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Background: Little is known about those vaccinated against influenza after pharmacists were added to the Ontario Universal Influenza Immunization Program, in 2012. Our aim was to identify characteristics of patients vaccinated against influenza and predictors of vaccination at a physician's office versus a community pharmacy. Methods: We conducted a cross-sectional study of Ontario residents who had a record of receipt of an influenza vaccine between October and March in the 2013/14 and 2015/16 influenza seasons in Ontario using health administrative databases. We used Poisson regression models to estimate associations between baseline characteristics and the receipt of influenza vaccination in a community pharmacy. All analyses were stratified by age group (≤ 65 yr or ≥ 66 yr). Results: Overall, we found a 7.9% decrease in vaccinations administered in 2015/16 (2 454 178) compared to 2013/14 (2 677 278). The number of patients vaccinated in community pharmacies increased between the 2 periods (757 729 [28.3%] in 2013/14 v. 859 794 [35.0%] in 2015/16). Living in nonurban areas or higher-income neighbourhoods, not identifying as an immigrant, not having a diagnosis of diabetes or hypertension, and receiving a pharmacist service on the same day as the vaccination were predictors of being vaccinated in a pharmacy, regardless of age group. Among patients aged 66 or more, those who had a hospital admission in the previous year were more likely to be vaccinated in a pharmacy than in a physician's office (adjusted incidence rate ratio [IRR] 1.08, 95% confidence interval [CI] 1.06–1.09), whereas those with higher annual medication costs were more likely to be vaccinated in a physician's office. The location of the previous season's vaccination predicted the current season's place of vaccination (age ≥ 66 yr: physician's office: adjusted IRR 0.56 [95% CI 0.56–0.57], pharmacy: adjusted IRR 2.37 [95% CI 2.35–2.39]; age ≤ 65 yr: physician's office: adjusted IRR 0.57 [95% CI 0.57–0.57], pharmacy: adjusted IRR 2.19 [95% CI 2.18–2.20]). Interpretation: For the 2013/14 and 2015/16 influenza seasons, the influenza vaccine was administered more frequently in physician offices than in community pharmacies, but the proportion of patients vaccinated in community pharmacies increased between the 2 periods. Physicians and pharmacists can encourage patients to take advantage of the availability of influenza vaccines across various settings. [ABSTRACT FROM AUTHOR]

Background: Denosumab inhibits the receptor activator of nuclear factor κB (RANK) pathway and is used to treat osteoporosis. Emerging evidence suggests RANK-blockade may play a role in mammary tumourigenesis. Thus, we undertook a population-based study of denosumab use and breast cancer risk in a large cohort of postmenopausal women.Methods: We included women 67+ years with prior bisphosphonate use who filled a first prescription for denosumab. They were matched on age, date, cumulative prior use of and time since last use of a bisphosphonate to women with no history of denosumab. Cox proportional hazards was used to estimate the hazard ratio (HR) of breast cancer with denosumab use.Results: A total of 100,368 women were included in the analysis with 1271 incident breast cancer events. Denosumab use was associated with a 13% decreased breast cancer risk (HR = 0.87; 95% CI 0.76-1.00). There was no relationship between increasing number of denosumab doses and breast cancer risk (P-trend = 0.15).Conclusion: These findings suggest a potential protective effect of ever denosumab use on breast cancer risk in a cohort of older women previously treated with bisphosphonates. [ABSTRACT FROM AUTHOR]

Background: Little information is available on the comparative effectiveness of osteoporosis pharmacotherapies. Objective: To compare the relative effectiveness of osteoporosis treatments to reduce nonvertebral fracture risk among older adults. Design: Cohort study. Setting: Enrollees in 2 statewide pharmaceutical benefit programs for persons age 65 years or older. Patients: 43 135 new recipients of oral bisphosphonates, nasal calcitonin, and raloxifene who began treatment from 2000 to 2005. The mean age was 79 years (SD, 6.9), and 96% were women. Measurements: The primary outcome was nonvertebral fracture (hip, humerus, or radius or ulna) within 12 months of treatment initiation. Cox proportional hazard models stratified by state and adjusted for risk factors for fracture were used to compare fracture rates. Alendronate was the reference category in all analyses. Results: A total of 1051 nonvertebral fractures were observed within 12 months (2.62 fractures per 100 person-years). No large differences in fracture risk were found between risedronate (hazard ratio [HR], 1.01 [95% CI, 0.85 to 1.21]) or raloxifene (HR, 1.18 [CI, 0.96 to 1.46]) and alendronate. However, among those with a fracture history, raloxifene recipients experienced more nonvertebral fractures within 12 months (HR, 1.78 [CI, 1.20 to 2.63]) compared with alendronate recipients. Patients who received calcitonin experienced more nonvertebral fractures than those who received alendronate (HR, 1.40, [CI, 1.20 to 1.63]). Results were similar in sensitivity analyses that examined different lengths of follow-up (6 months and 24 months), were restricted to hip fracture as the outcome, and were completed in various subgroups. Limitation: Confounder adjustment was limited to health care utilization data, and the confidence bounds of some comparisons were too wide to rule out potential clinically important differences between agents. Conclusion: Differences in fracture risk between risedronate or raloxifene and alendronate were small. Nasal calcitonin recipients may have a higher risk for nonvertebral fractures compared with alendronate recipients. Future studies that can better adjust for possible confounding may further clarify these relationships. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To examine the validity of both self-report of having had dual-energy x-ray absorptiometry (DXA) and self-reported DXA test results. Methods: Participants were recruited in 2003 and 2004 from a population-based study of women aged 65–90 years examining osteoporosis management in Ontario, Canada (N =871). Women reporting having had a DXA were eligible and asked to report the results of their most recent test. Participant responses were compared against DXA reports obtained from physicians. Results: We obtained 413 (81%) physician records among the 510 women who reported having had a DXA test. Of these, the positive predictive value for self-report of having had a DXA was 93%. The weighted kappa statistic for the agreement between self-report and actual DXA results was 0.42 (95% confidence interval=0.34–0.49). Although 84% of those with normal bone reported this, only 29% of those with osteopenia and 62% with osteoporosis reported their results correctly. Self-report of a clinical diagnosis of osteoporosis was better among those with a low trauma fracture, yet underestimated osteoporosis prevalence by 24%. Conclusion: There is minimal measurement error in self-report of having had a DXA test. Self-report of DXA results will underestimate osteoporosis prevalence and is not a good proxy for clinical diagnosis. [Copyright &y& Elsevier]

