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Background: Prior studies evaluating observation versus angioembolization (AE) for blunt liver injuries (BLT) with contrast extravasation (CE) on computed tomography imaging have yielded inconsistent conclusions, primarily due to limitations in single-center and/or retrospective study design. Therefore, this multicenter study aims to compare an observation versus AE-first approach for BLT, hypothesizing decreased liver-related complications (LRCs) with observation., Methods: We conducted a post hoc analysis of a multicenter, prospective observational study (2019-2021) across 23 centers. Adult patients with BLT + CE undergoing observation or AE within 8 hours of arrival were included. The primary outcome was LRCs, defined as perihepatic fluid collection, bile leak/biloma, pseudoaneurysm, hepatic necrosis, and/or hepatic abscess. A multivariable logistic regression analysis was used to evaluate risk factors associated with LRCs., Results: From 128 patients presenting with BLT + CE on imaging, 71 (55.5%) underwent observation-first and 57 (45.5%) AE-first management. Both groups were comparable in age, vitals, mechanism of injury, and shock index (all p > 0.05), however the AE group had increased frequency of American Association for the Surgery of Trauma Grade IV injuries (51.0% vs. 22.0%, p = 0.002). The AE cohort demonstrated increased rates of in-hospital LRCs (36.8% vs. 12.7%, p = 0.038), emergency department representation (25.0% vs. 10.0%, p = 0.025), and hospital readmission for LRCs (12.3% vs. 1.4%, p = 0.012). However, the two cohorts had similar mortality rates (5.7% vs. 5.3%, p = 0.912). After adjusting for age, ISS, and grade of liver injury, an AE-first approach had a similar associated risk of LRCs compared with observation-first management (odds ratio, 1.949; 95% confidence interval, 0.673-5.643; p = 0.219)., Conclusion: Patients with blunt liver injury and CE undergoing an observation-first approach were associated with a similar adjusted risk of LRCs and rate of mortality compared with AE-first approach. Overall, this calls for reevaluation of the role of routine AE in blunt liver trauma patients with CE. Future prospective randomized trials are needed to confirm these findings., Level of Evidence: Therapeutic/Care Management, Level IV., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Routine outcome monitoring (ROM) and feedback is an evidence-supported strategy for evaluating alcohol and other drug (AOD) treatment outcomes. However, the implementation of ROM and feedback into AOD services remains a significant challenge. Research aimed at understanding client perspectives on ROM and feedback is needed to facilitate successful implementation. This study examined experiences with and perceptions of ROM and feedback in a sample of clients receiving AOD treatment., Methods: Interviews and online surveys were conducted with N = 26 people (13 male; M age  = 36.12 years, SD = 10.29) enrolled in an AOD treatment program in Australia. Data analysis of the transcripts was guided by thematic analysis, while descriptive statistics were used to analyse quantitative survey data., Results: Four major themes were identified in the qualitative data: (i) ROM and feedback is valuable to AOD treatment; (ii) clear and concise outcome measures with an integrated feedback loop are vital to reliable ROM; (iii) desire for visual and verbal feedback that highlights progress; and (iv) ROM and feedback can be emotionally challenging., Discussion and Conclusions: Participants valued ROM when it was clearly integrated within AOD treatment and they received feedback on their responses. Potential facilitators to implementing and improving the provision of ROM and feedback in AOD treatment include: (i) a clear, treatment-based rationale to foster client buy-in for ROM and maximise AOD treatment benefit; (ii) brief outcome measure surveys; and (iii) graphical visualisations of ROM feedback., (© 2024 Australasian Professional Society on Alcohol and other Drugs.)

Introduction: The costs of providing medication-assisted treatment for opioid dependence can determine its scale of provision. To provide estimates of the costs of extended-release buprenorphine (BUP-XR), we performed a bottom-up costing analysis of provider operational treatment costs., Methods: Data were collected in a single-arm open label trial of BUP-XR injections conducted in specialist public drug treatment services and primary care private practices in three Australian states (the CoLAB study). The unit costs of resources used for each activity were combined with quantities used at each participating facility to arrive at the average annual cost per client., Results: One hundred participants across the six health facility sites received monthly subcutaneous BUP-XR injections administered by a health-care practitioner. The average cost of providing 1 year of treatment per participant was $6656 ($6026-$8326). Screening cost (initial assessment and medical history) was $282 while monthly follow-up appointments cost $531 per client. The main cost driver was the monthly treatment costs accounting for 79% of the average annual client cost, with medication costs comprising 95% of this cost., Discussion and Conclusion: With medication costs making up the largest proportion of treatment costs, treatment using BUP-XR has the potential to free up other health system resources, for example, staff time. The costs reported in this study can be used in an economic evaluation to estimate the net benefit or cost-effectiveness of BUP-XR especially when compared to other opioid agonist treatments., (© 2024 The Author(s). Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Background: A major alcohol-related harm is structural pathology affecting the brain. The study aimed to: 1. Determine the frequency and nature of neuropathology amongst cases of death due to acute alcohol toxicity; 2. Compare diagnoses of brain atrophy with pathology in other organs; 3. Determine the demographic, clinical and organ pathology correlates of brain atrophy., Methods: Retrospective study of 500 cases of death attributed to acute alcohol toxicity in Australia, 2011-2022. Data on clinical characteristics, toxicology, neuropathology and other organ pathology were retrieved from police reports, autopsies, toxicology and coronial findings., Results: Mean age was 49.5 years, 69.4 % were male, with alcohol use problems documented in 70.2 %. Brain atrophy was diagnosed in 60 cases (12.0 %), most commonly in the cerebellum (32 cases, 6.4 %). Atrophy at other sites was present in 37 (7.4 %). The presence of brain atrophy was lower than other major pathologies: cardiomegaly (32.6 %, p<.001), nephro/arteriosclerosis (30.2 %, p<.001), and chronic obstructive pulmonary disease (21.8 %, p<.001) but not hepatic cirrhosis (11.9 % p=1.0). Those diagnosed with atrophy were older (53.4v 49.0 years, p<.001), more likely to have documented alcohol problems (85.0v 68.2 %, Odds ratio: OR 2.53) and seizure history (10.0v 3.0 %, OR 2.92), to have cardiomegaly (43.3v 31.0 %, OR 1.90, COPD (48.3v 18.2 %, 3.57) and nephro/arteriosclerosis (50.0 v 27.4 %, OR 2.27)., Conclusions: Despite the majority of cases having a history of alcohol problems, the level of neuropathology amongst cases of death due to acute alcohol toxicity was comparatively low., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AP has received untied educational grants from Seqirus and Mundipharma for post-marketing surveillance of pharmaceutical opioids. This organisation had no role in study design, analysis and reporting, and funding support was for work unrelated to this project. MF has received untied educational grants from Seqirus, Mundipharma and Indivior for post-marketing surveillance of pharmaceutical opioids. This organisation had no role in study design, analysis and reporting, and funding support was for work unrelated to this project. AP is funded by an NHMRC Investigator Fellowship., (Copyright © 2024. Published by Elsevier B.V.)

Background: One third of organ donors suffer catastrophic brain injury (CBI). There are no standard guidelines for the management of traumatic CBI prior to brain death, and not all trauma centers have institutional CBI guidelines. In addition, there is high variability in management between institutions with guidelines. Catastrophic brain injury guidelines vary and may include various combinations of hormone therapy, vasopressors, fluid resuscitation, and other practices. We hypothesized that centers with CBI guidelines have higher organ donation rates than those without., Methods: This prospective, observational EAST-sponsored multicenter trial included adult (18+ years old) traumatic-mechanism CBI patients at 33 level I and II trauma centers from January 2022 to May 2023. Catastrophic brain injury was defined as a brain injury causing loss of function above the brain stem and subsequent death. Cluster analysis with linear mixed-effects model including UNOS regions and hospital size by bed count was used to determine whether CBI guidelines are associated with organ donation., Results: A total of 790 CBI patients were included in this analysis. In unadjusted comparison, CBI guideline centers had higher rates of organ donation and use of steroids, whole blood, and hormone therapy. In a linear mixed-effects model, CBI guidelines were not associated with organ donation. Registered organ donor status, steroid hormones, and vasopressin were associated with increased relative risk of donation., Conclusion: There is high variability in management of CBI, even at centers with CBI guidelines in place. While the use of institutional CBI guidelines was not associated with increased organ donation, guidelines in this study were not identical. Hormone replacement with steroids and vasopressin was associated with increased donation. Hormone resuscitation is a common feature of CBI guidelines. Further analysis of individual practices that increase organ donation after CBI may allow for more effective guidelines and an overall increase in donation to decrease the long waiting periods for organ transplant recipients., Level of Evidence: Prognostic; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

At the beginning of the COVID-19 pandemic, the Georgia Institute of Technology made the decision to keep the university doors open for on-campus attendance. To manage COVID-19 infection rates, internal resources were applied to develop and implement a mass asymptomatic surveillance program. The objective was to identify infections early for proper follow-on verification testing, contact tracing, and quarantine/isolation as needed. Program success depended on frequent and voluntary sample collection from over 40,000 students, faculty, and staff personnel. At that time, the nasopharyngeal (NP) swab, not saliva, was the main accepted sample type for COVID-19 testing. However, due to collection discomfort and the inability to be self-collected, the NP swab was not feasible for voluntary and frequent self-collection. Therefore, saliva was selected as the clinical sample type and validated. A saliva collection kit and a sample processing and analysis workflow were developed. The results of a clinical sample-type comparison study between co-collected and matched NP swabs and saliva samples showed 96.7% positive agreement and 100% negative agreement. During the Fall 2020 and Spring 2021 semesters, 319,988 samples were collected and tested. The program resulted in maintaining a low overall mean positivity rate of 0.78% and 0.54% for the Fall 2020 and Spring 2021 semesters, respectively. For this high-throughput asymptomatic COVID-19 screening application, saliva was an exceptionally good sample type.

