period in females for all lung cancers and the histological types, adenocarcinoma, squamous cell, and small cell carcinoma. In males, all lung cancer incidence increases until 1988 and then decreases. Adenocarcinoma incidence in males increases over the whole time period, while squamous cell and small cell carcinoma incidence decreases. For females born before 1939, the incidence of all lung cancer and the three histological types increases over birth cohorts for all age groups. For those born after 1939, there is a slight decline. Male lung cancer incidence shows no marked increases over birth cohorts. In males born after 1929, all lung cancer and squamous cell and small cell carcinoma incidence decreases over birth cohorts for all age groups. Incidence of adenocarcinoma increases over all birth cohorts in males. CONCLUSION: In Alberta, incidence of adenocarcinoma of the lung is increasing in both males and females, while squamous cell and small cell carcinoma are decreasing in males, but increasing in females. These trends may reflect changes in smoking habits.

Rubella IgG levels for 157,763 pregnant women residing in Alberta between 2009 and 2012 were analyzed. As there have been no reported cases of indigenous rubella infection in Canada since 2005, there has been a lack of naturally acquired immunity, and the current prenatal population depends almost entirely on vaccine induced immunity for protection. Rubella antibody levels are significantly lower in younger maternal cohorts with 16.8% of those born prior to universal vaccination programs (1971-1980), and 33.8% of those born after (1981-1990) having IgG levels that are not considered protective (

Background: The combination measles–mumps–rubella–varicella (MMRV) vaccine currently used in Canada (Priorix-Tetra) may increase the risk of febrile seizures relative to the separate vaccines (MMR and varicella) previously administered. We determined the risk of febrile seizure after the first dose of MMRV, as well as any additional risk for children at high risk for seizures because of pre-existing medical conditions. Methods: In this retrospective, population-based cohort study, we compared the risk of seizures after the first dose of MMRV with the risk after same-day administration of separate MMR and varicella vaccines (MMR+V) in children 12 to 23 months of age in the province of Alberta. We deterministically linked vaccination data to health service utilization data for seizures. We used Poisson regression, with adjustment for age and calendar year, to determine the risk for the full cohort and for high-risk children. Results: The risk of seizures 7 to 10 days after vaccination was twice as high with MMRV as with MMR+V (relative risk [RR] 1.99, 95% confidence interval [CI] 1.30–3.05). The excess absolute risk of seizures was 3.52 seizures per 10 000 doses of MMRV relative to MMR+V. In high-risk children, the risk was not differentially higher for MMRV (RR 1.30, 95% CI 0.60–2.79). Interpretation: Despite an increased risk of febrile seizures following MMRV (compared with MMR+V), the absolute level of risk was small. Policy-makers need to balance these findings with the potential benefits of administering the combination vaccine or determine whether the choice of vaccine rests with clinicians and/or parents.

Summary Background Recent studies have revealed geographical variations with respect to the risk of second primary malignancies (SPMs) following cutaneous malignant melanoma (CMM) and nonmelanoma skin cancer (NMSC). Objectives To provide the largest analysis of the risk of SPM following skin cancers in Canada and to detect associations that may shed light on common pathogeneses between linked malignancies. Methods Relative risks for development of SPMs following a diagnosis of CMM or NMSC were calculated via a retrospective analysis of data retrieved from the Alberta Cancer Registry (ACR) from 1979 to 2009. Results From 1979 to 2009, 85 967 NMSC and 6884 CMM incident cases were recorded in the ACR. In total 19 869 SPMs were identified following a primary NMSC (7709 cutaneous and 12 160 noncutaneous), while 1437 SPMs (908 cutaneous and 529 noncutaneous) followed CMM. Patients with a previous history of skin cancer had a 60% increased risk of developing an SPM compared with those without [observed/expected ratio (O/E) 1.6, 95% confidence interval (CI) 1.6–1.7; P

Background There have only been a few population-based, epidemiologic studies assessing dermatofibrosarcoma protuberans (DFSP). Objective To assess the epidemiology of DFSP in Alberta, Canada, over a 20-year period. Methods A population-based, retrospective analysis of all cases of DFSP in Alberta was conducted using data from the Alberta Cancer Registry. Sex-, age-, and anatomical location–specific incidence rates and trends were determined. Results The overall age-standardized incidence rate of DFSP remained stable at 0.93 per 100,000. DFSP prevalence was highest in individuals aged 20 to 39 (46.8%), followed by those aged 40 to 59 (34.0%), 60 and older (14.7%), and lastly younger than 20 (4.5%). The mean age at diagnosis was 41.1 (women) and 43.1 (men). The incidence of DFSP in men and women has shown a dramatic shift such that incidence in women has increased 3.2% per year, whereas in men it has decreased 2.7% per year. In women, DFSP incidence increased on the trunk and decreased on the upper extremities. Conclusion The age-standardized incidence of DFSP observed is nearly twice as high as previously reported and has remained stable. The incidence is increasing in women and decreasing in men. DFSP primarily affects young to middle-aged adults and most commonly presents on the trunk.

