Maternal diabetes and risk of attention-deficit/hyperactivity disorder in offspring in a multinational cohort of 3.6 million mother-child pairs.

Previous studies report an association between maternal diabetes mellitus (MDM) and attention-deficit/hyperactivity disorder (ADHD), often overlooking unmeasured confounders such as shared genetics and environmental factors. We therefore conducted a multinational cohort study with linked mother-child pairs data in Hong Kong, New Zealand, Taiwan, Finland, Iceland, Norway and Sweden to evaluate associations between different MDM (any MDM, gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (PGDM)) and ADHD using Cox proportional hazards regression. We included over 3.6 million mother-child pairs between 2001 and 2014 with follow-up until 2020. Children who were born to mothers with any type of diabetes during pregnancy had a higher risk of ADHD than unexposed children (pooled hazard ratio (HR) = 1.16, 95% confidence interval (CI) = 1.08-1.24). Higher risks of ADHD were also observed for both GDM (pooled HR = 1.10, 95% CI = 1.04-1.17) and PGDM (pooled HR = 1.39, 95% CI = 1.25-1.55). However, siblings with discordant exposure to GDM in pregnancy had similar risks of ADHD (pooled HR = 1.05, 95% CI = 0.94-1.17), suggesting potential confounding by unmeasured, shared familial factors. Our findings indicate that there is a small-to-moderate association between MDM and ADHD, whereas the association between GDM and ADHD is unlikely to be causal. This finding contrast with previous studies, which reported substantially higher risk estimates, and underscores the need to reevaluate the precise roles of hyperglycemia and genetic factors in the relationship between MDM and ADHD.

Patterns of opioid use in New Zealand older adults, 2007-2018.

OBJECTIVES: Opioid use has increased globally, dramatically increasing opioid overdose, dependence, abuse and mortality. Limited research is available on opioid use patterns in older adults in New Zealand and internationally. This study aims to address this gap by determining the incidence and prevalence of opioid use among older adults (age ≥65 years) in New Zealand from 2007 to 2018. METHODS: This was a population-based retrospective cohort study conducted using New Zealand national administrative healthcare databases. The annual opioid use incidence (2008-2018) and prevalence (2007-2018) in older adults were determined and stratified by sex, age, and opioid type and strength. We used descriptive statistics to summarise the patterns of opioid dispensing. Data analysis was conducted using MS Excel, and data linking was performed using SQL software. RESULTS: A total of 820,349 older adults were initiated on opioids during the study period. The overall incidence of opioid use in older adults showed a steady increase from 2008 to 2015; similarly, the prevalence steadily increased from 2007 to 2015, and thereafter, both rates fluctuated. A slight decrease in both prevalence and incidence rates was observed in 2018. Codeine and tramadol were the most commonly dispensed opioids during the study period. Females had a higher incidence and prevalence of all opioids than males. CONCLUSIONS: The incidence and prevalence of opioid dispensing increased in New Zealand older adults over time. Monitoring the trends of opioid use in older adults is critical to enable clinicians and policymakers to deliver early interventions to prevent future opioid-related adverse events.

Effect of the COVID-19 pandemic on asthma exacerbations in New Zealand: An interrupted time series analysis.

Background: New Zealand (NZ) implemented some of the strictest restrictions during the novel coronavirus pandemic (coronavirus disease 2019 [COVID-19]), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). How this impacted asthma exacerbation rates in NZ is unknown. Objective: We sought to explore the effects of the COVID-19 restrictions on asthma exacerbations in NZ during 2020. Methods: We used a population-based, interrupted time series to examine the impact of the first COVID-19 lockdown in NZ on asthma exacerbation rate. The primary outcome measure was change in the monthly exacerbation rate, defined as hospitalization and/or course of corticosteroids, before and after the first lockdown. In a secondary analysis, we quantified the number of patients with asthma, the actual asthma exacerbation rate from March to December 2019 versus March to December 2020, and the number of asthma hospitalizations. Results: There was a significant drop in the exacerbation rate immediately after lockdown (-3.02; P < .0001) followed by a significant and sustained increasing trend; the rate postlockdown increased relative to that prelockdown (0.27; P < .0001). Similar patterns were observed in all sociodemographic groups. In our secondary analysis, we identified 507,622 people with asthma; this reduced to 458,023 in 2020 postlockdown. The overall asthma exacerbation rate was 33.3% less in 2020 than in 2019 (reduction from 48.6/1000 patients to 32.4/1000 patients). The rate of asthma hospitalizations decreased from 9.5 per 1000 patients in 2019 to 6.2 per 1000 patients in 2020; this decrease was observed across all demographic groups. Conclusions: The first COVID-19 lockdown in 2020 in NZ significantly reduced asthma exacerbation rates across all sociodemographic groups. Whether these reductions are sustained requires further investigation.

