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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.

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 (

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 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

Discontinuation of statins may be considered for older individuals with a cancer, multi-morbidity, approaching end-of-life and in primary prevention. The aim of this study is to investigate the relationship between the rates of statin discontinuation in the last 12 months of life and a diagnosis of cancer, and in individuals using statins for primary or secondary prevention. A case-control study of matched cases and controls. Matching was based on age, Charlson comorbidity index scores and socioeconomic status. Prescription and diagnostic data for 20,482 individuals who were aged over 75 years, were in their last 12 months of life and were receiving statins during the study period (1 January 2007 to 31 December 2012). After propensity score matching, we identified 4832 cases with a diagnosis of cancer and 4809 matched controls. We used Cox regression to test the relationship between the relative risk of statin discontinuation and a diagnosis of cancer, and in individuals using statins for primary or secondary prevention. Statins were discontinued in 70.4% of older adults with a diagnosis of cancer and 55.8% of those without cancer (P < 0.05). The Cox regression analysis supports that a diagnosis of cancer can increase the rate of statin discontinuation compared with individuals without a diagnosis of cancer regardless of whether statins were used for primary or secondary prevention (P < 0.05). The findings from this study support that statins are likely to be discontinued in the last year of life in older people with limited life expectancy from cancer, even if statins were indicated for secondary prevention of cardiovascular disease.

Aim To examine psychotropic drug utilisation in older people in New Zealand by age, sex, health board domicile and deprivation status. Methods A repeated cross-sectional analysis of population-based drug utilisation data stratified by age, sex, ethnicity, health board and deprivation status was conducted from 2005 to 2013. Results Psychotropic utilisation increased between 2005 and 2013 (ranging from 7.0 to 74.0%) across all the health boards. In people aged 85 years and above, the hypnotic and sedative prevalence ratio compared to the 65- to 69-year age group was 1.45 (95% CI 1.44, 1.46). Between 2005 and 2013, the antidepressants prevalence ratio increased (1.27 (95% CI 1.22, 1.33)) relative to anxiolytics. Conclusions Overall psychotropic drug utilisation increased over time. Despite safety concerns, hypnotic and sedative utilisation increased in the oldest vulnerable group. Shifts from anxiolytics to antidepressants in some health boards were consistent with guidelines for extended indications of antidepressant drug use.

Introduction: Inappropriate prescribing in residential care is a particular health concern. This study aims to identify the prevalence of potentially inappropriate prescriptions (PIP) and potential prescribing omissions (PPO) in older people living in residential care in New Zealand. Method: The STOPP/START criteria was applied to the data collected from the medical notes of people aged >= 65 years-old living in two residential care homes in New Zealand. Prescribed medicines were classified using the World Health Organisation Anatomic Therapeutic Classification. Charlson Comorbidity Index and Katz Activities of Daily Living were computed for each resident and included in the regression analyses. Results: The mean age of residents (n = 137) was 85.4 (+/- 7.7) years. In total, 205 PIPs among 102 residents (74.5%) were identified and 66 PPOs were present among 49 residents (35.8%). Antipsychotics were the most common PIPs in residents with a medium/high falls risk (18.6%). Residents with higher comorbidity scores were less likely to be taking a PIP. Residents with a medium/high falls risk were more likely to have a PIP, than those with a low falls risk. Conclusion: Consistent with other countries, PIPs and PPOs were highly prevalent in older people in residential care in New Zealand. Antipsychotics, opiates and benzodiazepines accounted for approximately 50% of the 205 PIP exposures. Regarding PPO, the omission of aspirin and angiotensin converting enzyme inhibitors where clinically indicated was noted. The STOPP/START criteria could be used in multidisciplinary clinical reviews to help improve the medicine therapy in older people living in the residential care setting. Refereed/Peer-reviewed

