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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.

Importance Given that most common bacterial infections can be treated with antibiotic courses of 7 or fewer days, reducing standard antibiotic treatment durations may be an avenue to curtailing antibiotic overuse in long-term care. Objectives To describe the variability in the duration of antibiotic treatment courses in long-term care across resident recipients and prescribing physicians and to determine whether this variability is influenced by prescriber preference. Design and Setting Province-wide retrospective analysis of residents of Ontario, Canada, long-term care facilities in 2010. Participants All adults aged 66 years or older who received an incident treatment course with a systemic antibiotic while residing in an Ontario long-term care facility. Main Outcome Measure Antibiotic treatment duration was examined across residents and prescribing physicians. The proportion of a physician's treatment courses that exceeded 7 days was used to classify short-, average-, and long-duration prescribers. Results Of 66 901 long-term care residents from 630 long-term care facilities, 50 061 (77.8%) received an incident antibiotic treatment course (with 51 540 antibiotic courses prescribed). The most commonly selected antibiotic treatment course was 7 days (in 21 136 courses [41.0%]), but 23 124 (44.9%) exceeded 7 days. Among the 699 physicians responsible for 20 or more antibiotic treatment courses, the median (interquartile range) proportion of treatment courses beyond 7 days was 43.5% (26.9%-62.9%) (range, 0%-97.1%). Twenty-one percent of prescribers had a higher-than-expected proportion of prescriptions beyond the 7-day threshold. Patient characteristics were similar across short-, average-, and long-duration prescribers. A mixed logistic model confirmed that prescribers were an important determinant of treatment duration (P Conclusions and Relevance Antibiotic treatment courses in long-term care facilities are often prescribed for long durations, and this appears to be influenced by prescriber preference more than patient characteristics. Future trials should evaluate antibiotic stewardship interventions targeting prescriber preferences to systematically shorten average treatment durations to reduce the complications, costs, and resistance associated with antibiotic overuse.

6044Background: 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 asse...

285 Background: In the delivery of cancer care, barriers to access could potentially result in inferior outcomes and survival. Although a relationship has been demonstrated between disadvantaged socio-economic status and mortality, the impact of immigration on outcomes is less clear. Methods: Administrative databases were linked to create a cohort of all incident cases of colorectal, lung, prostate, head/neck, breast and hematologic malignancies from Jan 2000 to Dec 2012 in Ontario, Canada. Cases were defined according to immigration status and followed from diagnosis until death (or cancer-specific death). Cox proportional hazards models were constructed to study the impact of immigration status on survival after adjusting for relevant variables. Additional adjusted models studied the relationship of time since immigration on mortality. Results: During the study period, 11,485 cancer cases were diagnosed in recent immigrants (0-10 years in Canada), 17,844 cases in non-recent immigrants (11-25 years), and 416,118 cases in non-immigrants. Following adjustment for relevant predictors by Cox regression, survival was improved for recent immigrants (HR 0.843; 95% CI 0.814-0.873) and non-recent immigrants (HR 0.902; 95% CI 0.876-0.928) compared to non-immigrants. Cancer-specific survival was also better for recent immigrants (HR 0.857; 95% CI 0.823-0.893) and non-recent immigrants (HR 0.907; 95% CI 0.875-0.94) compared to non-immigrants. Amongst immigrants, each year from the original landing in Canada was associated with increased mortality (HR 1.004; 1.000-1.009) and a trend to increased cancer-specific mortality (HR 1.005; 0.999-1.010) that was not statistically significant. Immigrants from all WHO world regions were found to have similar reductions in mortality and cancer-specific mortality. Conclusions: Immigrants to Canada demonstrate a “healthy immigrant” effect, with lower mortality compared to Canadian-born individuals. This benefit appears to diminish over time, as the health of immigrants potentially converges with the Canadian norm. Potential contributors to the benefit include self-selection for immigration, health requirements for entrance, and differences in disease distribution related to ethnicity.

