Highlights • There are key areas within the striatum that receive convergent terminals from different functional cortical regions. • Subpopulations of dopamine neurons are involved in different ...functions including reward, cognition and motor control. • The striato-nigra system is a key factor in integrating information across functional domains.
Alcohol use disorders Connor, Jason P, PhD; Haber, Paul S, Prof; Hall, Wayne D, Prof
The Lancet (British edition),
03/2016, Volume:
387, Issue:
10022
Journal Article
Peer reviewed
Summary Alcohol use disorders are common in developed countries, where alcohol is cheap, readily available, and heavily promoted. Common, mild disorders often remit in young adulthood, but more ...severe disorders can become chronic and need long-term medical and psychological management. Doctors are uniquely placed to opportunistically assess and manage alcohol use disorders, but in practice diagnosis and treatment are often delayed. Brief behavioural intervention is effective in primary care for hazardous drinkers and individuals with mild disorders. Brief interventions could also encourage early entry to treatment for people with more-severe illness who are underdiagnosed and undertreated. Sustained abstinence is the optimum outcome for severe disorder. The stigma that discourages treatment seeking needs to be reduced, and pragmatic approaches adopted for patients who initially reject abstinence as a goal. To engage people in one or more psychological and pharmacological treatments of equivalent effectiveness is more important than to advocate a specific treatment. A key research priority is to improve the diagnosis and treatment of most affected people who have comorbid mental and other drug use disorders.
The basal ganglia and frontal cortex operate together to execute goal directed behaviors. This requires not only the execution of motor plans, but also the behaviors that lead to this execution, ...including emotions and motivation that drive behaviors, cognition that organizes and plans the general strategy, motor planning, and finally, the execution of that plan. The components of the frontal cortex that mediate these behaviors, are reflected in the organization, physiology, and connections between areas of frontal cortex and in their projections through basal ganglia circuits. This comprises a series of parallel pathways. However, this model does not address how information flows between circuits thereby developing new learned behaviors (or actions) from a combination of inputs from emotional, cognitive, and motor cortical areas. Recent anatomical evidence from primates demonstrates that the neuro-networks within basal ganglia pathways are in a position to move information across functional circuits. Two networks are: the striato-nigral-striatal network and the thalamo-cortical-thalamic network. Within each of these sets of connected structures, there are both reciprocal connections linking up regions associated with similar functions and non-reciprocal connections linking up regions that are associated with different cortical basal ganglia circuits. Each component of information (from limbic to motor outcome) sends both feedback connection, and also a feedforward connection, allowing the transfer of information. Information is channeled from limbic, to cognitive, to motor circuits. Action decision-making processes are thus influenced by motivation and cognitive inputs, allowing the animal to respond appropriate to environmental cues.
Aims
To report Australian population trends in subsidized prescribed opioid use, total costs to the Australian government to subsidize these medicines and opioid‐related harms based on ...hospitalizations and accidental poisoning deaths.
Methods
We utilized three national aggregated data sources including dispensing claims from the Pharmaceutical Benefits Scheme, opioid‐related hospitalizations from the National Hospital Morbidity Database and accidental poisoning deaths from the Australian Bureau of Statistics.
Results
Between 1992 and 2012, opioid dispensing episodes increased 15‐fold (500 000 to 7.5 million) and the corresponding cost to the Australian government increased 32‐fold ($8.5 million to $271 million). Opioid‐related harms also increased. Opioid‐related hospitalizations increased from 605 to 1464 cases (1998–2009), outnumbering hospitalizations due to heroin poisonings since 2001. Deaths due to accidental poisoning (pharmaceutical opioids and illicit substances combined) increased from 151 to 266 (2002–2011), resulting in a rise in the death rate of 0.78 to 1.19 deaths/100 000 population over 10 years. Death rates increased 1.8 fold in males and 1.4 fold in females.
Conclusions
The striking increase in opioid use and related harms in Australia is consistent with trends observed in other jurisdictions. Further, there is no evidence to suggest these increases are plateauing. There is currently limited evidence in Australia about individual patterns of opioid use and the associated risk of adverse events. Further research should focus on these important issues so as to provide important evidence supporting effective change in policy and practice.