Aims: To examine patient characteristics that predict adverse anticholinergic-type events in older people. Methods: This retrospective population-level study included 2,248 hospitalised patients. Individual data on medicines that are commonly associated with anticholinergic events (delirium, constipation and urinary retention) were identified. Patient characteristics examined were medicines with anticholinergic effects (ACh burden), age, sex, non-anticholinergic medicines (non-ACM), Charlson comorbidity index scores and ethnicity. The Akaike information criterion was used for model selection. The data were analysed using logistic regression models for anticholinergic events using the software NONMEM. Results: ACh burden was found to be a significant independent predictor for developing an anticholinergic event [adjusted odds ratio (aOR): 3.21, 95% CI: 1.23-5.81] for those taking an average of 5 anticholinergic medicines compared to those taking 1. Both non-ACM and age were also independent risk factors (aOR: 1.41, 95% CI: 1.31-1.51 and aOR: 1.08, 95% CI: 1.05-1.10, respectively). Conclusion: To our knowledge, this is the first study that has examined population-level data in a nonlinear model framework to predict anticholinergic-type adverse events. This study evaluated the relationship between important patient characteristics and the occurrence of anticholinergic-type events. These findings reinforce the clinical significance of reviewing anticholinergic medicines in older people.

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.

The primary objective of this study was to investigate the impact of Residential Medication Management Reviews (RMMRs) on anticholinergic burden quantified by seven anticholinergic risk scales.Retrospective analysis.Accredited pharmacists conducted RMMRs in aged-care facilities (ACFs) in Sydney, Australia.RMMRs pertained to 814 residents aged 65 years or older.Anticholinergic burden was quantified using seven scales at baseline, after pharmacists' recommendations and after the actual GP uptake of pharmacists' recommendations. Change in the anticholinergic burden was measured using the Wilcoxon sign rank test.At baseline, depending on the scale used to estimate the anticholinergic burden, between 36% and 67% of patients were prescribed at least one regular anticholinergic medication (ACM). Anticholinergic burden scores were significantly (p 0.001) lower after pharmacists' recommendations as determined by each of the seven scales. The reduction in anticholinergic burden was also significant (p 0.001) after GPs' acceptance of the pharmacists' recommendations according to all scales with the exception of one scale which reached borderline significance (p = 0.052).Despite the limitations of the retrospective design and differences in the estimation of anticholinergic burden, this is the first study to demonstrate that RMMRs are effective in reducing ACM prescribing in ACF residents, using a range of measures of anticholinergic burden. Future studies should focus on whether a decrease in anticholinergic burden will translate into improvement in clinical outcomes.

Adverse outcomes associated with advanced diseases are often exacerbated by polypharmacy.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.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.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.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.

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).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.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.Substantial agreement between multiple sources of health data can be a valuable resource for decision-making in older people with neurological conditions.

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.]

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. 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. 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

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. Our objective was to systematically review the literature to examine the discontinuation of preventive medicines in older people with LLE. 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. 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. 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.

Objective: There is some evidence that clozapine is significantly underutilised. Also, clozapine use is thought to vary by country, but so far no international study has assessed trends in clozapine prescribing. Therefore, this study aimed to assess clozapine use trends on an international scale, using standardised criteria for data analysis.Method: A repeated cross-sectional design was applied to data extracts (2005-2014) from 17 countries worldwide.Results: In 2014, overall clozapine use prevalence was greatest in Finland (189.2/100 000 persons) and in New Zealand (116.3/100 000), and lowest in the Japanese cohort (0.6/100 000), and in the privately insured US cohort (14.0/100 000). From 2005 to 2014, clozapine use increased in almost all studied countries (relative increase: 7.8-197.2%). In most countries, clozapine use was highest in 40-59-year-olds (range: 0.6/100 000 (Japan) to 344.8/100 000 (Finland)). In youths (1019 years), clozapine use was highest in Finland (24.7/100 000) and in the publicly insured US cohort (15.5/100 000).Conclusion: While clozapine use has increased in most studied countries over recent years, clozapine is still underutilised in many countries, with clozapine utilisation patterns differing significantly between countries. Future research should address the implementation of interventions designed to facilitate increased clozapine utilisation.