Introduction: Recent media reports highlight that drug-related fatalities can occur while individuals are immersed in water in domestic settings. We aimed to determine the case characteristics, circumstances of death and type of implicated drugs among individuals dying due to unintentional drug-related causes found immersed in a bath or hot tub., Methods: Retrospective cohort study in the United Kingdom using coronial records from the National Programme on Substance Abuse Deaths, 1997-2023. Information was available on decedent socio-demographics, characteristics of death and drugs implicated in death., Results: One hundred fifty-six decedents were found immersed in the bath and six in a hot tub, a mean of 6.4 deaths per year (SD 3.7; range 1-13). Overall decedents were predominantly male (n = 94, 58.0%), of White ethnicity (n = 98, 60.5%) with a mean age of 40 years (SD 13; range 19-74). Only 12 decedents had any physical contributory factor to death other than poisoning or drowning. The median number of drugs detected at post-mortem was 3 (interquartile range 2, 5) with multiple drug toxicity implicated in the majority of cases (n = 90, 55.6%). The most common implicated drugs were heroin (n = 53, 32.7%), alcohol (n = 46, 28.4%) and cocaine (n = 33, 20.4%)., Discussion and Conclusions: Over the last two decades in the United Kingdom there have been consistent numbers of unintentional drug-related deaths each year where individuals were found in a bath or hot tub. Polysubstance, opioid and alcohol use are overrepresented. Targeted advice to avoid bathing while intoxicated would appear to be an appropriate harm reduction message., (© 2024 The Author(s). Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Introduction: In recent years gamma hydroxybutyrate (GHB) use appears to have increased. This study aimed to determine: (i) population rates of GHB-related death in Australia, 2001-2021; and (ii) whether there have been changes in the characteristics of GHB-related death in Australia over the period 2001-2023., Methods: Retrospective study of all Australian cases in which GHB was a mechanism contributory to death retrieved from the National Coronial Information System (n = 217). Joinpoint regression models were used to analyse trends in overall rates., Results: Death rates were stable between 2001 and 2015 ('stable period') (annual percent change [APC] = 3.7) but showed marked acceleration between 2016 and 2021 ('accelerated period') (APC = 44.4). Circumstances of death were: unintentional toxicity (81.6%), intentional toxicity (5.1%), self-harm (6.0%), traumatic injury (7.4%). Compared to the stable period, later cases were slightly older (34.2 vs. 30.7 years, p < 0.05), less likely to be employed (odds ratio [OR] 0.4), but more likely to have substance use problems (OR 3.9), a history of injecting drug use (OR 3.5), mental health problems (OR 3.6), and to have present in their blood at toxicological screening opioids (OR 3.2) and hypnosedatives (OR 3.7). The median blood GHB concentration was 170 mg/L, (range 0-3210), which did not change significantly. There were no differences in major organ pathology, but the proportion with aspiration pneumonia declined (OR 0.4)., Discussion and Conclusions: GHB-related death rates increased from 2016, accompanied by changes in case characteristics. In recent years GHB use appears to have extended to a population more likely to have substance use problems and use other respiratory depressants., (© 2024 The Author(s). Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Background: Mortality, suicide, self-harm, and substance use are elevated among people who are incarcerated. There is a wide range of heterogeneous interventions aimed at reducing these harms in this population. Previous reviews have focused on specific interventions or limited their findings to drug use and recidivism and have not explored interventions delivered after release from prison. Our aim is to examine the effect of interventions delivered to people who use drugs during incarceration or after release from incarceration, on a wide range of outcomes., Methods: In this systematic review and meta-analysis, we searched Embase, MEDLINE, and PsycINFO databases up until Sept 12, 2023 for studies published from Jan 1, 1980 onwards. All studies evaluating the effectiveness of any intervention on drug use, recidivism outcomes, sexual or injecting risk behaviours, or mortality among people who use psychoactive drugs and who were currently or recently incarcerated were included. Studies without a comparator or measuring only alcohol use were excluded. Data extracted from each study included demographic characteristics, interventions, and comparisons. Pooled odds ratios and risk ratios were calculated using random-effects meta-analyses., Findings: We identified 126 eligible studies (47 randomised controlled trials and 79 observational studies) encompassing 18 interventions; receiving opioid-agonist treatment (OAT) in prison reduced the risk of death in prison (one study; hazard ratio 0·25; 95% CI 0·13-0·48), whereas receiving OAT in the first 4 weeks following release reduced risk of death in the community (two studies; relative risk 0·24; 95% CI 0·15-0·37). Therapeutic community interventions reduced re-arrest at 6-12 months (six studies; odds ratio [OR] 0·72; 95% CI 0·55-0·95) and reincarceration at 24 months (two studies; OR 0·66; 95% CI 0·48-0·96). There was scarce evidence that OAT and syringe service provision are effective in reducing injecting risk behaviours and needle and syringe sharing., Interpretation: There are effective interventions to reduce mortality and recidivism for people who use drugs who have been incarcerated. Nonetheless, there are also substantial gaps in the research examining the effect of interventions on risk behaviours and mortality during incarceration and a need for randomised designs examining outcomes for people who use drugs after release., Funding: Australian National Health and Medical Research Council., Competing Interests: Declaration of interests In the past 3 years, LD and MF have received investigator-initiated untied educational grants for studies of opioid medications in Australia from Indivior and Seqirus. FLA has had grants from the US National Institutes of Health, Gilead Sciences, and MSD over the past 3 years. JG is a consultant or advisor and has received research grants from AbbVie, bioLytical, Camurus, Cepheid, Gilead Sciences, Hologic, Indivior, and Merck or MSD. These companies and organisations had no knowledge of or role in the design, conduct, interpretation, or publication of these findings. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Lysergic acid diethylamide (LSD) and psilocybin are used as recreational drugs, and there is renewed interest in their clinical use. The current study aimed to (1) determine the circumstances of death and case characteristics of LSD- and psilocybin-related death in Australia, 2000-23; and (2) determine the toxicological profile and major autopsy findings of these cases., Methods: This was a retrospective exploratory study of all cases of LSD- and psilocybin-related death in Australia, 2000-23, retrieved from the National Coronial Information System., Results: A total of 43 cases were identified: 33 LSD and 10 psilocybin. The median ages were 24 years [interquartile range (IQR) = 13, range = 16-53] (LSD) and 26 years (IQR = 18.5, range = 20-58) (psilocybin), and fewer than five cases were female. The most common circumstance of death among both groups was traumatic accident (LSD 36.4%, psilocybin 40.0%). There were 12 cases of self-harm, all of which involved LSD, all by physical means. In a fifth, death was attributed to multiple drug toxicity (LSD 18.2%, psilocybin 20.0%). In one case, death was attributed solely to LSD toxicity, while in a further two cases death was attributed to a cardiovascular event following LSD consumption (one LSD only, one multiple drug toxicity). In four psilocybin cases, the cause of death was undetermined. The most common clinical presentation was severe agitation (LSD 27.3%, psilocybin 20.0%). Median blood concentrations were LSD 0.8 μg/l (IQR = 1.7, range = 0.1-3), psilocin 20 μg/l (IQR = 53.5, range = 6-83). LSD was the only drug present in 25.0% of LSD cases and psilocybin in 20.0% of psilocybin cases. Pre-existing organ pathology was uncommon., Conclusions: Lysergic acid diethylamide (LSD)- and psilocybin-related death in Australia from 2000 to 2023 was primarily due to traumatic injury, whether through accident or self-harm. Cases of acute toxic reactions that were attributed solely to LSD were rare., (© 2024 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Epilepsy is a neurological disease characterised by recurrent seizures with complex aetiology. Temporal lobe epilepsy, the most common form in adults, can be acquired following brain insults including trauma, stroke, infection or sustained status epilepticus. The mechanisms that give rise to the formation and maintenance of hyperexcitable networks following acquired insults remain unknown, yet an extensive body of literature points towards persistent gene and epigenomic dysregulation as a potential mediator of this dysfunction. While much is known about the function of specific classes of epigenetic regulators (writers and erasers) in epilepsy, much less is known about the enzymes, which read the epigenome and modulate gene expression accordingly. Here, we explore the potential role for the epigenetic reader bromodomain and extra-terminal domain (BET) proteins in epilepsy. Using the intra-amygdala kainic acid model of temporal lobe epilepsy, we initially identified widespread dysregulation of important epigenetic regulators including EZH2 and REST as well as altered BRD4 expression in chronically epileptic mice. BRD4 activity was also notably affected by epilepsy-provoking insults as seen by elevated binding to and transcriptional regulation of the immediate early gene Fos. Despite influencing early aspects of epileptogenesis, blocking BET protein activity with JQ1 had no overt effects on epilepsy development in mice but did alter glial reactivity and influence gene expression patterns, promoting various neurotransmitter signalling mechanisms and inflammatory pathways in the hippocampus. Together, these results confirm that epigenetic reader activity is affected by epilepsy-provoking brain insults and that BET activity may exert cell-specific actions on inflammation in epilepsy., (© 2024 The Author(s). European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Purpose: Deaths due to substance poisoning, alcohol-related disease, and suicide pose a critical public health issue, and have been categorized as "deaths of despair" in the US. Whether these deaths represent a distinct phenomenon requires exploration, particularly in other countries., Methods: This retrospective observational study examines age-period-cohort trends of (combined and cause-specific) substance poisoning, alcohol-related disease, and suicide deaths among Australians aged ≥15-years that occurred between 1980 and 2019 and compares trends between males and females., Results: Combined mortality rates were initially (1980-1999) relatively stable, reflecting a reduction in alcohol-related disease deaths offset by an increase in substance poisoning deaths. A decline (2000-2006) and subsequent increase (2007-2019) in combined rates were primarily attributable to corresponding changes in both substance poisoning and suicide deaths among males. Distinct age-period-cohort trends were observed between cause of death sub-types, with net drifts: increasing for male (net drift [95% CI]: 3.33 [2.84, 3.83]) and female (2.58 [2.18, 2.98]) substance poisoning deaths; decreasing among male alcohol-related disease (- 1.46 [- 1.75, - 1.16]) and suicide deaths (- 0.52[- 0.69, - 0.36]); and remaining relatively stable for female alcohol-related disease (- 0.28 [- 0.66, 0.09]) and suicide deaths (- 0.25 [- 0.52, 0.01])., Conclusions: Although combined age-specific trends were relatively stable over the study period, different and distinct patterns were observed within cause-specific deaths, challenging the notion that these causes of death represent a distinct epidemiological phenomenon. These data indicate a critical need to review the appropriateness of guidance for clinical practice, prevention strategies, and policy initiatives aimed at preventing future deaths., (© 2024. The Author(s).)

