A Real-World Comparative Effectiveness Analysis of Thromboprophylactic Use of Enoxaparin Versus Unfractionated Heparin in Abdominal Surgery Patients in a Large U.S. Hospital Database.

Introduction: Little is known about outcomes associated with enoxaparin versus unfractionated heparin (UFH) for venous thromboembolism (VTE) prophylaxis in abdominal surgery patients in U.S. clinical practice. The purpose of this study was to compare VTE, all-cause mortality, PE-related in-hospital mortality, and hospital costs during abdominal surgery hospitalization and the 90 days post-discharge between patients who received enoxaparin versus UFH prophylaxis. Materials and Methods: Using the Premier Healthcare Database, abdominal surgery patients who received at least 1 day of VTE prophylaxis with enoxaparin or UFH were identified between January 1, 2010 and September 30, 2016. Clinical outcomes were assessed using multivariable logistic regression models and cost outcomes were assessed using generalized linear models. Results: Of 363,669 patients identified, 59% received enoxaparin and 41% UFH. In adjusted analyses, there were statistically significant lower odds of VTE (OR 0.80; 95% CI 0.65-0.97), all-cause mortality (OR 0.67; 95% CI 0.60-0.75), and major bleeding (OR 0.88; 95% CI 0.82-0.94) during the hospitalization for enoxaparin versus UFH, but no differences during the 90-days post-discharge or for PE-related mortality. There was a statistically significant lower total hospital cost with enoxaparin versus UFH during index hospitalization ($8,913 vs $9,017, P < .0001), but not post-discharge ($3,342 vs $3,368, P = .42). Unadjusted rates of heparin-induced thrombocytopenia (index:0.1% vs 0.3%; post-discharge: 0.02% vs 0.06%) were reported for enoxaparin and UFH, respectively. Conclusion: In contemporary U.S. hospital practice, statistically significant lower odds of VTE, all-cause mortality and major bleeding with enoxaparin versus UFH prophylaxis were found during abdominal surgery hospitalizations.

DEVELOPING twin-specific 75-g oral glucose tolerance test diagnostic thresholds for gestational diabetes based on the risk of future maternal diabetes: a population-based cohort study.

OBJECTIVE: To develop twin-specific outcome-based oral glucose tolerance test (OGTT) diagnostic thresholds for GDM based on the risk of future maternal type-2 diabetes. DESIGN: A population-based retrospective cohort study (2007-2017). SETTING: Ontario, Canada. METHODS: Nulliparous women with a live singleton (n = 55 361) or twin (n = 1308) birth who underwent testing for gestational diabetes mellitus (GDM) using a 75-g OGTT in Ontario, Canada (2007-2017). We identified the 75-g OGTT thresholds in twin pregnancies that were associated with similar incidence rates of future type-2 diabetes to those associated with the standard OGTT thresholds in singleton pregnancies. RESULTS: For any given 75-g OGTT value, the incidence rate of future maternal type-2 diabetes was lower for women with a twin than women with a singleton pregnancy. Using women with a negative OGTT as reference, the risk of future maternal type-2 diabetes in twin pregnancies with a positive OGTT based on the standard OGTT thresholds (9.86 per 1000 person years, adjusted hazard ratio (aHR) 4.79, 95% CI 2.69-8.51) was lower than for singleton pregnancies with a positive OGTT (18.74 per 1000 person years, aHR 8.22, 95% CI 7.38-9.16). The twin-specific OGTT fasting, 1-hour and 2-hour thresholds identified in the current study based on correlation with future maternal type-2 diabetes were 5.8 mmol/l (104 mg/dl), 11.8 mmol/l (213 mg/dl) and 10.4 mmol/l (187 mg/dl), respectively. CONCLUSIONS: We identified potential twin-specific OGTT thresholds for GDM that are associated with a similar risk of future type-2 diabetes to that observed in women diagnosed with GDM in singleton pregnancies based on standard OGTT thresholds. TWEETABLE ABSTRACT: Potential twin-specific OGTT thresholds for GDM were identified.

Formulation and characterization of zein/chitosan complex particles stabilized Pickering emulsion with the encapsulation and delivery of vitamin D3.

