Exploring the use of experimental small area estimates to examine the relationship between individual-level and area-level community belonging and self-rated health.

Background: Small area estimation refers to statistical modelling procedures that leverage information or "borrow strength" from other sources or variables. This is done to enhance the reliability of estimates of characteristics or outcomes for areas that do not contain sufficient sample sizes to provide disaggregated estimates of adequate precision and reliability. There is growing interest in secondary research applications for small area estimates (SAEs). However, it is crucial to assess the analytic value of these estimates when used as proxies for individual-level characteristics or as distinct measures that offer insights at the area level. This study assessed novel area-level community belonging measures derived using small area estimation and examined associations with individual-level measures of community belonging and self-rated health. Data and methods: SAEs of community belonging within census tracts produced from the 2016-2019 cycles of the Canadian Community Health Survey (CCHS) were merged with respondent data from the 2020 CCHS. Multinomial logistic regression models were run between area-level SAEs, individual-level sense of community belonging, and self-rated health on the study sample of people aged 18 years and older. Results: Area-level community belonging was associated with individual-level community belonging, even after adjusting for individual-level sociodemographic characteristics, despite limited agreement between individual- and area-level measures. Living in a neighbourhood with low community belonging was associated with higher odds of reporting being in fair or poor health, versus being in very good or excellent health (odds ratio: 1.53; 95% confidence interval: 1.22, 1.91), even after adjusting for other factors such as individual-level sense of community belonging, which was also associated with self-rated health. Interpretation: Area-level and individual-level sense of community belonging were independently associated with self-rated health. The novel SAEs of community belonging can be used as distinct measures of neighbourhood-level community belonging and should be understood as complementary to, rather than proxies for, individual-level measures of community belonging.

A national cohort study of community belonging and its influence on premature mortality.

BACKGROUND: Community belonging, an important constituent of subjective well-being, is an important target for improving population health. Ageing involves transitioning across different social conditions thus, community belonging on health may vary across the life course. Using a nationally representative cohort, this study estimates the life stage-specific impact of community belonging on premature mortality. METHODS: Six cycles of the Canadian Community Health Survey (2000-2012) were combined and linked to the Canadian Vital Statistics Database (2000-2017). Respondents were followed for up to 5 years. Multivariable-adjusted modified Poisson regression models were used to estimate the relative risk of premature mortality for three life stages: early adulthood (18-35 years), middle adulthood (36-55 years) and late adulthood (56-70 years). RESULTS: The final analytical sample included 477 100 respondents. Most reported a 'somewhat strong' sense of belonging (45.9%). Compared with their 'somewhat strong' counterparts, young adults reporting a 'somewhat weak' sense of belonging exhibited an increased relative risk (RR) of 1.76 (95% CI 1.27 to 2.43) for premature mortality, whereas middle-aged adults reporting the same exhibited a decreased RR of 0.82 (95% CI 0.69, 0.98). Among older adults, groups reporting a 'very strong' (RR 1.10, 95% CI 1.01, 1.21) or a 'very weak' sense (RR 1.14, 95% CI 1.01, 1.28) of belonging exhibited higher RRs for premature mortality. CONCLUSION: The results demonstrate how community belonging relates to premature mortality differs across age groups underscoring the importance of considering life stage-specific perspectives when researching and developing approaches to strengthen belonging.

Gender and Racial Diversity Among Obstetrics and Gynecology Departments and Gynecologic Oncology Divisions in Canada: Are We There Yet?

