New opioid prescription claims and their clinical indications: results from health administrative data in Quebec, Canada, over 14 years.

OBJECTIVES: Describe new opioid prescription claims, their clinical indications and annual trends among opioid naïve adults covered by the Quebec's public drug insurance plan (QPDIP) for the fiscal years 2006/2007-2019/2020. DESIGN AND SETTING: A retrospective observational study was conducted using data collected between 2006/2007 and 2019/2020 within the Quebec Integrated Chronic Disease Surveillance System, a linkage administrative data. PARTICIPANTS: A cohort of opioid naïve adults and new opioid users was created for each study year (median number=2 263 380 and 168 183, respectively, over study period). INTERVENTION: No. MAIN OUTCOME MEASURE AND ANALYSES: A new opioid prescription was defined as the first opioid prescription claimed by an opioid naïve adult during a given fiscal year. The annual incidence proportion for each year was then calculated and standardised for age. A hierarchical algorithm was built to identify the most likely clinical indication for this prescription. Descriptive and trend analyses were performed. RESULTS: There was a 1.7% decrease of age-standardised annual incidence proportion during the study period, from 7.5% in 2006/2007 to 5.8% in 2019/2020. The decrease was highest after 2016/2017, reaching 5.5% annual percentage change. Median daily dose and days' supply decreased from 27 to 25 morphine milligram equivalent/day and from 5 to 4 days between 2006/2007 and 2019/2020, respectively. Between 2006/2007 and 2019/2020, these prescriptions' most likely clinical indications increased for cancer pain from 34% to 48%, for surgical pain from 31% to 36% and for dental pain from 9% to 11%. Inversely, the musculoskeletal pain decreased from 13% to 2%. There was good consistency between the clinical indications identified by the algorithm and prescriber's specialty or user's characteristics. CONCLUSIONS: New opioid prescription claims (incidence, dose and days' supply) decreased slightly over the last 14 years among QPDIP enrollees, especially after 2016/2017. Non-surgical and non-cancer pain became less common as their clinical indication.

Prevalence and incidence of Paget's disease of bone: Temporal trend over 20 years in the province of Quebec, Canada.

BACKGROUND: Paget's disease of bone (PDB) is a focal bone disorder characterized by an increased bone remodeling and an anarchic bone structure. A decline of prevalence and incidence of PDB has been observed in some countries. No epidemiological data are available on PDB in Canada. AIMS: We aimed at examining the evolution of the prevalence and incidence of PDB in Quebec (Canada) by analyzing health administrative databases. METHODS: PDB case definition relied on one or more hospitalizations, or one or more physician-billing claims with a diagnosis code of PDB. To identify incident cases, a 'run-in' period of four years (1996-1999) was used to exclude prevalent cases. For each fiscal year from 2000 to 2001 to 2019-2020 (population size 2,914,480), crude age and sex-specific prevalence and incidence rates of PDB among individuals aged ≥55 years were determined, and sex-specific rates were also standardized to the 2011 age structure of the Quebec population. Generalized linear regressions were used to test for linear changes in standardized prevalence and incidence rates. RESULTS: Over the study period, standardized prevalence of PDB has remained stable in Quebec, from 0.44 % in 2000/2001 to 0.43 % in 2019/2020 (mean change -0.002, p-value = 0.0935). For the 2019-2020 fiscal year, 13,165 men and women had been diagnosed with PDB and prevalence of PDB increased with age. Standardized incidence of PDB has decreased over time from 0.77/1000 in 2000/2001 to 0.28/1000 in 2019-2020 (mean change -0.228/year, p-value<0.0001), the incidence decreasing from 0.82/1000 to 0.37/1000 in men and from 0.76/1000 to 0.22/1000 in women, respectively. This decrease was observed in all age categories. CONCLUSION: With the exception of a slight increase in PDB prevalence up to 0.55 % in years 2005 to 2007, the prevalence of PDB has remained stable in Quebec over the past 20 years, 13,160 men and women being currently diagnosed with PDB. The incidence has decreased over time. Our results support the epidemiological changes of PDB reported in other countries.

Added value of waist circumference to body mass index for predicting fracture risk in obesity: a prospective study from the CARTaGENE cohort.

