Diagnostic Delays in Sepsis: Lessons Learned From a Retrospective Study of Canadian Medico-Legal Claims.

Although rapid treatment improves outcomes for patients presenting with sepsis, early detection can be difficult, especially in otherwise healthy adults. OBJECTIVES: Using medico-legal data, we aimed to identify areas of focus to assist with early recognition of sepsis. DESIGN SETTING AND PARTICIPANTS: Retrospective descriptive design. We analyzed closed medico-legal cases involving physicians from a national database repository at the Canadian Medical Protective Association. The study included cases closed between 2011 and 2020 that had documented peer expert criticism of a diagnostic issue related to sepsis or relevant infections. MAIN OUTCOMES AND MEASURES: We used univariate statistics to describe patients and physicians and applied published frameworks to classify contributing factors (provider, team, system) and diagnostic pitfalls based on peer expert criticisms. RESULTS: Of 162 involved patients, the median age was 53 years (interquartile range [IQR], 34-66 yr) and mortality was 49%. Of 218 implicated physicians, 169 (78%) were from family medicine, emergency medicine, or surgical specialties. Eighty patients (49%) made multiple visits to outpatient care leading up to sepsis recognition/hospitalization (median = two visits; IQR, 2-4). Almost 40% of patients were admitted to the ICU. Deficient assessments, such as failing to consider sepsis or not reassessing the patient prior to discharge, contributed to the majority of cases (81%). CONCLUSIONS AND RELEVANCE: Sepsis continues to be a challenging diagnosis for clinicians. Multiple visits to outpatient care may be an early warning sign requiring vigilance in the patient assessment.

Patterns and trends among physicians-in-training named in civil legal cases: a retrospective analysis of Canadian Medical Protective Association data from 1993 to 2017.

BACKGROUND: Medico-legal data show opportunities to improve safe medical care; little is published on the experience of physicians-in-training with medical malpractice. The purpose of this study was to examine closed civil legal cases involving physicians-in-training over time and provide novel insights on case and physicians characteristics. METHODS: We conducted a retrospective descriptive study of closed civil legal cases at the Canadian Medical Protective Association (CMPA), a mutual medico-legal defence organization for more than 105 000 physicians, representing an estimated 95% of physicians in Canada. Eligible cases involved at least 1 physician-in-training and were closed between 1993 and 2017 (for time trends) or 2008 and 2017 (for descriptive analyses). We analyzed case rates over time using Poisson regression and the annualized change rate. Descriptive analyses addressed case duration, medico-legal outcome and patient harm. We explored physician specialties and practice characteristics in a subset of cases. RESULTS: Over a 25-year period (1993-2017), 4921 physicians-in-training were named in 2951 closed civil legal cases, and case rates decreased significantly (ß = -0.04, 95% confidence interval -0.05 to -0.03, where ß was the 1-year difference in log case rates). The annualized change rate was -1.1% per year. Between 2008 and 2017, 1901 (4.1%) of 45 967 physicians-in-training were named in 1107 civil legal cases. Cases with physicians-in-training generally involved more severe patient harm than cases without physicians-in-training. In a subgroup with available information (n = 951), surgical specialties were named most often (n = 531, 55.8%). INTERPRETATION: The rate of civil legal cases involving physicians-in-training has diminished over time, but more recent cases featured severe patient harm and death. Efforts to promote patient safety may enhance medical care and reduce the frequency and severity of malpractice issues for physicians-in-training.

Trends and Contributing Factors in Medicolegal Cases Involving Spine Surgery.

STUDY DESIGN: Retrospective descriptive study. OBJECTIVE: The aim of this study was to describe closed medicolegal cases involving physicians and spine surgery in Canada from a trend and patient safety perspective. SUMMARY OF BACKGROUND DATA: Spine surgery is a source of medicolegal complaints against surgeons partly owing to the potential severity of associated complications. In previous medicolegal studies, researchers applied a medicolegal lens to their analyses without applying a quality improvement or patient safety lens. METHODS: The study comprised a 15-year medicolegal trend analysis and a 5-year contributing factors analysis of cases (civil legal and regulatory authority matters) from the Canadian Medical Protective Association (CMPA), representing an estimated 95% of physicians in Canada. Included cases were closed by the CMPA between 2004 and 2018 (trends) or 2014 and 2018 (contributing factors). We fit a linear trend line to the annual rates of spine surgery cases per 1000 physician-years of CMPA membership for physicians in a neurosurgery or orthopedic surgery specialty. We then applied an ANOVA type III sum of squares test to determine the statistical significance of the annualized change rate over time. For the contributing factors analysis, we reported descriptive statistics for patient and physician characteristics, patient harm, and peer expert criticisms in each case. RESULTS: Our trend analysis included 340 cases. Case rates decreased significantly at an annualized change rate of -4.7% (P  = 0.0017). Our contributing factors analysis included 81 civil legal and 19 regulatory authority cases. Most patients experienced health care-related harm (89/100, 89.0%). Peer experts identified intraoperative injuries (29/89, 32.6%), diagnostic errors (14/89, 15.7%), and wrong site surgeries (16/89, 18.0%) as the top patient safety indicators. The top factor contributing to medicolegal risk was physician clinical decision-making. CONCLUSION AND RELEVANCE: Although case rates decreased, patient harm was attributable to health care in the majority of recently closed cases. Therefore, crucial opportunities remain to enhance patient safety in spine surgery.Level of Evidence: 4.

