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1.
Addiction ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38771189

RESUMEN

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.

2.
Drug Alcohol Rev ; 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38704742

RESUMEN

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.

3.
Drug Alcohol Rev ; 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38634165

RESUMEN

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.

4.
J Clin Med ; 13(7)2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38610919

RESUMEN

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.

5.
Am J Surg ; 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38553335

RESUMEN

BACKGROUND: High-grade liver injuries with extravasation (HGLI â€‹+ â€‹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 â€‹+ â€‹Extrav. Therefore, we evaluated the management of HGLI â€‹+ â€‹Extrav patients, hypothesizing IR patients will have decreased rates of operation and mortality. METHODS: HGLI â€‹+ â€‹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 â€‹= â€‹0.049), but no difference in LRCs (44.4% vs. 43.5%) or mortality (5.6% vs. 8.7%) versus OBS patients (both p â€‹> â€‹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 â€‹+ â€‹Extrav patients.

6.
Eur Addict Res ; 30(2): 121-125, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38498995

RESUMEN

INTRODUCTION: Sleep disturbance is common during methamphetamine (MA) use and withdrawal; however, the feasibility of combined subjective-objective measurement of sleep-wake has not been shown in this population. Actigraphy is a well-established, non-invasive measure of sleep-wake cycles with good concordance with polysomnography. This study aimed to investigate the feasibility and utility of using actigraphy and sleep diaries to investigate sleep during MA withdrawal. METHODS: We conducted a feasibility and utility study of actigraphy and sleep diaries during a clinical trial of lisdexamfetamine for MA withdrawal. Participants were inpatients for 7 days, wore an actigraph (Philips Actiwatch 2) and completed a modified Consensus Sleep Diary each morning. Participants were interviewed between days 3-5. RESULTS: Ten participants (mean age 37 years, 90% male) were enrolled. No participant removed the device prematurely. Participants interviewed (n = 8) reported that the actigraph was not difficult or distracting to wear or completion of daily sleep diary onerous. Actigraphic average daily sleep duration over 7 days was 568 min, sleep onset latency 22.4 min, wake after sleep onset (WASO) 75.2 min, and sleep efficiency 83.6%. Sleep diaries underreported daily sleep compared with actigraphy (sleep duration was 56 min (p = 0.008) and WASO 47 min (p < 0.001) less). Overall sleep quality was 4.4 on a nine-point Likert scale within the diary. CONCLUSIONS: Continuous actigraphy is feasible to measure sleep-wake in people withdrawing from MA, with low participant burden. We found important differences in self-reported and actigraphic sleep, which need to be explored in more detail.


Asunto(s)
Dimesilato de Lisdexanfetamina , Síndrome de Abstinencia a Sustancias , Humanos , Masculino , Adulto , Femenino , Estudios de Factibilidad , Dimesilato de Lisdexanfetamina/efectos adversos , Sueño , Polisomnografía , Actigrafía , Síndrome de Abstinencia a Sustancias/diagnóstico , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico
7.
Psychiatr Psychol Law ; 31(1): 132-145, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38455267

RESUMEN

The current study aimed to advance our understanding of the factors that influence mental health diversion in Local Courts in New South Wales, Australia. Logistic regression was used to systematically identify the factors that are correlated with diversion in a cohort of individuals (N = 7283) diagnosed with psychosis. Those with a substance-induced psychotic disorder were less likely to be diverted than those with an affective psychosis or schizophrenia, after adjusting for age, gender, Indigenous status, offence seriousness, violence and criminal history. Unexpectedly, those with psychotic disorders committing violent or serious offences were more likely to be diverted than those committing non-violent, less serious offences. Legal representation should be provided to all individuals with serious mental illnesses facing criminal charges. The State-wide Community and Court Liaison Service should be expanded to more Local Courts. Further research is required into why Aboriginal defendants with a psychotic illness are less likely to be diverted.

8.
Int J Drug Policy ; 126: 104383, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38479162

RESUMEN

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.


Asunto(s)
Trastornos Relacionados con Anfetaminas , Metanfetamina , Síndrome de Abstinencia a Sustancias , Humanos , Metanfetamina/administración & dosificación , Metanfetamina/efectos adversos , Masculino , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Proyectos Piloto , Femenino , Adulto , Persona de Mediana Edad , Comunicación , Confianza , Entrevistas como Asunto , Ensayos Clínicos como Asunto
9.
Drug Alcohol Rev ; 2024 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-38462541

RESUMEN

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.

10.
Int J Drug Policy ; 127: 104390, 2024 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-38522175

RESUMEN

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.

11.
J Trauma Acute Care Surg ; 96(6): 965-970, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38407209

RESUMEN

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.


Asunto(s)
Consenso , Técnica Delphi , Pancreatitis Aguda Necrotizante , Pancreatitis Aguda Necrotizante/cirugía , Pancreatitis Aguda Necrotizante/mortalidad , Humanos , Evaluación de Resultado en la Atención de Salud
12.
Drug Alcohol Rev ; 43(4): 937-945, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38345860

RESUMEN

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.


Asunto(s)
Nivel de Alcohol en Sangre , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Australia/epidemiología , Adulto , Anciano , Adulto Joven , Etanol/envenenamiento , Etanol/efectos adversos , Adolescente , Autopsia , Bebidas Alcohólicas/efectos adversos , Causas de Muerte/tendencias , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/tendencias , Consumo de Bebidas Alcohólicas/mortalidad
13.
Drug Alcohol Rev ; 43(4): 997-1012, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38403293

RESUMEN

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.


Asunto(s)
Analgésicos Opioides , Calidad de Vida , Humanos , Masculino , Femenino , Estudios Transversales , Adulto , Persona de Mediana Edad , Analgésicos Opioides/uso terapéutico , Analgésicos Opioides/administración & dosificación , Trastornos Relacionados con Opioides/epidemiología , Australia , Encuestas y Cuestionarios , Adulto Joven
14.
Drug Alcohol Depend Rep ; 10: 100217, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38332901

RESUMEN

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.

15.
Brain Commun ; 6(1): fcae017, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38317856

RESUMEN

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.

17.
EBioMedicine ; 100: 104976, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38244293

RESUMEN

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.


Asunto(s)
Capsaicina , Hipersensibilidad , Humanos , Capsaicina/efectos adversos , Tos Crónica , Tos , Tronco Encefálico/diagnóstico por imagen , Adenosina Trifosfato
18.
Int J Drug Policy ; 123: 104255, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38029481

RESUMEN

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.


Asunto(s)
Buprenorfina , Trastornos Relacionados con Opioides , Humanos , Analgésicos Opioides/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Tratamiento de Sustitución de Opiáceos , Metadona/uso terapéutico , Buprenorfina/uso terapéutico , Australia
19.
Addiction ; 119(3): 559-569, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37921084

RESUMEN

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.


Asunto(s)
Sobredosis de Droga , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Masculino , Anciano , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Femenino , Heroína , Estudios Retrospectivos , Morfina , Australia/epidemiología
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