Evaluation of adherence monitoring in buprenorphine treatment: A pilot study using timed drug assays to determine accuracy of testing.

AIMS: Buprenorphine is effective at reducing relapse to opioid misuse, morbidity and mortality in opioid-dependent patients. Urine drug screening (UDS) to assess adherence is used routinely in opioid agonist treatment (OAT). The primary aim of this study was to determine factors which may be associated with a negative qualitative urine drug screen for buprenorphine in OAT patients. METHODS: This prospective pilot study was conducted at a tertiary addiction medicine centre. Twenty participants on stable treatment underwent supervised administration of sublingual buprenorphine. Matched urine and blood samples were collected prior to and 2, 4 and 6 hours after buprenorphine administration. Qualitative urine drug screen results were obtained using gas chromatography-mass spectrometry (GC-MS), while quantitative blood and urine results were obtained using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). RESULTS: Qualitative urine assay yielded a negative result for buprenorphine in 57% of tested samples. The median concentration of urinary buprenorphine was 167 mcg/L (range: 2-1730 mcg/L). Thirty percent of all blood samples did not detect buprenorphine (range 0-18 mcg/L). Positive qualitative urine drug screen results were associated with higher urine (343 mcg/L compared with 75 mcg/L; P < .05) and blood (4 mcg/L compared with 2 mcg/L; P < .05) buprenorphine concentrations. Median urine concentrations of buprenorphine were highest at 2 hours and were higher in participants receiving CYP3A4 inhibitors. CONCLUSION: Interpretation of qualitative urine drug screens to assess adherence in OAT is complex. Poor adherence with treatment cannot be assumed in patients returning a negative qualitative GC-MS urine drug screen.

Evaluation of the Prescribing Skills Assessment implementation, performance and medical student experience in Australia and New Zealand.

AIMS: The UK Prescribing Safety Assessment was modified for use in Australia and New Zealand (ANZ) as the Prescribing Skills Assessment (PSA). We investigated the implementation, student performance and acceptability of the ANZ PSA for final-year medical students. METHODS: This study used a mixed-method approach involving student data (n = 6440) for 2017-2019 (PSA overall score and 8 domain subscores). Data were also aggregated by medical school and included student evaluation survey results. Quantitative data were analysed using descriptive and multivariate analyses. The pass rate was established by a modified Angoff method. Thematic analyses of open-ended survey comments were conducted. RESULTS: The average pass rate was slightly higher in 2017 (89%) which used a different examination to 2018 (85%) and 2019 (86%). Little difference was identified between schools for the PSA overall performance or domain subscores. There was low intercorrelation between subscores. Most students provided positive feedback about the PSA regarding the interface and clarity of questions, but an average of 35% reported insufficient time for completion. Further, 70% on average felt unprepared by their school curricula for the PSA, which is in part explained by the low prescribing experience; 69% reported completing ≤10 prescriptions during training. CONCLUSION: The ANZ PSA was associated with high pass rates and acceptability, although student preparedness was highlighted as a concern for further investigation. We demonstrate how a collaboration of medical schools can adapt a medical education assessment resource (UK PSA) as a means for fulfilling an unmet need.

Clinical practice guideline for deprescribing opioid analgesics: summary of recommendations.

INTRODUCTION: Long term opioids are commonly prescribed to manage pain. Dose reduction or discontinuation (deprescribing) can be challenging, even when the potential harms of continuation outweigh the perceived benefits. The Evidence-based clinical practice guideline for deprescribing opioid analgesics was developed using robust guideline development processes and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, and contains deprescribing recommendations for adults prescribed opioids for pain. MAIN RECOMMENDATIONS: Eleven recommendations provide advice about when, how and for whom opioid deprescribing should be considered, while noting the need to consider each person's goals, values and preferences. The recommendations aim to achieve: implementation of a deprescribing plan at the point of opioid initiation; initiation of opioid deprescribing for persons with chronic non-cancer or chronic cancer-survivor pain if there is a lack of overall and clinically meaningful improvement in function, quality of life or pain, a lack of progress towards meeting agreed therapeutic goals, or the person is experiencing serious or intolerable opioid-related adverse effects; gradual and individualised deprescribing, with regular monitoring and review; consideration of opioid deprescribing for individuals at high risk of opioid-related harms; avoidance of opioid deprescribing for persons nearing the end of life unless clinically indicated; avoidance of opioid deprescribing for persons with a severe opioid use disorder, with the initiation of evidence-based care, such as medication-assisted treatment of opioid use disorder; and use of evidence-based co-interventions to facilitate deprescribing, including interdisciplinary, multidisciplinary or multimodal care. CHANGES IN MANAGEMENT AS A RESULT OF THESE GUIDELINES: To our knowledge, these are the first evidence-based guidelines for opioid deprescribing. The recommendations intend to facilitate safe and effective deprescribing to improve the quality of care for persons taking opioids for pain.

