Treatment Harms in Paediatric Primary Care.

The aim of this study was to describe the epidemiology in children of harms detectable from general practice records, and to identify risk factors. The SHARP study examined 9076 patient records from 44 general practices in New Zealand, with an enrolled population of 210,559 patients. "Harm" was defined as disease, injury, disability, suffering, and death, arising from the health system. The age group studied was ≤20 years of age. There were 193 harms to 141 children and adolescents during the 3-year study period. Harms were reported in one (3.5%) patient aged <2 years, 80 (6.6%) aged 2 to <12 years, 36 (4.9%) aged 12 to <18 years, and 24 (7.5%) aged 18 to ≤20 years. The annualised rates of harm were 36/1000 child and adolescent population for all harms, 20/1000 for medication-related harm (MRH), 2/1000 for severe MRH, and 0.4/1000 for hospitalisation. For MRH, the drug groups most frequently involved were anti-infectives (51.9%), genitourinary (15.4%), dermatologicals (12.5%), and the nervous system (9.6%). Treatment-related harm in children was less common than in a corresponding adult population. MRH was the most common type of harm and was related to the most common treatments used. The risk of harm increased with the number of consultations.

Low dose or very low dose phenylephrine and cyclopentolate microdrops for retinopathy of prematurity eye examinations (The Little Eye Drop Study): a randomised controlled non-inferiority trial.

OBJECTIVE: To determine if very low dose (VLD, 0.5% phenylephrine, 0.1% cyclopentolate) mydriatic microdrop (approximately 7 µL) administration (up to three doses) is non-inferior to low dose (LD, 1% phenylephrine, 0.2% cyclopentolate) mydriatic microdrop administration for ophthalmologist-determined successful retinopathy of prematurity eye examination (ROPEE). DESIGN: Multicentre, prospective, randomised controlled, non-inferiority clinical trial. SETTING: Four neonatal intensive care units in Aotearoa, New Zealand from October 2019 to September 2021. PATIENTS: Infants with a birth weight less than 1250 g or gestational age less than 30+6 weeks and who required a ROPEE. INTERVENTIONS: The intervention: microdrop (approximately 7 µL) of VLD (0.5% phenylephrine and 0.1% cyclopentolate) to both eyes, or the comparison: microdrop of LD (1% phenylephrine and 0.2% cyclopentolate) to both eyes. Up to three doses could be administered. MAIN OUTCOME MEASURES: The primary outcome measure was an ophthalmologist-determined successful ROPEE. RESULTS: One hundred and fifty preterm infants (LD mean GA=27.4±1.8 weeks, mean birth weight=1011±290 g, VLD mean GA=27.5±1.9 weeks, mean birth weight=1049±281 g,) were randomised. Non-inferiority for successful ROPEE was demonstrated for the VLD group compared with the LD group (VLD successful ROPEE=100%, LD successful ROPEE=100%, 95% CI no continuity correction -0.05 to 0.05) and for Maori (95% CI no continuity correction -0.02 to 0.19). CONCLUSION: VLD microdrops enable safe and effective screening for ROPEE in both Maori and non-Maori preterm infants. TRIAL REGISTRATION NUMBER: ACTRN12619000795190.

Medication-related harm in New Zealand general practice: a retrospective records review.