Consensus guidelines which are applicable in New Zealand and worldwide recommend that the duration of exposure to antipsychotics not exceed 12 weeks, unless justified for mental illnesses like schizophrenia and severe psychotic symptoms which require longer treatment. There has been limited information on time-to-first discontinuation (TTFD) for second-generation antipsychotics (SGAs) in a real world population setting in older people. The study objective was to compare TTFD, adherence, and persistence for individual SGA new users among people 65 years and older. A cohort of 30,297 SGA new users was followed up for antipsychotic discontinuation from January 1, 2006, to December 31, 2012. Data for oral formulations were extracted using health care databases from the New Zealand Ministry of Health. The TTFD, adherence, and persistence were defined using (dispensing gap ≥ 91 days, variable medication possession ratio ≥ 0.8, and gap duration < 91 days between refills), respectively. Kaplan-Meier curves and Cox regression analysis were used to estimate and adjust for outcomes. The overall TTFD in SGA new users was 192.3 days (95% confidence interval [CI], 177.6-206.9), mean age at dispensing was 80.9 years (SD, 8.1 years), and 60.3% were women. The TTFD for was shortest for risperidone, 101.3 days (95% CI, 85.0-117.7; P = 0.03) compared with clozapine, 68.3 days (95% CI: 43.7, 92.9). The adjusted all-cause TTFD risk for risperidone, olanzapine, quetiapine, or ziprasidone (hazard ratios, 0.54, 0.29, 0.22, and 0.08, respectively) was significantly lower than clozapine. The TTFD risk in the nonadherent compared with the adherent group was more than 3 times.

SummaryWhat is known and objective Centenarians represent a population of individuals with delayed disability and are an ideal representation of ageing well; however, studies related to medicine use in this population are scarce. Our study aimed to explore the temporal trends associated with the utilization of preventive medicines in centenarians. Methods A repeated cross-sectional analysis was conducted from 1st January 2006 to 31st December 2015 for all individuals ≥100 years old on the date of dispensing, captured in New Zealand's pharmaceutical claims data set. The variable medication possession ratio (VMPR) was used to identify medicines use as preventive, and was calculated by aggregating days’ supply from the first to the last prescription divided by time between the last prescription date plus days’ supply and the first prescription date. Poisson regression was used to examine the dispensing trends for low-dose aspirin, clopidogrel, warfarin, dabigatran, statins and bisphosphonates with a VMPR ≥0·8. Results Dispensing of aspirin [incident rate ratio (IRR) 0·92, 95% CI: 0·90–0·94], clopidogrel (IRR 0·91, 95% CI: 0·90–0·93) and aspirin with clopidogrel (IRR 0·81, 95% CI: 0·79–0·82) declined significantly over the study period. Similar trends were observed for statins (IRR 0·98, 95% CI: 0·96–1·00) and bisphosphonates (IRR 0·73, 95% CI: 0·71–0·75). Utilization of both the anticoagulants studied increased significantly: warfarin (IRR 1·04, 95% CI: 1·02–1·06) and dabigatran (IRR 1·11, 95% CI: 1·06–1·16). What is new and conclusion Over a decade, dispensing of preventive medicines for centenarians decreased marginally for antiplatelets and statins. A substantial decrease in bisphosphonates use and an increase in anticoagulant use were noted for the same period. Temporal trends provide an opportunity to investigate uptake of guideline-based prescribing in this age group.

