Prevalence and Persistence of Prescription Opioid Use Following Hospital Discharge After Childbirth: An Australian Population-Based Cohort Study.

BACKGROUND: Opioid analgesics are used for acute postpartum pain relief but carry risks, including persistent long-term opioid use. Our primary objective was to estimate the prevalence of persistent use following hospital discharge after childbirth. METHODS: We conducted a population-based cohort study of women discharged from public or private hospitals in New South Wales, Australia, between 2012 and 2018 following vaginal birth (VB) or cesarean delivery (CD). We used linked hospitalization and medicine dispensing data to calculate the prevalence of opioid use within 14 days of hospital discharge for childbirth using an external estimate of the total number of hospital admissions for childbirth per year as the denominator. Among women dispensed an opioid postdischarge, we estimated the prevalence of persistent use defined as ≥3 dispensings between 30- and 365-days postdischarge. To calculate the odds of persistent opioid use, we performed a series of logistic regressions each including a single characteristic of interest. Included characteristics were maternal and birth characteristics, maternal medical conditions, prior use of certain medicines, and the initial opioid dispensed following discharge for childbirth. RESULTS: The final cohort comprised of 38,832 women who were dispensed an opioid in the 14 days following discharge after childbirth. Between 2012 and 2018, the prevalence of opioid use was increased following CD (public hospital 16.6%-21.0%; private hospital 9.8%-19.5%) compared with VB (public hospital 1.5%-1.5%; private hospital 1.2%-1.4%) and was higher following discharge from public hospitals compared with private. The most commonly dispensed opioids following discharge for childbirth were oxycodone (44.8%; 95% confidence interval [CI], 44.3-45.3), codeine (42.1%; 95% CI, 41.6-42.6), and tramadol (12.9%; 95% CI, 12.6-13.2). Among women dispensed an opioid, the prevalence of persistent opioid use was 5.4% (95% CI, 5.1-5.6). This prevalence was 11.4% (95% CI, 10.5-12.3) following a VB as compared with 4.3% (95% CI, 4.1-4.6) among those who underwent a CD ( P < .001). Characteristics associated with persistent opioid use included smoking during pregnancy, age <25 years, living in remote areas, discharged from a public hospital, history of opioid use disorder, other substance use disorder, mental health diagnosis, or prior use of prescription opioids, nonopioid analgesics, or benzodiazepines. CONCLUSIONS: The results of this cohort study indicate that Australian women have a higher prevalence of opioid use following CD compared to VB. One in 19 women dispensed an opioid postdischarge used opioids persistently. Careful monitoring of opioid therapy following childbirth is warranted, particularly among women with characteristics we identified as high risk for persistent opioid use.

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.

Comparative effect of varenicline and nicotine patches on preventing repeat cardiovascular events.

OBJECTIVE: To determine the comparative effectiveness of postdischarge use of varenicline versus prescription nicotine replacement therapy (NRT) patches for the prevention of recurrent cardiovascular events and mortality and whether this association differs by sex. METHODS: Our cohort study used routinely collected hospital, pharmaceutical dispensing and mortality data for residents of New South Wales, Australia. We included patients hospitalised for a major cardiovascular event or procedure 2011-2017, who were dispensed varenicline or prescription NRT patches within 90day postdischarge. Exposure was defined using an approach analogous to intention to treat. Using inverse probability of treatment weighting with propensity scores to account for confounding, we estimated adjusted HRs for major cardiovascular events (MACEs), overall and by sex. We fitted an additional model with a sex-treatment interaction term to determine if treatment effects differed between males and females. RESULTS: Our cohort of 844 varenicline users (72% male, 75% <65 years) and 2446 prescription NRT patch users (67% male, 65% <65 years) were followed for a median of 2.93 years and 2.34 years, respectively. After weighting, there was no difference in risk of MACE for varenicline relative to prescription NRT patches (aHR 0.99, 95% CI 0.82 to 1.19). We found no difference (interaction p=0.098) between males (aHR 0.92, 95% CI 0.73 to 1.16) and females (aHR 1.30, 95% CI 0.92 to 1.84), although the effect among females deviated from the null. CONCLUSION: We found no difference between varenicline and prescription NRT patches in the risk of recurrent MACE. These results should be considered when determining the most appropriate choice of smoking cessation pharmacotherapy.

Uptake of prescription smoking cessation pharmacotherapies after hospitalization for major cardiovascular disease.

