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1.  Sedentary Behaviour, Visceral Fat Accumulation and Cardiometabolic Risk in Adults: A 6-Year Longitudinal Study from the Quebec Family Study 
PLoS ONE  2013;8(1):e54225.
Background
Sedentary behaviour has recently emerged as a unique risk factor for chronic disease morbidity and mortality. One factor that may explain this relationship is visceral adiposity, which is prospectively associated with increased cardiometabolic risk and mortality. The objective of the present study was to determine whether sedentary behaviour was associated with increased accumulation of visceral fat or other deleterious changes in cardiometabolic risk over a 6-year follow-up period among adult participants in the Quebec Family Study.
Methods
The current study included 123 men and 153 women between the ages of 18 and 65. Total sedentary time and physical activity were assessed by self-report questionnaire. Cross-sectional areas of visceral and subcutaneous abdominal adipose tissue were assessed using computed tomography. Cardiometabolic biomarkers including fasting insulin, glucose, blood lipids, HOMA-Insulin Resistance, and oral glucose tolerance were also measured. All variables of interest were collected at both baseline and follow-up.
Results
After adjustment for age, sex, baseline BMI, physical activity, energy intake, smoking, education, income and menopausal status, baseline sedentary behaviour was not associated with changes in visceral adiposity or any other marker of cardiometabolic risk. In the longitudinal model which adjusted for all studied covariates, every 15-minute increase in sedentary behaviour from baseline to follow-up was associated with a 0.13 cm increase in waist circumference (95% CI = 0.02, 0.25). However, there was no association between changes in sedentary behaviour and changes in visceral adiposity or other markers of cardiometabolic risk.
Conclusion
These results suggest that neither baseline sedentary behaviour nor changes in sedentary behaviour are associated with longitudinal changes in visceral adiposity in adult men and women. With the exception of waist circumference, the present study did not find evidence of a relationship between sedentary behaviour and any marker of cardiometabolic risk in this population.
doi:10.1371/journal.pone.0054225
PMCID: PMC3541147  PMID: 23326600
2.  Self-Reported Screen Time and Cardiometabolic Risk in Obese Dutch Adolescents 
PLoS ONE  2012;7(12):e53333.
Background
It is not clear whether the association between sedentary time and cardiometabolic risk exists among obese adolescents. We examined the association between screen time (TV and computer time) and cardiometabolic risk in obese Dutch adolescents.
Methods and Findings
For the current cross-sectional study, baseline data of 125 Dutch overweight and obese adolescents (12–18 years) participating in the Go4it study were included. Self-reported screen time (Activity Questionnaire for Adolescents and Adults) and clustered and individual cardiometabolic risk (i.e. body composition, systolic and diastolic blood pressure, low-density (LDL-C), high-density (HDL-C) and total cholesterol (TC), triglycerides, glucose and insulin) were assessed in all participants. Multiple linear regression analyses were used to assess the association between screen time and cardiometabolic risk, adjusting for age, gender, pubertal stage, ethnicity and moderate-to-vigorous physical activity. We found no significant relationship between self-reported total screen time and clustered cardiometabolic risk or individual risk factors in overweight and obese adolescents. Unexpectedly, self-reported computer time, but not TV time, was slightly but significantly inversely associated with TC (B = −0.002; CI = [−0.003;−0.000]) and LDL-C (B = −0.002; CI = [−0.001;0.000]).
Conclusions
In obese adolescents we could not confirm the hypothesised positive association between screen time and cardiometabolic risk. Future studies should consider computer use as a separate class of screen behaviour, thereby also discriminating between active video gaming and other computer activities.
doi:10.1371/journal.pone.0053333
PMCID: PMC3532349  PMID: 23285284
3.  Statistical and Biological Gene-Lifestyle Interactions of MC4R and FTO with Diet and Physical Activity on Obesity: New Effects on Alcohol Consumption 
PLoS ONE  2012;7(12):e52344.
Background
Fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) and are relevant genes associated with obesity. This could be through food intake, but results are contradictory. Modulation by diet or other lifestyle factors is also not well understood.
Objective
To investigate whether MC4R and FTO associations with body-weight are modulated by diet and physical activity (PA), and to study their association with alcohol and food intake.
Methods
Adherence to Mediterranean diet (AdMedDiet) and physical activity (PA) were assessed by validated questionnaires in 7,052 high cardiovascular risk subjects. MC4R rs17782313 and FTO rs9939609 were determined. Independent and joint associations (aggregate genetic score) as well as statistical and biological gene-lifestyle interactions were analyzed.