SummaryWhat is known and objective Prescription sequence symmetry analyses (PSSA) is a ubiquitous tool employed in pharmacoepidemiological research to predict adverse drug reactions (ADRs). Several studies have reported the advantage of PSSA as a method that can be applied to a large prescription database with computational ease. The objective of this study was to validate New Zealand (NZ) prescription database as a potential source for identifying ADRs using the PSSA method. Methods We analysed de-identified individual-level prescription data for people aged 65 years and above for the period 2005 to 2014 from the pharmaceutical collections supplied by the NZ Ministry of Health. We selected six positive controls that have been previously investigated and reported for causing ADRs. The six positive controls identified were amiodarone (repeated twice), frusemide, simvastatin, lithium and fluticasone. Amiodarone and lithium have been reported to induce thyroid dysfunction. Simvastatin reported to cause muscle cramps while fluticasone is well documented to cause oral candidiasis. Thyroxine was identified as a marker drug to treat hypothyroidism associated with amiodarone and lithium. Carbimazole was identified as a marker drug to treat hyperthyroidism associated with amiodarone use. Quinine sulphate was identified as a marker drug to treat muscle cramps associated with statins. In addition, we also analysed six negative controls that are unlikely to be associated with ADRs. The main outcome measure is to determine associations with ADRs using adjusted sequence ratios (ASR), and 95% confidence intervals Results and discussion Our analyses confirmed a significant signal for all six positive controls. Significant positive associations were noted for amiodarone [ASR = 3·57, 95% CI (3·17–4·02)], and lithium chloride induced hypothyroidism [ASR = 3·43, 95% CI (2·55–4·70)]. Amiodarone was also strongly associated with hyperthyroidism [ASR = 8·81 95% CI (5·86–13·77)]. Simvastatin was associated with muscle cramps [ASR = 1·69, 95% CI (1·61–1·77)]. Fluticasone was positively associated with oral candidiasis [ASR = 2·34, 95% CI (2·19–2·50)]. Frusemide was associated with hypokalaemia [ASR = 2·94, 95% CI (2·83–3·05]). No strong associations were noted for the negative pairs. It is important to highlight that PSSA automatically controls for all confounding factors including unknown and unmeasured confounding variables, plus the effect of temporal trend in prescriptions, and hence allows a more robust ADR detection especially when confounding factors are difficult to determine or measure. What is new and conclusion New Zealand prescription database can be a potential source to identify ADRs engaging the PSSA method, and this could complement pharmacovigilance surveillance in NZ. The PSSA can be an important method for post-marketing surveillance and monitoring of ADRs which have relatively short latency. However, the predictive validity of PSSA will be compromised in certain scenarios, particularly when sample size is small, when new drugs are in the market and data are sparse.

It is postulated that minimizing anticholinergic burden in older people may result in improved short-term memory and behavior, reduced confusion and delirium, and enhanced quality of life and daily functioning. The purpose of this opinion article was to investigate the current trends and future implications relating to the examination and estimation of anticholinergic burden in older people. Current evidence linking medicines with anticholinergic activity and cognitive impairment is derived mostly from observational data. Further research with larger trials or cohort studies with adequate power and appropriate follow-up periods is required to confirm associations between anticholinergic burden and adverse outcomes. This article provides insights into different approaches for the estimation of anticholinergic burden. Network-based systems pharmacology models could be an effective way of understanding anticholinergic drug-induced adverse effects. The emphasis on mechanistic models may open new opportunities for researchers to understand adverse drug effects in clinical practice. In the interim, medicines with high anticholinergic activity should be avoided in older people, unless considered clinically essential. In this instance, they should be used at a low/titrated dose and for the shortest duration possible. It is therefore important to reinforce the clinical significance of reviewing anticholinergic medicines in older people.

