The dual orexin receptor antagonist suvorexant in alcohol use disorder and comorbid insomnia: A case report.

Key Clinical Message: This case suggests using dual orexin receptor antagonists to treat alcohol use disorder and comorbid sleep disorders may be effective, commencing treatment in withdrawal and continuing it to prevent relapse. Abstract: Effective medications for the treatment of alcohol use disorder are limited. This is partially due to the heterogenous nature of the symptomatology associated with alcohol use disorder and the abundance of presenting comorbidities. One common, and often overlooked, symptom that occurs during withdrawal of alcohol use is sleep disruption. Here, we report a case study of a participant with comorbid alcohol use disorder and insomnia. This participant was treated with a dual orexin receptor antagonist, suvorexant (Belsomra®), currently approved to treat insomnia. We demonstrate improvements in alcohol cravings, physical and psychological health, and sleep outcomes with treatment. These data support abundant preclinical and emerging clinical data in this space. The findings from this case report highlight the potential for suvorexant to treat comorbid alcohol use disorder and insomnia with fully powered, randomized controlled trials moving forward.

The opioid industry document archive: New directions in research on corporate political strategy.

The opioid crisis in the United States has resulted in more than 500,000 deaths since 1999, and recent estimates suggest that attributable deaths could reach 842,000 by 2032. While heroin and synthetic products such as fentanyl now account for the majority of opioid overdoses, the prescription opioid crisis that emerged in the mid-1990s was the primary antecedent to the current situation. Recent settlements in litigation against opioid producers, suppliers and retailers has resulted in the release of almost 2.5 million previously confidential internal documents that have been made publicly accessible via the online Opioid Industry Documents Archive, a collaboration between the University of California, San Francisco and Johns Hopkins University. These corporate records provide critical insights into the operations and strategies of manufacturers and other actors in the opioid supply chain. This article describes the provenance of the opioid documents and their potential value as a research resource. It then outlines methodological approaches to their analysis, drawing on comparisons in conducting research using the Truth Tobacco Industry Documents. The Opioid Industry Documents Archive is a new and important addition to existing industry document collections that enable scrutiny and analysis of the role of corporate actors in determining health outcomes. Beyond their immediate application to researching the corporate and regulatory foundations of the current opioid crisis, the opioid document collections will contribute to a greater understanding of the commercial determinants of public health by providing means to better locate the causes of public health crises, identify politically acceptable solutions to their resolution, and inform strategies for preventing future corporate-driven epidemics.

A Placebo-Controlled Randomized Trial of Vigabatrin in the Management of Acute Alcohol Withdrawal.

OBJECTIVE: To undertake a double blinded randomised placebo-controlled trial to assess the efficacy of vigabatrin, a GABA-transaminase inhibitor, as a benzodiazepine sparing agent in the management of acute alcohol withdrawal syndrome in a residential setting. METHODS: We enrolled 120 patients with alcohol use disorder who were randomly assigned to either treatment with vigabatrin (2g/day for 4 days) or placebo. The primary outcome was defined as the number of participants in each treatment arm needing diazepam for withdrawal management. A secondary outcome prespecified was the total dose of diazepam received by participants in each treatment arm. Participants were recruited on admission to a residential withdrawal unit at St Vincent's Hospital Melbourne from December 2014 to April 2019. RESULTS: No significant difference was observed in the number of participants requiring benzodiazepines during their residential withdrawal stay with 44 participants (78.6%) in placebo arm requiring at least one dose of diazepam compared to 38 (66.7%) in vigabatrin arm (p = .156). An 18.1% difference was observed between the proportion of participants who received a total dose of >100mg of diazepam during their residential withdrawal stay in placebo arm (32.1%), compared to vigabatrin arm (14.0%, p = .022). There were higher rates of reported adverse events in placebo arm with nine (15.0%) participants reporting adverse events compared with two (3.3%) participants in vigabatrin arm (p = .027). CONCLUSION: Vigabatrin significantly reduced the number of participants requiring >100mg diazepam over the course of their alcohol withdrawal and was associated with a reduction in adverse effects when compared to placebo.