BACKGROUND: The extent of medication-related harm in general practice is unknown. AIM: To identify and describe all medication-related harm in electronic general practice records. The secondary aim was to investigate factors potentially associated with medication-related harm. DESIGN AND SETTING: Retrospective cohort records review study in 44 randomly selected New Zealand general practices for the 3 years 2011-2013. METHOD: Eight GPs reviewed 9076 randomly selected patient records. Medication-related harms were identified when the causal agent was prescribed in general practice. Harms were coded by type, preventability, and severity. The number and proportion of patients who experienced medication-related harm was calculated. Weighted logistic regression was used to identify factors associated with harm. RESULTS: In total, 976 of 9076 patients (10.8%) experienced 1762 medication-related harms over 3 years. After weighting, the incidence rate of all medication-related harms was 73.9 harms per 1000 patient-years, and the incidence of preventable, or potentially preventable, medication-related harms was 15.6 per 1000 patient-years. Most harms were minor (n = 1385/1762, 78.6%), but around one in five harms were moderate or severe (n = 373/1762, 21.2%); three patients died. Eighteen study patients were hospitalised; after weighting this correlates to a hospitalisation rate of 1.1 per 1000 patient-years. Increased age, number of consultations, and number of medications were associated with increased risk of medication-related harm. Cardiovascular medications, antineoplastic and immunomodulatory agents, and anticoagulants caused most harm by frequency and severity. CONCLUSION: Medication-related harm in general practice is common. This study adds to the evidence about the risk posed by medication in the real world. Findings can be used to inform decision making in general practice.

Randomised controlled pilot trial comparing low dose and very low- dose microdrop administration of phenylephrine and cyclopentolate for retinopathy of prematurity eye examinations in neonates.

AIMS: To determine ifVery low dose mydriatic eye microdrop regimen sufficiently dilates the pupil (above 4.1 mm) compared with the currently used low dose mydriatic eye microdrop regimen.Cardiovascular, gastrointestinal and respiratory adverse effects occur following eye drop instillation. METHODS: Seventeen premature infants were recruited into this prospective, randomised controlled pilot trial in January 2017 to November 2018. Data were collected from the single-centre Neonatal Intensive Care Unit, Dunedin Hospital, New Zealand. The inclusion criteria were birth weight less than 1500 g or gestational age less than 31 weeks, or any premature infant requiring red reflex testing. Infants were randomised to receive either phenylephrine 1% or 0.5% and cyclopentolate 0.2% or 0.1%, 1 microdrop in both eyes. Efficacy outcome measures were pupil size at retinopathy of prematurity eye examination (ROPEE) and ophthalmologist rating of ease of screen. RESULTS: All participants had sufficient pupillary dilation for a successful ROPEE. Ophthalmologists rated the ROPEE as easy for 90% of all examinations. Pupil dilation measurements at the time of examination, mean±SD, 4.8±0.2 (95% CI 4.5 to 5.2) mm for treatment A and 5±0.2 (95%CI 4.6 to 5.4) mm for treatment B (p=0.61). There were no statistically significant differences between the groups for safety data. CONCLUSIONS: Very low dose microdrop administration of phenylephrine and cyclopentolate appears to be effective at sufficiently dilating the neonatal pupil for ROPEEs. Low dose and very low dose microdrop mydriatic regimens may also reduce the risk of unwanted adverse effects associated with these medicines. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (reference ACTRN12616001266459p).

Monitoring the use of dabigatran etexilate for stroke prevention: compliance with renal function guidelines.

INTRODUCTION Dabigatran etexilate has become widely used in New Zealand, but information relating to when renal function monitoring is being undertaken is lacking. AIM To investigate if clinically appropriate renal function monitoring is being undertaken in New Zealand primary care for stroke prevention in non-valvular atrial fibrillation patients prescribed dabigatran etexilate. METHODS New Zealand non-valvular atrial fibrillation patients' prescription and primary care health data were extracted from national administrative databases for the period 1 July 2011 to 31 December 2015. The proportion of patients who had serum creatinine measurements at close proximity to treatment initiation and 12-months post initiation were assessed with 95% confidence intervals (CIs) and compared with Fisher's exact test. Log-rank tests for univariate analysis (gender, age, ethnicity and deprivation) effects on serum creatinine testing at dabigatran etexilate treatment initiation and 12-months post initiation were performed. RESULTS Overall, 1,948 patients who had been dispensed dabigatran etexilate with available primary care health data were identified. A total of 1,752 (89.9% [CI: 88.5-91.2]) patients had a renal function test at dabigatran etexilate initiation. There were 929 (72.8% [CI: 70.2-75.2]) patients who received ≥1 year supply of dabigatran etexilate and of these 207 (22.3% [CI: 19.6.6-25.1]) had a serum creatinine test 1 year after initiation. Demographic univariate analysis yielded insignificant log-rank tests for association with having serum creatinine measurements, except for Pacific Peoples. DISCUSSION There appears to be sub-optimal adherence to renal function monitoring for non-valvular atrial fibrillation patients who receive more than 12-months' treatment with dabigatran etexilate in New Zealand primary care.

