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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.

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.

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.

PurposeThe objectives of this study were to examine the overall utilisation of systematic antibiotics and the impact of the launch of the antimicrobial resistance action plan in older adults (65 years or more) living in New Zealand between 2005 and 2019, using data from a national database (Pharmaceutical collections), stratified by antibiotic class, patient age, and sex.MethodsPopulation-level systemic antibiotic dispensing data for older adults in New Zealand was analysed using repeated cross-sectional analysis between 01/01/2005 and 31/12/2019. Data were extracted on the prescribed systemic antibiotics using a unique identifier for each case. Antibiotic utilisation was measured in DDD/TOPD values. In addition, an interrupted time series (ITS) analysis using the autoregressive integrated moving average (ARIMA) models was performed to determine the impact of the antimicrobial resistance action plan.ResultsMost of the antibiotic classes included in this study showed a significant overall decrease in utilisation ranging from 38.64% for sulphonamides to 80.64% for fluoroquinolones compared to 2005. Systemic antibiotic utilisation decreased by 49.6% from the predicted usage between January 2018 and December 2019 following the launch of the antimicrobial resistance action plan. ARIMA model supported the reduction in utilisation with a step change of -0.2206 and slope change of -0.0029.ConclusionsThe ITS analysis has demonstrated that the intervention may have hugely impacted the antibiotic utilisation rate among older adults. Further studies are required to determine whether the reduced consumption rates of antibiotics are associated with reduced rates of antibiotic-associated adverse drug events such as acute kidney injury and haematological abnormalities.

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.

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 meta-analysis was conducted where the predictive models were compared based on their performance in predicting mortality. Outcome measures: Studies were grouped by the clinical outcome, and the models were compared based on the area under the receiver operating characteristic curve metric. Results 29 studies that satisfied the systematic review criteria were appraised and six 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 six studies included in the meta-analysis yielded a summary estimate of 0.82 (95%CI: 0.76–0.87), signifying good discriminatory power in predicting mortality. Conclusion The meta-analysis indicates that machine learning models can predict mortality. As electronic healthcare databases grow larger and more comprehensive, the available computational power increases and machine learning models become more sophisticated; they should be integrated into a larger research setting to predict various clinical outcomes.

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.

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.

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.

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.

Psychotropic medicine utilisation in older adults continues to be of interest because of overuse and concerns surrounding its safety and efficacy.This study aimed to characterise the utilisation of psychotropic medicines in older people in New Zealand.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).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.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.

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.This study aimed to identify the nervous system and gastrointestinal adverse drug events (ADEs) associated with solifenacin use in older adults (≥65 years).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.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).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.

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.

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.

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. Electronic supplementary material The online version of this article (10.1007/s10557-019-06867-z) contains supplementary material, which is available to authorized users.

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.

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 Psych INFO, PubMed, and EMBASE databases for relevant articles using MeSH terms where applicable. 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. The Cochrane collaboration's tool for risk of bias (version 2) was used to assess the risk of bias for randomised control trials. We explored the heterogeneity of the included studies using the Q test and I2 test and the publication bias using the funnel plot and Egger's test. Results: The overall absolute risks of acute kidney injury among older adults prescribed aminoglycosides, glycopeptides, and macrolides were 15.1%, 19.1%, and 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.

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 (

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

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.

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 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. Methodology: We will search for Psych INFO, 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 tool will be used to assess the risk of bias for randomised control trials. We will explore the potential sources of heterogeneity and bias using funnel and forest plots of the included studies. Discussion and registration: In this protocol, systematic review methods to identify relevant literature on antimicrobial exposure and associated organ injury have been described. The findings from the review are intended to increase our understanding of the different types of antimicrobials associated with organ injury among older adults, therefore has the potential for improving the prescribing practice for this vulnerable population. This protocol is registered in the PROSPERO database (registration number CRD42020152621).

Older people are susceptible to the adverse effects of anticholinergic medications, including cognitive impairment. A systematic review of observational studies reported mixed associations between high anticholinergic burden, a cumulative measure of anticholinergic medications, and cognitive performance in older people. Observational studies may have biased estimates of the impact of exposures, as the exposed and unexposed may systematically differ in covariates associated with the outcomes.

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.

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.

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.

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.