Results
FTO rs9939609 was associated with higher body mass index (BMI), waist circumference (WC) and obesity (P<0.05 for all). A similar, but not significant trend was found for MC4R rs17782313. Their additive effects (aggregate score) were significant and we observed a 7% per-allele increase of being obese (OR = 1.07; 95%CI 1.01–1.13). We found relevant statistical interactions (P<0.05) with PA. So, in active individuals, the associations with higher BMI, WC or obesity were not detected. A biological (non-statistical) interaction between AdMedDiet and rs9939609 and the aggregate score was found. Greater AdMedDiet in individuals carrying 4 or 3-risk alleles counterbalanced their genetic predisposition, exhibiting similar BMI (P = 0.502) than individuals with no risk alleles and lower AdMedDiet. They also had lower BMI (P = 0.021) than their counterparts with low AdMedDiet. We did not find any consistent association with energy or macronutrients, but found a novel association between these polymorphisms and lower alcohol consumption in variant-allele carriers (B+/−SE: −0.57+/−0.16 g/d per-score-allele; P = 0.001).
Conclusion
Statistical and biological interactions with PA and diet modulate the effects of FTO and MC4R polymorphisms on obesity. The novel association with alcohol consumption seems independent of their effects on BMI.
doi:10.1371/journal.pone.0052344
PMCID: PMC3528751  PMID: 23284998
4.  Effects of meal preparation training on body weight, glycemia, and blood pressure: results of a phase 2 trial in type 2 diabetes 
Background
Modest reductions in weight and small increases in step- related activity (e.g., walking) can improve glycemic and blood pressure control in type 2 diabetes mellitus (DM2). We examined changes in these parameters following training in time- efficient preparation of balanced, low- energy meals combined with pedometer- based step count monitoring.
Methods
Seventy- two adults with DM2 were enrolled in a 24- week program (i.e., 15 three- hour group sessions). They prepared meals under a chef’s supervision, and discussed eating behaviours/nutrition with a registered dietitian. They maintained a record of pedometer- assessed step counts. We evaluated changes from baseline to 24 weeks in terms of weight, step counts, hemoglobin A1c (HbA1c, glycemic control), blood pressure, and eating control ability (Weight Efficacy Lifestyle WEL Questionnaire). 53 participants (73.6%) completed assessments.
Results
There were improvements in eating control (11.2 point WEL score change, 95% CI 4.7 to 17.8), step counts (mean change 869 steps/day, 95% CI 198 to 1,540), weight (mean change −2.2%; 95% CI −3.6 to −0.8), and HbA1c (mean change −0.3% HbA1c, 95% CI −0.6 to −0.1), as well as suggestion of systolic blood pressure reduction (mean change −3.5 mm Hg, 95% CI −7.8 to 0.9). Findings were not attributable to medication changes. In linear regression models (adjusted for age, sex, ethnicity, insulin use, season), a −2.5% weight change was associated with a −0.3% HbA1c change (95% CI −0.4 to −0.2) and a −3.5% systolic blood pressure change (95% CI −5.5 to −1.4).
Conclusions
In this ‘proof of concept’ study, persistence with the program led to improvements in eating and physical activity habits, glycemia reductions, and suggestion of blood pressure lowering effects. The strategy thus merits further study and development to expand the range of options for vascular risk reduction in DM2.
doi:10.1186/1479-5868-9-125
PMCID: PMC3543247  PMID: 23075398
Body weight; Physical activity; Patient education; Risk factors; Type 2 diabetes
5.  Socioeconomic and Environmental Risk Factors among Rheumatic Heart Disease Patients in Uganda 
PLoS ONE  2012;7(8):e43917.
Background
Although low socioeconomic status, and environmental factors are known risk factors for rheumatic heart disease in other societies, risk factors for rheumatic heart disease remain less well described in Uganda.
Aims and Objective
The objective of this study was to investigate the role of socio-economic and environmental factors in the pathogenesis of rheumatic heart disease in Ugandan patients.
Methods
This was a case control study in which rheumatic heart disease cases and normal controls aged 5–60 years were recruited and investigated for socioeconomic and environmental risk factors such as income status, employment status, distance from the nearest health centre, number of people per house and space area per person.
