Basal Insulin Initiation in Adults With Type 2 Diabetes Mellitus: A Retrospective Cohort Study Using Administrative Health Data in Alberta, Canada.

OBJECTIVES: Pharmacologic treatment of type 2 diabetes mellitus (T2DM) follows a stepwise approach. Typically, metformin monotherapy is first-line treatment, followed by other noninsulin antihyperglycemic agents (NIAHAs) or progression to insulin if glycated hemoglobin (A1C) targets are not achieved. We aimed to describe real-world patterns of basal insulin initiation in people with T2DM, and A1C not at target despite treatment with at least 2 NIAHAs. METHODS: A retrospective cohort study was conducted using administrative health data from Alberta, Canada, among adults with T2DM, indexed on the first test with 7.0% < A1C < 9.5% (April 1, 2011 to March 31, 2019), with at least 2 previous NIAHAs but no insulin. Kaplan-Meier (KM) methodology was used to analyze time to basal insulin initiation, with stratification by index A1C. Annual patient status was categorized into 5 groups: basal insulin initiation, death, NIAHA intensification, no change in therapy (subgroups of A1C <7.1% and A1C ≥7.1% [clinical inertia]), or discontinuance. RESULTS: The cohort included 14,083 individuals. The KM cumulative probability of initiating basal insulin was 7.7% (95% confidence interval [CI] 7.3% to 8.2%) at 1 year, increasing to 43.1% (95% CI 42.1% to 44.1%) at 8 years of follow-up. Higher A1C levels were associated with greater proportions of basal insulin initiation. By year 8, proportions with NIAHA intensification and clinical inertia were 12.1% and 19.3%, respectively, relative to year 7. CONCLUSIONS: Despite current clinical practice guidelines recommending achieving A1C targets within 6 months, less than half of the individuals with T2DM and clear indications for basal insulin initiated treatment within 8 years. Efforts to reduce delays in basal insulin initiation are needed.

Real-World Risk of Recurrent Cardiovascular Events in Atherosclerotic Cardiovascular Disease Patients with LDL-C Above Guideline-Recommended Threshold: A Retrospective Observational Study.

INTRODUCTION: The 2021 Canadian Cardiovascular Society (CCS) guidelines recommend intensive low-density lipoprotein cholesterol (LDL-C) reduction for patients with atherosclerotic cardiovascular disease (ASCVD). For patients above LDL-C threshold on maximally tolerated statins, adding ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) is recommended. This population-based, real-world study examined cardiovascular (CV) events in patients with ASCVD who are on statins and above current guideline threshold LDL-C levels. METHODS: Using administrative health data in Alberta, Canada, we identified patients with myocardial infarction (MI), ischemic stroke (IS), or peripheral artery disease with LDL-C > 1.8 mmol/L on statins between April 1, 2010 and March 31, 2016. Exploratory subgroups included very high-risk patients with ASCVD shown to derive the most benefit from PCSK9i intensification as identified by the CCS guidelines, including those with acute coronary syndrome (ACS) or recent MI. Frequencies and rates of individual and composite CV events (primary outcome: MI, IS, hospitalization for unstable angina, coronary revascularization, cardiovascular death; secondary outcome: MI, IS, CV death) were calculated over follow-up. RESULTS: The study included 32,984 patients with a mean (standard deviation) follow-up of 40.8 (21.0) months. Overall, 17.7% and 15.6% experienced a primary and secondary outcome, respectively, with rates of 5.58 and 4.83 per 100 patient-years, respectively. CV death and MI were the most common events. Subgroups with recurrent MI and comorbid diabetes exhibited higher CV event rates (23.6% and 22.2% had a primary outcome, respectively). Rates of CV events were notably high in patients with ACS or recent MI (49.4% and 54.0% had a primary outcome, respectively). CONCLUSION: This real-world study confirms that statin-treated high-risk patients with ASCVD and above-threshold LDL-C levels have substantial incidence of recurrent CV events. These findings reinforce the opportunity for lipid-lowering therapy intensification in high-risk patients to levels below guideline-recommended threshold in order to reduce CV risk.

