Sonia Jean

Effects of combined calcium and vitamin D supplementation on insulin secretion, insulin sensitivity and β-cell function in multi-ethnic vitamin D-deficient adults at risk for type 2 diabetes: a pilot randomized, placebo-controlled trial.

Objectives To examine whether combined vitamin D and calcium supplementation improves insulin sensitivity, insulin secretion, β-cell function, inflammation and metabolic markers. Design 6-month randomized, placebo-controlled trial. Participants Ninety-five adults with serum 25-hydroxyvitamin D [25(OH)D] ≤55 nmol/L at risk of type 2 diabetes (with prediabetes or an AUSDRISK score ≥15) were randomized. Analyses included participants who completed the baseline and final visits (treatment n = 35; placebo n = 45). Intervention Daily calcium carbonate (1,200 mg) and cholecalciferol [2,000–6,000 IU to target 25(OH)D >75 nmol/L] or matching placebos for 6 months. Measurements Insulin sensitivity (HOMA2%S, Matsuda index), insulin secretion (insulinogenic index, area under the curve (AUC) for C-peptide) and β-cell function (Matsuda index x AUC for C-peptide) derived from a 75 g 2-h OGTT; anthropometry; blood pressure; lipid profile; hs-CRP; TNF-α; IL-6; adiponectin; total and undercarboxylated osteocalcin. Results Participants were middle-aged adults (mean age 54 years; 69% Europid) at risk of type 2 diabetes (48% with prediabetes). Compliance was >80% for calcium and vitamin D. Mean serum 25(OH)D concentration increased from 48 to 95 nmol/L in the treatment group (91% achieved >75 nmol/L), but remained unchanged in controls. There were no significant changes in insulin sensitivity, insulin secretion and β-cell function, or in inflammatory and metabolic markers between or within the groups, before or after adjustment for potential confounders including waist circumference and season of recruitment. In a post hoc analysis restricted to participants with prediabetes, a significant beneficial effect of vitamin D and calcium supplementation on insulin sensitivity (HOMA%S and Matsuda) was observed. Conclusions Daily vitamin D and calcium supplementation for 6 months may not change OGTT-derived measures of insulin sensitivity, insulin secretion and β-cell function in multi-ethnic adults with low vitamin D status at risk of type 2 diabetes. However, in participants with prediabetes, supplementation with vitamin D and calcium may improve insulin sensitivity. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12609000043235

Change in fracture risk and fracture pattern after bariatric surgery: nested case-control study

Objective To investigate whether bariatric surgery increases the risk of fracture. Design Retrospective nested case-control study. Setting Patients who underwent bariatric surgery in the province of Quebec, Canada, between 2001 and 2014, selected using healthcare administrative databases. Participants 12 676 patients who underwent bariatric surgery, age and sex matched with 38 028 obese and 126 760 non-obese controls. Main outcome measures Incidence and sites of fracture in patients who had undergone bariatric surgery compared with obese and non-obese controls. Fracture risk was also compared before and after surgery (index date) within each group and by type of surgery from 2006 to 2014. Multivariate conditional Poisson regression models were adjusted for fracture history, number of comorbidities, sociomaterial deprivation, and area of residence. Results Before surgery, patients undergoing bariatric surgery (9169 (72.3%) women; mean age 42 (SD 11) years) were more likely to fracture (1326; 10.5%) than were obese (3065; 8.1%) or non-obese (8329; 6.6%) controls. A mean of 4.4 years after surgery, bariatric patients were more susceptible to fracture (514; 4.1%) than were obese (1013; 2.7%) and non-obese (3008; 2.4%) controls. Postoperative adjusted fracture risk was higher in the bariatric group than in the obese (relative risk 1.38, 95% confidence interval 1.23 to 1.55) and non-obese (1.44, 1.29 to 1.59) groups. Before surgery, the risk of distal lower limb fracture was higher, upper limb fracture risk was lower, and risk of clinical spine, hip, femur, or pelvic fractures was similar in the bariatric and obese groups compared with the non-obese group. After surgery, risk of distal lower limb fracture decreased (relative risk 0.66, 0.56 to 0.78), whereas risk of upper limb (1.64, 1.40 to 1.93), clinical spine (1.78, 1.08 to 2.93), pelvic, hip, or femur (2.52, 1.78 to 3.59) fractures increased. The increase in risk of fracture reached significance only for biliopancreatic diversion. Conclusions Patients undergoing bariatric surgery were more likely to have fractures than were obese or non-obese controls, and this risk remained higher after surgery. Fracture risk was site specific, changing from a pattern associated with obesity to a pattern typical of osteoporosis after surgery. Only biliopancreatic diversion was clearly associated with fracture risk; however, results for Roux-en-Y gastric bypass and sleeve gastrectomy remain inconclusive. Fracture risk assessment and management should be part of bariatric care.

