A phase 3 randomised double-blind placebo-controlled trial of mirtazapine as a pharmacotherapy for methamphetamine use disorder: a study protocol for the Tina Trial.

BACKGROUND: There are no approved pharmacotherapies for methamphetamine use disorder. Two preliminary phase 2 randomised controlled trials have found mirtazapine, a tetracyclic antidepressant, to be effective in reducing methamphetamine use. The proposed Tina Trial is the first phase 3 placebo-controlled randomised trial to examine the effectiveness and safety of mirtazapine as an outpatient pharmacotherapy for methamphetamine use disorder. METHODS: This is a multi-site phase 3 randomised, double-blind, placebo-controlled parallel trial. Participants are randomly allocated (1:1) to receive either mirtazapine (30 mg/day for 12 weeks) or matched placebo, delivered as a take-home medication. The target population is 340 people aged 18-65 years who have moderate to severe methamphetamine use disorder. The trial is being conducted through outpatient alcohol and other drug treatment clinics in Australia. The primary outcome is measured as self-reported days of methamphetamine use in the past 4 weeks at week 12. Secondary outcomes are methamphetamine-negative oral fluid samples, depressive symptoms, sleep quality, HIV risk behaviour and quality of life. Other outcomes include safety (adverse events), tolerability, and health service use. Medication adherence is being monitored using MEMS® Smart Caps fitted to medication bottles. DISCUSSION: This trial will provide information on the safety and effectiveness of mirtazapine as a pharmacotherapy for methamphetamine use disorder when delivered as an outpatient medication in routine clinical practice. If found to be safe and effective, this trial will support an application for methamphetamine use disorder to be included as a therapeutic indication for the prescription of mirtazapine. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12622000235707. Registered on February 9, 2022.

Investigating hepatitis C screening among people receiving opioid agonist treatment: A retrospective audit study.

Background: Estimates of the prevalence of hepatitis C virus (HCV) amongst people who inject drugs are in the range of 50%. Opioid Agonist Treatment (OAT) clinics have a large proportion of people who inject drugs. These clinics, therefore, present an excellent opportunity to identify and treat patients with HCV. Despite this, it remains unclear as to how well these clinics screen patients for HCV. Aim: This study aims to quantify the rate of HCV screening of patients that enrolled into treatment at an OAT clinic attached to a large teaching hospital in NSW. Methods: A retrospective audit of the electronic medical record of patients commencing OAT at the clinic was performed to determine the rate of HCV screening. Findings: During the audit period, there were 99 episodes of care that involved the commencement of OAT at the clinic, for patients who had a history of injecting drugs. Successful screening for HCV occurred in 56% (55/99) of these episodes. Of those screened, 26% were ribonucleic acid positive. Analysis of demographics did not reveal a statistically significant difference between those that were screened and those that were not. Discussion: This study revealed a suboptimal rate of HCV screening at the OAT clinic. To improve the screening rate, the clinic could consider providing dried blood spot testing at the initial nurse assessment or having a clinician capable of venepuncture at the clinic.

Diagnostic accuracy for self-reported methamphetamine use versus oral fluid test as the reference standard in a methamphetamine-dependent intervention trial population.