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. 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. 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

The study of the magnitude and variation of drug response is defined as pharmacodynamics (PDs). PD models examine plasma concentration and effect relationship. It can predict the archetypal effect ([Formula: see text]) of a drug as a function of the drug concentration ([Formula: see text]) and estimate an unknown PD parameter ([Formula: see text]). The PD models have been described as fixed, linear, log-linear, [Formula: see text], sigmoid [Formula: see text], and indirect PD response. Ligand binding model is an example of a PD model that works on the underpinning PD principle of a drug, eliciting its pharmacological effect at the receptor site. The pharmacological effect is produced by the drug binding to the receptor to either activate or antagonise the receptor. Ligand binding models describe a system of interacting components, i.e. the interaction of one or more ligands with one or more binding sites. The [Formula: see text] model is the central method that provides an empirical justification for the concentration/dose-effect relationship. However, for ligand binding models justification is provided by theory of receptor occupancy. In essence, for ligand binding models, the term [Formula: see text] is best used to describe the fraction of receptors occupied at a particular ligand concentration. It is stated that the [Formula: see text], which means the effect of a drug should depend on the fraction of receptors that are occupied. In the future, network-based systems pharmacology models using ligand binding principles could be an effective way of understanding drug-related adverse effects. This will facilitate and strengthen the development of rational drug therapy in clinical practice.

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 (Q 1 = 0.0, Q 3 = 1.84) to 0.96 (Q 1 = 0.0, Q 3 = 1.90). DBI was significantly related to fracture incidence in unadjusted (p 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.

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 analysed using a multinomial logistic regression model.RESULTS: 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.

La reduction des medicaments potentiellement inappropries (MPI) chez les personnes âgees est un enjeu important selon de nombreux cliniciens et chercheurs a travers le monde, car ces medicaments accroissent significativement la morbidite et la mortalite dans la population plus âgee. La prevalence des MPI est un probleme repandu malgre l'existence de plusieurs criteres explicites et implicites de reduction des MPI chez les personnes âgees, les plus courants etant les criteres de Beers, les criteres STOPP/START et plusieurs criteres nationaux specifiques. Cette revue non systematique visait a examiner les criteres de reference pour la reduction des MPI et a clarifier le role de certaines mesures, dont la deprescription, pour optimiser la prescription des medicaments chez les personnes âgees. Des recherches par mots-cles et termes MeSH ont ete menees dans des bases de donnees electroniques. Les nombreux criteres disponibles ont chacun leurs avantages et inconvenients. La deprescription, qui vise a reduire l'utilisation des MPI, a considerablement gagne en importance dans les initiatives associees a l'amelioration des pratiques de prescription. La deprescription est une approche methodique qui implique l'arret graduel, eclaire et individualise des medicaments inappropries, avec un suivi rigoureux des patients pour assurer la detection d'evenements indesirables ou de symptomes de rebond. Une approche combinee centree sur le patient et le soignant favorise la collaboration entre les prescripteurs et les pharmaciens afin de reduire le nombre de MPI chez les personnes âgees. 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.

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.

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.

The primary aim was to examine and compare the increased risk of incident diabetes associated with second-generation antipsychotics (SGAs) and first-generation antipsychotics (FGAs), with and without adjusting for potential confounding factors. The secondary aim was to recalculate the relative risks of diabetes onset using a semi-symmetric bidirectional case-crossover (SSBC) design to adjust for time-trend bias. Prescription records (2005–2015) of antipsychotics were sourced from New Zealand Pharmaceutical Collections. The first-time diabetes diagnosis was extracted from the National Minimal Dataset. Relative risks (RRs) of diabetes onset were calculated using conditional logistic regression. Time-trend bias was corrected by recalculating the RR using a SSBC design. Among 645 individuals, the risk of diabetes onset is higher in SGA users (ARR = 8.72, 95% CI = [5.57, 13.67]) compared to FGA users (ARR = 5.68, 95% CI = [3.43, 9.39]). The increased risk of diabetes onset associated with quetiapine is higher (ARR = 7.47, 95% CI = [4.10, 13.62]), compared to haloperidol (ARR = 5.05, 95% CI = [2.91, 8.75]). However, the increased risk of diabetes onset associated with olanzapine (ARR = 2.27, 95% CI = [0.86, 5.98]) is insignificant after adjusting for concomitant use of effect modifiers and other antipsychotic drugs. The results support that the magnitude of the risk of diabetes is higher with SGA use compared with FGA use, and the risk is higher when co-prescribed. Confounding by indication and time-varying confounders such as body mass index could bias the risk of onset of diabetes. Marginal structural models could provide more precise estimates of the risk of onset of diabetes following exposure to antipsychotics.