Medico-Legal Cases Involving Cardiologists and Cardiac Test Underuse or Overuse.

BACKGROUND: Evidence-based campaigns are available to support appropriate diagnostic testing in cardiology, but medico-legal concerns can impede implementation. METHODS: We conducted a retrospective descriptive analysis of medico-legal cases (civil legal, regulatory authority, hospital matters) involving cardiologists in Canada. For eligibility, cases must have closed at the Canadian Medical Protective Association between January 1, 2009 and December 31, 2018. We defined test underuse and overuse using criticisms in the medico-legal record from peer experts, regulatory authorities, or hospitals. We used a contributing factors framework and descriptive statistics for analysis. RESULTS: From 2009 to 2018, the Canadian Medical Protective Association closed 60,598 cases with 368 (0.6%) involving a cardiologist. Within those cases, there was no criticism of cardiac diagnostic test overuse and 15 cases (4.1%) with criticism of underuse (tests not ordered, not expedited, delayed). In 12 of 15 cases of underuse (80.0%), the patient experienced severe harm or death. Of 8 civil legal cases, 6 were decided in favour of the plaintiff (75.0%) and 2 were dismissed by consent before proceeding to trial (25.0%). Decisions on regulatory authority matters did not favour the cardiologist (7 of 7 cases). In all cases of underuse, there was need for focused testing to investigate new or worsening symptoms. The most common contributing factors included clinical decision-making, situational awareness, and communication with teams and patients. CONCLUSIONS: Medico-legal cases involving cardiologists and the overuse or underuse of cardiac diagnostic tests were extremely rare in Canada, despite the potential for harm. The criticisms of cardiac diagnostic test underuse related to issues with diagnosing symptomatic patients.

CONTEXTE: Même s'il existe des campagnes fondées sur des données probantes visant à promouvoir le recours aux tests diagnostiques appropriés en cardiologie, il arrive que des préoccupations d'ordre médico-légal nuisent à la réalisation de ces tests. MÉTHODOLOGIE: Nous avons réalisé une analyse descriptive rétrospective des affaires médico-légales (poursuites au civil et plaintes déposées auprès d'organismes de réglementation et d'hôpitaux) touchant des cardiologues au Canada. Ont été retenus pour l'analyse les dossiers clos à l'Association canadienne de protection médicale entre le 1er janvier 2009 et le 31 décembre 2018. La sous-utilisation et la surutilisation de tests ont été définies à partir des critiques formulées dans les dossiers médico-légaux par des pairs spécialistes, des organismes de réglementation ou des hôpitaux. L'analyse reposait sur un cadre décrivant les facteurs contributifs et sur un modèle de statistique descriptive. RÉSULTATS: De 2009 à 2018, l'Association canadienne de protection médicale a clos 60 598 dossiers; de ce nombre, 368 (0,6 %) dossiers visaient un cardiologue. Parmi ces dossiers, aucun ne concernait la surutilisation de tests visant à diagnostiquer un trouble cardiaque, et 15 (4,1 %) concernaient la sous-utilisation de tels tests (test non demandé, non accéléré ou reporté). Dans 12 (80 %) des 15 cas de sous-utilisation, le patient a subi un tort grave ou est décédé. Sur les huit poursuites au civil, six (75 %) ont été jugées en faveur du demandeur, et deux (25 %) ont été rejetées d'un commun accord entre les parties avant le début du procès. Toutes les décisions relatives à des questions relevant des organismes de réglementation, au nombre de sept, ont été en défaveur du cardiologue. Dans tous les cas de sous-utilisation, le patient avait besoin de subir des tests ciblés afin d'évaluer l'apparition ou l'aggravation de symptômes. Les facteurs contributifs les plus fréquents comprenaient la prise de décisions cliniques, la connaissance de la situation et la communication avec les équipes et les patients. CONCLUSIONS: Les affaires médico-légales touchant des cardiologues et la surutilisation ou la sous-utilisation de tests de diagnostic cardiaque étaient extrêmement rares au Canada, malgré les préjudices qui peuvent en découler. Les critiques relatives à la sous-utilisation des tests de diagnostic cardiaque concernaient toutes des problèmes liés à l'investigation diagnostique chez des patients présentant des symptômes.