BACKGROUND: Pickering emulsions (PEs) which are stabilized by solid particles instead of surfactants have recently attracted tremendous attentions due to their non-toxic and long-term stable nature. In the current study, we fabricated and characterized zein (ZN)/chitosan (CS) complex particles (ZNCSPs) stabilized PE for the encapsulation and delivery of vitamin D3 . RESULTS: The ZNCSPs were synthesized with different ratios, i.e. 1:1, 1:1.5 and 1:2 to investigate the optimum ratio. Transmission electron microscopy observations showed the spherical nature with smooth surface of the obtained particles in the case of ZNCS ratio 1:1.5 and 1:2. Furthermore, ζ-potential values for the these particles were 32.53 ± 1.3 and 52.86 ± 0.68 mV respectively, indicating particles with (1:2) being more stable than 1:1.5. Thereafter, using these particles, the PEs were successfully formulated with different oil (medium chain triglyceride) fractions (330, 500 and 660 g kg-1 ). The emulsions were evaluated for stability during storage and against different environmental factors including pH, temperature and ionic strength on the creaming indices (CIs) of these emulsions. The results demonstrated that the PEs with oil fractions 330 and 500 g kg-1 exhibited significant stability during storage, particularly the ones with 500 g kg-1 oil fractions which were stable against all the tested parameters. Finally, the prepared PEs were evaluated as efficient delivery system by encapsulating and delivering vitamin D3 . In vitro drug release profile confirmed sustained and controlled release of the encapsulated vitamin D3 . CONCLUSION: Overall, our findings suggest that ZNCSPs can be promising stabilizers for stable PEs that can be used as potential delivery systems in food, cosmetic and pharmaceutical industries. © 2021 Society of Chemical Industry.

Universal drug coverage and income-related disparities in glycaemic control.

AIMS: To examine whether income-related disparities in glycaemic control decline after the age of 65 years, when publicly funded universal drug insurance is acquired in Ontario, Canada. METHODS: We conducted a population-based cross-sectional study using linked administrative healthcare databases. Adults with diabetes, aged 40-89 years, with available HbA1c data were included (N = 716 297). Income was based on median neighbourhood household income. Multiple linear regression was used to test for effect modification of age ≥65 years on the relationship between income and HbA1c . RESULTS: There was a significant inverse association between income and HbA1c level. After adjusting for baseline factors, the effect of income on HbA1c level was significantly greater for individuals aged <65 years (mean difference HbA1c for lowest vs highest income group +2.5 mmol/mol, 95% CI +2.3 to +2.7 [+0.23%, 95% CI 0.21 to 0.24]) than for those aged ≥65 years (+1.2 mmol/mol, 95% CI +1.0 to +1.3 [+0.11%, 95% CI 0.10 to 0.12]; P < 0.0001 for interaction). CONCLUSIONS: Despite universal access to healthcare, people with diabetes with lower incomes had significantly worse glycaemic control compared with their counterparts on higher incomes. However, income gradients in glycaemic control were markedly reduced after the age of 65 years, possibly as a result of access to prescription drug coverage.

Perinatal outcomes for untreated women with gestational diabetes by IADPSG criteria: a population-based study.

OBJECTIVE: To estimate the risk for adverse perinatal outcomes for women who met the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria but not the two-step criteria for gestational diabetes mellitus (GDM). DESIGN: Population-level cross-sectional study. SETTING: Ontario, Canada. POPULATION: A total of 90 140 women who underwent a 75-g oral glucose tolerance test. METHODS: Women were divided into those who met the diagnostic thresholds for GDM by two-step criteria and were therefore treated, those who met only the IADPSG criteria for GDM and so were not treated, and those who did not have GDM by either criteria. MAIN OUTCOME MEASURES: Hypertensive disorders of pregnancy, preterm delivery, primary caesarean section, large-for-gestational-age, shoulder dystocia and neonatal intensive care unit admission. RESULTS: Women who met the IADPSG criteria had an increased risk for all adverse perinatal outcomes compared with women who did not have GDM. Women with GDM by two-step criteria also had an increased risk of most outcomes. However, their risk for large-for-gestational-age neonates and for shoulder dystocia was actually lower than that of women who met IADPSG criteria. CONCLUSION: Women who met IADPSG criteria but who were not diagnosed with GDM based on the current two-step diagnostic strategy, and were therefore not treated, had an increased risk for adverse perinatal outcomes compared with women who do not have GDM. The current strategy for diagnosing GDM may be leaving women who are at risk for adverse events without the dietary and pharmacological treatments that could improve their pregnancy outcomes. TWEETABLE ABSTRACT: Women who meet IADPSG criteria for GDM have an increased risk for adverse perinatal outcomes compared with women without GDM.

