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Aims: This study evaluated the use of machine learning to leverage drug absorption, distribution, metabolism and excretion (ADME) data together with physicochemical and pharmacological data to develop a novel anticholinergic burden scale and compare its performance to previously published scales., Methods: Experimental and in silico ADME, physicochemical and pharmacological data were collected for antimuscarinic activity, blood-brain barrier penetration, bioavailability, chemical structure and P-glycoprotein (P-gp) substrate profile. These five drug properties were used to train an unsupervised model to assign anticholinergic burden scores to drugs. The model performance was evaluated through 10-fold cross-validation and compared with the clinical Anticholinergic Cognitive Burden (ACB) scale and nonclinical Anticholinergic Toxicity Scores (ATS) scale, which is based primarily on muscarinic binding affinity., Results: In silico software (ADMET Predictor) used for screening drugs for their blood-brain barrier (BBB) penetration correctly identified some drugs that do not cross the BBB. The mean area under the curve for the unsupervised and ACB scale based on the five selected variables was 0.76 and 0.64, respectively. The unsupervised model agreed with the ACB scale on the classification of more than half of the drugs (49 of 88) agreed on the classification of less than half the drugs in the ATS scale (12 of 25)., Conclusions: Our findings suggest that the commonly used ACB scale may misclassify certain drugs due to their inability to cross the BBB. By contrast, the ATS scale would misclassify drugs solely depending on muscarinic binding affinity without considering other drug properties. Machine learning models can be trained on these features to build classification models that are easy to update and have greater generalizability., (© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Objective: This study aimed to compare the approval of medicines for attention deficit/hyperactivity disorder (ADHD) for pediatric patients across five countries., Method: A document analysis was completed, using the drug labeling for ADHD medicines from five countries; United Kingdom, Australia, New Zealand, Canada and United States (US). Comparisons of available formulations and approval information for ADHD medicine use in pediatric patients were made., Results: The US had the highest number of approved medicines and medicine forms across the studied countries (29 medicine forms for 10 approved medicines). Approved age and dosage variations across countries and missing dosage information were identified in several drug labeling., Conclusions: The discrepancies in approval information in ADHD medicine drug labeling and differing availability of medicine formulations across countries suggest variations in the management of ADHD across countries. The update of drug labeling and further research into reasons for variability and impact on practice are needed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Older adults (≥65 years) account for a disproportionately high proportion of hospitalization and in-hospital mortality, some of which may be avoidable. Although machine learning (ML) models have already been built and validated for predicting hospitalization and mortality, there remains a significant need to optimize ML models further. Accurately predicting hospitalization may tremendously affect the clinical care of older adults as preventative measures can be implemented to improve clinical outcomes for the patient., Methods: In this retrospective cohort study, a data set of 14 198 community-dwelling older adults (≥65 years) with complex care needs from the International Resident Assessment Instrument-Home Care database was used to develop and optimize 3 ML models to predict 30-day hospitalization. The models developed and optimized were Random Forest (RF), XGBoost (XGB), and Logistic Regression (LR). Variable importance plots were generated for all 3 models to identify key predictors of 30-day hospitalization., Results: The area under the receiver-operating characteristics curve for the RF, XGB, and LR models were 0.97, 0.90, and 0.72, respectively. Variable importance plots identified the Drug Burden Index and alcohol consumption as important, immediately potentially modifiable variables in predicting 30-day hospitalization., Conclusions: Identifying immediately potentially modifiable risk factors such as the Drug Burden Index and alcohol consumption is of high clinical relevance. If clinicians can influence these variables, they could proactively lower the risk of 30-day hospitalization. ML holds promise to improve the clinical care of older adults. It is crucial that these models undergo extensive validation through large-scale clinical studies before being utilized in the clinical setting., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Objectives: Frailty is common in older people and is associated with increased use of healthcare services and ongoing use of multiple medications. This study provides insights into the healthcare cost structure of a frail group of older adults in Aotearoa, New Zealand. Furthermore, we investigated the relationship between participants' anticholinergic and sedative medication burden and their total healthcare costs to explore the viability of deprescribing interventions within this cohort., Methods: Healthcare cost analysis was conducted using data collected during a randomized controlled trial within a frail, older cohort. The collected information included participant demographics, medications used, frailty, cost of service use of aged residential care and outpatient hospital services, hospital admissions, and dispensed medications., Results: Data from 338 study participants recruited between 25 September 2018 and 30 October 2020 with a mean age of 80 years were analyzed. The total cost of healthcare per participant ranged from New Zealand $15 (US dollar $10) to New Zealand $270 681 (US dollar $175 943) over 6 months postrecruitment into the study. Four individuals accounted for 26% of this cohort's total healthcare cost. We found frailty to be associated with increased healthcare costs, whereas the drug burden was only associated with increased pharmaceutical costs, not overall healthcare costs., Conclusions: With no relationship found between a patient's anticholinergic and sedative medication burden and their total healthcare costs, more research is required to understand how and where to unlock healthcare cost savings within frail, older populations., Competing Interests: Author Disclosures Author disclosure forms can be accessed in the Supplemental Material section., (Copyright © 2023 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Drug-related acute kidney injury is quite common in older adults. The associated drugs, including antibiotics, are often co-prescribed. The objective of this study was to ascertain antibiotic-associated acute kidney injury (AKI) in older adults aged 65 years or above in New Zealand using a case-crossover study design., Methods: The International Statistical Classification of Diseases and Related Health Problems, tenth revision, Australian modification code N17.x was used to identify all individuals aged 65 years and above with a diagnosis of incident AKI on admission between 1 January 2005 and 31 December 2020, from the New Zealand National Minimum Data Set. A case-crossover cohort for antibiotic exposures, with a 3 day case period and two 30 day washout periods, summed up to a 66 day study period, was created. Using conditional logistic regression, the changed odds of AKI due to exposure to an antibiotic was calculated as matched odds ratios and their 95% confidence intervals., Results: A total of 2399 incident cases of AKI were identified between 2005 and 2020 among older adults. The adjusted odds of consuming sulfamethoxazole/trimethoprim antibiotic during the case period was 3.57 times (95% CI 2.86-4.46) higher than the reference period among the incident AKI cases. Fluoroquinolone utilization was also associated with incident AKI (adjusted OR = 2.56; 95% CI 1.90-3.46)., Conclusion: The potential of sulfamethoxazole/trimethoprim and fluoroquinolones to be associated with AKI raises the significant need for vigilant prescribing of these antibiotics in older adults., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Machine learning-based prediction models have the potential to have a considerable positive impact on geriatric care., Design: Systematic review and meta-analyses., Participants: Older adults (≥ 65 years) in any setting., Intervention: Machine learning models for predicting clinical outcomes in older adults were evaluated. A random-effects meta-analysis was conducted in two grouped cohorts, where the predictive models were compared based on their performance in predicting mortality i) under and including 6 months ii) over 6 months., Outcome Measures: Studies were grouped into two groups by the clinical outcome, and the models were compared based on the area under the receiver operating characteristic curve metric., Results: Thirty-seven studies that satisfied the systematic review criteria were appraised, and eight studies predicting a mortality outcome were included in the meta-analyses. We could only pool studies by mortality as there were inconsistent definitions and sparse data to pool studies for other clinical outcomes. The area under the receiver operating characteristic curve from the meta-analysis yielded a summary estimate of 0.80 (95% CI: 0.76 - 0.84) for mortality within 6 months and 0.81 (95% CI: 0.76 - 0.86) for mortality over 6 months, signifying good discriminatory power., Conclusion: The meta-analysis indicates that machine learning models display good discriminatory power in predicting mortality. However, more large-scale validation studies are necessary. As electronic healthcare databases grow larger and more comprehensive, the available computational power increases and machine learning models become more sophisticated; there should be an effort to integrate these models into a larger research setting to predict various clinical outcomes., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Medication adherence improves morbidity and mortality-related outcomes in heart failure, and knowledge of patterns of medication adherence supports patient and clinician decision-making. Routinely collected national data facilitate the exploration of medication adherence and associated factors in older adults with heart failure, including the association between ethnicity and adherence. There are known inequities in access to medicines between Māori (Indigenous People of Aotearoa New Zealand) and non-Māori, yet ethnic variation in medicines adherence in community-dwelling older adults with heart failure has not been explored., Objective: Here we identify medication adherence rates for community-dwelling older adults diagnosed with heart failure and differences in adherence rates between Māori and non-Māori., Methods: Cross-sectional analysis of interRAI (comprehensive standardised assessment) data in a continuously recruited national cohort from 2012 to 2019., Results: Overall, 13,743 assessments (Māori N = 1526) for older community-dwelling adults with heart failure diagnoses were included. The mean age of participants was 74.5 years [standard deviation (SD) 9.1 years] for Māori and 82.3 years (SD 7.8 years) non-Māori. In the Māori cohort, 21.8% did not adhere fully to their medication regimen, whereas in the non-Māori cohort, this figure was 12.8%. After adjusting for confounders, the Māori cohort were more likely to be medication non-adherent than non-Māori [prevalence ratio 1.53, 95% confidence interval (CI) 1.36-1.73]., Conclusions: There was a significant disparity between Māori and non-Māori concerning medication adherence. Given the international use of the interRAI-HC assessment tool, these results have significant transferability to other countries and allow the identification of underserved ethnic groups for which culturally appropriate interventions can be targeted., (© 2023. The Author(s).)