Predictors of persistent opioid use in non-cancer older adults: a retrospective cohort study.

BACKGROUND: Long-term opioid use and associated adverse outcomes have increased dramatically in recent years. Limited research is available on long-term opioid use in older adults. OBJECTIVE: We aimed to determine the incidence and predictors of long-term or persistent opioid use (POU) amongst opioid-naïve older adults without a cancer diagnosis. METHODS: This was a retrospective cohort study using five national administrative healthcare databases in New Zealand. We included all opioid-naïve older adults (≥65 years) who were initiated on opioid therapy between January 2013 and June 2018. The outcome of interest was POU, defined as having continuously filled ≥1 opioid prescription within 91-180 days after the index opioid prescription. Multivariable logistic regression was used to examine the predictors of POU. RESULTS: The final sample included 268,857 opioid-naïve older adults; of these, 5,849(2.2%) developed POU. Several predictors of POU were identified. The use of fentanyl (adjusted odds ratio (AOR) = 3.61; 95% confidence interval (CI) 2.63-4.95), slow-release opioids (AOR = 3.02; 95%CI 2.78-3.29), strong opioids (AOR = 2.03; 95%CI 1.55-2.65), Charlson Comorbidity Score ≥ 3 (AOR = 2.09; 95% CI 1.78-2.46), history of substance abuse (AOR = 1.52; 95%CI 1.35-1.72), living in most socioeconomically deprived areas (AOR = 1.40; 95%CI 1.27-1.54), and anti-epileptics (AOR = 2.07; 95%CI 1.89-2.26), non-opioid analgesics (AOR = 2.05; 95%CI 1.89-2.21), antipsychotics (AOR = 1.96; 95%CI 1.78-2.17) or antidepressants (AOR = 1.50; 95%CI 1.41-1.59) medication use were the strongest predictors of POU. CONCLUSION: A significant proportion of patients developed POU, and several factors were associated with POU. The findings will enable healthcare providers and policymakers to target early interventions to prevent POU and related adverse events.

Asthma exacerbations in New Zealand 2010-2019: A national population-based study.

INTRODUCTION: Asthma is one of the most common long-term conditions in the world, with New Zealand (NZ) having one of the highest rates of asthma symptoms. Despite the significant burden of asthma in NZ, there is a lack of data on asthma exacerbation rates in NZ and how these have varied over time. This study is a national population-based study of asthma exacerbation rates in NZ between 2010 and 2019, and explores how these rates vary amongst different demographic groups. METHODS: A retrospective population-based observational cohort study covering the ten years 2010-2019 to determine asthma prevalence, and asthma exacerbation and hospitalisation rates, using de-identified data from five national healthcare datasets. Exacerbations were defined based on hospital discharge diagnoses or oral corticosteroid dispensing. RESULTS: Total number of patients with asthma was 447,797 in 2010 to 512,627 in 2019, equating to approximately 10% of the population. Of these 19.4% experienced an exacerbation in 2010 (a population rate of 376.2 per 1000 patient-years); this exacerbation rate increased to 25.1% in 2019 (438.3 per 1000 patient-years). Exacerbations rates were consistently higher for females than males, and among Pacific peoples and Maori. In contrast, hospital admissions 25% lower in 2019 than 2010, decreasing from 1.4% to 0.9%, however over 50% of these admissions were in Maori and Pacific peoples. CONCLUSION: Asthma exacerbation rates in NZ have increased over 2010-2019, however hospitalisation rates have decreased. This potentially suggests a move away from secondary to primary care management of exacerbations and provides important information for asthma care planning.

Reduced community antibiotic dispensing in New Zealand during 2015-2018: marked variation in relation to primary health organisation.