AIMS: We determined the prevalence of prescription smoking cessation pharmacotherapy (SCP) use after hospitalization for major cardiovascular disease (MCD) among people who smoke and whether this varies by sex. METHODS AND RESULTS: We conducted a population-based cohort study including all people hospitalized in New South Wales, Australia, between July 2013 and December 2018 (2017 for private hospitals) with an MCD diagnosis. For patients who also had a diagnosis of current tobacco use, we used linked pharmaceutical dispensing records to identify prescription SCP dispensings within 90 days post-discharge. We determined the proportion who were dispensed an SCP within 90 days, overall and by type of SCP. We used logistic regression to estimate the odds of females being dispensed an SCP relative to males. Of the 150 758 patients hospitalized for an MCD, 20 162 (13.4%) had a current tobacco use diagnosis, 31% of whom were female. Of these, 11.3% (12.4% of females, 10.9% of males) received prescription SCP within 90 days post-discharge; 3.0% were dispensed varenicline, and 8.3% were dispensed nicotine replacement therapy patches. Females were more likely than males to be dispensed a prescription SCP [odds ratio (OR) 1.16, 95% confidence interval (CI) 1.06-1.27)]; however, this was not maintained after adjusting for potential confounders (adjusted OR 1.04, 95% CI 0.94-1.15). CONCLUSION: Very few females and males who smoke use prescription SCPs after hospitalization for an MCD. The use of varenicline, the SCP with the highest efficacy, was particularly low. This represents a missed opportunity to increase smoking cessation in this high-risk population, thereby reducing their risk of recurrent cardiovascular events.

Population-wide contribution of medically assisted reproductive technologies to overall births in Australia: temporal trends and parental characteristics.

STUDY QUESTION: In a country with supportive funding for medically assisted reproduction (MAR) technologies, what is the proportion of MAR births over-time? SUMMARY ANSWER: In 2017, 6.7% of births were conceived by MAR (4.8% ART and 1.9% ovulation induction (OI)/IUI) with a 55% increase in ART births and a stable contribution from OI/IUI births over the past decade. WHAT IS KNOWN ALREADY: There is considerable global variation in utilization rates of ART despite a similar infertility prevalence worldwide. While the overall contribution of ART to national births is known in many countries because of ART registries, very little is known about the contribution of OI/IUI treatment or the socio-demographic characteristics of the parents. Australia provides supportive public funding for all forms of MAR with no restrictions based on male or female age, and thus provides a unique setting to investigate the contribution of MAR to national births as well as the socio-demographic characteristics of parents across the different types of MAR births. STUDY DESIGN, SIZE, DURATION: This is a novel population-based birth cohort study of 898 084 births using linked ART registry data and administrative data including birth registrations, medical services, pharmaceuticals, hospital admissions and deaths. Birth (a live or still birth of at least one baby of ≥400 g birthweight or ≥20 weeks' gestation) was the unit of analysis in this study. Multiple births were considered as one birth in our analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study included a total of 898 084 births (606 488 mothers) in New South Wales and the Australian Capital Territory, Australia 2009-2017. We calculated the prevalence of all categories of MAR-conceived births over the study period. Generalized estimating equations were used to examine the association between parental characteristics (parent's age, parity, socio-economic status, maternal country of birth, remoteness of mother's dwelling, pre-existing medical conditions, smoking, etc.) and ART and OI/IUI births relative to naturally conceived births. MAIN RESULTS AND THE ROLE OF CHANCE: The proportion of MAR births increased from 5.1% of all births in 2009 to 6.7% in 2017, representing a 30% increase over the decade. The proportion of OI/IUI births remained stable at around 2% of all births, representing 32% of all MAR births. Over the study period, ART births conceived by frozen embryo-transfer increased nearly 3-fold. OI/IUI births conceived using clomiphene citrate decreased by 39%, while OI/IUI births conceived using letrozole increased 56-fold. Overall, there was a 55% increase over the study period in the number of ART-conceived births, rising to 56% of births to mothers aged 40 years and older. In 2017, almost one in six births (17.6%) to mothers aged 40 years and over were conceived using ART treatment. Conversely, the proportion of OI/IUI births was similar across different mother's age groups and remained stable over the study period. ART children, but not OI/IUI children, were more likely to have parents who were socio-economically advantaged compared to naturally conceived children. For example, compared to naturally conceived births, ART births were 16% less likely to be born to mothers who live in the disadvantaged neighbourhoods after accounting for other covariates (adjusted relative risk (aRR): 0.84 [95% CI: 0.81-0.88]). ART- or OI/IUI-conceived children were 25% less likely to be born to immigrant mothers than births after natural conception (aRR: 0.75 [0.74-0.77]). LIMITATIONS, REASONS FOR CAUTION: The social inequalities that we observed between the parents of children born using ART and naturally conceived children may not directly reflect disparities in accessing fertility care for individuals seeking treatment. WIDER IMPLICATIONS OF THE FINDINGS: With the ubiquitous decline in fertility rates around the world and the increasing trend to delay childbearing, this population-based study enhances our understanding of the contribution of different types of MARs to population profiles among births in high-income countries. The parental socio-demographic characteristics of MAR-conceived children differ significantly from naturally conceived children and this highlights the importance of accounting for such differences in studies investigating the health and development of MAR-conceived children. STUDY FUNDING/COMPETING INTEREST(S): This study was funded through Australian National Health and Medical Research Council (NHMRC) grant: APP1127437. G.M.C. is an employee of The University of New South Wales (UNSW) and Director of the National Perinatal Epidemiology and Statistics Unit (NPESU), UNSW. The NPESU manages the Australian and New Zealand Assisted Reproduction Database with funding support from the Fertility Society of Australia and New Zealand. C.V. is an employee of The University of New South Wales (UNSW), Director of Clinical Research of IVFAustralia, Member of the Board of the Fertility Society of Australia and New Zealand, and Member of Research Committee of School of Women's and Children's Health, UNSW. C.V. reports grants from Australian National Health and Medical Research Council (NHMRC), and Merck KGaA. C.V. reports consulting fees, and payment or honoraria for lectures, presentations, speakers, bureaus, manuscript, writing or educational events or attending meeting or travel from Merck, Merck Sparpe & Dohme, Ferring, Gedon-Richter and Besins outside this submitted work. C.V. reported stock or stock options from Virtus Health Limited outside this submitted work. R.J.N. is an employee of The University of Adelaide, and Chair DSMC for natural therapies trial of The University of Hong Kong. R.J.N. reports grants from NHMRC. R.J.N. reports lecture fees and support for attending or travelling for lecture from Merck Serono which is outside this submitted work. L.R.J. is an employee of The UNSW and Foundation Director of the Centre for Big Data Research in Health at UNSW Sydney. L.R.J. reports grants from NHMRC. The other co-authors have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Tobacco use during pregnancy.