OBJECTIVES: Gender and racial diversity in academic Canadian departments of obstetrics and gynecology (OBGYN) have not been previously described. We examined gender representation in leadership in academic OBGYN departments and gynecologic oncology (GO) divisions, and determined factors predictive of leadership and promotion including racialized status. METHODS: This cross-sectional study of Canadian residency-affiliated academic OBGYN departments queried institutional websites in January 2021 to compile a list of academic faculty. Subjective gender was assessed using photographs and pronouns, and racialized status was determined using photographs. Logistic regression analyses determined predictive factors for leadership roles. Fassiotto et al. rank equity indices (REI) and Hofler et al. representation ratios were calculated. RESULTS: Within 16 Canadian institutions there were 354 (33.6%) men and 699 (66.4%) women, with 18.3% racialized faculty. Men were more likely to reach full professorship (P < 0.00001) and leadership positions of department chair, vice-chair or division head (P = 0.01). Representation ratios for women in OBGYN were <1 for all administrative leadership positions, and pairwise comparisons of the probability of promotion for women OBGYNs using REI reveal significant disparities between senior and junior administrative leadership and professorial ranks. Racialized physicians were less likely to have attained full professorship (P = 0.002). Ninety-seven academic GOs were identified: 68 (70.1%) were women, 17 (17.5%) racialized. Seven GO divisions (44%) had no racialized members. On multivariate analysis, only year of completion of fellowship was predictive of leadership. CONCLUSION: In academic Canadian OBGYN departments women are underrepresented in leadership and full professor positions. Racialized faculty are underrepresented in full professorship.

Cervical PEComa: Challenges in diagnosis and prognosis of a rare neoplasm.

•Cervical PEComas are rare neoplasms which present a diagnostic challenge.•Large tumour size is an important clinical prognosticator in cervical PEComa.•All reported cases of cervical PEComa classified as benign by Folpe criteria behaved in benign fashion clinically.•Tumours ≤ 4 cm may be assessed with cone biopsy, and simple hysterectomy considered if no adverse pathologic features.•Molecular characterization and linkage with coordinated rare tumour registries may identify novel treatments.

Palliative care utilization across health sectors for patients with gynecologic malignancies in Ontario, Canada from 2006 to 2018.

OBJECTIVE: Early palliative care (PC) is associated with improved patient quality of life, less aggressive end-of-life care, and prolonged survival. We evaluated patterns of PC delivery in gynecologic oncology. METHODS: We conducted a population-based, retrospective cohort study of gynecologic cancer decedents in Ontario from 2006 to 2018 using linked administrative health care data. RESULTS: The cohort included 16,237 decedents; 51.1% died of ovarian cancer, 30.3% uterine cancer, 12.1% cervical cancer, and 6.5% vulvar/vaginal cancers. Palliative care was most often delivered in the hospital inpatient setting in 81%, and 53% received specialist PC. PC was first received during hospital admission in 53%, and by outpatient physician care in only 23%. Palliative care was initiated a median 193 days prior to death, with the lowest two quintiles initiating care ≤70 days before death. The average user of PC resources (third quintile) received 68 days of PC. While cumulative use of community PC gradually increased over the final year of life, institutional palliative care use exponentially rose from 12 weeks until death. On multivariable analyses, predictors of initiating palliative care during a hospital admission included age ≥70 years at death, ≤3 month cancer survival, having cervical or uterine cancer, not having a primary care provider, or being in the lowest 3 income quintiles. CONCLUSION: Most palliative care is initiated and delivered during hospital admission, and is initiated late in a significant proportion. Strategies to increase access to anticipatory and integrated palliative care may improve the quality of the disease course and the end of life.

Overcrowded housing during adolescence and future risk of premature mortality: a 28-year follow-up of 556,191 adolescents from Switzerland.

Background: Few large-scale studies have examined the health impacts of overcrowded housing in European countries. The aim of this study was to assess whether household crowding during adolescence increases the risk of all-cause and cause-specific mortality in Switzerland. Methods: Study participants were 556,191 adolescents aged 10-19 years at the 1990 census from the Swiss National Cohort. Household crowding at baseline was measured as the ratio between the number of persons living in the household and the number of available rooms, categorized as none (ratio ≤ 1), moderate (1 < ratio ≤ 1.5), and severe (ratio > 1.5). Participants were linked to administrative mortality records through 2018 and followed for premature mortality from all causes, cardiometabolic disease and self-harm or substance use. Cumulative risk differences between ages 10 and 45 were standardized by parental occupation, residential area, permit status and household type. Findings: Of the sample, 19% lived in moderately and 5% lived in severely crowded households. During an average follow-up of 23 years, 9766 participants died. Cumulative risk of death from all causes was 2359 (95% compatibility intervals: 2296-2415) per 100,000 persons when living in non-crowded households. Living in moderately crowded households led to 99 additional deaths (-63 to 256) per 100,000 persons and living in severely crowded households 258 additional deaths (-37 to 607) per 100,000 persons. The effect of crowding on mortality from cardiometabolic diseases, self-harm or substance use was negligible. Interpretation: Excess risk of premature mortality in adolescents living in overcrowded households appears to be small or negligible in Switzerland. Funding: University of Fribourg Scholarship Programme for foreign post-doctoral researchers.