AIMS: The overall rate of community antibiotic dispensing in New Zealand in recent decades has been high when compared with many other nations, but since 2015 has consistently declined each year. We aimed to determine whether the magnitude of reductions in community antibiotic dispensing in New Zealand between 2015 and 2018 differed in relation either to the patient's demographic features or in relation to the primary health organisation of the patient's registered general practitioner. METHODS: Demographic data on all patients registered with a general practice in New Zealand, and on all community pharmacy antibiotic dispensing for these patients during 2013-2018 were obtained from national healthcare databases. The rates of dispensing for patients registered with a general practitioner were measured as antibiotic courses dispensed per 1,000 population per day, and as defined daily doses per 1,000 population per day. RESULTS: Total community antibiotic dispensing in New Zealand, measured as defined daily doses per 1,000 inhabitants per day, decreased by 13.8% during 2015-2018, an average annual reduction of 4.6% per year, with especially large reductions in dispensing of amoxicillin/clavulanate, fluoroquinolones and macrolides. The reductions in dispensing were greatest in children aged 0-4 years old, but lesser reductions were seen in all age groups. Antibiotic dispensing declined regardless of patient ethnicity or level of socioeconomic deprivation. There were marked differences between primary health organisations in the size of the reductions in antibiotic dispensing during 2015-2018, which ranged between 4.8% for the Te Tai Tokerau PHO to 21.5% for the Ngati Porou Hauora Charitable Trust PHO. CONCLUSIONS: Total community antibiotic dispensing has reduced significantly in New Zealand between 2015 and 2018, with large disparities between primary health organisations in the size of the reductions. The overall rates of antibiotic dispensing remain high for non-Maori and non-Pacific people, and prescribers should aim to further reduce inappropriate antibiotic prescribing for these populations. However, the overall rate of antibiotic dispensing for Maori and Pacific people may now approximate an optimal level. Prescribers should aim to further reduce inappropriate antibiotic prescribing, but also to increase appropriate antibiotic prescribing for these populations.

Ethnic inequality in non-steroidal anti-inflammatory drug-associated harm in New Zealand: A national population-based cohort study.

PURPOSE: Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with many serious complications and they are widely used in New Zealand (NZ). However, differences in NSAID-associated risk for these complications between ethnic groups are largely unknown. We assessed ethnic disparities in risk of hospital admission for upper gastrointestinal bleeding (UGIB), heart failure, and acute kidney failure (AKF) in NZ's primary care population prescribed and dispensed NSAIDs. METHODS: Retrospective cohort study utilising national pharmaceutical dispensing and hospital admissions data 2007 to 2015. Patient follow-up included 90-day periods following the dispensing of NSAIDs. Risk for each adverse outcome in Maori, Pacific, European, and Asian patients was estimated using multivariable Poisson regression adjusting for age, sex, deprivation, comorbidity and concurrent drug use. RESULTS: 3 023 067 patients were dispensed NSAIDs between 2008 and 2015. Their total intended duration of NSAID treatment encompassed 2 353 140 patient-years. Maori, Pacific and Asian patients were younger than European patients (all P < .001). After adjusting for other risk factors, Maori (rate ratio: 2.54, 95% confidence interval: 2.23-2.90) and Pacific patients (3.17, 2.69-3.74) were more likely to be hospitalised for UGIB than Europeans (reference), and heart failure (Maori: 2.48, 2.24-2.74; Pacific: 1.97, 1.69-2.30). Risk of AKF was higher in Maori (1.46, 1.23-1.74). Higher risk for UGIB and HF in Maori and Pacific patients was most pronounced in males and patients aged <60 years. CONCLUSIONS: Inequalities exist in the incidence of serious adverse outcomes experienced by different ethnic groups in NZ while using NSAIDs. Interventions to promote safer use of these medicines are required to reduce this inequity.

Trends in prescription medicine use by older people in New Zealand 2010- 2015: a national population-based study.

BACKGROUND: Research investigating trends in the general prescription medicine use of older people in New Zealand is limited. AIM: To examine trends in the use of outpatient medicines by older adults and assess changing patterns in use from 2010 to 2015. METHODS: A retrospective cohort study including all New Zealand primary care patients over 65 years of age utilising data from the national pharmaceutical claims database. We calculated the prevalence of use within three age groups and by sex in each year by anatomical therapeutic class, therapeutic group and individual medicine. Rate ratios were calculated to compare the prevalence of use in 2010 and 2015. RESULTS: The study included 829,026 patients with a mean of 4.4 years of potential drug exposure. Overall prevalence of medicine use was 92% in 2010 and 93% in 2015. The mean number of prescriptions per patient-year for patients >=85 years of age (39.2) was almost double that of patients 65-74 years (21.8). Prevalence of use was similar between females (94%) and males (92%). Antibacterials, analgesics, cardiovascular drugs and proton pump inhibitors were the most widely used medicines. The use of systemic antibiotics increased by 2% between 2010 and 2015, but there were significant decreases in use of antithrombotics (6%), beta blockers (6%), diuretics (19%), nitrates (19%) and antiarrhythmics (24%). CONCLUSION: Our findings indicate both positive changes in response to guidance on safe and appropriate medicine use and several areas of concern. Continued monitoring of changing patterns in the medicine use of older people will be important, particularly with regard to the use of combinations of medicines that increase their risk of adverse events.