Background: The ability to locate those sampled has important implications for response rates and thus the success of survey research. The purpose of this study was to examine predictors of locating women requiring tracing using publicly available methods (primarily Internet searches), and to determine the additional benefit of vital statistics linkages. Methods: Random samples of women aged 65-89 years residing in two regions of Ontario, Canada were selected from a list of those who completed a questionnaire between 1995 and 1997 (n = 1,500). A random sample of 507 of these women had been searched on the Internet as part of a feasibility pilot in 2001. All 1,500 women sampled were mailed a newsletter and information letter prior to recruitment by telephone in 2003 and 2004. Those with returned mail or incorrect telephone number(s) required tracing. Predictors of locating women were examined using logistic regression. Results: Tracing was required for 372 (25%) of the women sampled, and of these, 181 (49%) were located. Predictors of locating women were: younger age, residing in less densely populated areas, having had a web-search completed in 2001, and listed name identified on the Internet prior to recruitment in 2003. Although vital statistics linkages to death records subsequently identified 41 subjects, these data were incomplete. Conclusion: Prospective studies may benefit from using Internet resources at recruitment to determine the listed names for telephone numbers thereby facilitating follow-up tracing and improving response rates. Although vital statistics linkages may help to identify deceased individuals, these may be best suited for post hoc response rate adjustment. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the validity of the Osteoporosis Risk Assessment Instrument (ORAI), Osteoporosis Self-Assessment Tool (OST) chart and equation, and a criterion based on body weight for identifying women with asymptomatic primary osteoporosis. Prospective recruitment and chart abstractions from family practices of three University affiliated hospitals were completed for women aged 45 years or more with baseline bone mineral density (BMD) testing results by dual energy X-ray absorptiometry. Those taking bone active medication other than hormone therapy, with prior fragility fracture or with risk factors for secondary osteoporosis were excluded. Women were categorized as being normal, osteopenic or osteoporotic by lowest BMD T-score at either the femoral neck or lumbar spine (L1–L4). Sensitivity, specificity and area under the receiver operating characteristic (ROC) curve to identify those with osteoporosis were determined for each decision rule. The positive predictive value (PPV) for detecting osteoporosis after using a second cut point to convert each decision rule into a risk index (low, moderate or high risk) was also determined. The sensitivity of the decision rules to identify women with osteoporosis ranged from 92% to 95% and specificity from 35% to 46%. The area under the ROC curves were significantly better for the ORAI (0.80), OST chart (0.82) and OST equation (0.82) compared with the body weight criterion (0.73). PPV for detecting osteoporosis ranged from 30% to 58% among women deemed at high risk. These data confirm the validity of the ORAI, the OST chart and the OST equation as screening tools for BMD testing. Further evidence is required to confirm the validity of the body weight criterion. [ABSTRACT FROM AUTHOR]

Objective: The Osteoporosis Health Belief Scale (OHBS) is a 42-item scale designed to measure general health motivation, perceived susceptibility to and seriousness of osteoporosis, and beliefs about calcium intake and exercise in preventing and treating osteoporosis. The purpose of this study was to examine the psychometric properties of the OHBS by telephone administration among older women.Study Design and Setting: A convenience sample of 425 women aged 61–93 years participating in a longitudinal arthritis study was recruited by telephone. Item clarity was evaluated and 22 additional items (6 reworded, 16 from other questionnaires) were considered to supplement or replace existing scale items. Multitrait scaling techniques and exploratory factor analysis were used to test scale structure. Construct validity was tested based on theoretical hypothesis between OHBS subscale scores and participant characteristics.Results: A few modifications to the OHBS scale were suggested, reducing the scale by five items (two redundant, three did not load), rewording one item and moving on item to a different subscale. The modified 37-item OHBS had a seven-factor uncorrelated solution explaining 48% of the model variance with internal consistency ranging from 0.73 to 0.88.Conclusion: Relatively minor changes to the OHBS results in reduced redundancy and improved internal structure of the scale for telephone administration among women over 60 years of age. Further examination is recommended to confirm these findings. [Copyright &y& Elsevier]