'It's a fragile open door'-enhancing COVID-19 vaccination rates in people receiving treatment for substance use disorder.

BACKGROUND: People with substance use disorder are at high risk of harms from COVID-19 infection. Vaccine hesitancy is common in this population and compounds pre-existing barriers to accessing health care. A drug and alcohol service in Sydney, Australia introduced strategies to enhance COVID-19 vaccination in people receiving opioid agonist treatment (OAT). We report vaccination outcomes and staff experiences of this. METHODS: This mixed methods study (i) retrospectively evaluated vaccine uptake in people accessing OAT and (ii) explored perceptions of staff who delivered vaccination interventions through surveys and semi-structured interviews. RESULTS: Of the 984 patients receiving OAT on 9 December 2021, 90.9% had received the first COVID-19 vaccination and 86.7% the second. Australia wide vaccination rates on that date were 93.1% and 88.7% for first and second doses, respectively. Staff commented that having a deep knowledge, understanding and connection with the patient group drove implementation and success of vaccination interventions. This was further supported by staff engagement with the vaccination interventions, and communication and sharing information, both between staff and with patients. CONCLUSION: High rates of COVID-19 vaccination can be achieved in a vulnerable population. Engaged staff providing information and facilitating access to healthcare underpin this success.

Gabapentinoids: a therapeutic review.

The Australian Therapeutic Goods Administration's approved indications for prescription of gabapentinoids are refractory focal epilepsy and neuropathic pain. Use of gabapentinoids outside of the approved indications is common, but evidence for this is limited, especially for chronic nonspecific back pain and nonradicular leg pain. Some effects of gabapentinoids encourage their nonmedical use (e.g. euphoria, sedation, disinhibition). Widespread nonmedical use has increased the incidence of accidental and deliberate poisonings. Dependence may develop with chronic use of gabapentinoids and abrupt cessation may induce withdrawal symptoms. If the indication for continued use is unclear, gradual dose tapering as a means of deprescribing is recommended. Clinicians should consider the indication, patient characteristics and harm-benefit profile when prescribing gabapentinoids. Some people, such as those with kidney disease, have an increased risk of harm when using these drugs.

The Effectiveness of Exercise as an Adjunct Intervention to Improve Quality of Life and Mood in Substance Use Disorder: A Systematic Review.

Introduction: Quality of life and affective outcomes offer a perspective of the burden of disease experienced by people with substance use disorder. This can be considered an alternative measure of substance use disorder severity. This review aims to evaluate the impact of exercise as a novel intervention on quality of life and affect in substance use disorder. Method: Medline, CINAHL, Amed, Web of Science core collections, Embase, PsychINFO and SportDISCUS databases were searched from inception to August 2021 for studies that assessed the impact of exercise on mood, depression, anxiety and quality of life outcomes in substance use disorder. Exercise interventions of any duration were included. Results: Forty-two studies met the inclusion criteria. Quality of life scores improved with larger effects seen in studies with two or more sessions per week. Depression and anxiety scores decreased, with 19 of the 25 data sets reporting a reduction in depression (effect size 0.2-1.86) and 13 of the 17 data sets reporting a reduction in anxiety (effect sizes 0.2-1.42). Mood improved in six of the seven data sets reviewed with effect sizes ranging from 0.34 to 1.13. Discussion: Included studies had numerous methodological flaws therefore results need to be interpreted with caution. Further research needs to be completed with more rigorous methodologies to support these results. Conclusions: Results indicate promising responses to exercise as a novel intervention for quality of life and mood in substance use disorder, however further research of high methodological quality is needed to confirm.