Reducing opioid prescribing on discharge after orthopedic surgery: Does a guideline improve opioid prescribing practice?

AIM: To investigate adherence to discharge advice in a prescription opioid prescribing guideline (GL) post-orthopedic surgery. METHODS: The guideline in draft form was introduced in February 2018. To assess longer-term adherence to discharge advice and to understand which components of that advice were adhered to, regular audits of discharge prescribing were performed after formal GL launch in February 2019, a year after the draft of the GL had been available. The post-GL audit was conducted for three months (March to May 2019) and results reviewed. When these audit results showed a need for improvement in prescribing practice, a 1-month education "booster" named prescription opioid practice improvement safe opioid supply (POPI SOS) took place. Audits for a further 3 months (July to Sept 2019) were then carried out to ascertain whether the additional effort improved adherence to the guideline. RESULTS: On average, adherence to all elements of the guideline was low at only 23.1 percent at 12 months post-draft GL and 1 month after its formal launch. After POPI SOS, a statistically significant improvement was achieved with an average increase in adherence to 52.5 percent (ρ < 0.001). Greatest improvement was seen in the percentage of patients discharged with an opioid plan included in the discharge summary, increasing from 35.8 to 77.7 percent (ρ < 0.001). The second significant improvement observed was in the supply of opioids being limited to four days or less, an increase from 38.1 to 61.9 percent (ρ < 0.001). CONCLUSION: Introduction of the guideline was not sufficient to promote sustained change in practice. Ongoing monitoring and education were required for its implementation. These findings highlight that comprehensive, locally adapted, evidence-based opioid stewardship is needed to increase the safety of patients and the community in relation to opioid therapy.

Reducing opioid prescribing on discharge after orthopaedic surgery: does a guideline and education improve prescribing practice 1 year later?

BACKGROUND: An intervention Prescription Opioid Practice Improvement (POPI), addressing opioid prescribing on discharge following orthopaedic surgery, demonstrated improved practice. Here we report the sustainability of improved practice at 12 months, and the impact of a booster education intervention, POPI SOS (Safe Opioid Supply). METHODS: Audits were performed using methodology described in previously published studies. RESULTS: High proportion of patients were discharged on opioids, 89.9% 12 months post-POPI (n = 149) and 82.2% post-POPI SOS (n = 169). Twelve months post-POPI there was a significant reduction in combination immediate (IR) and slow release (SR) opioids, 45.7% at the end of POPI program to 34.3% at 12 months (χ2 (1, N = 364) = 4.47, ρ = 0.034); a significant decrease in opioid-weaning plans, 87.4% at the end of POPI program to 35.8% at 12 months (χ2 (1, N = 365) = 104.19, ρ = <0.001); and a significant increase in provision of full quantities of SR-opioids, 6.1% after the POPI program to 15.7% (χ2 (1, N = 364) = 8.95, ρ = 0.003). The POPI SOS booster program significantly improved measures including reduction in combination IR and SR, 34.3-22.3% (χ2 (1, N = 273) = 4.87, ρ = 0.028) and an increase in opioid plans in discharge summaries, from 35.8% to 77.7% (χ2 (1, N = 273) = 48.87, ρ < 0.001). CONCLUSION: Better practice in relation to opioid prescribing is achievable but, for sustained improvement, opioid stewardship activities are needed to reduce the potential harms associated with prescription opioids.

Pharmacokinetics, Safety, and Tolerability of a Medicinal Cannabis Formulation in Patients with Chronic Non-cancer Pain on Long-Term High Dose Opioid Analgesia: A Pilot Study.

