Search

Purpose To assess prechemotherapy cardiac imaging practices in relation to patients’ heart failure (HF) risk. Methods We performed a population-based retrospective cohort study of women receiving chemotherapy for early-stage breast cancer in Ontario between 2007 and 2012. We surveyed for baseline cardiac imaging 6 months before chemotherapy or within 30 days thereafter. The proportion of patients who underwent imaging and cumulative incidence of major adverse cardiac event (MACE) rates was determined based on chemotherapy regimen and HF risk factors. Logistic regression was used to assess predictors of pretreatment cardiac imaging. Results We studied 18,444 women who had been treated with chemotherapy (median age, 55 years). There was near-universal imaging of women treated with trastuzumab-containing regimens, including those without additional HF risk factors. Women who received anthracyclines without trastuzumab underwent imaging more frequently if they had additional HF risk factors (73.3% v 62.6%; P < .001). The 5-year incidence of MACE was two to six times higher in patients with HF risk factors across all treatment regimens. Patients with HF risk factors who received anthracyclines without trastuzumab had a higher 5-year incidence of MACE (4.5%) than patients without HF risk factors who received trastuzumab without anthracyclines (2.6%). However, cardiac imaging was less frequent in the former group (73.3% v 93.6%; P < .001). Logistic regression indicated that most variation in baseline imaging was related to chemotherapy, followed by physician-level factors. The odds of imaging were doubled with female physicians. Patient-specific factors, including HF risk factors, made minimal contribution to variation in imaging. Conclusion Baseline cardiac imaging was driven by chemotherapy regimen rather than HF risk. This risk-imaging mismatch is an impetus to reconsider current cardiac imaging practices in patients who receive chemotherapy for breast cancer.

OBJECTIVE Women with breast cancer and diabetes face worse outcomes than those with breast cancer without diabetes; however, the contribution of comorbidity to these disparities remains unclear. We evaluated the impact of diabetes on receipt of cancer treatments as well as mortality while accounting for other comorbidities. RESEARCH DESIGN AND METHODS Ontario administrative databases were used to compare the rate of receipt of breast cancer treatments between women with and without diabetes. We also performed adjusted cause-specific hazard models to account for comorbidities when evaluating differences in treatments received and mortality outcomes between the two groups. RESULTS Women with diabetes and stage III breast cancer were slightly less likely to receive chemotherapy (relative risk [RR] 0.93 [95% CI 0.89–0.97]), although this difference was not significant when we adjusted for comorbidities (adjusted hazard ratio [aHR] 1.03 [95% CI 0.93–1.13]). We saw similar trends for receipt of guideline-adherent radiotherapy (RR 0.97 [0.95–0.99], aHR 0.98 [0.94–1.02]). All-cause mortality was increased in women with diabetes after adjusting for comorbidities (aHR 1.16 [1.06–1.27]), but breast cancer–specific mortality was not increased overall. Women with a longer duration of diabetes and those with preexisting cardiovascular disease had increased all-cause and cancer-specific mortality. CONCLUSIONS Although cancer treatments received were similar between women with and without diabetes, breast cancer–specific mortality remains higher among women with diabetes who have longer diabetes duration or preexisting cardiovascular disease. This study uncovers new information about key risk factors for poorer prognosis in women with diabetes and breast cancer.

BACKGROUND: In the United States, certain minority groups have been shown to have inferior cancer outcomes compared with the white majority population. However, to the authors' knowledge, the majority of research has not separated ethnicity from immigration status. The objective of the current study was to determine the impact of ethnicity, independent of immigration status, on cancer outcomes in Chinese and South Asian populations in Ontario, Canada. METHODS: The authors conducted a population-based retrospective cohort study using administrative databases in Ontario, Canada. Incident cancer cases were captured in Canadian-born Chinese and South Asian individuals, Chinese and South Asian immigrants, and the general Ontario reference population (non-Chinese/non-South Asian and non-immigrant) between 2000 and 2012. Subjects were followed until death (all-cause and cancer-specific), and Cox proportional hazard models were used to estimate the impact of Chinese and South Asian ethnicity on cancer outcomes after adjusting for explanatory variables. RESULTS: A total of 423,678 cancer cases were identified; at total of 6631 cases were identified in Canadian-born Chinese individuals and 2752 cases in Canadian-born South Asian individuals. After adjustment, the rate of all-cause mortality was lower for Canadian-born Chinese (hazard ratio [HR], 0.829; 95% confidence interval [95% CI], 0.795-0.865), Canadian-born South Asian (HR, 0.856; 95% CI, 0.797-0.919), and Chinese immigrant (recent immigrant: HR, 0.661 [95% CI, 0.610-0.716] and non-recent immigrant: HR, 0.853 [95% CI, 0.803-0.906]) populations compared with the general Ontario population. A similar effect was found for cancer-specific mortality. CONCLUSIONS: Chinese and South Asian ethnic groups appear to have lower cancer mortalities compared with the general Ontario population. After removing the well-documented protective effect of immigration, Chinese and South Asian ethnicities were found to be associated with a cancer survival advantage in Ontario, Canada. Cancer 2018;124:1473-82. © 2018 American Cancer Society.

Objective Lithium is an essential mood disorder treatment; however, it remains unclear whether lithium increases chronic kidney disease (CKD) risk. There are few data on this in the elderly, even though older adults may be particularly susceptible to CKD. We wished to determine whether lithium is associated with increased CKD risk relative to valproate in older adults. Methods This nested case-control study analyzed province-wide administrative health data from mental health service users aged ≥ 66 years in Ontario, Canada, from 2003 to 2014. Five-year incident CKD risk was compared in lithium users, valproate users, and patients who used neither medication. ICD-10 was used to assign CKD diagnosis. We used conditional logistic regression to control for hypertension, diabetes mellitus, acute kidney injury, medications associated with lithium toxicity, and other potential confounders. Results 21,741 cases and 86,930 age- and sex-matched controls were identified, including 529 lithium users and 498 valproate users. After controlling for confounders, we found that lithium use was associated with increased risk of incident CKD (adjusted odds ratio [OR] = 1.76 [95% CI, 1.41-2.19]), while valproate use was not (adjusted OR = 1.03 [95% CI, 0.81-1.29]). Conclusions Lithium is independently associated with an almost 2-fold increase in CKD risk in this community sample of older mental health service users. In the absence of clear information about certain contributing factors, such as inadequate monitoring and acute and chronic lithium level elevations, causes for this increase will need to be determined in future research.

There is limited information on stage at breast cancer diagnosis in Canadian immigrant women. We compared stage at diagnosis between immigrant women and Canadian-born women, and determined whether ethnicity was an independent factor associated with stage. 41,213 women with invasive breast cancer from 2007 to 2012 were identified from the Ontario Cancer Registry. Women were classified as either immigrants or Canadian-born by linkage with the Immigration, Refugees, and Citizenship Canada's Permanent Resident database. Women's ethnicity was classified as Chinese, South Asian, or remaining women in Ontario. Logistic regression was performed to calculate the odds ratio (OR) of being diagnosed at stage I breast cancer (versus stage II-IV). 4,353 (10.6%) women were immigrants and 36,860 (89.4%) were Canadian-born women. The mean age at breast cancer diagnosis was 53.5 years for immigrants versus 62.3 years for Canadian-born women (p < 0.0001). Immigrant women were less likely than Canadian-born women to be diagnosed with stage I breast cancers (adjusted OR = 0.85; 95% CI: 0.79-0.91; p < 0.0001). The adjusted OR of being stage I was 1.28 (95% CI: 1.14-1.43; p < 0.0001) for women of Chinese ethnicity and was 0.82 (95% CI: 0.70-0.96; p = 0.01) for women of South Asian ethnicity, compared to the remaining women in Ontario. Canadian immigrant women were less likely than Canadian-born women to be diagnosed with early-stage breast cancers. Ethnicity was a greater contributor to the stage disparity than was immigrant status. South Asian women, regardless of immigration status, might benefit from increased breast cancer awareness programs.