Larger waist circumference is significantly associated with an increased risk of distal lower limb fractures in individuals aged 40-70 years with a body mass index within the normal or overweight category. Therefore, waist circumference provides additive information to body mass index for the identification of individuals at risk of obesity-related fractures. INTRODUCTION: Waist circumference (WC) is a stronger risk factor of metabolic disorders than body mass index (BMI), but whether it holds true for fracture risk prediction remains unclear. We aimed to evaluate relationships between WC and fracture incidence within BMI categories and evaluate whether BMI modifies these relationships. METHODS: Men and women aged 40-70 years from the CARTaGENE cohort were divided by BMI category at baseline: normal weight, overweight, and obesity. Incident fractures were identified over 7 years via linkage with healthcare administrative databases. Cox proportional hazard models estimated the relationships between WC and incident fractures at any site and by skeletal site within each BMI category. Results are reported as adjusted hazard ratios (95% confidence intervals) per 10 cm increase in WC. Effect modification was evaluated qualitatively by comparing relationships between BMI categories. RESULTS: Of the 18 236 individuals included, 754 sustained a fracture. Significant relationships were found between WC and distal lower limb fractures in the normal (1.25 [1.08, 1.45]) and overweight (1.28 [1.07, 1.52]) BMI categories, but not in the obesity category. In the overweight category, we found an increased risk of distal upper limb fractures with increasing WC (1.49 [1.04, 2.15]). No significant relationship was observed regarding WC and fracture risk at any site or major osteoporotic fractures. An effect modification of BMI on the relationships between WC and distal lower limb fractures was observed. CONCLUSION: WC provides both independent and additive information to BMI for the identification of individuals at risk of obesity-related fractures.

Impact of chronic comorbidities on hospitalization, intensive care unit admission and death among adult vaccinated and unvaccinated COVID-19 confirmed cases during the Omicron wave.

Background: Comorbidities are important risk factors of severe COVID-19 complications. Their impact during the Omicron wave among vaccinated and unvaccinated COVID-19 cases is not well documented. Purpose: The objective of this study was to estimate the association between the number of comorbidities and the risk of hospitalization, intensive care unit (ICU) admission, and death among vaccinated and unvaccinated confirmed adult COVID-19 cases during the Omicron wave. Research Design and Study sample: We performed a cohort study of COVID-19 adult cases of primo-infection occurring during the Omicron wave, from December 5, 2021 to January 9, 2022 using surveillance database of the province of Québec, Canada. The database included all laboratory-confirmed cases in the province and the related information on 21 pre-existing comorbidities, hospitalization, ICU admission, death related to COVID-19 and vaccination status. Analysis: We performed a robust Poisson regression model to estimate the impact of the number of comorbidities on each complication by vaccination status adjusted for age, sex, socioeconomic status, and living environment. Results: We observed that the risk of complication increased for each additional comorbidity in both vaccinated and unvaccinated individuals and that this risk was systematically higher among unvaccinated individuals. Compared with vaccinated individuals without comorbidities (reference group), the risks of hospitalization, ICU admission, and death were respectively: 9X (95% CI [7.77-12.01]), 13X (95% CI [8.74-18.87]), and 12X (95% CI [7.57-18.91]) higher in vaccinated individuals with ≥3 comorbidities; 22X (95% CI [19.07-25.95]), 45X (95% CI [29.06-69.67]) and 38X (95% CI [23.62-61.14]) higher in unvaccinated individuals with ≥3 comorbidities. Conclusion: Our results support the importance of promoting vaccination in all individuals, and especially those with pre-existing medical conditions, to reduce severe complications, even during the Omicron wave.

Relationships between Obesity and Incidence of Fractures in a Middle-Aged Population: A Study from the CARTaGENE Cohort.

The association between obesity and fracture risk is complex and may vary by definition of obesity, skeletal site, and sex. We aimed to evaluate the relationships between obesity, defined using body mass index (BMI) or waist circumference (WC), and fracture incidence at any site and by skeletal site (i.e., major osteoporotic fractures [MOFs], distal lower limb fractures [tibia, ankle, feet], and distal upper limb fractures [forearm/elbow, wrist]). The secondary aim was to assess the aforementioned relationships by sex. We used CARTaGENE, a large population-based cohort of individuals aged 40-70 years from Quebec, Canada, who were assessed in 2009-2010. Incident fractures were identified via linkage with healthcare administrative databases over a 7-year period. Cox proportional hazard models adjusted for several potential confounders were used to estimate the relationships, with exposures treated as continuous variables. Results are reported as adjusted hazard ratios (aHRs) and 95% confidence intervals. We identified 19 357 individuals (mean ± standard deviation: age 54 ± 8 years, BMI 27 ± 5 kg/m2, WC 94 ± 14 cm; 51.6% women). During follow-up, 497 women and 323 men sustained a fracture. There was a linear relationship between fracture incidence and WC, while cubic splines best fitted the relationship for BMI. Greater WC was associated with an increased risk of fracture at the distal lower limbs in the whole cohort and in the subgroup of women: aHR for each 10 cm increased in WC of 1.12 (1.03, 1.21) and 1.12 (1.01, 1.24), respectively. In men, WC was not significantly associated with any fracture outcome. Higher BMI was also significantly associated with distal lower limb fracture risk in the whole cohort (p = 0.018). No significant relationships were found between either WC or BMI and the risk of any fracture, MOFs, and distal upper limb fractures. In middle-aged individuals, obesity, and mainly abdominal obesity, was associated with distal lower limb fracture risk. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Chronic diseases and variations in rates of antimicrobial use in the community: a population-based analysis of linked administrative data in Quebec, Canada, 2002-2017.