Background: The global burden of diabetes is increasing worldwide. The aim of the study was to investigate the trends in use of antidiabetic medicines among older New Zealanders between 2005 and 2013, and to perform a separate analysis by age, sex, ethnicity, district health board domicile and socioeconomic deprivation index. Methods: The study population included individuals’ aged 65 years and older living in New Zealand (NZ) captured in the pharmaceutical collections. Repeated cross-sectional analysis of population-level dispensing data was conducted from 1 January 2005 to 31 December 2013. Linear regression model using a gamma link function was used to estimate prevalence ratios and trends between 2005 and 2013. The main outcome measure was the prevalence of antidiabetic medicines in older New Zealanders. Results: The prevalence of antidiabetic medicines in older New Zealanders increased by 17.6% between 2005 and 2013. Individuals in the 70–74 age group had the highest utilization of each of the classes of antidiabetic medicines and those aged ⩾85 had the lowest utilization. Among the antidiabetic class of medicines, utilization of sulfonylureas was highest and alpha-glucosidase inhibitors the least. The utilization of thiazolidinediones increased over the study period. In 2013, insulin isophane and insulin glargine were the most common insulin analogues used. Insulin use was high in those aged ⩾85 years across the entire study period. The utilization of metformin increased gradually throughout the study period (by 43.9% in 2013 compared with 2005). Conclusion: This population-level study showed an increase in utilization of antidiabetic medicines in older people in NZ from 2005 to 2013; however, the increase does not seem to parallel the proportional increase in prevalence of diabetes for the study period. Improving access to newer antidiabetic medicines in line with emerging evidence should be a consideration for decision makers.

Aim Gaining an insight into the utilization of antihypertensive medicines against a background of evolving hypertension treatment guidelines that might not be relevant to the oldest old is important. The aim of the present study was to characterize the overall trends in the utilization of antihypertensive medicines in the oldest old by therapeutic class and chemical type, stratified by age and sex over a decade. Methods Antihypertensive medicines utilization was examined using the therapeutic and chemical groups based on the World Health Organization Collaborating Center for Drug Statistics Mythology's Anatomical Therapeutic Chemical classification system for all individuals aged ≥80 years. Regression and repeated cross-sectional analyses was carried out, and defined daily dose was used to describe the utilization per thousand older people per day. Results Utilization of antihypertensive medicines increased over the decade from 187.28 in 2005 to 205.01 defined daily dose per thousand older people per day in 2014, and shifted from mainly diuretics to angiotensin-converting enzyme inhibitors. Interestingly, with the exception of diuretics, utilization of all medicines decreased gradually with increasing age. Single products use increased by 1.48-fold in 2014 compared with 2005, and for fixed-dose combinations the increase was 1.41-fold for the same period. Conclusions The increased utilization of angiotensin-converting enzyme inhibitors is consistent with recommendations from cardiovascular guidelines formulated from large randomized control trials that often exclude the oldest old. Interestingly, the utilization of beta-blockers decreased and diuretics increased in centenarians. The utilization of calcium channel blockers and angiotensin-converting enzyme inhibitors across the study period increased in all age categories. Geriatr Gerontol Int 2016; ••: ••–••.

To examine and characterize overall donepezil and concomitant utilization with β-blockers, yearly, in older New Zealanders. Deidentified data from the Pharmaceutical claims database and the National Minimum Dataset were obtained for 2011 to 2013 from the Ministry of Health. Population-level data were extracted for donepezil and β-blockers utilization, measured by defined daily dose (DDD) per thousand older people per day (TOPD). Donepezil utilization increased from 5.2 to 8.2 DDD/TOPD between 2011 and 2013. In 2011, the number of prevalent users was 4634, the mean age was 79.4±6.6 years and 57.5% were women. Highest use by age for donepezil was in those aged 85 years or older (2.3 DDD/TOPD), followed by those aged 80-84 years (2.2 DDD/TOPD). The mean utilization volumes were significantly lower for donepezil 5 mg (Student t-test= 9.86; P< 0.05) and 10 mg (10.90; P