Key Points Question What are the population-based frequency, factors, and sex-specific differences in burdensome interventions and antibiotic therapy at the very end of life among nursing home residents with advanced dementia? Findings In this population-based cohort study of 27 243 decedent nursing home residents with advanced dementia, men were statistically significantly more likely than women to experience burdensome interventions (ie, transitions of care, invasive procedures, and physical restraints) and receive antibiotics; only a minority of residents saw a palliative care physician in the year before death, but those who did were significantly less likely to experience an end-of-life transition of care and to receive antibiotics. Meaning Study findings underscore the importance of sex-specific analysis in dementia research and the expanding roles of palliative care and antimicrobial stewardship in the nursing home setting., This population-based cohort study examines the sex-based variations in burdensome interventions (care transitions, invasive procedures, and use of physical restraints) and antibiotic therapy at the very end of life among nursing home residents with advanced dementia in Ontario, Canada., Importance Nursing home residents with advanced dementia have limited life expectancies yet are commonly subjected to burdensome interventions at the very end of life. Whether sex-specific differences in the receipt of these interventions exist and what levels of physical restraints and antibiotics are used in this terminal setting are unknown. Objective To evaluate the population-based frequency, factors, and sex differences in burdensome interventions and antibiotic therapy among nursing home residents with advanced dementia. Design, Setting, and Participants This population-based cohort study from Ontario, Canada, used linked administrative databases held at ICES, including the Continuing Care Resident Reporting System Long-Term Care database, which contains data from the Resident Assessment Instrument Minimum Data Set, version 2.0. Nursing home residents (n = 27 243) with advanced dementia who died between June 1, 2010, and March 31, 2015, at 66 years or older were included in the analysis. Initial statistical analysis was completed in May 2017, and analytical revisions were conducted from November 2018 to January 2019. Exposure Sex of the nursing home resident. Main Outcomes and Measures Burdensome interventions (transitions of care, invasive procedures, and physical restraints) and antibiotic therapy in the last 30 days of life. Results The final cohort included 27 243 nursing home residents with advanced dementia (19 363 [71.1%] women) who died between June 1, 2010, and March 31, 2015, at the median (interquartile range) age of 88 (83-92) years. In the last 30 days of life, burdensome interventions were common, especially among men: 5940 (21.8%) residents were hospitalized (3661 women [18.9%] vs 2279 men [28.9%]; P

OBJECTIVE Many patients with bipolar disorder are reaching old age, but whether they are receiving evidence-based psychotropic treatment remains unclear. Our objective was to describe current psychotropic prescribing patterns in a large Canadian late-life bipolar sample. METHODS Population-based cross-sectional study of 1443 bipolar disorder patients aged ≥ 66, discharged from a psychiatric hospitalization in Ontario, Canada from 1 April 2006 to 31 March 2012. We described psychotropic medication prescribing within 30 days post-discharge. RESULTS Prescription of ≥2 psychotropic medications was highly prevalent (81.5%). The most common medications were atypical antipsychotics (75.3%), benzodiazepines/zopiclone (42.3%), and antidepressants (38.5%), with less frequent use of valproate (35.4%) and lithium (23.4%). Only 1.4% of patients were on lithium monotherapy, while 4.4% and 15.7% of patients were on antidepressant or atypical antipsychotic monotherapy; 8.9% of all patients were using ≥2 atypical antipsychotics. CONCLUSIONS In clinical practice, older adults hospitalized with bipolar disorder are often prescribed multiple psychotropic medications upon discharge. In many instances, practices did not reflect bipolar treatment guidelines and may be putting patients at risk for poor physical health and psychiatric outcomes. One such example is the very infrequent use of lithium monotherapy. Future research should examine whether health system-wide protocolized late-life bipolar treatment may optimize prescribing to improve effectiveness and safety. Copyright © 2016 John Wiley & Sons, Ltd.

Aromatase inhibitors (AIs) may increase cardiovascular risk relative to tamoxifen in post-menopausal women with breast cancer. This risk has not been well-quantified outside of clinical trials.Observational population-based cohort study of women aged55 years diagnosed with stage I-III breast cancer between 2005 and 2010. Women treated with AIs or tamoxifen were followed to March 2012. The primary outcome was hospitalisation for myocardial infarction (MI). Cause-specific hazards were compared using tamoxifen as the reference group. Inverse probability of treatment weighting using the propensity score was used to reduce confounding due to measured baseline covariates. Results were confirmed using two cause-specific hazards models. Subgroup analyses included women aged ≥66 years, those with prior ischaemic heart disease, and a 'lower-risk group' aged74 years with stage I-II cancer and no prior ischaemic heart disease.In 7409 aromatase inhibitor-treated and 1941 tamoxifen-treated women, the median age was 71 versus 74 years, respectively (p 0.001). Baseline prevalence of ischaemic heart disease was similar (17.0% versus 16.9%, p = 0.96). Over a mean of 1184 d of follow-up, there were 123 hospitalisations for MI; the cause-specific hazard was higher with AIs (hazard ratio 2.02; 95% confidence interval 1.16-3.53 in the weighted sample). We observed comparable patterns within pre-defined subgroups and when adjusted using cause-specific hazards models.Aromatase inhibitors are associated with a higher risk of MI compared with tamoxifen. This risk should be accounted for when managing aromatase inhibitor-treated women.

We evaluated risk of adverse respiratory outcomes associated with incident opioid use among older adults with chronic obstructive pulmonary diseases (COPD).This was a retrospective population-based cohort study using a validated algorithm applied to health administrative data to identify adults aged 66 years and older with COPD. Inverse probability of treatment weighting using the propensity score was used to estimate hazard ratios comparing adverse respiratory outcomes within 30 days of incident opioid use compared to controls.Incident opioid use was associated with significantly increased emergency room visits for COPD or pneumonia (HR 1.14, 95% CI 1.00–1.29; p=0.04), COPD or pneumonia-related mortality (HR 2.16, 95% CI 1.61–2.88; pIncident opioid use, and in particular use of the generally more potent opioid-only agents, was associated with increased risk for adverse respiratory outcomes, including respiratory-related mortality, among older adults with COPD. Potential adverse respiratory outcomes should be considered when prescribing new opioids in this population.

BACKGROUND Diabetes is associated with an increased risk of several cancers; however, greater detection of cancer around the time of diabetes diagnosis may partly contribute to this relationship. The goal of the current study was to explore the temporal relationship between diabetes and cancer incidence. METHODS The authors conducted a retrospective, population-based cohort study of >1 million adults living in Ontario, Canada to evaluate the association between diabetes diagnosis and the incidence of cancer in 3 time periods: within the 10 years before a diabetes diagnosis, within the first 3 months after a diabetes diagnosis, and from 3 months to 10 years after a diabetes diagnosis. RESULTS Individuals with diabetes were significantly more likely to have been diagnosed with cancer within the 10 years before a diabetes diagnosis compared with individuals without diabetes (odds ratio, 1.23; 95% confidence interval [95% CI], 1.19-1.27). Cancer incidence also was found to be significantly higher in individuals with diabetes within the 3-month period after a diabetes diagnosis (hazard ratio, 1.62; 95% CI, 1.52-1.74), whereas the risk was not found to be elevated in the later period (hazard ratio, 0.97; 95% CI, 0.95-0.98). Similar trends were noted for individual cancers. CONCLUSIONS The results demonstrated that individuals with diabetes had a significantly higher risk of most cancers, which was limited to the time periods before and immediately after a diabetes diagnosis. The highest risk period was observed within the first 3 months after a diabetes diagnosis, suggesting a partial role of detection bias in the apparent relationship between diabetes and cancer. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2731–2738. © 2016 American Cancer Society.

Purpose Most women diagnosed with breast cancer are younger than 65 years of age. Population-based studies on cancer therapy–related cardiotoxicity have focused on older women. We sought to determine the risk of cardiotoxicity with breast cancer therapy in women with an age distribution representative of routine clinical practice. Methods This was a population-based retrospective cohort study including 14 regional cancer centers in Ontario, Canada. Adult women receiving chemotherapy for stage I to III breast cancer between 2007 and 2012 were included. Cancer treatment was categorized as follows: anthracycline-based chemotherapy without trastuzumab, trastuzumab with nonanthracycline chemotherapy, anthracyclines followed by trastuzumab (sequential therapy), and chemotherapy without anthracycline/trastuzumab (other chemotherapy). The primary outcome was a composite of hospitalization or emergency room visit for congestive heart failure (CHF), outpatient diagnosis of CHF, or cardiovascular death. A sensitivity analysis limited the outcomes to hospital-based CHF events. Cause-specific hazard models were used accounting for the competing risk of noncardiovascular death. Results Of 18,540 women included (median age, 54 years; interquartile range, 47 to 63 years), 79% were younger than age 65 years. The cumulative incidence of the primary outcome was 3.08% (95% CI, 2.81% to 3.36%) by 3 years of follow-up, whereas in an age-matched sample of Ontario women (n = 92,700) without breast cancer, it was 0.96% (95% CI, 0.89% to 1.04%). Compared with those receiving other chemotherapy, patients receiving trastuzumab with nonanthracycline chemotherapy and sequential therapy were at a higher risk of cardiotoxicity (hazard ratio, 1.76 [95% CI, 1.19 to 2.60] and 3.96 [95% CI, 3.01 to 5.22], respectively). Hospital-based CHF events were only increased with sequential therapy (hazard ratio, 1.86; 95% CI, 1.07 to 3.22). Conclusion In women with breast cancer and an age distribution representative of routine clinical practice, trastuzumab-based regimens, including those without anthracyclines, were associated with an increased risk of cardiotoxicity. Sequential therapy increased the risk of hospital-based CHF events.