AIMS: Treatment of methamphetamine dependence requires monitoring of recent use or abstinence. Self-report is commonly used for routine monitoring, but the accuracy of self-report is not established. For the treating clinician, the key accuracy statistic is the negative predictive value (NPV). The study aim was to estimate the NPV of self-reported non-use of methamphetamine compared with an oral fluid reference standard. DESIGN, SETTING AND PARTICIPANTS: This study was a secondary (subgroup) analysis from a randomized controlled pharmacotherapy trial. Three Australian outpatient addiction services took part. Particpants were 139 people dependent on methamphetamine. MEASUREMENTS: Weekly oral fluid samples over 12 weeks to determine methamphetamine (and amphetamine) concentrations were used as the reference standard. Self-report of any methamphetamine use in the previous 7 days by the time-line follow-back method was the index test. Standard diagnostic accuracy statistics were calculated for all available paired episodes (n = 1134). Three NPV values were calculated: unadjusted NPV and NPV adjusted for clustering of observations through logistic regression and generalized estimating equation (GEE). We also calculated the NPVs for a range of prevalence rates of methamphetamine use, for the calculated levels of sensitivity and specificity. FINDINGS: Sensitivity was 96.4% [95% confidence interval (CI) = 95-97.5], specificity was 63.7% (95% CI = 57.3-69.8) and positive predictive value (PPV) was 90.8% (95% CI = 88.8-92.6). The unadjusted NPV was 82.7% (95% CI = 76.5-87.9), adjusted NPV by logistic regression 82.7% (95% CI = 73.9-91.5) and GEE 76.8% (95% CI = 66.8-86.8). At a methamphetamine use prevalence of 5%, the estimated NPV would be 99.7% (95% CI = 99.6-99.9) and at 95% prevalence, 48.2% (95% CI = 39.6-57.0). CONCLUSIONS: Self-report of no recent methamphetamine use appears to be sufficiently accurate to be clinically useful at the expected prevalence rates of methamphetamine use in clinical treatment settings. If generalizable to clinical settings, where these tests are routinely conducted, this may permit a reduction in the frequency and cost of oral fluid assays.

Emergency department presentations of patients with alcohol use disorders in an Australian regional health district.

Background: This study aimed to investigate the longitudinal changes in emergency department (ED) presentations incurred by patients with alcohol use disorders. Methods: A retrospective quantitative analysis was conducted on patients' ED presentations between December 2011 and January 2019 in an Australian regional health district. The health district has five EDs serving rural, regional, and metropolitan areas. Patients with alcohol use disorders were divided into two groups for comparison: those who had interactions with the community-based Drug and Alcohol (D&A) services and those who did not. Results: A total of 2,519 individual patients with alcohol use disorders made 21,715 ED presentations. Among these patients, 75.4% did not have interactions with the community-based D&A services. Compared with those who had, these patients were older, more likely to be diagnosed with abdominal pain (26.9% vs 12.0%, p < 0.001) and chest pain (16.2% vs 8.6%, p < 0.001), and had longer mean length of ED stay (7 hours and 41.7 minutes vs 6 hours and 25.6 minutes, p < 0.001). For the patients who had interactions with the community-based D&A services, their 28-day re-presentation rates decreased from 55.5% (2013-14) to 45.1% (2017-18); however, were higher than that of those who had no interactions (41.1% to 32.8%). Overall, 21.9%-24.5% of the patients were frequent ED presenters (i.e., ≥4 visits per year). Frequent ED presenters were proportionately higher among the patients who had interactions with the community-based D&A services, consistently over the relevant years. Although patients with alcohol use disorders frequently presented to EDs, their alcohol use disorders were only identified in 8.9% of their presentations. Conclusions: Patients with alcohol use disorders were often unidentified in EDs. Those who did not have interactions with the community-based D&A services were less likely to be diagnosed with alcohol use disorders when presenting to EDs.

N-acetylcysteine (NAC) for methamphetamine dependence: A randomised controlled trial.