Introduction: The majority of older people with chronic diseases are prescribed multiple medicines resulting in polypharmacy. The extrapolation of the single disease model' represented by disease-specific guidelines is a major driver for polypharmacy. Polypharmacy is associated with negative health outcomes. Safely reducing or discontinuing harmful medicines, commonly referred to as deprescribing, has been shown to reduce adverse health outcomes, healthcare costs and mortality. However, there are barriers to deprescribing such as time constraints, limited appropriate clinical resources and the influence of multiple prescribers. Aim: To explore general practitioners' (GPs') opinions and awareness of deprescribing in an older multimorbid patient. Methods: A qualitative study design using face-to-face semi-structured interviews was implemented. GP practices were randomly selected from two cities in New Zealand. Face-to-face in depth interviews were carried out with participants. A hypothetical profile of a multimorbid patient was included to elicit discussions about whether medicines should be continued or discontinued. Interviews were transcribed verbatim for thematic analysis. Transcripts were read and re-read. Themes were identified with iterative building of a coding list until all data were accounted for. Interviews continued until saturation of ideas occurred. Results: Forty GPs were contacted and 10 consented to participate. Responses to each medicine in the hypothetical patient profile varied. Opinions on deprescribing preventive and symptomatic medicines varied a great deal. Conflicting opinions existed particularly around the prescription of statins, dipyridamole and bisphosphonates. Dilemmas around the appropriate clinical management of reflux disease and insomnia in older people also came to light. Conclusion: Gaining an insight into GPs' current prescribing patterns is important in designing any interventions aimed at reducing inappropriate prescribing. This study highlights the lack of clarity around deprescribing in multimorbidity. The participants' individual responses varied considerably. Deprescribing guidelines may help to clarify evidence based medicine relating to controversial areas and could hence decrease this variation. Refereed/Peer-reviewed

Introduction: Anticholinergics are a class of medicines that block the neurotransmitter, acetylcholine, in the brain and peripheral tissues. Medicines with anticholinergic activity are widely prescribed for and used by older people for various medical conditions. One-third to one-half of the medicines commonly prescribed for older people have anticholinergic activity. Several studies have reported anticholinergic burden to be a predictor of cognitive and functional impairments in older people. Areas covered: This article exemplifies the theoretical and clinical aspects of medicines with anticholinergic activity, including pharmacology (definition of medicines that possess anticholinergic activity, antimuscarinic receptors, therapeutic and adverse effects), epidemiology, measures and effects of cumulative anticholinergic burden in older adults, and clinical recommendations. In addition, the gaps in the literature have been identified for future research. Expert opinion: Many medicines that are commonly prescribed to older people have a degree of anticholinergic activity that can contribute to anticholinergic burden. Anticholinergic burden, measured in several ways that consider number, dose and/or degree of anticholinergic activity of medicines, has shown to be a predictor of adverse health and functional outcomes. The anticholinergic burden on older people should be minimised by avoiding, reducing dose and deprescribing medicines with anticholinergic activity where clinically possible.

Introduction Studies have reported associations between serum anticholinergic activity (SAA) and decline in cognitive performance, delirium, and functional impairment. The aim of this meta-analysis was to explore and quantify associations between SAA and adverse cognitive and functional outcomes in older people. Materials and Methods A literature search in Ovid MEDLINE, EMBASE, PsycINFO and IPA from 1946–2014 was completed. The primary outcomes of interest were cognitive and functional adverse outcomes associated with SAA in older people aged 55 years and above. The Cochrane Risk-Bias assessment tool was used to assess bias in randomised controlled trials (RCTs). The Newcastle-Ottawa Scale was used to assess the quality of non-RCTs. Meta-analyses were conducted for RCTs and cohort studies separately. Heterogeneity was assessed using I2 tests. Results The primary electronic literature search identified a total of 1559 records in the 4 different databases. On the basis of full-text analysis, 33 studies that met the inclusion criteria. The review included 4 RCTs, 5 prospective cohort studies, 3 longitudinal cohort studies, 17 cross-sectional studies, and 4 case-control studies. Twenty-four of the retrieved studies examined an association between SAA and cognitive outcomes, 2 studies examined an association with SAA and functional outcomes and 8 studies examined associations between SAA and both cognitive, and functional outcomes. The meta-analysis on 4 RCTs showed no association with higher SAA and cognitive performance (I2 = 89.38%, H2 = 25.53 and p-value =

