Population-based cohort study of hospital delivery volume, geographic accessibility, and obstetric outcomes.

OBJECTIVE: To determine associations between geographic accessibility, delivery volume, and obstetric outcomes. METHODS: Population-based cohort study of linked hospital administrative, census, and geospatial data (2006-2009) from all Canadian jurisdictions except Quebec. Perinatal mortality and major maternal morbidity/mortality were compared across categories of road distance and hospital delivery volume. RESULTS: Among 820 761 mothers delivering 827 504 neonates, travel distance had minimal effect on perinatal mortality. Compared with mothers travelling 0-9 km, the odds of adverse maternal outcomes was decreased for women travelling modest distances (20-49 km, odds ratio, 0.80 [95% confidence interval, 0.75-0.86]), and increased thereafter (50-99 km, 0.99 [0.89-1.10]; 200-299 km, 1.44 [1.10-1.87]; >400 km, 2.22 [1.06-4.63]). Relative to high-volume hospitals (>2500 deliveries/year), adverse maternal outcomes were less likely for hospitals with 1000-2499 (0.90 [0.86-0.95]), and roughly equivalent for hospitals with 200-499 (1.34 [1.22-1.48]) and 500-999 (1.27 [1.17-1.39]) deliveries/year. Odds of perinatal mortality ranged from 1.04 (0.73-1.49; 100-199 deliveries/year) to 1.50 (1.04-2.16; 50-99 deliveries/year); the pattern did not suggest causality. CONCLUSION: Maternal outcomes worsen when travel distance is greater than 200 km, and improve when delivery volume exceeds 1000 deliveries per year.

Prehypertension During Normotensive Pregnancy and Postpartum Clustering of Cardiometabolic Risk Factors: A Prospective Cohort Study.

The nonstratification of blood pressure (BP) levels may underestimate future cardiovascular risk in pregnant women who present with BP levels in the range of prehypertension (120-139/80-89 mm Hg). We prospectively evaluated the relationship between multiple antepartum BP measurements (from 11(+0) to 13(+6) weeks' gestation to term) and the occurrence of postpartum metabolic syndrome in 507 normotensive pregnant women after a live birth. By using latent class growth modeling, we identified the following 3 distinctive diastolic BP (DBP) trajectory groups: the low-J-shaped group (34.2%; DBP from 62.5±5.8 to 65.0±6.8 mm Hg), the moderate-U-shaped group (52.6%; DBP from 71.0±5.9 to 69.8±6.2 mm Hg), and the elevated-J-shaped group (13.2%; DBP from 76.2±6.7 to 81.8±4.8 mm Hg). Notably, the elevated-J-shaped trajectory group had mean DBP and systolic BP levels within the range of prehypertension from 37(+0) and 26(+0) weeks of pregnancy, respectively. Among the 309 women who completed the ≈1.6 years of postpartum follow-up, the women in the elevated-J-shaped group had greater odds of developing postpartum metabolic syndrome (adjusted odds ratio, 6.55; 95% confidence interval, 1.79-23.92; P=0.004) than the low-J-shaped group. Moreover, a parsimonious model incorporating DBP (membership in the elevated-J-shaped group but not in the DBP prehypertension group as identified by a single measurement) and elevated levels of fasting glucose (>4.99 mmol/L) and triglycerides (>3.14 mmol/L) at term was developed, with good discrimination and calibration for postpartum metabolic syndrome (c-statistic, 0.764; 95% confidence interval, 0.674-0.855; P<0.001). Therefore, prehypertension identified by DBP trajectories throughout pregnancy is an independent risk factor for predicting postpartum metabolic syndrome in normotensive pregnant women.

Precision test for precision medicine: opportunities, challenges and perspectives regarding pre-eclampsia as an intervention window for future cardiovascular disease.

Hypertensive disorders of pregnancy (HDP) comprise a spectrum of syndromes that range in severity from gestational hypertension and pre-eclamplsia (PE) to eclampsia, as well as chronic hypertension and chronic hypertension with superimposed PE. HDP occur in 2% to 10% of pregnant women worldwide, and impose a substantial burden on maternal and fetal/infant health. Cardiovascular disease (CVD) is the leading cause of death in women. The high prevalence of non-obstructive coronary artery disease and the lack of an efficient diagnostic workup make the identification of CVD in women challenging. Accumulating evidence suggests that a previous history of PE is consistently associated with future CVD risk. Moreover, PE as a maladaptation to pregnancy-induced hemodynamic and metabolic stress may also be regarded as a "precision" testing result that predicts future cardiovascular risk. Therefore, the development of PE provides a tremendous, early opportunity that may lead to changes in maternal and infant future well-being. However, the underlying pathogenesis of PE is not precise, which warrants precision medicine-based approaches to establish a more precise definition and reclassification. In this review, we proposed a stage-specific, PE-targeted algorithm, which may provide novel hypotheses that bridge the gap between Big Data-generating approaches and clinical translational research in terms of PE prediction and prevention, clinical treatment, and long-term CVD management.

Inflammatory monocyte/macrophage modulation by liposome-entrapped spironolactone ameliorates acute lung injury in mice.

AIM: To examine the therapeutic/preventive potential of liposome-encapsulated spironolactone (SP; Lipo-SP) for acute lung injury (ALI) and fibrosis. MATERIALS & METHODS: Lipo-SP was prepared by the film-ultrasonic method, and physicochemical and pharmacokinetic characterized for oral administration (10 and 20 mg/kg for SP-loaded liposome; 20 mg/kg for free SP) in a mouse model bleomycin-induced ALI. RESULTS: Lipo-SP enhanced bioavailability of SP with significant amelioration in lung pathology. Mechanistically, SP-mediated mineralocorticoid receptor antagonism contributes to inflammatory monocyte/macrophage modulation via an inhibitory effect on Ly6C(hi) monocytosis-directed M2 polarization of alveolar macrophages. Moreover, Lipo-SP at lower dose (10 mg/kg) exhibited more improvement in body weight gain. CONCLUSION: Our data highlight Lipo-SP as a promising approach with therapeutic/preventive potential for ALI and fibrosis.