BACKGROUND: Chronic diseases may increase risk of infection and complications from infections; fear of these risks may lower clinicians' tolerance threshold for the prescription of antimicrobials, thus increasing the risk of selecting resistant bacteria. We sought to describe rates of antimicrobial use in Quebec and measure the association between chronic diseases and utilization rates. METHODS: Using the Quebec Integrated Chronic Disease Surveillance System, we analyzed data of people covered by the public drug insurance plan in 2002-2017. Based on delivered prescriptions, we described trends in antimicrobial use in the population, and per category of select chronic diseases (i.e., none, respiratory, cardiovascular, diabetes, mental disorder), according to age group (0-17 yr, 18-64 yr and ≥ 65 yr). We computed ratios of extended-to-narrow-spectrum antimicrobials in 2014-2017. We used robust Poisson regression to quantify the association between chronic diseases and rates of antimicrobial use among children and adults (≥ 18 yr). RESULTS: Between 2002 and 2017, 4 231 724 prescriptions were received over 6 653 473 individual-years among children; 1 367 492 (20.6%) individual-years had at least 1 chronic disease. Among adults aged 18-64 years, 13 365 577 prescriptions were received over 24 935 592 individual-years; 9 533 493 (38.2%) individual-years had at least 1 chronic disease. Among adults 65 years or older, 11 689 365 prescriptions were received over 15 927 342 individual-years; 12 743 588 (80.0%) individual-years had least 1 chronic disease. Antimicrobial use decreased among children, remained stable among younger adults and increased among older adults. Trends were consistent across chronic disease categories in children and older adults. In 2014-2017, 19.9% of children, 39.1% of younger adults and 79.7% of older adults had at least 1 chronic disease. Claims for extended-spectrum antimicrobials were frequent in all age and chronic disease groups, relative to narrow-spectrum antimicrobials (ratios from 3.1:1 to 14.6:1). Antimicrobial use was higher among people with respiratory diseases (adults: relative rate [RR] 2.09, 95% confidence interval [CI] 2.07-2.10; children: RR 1.62, 95% CI 1.59-1.65), mental health diagnoses (adults: RR 1.48, 95% CI 1.46-1.49; children: RR 1.22, 95% 1.20-1.24), diabetes (adults: RR 1.40, 95% CI 1.28-1.41; children: RR 2.02, 95% CI 1.58-2.57) and cardiovascular diseases (adults: RR 1.31, 95% CI 1.30-1.32), compared with those with none of the studied chronic diseases. INTERPRETATION: During the study period, large proportions of antimicrobial prescriptions were for people with chronic diseases, across the age spectrum. Interventions to reduce antimicrobial use should be tailored for these populations.

Chronic diseases and compliance with provincial guidelines for outpatient antibiotic prescription in cases of otitis media and respiratory infections: a population-based study of linked data in Quebec, Canada, 2010-2017.

BACKGROUND: In Quebec, antibiotic use is higher among outpatients with chronic diseases. We sought to measure compliance with provincial guidelines for the treatment of otitis media and common respiratory infections, and to measure variations in compliance according to the presence of certain chronic diseases. METHODS: We conducted a population-based study of linked data on antibiotic dispensing covered by the public drug insurance plan between April 2010 and March 2017. We included patients who had consulted a primary care physician within 2 days before being dispensed an antibiotic for an infection targeted by provincial guidelines, including bronchitis in patients with chronic obstructive pulmonary disease, otitis media, pharyngitis, pneumonia and sinusitis. We computed proportions of prescriptions compliant with guidelines (use of recommended antibiotic for children, and use of recommended antibiotic and dosage for adults) by age group (children or adults) and chronic disease (respiratory, cardiovascular, diabetes, mental disorder or none). We measured the impact of chronic diseases on compliance using robust Poisson regression. RESULTS: We analyzed between 14 677 and 198 902 prescriptions for each infection under study. Compliance was greater than 87% among children, but was lower among children with asthma (proportion ratios between 0.97 and 1.00). In adults, the chosen antibiotic was compliant for at least 73% of prescriptions, except for pharyngitis (≤ 61%). Accounting for dosage lowered compliance to between 31% and 61%. Compliance was lower in the presence of chronic diseases (proportion ratios between 0.94 and 0.98). INTERPRETATION: It is possible that prescribing noncompliant prescriptions was sometimes appropriate, but the high frequency of noncompliance suggests room for improvement. Given that variations associated with chronic diseases were small, disease-specific guidelines for antibiotic prescriptions are likely to have a limited impact on compliance.

Temporal trends of aortic stenosis and comorbid chronic kidney disease in the province of Quebec, Canada.