Background: Gambling behaviours have become of increased public health interest, but data on prevalence remain scarce. In this study, we aimed to estimate for adults and adolescents the prevalence of any gambling activity, the prevalence of engaging in specific gambling activities, the prevalence of any risk gambling and problematic gambling, and the prevalence of any risk and problematic gambling by gambling activity., Methods: We performed a systematic review and meta-analysis. We systematically searched for peer-reviewed literature (on MEDLINE, Embase, and PsycInfo) and grey literature to identify papers published between Jan 1, 2010, and March 4, 2024. We searched for any gambling, including engagement with individual gambling activities, and problematic gambling data among adults and adolescents. We included papers that reported the prevalence or proportion of a gambling outcome of interest. We excluded papers of non-original data or based on a biased sample. Data were extracted into a bespoke Microsoft Access database, with the Joanna Briggs Institute Critical Appraisal Tool used to identify the risk of bias for each sample. Representative population survey estimates were firstly meta-analysed into country-level prevalence estimates, using metaprop, of any gambling, any risk gambling, problematic gambling, and by gambling activity. Secondly, population-weighted regional-level and global estimates were generated for any gambling, any risk gambling, problematic gambling, and specific gambling activity. This review is registered on PROSPERO (CRD42021251835)., Findings: We screened 3692 reports, with 380 representative unique samples, in 68 countries and territories. Overall, the included samples consisted of slightly more men or male individuals, with a mean age of 29·72 years, and most samples identified were from high-income countries. Of these samples, 366 were included in the meta-analysis. Globally, 46·2% (95% CI 41·7-50·8) of adults and 17·9% (14·8-21·2) of adolescents had gambled in the past 12 months. Rates of gambling were higher among men (49·1%; 45·5-52·6) than women (37·4%; 32·0-42·5). Among adults, 8·7% (6·6-11·3) were classified as engaging in any risk gambling, and 1·41% (1·06-1·84) were engaging in problematic gambling. Among adults, rates of problematic gambling were greatest among online casino or slots gambling (15·8%; 10·7-21·6). There were few data reported on any risk and problematic gambling among adolescent samples., Interpretation: Existing evidence suggests that gambling is prevalent globally, that a substantial proportion of the population engage in problematic gambling, and that rates of problematic gambling are greatest among those gambling on online formats. Given the growth of the online gambling industry and the association between gambling and a range of public health harms, governments need to give greater attention to the strict regulation and monitoring of gambling globally., Funding: Australian National Health and Medical Research Council., Competing Interests: Declaration of interests In the last 5 years, HW has received grant funding for gambling-related research from The Economic and Social Research Council, National Institute for Health Research, Wellcome Trust, the Gambling Commission (including their regulatory settlement fund), Office of Health Disparities and Improvements and Public Health England, Greater London Authority, Greater Manchester Combined Authority, Blackburn with Darwen Local Authority, and the Department of Digital Culture Media and Sport; received funding from GambleAware in 2018–19 for a project on gambling and suicide; received consulting fees from the Institute of Public Health, Ireland, and the National Institute for Economic and Social Research; received payment for the delivery of seminars from McGill University, the University of Birmingham, Johns Hopkins University, and from the British Broadcasting Corporation; has been paid as an expert witness by Lambeth and Middlesbrough Borough Councils; has received travel costs paid by Gambling Regulators European Forum, the Turkish Green Crescent Society, Alberta Gambling Research Institute, the REITOX Academy (administered through the Austrian National Public Health Institute), and the University of Helsinki; served as the Deputy Chair of the Advisory Board for Safer Gambling between 2015 and 2020, remunerated by the Gambling Commission; is a member of the WHO panel on gambling (ongoing); provided unpaid advice on research to GamCare for their Safer Gambling Standard (until mid-2021); runs a research consultancy for public and third sector bodies only, but has not, and does not, provide consultancy services to gambling industry actors; in researching the gambling industry and their practices, has occasionally attended events where gambling industry actors are present (including industry-sponsored conferences); and as part of her work on the Gambling Survey for Great Britain, is required by the Gambling Commission (the funder) to participate in events disseminating research findings to their stakeholders, which includes the industry, but is independently funded and does not involve collaborations or partnerships with industry. VM has received grant funding for gambling-related projects from the Academy of Finland (project numbers 349589 and 31834), the Finnish Ministry of Social Affairs and Health, and the Finnish Ministry of Justice; as a member of the Gambling Harms Evaluation Committee (2021 onwards) and the Indicators for Gambling Harms work group (2019–21) under the Finnish Ministry of Social Affairs and Health, she interacts with the Finnish gambling monopoly to evaluate company products and practices and to analyse company data; has received a fee for delivering a webinar from Bochum University; did a paid peer review for Routledge; received funding for travel from the Finnish Foundation for Alcohol Studies, University of Bergen, and the Council of Europe; and provides consultation for public and third sector actors, but not the gambling industry. CB has received grant funding for gambling-related projects from The British Academy, The Economic and Social Research Council, the National Institute of Health Research, Blackburn with Darwen Local Authority, and the Department for Culture, Media and Sport. RV has received grant funding for gambling-related projects from the Massachusetts Gaming Commission, the Connecticut Department of Mental Health & Addiction Services, the Evergreen Council for Problem Gambling, The University of Massachusetts Donahue Institute, Gambling Research Exchange Ontario, NORC Boston, North Dakota Department of Health & Human Services, British Gambling Commission, Public Health Agency of Sweden, Canadian Centre on Substance Abuse, and the Center for Gambling Studies, Rutgers University; has received consultancy fees for gambling-related research from the National Centre for Social Research UK, Gambling Research Exchange Ontario, and the Karolinska Institute; has received honorarium from McGill University for the delivery of a webinar, from the Evergreen Council on Problem Gambling, the Institut für Glücksspiel und Gesellschaft, and the New York State Council on Problem Gambling; and has received travel costs from the Alberta Gambling Research Institute in 2022 and 2023 and from the Nigerian National Lotteries Regulatory Commission in 2023. JR has received funding from various national and international public funding agencies (the Canadian Institutes of Health Research, US National Institutes of Health, the EU, and WHO); and funding for travel from WHO. In the past 5 years, LD and MF have received untied educational grant funding from Indivior and Seqirus for the study of new opioid medications in Australia. SS has been a senior advisor to the McKinsey Health Institute since 2023 for issues on mental health. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: High-grade liver injuries with extravasation (HGLI ​+ ​Extrav) are associated with morbidity/mortality. For low-grade injuries, an observation (OBS) first-strategy is beneficial over initial angiography (IR), however, it is unclear if OBS is safe for HGLI ​+ ​Extrav. Therefore, we evaluated the management of HGLI ​+ ​Extrav patients, hypothesizing IR patients will have decreased rates of operation and mortality., Methods: HGLI ​+ ​Extrav patients managed with initial OBS or IR were included. The primary outcome was need for operation. Secondary outcomes included liver-related complications (LRCs) and mortality., Results: From 59 patients, 23 (39.0%) were managed with OBS and 36 (61.0%) with IR. 75% of IR patients underwent angioembolization, whereas 13% of OBS patients underwent any IR, all undergoing angioembolization. IR patients had an increased rate of operation (13.9% vs. 0%, p ​= ​0.049), but no difference in LRCs (44.4% vs. 43.5%) or mortality (5.6% vs. 8.7%) versus OBS patients (both p ​> ​0.05)., Conclusion: Over 60% of patients were managed with IR initially. IR patients had an increased rate of operation yet similar rates of LRCs and mortality, suggesting initial OBS reasonable in appropriately selected HGLI ​+ ​Extrav patients., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Chronic pain involves communication between neural and immune systems. Recent data suggest localization of glial (brain immune cells) activation to the sensorimotor regions of the brain cortex (S1/M1) in chronic low back pain (LBP). As glia perform diverse functions that impact neural function, activation might contribute to sensorimotor changes, particularly in LBP maintained by increased nervous system sensitivity (i.e., nociplastic pain). This preliminary proof-of-concept study aimed to: (i) compare evidence of neuroinflammatory activation in S1/M1 between individuals with and without LBP (and between nociceptive and nociplastic LBP phenotypes), and (ii) evaluate relationships between neuroinflammatory activation and sensorimotor function., Methods: Simultaneous PET-fMRI measured neuroinflammatory activation in functionally defined S1/M1 in pain-free individuals (n = 8) and individuals with chronic LBP (n = 9; nociceptive: n = 4, nociplastic: n = 5). Regions of S1/M1 related to the back were identified using fMRI during motor tasks and thermal stimuli. Sensorimotor measures included single and paired-pulse transcranial magnetic stimulation (TMS) and quantitative sensory testing (QST). Sleep, depression, disability and pain questionnaires were administered., Results: Neuroinflammatory activation was greater in the lower back cortical representation of S1/M1 of the nociplastic LBP group than both nociceptive LBP and pain-free groups. Neuroinflammatory activation in S1/M1 was positively correlated with sensitivity to hot (r = 0.52) and cold (r = 0.55) pain stimuli, poor sleep, depression, disability and BMI, and negatively correlated with intracortical facilitation (r = -0.41)., Conclusion: This preliminary proof-of-concept study suggests that neuroinflammation in back regions of S1/M1 in individuals with nociplastic LBP could plausibly explain some characteristic features of this LBP phenotype., Significance Statement: Neuroinflammatory activation localized to sensorimotor areas of the brain in individuals with nociplastic pain might contribute to changes in sensory and motor function and aspects of central sensitization. If cause-effect relationships are established in longitudinal studies, this may direct development of therapies that target neuroinflammatory activation., (© 2024 The Author(s). European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®.)

