Use of privacy-preserving record linkage to examine the dispensing of pharmaceutical benefits scheme medicines to pregnant women in Western Australia.

PURPOSE: Medications are commonly used during pregnancy to manage pre-existing conditions and conditions that arise during pregnancy. However, not all medications are safe to use in pregnancy. This study utilized privacy-preserving record linkage (PPRL) to examine medications dispensed under the national Pharmaceutical Benefits Scheme (PBS) to pregnant women in Western Australia (WA) overall and by medication safety category. METHODS: In this retrospective, cross-sectional, population-based study, state perinatal records (Midwives Notification Scheme) were linked with national PBS dispensing data using PPRL. Live and stillborn neonates born between 2012 and 2019 in WA were included. The proportion of pregnancies during which the mother was dispensed a PBS medication was calculated, overall and by medication safety category. Factors associated with PBS medication dispensing were examined using logistic regression. RESULTS: PPRL linkage identified matching records for 97.4% of women with perinatal records. A total of 271 739 pregnancies were identified, with 158 585 (58.4%) pregnancies involving the dispensing of at least one PBS medication. Category A medications (those considered safe in pregnancy) were the most commonly dispensed (n = 119 126, 43.8%) followed by B3 (n = 51 135, 18.8%) and B1 (n = 42 388, 15.6%) medication (those with unknown safety). Over the study period, the dispensing of PBS medications in pregnancy increased (OR: 1.06, 95%CI: 1.06, 1.07). The strongest predictor of medication dispensing in pregnancy was pre-pregnancy dispensing (OR: 3.61, 95%CI: 3.54, 3.68). Other factors associated with medication use in pregnancy were smoking, older maternal age, obesity, and prior pregnancies. CONCLUSION: Privacy preserving record linkage provides a way to link cross-jurisdictional data while preserving patient confidentiality and data security. The dispensing of PBS medication in pregnancy was common and increased over time, with approximately 60% of women dispensed at least one medication during pregnancy.

Medicine utilization studies in Australian individual-level dispensing data: A blinded, multi-center replicated analysis.

PURPOSE: Medicine dispensing data require extensive preparation when used for research and decisions during this process may lead to results that do not replicate between independent studies. We conducted an experiment to examine the impact of these decisions on results of a study measuring discontinuation, intensification, and switching in a cohort of patients initiating metformin. METHODS: Four Australian sites independently developed a HARmonized Protocol template to Enhance Reproducibility (HARPER) protocol and executed their analyses using the Australian Pharmaceutical Benefits Scheme 10% sample dataset. Each site calculated cohort size and demographics and measured treatment events including discontinuation, switch to another diabetes medicine, and intensification (addition of another diabetes medicine). Time to event and hazard ratios for associations between cohort characteristics and each event were also calculated. Concordance was assessed by measuring deviations from the calculated median of each value across the sites. RESULTS: Good agreement was found across sites for the number of initiators (median: 53 127, range: 51 848-55 273), gender (56.9% female, range: 56.8%-57.1%) and age group. Each site employed different methods for estimating days supply and used different operational definitions for the treatment events. Consequently, poor agreement was found for incidence of discontinuation (median 55%, range: 34%-67%), switching (median 3.5%, range: 1%-7%), intensification (median 8%, range: 5%-12%), time to event estimates and hazard ratios. CONCLUSIONS: Differences in analytical decisions when deriving exposure from dispensing data affect replicability. Detailed analytical protocols, such as HARPER, are critical for transparency of operational definitions and interpretations of key study parameters.

Investigating maternal and neonatal health outcomes associated with continuing or ceasing dexamphetamine treatment for women with attention-deficit hyperactivity disorder during pregnancy: a retrospective cohort study.