BACKGROUND: Methamphetamine dependence is a significant global health concern for which there are no approved medications. The cysteine prodrug, N-acetylcysteine (NAC), has been found to ameliorate glutamate dysregulation in addiction, and to reduce craving for methamphetamine and other drugs. We evaluated the efficacy and safety of NAC as a pharmacotherapy for methamphetamine dependence. METHODS: A parallel double-blind randomised placebo-controlled trial of people dependent on methamphetamine recruited from Geelong, Melbourne and Wollongong, Australia, between July 2018 and December 2019. Participants were randomised to receive either 12 weeks of oral NAC (2400 mg/day) or matched placebo, delivered as a take-home medication. The primary outcome was methamphetamine use, measured in two ways: (a) change in days of use in the past 4 weeks from baseline to weeks 4, 8 and 12, assessed using the Timeline Followback; and (b) methamphetamine-positive oral fluid samples taken weekly. Analyses were intention-to-treat and based on imputed data. Secondary outcomes were craving, severity of dependence, withdrawal severity and psychiatric symptoms (depression, suicidality, hostility and psychotic symptoms). Significance levels were p < 0.025 for primary outcomes and p < 0.01 for secondary outcomes. Adverse events were compared between groups by system organ class. The study was prospectively registered, ACTRN12618000366257. RESULTS: Participants (N = 153; 59% male, mean [SD] age 38 [8]) were randomised to placebo (n = 77) or NAC (n = 76). Both groups had a median (IQR) of 24 (15-28) days of methamphetamine use in the 4 weeks prior to baseline. Both groups significantly reduced methamphetamine use (mean [SE] reduction of 7.3 [1.2]) days for placebo, 6.8 [1.2] for NAC) but NAC did not reduce days of methamphetamine use more than placebo (group difference of 0.5 days, 97.5% CI -3.4-4.3). There was no significant effect of NAC on methamphetamine-positive oral fluid samples (placebo 79%, NAC 76%; mean difference -2.6, 97.5% CI -12.6-7.4). NAC did not significantly reduce craving, severity of dependence, withdrawal, suicidality, depression, hostility or psychotic symptoms relative to placebo. Adverse events did not differ significantly between placebo and NAC groups. INTERPRETATION: These findings suggest that take-home oral NAC has no significant effect on methamphetamine use or most clinically related outcomes amongst people who are dependent on the drug.

Clinical and demographic characteristics of people who smoke versus inject crystalline methamphetamine in Australia: Findings from a pharmacotherapy trial.

INTRODUCTION AND AIMS: There has been a rapid increase in smoking crystalline methamphetamine in Australia. We compare the clinical and demographic characteristics of those who smoke versus inject the drug in a cohort of people who use methamphetamine. DESIGN AND METHODS: Participants (N = 151) were dependent on methamphetamine, aged 18-60 years, enrolled in a pharmacotherapy trial for methamphetamine dependence, and reported either injecting (n = 54) or smoking (n = 97) methamphetamine. Measures included the Timeline Followback, Severity of Dependence Scale, Amphetamine Withdrawal Questionnaire, Craving Experience Questionnaire and the Brief Psychiatric Rating Scale (symptoms of depression, hostility, psychosis and suicidality). Simultaneous regression was used to identify independent demographic correlates of smoking methamphetamine and to compare the clinical characteristics of participants who smoked versus injected. RESULTS: Compared to participants who injected methamphetamine, those who smoked methamphetamine were younger and less likely to be unemployed, have a prison history or live alone. Participants who smoked methamphetamine used methamphetamine on more days in the past 4 weeks than participants who injected methamphetamine (26 vs. 19 days, P = 0.001); they did not differ significantly in their severity of methamphetamine dependence, withdrawal, craving or psychiatric symptoms (P > 0.05). After adjustment for demographic differences, participants who smoked had lower craving [b (SE) = -1.1 (0.5), P = 0.021] and were less likely to report psychotic symptoms [b (SE) = -1.8 (0.7), P = 0.013] or antidepressant use [b (SE) = -1.1 (0.5), P = 0.022]. DISCUSSION AND CONCLUSIONS: Smoking crystalline methamphetamine is associated with a younger less marginalised demographic profile than injecting methamphetamine, but a similarly severe clinical profile.

Insight in substance use disorder: A systematic review of the literature.

Insight refers to a person's understanding of themselves and the world around them. Recent literature has explored people's insight into their substance use disorder (SUD) and how this is linked to treatment adherence, abstinence rates, and comorbid mental health symptoms. The aim of this systematic review was to synthesise and critically examine the existing literature on insight in SUD. Five academic databases (Medline, PsychINFO, SCOPUS, CINAHL, Web of Science) were searched for key terms related to insight and substance use. Included studies were on humans aged 18 years or over with SUD that examined the relationship between substance use and insight using a quantifiable measure of insight. Of 10,067 identified papers, 20 met the inclusion criteria, employing 13 different measures of insight. The most commonly used measure was the Hanil Alcohol Insight Scale (HAIS) which was the only measure designed for a substance use population and was specific to alcohol use. Based on a pooled sample from five studies (n = 585), 57% of participants had poor insight, 36% had fair insight, and 7% had good insight on the HAIS. Better insight was generally related to negative consequences from substance use, better treatment adherence and maintaining abstinence. Insight appears to be an important factor to consider within SUD. Exploring the most appropriate way to measure insight and assess its role in SUD has implications for intervention design, and engaging and maintaining people with SUD in treatment.