Competing Interests: The National Drug and Alcohol Research Centre is supported by funding from the Australian Government Department of Health under the Drug and Alcohol Programme. We declare no competing interests.

Introduction: Contingency management (CM) is the most effective treatment for reducing methamphetamine use. We sought to understand why CM has not been taken up to manage methamphetamine use disorder in Australia., Methods: Six focus groups (4-8 participants per group) were conducted with health workers from agencies in Australia that provided drug-related health care to people who use methamphetamine. These agencies had no previous experience delivering CM for substance use. The potential acceptability and feasibility of implementing CM in their services were discussed., Results: Participants felt that it would be beneficial to have an evidence-based treatment for methamphetamine use disorder. This sentiment was offset by concerns that CM conflicted with a client-centred harm-reduction approach and that it dictated the goal of treatment as abstinence. It was also perceived as potentially coercive and seen to reify the power imbalance in the therapeutic relationship and therefore potentially reinforce stigma. There was also concern about the public's perception and the political acceptability of CM, who would fund CM, and the inequity of providing incentives only to clients with a methamphetamine use disorder. Some concerns could be ameliorated if the goals and structure of CM could be tailored to a client's needs., Discussion and Conclusions: Many healthcare workers were keen to offer CM as an effective treatment option for people with methamphetamine use disorder, but CM would need to be sufficiently flexible to allow it to be tailored to client needs and implemented in a way that did not adversely impact the therapeutic relationship., (© 2024 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Introduction: The aim of this paper was to examine the client and psychosocial characteristics associated with polydrug use in patients with alcohol misuse as their primary drug of concern (PDC) seeking treatment from substance use treatment centres., Methods: Self-report surveys were undertaken with clients attending 1 of 34 community-based substance use treatment centres across Australia with alcohol as their PDC. Survey items included client's socio-demographic characteristics, level of alcohol dependence, use of other drugs including tobacco, health and wellbeing factors including health-related quality of life. The factors associated with polydrug use (alcohol use concurrent with at least one other drug) were examined., Results: In a sample of 1130 clients seeking treatment primarily for alcohol problems, 71% reported also using another drug. The most frequently used drug was tobacco (50%) followed by cannabis (21%) and benzodiazepines (15%). Excluding tobacco use, 35% of participants reported polydrug use. Factors associated with any polydrug use were younger age, lower education levels, lower levels of mental health related quality of life and housing risk (i.e., risk of eviction or experienced homelessness in past 4 weeks). When tobacco was excluded, factors associated with polydrug use were age, lower physical and mental health-related quality of life, and housing risk., Discussion and Conclusions: Most adults seeking treatment for alcohol misuse as their PDC reported using another drug in addition to alcohol. Treatment services should be designed accordingly to maximise the likelihood of treatment engagement and success., (© 2024 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

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., (© 2024. The Author(s).)

The use of prophylactic measures, including perioperative antibiotics, for the prevention of surgical site infections is a standard of care across surgical specialties. Unfortunately, the routine guidelines used for routine procedures do not always account for many of the factors encountered with urgent/emergent operations and critically ill or high-risk patients. This clinical consensus document created by the American Association for the Surgery of Trauma Critical Care Committee is one of a three-part series and reviews surgical and procedural antibiotic prophylaxis in the surgical intensive care unit. The purpose of this clinical consensus document is to provide practical recommendations, based on expert opinion, to assist intensive care providers with decision-making for surgical prophylaxis. We specifically evaluate the current state of periprocedural antibiotic management of external ventricular drains, orthopedic operations (closed and open fractures, silver dressings, local, antimicrobial adjuncts, spine surgery, subfascial drains), abdominal operations (bowel injury and open abdomen), and bedside procedures (thoracostomy tube, gastrostomy tube, tracheostomy)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The evaluation and workup of fever and the use of antibiotics to treat infections is part of daily practice in the surgical intensive care unit (ICU). Fever can be infectious or non-infectious; it is important to distinguish between the two entities wherever possible. The evidence is growing for shortening the duration of antibiotic treatment of common infections. The purpose of this clinical consensus document, created by the American Association for the Surgery of Trauma Critical Care Committee, is to synthesize the available evidence, and to provide practical recommendations. We discuss the evaluation of fever, the indications to obtain cultures including urine, blood, and respiratory specimens for diagnosis of infections, the use of procalcitonin, and the decision to initiate empiric antibiotics. We then describe the treatment of common infections, specifically ventilator-associated pneumonia, catheter-associated urinary infection, catheter-related bloodstream infection, bacteremia, surgical site infection, intra-abdominal infection, ventriculitis, and necrotizing soft tissue infection., Competing Interests: Competing interests: TC reports: Innovital—funding paid to my institution related to research performed; Cytovale—direct payments to me for research-related medical monitoring. SM reports: UpToDate—Author Royalty; AHRQ grant funding, but not related to this topic. LK reports: Eastern Association for the Surgery of Trauma Vice Chair Guidelines Committee; American Association for the Surgery of Trauma Palliative Care Committee, American Association for the Surgery of Trauma Critical Care Committee, American College of Surgeons Geriatric Surgery Verification Standards and Verification Committee, Journal of Surgical Research Editorial Board Member. DMS reports: grant funding from PCORI, DoD, NIH, NHTSA and consultant fees—CSL Behring., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objectives: Although factors associated with alcohol use have been researched at a population level, descriptions of the alcohol and other drug (AOD) treatment-seeking population in New South Wales (NSW), Australia, are limited. This study addresses this gap by analyzing sociodemographic and health characteristics in the NSW AOD treatment-seeking population., Methods: Self-reported Australian Treatment Outcomes Profile data on substance use, health ratings, and sociodemographic factors were acquired from public AOD services (offering services from counseling to ambulatory/inpatient withdrawal management) in 6 administrative health districts from 2016 to 2019 (n = 14,287). Gaussian and multiple logistic regressions were conducted to examine associations between these factors and alcohol consumption quantity., Results: Data were analyzed for patients seeking treatment for alcohol consumption specifically (n = 5929; median age, 44 years; 65% male). Valid alcohol consumption data were available for 5460 patients, among whom the mean volume of alcohol consumed was 311 standard drinks (3110 grams of ethanol) over the past 28 days and 15 standard drinks (150 grams of ethanol) per occasion. Higher volumes were consumed by males and those with recent experiences of violence and/or injecting drug use. Caring for children younger than 5 years and having above-median health ratings were associated with lower alcohol consumption., Conclusions: This study contributes to the characterization of the NSW public AOD treatment population and identifies associations between alcohol consumption, sociodemographic factors, and health ratings among people seeking treatment for alcohol consumption. Findings point towards multilevel assessment and comprehensive interventions for people engaging in treatment for alcohol use. Future research should address barriers to treatment., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 American Society of Addiction Medicine.)

Competing Interests: Competing interests: RG reports honoraria for lectures/presentations: Morristown Memorial Hospital—keynote speaker honorarium, payments made to the author; Leadership in Board/Society: Chair, Scientific Studies Committee, Surgical Infection Society—unpaid; Payment for Expert Testimony: Billing, Cochran, Lyles, Mauro & Ramsey PA; Rafi Law Firm; Foy & Associates PC. SM reports UpToDate—author royalty; AHRQ grant funding, but not related to this topic. TR reports receiving an honorarium from Stanford Hospital/Santa Clara Valley Medical Center for speaking at their annual trauma; support from the author's home institution (UC Davis) for attendance at meetings (WTA in 2022, 2023). DMS reports grant funding from PCORI, DoD, NIH, and NHTSA and consultant fees from CSL Behring.