OBJECTIVE: To investigate temporal trends of chronic kidney disease (CKD) among patients with incident aortic stenosis (AS) and to compare these trends with that of a matched control population. METHODS: Using the Quebec Integrated Chronic Disease Surveillance System, we performed a population-based nested case-control study including 108 780 patients newly hospitalised with AS and 543 900 age-matched, sex-matched and fiscal year-matched patients without AS from 2000 to 2016 in Quebec (Canada). Three subgroups were considered. Dialysis subgroup had at least two outpatient billing codes of dialysis. The predialysis subgroup had at least one hospital or two billing diagnostic codes of CKD. The remaining individuals were included in the non-CKD subgroup. We estimated overall and sex-specific standardised annual proportions of CKD subgroups through direct standardisation using the 2016-2017 age structure of the incident AS cohort. The trends overtime were estimated through fitting robust Poisson regression models. Age-specific distribution of AS and control population were assessed for each subgroup. RESULTS: From 2000 to 2016, age-standardised proportions of patients with AS with dialysis and predialysis increased by 41% (99% CI 12.0% to 78.1%) and by 45% (99% CI 39.1% to 51.6%), respectively. Inversely, age-standardised proportions of dialysis and pre-dialysis among non-AS patients decreased by 63% (99% CI 55.8% to 68.7%) and by 32% (99% CI 29.9% to 34.6%), respectively, during the same study period. In patients with and without AS, age-standardised annual proportions of males in predialysis were significantly higher than females in most of the study period. Patients with AS on dialysis and predialysis were younger than their respective controls (dialysis: 29.6% vs 45.1% had ≥80 years, predialysis: 60.8% vs 72.7% had ≥80 years). CONCLUSIONS: Over time, the proportion of patients with CKD increased significantly and remained consistently higher in incident AS individuals compared with controls. Our results highlight the need to investigate whether interventions targeting CKD risk factors may influence AS incidence in the future.

Long-term exposure to fine particulate matter and ozone and the onset of systemic autoimmune rheumatic diseases: an open cohort study in Quebec, Canada.

OBJECTIVES: To estimate associations between fine particulate matter (PM2.5) and ozone and the onset of systemic autoimmune rheumatic diseases (SARDs). METHODS: An open cohort of over 6 million adults was constructed from provincial physician billing and hospitalization records between 2000 and 2013. We defined incident SARD cases (SLE, Sjogren's syndrome, scleroderma, polymyositis, dermatomyositis, polyarteritis nodosa and related conditions, polymyalgia rheumatic, other necrotizing vasculopathies, and undifferentiated connective tissue disease) based on at least two relevant billing diagnostic codes (within 2 years, with at least 1 billing from a rheumatologist), or at least one relevant hospitalization diagnostic code. Estimated PM2.5 and ozone concentrations (derived from remote sensing and/or chemical transport models) were assigned to subjects based on residential postal codes, updated throughout follow-up. Cox proportional hazards models with annual exposure levels were used to calculate hazard ratios (HRs) for SARDs incidence, adjusting for sex, age, urban-versus-rural residence, and socioeconomic status. RESULTS: The adjusted HR for SARDS related to one interquartile range increase in PM2.5 (3.97 µg/m3) was 1.12 (95% confidence interval 1.08-1.15), but there was no clear association with ozone. Indirectly controlling for smoking did not alter the findings. CONCLUSIONS: We found associations between SARDs incidence and PM2.5, but no relationships with ozone. Additional studies are needed to better understand interplays between the many constituents of air pollution and rheumatic diseases.

Prediction of Osteoporotic Fractures in Elderly Individuals: A Derivation and Internal Validation Study Using Healthcare Administrative Data.

In Canada and other countries, osteoporosis is monitored as part of chronic disease population surveillance programs. Although fractures are the principal manifestation of osteoporosis, very few algorithms are available to identify individuals at high risk of osteoporotic fractures in current surveillance systems. The objective of this study was to derive and validate predictive models to accurately identify individuals at high risk of osteoporotic fracture using information available in healthcare administrative data. More than 270,000 men and women aged ≥66 years were randomly selected from the Quebec Integrated Chronic Disease Surveillance System. Selected individuals were followed between fiscal years 2006-2007 and 2015-2016. Models were constructed for prediction of hip/femur and major osteoporotic fractures for follow-up periods of 5 and 10 years. A total of 62 potential predictors measurable in healthcare administrative databases were identified. Predictor selection was performed using a manual backward algorithm. The predictive performance of the final models was assessed using measures of discrimination, calibration, and overall performance. Between 20 and 25 predictors were retained in the final prediction models (eg, age, sex, social deprivation index, most of the major and minor risk factors for osteoporosis, diabetes, Parkinson's disease, cognitive impairment, anemia, anxio-depressive disorders). Discrimination of the final models was higher for the prediction of hip/femur fracture than major osteoporotic fracture and higher for prediction for a 5-year than a 10-year period (hip/femur fracture for 5 years: c-index = 0.77; major osteoporotic fracture for 5 years: c-index = 0.71; hip/femur fracture for 10 years: c-index = 0.73; major osteoporotic fracture for 10 years: c-index = 0.68). The predicted probabilities globally agreed with the observed probabilities. In conclusion, the derived models had adequate predictive performance in internal validation. As a final step, these models should be validated in an external cohort and used to develop indicators for surveillance of osteoporosis. © 2021 American Society for Bone and Mineral Research (ASBMR).