A double-blinded, randomized trial comparing surgeon-administered transversus abdominis plane block with placebo after midline laparotomy in gynecologic oncology surgery.

BACKGROUND: Surgeon-administered transversus abdominis plane block is a contemporary approach to providing postoperative analgesia, and this approach is performed by transperitoneally administering local anesthetic in the plane between the internal oblique and transversus abdominis muscles to target the sensory nerves of the anterolateral abdominal wall. Although this technique is used in many centers, it has not been studied prospectively in patients undergoing a midline laparotomy. OBJECTIVE: This study aimed to evaluate whether surgeon-administered transversus abdominis plane block reduces postoperative opioid requirements and improves clinical outcomes. STUDY DESIGN: In this double-blind, randomized, placebo-controlled trial, patients with a suspected or proven gynecologic malignancy undergoing surgery through a midline laparotomy at 1 Canadian tertiary academic center were randomized to either the bupivacaine group (surgeon-administered transversus abdominis plane blocks with 40 mL of 0.25% bupivacaine) or the placebo group (surgeon-administered transversus abdominis plane blocks with 40 mL of normal saline solution) before fascial closure. The primary outcome was the total dose of opioids (in morphine milligram equivalents) received in the first 24 hours after surgery. The secondary outcomes included opioid doses between 24 and 48 hours, pain scores, postoperative nausea and vomiting, incidence of clinical ileus, time to flatus, and hospital length of stay. The exclusion criteria included contraindications to study medication, history of chronic opioid use, significant adhesions on the anterior abdominal wall preventing access to the injection site, concurrent nonabdominal surgical procedure, and the planned use of neuraxial anesthesia or analgesia. To detect a 20% decrease in opioid requirements with a 2-sided type 1 error of 5% and power of 80%, a sample size of 36 patients per group was calculated. RESULTS: From October 2020 to November 2021, 38 patients were randomized to the bupivacaine arm, and 41 patients were randomized to the placebo arm. The mean age was 60 years, and the mean body mass index was 29.3. A supraumbilical incision was used in 30 of 79 cases (38.0%), and bowel resection was performed in 10 of 79 cases (12.7%). Patient and surgical characteristics were evenly distributed. The patients in the bupivacaine group required 98.0±59.2 morphine milligram equivalents in the first 24 hours after surgery, whereas the patients in the placebo group required 100.8±44.0 morphine milligram equivalents (P=.85). The mean pain score at 4 hours after surgery was 3.1±2.4 (0-10 scale) in the intervention group vs 3.1±2.0 in the placebo group (P=.93). Clinically significant nausea or vomiting was reported in 1 of 38 patients (2.6%) in the intervention group vs 1 of 41 patients (2.4%) in the placebo group (P=.95). Time to first flatus, rates of clinical ileus, and length of stay were similar between groups. Subgroup analysis of patients with a body mass index of <25 and patients who received an infraumbilical incision showed similarly comparable outcomes. CONCLUSION: Surgeon-administered transversus abdominis plane block with bupivacaine was not found to be superior to the placebo intervention in reducing postoperative opioid requirements or improving other postoperative outcomes for patients undergoing a midline laparotomy. These results differed from previous reports evaluating the ultrasound-guided transversus abdominis plane block approach. Surgeon-administered transversus abdominis plane block should not be considered standard of care in postoperative multimodal analgesia.

Trends in quality indicators of end-of-life care for women with gynecologic malignancies in Ontario, Canada.