295 Background: The Choosing Wisely Canada (CWC) campaign aims to start conversations about unnecessary treatments and procedures in order to improve quality of care. In particular, the CWC campaign in cancer seeks to reduce interventions that are not supported by evidence and contribute to unnecessary rising costs of cancer care. We sought to document the performance of cancer screening for a new primary cancer in patients with existing metastatic cancer (CWC statement #2). Methods: We used population-based administrative health care databases from Ontario, Canada held at the Institute for Clinical Evaluative Sciences (ICES). The cohort included all adult residents of Ontario of eligible screening age (age 50 or older) diagnosed with incident, stage 4 (metastatic) colorectal cancer (CRC), lung, breast, or prostate cancer between January 1, 2007 and December 31, 2012. We examined screening tests for CRC and breast cancer in the first 1 and 3 years after diagnosis of an unrelated cancer. Given the high mortality rate in this population, screening rates were calculated using the cumulative incidence function which takes into account the competing risk of death or the occurrence of the cancer for which the patient was being screened (prior to being screened). Results: Among the 20,992 patients with stage 4 lung, breast, or prostate cancer, CRC screening within 1 year of cancer diagnosis occurred in 2.8%, 6.1%, and 13.0%, respectively. Within 3 years of diagnosis, screening rates were 3.9%, 11.9%, and 26.9%, respectively. Among the 10,034 women with metastatic CRC or lung cancer, breast cancer screening within 1 year of cancer diagnosis occurred in 8.0% and 8.7% of women, respectively. Within 3 years of diagnosis, screening rates were13.1% and 10.2%, respectively. Screening rates were higher in patients age 50-74 than those ≥75 years. Conclusions: Our findings indicate that up to one quarter of patients with metastatic cancer receive subsequent screening tests for other cancers, which are unnecessary as these patients are unlikely to benefit. Further studies are warranted to examine resource implications, potential patient and societal harms, and the future impact of the CWC campaign on this practice.

601 Background: The addition of oxaliplatin to fluorouracil-based regimens in the adjuvant treatment of colorectal cancer (CRC) has been shown to improve overall survival at the expense of increased toxicity. Toxicity may be higher among older patients who may also derive less benefit from oxaliplatin. The incidence of toxicity in the elderly is unknown. Methods: A cohort of patients ≥ 66 years old diagnosed with Stage II and III CRC between 2007 and 2011 in Ontario, Canada was identified using the Ontario Cancer Registry. Linked administrative databases were used to identify patients treated with oxaliplatin who were subsequently diagnosed with peripheral neuropathy (PN) or received a new prescription for a neuropathic pain medication. Patients were stratified into two age strata, ages 66-69 and ages ≥ 70, and each group was compared to a control cohort receiving non-oxaliplatin-based adjuvant chemotherapy (AC). Cause-specific hazard models were used to estimate the effect of Oxaliplatin exposure on the cause-specific hazard of PN and associated neurotoxicity outcomes after accounting for the competing risk of death. Results: We identified 3,607 patients aged ≥ 66 with Stage II and III CRC, of whom 1,541 were treated with an oxaliplatin-based AC regimen. Compared to control subjects receiving non-oxaliplatin based AC, patients ≥ 70 years old treated with oxaliplatin were more likely to be diagnosed with PN (cause-specific hazard ratio (CHR) age ≥ 70, 2.07 [95% CI, 1.43-3.00; p < 0.001]) and receive a new prescription for a neuropathic pain medication (CHR age ≥ 70, 1.86 [95% CI, 1.43-2.42;p < 0.001]). In patients aged 66-69, oxaliplatin use was not associated with a new diagnosis of PN (p = 0.903), but was associated with an increased likelihood of receiving a prescription for a neuropathic pain medication (CHR age 66-70, 1.92 [95% CI, 1.22-3.03; p = 0.005]). By the end of one year, the cumulative incidence of PN was 3.21% (95% CI, 2.02-4.81) for ages 66-69 and 5.51% (95% CI, 4.14-7.15) for age ≥ 70. Conclusions: In this population-based cohort of CRC patients ≥ 70 years old, treatment with oxaliplatin is associated with a significant risk of developing PN and requiring treatment with neuropathic pain medications.

