Low Risk of Cardiac Complications during Long-Term Follow-Up of Opioid Dependence.

OBJECTIVES: To prospectively assess rates of QT prolongation, arrhythmia, syncope, and sudden cardiac death (SCD) in a cohort of people with heroin dependence. METHODS: To estimate rates of QT prolongation, arrhythmia, and syncope, a subcohort (n = 130) from the Australian Treatment Outcomes Study, a prospective longitudinal cohort study of 615 people with heroin dependence, underwent medical history, venepuncture, and ECG at the 18- to 20-year follow-up.To estimate rates of SCD, probabilistic matching for the entire cohort was undertaken with the Australian Institute of Health and Welfare National Death Index. Deaths were classified into suicide, accidental overdose, trauma, unknown, and disease, which were then further subclassified by probability of SCD. SCD rate was the number of possible or probable SCDs divided by total patient years from the cohort. RESULTS: From the subcohort, 4 participants (3%) met the criteria for QT prolongation; 3 were prescribed methadone. Seven participants (5%) reported history of arrhythmia, including 2 transferred from methadone to buprenorphine. Thirty participants (23%) reported a previous syncopal event-14 diagnosed as nonarrhythmic syncope and 13 not investigated. In the previous 12 months, 66 participants (51%) reported heroin use; 55 participants (42%) were prescribed methadone. No participant had QTc greater than 500 milliseconds.There were 3 possible SCDs, translating to an estimated SCD rate of 0.29 (CI: 0.05, 0.8) events per 1000 patient years. More cohort members died of overdose (n = 50), suicide (n = 11), and hepatitis C (n = 4). CONCLUSIONS: Low rates of QT prolongation, arrhythmia, syncope, and SCD in the cohort despite high rates of heroin use and methadone treatment.

Topiramate Versus Naltrexone for Alcohol Use Disorder: A Genotype-Stratified Double-Blind Randomized Controlled Trial.

OBJECTIVE: There have been no well-controlled and well-powered comparative trials of topiramate with other pharmacotherapies for alcohol use disorder (AUD), such as naltrexone. Moreover, the literature is mixed on the effects of two polymorphisms-rs2832407 (in GRIK1) and rs1799971 (in OPRM1)-on response to topiramate and naltrexone, respectively. The authors sought to examine the comparative effectiveness of topiramate and naltrexone in improving outcomes in AUD and to examine the role of the rs2832407 and rs1799971 polymorphisms, respectively, on response to these medications. METHODS: In a 12-week, double-blind, placebo-controlled, randomized, multisite, genotype-stratified (rs2832407 and rs1799971) clinical trial comparing topiramate and naltrexone in treating AUD, 147 patients with AUD were randomly assigned to treatment with topiramate or naltrexone, stratified by genotype (rs2832407*CC and *AC/AA genotypes and rs1799971*AA and *AG/GG genotypes). The predefined primary outcome was number of heavy drinking days per week. Predefined secondary outcomes included standard drinks per drinking day per week, body mass index (BMI), craving, markers of liver injury, mood, and adverse events. RESULTS: For the number of heavy drinking days per week, there was a near-significant time-by-treatment interaction. For the number of standard drinks per drinking day per week, there was a significant time-by-treatment interaction, which favored topiramate. There were significant time-by-treatment effects, with greater reductions observed with topiramate than naltrexone for BMI, craving, and gamma-glutamyltransferase level. Withdrawal due to side effects occurred in 8% and 5% of the topiramate and naltrexone groups, respectively. Neither polymorphism showed an effect on treatment response. CONCLUSIONS: Topiramate is at least as effective and safe as the first-line medication, naltrexone, in reducing heavy alcohol consumption, and superior in reducing some clinical outcomes. Neither rs2832407 nor rs1799971 had effects on topiramate and naltrexone treatments, respectively.

N acetylcysteine in the treatment of alcohol use disorder: a randomized, double-blind, placebo-controlled trial.