Results
486 participants (243 cases and 243 controls) took part in the study. Average age was 32.37+/−14.6 years for cases and 35.75+/−12.6 years for controls. At univariate level, Cases tended to be more overcrowded than controls; 8.0+/−3.0 versus 6.0+/−3.0 persons per house. Controls were better spaced at 25.2 square feet versus 16.9 for cases. More controls than cases were employed; 45.3% versus 21.1%. Controls lived closer to health centers than the cases; 4.8+/−3.8 versus 3.3+/−12.9 kilometers. At multivariate level, the odds of rheumatic heart disease was 1.7 times higher for unemployment status (OR = 1.7, 95% CI = 1.05–8.19) and 1.3 times higher for overcrowding (OR = 1.35, 95% CI = 1.1–1.56). There was interaction between overcrowding and longer distance from the nearest health centre (OR = 1.20, 95% CI = 1.05–1.42).
Conclusion
The major findings of this study were that there was a trend towards increased risk of rheumatic heart disease in association with overcrowding and unemployment. There was interaction between overcrowding and distance from the nearest health center, suggesting that the effect of overcrowding on the risk of acquiring rheumatic heart disease increases with every kilometer increase from the nearest health center.
doi:10.1371/journal.pone.0043917
PMCID: PMC3428272  PMID: 22952810
6.  Effectiveness of Standardized Nursing Care Plans in Health Outcomes in Patients with Type 2 Diabetes Mellitus: A Two-Year Prospective Follow-Up Study 
PLoS ONE  2012;7(8):e43870.
Background
Implementation of a standardized language in Nursing Care Plans (SNCP) allows for increased efficiency in nursing data management. However, the potential relationship with patientś health outcomes remains uncertain. The aim of this study was to evaluate the effectiveness of SNCP implementation, based on North American Nursing Diagnosis Association (NANDA) and Nursing Interventions Classification (NIC), in the improvement of metabolic, weight, and blood pressure control of Type 2 Diabetes Mellitus (T2DM) patients.
Methods
A two-year prospective follow-up study, in routine clinical practice conditions. 31 primary health care centers (Spain) participated with 24,124 T2DM outpatients. Data was collected from Computerized Clinical Records; SNCP were identified using NANDA and NIC taxonomies. Descriptive and ANCOVA analyses were conducted.
Results
18,320 patients were identified in the Usual Nursing Care (UNC) group and 5,168 in the SNCP group. At the two-year follow-up, the SNCP group improved all parameters except LDL cholesterol and diastolic blood pressure. We analyzed data adjustming by the baseline value for these variables and variables with statistically significant differences between groups at baseline visit. Results indicated a lowering of all parameters except HbA1c, but a statistically significant reduction was only observed with diastolic blood pressure results. However, the adjusted reduction of diastolic blood pressure is of little clinical relevance. Greater differences of control values for diastolic blood pressure, HbA1c, LDL-cholesterol and Body Mass Index were found in the SNCP group, but only reached statistical significance for HbA1c. A greater proportion of patients with baseline HbA1c ≥7 decreased to <7% at the two-year follow-up in the SNCP group than in the UNC group (16.9% vs. 15%; respectively; p = 0.01).
Conclusions
Utilization of SNCP was helpful in achieving glycemic control targets in poorly controlled patients with T2DM (HbA1c ≥7%). Diastolic blood pressure results were slightly improved in the SNCP group compared to the UNC group.
Trial Registration
ClinicalTrials.gov NCT01482481
doi:10.1371/journal.pone.0043870
PMCID: PMC3428286  PMID: 22952794
7.  Long-Term Health Outcomes in Children Born to Mothers with Diabetes: A Population-Based Cohort Study 
PLoS ONE  2012;7(5):e36727.
Background
To examine whether prenatal exposure to parental type 1 diabetes, type 2 diabetes, or gestational diabetes is associated with an increased risk of malignant neoplasm or diseases of the circulatory system in the offspring.
Methods/Principal Findings
We conducted a population-based cohort study of 1,781,576 singletons born in Denmark from 1977 to 2008. Children were followed for up to 30 years from the day of birth until the onset of the outcomes under study, death, emigration, or December 31, 2009, whichever came first. We used Cox proportional hazards model to estimate hazard ratios (HR) with 95% confidence intervals (95% CI) for the outcomes under study while adjusting for potential confounders. An increased risk of malignant neoplasm was found in children prenatally exposed to maternal type 2 diabetes (HR = 2.2, 95%CI: 1.5–3.2). An increased risk of diseases of the circulatory system was found in children exposed to maternal type 1 diabetes (HR = 2.2, 95%CI: 1.6–3.0), type 2 diabetes (HR = 1.4, 95%CI: 1.1–1.7), and gestational diabetes (HR = 1.3, 95%CI: 1.1–1.6), but results were attenuated after excluding children with congenital malformations. An increased risk of diseases of the circulatory system was also found in children exposed to paternal type 2 diabetes (HR = 1.5, 95%CI: 1.1–2.2) and the elevated risk remained after excluding children with congenital malformations.