Background: Polypharmacy is associated with poor outcomes in older adults. Targeted deprescribing of anticholinergic and sedative medications may improve health outcomes for frail older adults. Our pharmacist-led deprescribing intervention was a pragmatic 2-arm randomized controlled trial stratified by frailty. We compared usual care (control) with the intervention of pharmacists providing deprescribing recommendations to general practitioners., Methods: Community-based older adults (≥65 years) from 2 New Zealand district health boards were recruited following a standardized interRAI needs assessment. The Drug Burden Index (DBI) was used to quantify the use of sedative and anticholinergic medications for each participant. The trial was stratified into low, medium, and high-frailty. We hypothesized that the intervention would increase the proportion of participants with a reduction in DBI ≥ 0.5 within 6 months., Results: Of 363 participants, 21 (12.7%) in the control group and 21 (12.2%) in the intervention group had a reduction in DBI ≥ 0.5. The difference in the proportion of -0.4% (95% confidence interval [CI]: -7.9% to 7.0%) provided no evidence of efficacy for the intervention. Similarly, there was no evidence to suggest the effectiveness of this intervention for participants of any frailty level., Conclusion: Our pharmacist-led medication review of frail older participants did not reduce the anticholinergic/sedative load within 6 months. Coronavirus disease 2019 (COVID-19) lockdown measures required modification of the intervention. Subgroup analyses pre- and post-lockdown showed no impact on outcomes. Reviewing this and other deprescribing trials through the lens of implementation science may aid an understanding of the contextual determinants preventing or enabling successful deprescribing implementation strategies., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Objectives: Anticholinergic burden is detrimental to cognitive health. Multiple studies found that a high anticholinergic burden is associated with an increased risk for dementia, changes to the brain structure, function, and cognitive decline. We performed a post hoc analysis of a randomized controlled deprescribing trial. We compared the effect of the intervention on baseline anticholinergic burden across the treatment and control groups and the time of recruitment before and after a lockdown due to the COVID pandemic with subgroup analyses by baseline frailty index., Design: Randomized controlled trial., Settings and Participants: We analyzed data from a de-prescribing trial of older adults (>65 years) previously conducted in New Zealand that was focused on reducing the Drug Burden Index (DBI)., Methods: We used the anticholinergic cognitive burden (ACB) to quantify the impact of the intervention on reducing the anticholinergic burden. Participants not taking anticholinergics at the start of the trial were excluded. The primary outcome for this subgroup analysis was a change in ACB, measured with the ĝ Hedges statistic describing the difference in standard deviation units of this change between intervention and control. For this analysis, the trial participants were stratified into low, medium, and high frailty and timing into prior- and post-lockdown (public health measures for COVID-19)., Results: Among the 295 participants in this analysis, the median (IQR) age was 79 (74, 85), and 67% were women. For the primary outcome ĝ Hedges  = -0.04 (95% CI -0.26 to 0.19) with a -0.23 mean reduction in ACB in the intervention arm and -0.19 in the control arm. Before lockdown ĝ Hedges  = -0.38 (95% CI -0.84 to 0.04) and post-lockdown ĝ Hedges  = 0.07 (95% CI -0.19 to 0.33). The mean change in ACB for each of the frailty strata was as follows: low frailty (-0.02; 95% CI -0.65 to 0.18); medium frailty (0.05; 95% CI -0.28 to 0.38); high frailty (0.08; 95% CI -0.40 to 0.56)., Conclusions and Implications: The study did not provide evidence for the effect of pharmacist deprescribing intervention on reducing the anticholinergic burden. However, this post hoc analysis examined the impact of COVID on the effectiveness of the intervention, and further research in this area may be warranted., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: As people age, they accumulate several health conditions, requiring the use of multiple medications (polypharmacy) to treat them. One of the challenges with polypharmacy is the associated increase in anticholinergic exposure to older adults. In addition, several studies suggest an association between anticholinergic burden and declining physical function in older adults., Objective/purpose: This systematic review aimed to synthesise data from published studies regarding the association between anticholinergic burden and mobility. The studies were critically appraised for the strength of their evidence., Methods: A systematic literature search was conducted across five electronic databases, EMBASE, CINAHL, PSYCHINFO, Cochrane CENTRAL and MEDLINE, from inception to December 2021, to identify studies on the association of anticholinergic burden with mobility. The search was performed following a strategy that converted concepts in the PECO elements into search terms, focusing on terms most likely to be found in the title and abstracts of the studies. For observational studies, the risk of bias was assessed using the Newcastle Ottawa Scale, and the Cochrane risk of bias tool was used for randomised trials. The GRADE criteria was used to rate confidence in evidence and conclusions. For the meta-analyses, we explored the heterogeneity using the Q test and I 2 test and the publication bias using the funnel plot and Egger's regression test. The meta-analyses were performed using Jeffreys's Amazing Statistics Program (JASP)., Results: Sixteen studies satisfied the inclusion criteria from an initial 496 studies. Fifteen studies identified a significant negative association of anticholinergic burden with mobility measures. One study did not find an association between anticholinergic intervention and mobility measures. Five studies included in the meta-analyses showed that anticholinergic burden significantly decreased walking speed (0.079 m/s ± 0.035 MD ± SE,95% CI: 0.010 to 0.149, p = 0.026), whilst a meta-analysis of four studies showed that anticholinergic burden significantly decreased physical function as measured by three variations of the Instrumental Activities of Daily Living (IADL) instrument 0.27 ± 0.12 (SMD ± SE,95% CI: 0.03 to 0.52), p = 0.027. The results of both meta-analyses had an I 2 statistic of 99% for study heterogeneity. Egger's test did not reveal publication bias., Conclusion: There is consensus in published literature suggesting a clear association between anticholinergic burden and mobility. Consideration of cognitive anticholinergic effects may be important in interpreting results regarding the association of anticholinergic burden and mobility as anticholinergic drugs may affect mobility through cognitive effects., (© 2023. The Author(s).)

Background: Recently, antivirals, including remdesivir, have been repurposed to treat COVID-19 infections. Initial concerns have been raised about the adverse renal and cardiac events associated with remdesivir., Objective: This study aimed to analyse the adverse renal and cardiac events associated with remdesivir in patients with COVID-19 infections using the US FDA adverse event reporting system., Method: A case/non-case method was used to determine adverse drug events associated with remdesivir as the primary suspect drug between January 1, 2020, and November 11, 2021, for patients with COVID-19 infections. Cases were reports for remdesivir with ≥1 ADEs as preferred terms included in the Medical Dictionary of Regulatory Activities (MedDRA) system organ classes 'Renal and urinary disorders' or 'cardiac' disorders. To measure disproportionality in reporting of ADEs, frequentist approaches, including the proportional reporting ratio (PRR) and reporting odds ratio (ROR), were used. The empirical Bayesian Geometric Mean (EBGM) score and information component (IC) value were calculated using a Bayesian approach. A signal was defined as the lower limit of 95% confidence intervals of ROR ≥ 2, PRR ≥ 2, IC > 0, and EBGM > 1 for ADEs with ≥4 reports. Sensitivity analyses were undertaken by excluding reports for non-Covid indications and medications strongly associated with AKI and cardiac arrhythmias., Results: In the main analysis for remdesivir use in patients with COVID-19 infections, we identified 315 adverse cardiac events comprising 31 different MeDRA PTs and 844 adverse renal events comprising 13 different MeDRA PTs. Regarding adverse renal events, disproportionality signals were noted for "renal failure" (ROR = 2.8 (2.03-3.86); EBGM = 1.92 (1.58-2.31), "acute kidney injury" (ROR = 16.11 (12.52-20.73); EBGM = 2.81 (2.57-3.07), "renal impairment" (ROR = 3.45 (2.68-4.45); EBGM = 2.02 (1.74-2.33). Regarding adverse cardiac events, strong disproportionality signals were noted for "electrocardiogram QT prolonged" (ROR = 6.45 (2.54-16.36); EBGM = 2.04 (1.65-2.51), "pulseless electrical activity" (ROR = 43.57 (13.64-139.20); EBGM = 2.44 (1.74-3.33), "sinus bradycardia" (ROR = 35.86 (11.16-115.26); EBGM = 2.82 (2.23-3.53), "ventricular tachycardia" (ROR = 8.73 (3.55-21.45); EBGM = 2.52 (1.89-3.31). The risk of AKI and cardiac arrythmias were confirmed by sensitivity analyses., Conclusion: This hypothesis-generating study identified AKI and cardiac arrhythmias associated with remdesivir use in patients with COVID-19 infections. The relationship between AKI and cardiac arrhythmias should be further investigated using registries or large clinical data to assess the impact of age, genetics, comorbidity, and the severity of Covid infections as potential confounders.

Introduction: Current safety data from Phase 3 clinical trials have concluded that apart from transient local and systemic reactions, no safety concerns were identified for the Moderna COVID-19 vaccine (mRNA-1273). However, Phase 3 studies are insufficient to detect rare adverse events (AEs). A literature search of the two major electronic databases, Embase and PubMed, was performed to enable the identification and characterization of all relevant articles from December 2020 to November 2022., Areas Covered: This narrative review summarizes the key safety outcomes associated with the mRNA-1273 vaccine to inform healthcare decisions and increase public awareness of mRNA-1273 vaccine safety. The primary adverse events (AEs) reported within a diverse population, receiving the mRNA-1273 vaccine, were; localized injection site pain, fatigue, headache, myalgia, and chills. In addition, the mRNA-1273 vaccine was also associated with; less than a 1-day change in the menstrual cycle, a 10-fold higher risk of myocarditis and pericarditis within young males aged 18-29 years and increased levels of anti-polyethylene glycol (PEG) antibodies., Expert Opinion: The transient nature of commonly observed AEs and the rare occurrence of severe events within mRNA-1273 recipients show no significant safety concerns which should prevent vaccination. However, large-scale epidemiological studies with longer follow-up periods are required to surveillance rare safety outcomes.