Differences in prevalence of diabetes among immigrants to Canada from South Asian countries.

AIMS: The prevalence of diabetes is high in South Asians migrants. However, most previous research has studied South Asians as a collective whole. The aim of this study was to examine diabetes prevalence among immigrants from five South Asian countries living in Ontario, Canada. METHODS: Population-based health care and immigration databases were used to compare crude and adjusted diabetes prevalence on 1 January 2012 between immigrants to Ontario from different South Asians countries and the non-immigrant population. The prevalence of diabetes was also stratified by various sociodemographic factors. RESULTS: There were 431 765 first-generation South Asian immigrants; 68 440 (crude prevalence of 15.9%) of whom had a diagnosis of diabetes. After standardization for age, sex and income, diabetes prevalence was highest among South Asians from Sri Lanka (26.8%) followed by Bangladesh (22.2%), Pakistan (19.6%), India (18.3%) and Nepal (16.5%) in comparison with the non-immigrant population (11.6%). Increased prevalence was evident among men compared with women in each country of South Asia. Sociodemographic indicators including income, education, English proficiency and refugee status were associated with increased prevalence of diabetes in specific populations from South Asia. CONCLUSION: Striking differences in the prevalence of diabetes are evident among immigrants from different countries of South Asia. Awareness of the heterogeneity will help in recognizing priorities for the delivery of primary care for specific South Asian migrant populations with a range of settlement needs that also encompass social determinants of health.

Mental health visits and low socio-economic status in adolescence are associated with complications of Type 1 diabetes in early adulthood: a population-based cohort study.

AIM: To determine the association of mental health visits and socio-economic status in late adolescence with the risk of mortality and acute and chronic diabetes complications in early adulthood. METHODS: We conducted a population-based cohort study of individuals in Ontario, Canada, who had their 20th birthday between January 1999 and March 2015 and a diagnosis of diabetes prior to their 15th birthday, using linked administrative databases (n=8491). The main outcome was death; other outcomes were hypoglycaemia or hyperglycaemia-related hospitalizations and emergency department visits and chronic diabetes complications (dialysis, ophthalmological and macrovascular complications). RESULTS: Over the course of 59 361 person-years there were 127 deaths.. Low socio-economic status and mental health visits were both associated with a higher risk of death [hazard ratio 2.03, (95% CI 1.13 to 3.64) and 2.45 (95% CI 1.71 to 3.51), respectively]. Those with the lowest socio-economic status and a mental health visit had a higher rate of diabetes-related hospitalizations (rate ratio 4.84, 95% CI 3.64 to 6.44) and emergency department visits (rate ratio 3.15, 95% CI 1.79 to 5.54). Low socio-economic status and mental health visits were both associated with an increased risk of any chronic complication [hazard ratio 1.54 (95% CI 1.21 to 1.96) and 1.57 (95% CI 1.35 to 1.81), respectively]. CONCLUSION: We identified significant socio-economic and mental health disparities in the risk of death and acute and chronic complications in early adulthood for people with childhood-onset diabetes. Targeted interventions to prevent adverse events for these adolescents at highest risk should be evaluated.

Diabetes transition care and adverse events: a population-based cohort study in Ontario, Canada.