Polypharmacy, with its resulting negative health outcomes, is increasing worldwide alongside our ageing population. In specific, anticholinergic and sedative medicines contribute to the decline in cognitive and physical functioning of older people. The Drug Burden Index (DBI) measures the cumulative daily sedative and anticholinergic load. Our aim was to examine the feasibility of reducing the DBI of older people living in residential aged care facilities (RACFs). Residents aged ≥65 years prescribed one or more anticholinergic or sedative medicine, were recruited from three RACFs in New Zealand. A patient-centred approach was implemented; where a clinically trained pharmacist conducted a resident interview and a comprehensive medicine review for each participant. Deprescribing recommendations were put forward to the residents’ general practitioner (GP). We recruited 37 participants with a mean age of 82.8 ± 8.2. Residents were followed up three months after their GP deprescribed one or more of their medicine(s). A Wilcoxon Signed-Rank test indicated that post DBI test ranks, were statistically significantly less than pre DBI test ranks (p= 0.00016) and post-Cognition Performance Score (CPS) test ranks were statistically significantly less than pre-CPS test ranks (p=0.02). In addition, a one-sided paired t-test showed that potential adverse drug reactions (ADRs) decreased by a mean of 2.92 (p=0.0001). Therefore, the pharmacist’s deprescribing intervention resulted in a statistically significant reduction in both residents’ DBI and potential ADRs; as well as an improvement in residents’ cognition. This supports existing research that deprescribing can reverse negative polypharmacy effects and result in several potential health benefits.

Summary What is known and objective Antithrombotics reduce the risk of stroke in individuals with atrial fibrillation (AF). However, optimal prescribing of antithrombotics in older people remains a challenge. The objective of this study was to assess the risk of stroke for aged care home residents with AF and to examine the pharmacist-led medication reviews on the utilization of antithrombotic therapy. Methods This retrospective study included a random sample of de-identified residential medication management reviews (RMMRs) conducted by accredited pharmacists in aged care homes in Sydney, Australia, between August 2011 and December 2012. The study participants were 146 residents aged 65 years and older with AF living in low- and high-care residential aged care facilities. Antithrombotic therapy was examined among the residents, before and after medication review. CHADS2, CHA2DS2-VASc, and HEMORR2HAGES scoring tools were used to assess the risk of stroke and bleeding and indicate the appropriateness of antithrombotic therapy. Results and discussion The mean age (±SD) of individuals was 88·4 (7·5) years, and 63·7% (n = 93) were female. The majority of residents (n = 99, 67·8%) were aged between 85 and 99 years. The mean (±SD) CHADS2 score was 3·1 (1·1), CHA2DS2-VASc was 4·6 (1·5), and HEMORR2HAGES was 2·3 (1·0). All residents were classified as being at high risk of developing stroke. A total of 115 of 146 (78·8%) residents with AF were prescribed antithrombotics. There was a relatively low usage of anticoagulation (28·1%), and few recommendations from the medication review pharmacists to alter the thromboprophylactic therapy in AF. Application of the CHA2DS2-VASc risk tool indicated that 146 residents were eligible for antithrombotic treatments; of these, 74 (50·7%) were prescribed antiplatelets and 41 (28·1%) were prescribed anticoagulants. Of the 31 (21·2%) residents with AF were not prescribed antithrombotics, 21 (67·7%) had relative contraindications for anticoagulant treatments. What is new and conclusion Although there was a high overall use of antithrombotic agents, the study found a reluctance to prescribe or recommend anticoagulants in eligible older people with AF, potentially due to associated contraindications and multimorbidity. The use of guideline-recommended stroke risk tools could assist medication review pharmacists in optimizing antithrombotic therapy in older adults with AF.