Objective: This study aims to characterize the adverse events (AEs) following the administration of the mRNA-1273 COVID-19 vaccine from the Vaccine Adverse Event Reporting System (VAERS) data., Methods: In this case/non-case analysis, reports between 1 January 2021, and 27 October 2022, were extracted from VAERS. AEs were defined as preferred terms (PTs) by Medical Dictionary for Regulatory Activities (MedDRA) terminology. Disproportionality analyses were conducted to calculate the reporting odds and proportional reporting ratios. The Bayesian approach was used to calculate information component (IC) values and Empirical Bayesian Geometric Mean scores for all the AEs detected., Results: 186 MedDRA PTs compromising 702,495 AEs associated with the mRNA-1273 vaccine were identified. Three statistically significant signals were identified for general and systemic AEs, administration site conditions, and product issues. Cardiac disorders were rarely reported, the most common being; 489 reports for 'myocarditis' (19.44%), 475 for 'acute myocardial infarction' (18.88%), 457 for 'myocardial infarction' (18.16%), 290 for 'bradycardia' (11.53%) and 281 for 'pericarditis' (11.17%)., Conclusions: The most frequently identified AEs following mRNA-1273 vaccination agree with those listed within the Summary of Product Characteristics. In addition, disproportionality analysis did not find any statistically significant signals for myocarditis or pericarditis.

Background: Antimuscarinics are the backbone of the pharmacological management of overactive bladder. Still, concerns have been raised over the nervous system (NS) adverse drug events (AEs) due to their dissimilarities to muscarinic receptor-subtype affinities., Objective: This study aimed to identify the nervous system and gastrointestinal adverse drug events (ADEs) associated with solifenacin use in older adults (≥65 years)., Methods: A case/non-case analysis was performed on the reports submitted to the FDA Adverse Event Reporting System (FAERS) between 01/01/2004 and 30/06/2020. Cases were reports for solifenacin with ≥1 ADEs as preferred terms included in the Medical Dictionary of Regulatory Activities (MedDRA) system organ classes 'nervous system' or 'gastrointestinal' disorders. Non-cases were all other remaining reports for solifenacin. The case/non-cases was compared between solifenacin and other bladder antimuscarinics. Frequentist approaches, including the proportional reporting ratio (PRR) and reporting odds ratio (ROR), were used to measure disproportionality. The empirical Bayesian Geometric Mean (EBGM) score and information component (IC) value were calculated using a Bayesian approach. A signal was defined as the lower limit of 95% confidence intervals of ROR ≥ 2, PRR ≥ 2, IC > 0, EBGM > 1, for ADEs with ≥4 reports., Results: 107 MedDRA preferred terms (PTs) comprising 970 ADE reports were retrieved for nervous system disorders associated with solifenacin. For gastrointestinal disorders, 129 MedDRA PTs comprising 1817 ADE reports were retrieved. Statistically significant results were found for 'altered state of consciousness': ROR = 9.71 (2.13-44.35), PRR = 9.69 (2.12-44.2) and IC = 1.29 (0.93-1.66)., Conclusions: The disproportionality reporting of 'altered state of consciousness', a previously unidentified ADE, was unexpected. Further monitoring of this ADE is needed to ensure patient safety, as this could be linked to poor balance and falls in older adults.

General practitioner (GP) prescribing of psychotropic medicines to paediatric patients is increasing across countries, sparking the need for additional research into this field. We examined prescribing rates, GP and patient characteristics and indications associated with prescribing psychotropic medicines to paediatric patients in Australian general practice, using data from the Bettering the Evaluation and Care of Health (BEACH) program. We extracted all encounters with children aged 3 to 17 from 2000 to 2016. Psychotropic medicines were defined as those in the ATC codes N05 (Psycholeptics) and N06 (Psychoanaleptics). Of the 144,397 encounters, GPs prescribed 1829 psychotropic medicines to paediatric patients at an average rate of 1.16 prescriptions per 100 encounters (95% confidence interval 1.09-1.23). We found that the rate of psychotropic medicines prescribed to paediatric patients in Australian general practice increased. Patients who were adolescent, female, socio-economically disadvantaged or from an English-speaking background were significantly more likely to be prescribed a psychotropic medicine. GP practices in remote or regional areas and Australian graduate GPs were more likely to prescribe psychotropic medicines to paediatric patients. Depression, attention deficit hyperactivity disorder, anxiety and autism were the most common psychiatric indications managed with psychotropic medicines. Antidepressants, psychostimulants, benzodiazepines, antipsychotics and other psychotropic medicines were prescribed, signifying a high rate of off-label use. Sertraline was the most common psychotropic medicine prescribed, followed by fluoxetine and methylphenidate. Future studies involving data from other prescribers, e.g. paediatricians and psychiatrists, and studies linking prescribed medicines to their indications may widen our understanding of psychotropic medicine prescribing in Australian paediatric patients., Competing Interests: Declaration of Competing Interest L.T., C.H., P.S.N., T.F.C.: There are no competing interests to declare., (Copyright © 2022 Elsevier B.V. and ECNP. All rights reserved.)