Exploring polypharmacy with artificial intelligence: data analysis protocol.

BACKGROUND: Polypharmacy is common among older adults and it represents a public health concern, due to the negative health impacts potentially associated with the use of several medications. However, the large number of medication combinations and sequences of use makes it complicated for traditional statistical methods to predict which therapy is genuinely associated with health outcomes. The project aims to use artificial intelligence (AI) to determine the quality of polypharmacy among older adults with chronic diseases in the province of Québec, Canada. METHODS: We will use data from the Quebec Integrated Chronic Disease Surveillance System (QICDSS). QICDSS contains information about prescribed medications in older adults in Quebec collected over 20 years. It also includes diagnostic codes and procedures, and sociodemographic data linked through a unique identification number for each individual. Our research will be structured around three interconnected research axes: AI, Health, and Law&Ethics. The AI research axis will develop algorithms for finding frequent patterns of medication use that correlate with health events, considering data locality and temporality (explainable AI or XAI). The Health research axis will translate these patterns into polypharmacy indicators relevant to public health surveillance and clinicians. The Law&Ethics axis will assess the social acceptability of the algorithms developed using AI tools and the indicators developed by the Heath axis and will ensure that the developed indicators neither discriminate against any population group nor increase the disparities already present in the use of medications. DISCUSSION: The multi-disciplinary research team consists of specialists in AI, health data, statistics, pharmacy, public health, law, and ethics, which will allow investigation of polypharmacy from different points of view and will contribute to a deeper understanding of the clinical, social, and ethical issues surrounding polypharmacy and its surveillance, as well as the use of AI for health record data. The project results will be disseminated to the scientific community, healthcare professionals, and public health decision-makers in peer-reviewed publications, scientific meetings, and reports. The diffusion of the results will ensure the confidentiality of individual data.

Association between obesity and risk of fracture, bone mineral density and bone quality in adults: A systematic review and meta-analysis.

BACKGROUND: The association between obesity and fracture risk may be skeletal site- and sex-specific but results among studies are inconsistent. Whilst several studies reported higher bone mineral density (BMD) in patients with obesity, altered bone quality could be a major determinant of bone fragility in this population. OBJECTIVES: This systematic review and meta-analysis aimed to compare, in men, premenopausal women and postmenopausal women with obesity vs. individuals without obesity: 1) the incidence of fractures overall and by site; 2) BMD; and 3) bone quality parameters (circulating bone turnover markers and bone microarchitecture and strength by advanced imaging techniques). DATA SOURCES: PubMed (MEDLINE), EMBASE, Cochrane Library and Web of Science were searched from inception of databases until the 13th of January 2021. DATA SYNTHESIS: Each outcome was stratified by sex and menopausal status in women. The meta-analysis was performed using a random-effect model with inverse-variance method. The risks of hip and wrist fracture were reduced by 25% (n = 8: RR = 0.75, 95% CI: 0.62, 0.91, P = 0.003, I2 = 95%) and 15% (n = 2 studies: RR = 0.85, 95% CI: 0.81, 0.88), respectively, while ankle fracture risk was increased by 60% (n = 2 studies: RR = 1.60, 95% CI: 1.52, 1.68) in postmenopausal women with obesity compared with those without obesity. In men with obesity, hip fracture risk was decreased by 41% (n = 5 studies: RR = 0.59, 95% CI: 0.44, 0.79). Obesity was associated with increased BMD, better bone microarchitecture and strength, and generally lower or unchanged circulating bone resorption, formation and osteocyte markers. However, heterogeneity among studies was high for most outcomes, and overall quality of evidence was very low to low for all outcomes. CONCLUSIONS: This meta-analysis highlights areas for future research including the need for site-specific fracture studies, especially in men and premenopausal women, and studies comparing bone microarchitecture between individuals with and without obesity. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42020159189.

The long-term postoperative trajectory of geriatric patients admitted for a hip fracture: A prospective observational cohort study.