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.

Exposure Response Supports Therapeutic Drug Monitoring for Dabigatran Etexilate in Patients with Atrial Fibrillation.

Background Dabigatran etexilate has become widely used for the prevention of stroke in patients with nonvalvular atrial fibrillation (NVAF). Currently, there is limited information in real-world patients relating to dabigatran etexilate exposure and response. Methods This retrospective cohort study used administrative health data for NVAF patients dispensed dabigatran etexilate between July 1, 2011 and December 31, 2015. Outcomes of cerebrovascular accident (CVA), systemic embolism, and hemorrhage were extracted. Simulated pharmacokinetic parameters were obtained using a published population pharmacokinetic model of dabigatran etexilate. Area under the curve calculated for a 24-hour period at steady state (AUC ss ), the exposure parameter, was derived using these simulations and the dosing data and the exposure-response relationship were investigated. The risk of adverse outcomes at AUC ss quartiles was compared using Poisson regression and expressed using incidence rate ratios (95% confidence interval) adjusted for known potential confounders. Results In total, 2,660 NVAF patients had been dispensed dabigatran etexilate. For these patients there was a decreased risk of hemorrhage (0.51, 0.32-0.79) when dabigatran AUC ss was in the second quartile range of 1.70 to 1.96 mg h/L and thromboembolism/CVA (0.34, 0.16-0.76) when in the third quartile range of 1.97 to 2.26 mg h/L. An increased risk of hemorrhage (1.68, 1.18-2.38) was observed when AUC ss was in the fourth quartile range of 2.27 to 12.76 mg h/L. Conclusion An exposure-response relationship for dabigatran etexilate was described, where the most effective response was observed when AUC ss was in the range of 1.70 to 2.26 mg h/L. Hence, it is feasible to develop guidance for optimal dosing to improve outcomes for patients with NVAF.

In vitro validation of a method for neonatal urine collection and analysis.

OBJECTIVE: Urine collection and analysis is important for diagnosis, monitoring of clinical progress, and research in neonates. This study aims to validate a novel methodology for neonatal urine collection, which combines the convenience of cotton ball collection with accurate timing via a urine continence monitor. DESIGN: Laboratory model using a combined cotton ball and urinary incontinence monitor method with and without the presence of an impermeable membrane to prevent desiccation. MAIN OUTCOME MEASURES: Accuracy, bias and precision in measurement of urine volume, electrolytes (sodium, potassium, chloride), creatinine and gentamicin. Changes in analyte concentration over time, and evaporative loss of water, were tested using analysis of variance. The effects of time, temperature and humidity were explored using multivariate analysis of variance. RESULTS: With the use of an impermeable membrane, sodium concentration increased from a mean (SD) of 3.57% (0.68) at 1 min to 5.03% (0.74) at 120 min. There was no significant change in potassium, chloride or creatinine concentrations. Gentamicin concentration decreased by a mean (SD) of 9.05% (1.37) by 30 min. Multivariate analysis found that absolute change in weight, sodium and chloride were only dependent on duration. Gentamicin concentration was affected by duration, humidity and temperature. Relative evaporative loss was minimal at -0.58% (0.31), and the urinary continence monitor was 100% successful at detecting urination for all time points. CONCLUSIONS: This novel methodology provides a standardisable and practical method to collect small volumes of neonatal urine for accurate measurement of both urine output and analyte concentrations.