The effect of daily aerobic cycling exercise on sleep quality during inpatient cannabis withdrawal: A randomised controlled trial.

Sleep disturbance is a common symptom encountered by cannabis-dependent individuals abstaining from cannabis use. In the present study, we investigated the effect of daily aerobic cycling exercise versus control stretching on sleep quality during inpatient cannabis withdrawal in treatment-seeking dependent cannabis users. The protocol incorporated three consecutive phases: a 4-Day (4-Night) (at-home) 'Baseline' phase, a 6-Day (5-Night) 'Treatment' phase (within a 7-Day inpatient hospital stay) and a 3-Day (4-Night) (at-home) 'Post-Treatment' phase. Participants performed 35 min of monitored activity per day during the Treatment phase. The intervention group (n = 19) cycled at ~60% aerobic capacity (VO2max ), while the control group (n = 12) performed a stretching routine. Objective sleep quality was measured nightly throughout the study using wrist actigraphy ratings of subjective sleep quality were also recorded during the Treatment phase. There were no group differences in sleep measures during the Baseline phase (all p > .05). Objective sleep onset latency increased from the Baseline to the Treatment phase in the control (stretching) group (p = .042). In contrast, the Cycling group exhibited improvements in sleep duration (p = .008) and sleep efficiency (p = .023) during the Treatment phase compared to the Baseline phase. Cycling also increased sleep duration (p = .005), decreased average wake bout (p = .040) and tended to increase sleep efficiency (p = .051) compared to stretching during the Treatment phase. Subjective sleep quality ratings did not differ between groups (p > .10). These preliminary findings suggest that moderate-intensity aerobic exercise may attenuate the sleep disturbances associated with cannabis withdrawal.

Patient characteristics predicting attendance for elective in-patient treatment of substance use disorder.

OBJECTIVE: Consumption of alcohol and other drugs constitutes a significant health burden. Treatment access is poor, and a number of barriers are recognised. The objective of this retrospective cohort study is to examine patient characteristics of those attending/not attending for elective in-patient withdrawal management (IWM). METHODS: Records of all elective admissions for IWM between 1 March and 30 June 2019 were reviewed. Data were extracted on attendance, age, substance(s) used, pre-arranged rehabilitation admissions following discharge, wait time, legal issues and child welfare agency involvement. RESULTS: Of 274 planned admissions, 193 (70%) attended. Attendance was predicted by residential treatment planned after withdrawal management and older age. People using amphetamines were less likely to attend. CONCLUSION: There are low attendance rates for elective IWM. Patient characteristics predicting lower attendance include younger age, amphetamine use and not planning rehabilitation. Further research is required to improve attendance.

Acute Experimental Pain Responses in Methadone- and Buprenorphine/Naloxone-Maintained Patients Administered Additional Opioid or Gabapentin: A Double-Blind Crossover Pilot Study.

OBJECTIVE: The study objective was to identify the analgesic efficacy of three different pharmacological strategies in patients receiving methadone or buprenorphine as opioid agonist treatment (OAT). The three pharmacological approaches, a) increasing maintenance methadone/buprenorphine dose by 30%, b) adding oxycodone, or c) adding a single dose of gabapentin, were compared with a control condition of the participant's usual OAT dose. DESIGN: A randomized, controlled, double-blinded, double-dummy, within-subject crossover study. SUBJECTS: Nine participants on stable doses of methadone and eight participants on stable doses of buprenorphine were recruited. SETTING: An outpatient opioid treatment clinic in inner city Sydney, Australia. METHODS: The cold pressor tolerance test was used to examine experimental pain threshold and tolerance. Ratings of subjective drug effects and safety measures (physiological and cognitive) were assessed. RESULTS: There was no difference in the primary outcome measures of pain thresholds or tolerance between the conditions examined. Interindividual variability was evident. Differences in some subjective measures were identified, including lower pain recall, lower "bad effects," and higher global satisfaction in the additional methadone condition. In the buprenorphine arm, increased drug liking and "bad effects" were detected with oxycodone administration, while increased subjective intoxication was identified with gabapentin. CONCLUSIONS: There was no evidence of an objective improvement in analgesia with any condition compared with control. Further research is required to optimize pain management strategies in this population.