The use of tobacco during pregnancy is the leading preventable cause of pregnancy complications and adverse birth outcomes. In high-income countries, around one in 10 pregnant women smokes tobacco, while smokeless tobacco is the primary form of tobacco used in many low- and middle-income countries. Although the risk of tobacco-related harms can be reduced substantially if mothers cease smoking in the first trimester of pregnancy, the proportion of women who successfully quit smoking during pregnancy remains modest. Psychosocial interventions are first-line treatment, with some high-quality evidence showing that counselling is effective in promoting smoking cessation among pregnant women. There is insufficient evidence regarding the efficacy and safety of smoking cessation pharmacotherapies when used during pregnancy, although in some countries nicotine replacement therapy is recommended for pregnant women who have been unable to quit without pharmacological assistance. E-cigarettes are increasingly being used as a smoking cessation aid in the general population of smokers, but more research is needed to determine if e-cigarettes are a safe and effective treatment option for pregnant women.

Comparison of Cardiovascular Safety for Smoking Cessation Pharmacotherapies in a Population-Based Cohort in Australia.

Importance: Although concerns exist regarding a potential increased risk of cardiovascular events for smoking cessation pharmacotherapies, there is general consensus that any increased risk associated with their use would be outweighed by the benefits of smoking cessation; thus, clinical guidelines recommend that such pharmacotherapies be offered to everyone who wants to quit smoking. In the interest of minimizing risk to patients, prescribers need evidence indicating how these pharmacotherapies compare with one another in terms of cardiovascular safety. Objective: To compare the risk of major adverse cardiovascular events (MACE) among individuals initiating varenicline, nicotine replacement therapy (NRT) patches, or bupropion. Design, Setting, and Participants: This retrospective, population-based cohort study using linked pharmaceutical dispensing, hospital admissions, and death data was conducted in New South Wales, Australia. Participants included adults who were dispensed a prescription smoking cessation pharmacotherapy between 2008 and 2015 or between 2011 and 2015, depending on the availability of the pharmacotherapies being compared. Pairwise comparisons were conducted for risk of MACE among 122 932 varenicline vs 92 148 NRT initiators; 342 064 varenicline vs 10 457 bupropion initiators; and 102 817 NRT vs 6056 bupropion initiators. Exposure: First course of the smoking cessation pharmacotherapy of interest. Main Outcomes and Measures: The primary outcome was MACE, defined as a composite of acute coronary syndrome, stroke, and cardiovascular death. Secondary outcomes were the individual components of MACE. Inverse probability of treatment weighting with high-dimensional propensity scores was used to account for potential confounding. Cox proportional hazards regression models with robust variance were used to estimate hazard ratios (HRs) and 95% CIs. Data were analyzed January 24, 2019, to September 1, 2021. Results: The mean (SD) age of included individuals ranged from 41.9 (14.2) to 49.8 (14.9) years, and the proportion of women ranged from 42.8% (52 702 of 123 128) to 52.2% (53 693 of 102 913). The comparison of 122 932 varenicline initiators and 92 148 NRT patch initiators showed no difference in the risk of MACE (HR, 0.87; 95% CI, 0.72-1.07) nor in the risk of the secondary outcomes of acute coronary syndrome (HR, 0.96; 95% CI, 0.76-1.21) and stroke (HR, 0.72; 95% CI, 0.45-1.14). However, decreased risk of cardiovascular death was found among varenicline initiators (HR, 0.49; 95% CI, 0.30-0.79). The results of comparisons involving bupropion were inconclusive owing to wide confidence intervals (eg, risk of MACE: 342 064 varenicline vs 10 457 bupropion initiators, HR, 0.87 [95% CI, 0.53-1.41]; 102 817 NRT patch vs 6056 bupropion initiators, HR, 0.79 [95% CI, 0.39-1.62]). Conclusions and Relevance: The finding of this cohort study that varenicline and NRT patch use have similar risk of MACE suggests that varenicline, the most efficacious smoking cessation pharmacotherapy, may be prescribed instead of NRT patches without increasing risk of major cardiovascular events. Further large-scale studies of the cardiovascular safety of varenicline and NRT relative to bupropion are needed.