The management of neuropsychiatric symptoms, including psychosis, in Parkinson’s Disease (PD) is complicated by the fact that treatment with antipsychotics can worsen the movement disorder, which may necessitate changes to antiparkinsonian medications. The objectives of this study were to determine what antipsychotics are prescribed to residents in long-term care with PD and document subsequent changes in levodopa dosage. A retrospective cohort study using administrative health database information from Ontario, Canada, was conducted. PD diagnostic codes were obtained from the Ontario Health Insurance Plan (physician diagnostic codes) and the Canadian Institute of Health Information (hospitalization discharge diagnoses). The Ontario Drug Benefit database provided information on the use of antiparkinsonian medications and antipsychotics. Residents diagnosed with PD in long-term care were included if they were treated with stable doses of levodopa monotherapy and received a new prescription for an antipsychotic. The type of antipsychotic and the changes in levodopa dosage were determined. There were 479 residents who met inclusion criteria. The prescribed antipsychotics were quetiapine (n = 192; 40 %), risperidone (n = 185; 39 %) and olanzapine (n = 81; 17 %), and only 21 (4 %) received a prescription for a typical antipsychotic. The first levodopa dosage change was a dose reduction in 469 (98 %) patients, and a dose increase in ten (2 %) patients. Many PD patients in long-term care are treated with potentially inappropriate antipsychotic medications. However, there is no evidence that this treatment results in a prescribing cascade that leads to inappropriate increases in levodopa dosage.

Background: Cholinesterase inhibitors (ChEIs) are a mainstay treatment for individuals with dementia. ChEIs may worsen airflow obstruction because of their pro-cholinergic properties. Objective: The objective of this study was to evaluate the risk of serious pulmonary complications in the elderly with concomitant chronic obstructive pulmonary disease (COPD) and dementia who were receiving ChEIs. Methods: This was a population-based, cohort study conducted between 2003 and 2010 in residents of Ontario, Canada. Subjects were over the age of 66 years and had concomitant dementia and COPD, identified using linked administrative databases. Exposure to ChEIs was determined using a drug benefits database. The primary outcome was an emergency room (ER) visit or hospitalization for COPD. The risk difference at 60 days and the relative risk (RR) for study outcomes were estimated in the propensity score-matched sample. Results: Of 266 840 individuals with COPD, 45 503 had a concomitant diagnosis of dementia. A total of 7166 unexposed subjects were matched to subjects newly exposed to ChEIs. New users of ChEIs were not at significantly higher risk of ER visits or hospitalizations for COPD (RR 0.90; 95% CI 0.76, 1.07) or COPD exacerbations (RR 1.02; 95% CI 0.91,1.15). Furthermore, ER visits for any respiratory diagnoses were not increased among new users of ChEIs (RR 1.02; 95% CI 0.87, 1.19) when compared with non-users. Subgroup analyses were consistent with the main analysis. Conclusions: In a large cohort of elderly individuals with COPD and dementia, new users of ChEIs had a similar risk for adverse pulmonary outcomes as those who were not receiving ChEIs.

Background The use of antipsychotic medications is associated with an increased risk of death in older adults with dementia. The risk of death in patients with preexisting parkinsonism who receive antipsychotic drugs is not known. Methods Using a nested case–control design, we examined the risk of death within 30 days of newly starting antipsychotic medications among people with Parkinsonism aged 70 years and older in Ontario, Canada. Data were obtained from Ontario's healthcare administrative databases. Results Among 5,391 individuals with parkinsonism who died during the study period (2002–2008) and a matched comparison group of 25,937 who were still alive, individuals exposed to atypical antipsychotic drugs had a higher risk of death (unadjusted odds ratio [OR] = 2.8, 95% CI: 2.1–3.8, adjusted OR: 2.0, 95% CI: 1.4–2.7). Results were similar for quetiapine use compared with no antipsychotic use (unadjusted OR: 2.5, 95% CI: 1.6–4.0, adjusted OR=1.8, 95% CI: 1.1–3.0). Typical antipsychotics were associated with an increased odds of death compared with atypical antipsychotics (unadjusted OR=2.4, 95% CI 1.1–5.2, adjusted OR=2.4, 95% CI: 1.1–5.7). Conclusions Individuals with parkinsonism who are newly prescribed antipsychotic medications have a higher risk of death within 30 days than those who do not start these medications. Although it is not possible to establish causality, the results suggest an increased risk. It is important to be vigilant for accompanying serious medical conditions that may increase mortality in individuals requiring treatment with antipsychotics and to consider alternative approaches to treating psychosis, agitation, and aggression in this population.