Background For older individuals with multimorbidity the appropriateness of prescribing preventive medicines remains a challenge. Objective Investigate the prevalence and temporal trends in utilisation of preventive medicines in older New Zealanders from 2005 to 2013 stratified according to age, sex, ethnicity and district health board domicile. Methods A repeated cross-sectional analysis was conducted on pharmaceutical dispensing data for all individuals’ ≥65 years. Variable medication possession ratio (VMPR) was used to measure adherence. Prescribing of low-dose aspirin, clopidogrel, dipyridamole, warfarin, dabigatran, statins and bisphosphonates with a VMPR ≥ 0.8 were examined. Results Aspirin utilisation increased by 19.55% (95% CI: 19.39–19.70), clopidogrel by 2.93% (95% CI: 2.88–2.97) and dipyridamole decreased by 0.65% (95% CI: −0.70 to −0.59). Utilisation of aspirin with clopidogrel increased by 1.78% (95% CI: 1.74–1.81) and aspirin with dipyridamole increased by 0.54% (95% CI: 0.50–0.58%).Warfarin decreased by 0.87% (95% CI: −0.96 to −0.78) and dabigatran increased by 0.65% (95% CI: 0.60–0.70). Statins increased by 7.0% (95% CI: 6.82–7.18) and bisphosphonates decreased by 2.37% (95% CI: −2.44 to −2.30). Aspirin, clopidogrel, dabigatran and statins utilisation showed a greater increase in males. Interestingly, clopidogrel, warfarin and statins use increased in older adults aged 85+ compared to the younger age groups (65–84 years). Conclusion To our knowledge, this is the first study investigating the prevalence and trends of preventive medicines use in older people in New Zealand. This study may facilitate further research to examine the appropriateness of prescribing these medicines in older people with multimorbidity.

Objectives The primary objective was to evaluate the risk of fractures associated with use of zopiclone, a new Z-hypnotic, in a population-based cohort of older people in New Zealand (NZ) in a real-world setting. The secondary objective was to examine a nonlinear relationship with age and risk for fractures in zopiclone users. Design Population-based cohort study with a case-crossover design. Setting A nationwide representative sample of New Zealanders aged 65 years and older sourced from the pharmaceutical collections and hospital discharges. Participants 74,787 older individuals with a first-time fracture between January 1, 2005, and December 31, 2015, were analyzed using a case-crossover design for fracture risk with zopiclone use. Measurements Prescription records (2005–2014) of zopiclone were sourced from NZ Pharmaceutical Collections (Pharms). The first-time coded diagnosis of fracture was extracted from the National Minimal Datasets. Datasets were linked by a unique patient identifier to set up case-crossover designs. Relative risks (RRs) of fracture associated with zopiclone was calculated using conditional logistic regression. A varying-coefficient conditional logistic model was employed to examine the influence of age as a risk factor for fractures. Results The risk of fracture associated with zopiclone is higher [RR = 1.45, 95% confidence interval (CI) = 1.37–1.55], compared to non-use. The increased risk of fracture associated with zopiclone [adjusted relative risk (ARR) = 1.36, 95% CI = 1.28–1.45] remained significant after adjusting for concomitant use of alpha blockers, antipsychotics, beta blockers, benzodiazepines, and tricyclic antidepressants. The varying coefficient model showed that the risk of fracture increases significantly and monotonically with age. Conclusion The results support that the magnitude of the risk of fracture is higher with use of zopiclone compared to non-use. Prescribers must be aware that the relationship between age and fracture risk is nonlinear, and the oldest old are highly vulnerable to fractures with zopiclone use.

