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Objectives: To examine dose‐related prescribing and short‐term serious events associated with initiation of cholinesterase inhibitor (ChEI) therapy. Design: Retrospective, population‐based cohort study. Setting: Ontario, Canada. Participants: Women (n=47,829) and men (n=32,503) aged 66 and older who initiated a ChEI between April 1, 2010, and June 30, 2016. Measurements: All‐cause serious events (emergency department (ED) visits, inpatient hospitalizations, death) within 30 days of ChEI initiation. Multivariable Cox proportional hazards models were used to estimate adjusted rates of serious events. Results: Overall, 4.8% of older adults were dispensed a lower‐than‐recommended ChEI starting dose, 87.9% a recommended dose, and 7.3% a higher‐than‐recommended starting dose. Eight thousand six hundred seventy‐one (10.8%) individuals experienced a serious event within 30 days of initiating therapy, primarily ED visits (8,540, 10.6%). Relative to those initiated on a recommended starting dose, those initiated on a higher dose had a significantly increased rate of serious events (women adjusted hazard ratio (aHR) 1.50, 95% confidence interval (CI) =1.38–1.63; men aHR 1.31, 95% CI=1.19–1.45). Similar patterns were found for ED visits and inpatient hospitalizations but not death. The relative effect of higher‐than‐recommended starting dose dispensed vs. recommended starting dose dispensed was greater in women than it was in men: the number needed to harm was 22 (95% confidence interval (CI)=18–29) for women and 36 (95% CI= 26–61) for men. Conclusion: Serious events immediately after initiation of ChEIs were associated with starting ChEI dose. This association was stronger in women. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article presents a study to determine the relationship of cholinesterase inhibitors and syncope-related events in patients with dementia. It utilized the health care database information in Ontario from April 1, 2002 to March 31, 2004. The study employed 19,803 community-dwelling adults with dementia who were given cholinesterase inhibitors and 61,499 patients who were not taking cholinesterase inhibitors. The study found out that those who receive cholinesterase inhibitors have frequent hospital visits for syncope. Results showed that cholinesterase inhibitors offer risks for syncope incidence in dementia patients.

The article reports on the relationship between lung function and environmental factors in a study done on asthmatic and nonasthmatic children in Lake Couchiching in Canada in June 1983. The link between forced vital capacity (FVC) and forced expiratory volume (FEV) and the environmental variables such as ozone, fine particulate matter and sulphate were studied using the ordinary least-squares regression (OLS) approach. A larger sample size in both groups of children is deemed needed to decrease the variability of environmental effects on lung function.

Objectives To quantify the influence of physicians' experiences of adverse events in patients with atrial fibrillation who were taking warfarin. Design Population based, matched pair before and after analysis. Setting Database study in Ontario, Canada. Participants The physicians of patients with atrial fibrillation admitted to hospital for adverse events (major haemorrhage while taking warfarin and thromboembolic strokes while not taking warfarin). Pairs of other patients with atrial fibrillation treated by the same physicians were selected. Main outcome measures Odds of receiving warfarin by matched pairs of a given physician's patients (one treated after and one treated before the event) were compared, with adjustment for stroke and bleeding risk factors that might also influence warfarin use. The odds of prescriptions for angiotensin converting enzyme (ACE) inhibitor before and after the event was assessed as a neutral control. Results For the 530 physicians who had a patient with an adverse bleeding event (exposure) and who treated other patients with atrial fibrillation during the 90 days before and the 90 days after the exposure, the odds of prescribing warfarin was 21% lower for patients after the exposure (adjusted odds ratio 0.79, 95% confidence interval 0.62 to 1.00). Greater reductions in warfarin prescribing were found in analyses with patients for whom more time had elapsed between the physician's exposure and the patient's treatment. There were no significant changes in warfarin prescribing after a physician had a patient who had a stroke while not on warfarin or in the prescribing of ACE inhibitors by physicians who had patients with either bleeding events or strokes. Conclusions A physician's experience with bleeding events associated with warfarin can influence prescribing warfarin. Adverse events that are possibly associated with underuse of warfarin may not affect subsequent prescribing. [ABSTRACT FROM AUTHOR]