BACKGROUND: There is increasing evidence linking breast cancer and diabetes; however, few studies have explored the association between cancer treatments and risk of diabetes. Tamoxifen may increase diabetes incidence through its estrogen-inhibiting effects. This study assessed whether tamoxifen treatment in older breast cancer survivors is associated with an increased risk of diabetes. METHODS: This nested case-control study used population-based health databases in Ontario, Canada to identify women older than 65 years with early stage breast cancer between April 1, 1996 and March 31, 2006. Cases were defined as cohort members diagnosed with diabetes during follow-up (March 31, 2008), and each case was age-matched with up to 5 controls who did not develop diabetes. After adjusting for other risk factors, the authors compared the likelihood of diabetes between current tamoxifen users and tamoxifen nonusers, based on prescriptions at diabetes diagnosis. They also compared diabetes risk in current aromatase inhibitor users versus nonusers. RESULTS: Of 14,360 breast cancer survivors identified, mean age 74.9 years, 1445 (10%) developed diabetes over a mean follow-up of 5.2 years. Current tamoxifen therapy was associated with a significantly higher risk of diabetes compared with no tamoxifen therapy (adjusted odds ratio, 1.24; 95% confidence interval, 1.08-1.42; P = .002). There was no association between aromatase inhibitor therapy and diabetes. CONCLUSIONS: Current tamoxifen therapy is associated with an increased incidence of diabetes in older breast cancer survivors. These findings suggest that tamoxifen treatment may exacerbate an underlying risk of diabetes in susceptible women; further studies are needed to better explore this association. Cancer 2011. © 2011 American Cancer Society.

Objective To quantify the effect of levothyroxine dose on risk of fractures in older adults. Design Nested case-control study. Setting Population based health databases, Ontario, Canada. Participants Adults aged 70 or more prescribed levothyroxine between 1 April 2002 and 31 March 2007 and followed for fractures until 31 March 2008. Cases were cohort members admitted to hospital for any fracture, matched with up to five controls from within the cohort who had not yet had a fracture. Main outcome measure Primary outcome was fracture (wrist or forearm, shoulder or upper arm, thoracic spine, lumbar spine and pelvis, hip or femur, or lower leg or ankle) in relation to levothyroxine use (current, recent past, remote). Risk among current users was compared between those prescribed high, medium, and low cumulative levothyroxine doses in the year before fracture. Results Of 213 511 prevalent levothyroxine users identified, 22 236 (10.4%) experienced a fracture over a mean 3.8 years of follow-up, 18 108 (88%) of whom were women. Compared with remote levothyroxine use, current use was associated with a significantly higher risk of fracture (adjusted odds ratio 1.88, 95% confidence interval 1.71 to 2.05), despite adjustment for numerous risk factors. Among current users, high and medium cumulative doses (>0.093 mg/day and 0.044-0.093 mg/day) were associated with a significantly increased risk of fracture compared with low cumulative doses (

Background Depression occurs in approximately one-third of patients following stroke based on studies that screen entire stroke populations. Less is known about the detection and treatment of post stroke depression (PSD) in routine clinical practice. Methods This was a prospective cohort study of 7643 consecutive stroke patients >66 years of age, from 13 designated stroke centres in Ontario, Canada. PSD was defined as (a) presence of strong evidence of depression documented in the patient chart plus a prescribed antidepressant and a psychiatric consult, or (b) prescription of a new antidepressant following admission. The prevalence of PSD was determined and patients with and without PSD were compared on a variety of measures. Patients admitted to specialized stroke units were compared to patients admitted to standard units in order to determine if PSD detection and treatment rates differed. Results PSD was diagnosed in 4.8%, and 6.7% were treated with a new antidepressant. Patients with PSD had more severe strokes, more functional handicap, longer hospital stays and were less likely to be discharged home (all p