INTRODUCTION: This phase I open-label study examined pharmacokinetics, safety, and tolerability of escalating doses of a novel combination cannabinoid medication (1:1 tetrahydrocannabinol [THC]/cannabidiol [CBD]) in patients with chronic non-cancer pain (CNCP) on high dose opioid analgesia. METHODS: Nine people with CNCP and oral morphine equivalent daily dose of 60 mg or higher were recruited. Blood concentrations of THC, 11-hydroxytetrahydrocannabinol (OH-THC), 11-nor-9-carboxy-tetrahydrocannabinol (COOH-THC), and CBD were assayed weekly. Concentrations were measured after a single dose of 2.5 mg THC/2.5 mg CBD on day 1, and daily escalating doses up to a single dose of 12.5 mg THC/12.5 mg CBD on day 29. Follow-up was on day 36 after a 7-day washout. Secondary outcome data encompassed pain, mood, and sleep parameters. RESULTS: The parent compounds THC, and CBD, and metabolites OH-THC and COOH-THC were detected at most time points. In general, the concentration of all analytes increased until 2 h post-administration, decreasing to approximately pre-dose concentrations by 8 h. There was considerable inter- and intra-individual variability. The study medication was well tolerated. Eight participants reported at least one adverse event (AE), with a total of 62 AEs; most common were euphoric mood, headache, and agitation, none classified as severe. There was no significant change to pain severity self-ratings, nor use of pain medications. Improvements in pain interference scores, mood, and some sleep parameters were observed. CONCLUSION: The THC/CBD formulation was tolerated well in a group of patients with CNCP. Between-participant variability supports personalized dosing and "start low-go slow" titration. To validate and quantify improvements in secondary efficacy outcomes a randomized placebo-controlled study is needed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Register (CT-2019-CTN-01224-1).

Many studies use healthy volunteers when they look at the way medicines are absorbed in the body and their clinical effects. The aim of this project was to examine a new formulation of medicinal cannabis in people who have chronic pain and other health conditions to help us to plan a larger study. We wanted information on how quickly it was absorbed and whether there were any negative effects of the medicine. We wondered whether the fact that participants were on a number of other medications might mean that we see different results to those seen with healthy volunteers. We found that the results of our group were very similar to those seen in other studies. Although we only tested a small number of participants we did not observe serious negative effects of the medication, and saw some positive effects on mood and sleep. We now have the data to assist us in planning a larger study which should provide important guidance to prescribers of medicinal cannabis in the future.

Systematic review and meta-analysis of opioid use at 3, 6 and 12 months post-operatively by opioid naïve orthopaedic surgery patients.

BACKGROUND AND OBJECTIVE: There is evidence that opioid initiation post-surgery is contributing to the problem of chronic misuse and/or abuse of over the counter medications in the community, and that orthopedic patients may be particularly at risk. The aim of the systematic review with meta-analysis was to identify research that examined opioid use at 3, 6, and 12 months post-operatively by previously opioid naïve orthopedic surgery patients. Design, databases, and data treatment: A searched review with meta-analysis was undertaken. Eight databases were search. Meta-analyses conducted at all three time points (3 months, 6 months, and 12 months). RESULTS: The search yielded 779 records, and after screening, 13 papers were included in meta-analysis. Results provide strong evidence that post-operative opioid use amongst the opioid naïve is a real effect (7 percent at 3 months, 4 percent at 6 months, and 2 percent at 12 months). A Z-test for overall effect revealed strong evidence that this proportion was nonzero for opioid use at 3, 6, and 12 months (p < 0.001 for all time points). A small but significant proportion of opioid naïve patients who are prescribed opioids remain on these medications up to 12 months post-operatively. CONCLUSIONS: The nature of the studies included in the meta-analysis were varied, hence subanalyses regarding surgery type, characteristics of the patient group or other potential factors that might influence the progression to longer term opioid use after these surgeries could not be explored. Given this, further research in this area should explore such specific orthopedic subgroups.

New Australian guidelines for the treatment of alcohol problems: an overview of recommendations.