OBJECTIVE: A large body of research has validated several quality indicators of end-of-life (EOL) cancer care, but few have examined these in gynecologic cancer at a population-level. We examined patterns of EOL care quality in patients with gynecologic cancers across 13 years in Ontario, Canada. METHODS: We conducted a population-based, retrospective cohort study of gynecologic cancer decedents in Ontario from 2006 to 2018 using linked administrative health care databases. Proportions of quality indices were calculated, including: emergency department (ED) use, hospital or intensive care unit (ICU) admission, chemotherapy ≤14 days of death, cancer-related surgery, tube or intravenous feeds, palliative home visits, and hospital death. We used multivariable logistic regression to examine factors associated with receipt of aggressive and supportive care. RESULTS: There were 16,237 included decedents over the study period; hospital death rates decreased from 47% to 37%, supportive care use rose from 65% to 74%, and aggressive care remained stable (16%). Within 30 days of death, 50% were hospitalized, 5% admitted to ICU, and 67% accessed palliative homecare. Within 14 days of death, 31% visited the ED and 4% received chemotherapy. Patients with vulvovaginal cancers received the lowest rates of aggressive and supportive care. Using multivariable analyses, factors associated with increased aggressive EOL care use included younger age, shorter disease duration, lower income quintiles, and rural residence. CONCLUSIONS: Over time, less women dying with gynecologic cancers in Ontario experienced death in hospital, and more accessed supportive care. However, the majority were still hospitalized and a significant proportion received aggressive care in the final 30 days of life.

The five-factor modified frailty index predicts adverse postoperative and chemotherapy outcomes in gynecologic oncology.

INTRODUCTION: Frailty is increasingly recognized as a predictor of postoperative morbidity and oncologic outcomes. Evidence of the predictive value of frailty assessment in gynecologic oncology remains sparse. OBJECTIVES: To evaluate the National Surgical Quality Improvement Program (NSQIP) comorbidity-based modified Frailty Index-5 (mFI-5) as predictor of severe postoperative complications, non-completion of chemotherapy and other patient-centered outcomes in gynecologic oncology patients >70 years-old undergoing surgery. METHODS: Prospectively-collected NSQIP data and retrospective chart review of patients undergoing elective laparotomies for gynecologic malignances at a tertiary academic center in Ontario, Canada, between 01/2016-09/2020 were reviewed. Primary outcome was rate of 30-day Clavien-Dindo (Clavien) grade III-V complications. Secondary outcomes included Clavien II-V complications, postoperative length of stay (LOS), non-home discharge and non-completion of chemotherapy. Logistic regression analyses and receiver-operator curves were performed. RESULTS: Two-hundred and fifty-nine patients were included; 103 were planned to receive adjuvant chemotherapy. Fifty-three patients (20.5%) had an mFI ≥ 2 and were categorized as frail. On multivariable analyses, frailty independently predicted grade III-V complications (OR 24.49, 95%CI 9.72-70.67, p < 0.0001), grade II-V complications (OR 4.64, 95%CI 2.31-9.94, p < 0.0001), non-home discharge (OR 7.37, 95%CI 2.81-20.46, p < 0.0001), LOS ≥ 7d (OR 3.6, 95% CI 1.54-8.6, p = 0.003) and non-completion of chemotherapy (OR 8.42, 95%CI 2.46-32.79, p = 0.001). Adjusted C-statistics demonstrated strong predictive value of the mFI-5 for grade III-V (0.92, 95%CI 0.86-0.97) and grade II-V (0.74, 95%CI 0.68-0.8) complications as well as non-home discharge (0.86, 95%CI 0.78-0.95) and chemotherapy non-completion (0.87, 95%CI 0.8-0.95). CONCLUSION: Frailty as assessed with the mFI-5 predicted adverse postoperative and chemotherapy outcomes in gynecologic oncology patients aged ≥70 undergoing a laparotomy. The mFI-5 is a concise tool that can be used for routine frailty screening and risk stratification.

An international comparative study of active living environments and hospitalization for Wales and Canada.