Presents a study which assesses the diagnostic properties of four decision rules for selecting women for dual-energy x-ray absorptiometry testing for bone mineral density as a strategy for reducing the incidence of osteoporotic fractures. Context; Objectives; Design and setting; Participants; Main outcome measures; Results; Conclusion.

Offers a study that attempts to develop and validate a clinical tool to determine which women are at increased risk for osteoporosis and should be selected to undergo bone densitometry. Study of women aged 45 or more with low bone mineral density at the femoral neck or lumbar spine; Results and interpretation.

Résumé: Contexte: Au Canada, plus de 2 millions de personnes vivent avec l'ostéoporose, une maladie qui accroît le risque de fracture, ce qui fait augmenter la morbidité et la mortalité, et entraîne une perte de qualité de vie et d'autonomie. La présente actualisation des lignes directrices vise à accompagner les professionnelles et professionnels de la santé au Canada dans la prestation de soins visant à optimiser la santé osseuse et à prévenir les fractures chez les femmes ménopausées et les hommes de 50 ans et plus. Méthodes: Le présent document fournit une actualisation des lignes directrices de pratique clinique de 2010 d'Ostéoporose Canada sur le diagnostic et la prise en charge de l'ostéoporose au pays. Nous avons utilisé l'approche GRADE (Grading of Recommendations Assessment, Development and Evaluation) et effectué l'assurance de la qualité conformément aux normes de qualité et de présentation des rapports de la grille AGREE II (Appraisal of Guidelines for Research & Evaluation). Les médecins de premier recours et les patientes et patients partenaires ont été représentés à tous les niveaux des comités et des groupes ayant participé à l'élaboration des lignes directrices, et ont participé à toutes les étapes du processus pour garantir la pertinence des informations pour les futurs utilisateurs et utilisatrices. Le processus de gestion des intérêts concurrents a été entamé avant l'élaboration des lignes directrices et s'est poursuivi sur toute sa durée, selon les principes du Réseau international en matière de lignes directrices. Dans la formulation des recommandations, nous avons tenu compte des avantages et des risques, des valeurs et préférences de la patientèle, des ressources, de l'équité, de l'acceptabilité et de la faisabilité; la force de chacune des recommandations a été déterminée en fonction du cadre GRADE. Recommandations: Les 25 recommandations et les 10 énoncés de bonne pratique sont répartis en sections : activité physique, alimentation, évaluation du risque de fracture, instauration du traitement, interventions pharmacologiques, durée et séquence du traitement, et monitorage. La prise en charge de l'ostéoporose devrait se fonder sur le risque de fracture, établi au moyen d'une évaluation clinique réalisée avec un outil d'évaluation du risque de fracture validé. L'activité physique, l'alimentation et la pharmacothérapie sont des éléments essentiels à la stratégie de prévention des fractures, qui devraient être personnalisés. Interprétation: Les présentes lignes directrices ont pour but d'outiller les professionnelles et professionnels de la santé et la patientèle afin qu'ensemble ils puissent parler de l'importance de la santé osseuse et du risque de fracture tout au long de la vie adulte avancée. La détection et la prise en charge efficace de la fragilité osseuse peuvent contribuer à réduire les fractures et à préserver la mobilité, l'autonomie et la qualité de vie. [ABSTRACT FROM AUTHOR]

Background: In Canada, more than 2 million people live with osteoporosis, a disease that increases the risk for fractures, which result in excess mortality and morbidity, decreased quality of life and loss of autonomy. This guideline update is intended to assist Canadian health care professionals in the delivery of care to optimize skeletal health and prevent fractures in postmenopausal females and in males aged 50 years and older. Methods: This guideline is an update of the 2010 Osteoporosis Canada clinical practice guideline on the diagnosis and management of osteoporosis in Canada. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework and quality assurance as per Appraisal of Guidelines for Research and Evaluation (AGREE II) quality and reporting standards. Primary care physicians and patient partners were represented at all levels of the guideline committees and groups, and participated throughout the entire process to ensure relevance to target users. The process for managing competing interests was developed before and continued throughout the guideline development, informed by the Guideline International Network principles. We considered benefits and harms, patient values and preferences, resources, equity, acceptability and feasibility when developing recommendations; the strength of each recommendation was assigned according to the GRADE framework. Recommendations: The 25 recommendations and 10 good practice statements are grouped under the sections of exercise, nutrition, fracture risk assessment and treatment initiation, pharmacologic interventions, duration and sequence of therapy, and monitoring. The management of osteoporosis should be guided by the patient's risk of fracture, based on clinical assessment and using a validated fracture risk assessment tool. Exercise, nutrition and pharmacotherapy are key elements of the management strategy for fracture prevention and should be individualized. Interpretation: The aim of this guideline is to empower health care professionals and patients to have meaningful discussions on the importance of skeletal health and fracture risk throughout older adulthood. Identification and appropriate management of skeletal fragility can reduce fractures, and preserve mobility, autonomy and quality of life. [ABSTRACT FROM AUTHOR]