Prevalence of Adult Type 2 Diabetes Mellitus and Related Complications in Alberta, Canada: A Retrospective, Observational Study Using Administrative Data.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) is a prevalent chronic disease and a leading cause of morbidity/mortality in Canada. We evaluated the burden of T2DM in Alberta, Canada, by estimating the 5-year period prevalence of T2DM and rates of comorbidities and complications/conditions after T2DM. METHODS: We conducted a population-based, retrospective study linking administrative health databases. Individuals with T2DM (≥18 years of age) were identified between 2008-2009 and 2018-2019 using a published algorithm, with follow-up data to March 2020. The 5-year period prevalence was estimated for 2014-2015 to 2018-2019. Individuals with newly identified T2DM, ascertained between 2010-2011 and 2017-2018 with a lookback period between 2008-2009 and 2009-2010 and a minimum 1 year of follow-up data, were evaluated for subsequent cardiovascular, diabetic, renal, and other complication/condition frequencies (%) and rates (per 100 person-years). Complications/conditions were stratified by atherosclerotic cardiovascular disease (ASCVD) status at index and age. RESULTS: The 5-year period prevalence of T2DM was 11,051 per 100,000 persons, with the highest prevalence in men 65 to <75 years of age. There were 195,102 individuals included in the cohort (mean age 56.7±14.7 years). The most frequently reported complications/conditions (rates per 100 person-years) were acute infection (23.10, 95% confidence interval [CI] 23.00 to 23.30), hypertension (17.30, 95% CI 16.80 to 17.70), and dyslipidemia (12.20, 95% CI 11.90 to 12.40). Individuals who had an ASCVD event/procedure and those ≥75 years of age had higher rates of complications/conditions. CONCLUSIONS: We found that over half of the individuals had hypertension or infection after T2DM. Also, those with ASCVD had higher rates of complications/conditions. Strategies to mitigate complications/conditions after T2DM are required to reduce the burden of this disease on individuals and health-care systems.

Guideline LDL-C Threshold Achievement in Acute Myocardial Infarction Patients: A Real-World Evidence Study Demonstrating the Impact of Treatment Intensification with PCSK9i.

INTRODUCTION: A high proportion of Canadian patients with acute myocardial infarction (AMI) do not achieve the threshold low-density lipoprotein cholesterol (LDL-C) levels recommended by the Canadian Cardiovascular Society in 2021. This increases the risk of subsequent atherosclerotic cardiovascular disease (ASCVD) events. Here, we assess LDL-C levels and threshold achievement among patients by lipid-lowering therapies (LLT) received post-AMI. METHODS: A retrospective cohort study of patients identified with AMI between 2015 and 2019 was conducted using administrative health databases in Alberta, Canada. Patients were grouped by their highest-intensity LLT post-AMI (proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) + another LLT; PCSK9i alone; ezetimibe + statin; statins (high, moderate, low intensity); or ezetimibe alone), and available LDL-C levels were examined in the year before and after LLT dispense date. RESULTS: The cohort included 15,283 patients. In patients on PCSK9i + LLT, the median [95% confidence interval (CI)] LDL-C levels decreased from 2.7 (2.3-3.4) before to 0.9 (0.5-1.2) mmol/l after treatment, the largest decrease among treatment groups. In the ezetimibe + statin and high-intensity statin groups, median (95% CI) values after treatment were 1.5 (1.5-1.6) and 1.4 (1.4-1.4) mmol/l, respectively. The proportion of patients below the 1.8 mmol/l threshold increased by 77.7% in the PSCK9i + LLT group after treatment, compared to 45.4 and 32.4% in the ezetimibe + statin and high-intensity statin groups, respectively. CONCLUSIONS: Intensification with PCSK9i in AMI patients results in a greater proportion of patients achieving below the recommended LDL-C threshold versus statins and or ezetimibe alone. Increased focus on achieving below the LDL-C thresholds with additional LLT as required may benefit patient cardiovascular outcomes.