Rationale: Previous studies indicate active living environments (ALEs) are associated with higher physical activity levels across different geographic contexts, and could lead to reductions in hospital burden. Both Wales UK and Canada have advanced data infrastructure that allows record linkage between survey data and administrative health information. Objective: To assess the relationship between ALEs and hospitalization in Wales and Canada. Methods: We performed a population-based comparison using individual-level survey data from the Welsh Health Survey (N = 9968) linked to the Patient Episode Database for Wales, and the Canadian Community Health Survey (N = 40,335) linked to the Discharge Abstract Database. Using equivalent protocols and open-source data for street networks, destinations, and residential density, we derived 5-class measures of the ALE for Wales and Canada (classed 1 through 5, considered least favourable to most favourable for active living, respectively). We evaluated relationships of ALEs to health, behaviours and hospitalization using multivariate regression (reference group was the lowest ALE class 1, considered least favourable for active living). Results: For Canada, those living in the highest ALE class 5 had lower odds of all-cause hospitalization (OR 0.66, 95% CI 0.54 to 0.81; as compared to the lowest ALE class 1). In contrast, those living in the highest ALE class 5 in Wales had higher odds of all-cause hospitalization (OR 1.37, 95% CI 1.04 to 1.80). The relationship between ALEs and cardiometabolic hospitalization was inconclusive for Canada (OR 0.75, 95% CI 0.50 to 1.12), but we observed higher odds of cardiometabolic hospitalization for respondents living in higher ALE classes for Wales (OR 1.46, 95% CI 1.10 to 1.78; comparing ALE class 4 to ALE class 1). Conclusion: Canadian respondents living in high ALE neighbourhoods that are understood to be favourable for active living had lower odds of all-cause hospitalization, whereas Welsh respondents living in high ALEs that were deemed favourable for active living exhibited higher odds of all-cause hospitalization. Environments which promote physical activity in one geographic context may not do so in another. There remains a need to identify relevant context-specific factors that encourage active living.

Gender imbalance in gynecologic oncology authorship and impact of COVID-19 pandemic.

OBJECTIVE: Despite increased participation of women in academic medicine in recent decades, gender disparities persist. The gender gap in authorship and editorial boards in gynecologic oncology, and impact of the COVID-19 pandemic, have not been recently evaluated. We examined gender representation and the impact of COVID-19 on authorship and editorial boards of two major peer-reviewed gynecologic oncology journals. METHODS: We conducted a bibliometric analysis of original articles published in Gynecologic Oncology and the International Journal of Gynecological Cancer, comparing the most contemporary 5-year period (2016-2020) to single years in the two prior decades (1996, 2006). To assess the early impact of COVID-19, we compared publications from May 2020-April 2021 to 2019. Editorial boards were analyzed for gender composition. First names, pronouns, and institutional photographs were used to determine gender. RESULTS: There were 3022 original articles published between 2016 and 2020, 763 in 2006, and 203 in 1996. Gender was identified for 91.3% of first authors (3641 articles) and 95.6% of senior authors (3813 articles). Men comprised the majority of the editorial boards in 2021 at 57% and 61% for Gynecologic Oncology and the International Journal of Gynecological Cancer, respectively. Men were overrepresented as senior authors across all study periods: 93% in 1996, 77% in 2006, and 58% in 2016-2020. Over time, representation of women as first and senior authors increased (7% in 1996, 42% in 2016-2020, p<0.00001). There was no immediate impact of the early pandemic on gender distribution of authorship. CONCLUSIONS: Despite greater representation of women over time as authors in gynecologic oncology journals, there remains gender disparity in senior authorship and editorial board representation. This presents an opportunity for the academic publishing community to advocate for deliberate strategies to achieve gender parity. Although no impact of the early COVID-19 pandemic was found, this requires ongoing surveillance.

Does living near hospital obscure the association between active living environments and hospitalization?

Hospitals tend to be among the destinations that make densely populated, well-connected neighbourhoods more conducive to active living. In this study, we determined whether living near a hospital distorts the association between living in favourable ALEs and hospitalization for physical inactivity-related cardiometabolic diseases. We used a record linkage of 442,345 respondents of the Canadian Community Health Survey and their hospitalization records for cardiometabolic disease. We then assessed respondents' neighbourhoods using the Canadian Active Living Environments measure (Can-ALE), a measure based on ≥3-way intersection density, residential density, and points of interest. We then calculated the distance in kilometers between the centroids of respondents' assigned dissemination areas and the nearest user-contributed location for hospitals from OpenStreetMap. We monitored changes in estimates for the association between ALEs and odds of cardiometabolic disease hospitalization using a series of logistic regressions with indicator variables for distances to hospital of 500 meters to 10 kilometers. We found that living between 500 meters and six kilometers of a hospital and was associated with modestly higher odds of cardiometabolic hospitalization (OR 1.10, 95% CI 1.02 to 1.18 for 500 meters; OR 1.05, 95% CI 1.01 to 1.09 for six kilometers). Living in more favourable ALEs was associated with lower odds of hospitalization (OR 0.79, 95% CI 0.68 to 0.91; comparing the most favourable to least favourable ALEs). Effect estimates between more favourable ALEs and lower odds of hospitalization were marginally strengthened when living within 2-6 kilometers to a hospital was accounted for. This study demonstrates the importance of disentangling interrelated geographic factors and underlines the potential for built environments to elicit reductions in health care.