Background Unplanned hospital readmissions are common, expensive and often preventable. Strategies designed to reduce readmissions should target patients at high risk. The purpose of this study was to describe medical patients identified using a recently published and validated algorithm (the LACE index) as being at high risk for readmission and to examine their actual hospital readmission rates. Methods We used population-based administrative data to identify adult medical patients discharged alive from 6 hospitals in Toronto, Canada, during 2007. A LACE index score of 10 or higher was used to identify patients at high risk for readmission. We described patient and hospitalization characteristics among both the high-risk and low-risk groups as well as the 30-day readmission rates. Results Of 26 045 patients, 12.6% were readmitted to hospital within 30 days and 20.9% were readmitted within 90 days of discharge. High-risk patients (LACE ≥ 10) accounted for 34.0% of the sample but 51.7% of the patients who were readmitted within 30 days. High-risk patients were readmitted with twice the frequency as other patients, had longer lengths of stay and were more likely to die during the readmission. Interpretation Using a LACE index score of 10, we identified patients with a high rate of readmission who may benefit from improved post-discharge care. Our findings suggest that the LACE index is a potentially useful tool for decision-makers interested in identifying appropriate patients for post-discharge interventions.

Background Some antibiotic agents, including cotrimoxazole, inhibit the metabolism of warfarin sodium and possibly increase the risk of hemorrhage. We examined the risk of upper gastrointestinal (UGI) tract hemorrhage in older patients receiving warfarin in combination with antibiotics commonly used to treat urinary tract infection, with a focus on cotrimoxazole. Methods This population-based, nested case-control study using health care databases in Ontario, Canada, between April 1, 1997, and March 31, 2007, identified residents 66 years or older who were continuously treated with warfarin. Cases were hospitalized with UGI tract hemorrhage. For each case, we selected up to 10 age- and sex-matched control subjects. We calculated adjusted odds ratios (aORs) for exposure to cotrimoxazole, amoxicillin trihydrate, ampicillin trihydrate, ciprofloxacin hydrochloride, nitrofurantoin, and norfloxacin within 14 days before the UGI tract hemorrhage. Results We identified 134 637 patients receiving warfarin, of whom 2151 cases were hospitalized for UGI tract hemorrhage. Cases were almost 4 times more likely than controls to have recently received cotrimoxazole (aOR, 3.84; 95% confidence interval [CI], 2.33-6.33). Treatment with ciprofloxacin was also associated with increased risk (aOR, 1.94; 95% CI, 1.28-2.95), but no significant association was observed with amoxicillin or ampicillin (1.37; 0.92-2.05), nitrofurantoin (1.40; 0.71-2.75), or norfloxacin (0.38; 0.12-1.26). Compared with amoxicillin or ampicillin, cotrimoxazole prescription was associated with an almost 3-fold risk (ratio of ORs, 2.80; 95% CI, 1.48-5.32). Conclusions Among older patients receiving warfarin, cotrimoxazole is associated with a significantly higher risk of UGI tract hemorrhage than other commonly used antibiotics. Whenever possible, clinicians should prescribe alternative antibiotics in patients receiving warfarin.