Background: The management of acute necrotizing pancreatitis (ANP) has changed dramatically over the past 20 years including the use of less invasive techniques, the timing of interventions, nutritional management, and antimicrobial management. This study sought to create a core outcome set (COS) to help shape future research by establishing a minimal set of essential outcomes that will facilitate future comparisons and pooling of data while minimizing reporting bias., Methods: A modified Delphi process was performed through involvement of ANP content experts. Each expert proposed a list of outcomes for consideration, and the panel anonymously scored the outcomes on a 9-point Likert scale. Core outcome consensus defined a priori as >70% of scores receiving 7 to 9 points and <15% of scores receiving 1 to 3 points. Feedback and aggregate data were shared between rounds with interclass correlation trends used to determine the end of the study., Results: A total of 19 experts agreed to participate in the study with 16 (84%) participating through study completion. Forty-three outcomes were initially considered with 16 reaching consensuses after four rounds of the modified Delphi process. The final COS included outcomes related to mortality, organ failure, complications, interventions/management, and social factors., Conclusion: Through an iterative consensus process, content experts agreed on a COS for the management of ANP. This will help shape future research to generate data suitable for pooling and other statistical analyses that may guide clinical practice., Level of Evidence: Therapeutic/Care Management; Level V., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: A better understanding of global patterns of drug use among people who inject drugs can inform interventions to reduce harms related to different use profiles. This review aimed to comprehensively present the geographical variation in drug consumption patterns among this population., Methods: Systematic searches of peer reviewed (PsycINFO, Medline, Embase) and grey literature published from 2008-2022 were conducted. Data on recent (past year) and lifetime drug use among people who inject drugs were included. Data were extracted on use of heroin, amphetamines, cocaine, benzodiazepines, cannabis, alcohol, and tobacco; where possible, estimates were disaggregated by route of administration (injecting, non-injecting, smoking). National estimates were generated and, where possible, regional, and global estimates were derived through meta-analysis., Results: Of 40,427 studies screened, 394 were included from 81 countries. Globally, an estimated 78.1 % (95 %CI:70.2-84.2) and 71.8 % (65.7-77.2) of people who inject drugs had recently used (via any route) and injected heroin, while an estimated 52.8 % (47.0-59.0) and 19.8 % (13.8-26.5) had recently used and injected amphetamines, respectively. Over 90 % reported recent tobacco use (93.5 % [90.8-95.3]) and recent alcohol use was 59.1 % (52.6-65.6). In Australasia recent heroin use was lowest (49.4 % [46.8-52.1]) while recent amphetamine injecting (64.0 % [60.8-67.1]) and recent use of cannabis (72.3 % [69.9-74.6]) were higher than in all other regions. Recent heroin use (86.1 % [78.3-91.4]) and non-injecting amphetamine use (43.3 % [38.4-48.3]) were highest in East and Southeast Asia. Recent amphetamine use (75.8 % [72.7-78.8]) and injecting heroin use (84.8 % (81.4-87.8) were highest in North America while non-injecting heroin use was highest in Western Europe (45.0 % [41.3-48.7])., Conclusion: There is considerable variation in types of drugs and routes of administration used among people who inject drugs. This variation needs to be considered in national and global treatment and harm reduction interventions to target the specific behaviours and harms associated with these regional profiles of use., Competing Interests: Declaration of competing interest In the past 3 years, L.D. and M.F. have received investigator-initiated untied educational grants for studies of opioid medications in Australia from Indivior and Seqirus. A.P. has received investigator-initiated untied educational grants from Seqirus. JG is a consultant or advisor and has received research grants from AbbVie, bioLytical, Camurus, Cepheid, Gilead Sciences, Hologic, Indivior, and Merck or MSD. These companies and organisations had no knowledge of or role in the design, conduct, interpretation, or publication of these findings. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Studies of health utilities among people who use opioids have mostly been based on in-treatment populations. We aim to report utility-based quality of life by participants' socio-demographic, drug and treatment characteristics, and to examine the determinants of health utility among people who use opioids regularly., Methods: Cross-sectional study of participants who used opioids regularly, recruited across New South Wales, Victoria and Tasmania in 2018-2019. Differences in European Quality of Life (EQ-5D-5L) heath utility scores between socio-demographic and clinical subgroups were assessed using non-parametric Kruskal-Wallis test by rank. To address the unique distribution of EQ-5D-5L health utility scores in the current sample, a two-part model was applied to assess factors associated with health utility., Results: Among 402 participants enrolled in the study, 385 (96%) completed the EQ-5D-5L questionnaire. The mean health utility of the total sample was 0.63 (SD 0.29). Participants who previously received opioid agonist treatment [OAT] (adj marginal effect (ME) -0.11; 95% confidence interval [CI] -0.20 to -0.02) and those currently in OAT (adj ME -0.13; 95% CI -0.22 to -0.06) reported lower health utility than those who had never received OAT. Participants who used both pharmaceutical opioids and benzodiazepines had lower health utility compared to no pharmaceutical opioids and no benzodiazepines use (adj ME -0.17; 95% CI -0.28 to -0.07)., Discussion and Conclusions: Findings provide important health utility data for economic evaluations, useful for guiding allocation of resources for treatment strategies among people who use opioids. Lower health utilities among those using benzodiazepines and pharmaceutical opioids suggests interventions targeting these subgroups may be beneficial., (© 2024 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Background: The most recent formulation of buprenorphine treatment is extended-release depot injections (BUP-XR) that are administered subcutaneously by health care professionals. This study aimed to observe treatment outcomes of BUP-XR delivered in standard practice during a 96-week follow-up period in a community setting., Methods: This study is an extension of the CoLAB study, a prospective single-arm, multicentre, open label trial (N=100, 7 sites in Australia) among people with opioid dependence who received monthly injections of BUP-XR to evaluate the retention in treatment. Participants were followed for 96 weeks, comprising 48 weeks of the CoLAB study followed by a 48-week extension., Results: Of 100 participants at baseline, 47 were retained on BUP-XR at 96 weeks. The median time retained on monthly depot was 90 weeks. Heroin use (adjusted OR=0.19, P=0.012) in the month prior to baseline was associated with lower odds of retention on BUP-XR. Older age at first opioid use (adjusted OR= 1.08, P=0.009) and longer duration in OAT at baseline (adjusted OR= 1.12, P=0.001) were associated with increased retention. Prevalence of past four-weeks opioid use was estimated at 4% at 96 weeks of treatment (prevalence 0.04, 95%CI: 0.00-0.11) compared to 15% at baseline. Quality of life and medication treatment satisfaction improved over time for those retained in treatment., Conclusion: This is one of the few studies to describe long term (96 week) retention in treatment with BUP-XR in a community setting. It displayed retention rates with 47% of participants completing 96 weeks of treatment with BUP-XR. Patient reported outcomes suggest improvements in client wellbeing., Funding: Indivior., Competing Interests: Declaration of competing interest This study was supported by an Externally Sponsored Collaborative Research grant from Indivior PLC (MF, BL, LD, NL, AD, RA, SN, GD, J Grebely). In the past three years, MF and LD have received funding from Indivior for studies of new opioid medications in Australia. J Grebely reports grants and personal fees from Abbvie, bioLytical, Camurus, Cepheid, Hologic, Indivior, and Gilead Sciences. NL has received reimbursement for participation in Advisory Boards for Mundipharma, Indivior and Chiesi Pharmaceuticals; he received funding from Camurus for a company-sponsored trial of BUP-XR. RA has received untied educational grants from Reckitt Benckiser and an untied educational grant from Mundipharma. AJD reports grants from Braeburn/Camurus AB, to conduct clinical studies with buprenorphine products and travel support to Hunter New England Local Health District, which employs AJD. GJD has received research grant funding from Gilead and Abbvie. MM has served as an honorary on advisory boards for Pfizer and AbbVie. MC, JS, MB, JG, and EZ have no conflicts to declare. SN has received untied research funding from Seqirus to conduct research on prescription opioid related harms., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Introduction: Acute alcohol toxicity is a significant component of alcohol-related mortality. The study aimed to: (i) determine the circumstances of death and characteristics of fatal alcohol toxicity cases, 2011-2022; (ii) determine their toxicological profile and major autopsy findings; and (iii) determine trends in population mortality rates., Methods: Retrospective study of acute alcohol toxicity deaths in Australia, 2011-2022, retrieved from the National Coronial Information System., Results: A total of 891 cases were identified, with a mean age of 49.2 years, 71.0% being male. Alcohol use problems were noted in 71.3%. In 57.5% death was attributed solely to acute alcohol toxicity, and combined acute alcohol toxicity/disease in 42.5%. There was evidence of sudden collapse in 24.9% of cases. The mean BAC was 0.331 g/100 mL (range 0.107-0.936), and spirits were the most commonly reported beverages (35.8%). Cases of combined toxicity/disease had significantly lower BACs than those attributed solely to alcohol toxicity (0.296 vs. 0.358 g/100 mL). Cardiomegaly was diagnosed in 32.5%, and severe coronary artery disease in 22.1%. Aspiration of vomitus was noted in 18.0%, and chronic obstructive pulmonary disease in 19.6%. Severe liver steatosis was present in 33.4% and 13.6% had cirrhosis. There was an average annual percentage increase in deaths of 7.90., Discussion and Conclusions: The 'typical' case was a long-standing, heavy spirits drinker. BACs showed enormous variation and no arbitrary concentration may be deemed lethal. Clinically significant disease was associated with death at a lower BAC and people with such disease may be at increased risk of alcohol poisoning., (© 2024 Australasian Professional Society on Alcohol and other Drugs.)