Mortality and morbidity of patients with treated and untreated epilepsy in New Zealand.

OBJECTIVE: To investigate whether delayed or no treatment was associated with increased mortality and morbidity risks in people with newly diagnosed epilepsy. METHODS: We examined New Zealand hospitalization and antiseizure medication prescription data from 2007-2015. Mortality and hospital-diagnosed morbidities were compared between patients immediately treated after epilepsy diagnosis, treated after a delay, or untreated for the duration of follow-up, adjusted for age, sex, and ethnicity. RESULTS: Three thousand three hundred sixty-six patients (54.7% male, median age = 37.5 years) were included and followed up for a median of 3.39 years. A total of 3123 (92.8%) patients were treated immediately, 125 (3.7%) had delayed treatment, and 118 (3.5%) were untreated. Compared to the general New Zealand population, the cohort had a standardized mortality ratio of 4.60 (95% confidence interval [CI] = 4.24-4.99). Maori patients were less likely to be treated (Holm-Bonferroni adjusted P = .024) and had higher mortality (hazard ratio [HR] = 1.41, 95% CI = 1.08-1.83). There was a trend of increased mortality in the untreated or delayed treatment group compared to the immediate treatment group (HR = 1.36, 95% CI = 0.99-1.87). Hospitalization risk was similar between untreated and immediately treated periods (P = .83). Untreated or delayed treatment patients had higher risk of acute myocardial infarction (HR = 9.64, 95% CI = 1.83-50.8). Maori patients were more likely to develop liver disease (HR = 4.67, 95% CI = 1.32-16.4) and alcohol or drug dependence (HR = 2.55, 95% CI = 1.44-4.51). SIGNIFICANCE: Most epilepsy patients were treated at diagnosis in New Zealand, but Maori patients had lower treatment rates and worse health outcomes. The apparent increased risk of acute myocardial infarction among the untreated or delayed treatment patients warrants further research.

Fatal Toxicity Indices for Medicine-Related Deaths in New Zealand, 2008-2013.

INTRODUCTION: The fatal toxicity index (FTI) is a measure for assessing the relative risks of death due to the medicines prescribed in a population. This knowledge is useful for prescribers and informs medicine safety initiatives. This study aimed to calculate FTIs for the New Zealand population using three methodologies. METHODS: New Zealand coronial data describing medicine-related deaths from 1 January 2008 to 31 December 2013 were retrospectively extracted from the National Coronial Information System. Three fatal toxicity indices were derived using the number of deaths attributed to each pharmaceutical as the numerator and the total defined daily doses, number of patients and number of prescriptions as denominators. RESULTS: There were 703 medicine-related deaths, of which 627 were assessed as due to one primary contributor. Median decedent age was 48 years (interquartile range 37-58), and 319 (51%) were male. Deaths were intentional in 252 cases (40%), unintentional in 284 (45%) and unknown in 91 (15%). The majority of deaths (n = 486, 78%) occurred in the community. Opioids, antidepressants, antipsychotics and hypnotic-anxiolytics caused most fatalities. While the FTIs for individual medicines varied by denominator applied, methadone and clozapine fatalities were prominent in all three indices. The antidepressants clomipramine, dosulepin and doxepin consistently returned the highest FTIs in their group. CONCLUSION: New Zealand prescribers should be aware of the high relative risk of death associated with methadone and clozapine; that clomipramine, dosulepin and doxepin were identified as the most dangerous antidepressants; and that zopiclone carries a similar fatal risk to benzodiazepines. Varying results were found between the FTIs calculated, making comparisons, particularly between populations, difficult.

Deaths by poisoning in New Zealand, 2008-2013.