AIMS: To describe patterns of primary and diabetes care during transition age (17 to < 19 years) into early adulthood (age 19 to 26 years), and to evaluate the association of primary and diabetes care patterns during transition age with the risk of adverse events in early adulthood. METHODS: We conducted a population-based cohort study of individuals in Ontario, Canada who were diagnosed with diabetes aged < 15 years and who turned 17 between November 2006 and March 2011, followed until March 2015 (n = 2525). Using linked administrative databases, we examined healthcare use during: 'pre-transition-age' (15 to < 17 years), 'transition-age' (17 to < 19 years), and 'early adulthood' (19 to 26 years). The main outcomes were time to death or ketoacidosis and rate of diabetes-related admissions. The main exposures were the gap in diabetes care and primary care visits during transition age. RESULTS: There were < 6 deaths and 446 individuals (17.7%) had at least one admission for ketoacidosis during early adulthood. In all, 1188 individuals (47.0%) had a > 12-month gap in diabetes care and 241 (9.5%) had no primary care visits during transition age. A gap in diabetes care of > 12 months and no primary care visits during transition age were associated with an increased risk of ketoacidosis or death (adjusted hazard ratio 1.31, 95% CI 1.04-1.66 and adjusted hazard ratio 1.42, 95% CI 1.02-1.97, respectively). CONCLUSIONS: In Ontario, Canada, where physician and hospital-based services are universally covered, a high proportion of young adults with diabetes have insufficient care during transition age and this is associated with a higher risk of important adverse outcomes in early adulthood. Ensuring primary care involvement during transition may be a strategy to reduce morbidity.

Smoking, Pain Intensity, and Opioid Consumption 1-3 Months After Major Surgery: A Retrospective Study in a Hospital-Based Transitional Pain Service.

Introduction: The present study investigated the associations between smoking, pain, and opioid consumption in the 3 months after major surgery in patients seen by the Transitional Pain Service. Current smoking status and lifetime pack-years were expected to be related to higher pain intensity, more opioid use, and poorer opioid weaning after surgery. Methods: A total of 239 patients reported smoking status in their presurgical assessment (62 smokers, 92 past smokers, and 85 never smokers). Pain and daily opioid use were assessed in hospital before postsurgical discharge, at first outpatient visit (median of 1 month postsurgery), and at last outpatient visit (median of 3 months postsurgery). Pain was measured using numeric rating scale. Morphine equivalent daily opioid doses were calculated for each patient. Results: Current smokers reported significantly higher pain intensity (p < .05) at 1 month postsurgery than never smokers and past smokers. Decline in opioid consumption differed significantly by smoking status, with both current and past smokers reporting a less than expected decline in daily opioid consumption (p < .05) at 3 months. Decline in opioid consumption was also related to pack-years, with those reporting higher pack-years having a less than expected decline in daily opioid consumption at 3 months (p < .05). Conclusions: Smoking status may be an important modifiable risk factor for pain intensity and opioid use after surgery. Implications: In a population with complex postsurgical pain, smoking was associated with greater pain intensity at 1 month after major surgery and less opioid weaning 3 months after surgery. Smoking may be an important modifiable risk factor for pain intensity and opioid use after surgery.

A systematic model improves hepatitis C virus birth cohort screening in hospital-based primary care.

Despite national and local governing board recommendations in the United States of America to perform an HCV screening test in baby boomers, screening rates remain low. Our goal was to study the impact of an HCV screening and link-to-care programme with patient navigation in two New York City primary care practices. This was a 2-year prospective study of patients born between 1945-1965 ("baby boomers") with encounters at two primary care practices at the Mount Sinai Hospital between November 1, 2013 and November 30, 2015. Baseline HCV screening rates were collected for four months. A multifaceted intervention was sequentially implemented involving electronic alerts, housestaff education, data feedback and patient navigation. HCV screening rates and link to care, defined as attending an appointment with a viral hepatitis specialist, were compared before and after these interventions. There were 14 642 primary care baby boomer patients of which 4419 (30.2%) were newly screened during the study. There was a significant increase in HCV screening rates from 55% to 75% (P<.01) with an HCV seropositive rate of 3.3%. Factors associated with being HCV seropositive included older age (P<.01), male sex (P<.01), African American race (P<.01) and receiving care in the housestaff practice (P<.01). With patient navigation, 78 of 84 (93%) newly diagnosed HCV-infected persons were referred to a specialist and 60 (77%) attended their first appointment. A structured, multifaceted HCV screening programme using well-studied principles identifies a large number of undiagnosed baby boomers within hospital-based primary care and improves access to specialty providers in a timely manner.