Although alcohol and other drug use is increasingly the focus of policy and research efforts, there are challenges identifying and applying evidence-based strategies to minimise harms for alcohol and other drugs in health care and community settings. These challenges include limited available research, variability across settings, and lack of 'fit' between research evidence and their intended settings. In this commentary, we describe a novel approach to develop and evaluate tailored, sustainable strategies to enhance the uptake of evidence-based activities into health services and community settings. Our approach involves four key principles: (i) identifying evidence-based alcohol and other drug harm minimisation strategies; (ii) partnering with local experts to identify and tailor strategies; (iii) implementing strategies into existing practice/infrastructure to build in sustainability; and (iv) using sustainable co-designed outcome measures including value-based health-care principles to measure uptake, feasibility and acceptability, health outcomes and economic implications. We propose that this approach offers a way forward to enhance the relevance and suitability of research in health services and community settings and has potential to be applied in other sectors., (© 2024 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Background: In 1990, the United States' Institute of Medicine promoted the principles of outcomes monitoring in the alcohol and other drugs treatment field to improve the evidence synthesis and quality of research. While various national outcome measures have been developed and employed, no global consensus on standard measurement has been agreed for addiction. It is thus timely to build an international consensus. Convened by the International Consortium for Health Outcomes Measurement (ICHOM), an international, multi-disciplinary working group reviewed the existing literature and reached consensus for a globally applicable minimum set of outcome measures for people who seek treatment for addiction. Methods: To this end, 26 addiction experts from 11 countries and 5 continents, including people with lived experience ( n = 5; 19%), convened over 16 months (December 2018-March 2020) to develop recommendations for a minimum set of outcome measures. A structured, consensus-building, modified Delphi process was employed. Evidence-based proposals for the minimum set of measures were generated and discussed across eight videoconferences and in a subsequent structured online consultation. The resulting set was reviewed by 123 professionals and 34 people with lived experience internationally. Results: The final consensus-based recommendation includes alcohol, substance, and tobacco use disorders, as well as gambling and gaming disorders in people aged 12 years and older. Recommended outcome domains are frequency and quantity of addictive disorders, symptom burden, health-related quality of life, global functioning, psychosocial functioning, and overall physical and mental health and wellbeing. Standard case-mix (moderator) variables and measurement time points are also recommended. Conclusions: Use of consistent and meaningful outcome measurement facilitates carer-patient relations, shared decision-making, service improvement, benchmarking, and evidence synthesis for the evaluation of addiction treatment services and the dissemination of best practices. The consensus set of recommended outcomes is freely available for adoption in healthcare settings globally.

Introduction: There is little knowledge of the perspectives of people who use methamphetamine and have participated in clinical trials, and none for interventions not intended to address abstinence. A better understanding of these experiences could lead to more patient centred clinical trial design. This study seeks to understand the experiences of people who completed a clinical trial of lisdexamfetamine for the treatment of acute methamphetamine withdrawal., Methods: Thematic analysis of open-ended, semi-structured interviews with eight people who participated in an inpatient clinical trial of lisdexamfetamine for acute methamphetamine withdrawal. Interviews were conducted between days 3 and 6 of admission to an inner-city Sydney hospital., Results: Participants described how research procedures, the research setting, and the investigational product affected their experiences while enrolled in a clinical trial. Of particular importance to participants were transparent and low burden trial procedures, a welcoming trial environment, trusting relationships and effective communication, which were linked with the participants' subsequent decision to remain enrolled in the trial., Discussion: The experiences of participants in this clinical trial can be distilled into four meta-themes: agency, caring-trust, safety, and communication. Participants spontaneously linked these experiences with a capacity to remain enrolled in the study. By considering the experiences of trial participants in clinical trial design, researchers can improve the experiences of future trial participants and facilitate their choice to remain enrolled in clinical trials., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: LSA is supported by an NDARC PhD Scholarship. MF has received unrestricted funding for research purposes from Indivior and Sequiiris. SS has received clinical research supplies from Alkermes. NE and KJS are employed by NCCRED. No other investigators have any conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Background and Aims: Mortality rates among people who use heroin are estimated to be 15 times that of the general population. The study aimed to determine (1) the case characteristics and circumstances of death of heroin-related toxicity deaths in Australia, 2020-2022; (2) their toxicological profile and major autopsy findings; (3) the proportion of cases in which blood 6-acetyl morphine (6AM) was detected, as a proxy measure of survival times; and (4) compare 6AM positive and negative cases on toxicology, circumstances of death and acute clinical presentation., Design: Retrospective study of heroin toxicity deaths in Australia, 2020-2022, retrieved from the National Coronial Information System., Setting: This study was conducted Australia-wide., Cases: There were 610 cases of fatal heroin-related drug toxicity., Measurements: Information was collected on characteristics, manner of death, toxicology and autopsy results., Findings: The mean age was 42.6 years (range 18-73 years), 80.5% were male and 7.5% were enrolled in a drug treatment programme. The circumstances of death were as follows: unintentional drug toxicity (86.2%), combined unintentional drug toxicity/disease (11.3%) and intentional drug toxicity (2.5%). The median free morphine concentration was 0.17 mg/L (range 0.00-4.20 mg/L). Psychoactive drugs other than heroin were present in 95.2% (Confidence Interval 93.1%-96.8%), most commonly hypnosedatives (62.3%, 58.2%-66.4%) and psychostimulants (44.8%, 40.7%-49.1%). Major autopsy findings of clinical significance included acute bronchopneumonia (14.8%, 11.3%-18.8%), emphysema (16.9%, 13.2%-21.1%), cardiomegaly (30.1%, 12.7%-28.2%), coronary artery disease (27.4%, 23.0%-32.3%), coronary replacement fibrosis (13.4%, 10.1%-17.3%), hepatic cirrhosis (8.8%, 6.6%-12.2%) and renal fibrosis (10.3%, 7.3%-14.0%). In 47.0% (42.3%-51.2%), 6AM was present in blood., Conclusions: The 'typical' heroin overdose case in Australia from 2020 to 2022 was a male who injected heroin, aged in the 40s, not enrolled in a treatment programme and had used multiple drugs. In over half of cases, there had been a sufficient survival time for 6-acetyl morphine to have been metabolised, which may indicate times in excess of 20-30 min., (© 2023 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: Chronic cough is a prevalent and difficult to treat condition often accompanied by cough hypersensitivity, characterised by cough triggered from exposure to low level sensory stimuli. The mechanisms underlying cough hypersensitivity may involve alterations in airway sensory nerve responsivity to tussive stimuli which would be accompanied by alterations in stimulus-induced brainstem activation, measurable with functional magnetic resonance imaging (fMRI)., Methods: We investigated brainstem responses during inhalation of capsaicin and adenosine triphosphate (ATP) in 29 participants with chronic cough and 29 age- and sex-matched controls. Psychophysical testing was performed to evaluate individual sensitivities to inhaled stimuli and fMRI was used to compare neural activation in participants with cough and control participants while inhaling stimulus concentrations that evoked equivalent levels of urge-to-cough sensation., Findings: Participants with chronic cough were significantly more sensitive to inhaled capsaicin and ATP and showed a change in relationship between urge-to-cough perception and cough induction. When urge-to-cough levels were matched, participants with chronic cough displayed significantly less neural activation in medullary regions known to integrate airway sensory inputs. By contrast, neural activations did not differ significantly between the two groups in cortical brain regions known to encode cough sensations whereas activation in a midbrain region of participants with chronic cough was significantly increased compared to controls., Interpretation: Cough hypersensitivity in some patients may occur in brain circuits above the level of the medulla, perhaps involving midbrain regions that amplify ascending sensory signals or change the efficacy of central inhibitory control systems that ordinarily serve to filter sensory inputs., Funding: Supported in part by a research grant from Investigator-Initiated Studies Program of Merck Sharp & Dohme Pty Ltd. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme (Australia) Pty Ltd., Competing Interests: Declaration of interests SBM reports receiving grants from the National Health and Medical Research Council (NHMRC) of Australia and the Australian Research Council (ARC), Merck, Bellus Health and Reckitt Benkiser, and remuneration for consultancy from Merck, Trevi Therapeutics, Reckitt Benkiser and Nerre Therapeutics, has served on advisory committees for Reckitt Benkiser and has received payment from Reckitt Benkiser for assistance with manuscript writing. KFC reports research grants from Merck and GSK, remuneration for lectures from Novartis and AstraZeneca; has served on advisory boards for Roche, Merck, Reckitt Benckiser, and Shionogi & Co., Ltd., and a Data Safety Monitoring Board for Nocion. LMG reports research grants from Bayer AG, Bellus Health, Chiesi, Merck, and Shionogi, remuneration for lectures from Bayer AG, Bellus Health, Chiesi, GlaxoSmithKline, Merck, and Shionogi, remuneration for consultancy from Bayer AG, Bellus Health, Chiesi, Merck, NeRRe Therapeutics, Nocion Therapeutics, and Shionogi, and has served on advisory committees for Applied Clinical Intelligence, Bayer AG, Bellus Health, Chiesi, Merck, NeRRe Therapeutics, Nocion Therapeutics, and Shionogi and on a Data and Safety Monitoring Board for Bayer AG. All other authors declare no relevant conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The immunoproteasome is a central protease complex required for optimal antigen presentation. Immunoproteasome activity is also associated with facilitating the degradation of misfolded and oxidized proteins, which prevents cellular stress. While extensively studied during diseases with increasing evidence suggesting a role for the immunoproteasome during pathological conditions including neurodegenerative diseases, this enzyme complex is believed to be mainly not expressed in the healthy brain. In this study, we show an age-dependent increase in polyubiquitination in the brains of wild-type mice, accompanied by an induction of immunoproteasomes, which was most prominent in neurons and microglia. In contrast, mice completely lacking immunoproteasomes (triple-knockout mice), displayed a strong increase in polyubiquitinated proteins already in the young brain and developed spontaneous epileptic seizures, beginning at the age of 6 months. Injections of kainic acid led to high epilepsy-related mortality of aged triple-knockout mice, confirming increased pathological hyperexcitability states. Notably, the expression of the immunoproteasome was reduced in the brains of patients suffering from epilepsy. In addition, the aged triple-knockout mice showed increased anxiety, tau hyperphosphorylation and degeneration of Purkinje cell population with the resulting ataxic symptoms and locomotion alterations. Collectively, our study suggests a critical role for the immunoproteasome in the maintenance of a healthy brain during ageing., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: The age of people who use illicit opioids has increased, with a clinical picture of accelerated ageing. The study aimed to determine, stratified by age: 1. The circumstances and characteristics of heroin-related toxicity deaths in Australia, 2020-2022; 2. The toxicological profile and autopsy findings; 3. The proportion of cases in which blood 6-acetyl morphine (6AM) was detected, as a measure of survival time., Methods: Retrospective study of 610 cases of fatal heroin-related drug toxicity in Australia, 2020-2022. Cases were stratified as: <30 years, 30-39 years, 40-49 years, ≥50 years., Results: Compared to the youngest group, those aged ≥50 years were more likely to have a history of chronic pain (12.4 v 3.3 %), to have their death attributed to combined drug toxicity/disease (20.1 v 3.3 %), and to have evidence of a sudden collapse (21.3 v 11.1 %). There were no differences in free morphine concentrations or glucuronide concentrations. Compared to the youngest group, however, the two older groups were significantly more likely to have 6AM present in blood, a proxy measure of a shorter survival time (52.0, 55.2 v 34.5 %). Compared to the youngest group, cases aged ≥50 years were more likely to be diagnosed with cardiomegaly (44.0 v 16.7 %), coronary artery disease (46.0 v 15.0 %), emphysema (35.0 v 5.1 %), hepatic steatosis (15.4 v 3.4 %), hepatic fibrosis (17.6 v 3.4 %), and cirrhosis (19.8 v 0.0 %)., Conclusions: Older cases of heroin overdose had more extensive heart, lung, and liver disease, and appeared more likely to have shorter survival times., Competing Interests: The author confirm that there is no financial, or personal interest or belief that could affect their objectivity in the conduct of this study., (© 2024 The Authors.)