OF RECOMMENDATIONS AND LEVELS OF EVIDENCE: Chapter 2: Screening and assessment for unhealthy alcohol use Screening Screening for unhealthy alcohol use and appropriate interventions should be implemented in general practice (Level A), hospitals (Level B), emergency departments and community health and welfare settings (Level C). Quantity-frequency measures can detect consumption that exceeds levels in the current Australian guidelines (Level B). The Alcohol Use Disorders Identification Test (AUDIT) is the most effective screening tool and is recommended for use in primary care and hospital settings. For screening in the general community, the AUDIT-C is a suitable alternative (Level A). Indirect biological markers should be used as an adjunct to screening (Level A), and direct measures of alcohol in breath and/or blood can be useful markers of recent use (Level B). Assessment Assessment should include evaluation of alcohol use and its effects, physical examination, clinical investigations and collateral history taking (Level C). Assessment for alcohol-related physical problems, mental health problems and social support should be undertaken routinely (GPP). Where there are concerns regarding the safety of the patient or others, specialist consultation is recommended (Level C). Assessment should lead to a clear, mutually acceptable treatment plan which specifies interventions to meet the patient's needs (Level D). Sustained abstinence is the optimal outcome for most patients with alcohol dependence (Level C). Chapter 3: Caring for and managing patients with alcohol problems: interventions, treatments, relapse prevention, aftercare, and long term follow-up Brief interventions Brief motivational interviewing interventions are more effective than no treatment for people who consume alcohol at risky levels (Level A). Their effectiveness compared with standard care or alternative psychosocial interventions varies by treatment setting. They are most effective in primary care settings (Level A). Psychosocial interventions Cognitive behaviour therapy should be a first-line psychosocial intervention for alcohol dependence. Its clinical benefit is enhanced when it is combined with pharmacotherapy for alcohol dependence or an additional psychosocial intervention (eg, motivational interviewing) (Level A). Motivational interviewing is effective in the short term and in patients with less severe alcohol dependence (Level A). Residential rehabilitation may be of benefit to patients who have moderate-to-severe alcohol dependence and require a structured residential treatment setting (Level D). Alcohol withdrawal management Most cases of withdrawal can be managed in an ambulatory setting with appropriate support (Level B). Tapering diazepam regimens (Level A) with daily staged supply from a pharmacy or clinic are recommended (GPP). Pharmacotherapies for alcohol dependence Acamprosate is recommended to help maintain abstinence from alcohol (Level A). Naltrexone is recommended for prevention of relapse to heavy drinking (Level A). Disulfiram is only recommended in close supervision settings where patients are motivated for abstinence (Level A). Some evidence for off-label therapies baclofen and topiramate exists, but their side effect profiles are complex and neither should be a first-line medication (Level B). Peer support programs Peer-led support programs such as Alcoholics Anonymous and SMART Recovery are effective at maintaining abstinence or reductions in drinking (Level A). Relapse prevention, aftercare and long-term follow-up Return to problematic drinking is common and aftercare should focus on addressing factors that contribute to relapse (GPP). A harm-minimisation approach should be considered for patients who are unable to reduce their drinking (GPP). Chapter 4: Providing appropriate treatment and care to people with alcohol problems: a summary for key specific populations Gender-specific issues Screen women and men for domestic abuse (Level C). Consider child protection assessments for caregivers with alcohol use disorder (GPP). Explore contraceptive options with women of reproductive age who regularly consume alcohol (Level B). Pregnant and breastfeeding women Advise pregnant and breastfeeding women that there is no safe level of alcohol consumption (Level B). Pregnant women who are alcohol dependent should be admitted to hospital for treatment in an appropriate maternity unit that has an addiction specialist (GPP). Young people Perform a comprehensive HEEADSSS assessment for young people with alcohol problems (Level B). Treatment should focus on tangible benefits of reducing drinking through psychotherapy and engagement of family and peer networks (Level B). Aboriginal and Torres Strait Islander peoples Collaborate with Aboriginal or Torres Strait Islander health workers, organisations and communities, and seek guidance on patient engagement approaches (GPP). Use validated screening tools and consider integrated mainstream and Aboriginal or Torres Strait Islander-specific approaches to care (Level B). Culturally and linguistically diverse groups Use an appropriate method, such as the "teach-back" technique, to assess the need for language and health literacy support (Level C). Engage with culture-specific agencies as this can improve treatment access and success (Level C). Sexually diverse and gender diverse populations Be mindful that sexually diverse and gender diverse populations experience lower levels of satisfaction, connection and treatment completion (Level C). Seek to incorporate LGBTQ-specific treatment and agencies (Level C). Older people All new patients aged over 50 years should be screened for harmful alcohol use (Level D). Consider alcohol as a possible cause for older patients presenting with unexplained physical or psychological symptoms (Level D). Consider shorter acting benzodiazepines for withdrawal management (Level D). Cognitive impairment Cognitive impairment may impair engagement with treatment (Level A). Perform cognitive screening for patients who have alcohol problems and refer them for neuropsychological assessment if significant impairment is suspected (Level A). SUMMARY OF KEY RECOMMENDATIONS AND LEVELS OF EVIDENCE: Chapter 5: Understanding and managing comorbidities for people with alcohol problems: polydrug use and dependence, co-occurring mental disorders, and physical comorbidities Polydrug use and dependence Active alcohol use disorder, including dependence, significantly increases the risk of overdose associated with the administration of opioid drugs. Specialist advice is recommended before treatment of people dependent on both alcohol and opioid drugs (GPP). Older patients requiring management of alcohol withdrawal should have their use of pharmaceutical medications reviewed, given the prevalence of polypharmacy in this age group (GPP). Smoking cessation can be undertaken in patients with alcohol dependence and/or polydrug use problems; some evidence suggests varenicline may help support reduction of both tobacco and alcohol consumption (Level C). Co-occurring mental disorders More intensive interventions are needed for people with comorbid conditions, as this population tends to have more severe problems and carries a worse prognosis than those with single pathology (GPP). The Kessler Psychological Distress Scale (K10 or K6) is recommended for screening for comorbid mental disorders in people presenting for alcohol use disorders (Level A). People with alcohol use disorder and comorbid mental disorders should be offered treatment for both disorders; care should be taken to coordinate intervention (Level C). Physical comorbidities Patients should be advised that alcohol use has no beneficial health effects. There is no clear risk-free threshold for alcohol intake. The safe dose for alcohol intake is dependent on many factors such as underlying liver disease, comorbidities, age and sex (Level A). In patients with alcohol use disorder, early recognition of the risk for liver cirrhosis is critical. Patients with cirrhosis should abstain from alcohol and should be offered referral to a hepatologist for liver disease management and to an addiction physician for management of alcohol use disorder (Level A). Alcohol abstinence reduces the risk of cancer and improves outcomes after a diagnosis of cancer (Level A).