BACKGROUND: Worldwide, 1.3 million patients sustain a hip fracture every year. In Canada, 23 621 patients over 60 have been admitted with a hip fracture in 2003. Few authors have yet investigated the full postoperative trajectory of patients admitted for a hip fracture, in terms of orientation. HYPOTHESIS: Most geriatric patients undergoing surgery for a hip fracture will not be able to return to their original residence at one-year of follow-up. OBJECTIVE: To characterize the full one-year postoperative trajectory of patients admitted for a hip fracture, in terms of orientation. PATIENTS AND METHODS: This is a prospective observational cohort study of geriatric patients undergoing surgery for a hip fracture from 2011 to 2017 in an academic center. A total of 254 patients were enrolled in this cohort. Demographic data and scores were collected throughout the hospitalisation. Patients' residences were assessed pre-fracture and at 1, 3, 6 and 12-month post-hospitalisation. RESULTS: Most patients evolved in one of the following trajectories at one-year; (1) 30% (n=63) went back at home, (2) 11% (n=22) went back to a senior residence, (3) 16% (n=36) needed rehabillitation, (4) 13% (n=28) were discharged to a different location than prior to admission and (5) 18% (n=37) were deceased. Patients evolving in trajectory 1 were younger (mean, 80.8±11.1, p<0.0001). Patients evolving in trajectory 5 had lower MNA1 scores (mean, 19.9±5.2, p.<0.0001) and lower MMSE2 scores (mean, 16.0±10.9, p<0.0001). The delay between discharge from the attending staff and real departure from the hospital was correlated to low MNA scores (-0.35627, p<0.0001), low MMSE scores (-0.35910, p=0.0004) and associated with the need for a rehabilitation center (trajectory 3) (mean, 2.67±4.36 days, p=0.0002). DISCUSSION: The postoperative evolution of geriatric patients with a hip fracture will continue to worsen due to the aging of the population. However, this study highlights important issues such as nutritional assessment, cognitive disorders and access to rehabilitation centers. LEVEL OF EVIDENCE: II, prospective cohort study.

Comparison of Fracture Prediction Tools in Individuals Without and With Early Chronic Kidney Disease: A Population-Based Analysis of CARTaGENE.

Whether fracture prediction tools developed for the management of osteoporosis can be used in chronic kidney disease (CKD) is poorly known. We aimed to compare the performance of fracture prediction tools in non-CKD and CKD. We analyzed CARTaGENE, a population-based survey of 40-year-old to 69-year-old individuals recruited between 2009 and 2010. Renal function was assessed using baseline creatinine and categorized according to Kidney Disease Improving Global Outcomes (KDIGO) guidelines (non-CKD, stage 2, stage 3). Individuals without creatinine measurements or with advanced CKD (stage 4 or 5; prevalence <0.25%) were excluded. Predicted 5-year fracture probabilities (using Fracture Risk Assessment Tool [FRAX], QFracture, and Garvan) were computed at baseline. Fracture incidence (major fracture [MOF] or any fracture) was evaluated in administrative databases from recruitment to March 2016. Discrimination (hazard ratios [HRs] per standard deviation [SD] increase in Cox models; c-statistics) and calibration (standardized incidence ratios [SIRs] before and after recalibration) were assessed in each CKD strata. We included 19,393 individuals (9522 non-CKD; 9114 stage 2; 757 stage 3). A total of 830 patients had any fracture during follow-up, including 352 MOF. FRAX (HR = 1.89 [1.63-2.20] non-CKD; 1.64 [1.41-1.91] stage 2; 1.76 [1.10-2.82] stage 3) and QFracture (HR = 1.90 [1.62-2.22] non-CKD; 1.57 [1.35-1.82] stage 2; 1.86 [1.19-2.91] stage 3) discriminated MOF similarly in non-CKD and CKD. In contrast, the discrimination of Garvan for any fracture tended to be lower in CKD stage 3 compared to non-CKD and CKD stage 2 (HR = 1.36 [1.22-1.52] non-CKD; 1.34 [1.20-1.50] stage 2; 1.11 [0.79-1.55] stage 3). Before recalibration, FRAX globally overestimated fracture risk while QFracture and Garvan globally underestimated fracture risk. After recalibration, FRAX and QFracture were adequately calibrated for MOF in all CKD strata whereas Garvan tended to underestimate any fracture risk in CKD stage 3 (SIR = 1.31 [0.95-1.81]). In conclusion, the discrimination and calibration of FRAX and QFracture is similar in non-CKD and CKD. Garvan may have a lower discrimination in CKD stage 3 and underestimate fracture risk in these patients. © 2020 American Society for Bone and Mineral Research.

Chronic respiratory disease should be considered when interpreting indicators of community antimicrobial use in people over 65 years old.