Epidemiology and treatment utilization for Canadian patients with migraine: a literature review.

The objective of this narrative review was to identify real-world evidence regarding the burden of migraine in Canada. We conducted a literature search in MEDLINE, Embase, and the Cochrane Database of Systematic Reviews for studies published between August 2010 and August 2020. Of the 3269 publications identified, 29 studies were included. Prevalence estimates varied widely across Canada, and mental health comorbidities were common. Individuals with migraine have a lower quality of life, detrimental impact on workforce productivity, and higher rates of health care resource utilization (HCRU), with HCRU and costs highest among those with chronic migraine. We found inconsistencies in care, including underutilization of medications such as triptans, and varied utilization of over-the-counter and prescription medications. Increased medication use was identified among those with chronic migraine, and only a small number of patients used migraine preventive medications. The burden of migraine in Canada is substantial. Reduced quality of life and workforce productivity, increased HCRU and costs, and underutilization of triptans and migraine preventive medications highlight an important need for more effective management of individuals with migraine.

Real-world treatment patterns for patients with newly diagnosed multiple myeloma in Alberta, Canada.

The purpose of this study is to describe the real-world multiple myeloma (MM) population in Alberta by examining patient/clinical characteristics and the treatment landscape. A retrospective, observational study was conducted using province-wide, administrative health data from Alberta, Canada evaluating newly diagnosed MM (NDMM) patients. Between 1 April 2011 and 31 March 2017, 1377 treated NDMM cases were identified. Of those, 328 (23.8%) received an autologous stem cell transplant (ASCT) within the first year of diagnosis. In the ASCT group, 189 advanced to second-line (57.6%), 103 (32.6%) to third-line and 97 (29.5%) had four or more lines of therapy. In non-ASCT patients, 553 (52.7%) advanced to second-line, 238 (22.7%) to third-line, and 154 (14.7%) had 4 or more lines of therapy. We observed a significant treatment attrition rate in NDMM. Therefore, the use of best therapy upfront and novel strategies aiming to decrease attrition rates in MM is encouraged.

Disease Burden of Huntington's Disease (HD) on People Living with HD and Care Partners in Canada.

BACKGROUND: Huntington's disease (HD) has been shown to reduce health-related quality of life (HRQoL) and affect healthcare resource utilization (HRU) among patients and care partners internationally but has not been studied specifically in the Canadian context. OBJECTIVE: To characterize the burden of HD on individuals with HD and care partners of individuals with HD in Canada. METHODS: An online survey was distributed (September 14-November 23, 2020) through patient organizations to collect data on demographic and clinical characteristics, as well as: HRQoL, measured using the 36-Item Short-Form Health Survey (SF-36v1); HRU, measured using the Client Service Receipt Inventory (CSRI); and care partner burden, measured using the Caregiver Strain Index (CSI) and Huntington's Disease Quality of Life Battery for Carers (HDQoL-C). Descriptive statistics were used to report data and compare subgroups. RESULTS: A total of 62 adult individuals with HD (or their proxies) and 48 care partners met defined eligibility criteria. The mean [standard deviation] age was 51.2 [13.8] and 58.1 [13.9] years for individuals with HD and care partner respondents, respectively. For individuals with HD, the greatest HRQoL burden (i.e., lowest score) was for the SF-36v1 Role -Physical scale (46.8 [42.9]). HRU was higher for some services (e.g., general practitioner visits) for respondents who had experienced motor onset transition. Among care partners, 55.3% experienced high strain, as indicated by the CSI. The HDQoL-C showed the greatest HRQoL burden in feelings about life (45.1 [17.9]). CONCLUSION: This study quantified the substantial burden on individuals with HD and care partners in Canada, addressing a critical knowledge gap that can affect the availability of and access to healthcare services.