The 5-HT2C receptor as a therapeutic target for alcohol and methamphetamine use disorders: A pilot study in treatment-seeking individuals.

Alcohol use disorder (AUD) and methamphetamine use disorder (MUD) are prevalent and have high adverse impacts on both the individual and society. Current treatment strategies for these disorders are ineffective at a population level. Lorcaserin, a 5-HT2C receptor agonist, has shown potential at reducing the symptoms of substance use disorder. This pilot study (initiated prior to market withdrawal) examined feasibility and safety of lorcaserin treatment in people undergoing residential detoxification and treatment for AUD and MUD. This was an open label pilot study of lorcaserin where participants (n = 10 AUD; n = 8 MUD) received 10-mg lorcaserin daily for 4 days then twice daily for 1 month. Primary outcome measures included recruitment and retention rate, incidence of treatment-emergent events, incidence of methamphetamine or alcohol withdrawal-related events, heart rate, and blood pressure. Secondary measures included pharmacokinetic data and self-reported alcohol or methamphetamine use, craving, and psychological distress. AUD participants were recruited faster and had a greater retention rate compared with MUD participants. Lorcaserin did not alter vital signs, was well tolerated, and had a similar pharmacokinetic profile to individuals with obesity. Lorcaserin reduced self-reported alcohol and amphetamine-type substance use and craving in AUD and MUD participants, respectively. Self-reported psychological health also improved over the treatment period for all participants. Despite the pilot nature of this study, our data support the notion of 5-HT2C receptors as a therapeutic target for drug and alcohol abuse.

The fentanyls: pharmacological and clinical aspects relevant to Australia.