Objective To test the hypothesis of an increased incidence of antiparkinson drug prescribing or Parkinson disease (PD) diagnostic codes after chronic lithium treatment compared with chronic valproic acid or antidepressant treatment among older adults. Methods A retrospective cohort study using healthcare administrative databases in Ontario, Canada included 1,749 lithium users, 1,787 valproic acid users, and 285,154 other antidepressant users ≥ 66 years old having used the drug continuously in monotherapy for at least 1 year. Outcome measures were start of (1) a dopaminergic medication (levodopa or a dopamine agonist), (2) any antiparkinson drug (levodopa, dopamine agonists, anticholinergic medication, amantadine, monoamine oxidase B inhibitors), (3) any antiparkinson drug or a diagnostic code for PD, and (4) any antiparkinson drug in the absence of a diagnostic code for PD. Results For patients with no previous antipsychotic use, lithium monotherapy was associated with an increased incidence of dopaminergic drug use (adjusted HR: 1.87; 95% CI: 1.06–3.30) and an increased incidence of antiparkinson drug use or a PD diagnosis (adjusted HR: 1. 68; 95% CI: 1.13–2.48) compared with antidepressant monotherapy. Conclusion Chronic lithium use is associated with an increased incidence of dopaminergic drug use compared with antidepressants, identifying a prescribing cascade related to lithium use in the elderly. Whether this reflects inappropriate treatment of action tremor or treatment of drug-induced parkinsonism should be addressed by a close examination of prescribing practices.

Medications used to manage a variety of clinical conditions (e.g., urinary incontinence, depression, Parkinson's disease) have anticholinergic effects that can cause adverse events, including cognitive decline.1, 2, 3, 4 The use of drug therapies that might worsen cognitive status is especially troubling in older adults with preexisting cognitive deficits and age‐related changes in pharmacodynamics that lead to heightened sensitivity to central anticholinergic adverse effects.5, 6 Although prescribing anticholinergic drugs to persons with dementia is generally considered inappropriate,7 it often happens in clinical practice.8, 9 Anticholinergic drug therapy combined with cholinesterase inhibitor drug therapy10 is particularly troubling. In this case, the directly opposing action of the anticholinergic drugs may reduce or eliminate the cognitive benefits gained from cholinesterase inhibitors.11 Efforts to identify drug therapies that are potentially inappropriate have largely targeted individual drug therapies12, 13 rather than considering the cumulative burden of different drugs with similar mechanisms of action. It is important to consider how overall drug burden may contribute to adverse events. Anticholinergic drug therapies with varying degrees of anticholinergic activity illustrate this situation. Although the anticholinergic effects of the individual drug therapies are important, estimating the cumulative anticholinergic burden from all prescribed drug therapies may more accurately predict the risk of adverse events. Having multiple prescribers has been linked to polypharmacy, potential drug interactions, and adverse events.14, 15, 16 Older adults with dementia and multiple comorbid conditions are particularly vulnerable to inadvertent prescription of inappropriate drug combinations because they often receive care from multiple physicians. Poor communication among physicians caring for the same individual may lead to prescription of inappropriate drug combinations from different sources. Through the Choosing Wisely campaign, the American Geriatrics Society suggests a medication review before starting any new drug therapy to improve the quality of prescribing in vulnerable elderly adults.17 Given the potential risks of anticholinergic drug use in older adults, a better understanding of the causes of frequent prescription is needed. The objective of this study was to examine the relationship between the number of physicians providing care and anticholinergic drug burden in older adults newly initiated on cholinesterase inhibitor therapy for dementia. It was hypothesized that having more physicians involved in care would be associated with greater risk of high anticholinergic drug burden.

Background Cancer screening aims to detect malignant disease early in its natural history when interventions might improve patient outcomes. Such benefits are unclear when screening occurs for patients with an existing high risk of death. Our aim was to study the extent of routine cancer screening for a new primary cancer in patients with existing metastatic cancer. Methods We used administrative databases from Ontario to identify a retrospective cohort of adults of eligible screening age (≥ 50 yr) who had a diagnosis of stage IV (metastatic) colorectal, lung, breast or prostate cancer between 2007 and 2012. We calculated the cumulative incidence of cancer screening over time for colorectal and breast cancer. Results Among the 20 992 patients with metastatic lung, breast or prostate cancer, 2.9%, 6.3% and 13.3% of patients, respectively, underwent testing for colorectal cancer within 1 year of cancer diagnosis. Within 3 years of diagnosis, rates reached 4.1%, 12.3% and 27.5%, respectively (8.5% of all patients). Incidence of colorectal cancer testing was higher among patients who received their diagnoses more recently compared with patients with diagnoses from earlier time periods (p = 0.0143). Among the 10 034 women with metastatic lung or colorectal cancer, 8.7% and 8.0% of patients, respectively, underwent breast cancer screening within 1 year of cancer diagnosis. Within 3 years of diagnosis, screening rates reached 10.2% and 13.1%, respectively. Interpretation Our findings indicate excessive rates of cancer screening among patients with metastatic cancer who are unlikely to benefit. Further studies are warranted to identify predictors for screening, resource implications, potential and real harms borne by patients, and the impact of a recent Choosing Wisely statement recommending against the practice.

Background Catheter ablation of ventricular tachycardia (VT) can reduce the burden of ventricular arrhythmia (VA) but its effect on health care utilization and costs after such therapy is poorly known. We sought to compare the rates of cardiovascular (CV)-related hospitalizations, survival, and health care costs in patients with recurrent VT treated either with VT ablation or with medical therapy. Methods One-hundred implantable cardioverter-defibrillator patients with structural heart disease who underwent VT ablation were included. Propensity score-matched patients with recurrent VT treated with medical therapy were identified from a prospective registry of approximately 7000 de novo implantable cardioverter-defibrillator patients. Outcomes and costs were ascertained using health administrative databases. Results Among patients who underwent VT ablation, the cumulative rates of VA-related hospitalizations were lower in the 2 years after their ablation procedure compared with the year before (rate ratio, 0.3; 95% confidence interval [CI], 0.22-0.43). Rates of CV-related hospitalization and hospitalization because of VA post index date were similar between the VT ablation and medical therapy groups (hazard ratio [HR], 0.94; 95% CI, 0.57-1.54 and HR, 1.04; 95% CI, 0.57-1.91, respectively). Health care costs in the VT ablation patients were not increased post-ablation compared with the medical management group. The risk of all-cause mortality was lower among patients in the VT ablation group relative to the medical therapy group (HR, 0.64; 95% CI, 0.4-0.99). Conclusions Patients who underwent VT ablation experienced a significant reduction in their rate of VA-related hospitalizations. Patients treated with VT ablation had similar rates of CV-related hospitalization compared with those treated with medical therapy without increased health care-related costs.

BACKGROUND: Starting insulin therapy in hospitalized patients may be associated with an increase in serious adverse events after discharge. OBJECTIVE: Determine whether post-discharge risks of death and rehospitalization are higher for older hospitalized patients prescribed new insulin therapy compared with oral hypoglycemic agents (OHAs). DESIGN: Retrospective population-based cohort study including hospital admissions in Ontario, Canada, between April 1, 2004, and Nov 30, 2013. PATIENTS: Persons aged 66 and over discharged after a hospitalization and dispensed a prescription for insulin and/or an OHA within 7 days of discharge. We included 104,525 individuals, subcategorized into four mutually exclusive exposure groups based on anti-hyperglycemic drug use in the 7 days post-discharge and the 365 days prior to the index admission. MAIN MEASURES: Prescriptions at discharge were categorized as new insulin (no insulin before admission), prevalent insulin (prescribed insulin before admission), new OHA(s) (no OHA or insulin before admission), and prevalent OHA (prescribed OHA only before admission) as the referent category. The primary and secondary outcomes were 30-day deaths and emergency department (ED) visits or readmissions respectively. KEY RESULTS: Of 104,525 patients, 9.2% were initiated on insulin, 4.1% died, and 26.2% had an ED visit or readmission within 30 days of discharge. Deaths occurred in 7.14% of new insulin users, 4.86% of prevalent insulin users, 3.25% of new OHA users, and 3.45% of prevalent OHA users. After adjustment for covariates, new insulin users had a significantly higher risk of death (adjusted hazard ratio (aHR) 1.59, 95% confidence interval (CI) 1.46 to 1.74) and ED visit/readmissions (aHR 1.17, 95% CI 1.12 to 1.22) than prevalent OHA users. CONCLUSIONS: Initiation of insulin therapy in older hospitalized patients is associated with a higher risk of death and ED visits/readmissions after discharge, highlighting a need for better transitional care of insulin-treated patients.