The diagnostic indicators of gestational diabetes mellitus from second trimester to birth: a systematic review.

BACKGROUND: Gestational diabetes mellitus (GDM) is glucose intolerance first recognised during pregnancy. Both modalities and thresholds of the GDM diagnostic test, the Oral Glucose Tolerance Test (OGTT), have varied widely over time and among countries. Additionally, OGTT limitations include inconsistency, poor patient tolerability, and questionable diagnostic reliability. Many biological parameters have been reported to be modified by GDM and could potentially be used as diagnostic indicators. This study aimed to 1) systematically explore biomarkers reported in the literature as differentiating GDM from healthy pregnancies 2) screen those indicators assessed against OGTT to propose OGTT alternatives. MAIN BODY: A systematic review of GDM diagnostic indicators was performed according to PRISMA guidelines (PROSPERO registration CRD42020145499). Inclusion criteria were full-text, comprehensible English-language articles published January 2009-January 2021, where a biomarker (from blood, ultrasound, amniotic fluid, placenta) was compared between GDM and normal glucose tolerance (NGT) women from the second trimester onward to immediately postpartum. GDM diagnostic method had to be clearly specified, and the number of patients per study higher than 30 in total or 15 per group. Results were synthesised by biomarkers. RESULTS: Of 13,133 studies identified in initial screening, 174 studies (135,801 participants) were included. One hundred and twenty-nine studies described blood analytes, one amniotic fluid analytes, 27 ultrasound features, 17 post-natal features. Among the biomarkers evaluated in exploratory studies, Adiponectin, AFABP, Betatrophin, CRP, Cystatin-C, Delta-Neutrophil Index, GGT, TNF-A were those demonstrating statistically and clinically significant differences in substantial cohorts of patients (> 500). Regarding biomarkers assessed versus OGTT (i.e. potential OGTT alternatives) most promising were Leptin > 48.5 ng/ml, Ficolin3/adiponectin ratio ≥ 1.06, Chemerin/FABP > 0.71, and Ultrasound Gestational Diabetes Score > 4. These all demonstrated sensitivity and specificity > 80% in adequate sample sizes (> / = 100). CONCLUSIONS: Numerous biomarkers may differentiate GDM from normoglycaemic pregnancy. Given the limitations of the OGTT and the lack of a gold standard for GDM diagnosis, advanced phase studies are needed to triangulate the most promising biomarkers. Further studies are also recommended to assess the sensitivity and specificity of promising biomarkers not yet assessed against OGTT. TRIAL REGISTRATION: PROSPERO registration number CRD42020145499.

The Comparative Effectiveness of Varenicline and Nicotine Patches for Smoking Abstinence During Pregnancy: Evidence From a Population-based Cohort Study.

INTRODUCTION: In the general population, varenicline is consistently shown to be more efficacious for smoking cessation than nicotine replacement therapy (NRT). Current clinical guidelines for the management of smoking during pregnancy recommend against the use of varenicline, whilst supporting the use of NRT. However, little is known about the comparative effectiveness of these smoking cessation therapies among pregnant women. AIMS AND METHODS: Routinely-collected records of all births in two Australian States during 2011 and 2012 were used to create a population-based cohort of women who smoked during the first half of pregnancy. Pharmaceutical dispensing data were used to identify varenicline and nicotine patch dispensings in the first half of pregnancy. Propensity score matching was used to account for the potentially different distribution of confounding factors between the treatment groups. The outcome was defined as smoking abstinence during the second half of pregnancy. RESULTS: After propensity score-matching, our cohort comprised 60 women who used varenicline and 60 who used nicotine patches during the first half of pregnancy. More varenicline users (33.3%, 95% CI: 21.7%-46.7%) quit smoking than nicotine patch users (13.3%, 95% CI: 5.9%-24.6%). The adjusted rate difference was 24.2% (95% CI: 10.2%-38.2%) and the adjusted relative risk was 2.8 (95% CI: 1.4-5.7). CONCLUSIONS: Varenicline was almost three times more effective than nicotine patches in assisting pregnant women to quit smoking. Further studies are needed to corroborate our results. Together with data on the safety of varenicline during pregnancy, evidence regarding the relative benefit of varenicline and NRT during pregnancy important for informing clinical decisions for pregnant smokers. IMPLICATIONS: This study is the first to measure the comparative effectiveness of varenicline and nicotine patches during pregnancy - women using varenicline were almost three times as likely to quit smoking than those using nicotine patches. This study addressed a clinically important question using an observational study, noting that there is an absence of evidence from randomized controlled trials because of the ethical issues associated with including pregnant women in clinical trials of medicines of unknown safety.