Intraoperative injuries from abdominopelvic surgery: an analysis of national medicolegal data.

Background: Intraoperative injuries during abdominopelvic surgery can be associated with substantial patient harm. The objective of this study was to describe abdominopelvic intraoperative injuries and their contributing factors among medicolegal cases. Methods: This study was a descriptive analysis of medicolegal matters reported to a national body, with subgroup analyses by type of surgery. We reviewed medicolegal matters involving a population-based sample of physicians who were subject to a civil legal action or complaint to a regulatory authority that was closed between 2013 and 2017 in Canada. Results: Our analysis included 181 civil legal cases and 88 complaints to a regulatory authority. Among legal cases, 155 patients (85.6%) (median age 47 yr) underwent elective procedures. The most common injury site was the bowel (53 cases [29.3%]). Injuries frequently occurred during dissection (79 [43.6%]) and ligation (38 [21.0%]), were identified postoperatively (138 [76.2%]) and necessitated further surgery (139 [76.8%]). Many patients experienced severe harm (55 [30.4%]) or died (25 [13.8%]). Peer experts in nongynecologic cases were more likely than those in gynecologic cases to include criticisms of a provider in a harmful incident (79 [71.2%] v. 30 [42.9%], p < 0.01). Peer expert criticisms often related to clinical evaluation, decision-making and misidentification of anatomy. Criticisms of nontechnical skills identified documentation and communication deficiencies. Conclusion: This study confirms the importance of provider and team training to improve clinical evaluation and decision-making, documentation and communication. Effective protocols may help support clinicians in providing safer surgical care.

Contexte: Les blessures survenant durant une chirurgie abdominopelvienne peuvent être associées à d'importants préjudices chez les patients. La présente étude avait pour but de décrire les blessures peropératoires abdominopelviennes faisant l'objet d'enquêtes médicolégales et à connaître leurs facteurs contributifs. Méthodes: Cette étude comprend une analyse descriptive d'affaires médicolégales signalées à un organisme de réglementation national, ainsi que des analyses par sousgroupes selon le type de chirurgie. Nous avons examiné des cas impliquant un échantillon de médecins canadiens représentatifs de la population qui avaient fait l'objet d'une poursuite au civil ou d'une plainte auprès d'un organisme de réglementation. Toutes les poursuites et plaintes étudiées ont été résolues entre 2013 et 2017. Résultats: Notre analyse comprenait 181 poursuites au civil et 88 plaintes auprès d'un organisme de réglementation. En ce qui concerne les poursuites au civil, 155 patients (85,6 %) (âge médian 47 ans) avaient subi une intervention non urgente. Les blessures déclarées touchaient généralement les intestins (53 cas [29,3 %]). Elles sont fréquemment survenues durant la dissection (79 cas [43,6 %]) et la ligature (38 cas [21,0 %]), ont été repérées en période postopératoire (138 cas [76,2 %]) et ont nécessité une autre chirurgie (139 cas [76,8 %]). De nombreux patients ont subi de graves préjudices (55 cas [30,4 %]) ou sont décédés (25 cas [13,8 %]). Les pairs experts dans un domaine autre que la gynécologie étaient plus susceptibles que ceux experts en gynécologie de critiquer un fournisseur en cas d'incident avec préjudice (79 cas [71,2 %] c. 30 cas [42,9 %]; p < 0,01). Les critiques formulées par les pairs experts portaient souvent sur l'évaluation clinique, la prise de décision et les erreurs d'identification des structures anatomiques. Les critiques visant les habiletés non techniques avaient trait aux lacunes dans la documentation et la communication. Conclusion: Cette étude vient confirmer l'importance que revêt la formation des fournisseurs et de leur équipe dans l'amélioration de la prise de décision, de la documentation et de la communication. Des protocoles efficaces pourraient soutenir l'offre de soins chirurgicaux sûrs par les professionnels de la santé.

Surgical Fires and Burns: A 5-Year Analysis of Medico-legal Cases.