PURPOSE: Attention-deficit hyperactivity disorder (ADHD) is becoming more commonly diagnosed in women, consequently, more women of reproductive age are taking ADHD medication, such as dexamphetamine. However, the safety associated with continuing or ceasing dexamphetamine during pregnancy is unclear. This study investigates outcomes associated with the continuation of dexamphetamine during pregnancy compared to those who ceased or were unexposed. METHODS: A population-based retrospective cohort of women from Western Australia who had been dispensed dexamphetamine during pregnancy and gave birth between 2003 and 2018. Women had either continued to take dexamphetamine throughout pregnancy (continuers, n = 547) or ceased dexamphetamine before the end of the second trimester (ceasers, n = 297). Additionally, a matched (1:1) comparison group of women who were dispensed an ADHD medication prior to pregnancy but not during pregnancy (unexposed) was included in the study (n = 844). Multivariable generalised linear models were used to compare maternal and neonatal health outcomes. RESULTS: Compared to continuers, ceasers had greater odds of threatened abortion (OR: 2.28; 95%CI: 1.00, 5.15; p = 0.049). The unexposed had some benefits compared to the continuers, which included lower risk of preeclampsia (OR: 0.58; 95%CI: 0.35, 0.97; p = 0.037), hypertension (OR: 0.32; 95%CI: 0.11, 0.93; p = 0.036), postpartum haemorrhage (OR: 0.57; 95%CI: 0.41, 0.80; p = 0.001), neonatal special care unit admittance (OR: 0.16; 95%CI: 0.12, 0.20; p < 0.001) and fetal distress (OR: 0.73; 95%CI: 0.54, 0.99; p = 0.042). CONCLUSION: Continuing dexamphetamine throughout pregnancy was not associated with an increase in adverse neonatal and maternal health outcomes compared to ceasing. Ceasing dexamphetamine during pregnancy was associated with increased odds of threatened abortion compared with continuing dexamphetamine. However, this is something that requires further investigation due to the small sample size, difficulties examining timing, and the inability to examine spontaneous abortions. The unexposed showed some benefits compared to the continuers, suggesting that where possible the cessation of dexamphetamine prior to pregnancy may be advisable.

Exposure to family and domestic violence in the prenatal period is associated with an increased risk of hospitalization for bronchiolitis in children under 2 years.

BACKGROUND: Existing research has acknowledged a correlation between stress in pregnancy and poorer respiratory health in offspring. However, research focusing on stress caused by family and domestic violence in the prenatal period is missing. METHODS: A retrospective cohort study included children born 1987-2010 who were identified as being exposed to FDV in the prenatal period (n = 1477) from two sources: WA Police Information Management System and WA Hospital Morbidity Data Collection (HMDC) and a non-exposed comparison group (n = 41 996). Hospitalization for bronchiolitis was identified in HMDC. Cox regression was used to estimate the adjusted and unadjusted hazard ratio and 95% confidence interval for bronchiolitis hospitalizations contact. RESULTS: Children exposed to FDV had a 70% (HR 1.70, 95% CI: 1.49-1.94) increased risk of hospitalization for bronchiolitis than non-exposed counterparts by age two. Children exposed to FDV had a longer average hospital stay for bronchiolitis than non-exposed children (4.0 days vs. 3.8 days, P < 0.001). CONCLUSIONS: Prenatal exposure to FDV is associated with bronchiolitis hospitalization in children <2 years. Along with other risk factors, clinicians should give consideration to maternal stress factors, including experiencing FDV as a potential contributor to bronchiolitis.

Lithium Dispensed for Adults Aged ≥ 50 Years Between 2012 and 2021: Analyses of a 10% Sample of the Australian Pharmaceutical Benefits Scheme.

BACKGROUND: Lithium use seems to be declining in clinical practice. We examined the proportion of adults aged ≥ 50 years dispensed lithium between 2012 and 2021, and investigated the proportion of lithium users dispensed other medications. METHODS: We used a 10% random sample data of the Australian Pharmaceutical Benefits Scheme from 2012 to 2021, and limited our analyses to adults aged ≥ 50 years. We retrieved data on lithium, other mood stabilisers, antipsychotics, antidepressants, anxiolytics and hypnotics, and medications for the treatment of other health systems. RESULTS: We received 7081939 person-years records (53.2% women). The proportion of participants dispensed lithium decreased with age: 0.4% for those aged 50-59 years to < 0.1% for people aged ≥ 90 years. The dispensing of lithium increased over 10 years for those aged 50-69 and decreased in those older than 80 years. Among people dispensed lithium, nearly 1 in 5 were dispensed another mood stabiliser. Antipsychotics and antidepressants were dispensed to about 60% of participants dispensed lithium, with antidepressants dispensed more frequently to women than men. About 20% of people dispensed lithium were dispensed anxiolytics/hypnotics, more frequently for women than men. Medications to treat diseases of the alimentary, cardiovascular, endocrine and nervous systems were commonly dispensed to those dispensed lithium, as were antibiotics. CONCLUSIONS: While the dispensing of lithium increased among young older adults since 2015 when guidelines for the management of mood disorders were published, our findings suggest that lithium may be under-utilised for the management of bipolar disorder in later life.

Trends in prenatal diagnosis of congenital anomalies in Western Australia between 1980 and 2020: A population-based study.