Patients receiving Bevacizumab, a vascular endothelial growth factor inhibitor used to treat metastatic colorectal cancer, may be at greater risk of complications after colorectal surgery because of impaired healing.The purpose of this study was to describe population-based rates of complications of colorectal surgery after Bevacizumab treatment and evaluate the relationship between time since last treatment and risk of complications.This was a population-based retrospective cohort study using administrative and cancer registry data.The study was conducted in Ontario, Canada.Patients with metastatic colorectal cancer receiving Bevacizumab between January 2008 and December 2011 were followed for a year after treatment or until death.Administrative data were used to identify patients who underwent colorectal surgery after initiation of Bevacizumab and to determine whether they experienced a complicated postoperative course. The relationship between time since last Bevacizumab treatment (≤28 d, 29 d to 3 mo, and3 mo) and risk of postoperative complications was evaluated using logistic regression.Of the 2759 patients who received Bevacizumab for the treatment of metastatic colorectal cancer, 265 underwent a colorectal procedure after exposure. The majority had a bowel resection or repair with no stoma (47.5%) and had emergency surgery (61.1%). Overall, 96 (36.2%) had a complicated postoperative course, including 20.4% readmission, 12.5% wound complications, and 7.9% mortality rate within 30 days of surgery. Adjusted multivariate analysis showed no difference in the likelihood of a complicated postoperative course among patients undergoing surgery within 28 days of receiving their last Bevacizumab dose compared with 29 days to 3 months (OR = 1.23 (95% CI, 0.53-2.84), or 3 to 12 months (OR = 0.98 (95% CI, 0.46-2.09) after receiving Bevacizumab.Reliance on administrative data to measure complications limited the scope of this study.Patients with metastatic colorectal cancer requiring colorectal surgery after exposure to Bevacizumab experience substantial morbidity and mortality. The risk of complications is not detectably associated with time since exposure. See Video Abstract at http://links.lww.com/DCR/A474.

Background Mucosal head and neck squamous cell cancers are often managed with multimodality treatment which can be associated with significant toxicity. The objective of this study was to assess emergency department visits and unplanned hospitalizations for these patients during and immediately after their treatment. Methods A cohort of patients treated for head and neck squamous cell carcinoma was developed using administrative data. Emergency department visits and hospitalizations in the 90-day post-treatment period was determined. If a second treatment was initiated prior to the completion of 90 days, the attributable risk period was changed to the second treatment. Results Cohort of 3898 patients (1312 larynx/hypopharynx; 2586 oral cavity/oropharynx) from 2008 to 2012. The number of unplanned hospitalizations or ED visits (per 100 patient days) were 0.69 for surgery, 0.78 for surgery followed by concurrent chemoradiotherapy (CCRT), 0.55 for surgery followed by radiotherapy, 0.86 for CCRT, and 0.50 for radiation. Patients receiving CCRT had a statistically higher likelihood of treatment period events. The larynx/hypopharynx cancer subsite, higher comorbidity and more advanced stage of disease were all independent predictors of events. Conclusions Patients undergoing treatment for head and neck cancer have significant unplanned hospitalizations and visits to the emergency department in the treatment period. Rates are higher in patients receiving CCRT. Quality improvement interventions should be used to improve these rates.

BackgroundA cancer diagnosis may disrupt diabetes management, increasing the risk of preventable complications. The objective was to determine whether a cancer diagnosis in patients with diabetes is associated with an increased risk of diabetic complications.MethodsThis retrospective cohort study using health care data from Ontario, Canada, included persons age 50 years or older diagnosed with diabetes from 2007 to 2011 and followed until 2014. We examined the effects of cancer as a time-varying covariate: breast cancer (in women), prostate cancer (in men), colorectal cancer, and other cancers (in men and women). Each cancer exposure was categorized as stage I–III, IV, or unknown, and by time since cancer diagnosis (0–1 year, >1–3 years, and >3 years). The primary outcome was hospital visits for diabetic emergencies. Secondary outcomes were hospital visits for skin and soft tissue infections and cardiovascular events.ResultsOf 817 060 patients with diabetes (mean age = 64.9 +/- 10.7 years), there were 9759 (1.2%) colorectal and 45 705 (5.6%) other cancers, 6714 (1.7%) breast cancers among 384 257 women and 10 331 (2.4%) prostate cancers among 432 803 men. For all cancers except stage I–III prostate cancer, rates of diabetic complications were significantly higher zero years to one year after diagnosis compared with no cancer (adjusted relative rates ranging from 1.26, 95% confidence interval [CI] = 1.08 to 1.49, to 4.07, 95% CI = 3.80 to 4.36); these differences were attenuated in the subsequent periods after cancer diagnosis.ConclusionsPatients with diabetes are at increased risk for preventable complications after a cancer diagnosis. Better diabetes care is needed during this vulnerable period.

Clinical outcomes after a hospital discharge are poorly defined for patients receiving maintenance in-center (outpatient) hemodialysis. To describe the proportion and characteristics of these patients who are rehospitalized, visit an emergency department, or die within 30 days after discharge from an acute hospitalization, we conducted a population-based study of all adult patients receiving maintenance in-center hemodialysis who were discharged between January 1, 2003, and December 31, 2011, from 157 acute care hospitals in Ontario, Canada. For patients with more than one hospitalization, we randomly selected a single hospitalization as the index hospitalization. Of the 11,177 patients included in the final cohort, 1926 (17%) were rehospitalized, 2971 (27%) were treated in the emergency department, and 840 (7.5%) died within 30 days of discharge. Complications of type 2 diabetes mellitus were the most common reason for rehospitalization, whereas heart failure was the most common reason for an emergency department visit. In multivariable analysis using a cause-specific Cox proportional hazards model, the following characteristics were associated with 30-day rehospitalization: older age, the number of hospital admissions in the preceding 6 months, the number of emergency department visits in the preceding 6 months, higher Charlson comorbidity index score, and the receipt of mechanical ventilation during the index hospitalization. Thus, a large proportion of patients receiving maintenance in-center hemodialysis will be readmitted or visit an emergency room within 30 days of an acute hospitalization. A focus on improving care transitions from the inpatient setting to the outpatient dialysis unit may improve outcomes and reduce healthcare costs.

Objective Bipolar disorder is associated with high rates of medical comorbidity, particularly in late life. Little is known about medical health service utilization and potential effects of bipolar pharmacotherapy. We hypothesized that lithium use would not be associated with higher rates of medical hospitalization. Methods Population-based retrospective cohort study of 1388 bipolar disorder patients aged ≥ 66 years discharged from a psychiatric hospitalization in Ontario, Canada, between 2006 and 2012. Patients were divided into lithium users, valproate users, and non-lithium/non-valproate users. The main outcome was acute non-psychiatric, medical/surgical hospitalization during 1-year follow-up. Results The rate of medical hospitalizations was 0.22 per patient-year. Time-to-medical hospitalization did not differ among lithium, valproate, and non-lithium/non-valproate users after adjusting for age, sex, past medical hospitalization, and antipsychotic use. Lithium, valproate, and non-lithium/non-valproate users did not differ markedly in terms of reason for medical hospitalization, 1-year acute medical health utilization outcomes, and medical comorbidity rates. Conclusion There were high rates of health service use for medical conditions among older adults with bipolar disorder, but this did not appear to be associated with lithium use, compared to valproate and other medication use (e.g., antipsychotics). A proactive collaborative care approach may prevent medical service utilization in severe late-life bipolar disorder.

Aims The purpose of the present study was to describe the scope, pattern and patient characteristics associated with incident opioid use among older adults with chronic obstructive pulmonary disease (COPD). Methods This was a retrospective population-based cohort study using Ontario, Canada, healthcare administrative data. Study participants were individuals aged 66 years and older with physician-diagnosed COPD, identified using a validated algorithm, who were not receiving palliative care. We examined the incidence of oral opioid receipt between 1 April 2003 and 31 March 2012, as well as several patterns of incident opioid drug use. Results Among 107 109 community-dwelling and 16 207 long-term care resident older adults with COPD, 72 962 (68.1%) and 8811 (54.4%), respectively, received an incident opioid drug during the observation period. Among long-term care residents, multiple opioid dispensings (8.8%), dispensings for >30 days' duration (up to 19.8%), second dispensings (35–43%) and early refills (24.2%) were observed. Incident opioid dispensing was also observed to occur during COPD exacerbations (6.9% among all long-term care residents; 18.1% among long-term care residents with frequent exacerbations). These same patterns of incident opioid use occurred among community-dwelling individuals, but with relatively lower frequencies. Conclusions New opioid use was high among older adults with COPD. Potential safety concerns are raised by the degree and pattern of new opioid use, but further studies are needed to evaluate if adverse events are associated with opioid drug use in this older and respiratory-vulnerable population.