Surgical fires and unintended intraoperative burns cause serious patient harm, yet surveillance data are lacking in Canada. Medico-legal data provide unique descriptions of these events which can inform burn prevention strategies. We extracted 5 years of data on closed (2012-2016) medico-legal cases involving surgical fires and burns from the database of our organization which, in 2016, provided medico-legal support to >93,000 Canadian physicians. We performed a retrospective descriptive analysis of contributing factors using an in-house coding system and case reviews. We identified 53 eligible burn cases: 26 from thermal sources (49.1%), 16 from fires (30.2%), 5 from chemical sources (9.4%), and 6 from undetermined sources (11.3%). Common burn sources were electrosurgical equipment, lasers, lighting, and improper temperatures (causing thermal burns), cautery or lasers combined with supplemental oxygen and/or a flammable fuel source (causing fire), and improperly applied solutions including antiseptics (causing chemical burns). Nontechnical factors also contributed to patient outcomes, such as nonadherence to protocols (15 cases, 28.3%), failures in surgical team communication (3 cases, 5.7%), and lost situational awareness leading to delays in recognizing and treating burns (7 cases, 13.2%). This retrospective study highlights a need for improved surgical safety interventions to address surgical fires and burns. These interventions could include: effectively implemented surgical safety protocols, surgical team communication strategies, and raising awareness about preventing, diagnosing, and managing surgical burns.

Is Cannabis Use Associated with Sedentary Behavior during Leisure Time? A Study in Canada, 2011-2012.

BACKGROUND: Sedentary behavior, defined as lying or sitting, is a global health concern. As researchers continue to identify modern-day risk factors for sedentary behavior, few have explored the role of illicit drug use. OBJECTIVE: To examine the association between leisure-time sedentary behavior and cannabis use, in adolescents and adults. METHODS: We conducted a cross-sectional study relating cannabis use to total leisure-time sedentary behavior (hr/wk using the computer, playing video games, watching television or videos, and reading for leisure) using data from the 2011-2012 Canadian Community Health Survey (CCHS), a population-based survey of Canadians age ≥12 years. Analyses were possible for 48,240 respondents in Saskatchewan, Ontario, and Nunavut who reported on sedentary behavior. We used logistic regression modeling to relate frequency of cannabis use (never, occasional, heavy) to high-risk sedentary behavior (<35 versus ≥35 hr/wk) overall and stratified by sex, age, and rural location. RESULTS: Approximately 80% of respondents were ≥25 years old. In the fully-adjusted model, the odds of ≥35 hr/wk of sedentary behavior were 80% higher for heavy cannabis users versus never users (OR = 1.8, 95% CI: 1.4-2.3); in occasional cannabis users, the odds were 30% higher (OR = 1.3, 95% CI: 1.1-1.5). In stratified analyses, odds ratios were statistically significant among adults age 25-44 years and people living in nonrural settings. Conclusions/Importance: Our findings support dual lifestyle interventions targeting heavy cannabis use and excessive sedentary behavior simultaneously. Moreover, leisure-time sedentary behavior should be considered as a covariate in future epidemiologic models relating cannabis to health.

Associations between postmenopausal endogenous sex hormones and C-reactive protein: a clearer picture with regional adiposity adjustment?

OBJECTIVE: To better understand the pathogenesis of inflammatory-related diseases after menopause, we studied the adiposity-independent association between endogenous sex hormones and C-reactive protein (CRP), a biomarker of inflammation. METHODS: We conducted a secondary, cross-sectional analysis of baseline data from the Alberta Physical Activity and Breast Cancer Prevention Trial (2003-2007), including 319 healthy, postmenopausal women not using hormone therapy. Multivariable linear regression models related serum CRP levels to estrogens, androgens, and sex hormone-binding globulin (SHBG), all on the natural logarithmic scale. Models were adjusted for age, lipids, medication, and former menopausal hormone therapy use, and also for adiposity (body mass index [BMI], per cent body fat [via whole-body dual x-ray absorptiometry], or intra-abdominal fat area [via computed tomography]). RESULTS: Without adiposity adjustment, estrone, total estradiol, and free estradiol were significantly positively associated with CRP, whereas SHBG was significantly inversely associated with CRP. Of all adiposity measures, adjustment for BMI caused the greatest attenuation of CRP-estrogen associations; only free estradiol (ß = 0.24, 95% confidence interval [CI] 0.06, 0.43) and SHBG (ß = -0.37, 95% CI -0.60, -0.13) associations remained significant. Inverse associations between CRP-total testosterone became stronger with BMI adjustment (ß = -0.20, 95% CI -0.40, -0.01). Differential associations across categories of BMI, former hormone therapy use, and years since menopause were suggestive, but not statistically significant (Pheterogeneity > 0.05). CONCLUSIONS: Prospective and systems epidemiological studies are needed to understand whether or not the cross-sectional associations we observed, independent of adiposity, between CRP-SHBG, CRP-total testosterone, and CRP-free estradiol, are causal.

