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.

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.

Ethnic disparities in asthma treatment and outcomes in children aged under 15 years in New Zealand: analysis of national databases.

BACKGROUND: Mãori and Pacific children experience poorer outcomes relating to asthma management than other ethnicities. AIMS: To measure recommended treatment and outcomes for asthma in all New Zealand children by age, sex, and ethnic group. METHODS: Children aged <15 years dispensed >2 asthma medicines (N=80,514) were identified from the national pharmaceutical claims database. We measured the number of children dispensed oral steroids >2 times and hospital admissions with a primary diagnosis of asthma and compared asthma treatment steps and hospitalisation by age and ethnicity. RESULTS: 16.0% of children were dispensed asthma medicines, 9.2% were dispensed medicine >2 times, 3.6% of children were hospitalised at least once for asthma and 98.9% of admissions were acute. Mãori (OR 1.46, 95% CI 1.41 to 1.51) and Pacific children (OR 2.38, 95% CI 2.28 to 2.47) were more likely to remain on the lowest step of treatment. At all steps of treatment, Mãori and Pacific children had higher rates of oral steroid use. In all age groups, more Mãori children (5.1%, OR 1.88, 95% CI 1.73 to 2.04) and Pacific children (5.6%, OR 2.05, 95% CI 1.84 to 2.29) were hospitalised for asthma than children of other ethnicities (2.8%). CONCLUSIONS: Mãori and Pacific children are less likely to have their treatment escalated to a higher step than other children. They are also more likely to use oral steroids to control asthma exacerbations and be admitted to hospital for severe asthma episodes. New Zealand databases can be used to monitor these outcomes.

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.

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.

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.

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.

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.

Hospital admissions in diabetic and non-diabetic patients: a case-control study.

AIM: To examine differences in morbidity and rates of hospital admission between diabetes patients and patients without diabetes in New Zealand. METHODS: A 1,123 and 11,325 patients with Types 1 and 2 diabetes in the Southlink Health diabetes register were identified. Types 1 and 2 diabetes patients were matched with non-diabetic patients drawn from primary care patient registers. Hospital admission rates for diabetic complications and general medical conditions, length of stay in hospital, patients readmitted, deaths in hospital and hospital procedures were analyzed for the 3-year period from 2000 to 2002. RESULTS: Diabetes patients were more likely to be admitted to hospital for any reason than patients without diabetes (odds ratio (OR) 2.55, 95% confidence interval (CI) 2.13-3.04, p<0.001 for Type 1 patients; OR 1.40, CI 1.33-1.48, p<0.001 for Type 2 patients). A 46% (770) of all admissions for Type 1 patients were due to complications arising from diabetes and 33% (4685) for Type 2 patients. Major complications included ischaemic heart disease, heart failure, cataracts and conditions specific to diabetes. CONCLUSIONS: Increasing prevalence of diabetes will increase demand for hospital services overall, and particularly for inpatient care related to macroangiopathy, ophthalmic and renal problems and peripheral circulatory disorders.

Risk stratification of New Zealand general practice patients for emergency admissions in the next year: adapting the PEONY model for use in New Zealand.

INTRODUCTION Patient-centred case management programmes in general practice are needed for patients at high risk for emergency admissions to hospital. AIM To adapt and assess the Predicting Emergency Admissions Over the Next Year (PEONY) model for use in New Zealand to provide risk stratification of general practice patients aged ≥40 years for emergency hospital admissions in the next year. METHODS A retrospective observational cohort study modelling 2008-2010 hospital utilisation and medicine use was undertaken to estimate for each patient a risk of emergency admissions in 2011. Health care data were integrated from four national data collections relating to general practice patient registers, hospital admissions, pharmacy dispensed medicines, and mortality. Logistic regression was used to estimate coefficients for variables in the model. Model performance was assessed by calculating its positive predictive value (PPV), sensitivity, and specificity at incremental risk thresholds and receiver operating characteristic. RESULTS The patient cohort included 1,409,506 registered patients; 154,892 (11.0%) had an emergency admission in the follow-up year. Patient age, sex, ethnic group, deprivation status, prior emergency admissions and use of medicines for chronic conditions were all strong predictors of admissions in the next year. The model's PPV for the validation dataset was 58.2% for patients with risk ≥ 50%, and the area under its receiver operating curve = 0.72. DISCUSSION The PEONY model provides an effective methodology for stratifying New Zealand general practice patients' risk for future emergency admissions. High-risk patients may benefit from patient-centred case management programs to address risk and reduce unplanned admissions.