Cannabinoids for the treatment of spasticity.

This review summarizes studies that examined the effectiveness of cannabinoids in treating spasticity, with a focus on understanding the relevance of the existing evidence to paediatric populations. MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched to identify studies that examined the use of cannabinoids in spasticity. We identified 32 studies in adult and paediatric populations. Results were summarized by condition, with adult and paediatric studies considered separately. There is evidence from randomized controlled clinical trials that cannabinoids are more effective than placebo in reducing symptoms of spasticity in adults with multiple sclerosis. Most positive effects were based on patient-rated rather than clinician-rated measures, were modest in size, and should be considered in the context of the narrow therapeutic index of cannabinoids for spasticity and adverse effects. There were comparatively few, and no large studies, of spasticity in conditions other than multiple sclerosis. Few studies have been conducted in paediatric populations. Paediatric studies of spasticity provide low quality evidence and are inadequate to inform clinical practice. Cannabinoids have modest efficacy in reducing muscle spasticity in adults with multiple sclerosis. There is limited evidence of efficacy for cannabinoid use in other conditions, particularly in paediatric populations. Studies in paediatric populations have been of low quality and are insufficient to inform clinical practice.

CANNABINOIDES PARA EL TRATAMIENTO DE LA ESPASTICIDAD: Esta revisión resume los estudios que examinaron la efectividad de los cannabinoides en el tratamiento de la espasticidad, con un enfoque en la comprensión de la relevancia de la evidencia existente para las poblaciones pediátricas. Se realizaron búsquedas en Medline, Embase, PsycINFO y la Biblioteca Cochrane para identificar estudios que examinaron el uso de cannabinoides en la espasticidad. Se identificaron 32 estudios en poblaciones adultas y pediátricas. Los resultados se resumieron por condición, con estudios en adultos y pediátricos considerados por separado. Existe evidencia de ensayos clínicos controlados aleatorios de que los cannabinoides son más efectivos que el placebo para reducir los síntomas de la espasticidad en adultos con esclerosis múltiple. La mayoría de los efectos positivos se basaron en las medidas clasificadas por el paciente en lugar de las clasificadas por el médico, fueron de tamaño modesto y deben considerarse en el contexto del estrecho índice terapéutico de los cannabinoides para la espasticidad y los efectos adversos. Hubo comparativamente pocos, y no hay estudios grandes, de espasticidad en afecciones distintas a la esclerosis múltiple. Se han realizado pocos estudios en poblaciones pediátricas. Los estudios pediátricos de espasticidad proporcionan evidencia de baja calidad y son inadecuados para informar la práctica clínica.

CANABINÓIDES PARA O TRATAMENTO DA ESPASTICIDADE: Esta revisão sintetiza estudos que examinaram a efetividade de canabinóides no tratamento da espasticidade, com foco na compreensão da relevância da evidência existente para populações pediátricas. Medline, Embase, PsycINFO, e Cochrane Library foram pesquisados para identificar estudos que examinaram o uso de canabinóides na espasticidade. Identificamos 32 estudos em populações adultas e pediátricas. Os resultados foram sintetizados por condição com estudos em adultos e pediátricos considerados separadamente. Há evidência de ensaios clínicos randomizados controlados de que os canabinóides são mais efetivos do que placebos na redução de sintomas de espasticidade em adultos com esclerose múltipla. A maioria dos efeitos positivos foram baseados em medidas fornecidas por pacientes e não por clínicos, eram de tamanho modesto, e devem ser considerados no contexto do estreito índice terapêutico dos canabinóides para espasticidade e efeitos adversos. Houve comparativamente menos, e nenhum grande estudo, da espasticidade em condições diferentes da esclerose múltipla. Poucos estudos foram conduzidos em populações pediátricas. Estudos pediátricos da espasticidade fornecem baixa evidência de qualidade e são inadequados para informar a prática clínica.

Unique approach to continuing medical education in clinical pharmacology across Australia and New Zealand.