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.

Moderate-vigorous recreational physical activity and breast cancer risk, stratified by menopause status: a systematic review and meta-analysis.

OBJECTIVE: Physical inactivity increases postmenopausal and possibly premenopausal breast cancer risk, although different biologic mechanisms are proposed. Our primary objective was to estimate breast cancer risk associated with high versus low levels of moderate-vigorous recreational activity, separately for premenopausal and postmenopausal women. METHODS: We conducted a systematic review of literature published to July 2015. Included reports were cohort or case-control studies relating moderate-vigorous recreational physical activity (metabolic equivalent ≥3.0) to breast cancer incidence, exclusively (≥90%) in premenopausal or postmenopausal women. We appraised study quality and performed meta-analyses using random effects modeling. Subgroup meta-analyses were based on tumor subtype, race, body mass index, parity, hormone therapy use, family history of cancer, and statistical adjustment for body fatness. Dose-response relations were examined. RESULTS: Pooled relative risks (RRs, 95% CI) for women with higher versus lower levels of moderate-vigorous recreational activity were RR = 0.80 (0.74-0.87) and RR = 0.79 (0.74-0.84) for premenopausal (43 studies) and postmenopausal (58 studies) breast cancer, respectively, with high heterogeneity. Inverse associations were weaker among postmenopausal cohort studies (RR = 0.90 [0.85-0.95]) and studies that statistically adjusted for nonrecreational (eg, occupational, household) activity (RR = 0.91 [0.77-1.06] premenopausal, RR = 0.96 [0.86-1.08] postmenopausal). Risk estimates with versus without body fatness adjustment did not vary by menopause status, although other subgroup effects were menopause-dependent. Among studies of overweight/obese women, there was an inverse association with postmenopausal but not premenopausal breast cancer (RR = 0.88 [0.82-0.95] and RR = 0.99 [0.98-1.00], respectively). Dose-response curves were generally nonlinear. CONCLUSIONS: Although risk estimates may be similar for premenopausal and postmenopausal breast cancer, subgroup effects may be menopause-dependent.

Physical Activity and Cancer Outcomes: A Precision Medicine Approach.

There is increasing interest in applying a precision medicine approach to understanding exercise as a potential treatment for cancer. We aimed to inform this new approach by appraising epidemiologic literature relating postdiagnosis physical activity to cancer outcomes overall and by molecular/genetic subgroups. Across 26 studies of breast, colorectal, and prostate cancer patients, a 37% reduction was seen in risk of cancer-specific mortality, comparing the most versus the least active patients (pooled relative risk = 0.63; 95% confidence interval: 0.54-0.73). Risks of recurrence or recurrence/cancer-specific death (combined outcome) were also reduced based on fewer studies. We identified ten studies of associations between physical activity and cancer outcomes by molecular or genetic markers. Two studies showed statistically significant risk reductions in breast cancer mortality/recurrence for the most (versus least) physically active estrogen receptor-positive/progesterone receptor-positive (ER+/PR+) patients, while others showed risk reductions among ER-PR- and triple-negative patients. In colorectal cancer, four studies showed statistically significant risk reductions in cancer-specific mortality for patients with high (versus low) physical activity and P21 expression, P27 expression, nuclear CTNNB1-, PTGS2 (COX-2)+, or IRS1 low/negative status. One prostate cancer study showed effect modification by Gleason score. As a means to enhance this evidence, future observational studies are needed that will measure physical activity objectively before and after diagnosis, use standardized definitions for outcomes, control for competing risks, assess nonlinear dose-response relations, and consider reverse causality. Ultimately, randomized controlled trials with clinical cancer outcomes and a correlative component will provide the best evidence of causality, relating exercise to cancer outcomes, overall and for molecular and genetic subgroups. Clin Cancer Res; 22(19); 4766-75. ©2016 AACR.

Physical Activity and Survival After Prostate Cancer.