Conclusions
This study suggests that susceptibility to malignant neoplasm is modified partly by fetal programming. Diseases of the circulatory system may be modified by genetic factors, other time-stable family factors, or fetal programming.
doi:10.1371/journal.pone.0036727
PMCID: PMC3359312  PMID: 22649497
8.  Objective vs. Self-Reported Physical Activity and Sedentary Time: Effects of Measurement Method on Relationships with Risk Biomarkers 
PLoS ONE  2012;7(5):e36345.
Purpose
Imprecise measurement of physical activity variables might attenuate estimates of the beneficial effects of activity on health-related outcomes. We aimed to compare the cardiometabolic risk factor dose-response relationships for physical activity and sedentary behaviour between accelerometer- and questionnaire-based activity measures.
Methods
Physical activity and sedentary behaviour were assessed in 317 adults by 7-day accelerometry and International Physical Activity Questionnaire (IPAQ). Fasting blood was taken to determine insulin, glucose, triglyceride and total, LDL and HDL cholesterol concentrations and homeostasis model-estimated insulin resistance (HOMAIR). Waist circumference, BMI, body fat percentage and blood pressure were also measured.
Results
For both accelerometer-derived sedentary time (<100 counts.min−1) and IPAQ-reported sitting time significant positive (negative for HDL cholesterol) relationships were observed with all measured risk factors – i.e. increased sedentary behaviour was associated with increased risk (all p≤0.01). However, for HOMAIR and insulin the regression coefficients were >50% lower for the IPAQ-reported compared to the accelerometer-derived measure (p<0.0001 for both interactions). The relationships for moderate-to-vigorous physical activity (MVPA) and risk factors were less strong than those observed for sedentary behaviours, but significant negative relationships were observed for both accelerometer and IPAQ MVPA measures with glucose, and insulin and HOMAIR values (all p<0.05). For accelerometer-derived MVPA only, additional negative relationships were seen with triglyceride, total cholesterol and LDL cholesterol concentrations, BMI, waist circumference and percentage body fat, and a positive relationship was evident with HDL cholesterol (p = 0.0002). Regression coefficients for HOMAIR, insulin and triglyceride were 43–50% lower for the IPAQ-reported compared to the accelerometer-derived MVPA measure (all p≤0.01).
Conclusion
Using the IPAQ to determine sitting time and MVPA reveals some, but not all, relationships between these activity measures and metabolic and vascular disease risk factors. Using this self-report method to quantify activity can therefore underestimate the strength of some relationships with risk factors.
doi:10.1371/journal.pone.0036345
PMCID: PMC3348936  PMID: 22590532
9.  Risk of bleeding associated with combined use of selective serotonin reuptake inhibitors and antiplatelet therapy following acute myocardial infarction 
Background:
Patients prescribed antiplatelet treatment to prevent recurrent acute myocardial infarction are often also given a selective serotonin reuptake inhibitor (SSRI) to treat coexisting depression. Use of either treatment may increase the risk of bleeding. We assessed the risk of bleeding among patients taking both medications following acute myocardial infarction.
Methods:
We conducted a retrospective cohort study using hospital discharge abstracts, physician billing information, medication reimbursement claims and demographic data from provincial health services administrative databases. We included patients 50 years of age or older who were discharged from hospital with antiplatelet therapy following acute myocardial infarction between January 1998 and March 2007. Patients were followed until admission to hospital due to a bleeding episode, admission to hospital due to recurrent acute myocardial infarction, death or the end of the study period.
Results:
The 27 058 patients in the cohort received the following medications at discharge: acetylsalicylic acid (ASA) (n = 14 426); clopidogrel (n = 2467), ASA and clopidogrel (n = 9475); ASA and an SSRI (n = 406); ASA, clopidogrel and an SSRI (n = 239); or clopidogrel and an SSRI (n = 45). Compared with ASA use alone, the combined use of an SSRI with antiplatelet therapy was associated with an increased risk of bleeding (ASA and SSRI: hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.08–1.87; ASA, clopidogrel and SSRI: HR 2.35, 95% CI 1.61–3.42). Compared with dual antiplatelet therapy alone (ASA and clopidogrel), combined use of an SSRI and dual antiplatelet therapy was associated with an increased risk of bleeding (HR 1.57, 95% CI 1.07–2.32).