Background: An osteoporosis drug holiday is recommended for most patients after 3 to 5 years of therapy. Risedronate has a shorter half-life than alendronate, and thus the residual length of fracture protection may be shorter.Objective: To examine the comparative risks of drug holidays after long-term (≥3 years) risedronate versus alendronate therapy.Design: Population-based, matched, cohort study.Setting: Province-wide health care administrative databases providing comprehensive coverage to Ontario residents aged 65 years or older between November 2000 and March 2020.Patients: Persons aged 66 years or older who had long-term risedronate therapy and a drug holiday were matched 1:1 on propensity score to those who had long-term alendronate therapy and a drug holiday.Measurements: The primary outcome was hip fracture within 3 years after a 120-day ascertainment period. Secondary analyses included shorter follow-up and sex-specific estimates. Cox proportional hazards models were used to estimate hazard ratios (HRs) for fracture risk between groups.Results: A total of 25 077 propensity score-matched pairs were eligible (mean age, 81 years; 81% women). Hip fracture rates were higher among risedronate than alendronate drug holidays (12.4 and 10.6 events, respectively, per 1000 patient-years; HR, 1.18 [95% CI, 1.04 to 1.34]; 915 total hip fractures). The association was attenuated when any fracture was included as the outcome (HR, 1.07 [CI, 1.00 to 1.16]) and with shorter drug holidays (1 year: HR, 1.03 [CI, 0.85 to 1.24]; 2 years: HR, 1.14 [CI, 0.96 to 1.32]).Limitation: Analyses were limited to health care administrative data (potential unmeasured confounding), and some secondary analyses contained few events.Conclusion: Drug holidays after long-term therapy with risedronate were associated with a small increase in risk for hip fracture compared with alendronate drug holidays. Future research should examine how best to mitigate this risk.Primary Funding Source: Canadian Institutes of Health Research. [ABSTRACT FROM AUTHOR]

For self-controlled studies of medication-related effects, time-varying confounding by indication can occur if the indication varies over time. We describe how active comparators might mitigate such bias, using an empirical example. Approaches to using active comparators are described for case-crossover design, case-time-control design, self-controlled case-series, and sequence symmetry analyses. In the empirical example, we used Danish data from 1996–2018 to study the association between penicillin and venous thromboembolism (VTE), using roxithromycin, a macrolide antibiotic, as comparator. Upper respiratory infection is a transient risk factor for VTE, thus representing time-dependent confounding by indication. Odds ratios for case-crossover analysis were 3.35 (95% confidence interval: 3.23, 3.49) for penicillin and 3.56 (95% confidence interval: 3.30, 3.83) for roxithromycin. We used a Wald-based method or an interaction term to estimate the odds ratio for penicillin with roxithromycin as comparator. These 2 estimates were 0.94 (95% confidence interval: 0.87, 1.03) and 1.03 (95% confidence interval: 0.95, 1.13). Results were similar for the case-time-control analysis, but both the self-controlled case-series and sequence symmetry analysis suggested a weak protective effect of penicillin, seemingly explained by VTE affecting future exposure exclusively for penicillin. The strong association of antibiotics with VTE suggests presence of confounding by indication. Such confounding can be mitigated by using an active comparator. [ABSTRACT FROM AUTHOR]

Bisphosphonates are first-line therapy for osteoporosis, with alendronate, risedronate, and zoledronate as the main treatments used globally. After one year of therapy, bisphosphonates are retained in bone for extended periods with extended anti-fracture effects after discontinuation. Due to this continued fracture protection and the potential for rare adverse events associated with long-term use (atypical femoral fractures and osteonecrosis of the jaw), a drug holiday of two to three years is recommended for most patients after long-term bisphosphonate therapy. The recommendation for a drug holiday up to three years is derived primarily from extensions of pivotal trials with alendronate and zoledronate and select surrogate marker studies. However, certain factors may modify the duration of bisphosphonate effects on a drug holiday and warrant consideration when determining an appropriate time off-therapy. In this narrative review, we recall what is currently known about drug holidays and discuss what we believe to be the primary considerations and areas for future research regarding drug holiday duration: total bisphosphonate exposure, type of bisphosphonate used, bone mineral density and falls risk, and patient sex and body weight. [ABSTRACT FROM AUTHOR]