BACKGROUND: Despite the high global prevalence of prostate cancer (PCa), few epidemiologic studies have assessed physical activity in relation to PCa survival. OBJECTIVE: To evaluate different types, intensities, and timing of physical activity relative to PCa survival. DESIGN, SETTING, AND PARTICIPANTS: A prospective study was conducted in Alberta, Canada, in a cohort of 830 stage II-IV incident PCa cases diagnosed between 1997 and 2000 with follow-up to 2014 (up to 17 yr). Prediagnosis lifetime activity was self-reported at diagnosis. Postdiagnosis activity was self-reported up to three times during follow-up. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox proportional hazards models related physical activity to all-cause and PCa-specific deaths and to first recurrence/progression of PCa. RESULTS AND LIMITATIONS: A total of 458 deaths, 170 PCa-specific deaths, and, after first follow-up, 239 first recurrences/progressions occurred. Postdiagnosis total activity (>119 vs ≤42 metabolic equivalent [MET]-hours/week per year) was associated with a significantly lower all-cause mortality risk (hazard ratio [HR]: 0.58; 95% confidence interval [CI], 0.42-0.79; p value for trend <0.01). Postdiagnosis recreational activity (>26 vs ≤4 MET-hours/week per year) was associated with a significantly lower PCa-specific mortality risk (HR: 0.56; 95% CI, 0.35-0.90; p value for trend = 0.01). Sustained recreational activity before and after diagnosis (>18-20 vs <7-8 MET-hours/week per year) was associated with a lower risk of all-cause mortality (HR: 0.66; 95% CI, 0.49-0.88). Limitations included generalisability to healthier cases and an observational study design. CONCLUSIONS: These findings support emerging recommendations to increase physical activity after the diagnosis of PCa and would inform a future exercise intervention trial examining PCa outcomes. PATIENT SUMMARY: In a 17-yr prostate cancer (PCa) survival study, men who survived at least 2 yr who were more physically active postdiagnosis or performed more recreational physical activity before and after diagnosis survived longer. Recreational physical activity after diagnosis was associated with a lower risk of PCa death.

Effects of exercise dose on endogenous estrogens in postmenopausal women: a randomized trial.

Exercise dose comparison trials with biomarker outcomes can identify the amount of exercise required to reduce breast cancer risk and also strengthen the causal inference between physical activity and breast cancer. The Breast Cancer and Exercise Trial in Alberta (BETA) tested whether or not greater changes in estradiol (E2), estrone, and sex hormone-binding globulin (SHBG) concentrations can be achieved in postmenopausal women randomized to 12 months of HIGH (300 min/week) vs MODERATE (150 min/week) volumes of aerobic exercise. BETA included 400 inactive postmenopausal women aged 50-74 years with BMI of 22-40 kg/m(2). Blood was drawn at baseline and 6 and 12 months. Adiposity, physical fitness, diet, and total physical activity were assessed at baseline and 12 months. Intention-to-treat analyses were performed using linear mixed models. At full prescription, women exercised more in the HIGH vs MODERATE group (median min/week (quartiles 1,3): 253 (157 289) vs 137 (111 150); P<0.0001). Twelve-month changes in estrogens and SHBG were <10% on average for both groups. No group differences were found for E2, estrone, SHBG or free E2 changes (treatment effect ratios (95% CI) from linear mixed models: 1.00 (0.96-1.06), 1.02 (0.98-1.05), 0.99 (0.96-1.02), 1.01 (0.95, 1.06), respectively, representing the HIGH:MODERATE ratio of geometric mean biomarker levels over 12 months; n=382). In per-protocol analyses, borderline significantly greater decreases in total and free E2 occurred in the HIGH group. Overall, no dose effect was observed for women randomized to 300 vs 150 min/week of moderate to vigorous intensity exercise who actually performed a median of 253 vs 137 min/week. For total and free E2, the lack of differential effect may be due to modest adherence in the higher dose group.

Effects of a High vs Moderate Volume of Aerobic Exercise on Adiposity Outcomes in Postmenopausal Women: A Randomized Clinical Trial.

IMPORTANCE: Body fat increases postmenopausal breast cancer risk. Physical activity may decrease risk through adiposity changes, but the optimal dose of activity is unknown. OBJECTIVE: To compare the effects of 300 vs 150 min/wk of moderate to vigorous aerobic exercise on body fat in postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: The Breast Cancer and Exercise Trial in Alberta was a 12-month, 2-armed, 2-center randomized dose-comparison trial conducted from June 2010 through June 2013. Participants were 400 inactive postmenopausal women with body mass index 22 to 40, disease-free, nonsmokers, and nonusers of exogenous hormones. INTERVENTIONS: Five d/wk of aerobic exercise (3 d/wk supervised, 2 d/wk unsupervised) for 30 min/session (moderate-volume) or 60 min/session (high volume) achieving 65% to 75% of heart rate reserve for at least 50% of each session. Participants were asked not to change usual diet. MAIN OUTCOMES AND MEASURES: Total body fat, measured from dual energy x-ray absorptiometry scans, was the primary outcome. Other measures included subcutaneous and intra-abdominal fat from computed tomography scans, weight, and waist and hip circumferences. RESULTS: Of 400 women, 384 provided baseline and follow-up adiposity measurements. Median (interquartile range) adherence at full prescription for the high- and moderate-volume groups was 254 (166-290) and 137 (111-150) min/wk, respectively. Mean reductions in total fat were significantly larger in the high- vs moderate-volume group (least-squares mean difference, -1.0% [95% CI, -1.6% to -0.4%], P = .002). Subcutaneous abdominal fat and waist to hip ratio decreased significantly more in the high-volume group (least-squares mean difference, -10.8 [95% CI, -19.5 to -2.2] cm², P = .01, and -0.01 [95% CI, -0.02 to 0.00], P = .04, respectively). Changes in weight and intra-abdominal fat were not significantly different between groups (least-squares mean difference, -0.7 [95% CI, -1.6 to 0.2] kg, P = .11, and -1.5 [95% CI, -5.9 to 2.9] cm², P = .50, respectively). Some dose-response effects were stronger for obese women. CONCLUSIONS AND RELEVANCE: In previously inactive postmenopausal women, a 1-year prescription of moderate to vigorous exercise for 300 min/wk was superior to 150 min/wk for reducing total fat and other adiposity measures, especially in obese women. These results suggest additional benefit of higher-volume aerobic exercise for adiposity outcomes and possibly a lower risk of postmenopausal breast cancer. TRIAL REGISTRATION: clinicaltrials.gov: NCT01435005.