Operative intervention rates for acute diverticulitis: a multicentre state-wide study.

BACKGROUND: Acute colonic diverticulitis is placing an increasing strain on our health care resources. Measurement of the problem is difficult at a regional level, yet essential to improve and optimize treatment of this condition. Therefore, we aimed to use Australian state-level administrative data to determine the current practice and outcomes in major metropolitan hospitals. METHODS: Coding algorithms designed to increase the yield and accuracy of administrative data were used to find emergency admissions from the Victorian Admitted Episodes Dataset. Eight tertiary referral centres with specialist colorectal services from 2009 to 2013 were studied. Key metrics including the operative intervention rate were measured. RESULTS: There were 2829 emergency admissions for acute diverticulitis across 4 years in eight hospitals, with 724 being complicated. The emergency operative intervention rate was 10.4%, with a third of admissions for complicated diverticulitis having an operation. Hartmann's procedure was the most commonly performed emergency operation, accounting for 72% of resections. Patient characteristics were consistent across the hospitals, including a median length of stay of 3 and 6 days for uncomplicated and complicated diverticulitis, respectively. CONCLUSION: Hartmann's procedure is currently the most common emergency operation for acute complicated diverticulitis in Victorian metropolitan hospitals. Our practice and outcomes can be measured meaningfully using administrative data.

Patient outcomes from 10 years of annual diabetes reviews in New Zealand.

AIMS: To examine trends in patient health outcomes 2001-2010 for patients receiving free annual diabetes reviews in New Zealand. METHODS: Clinical, demographic and hospital admissions data were analysed for 2175 Type 1 and 25,436 Type 2 diabetes mellitus patients presenting at 170 general practices. Changes in clinical measures and proportions of patients achieving guideline targets and receiving recommended processes of care were assessed by calendar year and for patients returning for successive annual diabetes reviews. We also examined trends in hospital admission rates for diabetes complications over the ten years. RESULTS: The proportion of patients achieving guideline levels for blood pressure and cholesterol increased significantly and there were decreases in smoking rates and mean BMI for patients reviewed five times. The proportion of patients meeting guideline levels for HbA1c increased by year but decreased in patients returning for five reviews. There was also a reduction in the proportion of patients with poor glycaemic control (HbA1c>9.0% (75 mmol/mol)). The proportion of Type 2 patients using oral hypoglycaemic agents or insulin and receiving a retinal exam in the last two years increased significantly, and over 90% of patients received foot checks. Hospital admission rates for ischaemic heart disease, peripheral circulatory disorders, and ketoacidosis all decreased over the period 2001-2010 but inpatient admissions for eye, neurological and renal problems specific to diabetes increased. CONCLUSIONS: There have been many improvements in health outcomes for these diabetes patients participating in the New Zealand government's programme to provide free annual health checks, despite the increasing age and diabetes duration of the patient cohorts.

Risk factors for hospitalization due to diabetes complications.

AIM: To determine risk factors monitored in primary care that were significantly associated with diabetes complications requiring hospitalization. METHODS: We examined clinical and demographic data for 1080 Type 1 and 11,283 Type 2 New Zealand diabetes patients attending a free primary care diabetes examination between 2000 and 2002. Hospital admissions data for the 2 years following the index examination were linked for each patient using a unique National Health Index code. Logistic regression was used to determine odds ratios for the likelihood of developing diabetic complications adjusted for each variable. RESULTS: In the Type 1 cohort, 222 patients (20.6%) were hospitalized for diabetes complications and 1948 patients (17.3%) in the Type 2 cohort. In both cohorts, patients admitted with diabetes complications had significantly higher mean glycosylated haemoglobin (HbA1c) (p<0.001) and triglyceride levels (p<0.001), urine albumin:creatinine ratios (p<0.001) and duration of diabetes (p<0.01 Type 1: p<0.001 Type 2) than patients not admitted. In Type 2 patients, age, obesity, HbA1c, urine albumin:creatinine ratios, HDL levels and treatment with insulin or oral medication were all associated with increased odds of admission. CONCLUSIONS: Although it is well known that HbA1c is a significant predictor of diabetes complications, this study shows that urine albumin:creatinine ratio, body mass index, triglycerides and high density lipoproteins are also independent predictors of hospitalization for diabetes complications. Attention to all these factors in the primary care setting is indicated if the burden of diabetes complications to hospital services is to be minimized.