Purpose: Antibacterials induce a differential risk of acute kidney injury (AKI) in older adults. This study investigated the reporting risk of AKI associated with antibacterials using the individual case safety reports (ICSRs) submitted to the Food and Drug Administration Adverse Event Reporting System (FAERS) database., Methods: A case/non-case method was used to assess AKI risk associated with antibacterials between 1 January 2000 and 30 September 2021. Cases were ICSRs for antibacterials with AKI as preferred terms included in the Medical Dictionary of Regulatory Activities (MedDRA) system organ classes 'Renal and urinary disorders' disorders. The analyses were completed on a de-duplicated data set containing only the recent version of the ICSR. Signals were defined by a lower 95% confidence interval (CI) of reporting odds ratio (ROR) ≥ 2, proportional reporting ratio (PRR) ≥ 2, information component (IC) > 0, Empirical Bayes Geometric Mean (EBGM) > 1 and reports ≥4. Sensitivity analyses were conducted a priori to assess the robustness of signals., Results: A total of 3 680 621 reports on ADEs were retrieved from FAERS over the study period, of which 92 194 were antibacterial reports. Gentamicin, sulfamethoxazole, trimethoprim and vancomycin consistently gave strong signals of disproportionality on all four disproportionality measures and across the different sensitivity analyses: gentamicin (ROR = 2.95[2.51-3.46]), sulfamethoxazole (ROR = 2.97[2.68-3.29]), trimethoprim (ROR = 2.81[2.29-3.46]) and vancomycin (ROR = 3.35[3.08-3.64])., Conclusion: Signals for gentamicin, sulfamethoxazole, trimethoprim and vancomycin were confirmed by using antibacterials as a comparator, adjusting for drug-related competition bias and event-related competition bias., (© 2022 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Background: a Frailty Index (FI) calculated by the accumulation of deficits is often used to quantify the extent of frailty in individuals in specific settings. This study aimed to derive a FI that can be applied across three standardised international Residential Assessment Instrument assessments (interRAI), used at different stages of ageing and the corresponding increase in support needs., Methods: deficit items common to the interRAI Contact Assessment (CA), Home Care (HC) or Long-Term Care Facilities assessment (LTCF) were identified and recoded to form a cumulative deficit FI. The index was validated using a large dataset of needs assessments of older people in New Zealand against mortality prediction using Kaplan Meier curves and logistic regression models. The index was further validated by comparing its performance with a previously validated index in the HC cohort., Results: the index comprised 15 questions across seven domains. The assessment cohort and their mean frailty (SD) were: 89,506 CA with 0.26 (0.15), 151,270 HC with 0.36 (0.15) and 83,473 LTCF with 0.41 (0.17). The index predicted 1-year mortality for each of the CA, HC and LTCF, cohorts with area under the receiver operating characteristic curves (AUCs) of 0.741 (95% confidence interval, CI: 0.718-0.762), 0.687 (95%CI: 0.684-0.690) and 0.674 (95%CI: 0.670-0.678), respectively., Conclusions: the results for this multi-instrument FI are congruent with the differences in frailty expected for people in the target settings for these instruments and appropriately associated with mortality at each stage of the journey of progressive ageing., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Older adults are at an increased risk of delirium because of age, polypharmacy, multiple comorbidities and acute illness. Antimuscarinics are the backbone of the pharmacological management of overactive bladder. However, the safety profiles of antimuscarinics vary because of their dissimilarities to muscarinic receptor-subtype affinities and are associated with differential central anticholinergic adverse effects., Objective: This study aimed to examine delirium risk in new users of oxybutynin and solifenacin in older adults (≥ 65 years). In the secondary analyses, we examined the risk of delirium by type and dose of antimuscarinic., Method: We applied a case-time-control design to investigate delirium risk in older adults who started taking oxybutynin and solifenacin. We used a nationwide inpatient hospital data (2005-2016), National Minimum Data Set, maintained by the Ministry of Health, New Zealand (NZ), to identify older adults with a new-onset diagnosis of delirium. Eligible patients were older adults aged 65 at entry into the cohort on 1/1/2006. We used dispensing claims data to determine antimuscarinic treatment exposure. The antimuscarinic included in the study were new users of oxybutynin and solifenacin. These two antimuscarinics are subsidised by the Pharmaceutical Management Agency and are the most frequently used antimuscarinic in NZ. A conditional logistic regression model was used to compute matched odds ratios (MORs) and 95% confidence intervals (CIs). In the case-time-control design, we made separate analyses to evaluate the dose-response risk of delirium., Results: We identified 4818 individuals (mean age 82.14) from 2005 to 2015 with incident delirium and were exposed to at least one of the antimuscarinic of interest. The case-time-control matched odds ratio (MOR) for delirium with oxybutynin was (2.06, 95% confidence interval [CI] 1.07-3.96). Solifenacin was not associated with delirium (0.89 95%CI 0.64-1.23). In the sensitivity analyses, the case-time-control MOR for delirium using a shorter risk period (0-3 days) did not change the results. The dose-response risk of delirium was significant for oxybutynin (0.05, 95%CI 0.02-0.08) but not for solifenacin (-0.01, 95%CI -0.03 to 0.00). In addition, in the subgroup analyses, a statistically significant association of delirium was found for oxybutynin but not for solifenacin in the non-dementia cohort (2.11,95% CI 1.08-4.13) and the dementia cohort (1.25, 95%CI 0.05-26.9)., Conclusion: The study found that oxybutynin but not solifenacin is associated with a risk of new-onset delirium in older adults. The higher blockade of M1 and M2 receptors by oxybutynin is likely to contribute to delirium than solifenacin, which is highly selective for the M3 receptor subtype. Therefore, the treatment choice with an M3 selective agent must be given due consideration, particularly in those with pre-existing cognitive impairment., (© 2022 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Background: Psychotropic medicine utilisation in older adults continues to be of interest because of overuse and concerns surrounding its safety and efficacy., Objective: This study aimed to characterise the utilisation of psychotropic medicines in older people in New Zealand., Methods: We conducted a repeated cross-sectional analysis of national dispensing data from 1 January, 2005 to 31 December, 2019. We defined utilisation using the Anatomical Therapeutic Chemical classification defined daily dose system. Utilisation was measured in terms of the defined daily dose (DDD) per 1000 older people per day (TOPD)., Results: Overall, the utilisation of psychotropic medicines increased marginally by 0.42% between 2005 and 2019. The utilisation increased for antidepressants (72.42 to 75.21 DDD/TOPD) and antipsychotics (6.06-19.04 DDD/TOPD). In contrast, the utilisation of hypnotics and sedatives (53.74-38.90 DDD/TOPD) and anxiolytics decreased (10.20-9.87 DDD/TOPD). The utilisation of atypical antipsychotics increased (4.06-18.72 DDD/TOPD), with the highest percentage change in DDD/TOPD contributed by olanzapine (520.6 %). In comparison, utilisation of typical antipsychotics was relatively stable (2.00-2.06 DDD/TOPD). The utilisation of venlafaxine increased remarkably by 5.7 times between 2005 and 2019. The utilisation of zopiclone was far greater than that of other hypnotics in 2019., Conclusions: There was only a marginal increase in psychotropic medicines utilisation from 2005 to 2019 in older adults in New Zealand. There was a five-fold increase in the utilisation of antipsychotic medicines. Continued monitoring of psychotropic medicine utilisation will be of interest to understand the utilisation of antidepressants and antipsychotic medicines during the coronavirus disease 2019 pandemic year., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: Older adults (aged 65 years and above) constitute the fastest growing population cohort in the western world. There is increasing evidence that the burden of infections disproportionately affects this cohort of older adults and hence this vulnerable population is frequently exposed to antimicrobials. There is currently no systematic review summarising the evidence for risk of organ injury following antimicrobial exposure among older adults. This protocol will outline how we will conduct a systematic review and meta-analyses to examine the relationship between antimicrobial exposure and organ injury in older adults., Methods and Analysis: We will search for PsycINFO, PubMed and EMBASE databases for relevant articles using MeSH terms where applicable. After removing duplicates, articles will be screened for inclusion into or exclusion from the study by two reviewers. Title and abstract screening will be done first, followed by full-text screening. The Newcastle-Ottawa scale will be used to assess the risk of bias for cohort and case control studies, and the Cochrane collaboration's risk of bias tool will be used for randomised control trials. We will explore the potential sources of heterogeneity and bias using funnel and forest plots of the included studies., Ethics and Dissemination: During the conduct of the review, ethical principles will be observed to ensure integrity. Any potential conflicts of interests will be declared, all contributors acknowledged and no plagiarised material will be included in the review.The systematic review and meta-analysis will be submitted for publication in a peer-reviewed journal in geriatrics. The findings will also be presented at international conferences in geriatrics or pharmacoepidemiology. The results will be communicated to patient and public engagement networks supported by the NHS Research and Development., Prospero Registration Number: This protocol is registered in the PROSPERO database (registration number CRD42020152621)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Targeted deprescribing of anticholinergic and sedative medications in older people may improve their health outcomes. This trial will determine if pharmacist-led reviews lead to general practitioners deprescribing anticholinergic and sedative medications in older people living in the community., Methods and Analysis: The standard protocol items: Recommendations for Interventional Trials (SPIRIT) checklist was used to develop and report the protocol. The trial will involve older adults stratified by frailty (low, medium, and high). This will be a pragmatic two-arm randomized controlled trial to test general practitioner uptake of pharmacist recommendations to deprescribe anticholinergic and sedative medications that are causing adverse side effects in patients., Study Population: Community-dwelling frail adults, 65 years or older, living in the Canterbury region of New Zealand, seeking publicly funded home support services or admission to aged residential care and taking at least one anticholinergic or sedative medication regularly., Intervention: New Zealand registered pharmacists using peer-reviewed deprescribing guidelines will visit participants at home in the community, review their medications, and recommend anticholinergic and sedative medications that could be deprescribed to the participant's general practitioner. The total use of anticholinergic and sedative medications will be quantified using the Drug Burden Index (DBI)., Outcomes: The primary outcome will be the change in total DBI between baseline and 6-month follow-up. Secondary outcomes will include entry into aged residential care, prolonged hospitalization, and death., Data Collection Points: Data will be collected at the time of interRAI assessments (T0), at the time of the baseline review (T1), at 6 months following the baseline review (T2), and at the end of the study period, or end of study participation for participants admitted into aged residential care, or who died (T3)., Ethics and Dissemination: Ethical approval has been obtained from the Human, Disability and Ethics Committee: ethical number (17CEN265)., Trial Registration: ClinicalTrials.gov ACTRN12618000729224 . Registered on May 2, 2018, with the Australian New Zealand Clinical Trials Registry., (© 2021. The Author(s).)

Background: Older adults (aged 65 years and above) constitute the fastest growing population cohort in the western world. There is increasing evidence that the burden of infections disproportionately affects older adults, and hence this vulnerable population is frequently exposed to antimicrobials. There is currently no systematic review summarising the evidence for organ injury risk among older adults following antimicrobial exposure. This systematic review and meta-analysis examined the relationship between antimicrobial exposure and organ injury in older adults., Methodology: We searched for original research articles in PubMed, Embase.com , Web of Science core collection, Web of Science BIOSIS citation index, Scopus, Cochrane Central Register of Controlled Trials, ProQuest, and PsycINFO databases, using key words in titles and abstracts, and using MeSH terms. We searched for all available articles up to 31 May 2021. After removing duplicates, articles were screened for inclusion into or exclusion from the study by two reviewers. The Newcastle-Ottawa scale was used to assess the risk of bias for cohort and case-control studies. We explored the heterogeneity of the included studies using the Q test and I 2 test and the publication bias using the funnel plot and Egger's test. The meta-analyses were performed using the OpenMetaAnalyst software., Results: The overall absolute risks of acute kidney injury among older adults prescribed aminoglycosides, glycopeptides, and macrolides were 15.1% (95% CI: 12.8-17.3), 19.1% (95% CI: 15.4-22.7), and 0.3% (95% CI: 0.3-0.3), respectively. Only 3 studies reported antimicrobial associated drug-induced liver injury. Studies reporting on the association of organ injury and antimicrobial exposure by age or duration of treatment were too few to meta-analyse. The funnel plot and Egger's tests did not indicate evidence of publication bias., Conclusion: Older adults have a significantly higher risk of sustaining acute kidney injury when compared to the general adult population. Older adults prescribed aminoglycosides have a similar risk of acute kidney injury to the general adult population., (© 2021. The Author(s).)