Epidemiology and economic burden of Huntington's disease: a Canadian provincial public health system perspective.

AIMS: To evaluate the epidemiology, healthcare resource utilization, and direct healthcare costs associated with Huntington's disease in a Canadian setting with a universal healthcare system. MATERIALS AND METHODS: Using Albertan administrative health data, a retrospective cohort was identified applying an algorithm requiring two HD diagnostic codes within two years, using the first record as the index date (i.e. proxy for diagnosis date), from 1 April 2010 to 31 March 2019 for patients ≥21 years old. Incidence/prevalence measures were evaluated from 1 April 2010 to 31 March 2019, while healthcare resource utilization and healthcare costs per person-year (inflated to 2020 Canadian dollars) were evaluated from index to the end of follow-up (death, moved out of province, or 31 March 2020). RESULTS: Mean [standard deviation] age at index (n = 395) was 53.9 [13.8] years and 53.7% were female. From 2010 to 2019, annual HD incidence varied between 0.47 and 1.21/100,000 person-years and HD prevalence increased from 7.25 to 9.33/100,000 persons. The mean number of visits per person-year for general and specialist practitioners was 19.2 [18.8] and 12.2 [25.5], respectively. The mean total all-cause direct healthcare costs were $23,211 [$38,599] per person-year, with hospitalizations accounting for 57.8% of all-cause costs. Costs were higher among individuals with a long-term care stay, a proxy for disease severity. LIMITATIONS AND CONCLUSIONS: This study utilizes administrative health data to describe the epidemiology of HD and utilization of publicly funded care by individuals with HD. While administrative data presents limitations since it is not collected for research purposes, it provides a population-level examination of the burden of HD. There was a substantial economic burden associated with HD in a Canadian setting.

Age-standardized cancer-incidence trends in Canada, 1971-2015.

BACKGROUND: Although cancer incidence over time is well documented in Canada, trends by birth cohort and age group are less well known. We analyzed age- and sex-standardized incidence trends in Canada for 16 major cancer sites and all cancers combined. METHODS: We obtained nationally representative population-based cancer incidence data in Canada between 1971 and 2015 from the National Cancer Incidence Reporting System (1969-1992) and the Canadian Cancer Registry (1992-2015). We analyzed cancer-incidence trends, reported as annual percent change (APC) for each 10-year group from age 20 to 89 years. We also estimated age-adjusted incidence rate ratios from fitted birth cohort models. RESULTS: Across most age categories, the most recent trends show significant decreases in the incidence of cervical (APC -8.8% to -0.33%), lung (men: -7.42% to -0.36%; women: -6.27% to 1.07%), bladder (women: -4.12% to -0.07%; men: -5.13% to -0.38%) and prostate cancer (-11.11% to -1.11%). Significant increasing trends were observed for kidney, thyroid and uterine cancers. Overall incidence has increased among both sexes younger than 50 years of age, with recent increases in pancreatic cancer among men, breast cancer among women and colorectal cancer among both sexes. From the birth cohort analysis, we observed increasing trends in colorectal, liver and prostate cancers among men; kidney cancer and melanoma among women; and thyroid cancer among both sexes. We observed decreasing trends in cervical and ovarian cancers, and in bladder and lung cancers among men. INTERPRETATION: Cancer incidence is decreasing at many sites targeted by primary-prevention efforts, such as smoking cessation and screening programs. Substantial increases in incidence among younger populations are driven by cancers possibly associated with obesity.

The effect of prescribed exercise volume on biomarkers of chronic stress in postmenopausal women: Results from the Breast Cancer and Exercise Trial in Alberta (BETA).