Background Public health surveillance is often concerned with the analysis of health outcomes over small areas. Funnel plots have been proposed as a useful tool for assessing and visualizing surveillance data, but their full utility has not been appreciated (for example, in the incorporation and interpretation of risk factors). Methods We investigate a way to simultaneously focus funnel plot analyses on direct policy implications while visually incorporating model fit and the effects of risk factors. Health survey data representing modifiable and nonmodifiable risk factors are used in an analysis of 2007 small area motor vehicle mortality rates in Alberta, Canada. Results Small area variations in motor vehicle mortality in Alberta were well explained by the suite of modifiable and nonmodifiable risk factors. Funnel plots of raw rates and of risk adjusted rates lead to different conclusions; the analysis process highlights opportunities for intervention as risk factors are incorporated into the model. Maps based on funnel plot methods identify areas worthy of further investigation. Conclusions Funnel plots provide a useful tool to explore small area data and to routinely incorporate covariate relationships in surveillance analyses. The exploratory process has at each step a direct and useful policy-related result. Dealing thoughtfully with statistical overdispersion is a cornerstone to fully understanding funnel plots.

Background: Survival for ALL has improved substantially: current five-year survival rates are approximately 80% yet survivors continue to experience late medical and social effects. Objective: To report rates of mortality and second neoplasm (SN) and selected social outcomes from a large cohort of childhood ALL survivors. Methods: Five year survivors of ALL (n=4151) diagnosed < age 21, from 1970–1986 were compared to population rates or a sibling control group (n=3899) for mortality, SN, education, marriage, health insurance and employment. Results: Survivors and siblings were 53% and 48% male; median ages were 26 and 31yrs respectively. Survivors had a mean age of 6 yrs (range 0–20) at diagnosis and had a mean follow-up of 22 yrs (range 16–34). Sixty two percent received chemotherapy (CT) + radiation therapy (RT), 5.2% underwent marrow transplant with CT +/− RT, while 27% received CT only. Among 5yr survivors, 417 deaths occurred; cumulative mortality was 12% at 25 yrs. Recurrent ALL accounted for 67% of deaths, while 13% (n=55) died of SN. Standardized mortality rate (95% confidence intervals) for malignant SNs was 14.0 (10.7–17.9). Survival at 25 yrs was 94% for patients who never reported relapse and 59% for patients who reported a relapse (p Conclusion: In the largest long-term follow-up study of its kind, the CCSS cohort demonstrated a significant improvement in survival over time among 5-yr survivors of ALL with and without history of relapse. Death after cohort entry was due most commonly to ALL, although SNs contributed substantially. HS graduation rates for survivors were comparable to the sibling cohort, but the rates were significantly lower for college graduation and for marraige. Although lower than siblings, majority of survivors reported being employed and having health insurance. There was no significant difference between the survivors of relapsed and non-relapsed ALL, with respect to their socioeconomic outcomes. Rates (percentage), Age Standardized to Siblings Sibling Non-relapse Relapse p-value Relapse vs. Non * p for rows 1 & 2 HS grad 97 93 97 College grad 52 41 41 .78* Never married 21 34 46 .10 Ever employed 100 98 97 .07 Health Insurance 90 86 88 .86

Survival rates for childhood AML continue to improve. Limited data exist on the comprehensive assessment of late medical and social effects experienced by these aggressively treated individuals. This analysis includes 272 5-yr survivors of AML participating in the CCSS diagnosed ≤ age 21, between 1970–1986. AML survivors who received a blood or marrow transplant are excluded from the current analysis. Comparisons among treatment groups and to a sibling control group are age and gender adjusted. Survivors (55% female) were on average 7 yrs old at dx and 28 yrs at follow-up, 56% received chemotherapy only, 34% chemotherapy/RT. Average follow-up was 22.6 yrs (16.1–33.5). Among these 5-yr survivors, overall survival was 97% (95% CI, 94–98%) at 10 yrs and 94% (95% CI, 92–97%) at 20 yrs. Six individuals reported 8 recurrences a mean of 11.1 yrs (5.6–16.6) from diagnosis, 2 died from relapse, 1 from congestive heart failure (CHF), and 1 from a myocardial infarction (MI). All cause standardized mortality ratio was 4.7 (95% CI 2.8–7.5). Cumulative incidence of recurrent AML at 10 and 20 years was 1.8% (95% CI 0.2–3.4%) and 3.7% (95% CI 1.4–5.9%), respectively. Eight survivors reported 10 subsequent malignant neoplasms (SMN) (5 breast cancers, 3 CNS tumors, 1 ovarian tumor, 1 salivary gland tumor) a mean of 18.7 yrs (9.2–26.4) from diagnosis, 3 with a history of RT exposure. SMN cumulative incidence at 20 yrs was 1.6% (95% CI 0.02–3.3%) with a standardized incidence ratio of 3.2 (95% CI 1.4–6.0). Six cardiac events (5 CHF and 1 MI) occurred a mean of 16.4 yrs (12.8–18.4) from diagnosis, 20-yr cumulative incidence 2.4% (95% CI 0.5–4.4%). Among those aged 25 yrs or more, marriage rates were similar among AML survivors and the general U.S. population (59%), but lower compared to siblings (69%) (p