Gestational diabetes care and outcomes for refugee women: a population-based cohort study.

AIM: To determine the prevalence of adverse clinical outcomes, the rates of healthcare utilization, and the incidence of post-partum Type 2 diabetes in refugees with gestational diabetes (GDM), compared with other immigrants and non-immigrants. METHODS: A population-based cohort study was conducted using healthcare databases in Ontario, Canada. Over 40 000 women with GDM having singleton live births between 2002 and 2014 were identified. We identified GDM adverse outcomes such as macrosomia, pre-eclampsia and respiratory distress syndrome. Antenatal and newborn healthcare utilization were ascertained. Women were then followed for diagnosis of diabetes post-partum. RESULTS: Both refugees and other immigrants had a lower rate than non-immigrants of many adverse GDM outcomes, including pre-eclampsia [relative risk (RR) 0.65, 95% confidence interval (95% CI) 0.44-0.95 and 0.61, 95% CI 0.52-0.72, respectively], preterm birth (RR 0.87, 95% CI 0.75-0.995 and 0.85, 95% CI 0.80-0.91, respectively), and respiratory distress syndrome (RR 0.83, 95% CI 0.70-0.97 and 0.78, 95% CI 0.72-0.84, respectively). However, refugees were less likely to attend well-baby care in time for the first routine vaccination (RR 0.92, 95% CI 0.88-0.95). Incidence of post-partum diabetes was high in all groups, but refugee women were at increased risk (hazard ratio 1.23, 95% CI 1.11-1.37). CONCLUSIONS: Despite different circumstances leading to migration, refugees have a similar 'healthy immigrant effect' to other immigrants, with respect to adverse GDM outcomes. However, newborns of refugees were less likely to have well-baby care, and refugee women were also at especially high risk of developing diabetes post-partum. These are both important public health issues.

Effect of multiparity and ethnicity on the risk of development of diabetes: a large population-based cohort study.

AIMS: To investigate the relationship between increasing parity and diabetes in a large, population-based cohort, and to examine if this relationship is different among high-risk ethnic groups. METHODS: A population-based, retrospective cohort study was performed in 738 440 women aged 18-50 years, who delivered babies in Ontario between 1 April 2002 and 31 March 2011. Diabetes incidence postpartum was calculated for each parity and ethnic group. A multivariable analysis of the effect of parity and ethnicity on the incidence of diabetes was performed using a Cox proportional hazards model, adjusting for confounders. RESULTS: The diabetes incidence rate per 1000 person-years was 3.69 in women with 1 delivery, 4.12 in women with 3 deliveries and 7.62 in women with ≥5 deliveries. Women with ≥3 deliveries had a higher risk of developing diabetes compared with women with 1 delivery [adjusted hazard ratios 1.06 (95% CI 1.01-1.11) for 3 deliveries, 1.33 (95% CI 1.25-1.43) for 4 deliveries and 1.53 (95% CI 1.41-1.66) for ≥5 deliveries). A similar rise in risk could be seen in Chinese and South-Asian women, with the most influence in Chinese women [hazard ratio 4.59 (95% CI 2.36-8.92) for ≥5 deliveries]. CONCLUSIONS: There was a positive and graded relationship between increasing parity and risk of development of diabetes. The influence of parity was seen in all ethnicities. This association may be partly related to increasing weight gain and retention with increasing parity, or deterioration in ß-cell function. This merits further exploration.

Clinical experience with lenalidomide alone or in combination with rituximab in indolent B-cell and mantle cell lymphomas.

Lenalidomide is an oral immunomodulatory drug with significant activity in indolent B-cell and mantle cell lymphomas. Lenalidomide has a manageable safety profile whether administered as a single agent or in combination with rituximab. The combination of lenalidomide with rituximab, known as the 'R(2)' regimen, enhances efficacy over what has been shown with monotherapy and has demonstrated activity in patients considered resistant to rituximab. Tolerability of these regimens has been consistent among studies. Asymptomatic neutropenia is the most common grade 3/4 adverse event, typically managed by dose interruption, followed by dose reduction once neutrophils have recovered. Nonhematologic toxicities (e.g. fatigue) are generally low-grade, manageable with concomitant treatment, and/or lenalidomide dose modification. More frequent with R(2), immune-related symptoms such as rash and tumor flare are important to recognize as lenalidomide-associated treatment effects in patients with lymphoma who require supportive care and potential dose modifications. Severe tumor flare reactions with painful lymphadenopathy are not typically observed outside of chronic lymphocytic leukemia/small lymphocytic lymphoma. Venous thromboembolism is uncommon in lymphomas, though prophylaxis is recommended. The general safety profile, differences between lenalidomide monotherapy and R(2) treatment, and optimal strategies for managing adverse events are discussed here.