OBJECTIVES: Chronic respiratory diseases (CRD) put patients at increased risk of respiratory infection and antimicrobial use, but surveillance results on community antimicrobial use are generally not adjusted for this risk factor. The objective of this study was to demonstrate the importance of accounting for CRD when interpreting indicators of community antimicrobial use in people over 65 years old, in Québec, Canada. METHODS: Retrospective cohort study of antimicrobial use according to CRD status in individuals over 65 years old covered by Québec's public drug insurance plan between 2010 and 2015. Defined daily doses per 1000 person-days (DID) were computed per antimicrobial class and were further stratified according to chronic disease group, fiscal year, gender and age group. RESULTS: Antimicrobial use was 2.3 times higher in the CRD group (29.7 DID) compared with the other chronic disease group (13.1 DID) and 3.1 times higher than in the no chronic disease group (9.6 DID). The same gradient was reflected as well in use per antimicrobial class, per age group, per gender, and in time. Antimicrobial use increased throughout the study period and was higher in older age groups and in women. CONCLUSIONS: Interpretation of results of antimicrobial use surveillance should consider the prevalence of CRD in populations. In order to identify opportunities for adapted interventions targeting inappropriate use, finer analyses are necessary.

Fracture Risk in Dialysis and Kidney Transplanted Patients: A Systematic Review.

Chronic kidney disease is associated with an increased risk of fracture and cardiovascular mortality. The risk of fracture in hemodialysis (HD), peritoneal dialysis (PD) and kidney transplant (KT) patients is higher when compared with the general population. However, there exists a knowledge gap concerning which group has the highest risk of fracture. We aimed to compare the risk of fracture in HD, PD, and KT populations. We conducted a systematic review of observational studies evaluating the risk of fracture in HD, PD, or KT patients. Eligible studies were searched using MEDLINE, Embase, Web of Science, and Cochrane Library from their inception to January 2016, and in grey literature. Incidences (cumulative and rate) of fracture were described together using the median, according to fracture sites, the data source (administrative database or cohort and clinical registry), and fracture diagnosis method. Prevalence estimates were described separately. We included 47 studies evaluating the risk of fracture in HD, PD, and KT populations. In administrative database studies, incidence of hip fracture in HD (median 11.45 per 1000 person-years [p-y]), range: 9.3 to 13.6 was higher than in KT (median 2.6 per 1000 p-y; range 1.5 to 3.8) or in PD (median 5.2 per 1000 p-y; range 4.1 to 6.3). In dialysis (HD+PD), three studies reported a higher incidence of hip fracture than in KT. Prevalent vertebral fracture (assessed by X-rays or questionnaire) reported in HD was in a similar range as that reported in KT. Incidence of overall fracture was similar in HD and KT, from administrative databases studies, but lower in HD compared with KT, from cohorts or clinical registry studies. This systematic review suggests an important difference in fracture risk between HD, PD, and KT population, which vary according to the diagnosis method for fracture identification. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Frailty and health services use among Quebec seniors with non-hip fractures: a population-based study using adminsitrative databases.

BACKGROUND: The number of frail elderly will increase as the world population ageing accelerates. Since frail elders are at risk of falls, hospitalizations and disabilities, they will require more health care and services. To assess frailty prevalence using health administrative databases, to examine the association between frailty and the use of medical services and to measure the excess use of health services following a non-hip fracture across frailty levels among community-dwelling seniors. METHODS: A population-based cohort study was built from the Quebec Integrated Chronic Disease Surveillance System, including men and women ≥65 years old, non-institutionalized in the pre-fracture year. Frailty was measured using the Elders Risk Assessment (ERA) index. Multivariate Generalized Estimating Equation models were used to examine the relationship between frailty levels and health services while adjusting for covariates. The excess numbers of visits to Emergency Departments (ED) and to Primary Care Practitioners (PCP) as well as hospitalizations were also estimated. RESULTS: The cohort included 178,304 fractures. There were 13.6 and 5.2% frail and robust seniors, respectively. In the post-fracture year, the risks of ED visits, PCP visits and hospitalizations, were significantly higher in frail vs. non-frail seniors: adjusted relative risk (RR) = 2.69 [95% CI: 2.50-2.90] for ED visits, RR = 1.28 [95% CI: 1.23-1.32] for PCP visits and RR = 2.34 [95% CI: 2.14-2.55] for hospitalizations. CONCLUSION: Our results suggest that it is possible to characterize seniors' frailty status at a population level using health administrative databases. Furthermore, this study shows that non-institutionalized frail seniors require more health services after an incident fracture. Screening for frailty in seniors should be part of clinical management in order to identify those at a higher risk of needing health services.

Gene-environment interactions in Paget's disease of bone.