Background: Several clinical prediction rules (CPRs) for complications and mortality of Clostridioides difficile infection (CDI) have been developed but only a few have gone through external validation, and none is widely recommended in clinical practice. Methods: CPRs were identified through a systematic review. We included studies that predicted severe or complicated CDI (cCDI) and mortality, reported at least an internal validation step, and for which data were available with minimal modifications. Data from a multicenter prospective cohort of 1380 adults with confirmed CDI were used for external validation. In this cohort, cCDI occurred in 8% of the patients and 30-day all-cause mortality occurred in 12%. The performance of each tool was assessed using individual outcomes, with the same cut-offs and standard parameters. Results: Seven CPRs were assessed. Three predictive scores for cCDI showed low sensitivity (25–61%) and positive predictive value (PPV; 9–31%), but moderate specificity (54–90%) and negative predictive value (NPV; 82–95%). One model [using age, white blood cell count (WBC), narcotic use, antacids use, and creatinine ratio > 1.5× the normal level as covariates] showed a probability of 25% of cCDI at the optimal cut-off point with 36% sensitivity and 84% specificity. Two scores for mortality had low sensitivity (4–55%) and PPV (25–31%), and moderate specificity (71–78%) and NPV (87–92%). One predictive model for 30-day all-cause mortality [Charlson comorbidity index, WBC, blood urea nitrogen (BUN), diagnosis in ICU, and delirium] showed an AUC-ROC of 0.74. All other CPRs showed lower AUC values (0.63–0.69). Errors in calibration ranged from 12%- 27%. Conclusions: Included CPRs showed moderate performance for clinical use in a large validation cohort with a majority of patients infected with ribotype 027 strains and a low rate of cCDI and mortality. These data show that better CPRs need to be developed and validated. [ABSTRACT FROM AUTHOR]

Background and Aims: Methadone maintenance therapy (MMT) is associated with improved outcomes for children exposed to maternal opioid dependence in utero. We examined Ontario's population of pregnant women on MMT and determined the impact of timing of MMT initiation on perinatal outcomes. Design Cohort study. Setting: Ontario, Canada. Participants: Women eligible for public drug benefits and on MMT during pregnancy between 2005 and 2015. Measurements We stratified women based on their timing of MMT initiation: (1) stabilized prior to conception, (2) newly initiated prior to conception, (3) initiation in trimester 1, (4) initiation in trimester 2 or (5) initiation in trimester 3. The primary outcomes in the multivariable logistic regression analysis were key perinatal health indicators: small for gestational age, preterm birth, congenital anomalies, severe maternal morbidity, caesarean section and induced labor. Secondary outcomes were specific to maternal opioid dependence: neonatal abstinence syndrome (NAS), admission to a neonatal intensive care unit (NICU), NAS treatment, removal from mother's custody at hospital discharge and neonatal death. Findings Among 1842 women on MMT during pregnancy, 87.6% (n = 1614) initiated MMT before conception. Almost a quarter of their infants (22.2%; n = 408) were born small for gestational age, 17.5% (n = 323) were preterm and 5.9% (n = 109) were born with a congenital anomaly. The odds of primary outcomes occurring did not differ based on timing of methadone initiation; however, infants of mothers who initiated methadone during pregnancy had up to a fourfold increase in the odds of social services removal at the hospital [adjusted odds ratio (aOR) range = 3.70–4.19] compared with those whose mothers were stabilized on MMT prior to conception. Conclusions: Later initiation of methadone maintenance therapy among pregnant women in Ontario, Canada has not been found to be clearly related to most key perinatal adverse health outcomes. [ABSTRACT FROM AUTHOR]

Aims: Domperidone is used to treat gastrointestinal symptoms in patients with Parkinson's disease (PD) and is linked to an increased risk of mortality. We sought to examine the risk of all‐cause mortality associated with domperidone exposure in PD. Methods: We conducted a cohort study using data from the Clinical Practice Research Datalink database (1987–2011). The first recorded PD diagnosis defined index date. Time‐dependent Cox proportional hazards models estimated hazard ratios (HRs) of all‐cause mortality associated with domperidone use. PD patients were stratified by domperidone use (current/recent/past), with never used as the referent. Current domperidone users were stratified by daily dose, domperidone duration and other anti‐Parkinson's medications. A secondary analysis compared PD patients to matched (1:1) non‐PD patients. Results: A total of 5114 PD patients were identified. Current use of domperidone among PD patients was associated with a two‐fold increase in all‐cause mortality (HRadj = 2.00, 95% confidence interval [CI]: 1.64–2.45), as compared to patients never exposed to domperidone. All‐cause mortality risk was highest in those starting domperidone in the previous month [HRadj = 2.97, 95% CI: 2.06–4.27]. When compared to matched non‐PD patients, PD was associated with a 43% increased risk of all‐cause mortality, yet this increased to a 2.4‐fold increased risk among PD patients currently using domperidone. Conclusion: Current use of domperidone was associated with a two‐fold increased mortality risk in PD patients, as compared to PD patients that never used domperidone. The risk is highest in the first month of use and does not appear to be attributable to PD alone. [ABSTRACT FROM AUTHOR]

The article provides an overview of the STRengthening Analytical Thinking for Observational Studies (STRATOS) initiative as an international collaboration which was formed to offer guidance to help bridge the gap between methodological application and innovation. STRATOS is focused on distinguishing issues and promising approaches for analysing and planning observational studies.