Sex of the baby and future maternal risk of Type 2 diabetes in women who had gestational diabetes.

AIMS: Women who develop gestational diabetes mellitus have a chronic defect in the secretion of insulin by the pancreatic ß cells that underlies both their diagnostic hyperglycaemia in pregnancy and their elevated lifetime risk of developing Type 2 diabetes in the future. It has recently emerged that carrying a male fetus is associated with poorer maternal ß-cell function and an increased risk of gestational diabetes, whereas the development of gestational diabetes when carrying a girl (as compared with a boy) predicts a comparatively higher risk of early progression to Type 2 diabetes before any subsequent pregnancy. In this context, we sought to determine the impact of fetal sex on the long-term risk of Type 2 diabetes in women with gestational diabetes. METHODS: Using population-based administrative databases, we identified all women in Ontario, Canada, with a singleton live-birth first pregnancy complicated by gestational diabetes between April 2000 and March 2010 (n = 23 363). We compared the risk of subsequent Type 2 diabetes after pregnancy in those who carried a girl (n = 11 229) vs. those who carried a boy (n = 12 134). RESULTS: Over median 5.5 years follow-up, 5483 women (23.5%) were diagnosed with diabetes. Compared with those who carried a boy, women who had a girl had an elevated risk of subsequently developing diabetes (adjusted hazard ratio = 1.06, 95% CI 1.01-1.12). CONCLUSIONS: Among women with gestational diabetes, those who are carrying a girl have a slightly higher overall future risk of Type 2 diabetes.

Short-term risk of cancer among women with previous gestational diabetes: a population-based study.

AIMS: To evaluate the relationship between gestational diabetes (GDM) and incidence of cancer in women within the first decade postpartum. METHODS: This population-based retrospective cohort study compared the risk of cancer in women with GDM with that of a matched control group comprising pregnant women without diabetes. We included women from Ontario, Canada aged 20-50 years with no history of cancer who had given birth between 1995 and 2008 (N = 149 049). Women with GDM (N = 49 684) were matched on age and year of giving birth, in a ratio of 1:2, to pregnant women without diabetes (N = 99 365). RESULTS: Over a median 8-year follow-up, there were a total of 2927 (1.5%) cancers. After adjustment for covariates, we found no significant difference in overall risk of cancer between women with GDM and matched control subjects; however, GDM was associated with a significantly greater risk of thyroid cancer (adjusted hazard ratio 1.24, 95% CI 1.05, 1.46) and a significantly lower risk of premenopausal breast cancer (hazard ratio 0.86, 95% CI 0.75, 0.98) compared with matched control subjects. CONCLUSIONS: This large population-based study did not find a greater risk of cancers among women with GDM during the first decade postpartum; however, GDM was associated with a higher risk of thyroid cancer and a lower risk of premenopausal breast cancer. Further studies are needed to confirm these findings.

Early specialist care for diabetes: who benefits most? A propensity score-matched cohort study.