Background: Prescribing cascades occur when a drug adverse event is misinterpreted as a new medical condition and a second, potentially unnecessary drug, is prescribed to treat the adverse event. The population-level consequences of prescribing cascades remain unknown., Methods: This population-based cohort study used linked health administrative databases in Ontario, Canada. The study included community-dwelling adults, 66 years of age or older with hypertension and no history of heart failure (HF) or diuretic use in the prior year, newly dispensed a calcium channel blocker (CCB). Individuals subsequently dispensed a diuretic within 90 days of incident CCB dispensing were classified as the prescribing cascade group, and compared to those not dispensed a diuretic, classified as the non-prescribing cascade group. Those with and without a prescribing cascade were matched one-to-one on the propensity score and sex. The primary outcome was a serious adverse event (SAE), which was the composite of emergency room visits and hospitalizations in the 90-day follow-up period. We estimated hazard ratios (HRs) with 95% confidence intervals (CI) for SAE using an Andersen-Gill recurrent events regression model., Results: Among 39,347 older adults with hypertension and no history of HF who were newly dispensed a CCB, 1881 (4.8%) had a new diuretic dispensed within 90 days after CCB initiation. Compared to the non-prescribing cascade group, those in the prescribing cascade group had higher rates of SAEs (HR: 1.21, 95% CI: 1.02-1.43)., Conclusions: The CCB-diuretic prescribing cascade was associated with an increased rate of SAEs, suggesting harm beyond prescribing a second drug therapy. Our study raises awareness of the downstream impact of the CCB-diuretic prescribing cascade at a population level and provides an opportunity for clinicians who identify this prescribing cascade to review their patients' medications to determine if they can be optimized., (© 2023 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Background/objectives: Gabapentinoids are commonly prescribed to relieve pain. The development of edema, an established adverse effect of gabapentinoids, may lead to a potentially harmful prescribing cascade whereby individuals are subsequently prescribed diuretics and exposed to diuretic-induced adverse events. The frequency of this prescribing cascade is unknown. Our objective was to measure the association between new dispensing of a gabapentinoid and the subsequent dispensing of a diuretic in older adults with new low back pain., Design: Population-based cohort study., Setting: Ontario, Canada., Participants: A total of 260,344 community-dwelling adults aged 66 years or older, newly diagnosed with low back pain between April 1, 2011, and March 31, 2019., Measurements: Exposure status was assigned using dispensed medications in the 1 week after low back pain diagnosis. Older adults newly dispensed a gabapentinoid (N = 7867) were compared with older adults who were not newly dispensed a gabapentinoid (N = 252,477). Hazard ratios (HRs) with 95% confidence intervals (CIs) for dispensing of a diuretic within 90 days of follow-up among older adults prescribed gabapentin relative to those who were not., Results: Older adults newly dispensed a gabapentinoid had a higher risk of being subsequently dispensed a diuretic within 90 days compared with older adults who were not prescribed a gabapentinoid (2.0% vs. 1.3%). After covariate adjustment, new gabapentinoid users had a higher rate of being dispensed a diuretic compared with those not prescribed a gabapentinoid (HR: 1.44, 95% CI: 1.23, 1.70). The rate of diuretic prescription among new gabapentinoid users increased with increasing gabapentinoid dosages., Conclusions: We have demonstrated the presence of a potentially inappropriate and harmful prescribing cascade. Given the widespread use of gabapentinoids, the population-based scale of this problem may be substantial. Increased awareness of this prescribing cascade is required to reduce the unnecessary use of diuretics and the exposure of patients to additional adverse drug events., (© 2021 The American Geriatrics Society.)