Few studies have evaluated the mortality or quantified the economic burden of community-onset Clostridium difficile infection (CDI). We estimated the attributable mortality and costs of community-onset CDI. We conducted a population-based matched cohort study. We identified incident subjects with community-onset CDI using health administrative data (emergency department visits and hospital admissions) in Ontario, Canada between January 1, 2003 and December 31, 2010. We propensity-score matched each infected subject to one uninfected subject and followed subjects in the cohort until December 31, 2011. We evaluated all-cause mortality and costs (unadjusted and adjusted for survival) from the healthcare payer perspective (2014 Canadian dollars). During our study period, we identified 7,950 infected subjects. The mean age was 63.5 years (standard deviation = 22.0), 62.7% were female, and 45.0% were very high users of the healthcare system. The relative risk for 30-day, 180-day, and 1-year mortality were 7.32 (95% confidence interval [CI], 5.94–9.02), 3.55 (95%CI, 3.17–3.97), and 2.59 (95%CI, 2.37–2.83), respectively. Mean attributable cumulative 30-day, 180-day, and 1-year costs (unadjusted for survival) were $7,434 (95%CI, $7,122-$7,762), $12,517 (95%CI, $11,687-$13,366), and $13,217 (95%CI, $12,062-$14,388). Mean attributable cumulative 1-, 2-, and 3-year costs (adjusted for survival) were $10,700 (95%CI, $9,811-$11,645), $13,312 (95%CI, $12,024-$14,682), and $15,812 (95%CI, $14,159-$17,571). Infected subjects had considerably higher risk of all-cause mortality and costs compared with uninfected subjects. This study provides insight on an understudied patient group. Our study findings will facilitate assessment of interventions to prevent community-onset CDI. [ABSTRACT FROM AUTHOR]

Background: Medication reviews have become part of pharmacy practice across developed countries. This study aimed to identify factors affecting the likelihood of eligible Ontario seniors receiving a pharmacy-led medication review called MedsCheck annual (MCA). Methods: We designed a cohort study using a random sample of pharmacy claims for MCA-eligible Ontario seniors using linked administrative data from April 2012 to March 2013. Guided by a conceptual framework, we constructed a generalized-estimating-equations model to estimate the effect of patient, pharmacy and community factors on the likelihood of receiving MCA. Results: Of the 2,878,958 eligible claim-dates, 65,605 included an MCA. Compared to eligible individuals who did not receive an MCA, recipients were more likely to have a prior MCA (OR = 3.03), receive a new medication on the claim-date (OR = 1.78), be hypertensive (OR = 1.18) or have a recent hospitalization (OR = 1.07). MCA recipients had fewer medications (e.g., OR = 0.44 for ≥12 medications versus 0-4 medications), and were less likely to receive an MCA in a rural (OR = 0.74) or high-volume pharmacy (OR = 0.65). Conclusions: The most important determinant of receiving an MCA was having had a prior MCA. Overall, MCA recipients were healthier, younger, urban-dwelling, and taking fewer medications than non-recipients. Policies regarding current and future medication review programs may need to evolve to ensure that those at greatest need receive timely and comprehensive medication reviews. [ABSTRACT FROM AUTHOR]

Background. Clostridium difficile infection (CDI) is the most common cause of nosocomial infectious diarrhea and may result in severe complications including death. We conducted a prospective study to identify risk factors for complications of CDI (cCDI). Methods. Adult inpatients with confirmed CDI in 10 Canadian hospitals were enrolled and followed for 90 days. Potential risk factors were measured within 24 hours of diagnosis. Isolates were typed by polymerase chain reaction ribotyping. cCDI was defined as 1 or more of the following: colonic perforation, toxic megacolon, colectomy, admission to an intensive care unit for cCDI, or if CDI contributed to death within 30 days of enrollment. Risk factors for cCDI were investigated by logistic regression. Results. A total of 1380 patients were enrolled. cCDI was observed in 8% of patients. The ribotype was identified in 922 patients, of whom 52% were infected with R027. Age =80 years, heart rate >90/minute, respiratory rate >20/ minute, white cell count <4 × 109/L or =20 × 109/L, albumin <25 g/L, blood urea nitrogen >7 mmol/L, and C-reactive protein =150 mg/L were independently associated with cCDI. A higher frequency of cCDI was observed among R027-infected patients (10.9% vs 7.2%), but the association was not significant in adjusted analysis. Conclusions. CDI complications were associated with older age, abnormal blood tests, and abnormal vital signs. These factors, which are readily available to clinicians at the time of diagnosis, could be used for outcome prediction and risk stratification to select patients who may need closer monitoring or more aggressive therapy. [ABSTRACT FROM AUTHOR]