There is epidemiologic and biologic evidence for a role of stress in breast cancer etiology and physical activity mitigates the negative effects of stress. We examined the potential for a dose-response relationship between two volumes of aerobic exercise and biomarkers of chronic stress in post-menopausal women. The Breast Cancer and Exercise Trial in Alberta is a randomized controlled trial with post-menopausal women randomized to either a MODERATE (150 min per week) or HIGH (300 min per week) volume of exercise over a one year intervention period. Fasting serum concentrations of cortisol, cortisone, corticosterone and 11-deoxycortisol at baseline, 12 months (the end of the intervention), and 24 months. Intention-to-treat analyses were performed using general linear models, adjusted for baseline biomarker concentrations. There were modest but non-statistically significant decreases in cortisol (HIGH: -4%, 95% CI: -7%, 2%; MODERATE: -1%, 95%: CI: -14%, 4%) and corticosterone (HIGH: -4%, 95% CI: -12%, 6%; MODERATE: -5%, 95% CI: -14%, 4%) concentrations for both exercise groups between baseline and 12 months, and no difference in cortisone concentrations. Intention-to-treat analysis of 386 (97%) participants showed no statistically significant group differences for changes in biomarker levels at 12 months. Between baseline and 12 months, there were no differences in cortisol or cortisone and, at 24 months all stress hormone levels increased to near-baseline levels with no significant differences between the two intervention groups.

Effects of physical activity on colorectal cancer risk among family history and body mass index subgroups: a systematic review and meta-analysis.

BACKGROUND: Physical activity is consistently associated with a reduced risk of colorectal cancer in epidemiologic studies. This association among higher risk subgroups, such as those with a first-degree family history of colorectal cancer or high body mass index remains unclear. METHODS: We searched MEDLINE for studies examining physical activity and colorectal cancer risk among higher risk subgroups through July 11, 2017. Fifteen and three studies were eligible for inclusion for body mass index and first-degree family history of colorectal cancer subgroups, respectively. Estimates of the highest to lowest comparison of physical activity for each subgroup of risk were pooled using random-effects models. RESULTS: The pooled associations of physical activity and colorectal cancer risk for those without and with a first-degree family history of colorectal cancer were 0.56 (95% confidence interval (CI) = 0.39-0.80) and 0.72 (95% CI = 0.39-1.32), respectively (pheterogeneity = 0.586). The pooled associations of physical activity and colorectal cancer risk for the low and high body mass index groups were 0.74 (95% CI = 0.66-0.83) and 0.65 (95% CI = 0.53-0.79), respectively (pheterogeneity = 0.389). CONCLUSIONS: Overall, a stronger relative risk of physical activity on colorectal cancer risk was observed in the higher body mass index group, although the difference was not statistically significant, suggesting an added benefit of physical activity as a cancer prevention strategy in population groups with strong risk factors for colorectal cancer. Additional research among these subgroups is warranted.

The association between recreational physical activity, sedentary time, and colorectal polyps in a population screened for colorectal cancer.

PURPOSE: Regular recreational moderate to vigorous physical activity (rMVPA) has been previously associated with a reduced risk of colorectal cancer (CRC), however, few studies have examined the association of rMVPA with colorectal polyps, the pre-malignant precursor lesions. The objective of this study was to examine the associations between physical activity and sitting time and polyps at the time of screening. METHODS: We conducted a cross-sectional study of 2496 individuals undergoing screening-related colonoscopy in Calgary, Alberta, Canada. Physical activity and sitting time were characterized using hours of rMVPA, meeting physical activity recommendations and hours of sitting time using self-reported data obtained from the International Physical Activity Questionnaire. Logistic regression models were used to estimate the crude and adjusted odds ratios (OR) for presence of polyps associated with rMVPA and sitting time. RESULTS: Meeting physical activity guidelines of ≥150 min/week was non-significantly associated with a modest decrease in odds of having ≥1 polyp at screening (ORadj = 0.95, 95% CI: 0.80-1.14). In males, threshold effects for sitting time were observed for up to 20 h/week (ORadj per hour sitting = 1.07, 95% CI: 1.01-1.13). In stratified analysis, larger inverse associations were observed between physical activity and the presence of polyps in females, obese individuals, and ever smokers, compared to pooled findings. CONCLUSIONS: In this large CRC screening population, there was a suggestive association between increased rMVPA and reduced prevalence of polyps at screening, particularly among females. Even low amounts of regular sitting time (0-20 h/day) were associated with the presence of polyps, particularly among males. Further research on rMVPA and sitting time is necessary to better inform strategies to reduce the frequency of pre-malignant colorectal lesions.