Background: There are limited longitudinal data on national patterns of opioid agonist treatment (OAT). This study describes 10-year trends in the sales of OAT medicines in Australia., Methods: A descriptive and time-series analysis of methadone, sublingual (SL) buprenorphine (+/-naloxone), and long-acting injectable (LAI) buprenorphine sold in Australia between 2013 and 2022 was performed. Total units sold were converted into an estimate of the number of clients that could be treated over a 28-day period with that amount of medicine ('client-months')., Results: Between January 2013 and December 2022, the estimated number of client-months on: any OAT increased by 50 % to 53,501, methadone decreased (-8.5%), SL buprenorphine increased (+78%), and LAI buprenorphine increased substantially after September 2019. In January 2013, 78 % of OAT client-months received methadone. By December 2022, 48 % received methadone, 26 % SL buprenorphine, and 26 % LAI buprenorphine. Between 2013 to 2022, OAT client-months per capita were highest in the state of New South Wales. Over the study period, greater increases in OAT were observed in very remote areas (88%) compared to major cities (53%). The number of client-months in non-community pharmacy settings remained stable from 2013 to 2019/20, before increasing markedly. The introduction of LAI buprenorphine was associated with an immediate, sustained increase of 1,636 OAT client-months, and further increases of 190 OAT client-months each month., Conclusion: Patterns of OAT have shifted over the last 10-years with buprenorphine (SL/LAI) now the most common OAT used in Australia. The introduction of LAI buprenorphine has expanded OAT access, particularly in non-community pharmacy settings, and in remote areas., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: L.D. has received untied educational funding from Reckitt Benckiser, Indivior, Mundipharma Pty Ltd, and Seqirus. M.F. has received untied funding from Indivior and Seqirus. These untied grants are all unrelated to the current study. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Transitional times in opioid use, such as release from prison and discontinuation of opioid agonist treatment (OAT), are associated with health harms due to changing drug consumption practices and limited access to health and social supports. Using a self-controlled (within-person) study design, we aimed to understand if these transitions increase risks of injection drug use-associated bacterial infections., Methods: We performed a self-controlled case series among a cohort of people with opioid use disorder (who had all previously accessed OAT) in New South Wales, Australia, 2001-2018. The outcome was hospitalisation with injecting-related bacterial infections. We divided participants' observed days into time windows related to incarceration and OAT receipt. We compared hospitalization rates during focal (exposure) windows and referent (control) windows (i.e., 5-52 weeks continuously not incarcerated or continuously receiving OAT). We estimated adjusted incidence rate ratios (aIRR) using conditional logistic regression, adjusted for time-varying confounders., Results: There were 7590 participants who experienced hospitalisation with injecting-related bacterial infections (35% female; median age 38 years; 78% hospitalised with skin and soft-tissue infections). Risk for injecting-related bacterial infections was elevated for two weeks following release from prison (aIRR 1.45; 95%CI 1.22-1.72). Risk was increased during two weeks before (aIRR 1.89; 95%CI 1.59-2.25) and after (aIRR 1.91; 95%CI 1.54-2.36) discontinuation of OAT, and during two weeks before (aIRR 3.63; 95%CI 3.13-4.22) and after (aIRR 2.52; 95%CI 2.09-3.04) OAT initiation., Conclusion: Risk of injecting-related bacterial infections varies greatly within-individuals over time. Risk is raised immediately after prison release, and around initiation and discontinuation of OAT. Social contextual factors likely contribute to excess risks at transitions in incarceration and OAT exposure., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MB reports personal fees from AbbVie, a pharmaceutical research and development company, and grants and personal fees from Gilead Sciences, a research-based biopharmaceutical company, outside of the submitted work. JG is a consultant/advisor and has received research grants from AbbVie, bioLytical, Camurus, Cepheid, Gilead Sciences, Hologic, and Indivior. LD and MF have received untied educational grant funding from Indivior and Seqirus. The other authors report no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Background: People who inject drugs are disproportionately affected by HIV and hepatitis C virus (HCV) infections, while there is little global data on HIV and HCV testing and treatment coverage of this population. We conducted a systematic review to evaluate country-level, regional, and global coverage of HIV and HCV testing and treatment among people who inject drugs., Methods: We did a systematic review, and searched bibliographic databases (MEDLINE, Embase, and PsycINFO) and grey literature for studies published between Jan 1, 2017, and April 30, 2022, that evaluated the proportion of people who inject drugs who received testing or treatment for HIV or HCV. For each country, we estimated the proportion of people who inject drugs tested for HIV antibodies in the past 12 months (recent), people who inject drugs ever tested for HCV antibodies and HCV RNA, people who inject drugs with HIV currently receiving antiretroviral therapy, and people who inject drugs with HCV ever receiving HCV antiviral treatment. Regional and global estimates, weighted by the population size of people who inject drugs, were generated where sufficient data were available. This study is registered with PROSPERO (CRD42020173974)., Findings: 512 documents reported data eligible for analyses, including 337 peer-reviewed articles, 27 conference abstracts or presentations, and 148 documents from grey literature or supplementary searches. Data of recent HIV antibody testing were available for 67 countries and ever having had HCV antibody testing were available for 49 countries. Globally, an estimated 48·8% of people who inject drugs were recently tested for HIV antibodies (95% uncertainty interval [UI] 43·3-54·2%; range 0·9-86·0%), and 47·1% had ever been tested for HCV antibodies (95% UI 43·4-51·0%; range 0·0-93·3%). HCV RNA testing data were available from three countries. Coverage of HIV antibody testing was high (>75%) in four countries and for HCV antibody testing in 15 countries. The estimated uptake of current HIV treatment (18 countries) ranged from 2·6% to 81·9%, and the estimated uptake of ever having HCV treatment (23 countries) ranged from 1·8% to 88·6% across countries. Uptake of HIV treatment was high in two countries, and of HCV treatment in one country., Interpretation: HIV and HCV testing and treatment uptake among people who inject drugs was highly variable, and suboptimal in most countries. Strategies to improve access to HIV and HCV care among people who inject drugs and the availability of public health surveillance are urgently required., Funding: Australian National Health and Medical Research Council and UK National Institute for Health and Care Research Health Protection Research Unit in Behavioural Science and Evaluation., Competing Interests: Declaration of interests In the past 3 years, LD and MF have received investigator-initiated untied educational grants for studies of opioid medications in Australia from Indivior and Seqirus. JG is a consultant or adviser for and has received research grants from AbbVie, Camurus, Cepheid, Gilead Sciences, Hologic, Indivior, and Merck/MSD. GJD has received research grants from AbbVie, Gilead Sciences, and Merck/MSD. EC has received funding from the Canadian Network on Hepatitis C. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background and Objectives: Canadian out-of-hospital blood transfusion programmes (OHBTPs) are emerging, to improve outcomes of trauma patients by providing pre-hospital transfusion from the scene of injury, given prolonged transport times. Literature is lacking to guide its implementation. Thus, we sought to gather technical transfusion medicine (TM)-specific practices across Canadian OHBTPs., Materials and Methods: A survey was sent to TM representatives of Canadian OHBTPs from November 2021 to March 2022. Data regarding transport, packaging, blood components and inventory management were included and reported descriptively. Only practices involving Blood on Board programme components for emergency use were included., Results: OHBTPs focus on helicopter emergency medical service programmes, with some supplying fixed-wing aircraft and ground ambulances. All provide 1-3 coolers with 2 units of O RhD/Kell-negative red blood cells (RBCs) per cooler, with British Columbia trialling coolers with 2 units of pre-thawed group A plasma. Inventory exchanges are scheduled and blood components are returned to TM inventory using visual inspection and internal temperature data logger readings. Coolers are validated to storage durations ranging from 72 to 124 h. All programmes audit to manage wastage, though there is no consensus on appropriate benchmarks. All programmes have a process for documenting units issued, reconciliation after transfusion and for transfusion reaction reporting; however, training programmes vary. Common considerations included storage during extreme temperature environments, O-negative RBC stewardship, recipient notification, traceability, clinical practice guidelines co-reviewed by TM and a common audit framework., Conclusion: OHBTPs have many similarities throughout Canada, where harmonization may assist in further developing standards, leveraging best practice and national coordination., (© 2023 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide. TBI ranges from mild to severe and is a recognized risk factor for later neurodegenerative conditions including chronic traumatic encephalopathy (CTE), Alzheimer disease (AD) and Parkinson disease (PD). The development of CTE is typically associated with repetitive exposure to mild TBI (mTBI), while a single moderate-to-severe TBI is considered a risk factor for AD and PD. Polypathology is common, and the lines between these conditions post TBI can be somewhat blurred. The mechanisms through which TBI leads to future neurodegeneration are not well understood. Heterogeneity and distance from the injury or injuries and individual genetic and environmental factors make clinical studies difficult. We present the case of an 82-year-old man who died 4 years after developing a phenotypically mixed dementia with neuropsychiatric features and parkinsonism. He had a remote history of a severe TBI 40 years prior, following a road traffic accident which caused a large right frontal injury, requiring neurosurgical intervention. Post-mortem neuropathological examination demonstrated abnormal phosphorylated-Tau (p-Tau), beta-amyloid plaques (Aβ) and α-synuclein deposition. Spatial immunohistochemical analysis demonstrated increased perivascular accumulation of p-Tau with blood-brain barrier (BBB) disruption at the site of injury, which decreased with distance from the injury site. The appearances are suggestive of initial vascular disruption with persisting BBB disruption as a driver of the pathology.