Systematic review of mydriatics used for screening of retinopathy in premature infants.

INTRODUCTION: Routine retinopathy of prematurity eye examinations are an important part of neonatal care, and mydriatic medicines are essential in dilating the pupil for the eye examination. There are concerns about the level of evidence for efficacy and safety of these mydriatic medicines. OBJECTIVE: This review evaluates both efficacy and safety evidence of mydriatics used during the retinopathy of prematurity eye examination. METHOD: Systematic literature review. RESULTS: There is limited evidence guiding clinical practice for safety and efficacy of mydriatics. The majority of publications are underpowered and with an unclear to high level of bias. There are a wide variety of mydriatic regimens evaluated for efficacy and safety, and multiple regimens are associated with case reports. CONCLUSIONS: Current international guideline seems unnecessarily high, especially when the reviewed literature suggest that lower doses are effective, albiet from underpowered studies. The lowest effective combination regimen appears to be phenylephrine 1% and cyclopentolate 0.2% (1 drop). Microdrop administration of this regimen would further increase the safety profile, however, efficacy needs to be assessed.

Management of childhood obesity: An audit of clinical practice in secondary care.

AIM: Childhood obesity continues to be a major health issue for children world-wide, with well-recognised major health effects. This study evaluated the prevalence of obesity in children presenting to secondary care in Southern New Zealand, as well as their clinical management. METHODS: Obesity prevalence was determined by a review of data contained in the electronic anthropometry database in the region for the period 19 July 2010-16 July 2015. All clinical records were further examined using a standard data extraction form for 333 obese children regarding their clinical management. RESULTS: A total of 8551 individuals were identified in the database for review. The prevalence of overweight and obesity was higher than the average national rates but stable over the 5-year period. Children of Maori and Pacific Island ethnicity, those most deprived and males were over-represented in terms of obesity. Of the 333 obese children whose clinical management was examined, 45.0% received a diagnosis of obesity. Of those diagnosed, 24.7% had further investigations related to possible obesity complications, and 72.7% were given management plans. Older females were more likely to receive clinical intervention, while Maori and Pacific Island children were less likely. CONCLUSIONS: Of the children seen in this secondary care setting, 40% are overweight or obese, and yet the rate of clinical intervention left room for improvement, suggesting a need for further staff education and clear guidelines. Maori and Pacific Island children have higher obesity burden but were less likely to receive clinical intervention. This may highlight a need for specific education regarding cultural practices.

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.

Introduction and uptake of electronic growth charts in southern New Zealand.

AIM: The introduction of an electronic system for recording and displaying growth measurements replaces multiple paper growth charts and theoretically improves the availability and consistency of information to support clinical decision-making. Introducing this in a single New Zealand District Health Board provided the opportunity to evaluate usage in hospital settings and determine the uptake of growth recording in a defined population. METHODS: All records between 2010 and 2015 in the Southern District Health Board (SDHB) anthropometry database were downloaded and examined in a retrospective cohort analysis. Records were extracted after matching to demographic and clinical setting data from the hospital patient management system. RESULTS: Analysis included 30 670 data entry points, representing 8551 children. Data entry increased over time to a maximum of 8407 observations in 2015. By the fifth year of use, up to 67% of available clinical encounters had anthropometry recorded in the outpatient department. Rates were lower in the inpatient setting, where only up to 18.4% had anthropometry recorded. The errors identified were low (0.2% of all data). Weight was the most commonly recorded measurement (98.2% of anthropometry entries, 35.1% of available clinical presentations). Height was available for 82.6% of entries and 29.5% of presentations. A body mass index z-score was available for 81.5% of entries and 29.1% of presentations. A head circumference was available for 50.2% of children <2 years age who had anthropometry recorded. CONCLUSIONS: The introduction of an electronic anthropometry database has been successful with increasing rates of use over time, especially in outpatient clinics. Further focus to improve inpatient recording of height and weight is needed.

Characteristics of a stratified random sample of New Zealand general practices.