Exposure to Tobacco, Environmental Tobacco Smoke and Nicotine in Pregnancy: A Pragmatic Overview of Reviews of Maternal and Child Outcomes, Effectiveness of Interventions and Barriers and Facilitators to Quitting.

The aim of this review of reviews was to collate the latest evidence from systematic reviews about the maternal and child health outcomes of being exposed to tobacco and nicotine during pregnancy; the effectiveness of interventions designed to reduce these exposures, and barriers to and facilitators of smoking cessation during pregnancy. Two databases were searched to obtain systematic reviews published from 2010 to 2019. Pertinent data from 76 articles were summarized using a narrative synthesis (PROSPERO reference: CRD42018085896). Exposure to smoke or tobacco in other forms during pregnancy is associated with an increased risk of obstetric complications and adverse health outcomes for children exposed in-utero. Counselling interventions are modestly effective, while incentive-based interventions appear to substantially increase smoking cessation. Nicotine replacement therapy is effective during pregnancy but the evidence is not conclusive. Predictors and barriers to smoking cessation in pregnancy are also discussed. Smoking during pregnancy poses substantial risk to mother's and child's health. Psychosocial interventions and nicotine replacement therapy (NRT) appear to be effective in helping pregnant women quit smoking. Barriers to smoking cessation must be identified and steps taken to eradicate them in order to reduce smoking among pregnant women. More research is needed on smoking cessation medications and e-cigarettes.

Use of smoking cessation pharmacotherapies during pregnancy is not associated with increased risk of adverse pregnancy outcomes: a population-based cohort study.

BACKGROUND: Varenicline, bupropion and nicotine replacement therapy (NRT) are three effective pharmacotherapies for smoking cessation, but data about their safety in pregnancy are limited. We assessed the risk of adverse perinatal outcomes and major congenital anomalies associated with the use of these therapies in pregnancy in Australia. METHODS: Perinatal data for 1,017,731 deliveries (2004 to 2012) in New South Wales and Western Australia were linked to pharmaceutical dispensing, hospital admission and death records. We identified 97,875 women who smoked during pregnancy; of those, 233, 330 and 1057 were exposed to bupropion, NRT and varenicline in pregnancy, respectively. Propensity scores were used to match exposed women to those who were unexposed to any smoking therapy (1:10 ratio). Propensity scores and gestational age at exposure were used to match varenicline-exposed to NRT-exposed women (1:1 ratio). Time-dependent Cox proportional hazards models estimated hazard ratios (HR) with 95% confidence intervals (95% CI) for any adverse perinatal event (a composite of 10 unfavourable maternal and neonatal outcomes) and any major congenital anomaly. RESULTS: The risk of any adverse perinatal event was not significantly different between bupropion-exposed and unexposed women (39.2% versus 39.3%, HR 0.93, 95% CI 0.73-1.19) and between NRT-exposed and unexposed women (44.8% vs 46.3%, HR 1.02, 95% CI 0.84-1.23), but it was significantly lower in women exposed to varenicline (36.9% vs 40.1%, HR 0.86, 95% CI 0.77-0.97). Varenicline-exposed infants were less likely than unexposed infants to be born premature (6.5% vs 8.9%, HR 0.72, 95% CI 0.56-0.92), be small for gestational age (11.4% vs 15.4%, HR 0.68, 95% CI 0.56-0.83) and have severe neonatal complications (6.6% vs 8.2%, HR 0.74, 95% CI 0.57-0.96). Among infants exposed to varenicline in the first trimester, 2.9% had a major congenital anomaly (3.5% in unexposed infants, HR 0.91, 95% CI 0.72-1.15). Varenicline-exposed women were less likely than NRT-exposed women to have an adverse perinatal event (38.7% vs 51.4%, HR 0.58, 95% CI 0.33-1.05). CONCLUSIONS: Pregnancy exposure to smoking cessation pharmacotherapies does not appear to be associated with an increased risk of adverse birth outcomes. Lower risk of adverse birth outcomes in varenicline-exposed pregnancies is inconsistent with recommendations that NRT be used in preference to varenicline.

Health-care providers' concern regarding smoking cessation pharmacotherapies during pregnancy: Calls to a teratology information service.