Social Cohesion and Community Resilience During COVID-19 and Pandemics: A Rapid Scoping Review to Inform the United Nations Research Roadmap for COVID-19 Recovery.

Shock events uncover deficits in social cohesion and exacerbate existing social inequalities at the household, community, local, regional, and national levels. National and regional government recovery planning requires careful stakeholder engagement that centers on marginalized people, particularly women and marginalized community leaders. The aim of this rapid scoping review was to inform the United Nations Research Roadmap for the COVID-19 Recovery, based on Pillar 5 of the United Nations Framework for the Immediate Socioeconomic Response to COVID-19: Social Cohesion and Community Resilience. We present a summary of key concepts across the literature that helped situate this review. The results include a description of the state of the science and a review of themes identified as being crucial to sustainable and equitable recovery planning by the United Nations. The role of social cohesion during a disaster, particularly its importance for upstream planning and relationship building before a disaster occurs, is not well understood and is a promising area of future research. Understanding the applicability of social cohesion measurement methodologies and outcomes across different communities and geographies, as well as the development of new and relevant instruments and techniques, is urgently needed in the context of the global COVID-19 pandemic.

Evaluating the diagnostic performance of preoperative endometrial biopsies in patients diagnosed with high grade endometrial cancer: A study of the Society of Gynecologic Oncology (GOC) Community of Practice (CoP).

BACKGROUND: High grade cancers account for a disproportionate number of recurrences in patients with endometrial cancer. Accurately identifying these cases on endometrial biopsies allows for better surgical planning. This study evaluates the diagnostic accuracy of general pathologists (GP) compared to gynecological pathologists (GYNP) in interpreting preoperative biopsies. METHODS: A retrospective cohort study was conducted of patients diagnosed with high grade endometrial cancer (HGEC) between 2012 and 2016 at eight Canadian cancer centres. Data was collected from medical records. Pre-operative biopsies were categorized into groups; biopsies read by GP, GYNP and GP reviewed by GYNP. Rates of HGEC on pre-operative biopsy were calculated. Fisher exact test was used to compare differences between the groups. Univariate logistic regression analysis was conducted for HGEC prediction. RESULTS: Of 1237 patients diagnosed with HGEC, 245 (19.8%) did not have a preoperative diagnosis of high-grade disease. Discordancy was identified in 91/287 (31.71%) of biopsies reported by GP, and in 114/910 (12.53%) of biopsies reported by a GYNP (p < 0.0001). Compared to GP, GYNP were 3.24 (CI 2.36-4.45) times more likely to identify high grade disease on preoperative biopsy. Patients whose biopsy was reported by a GYNP were more likely to have a comprehensive staging procedure (OR 1.77 CI 1.33-2.38) and less likely to receive adjuvant therapy (OR 0.71 CI 0.52-0.96). CONCLUSION: GYNP are more likely to identify HGEC on pre-operative biopsies. Due to high rates of overall discordancy, it is possible that surgical staging procedures should not be based solely on preoperative biopsy. Further strategies to improve pre-operative biopsies' accuracy are needed.

Active living environments, physical activity and premature cardiometabolic mortality in Canada: a nationwide cohort study.