BACKGROUND: Advances in screening and diagnostics have changed the way in which we identify and diagnose congenital anomalies. OBJECTIVE: To examine changes in rates of prenatal diagnosis of congenital anomalies over time and by demographic characteristics. METHODS: We undertook a population-based retrospective cohort study of all children born in Western Australia between 1980 and 2020 and diagnosed with a congenital anomaly. Age at diagnosis (prenatal, neonatal, infancy, early childhood or childhood) prevalence (all-type and type-specific), and prevalence ratios (PR) were calculated. We fit joinpoint regression models to describe the average annual percentage change (APC) in prenatal diagnosis over time, and log-binomial regression models to estimate the association between prenatal diagnosis and demographic characteristics. RESULTS: Prenatal diagnosis prevalence between the first (1980-1989: 28.3 per 10,000 births) and last (2005-2014: 156.1 per 10,000 births) decades of the study increased 5.5-fold (95% confidence interval [CI] 5.0, 5.9). Substantial increases were observed for cardiovascular (PR 10.7, 95% CI 8.0, 14.6), urogenital (PR 10.5, 95% CI: 8.7, 12.6) and chromosomal anomalies (PR 7.0, 95% CI 5.9, 8.3). Prenatal diagnosis was positively associated with the birth year (adjusted risk ratio [RR] 1.04, 95% CI 1.03, 1.04), advanced maternal age (RR 1.14, 95% CI 1.11, 1.18), multiple anomalies (RR 2.86, 95% CI 2.77, 2.96) and major anomalies (RR 3.75, 95% CI 3.36, 4.19), and inversely associated with remoteness (RR 0.89, 95% CI: 0.83, 0.95) and Aboriginality (RR 0.90, 95% CI 0.83, 0.97). CONCLUSIONS: Increases in prenatal diagnosis of congenital anomalies were observed in Western Australia from 1980 to 2020, reflecting advances in screening. Prenatal diagnosis was less common in remote regions and in Aboriginal children, strengthening calls for increased provision of antenatal care services for these populations.

The lasting impact of family and domestic violence on neonatal health outcomes.

OBJECTIVES: To compare the health of neonates born to women who experienced family and domestic violence (FDV) 12 months prior to birth, with the health of neonates born to women with an earlier history of FDV and women with no history of FDV. METHODS: A retrospective cohort of women who experienced FDV within 12 months of birth (antenatal FDV [AFDV]) (n = 1230) was identified using data from the Western Australia (WA) Police Force Incident Management System and WA Hospital Morbidity Data Collection. Two comparison cohorts were used, the first including women with a history of FDV (HFDV) 12-60 months prior to birth (n = 1549) and the second with no history of FDV (NFDV) recorded (n = 3690). Hospital, birth, mortality, and congenital anomaly data were used in generalized linear models to examine and compare neonatal health outcomes. RESULTS: Women in the AFDV group had higher proportions of factors associated with poor neonatal outcomes including smoking (42.4%), substance use (23.0%), and mental health disorders (34.8%). Neonates born to AFDV mothers had significantly higher odds of congenital anomalies (OR: 1.51, 95% CI: 1.18-1.94), low birth weight (1.74, 1.45-2.10), and preterm birth (1.48, 1.22-1.79) compared with neonates born to NFDV mother. Neonatal health outcomes in those born to AFDV women were not significantly different from those born to HFDV women. CONCLUSIONS: Antenatal and historical FDV were associated with poor neonatal health outcomes. Additional pregnancy and social support should be offered to women who have experienced FDV during or prior to pregnancy.

Trends in smoking during pregnancy stratified by the use of opioid agonist therapy and the contribution of smoking to poor outcome in neonates prenatally exposed to opioid agonist treatment.