INTRODUCTION Practice size and location may affect the quality and safety of health care. Little is known about contemporary New Zealand general practice characteristics in terms of staffing, ownership and services. AIM To describe and compare the characteristics of small, medium and large general practices in rural and urban New Zealand. METHODS Seventy-two general practices were randomly selected from the 2014 Primary Health Organisation database and invited to participate in a records review study. Forty-five recruited practices located throughout New Zealand provided data on staff, health-care services and practice ownership. Chi-square and other non-parametric statistical analyses were used to compare practices. RESULTS The 45 study practices constituted 4.6% of New Zealand practices. Rural practices were located further from the nearest regional base hospital (rural median 65.0 km, urban 7.5 km (P < 0.001)), nearest local hospital (rural 25.7 km, urban 7.0 km (P = 0.002)) and nearest neighbouring general practitioner (GP) (rural 16.0 km, urban 1.0 km (P = 0.007)). In large practices, there were more enrolled patients per GP FTE than both medium-sized and small practices (mean 1827 compared to 1457 and 1120 respectively, P = 0.019). Nurses in large practices were more likely to insert intravenous lines (P = 0.026) and take blood (P = 0.049). There were no significant differences in practice ownership arrangements according to practice size or rurality. CONCLUSION Study practices were relatively homogenous. Unsurprisingly, rural practices were further away from hospitals. Larger practices had higher patient-to-doctor ratios and increased nursing scope. The study sample is small; findings need to be confirmed by specifically powered research.

The role of parent and child self-regulation in children's glycemic control.

OBJECTIVE: Type 1 diabetes mellitus (T1DM) is a lifelong, metabolic disorder, typically arising in childhood and adolescence. Despite recent advances in diabetes management techniques, glycemic control remains substandard for many individuals This study examined the role of parental and child self-regulation in predicting effective glycemic control in children and adolescents with Type 1 diabetes mellitus (T1DM). METHOD: Sixty-three families (with children aged 3-18 years) with T1DM participated. Child, maternal, and paternal measures of temperament, including surgency (behavioral self-regulation), negative affect (emotional selfregulation), and effortful control (cognitive self-regulation) were collected, along with demographic information and haemoglobin A1c (glycemic control). RESULTS: Higher parental and child effortful control was associated with better glycemic control. Higher child negative emotionality was associated with poorer glycemic control. No significant interactions between child and parent measures were identified. CONCLUSIONS: Both parental and child self-regulation play an independent role in glycemic control, and serve as targets for intervention in improving diabetes management in children and adolescents. (PsycINFO Database Record

The influence of patient variables on insulin total daily dose in paediatric inpatients with new onset type 1 diabetes mellitus.

PURPOSE: Insulin dose requirements at new diagnosis of type 1 diabetes mellitus (T1DM) vary widely. Current guidelines recommend an initial total daily dose (TDD) ranging from 0.5 to 1.0 IU/kg/day. It often takes several days of frequent dose adjustments before an optimal insulin dose is achieved. The aim of this study was to identify the influence of patient variables on the dose-requirement of insulin in newly diagnosed children with T1DM. METHODS: A retrospective chart review of children (≤ 18 years old) admitted to hospital between 2010 and 2016 due to new onset T1DM was undertaken. Demographic, clinical, insulin dosing, and laboratory data were recorded. The influence of patient characteristics on insulin TDD was analysed statistically by performing univariate and multivariate linear regression analyses. RESULTS: Complete clinical records for 70 patients were available for analysis. The median insulin TDD on first day of admission was 21 (4.5 to 75 units) and that on the day before discharge was 27 (5.5 to 124 units). In the multivariate regression analysis, body size (total body weight and fat-free mass), glycated haemoglobin (HbA1C), and blood ketone concentration were found to be significant predictors of optimal insulin TDD (p < 0.05). CONCLUSION: In addition to body size, HbA1c and ketone concentrations are useful in calculating initial TDD in newly diagnosed children with T1DM. This could potentially decrease the number of days needed to reach a stable dose and result in improved early glycaemic control.