Objectives To describe the use and reporting of interrupted time series methods in drug utilization research. Study Design and Setting We completed a systematic search of MEDLINE, Web of Science, and reference lists to identify English language articles through to December 2013 that used interrupted time series methods in drug utilization research. We tabulated the number of studies by publication year and summarized methodological detail. Results We identified 220 eligible empirical applications since 1984. Only 17 (8%) were published before 2000, and 90 (41%) were published since 2010. Segmented regression was the most commonly applied interrupted time series method (67%). Most studies assessed drug policy changes (51%, n = 112); 22% (n = 48) examined the impact of new evidence, 18% (n = 39) examined safety advisories, and 16% (n = 35) examined quality improvement interventions. Autocorrelation was considered in 66% of studies, 31% reported adjusting for seasonality, and 15% accounted for nonstationarity. Conclusion Use of interrupted time series methods in drug utilization research has increased, particularly in recent years. Despite methodological recommendations, there is large variation in reporting of analytic methods. Developing methodological and reporting standards for interrupted time series analysis is important to improve its application in drug utilization research, and we provide recommendations for consideration. [ABSTRACT FROM AUTHOR]

Objectives:With Clostridium difficile infection (CDI) on the rise, knowledge of the current economic burden of CDI can inform decisions on interventions related to CDI. We systematically reviewed CDI cost-of-illness (COI) studies.Methods:We performed literature searches in six databases: MEDLINE, Embase, the Health Technology Assessment Database, the National Health Service Economic Evaluation Database, the Cost-Effectiveness Analysis Registry, and EconLit. We also searched gray literature and conducted reference list searches. Two reviewers screened articles independently. One reviewer abstracted data and assessed quality using a modified guideline for economic evaluations. The second reviewer validated the abstraction and assessment.Results:We identified 45 COI studies between 1988 and June 2014. Most (84%) of the studies were from the United States, calculating costs of hospital stays (87%), and focusing on direct costs (100%). Attributable mean CDI costs ranged from $8,911 to $30,049 for hospitalized patients. Few studies stated resource quantification methods (0%), an epidemiological approach (0%), or a justified study perspective (16%) in their cost analyses. In addition, few studies conducted sensitivity analyses (7%).Conclusions:Forty-five COI studies quantified and confirmed the economic impact of CDI. Costing methods across studies were heterogeneous. Future studies should follow standard COI methodology, expand study perspectives (e.g., patient), and explore populations least studied (e.g., community-acquired CDI). [ABSTRACT FROM AUTHOR]

Background: Bisphosphonates are the first-line therapy for the treatment of osteoporosis. In the province of Ontario, the Ontario Drug Benefit Program funds medications for patients aged 65 years and older. The Ontario Drug Benefit Program has a generic substitution policy that requires lower-cost generic drugs to be dispensed when they are available. However, there is controversy surrounding the efficacy and tolerability of generic bisphosphonates. The objective of this study was to describe patterns in the use of brand-name versus generic formulations when dispensing oral bisphosphonate over a 13-year period. Methods: We identified all osteoporotic preparations for alendronate and risedronate that were dispensed through the Ontario Drug Benefit Program from 2001 to 2014. We stratified our sample into community-dwelling residents and residents in long-term care facilities. The number of prescriptions dispensed per month were plotted to illustrate trends over time. Results: We found a rapid switch from brand-name to generic bisphosphonate equivalents immediately after the generic became available on the Ontario Drug Benefit formulary, with generics accounting for > 88% of dispensed drug within 2 months. We also observed a reduction in the number of generic drugs dispensed each time a new brand-name alternative (e.g., monthly risedronate, weekly alendronate plus vitamin D) was introduced to the formulary. The dispensing trends were similar in the community and long-term care settings. Interpretation: The Ontario Drug Benefit Program generic substitution policy resulted in rapid uptake of generic oral bisphosphonates among seniors in Ontario. However, there was a switch away from generic medications to new brand-name alternatives whenever they were introduced to the formulary. Therefore, some patients continued to use brand-name bisphosphonate despite the availability of generic options. [ABSTRACT FROM AUTHOR]

Knowing a person's fracture risk according to their kidney function, gender, and age may influence clinical management and decision-making. Using healthcare databases from Ontario, Canada, we conducted a cohort study of 679,114 adults of 40 years and over (mean age 62 years) stratified at cohort entry by estimated glomerular filtration rate ((eGFR) 60 and over, 45-59, 30-44, 15-29, and under 15 ml/min per 1.73 m2), gender, and age (40-65 and over 65 years). The primary outcome was the 3-year cumulative incidence of fracture (proportion of adults who fractured (hip, forearm, pelvis, or proximal humerus) at least once within 3-years of follow-up). Additional analyses examined the fracture incidence per 1000 person-years, hip fracture alone, stratification by prior fracture, stratification by eGFR and proteinuria, and 3-year cumulative incidence of falls with hospitalization. The 3-year cumulative incidence of fracture significantly increased in a graded manner in adults with a lower eGFR for both genders and both age groups. The 3-year cumulative incidence of fracture in women over 65 years of age across the 5 eGFR groups were 4.3%, 5.8%, 6.5%, 7.8%, and 9.6%, respectively. Corresponding estimates for men over 65 years were 1.6%, 2.0%, 2.7%, 3.8%, and 5.0%, respectively. Similar graded relationships were found for falls with hospitalization and additional analyses. Thus, many adults with chronic kidney disease will fall and fracture. Results can be used for prognostication and guidance of sample size requirements for fracture prevention trials. [ABSTRACT FROM AUTHOR]