High rates of cigarette smoking have been observed in pregnant women on opioid agonist therapy (OAT). However, it is unclear if these rates have changed overtime in line with the general population and the degree to which smoking contributes to poor outcomes in neonates born to women on OAT. Women who gave birth in Western Australia (WA) between 2003 and 2018 were identified from whole-population midwives records. Linked records were used to identify women who had been dispensed OAT during pregnancy and those who had smoking during pregnancy. Temporal changes in smoking during pregnancy were examined for women on OAT (n = 1059) and women not on OAT (n = 397,175) using Joinpoint regression. In women treated with OAT during pregnancy, neonatal outcomes were compared between smoking and non-smoking women using generalised linear models. During the study period, 76.3% of women on OAT smoked during pregnancy compared with 12.0% of the general population. There was a decrease in the prevalence of smoking during pregnancy among women not on OAT (APC: - 5.7, 95%CI: - 6.3, - 5.2), but not in women on OAT (APC: 0.8, 95%CI: - 0.4, 2.1). For women receiving OAT, smoking was associated with an increased odds of low birth weight (OR: 1.57, 95%CI: 1.06, 2.32) and neonatal abstinence syndrome (OR: 1.34, 95%CI: 1.01, 1.78) compared with non-smoking. Despite reductions in the prevalence of smoking during pregnancy in the general population, similar reductions have not occurred in pregnant women on OAT. The high prevalence of smoking in pregnant women on OAT is contributing to poor neonatal outcomes.

Systemic juvenile idiopathic arthritis: frequency and long-term outcome in Western Australia.

Systemic juvenile idiopathic arthritis (S-JIA) is a rare but potentially life threatening autoinflammatory condition of childhood. Given the limited data on S-JIA from the Australasian region, we investigated the epidemiological characteristics and long-term disease outcome in S-JIA. All hospitalised patients under the age of 16 years registered with ICD-10-AM code M08.2 in in the period 1999-2014 were identified in longitudinally linked administrative health data across all Western Australian (WA) hospitals. Incidence and point prevalence estimate were per 100,000 population with Poisson regression to analyse the incidence trend. Readmissions with S-JIA as primary diagnosis were considered flares with rates for flare and other complication reported per 100 person years with 95% confidence intervals (CI). Annual S-JIA incidence was 0.61/100,000 (CI 0.28-1.25) (46 incident cases, 71.7% girls, median age 6.5 years) and stable over time as S-JIA point prevalence reached 7.15/100,000 (CI 5.29-7.45) at the end of study. Most incident cases were diagnosed in winter and spring, but documented preceding infections were rare. During a median follow-up of 8 years, disease flares occurred in 24% of patients with higher flares rate in boys (58.3; CI 44.5-74.9) than girls (14.7; CI 9.9-20.9). No deaths occurred and arthroplasty was the main, but uncommon S-JIA complication (4%). However, readmission (86.3; CI 76.4-97.2) and ED visit (73.3; CI 64.2-83.4) rates for illnesses other than S-JIA were substantial. S-JIA is as rare in WA as in other regions and while s-JIA incurred no deaths in the era of biologics, it associated with a significant long-term burden of (co-) morbidity.

Opioid poisoning during pregnancy: prevalence, characteristics, and neonatal outcomes.

While it has been postulated that opioid poisoning during pregnancy may cause adverse maternal and neonatal outcomes, the harm associated with opioid poisoning during pregnancy has not been robustly examined. Pregnant women admitted to hospital or presenting to the emergency department (ED) in Western Australia (WA) with a diagnosis of opioid poisoning were identified by linking state midwifery records with hospital and ED administrative data. Maternal and neonatal outcomes were compared with opioid poisoning that occurred in the 12 months prior to conception or the 12 months following birth. Between 2003 and 2018, 57 neonates were born to women who had experienced opioid poisoning during pregnancy (14.1 per 100,000 births) in WA. The incidence of opioid poisoning in the year prior to pregnancy (IRR: 3.04, 95%CI: 2.30, 4.02) and the year following pregnancy (IRR: 1.96, 95%CI: 1.46, 2.64) was significantly higher than during pregnancy. Opioid poisoning during pregnancy was less likely to involve multiple substances and be intentional (rather than accidental). Neonatal conditions associated with in utero hypoxia were significantly less common in neonates born to women who experience opioid poisoning prior to pregnancy compared with during pregnancy (OR: 0.17, 95%CI: 0.04, 0.80). Opioid poisoning in pregnancy was not associated with an increased risk of other serious adverse neonatal outcomes. Opioid poisoning during pregnancy is uncommon and less likely to be intentional and involve multiple substances. Opioid poisoning during pregnancy is likely associated with an increased risk of conditions associated with in utero hypoxia.

Can the CHA2 DS2 -VA schema be used to decide on anticoagulant therapy in Aboriginal and other Australians with non-valvular atrial fibrillation?