Background: Older adults are at an increased risk of delirium because of age, polypharmacy, multiple comorbidities, frailty, and acute illness. Although medication-induced delirium in older adults is well understood, limited population-level evidence is available, particularly on combinations of medications associated with delirium in older adults., Objectives: We aimed to apply association rule analysis to identify drug combinations contributing to delirium risk in adults aged 65 and older using a case-time-control design., Method: We sourced a nationwide representative sample of New Zealander's aged ≥65 years from the pharmaceutical collections and hospital discharge information. Prescription records (2005-2015) were obtained from New Zealand pharmaceutical collections (Pharms). Medication exposures were coded as binary variables (exposed vs. not exposed) at the individual drug level. All medications, including antimicrobials, antihistamines, diuretics, opioids, and nonsteroidal anti-inflammatory medications, were considered drugs of interest. The first-time coded diagnosis of delirium was extracted from the National Minimal Dataset (NMDS). A unique patient identifier linked the prescription dataset to the event dataset to set up a case-time-control cohort, indexed at the first delirium event. Association rules were then applied to identify frequent drug combinations in the case and the control periods (l-day with a 35-day washout period) that are statistically associated with delirium, and the association was tested by computing a time-trend adjusted matched odds-ratio (MOR) and its 95% confidence interval (CI)., Results: We identified 28 503 individuals (mean age 84.1 years) from 2005 to 2015 with delirium. Our combined association rule and case-time-control analysis identified several drug classes, including antipsychotics, benzodiazepines, opioids, and diuretics associated with delirium. Our analysis also identified frequently used drug combinations that are associated with delirium. Examples include combined exposures to quetiapine and furosemide (MOR = 6.17; 95%CI = [2.05-18.54]), haloperidol (MOR = 4.81; 95%CI = [3.16-6.69]), combined exposures to furosemide, omeprazole, and lorazepam (MOR = 3.94; 95%CI = [3.03-5.10]), and fentanyl exposure (MOR = 3.46; 95%CI [2.05-9.21])., Conclusion: The association rule method applied to a case-time-control design is a novel approach to identifying drug combinations contributing to delirium with adjustment for any temporal trends in exposures. The study provides new insight into the combination of medicines linked to delirium., (© 2021 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Background: Little is known about the prevalence of frailty in indigenous populations. We developed a frailty index (FI) for older New Zealand Māori and Pasifika who require publicly funded support services., Methods: An FI was developed for New Zealand adults aged 65 and older who had an interRAI Home Care assessment between June 1, 2012 and October 30, 2015. A frailty score for each participant was calculated by summing the number of deficits recorded and dividing by the total number of possible deficits. This created a FI with a potential range from 0 to 1. Linear regression models for FIs with ethnicity were adjusted for age and sex. Cox proportional hazards models were used to assess the association between the FI and mortality for Māori, Pasifika, and non-Māori/non-Pasifika., Results: Of 54 345 participants, 3096 (5.7%) identified as Māori, 1846 (3.4%) were Pasifika, and 49 415 (86.7%) identified as neither Māori nor Pasifika. New Zealand Europeans (48 178, 97.5%) constituted most of the latter group. Within each sex, the mean FIs for Māori and Pasifika were greater than the mean FIs for non-Māori and non-Pasifika, with the difference being more pronounced in women. The FI was associated with mortality (Māori subhazard ratio [SHR] 2.53, 95% CI 1.63-3.95; Pasifika SHR 6.03, 95% CI 3.06-11.90; non-Māori and non-Pasifika SHR 2.86, 95% CI 2.53-3.25)., Conclusions: This study demonstrated differences in FI between the ethnicities in this select cohort. After adjustment for age and sex, increases in FI were associated with increased mortality. This suggests that FI is predictive of poor outcomes in these ethnic groups., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To determine the differences in information between prescribing guidelines and drug labeling, as well as to compare the approval of psychotropic medicines for major depression in pediatric patients ("pediatric depression") across countries. Methods: The recommendations of The Maudsley Prescribing Guidelines in Psychiatry (MPGP) for the treatment of pediatric depression (<18 years) were compared against the regulatory-approved drug-labeling documents from the United Kingdom, Australia, New Zealand, Canada, and the United States. The use of medicines outside of their regulatory approval is defined as off-label use, so differences between the drug labeling and MPGP were characterized according to unapproved age, indication, dosage, or route of administration. Information in the drug labeling was also compared across countries. Results: MPGP provides recommendations for 6 medicines for the treatment of pediatric depression, for which, 30 drug labeling were retrieved. Three of 30 drug labeling were consistent with MPGP recommendations (fluoxetine in the United Kingdom, fluoxetine and escitalopram in the United States). Differences in information between MPGP and the drug labeling were identified in 26 of 30 drug labeling analyzed, most often due to age (24/26) followed by indication (2/26). No differences pertaining to dosage or route of administration information were identified. The number of approved psychotropic medicines varied across the studied countries and we found cross-country discrepancies in information in the drug labeling. Conclusion: Significant differences in information exists between MPGP and the drug labeling for psychotropic medicines for pediatric depression, due to unapproved ages or indications. Additionally, approval information in the drug labeling are not consistent across countries. Further research into reasons for variability and impact on practice may be warranted.

Purpose: The purpose of this study is to analyze the US FDA Adverse Event Reporting System (FAERS) to identify adverse cardiac events of hydroxychloroquine in older adults., Method: A case/non-case method was used to determine adverse events associated with hydroxychloroquine as the primary suspect drug between January 1, 2004, and December 31, 2019, for older adults (≥65 years). Adverse events are preferred terms (PTs) defined in MedDRA. We used frequentist approaches, including the reporting odds ratio (ROR) and the proportional reporting ratio (PRR) to measure disproportionality. We used Bayesian approaches to derive information component (IC) value and Empirical Bayesian Geometric Mean (EBGM) score. Signals were defined as the number of reports > 3 and the lower limit of 95% confidence intervals (CI) of ROR ≥ 2, PRR ≥ 2, IC > 0, EBGM > 1., Results: We identified 334 adverse cardiac events comprising 71 different MedDRA PTs from 2004 to 2019 for hydroxychloroquine in older adults. Strong disproportionality signals were noted for "Restrictive cardiomyopathy" (ROR = 272.43 (138.09-537.47); EBGM = 149.78 (77.34-264.67), "Right ventricular hypertrophy" (219.49 (85.32-564.70); 102.74 (39.67-222.81), "Cardiac septal hypertrophy" (226.77 (78.65-653.80); 93.82 (32.19-219.81), "Myocardial fibrosis" (57.29 (21.06-155.85); 42.99 (14.74-100.75), and "Cardiotoxicity" (43.90 (26.66-72.27); 40.28 (24.02-63.72)., Conclusions: The risk of cardiomyopathy and myocardial disorders is high following exposure to hydroxychloroquine in older adults. Due to the current lack of safety data from randomized controlled trials as well as large observational studies to confirm the risk of adverse cardiac events associated with hydroxychloroquine, findings from analyses of post-marketing data may serve as interim guidance., (© 2020 John Wiley & Sons Ltd.)

Objectives: The objectives of this study were to identify variables associated with dementia and entry into aged residential care (ARC) and derive and validate a risk prediction model for dementia and entry into ARC., Design: This was an observational study of prospectively collected Home Care International Residential Assessment Instrument (interRAI-HC) assessment data., Setting and Participants: Participants included all people age ≥65 years who had completed an interRAI-HC assessment between July 1, 2012 and June 30, 2018. Exclusion criteria included death or entry into ARC within 30 days of assessment and not living at home at the time of the assessment., Measures: InterRAI data from 94,202 older New Zealanders were evaluated for presence or absence of dementia. A multivariable competing-risks model for entry into ARC with death as the competing event was used to estimate subdistribution hazard ratios (SHR)., Results: In total, there were 18,672 (19.8%) persons with dementia (PWD). PWD were almost twice as likely to enter ARC as persons without dementia [42.8% vs 25.3%; difference 17.5% (95% confidence interval 16.7%‒18.2%)]. PWD at highest risk of entering ARC were those where there was a desire to live elsewhere (SHR 1.44), depression (indicated, SHR 1.15), poor cognitive performance (Cognitive Performance Scale minimal SHR 1.32 and severe plus SHR 1.91), and wandering (SHR 1.19). Factors associated with reduced risks of PWD entering ARC were living with a child or relative, alcohol consumption, and comorbidities., Conclusions and Implications: A desire to live elsewhere, social isolation, independent activities of daily living, and depression were independently associated with entry into ARC. Supporting caregivers may improve outcomes for PWD that delay entry into ARC. Future revisions of the interRAI questionnaire could provide more insight on this matter., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to examine the incidence of Parkinsonism in new users of second-generation antipsychotics (SGAs) in older adults (≥65 years). In the secondary analyses, we examined the risk of Parkinsonism by type and dose of SGA and conducted age-sex interactions., Method: This population-based study included older adults who had a new-onset diagnosis of Parkinsonism and who started taking olanzapine, risperidone or quetiapine between 1 January 2005, and 30 December 2016. The Cox proportional hazard (COXPH) model with inverse probability treatment weighted (IPTW) covariates was used to evaluate the risk of new-onset Parkinsonism associated with SGAs, using quetiapine as the reference. We used the Generalized Propensity Score method to evaluate the dose-response risk of Parkinsonism associated with SGAs., Results: After IPTW adjustment for covariates, the COXPH model showed that compared to quetiapine, the use of olanzapine and risperidone were associated with an increased risk of Parkinsonism. The IPTW-hazard ratios are 1.76 (95% confidence interval 1.57-1.97) and 1.31 (95%CI 1.16-1.49), respectively. The dose-response risk of Parkinsonism was highest for olanzapine with a hazard ratio of 1.69 (95%CI 1.40-2.05) and the least for quetiapine with a hazard ratio of 1.22 (95%CI 1.14-1.31). The risk of Parkinsonism in the 65 to 74-year age group was higher for both sexes with risperidone compared to olanzapine, but the risk increased with olanzapine for both sexes in the 85+ age group., Conclusion: The study found that the risk of new-onset Parkinsonism in older adults is 31% and 76% higher with risperidone and olanzapine respectively compared to quetiapine., (© 2020 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Background: Older adults are at an increased risk of acute kidney injury (AKI) because of aging, multiple comorbidities, and polypharmacy., Objectives: The aim of this case-crossover study was to apply association rule (AR) analysis to ascertain drug combinations contributing to the risk of AKI in adults aged 65 years and older., Methods: We sourced a nationwide representative sample of New Zealanders aged ≥65 years from the pharmaceutical collections and hospital discharge information. Prescription records (2005-2015) of drugs of interest were sourced from New Zealand pharmaceutical collections (Pharms). We classified medication exposure, as a binary variable, at individual drug level belonging to medication classes including antimicrobials, antihistamines, diuretics, opioids, nonsteroidal anti-inflammatory medications. Several studies have associated the drugs of interest from these medication classes with AKI in older adults. We extracted the first-time coded diagnosis of AKI from the National Minimal Data Set. A unique patient identifier linked the prescription data set to the event data set, to set up a case-crossover cohort, indexed at the first AKI event. ARs were then applied to identify frequent drug combinations in the case and the control periods (l-day observation with a 35-day washout period), and the association of AKI with each frequent drug combination was tested by computing a matched odds ratio (MOR) and its 95% confidence interval (CI)., Results: We identified 55 747 individuals (mean age 82.14) from 2005 to 2014 with incident AKI and exposed to at least one of the drugs of interest. ARs identified several medication classes including antimicrobials, nonsteroidal anti-inflammatory drugs, and opioids are associated with AKI. The frequently used medicines associated with AKI are trimethoprim (MOR = 1.68; 95% CI = [1.54-1.80]), ondansetron (MOR = 1.43; 95% CI = [1.25-1.64]), codeine phosphate plus metoclopramide (MOR = 1.37; 95% CI = [1.11-1.63]), and norfloxacin (MOR = 1.24; 95% CI [1.05-1.42])., Conclusions: We applied ARs, a novel methodology, to big data to ascertain drug combinations associated with AKI. ARs uncovered previously implicated medication classes that increase the risk of AKI in older adults. The finding that ondansetron increases the risk of AKI requires further investigation., (© 2020 John Wiley & Sons Ltd.)