Objective To evaluate the incidence, characteristics, and correlates of antidepressant drug therapy initiation among community-dwelling older adults following hip fracture. Design Retrospective cohort study using linked, population-based administrative data. Setting Province of Ontario, Canada. Participants Older adults, aged 65 years or older, with a hip fracture and hip fracture surgery between April 1, 2003, and February 28, 2011. The study sample was restricted to individuals who returned home following surgery and who had not been dispensed an antidepressant in the year prior to their fracture (N = 25,436). Measurements We determined the incidence of new antidepressant use defined by the dispensing of antidepressant drug therapy within 90 days of discharge home. We identified independent correlates of antidepressant initiation using multivariate regression. Results Overall, antidepressants were newly initiated in 8.8% of older adults with hip fracture in the 90 days following hospital discharge. There was a statistically significant, 1.3-fold increase in incidence of antidepressant prescribing from 2003 to 2010. Trazodone, frequently prescribed at a low dose, accounted for 39.0% of newly dispensed antidepressants, followed by selective serotonin reuptake inhibitors (36.9%). Rehabilitation admission, psychiatric evaluation, a diagnosis of dementia, and baseline benzodiazepine use were the strongest independent correlates of antidepressant initiation. Conclusion The period after a hip fracture is associated with a high rate of initiation of antidepressant therapy. The data raise the possibility that antidepressants are frequently prescribed off-label in these patients. Further research is needed to investigate the safety and efficacy of antidepressant use in this vulnerable population.

Background We sought to examine the mortality impact of appropriate implantable cardioverter defibrillator ( ICD ) therapy between patients who received ICD for primary versus secondary prevention purposes. Methods and Results From a prospective, population‐based registry, we identified 7020 patients who underwent de novo ICD implantation between February 2007 and May 2012 in Ontario, Canada. The primary outcome was all‐cause mortality. We used multivariable Cox proportional hazard modeling to adjust for differences in baseline characteristics and analyzed the mortality impact of first appropriate ICD therapy (shock and antitachycardia pacing [ ATP ]) as a time‐varying covariate. There were 1929 (27.5%) patients who received ICD s for secondary prevention purposes. The median follow‐up period was 5.02 years. Compared with those with secondary prevention ICD s, patients with primary prevention ICD s had more medical comorbidities, and lower ejection fraction. Patients who experienced appropriate ICD shock or ATP had greater risk of death compared with those who did not, irrespective of implant indication. In the primary prevention group, the adjusted hazard ratios of death for appropriate shock and ATP were 2.00 (95% CI : 1.72–2.33) and 1.73 (95% CI : 1.52–1.97), respectively. In the secondary prevention group, the adjusted hazard ratios of death for appropriate ICD shock and ATP were 1.46 (95% CI : 1.20–1.77) and 1.38 (95% CI : 1.16–1.64), respectively. Conclusions Despite having a more favorable clinical profile, occurrence of appropriate ICD shock or ATP in patients with secondary prevention ICD s was associated with similar magnitudes of mortality risk as those with primary prevention ICD s. A heightened degree of care is warranted for all patients who experience appropriate ICD shock or ATP therapy.

Background: Prior studies have documented inferior health outcomes in vulnerable populations, including racial minorities and those with disadvantaged socioeconomic status. The impact of immigration on cancer-related outcomes is less clear. Methods: Administrative databases were linked to create a cohort of incident cancer cases (colorectal, lung, prostate, head and neck, breast, and hematologic malignancies) from 2000 to 2012 in Ontario, Canada. Cancer patients who immigrated to Canada (from 1985 onward) were compared with those who were Canadian born (or immigrated before 1985). Patients were followed from diagnosis until death (cancer-specific or all-cause). Cox proportional hazards models were estimated to determine the impact of immigration on mortality after adjusting for explanatory variables. Additional adjusted models studied the relationship of time since immigration and cancer-specific and overall mortality. Results: From 2000 to 2012, 11,485 cancer cases were diagnosed in recent immigrants (0 to 10 years in Canada), 17,844 cases in nonrecent immigrants (11 to 25 years), and 416,118 cases in nonimmigrants. After adjustment, the hazard of mortality was lower for recent immigrants (hazard ratio [HR], 0.843; 95% CI, 0.814 to 0.873) and nonrecent immigrants (HR, 0.902; 95% CI, 0.876 to 0.928) compared with nonimmigrants. Cancer-specific mortality was also lower for recent immigrants (HR, 0.857; 95% CI, 0.823 to 0.893) and nonrecent immigrants (HR, 0.907; 95% CI, 0.875 to 0.94). Among immigrants, each year from the original landing was associated with increased mortality (HR, 1.004; 95% CI, 1.000 to 1.009) and a trend to increased cancer-specific mortality (HR, 1.005; 95% CI, 0.999 to 1.010). Conclusion: Immigrants demonstrate a healthy immigrant effect, with lower cancer-specific mortality compared with Canadian-born individuals. This benefit seems to diminish over time, as the survival of immigrants from common cancers potentially converges with the Canadian norm.

Objectives To determine the prevalence of and resident characteristics associated with the prescription of medications of questionable benefit (MQBs) near the end of life in older adults with advanced dementia in nursing homes. Design Population-based, cross-sectional study using Resident Assessment Instrument Minimum Data Set 2.0 linked to health administrative data. Setting Ontario, Canada. Participants All 9,298 nursing home residents with advanced dementia who died between June 1, 2010, and March 31, 2013; were aged 66 and older at time of death; and received at least one MQB in their last year of life. Measurements Prevalence of eight classes of MQBs (e.g., lipid-lowering agents, antidementia drugs) used in the last 120 days and last week of life. Results Of older nursing home residents with advanced dementia who received at least one MQB in the last year of life, 8,027 (86.3%) received them in the last 120 days and 4,180 (45.0%) in the last week of life. The most commonly prescribed MQB were antidementia (63.6%) and lipid-lowering agents (47.8%). Severe cognitive impairment (adjusted odds ratio (aOR) = 1.19, 95% confidence interval (CI) = 1.07–1.33, P = .002) and fewer signs and symptoms of health instability (aOR = 1.58, 95% CI = 1.44–1.74, P < .001) were associated with MQB use into the last week of life. Seeing a neurologist or psychiatrist was associated with less likelihood of MQB use in the last week of life. Conclusion Many nursing home residents with advanced dementia are dispensed MQBs in the last week of life. Given that MQBs may cause more harm than benefit in this vulnerable population, it is important for physicians to actively reassess the role of all medications toward the end of life.

Objective Lithium is an important treatment for mood disorders, but concern about its association with renal disease has contributed to its limited use, particularly in older adults. Because high-quality evidence examining renal disease in this population is lacking, this study aims to quantify the prevalence and identify clinical correlates of renal disease in geriatric lithium users. Methods In a population-based cross-sectional study on 2,480 lithium users aged 70 or more years, the authors searched the provincial administrative health data from Ontario, Canada between April 1, 2005 and March 31, 2011. Prevalence of chronic kidney disease (CKD), acute kidney injury (AKI), and nephrogenic diabetes insipidus (NDI) was measured using International Classification of Diseases, Tenth Revision codes. Logistic regression analyses were used to identify independent correlates of renal disease. Results The 6-year prevalence rates of CKD, AKI, and NDI were 13.9%, 1.3%, and 3.0%, respectively. Hypertension (odds ratio [OR]: 2.05; 95% confidence interval [CI]: 1.50–2.79), diabetes mellitus (OR: 1.86; 95% CI: 1.45–2.38), ischemic heart disease (OR: 1.65; 95% CI: 1.24–2.20), NDI (OR: 2.54; 95% CI: 1.47–4.40), AKI (OR: 11.7; 95% CI: 5.26–26.1), lithium use for more than 2 years (OR: 1.71; 95% CI: 1.05–2.81), loop diuretic use (OR: 1.74; 95% CI: 1.26–2.41), hydrochlorothiazide use (OR: 1.48; 95% CI: 1.07–2.05), and atypical antipsychotic use (OR: 1.49; 95% CI: 1.17–1.89) were all independently associated with CKD. Conclusion Older lithium users have high rates of CKD. Lithium use duration was independently associated with CKD. Longitudinal studies including individuals without lithium exposure will be necessary to confirm whether lithium is indeed a risk factor for CKD in older adults.