Introduction: While a number of developed countries have witnessed a decline in carbon monoxide (CO) deaths and increasing numbers of opioid-related fatalities, it is not known whether these or other trends have occurred in New Zealand. The aim of this study was, therefore, to review deaths due to poisoning in New Zealand, describe the causative substances, and identify any trends. Methods: Retrospective study reviewing New Zealand's poison-related death findings recorded in the National Coronial Information System (NCIS) database over the 6-year period 2008-2013. Results: We identified 1402 poisoning-related deaths recorded in the NCIS database representing a mortality rate of 5.4 deaths/100,000 population per year. The mortality rate due to poisoning was higher in males (6.96/100,000) than females (3.83/100,000). Fatalities peaked in the 40-50-year age group with the highest proportion of intentional deaths occurring in people aged 80-90 years. Pharmaceuticals accounted for 731 fatalities (52%) and chemicals 431 (31%), with multiple exposures occurring in 399 cases (28.5%). While CO was the leading cause of death throughout the period (n = 303, 21.6%), there was a significant reduction in the rate of CO fatalities from 1.69/100,000 population in 2008 to 0.94/100,000 in 2013 (IRR (95% CI) 2013/2008 0.56 (0.37-0.83)). There was, however, no statistically significant change in either the opioid-related death rate or the total number of deaths. Methadone was the leading pharmaceutical cause of fatality and the third most common cause overall, followed by morphine and codeine, with zopiclone and clozapine equally ranked as the sixth most common cause. Conclusion: While New Zealand has not suffered an "opioid epidemic" and has experienced a significant decline in CO deaths, the overall death rate due to poisoning has remained high. The development of accessible, timely, and relevant toxicovigilance systems would support the early implementation of interventions to reduce the leading causes of fatal poisoning.

Prevalence and risk factors for chronic kidney disease in primary health care in the southern region of New Zealand.

AIM: While the prevalence of end stage kidney disease in New Zealand (NZ) is well defined, the prevalence of chronic kidney disease (CKD) in NZ is unknown. To estimate the prevalence of and risk factors for CKD in the southern region of New Zealand. METHODS: A retrospective electronic health record cohort study using data from the Southern Primary Care register covering 94% of the population. Patients, 20 years or older were identified and linked to laboratory results for serum creatinine and urinary albumin excretion. Chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 mL/min per 1.73 m2 (G3-5) or the presence of albuminuria of greater than 3 mg/mmol (A2-3). Diabetes was identified from a national virtual diabetes database. From this, we estimated the prevalence of CKD by age, gender, ethnicity, deprivation and the presence of diabetes mellitus. RESULTS: Of a total adult population of 211 980, 159 799 had a serum creatinine checked and 27 905 had an estimate of albuminuria. The estimated prevalence of CKD was 11.8%. 6.3% of total population had CKD stage G3a, 2.4% G3b, 0.8% G4, 0.2% G5, 1.8% A2 albuminuria and 0.3% A3 albuminuria. Increasing age, female sex, ethnic group, social deprivation and diabetes mellitus were associated with an increased risk of CKD. 11 351 patients had a diagnosis of diabetes mellitus and were almost universally tested (99.3%) for CKD. The presence of albuminuria was strongly correlated with ethnic group, male sex and living in a deprived area. The retrospective electronic health record study with associated selection and testing bias are potential limitations of the present study. CONCLUSION: Chronic kidney disease prevalence in this region appears to be similar to other reported populations. The majority of those at risk for CKD were tested for reduced eGFR. The presence of albuminuria, an integral component of CKD diagnostic criteria, was under utilized in the non-diabetic population.

Ethnic disparities in community antibacterial dispensing in New Zealand, 2015.

AIMS: There are significant ethnic disparities in the incidence of various infectious diseases in New Zealand. Antimicrobial stewardship interventions which ignore these disparities may have negative effects on the health of some ethnic groups. We aimed to determine the relationship between ethnicity and community antimicrobial dispensing in New Zealand, to inform the development of antimicrobial stewardship interventions in New Zealand. METHODS: Demographic data on all patients registered with a general practice in New Zealand and on all community pharmacy antibacterial dispensings during 2015 were obtained from national healthcare databases. The rates of dispensing were measured as the number of dispensings per 1,000 population per day and as defined daily doses per 1,000 population per day. RESULTS: The rate of community antibacterial dispensing for the total population surveyed was 3.01 dispensings per 1,000 population per day, and was 3.49 for Pacific, 3.23 for Maori, 3.02 for European, 2.70 for Middle Eastern, Latin American and African, and 2.35 for Asian people. In all ethnic groups the rate of community antibacterial dispensing increased with increasing socioeconomic deprivation. Seasonal variation in antibacterial dispensing ranged between 34% in Asian people and 24% in European people. CONCLUSIONS: The ethnic disparities in the rates of antibacterial dispensing in New Zealand are consistent with, but less marked than, the ethnic disparities in the incidence of infectious diseases in New Zealand. Improved community-wide understanding of both the benefits and the harms of antibacterial medicines is necessary to support improved antibacterial use in New Zealand in the future.