Nursing Students' Perceived Self-Efficacy and the Generation of Medication Errors with the Use of an Electronic Medication Administration Record (eMAR) in Clinical Simulation.

Medication errors continue to be a significant issue, posing substantial threats to the safety and well-being of patients. Through Bandura's theory of self-efficacy, nursing students' self-efficacy (confidence) related to medication administration was examined to investigate its influence on the generation of medication errors with the use of an Electronic Medication Administration Record (eMAR) in clinical simulation. This study examined the generation of medication errors and the differences that may exist based on nursing students' perceived confidence. The findings of this study demonstrated that nursing students continue to generate medication errors within clinical simulation. No differences in the generation of medication errors were found between nursing students with perceived high levels of confidence and those with perceived low levels of confidence (one exception noted). Further examination of the variables and contextual factors related to safe medication administration practices is required to inform nursing education and practice.

A study protocol for the N-ICE trial: A randomised double-blind placebo-controlled study of the safety and efficacy of N-acetyl-cysteine (NAC) as a pharmacotherapy for methamphetamine ("ice") dependence.

BACKGROUND: There are currently no approved pharmacotherapies for managing methamphetamine dependence. N-acetylcysteine (NAC) has been found to reduce the craving for methamphetamine and other drugs, but its effect on methamphetamine use and other clinically related endpoints are uncertain. The N-ICE trial is evaluating the safety and efficacy of NAC as a take-home pharmacotherapy for methamphetamine dependence. METHODS/DESIGN: This is a two-arm parallel double-blind placebo-controlled three-site randomised trial (ratio 1:1) using permuted block randomisation, with variable block sizes. It is stratified by site, sex and whether the methamphetamine is injected or not. Participants (N = 180; 60 per site) need to be dependent on methamphetamine, interested in reducing their methamphetamine use and not currently receiving treatment for substance use disorders. The trial is being conducted in outpatient settings in Melbourne, Geelong and Wollongong, Australia. Participants will receive either 2400 mg oral NAC or a matched placebo, delivered as a take-home medication for 12 weeks. Two 600 mg capsules are self-administered in the morning and two more in the evening. Adherence is being monitored using eCAP™ medication bottle lids, which record the date and time of each occasion the bottle is opened. The primary outcome is methamphetamine use during the 12-week trial medication period, measured as (a) days of use, assessed using the timeline followback, and (b) methamphetamine-positive saliva tests, taken weekly. Secondary measures include weekly assessment of methamphetamine craving, severity of methamphetamine dependence, methamphetamine withdrawal symptoms and psychiatric symptoms (depression, suicidality, psychotic symptoms and hostility). Adverse events are monitored at each weekly assessment. Tolerability is assessed using the Treatment Satisfaction Questionnaire for Medication. DISCUSSION: The N-ICE trial is the first clinical trial to assess whether NAC can reduce methamphetamine use. This trial will improve our understanding of the potential utility of NAC in managing methamphetamine dependence and clinically related outcomes. If found to be effective, take-home NAC could be a potentially scalable and affordable pharmacotherapy option for treating methamphetamine dependence. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12618000366257 . Registered on 29 May 2018.

Investigating the management of alcohol-related presentations in an Australian teaching hospital.