Our purpose was to evaluate the association of new benzodiazepine use relative to non-use with adverse clinical respiratory outcomes among older adults with chronic obstructive pulmonary disease (COPD). This was a retrospective population-based cohort study of Ontario, Canada, residents between 2003 and 2010. A validated algorithm was applied to health administrative data to identify adults aged 66 years and older with COPD. Relative risks (RRs) of several clinically important respiratory outcomes were examined within 30 days of incident benzodiazepine use compared with non-use, applying propensity score matching. New benzodiazepine users were at significantly higher risk for outpatient respiratory exacerbations (RR 1.45, 95% CI 1.36-1.54) and emergency room visits for COPD or pneumonia (RR 1.92, 95% CI 1.69-2.18) compared to non-users. Risk of hospitalisation for COPD or pneumonia was also increased in benzodiazepine users, but was nonsignificant (RR 1.09, 95% CI 1.00-1.20). There were no significant differences in intensive care unit admissions between the two groups and all-cause mortality was slightly lower among new versus non-users. Benzodiazepines were associated with increased risk for several serious adverse respiratory outcomes among older adults with COPD. The findings suggest that decisions to use benzodiazepines in older patients with COPD need to consider potential adverse respiratory outcomes.

Objectives: To understand how drug therapy differently affects older women and men. Design: Population-based, retrospective cohort study. Setting: Ontario, Canada. Participants: Twenty-one thousand five hundred twenty-six older adults (13,760 women, 7,766 men) with dementia newly started on oral atypical antipsychotic therapy between April 1, 2007, and March 1, 2010. Measurements: Numbers and rates of serious events. Serious events were defined as a hospital admission or death within 30 days of treatment initiation. Unadjusted and adjusted odds ratios of women and men were compared in the full cohort and in strata based on setting of care, age, Charlson Comorbidity Index (CCI), and antipsychotic dose. Results: Of 21,526 older adults with a median age of 84, 1,889 (8.8%) had a serious event (1,044 women, 7.6%; 845 men, 10.9%). Of these, 363 women (2.6%) and 355 men (4.6%) died. Men were more likely than women to be hospitalized or die during the 30-day follow-up period (adjusted odds ratio = 1.47, 95% confidence interval = 1.33�1.62) and consistently more likely to experience a serious event in each stratum. A gradient of risk according to drug dose was found for the development of a serious event in women and men. Conclusion: The risk of developing a serious event shortly after the initiation of antipsychotic therapy was high in women and men with dementia but was consistently higher in older men. This pattern remained the same in strata based on setting of care, age, CCI, and antipsychotic dose.

The addition of oxaliplatin to adjuvant treatment regimens for colorectal cancer has been shown to improve overall survival at the expense of increased toxicity. The incidence and severity of toxicity might be greater among older patients who might also derive less benefit from oxaliplatin. We evaluated the association between adjuvant oxaliplatin-based chemotherapy and neurotoxicity outcomes in an elderly cohort of patients.A population-based cohort of patients aged65 years with stage II and III colorectal cancer treated with adjuvant therapy in Ontario, Canada was identified using the Ontario Cancer Registry. Cause-specific hazard models were used to estimate the effect of oxaliplatin exposure on the cause-specific hazard ratio (CHR) of peripheral neuropathy after accounting for the competing risk of death.We identified 3607 patients aged65 years with stage II and III colorectal cancer. Of these patients, 1541 (43%) had been treated with an oxaliplatin-based regimen. Compared with subjects receiving non-oxaliplatin-based regimens, patients aged ≥ 70 years at the time of cancer diagnosis who are subsequently treated with oxaliplatin were more likely to develop peripheral neuropathy (CHR, 2.3; 95% confidence interval [CI], 1.53-3.35; P .0001). This association was not significant in patients aged 66 to 69 years (CHR, 0.93; 95% CI, 0.50-1.72; P = .812). Formal interaction testing confirmed that the effect of oxaliplatin on neuropathy was more pronounced in patients aged ≥ 70 years compared with patients aged 66 to 69 years (P = .03).Colorectal cancer patients aged ≥ 70 years at the time of cancer diagnosis who are subsequently treated with oxaliplatin have a significant risk of developing peripheral neuropathy. This should be considered in clinical decision making, especially because of the limited data supporting an oxaliplatin benefit in this age group.

Women with diabetes have a higher breast cancer incidence and mortality. They are also significantly less likely to undergo screening mammography and present with more advanced stage than women without diabetes. The purpose of this study was to examine if women with diabetes are more likely to have delays in follow‐up of abnormal mammograms, compared to women without diabetes. Using population‐based health databases, this retrospective cohort study examined women between the ages of 50 and 74, with and without diabetes, living in the province of Ontario, Canada, who underwent screening through a centralized program and who had an abnormal mammogram between 2003 and 2012. We compared rates of follow‐up of a diagnostic test within 180 days, as well as likelihood of mastectomy or excision procedure and a diagnosis of breast cancer. Following an abnormal screening mammogram, 97.5% of women with diabetes had a diagnostic procedure within 180 days compared to 97.9% of women without diabetes. After adjustment for other factors, women with diabetes were only 3% less likely to have follow‐up testing after an abnormal mammogram than women without diabetes (hazard ratio [HR] 0.97, 95% CI: 0.96–0.99, P

Inhaled, long-acting anticholinergic medication (LAA), commonly used for moderate-to-severe chronic obstructive pulmonary disease (COPD), has been shown to decrease COPD hospitalizations, emergency department visits, and acute exacerbations but has also been associated with urinary tract infection (UTI) in a prior meta-analysis. The objective of this study was to verify if there was an association between LAA and UTI in older individuals with COPD. A population-based, real-world cohort study using health administrative data from Ontario, Canada was conducted. Incidence of UTI was compared between older people with physician-diagnosed COPD, who were new users of inhaled long-acting anticholinergics and new users of inhaled corticosteroids–a reference medication used in similar clinical settings that has no known association with UTI. Propensity score matching was used to minimize the effects of confounding. An overall association between LAA and various measures of UTI in older individuals was not found. However, in a priori defined stratified analyses, men newly initiated on LAA were 75% more likely to develop a UTI than men newly started on an inhaled corticosteroid (hazard ratio 1.75; 95% confidence interval 1.05–2.92). No significant association was seen in women. In conclusion, older men with COPD newly started on LAA are at increased risk of UTI. Men considering an inhaled LAA should be informed of this risk and, if they decide to take it, be provided with appropriate monitoring.

Donepezil is a commonly used drug in older people that due to its procholinergic effects can provoke bradycardia and neurocardiogenic syncope. Donepezil is metabolized by the cytochrome P450 isozyme 3A4 (CYP3A4). Clarithromycin is a potent inhibitor of CYP3A4, and patients taking both of these drugs may be at increased risk of cardiac adverse events.The aim of this study was to evaluate the association between recent use of clarithromycin and adverse cardiovascular events in elderly patients receiving donepezil.A population-based, nested case-control study using provincial healthcare databases was conducted. The base cohort was made up of persons 66 years of age or older who were prescribed donepezil and also were prescribed clarithromycin, erythromycin, azithromycin, cefuroxime, moxifloxacin or levofloxacin. Cases were those members of the base cohort hospitalized for bradycardia, syncope or complete atrioventricular block. For each case patient, five controls were matched according to age, sex and residence (community or long-term care).Between July 2002 and March 2010, 17,712 patients continuously receiving donepezil were prescribed one of the antibacterials. In 1400 person-years of follow-up, 59 cases were identified. As compared with azithromycin, there was no statistically significant association between use of clarithromycin in donepezil users and subsequent adverse cardiovascular events (odds ratio 0.67; 95% CI 0.28, 1.63). There was no significant risk associated with exposure to either cefuroxime or respiratory quinolones.The use of clarithromycin in elderly donepezil users did not significantly increase the risk of adverse cardiovascular outcomes. However, our study cannot rule out a possible small increase in risk. Although antibacterials can be beneficial, care should be taken in selecting antibacterials for use in older people receiving donepezil.

Older nursing home residents with advanced dementia have limited life expectancies. These individuals often receive intensive medical care towards the end-of-life thereby incurring burdensome interventions and antimicrobials of questionable benefit. We aimed to describe the frequency, nature, and predictors of burdensome interventions and antimicrobials received by Ontario nursing home residents with advanced dementia during the last 30 days of life. A population-based retrospective cohort study was conducted using linked administrative records. Logistic regression was used to determine the patient and facility characteristics associated with receipt of burdensome interventions. We included 27,243 Ontario nursing home residents with advanced dementia who died between June 2010 and March 2015. The majority (71.1%) were women and the average age of death was 87.1 ± 7.2 years. Nearly half (46.8%) were dependent for their basic activities of daily living with 8.1% being totally bedbound. In the last 30 days of life, 21.8% were hospitalized, 8.9% visited an emergency department, and 9.8% received medical resuscitation. More than 1 in 3 (36.2%) were dispensed an antibiotic, and 86.6% of residents received a physical restraint. Male sex, fewer days in nursing home prior to death, and lower income were all independently associated with transfer to acute care and medical resuscitation, while palliative care consultation, bedbound status, and older age were negative predictors. We conclude that many older Ontario nursing home residents with advanced dementia receive burdensome interventions and antimicrobial agents at the end-of-life. The provision of care for these patients must align with their life expectancies and goals of care.