The Australasian guidelines recommend use of the CHA2 DS2 -VA schema to stratify ischaemic stroke risk in patients with non-valvular atrial fibrillation (N-VAF) and determine risk thresholds for recommending oral anticoagulant (OAC) therapy. However, the CHA2 DS2 -VA score has not been validated in a representative Australian population cohort with N-VAF, including in Aboriginal people who are known to have a higher age-adjusted stroke risk than other Australians. In a retrospective data-linkage study of 49 114 patients aged 24-84 years with N-VAF, 40.0% women and 2.5% Aboriginal, we found that patients with a CHA2 DS2 -VA score >2 had high annual stroke rates (>2%) that would justify OAC therapy. This occurred regardless of Aboriginal status. Non-Aboriginal patients with a CHA2 DS2 -VA score of 0 had a mean annual stroke rate of 0.4%, and hence were not likely to benefit from antithrombotic therapy. However, Aboriginal patients with a zero CHA2 DS2 -VA score had a significantly higher annual stroke rate of 0.9%, and could potentially obtain net clinical benefit from anticoagulation, primarily with the safer non-vitamin K antagonist OAC. We conclude that clinicians can confidently use the CHA2 DS2 -VA score to make decisions regarding anticoagulation in accordance with stroke risk in patients with N-VAF, except in Aboriginal people in whom the risk score was unable to identify those at truly low risk of stroke.

Trends in incidence, mortality rates, and survival of colorectal cancer in Western Australia from 1990 to 2014: a retrospective whole-population longitudinal study.

PURPOSE: This study aimed to investigate the trends in colorectal cancer (CRC) incidence and mortality rates among the Western Australian (WA) population. This study further compared the trends with the timing of the implementation and rollout of the National Bowel Cancer Screening Program (NBCSP) and examined the survival predictors in CRC cases. METHODS: This study was a whole-population, retrospective longitudinal study and included all individuals with a confirmed histological diagnosis of primary invasive CRC diagnosed in WA from 1990 to 2014 (n = 25,932). The temporal trends were assessed by Joinpoint regression models and Kaplan-Meier survival curves were used to asses 5-year survival. Predictors of survival were examined using multivariable Cox proportional hazard regression models, adjusting for age of diagnosis. RESULTS: The overall CRC incidence showed an upward trend between 1990 and 2010 (annual percent change (APC) = 1.1%); then, there was a downward trend from 2010 to 2014 (APC = - 5.0%). In younger people (< 50 years), the incidence rate increased steadily (APC = 0.9%) over the study period. The overall CRC mortality trend increased from 1990 to 1999 (APC = 1.6%), decreasing after that (APC = - 2.1%). Younger people had better CRC-related 5-year survival than older people (HR = 0.81, 95%CI 0.75-0.87, p = < 0.001). CONCLUSION: This study found that CRC incidence and mortality rates decreased among older people over the last 10 years in Western Australia. However, incidence continues to rise for younger people. Hence, more widespread adoption of the screening program, and potential preventive and early diagnostic strategies should become key priorities for the CRC control in WA.

Differences in stroke risk and cardiovascular mortality for Aboriginal and other Australian patients with atrial fibrillation.

OBJECTIVES: To assess the risks of stroke and cardiovascular mortality for Aboriginal and non-Aboriginal Australians with atrial fibrillation. DESIGN: Retrospective data linkage cohort study. SETTING, PARTICIPANTS: All people aged 20-84 years hospitalised with atrial fibrillation in Western Australia during 2000-2012. MAIN OUTCOME MEASURES: Stroke incidence rates and mortality after hospitalisation for atrial fibrillation, and 10-year risks of stroke and of cardiovascular and all-cause mortality. RESULTS: Among 55 482 index admissions with atrial fibrillation, 7.7% of 20-59-year-old patients and 1.3% of 60-84-year-old patients were Aboriginal Australians. A larger proportion of Aboriginal patients aged 20-59 years had CHA2 DS2 -VASc scores of 2 or more (59.8% v 21.8%). In 20-59-year-old Aboriginal patients, the incidence during follow-up (maximum, 10 years; median, 7.1 years) of stroke (incidence rate ratio [IRR], 3.2; 95% CI, 2.5-4.1) and fatal stroke (IRR, 5.7; 95% CI, 3.9-8.9) were markedly higher than for non-Aboriginal patients. Stroke incidence was higher for 60-84-year-old patients, but the difference between Aboriginal and non-Aboriginal patients was smaller (IRR, 1.6; 95% CI, 1.3-2.0). Cardiovascular mortality during follow-up was also higher for 20-59-year-old Aboriginal patients (IRR, 4.4; 95% CI, 4.3-5.9). The hazards of stroke (adjusted HR [aHR], 1.67; 95% CI, 1.22-2.28) and cardiovascular mortality (aHR, 1.47; 95% CI, 1.18-1.83) in younger Aboriginal patients remained significantly higher after multivariable adjustment; age/sex, principal diagnosis of atrial fibrillation, and CHA2 DS2 -VASc score were the most influential factors. CONCLUSION: Stroke risk and cardiovascular mortality are markedly higher for Aboriginal than non-Aboriginal patients with atrial fibrillation, particularly for patients under 60. Strategies for providing evidence-based therapies and cardiovascular prevention to Aboriginal people with atrial fibrillation must be improved.