Understanding medicines with a propensity to increase the risk of heart failure: Combining existing knowledge with targeted population assessment.

PURPOSE: Existing knowledge of medicines that increase the risk of an adverse event may be corroborated and augmented by population studies specifically assessing the risk associated with the concurrent use of these medicines and use by patients with existing comorbidity. An American Heart Association review recently identified a variety of medicines that may cause or exacerbate heart failure (HF), many with evidence from limited evaluation of population data. We assessed the risk of first-time HF associated with the use of 50 of these medicines by New Zealand's primary care population. METHODS: Case-control study utilising national pharmaceutical use and hospital admissions data 2007-2015; 22,989 patients with first-time HF 2008-2015 were matched with 114 498 control patients. The primary outcome was first-time HF and its association with medicine exposure in the prior 90 days, estimated using conditional logistic regression. We also assessed the risk associated with new use of medicines in the prior month, concurrent use, and in patients with existing comorbidity. RESULTS: Eleven medicines were significantly associated with HF with several other infrequently used medicines providing signals of increased risk. A high risk was associated with the use of salbutamol (adjusted odds ratio 2.63; 95% CI, 2.48-2.78), clozapine (2.70; 2.46-4.98), diltiazem (1.52; 1.44-1.60), indomethacin (2.51; 1.54-4.10), pioglitazone (1.50; 1.16-1.95), and antifungal medicines. New use of medicines and use of medicine combinations increased this risk in many cases. CONCLUSIONS: Our study provides further evidence to inform cautious use of these medicines in patients with HF or at risk of developing HF.

Trends in Outpatient Prescription Medicine Use in New Zealand Children 2010-2015: A National Population-Based Study.

BACKGROUND: Research examining trends in the outpatient prescription medicine use of New Zealand children is limited. OBJECTIVES: Our objective was to provide an overview of prescription medicine use in New Zealand children and assess changing patterns in use from 2010 to 2015. METHODS: We conducted a retrospective cohort study including all New Zealand primary care-registered children aged < 18 years using data from the national pharmaceutical claims database. We calculated the prevalence of use within four age groups in each year by anatomical therapeutic class, therapeutic group and drug. Rate ratios were calculated to compare the prevalence of use in 2010 and 2015. RESULTS: In total, 1,496,026 children with a mean of 2.7 years of potential drug exposure were included. The overall prevalence of drug use was 70% in 2010 and 73% in 2015. In 2015, medicine use was highest in children aged < 2 years (90%) and lowest in children aged 12-17 years (65%). Antibacterials, analgesics, topical corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) and antihistamines were the most widely used medicines. The prevalence of use of systemic and topical antibiotics decreased by 2 and 10%, respectively, between 2010 and 2015, but there was increased use of analgesics (10%), NSAIDs (39%), antihistamines (15%) and antinausea and vertigo agents (306%). CONCLUSIONS: Our findings indicate areas for further research focusing on inappropriate prescribing to children and safety issues in children's medicine use. Monitoring changing patterns of use over time is important for the evaluation of effective therapies in children and any potential harmful consequences of prescribing.

A Pharmacoepidemiology Database System for Monitoring Risk Due to the Use of Medicines by New Zealand Primary Care Patients.