OBJECTIVE: North American and other jurisdictions have seen an alarming rise in the abuse of the fentanyls, with related overdose deaths. We sought to review this group of drugs to alert Australian psychiatrists and drug and alcohol clinicians to their clinical effects and potential harms. CONCLUSIONS: The extreme potency of the fentanyls underlie their lethality. Vigilance and investment from both policy makers and health care providers are required to mitigate harm from a possible future Australian fentanyl epidemic.

The fentanyls: a 'future threat' for Australia?

OBJECTIVE: The fentanyls have emerged as a significant public health threat in North America but much less so in Australia. We sought to identify reasons for this discrepancy and highlight harm reduction approaches that may mitigate a future Australian fentanyl epidemic. CONCLUSIONS: Differences in drug use 'culture' and a supply of cheap high-quality methamphetamine in Australia may be reasons for the observed difference in fentanyl-related harm. More worryingly, it is possible that Australia is following North American trends and that the fentanyl epidemic is still to come.

Opioid prescribing in the emergency department of a tertiary hospital: A retrospective audit of hospital discharge data.

OBJECTIVE: EDs are a common source of prescription opioids on discharge. We explored opioid prescribing practices in an ED at a tertiary hospital in Victoria, Australia. METHODS: A retrospective audit over a 6 month period of patients discharged from the ED to the community with the maximum allowable quantities of prescription opioids. RESULTS: There was a total of 3301 patient-episodes discharged with a prescription from the ED. Of these, 766 (23.2%, 95% confidence interval [CI] 21.8-24.6) were prescribed opioids, with over half discharged with the maximum allowable quantities of prescription opioids. Immediate-release opioids were prescribed in 362 (85.8%, 95% CI 82.5-89.1) patient-episodes, a combination of immediate-release and slow-release preparations were prescribed in 29 (6.9%, 95% CI 4.5-9.3) and 31 (7.3%, 95% CI 4.8-9.8) were prescribed as slow-release opioids alone. Co-prescription of other analgesia with opioids occurred in 152 (36.0%, 95% CI 31.4-40.6) patient-episodes. Possible drug interactions between opioids and other medications were noted in 117 (27.7%, 95% CI 23.4-32.0) patient-episodes. Discharge summaries were prepared for 360 (85.3%, 95% CI 81.9-88.7) patient-episodes, but only 171 (40.5%, 95% CI 35.8-45.2) included a plan to address the opioids, be that an opioid-weaning regimen, analgesia review or referral to a pain specialist on discharge. CONCLUSION: Opioid prescribing was common in this ED, with almost one-quarter of discharge prescriptions being for a prescription opioid. This audit highlights potential areas for practice improvement including review of the quantity of opioid tablets prescribed as well as an opioid plan on discharge from the ED.

Suvorexant to treat alcohol use disorder and comorbid insomnia: Plan for a phase II trial.

Alcohol use disorder (AUD) is a complex neuropsychiatric disease state in which currently approved pharmacotherapeutics are of relatively low effect at a population level. One reason for this may be that current pharmacotherapeutics focus on the reward pathway in relapse prevention, rather than addressing AUD from a holistic perspective. Importantly, one often overlooked symptom of AUD is sleep disruption. In recent years, an efficient, relatively low risk and economic strategy that has proven successful in other disorders is the repositioning or repurposing of drugs approved for the treatment of other indications. Suvorexant, a dual orexin receptor antagonist, has been licensed for the treatment of insomnia in the USA, Australia and Japan. The orexin system also plays a role in the emotional dysregulation that occurs during withdrawal from alcohol use and in alcohol-seeking behaviours. These two factors prompted the planning of a clinical trial into the use of suvorexant to treat insomnia in alcohol dependent individuals during and 24 weeks post-acute alcohol withdrawal. In this review we outline the comorbid nature of AUD and sleep disruptions. We then highlight the role of the orexin system in both sleep-wake regulation and AUD. Finally, we discuss our plan for a Phase II double blind placebo controlled trial examining the effectiveness of suvorexant for the treatment of comorbid insomnia and AUD.

Opioid prescribing improvement in orthopaedic specialty unit in a tertiary hospital: a retrospective audit of hospital discharge data pre- and post-intervention for better opioid prescribing practice.

