Machelle Wilchesky

Bronchodilator Use and the Risk of Arrhythmia in COPD: Part 2: Reassessment in the Larger Quebec Cohort

BACKGROUND A previous study suggested a potential increased risk of cardiac arrhythmia with new use of long-acting β-agonists and ipratropium bromide in patients with COPD, although conclusions were limited by the small cohort size. METHODS We reassessed this association in a larger cohort formed from the health-care databases of the province of Quebec, Canada. We identified a cohort of patients with COPD aged ≥ 67 years who began treatment between 1990 and 1999 and followed them until December 2003. A nested case-control approach matched each subject who developed severe arrhythmia during follow-up with 20 control subjects from the cohort on age, sex, and calendar time. The rate ratio (RR) of arrhythmia associated with new use of bronchodilators was estimated using conditional logistic regression, adjusting for COPD disease severity, cardiovascular disease, and other comorbidities. RESULTS The cohort included 76,661 patients with COPD, of whom 5,307 developed an arrhythmia (10.3 arrhythmias per 1,000 per year), 621 of which were fatal. The rate of cardiac arrhythmias was elevated with the new use of short-acting (RR, 1.27; 95% CI, 1.03-1.57) and long-acting (RR, 1.47; 95% CI, 1.01-2.15) β-agonists. The rate was slightly elevated, although not statistically significantly, with new use of ipratropium bromide (RR, 1.23; 95% CI, 0.95-1.57) and methylxanthines (RR, 1.28; 95% CI, 0.93-1.77). These effects waned with longer-term use. CONCLUSIONS New use of short- and long-acting β-agonists may slightly increase the risk of cardiac arrhythmia in patients with COPD. It remains unclear whether ipratropium bromide also increases this risk, despite the use of a larger study population.

Fluoroquinolones and the risk of serious arrhythmia: a population-based study

BACKGROUND Fluoroquinolones have been suspected to cause cardiac arrhythmia but data are lacking, particularly for the individual fluoroquinolones. We assessed the risk of serious arrhythmia, defined as ventricular arrhythmia or sudden/unattended death identified in hospital discharge diagnoses, related to fluoroquinolones as a class as well as for each individual molecule. METHODS We used a cohort of patients treated for respiratory conditions from 1 January 1990 to 31 December 2005, identified using the healthcare databases from the province of Quebec (Canada), with follow-up until 31 March 2007. A nested case-control analysis was performed within this cohort, with all cases of serious arrhythmia occurring during follow-up identified from hospitalization records. These cases were matched with up to 20 controls. Conditional logistic regression was used to compute adjusted rate ratios (RRs) of serious arrhythmia associated with fluoroquinolone use. RESULTS Within the cohort of 605127 subjects, 1838 cases were identified (incidence rate=4.7/10000 person-years). The rate of serious arrhythmia was elevated with current fluoroquinolone use (RR=1.76; 95% confidence interval [CI], 1.19-2.59), in particular with new current use (RR=2.23; 95% CI, 1.31-3.80). Gatifloxacin use was associated with the highest rate (RR=7.38; 95% CI, 2.30-23.70); moxifloxacin and ciprofloxacin were also associated with elevated rates of serious arrhythmia (RR=3.30; 95% CI, 1.47-7.37 and RR=2.15; 95% CI, 1.34-3.46, respectively). CONCLUSIONS The use fluoroquinolones is associated with an elevated risk of serious arrhythmia, with some differences among molecules. Given that the individual fluoroquinolones share various indications, the relative risks of serious arrhythmia could inform the choice of different molecules in high-risk patients.