INTRODUCTION: The use of large record-linked healthcare databases for drug safety research and surveillance is now accepted practice. New Zealand's standardized national healthcare datasets provide the potential to automate the conduct of pharmacoepidemiological studies to provide rapid validation of medicine safety signals. OBJECTIVES: Our objectives were to describe the methodology undertaken by a semi-automated computer system developed to rapidly assess risk due to drug exposure in New Zealand's population of primary care patients and to compare results from three studies with previously published findings. METHODS: Data from three national databases were linked at the patient level in the automated studies. A retrospective nested case-control design was used to evaluate risk for upper gastrointestinal bleeding (UGIB), acute kidney failure (AKF), and serious arrhythmia associated with individual medicines, therapeutic classes of medicines, and concurrent use of medicines from multiple therapeutic classes. RESULTS: The patient cohort available for each study included 5,194,256 patients registered between 2007 and 2014, with a total of 34,630,673 patient-years at risk. An increased risk for UGIB was associated with non-steroidal anti-inflammatory drugs (NSAIDs) (adjusted odds ratio [AOR] 4.16, 95% confidence interval [CI] 3.90-4.43, p < 0.001) and selective serotonin reuptake inhibitors (AOR 1.39, 95% CI 1.20-1.62, p < 0.001); an increased risk for AKF was associated with NSAIDs (AOR 1.78, 95% CI 1.73-1.83, p < 0.001) and proton pump inhibitors (AOR 1.78, 95% CI 1.72-1.83, p < 0.001); and an increased risk for serious arrhythmia was associated with fluoroquinolones (AOR 1.38, 95% CI 1.26-151, p < 0.001) and penicillins (AOR 1.69, 95% CI 1.61-1.77, p < 0.001). CONCLUSIONS: Automated case-control studies using New Zealand's healthcare datasets can replicate associations of risk with drug exposure consistent with previous findings. Their speed of conduct enables systematic monitoring of risk for adverse events associated with a wide range of medicines.

Atrial fibrillation in New Zealand primary care: Prevalence, risk factors for stroke and the management of thromboembolic risk.

Background Atrial fibrillation is a major risk factor for stroke and heart disease but there is limited information on its prevalence in New Zealand primary care or the treatment provided to manage thromboembolic risk. Our aim was to estimate the prevalence of atrial fibrillation, assess patient risk for thromboembolism and evaluate the appropriateness of risk reduction using antiplatelet and oral anticoagulation therapy. Design A retrospective cohort study utilising electronic medical records for 739,000 patients registered with 170 general practices in 2014. Methods Patient diagnoses and prescriptions from 2010-2014 were analysed to identify patients with atrial fibrillation in 2014 and co-morbidities included in the CHA2DS2-VASc algorithm. Adjusted prevalence of atrial fibrillation by patient demographic group and the proportion of patients following recommended antithrombotic therapy were calculated. Results 12,712 patients were identified with AF (1.72%, 95% confidence interval 1.69%-1.75%). Prevalence was significantly higher for Maori (odds ratio 1.91, 95% confidence interval 1.80-2.03) than Europeans after adjusting for age, sex, deprivation and clinical risk factors. Stroke risk for Maori and Pacific Island patients was higher than for Europeans across all age groups. Of the 10,406 patients (81.9%) at high risk for thromboembolism, 60.5% were using anticoagulants, 24.1% aspirin monotherapy and 15.4% neither anticoagulants nor aspirin. Oral anticoagulants were used by 31.5% of patients at low risk (CHA2DS2-VASc <2). Conclusions Oral anticoagulants are under-utilised in the management of thromboembolic risk in high risk patients with atrial fibrillation. Better promotion of guideline recommendations for the treatment of patients with atrial fibrillation may be required to improve clinician and patient decision-making.

Variation in the pharmaceutical costs of New Zealand general practices: a national database linkage study.

BACKGROUND: Variation in prescription costs between general practices and within practices over time is poorly understood. METHODS: From New Zealand's national health data collections, we extracted dispensed medicines data for 1045 general practices in 2011 and 917 practices continuously existing 2008-11. Using indirect standardization to account for patient demographics and morbidity, a standardized prescribing cost ratio (SPR: the ratio of actual : expected prescription costs) was calculated for each practice in each year. Case studies of three outlier clinics explored reasons for their status. RESULTS: SPRs ranged from 0.53 to 2.28 (median = 0.98). Of 469 practices with higher than expected costs (SPR > 1.0) in 2011, 204 (43.5%) had a single medicine or therapeutic drug class accounting for >15% of total costs. Case studies contrasted practices with overall pharmaceutical expenditure influenced strongly by a few patients needing high-cost medicines, more patients using medicines in one high-cost therapeutic drug class (antiretrovirals), and high medicine use across all therapeutic drug classes. CONCLUSIONS: Routine data collections can measure inter-practice variation in prescription costs, adjusted for differences in the demography and morbidity profile of each practice's patients. Small groups of patients using high-cost medicines influence general practices' expenditure on pharmaceuticals.