AIMS: To examine whether early endocrinologist care reduces the risk of cardiovascular complications among newly diagnosed patients with diabetes of differing complexity. METHODS: We conducted a population-based propensity score-matched cohort study using provincial health data from Ontario, Canada. Adults (≥ 30 years) diagnosed with diabetes between 1 April 1998 and 31 March 2006 who received endocrinologist care in the first year of diagnosis were matched to a comparison group receiving primary care alone (N = 79 020) based on propensity scores and medical complexity (assigned using information on chronic conditions). Individuals were followed for 3- and 5-year outcomes, including non-fatal acute myocardial infarction or coronary heart disease death (primary endpoint), major cardiovascular events (acute myocardial infarction, stroke) or all-cause death, amputation and end-stage renal disease. RESULTS: Among medically complex patients, early endocrinologist care was associated with a lower 3-year incidence of the primary endpoint (hazard ratio 0.89, 95% CI 0.78-1.01) and major cardiovascular events or all-cause death (hazard ratio 0.91, 95% CI 0.85-0.97). These effects persisted after accounting for a higher incidence of end-stage renal disease on follow-up and were greatest in those with ≥ 3 visits to an endocrinologist (primary endpoint: hazard ratio 0.69, 95% CI 0.56-0.86 and 0.61, 95% CI 0.45-0.82, for unadjusted and end-stage renal disease adjusted analyses, respectively). In contrast, no benefit was observed in the non-medically complex subgroup. Overall effects were similar at 5 years. CONCLUSIONS: Early endocrinologist care is associated with a lower incidence of cardiovascular events and death among newly diagnosed patients with diabetes who have comorbid medical conditions.

Depressive symptoms predict non-completion of a structured exercise intervention for people with Type 2 diabetes.

AIM: To quantify the impact of depressive symptoms on completion of exercise-based rehabilitation for Type 2 diabetes management. METHODS: Depressive symptoms were assessed using the Center for Epidemiological Studies Depression scale in a prospective cohort of consecutive patients with Type 2 diabetes entering a 6-month hybrid (home- and clinic-based) exercise rehabilitation programme. Attendance at exercise sessions was monitored and programme completion/non-completion was ascertained. RESULTS: Of the programme participants (n=624, mean age 55.6±10.5 years, 47% male), 26.8% endorsed significant depressive symptoms (depression score ≥16) and 68.1% completed the intervention, attending 54.6±30.0% of supervised exercise sessions. Baseline depressive symptoms (depression scale score ≥16) increased the risk of non-completion [hazard ratio 1.49 (95% CI 1.10-2.03); P = 0.010], and predicted fewer sessions attended (ß=-2.1, P= 0.002) in adjusted models. A depression score threshold of ≥10 (48.4% of participants) predicted non-completion [hazard ratio 1.60 (95% CI 1.19-2.17); P= 0.002) with optimum accuracy. Non-completions resulting from lack of interest (18.9 vs. 11.0%; P= 0.026) and medical complications (14.6 vs. 6.6%; P= 0.006) were more common among participants with depression scores ≥10. Greater hazard ratios for depression scores ≥10 were observed in subgroups not currently using insulin [hazard ratio 1.70 (95% CI 1.24-2.33); P= 0.001), or an antidepressant [hazard ratio 1.83 (95% CI 1.32-2.54); P<0.001]. CONCLUSIONS: Depressive symptoms were highly prevalent among participants with Type 2 diabetes entering exercise-based rehabilitation, and even mild depressive symptoms posed a significant barrier to completion. Depression screening may help target additional supports to facilitate completion of exercise interventions for people with Type 2 diabetes.

A population-based study of ethnicity and breast cancer stage at diagnosis in Ontario.

BACKGROUND: Breast cancer stage at diagnosis is an important predictor of survival. Our goal was to compare breast cancer stage at diagnosis (by American Joint Committee on Cancer criteria) in Chinese and South Asian women with stage at diagnosis in the remaining general population in Ontario. METHODS: We used the Ontario population-based cancer registry to identify all women diagnosed with breast cancer during 2005-2010, and we applied a validated surname algorithm to identify South Asian and Chinese women. We used logistic regression to compare, for Chinese or South Asian women and for the remaining general population, the frequency of diagnoses at stage ii compared with stage i and stages ii-iv compared with stage i. RESULTS: The registry search identified 1304 Chinese women, 705 South Asian women, and 39,287 women in the remaining general population. The Chinese and South Asian populations were younger than the remaining population (mean: 54, 57, and 61 years respectively). Adjusted for age, South Asian women were more often diagnosed with breast cancer at stage ii than at stage i [odds ratio (or): 1.28; 95% confidence interval (ci): 1.08 to 1.51] or at stages ii-iv than at stage i (or: 1.27; 95% ci: 1.08 to 1.48); Chinese women were less likely to be diagnosed at stage ii than at stage i (or: 0.82; 95% ci: 0.72 to 0.92) or at stages ii-iv than at stage i (or: 0.73; 95% ci: 0.65 to 0.82). CONCLUSIONS: Breast cancers were diagnosed at a later stage in South Asian women and at an earlier stage in Chinese women than in the remaining population. A more detailed analysis of ethnocultural factors influencing breast screening uptake, retention, and care-seeking behavior might be needed to help inform and evaluate tailored health promotion activities.