Increasing colorectal cancer incidence trends among younger adults in Canada.

Recent analyses in the United States have shown an overall decrease in the incidence of colorectal cancer despite contrasting increases in younger age groups. We examined whether these cohort trends are occurring in Canada. Age-specific trends in colon and rectal cancer incidence in Canada from the National Cancer Incidence Reporting System (1969-1992) and the Canadian Cancer Registry (1992-2012) were analyzed. We estimated annual percent changes (APC) with the Joinpoint Regression Program from the Surveillance Epidemiology, and End Results Program. Birth cohort effects were estimated using 5-year groups starting in 1888. Age-specific prevalence of class I, II and III obesity in Canada was examined from the National Population Health Survey (1994-2001) and the Canadian Community Health Survey (2001-2011). The reductions in CRC incidence among Canadians are limited to older populations. While reductions among younger age groups (20-29year olds (yo), 30-39yo and 40-50yo) were observed between 1969 and 1995, rates have returned to and surpassed historical levels (APCs 20-29yo colon cancer=6.24%, APCs 20-29yo rectal cancer=1.5%). Recent birth cohorts (1970-1990) have the highest incidence rate ratios ever recorded. Ecologic trends in obesity prevalence among these birth cohorts in Canada are suggestive of an impact on increasing incidence trends. Furthermore, obesity prevalence estimates suggest that these trends may continue to increase justifying further examination of the etiologic associations and biological impacts of excess adipose tissue among younger populations. While population-based screening of younger age groups deserves careful consideration, these concerning observed trends warrant public health action to address the growing obesity epidemic.

Intake of dietary fibre and lifetime non-steroidal anti-inflammatory drug (NSAID) use and the incidence of colorectal polyps in a population screened for colorectal cancer.

BACKGROUND: There is suggestive evidence that increased intake of dietary fibre and the use of non-steroidal anti-inflammatory drugs (NSAIDs) are generally associated with decreased colorectal cancer risk. However, the effects on precursors of colorectal cancer, such as adenomatous polyps, are mixed. We present the associations between dietary fibre intake and NSAID use on the presence and type of colorectal polyps in a screening population. METHODS: A cross-sectional study of 2548 individuals undergoing colonoscopy at the Forzani & MacPhail Colon Cancer Screening Centre (Calgary, Canada) was conducted. Dietary fibre intake and NSAID use were assessed using the Diet History Questionnaire I or II and the Health and Lifestyle Questionnaire. Colorectal outcomes were documented as a polyp or high-risk adenomatous polyp (HRAP; villous histology, high-grade dysplasia, ≥10 mm or ≥3 adenomas). Crude and ORs and 95% CIs were estimated using unconditional logistic regression. RESULTS: There were 1450 negative colonoscopies and 1098 patients with polyps, of which 189 patients had HRAPs. Total dietary fibre intake was associated with a decreased presence of HRAPs (OR=0.50, 95% CI: 0.29 to 0.86) when comparing the highest to lowest quartiles and was observed with both soluble (OR=0.51, 95% CI: 0.30 to 0.88) and insoluble (OR=0.51, 95% CI: 0.30 to 0.86) fibres. Ever use of NSAIDs was also inversely associated with HRAPs (OR=0.65, 95% CI: 0.47 to 0.89), observed with monthly (OR=0.60, 95% CI: 0.37 to 0.95) and daily (OR=0.53, 95% CI: 0.32 to 0.86) use. CONCLUSIONS: Dietary fibre intake and NSAID use were associated with a decreased risk of having a HRAP at screening.

Epidemiology and biology of physical activity and cancer recurrence.