Trends in hip fracture rates in Canada: An age‐period‐cohort analysis

Age‐standardized rates of hip fracture in Canada declined during the period 1985 to 2005. We investigated whether this incidence pattern is explained by period effects, cohort effects, or both. All hospitalizations during the study period with primary diagnosis of hip fracture were identified. Age‐ and sex‐specific hip fracture rates were calculated for nineteen 5‐year age groups and four 5‐year calendar periods, resulting in 20 birth cohorts. The effect of age, calendar period, and birth cohort on hip fracture rates was assessed using age‐period‐cohort models as proposed by Clayton and Schiffers. From 1985 to 2005, a total of 570,872 hospitalizations for hip fracture were identified. Age‐standardized rates for hip fracture have progressively declined for females and males. The annual linear decrease in rates per 5‐year period were 12% for females and 7% for males (both p < 0.0001). Significant birth cohort effects were also observed for both sexes (p < 0.0001). Cohorts born before 1950 had a higher risk of hip fracture, whereas those born after 1954 had a lower risk. After adjusting for age and constant annual linear change (drift term common to both period and cohort effects), we observed a significant nonlinear birth cohort effect for males (p = 0.0126) but not for females (p = 0.9960). In contrast, the nonlinear period effect, after adjustment for age and drift term, was significant for females (p = 0.0373) but not for males (p = 0.2515). For males, we observed no additional nonlinear period effect after adjusting for age and birth cohort, whereas for females, we observed no additional nonlinear birth cohort effect after adjusting for age and period. Although hip fracture rates decreased in both sexes, different factors may explain these changes. In addition to the constant annual linear decrease, nonlinear birth cohort effects were identified for males, and calendar period effects were identified for females as possible explanations.

The validity of administrative data to identify hip fractures is high—a systematic review

OBJECTIVE To determine the validity of the diagnostic algorithms for osteoporosis and fractures in administrative data. STUDY DESIGN AND SETTING A systematic search was conducted to identify studies that reported the validity of a diagnostic algorithm for osteoporosis and/or fractures using administrative data. RESULTS Twelve studies were reviewed. The validity of the diagnosis of osteoporosis in administrative data was fair when at least 3 years of data from hospital and physician visit claims were used (area under the receiver operating characteristic [ROC] curve [AUC]=0.70) or when pharmacy data were used (with or without the use of hospital and physician visit claims data, AUC>0.70). Nonetheless, the positive predictive values (PPVs) were low (<0.60). There was good evidence to support the use of hospital data to identify hip fractures (sensitivity: 69-97%; PPV: 63-96%) and the addition of physician claims diagnostic and procedural codes to hospitalization diagnostic codes improved these characteristics (sensitivity: 83-97%; PPV: 86-98%). Vertebral fractures were difficult to identify using administrative data. There was some evidence to support the use of administrative data to define other fractures that do not require hospitalization. CONCLUSIONS Administrative data can be used to identify hip fractures. Existing diagnostic algorithms to identify osteoporosis and vertebral fractures in administrative data are suboptimal.

Incidence and Characteristics of Atypical Femoral Fractures: Clinical and Geometrical Data

Despite the multitude of studies published on atypical femoral fractures (AFFs), a profile for patients at risk does not exist. This study aimed first at estimating AFF incidence over a 19‐month‐period in Quebec City using the ASBMR Task force criteria to define AFF. The medical records of patients hospitalized for hip or femoral fracture between June 1, 2009, and December 31, 2010, were reviewed. Thirty‐six cases of atypical fractures were identified during the 19‐month period, representing an AFF incidence of 7.0 (range, 4.7 to 9.3) cases per 100,000 person‐years. In the second part of the study, data regarding the characteristics suspected of increasing the risks of AFF were collected from medical and pharmacological records, proximal femur radiographs, and patient interviews. The data regarding each patient with an AFF during years 2008‐2011 were compared to two controls with a hip or femoral fragility fracture or a traumatic fracture, paired for age and sex. Twenty patients with AFF were added to the 36 patients with AFF selected in the first part, thereby 56 patients with AFF were investigated. The association between the occurrence of AFF and bisphosphonates (BPs) use was proven statistically significant in multivariate analysis, odds ratio (OR) = 10.39 (95% CI, 2.22 to 48.58; p = 0.0029). Compared to controls, patients with AFF had excessive femoral offset (43.1 mm versus 38.3 mm, p = 0.0007), proximal femoral neck angle in varus (128.9 degrees versus 134.0 degrees, p < 0.0001), and had greater proximal cortical thickness. This retrospective study confirms the low incidence of AFF, confirms its significant association with exposure to BPs, and reveals the possible contribution of proximal femoral geometry in AFF occurrence.