Intravenous bisphosphonates can cause acute kidney injury; however, this risk was not found with oral bisphosphonates in randomized clinical trials with restrictive eligibility criteria. In order to provide complementary safety data, we studied the risk of acute kidney injury in a population-based cohort of 122,727 patients aged 66 years and older discharged from hospital following a new fragility fracture and no history of bisphosphonate use in the prior year. Bisphosphonate treatment was identified within 120 days after discharge and event rates were measured from 90 days of therapy initiation. The primary outcome was hospitalization with acute kidney injury with secondary outcomes of new nephrology consultation and, in a subset of patients with laboratory values, acute kidney injury was defined as an increase in serum creatinine. We identified 18,286 bisphosphonate users and 104,441 non-users with a mean age of 81 years. Of 5772 patients with laboratory values, 40% had chronic kidney disease (eGFR <60 ml/min per 1.73 m2). Overall, there was no statistically significant difference in the risk of acute kidney injury among bisphosphonate users compared to non-users (adjusted odds ratio 1.03), and no significant differences in other outcomes or in subgroups of patients with baseline chronic kidney disease. Thus, in this older population-based cohort, oral bisphosphonate use was not associated with acute kidney injury. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about the existence of bias during prescription and over-the-counter calcium and vitamin D supplementation in older people with osteoporosis and fracture risk.

Abstract: Objective: To explore the “healthy user” and “healthy adherer” effects—hypothetical sources of bias thought to arise when patients who initiate and adhere to preventive therapies are more likely to engage in healthy behaviors than are other subjects. Methods: The authors examined the association between statin initiation and adherence, and the subsequent use of preventive health services and incidence of clinical outcomes unlikely to be associated with the need for, or use of, a statin among older enrollees in two state-sponsored drug benefit programs. Results: After adjustment for demographic and clinical covariates, patients who initiated statin use were more likely to receive recommended preventive services than noninitiators matched on age, sex, and state (hazard ratio [HR]: 1.10, 1.06–1.14 for males, HR: 1.09, 1.07–1.11 for females) and appeared to have a lower risk of a range of adverse outcomes (HR: 0.87, 0.85–0.89) thought to be unrelated to statin use. Adherence to a statin regimen was also associated with increased rates of preventive service use and a decreased rate of adverse clinical outcomes (HR: 0.93, 0.88–0.99). Conclusions: These results suggest that patients initiating and adhering to chronic preventive drug therapies are more likely to engage in other health-promoting behaviors. Failure to account for this relationship may introduce bias in any epidemiologic study evaluating the effect of a preventive therapy on clinical outcomes. [Copyright &y& Elsevier]

Background: Undertreatment of osteoporosis after hip or wrist fracture has been well documented, but the reasons for current patterns of care are poorly understood.Objective: We tested the role of physician and patient characteristics in predicting undertreatment when osteoporosis management was clearly indicated after a hip or wrist fracture in women over age 65.Methods: We assembled a cohort of 9,698 female Medicare beneficiaries aged > or = 65 years who experienced hip or wrist fracture between 2000 and 2004 and their prescribing physicians.Measurements: The dominant prescriber was identified as the physician prescribing at least 50% of patient prescriptions in the year after the fracture. Multivariate logistic regression estimated the role of physician and patient characteristics on osteoporosis management after hip or wrist fracture.Results: Patients older than 90 and black patients were less likely to be treated for osteoporosis relative to patients aged 65-69 and white patients. Female providers were more likely to manage osteoporosis. Models including patient characteristics discriminated well between managed and unmanaged patients (C statistic 0.81), while adding physician predictors to the model provided no additional discriminatory ability (C statistic 0.81).Conclusions: Our findings highlight that osteoporosis management rates are similar across providers, but vary considerably by patient types. [ABSTRACT FROM AUTHOR]

The article investigates the rate at which patients reinitiate treatment after long periods of nonadherence among users of statins in British Columbia. It also explores whether reinitiation of treatment is associated with potentially modifiable factors such as physician visits, or cholesterol testing. Results reveal that continuity of care combined with increased follow-up and cholesterol testing could promote long-term compliance by shortening or eradicating long gaps in statin use.

Presents letters to the editor. Response to an article about the use of antidepressant medication for chronic tension headaches; Who should be screened for osteoporosis; Discussion of studies regarding violence in children's films and video games; Others.

Background: There is ongoing controversy about who should be referred for bone mineral density (BMD) testing to estimate fracture risk and diagnose osteoporosis. The purpose of this study was to examine patterns of use of BMD testing in Ontario between 1992 and 1998. [ABSTRACT FROM AUTHOR]