OBJECTIVE: To evaluate sex-specific and age-specific associations of active living environments (ALEs) with premature cardiometabolic mortality. DESIGN: Population-based retrospective cohort study. SETTING: Residential neighbourhoods (1000-metre circular buffers from the centroids of dissemination areas) across Canada for which the Canadian ALE Measure was derived, based on intersection density, points of interest and dwelling density. PARTICIPANTS: 249 420 survey respondents from an individual-level record linkage between the Canadian Community Health Survey (2000-2010) and the Canadian Mortality Database until 2011, comprised of older women (65-85 years), older men (65-81 years), middle-aged women (45-64 years) and middle-aged men (45-64 years). PRIMARY OUTCOME MEASURES: Premature cardiometabolic mortality and average daily energy expenditure attributable to walking. Multivariable proportional hazards regression models were adjusted for age, educational attainment, dissemination area-level median income, smoking status, obesity, the presence of chronic conditions, season of survey response and survey cycle. RESULTS: Survey respondents contributed a total of 1 451 913 person-years. Greater walking was observed in more favourable ALEs. Walking was associated with lower cardiometabolic death in all groups except for middle-aged men. Favourable ALEs conferred a 22% reduction in death from cardiometabolic causes (HR 0.78, 95% CI 0.63 to 0.97) for older women. CONCLUSIONS: On average, people walk more in favourable ALEs, regardless of sex and age. With the exception of middle-aged men, walking is associated with lower premature cardiometabolic death. Older women living in neighbourhoods that favour active living live longer.

Crossed Cerebellar Atrophy in Perinatal Stroke.

Background and Purpose- Perinatal stroke causes most hemiparetic cerebral palsy and lifelong disability. Crossed cerebellar atrophy (CCA) is chronic cerebellar volume loss following contralateral motor pathway injury. We hypothesized that CCA is quantifiable in perinatal stroke and associated with poor motor outcome. Methods- Term-born children with perinatal stroke, magnetic resonance imaging beyond 6 months of age, and no additional neurological disorders were recruited. Blinded scorers measured cerebellar volumes expressed as ratios (contralesional/ipsilesional), with values <1 suggesting CCA. Motor outcomes including perinatal stroke outcome measure (PSOM) motor and cognitive scores (good/poor), Assisting Hand Assessment, and Melbourne Assessment were compared with cerebellar volume measures. Results- Seventy-three children met criteria (53% male). Mean cerebellar ratios were <1.0 (0.975±0.04; range, 0.885-1.079; P<0.001) suggesting occurrence of CCA. Cerebellar ratios did not differ between stroke types or across PSOM motor outcomes. Larger ipsilesional cerebellar volume was associated with poor PSOM cognitive outcome (P=0.042), possibly with poor PSOM motor outcome (P=0.063), and overall PSOM score (P=0.034). Conclusions- CCA occurs in perinatal stroke but is not strongly associated with motor outcome. However, ipsilesional cerebellar volume is associated with poor cognitive and overall outcomes.

The early care environment and DNA methylome variation in childhood.

Prenatal adversity shapes child neurodevelopment and risk for later mental health problems. The quality of the early care environment can buffer some of the negative effects of prenatal adversity on child development. Retrospective studies, in adult samples, highlight epigenetic modifications as sentinel markers of the quality of the early care environment; however, comparable data from pediatric cohorts are lacking. Participants were drawn from the Maternal Adversity Vulnerability and Neurodevelopment (MAVAN) study, a longitudinal cohort with measures of infant attachment, infant development, and child mental health. Children provided buccal epithelial samples (mean age = 6.99, SD = 1.33 years, n = 226), which were used for analyses of genome-wide DNA methylation and genetic variation. We used a series of linear models to describe the association between infant attachment and (a) measures of child outcome and (b) DNA methylation across the genome. Paired genetic data was used to determine the genetic contribution to DNA methylation at attachment-associated sites. Infant attachment style was associated with infant cognitive development (Mental Development Index) and behavior (Behavior Rating Scale) assessed with the Bayley Scales of Infant Development at 36 months. Infant attachment style moderated the effects of prenatal adversity on Behavior Rating Scale scores at 36 months. Infant attachment was also significantly associated with a principal component that accounted for 11.9% of the variation in genome-wide DNA methylation. These effects were most apparent when comparing children with a secure versus a disorganized attachment style and most pronounced in females. The availability of paired genetic data revealed that DNA methylation at approximately half of all infant attachment-associated sites was best explained by considering both infant attachment and child genetic variation. This study provides further evidence that infant attachment can buffer some of the negative effects of early adversity on measures of infant behavior. We also highlight the interplay between infant attachment and child genotype in shaping variation in DNA methylation. Such findings provide preliminary evidence for a molecular signature of infant attachment and may help inform attachment-focused early intervention programs.