Bronchodilator Use and the Risk of Arrhythmia in COPD: Part 1: Saskatchewan Cohort Study

BACKGROUND Bronchodilators are first-line therapy for COPD. There is some evidence that they may increase the risk of cardiac arrhythmias. METHODS We used the computerized health-care databases of the Province of Saskatchewan, Canada, to identify a cohort of subjects with COPD, aged ≥ 55 years, between 1990 and 1999. The subjects were followed until December 2003 for a hospital admission for, or death from, arrhythmia. A nested case-control approach was used to match each arrhythmia case on age, sex, and calendar time to 20 control subjects selected from the corresponding cohort risk set. Conditional logistic regression was used to estimate the rate ratio (RR) of arrhythmia associated with new use of bronchodilators, adjusted for disease severity and comorbidity. RESULTS The cohort included 6,018 patients with COPD in whom 469 arrhythmia cases occurred, including 56 deaths, for an overall rate of 1.37 arrhythmias per 100 per year. The rate of arrhythmia was elevated with the new use of ipratropium (RR, 2.4; 95% CI, 1.4-4.0) and of long-acting β-agonists (LABAs) (RR, 4.5; 95% CI, 1.4-14.4). It was not elevated with new use of short-acting β-agonists (RR, 0.9; 95% CI, 0.5-1.6) or methylxanthines (RR, 1.6; 95% CI, 0.7-3.7). CONCLUSIONS The new use of bronchodilators, particularly ipratropium and LABAs, may increase the risk of cardiac arrhythmias in patients with COPD. Although these results raise concerns regarding LABAs, they were based on few cases and require confirmation in larger cohorts.

Adverse Drug Reactions Reported With Cholinesterase Inhibitors An Analysis of 16 Years of Individual Case Safety Reports From VigiBase

Background: No worldwide pharmacovigilance study evaluating the spectrum of adverse drug reactions (ADRs) induced by cholinesterase inhibitors (ChEI) in Alzheimer’s disease has been conducted since their emergence on the market. Objective: To describe ChEI related ADRs in Alzheimer’s disease (donepezil, rivastigmine, and galantamine) and characterize their seriousness as reported by national pharmacovigilance systems to VigiBase, a World Health Organization International Drug Monitoring Program database, between 1998 and 2013. Methods: All ChEI related reports, submitted to VigiBase between 1998 and 2013 from the five continents were extracted. Analyses were carried out for general, serious, and nonserious ADRs. Results: A total of 18 955 reports (43 753 ADRs) from 58 countries were reported: 60.1% in women; mean age 77.4 ± 9.1 years. Most reports originated from Europe (47.6%) and North America (40.4%). Rivastigmine and donepezil were involved in most reports (41.4% each). The most frequently reported ADRs were neuropsychiatric (31.4%), gastrointestinal (15.9%), general (11.9%), and cardiovascular (11.7%) disorders. During the 2006-2013 period, serious ADRs remained more often reported than nonserious ones; the most serious were neuropsychiatric (34.0%), general (14.0%), cardiovascular (12.1%), and gastrointestinal (11.6%) disorders. Medication errors were reported in 2.0% of serious cases. Death occurred in 2.3% of the reports. Conclusions: This international pharmacovigilance study highlights the ADR pattern induced by ChEIs. Neuropsychiatric events were the most frequently reported ADRs. Serious cardiovascular events were frequently reported, suggesting that their significance has probably been previously underestimated. Given the frailty of the patients and the frequent comedications, caution is advised before introducing a ChEI.

Prescription of antidepressants and the risk of road traffic crash in the elderly: a case-crossover study.

AIM To investigate the impact of antidepressants on the risk of road traffic crash in the elderly. METHODS Reports from the Universal Quebec Automobile Insurance Agency database were matched with data on antidepressant prescription from the Quebec Health Insurance Agency. The case-crossover analysis consisted in comparing exposure during a period immediately before the crash with exposure during earlier periods, for the same subject. RESULTS One hundred and nine thousand four hundred and six drivers between 66 and 84 years of age involved in a traffic crash between 1988 and 2000 were included. Two thousand nine hundred and nineteen (2.7%) were exposed to an antidepressant on the day of the crash. Case-crossover analysis found an increased risk of crash in drivers with a prescription of antidepressants before their crash when compared with a prescription of antidepressants 4 to 8 months before the crash (OR = 1.19, 95% CI 1.08, 1.30 to 1.42. 95% CI 1.30, 1.55). With the most recent control periods, results were not significant. CONCLUSION A patients mental state is probably more similar between two periods that are close to each other than up to 8 months before. Consequently, the risk of crash is likely to be linked to symptoms of depression.