La réduction des médicaments potentiellement inappropriés (MPI) chez les personnes âgées est un enjeu important selon de nombreux cliniciens et chercheurs à travers le monde, car ces médicaments accroissent significativement la morbidité et la mortalité dans la population plus âgée. La prévalence des MPI est un problème répandu malgré l'existence de plusieurs critères explicites et implicites de réduction des MPI chez les personnes âgées, les plus courants étant les critères de Beers, les critères STOPP/START et plusieurs critères nationaux spécifiques. Cette revue non systématique visait à examiner les critères de référence pour la réduction des MPI et à clarifier le rôle de certaines mesures, dont la déprescription, pour optimiser la prescription des médicaments chez les personnes âgées. Des recherches par mots-clés et termes MeSH ont été menées dans des bases de données électroniques. Les nombreux critères disponibles ont chacun leurs avantages et inconvénients. La déprescription, qui vise à réduire l'utilisation des MPI, a considérablement gagné en importance dans les initiatives associées à l'amélioration des pratiques de prescription. La déprescription est une approche méthodique qui implique l'arrêt graduel, éclairé et individualisé des médicaments inappropriés, avec un suivi rigoureux des patients pour assurer la détection d'événements indésirables ou de symptômes de rebond. Une approche combinée centrée sur le patient et le soignant favorise la collaboration entre les prescripteurs et les pharmaciens afin de réduire le nombre de MPI chez les personnes âgées., Reducing potentially inappropriate medications (PIMs) in older adults is an area of sustained interest for many clinicians and researchers across the globe, as PIMs contribute to a significant burden of morbidity and mortality in the aging population. The prevalence of PIMs is a pervasive problem despite the presence of several explicit and implicit criteria for reducing PIMs in older adults, the most common being the Beers criteria, the Screening Tool of Older Persons’ potentially inappropriate Prescriptions/Screening Tool to Alert doctors to the Right Treatment (STOPP/START) criteria, and several country-specific criteria. This narrative review aims to discuss the frequently used published criteria for reducing PIMs, and elucidates the role of certain measures, especially de-prescribing, to optimise medication prescription in older adults. Electronic databases were searched using keywords and MeSH terms. The numerous available criteria have their specific advantages and drawbacks. De-prescribing, an initiative to reduce the use of PIMs, has gained significant importance in improving appropriate prescribing practices. De-prescribing is a methodical approach to gradually stopping inappropriate medications judiciously for each patient and simultaneously monitoring the patient carefully for the onset of adverse events or rebound symptoms. A combined caregiver–patient-centred approach encourages the collaboration between prescribers and pharmacists to reduce PIMs in older adults.

Objective : To summarize studies that used the international Resident Assessment home care instrument (interRAI HC) to examine study outcomes for older people. Methods : A comprehensive systematic search was performed to identify relevant studies, using five databases from 1990 until October 2016. The Cochrane Risk-Bias assessment tool and Newcastle-Ottawa Scale was used to assess the quality of RCTs and non-RCTs, respectively. Results : Based on the full-text analysis, 40 studies met the inclusion criteria out of 506 total records. The review included 6 RCTs, 2 quasi-experimental, 17 prospective and retrospective studies, 13 cross-sectional and 2 longitudinal studies. A series of interventions and/or applications were identified from this review that employed the use of interRAI HC instrument: (a) in health services, (b) as a new integrated care model and for implementing machine learning algorithm, (c) as a comprehensive geriatric assessment tool, (d) in case management, (e) for care planning and screening, (f) in drug therapy assessment, (g) to assess caregiver burden, and (h) for various risk assessments. Studies that employed the interRAI HC instrument reported an array of health-outcome measures mostly related to functional, cognition, hospitalization and mortality. Conclusions : Application of the interRAI HC tool varied markedly across all studies, and the outcomes measures were heterogeneous. Future research directions are discussed. Clinical Implications : The results from this study facilitate the use of interRAI HC as a tool to measure an intervention's effect that leads to improvements in specific geriatric-related health outcome measures emphasizes on functional status and quality of life and ascertain its utility as a quality indicator for the care of older individuals.

Background: The Drug Burden Index (DBI) calculates the total sedative and anticholinergic load of prescribed medications and is associated with functional decline and hip fractures in older adults. However, it is unknown if confounding factors influence the relationship between the DBI and hip fractures. The objective of this study was to evaluate the association between the DBI and hip fractures, after correcting for mortality and multiple potential confounding factors., Methods: A competing-risks regression analysis conducted on a prospectively recruited New Zealand community-dwelling older population who had a standardized (International Resident Assessment Instrument) assessment between September 1, 2012, and October 31, 2015, the study's end date. Outcome measures were survival status and hip fracture, with time-varying DBI exposure derived from 90-day time intervals. The multivariable competing-risks regression model was adjusted for a large number of medical comorbidities and activities of daily living., Results: Among 70,553 adults assessed, 2,249 (3.2%) experienced at least one hip fracture, 20,194 (28.6%) died without experiencing a fracture, and 48,110 (68.2%) survived without a fracture. The mean follow-up time was 14.9 months (range: 1 day, 37.9 months). The overall DBI distribution was highly skewed, with median time-varying DBI exposure ranging from 0.93 (Q1 = 0.0, Q3 = 1.84) to 0.96 (Q1 = 0.0, Q3 = 1.90). DBI was significantly related to fracture incidence in unadjusted (p < .001) and adjusted (p < .001) analyses. The estimated subhazard ratio was 1.52 (95% confidence interval: 1.28-1.81) for those with DBI > 3 compared with those with DBI = 0 in the adjusted analysis., Conclusions: In this study, increasing DBI was associated with a higher likelihood of fractures after accounting for the competing risk of mortality and adjusting for confounders. The results of this unique study are important in validating the DBI as a guide for medication management and it could help reduce the risk of hip fractures in older adults., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Real-world evidence for the safety of using antithrombotics in older people with multimorbidity is limited. We investigated the risks of gastrointestinal bleeding (GI-bleeding) and intracranial (IC-bleeding) associated with antithrombotics either as monotherapy, dual antiplatelet therapy (DAPT) or as triple therapy (TT) [DAPT plus anticoagulant] in older individuals aged 65 years and above., Methods: We identified all individuals, 65 years and above, who had a first-time event of either IC- or GI-bleeding event from the hospital discharge data. We employed a case-crossover design and conditional logistic regression analyses to estimate the adjusted relative risks (ARR) of bleeding., Results: We found 66,500 individuals with at least one event of IC- or GI-bleeding between 01/01/2005 and 31/12/2014. DAPT use was associated with an increased risk relative to non-use of any antithrombotics in IC-bleeding (ARR = 3.13, 95% CI = [2.64, 3.72]) and GI-bleeding (ARR = 1.34, 95% CI = [1.14, 1.57]). The increased bleeding risk relative to non-use of any antithrombotics was highest with TT use (IC-bleeding, ARR = 17.28, 95% CI = [6.69, 44.61]; GI-bleeding, ARR = 4.85, 95% CI = [1.51, 15.57])., Conclusions: Using population-level data, we were able to obtain estimates on the bleeding risks associated with antithrombotic agents in older people often excluded from clinical trials because of either age or comorbidities.