Physical activity is emerging from epidemiologic research as a lifestyle factor that may improve survival from colorectal, breast, and prostate cancers. However, there is considerably less evidence relating physical activity to cancer recurrence and the biologic mechanisms underlying this association remain unclear. Cancer patients are surviving longer than ever before, and fear of cancer recurrence is an important concern. Herein, we provide an overview of the current epidemiologic evidence relating physical activity to cancer recurrence. We review the biologic mechanisms most commonly researched in the context of physical activity and cancer outcomes, and, using the example of colorectal cancer, we explore hypothesized mechanisms through which physical activity might intervene in the colorectal recurrence pathway. Our review highlights the importance of considering pre-diagnosis and post-diagnosis activity, as well as cancer stage and timing of recurrence, in epidemiologic studies. In addition, more epidemiologic research is needed with cancer recurrence as a consistently defined outcome studied separately from survival. Future mechanistic research using randomized controlled trials, specifically those demonstrating the exercise responsiveness of hypothesized mechanisms in early stages of carcinogenesis, are needed to inform recommendations about when to exercise and to anticipate additive or synergistic effects with other preventive behaviors or treatments.

Effects of exercise on markers of oxidative stress: an Ancillary analysis of the Alberta Physical Activity and Breast Cancer Prevention Trial.

BACKGROUND: Oxidative stress may contribute to cancer aetiology through several mechanisms involving damage to DNA, proteins and lipids leading to genetic mutations and genomic instability. The objective of this study was to determine the effects of aerobic exercise on markers of oxidative damage and antioxidant enzymes in postmenopausal women. METHODS: The Alberta Physical Activity and Breast Cancer Prevention Trial (ALPHA) was a two-centre, two-armed randomised trial of 320 inactive, healthy, postmenopausal women aged 50-74 years. Participants were randomly assigned to a year-long exercise intervention (225 min/week) or a control group while being asked to maintain a normal diet. Fasting blood samples were obtained and plasma concentrations of two oxidative damage markers (8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostaglandin F2α (8-Iso-PGF2α)) and two antioxidant enzymes (superoxide dismutase and catalase) were measured at baseline, 6 months and 12 months. Intention-to-treat (ITT) and per-protocol analyses were performed using linear mixed models adjusted for baseline biomarker concentrations. A further exercise adherence analysis, based on mean minutes of exercise per week, was also performed. RESULTS: In the ITT and per-protocol analyses, the exercise intervention did not have any statistically significant effect on either oxidative damage biomarkers or antioxidant enzyme activity. CONCLUSIONS: A year-long aerobic exercise intervention did not have a significant impact on oxidative stress in healthy, postmenopausal women. TRIAL REGISTRATION NUMBER: NCT00522262.

Obesity and Endometrial Cancer.

Endometrial cancer is the sixth most common cancer in women worldwide and the most common gynecologic malignancy in the developed world. This chapter explores the current epidemiologic evidence on the association between obesity and endometrial cancer risk and mortality. Using body mass index (BMI) as a measure of obesity, we found that obesity (defined as BMI > 30 and < 35 kg/m2) was associated with a 2.6-fold increase in endometrial cancer risk, while severe obesity (BMI > 35 kg/m2) was associated with a 4.7-fold increase compared to normal-weight women (BMI < 25 kg/m2). Increased central adiposity also increased endometrial cancer risk by 1.5- to twofold. Among both healthy and endometrial cancer patient populations, obesity was associated with a roughly twofold increase in endometrial cancer-specific mortality. This risk reduction was also observed for obesity and all-cause mortality among endometrial cancer patients. In the few studies that assessed risk associated with weight change, an increased endometrial cancer risk with weight gain and weight cycling was observed, whereas some evidence for a protective effect of weight loss was found. Furthermore, early-life obesity was associated with a moderately increased risk of endometrial cancer later in life. There are several mechanisms whereby obesity is hypothesized to increase endometrial cancer risk, including increased endogenous sex steroid hormones, insulin resistance, chronic inflammation and adipokines. Further research should focus on histological subtypes or molecular phenotypes of endometrial tumors and population subgroups that could be at an increased risk of obesity-associated endometrial cancer. Additionally, studies on weight gain, loss or cycling and weight loss interventions can provide mechanistic insight into the obesity-endometrial cancer association. Sufficient evidence exists to recommend avoiding obesity to reduce endometrial cancer risk.