OBJECTIVES: This study explored the role of outdoor and indoor air pollutants in Paget's disease of bone (PDB). METHODS: We performed a survey in 140 French-Canadian patients with PDB, including 39 carriers of p.Pro392Leu mutation (SQSTM1 gene) and 113 healthy not mutated controls. The survey covered outdoor air pollution near the residence and indoor air pollutants by focusing on heating fuels and exposure to tobacco smoke. In a subgroup of patients, urinary concentrations of 17 heavy metals and 11 polycyclic aromatic hydrocarbons were measured by mass spectrometry. In light of what we learned from the survey and urinary assays, we explored the in vitro effects of certain toxics on osteoclasts in PDB. We conducted in vitro monocytes differentiation from peripheral blood of more than 40 participants, whose osteoclasts were treated with or without the toxic. The morphology of osteoclasts, their bone resorption abilities, gene and protein expression levels, and cellular oxidative stress levels were assayed. RESULTS: An inhibitory effect of cigarette smoke condensate and heavy metals was observed on morphology and bone resorption activity of patients' osteoclasts. SQSTM1 gene expression was upregulated in osteoclasts from patients with PDB versus healthy controls in presence of cadmium, and SQSTM1 protein expression was upregulated in presence of bismuth and tobacco smoke condensates, in particular in osteoclasts from carriers of the SQSTM1 mutation. Furthermore, high levels of oxidative stress in patients' osteoclasts were observed. CONCLUSIONS: Our in vitro experiments suggest an interaction between SQSTM1 gene and exposure to cadmium and tobacco smoke condensates.

Number, Location, and Time Since Prior Fracture as Predictors of Future Fracture in the Elderly From the General Population.

Prognostic tools are available to identify individuals at high risk of osteoporotic fracture and to assist physicians in management decisions. Some authors have suggested improving the predictive ability of these tools by integrating characteristics of prior fractures (number, location, and time since prior fracture). The objectives of this study were: (1) to evaluate the sex- and age-specific associations between characteristics of prior fractures and the occurrence of a future osteoporotic fracture; and (2) to assess whether the characteristics of prior fractures could increase the discriminative ability of fracture risk prediction tools. A retrospective cohort study was conducted using administrative data. Men and women aged ≥66 years were selected and grouped into two cohorts. In cohort #1 (N = 759,500), history of fractures was measured between fiscal years 1997-1998 and 2003-2004, and future fractures were identified between 2004-2005 and 2013-2014. In cohort #2 (N = 807,245), history of fractures was measured between 1997-1998 and 2008-2009, and future fractures were identified between 2009-2010 and 2013-2014. Time until a first hip/femur and major osteoporotic fracture were the outcomes of interest. Adjusted HRs and c-indices were calculated. The association between history of prior fractures and future fracture was stronger in men and younger individuals. The locations of prior fractures associated with the lowest and highest risks were foot/ankle/tibia/fibula (maximal HR = 1.64) and hip/femur (maximal HR = 9.02), respectively. The association was stronger for recent fractures (maximal HR = 4.93), but was still significant for fractures occurring 10 to 12 years prior to the beginning of follow-up (maximal HR = 1.99). Characteristics of prior fractures did not increase model discrimination. Our study confirms that the risk of future fracture increases with the number of prior fractures, varies according to prior fracture location, and decreases with time since prior fracture. However, the integration of these characteristics in current fracture risk prediction tools is not required because it does not improve predictive ability. © 2018 American Society for Bone and Mineral Research.

The Canadian Chronic Disease Surveillance System: A model for collaborative surveillance.

Chronic diseases have a major impact on populations and healthcare systems worldwide. Administrative health data are an ideal resource for chronic disease surveillance because they are population-based and routinely collected. For multi-jurisdictional surveillance, a distributed model is advantageous because it does not require individual-level data to be shared across jurisdictional boundaries. Our objective is to describe the process, structure, benefits, and challenges of a distributed model for chronic disease surveillance across all Canadian provinces and territories (P/Ts) using linked administrative data. The Public Health Agency of Canada (PHAC) established the Canadian Chronic Disease Surveillance System (CCDSS) in 2009 to facilitate standardized, national estimates of chronic disease prevalence, incidence, and outcomes. The CCDSS primarily relies on linked health insurance registration files, physician billing claims, and hospital discharge abstracts. Standardized case definitions and common analytic protocols are applied to the data for each P/T; aggregate data are shared with PHAC and summarized for reports and open access data initiatives. Advantages of this distributed model include: it uses the rich data resources available in all P/Ts; it supports chronic disease surveillance capacity building in all P/Ts; and changes in surveillance methodology can be easily developed by PHAC and implemented by the P/Ts. However, there are challenges: heterogeneity in administrative databases across jurisdictions and changes in data quality over time threaten the production of standardized disease estimates; a limited set of databases are common to all P/Ts, which hinders potential CCDSS expansion; and there is a need to balance comprehensive reporting with P/T disclosure requirements to protect privacy. The CCDSS distributed model for chronic disease surveillance has been successfully implemented and sustained by PHAC and its P/T partners. Many lessons have been learned about national surveillance involving jurisdictions that are heterogeneous with respect to healthcare databases, expertise and analytical capacity, population characteristics, and priorities.