Aim: To identify factors associated with prescribing potentially inappropriate medications (PIMs) in older adults (≥65 years) with complex care needs, who have undertaken a comprehensive geriatric risk assessment., Methods: A nationwide cross-sectional (retrospective, observational) study was performed. The national interRAI Home Care assessments conducted in New Zealand in 2015 for older adults were linked to the national pharmaceutical prescribing data (PHARMS). The 2015 Beers criteria were applied to the cross-matched data to identify the prevalence of PIMs. The factors influencing PIMs were analyzed using a multinomial logistic regression model., Results: In total, 16,568 older adults were included in this study. Individuals diagnosed with cancer, dementia, insomnia, depression, anxiety, and who were hospitalized in the last 90 days were more likely to be prescribed PIMs than those who were not diagnosed with the above disorders, and who were not hospitalized in the last 90 days. Individuals over 75 years of age, the Māori ethnic group among other ethnicities, individuals who were diagnosed with certain clinical conditions (diabetes, chronic obstructive pulmonary disease, stroke, or congestive cardiac failure), individuals requiring assistance with activities of daily living, and better self-reported health, were associated with a lesser likelihood of being prescribed PIMs., Conclusion: The study emphasizes the identification of factors associated with the prescription of PIMs during the first completed comprehensive geriatric assessment. Targeted strategies to reduce modifiable factors associated with the prescription of PIMs in subsequent assessments has the potential to improve medication management in older adults.

Background Prolonged use of anticholinergic and sedative medicines is correlated with worsening cognition and physical function decline. Deprescribing is a proposed intervention that can help to minimise polypharmacy whilst potentially improving several health outcomes in older people. Objective This study aimed to examine the feasibility of implementing a deprescribing intervention that utilises a patient-centred pharmacist-led intervention model; in order to address major deprescribing challenges such as general practitioner time constraints and lack of accessible deprescribing guidelines and processes. Setting Three residential care facilities. Methods The intervention involved a New Zealand registered pharmacist utilising peer-reviewed deprescribing guidelines to recommend targeted deprescribing of anticholinergic and sedative medicines to GPs. Main outcome measure The change in the participants' Drug Burden Index (DBI) total and DBI 'as required' (PRN) was assessed 3 and 6 months after implementing the deprescribing intervention. Results Seventy percent of potential participants were recruited for the study (n = 46), and 72% of deprescribing recommendations suggested by the pharmacist were implemented by General Pratitioners (p = 0.01; Fisher's exact test). Ninety-six percent of the residents agreed to the deprescribing recommendations, emphasising the importance of patient centred approach. Deprescribing resulted in a significant reduction in participants' DBI scores by 0.34, number of falls and adverse drug reactions, 6 months post deprescribing. Moreover, participants reported lower depression scores and scored lower frailty scores 6 months after deprescribing. However, cognition did not improve; nor did participants' reported quality of life. Conclusion This patient-centred deprescribing approach, demonstrated a high uptake of deprescribing recommendations and success rate. After 6 months, significant benefits were noted across a range of important health measures including mood, frailty, falls and reduced adverse reactions. This further supports deprescribing as a possible imperative to improve health outcomes in older adults.

Objective: To identify the prevalence and predictors of prescribing potentially inappropriate medications (PIMs) in a nationwide cohort of community dwellers with dementia requiring complex care needs., Methods: A cross-matched data of the International Resident Assessment Instrument-Home Care (9.1) (interRAI-HC) and prescribing data obtained from the Pharmaceutical Claims Data Mart (Pharms) extract files for older adults (≥65 y) requiring complex care needs were utilized for this study. The 2015 Beers criteria were applied to identify the prevalence of PIMs in older adults with dementia. Sociodemographic and clinical predictors of PIMs were analysed using a logistic regression model., Results: The study population consisted of 16 568 individuals who had their first interRAI assessment from 1 January 2015 to 31 December 2015. The estimated prevalence of dementia was 13.2% (2190/16 568). 66.9% (1465/2190) of the older adults diagnosed with dementia were prescribed PIMs, of which anticholinergic medications constituted 59.6% (873/1465). Males and individuals who were prescribed a greater number of medications were more likely to be prescribed PIMs. Individuals over 85 years of age, Māori ethnic group of individuals, older adults who were being supervised with respect to their activities of daily living, and individuals who reported good or excellent self-reported health had a lesser likelihood of being prescribed PIMs., Conclusion: We found that PIMs are prescribed frequently in older adults with dementia. Comprehensive geriatric assessments can serve as a potential tool to decrease the occurrence of PIMs in vulnerable groups with poor functional and cognitive status., (© 2018 John Wiley & Sons, Ltd.)

Background: The association rules method is a novel methodology to ascertain patterns of medication use and combinations associated with adverse drug events., Objectives: The aim of this case-crossover study was to apply the association rules method to ascertain medication combinations contributing to the risk of fractures in older adults., Methods: A nationwide representative sample of New Zealanders aged ≥65 years was sourced from the pharmaceutical collection. The first-time coded diagnosis of fracture was extracted from the National Minimum Dataset. Association rule method is a data mining technique that can be used to quickly traverse big datasets to identify a combination of items that co-occur. The association rules method were applied to identify frequent 11 medication combinations in the case and the control periods (1-14 days as hazard period, with 35-day washout period), and the association of fractures with each frequent medication combination were tested by computing a matched odd ratio (OR) and its 95% CI., Results: We identified a total of 72 184 individuals (mean age 81.5 years) from 2005 to 2014 with incident fracture and exposed to at least 1 medication of interest. The association rules method revealed codeine phosphate (aOR = 11.50, 95% CI, 7.09-15.20, concomitantly with ibuprofen), zopiclone (aOR = 2.34, 95% CI, 1.49-3.67, concomitantly with morphine) and quetiapine (OR = 1.95, 95% CI, 1.28-2.98, concomitantly with zopiclone) were associated with fractures., Conclusion: The association rules method identified medication exposure combinations containing psychotropic medications and codeine are frequently associated with fractures. This novel methodology applied to big data can be an important tool to ascertain medication combinations associated with adverse drug events., (Copyright © 2018 John Wiley & Sons, Ltd.)

Objectives: The primary objective of this study was to investigate the impact of RMMRs on medication regimen complexity, as assessed by a validated measure., Methods: Retrospective analysis of RMMRs pertaining to 285 aged care residents aged ≥ 65 years in Sydney, Australia. Medication regimen complexity was measured using the Medication Regimen Complexity Index (MRCI) at baseline, after pharmacists' recommendations (assuming that all of the pharmacists' recommendations were accepted by the General Practitioner (GP)), and after the actual uptake of pharmacists' recommendations by the GP. Differences in the regimen complexity was measured using the Wilcoxon sign rank test., Results: Pharmacists made 764 recommendations (average 2.7 recommendations per RMMR), of which 569 (74.5%) were accepted by GPs. The median MRCI at baseline in the sample was 25.5 (IQR = 19.0-32.5). No statistically significant differences were demonstrated in the MRCI scores after pharmacists' recommendations (p = 0.53) or after GPs' acceptance of these recommendations (p = 0.07) compared to the baseline., Conclusion: Our study revealed high acceptance of pharmacists' recommendations by GPs. This suggests that RMMRs are useful for identifying and resolving drug-related issues among residents of ACFs. However, our study failed to show a significant effect of RMMRs in reducing the medication regimen complexity, as measured by the MRCI. Further studies are needed to establish the association of medication regimen complexity and clinical outcomes in residents of ACFs.

Aim: To examine the patterns of preventive medicines (PM) use in the last year of life of older adults., Methods: This study cohort included individuals (n = 99 809) aged ≥75 years who were in their last year of life. PM examined in this study included low-dose aspirin (≤325 mg/day), clopidogrel, dipyridamole, warfarin, dabigatran, statins and bisphosphonates. Logistic regression models examined the influence of age, sex, multimorbidity, socioeconomic status, and a diagnosis of cancer on the number and type of PM prescribed from 2007 to 2012., Results: The number of PM prescribed was higher for men compared with women (OR 1.11, 95% CI 1.08-1.14). Increasing age did not have an effect on the number of PM prescribed. The use of clopidogrel increased almost threefold from 2007 to 2012 (OR 5.53, 95% CI 4.61-6.65). In contrast, bisphosphonates use decreased significantly during the same period (OR 0.35, 95% CI 0.32-0.39). Individuals with a diagnosis of cancer had increased odds of PM utilization for antiplatelets, aspirin monotherapy and statins, which had remarkably high odds (OR 4.11, 95% CI 3.88-4.34, P < 0.001)., Conclusions: The present explorative study highlighted that some PM, such as statins, continue to be prescribed until death, particularly those that might have been beneficial earlier in life, but have an uncertain or unfavorable risk-benefit ratio towards the end-of-life. Geriatr Gerontol Int 2018; 18: 892-898., (© 2018 Japan Geriatrics Society.)