Interpretation:
Patients taking an SSRI together with ASA or dual antiplatelet therapy following acute myocardial infarction were at increased risk of bleeding.
doi:10.1503/cmaj.100912
PMCID: PMC3216455  PMID: 21948719
10.  Daily steps are low year-round and dip lower in fall/winter: findings from a longitudinal diabetes cohort 
Background
Higher walking levels lead to lower mortality in type 2 diabetes, but inclement weather may reduce walking. In this patient population, we conducted a longitudinal cohort study to objectively quantify seasonal variations both in walking and in two vascular risk factors associated with activity levels, hemoglobin A1C and blood pressure.
Methods
Between June 2006 and July 2009, volunteer type 2 diabetes patients in Montreal, Quebec, Canada underwent two weeks of pedometer measurement up to four times over a one year follow-up period (i.e. once/season). Pedometer viewing windows were concealed (snap-on cover and tamper proof seal). A1C, blood pressure, and anthropometric parameters were also assessed. Given similarities in measures for spring/summer and fall/winter, and because not all participants completed four assessments, spring and summer values were collapsed as were fall and winter values. Mean within-individual differences (95% confidence intervals) were computed for daily steps, A1C, and systolic and diastolic blood pressure, by subtracting spring/summer values from fall/winter values.
Results
Among 201 participants, 166 (82.6%) underwent at least one fall/winter and one spring/summer evaluation. Approximately half were women, the mean age was 62.4 years (SD 10.8), and the mean BMI was 30.1 kg/m2 (SD 5.7). Step counts averaged at a sedentary level in fall/winter (mean 4,901 steps/day, SD 2,464) and at a low active level in spring/summer (mean 5,659 steps/day, SD 2,611). There was a -758 (95% CI: -1,037 to -479) mean fall/winter to spring/summer within-individual difference. There were no significant differences in A1C or in anthropometric parameters. Systolic blood pressure was higher in fall/winter (mean 137 mm Hg, SD 16) than spring/summer (133 mm Hg, SD 14) with a mean difference of 4.0 mm Hg (95% CI: 2.3 to 5.7).
Conclusions
Daily step counts in type 2 diabetes patients are low, dipping lower during fall/winter. In this medication-treated cohort, A1C was stable year-round but a fall/winter systolic blood pressure increase was detected. Our findings signal a need to develop strategies to help patients increase step counts year-round and prevent both reductions in step counts and increases in blood pressure during the fall and winter.
doi:10.1186/1475-2840-9-81
PMCID: PMC3004821  PMID: 21118567
11.  Sex Differences in Step Count-Blood Pressure Association: A Preliminary Study in Type 2 Diabetes 
PLoS ONE  2010;5(11):e14086.
Background
Walking and cardiovascular mortality are inversely associated in type 2 diabetes, but few studies have objectively measured associations of walking with individual cardiovascular risk factors. Such information would be useful for “dosing” daily steps in clinical practice. This study aimed to quantify decrements in blood pressure and glycated hemoglobin (A1C) per 1,000 daily step increments.
Methodology/Principal Findings
Two hundred and one subjects with type 2 diabetes underwent assessments of step counts (pedometer-measured), blood pressure, A1C and anthropometric parameters. Due to missing data, the final analysis was conducted on 83 women and 102 men, with a mean age of 60 years. Associations of daily steps with blood pressure and A1C were evaluated using sex-specific multivariate linear regression models (adjusted for age, ethnicity, and BMI). Potential sex differences were confirmed in a combined model (women and men) with interaction terms. Mean values for daily steps, blood pressure, A1C and BMI were 5,357 steps/day; 137/80 mm Hg; 7.7% and 30.4 kg/m2 respectively. A 1,000 daily step increment among women was associated with a −2.6 (95% CI: −4.1 to −1.1) mm Hg change in systolic and a −1.4 (95% CI: −2.2 to −0.6) mm Hg change in diastolic blood pressure. Among men, corresponding changes were −0.7 (95% CI: −2.1 to 0.7) and −0.6 (95% CI: −1.4 to 0.3) mm Hg, respectively. Sex differences were confirmed in combined models. Step counts and A1C did not demonstrate clinically important associations.