INTRODUCTION AND AIMS: Few smokers use smoking cessation pharmacotherapies during pregnancy. It is hypothesised that health-care providers' reluctance due to safety concerns contributes to their low use. This study examined the extent of providers' concern regarding smoking cessation pharmacotherapies, relative to other medications in the same and other pregnancy risk categories. Calls made to a teratology information service (MotherSafe, Australia) were taken as a proxy indicator of concern regarding safety during pregnancy. DESIGN AND METHODS: The primary exposure discussed in 66 687 calls made to MotherSafe between 2001 and 2016 was categorised as nicotine replacement therapy (NRT), bupropion, varenicline or category A (low risk), B1, B2, B3, C, D or X (teratogenic). Separate logistic regression models estimated the odds that calls regarding pharmacotherapies were from providers, relative to medications in the same and other risk categories. Models adjusted for caller remoteness and socio-economic status. RESULTS: Calls regarding bupropion were more likely to be made by providers than calls regarding other medications in its corresponding risk category [B2, adjusted odds ratio (aOR): 2.77, 95% confidence interval (CI) 1.17, 6.59]. Calls about varenicline were also more likely to be from providers than calls regarding other category B3 medications (aOR 95% CI 2.33:1.30, 4.17). Calls regarding NRT were not more or less likely to be from providers than calls regarding other category D medications. DISCUSSION AND CONCLUSIONS: Providers were more concerned about bupropion and varenicline than other medications within the same pregnancy risk categories. As this overestimation of risk may limit cessation pharmacotherapy use during pregnancy, research investigating strategies for correcting this imbalance is warranted.

Algorithm for resolving discrepancies between claims for smoking cessation pharmacotherapies during pregnancy and smoking status in delivery records: The impact on estimates of utilisation.

BACKGROUND: The linkage of routine data collections are valuable for population-based evaluation of smoking cessation pharmacotherapy in pregnancy where little is known about the utilisation or safety of these pharmacotherapies antenatally. The use of routine data collections to study smoking cessation pharmacotherapy is limited by disparities among data sources. This study developed an algorithm to resolve disparity between the evidence of pharmacotherapy utilisation for smoking cessation and the recording of smoking in pregnancy, examined its face validity and assessed the implications on estimates of smoking cessation pharmacotherapy utilisation. METHODS: Perinatal records (n = 1,098,203) of women who gave birth in the Australian States of Western Australia and New South Wales (2004-2012) were linked to hospital admissions and pharmaceutical dispensing data. An algorithm, based on dispensing information about the type of smoking therapy, timing and quantity of supply reclassified certain groups of women as smoking during pregnancy. Face validity of the algorithm was tested by examining the distribution of factors associated with inaccurate recording of smoking status among women that the algorithm classified as misreporting smoking in pregnancy. Rate of utilisation among smokers, according to original and reclassified smoking status, was measured, to demonstrate the utility of the algorithm. RESULTS: Smoking cessation pharmacotherapy were dispensed to 2184 women during pregnancy, of those 1013 women were originally recorded as non-smoking as per perinatal and hospital data. Application of the algorithm reclassified 730 women as smoking during pregnancy. The algorithm satisfied the test of face validity-the expected demographic factors of marriage, private hospital delivery and higher socioeconomic status, were more common in women whom the algorithm identified as misreporting their smoking status. Application of the algorithm resulted in smoking cessation pharmacotherapy utilisation estimates ranging from 2.3-3.6% of all pregnancies. CONCLUSION: Researchers can use the algorithm presented herein to improve the identification of smoking among women who use cessation pharmacotherapies during pregnancy. Improved identification can improve the validity of safety analyses of smoking cessation pharmacotherapy-providing clinicians with valuable evidence to use when counselling women on the role of pharmacotherapy for smoking cessation during pregnancy.

Tobacco policy reform and population-wide antismoking activities in Australia: the impact on smoking during pregnancy.

INTRODUCTION: This study examined the impact of antismoking activities targeting the general population and an advertising campaign targeting smoking during pregnancy on the prevalence of smoking during pregnancy in New South Wales (NSW), Australia. METHODS: Monthly prevalence of smoking during pregnancy was calculated using linked health records for all pregnancies resulting in a birth (800 619) in NSW from 2003 to 2011. Segmented regression of interrupted time series data assessed the effects of the extension of the ban on smoking in enclosed public places to include licensed premises (evaluated in combination with the mandating of graphic warnings on cigarette packs), television advertisements targeting smoking in the general population, print and online magazine advertisements targeting smoking during pregnancy and increased tobacco tax. Analyses were conducted for all pregnancies, and for the population stratified by maternal age, parity and socioeconomic status. Further analyses adjusted for the effect of the Baby Bonus maternity payment. RESULTS: Prevalence of smoking during pregnancy decreased from 2003 to 2011 overall (0.39% per month), and for all strata examined. For pregnancies overall, none of the evaluated initiatives was associated with a change in the trend of smoking during pregnancy. Significant changes associated with increased tobacco tax and the extension of the smoking ban (in combination with graphic warnings) were found in some strata. CONCLUSIONS: The declining prevalence of smoking during pregnancy between 2003 and 2011, while encouraging, does not appear to be directly related to general population antismoking activities or a pregnancy-specific campaign undertaken in this period.

Data cleaning and management protocols for linked perinatal research data: a good practice example from the Smoking MUMS (Maternal Use of Medications and Safety) Study.