An economic evaluation: Simulation of the cost-effectiveness and cost-utility of universal prevention strategies against osteoporosis-related fractures

A patient‐level Markov decision model was used to simulate a virtual cohort of 500,000 women 40 years old and over, in relation to osteoporosis‐related hip, clinical vertebral, and wrist bone fractures events. Sixteen different screening options of three main scenario groups were compared: (1) the status quo (no specific national prevention program); (2) a universal primary prevention program; and (3) a universal screening and treatment program based on the 10‐year absolute risk of fracture. The outcomes measured were total directs costs from the perspective of the public health care system, number of fractures, and quality‐adjusted life‐years (QALYs). Results show that an option consisting of a program promoting physical activity and treatment if a fracture occurs is the most cost‐effective (CE) (cost/fracture averted) alternative and also the only cost saving one, especially for women 40 to 64 years old. In women who are 65 years and over, bone mineral density (BMD)‐based screening and treatment based on the 10‐year absolute fracture risk calculated using a Canadian Association of Radiologists and Osteoporosis Canada (CAROC) tool is the best next alternative. In terms of cost‐utility (CU), results were similar. For women less than 65 years old, a program promoting physical activity emerged as cost‐saving but BMD‐based screening with pharmacological treatment also emerged as an interesting alternative. In conclusion, a program promoting physical activity is the most CE and CU option for women 40 to 64 years old. BMD screening and pharmacological treatment might be considered a reasonable alternative for women 65 years old and over because at a healthcare capacity of

Effect of ABT‐627 (A‐147627), a potent selective ETA receptor antagonist, on the cardiopulmonary profile of newborn lambs with surgically‐induced diaphragmatic hernia

50,000 Canadian dollars (

Access to a Canadian provincial integrated trauma system: A population-based cohort study

CAD) for each additional fracture averted or for one QALY gained its probabilities of cost‐effectiveness compared to the program promoting physical activity are 63% and 75%, respectively, which could be considered socially acceptable. Consideration of the indirect costs could change these findings.

Direct medical resource utilization associated with osteoporosis‐related nonvertebral fractures in postmenopausal women

Postnatal mortality in isolated congenital diaphragmatic hernia (CDH) is mainly related to the associated pulmonary hypertension (PH) and to right‐to‐left shunting. Endothelins (ETs) are potent vasoconstrictors and pro‐mitogenic peptides. Strong evidences support their participation in CDH and in the etiology of PH via the activation of ETA receptors (ETA‐Rs). Evaluation of the effect of ABT‐627, a selective non‐peptidic ETA‐R antagonist, given from −15 to 210 min post‐delivery (1 mg kg−1 bolus +0.01 mg kg−1 h−1 infusion, i.v.), was conducted in the lamb model of CDH. Severity of CDH was assessed in comparison to untreated controls (n=5). Untreated CDH lambs (n=7) had a higher mean pulmonary arterial pressure (MPAP; P<0.0001), lower mean blood pressure (MBP; P=0.0004), higher MPAP / MBP ratio (P<0.0001), lower arterial pH (P<0.0001), higher paCO2 (P<0.0001), lower paO2 (P<0.0001) and lower post‐ductal pulsatile SaO2 (P<0.0001) than untreated controls. Treated controls (n=7) showed a higher MPAP, lower MBP, higher MPAP/MBP ratio, lower arterial pH, higher paCO2, lower paO2, lower post‐ductal pulsatile SaO2 and lower plasmatic ir‐ET ratios compared to untreated controls (P<0.0001). Treated CDH lambs (n=8) showed a higher MBP (P<0.0001), lower MPAP / MBP ratio (P<0.0001), higher arterial pH (P<0.0001), lower paCO2 (P<0.0001), higher paO2 (P=0.0228), higher post‐ductal pulsatile SaO2 (P=0.0016) and lower plasmatic ir‐ET ratios (P=0.0247) when compared to untreated CDH lambs. These observations revealed that, although acute perinatal treatment with a selective non‐peptidic ETA‐R antagonist had some adverse effects in controls, it attenuated the progressive cardiopulmonary deterioration that occurred after birth in CDH lambs.

Partnership for fragility bone fracture care provision and prevention program (P4Bones): study protocol for a secondary fracture prevention pragmatic controlled trial

BACKGROUND Access to specialised trauma care is an important measure of trauma system efficiency. However, few data are available on access to integrated trauma systems. We aimed to describe access to trauma centres (TCs) in an integrated Canadian trauma system and identify its determinants. METHODS We conducted a population-based cohort study including all injured adults admitted to acute care hospitals in the province of Québec between 2006 and 2011. Proportions of injured patients transported directly or transferred to TCs were assessed. Determinants of access were identified through a modified Poisson regression model and a relative importance analysis was used to determine the contribution of each independent variable to predicting access. RESULTS Of the 135,653 injury admissions selected, 75% were treated within the trauma system. Among 25,522 patients with major injuries [International Classification of diseases Injury Severity Score (ICISS<0.85)], 90% had access to TCs. Access was higher for patients aged under 65, men and among patients living in more remote areas (p-value <0.001). The region of residence followed by injury mechanism, number of trauma diagnoses, injury severity and age were the most important determinants of access to trauma care. CONCLUSIONS In an integrated, mature trauma system, we observed high access to TCs. However, problems in access were observed for the elderly, women and in urban areas where there are many non-designated hospitals. Access to trauma care should be monitored as part of quality of care improvement activities and pre-hospital guidelines for trauma patients should be applied uniformly throughout the province.