Vitamin D intake is negatively associated with promoter methylation of the Wnt antagonist gene DKK1 in a large group of colorectal cancer patients.

Diet and lifestyle influence colorectal cancer (CRC) risk but the molecular events that mediate these effects are poorly characterized. Several dietary and lifestyle factors can modulate DNA methylation suggesting that they may influence CRC risk through epigenetic regulation of cancer-related genes. The Wnt regulatory genes DKK1 and Wnt5a are important contributors to colonic carcinogenesis and are often silenced by promoter hypermethylation in CRC; however, the dietary contributions to these events have not been explored. To investigate the link between dietary/lifestyle factors and epigenetic regulation of these Wnt signaling genes, we assessed promoter methylation of these genes in a large cohort of Canadian CRC patients from Ontario (n = 549) and Newfoundland (n = 443) and examined associations to dietary/lifestyle factors implicated in CRC risk and/or DNA methylation including intake of vitamins, fats, cholesterol, fiber, and alcohol as well as body mass index (BMI), and smoking status. Several factors were associated with methylation status including alcohol intake, BMI, and cigarette smoking. Most significantly, however, dietary vitamin D intake was strongly negatively associated with DKK1 methylation in Newfoundland (P = 0.001) and a similar trend was observed in Ontario. These results suggest that vitamin D and other dietary/lifestyle factors may alter CRC risk by mediating extracellular Wnt inhibition.

Physicians' attitudes and practice toward treating injection drug users with hepatitis C: results from a national specialist survey in Canada.

BACKGROUND: In Canada, more than 70% of new cases of hepatitis C virus (HCV) infection per year involve injection drug users (IDUs) and, currently, there is no consensus on how to offer them medical care. OBJECTIVE: To examine the characteristics of Canadian specialist physicians and their likelihood to provide treatment to HCV patients who are IDUs. METHODS: A nationwide, cross-sectional study was conducted in the specialty areas of hepatology, gastroenterology and infectious diseases to examine HCV services. The questionnaire requested information regarding basic demographics, referral pathways and opinions (yes/no), and examined how a physician's treatment regimen is influenced by factors such as treatment eligibility, HCV care management and barriers to providing quality service. RESULTS: Despite the fact that the majority of prevalent and incident cases of HCV are associated with injection drug use, very few specialist physicians actually provide the necessary therapy to this population. Only 19 (19.79%) comprehensive service providers were likely to provide treatment to a current IDU who uses a needle exchange on a regular basis. The majority of comprehensive service providers (n=86 [89.58%]) were likely to provide treatment to a former IDU who was stable on substitution therapy. On bivariate analysis, factors associated with the likelihood to provide treatment to current IDUs included physicians' type, ie, infectious disease specialists compared with noninfectious specialists (OR 3.27 [95% CI 1.11 to 9.63]), and the size of the community where they practice (OR 4.16 [95% CI 1.36 to 12.71] [population 500,000 or greater versus less than 500,000]). Results of the multivariate logistic regression analysis were largely consistent with the results observed in the bivariate analyses. After controlling for other confounding variables, only community size was significantly associated with providing treatment to current IDUs (OR 3.89 [95% CI 1.06 to 14.26] [population 500,000 or greater versus less than 500,000]). CONCLUSION: The present study highlighted the reluctance of specialists to provide treatment to current IDUs infected with HCV. Providing treatment services for HCV-infected substance abusers is challenging and there are many treatment barriers. However, effective delivery of treatment to this population will help to limit the spread of HCV. The present study clearly identified a need for improved HCV treatment accessibility for IDUs.

Consistent low prevalence of arthritis in quebec: findings from a provincial variation study in Canada based on several canadian population health surveys.

OBJECTIVE: To examine interprovincial variations of arthritis prevalence focusing on comparisons between Quebec and the rest of Canada. METHODS: Data were derived from the 1991 General Social Survey (GSS), the 1991 Health and Activity Limitation Survey (HALS), and the 1994 and 1996 National Population Health Surveys (NPHS). Arthritis was variously ascertained through self-report of people aged 15 years or older. Prevalence in Quebec was compared with other provinces using extremal quotients (EQ) and correlation analysis. Multiple logistic regression analysis (1996 NPHS) was used to determine whether the low prevalence in Quebec persisted after controlling for confounding factors including age, sex, education, marital status, occupation, body mass index (BMI), comorbidity, and smoking. RESULTS: Quebec consistently had the lowest provincial prevalence of arthritis, with age-sex adjusted prevalences of 18.4% (GSS), 1.9% (HALS), 8.8%, and 10.1% (1994 and 1996 NPHS), which were significantly lower than the corresponding national estimates: 21.2%, 3.1%, 12.9%, and 13.3%. EQ from different surveys varied from 1.5 to 3.0 (significantly > 1). Correlation analyses reveal that relative rankings for provinces were consistent in all surveys. Logistic regression analyses showed a low risk of arthritis for Quebecois: odds ratio 0.75 (95% confidence interval 0.65, 0.87) after controlling for potential confounding factors. CONCLUSION: The low prevalence of arthritis observed in Quebec cannot be explained by potential confounding factors included in the NPHS and warrants further epidemiological studies.