Both benign prostatic hyperplasia (BPH) and cataract formation are common in older men. The alpha-adrenergic receptor blocker tamsulosin is frequently prescribed to treat BPH, and research suggests this drug may increase the intraoperative difficulty of cataract surgery. No studies have documented whether use of tamsulosin or other alpha-blocker drug therapies affect the risk of serious postoperative adverse events.To assess the risk of adverse events following cataract surgery in older men prescribed tamsulosin or other alpha-blocking drugs used to treat BPH.Nested case-control analysis of a population-based retrospective cohort study using linked health care databases from Ontario, Canada. We included all men aged 66 years or older who had cataract surgery between 2002 and 2007 (N = 96 128).A composite of procedures signifying retinal detachment, lost lens or lens fragment, or endophthalmitis occurring within 14 days after cataract surgery. The risk of these adverse events was compared between men treated with tamsulosin or other alpha-blockers and men with no exposure to these medications in the year prior to cataract surgery. We separately examined the association of drug exposure that was either recent (within the 14 days before surgery) or previous (15-365 days before surgery).Overall, 3550 patients (3.7%) in the cohort had recent exposure to tamsulosin and 7426 patients (7.7%) had recent exposure to other alpha-blockers. Two hundred eighty-four patients (0.3%) had an adverse event. We randomly matched 280 of the cases to 1102 controls according to their age, surgeon, and year of surgery. Adverse events were significantly more common among patients with recent tamsulosin exposure (7.5% vs 2.7%; adjusted odds ratio [OR], 2.33; 95% confidence interval [CI], 1.22-4.43) but were not associated with recent exposure to other alpha-blockers (7.5% vs 8.0%; adjusted OR, 0.91; 95% CI, 0.54-1.54) or to previous exposure to either tamsulosin (or = 1.8% vs 1%; adjusted OR, 0.94; 95% CI, 0.27-3.34) or other alpha-blockers (2.9% vs 2.1%; adjusted OR, 1.08; 95% CI, 0.47-2.48). This corresponds to an estimated number needed to harm (NNH) of 255 (95% CI, 99-1666).Exposure to tamsulosin within 14 days of cataract surgery was significantly associated with serious postoperative ophthalmic adverse events. There were no significant associations with exposure to other alpha-blocker medications used to treat BPH.

Background Cholinesterase inhibitors are commonly prescribed to treat dementia, but their adverse effect profile has received little attention. These drugs can provoke symptomatic bradycardia and syncope, which may lead to permanent pacemaker insertion. Drug-induced syncope may also precipitate fall-related injuries, including hip fracture. Methods In a population-based cohort study, we investigated the relationship between cholinesterase inhibitor use and syncope-related outcomes using health care databases from Ontario, Canada, with accrual from April 1, 2002, to March 31, 2004. We identified 19 803 community-dwelling older adults with dementia who were prescribed cholinesterase inhibitors and 61 499 controls who were not. Results Hospital visits for syncope were more frequent in people receiving cholinesterase inhibitors than in controls (31.5 vs 18.6 events per 1000 person-years; adjusted hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.57-1.98). Other syncope-related events were also more common among people receiving cholinesterase inhibitors compared with controls: hospital visits for bradycardia (6.9 vs 4.4 events per 1000 person-years; HR, 1.69; 95% CI, 1.32-2.15), permanent pacemaker insertion (4.7 vs 3.3 events per 1000 person-years; HR, 1.49; 95% CI, 1.12-2.00), and hip fracture (22.4 vs 19.8 events per 1000 person-years; HR, 1.18; 95% CI, 1.04-1.34). Results were consistent in additional analyses in which subjects were either matched on their baseline comorbidity status or matched using propensity scores. Conclusions Use of cholinesterase inhibitors is associated with increased rates of syncope, bradycardia, pacemaker insertion, and hip fracture in older adults with dementia. The risk of these previously underrecognized serious adverse events must be weighed carefully against the drugs' generally modest benefits.

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.A population-based healthcare administrative database study.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).Twenty-eight thousand nine hundred and sixty-one patients, including 4,601 residing in long-term care, mean age 80, 63% female.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.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.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.

To estimate the rate of new chronic benzodiazepine use after hospitalization in older adults not previously prescribed with benzodiazepines.Retrospective cohort study using linked, population-based administrative data.Ontario, Canada between April 1, 1992 and March 31, 2005.Community-dwelling seniors who had not been prescribed benzodiazepine drugs in the year before hospitalization were selected from all 1.4 million Ontario residents aged 66 years and older.New chronic benzodiazepine users, defined as initiation of benzodiazepines within 7 days after hospital discharge and an additional claim within 8 days to 6 months. We used multivariate logistic regression to examine for the effect of hospitalization on the primary outcome after adjusting for confounders.There were 405,128 patient hospitalizations included in the cohort. Benzodiazepines were prescribed to 12,484 (3.1%) patients within 7 days of being discharged from hospital. A total of 6,136 (1.5%) patients were identified as new chronic benzodiazepine users. The rate of new chronic benzodiazepine users decreased over the study period from 1.8% in the first year to 1.2% in the final year (P.001). Multivariate logistic regression found that women, patients admitted to the intensive care unit or nonsurgical wards, those with longer hospital stays, higher overall comorbidity, a prior diagnosis of alcoholism, and those prescribed more medications had significantly elevated adjusted odds ratios for new chronic benzodiazepine users. Older individuals had a lower risk for the primary outcome.New benzodiazepine prescription after hospitalization occurs frequently in older adults and may result in chronic use. A systemic effort to address this risky practice should be considered.