BACKGROUND: Advanced physician training in clinical pharmacology lacks a continuing education programme. There is a need for continuing medical education but how to introduce and develop education remains unclear. AIMS: The primary aim was to develop and implement a peer-led, web-based multiple choice question approach to continuing education in clinical pharmacology training across Australia and New Zealand. Secondary aims included determining, quality, difficulty, utility, relevance, user-friendliness, sustainability and potential to form part of formal clinical pharmacology physician training. METHODS: In February 2018, a survey of clinical pharmacology trainees identified topics for question development. Questions covering requested topics were developed and piloted in PeerWise between March and October 2018. Participants could rate quality and difficulty of questions using categorical rating scales and make free text comments. After questions were piloted, a survey using a 0-10-point Likert scale and yes/no responses assessed utility, relevance, user-friendliness, sustainability and formalisation potential. RESULTS: Twenty-four trainees were invited to participate. Nine (38%) of trainees completed the initial survey, 10 (42%) attempted questions and 7 (29%) completed the end survey. Median scores of 8.00 (IQR 6.50 - 9.00), 7.00 (IQR 6.50 - 7.50) and 8.00 (IQR 6.50 - 8.00) using a 0-10-point Likert scale indicated trainees found this approach useful, relevant and user-friendly. Five (71%) out of seven responding trainees felt this approach was sustainable and could be incorporated as part of formal clinical training. CONCLUSION: This study suggests that peer-led multiple choice questions could form an enduring education modality which could be incorporated into clinical pharmacology training.

Inpatient management of gamma-hydroxybutyrate withdrawal.

OBJECTIVES: To describe the baseline characteristics, treatment and retention in patients electively admitted for gamma-hydroxybutyrate (GHB) withdrawal management. METHODS: All patients admitted between July 2010 to June 2016 who used GHB two or more times per week with a minimum duration of 3 months were identified and data extracted by file review. RESULTS: Twelve cases satisfied the inclusion criteria, of whom 50% were female; 75% were using GHB daily, with an average daily amount of 16 ml. Average duration of use was 60 months. All subjects were using amphetamine type stimulants and nicotine. Psychiatric comorbidity and unintentional overdose were common; 50% completed treatment. Medications used included diazepam and neuroleptic. Two patients completed withdrawal with no medications. No subject using greater than 90 ml GHB in the preceding week completed treatment. Pattern of GHB use did not predict medication requirements during withdrawal management. CONCLUSIONS: There were low numbers attending for elective treatment for GHB use. Heavier GHB use predicted poor treatment retention. Polysubstance use and psychiatric co-morbidities need consideration in treatment planning.

Medicinal cannabis.

A number of therapeutic uses of cannabis and its derivatives have been postulated from preclinical investigations. Possible clinical indications include spasticity and pain in multiple sclerosis, cancer-associated nausea and vomiting, cancer pain and HIV neuropathy. However, evidence is limited, may reflect subjective rather than objective outcomes, and is not conclusive. Controversies lie in how to produce, supply and administer cannabinoid products. Introduction of cannabinoids therapeutically should be supported by a regulatory and educational framework that minimises the risk of harm to patients and the community. The Regulator of Medicinal Cannabis Bill 2014 is under consideration in Australia to address this. Nabiximols is the only cannabinoid on the Australian Register of Therapeutic Goods at present, although cannabidiol has been recommended for inclusion in Schedule 4.

Management of benzodiazepine misuse and dependence.

There are well-recognised harms from long-term use of benzodiazepines. These include dependency, cognitive decline and falls. It is important to prevent and recognise benzodiazepine dependence. A thorough risk assessment guides optimal management and the necessity for referral. The management of dependence involves either gradual benzodiazepine withdrawal or maintenance treatment. Prescribing interventions, substitution, psychotherapies and pharmacotherapies can all contribute. Unless the patient is elderly, it is helpful to switch to a long-acting benzodiazepine in both withdrawal and maintenance therapy. The dose should be gradually reduced over weeks to lower the risk of seizures. Harms from drugs such as zopiclone and zolpidem are less well characterised. Dependence is managed in the same manner as benzodiazepine dependence.