Objective To determine whether current antipsychotic use among older persons without diabetes is associated with a higher risk of hospital visits for hyperglycemia, as previous studies in this population have yielded conflicting results. Design, Setting and Participants A nested case-control study within a population-based cohort of persons aged 66 years or older without diabetes, who initiated antipsychotic therapy between April 1, 2002, and March 31, 2006. Cohort members were identified using health databases from Ontario, Canada, and were followed from treatment start until March 31, 2007. Measurements Cases were patients with a hospital visit (emergency department visit or hospital admission) for hyperglycemia. We matched each case with up to 10 controls. We compared the risk of hyperglycemia among current antipsychotic users to that of remote users (discontinued > 180 days). Results The cohort consisted of 44,121 subjects, mean age of 78.3 years, followed for a mean of 2.2 years. Compared to remote antipsychotic use, current treatment with any antipsychotic was associated with a significantly increased risk of hospital visits for hyperglycemia (adjusted odds ratio [aOR]: 1.52; 95% confidence interval [CI]: 1.07–2.17). The risk was elevated for both atypical (aOR: 1.44; 95% CI: 1.01–2.07) and typical (aOR: 2.86; 95% CI: 1.46–5.59) antipsychotic agents. Conclusions Current use of either atypical or typical antipsychotic agents was associated with a significantly increased risk of hospital visits for hyperglycemia among older persons without diabetes. These findings highlight the need for close glucose monitoring during antipsychotic therapy in older populations.

Evaluation and optimization of antibiotic use (antibiotic stewardship) is being increasingly promoted as a means to reduce antibiotic resistance, adverse events, treatment complications and costs within institutions. Our goal was to examine the prevalence of antibiotic use among long-term care facility residents and the extent of variability across these institutions.We conducted a population-based, point-prevalence study of antibiotic use among elderly individuals (n = 37,371) residing in long-term care facilities (n = 363 institutions) in Ontario between April and June 2009, using linked healthcare databases from Canada's largest province. Facilities were grouped into quintiles according to their mean antibiotic dispensing rates and variation was compared across quintiles.There were 2190 (5.9%) long-term care residents receiving antibiotic prescriptions on the study date. The three most prevalent antibiotics were agents most commonly used for the treatment of urinary tract infections, including nitrofurantoin (365, 15.4%), trimethoprim/sulfamethoxazole (338, 14.3%) and ciprofloxacin (304, 12.8%). The majority of treatment courses were at least 10 days in duration (1482, 62.6%), and many exceeded 90 days (495, 20.9%), suggesting chronic prophylaxis. There was substantial variability in antibiotic use across facilities, with a 5-fold variation from the highest-use quintile (10.8%) to the lowest-use quintile (2.2%). This variation persisted after adjustment for multiple facility-level and resident-level factors, including demographic characteristics, healthcare utilization statistics, co-morbidity prevalence, functional status and device dependence.Antibiotic use is common among long-term care residents, variable across institutions, and may benefit from focused antimicrobial stewardship interventions to standardize treatment indications and duration.

Purpose An intermediary falls within the exposure–outcome pathway and is distinct from a confounder. In case–control studies, it may be difficult to discern between the two when both are measured by the same variable. Using data from a study on the effects of antipsychotic initiation on risk of death among older adults, where hospital use is both a confounder and intermediary, we illustrate the bias introduced when this distinction is overlooked and propose a modified exposure classification strategy to mitigate this. Methods We identified 5391 cases and 25 937 controls. Three analyses were completed: traditional analytic adjustment including hospital use (full), traditional analytic adjustment excluding hospital use (reduced) and exposure classification incorporating hospital use prior to antipsychotic initiation (extended). Results The unadjusted odds ratio (OR) was 2.8 (95% confidence interval (CI) 2.1–3.8). Full and reduced analytic adjustment resulted in ORs of 0.8 (95% CI 0.6–1.2) and 1.4 (95% CI 1.0–1.9), respectively. The extended exposure classification strategy produced an OR of 1.4 (95% CI 0.9–2.1) among those without hospital use prior to antipsychotic initiation. Conclusions Full analytic adjustment resulted in a biased estimate of effect. The extended exposure analysis differentiated between hospital use that occurred prior (confounder) and subsequent (intermediary) to antipsychotic initiation. This strategy may overcome the limitations of analytic adjustment alone. Copyright © 2010 John Wiley & Sons, Ltd.

This cohort study examines recurrence outcomes in patients with fully resected gastroenteropancreatic neuroendocrine tumors.

Objective To determine the prescription pattern and safety profile for irreversible monoamine oxidase inhibitors (MAOIs) in older adults over the past decade. Method A population-based observational cohort study of older adults was conducted from January 1, 1997, to April 14, 2007, utilizing large administrative health care databases in Ontario, Canada. We examined the prevalence and incidence of irreversible MAOI use, as well as the frequency of coprescribing of MAOIs with contraindicated medications such as serotonergic and sympathomimetic drugs. We reviewed the most responsible diagnosis of emergency department (ED) visits and acute care admissions to assess for serious adverse events that may occur during MAOI treatment (ie, serotonin syndrome and hypertensive crisis). Results Over a 10-year period, there were 348 new users of irreversible MAOIs. The majority of patients showed a previous treatment pattern consistent with recurrent major depressive disorder, including prior use of antidepressant treatment and electroconvulsive therapy. The yearly incidence of MAOI prescriptions remained low and decreased from a rate of 3.1/100,000 to 1.4/100,000. Concomitant exposure to at least 1 serotonergic drug occurred in 18.1% of patients treated with an MAOI. No ED visits or acute care admissions for serotonin syndrome or hypertensive crisis were identified. Conclusions The low prescription rate of MAOIs is not consistent with the continued recommendation of MAOIs by expert opinion leaders and consensus guidelines for use in atypical depression and treatment-refractory depression. While their use appeared safe, heightened awareness of the potential risk of concomitant use of serotonergic agents is necessary. Relative underuse of the MAOIs for a significant subgroup of depressed patients with atypical and treatment-refractory depression remains a concern.

OBJECTIVES: To examine current utilization patterns of cholinesterase inhibitor (ChEI) therapy for dementia to determine treatment duration, use in long-term care, how often patients receive these drugs until death, and frequency of switching between the available ChEIs. DESIGN: A population-based healthcare administrative database study. SETTING: Patients aged 66 and older from the Canadian province of Ontario who received a new prescription for a ChEI between June 1, 2000, and December 31, 2002. Patients were followed until discontinuation of ChEI therapy, death, or end of the observation period (March 31, 2005). PARTICIPANTS: Twenty-eight thousand nine hundred and sixty-one patients, including 4,601 residing in long-term care, mean age 80, 63% female. MEASUREMENTS: Information on diagnosis, medical comorbidity, physician visits, and concomitant medication use was obtained. Estimates of duration of continuous use were determined. The percentage of patients who remained on the initial dose prescribed, the proportion who switched to a second ChEI, and the percentage who remained on ChEIs until death were calculated. RESULTS: Patients had on average more than 26 physician visits in the year before ChEI therapy, but only 28% had seen a dementia specialist. Concomitant use of potentially inappropriate medications (strongly anticholinergic medications and benzodiazepines) was noted in 37% of patients. The average length of treatment for all patients was 866 days. Many patients (43%) remained on the initial dose prescribed, 6% switched to another ChEI, and 19% died while on ChEI therapy. CONCLUSION: Elderly patients with dementia are treated for lengthy periods of time with ChEIs in the community and in long-term care facilities. Further research is required to determine whether these utilization patterns are appropriate. It is also unclear whether these results are generalizable to other populations without universal health coverage or drug formulary benefits.

Patients are vulnerable to medication-related errors during transitions in care. Patients discharged from acute care hospitals may be at an elevated risk for the unintentional continuation of medications prescribed to prevent or treat complications that are associated with acute illness but are no longer indicated. We sought to evaluate rates of (primary objective) and risk factors for (secondary objective) potentially unintentional medication continuation following hospitalization. A population-based cohort study of more than one million patients 66 years of age or older who were hospitalized in Ontario, Canada, between 2003 and 2011 and followed for 1 year (2004 to 2012). We created distinct cohorts by identifying seniors not previously receiving four classes of medications typically used to treat or prevent complications of acute illness: (1) antipsychotic medications, (2) gastric acid suppressants (histamine-2 blockers and proton pump inhibitors), (3) benzodiazepines, and (4) inhaled bronchodilators and steroids. After excluding documented indications, we followed patients to ascertain whether these medications were continued after hospital discharge, and assessed risk factors for their continuation using generalized estimating equations. The primary outcome was the new dispensation of any of the selected medications within 7 days of hospital discharge. Prescription without documented indication occurred across all medication classes, from 12,209 patients (1.4 %) for antipsychotic medications to 34,140 patients (6.1 %) for gastric acid suppressants. Risk factors for unintentional continuation varied across medication groups, but rates were consistently higher for older patients, those with multiple comorbidities, and emergency hospitalizations. The largest absolute risk factor across all medications was a hospitalization > 7 days [OR 2.03 (95 % CI 1.94–2.11) for respiratory inhalers, 6.35 (95 % CI 5.91–6.82) for antipsychotic medications]. These medications were often continued at 1 year of follow-up, and accounted for a total additional medication cost of over CAD$18 million for the study population. Discharged patients are at risk of being prescribed and dispensed medications that are typically intended to prevent or treat complications of acute illness, despite having no documented indication for chronic use.