Conclusions/Significance
A 1,000 steps/day increment is associated with important blood pressure decrements among women with type 2 diabetes but the data were inconclusive among men. Targeted “dose increments” of 1,000 steps/day in women may lead to measurable blood pressure reductions. This information may be of potential use in the titration or “dosing” of daily steps. No associations were found between step count increments and A1C.
doi:10.1371/journal.pone.0014086
PMCID: PMC2989914  PMID: 21124929
12.  Short-term mortality associated with failure to receive home care after hemiarthroplasty 
Background
Hemiarthroplasty is often the treatment of choice after hip fracture, particularly in frail elderly patients. Such patients may benefit from home care after discharge. We assessed factors associated with the receipt of home care and evaluated the risk of death within three months after discharge.
Methods
We obtained administrative data for patients 65 years or older in the province of Quebec who were discharged alive from hospital after hemiarthroplasty during the period 1997–2004. We evaluated destination after discharge and mortality within three months after discharge.
Results
Of 11 326 study patients, 5.6% were discharged home with home care, 29.9% home without home care, 2.0% to a rehabilitation centre, 24.2% to a nursing home and 38.3% to another hospital. Among patients who were discharged home, those who were older, had osteoarthritis, had an emergent admission and were admitted to a high-volume hospital were less likely to receive home care. Discharge with home care was most likely among patients admitted to teaching hospitals, those in hospital for more than seven days, those with atrial fibrillation and those with acute renal failure. Patients who received home care were at lower risk of death than those discharged home without care (hazard ratio 0.57, 95% confidence interval 0.39–0.85).
Interpretation
Less than 16% of the patients discharged home after hemiarthroplasty received home care. Those who received such care had a lower risk of death within three months after discharge.
doi:10.1503/cmaj.091209
PMCID: PMC2942914  PMID: 20713576
13.  Outcomes in a diabetic population of south Asians and whites following hospitalization for acute myocardial infarction: a retrospective cohort study 
Background
The aim of this study was to determine whether South Asian patients with diabetes have a worse prognosis following hospitalization for acute myocardial infarction (AMI) compared with their White counterparts. We measured the risk of developing a composite cardiovascular outcome of recurrent AMI, congestive heart failure (CHF) requiring hospitalization, or death, in these two groups.
Methods
Using hospital administrative data, we performed a retrospective cohort study of 41,615 patients with an incident AMI in British Columbia and the Calgary Health Region between April 1, 1995, and March 31, 2002. South Asian ethnicity was determined using validated surname analysis. Baseline demographic characteristics and co-morbidities were included in Cox proportional hazard models to compare time to reaching the composite outcome and its individual components.
Results
Among the AMI cohort, 29.7% of South Asian patients and 17.6% of White patients were identified as having diabetes (n = 7416). There was no significant difference in risk of developing the composite cardiovascular outcome (Hazard Ratio = 0.90, 95% CI = 0.80-1.01). However, South Asian patients had significantly lower mortality at long term follow-up (HR = 0.62, 95% CI = 0.51-0.74) compared to their White counterparts.
Conclusions
Following hospitalization for AMI, South Asian patients with diabetes do not have a significantly different long term risk of a composite cardiovascular outcome compared to White patients with diabetes. While previous research has suggested worse cardiovascular outcomes in the South Asian population, we found lower long-term mortality among South Asians with diabetes following AMI.
doi:10.1186/1475-2840-9-4
PMCID: PMC2816974  PMID: 20096107
14.  Pancytopenia and atrial fibrillation associated with chronic hepatitis C infection and presumed hepatocellular carcinoma: a case report 
Introduction
Pancytopenia secondary to hepatitis viral infection is a rare but noted clinical entity. An acute aplastic crisis usually occurs shortly after viral infection, however, viral serologies are usually negative and the pancytopenia is often fatal if left untreated.
Case presentation
A 66-year-old woman presented to the emergency department with shortness of breath and palpitations. She was found to have pulmonary edema secondary to a newly diagnosed atrial fibrillation and was treated with rate control and anticoagulation. She was found to have an anemia that was reported to be longstanding and that was apparently being investigated by a hematologist, although no diagnosis had yet been achieved. Her blood work also revealed a mild leucopenia and pronounced thrombocytopenia. The patient was admitted to ensure appropriate rate control of her atrial fibrillation and for work-up of her pancytopenia. Review of the bone marrow biopsy performed by the hematologist revealed a normal marrow with no infiltrative process. The results of the patient's blood tests ruled out a hemolytic process. There was also no evidence of infection, toxin ingestion, or recent medication that could be associated with pancytopenia. An abdominal ultrasound was ordered to rule out enlargement of the spleen and a possible consumptive coagulopathy. The spleen was mildly enlarged with a diameter of 13 cm. The liver, however, was mildly cirrhotic and a small solitary liver lesion was seen. A magnetic resonance imaging scan of the liver confirmed a single solitary solid mass and the α-fetal protein level in the serum was elevated. The patient's preliminary viral serologies were positive for hepatitis C. The patient was diagnosed with presumed hepatocellular carcinoma and referred to a hepatic surgeon for evaluation of treatment options.