N-acetyl cysteine (NAC) is a potent antioxidant that modulates glutamatergic signalling which is thought to play a role in alcohol use disorder (AUD). There have been no clinical trials investigating NAC for AUD. We aimed to conduct a 28 day double-blind, placebo-controlled (PL) randomized trial of NAC in the treatment of AUD (NCT03879759). A total of 42 participants with AUD (56% alcohol-related liver disease) were randomized to receive placebo or NAC 2400 mg/day. Feasibility outcomes included treatment retention and adverse events. Primary clinical outcomes included alcohol consumption (heavy drinking days, standard drinks per drinking day). Secondary clinical outcome measures included craving, liver tests, and psychological outcomes. There were no significant differences in overall retention between treatment groups (χ2(1) = 0.14, P = 0.71: 86% vs 76% for placebo and NAC, respectively). The most commonly reported adverse event in NAC-treated individuals included headache (14%). For standard drinks per drinking day, there was a significant overall effect of time (F = 9.18, P < 0.001), no significant effect of treatment (F = 0.75, P = 0.79), and a significant time x treatment (NAC vs PL) effect (F = 2.73, P < 0.05). For number of heavy drinks per day, there was a significant overall effect of time (F = 3.16, P < 0.05) but no significant effect of treatment or time x treatment (P = 0.17). There were no significant NAC vs PL effects on secondary clinical outcome measures. In the first trial of NAC for the management of AUD, NAC appears to be feasible and safe. Although there was a significant effect of NAC vs placebo on some alcohol measures such as drinks per drinking day, there does appear to be a variable pattern of effect across time suggesting that a larger trial incorporating a longer treatment duration is now required to determine efficacy.

Patterns and Predictors of Heroin Use, Remission, and Psychiatric Health Among People with Heroin Dependence: Key Findings from the 18-20-Year Follow-Up of the Australian Treatment Outcome Study (ATOS).

This study aimed to investigate the long-term patterns and predictors of heroin use, dependence, and psychiatric health over 18-20 years among a cohort of Australians with heroin dependence, using a prospective longitudinal cohort study conducted in Sydney, Australia. The original cohort consisted of 615 participants, who were followed up at 3 months and 1, 2, 3, 11, and 18-20 years post-baseline; 401 (65.2%) were re-interviewed at 18-20 years. The Australian Treatment Outcome Study structured interview with established psychometric properties was administered to participants at each follow-up, addressing demographics, treatment and drug use history, overdose, crime, and physical and mental health. Overall, 96.7% completed at least one follow-up interview. At 18-20 years, 109 participants (17.7%) were deceased. Past-month heroin use decreased significantly over the study period (from 98.7 to 24.4%), with one in four using heroin at 18-20 years. Just under half were receiving treatment. Reductions in heroin use were accompanied by reductions in heroin dependence, other substance use, needle sharing, injection-related health, overdose, crime, and improvements in general physical and mental health. Major depression and borderline personality disorder (BPD) were consistently associated with poorer outcome. At 18-20 years, there is strong evidence that clinically significant levels of improvement can be maintained over the long term. The mortality rate over 18-20 years was devastating, with over one in six participants deceased. More sustained and targeted efforts are needed in relation to major depression and BPD to ensure evidence-based treatments are delivered to people with heroin dependence. Supplementary Information: The online version contains supplementary material available at 10.1007/s11469-022-01006-6.

Transferring patients from high-dose methadone to buprenorphine: A retrospective case series.

OBJECTIVE: Transferring from methadone to buprenorphine can be difficult, -particularly at higher methadone doses. Precipitated withdrawal (PW) and severe opioid withdrawal can compromise transfers and limited data guide high-dose transfers. This study describes processes and outcomes of transfers to buprenorphine from methadone. DESIGN: A retrospective case series of transfers from methadone to buprenorphine. SETTING: Two elective, voluntary, specialized in-patient drug and alcohol facilities in Sydney, New South Wales, Australia. PARTICIPANTS: All admissions between July 1, 2015 and April 30, 2019 were screened using routinely collected coding data. The medical record was reviewed to identify subjects meeting the inclusion criteria of daily methadone use for at least 1 month, age > 18, and a treatment plan that included transfer from methadone to buprenorphine. Data were extracted on methadone dose, transfer medications, time to buprenorphine initiation, and transfer outcome. INTERVENTIONS: Subjects were transferred via two methods: morphine bridged and nonbridged. MAIN OUTCOME MEASURE: The primary outcome measure was successful transition to buprenorphine. RESULTS: Seventy-one subjects met inclusion criteria, of whom 62 initiated buprenorphine and 53 discharged on buprenorphine. Longer delay to buprenorphine initiation was seen with higher methadone doses. The highest daily methadone dose in subjects completing transfer was 180 mg. Outcomes with morphine bridging, using a steady state methadone: morphine ratio of 1:4, were similar to direct transfer. Only one subject discontinued buprenorphine because of PW. CONCLUSIONS: Transfer from high doses of methadone to buprenorphine can be achieved with high success rates in the in-patient setting.