Purpose: The prescription of potentially inappropriate medications (PIMs) is associated with an increase in adverse events, prescribing cascades, high health-care costs, morbidity, and mortality in the elderly. The overarching objective of this study is to examine the prevalence of PIMs in the elderly, applying the 2012 American Geriatrics Society Beers criteria for the study period 2012-2014, and the updated 2015 Beers criteria for 2015., Methods: The study population (N = 70,479) included a continuously recruited national cohort of community-dwelling older (aged ≥ 65 years) New Zealanders who had undertaken the International Resident Assessment Instrument-Home Care (interRAI-HC) assessments between September 2012 and October 2015. Exposure of PIMs 90 days before and after assessment, and 90-180 days after assessment are reported., Results: Exposure to PIMs was highest in individuals aged over 95 years and in males. The average number of PIMs prescribed 90 days before assessment during the period 2015 was marginally higher compared to 2012-2014 (0.19 versus 0.04), and a greater number of individuals were exposed to one or more PIMs in 2015 compared to 2012-2014 (7.13 versus 2.17%). The prevalence of PIMs 90 days before and after assessment was 2.17 and 6.92% for 2012-2014, and 7.13 and 24.7% for 2015, respectively. The percent change in PIMs in 2012-2014 and 2015 after 90 days of assessment were 4.70% (confidence interval (CI) 4.50%, 5.00%, p < 0.001) and 17.60% (95% CI 16.80%, 18.30%, p < 0.001), respectively. The majority of PIMs prescribed belonged to the therapeutic class of medications acting on the central nervous system and the gastrointestinal system., Conclusion: Geriatric risk assessments may provide a vital opportunity to review medication lists by multidisciplinary teams with a view to reducing PIMs and unnecessary polypharmacy in older adults. Comprehensive geriatric risk assessment has the potential to reduce adverse medication outcomes and costs associated with inappropriate prescribing in a vulnerable population of older adults.

Background: Adverse outcomes associated with advanced diseases are often exacerbated by polypharmacy., Objectives: The current study investigated an association between exposure to anticholinergic and sedative medicines and falls in community-dwelling older people, after controlling for potential confounders., Methods: We conducted a retrospective cross-sectional study of a continuously recruited national cohort of community-dwelling New Zealanders aged 65 years and over. Participants had an International Resident Assessment Instrument-Home Care (interRAI-HC) assessment between 1 September 2012 and 31 January 2016. InterRAI-HC is a comprehensive, multi-domain, standardised assessment. This study captured 18 variables, including fall frequency, from the interRAI. These data were deterministically matched with the Drug Burden Index (DBI) for each participant, derived from an anonymised national dispensed pharmaceuticals database. DBI groupings were statistically ascertained, and ordinal regression models employed., Results: Overall, there were 71,856 participants, with a mean age of 82.7 years (range 65-106); 43,802 (61.0%) were female, and 63,578 (88.5%) were New Zealand European. In unadjusted and adjusted analyses, DBI groupings were related to falls (p < 0.001). A DBI score > 3 was associated with a 41% increase in falls compared with a DBI score of 0 (p < 0.001). There was a 'dose-response' relationship between DBI levels and falls risk., Conclusions: DBI was found to be independently and positively associated with a greater risk of falls in this cohort after adjustment for 18 known confounders. We suggest that the DBI could be a valuable tool for clinicians to use alongside electronic prescribing to help reduce falls in older people.

Purpose: An index for estimating multimorbidity based on prescription claims data is important for predicting health outcomes for older people in pharmacoepidemiological studies. We aimed to develop a Medicines Comorbidity Index (MCI) based on nationwide prescription claims data and evaluate its performance in predicting adverse outcomes in older individuals., Methods: The index was developed on a retrospective cohort comprising of all individuals aged ≥ 65 years old, captured in the claims dataset from 1st January to 31st December 2012. The cohort was followed for 1 year to identify an event of hospitalisation or mortality. A list of medications for 20 comorbidities based on the Chronic Disease Score framework was collated. Predictive performance of the MCI was evaluated against the Charlson Comorbidity Index (CCI) using measures of discrimination (Receiver Operating Characteristic curves), sensitivity and specificity (c-statistic) and calibration (Brier scores) for regression models., Results: The MCI was validated for an outcome of mortality (n = 161,461) and hospitalisation (n = 149,729). For mortality, MCI had a marginally lower c-statistic in comparison to CCI (0.70, 95% CI 0.70-0.71 vs 0.72, 95% CI 0.71-0.72 at p < 0.05) with Brier scores of 0.07 at p < 0.05. For hospitalisation, the Hazard Ratio was higher with MCI (1.08, 95% CI 1.08-1.08, p < 0.001) compared to CCI (0.92, 95% CI 0.91-0.92, p < 0.001)., Conclusion: Initial testing indicates that the MCI is a valid and appropriate tool for measuring multimorbidity and predicting health outcomes for older individuals, and can be an important index for adjusting comorbidity in pharmacoepidemiological studies.

Aim: To evaluate the National Minimum Data Set (NMDS) against the International Resident Assessment Instrument-Home Care (interRAI-HC) in diagnosing dementia or Parkinson disease (PD)., Method: The NMDS data were matched with interRAI-HC for all older individuals in New Zealand. Dementia or PD was compared within 90 and 180 days and 1 to 4 years preceding and subsequent to the date of diagnosis in interRAI-HC. Consistency was measured through sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), weighted kappa (κ), and McNemar test., Results: For a diagnosis within 90 days, dementia showed 60.77% sensitivity, 95.33% specificity, 68.46% PPV, and 93.58% NPV. The PD showed 65.74% sensitivity, 99.52% specificity, 80.43% PPV, and 98.98% NPV. κ for dementia (κ = 0.59), PD (κ = 0.720), and McNemar test was significant ( P < .001) for all lengths of follow-up., Conclusion: Substantial agreement between multiple sources of health data can be a valuable resource for decision-making in older people with neurological conditions.

Background: In the presence of multimorbidity and limited life expectancy (LLE), the need for continued use of preventive medicines becomes uncertain as they may neither improve health nor confer continued health benefits., Objective: Our objective was to systematically review the literature to examine the discontinuation of preventive medicines in older people with LLE., Methods: A systematic literature search was conducted using the Ovid MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Central Register databases. Studies investigating discontinuation of preventive medicines in older individuals (mean age ≥65 years) with LLE (≤12 months) published between 1 January 1997 and 28 February 2017 were included. The Cochrane risk-of-bias assessment criteria and the Newcastle-Ottawa Scale were used to assess the quality of the studies., Results: Ten studies-a randomized controlled trial (RCT), two case-control studies, and seven cohort studies-involving 26,854 participants with a mean age ranging from 66.0 to 85.0 years were included in this review. The studies were primarily conducted in palliative care (n = 3), residential facility (n = 2), and community (n = 1) settings, and the remainder were pharmacoepidemiological studies (n = 4). The most common life-limiting illnesses were cancer (n = 5), followed by other unspecified illnesses (n = 4) and advanced dementia (n = 1). The most common preventive medicine discontinued was statins, followed by warfarin and aspirin. LLE potentially prompted discontinuation; however, some individuals continued to receive preventive medicines until they died., Conclusions: The review found that withdrawal of preventive medicines at the end of life is challenging. Decisions about the discontinuation of preventive medicines for individuals approaching the end of life are increasingly complicated by the lack of clear deprescribing guidelines for these medicines.

A cross-sectional survey was mailed to 307 RNs of a nationally representative sample of residential aged care facilities to investigate their views and perceptions on medication use and deprescribing in older adults. Questions were grouped according to each stage of the medication use process, and a dedicated section to explore nurses' views on deprescribing was included. Ninety-one questionnaires were received, yielding a 29.6% response rate. Respondents highlighted several challenges including achieving medication reconciliation for new residents, access to physicians to admit patients in a timely fashion, and issues pertaining to lack of clear medical information transcribing when transferring patients between health care settings. More than one half (67.4%) of nurses agreed or strongly agreed that deprescribing implemented with the help of a clinical pharmacist would be beneficial to residents and could improve medication adherence (44%), benefit residents' quality of life (50.5%), and reduce the length of time spent by nurses on medication administration (35.2%). Increased awareness regarding polypharmacy and potential deprescribing benefits is necessary to improve appropriate prescribing and medication use. [Journal of Gerontological Nursing, 43(10), 13-20.]., (Copyright 2017, SLACK Incorporated.)

The objective of this study was to assess international trends in antipsychotic use, using a standardised methodology. A repeated cross-sectional design was applied to data extracts from the years 2005 to 2014 from 16 countries worldwide. During the study period, the overall prevalence of antipsychotic use increased in 10 of the 16 studied countries. In 2014, the overall prevalence of antipsychotic use was highest in Taiwan (78.2/1000 persons), and lowest in Colombia (3.2/1000). In children and adolescents (0-19 years), antipsychotic use ranged from 0.5/1000 (Lithuania) to 30.8/1000 (Taiwan). In adults (20-64 years), the range was 2.8/1000 (Colombia) to 78.9/1000 (publicly insured US population), and in older adults (65+ years), antipsychotic use ranged from 19.0/1000 (Colombia) to 149.0/1000 (Taiwan). Atypical antipsychotic use increased in all populations (range of atypical/typical ratio: 0.7 (Taiwan) to 6.1 (New Zealand, Australia)). Quetiapine, risperidone, and olanzapine were most frequently prescribed. Prevalence and patterns of antipsychotic use varied markedly between countries. In the majority of populations, antipsychotic utilisation and especially the use of atypical antipsychotics increased over time. The high rates of antipsychotic prescriptions in older adults and in youths in some countries merit further investigation and systematic pharmacoepidemiologic monitoring., (Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.)