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.</p

Perceived stigma and social support in treatment for pharmaceutical opioid dependence

Introduction and Aims The dramatic increase in pharmaceutical opioid (PO) use in high‐income countries is a growing public health concern. Stigma and social support are important as they may influence treatment uptake and outcomes, yet few studies exist regarding perceived stigma and social support among people with PO dependence. The aims of the study are to: (i) compare characteristics of those with PO dependence from iatrogenic and non‐iatrogenic causes; (ii) document perceived stigma and its correlates in people in treatment for PO dependence; and (iii) examine correlates of social support in people in treatment for PO dependence. Design and Methods This prospective cohort study included (n = 108) PO‐dependent people referred from treatment services. Telephone interviews were conducted at baseline, 3, 12 and 24 months. Multivariate linear regression was used to examine correlations. Results Mean age was 41 (SD = 10.5). Half (n = 56, 52%) were female. Two in five met the criteria for iatrogenic dependence (n = 41, 38%), with iatrogenic dependence associated with chronic pain, and no history of injection or heroin use. One quarter of study subjects reported past month unsanctioned opioid use (n = 25, 23%). Being married/de facto or female was associated with higher levels of perceived stigma. Unsanctioned opioid use, iatrogenic dependence and mental health conditions were associated with lower social support. Discussion and Conclusions Stigma affects all people in treatment. Those who are married/de facto and female may benefit from interventions to address stigma. The association of low social support with poorer mental health and ongoing substance use indicate that treatment could focus more on this area

Current insights on the impact of gamma-hydroxybutyrate (GHB) abuse.

Recreational gamma-hydroxybutyrate (GHB) use, although less common than other substance use, is increasingly recognised and is over-represented in emergency toxicology presentations. This narrative review summarizes GHB pharmacology, current patterns of use, potential harms and management of GHB toxicity and withdrawal. There is a complex interplay between GHB and GABA as GHB is both a prodrug and metabolite of GABA and GHB activates both GHB and GABA receptors. GHB is rapidly absorbed, with effects seen within minutes of ingestion. Metabolism is non-linear at higher doses. While GHB is listed as a controlled substance, its precursor's gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are easily available as both have industrial applications. National surveys indicate low rates of GHB use, with identification of high-risk populations in men who have sex with men and polysubstance users. GHB is one of the three drugs most commonly used in chemsex. GHB is often co-ingested with other interacting psychoactive substances. Acute toxicity is dose-dependent, and management is supportive care. Withdrawal management is generally with benzodiazepines with addition of baclofen for more severe withdrawal. Barbiturates may have a role. Titration and tapering of pharmaceutical GHB is commonly used in the Netherlands. Complicated withdrawal with delirium may require intensive care and treatment with intravenous sedation. There are high rates of relapse after withdrawal and medications for longer-term management are currently being investigated. Chronic use is associated with poorer mental, physical and sexual health, social dysfunction and poor work performance. Laboratory detection is complicated as GHB is an endogenous substance with a short half-life, and therefore not often routinely assayed in the clinical setting. Future research should focus on improving GHB detection and management of GHB withdrawal and dependence. Interventions specific for high-risk groups should be developed and assessed

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

Do gabapentin or pregabalin directly modulate the µ receptor?

Background Pregabalin and gabapentin improve neuropathic pain symptoms but there are emerging concerns regarding their misuse. This is more pronounced among patients with substance use disorder, particularly involving opioids. Co-ingestion of gabapentinoids with opioids is increasingly identified in opioid related deaths, however, the molecular mechanism behind this is still unclear. We have sought to determine whether pregabalin or gabapentin directly modulates acute μ receptor signaling, or μ receptor activation by morphine. Methods The effects of pregabalin and gabapentin were assessed in HEK 293 cells stably transfected with the human μ receptor. Their effect on morphine induced hyperpolarization, cAMP production and ERK phosphorylation were studied using fluorescent-based membrane potential assay, bioluminescence based CAMYEL assay and ELISA assay, respectively. Pregabalin/gabapentin effects on morphine-induced hyperpolarization were also investigated in AtT20 cells. Results Pregabalin or gabapentin (1 µM, 100 µM each) did not activate the µ receptor or affect K channel activation or ERK phosphorylation produced by morphine. Neither drug affected the desensitization of K channel activation produced by prolonged (30 min) application of morphine. Gabapentin (1 µM, 100 µM) and pregabalin (1 µM) did not affect inhibition of forskolin-stimulated cAMP production by morphine. However, pregabalin (100 µM) potentiated forskolin mediated cAMP production, although morphine still inhibited cAMP levels with a similar potency to control. Discussion Pregabalin or gabapentin did not activate or modulate µ receptor signaling in three different assays. Our data do not support the hypothesis that gabapentin or pregabalin augment opioid effects through direct or allosteric modulation of the µ receptor. Pregabalin at a high concentration increases cAMP production independent of morphine. The mechanism of enhanced opioid-related harms from co-ingestion of pregabalin or gabapentin with opioids needs further investigation