Childbirth-Related Hospital Burden by Socioeconomic Status in a Universal Health Care Setting.

INTRODUCTION: Hospital utilization varies across socioeconomic and demographic strata in Canada, a country with a universal health care system. Rates of adverse birth outcomes are known to differ among women of high and low socioeconomic status (SES), but less is known of the excess hospital burden related to SES over the course of childbirth across Canadian provinces. OBJECTIVE: To examine length of stay and risk of hospitalization surrounding delivery, relative to women's socio-demographic characteristics. METHODS: A population-based record linkage between the Canadian Community Health Survey (CCHS) years 2005-2011 and the Discharge Abstract Database (DAD) allowed the tracking of hospital utilization for linked survey respondents between 2005 and 2011. Hourly length of stay for delivery, risk of readmission, and risk of admission prior to delivery was modeled by socio-demographic factors, controlling for other clinical and individual-level characteristics. RESULTS: There were 21,914 complete delivery records from 15,458 female CCHS respondents who agreed to link and share their information. Average length of stay (for both vaginal and Caesarian deliveries) dropped over the study period from 67.86 hours in 2005 to 59.37 hours in 2011. In multivariate analyses, women with the lowest income had on average, two-hour longer stays for vaginal delivery as compared to high-income women (IRR 1.04, 95% CI 1.00-1.08) and higher risk of admission prior to delivery (OR 1.43, CI 1.13-1.81). Low-income women, Aboriginal women and women living in rural areas were also at elevated risk for longer hospital stays and for hospital admission prior to delivery. There was no consistent socioeconomic patterning of hospital burden for Caesarian deliveries. CONCLUSION: The length of hospital stays for childbirth has declined in Canada. Length of stay remains modestly longer, and risk of hospitalization in the perinatal period higher, for low income women, Aboriginal women and rural women. The absence of egregious income-related differences in hospital burden related to childbirth is reassuring for the equity goals of the Canadian health care system. The persistence of marginally longer, and in turn, costlier visits for low-income and Aboriginal women before and during delivery is, however, suggestive that resources targeted to the prenatal period might be highly cost-effective if they achieve population-wide reductions in length of stay and hospitalization in the perinatal period.

Epigenetic correlates of neonatal contact in humans.

Animal models of early postnatal mother-infant interactions have highlighted the importance of tactile contact for biobehavioral outcomes via the modification of DNA methylation (DNAm). The role of normative variation in contact in early human development has yet to be explored. In an effort to translate the animal work on tactile contact to humans, we applied a naturalistic daily diary strategy to assess the link between maternal contact with infants and epigenetic signatures in children 4-5 years later, with respect to multiple levels of child-level factors, including genetic variation and infant distress. We first investigated DNAm at four candidate genes: the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), µ-opioid receptor M1 (OPRM1) and oxytocin receptor (OXTR; related to the neurobiology of social bonds), and brain-derived neurotrophic factor (BDNF; involved in postnatal plasticity). Although no candidate gene DNAm sites significantly associated with early postnatal contact, when we next examined DNAm across the genome, differentially methylated regions were identified between high and low contact groups. Using a different application of epigenomic information, we also quantified epigenetic age, and report that for infants who received low contact from caregivers, greater infant distress was associated with younger epigenetic age. These results suggested that early postnatal contact has lasting associations with child biology.

Worldwide patterns of human epigenetic variation.

DNA methylation is an epigenetic modification, influenced by both genetic and environmental variation, that plays a key role in transcriptional regulation and many organismal phenotypes. Although patterns of DNA methylation have been shown to differ between human populations, it remains to be determined how epigenetic diversity relates to the patterns of genetic and gene expression variation at a global scale. Here we measured DNA methylation at 485,000 CpG sites in five diverse human populations, and analysed these data together with genome-wide genotype and gene expression data. We found that population-specific DNA methylation mirrors genetic variation, and has greater local genetic control than mRNA levels. We estimated the rate of epigenetic divergence between populations, which indicates far greater evolutionary stability of DNA methylation in humans than has been observed in plants. This study provides a deeper understanding of worldwide patterns of human epigenetic diversity, as well as initial estimates of the rate of epigenetic divergence in recent human evolution.