BACKGROUND: This study aimed to investigate the effects of an intervention focusing on better opioid prescription practice in a tertiary metropolitan hospital orthopaedic unit. METHODS: Following a previous audit of opioid prescribing in the orthopaedics unit, an intervention comprising the (i) Expert Advisory Group oversight of opioid prescribing, (ii) development of a prescription opioid guideline for various hospital contexts and (iii) a series of education sessions was undertaken to improve opioid prescription practice. A re-audit was subsequently carried out to determine whether the intervention had had an impact on the previously audited orthopaedic unit. RESULTS: Each audit period was 6 months. There were 281 orthopaedic patients in the original audit (1 January 2017-30 June 2017) and 289 in the re-audit (1 March 2018-31 August 2018). In both audits, a high proportion of patients were discharged to the community on opioids, 82.2% (n = 231) pre-intervention and 79.6% (n = 230) post-intervention. Statistically significant differences in opioid prescribing were found between audits, including: a reduction in the number of patients discharged on combination opioids from 71.4% to 45.7% (P < 0.001), a reduction in the provision of full pharmaceutical quantities of opioid on discharge from 29.4% to 6.1% (P < 0.001) and an increase in opioid weaning plans included in discharge summaries from 6.9% to 87.4% (P < 0.001). CONCLUSION: Raised awareness across the organization and education for staff more than halved the post-operative opioid prescription levels. This highlights the capacity for change in hospitals and the ability to work towards safer prescribing of post-operative opioid therapy.

The Australian drug harms ranking study.

BACKGROUND/AIM: The aim of the current study was to review drug harms as they occur in Australia using the Multi-criteria Decision Analysis (MCDA) methodology adopted in earlier studies in other jurisdictions. METHOD: A facilitated workshop with 25 experts from across Australia, was held to score 22 drugs on 16 criteria: 9 related to harms that a drug produces in the individual and 7 to harms to others. Participants were guided by facilitators through the methodology and principles of MCDA. In open discussion, each drug was scored on each criterion. The criteria were then weighted using a process of swing weighting. Scoring was captured in MCDA software tool. RESULTS: MCDA modelling showed the most harmful substances to users were fentanyls (part score 50), heroin (part score 45) and crystal methamphetamine (part score 42). The most harmful substances to others were alcohol (part score 41), crystal methamphetamine (part score 24) and cigarettes/tobacco (part score 14). Overall, alcohol was the most harmful drug when harm to users and harm to others was combined. A supplementary analysis took into consideration the prevalence of each substance in Australia. Alcohol was again ranked the most harmful substance overall, followed by cigarettes, crystal methamphetamine, cannabis, heroin and pharmaceutical opioids. CONCLUSIONS: The results of this study make an important contribution to the emerging international picture of drug harms. They highlight the persistent and pervasive harms caused by alcohol. Policy implications and recommendations are discussed. Policies to reduce harm from alcohol and methamphetamine should be a priority.

Opioid prescribing in orthopaedic and neurosurgical specialties in a tertiary hospital: a retrospective audit of hospital discharge data.

BACKGROUND: To understand patterns of opioid prescribing on discharge in the orthopaedic and neurosurgical wards of a tertiary metropolitan hospital. METHODS: A retrospective audit of medical records and discharge summaries for all orthopaedic and neurosurgical patients admitted for at least 2 days on two surgical wards over a 6-month period between 1 January and 30 June 2017. RESULTS: A combined total of 355 patients (281 orthopaedic and 74 neurosurgical patients) were included in the audit. Approximately 82% were discharged on opioids. Of patients discharged on opioids, 71.4% of the orthopaedic group and 73.8% of the neurosurgical group were discharged on combinations of two or more opioids (immediate release together with slow release). Around 65% of the sample discharged on opioids was opioid naïve on admission. About 32.5% of the orthopaedic patients and 68.9% of the neurosurgical patients were discharged on a combination of opioid and other pharmacotherapy that could potentiate the central nervous system depressant effect of the opioids. Only 6.9% of orthopaedic patients and 11.5% of the neurosurgical patients had discharge summaries that included any reference to opioid management after discharge. CONCLUSION: Orthopaedic and neurosurgical units had high opioid prescribing rates on discharge from hospital. This highlights the need for clear communication of the intended medication management plan post-discharge in order to minimize inappropriate and ongoing use of opioids post-surgery.