Choice of Renal Function Estimator Influences Adverse Outcomes with Dabigatran Etexilate in Patients with Atrial Fibrillation.

Background Clinical significance of dosing dabigatran with different estimates of renal function for treatment of atrial fibrillation (AF) is unknown. Renal function is routinely estimated by the chronic kidney disease epidemiology initiative equation (CKD-EPI) and used to guide dosing. The aim of this study was to investigate the risk of adverse outcomes for patients with AF when different estimators of renal function are used. Material and Methods AF patient data were extracted from national administrative databases. Renal function was estimated using Cockcroft-Gault, CKD-EPI, and CKD-EPI adjusted for body surface area (CKD-EPI-BSA). Outcomes of cerebrovascular accident (CVA), systemic embolism (SE), and hemorrhage were extracted. Results In total, 2,425 patients were identified, of which there were hospitalizations for 138 (5.7%) hemorrhagic events, 45 (1.9%) CVA/SE, and 33 (1.4%) unspecified CVA. The level of agreement between Cockcroft-Gault with CKD-EPI and CKD-EPI-BSA yielded a weighted kappa statistic of 0.47 and 0.71, respectively. CKD-EPI and CKD-EPI-BSA significantly overestimated renal function in elderly patients resulting in higher recommended doses compared with Cockcroft-Gault. The hazard ratio for a hemorrhagic event was 2.32 (95% confidence interval, 1.22-4.42; p = 0.01) when a high dose was given compared with normal dose, based on Cockcroft-Gault. Conclusion Both CKD-EPI and CKD-EPI-BSA equations significantly overestimated renal function in the elderly population compared with the Cockcroft-Gault equation. This may lead to dose selection errors for dabigatran, particularly for those with severe impairment, increasing the risk of adverse outcome. Hence, CKD-EPI and CKD-EPI-BSA equations should not be substituted for the Cockcroft-Gault equation in the elderly for the purpose of renal dosage adjustments.

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.

Epidemiology of Patient Harms in New Zealand: Protocol of a General Practice Records Review Study.

BACKGROUND: Knowing where and why harm occurs in general practice will assist patients, doctors, and others in making informed decisions about the risks and benefits of treatment options. Research to date has been unable to verify the safety of primary health care and epidemiological research about patient harms in general practice is now a top priority for advancing health systems safety. OBJECTIVE: We aim to study the incidence, distribution, severity, and preventability of the harms patients experience due to their health care, from the whole-of-health-system lens afforded by electronic general practice patient records. METHODS: "Harm" is defined as disease, injury, disability, suffering, and death, arising from the health system. The study design is a stratified, 2-level cluster, retrospective records review study. Both general practices and patients will be randomly selected so that the study's results will apply nationally, after weighting. Stratification by practice size and rurality will allow comparisons between 6 study groups (large, medium-sized, small; urban and rural practices). Records of equal numbers of patients from each study group will be included in the study because there may be systematic differences in patient harms in different types of practices. Eight general practitioner investigators will review 3 years of electronic general practice health records (consultation notes, prescriptions, investigations, referrals, and summaries of hospital care) from 9000 patients registered in 60 general practices. Double-blinded reviews will check the concordance of reviewers' assessments. Study data will comprise demographic data of all 9000 patients and reviewers' assessments of whether patients experienced harm arising from health care. Where patient harm is identified, their types, preventability, severity, and outcomes will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 18.0. RESULTS: We have recruited practices and collected electronic records from 9078 patients. Reviews of these records are under way. The study is expected to be completed in August 2017. CONCLUSIONS: The design of this complex study is presented with discussion on data collection methods, sampling weights, power analysis, and statistical approach. This study will show the epidemiology of patient harms recorded in general practice records for all of New Zealand and will show whether this epidemiology differs by rural location and clinic size.