Study design and methods for the Breast Cancer and Exercise Trial in Alberta (BETA).

BACKGROUND: Exercise has favorable effects on biomarkers associated with a lower risk of breast cancer, however it is unclear if higher doses of exercise provide additional effects. No clinical trial has systematically examined how different exercise volumes influence the mechanisms underlying breast cancer etiology. The Breast Cancer and Exercise Trial in Alberta (BETA) - a follow-up study to the Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial - is examining how a one-year, high versus moderate volume aerobic exercise intervention influences several biomechanisms hypothesized to influence breast cancer risk in a group of postmenopausal women. Secondary aims are to compare intervention effects on psychosocial and quality of life outcomes as well as understand exercise adherence at 12 and 24 months, and maintenance of all study outcomes at 24 months. METHODS/DESIGN: The BETA Trial is a two-center, two-armed randomized controlled exercise intervention trial conducted in 400 previously inactive, postmenopausal women aged 50-74 years, in Alberta, Canada. Participants were randomly assigned to a one-year aerobic exercise intervention of either high volume (300 minutes/week) or moderate volume (150 minutes/week). Blood draws and accelerometry were performed at baseline, six and 12 months. Baseline and 12-month measurements were taken of adiposity (including dual energy X-ray absorptiometry and computed tomography scans), physical fitness, dietary intake, self-reported physical activity and sedentary behavior, quality of life, perceived stress, happiness, sleep, and determinants of exercise adherence. Exercise maintenance was assessed and all study measurements were repeated at 24 months. Blood will be analyzed for endogenous estrogens, insulin resistance indicators, and inflammatory markers. DISCUSSION: The BETA Trial will compare the impact of a high versus moderate volume of aerobic exercise on a variety of biological, physiological, and psychological outcomes of relevance to postmenopausal women. A tightly controlled exercise intervention and objective outcome measurements are methodological strengths. The BETA Trial will inform future prevention initiatives by assessing adherence to a high volume of exercise over 12 months by postmenopausal women, and the ability of these women to maintain activity over the longer-term. The ultimate objective is to inform public health guidelines for reducing breast cancer risk through physical activity. CLINICAL TRIALS REGISTRATION NUMBER: NCT01435005.

The Sedentary Time and Activity Reporting Questionnaire (STAR-Q): reliability and validity against doubly labeled water and 7-day activity diaries.

We determined measurement properties of the Sedentary Time and Activity Reporting Questionnaire (STAR-Q), which was designed to estimate past-month activity energy expenditure (AEE). STAR-Q validity and reliability were assessed in 102 adults in Alberta, Canada (2009-2011), who completed 14-day doubly labeled water (DLW) protocols, 7-day activity diaries on day 15, and the STAR-Q on day 14 and again at 3 and 6 months. Three-month reliability was substantial for total energy expenditure (TEE) and AEE (intraclass correlation coefficients of 0.84 and 0.73, respectively), while 6-month reliability was moderate. STAR-Q-derived TEE and AEE were moderately correlated with DLW estimates (Spearman's ρs of 0.53 and 0.40, respectively; P < 0.001), and on average, the STAR-Q overestimated TEE and AEE (median differences were 367 kcal/day and 293 kcal/day, respectively). Body mass index-, age-, sex-, and season-adjusted concordance correlation coefficients (CCCs) were 0.24 (95% confidence interval (CI): 0.07, 0.36) and 0.21 (95% CI: 0.11, 0.32) for STAR-Q-derived versus DLW-derived TEE and AEE, respectively. Agreement between the diaries and STAR-Q (metabolic equivalent-hours/day) was strongest for occupational sedentary time (adjusted CCC = 0.76, 95% CI: 0.64, 0.85) and overall strenuous activity (adjusted CCC = 0.64, 95% CI: 0.49, 0.76). The STAR-Q demonstrated substantial validity for estimating occupational sedentary time and strenuous activity and fair validity for ranking individuals by AEE.