Outbreak of serotype W135 Neisseria meningitidis in central river region of the Gambia between February and June 2012: a hospital-based review of paediatric cases.

BACKGROUND: Meningitis still accounts for many deaths in children especially during epidemics in countries within the African meningitis belt. Between February and May 2012, the Gambia witnessed an outbreak of meningitis in two of its six regions. This study presents a clinical perspective of this outbreak in central river region of the Gambia. It evaluated the outbreak pattern, clinical features, and mortality among suspected cases that presented to the hospital during the outbreak. METHODOLOGY: This is a prospective observational study of suspected cases of meningitis that presented to the pediatric ward of the Bansang Hospital during the outbreak period. Confirmed cases of meningitis were consecutively enrolled, and those with negative blood cultures presenting during the same period were employed as controls. RESULT: Two hundred and four suspected cases of meningitis presented to the pediatric ward during the outbreak. Ninety were confirmed as meningitis cases. The W135 strain of Neisseria meningitidis was responsible for 89 (98.9%) of meningitis cases seen with an incidence rate of 74.9/100,000 in children (0-14 years) and in-hospital case fatality rate of 7.9%. Highest attack rate was among the 12-49 months age group. Clinical features such as meningeal signs (neck stiffness), conjunctivitis, and joint swelling were seen more in cases than controls. Contact history with relatives, who had fever in previous 2 weeks prior to illness was significantly seen more in cases. Adjusted regression analysis showed 7.5 more likelihood of infection with positive contact history (odds ratio [OR]: 7.2 confidence interval [CI]: [3.39-15.73]). There was no significant difference in death outcome between cases and controls (OR: 0.78 CI: [0.29-2.13]). The double peak wave-like pattern of the epidemic curve noted during this outbreak suggests a disseminated outbreak originating from an index case with propagated spread. CONCLUSION: There is need for more effective surveillance and incorporation of vaccine against meningitis into the expanded program on immunization schedule of the Gambia and other countries within the meningitic epidemic belt.

Positive effects of methylphenidate on hyperactivity are moderated by monoaminergic gene variants in children with autism spectrum disorders.

Methylphenidate (MPH) reduces hyperactive-impulsive symptoms common in children with autism spectrum disorders (ASDs), however, response and tolerability varies widely. We hypothesized monoaminergic gene variants may moderate MPH effects in ASD, as in typically developing children with attention-deficit/hyperactivity disorder. Genotype data were available for 64 children with ASD and hyperactivity who were exposed to MPH during a 1-week safety/tolerability lead-in phase and 58 who went on to be randomized to placebo and three doses of MPH during a 4-week blinded, crossover study. Outcome measures included the Clinical Global Impression-Improvement (CGI-I) scale and the Aberrant Behavior Checklist (ABC-hyperactivity index). A total of 14 subjects discontinued the study because of MPH side effects. Subjects were genotyped for variants in DRD1-DRD5, ADRA2A, SLC6A3, SLC6A4, MAOA and MAOB, and COMT. Forty-nine percent of the sample met positive responder criteria. In this modest but relatively homogeneous sample, significant differences by DRD1 (P=0.006), ADRA2A (P<0.02), COMT (P<0.04), DRD3 (P<0.05), DRD4 (P<0.05), SLC6A3 (P<0.05) and SLC6A4 (P<0.05) genotypes were found for responders versus non-responders. Variants in DRD2 (P<0.001) and DRD3 (P<0.04) were associated with tolerability in the 14 subjects who discontinued the trial. For this first MPH pharmacogenetic study in children with ASD, multiple monoaminergic gene variants may help explain individual differences in MPH's efficacy and tolerability.