Conclusion
Hepatitis associated aplastic anemia is an acute condition while milder more chronic presentations, such as this case, likely result from increased portal pressure generated from the resulting cirrhosis, which leads to a relative hypersplenism.
doi:10.1186/1752-1947-2-264
PMCID: PMC2518155  PMID: 18694489
15.  Postdischarge thromboprophylaxis and mortality risk after hip-or knee-replacement surgery 
Background
Patients undergoing hip or knee replacement are at high risk of developing a postoperative venous thromboembolism even after discharge from hospital. We sought to identify hospital and patient characteristics associated with receiving thromboprophylaxis after discharge and to compare the risk of short-term mortality among those who did or did not receive thromboprophylaxis.
Methods
We conducted a retrospective cohort study using system-wide hospital discharge summary records, physician billing information, medication reimbursement claims and demographic records. We included patients aged 65 years and older who received a hip or knee replace ment and who were discharged home after surgery.
Results
In total we included 10 744 patients. Of these, 7058 patients who received a hip replacement and 3686 who received a knee replacement. The mean age was 75.4 (standard deviation [SD] 6.8) years and 38% of patients were men. In total, 2059 (19%) patients received thomboprophylaxis at discharge. Patients discharged from university teaching hospitals were less likely than those discharged from community hospitals to received thromboprophylaxis after discharge (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.80–1.00). Patients were less likely to receive thromboprophylaxis after discharge if they had a longer hospital stay (15–30 days v. 1–7 days, OR 0.69, 95% CI 0.59–0.81). Patients were more likely to receive thromboprophylaxis if they had hip (v. knee) replacement, osteoarthritis, heart failure, atrial fibrillation or hypertension, higher (v. lower) income or if they were treated at medium-volume hospitals (69–116 hip and knee replacements per year). In total, 223 patients (2%) died in the 3-month period after discharge. The risk of short-term mortality was lower among those who received thromboprophylaxis after discharge (hazard ratio [HR] 0.34, 95% CI 0.20–0.57).
Interpretation
Fewer than 1 in 5 elderly patients discharged home after a hip-or knee-replacement surgery received postdischarge thromboprophylaxis. Those prescribed these medications had a lower risk of short-term mortality. The benefits of and barriers to thromboprophylaxis therapy after discharge in this population requires further study.
doi:10.1503/cmaj.071388
PMCID: PMC2396368  PMID: 18519902
16.  A comprehensive view of sex-specific issues related to cardiovascular disease 
Cardiovascular disease (CVD) is the leading cause of mortality in women. In fact, CVD is responsible for a third of all deaths of women worldwide and half of all deaths of women over 50 years of age in developing countries. The prevalence of CVD risk factor precursors is increasing in children. Retrospective analyses suggest that there are some clinically relevant differences between women and men in terms of prevalence, presentation, management and outcomes of the disease, but little is known about why CVD affects women and men differently. For instance, women with diabetes have a significantly higher CVD mortality rate than men with diabetes. Similarly, women with atrial fibrillation are at greater risk of stroke than men with atrial fibrillation. Historically, women have been underrepresented in clinical trials. The lack of good trial evidence concerning sex-specific outcomes has led to assumptions about CVD treatment in women, which in turn may have resulted in inadequate diagnoses and suboptimal management, greatly affecting outcomes. This knowledge gap may also explain why cardiovascular health in women is not improving as fast as that of men. Over the last decades, mortality rates in men have steadily declined, while those in women remained stable. It is also becoming increasingly evident that gender differences in cultural, behavioural, psychosocial and socioeconomic status are responsible, to various degrees, for the observed differences between women and men. However, the interaction between sex-and gender-related factors and CVD outcomes in women remains largely unknown.
doi:10.1503/cmaj.051455
PMCID: PMC1817670  PMID: 17353516
17.  Walking behaviour and glycemic control in type 2 diabetes: seasonal and gender differences-Study design and methods 
Background
The high glucose levels typically occurring among adults with type 2 diabetes contribute to blood vessel injury and complications such as blindness, kidney failure, heart disease, and stroke. Higher physical activity levels are associated with improved glycemic control, as measured by hemoglobin A1C. A 1% absolute increase in A1C is associated with an 18% increased risk for heart disease or stroke. Among Canadians with type 2 diabetes, we postulate that declines in walking associated with colder temperatures and inclement weather may contribute to annual post-winter increases in A1C levels.