The Influence of Energetic Factors on Biomarkers of Postmenopausal Breast Cancer Risk.

Strong and consistent evidence exists that physical activity reduces breast cancer risk by 10-25 %, and several proposed biologic mechanisms have now been investigated in randomized, controlled, exercise intervention trials. Leading hypothesized mechanisms relating to postmenopausal breast cancer include adiposity, endogenous sex hormones, insulin resistance, and chronic low-grade inflammation. In addition, other pathways are emerging as potentially important, including those involving oxidative stress and telomere length, global DNA hypomethylation, immune function, and vitamin D exposure. Recent exercise trials in overweight/obese postmenopausal women implicate weight loss as a mechanism whereby exercise induces favorable changes in circulating estradiol levels and other biomarkers as well. Still it is plausible that some exercise-induced biomarker changes do not require loss of body fat, whereas others depend on abdominal fat loss. We highlight the latest findings from randomized, controlled trials of healthy postmenopausal women, relating exercise to proposed biomarkers for postmenopausal breast cancer risk.

Reliability of self-reported sun exposure in Canadian women and estimation of lifetime exposure to vitamin D from sun and diet.

OBJECTIVE: To assess the inter-method reliability of the Ovarian Cancer in Alberta (OVAL) survey developed to estimate adult vitamin D exposure from sun and diet for every tenth year, against the longer Geraldton Skin Cancer Prevention Survey (the assumed 'gold standard'). We also estimated total vitamin D exposure using the OVAL survey. DESIGN: A randomized crossover design to assess the inter-method reliability of sun exposure (OVAL v. Geraldton survey), using intra-class correlation and estimated total vitamin D exposure from sun and diet. SETTING: Calgary, Alberta, Canada. SUBJECTS: Randomly selected women (n 90) aged 40-79 years. RESULTS: The average lifetime sun exposure of 13,913 h (average 411 h/year) from the Geraldton survey was not significantly different from the 13,034 h (average 385 h/year) from the OVAL survey for periods with sufficient UV radiation to stimulate vitamin D production. The intra-class correlation coefficient for average lifetime sun exposure was 0.77 (95% CI 0.69, 0.86); the annual average was 0.60 (95% CI 0.47, 0.74). Estimated vitamin D from diet and supplements increased with age. CONCLUSIONS: Our OVAL survey reliably estimated adult sun exposure relative to the Geraldton survey, suggesting that assessing sun exposure every tenth year is a reliable and efficient method for estimating sun contributions to lifetime vitamin D exposure.

Case-control study of lifetime alcohol consumption and endometrial cancer risk.

PURPOSE: Alcohol consumption is hypothesized to increase the risk of endometrial cancer by increasing circulating estrogen levels. This study sought to investigate the association between lifetime alcohol consumption and endometrial cancer risk. METHODS: We recruited 514 incident endometrial cancer cases and 962 frequency age-matched controls in this population-based case-control study in Alberta, Canada, from 2002 to 2006. Participants completed in-person interviews querying lifetime alcohol consumption and other relevant health and lifestyle factors. Participants reported the usual number of drinks of beer, wine, and liquor consumed; this information was compiled for each drinking pattern reported over the lifetime to estimate average lifetime exposure to alcohol. RESULTS: Lifetime average alcohol consumption was relatively low (median intake: 3.9 g/day for cases, 4.9 g/day for controls). Compared with lifetime abstainers, women consuming >2.68 and ≤8.04 g/day alcohol and >8.04 g/day alcohol on average over the lifetime showed 38 and 35 % lower risks of endometrial cancer, respectively (p trend = 0.023). In addition, average lifetime consumption of all types of alcohol was associated with decreased risks. There was no evidence for effect modification by body mass index, physical activity, menopausal status, and hormone replacement therapy use combined and effects did not differ by type of endometrial cancer (type I or II). CONCLUSION: This study provides epidemiologic evidence for an inverse association between relatively modest lifetime average alcohol consumption (approximately 1/4 to 1/2 drink/day) and endometrial cancer risk. The direction of this relation is consistent with previous studies that examined similar levels of alcohol intake.