Predictive and concurrent validity of the Braden scale in long-term care: a meta-analysis.

Pressure ulcer prevention is an important long‐term care (LTC) quality indicator. While the Braden Scale is a recommended risk assessment tool, there is a paucity of information specifically pertaining to its validity within the LTC setting. We, therefore, undertook a systematic review and meta‐analysis comparing Braden Scale predictive and concurrent validity within this context. We searched the Medline, EMBASE, PsychINFO and PubMed databases from 1985–2014 for studies containing the requisite information to analyze tool validity. Our initial search yielded 3,773 articles. Eleven datasets emanating from nine published studies describing 40,361 residents met all meta‐analysis inclusion criteria and were analyzed using random effects models. Pooled sensitivity, specificity, positive predictive value (PPV), and negative predictive values were 86%, 38%, 28%, and 93%, respectively. Specificity was poorer in concurrent samples as compared with predictive samples (38% vs. 72%), while PPV was low in both sample types (25 and 37%). Though random effects model results showed that the Scale had good overall predictive ability [RR, 4.33; 95% CI, 3.28–5.72], none of the concurrent samples were found to have “optimal” sensitivity and specificity. In conclusion, the appropriateness of the Braden Scale in LTC is questionable given its low specificity and PPV, in particular in concurrent validity studies. Future studies should further explore the extent to which the apparent low validity of the Scale in LTC is due to the choice of cutoff point and/or preventive strategies implemented by LTC staff as a matter of course.

A long-term care center interdisciplinary education program for antipsychotic use in dementia: program update five years later.

BACKGROUND While antipsychotic (AP) medications are frequently used in long-term care, current evidence suggests that the risks may offset the benefits, necessitating periodic reassessment of their use. The aims of this present study were: (1) to assess rates of AP use five years after our first intervention to determine the long-term impact; and (2) to implement an updated AP reduction educational intervention program at the same center five years later in order to determine whether AP use could be further reduced. METHODS Participants were residents with dementia receiving AP medication. The educational program component included separate lectures on pharmacologic and non-pharmacologic treatment of behavioral and psychological symptoms of dementia (BPSD). Completion of the Nursing Home Behavior Problems Scale (NHBPS), physician interviews concerning AP treatment plans for subjects with dementia, and AP administration and dose assessment occurred both at baseline and again between four to five months after the educational program. RESULTS Of 308 long-term residents with dementia, 53 (17.2%) were receiving regular APs, primarily for agitation, aggressivity, other behavioral problems and psychosis. Of these, six died and one was transferred, leaving 46 participants. At five months, ten (21.7%) residents were no longer receiving APs and seven (15.2%) were on a lower dose; thus, 17 (37.0%) were either discontinued or on a lower dose. There was no worsening of NHBPS scores. CONCLUSION Despite the low prevalence (17.2%) of AP users at the beginning of the current study compared to that observed five years prior (30.5%), it is still possible to further decrease the proportion of users.

Performance of the French version of the 4AT for screening the elderly for delirium in the emergency department