BACKGROUND: Data cleaning is an important quality assurance in data linkage research studies. This paper presents the data cleaning and preparation process for a large-scale cross-jurisdictional Australian study (the Smoking MUMS Study) to evaluate the utilisation and safety of smoking cessation pharmacotherapies during pregnancy. METHODS: Perinatal records for all deliveries (2003-2012) in the States of New South Wales (NSW) and Western Australia were linked to State-based data collections including hospital separation, emergency department and death data (mothers and babies) and congenital defect notifications (babies in NSW) by State-based data linkage units. A national data linkage unit linked pharmaceutical dispensing data for the mothers. All linkages were probabilistic. Twenty two steps assessed the uniqueness of records and consistency of items within and across data sources, resolved discrepancies in the linkages between units, and identified women having records in both States. RESULTS: State-based linkages yielded a cohort of 783,471 mothers and 1,232,440 babies. Likely false positive links relating to 3703 mothers were identified. Corrections of baby's date of birth and age, and parity were made for 43,578 records while 1996 records were flagged as duplicates. Checks for the uniqueness of the matches between State and national linkages detected 3404 ID clusters, suggestive of missed links in the State linkages, and identified 1986 women who had records in both States. CONCLUSIONS: Analysis of content data can identify inaccurate links that cannot be detected by data linkage units that have access to personal identifiers only. Perinatal researchers are encouraged to adopt the methods presented to ensure quality and consistency among studies using linked administrative data.

Access to Subsidized Smoking Cessation Medications by Australian Smokers Aged 45 Years and Older: A Population-Based Cohort Study.

INTRODUCTION: The principal aim of this study was to assess the accessibility of subsidized cessation medications to socioeconomically disadvantaged smokers, including smokers living in regional and remote communities. METHODS: Analyses used baseline questionnaire and linked Pharmaceutical Benefits Scheme data for 18 686 regular smokers participating in the 45 and Up Study, a large-scale Australian cohort study of people aged 45 years and older. Participants who were dispensed nicotine replacement therapy, varenicline, or bupropion were identified from the Pharmaceutical Benefits Scheme data, which provide an essentially complete record of participants' access to subsidized pharmaceuticals. Associations between the supply of each pharmacotherapy and a range of sociodemographic and health-related variables were evaluated using multiple logistic regression. RESULTS: The odds that participants were supplied with a cessation medication declined markedly with increasing age for participants older than 60 years and were substantially higher for participants who smoked 20 or more cigarettes/day than for participants who smoked fewer than 10 cigarettes/day. Participants with no formal qualification and those residing in socioeconomically disadvantaged areas had higher odds of receiving nicotine replacement therapy or varenicline than university-educated participants and participants living in the least disadvantaged areas. There was no evidence that participants residing in regional and remote communities had lower odds of receiving a cessation medication than participants residing in major cities. CONCLUSIONS: Older Australian smokers' access to cessation pharmacotherapies is determined predominantly by age and daily cigarette consumption and does not appear to be limited by educational achievement, socioeconomic disadvantage, or remoteness. IMPLICATIONS: Promoting the use of cessation medications is a principal measure proposed to achieve Australia's National Tobacco Strategy 2012-2018 goal of reducing cigarette consumption among socioeconomically disadvantaged smokers. The results of this large-scale cohort study indicate that access to cessation pharmacotherapies is determined primarily by age and daily cigarette consumption, and is not limited by socioeconomic circumstances, providing some reassurance that existing government subsidies are sufficient to ensure that pharmaceutical aids are accessible to all Australian smokers.

Linking birth records to hospital admission records enhances the identification of women who smoke during pregnancy.

OBJECTIVE: Birth records and hospital admission records are valuable for research on maternal smoking, but individually are known to under-estimate smokers. This study investigated the extent to which combining data from these records enhances the identification of pregnant smokers, and whether this affects research findings such as estimates of maternal smoking prevalence and risk of adverse pregnancy outcomes associated with smoking. METHODS: A total of 846,039 birth records in New South Wales, Australia, (2001-2010) were linked to hospital admission records (delivery and antenatal). Algorithm 1 combined data from birth and delivery admission records, whereas algorithm 2 combined data from birth record, delivery and antenatal admission records. Associations between smoking and placental abruption, preterm birth, stillbirth, and low birthweight were assessed using multivariable logistic regression. RESULTS: Algorithm 1 identified 127,612 smokers (smoking prevalence 15.1%), which was a 9.6% and 54.6% increase over the unenhanced identification from birth records alone (prevalence 13.8%), and delivery admission records alone (prevalence 9.8%), respectively. Algorithm 2 identified a further 2,408 smokers from antenatal admission records. The enhancement varied by maternal socio-demographic characteristics (age, marital status, country of birth, socioeconomic status); obstetric factors (multi-fetal pregnancy, diabetes, hypertension); and maternity hospital. Enhanced and unenhanced identification methods yielded similar odds ratios for placental abruption, preterm birth, stillbirth and low birthweight. CONCLUSIONS: Use of linked data improved the identification of pregnant smokers. Studies relying on a single data source should adjust for the under-ascertainment of smokers among certain obstetric populations.