INTRODUCTION AND AIMS: Alcohol-related morbidity is estimated to range from 10-38% of the presentations to hospital emergency departments. This study aims to investigate the actual management process for alcohol-related presentations in a teaching hospital in Australia. DESIGN AND METHODS: Retrospective audit was conducted on the electronic medical records of 210 presentations with a primary or secondary diagnosis of 'alcohol use disorder' at discharge between November 2016 and February 2017. Six key management steps were investigated: identification of alcohol use disorder, documentation, thiamine, alcohol withdrawal assessment, benzodiazepine for alcohol withdrawal and referral to the drug and alcohol consultation liaison service. RESULTS: Of all the 210 presentations, 77.1% (162) were identified with alcohol use disorder in the initial assessments; 64.3% (135) were documented with alcohol use history, 49.5% (104) were prescribed with thiamine, 48.1% (101) were assessed with the alcohol withdrawal scale, 41% (86) were prescribed with benzodiazepine for alcohol withdrawal and only 38.6% (81) were referred to the drug and alcohol consultation liaison service. Only 8.6% (18) of the initial presentations were directly related to alcohol. These presentations had a higher completion rate in each of the six steps than those (91.4%, 192) not directly related to alcohol. Only 6.2% (13) were formally screened for alcohol use. DISCUSSION AND CONCLUSIONS: The findings suggest a need to improve the alcohol management practice in the hospital. Routine use of an alcohol screening tool can enable early identification of the alcohol use disorder and to improve the management of this problem in the hospital.

Evaluating a Serious Gaming Electronic Medication Administration Record System Among Nursing Students: Protocol for a Pragmatic Randomized Controlled Trial.

BACKGROUND: Although electronic medication administration record systems have been implemented in settings where nurses work, nursing students commonly lack robust learning opportunities to practice the skills and workflow of digitalized medication administration during their formative education. As a result, nursing students' performance in administering medication facilitated by technology is often poor. Serious gaming has been recommended as a possible intervention to improve nursing students' performance with electronic medication administration in nursing education. OBJECTIVE: The objectives of this study are to examine whether the use of a gamified electronic medication administration simulator (1) improves nursing students' attention to medication administration safety within simulated practice, (2) increases student self-efficacy and knowledge of the medication administration process, and (3) improves motivational and cognitive processing attributes related to student learning in a technology-enabled environment. METHODS: This study comprised the development of a gamified electronic medication administration record simulator and its evaluation in 2 phases. Phase 1 consists of a prospective, pragmatic randomized controlled trial with second-year baccalaureate nursing students at a Canadian university. Phase 2 consists of qualitative focus group interviews with a cross-section of nursing student participants. RESULTS: The gamified medication administration simulator has been developed, and data collection is currently under way. CONCLUSIONS: If the gamified electronic medication administration simulator is found to be effective, it could be used to support other health professional simulated education and scaled more widely in nursing education programs. TRIAL REGISTRATION: ClinicalTrials.gov NCT03219151; https://clinicaltrials.gov/show/NCT03219151 (Archived by WebCite at http://www.webcitation.org/6yjBROoDt). REGISTERED REPORT IDENTIFIER: RR1-10.2196/9601.

Deconstructing Clinical Workflow: Identifying Teaching-Learning Principles for Barcode Electronic Medication Administration With Nursing Students.

The purpose of this quality improvement project was to better understand how to teach medication administration underpinned by an electronic medication administration record (eMAR) system used in simulated, prelicensure nursing education. Methods included a workflow and integration analysis and a detailed process mapping of both an oral and a sublingual medication administration. Procedural and curriculum development considerations related to medication administration using eMAR technology are presented for nurse educators.

Exploring learning content and knowledge transfer in baccalaureate nursing students using a hybrid mental health practice experience.

BACKGROUND: Little research has been completed exploring knowledge development and transfer from and between simulated and clinical practice settings in nurse education. OBJECTIVES: This study sought to explore the content learned, and the knowledge transferred, in a hybrid mental health clinical course consisting of simulated and clinical setting experiences. DESIGN: A qualitative, interpretive descriptive study design. SETTINGS: Clinical practice consisted of six 10-hour shifts in a clinical setting combined with six two-hour simulations. PARTICIPANTS: 12 baccalaureate nursing students enrolled in a compressed time frame program at a large, urban, Canadian university participated. METHODS: Document analysis and a focus group were used to draw thematic representations of content and knowledge transfer between clinical environments (i.e., simulated and clinical settings) using the constant comparative data analysis technique. RESULTS: Four major themes arose: (a) professional nursing behaviors; (b) understanding of the mental health nursing role; (c) confidence gained in interview skills; and, (d) unexpected learning. CONCLUSIONS: Nurse educators should further explore the intermingling of simulation and clinical practice in terms of knowledge development and transfer with the goal of preparing students to function within the mental health nursing specialty.