A comparison of blood toxicology in fatalities involving alcohol and other drugs in patients with an opioid use disorder treated with methadone, buprenorphine, and implant naltrexone.

Background: Methadone, buprenorphine, and implant naltrexone have comparable efficacy in preventing death from drug intoxication during treatment, but there may be differences between treatments in the specific drugs contributing to death and in the risk of death during different phases of treatment.Objective: The objective of this study was to compare concentrations of individual drugs in decedents for evidence that the three medications use to treat opioid use disorders differed in the protection they offered against fatal overdose.Methods: Fatalities with a primary or co-diagnosis of alcohol or other drug poisoning in patients treated with methadone (n = 66, 74.2% male), buprenorphine (n = 54, 74.1% male), or naltrexone (n = 28, 85.7% male) were identified by combining treatment (Monitoring of Drugs of Dependence System and clinical records) and mortality records (Western Australian Death Registry). Quantitative postmortem blood drug analysis data were obtained for drug-related deaths. The presence/absence of drugs were compared between the three medication groups and between phases of treatment (on-treatment/off-treatment).Results: Opioids (89.8%) and benzodiazepines (76.2%) were most commonly identified in postmortem blood. The three medication groups did not differ materially in the drugs present postmortem, except that alcohol was less prevalent in naltrexone-treated cases. Morphine or heroin intoxication was implicated in more patients dying off-treatment than on-treatment but levels of morphine and other drugs were comparable across the two phases.Conclusion: Comparisons of postmortem concentrations of specific drugs indicated that patients treated with methadone, buprenorphine, and implant naltrexone had comparable susceptibilities to lethal co-intoxication and that similar drug mixtures contributed to death.

Familial and non-familial risk factors associated with colorectal cancer survival in young and middle-aged patients.

BACKGROUND: Survival following colorectal cancer (CRC) survival may be influenced by a number of factors including family history, individual medical history, and comorbidities. The impact of these factors may vary based on the patient's age. METHODS: The study cohort consisted of individuals born in Western Australia between 1945 and 1996, who had been diagnosed with CRC prior to 2015 (n = 3220). Hospital, cancer, and mortality data were extracted for each patient from state health records and were used to identify potential risk factors associated with CRC survival. Family linkage data, in combination with cancer registry data, were used to identify first-degree family members with a history of CRC. The association between survival following CRC diagnosis and identified risk factors was examined using Cox proportional hazard models. RESULTS: Age and sex were not significantly associated with survival in young patients. However, in middle-aged patients increasing age (HR 1.03, 95% CI 1.01-1.05, p = 0.003) and being male (HR 0.72, 95% CI 0.60-0.87, p < 0.001) were associated with reduced survival. Being diagnosed with polyps and having a colonoscopy prior to CRC diagnosis were associated with improved survival in both young and middle-aged patients, while a history of non-CRC and liver disease was associated with reduced survival. In middle-aged patients, having diabetes-related hospital admissions (HR 1.53, 95% CI 1.15-2.03, p = 0.004) was associated with reduced survival. CONCLUSIONS: In both young and middle-aged patients with CRC, factors associated with early screening and detection were associated with increased CRC survival while a history of liver disease and non-CRC was associated with decreased CRC survival.

A retrospective cohort study of mortality rates in patients with an opioid use disorder treated with implant naltrexone, oral methadone or sublingual buprenorphine.

