International trends in clozapine use: a study in 17 countries.

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 (10-19 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.

Exploring New Zealand prescription data using sequence symmetry analyses for predicting adverse drug reactions.

WHAT 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.

Decade-long temporal trends in the utilization of preventive medicines by centenarians.

WHAT 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.

Discontinuation of statins in a population of older New Zealanders with limited life expectancy.

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.

Residential medication management reviews of antithrombotic therapy in aged care residents with atrial fibrillation: assessment of stroke and bleeding risk.

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 , CHA2 DS2 -VASc, and HEMORR2 HAGES 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), CHA2 DS2 -VASc was 4·6 (1·5), and HEMORR2 HAGES 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 CHA2 DS2 -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.

General practitioners' insight into deprescribing for the multimorbid older individual: a qualitative study.

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.

Proton pump inhibitors utilisation in older people in New Zealand from 2005 to 2013.

BACKGROUND: The prescriptions for proton pump inhibitors (PPI) to treat acid-related disorders continue to rise internationally and in New Zealand. Concerns have been raised regarding its widespread use, costs and potential adverse effects in older people. AIMS: This study aimed to characterise the utilisation of PPI by older people (aged 65 years and older) in New Zealand from 2005 to 2013. METHODS: Repeated cross-sectional analysis of population-level dispensing data was conducted from 1 January 2005 to 31 December 2013. Dispensing data for all PPI prescriptions from 2005 to 2013 were obtained from the Ministry of Health, New Zealand. Utilisation was measured in defined daily doses (DDD) per 1000 older people per day using the World Health Organization Collaborating Centre for Drug Statistics Methodology anatomic, therapeutic and chemical classification system. Utilisation was standardised by sex, age, ethnicity and district health board. RESULTS: Overall PPI utilisation showed a 26.7% increase from 2005 to 2013, from 273.41 to 346.53 DDD/1000/day. The greatest utilisation was observed in individuals aged between 80 and 84 years. Middle Eastern/Latin American/African utilised more PPI compared with other ethnic groups. CONCLUSIONS: Utilisation of PPI among older people in New Zealand increased by a fifth from 2005 to 2013. Given the concerns surrounding the long-term PPI use in older people, the appropriateness of the increased utilisation needs to be continuously re-evaluated by prescribers and health policy makers.