Developing and Implementing a Simulated Electronic Medication Administration Record for Undergraduate Nursing Education: Using Sociotechnical Systems Theory to Inform Practice and Curricula.

Knowledge and skills related to medication administration are a fundamental element of nursing education. With the increased use of electronic medication administration technology in practice settings where nurses work, nursing educators need to consider how best to implement these forms of technology into clinical simulation. This article describes the development of a simulated electronic medication administration system, including the use of sociotechnical systems theory to inform elements of the design, implementation, and testing of the system. Given the differences in the medication administration process and workflow generated by electronic medication administration technology, nursing educators should explore sociotechnical theory as a potentially informative lens from which to plan and build curricula related to simulation activities involving clinical technology.

Treatment Resistant and Resistant to Treatment? Evaluation of 40 Alcohol Dependent Patients Admitted for Involuntary Treatment.

AIMS: To describe the clinical outcomes for a group of patients with severe alcohol dependence discharged from an Involuntary Drug and Alcohol Treatment (IDAT) program. METHODS: Forty patients admitted to an inpatient IDAT program were prospectively followed up over 6 months using standardized questionnaires. RESULTS: Patients had high rates of mental health comorbidities (97.5%), cortical atrophy (40%) and socioeconomic disadvantage (92.5% were beneficiaries). Six months after discharge, 25% of patients were abstinent and living in the community and 17.5% had notably reduced alcohol use. A further 7.5% were abstinent due to involuntary hospitalization. A total of 10% of patients were deceased and 40% of patients had relapsed or were lost to follow-up. Number of admissions and admission days reduced by 51 and 45% respectively for the 17 abstinent or improved community-based patients. A total of 82% of this patient group were actively engaged with an Assertive Community Treatment (ACT) team. CONCLUSIONS: While patient numbers are small, treatment responsiveness was evident for 42.5% of patients, most of whom were followed up with ACT. Evaluation with a comparator group is required to determine whether outcomes are a function of involuntary treatment or an assertive treatment approach.

Integrating simulated teaching/learning strategies in undergraduate nursing education.

In this article, the results of a mixed-methods study integrating the use of simulations in a nursing theory course in order to assess students' perceptions of self-efficacy for nursing practice are presented. Nursing students in an intervention group were exposed to a combination of lecture and simulation, and then asked to rate their perceptions of self-efficacy, satisfaction and effectiveness of this combined teaching and learning strategy. Based on Bandura's (1977, 1986) theory of self-efficacy, this study provides data to suggest that students' self-confidence for nursing practice may be increased through the use of simulation as a method of teaching and learning. Students also reported higher levels of satisfaction, effectiveness and consistency with their learning style when exposed to the combination of lecture and simulation than the control group, who were exposed to lecture as the only method of teaching and learning.

Neuropsychological functioning in a cohort of HIV infected women: importance of antiretroviral therapy.

We evaluated neurocognitive function in 149 HIV-seropositive and 82 seronegative women enrolled in the Women's Interagency HIV Study (WIHS), a large multi-center study of disease progression in women living with HIV/AIDS. We evaluated the prevalence of abnormal neuropsychological (NP) test findings in HIV-seropositive and seronegative women and factors associated with increased risk of abnormal NP test performance. Risk of NP impairment was no higher for HIV positive women receiving antiretroviral therapy at testing than for HIV-negative women (OR = 1.00). However, the risk of abnormal NP performance increased significantly for seropositive women not receiving antiretroviral therapy (OR = 2.43). Further, treatment status was a significant predictor of NP impairment in a multivariate analysis that included viral load (OR = 1.48) and CD4 count (OR = 1.08) which were not significant. The multivariate analyses controlled for substance use, age, education, head injury, ethnicity, estimated IQ, and psychological distress. This study emphasizes the critical association of antiretroviral therapy with the risk of neurocognitive impairment in women living with HIV/AIDS.