Acceleration of cardiovascular-biological age by amphetamine exposure is a power function of chronological age.

BACKGROUND: Amphetamine abuse is becoming more widespread internationally. The possibility that its many cardiovascular complications are associated with a prematurely aged cardiovascular system, and indeed biological organism systemically, has not been addressed. METHODS: Radial arterial pulse tonometry was performed using the SphygmoCor system (Sydney). 55 amphetamine exposed patients were compared with 107 tobacco smokers, 483 non-smokers and 68 methadone patients (total=713 patients) from 2006 to 2011. A cardiovascular-biological age (VA) was determined. RESULTS: The age of the patient groups was 30.03±0.51-40.45±1.15 years. This was controlled for with linear regression. The sex ratio was the same in all groups. 94% of amphetamine exposed patients had used amphetamine in the previous week. When the (log) VA was regressed against the chronological age (CA) and a substance-type group in both cross-sectional and longitudinal models, models quadratic in CA were superior to linear models (both p<0.02). When log VA/CA was regressed in a mixed effects model against time, body mass index, CA and drug type, the cubic model was superior to the linear model (p=0.001). Interactions between CA, (CA)2 and (CA)3 on the one hand and exposure type were significant from p=0.0120. The effects of amphetamine exposure persisted after adjustment for all known cardiovascular risk factors (p<0.0001). CONCLUSIONS: These results show that subacute exposure to amphetamines is associated with an advancement of cardiovascular-organismal age both over age and over time, and is robust to adjustment. That this is associated with power functions of age implies a feed-forward positively reinforcing exacerbation of the underlying ageing process.

Cannabis exposure as an interactive cardiovascular risk factor and accelerant of organismal ageing: a longitudinal study.

OBJECTIVES: Many reports exist of the cardiovascular toxicity of smoked cannabis but none of arterial stiffness measures or vascular age (VA). In view of its diverse toxicology, the possibility that cannabis-exposed patients may be ageing more quickly requires investigation. DESIGN: Cross-sectional and longitudinal, observational. Prospective. SETTING: Single primary care addiction clinic in Brisbane, Australia. PARTICIPANTS: 11 cannabis-only smokers, 504 tobacco-only smokers, 114 tobacco and cannabis smokers and 534 non-smokers. EXCLUSIONS: known cardiovascular disease or therapy or acute exposure to alcohol, amphetamine, heroin or methadone. INTERVENTION: Radial arterial pulse wave tonometry (AtCor, SphygmoCor, Sydney) performed opportunistically and sequentially on patients between 2006 and 2011. MAIN OUTCOME MEASURE: Algorithmically calculated VA. SECONDARY OUTCOMES: other central haemodynamic variables. RESULTS: Differences between group chronological ages (CA, 30.47±0.48 to 40.36±2.44, mean±SEM) were controlled with linear regression. Between-group sex differences were controlled by single-sex analysis. Mean cannabis exposure among patients was 37.67±7.16 g-years. In regression models controlling for CA, Body Mass Index (BMI), time and inhalant group, the effect of cannabis use on VA was significant in males (p=0.0156) and females (p=0.0084). The effect size in males was 11.84%. A dose-response relationship was demonstrated with lifetime exposure (p<0.002) additional to that of tobacco and opioids. In both sexes, the effect of cannabis was robust to adjustment and was unrelated to its acute effects. Significant power interactions between cannabis exposure and the square and cube of CA were demonstrated (from p<0.002). CONCLUSIONS: Cannabis is an interactive cardiovascular risk factor (additional to tobacco and opioids), shows a prominent dose-response effect and is robust to adjustment. Cannabis use is associated with an acceleration of the cardiovascular age, which is a powerful surrogate for the organismal-biological age. This likely underlies and bi-directionally interacts with its diverse toxicological profile and is of considerable public health and regulatory importance.