Therapeutic drug monitoring in oncology - What's out there: A bibliometric evaluation on the topic

International audiencePharmacological therapy is the mainstay of treatment for cancer patients. Despite wide interpatient variability in systemic drug concentrations for numerous antineoplastics, dosing based on body size remains the predominant approach. Therapeutic drug monitoring (TDM) is used for few antineoplastics in specific scenarios. We conducted a rapid bibliometric evaluation of TDM in oncology to capture a snapshot of research in this area over time and explore topics that reflect development in the field. Reports with the composite, indexed term 'therapeutic drug monitoring' in the title and abstract were extracted from MEDLINE (inception to August 2021). Reports related to applications in cancer were selected for inclusion and were tagged by study design, antineoplastic drugs and concepts related to TDM. We present a timeline from 1980 to the present indicating the year of first report of antineoplastic agents and key terms. The reports in our sample primarily reflected development and validation of analytical methods with few relating to clinical outcomes to support implementation. Our work emphasises evidence gaps that may contribute to poor uptake of TDM in oncology

Correlates of pain in an in-treatment sample of opioid-dependent people

Introduction and Aims: The limited literature on pain in opioid-treatment samples indicates that it is highly prevalent. Understanding the implications of pain on treatment outcomes is important, particularly in light of ageing opioid-treatment cohorts. This study explores correlates of pain, including aberrant behaviours related to prescribed opioids. Our hypothesis is that pain may increase aberrant opioid-related behaviours, including illicit substance use, among opioid-dependent people. Design and Methods: We examined pain in methadone or buprenorphine patients (n = 141) from three treatment services. Measures included basic demographics, Brief Pain Inventory, general mental health, physical health and quality of life measures, pain history and treatments, and an aberrant opioid-related behaviour scale. Univariate and multivariate analyses were used to examine correlates of pain. Results: Forty percent reported current pain, measured with the first question of the Brief Pain Inventory. Correlates of pain were depression ratings [adjusted odds ratio (OR) 2.24, 95% confidence interval (CI) 1.04, 4.83], anxiety ratings (adjusted OR 4.29, 95% CI 1.88, 9.80) and self-reported health ratings (adjusted OR 0.35, 95% CI 0.16, 0.76). Contrary to our hypothesis, pain was not associated with greater use of illicit opioids, nor any aberrant opioid-related behaviours. Pain was comparable among methadone and buprenorphine patients. Discussion and Conclusions: The lack of association with pain and aberrant behaviours suggest that it should not be assumed that those in opioid treatment misuse medications in response to pain. The high prevalence of depression/anxiety symptoms indicates a need for further work with larger samples to explore pain and co-morbidity among opioid-dependent people

Cannabis and cannabinoids for the treatment of people with chronic noncancer pain conditions: a systematic review and meta-analysis of controlled and observational studies

This review examines evidence for the effectiveness of cannabinoids in chronic noncancer pain (CNCP) and addresses gaps in the literature by: considering differences in outcomes based on cannabinoid type and specific CNCP condition; including all study designs; and following IMMPACT guidelines. MEDLINE, Embase, PsycINFO, CENTRAL, and clinicaltrials. gov were searched in July 2017. Analyses were conducted using Revman 5.3 and Stata 15.0. A total of 91 publications containing 104 studies were eligible (n = 9958 participants), including 47 randomised controlled trials (RCTs) and 57 observational studies. Forty-eight studies examined neuropathic pain, 7 studies examined fibromyalgia, 1 rheumatoid arthritis, and 48 other CNCP (13 multiple sclerosis-related pain, 6 visceral pain, and 29 samples with mixed or undefined CNCP). Across RCTs, pooled event rates (PERs) for 30% reduction in pain were 29.0% (cannabinoids) vs 25.9% (placebo); significant effect for cannabinoids was found; number needed to treat to benefit was 24 (95% confidence interval [CI] 15-61); for 50% reduction in pain, PERs were 18.2% vs 14.4%; no significant difference was observed. Pooled change in pain intensity (standardised mean difference:-0.14, 95% CI-0.20 to -0.08) was equivalent to a 3mm reduction on a 100 mm visual analogue scale greater than placebo groups. In RCTs, PERs for all-cause adverse events were 81.2% vs 66.2%; number needed to treat to harm: 6 (95% CI 5-8). There were no significant impacts on physical or emotional functioning, and low-quality evidence of improved sleep and patient global impression of change. Evidence for effectiveness of cannabinoids in CNCP is limited. Effects suggest that number needed to treat to benefit is high, and number needed to treat to harm is low, with limited impact on other domains. It seems unlikely that cannabinoids are highly effective medicines for CNCP