Importance Antibiotics are frequently and often inappropriately prescribed to patients in nursing homes. These antibiotics pose direct risks to recipients and indirect risks to others residing in the home. Objective To examine whether living in a nursing home with high antibiotic use is associated with an increased risk of antibiotic-related adverse outcomes for individual residents. Design, Setting, and Participants In this longitudinal open-cohort study performed from January 1, 2010, through December 31, 2011, we studied 110 656 older adults residing in 607 nursing homes in Ontario, Canada. Exposures Nursing home–level antibiotic use was defined as use-days per 1000 resident-days, and facilities were classified as high, medium, and low use according to tertile of use. Multivariable logistic regression modeling was performed to assess the effect of nursing home–level antibiotic use on the individual risk of antibiotic-related adverse outcomes. Main Outcomes and Measures Antibiotic-related harms included Clostridium difficile , diarrhea or gastroenteritis, antibiotic-resistant organisms (which can directly affect recipients and indirectly affect nonrecipients), allergic reactions, and general medication adverse events (which can affect only recipients). Results Antibiotics were provided on 2 783 000 of 50 953 000 resident-days in nursing homes (55 antibiotic-days per 1000 resident-days). Antibiotic use was highly variable across homes, ranging from 20.4 to 192.9 antibiotic-days per 1000 resident-days. Antibiotic-related adverse events were more common (13.3%) in residents of high-use homes than among residents of medium-use (12.4%) or low-use homes (11.4%) ( P P = .003). A sensitivity analysis examining nursing home–level antibiotic use as a continuous variable confirmed an increased risk of resident-level antibiotic-related harms (adjusted odds ratio, 1.004 per additional day of nursing home antibiotic use; 95% CI, 1.001-1.006; P = .01). Conclusions and Relevance Antibiotic use is highly variable across nursing homes; residents of high-use homes are exposed to an increased risk of antibiotic-related harms even if they have not directly received these agents. Antibiotic stewardship is needed to improve the safety of all nursing home residents.

393 Background: Emerging data show an increasingly recognized risk of colorectal cancer (CRC) in patients with type 2 diabetes (DM) likely due to common biologic pathways. Few data are available on DM incidence among patients with CRC. Our objective was to determine whether patients with CRC have a higher incidence of DM compared to those without CRC. Methods: We conducted a population-based retrospective cohort study in Ontario, Canada, using administrative databases comparing the incidence of DM among all CRC patients identified in the Ontario Cancer registry from Jan 1, 2002 to Dec 31, 2011 with an age-matched control population without CRC. We used Cox proportional hazard to study the association. We modeled the effect of CRC on the cause-specific hazard of developing DM and censored subjects at the time of a competing event. Subgroup analysis was performed on patients receiving chemotherapy vs. not, metastatic disease vs. not and colon vs. rectal cancer. Results: We identified 39,707 persons with CRC and 198,535 controls. The mean age was 68 and 48.6% were female. We found an overall DM incidence of 8.7% over a mean follow up time of 4.8 years. On multivariable analysis, the effect of CRC on the instantaneous hazard of the DM incidence varied over time, and thus we estimated instantaneous hazard ratios (IHR) for years 1-5 of follow up. The risk of DM among CRC patients was significantly higher than controls for at least five years post CRC diagnosis. The overall DM incidence was higher in patients with no metastasis (10.6% vs 8.6%, p