BACKGROUND: Sustained release naltrexone has been shown to be a safer alternative to oral naltrexone in terms of mortality in patients with an opioid use disorder; however, a direct large-scale comparison has not been made between sustained release naltrexone and the more popular opioid pharmacotherapies: methadone and buprenorphine. OBJECTIVE: To examine and compare mortality rates in patients with an opioid use disorder treated with implant naltrexone, methadone, and buprenorphine. METHODS: Patients treated with implant naltrexone (n = 1461, 35.6% female), methadone (n = 3515, 33.3% female), or buprenorphine (n = 3250, 34.5% female) for the first time between 2001 and 2010 in Western Australia (WA) were cross-matched against the WA Death Registry. RESULTS: Crude mortality rates in patients treated with methadone (8.1 per 1000 patient years (ptpy) (HR:1.13, CI:0.82-1.55, p = 0.447) or buprenorphine (7.2 ptpy) (HR:1.01, CI:0.72-1.42, p = 0.948) were not significantly different to those treated with implant naltrexone (7.1 ptpy). Similarly, no differences were observed between the three treatments in terms of cause-specific or age-specific mortality. However, high rates of mortality were observed in methadone-treated patients during the first 28 days of treatment (HR:8.19, CI:1.08-62.21, p = 0.042) compared to naltrexone-treated patients. Female patients treated with methadone (HR:2.96, CI:1.34-6.51, p = 0.007) also experienced a higher overall mortality rate compared to naltrexone-treated patients. CONCLUSIONS: Crude mortality rates are comparable in patients with an opioid use disorder treated with implant naltrexone, methadone, and buprenorphine. However, implant naltrexone may be associated benefits during the first 28 days of treatment and in female patients compared to methadone.

Morbidity and mortality in opioid dependent patients after entering an opioid pharmacotherapy compared with a cohort of non-dependent controls.

Aims: To compare morbidity and mortality in opioid dependence patients following the commencement of treatment with the general population. Methods: Morbidity and mortality in all patients treated with methadone, buprenorphine or implant naltrexone for opioid dependence for the first time between 2001 and 2010 in Western Australia was compared to a cohort of age and gender matched controls using state health records. Results: Compared to community controls rates of all-cause mortality, hospital admissions and Emergency Department attendances are significantly elevated in opioid dependent persons following the commencement of their first treatment. Not surprisingly, rates of opioid and non-opioid drug poisoning, and intentional self-harm/suicide mortality and hospital admissions were significantly elevated in opioid dependent patients compared with non-dependent controls. However, significant increases in mortality and hospital admissions for conditions which are not generally associated with opioid use were also identified including cardiovascular, respiratory and traffic accidents. Life-time prevalence of both HBV and HCV were significantly elevated in opioid dependent patients compared with non-dependent patients. Conclusions: Even after the commencement of treatment, opioid dependent patients are at a high risk of morbidity and mortality compared with non-dependent age and gender matched controls.

A retrospective cohort study of the health of children prenatally exposed to methadone, buprenorphine or naltrexone compared with non-exposed control children.

BACKGROUND AND OBJECTIVES: Little is known about the health of children exposed to opioid pharmacotherapies in utero. This study aims to examine the health of children from birth to 5 years of age, who were exposed to methadone, buprenorphine, or naltrexone with non-exposed children. METHODS: Children were identified by linking the treatment records of women treated with one of the three opioid pharmacotherapies with midwife notifications. Live-born children exposed to methadone (n = 198), buprenorphine (n = 122), naltrexone (n = 67) in utero, and neonates not prenatally exposed to opioids (n = 387) born between 2001 and 2011 in Western Australia were included in the study. The children were then linked to state mortality, hospital, emergency department (ED), mental health, cancer, and reportable diseases from birth up to their 5th birthday. RESULTS: Overall rates of hospital admission were elevated in all three treatments as compared with the control children, while rates of ED attendances were only significantly elevated in the methadone (p = .002) and naltrexone (p = .044) exposed children. In terms of both hospital and ED attendances, the differences between the exposed and control children was most apparent in the neonatal period. Rates of mental health out-patient attendances were elevated in buprenorphine-exposed children as compared with the control (p = .005). DISCUSSION AND CONCLUSIONS: The study provides evidence to suggest a disparity in the health of children exposed to opioid pharmacotherapies in utero compared with non-exposed control children. SCIENTIFIC SIGNIFICANCE: Exposure to opioid pharmacotherapies in utero may influence the health of children beyond the neonatal period. (Am J Addict 2017;26:845-851).

Retrospective assessment of the use of extended-release cabergoline in the management of equine pituitary pars intermedia dysfunction.