Methods
During this prospective cohort study being conducted in Montreal, Quebec, Canada, 100 men and 100 women with type 2 diabetes will undergo four assessments (once per season) over a one-year period of observation. These assessments include (1) use of a pedometer with a concealed viewing window for a two-week period to measure walking (2) a study centre visit during which venous blood is sampled for A1C, anthropometrics are assessed, and questionnaires are completed for measurement of other factors that may influence walking and/or A1C (e.g. food frequency, depressive symptomology, medications). The relationship between spring-fall A1C difference and winter-summer difference in steps/day will be examined through multivariate linear regression models adjusted for possible confounding. Interpretation of findings by researchers in conjunction with potential knowledge "users" (e.g. health professionals, patient groups) will guide knowledge translation efforts.
Discussion
Although we cannot alter weather patterns to favour active lifestyles, we can design treatment strategies that take seasonal and weather-related variations into account. For example, demonstration of seasonal variation of A1C levels among Canadian men and women with T2D and greater understanding of its determinants could lead to (1) targeting physical activity levels to remain at or exceed peak values achieved during more favourable weather conditions. Strategies may include shifting to indoor activities or adapting to less favourable conditions (e.g. appropriate outdoor garments, more frequent but shorter duration periods of activity) (2) increasing dose/number of glucose-lowering medications during the winter and reducing these during the summer, in anticipation of seasonal variations (3) examining the impact of bright light therapy on activity and A1C among T2D patients with an increase in depressive symptomology when sunlight hours decline.
doi:10.1186/1475-2840-6-1
PMCID: PMC1783642  PMID: 17224062
18.  Association between frequent use of nonsteroidal anti-inflammatory drugs and breast cancer 
BMC Cancer  2005;5:159.
Background
Eighty percent of all breast cancers and almost 90% of breast cancer deaths occur among post-menopausal women. We used a nested case control design to examine the association between nonsteroidal anti-inflammatory drug (NSAID) use and breast cancer occurrence among women over 65 years of age. The cyclooxygenase (COX)-2 enzyme is expressed more in breast cancers than in normal breast tissue. COX-2 inhibition may have a role in breast cancer prevention.
Methods
In the Canadian province of Quebec, physician services are covered through a governmental insurance plan. Medication costs are covered for those ≥ 65 years of age and a publicly funded screening program for breast cancer targets all women 50 years of age or older. We obtained encrypted data from these insurance databases on all women ≥ 65 years of age who filled a prescription for COX-2 inhibitors, non-selective NSAIDs (ns-NSAIDs), aspirin, or acetaminophen between January 1998 and December 2002. Cases were defined as those women who have undergone mammography between April 2001 and June 2002 and had a diagnosis of breast cancer within six months following mammography. Controls included those who have undergone mammography between April 2001 and June 2002 without a diagnosis of any cancer during the six months following mammography. The exposure of interest, frequent NSAID use, was defined as use of ns-NSAIDs and/or COX-2 inhibitors for ≥ 90 days during the year prior to mammography. Frequent use served as a convenient proxy for long term chronic use.
Results
We identified 1,090 cases and 44,990 controls. Cases were older and more likely to have breast cancer risk factors. Logistic regression models adjusting for potential confounders showed that frequent use of ns-NSAIDs and/or COX-2 inhibitors was associated with a lower risk of breast cancer (OR: 0.75, 95% confidence interval 0.64–0.89). Results were similar for COX-2 inhibitors (0.81, 0.68–0.97) and ns-NSAIDs (0.65, 0.43–0.99), when assessed separately. Frequent use of aspirin at doses > 100 mg/day in the year prior to mammography was also associated with a lower risk of breast cancer (0.75, 0.64–0.89). However, use of aspirin at doses ≤ 100 mg/day did not have any association with breast cancer (0.91, 0.71–1.16).
Conclusion
Women who use NSAIDs or doses of aspirin > 100 mg frequently may have a lower risk of breast cancer.
doi:10.1186/1471-2407-5-159
PMCID: PMC1334211  PMID: 16343343

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