Impact of aerobic exercise on levels of IL-4 and IL-10: results from two randomized intervention trials.

The mechanisms whereby regular exercise reduces chronic inflammation remain unclear. We investigated whether regular aerobic exercise alters basal levels of interleukin (IL)-10 and IL-4 in two randomized trials of physical activity. The Alberta Physical Activity and Breast Cancer Prevention Trial (ALPHA, n = 320) and the Breast Cancer and Exercise Trial in Alberta (BETA, n = 400) were two-center, two-armed randomized trials in inactive, healthy, postmenopausal women. Both trials included an exercise intervention prescribed five times/week and no dietary changes. In ALPHA, the exercise group was prescribed 225 min/week versus no activity in the controls. BETA examined dose-response effects comparing 300 (HIGH) versus 150 (MODERATE) min/week. Plasma concentrations of IL-10 and IL-4 were measured at baseline, 6, and 12 months. Intention-to-treat (ITT) analysis was performed using linear mixed models adjusted for baseline biomarker concentrations. Circulating anti-inflammatory cytokine levels decreased among all groups, with percent change ranging from -3.4% (controls) to -8.2% (HIGH) for IL-4 and -1.6% (controls) to -7.5% (HIGH) for IL-10. No significant group differences were found for IL-4 (ALPHA P = 0.54; BETA P = 0.32) or IL-10 (ALPHA P = 0.84; BETA P = 0.68). Some evidence for moderation of the effect of exercise by baseline characteristics was found for IL-10 but not for IL-4. Results from these two large randomized aerobic exercise intervention trials suggest that aerobic exercise does not alter IL-10 or IL-4 in a manner consistent with chronic disease and cancer prevention.

Reproductive and genital health and risk of cervical human papillomavirus infection: results from the Ludwig-McGill cohort study.

BACKGROUND: There are inconsistencies in the literature on reproductive and genital health determinants of human papillomavirus (HPV) infection, the primary cause of cervical cancer. We examined these factors in the Ludwig-McGill Cohort Study, a longitudinal, repeated-measurements investigation on the natural history of HPV infection. METHODS: We analyzed a cohort subset of 1867 women with one complete year of follow-up. We calculated odds ratios (OR) and 95% confidence intervals (CI) for reproductive and genital health characteristics from questionnaire and laboratory data in relation to 1-year period prevalence of HPV infection. Two outcomes were measured; the first based on phylogenetic grouping of HPV types based on tissue tropism and oncogenicity (Alphapapillomavirus Subgenus 1: species 1, 8, 10 and 13; Subgenus 2: species 5, 6, 7, 9, 11; Subgenus 3: species 3, 4 and 14) and the second based on transient or persistent HPV infections. RESULTS: Lifetime (Subgenus 3 OR = 2.00, CI: 1.23-3.24) and current (Subgenus 3 OR =2.00, CI: 1.15-3.47) condom use and use of contraceptive injections (Subgenus 1 OR = 1.96, CI: 1.22-3.16, Subgenus 2 OR = 1.34, CI: 1.00-1.79) were associated with increased risk of HPV infection. Intrauterine device use was protective (Subgenus 1 OR = 0.48, CI: 0.30-0.75, Subgenus 2 OR = 0.78, CI: 0.62-0.98). These factors were not associated with persistence of HPV infection. Tampon use, previous gynecologic infections and cervical inflammation were associated with an overall increased risk of HPV infection. CONCLUSIONS: Cervical HPV infection was associated with reproductive and genital health factors. Further studies are necessary to confirm the low to moderate associations observed.