Commentary on: Risacher SL, McDonald BC, Tallman EF, et al. Association between anticholinergic medication use and cognition, brain metabolism, and brain atrophy in cognitively normal older adults. JAMA Neurol 2016;73:721–32[OpenUrl][1]. Older people are particularly vulnerable to adverse cognitive effects and risk of dementia following exposure to medicines with anticholinergic activity;1 however, the biological basis for these effects remains unclear.2 The risk of anticholinergic adverse effects increases with age, polypharmacy, comorbidities, pre-existing cognitive impairment, cholinergic neuronal degeneration and changes in pharmacokinetic and pharmacodynamic properties. This study examined whether medicines with anticholinergic activity alter brain glucose metabolism, and the impact this has on brain structure, function and cognitive decline. This retrospective cohort study involved 402 participants from the Alzheimer's Disease Neuroimaging Initiative … [1]: {openurl}?query=rft.jtitle%253DJAMA%2BNeurol%26rft.volume%253D73%26rft.spage%253D721%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx

Aims: Deprescribing is the process of reducing or discontinuing medicines that are unnecessary or deemed to be harmful. We aimed to investigate general practitioner (GP) perceived challenges to deprescribing in residential care and the possible enablers that support GPs to implement deprescribing. Methods: A qualitative study was undertaken using semi-structured, face-to-face interviews from two cities in New Zealand and a purpose-developed pilot-tested interview schedule. Interviews were recorded with permission and transcribed verbatim. Transcripts were read and re-read and themes were identified with iterative building of a coding list until all data was accounted for. Interviews continued until saturation of ideas occurred. Analysis was carried out with the assistance of a Theoretical Domains Framework (TDF) and constant comparison techniques. Several themes were identified. Challenges and enablers of deprescribing were determined based on participants’ answers. Results: Ten GPs agreed to participate. Four themes were identified to define the issues around prescribing for older people, from the GPs’ perspectives. Theme 1, the ‘recognition of the problem’, discusses the difficulties involved with prescribing for older people. Theme 2 outlines the identified behaviour change factors relevant to the problem. Deprescribing challenges were drawn from these factors and summarised in Theme 3 under three major headings; ‘prescribing factors’, ‘social influences’ and ‘policy and processes’. Deprescribing enablers, based on the opinions and professional experience of GPs, were retrieved and summarised in Theme 4. Conclusion: The process of deprescribing is laced with many challenges for GPs. The uncertainty of research evidence in older people and social factors such as specialists’ and nurses’ influences were among the major challenges identified. Deprescribing enablers encompassed support for GPs’ awareness and knowledge, improvement of communication between multiple prescribers, adequate reimbursement and pharmacists being involved in the multidisciplinary team. Refereed/Peer-reviewed

ABSTRACT INTRODUCTION Antipsychotic medicines are used regularly or when required in residential aged care facilities to treat symptoms of dementia, but have been associated with several adverse effects. AIM The aim of this study was to examine ‘quality use’ of antipsychotic medicines in residential aged care facilities in New Zealand, by surveying nurse managers. METHODS A cross-sectional survey was mailed to 318 nurse managers working in a nationally representative sample of aged care facilities. A purpose-developed, pre-tested, 22-item structured questionnaire was used to explore practice related to the quality use of antipsychotic medicines. RESULTS Overall, 31.4% of nurse managers responded to the survey. They mostly (88%) had ≥ 1 year’s relevant work experience and 83% of facilities provided care for those within the range of 21 to 100 residents. Respondents reported that staff education on dementia management occurred early in employment. Two-thirds of participants reported non-pharmacological interventions were commonly used for managing challenging behaviours, while less than half (45%) cited administering antipsychotic medicine. Respondents reported ‘managing behavioural symptoms’ (81%) as one of the main indications for antipsychotic use. Frequently identified adverse effects of antipsychotic medicines were drowsiness or sedation (64%) and falls (61%). Over 90% reported general practitioners reviewed antipsychotic use with respect to residents’ target behaviour 3-monthly, and two-thirds used an assessment tool to appraise residents’ behaviour. DISCUSSION Staff education on dementia management soon after employment and resident 3-monthly antipsychotic medicine reviews were positive findings. However, a wider use of behavioural assessment tools might improve the care of residents with dementia and the quality use of antipsychotic medicines.