Importance: Subtle but important differences have been described in the way that male and female physicians care for their patients, with some evidence suggesting women are more likely to adhere to best practice recommendations., Objective: To determine if male and female physicians differ in their prescribing practices as measured by the initiation of lower-than-recommended dose cholinesterase inhibitor (ChEI) drug therapy for dementia management., Design, Setting, and Participants: All community-dwelling Ontario residents aged 66 years and older with dementia and newly dispensed an oral ChEI drug (donepezil, galantamine, or rivastigmine) between April 1, 2010 and June 30, 2016 were included., Main Outcome and Measures: The association between physician sex and the initiation of a lower than recommended-dose ChEI was examined using generalized linear mixed regression models, adjusting for patient and physician characteristics. Data were stratified by specialty. Secondary analyses explored the association between physician sex and cardiac screening as well as shorter duration of the initial prescription., Results: The analysis included 3,443 female and 5,811 male physicians and the majority (83%) were family physicians, Female physicians were more likely to initiate ChEI therapy at a lower-than-recommended dose (Adjusted odds ratio = 1.43,95% confidence interval = 1.17 to 1.74). Compared to their male counterparts, female physicians were also more likely to follow other conservative prescribing practices including cardiac screening (55.1% vs. 49.2%, P-value<0.001) around the time of ChEI initiation, and dispensing a shorter duration of initial prescription (41.8% vs 35.5% P-value<0.001)., Conclusions: There is a statistically significant and important difference in ChEI prescribing patterns between female and male physicians, suggesting that female physicians may be more careful and conservative in their approaches. This will inform future research to determine if patients receiving lower-than-recommended initial doses also have better outcomes., Competing Interests: There is a data sharing agreement between the Institute for Clinical Evaluative Sciences (ICES) (a not for profit corporation) and the commercial company, IMS Brogan Inc., which governs a piece of the ICES data used to generate the project dataset. No employment relationship should be inferred in connection with this statement. No author on this work is employed by IMS Brogan. Dr. Gurwitz serves as a member of the UnitedHealthcare Pharmacy & Therapeutics Committee. Dr. Seitz involves in a clinical trial sponsored by Hoffman La Roche. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Background: Antipsychotic drugs are widely used to manage behavioral and psychological symptoms in dementia despite concerns about their safety., Objective: To examine the association between treatment with antipsychotics (both conventional and atypical) and all-cause mortality., Design: Population-based, retrospective cohort study., Setting: Ontario, Canada., Patients: Older adults with dementia who were followed between 1 April 1997 and 31 March 2003., Measurements: The risk for death was determined at 30, 60, 120, and 180 days after the initial dispensing of antipsychotic medication. Two pairwise comparisons were made: atypical versus no antipsychotic use and conventional versus atypical antipsychotic use. Groups were stratified by place of residence (community or long-term care). Propensity score matching was used to adjust for differences in baseline health status., Results: A total of 27,259 matched pairs were identified. New use of atypical antipsychotics was associated with a statistically significant increase in the risk for death at 30 days compared with nonuse in both the community-dwelling cohort (adjusted hazard ratio, 1.31 [95% CI, 1.02 to 1.70]; absolute risk difference, 0.2 percentage point) and the long-term care cohort (adjusted hazard ratio, 1.55 [CI, 1.15 to 2.07]; absolute risk difference, 1.2 percentage points). Excess risk seemed to persist to 180 days, but unequal rates of censoring over time may have affected these results. Relative to atypical antipsychotic use, conventional antipsychotic use was associated with a higher risk for death at all time points. Sensitivity analysis revealed that unmeasured confounders that increase the risk for death could diminish or eliminate the observed associations., Limitations: Information on causes of death was not available. Many patients did not continue their initial treatments after 1 month of therapy. Unmeasured confounders could affect associations., Conclusions: Atypical antipsychotic use is associated with an increased risk for death compared with nonuse among older adults with dementia. The risk for death may be greater with conventional antipsychotics than with atypical antipsychotics.

Objective: To compare the incidence of admissions to hospital for stroke among older adults with dementia receiving atypical or typical antipsychotics., Design: Population based retrospective cohort study., Setting: Ontario, Canada. Patients 32,710 older adults (< or = 65 years) with dementia (17,845 dispensed an atypical antipsychotic and 14,865 dispensed a typical antipsychotic)., Main Outcome Measures: Admission to hospital with the most responsible diagnosis (single most important condition responsible for the patient's admission) of ischaemic stroke. Observation of patients until they were either admitted to hospital with ischaemic stroke, stopped taking antipsychotics, died, or the study ended., Results: After adjustment for potential confounders, participants receiving atypical antipsychotics showed no significant increase in risk of ischaemic stroke compared with those receiving typical antipsychotics (adjusted hazard ratio 1.01, 95% confidence interval 0.81 to 1.26). This finding was consistent in a series of subgroup analyses, including ones of individual atypical antipsychotic drugs (risperidone, olanzapine, and quetiapine) and selected subpopulations of the main cohorts., Conclusion: Older adults with dementia who take atypical antipsychotics have a similar risk of ischaemic stroke to those taking typical antipsychotics.