Supplemental Digital Content is available in the text, Transitions of care leave patients vulnerable to the unintentional discontinuation of medications with proven efficacy for treating chronic diseases. Older adults residing in nursing homes may be especially susceptible to this preventable adverse event. The effect of large-scale policy changes on improving this practice is unknown. The objective of this study was to analyze the effect of a national medication reconciliation accreditation requirement for nursing homes on rates of unintentional medication discontinuation after hospital discharge. It was a population-based retrospective cohort study that used linked administrative records between 2003 and 2012 of all hospitalizations in Ontario, Canada. We identified nursing home residents aged ≥66 years who had continuous use of ≥1 of the 3 selected medications for chronic disease: levothyroxine, HMG-CoA reductase inhibitors (statins), and proton pump inhibitors (PPIs). In 2008 medication reconciliation became a required practice for accreditation of Canadian nursing homes. The main outcome measures included the proportion of patients who restarted the medication of interest after hospital discharge at 7 days. We also performed a time series analysis to examine the impact of the accreditation requirement on rates of unintentional medication discontinuation. The study included 113,088 adults aged ≥66 years who were nursing home residents, had an acute hospitalization, and were discharged alive to the same nursing home. Overall rates of discontinuation at 7-days after hospital discharge were highest in 2003–2004 for all nursing homes: 23.9% for thyroxine, 26.4% for statins, and 23.9% for PPIs. In most of the cases, these overall rates decreased annually and were lowest in 2011–2012: 4.0% for thyroxine, 10.6% for statins, and 8.3% for PPIs. The time series analysis found that nursing home accreditation did not significantly lower medication discontinuation rates for any of the 3 drug groups. From 2003 to 2012, there were marked improvements in rates of unintentional medication discontinuation among hospitalized older adults who were admitted from and discharged to nursing homes. This change was not directly associated with the new medication reconciliation accreditation requirement, but the overall improvements observed may have been reflective of multiple processes and not 1 individual intervention.

Background: A higher risk of colorectal cancer (CRC) in patients with diabetes has been well documented. However, little is known regarding diabetes incidence in CRC survivors. This may have substantial impact on CRC survivorship care as well as enhancing the understanding of the interplay between the two diseases. We explored whether the incidence of diabetes was higher among patients with CRC than matched control subjects. Methods: Using population-based data from Ontario, Canada, we generated a dataset comprising 39 707 incident CRC cases and 198 535 age-and sex-matched control subjects (1:5) dating from April 2002 to March 2010. We used cause-specific hazard models to estimate the hazard ratios (HRs) for diabetes overall and in subgroups stratified by receipt of systemic chemotherapy, diagnosis of metastatic disease, and site of cancer. Results: During a mean follow-up of 4.81 years, the association between CRC and diabetes varied: The rate of developing diabetes was 53% higher among CRC patients compared with control subjects in the first year postdiagnosis (HR = 1.53, 95% confidence interval [CI] = 1.42 to 1.64) and remained increased by 19% in the fifth year postdiagnosis (HR = 1.19, 95% CI = 1.05 to 1.35). Findings were similar in subgroups of patients who had colon cancer, received systemic chemotherapy, or had no evidence of metastasis. Conclusion: We found that CRC patients were statistically significantly more likely to develop subsequent diabetes than persons without CRC for up to five years after the diagnosis. Our study suggests that active screening and counseling regarding modifiable risk factors may be warranted in this high-risk group.

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

PurposeMost women diagnosed with breast cancer are younger than 65 years of age. Population-based studies on cancer therapy–related cardiotoxicity have focused on older women. We sought to determine the risk of cardiotoxicity with breast cancer therapy in women with an age distribution representative of routine clinical practice.MethodsThis was a population-based retrospective cohort study including 14 regional cancer centers in Ontario, Canada. Adult women receiving chemotherapy for stage I to III breast cancer between 2007 and 2012 were included. Cancer treatment was categorized as follows: anthracycline-based chemotherapy without trastuzumab, trastuzumab with nonanthracycline chemotherapy, anthracyclines followed by trastuzumab (sequential therapy), and chemotherapy without anthracycline/trastuzumab (other chemotherapy). The primary outcome was a composite of hospitalization or emergency room visit for congestive heart failure (CHF), outpatient diagnosis of CHF, or cardiovascular death. A sensitivity a...

Women with diabetes have higher breast cancer incidence and mortality. The purpose of this study was to examine the impact of diabetes on stage at breast cancer diagnosis, as a possible reason for their higher mortality. Using population-based health databases from Ontario, Canada, this retrospective cohort study examined stage at diagnosis (II, III, or IV vs I) among women aged 20–105 years who were newly diagnosed with invasive breast cancer between 2007 and 2012. We compared those with diabetes to those without diabetes. Diabetes was defined based on medical records using a validated algorithm. Among 38,407 women with breast cancer, 6115 (15.9 %) women had diabetes. Breast cancer patients with diabetes were significantly more likely to present with advanced-stage breast cancer than those without diabetes. After adjustment for mammograms and other covariates, diabetes was associated with a significantly increased risk of Stage II [adjusted odds ratio (aOR) 1.14, 95 % confidence interval (CI) 1.07, 1.22], Stage III (aOR 1.21, 95 % CI 1.11, 1.33), and Stage IV (aOR 1.16, 95 % CI 1.01, 1.33) versus Stage I breast cancer. Women with diabetes had a higher risk of lymph node metastases (aOR 1.16, 95 % CI 1.06, 1.27) and tumors with size over 2 cm (aOR 1.16, 95 % CI 1.06, 1.28). Diabetes was associated with more advanced-stage breast cancer, even after accounting for differences in screening mammogram use and other factors. Our findings suggest that diabetes may predispose to more aggressive breast cancer, which may be a contributor to their higher cancer mortality.

Domperidone is commonly used to treat nausea and gastrointestinal disorders. Recent data suggests that it may increase the risk of sudden cardiac death, particularly in older people. Little is known about how it is used in contemporary practice. This study sought to characterize the population of older adults newly dispensed domperidone, describe dosages of domperidone used, and determine the frequency of co-prescribing domperidone with medications that may increase the arrhythmogenic potential of domperidone. This is a retrospective cohort study using administrative health database information from Ontario, Canada. Prescription medication records were obtained from the Ontario Drug Benefit Claims Database. Diagnostic codes were obtained from the Ontario Health Insurance Plan Database, the Canadian Institute for Health Information Discharge Abstract Database, and the same-day surgery database. Patients who received a new prescription for domperidone between April 1, 2003 and March 31, 2010 were included. A total of 122,233 patients met inclusion criteria; 85 % were between 66 and 84 years old and 63 % were female. The mean estimated daily domperidone dose was 35 mg, and the estimated daily dose was

Objectives To better understand how centenarians use the healthcare system as an important step toward improving their service delivery. Desig Population-based retrospective cohort study using linked health administrative data. Setting Ontario�Canada's largest province. Participants All individuals living in Ontario aged 65 and older on April 1 of each year between 1995 and 2010 were identified and divided into three age groups (65�84, 85�99, ?100). A detailed description was obtained on 1,842 centenarians who were alive on April 1, 2010. Measurements Sociodemographic characteristics and use of health services. Results The number of centenarians increased from 1,069 in 1995 to 1,842 in 2010 (72.3%); 6.7% were aged 105 and older. Over the same period, the number of individuals aged 85 to 99 grew from 119,955 to 227,703 (89.8%). Women represented 85.3% of all centenarians and 89.4% of those aged 105 and older. Almost half of centenarians lived in the community (20.0% independently, 25.3% with publicly funded home care). Preventive drug therapies (bisphosphonates and statins) were frequently dispensed. In the preceding year, 18.2% were hospitalized and 26.6% were seen in an emergency department. More than 95% saw a primary care provider, and 5.3% saw a geriatrician. Conclusion The number of centenarians in Ontario increased by more than 70% over the last 15 years, with even greater growth among older people who could soon become centenarians. Almost half of centenarians live in the community, most are women, and almost all receive care from a primary care physician.