OBJECTIVES Delirium is very frequent in older patients presenting to the emergency department (ED), but is often undetected. The purpose of this study was to evaluate the performance of the French version of the 4 A’s Test (4AT-F) for the detection of delirium and cognitive impairment in older patients. METHODS The study was conducted in four Canadian ED. Participants (n= 320) were independent or semi-independent patients (able to perform ≥5 activities of daily living) aged 65 and older and had an 8-hour exposure to the ED environment. The Telephone Interview for Cognitive Status (TICS-m), the Confusion Assessment Method (CAM) as well as the 4AT-F were administered to patients at the initial interview. The CAM and 4AT-F were then administered twice a day during the patients’ ED or hospital stay. The 4AT-F’s sensitivity and specificity were compared to those of the CAM (for delirium), and to that of the TICS (for cognitive impairment). RESULTS Our results suggest that the 4AT-F has a sensitivity of 84% (95% CI: [76, 93]) and a specificity of 74% (95% CI: [70, 78]) for delirium, as well as a sensitivity of 49% (95% CI: [34, 64]) and a specificity of 87% (95% CI: [82, 92]) for cognitive impairment. CONCLUSION The 4AT-F is a fast and reliable screening tool for delirium and cognitive impairment in ED. Due to its quick administration time, it allows a systematic screening of patients at risk of delirium, without significantly increasing the workload of the ED staff.

TREATMENT INITIATION CHARACTERISTICS OF ANTI-DEMENTIA DRUG THERAPIES IN THE UNITED KINGDOM: A POPULATION-BASED INCEPTION COHORT

Figure 1. Dist strategy, overa Date cut-point Excellence (N respectively], itor access. Female, n (%) 58,342 (64%) Age at MND diagnosis, mean (standard deviation) 83(7) CHARACTERISTICS OFANTI-DEMENTIA DRUG THERAPIES IN THE UNITED KINGDOM: A POPULATION-BASED INCEPTION COHORT Year of MND diagnosis by 5-year periods, n (%) 1997-2001 9,555 (11%) 2002-2006 21,016 (23%) 2007-2011 29,443 (32%) 2012-2017 31,911 (34%) Year of MND diagnosis, by NICE guideline period 1997-2005 30,743 (34%) 2006-2011 24,639 (27%) 2011-2017 35,643 (39%) Smoking status, n (%) Ever 24,701 (27%) Never 19,774 (22%) Unknown 46,550 (51%) Alcohol-related disorder in prior year, n (%) 1,063 (1%) Body Mass Index (kg/m), n (%) Underweight (< 18.5) 4,074 (4%) Normal (18.5–24.9) 29,042 (32%) Overweight (25.0-29.9) 19,991 (22%) Obese (>30) 9,282 (10%) Unknown 28,636 (31%) MND sub-type, n (%) Alzheimer’s 51,230 (56%) Vascular dementia 20,656 (23%) Non-specific dementia 16,766 (18%) Other 2,373 (3%) Indicators of dementia severity in year prior to diagnosis, n (%) Urinary & faecal incontinence 4,582 (5%) Kathleen M. Andersen, Kristian B. Filion, Edeltraut Kr€oger, Nathalie Champoux, Pauline Reynier, Machelle Wilchesky, McGill University, Montreal, QC, Canada; Universit e Laval, Quebec City, QC, Canada; Universit e de Montr eal, Montreal, QC, Canada; Lady Davis Institute, Montreal, QC, Canada. Contact e-mail: kathleen.andersen@mail. mcgill.ca

Adapting the Elder Abuse Suspicion Index© for Use in Long-Term Care: A Mixed-Methods Approach:

Currently available elder abuse screening and identification tools have limitations for use in long-term care (LTC). This mixed-methods study sought to explore the appropriateness of using the Elder Abuse Suspicion Index© (a suspicion tool originally created for use with older adults in the ambulatory setting with Mini-Mental State Examination scores ≥ 24) with similarly cognitively functioning persons residing in LTC. Results were informed by a literature review, Internet-based consultations with elder abuse experts across Canada (n = 19), and data obtained from two purposively selected focus groups (n = 7 local elder abuse experts; n = 7 experienced front-line LTC clinicians). Analyses resulted in the development of a nine-question tool, the EASI-ltc, designed to raise suspicion of EA in cognitively intact older adults residing in LTC (with little or no cognitive impairment). Notable modifications to the original Elder Abuse Suspicion Index© (EASI) included three new questions to further address neglect and psychological abuse, and a context-specific preamble to orient responders.