Drugs in secondary stroke prevention.

After an ischaemic stroke or transient ischaemic attack, patients have a high risk of having another stroke. Secondary stroke prevention includes antiplatelet therapy, statins and antihypertensives Aspirin, clopidogrel, or a combination of aspirin with dipyridamole are first-line options for secondary stroke prevention in the absence of atrial fibrillation Dual antiplatelet therapy has a benefit in the first three weeks after stroke, but patients should change to a single antiplatelet drug after this time Anticoagulants are indicated if the patient has atrial fibrillation. Avoid combinations of anticoagulants and antiplatelet drugs Patients should be started on statins after an ischaemic stroke. High doses are recommended even if cholesterol concentrations are normal Antihypertensive drugs are recommended for all patients with systolic blood pressures greater than 140/90 mmHg. ACE inhibitors, calcium channel blockers and diuretics are first-line options.

Australian treatment outcome study: protocol for the 18-20-year follow-up of a prospective longitudinal cohort examining the natural history of heroin dependence and associated mortality, psychiatric and physical health, and health service use.

INTRODUCTION: Opioid dependence is a global health priority, currently making the biggest contribution to drug-related deaths. The chronic, long-term persistence of heroin dependence over the life course requires investigation in prospective longitudinal studies, to better understand patterns and predictors of remission and relapse, as well as the impact of changes in substance use on a range of physical and mental health outcomes. Such knowledge is critical in order to identify modifiable risk factors that can be targeted for intervention. Crucial unanswered questions include the following: What are the long-term rates of mortality? What are the long-term patterns and predictors of heroin use, remission, psychiatric health and health service use? What are the long-term physical health consequences of heroin use? METHODS AND ANALYSIS: The 18-20-year follow-up of the Australian Treatment Outcome Study (ATOS) cohort will examine the natural history of heroin dependence of an existing cohort of 615 people with heroin dependence, who were recruited into the study in 2001-2002. Five waves of follow-up interviews have since been completed, at 3-month, 1-year, 2-year, 3-year and 10-11-year post-baseline. At the 18-20-year follow-up, the ATOS cohort is (on average) approaching their 50s and an average of 30 years have passed since they first used heroin. The 18-20-year follow-up will consist of: (1) a structured interview; (2) physical health assessment; and (3) data linkage. The results of this follow-up will improve our understanding and management of age-related disorders in this population, which if not addressed in the immediate future, has the capacity to overwhelm treatment centres and aged care facilities. ETHICS AND DISSEMINATION: Ethical approval has been granted for the study (Sydney Local Health District Royal Prince Alfred Zone, Human Research Ethics Committee X18-0512 & HREC/18/RPAH/733). The results of the study will be disseminated through published manuscripts, bulletins and technical reports, as well as conference, seminars, webinar and workshop presentations.

Reliability of home blood pressure monitoring devices in pregnancy.

Home blood pressure monitors are freely available and used for women during pregnancy. The exact role of home blood pressure monitoring in pregnancy remains uncertain, and few such monitors have been validated for use in pregnancy. As it has been our Unit's policy to test these devices against sphygmomanometry (as the gold standard) before clinical use for some years now, we undertook this study to ascertain the degree of accuracy or inaccuracy of these devices in usual clinical practice. We analysed 9 consecutive blood pressures (BP) alternately using an automated home BP device and sphygmomanometry in 127 pregnant women with hypertension using two different methods: a) a modified version of the British Hypertension Society's guidelines for analysing automated devices, and b) examining the difference between the mean of blood pressure readings by the device and sphygmomanometry for each patient. 87 devices (69%) had systolic BP within 5mmHg or less and 98 (77%) were within 5mmHg for diastolic BP. The frequency of systolic BPs within 5mmHg was similar for non-validated vs. validated devices (75vs. 60%; p=0.23). Similarly, diastolic BP within 5mmHg was similar for non-validated vs. validated devices (86vs. 68%, p=0.06). Our findings showed that a wide variety of devices are used and few if any have been formally validated for use in pregnancy. As a group the devices provide accurate BP in the majority of women, but up to a quarter will have a BP difference of at least 5mmHg, and this is not related to the absolute BP. Furthermore using a home BP device validated for general use in non-pregnant subjects appeared as reliable as using other non-validated devices. On the basis of these data we recommended clinicians always perform their own analysis of a patient's home BP machine accuracy prior to home use using a simple protocol as described here, even if the machine has been validated for general use.