Risk adjustment for smoking identified through tobacco use diagnoses in hospital data: a validation study.

Adjustment for the differing risk profiles of patients is essential to the use of administrative hospital data for epidemiological research. Smoking is an important factor to include in such adjustments, but the accuracy of the diagnostic codes denoting smoking in hospital records is unknown. The aims of this study were to measure the validity of current smoking and ever smoked status identified from diagnoses in hospital records using a range of algorithms, relative to self-reported smoking status; and to examine whether the misclassification of smoking identified through hospital data is differential or non-differential with respect to common exposures and outcomes. Data from the baseline questionnaire of the 45 and Up Study, completed by 267,153 residents of New South Wales (NSW), Australia, aged 45 years and older, were linked to the NSW Admitted Patient Data Collection. Patients who had been admitted to hospital for an overnight stay between 1 July 2005 and the date of completion of the questionnaire (1 January 2006 to 2 March 2009) were included. Smokers were identified by applying a range of algorithms to hospital admission histories, and compared against self-reported smoking in the questionnaire ('gold standard'). Sensitivities for current smoking ranged from 59% to 84%, while specificities were 94% to 98%. Sensitivities for ever smoked ranged from 45% to 74% and specificities were 93% to 97%. For the majority of algorithms, sensitivities and/or specificities differed significantly according to principal diagnosis, number of comorbidities, socioeconomic status, residential remoteness, Indigenous status, 28 day readmission and 365 day mortality. The identification of smoking through diagnoses in hospital data results in differential misclassification. Risk adjustment based on smoking identified from these data will yield potentially misleading results. Systematic capture of information about smoking in hospital records using a mandatory item would increase the utility of administrative data for epidemiological research.

The Smoking MUMS (Maternal Use of Medications and Safety) Study: protocol for a population-based cohort study using linked administrative data.

INTRODUCTION: Approximately 14% of Australian women smoke during pregnancy. Although the risk of adverse outcomes is reduced by smoking cessation, less than 35% of Australian women quit smoking spontaneously during pregnancy. Evidence for the efficacy of bupropion, varenicline or nicotine replacement therapy as smoking cessation aids in the non-pregnant population suggest that pharmacotherapy for smoking cessation is worth exploring in women of childbearing age. Currently, little is known about the utilisation, effectiveness and safety of pharmacotherapies for smoking cessation during pregnancy; neither the extent to which they are used prior to pregnancy nor whether their use has changed in response to related policy reforms. The Smoking MUMS (Maternal Use of Medications and Safety) Study will explore these issues using linked person-level data for a population-based cohort of Australian mothers. METHODS AND ANALYSIS: The cohort will be assembled by linking administrative health records for all women who gave birth in New South Wales or Western Australia since 2003 and their children, including records relating to childbirth, use of pharmaceuticals, hospital admissions, emergency department presentations and deaths. These longitudinal linked data will be used to identify utilisation of smoking cessation pharmacotherapies during and between pregnancies and to explore the associated smoking cessation rates and maternal and child health outcomes. Subgroup and temporal analyses will identify potential differences between population groups including indigenous mothers and social security recipients and track changes associated with policy reforms that have made alternative smoking cessation pharmacotherapies available. ETHICS AND DISSEMINATION: Ethical approval has been obtained for this study. To enhance the translation of the project's findings into policy and practice, policy and clinical stakeholders will be engaged through a reference group and a policy forum will be held. Outputs from the project will include scientific papers and summary reports designed for policy audiences.

Benzodiazepine use among heroin users: baseline use, current use and clinical outcome.

INTRODUCTION AND AIMS: Benzodiazepine use is associated with elevated levels of harm. The current study aimed to ascertain the long-term nature of the relationship between benzodiazepine use and clinical profile among heroin users. DESIGN AND METHODS: Longitudinal cohort, with follow-up at 3, 12, 24 and 36 months. Participants were 615 heroin users recruited for the Australian Treatment Outcome Study. RESULTS: At baseline, current benzodiazepine users were more likely to be committing crime, had poorer psychological health and poorer physical health. Baseline benzodiazepine use was not associated with the likelihood across follow-up of heroin use (P = 0.44), committing crime (P = 0.17), poorer psychological health (P = 0.31) or poorer physical health (P = 0.48). Current benzodiazepine use was, however, associated with a greater likelihood of concurrent heroin use (OR 2.77), crime (OR 2.04), poorer psychological health (beta = -4.47) and poorer physical health (beta = -2.33). DISCUSSION AND CONCLUSIONS: Clinicians should be aware that reductions in benzodiazepine use are associated with reductions in harm, and that baseline benzodiazepine status does not equate to poor long-term outcome.