Interconnections between unintended pregnancy, alcohol and other drug use, and pregnancy, birth, infant, childhood and socioeconomic outcomes: a scoping review.

BACKGROUND: Unintended pregnancy (UIP) and substance use disorder share underlying root causes with similar impacts for women and their offspring in pregnancy, birth and beyond. Furthermore, intoxication with alcohol and other drugs (AOD) increases the risk of UIP. OBJECTIVES: To assess the available evidence on associations between UIP and health, social and economic outcomes, in women who use AOD. SEARCH STRATEGY: The review utilised the Joanna Briggs Institute Methodology for Scoping Reviews and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) reporting guidelines. The search was conducted across multiple databases, including Scopus and Medline, and limited to studies published between January 2000 to June 2023. SELECTION CRITERIA: Studies reporting on interactions between AOD use and UIP, and pregnancy, birth, infant, childhood, social or economic outcomes. All patterns and types of AOD use, except isolated use of tobacco, were included. Studies were available in English and conducted in high-income countries. DATA COLLECTION AND ANALYSIS: Selected articles were reviewed, and data collected by two independent reviewers using a standardised data extraction sheet. Findings were summarised and reported descriptively. MAIN RESULTS: A total of 2536 titles and abstracts were screened, 97 full texts were reviewed, and three studies were selected for inclusion in the scoping review. There was heterogeneity in types and patterns of AOD use, differences in study design and tools to assess pregnancy intention, and each focused on disparate outcomes. No study assessed or reported on birth outcomes. CONCLUSION: There is a paucity of data examining the intersection between AOD use and UIP and further research is needed.

Context matters: using an Evidence to Decision (EtD) framework to develop and encourage uptake of opioid deprescribing guideline recommendations at the point-of-care.

OBJECTIVES: To describe the development and use of an Evidence to Decision (EtD) framework when formulating recommendations for the Evidence-Based Clinical Practice Guideline for Deprescribing Opioid Analgesics. STUDY DESIGN AND SETTING: Evidence was derived from an overview of systematic reviews and qualitative studies conducted with healthcare professionals and people who take opioids for pain. A multidisciplinary guideline development group conducted extensive EtD framework review and iterative refinement to ensure that guideline recommendations captured contextual factors relevant to the guideline target setting and audience. RESULTS: The guideline development group considered and accounted for the complexities of opioid deprescribing at the individual and health system level, shaping recommendations and practice points to facilitate point-of-care use. Stakeholders exhibited diverse preferences, beliefs, and values. This variability, low certainty of evidence, and system-level policies and funding models impacted the strength of the generated recommendations, resulting in the formulation of four 'conditional' recommendations. CONCLUSION: The context within which evidence-based recommendations are considered, as well as the political and health system environment, can contribute to the success of recommendation implementation. Use of an EtD framework allowed for the development of implementable recommendations relevant at the point-of-care through consideration of limitations of the evidence and relevant contextual factors.

Experiences of misuse and symptoms of dependence among people who use gabapentinoids: a qualitative systematic review protocol.

INTRODUCTION: Gabapentinoids are among the most widely prescribed pain medications. However, there is growing evidence to suggest that gabapentinoids may be associated with dependence and misuse. The aim of this systematic review is to synthesise the qualitative literature on gabapentinoid misuse and symptoms of dependence. The findings of this study will inform efforts to mitigate emerging harms. METHODS AND ANALYSIS: A systematic review of qualitative research will explore lived experiences of misuse and symptoms of dependence among people who use gabapentinoids. Six databases (MEDLINE, Scopus, Web of Science, CINAHL, EMBASE and PsycINFO) and grey literature sources will be searched from inception to May 2023. Qualitative studies that include people with lived experiences of gabapentinoid misuse and symptoms of gabapentinoid dependence will be included. Reference lists of included studies will also be screened for additional studies. The methodological quality of included studies will be appraised using the Critical Appraisal Skills Programme qualitative checklist, and higher quality studies will be prioritised in the thematic synthesis. The GRADE-CERQual approach will be used to assess confidence in the overall findings of the review. ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review. The findings of this review will be disseminated in peer-reviewed journals, at conferences and on social media. PROSPERO REGISTRATION NUMBER: CRD42023401832.