Aims: To estimate the prevalence of, and number of unobserved people with opioid dependence by sex and age group in New South Wales (NSW), Australia., Design: We applied a Bayesian statistical modelling approach to opioid agonist treatment records linked to adverse event rate data. We estimated prevalence from three types of adverse event separately: opioid mortality, opioid-poisoning hospitalizations and opioid-related charges. We extended the model and produced prevalence estimates from a 'multi-source' model based on all three types of adverse event data., Setting, Participants and Measurements: This study was conducted in NSW, Australia, 2014-16 using data from the Opioid Agonist Treatment and Safety (OATS) study, which included all people who had received treatment for opioid dependence in NSW. Aggregate data were obtained on numbers of adverse events in NSW. Rates of each adverse event type within the OATS cohort were modelled. Population data were provided by State and Commonwealth agencies., Findings: Prevalence of opioid dependence among those aged 15-64 years in 2016 was estimated to be 0.96% (95% credible interval [CrI] = 0.82%, 1.12%) from the mortality model, 0.75% (95% CrI = 0.70%, 0.83%) from hospitalizations, 0.95% (95% CrI = 0.90%, 0.99%) from charges and 0.92% (95% CrI = 0.88%, 0.96%) from the multi-source model. Of the estimated 46 460 (95% CrI = 44 680, 48 410) people with opioid dependence in 2016 from the multi-source model, approximately one-third (16 750, 95% CrI = 14 960, 18 690) had no record of opioid agonist treatment within the last 4 years. From the multi-source model, prevalence in 2016 was estimated to be 1.24% (95% CrI = 1.18%, 1.31%) in men aged 15-44, 1.22% (95% CrI = 1.14%, 1.31%) in men 45-64, 0.63% (95% CrI = 0.59%, 0.68%) in women aged 15-44 and 0.56% (95% CrI = 0.50%, 0.63%) in women aged 45-64., Conclusions: A Bayesian statistical approach to estimate prevalence from multiple adverse event types simultaneously calculates that the estimated prevalence of opioid dependence in NSW, Australia in 2016 was 0.92%, higher than previous estimates., (© 2023 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Introduction: A difficult question in autopsy practice is whether intracranial haemorrhage has resulted from or brought about a fall., Material and Methods: To address this we undertook a retrospective study of all autopsy reports (N = 2126) complied over a 10 year period (2009-2018). Of 720 patients who underwent a comprehensive post mortem neuropathologic examination we found 226 patients who had a history of a fall., Results: Of the 226 with a history of fall, 175 (79%) had an intracranial haemorrhage which was classified as truamatic (n = 134, 77%) or spontaneous (n = 41, 23%. Within the traumatic group, falls from a standing height (51%) were more common than falls involving stairs (31%) or falls from a height (12%). Cerebral contusional injury (51%) and subdural haemorrhage (45%) were the most common type of haemorrhage in the traumatic group. In the spontaneous haemorrhage group cerebral amyloid angiopathy (49%) was the commonest detected cause and was typically lobar in distribution)., Conclusion: We are of the view that a comprehensive analysis of fatal falls with intracranial haemorrhage warrants a detailed neuropathologic examination as part of the overall death analysis., (© 2022. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Objective: Posttranscriptional mechanisms are increasingly recognized as important contributors to the formation of hyperexcitable networks in epilepsy. Messenger RNA (mRNA) polyadenylation is a key regulatory mechanism governing protein expression by enhancing mRNA stability and translation. Previous studies have shown large-scale changes in mRNA polyadenylation in the hippocampus of mice during epilepsy development. The cytoplasmic polyadenylation element-binding protein CPEB4 was found to drive epilepsy-induced poly(A) tail changes, and mice lacking CPEB4 develop a more severe seizure and epilepsy phenotype. The mechanisms controlling CPEB4 function and the downstream pathways that influence the recurrence of spontaneous seizures in epilepsy remain poorly understood., Methods: Status epilepticus was induced in wild-type and CPEB4-deficient male mice via an intra-amygdala microinjection of kainic acid. CLOCK binding to the CPEB4 promoter was analyzed via chromatin immunoprecipitation assay and melatonin levels via high-performance liquid chromatography in plasma., Results: Here, we show increased binding of CLOCK to recognition sites in the CPEB4 promoter region during status epilepticus in mice and increased Cpeb4 mRNA levels in N2A cells overexpressing CLOCK. Bioinformatic analysis of CPEB4-dependent genes undergoing changes in their poly(A) tail during epilepsy found that genes involved in the regulation of circadian rhythms are particularly enriched. Clock transcripts displayed a longer poly(A) tail length in the hippocampus of mice post-status epilepticus and during epilepsy. Moreover, CLOCK expression was increased in the hippocampus in mice post-status epilepticus and during epilepsy, and in resected hippocampus and cortex of patients with drug-resistant temporal lobe epilepsy. Furthermore, CPEB4 is required for CLOCK expression after status epilepticus, with lower levels in CPEB4-deficient compared to wild-type mice. Last, CPEB4-deficient mice showed altered circadian function, including altered melatonin blood levels and altered clustering of spontaneous seizures during the day., Significance: Our results reveal a new positive transcriptional-translational feedback loop involving CPEB4 and CLOCK, which may contribute to the regulation of the sleep-wake cycle during epilepsy., (© 2023 International League Against Epilepsy.)

Introduction: Effective communication is a central tenet of family centered care, yet parent concerns are sometimes un- or underattended to by pediatric providers. This study aimed to explore the prevalence of, and factors related to, parental perceptions of concern dismissal by pediatric providers., Method: In Spring 2020, 270 community-recruited parents of children ages 6-12 years (74% White, 74% female, 69% married) responded to an online survey about perceived concern dismissal experiences with their children. Characteristics of concern dismissal, differences in concern dismissal occurrence by parent factors, and emotional and practical impacts were assessed and explored., Results: Thirty-three percent reported having experienced concern dismissal, most often in pediatric primary care settings. Concern dismissal was reported more frequently among parents employed in health care settings than those without health care employment histories. Most dismissed concerns related to the child's physical health and many incidents were characterized by provider impoliteness or provision of less testing or treatment than expected or desired. Many parents expressed disappointment in the health care system after experiences of concern dismissal., Discussion: Concern dismissal was found to be common and upsetting for community-recruited parents. Future research should incorporate child and provider perspectives with demographically diverse samples. Pediatric providers should continue to work toward implementation of family centered care to decrease the likelihood of perceived dismissal by thoroughly recognizing and responding to concerns presented by parents and caregivers of pediatric patients. (PsycInfo Database Record (c) 2023 APA, all rights reserved).