Introduction: Dopaminergic agonists are accepted as the most effective treatment for pituitary pars intermedia dysfunction. However, some horses are refractory to daily oral pergolide, the recommended registered treatment. Extended-release cabergoline (ERC) injection may offer an alternative. The objective of this retrospective case series was to describe clinical and endocrinological responses to ERC. Methods: Medical records of horses treated with weekly intramuscular injections of ERC (5 mg/mL, BOVA Aus) at either 0.01 mg/kg (high dose, HD) (n = 10) or 0.005 mg/kg (low dose, LD) (n = 30) were reviewed. Short-term ACTH responses were assessed at 5-8 days using a Wilcoxon signed ranked test. Longer-term ACTH responses (30 to 365 days) were assessed using generalised estimating equations. Results: Five to eight days after the first dose of LDERC, median adrenocorticotropic hormone (ACTH) concentration was lower (p = 0.001), changing from 153 pg/mL (IQR: 78, 331) to 57 pg/mL (IQR: 30, 102). With HDERC, median ACTH concentration was also 153 pg/mL (IQR: 96, 185) before and then 56 pg/mL (IQR: 29, 86) after 5-8 days of treatment (p = 0.047). Over 12 months of treatment, ACTH concentration ranged from 14 to >1,250 pg/mL (median: 51 pg/mL) in horses treated with LDERC and 20 to 472 pg/mL (median: 50 pg/mL) in horses treated with HDERC. Measurements remained above the seasonal reference range in 39.3 and 52.3% of horses treated with LDERC and HDERC, respectively. Clinical improvement was reported by owners in 78.3 and 100% of horses treated with LDERC and HDERC, respectively. Partial, self-limiting inappetence was reported in 30.0% of LDERC and 60% HDERC cases. Seven horses exhibited lethargy (5 LDERC, 2 HDERC). Insulin concentrations measured 30 days post-ERC treatment were no different from baseline. Discussion: Clinical and endocrinological responses were consistent with results of previous reports of oral pergolide treatment. Weekly injection of ERC may be an effective alternative to pergolide; the 0.005 mg/kg dose appeared to be as effective, with less risk of inappetence, than the 0.01 mg/kg dose that has been reported previously.

Prenatal Opioid Exposure and Immune-Related Conditions in Children.

Importance: Prenatal opioid exposure (POE) may alter with fetal development of the immune system, which may influence long-term health and susceptibility to immune-related conditions. Objective: To compare the risk of hospitalization and emergency department presentation for immune-related conditions in children with and without POE. Design, Setting, and Participants: This retrospective, population-based cohort study used linked administrative health records of all children born in Western Australia between January 1, 2003, and December 31, 2018 (N = 401 462). Exposure: Prenatal exposure to prescription opioids (overall and by trimester), neonatal abstinence syndrome diagnosis, and opioid indication (pain or opioid use disorder [OUD]). Main Outcomes and Measures: The main outcome was hospital admissions and emergency department presentations during which a child was diagnosed with an immune-related condition, including infections, conditions associated with an overactive immune system (eg, asthma, eczema, and allergy and anaphylaxis), and autoimmune diseases diagnosed before age 5 years or June 30, 2020. Data were analyzed between August 30, 2022, and February 27, 2023. Results: Neonates with POE (1656 [0.4%]; mean [SD] gestational age, 37.7 [2.1] weeks; 836 females [50.5%]; 820 males [49.5%]) were more likely to be born preterm, have low birth weight for gestational age, and be coexposed to cigarette smoke compared with nonexposed neonates. Perinatal opioid exposure was associated with an increased risk of perinatal infection (adjusted odds ratio [AOR], 1.62; 95% CI, 1.38-1.90) and eczema and dermatitis (AOR, 11.91; 95% CI, 9.84-14.41) compared with nonexposure. Neonatal abstinence syndrome was also associated with both conditions (AOR, 2.91 [95% CI, 2.36-3.57] and 31.11 [95% CI, 24.64-39.28], respectively). Prenatal opioid exposure was also associated with an increased risk of childhood asthma (adjusted hazard ratio [AHR], 1.44; 95% CI, 1.16-1.79), but not allergies and anaphylaxis. It was also associated with an increased risk of childhood eczema and dermatitis, but only in children with POE from opioids used to treat OUD (AHR, 1.47; 95% CI, 1.08-1.99) rather than pain. In contrast, POE from opioids used for pain was associated with an increased risk of infection (AHR, 1.44; 95% CI, 1.32-1.58), but POE to opioids used to treat OUD was not. Autoimmune conditions were rare and were not observed to be associated with POE. Conclusions and Relevance: In this cohort study, POE was associated with an increased risk of infection, eczema and dermatitis, and asthma, but not allergies and anaphylaxis or autoimmune conditions. These findings highlight the importance of further study of opioid-induced immune changes during pregnancy, the potential impact on long-term health in exposed children, and the mechanisms of opioid-induced immune dysregulation.