Methamphetamine use is a serious public health concern in many countries and is second to cannabis as the most widely abused illicit drug in the world. Effective management for methamphetamine ...dependence remains elusive and the large majority of methamphetamine users relapse following treatment. Areas covered: Progression in the understanding of the pharmacological basis of methamphetamine use has provided us with innovative opportunities to develop agents to treat dependence. The current review summarizes relevant literature on the neurobiological and clinical correlates associated with methamphetamine use. We then outline agents that have been explored for potential treatments in preclinical studies, human laboratory phase I and phase II trials over the last ten years. Expert opinion: No agent has demonstrated a broad and strong effect in achieving MA abstinence in Phase II trials. Agents with novel therapeutic targets appear promising. Advancement in MA treatment, including translation into practice, faces several clinical challenges.
Summary Background Intervention to achieve alcohol abstinence represents the most effective treatment for alcohol-dependent patients with liver cirrhosis; however, anticraving drugs might worsen ...liver disease. We aimed to investigate the effectiveness and safety of baclofen in achieving and maintaining alcohol abstinence in patients with liver cirrhosis. Methods Between October, 2003, and November, 2006, 148 alcohol-dependent patients with liver cirrhosis were referred to the Institute of Internal Medicine, Rome, Italy. 84 were randomly allocated either oral baclofen or placebo for 12 weeks. Primary outcome was proportion of patients achieving and maintaining alcohol abstinence. Measures of this outcome were total alcohol abstinence and cumulative abstinence duration, which were assessed at outpatient visits. Relapse was defined as alcohol intake of more than four drinks per day or overall consumption of 14 or more drinks per week over a period of at least 4 weeks. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00525252. Findings Of 42 patients allocated baclofen, 30 (71%) achieved and maintained abstinence compared with 12 (29%) of 42 assigned placebo (odds ratio 6·3 95% CI 2·4–16·1; p=0·0001). The number of dropouts (termination of treatment) did not differ between the baclofen (6/42 14%) and placebo (13/42 31%) groups (p=0·12). Cumulative abstinence duration was about twofold higher in patients allocated baclofen than in those assigned placebo (mean 62·8 SE 5·4 vs 30·8 5·5 days; p=0·001). No hepatic side-effects were recorded. Interpretation Baclofen is effective at promoting alcohol abstinence in alcohol-dependent patients with liver cirrhosis. The drug is well tolerated and could have an important role in treatment of these individuals.
To conduct a double-blind, placebo-controlled randomized clinical trial of baclofen in the treatment of alcohol dependence.
Out of 69 participants consecutively screened, 42 alcohol-dependent ...patients were randomized to receive placebo, baclofen 30 mg/day or baclofen 60 mg/day for 12 weeks. All subjects were offered BRENDA, a structured psychosocial therapy for alcohol dependence that seeks to improve motivation for change, enhance strategies to prevent relapse and encourage compliance with treatment.
Intention-to-treat analyses revealed that alcohol consumption (heavy drinking days, drinks per drinking day) significantly reduced across all three groups during the treatment period. There were no statistically significant advantages to treatment on time to first heavy drinking day (relapse) (P = 0.08), nor time to first drink (lapse) (P = 0.18). A post hoc analysis stratifying according to whether there had been a comorbid anxiety disorder, revealed a beneficial effect of baclofen 30 mg/day versus placebo on time to lapse and relapse (P < 0.05). There was also a beneficial effect for baclofen 60 mg/day relative to placebo on time to relapse in this comorbid group (P < 0.05). Both doses of baclofen were well tolerated. There were no serious adverse events.
In spite of the small sample for a 3-arm clinical trial, this study suggests a specific role of baclofen in alcohol-dependent individuals with comorbid anxiety. Replication in larger, fully-powered studies is required.
Differential uptake of water and solutes by plant roots generates heterogeneous concentration distributions in soils. Noninvasive observations of root system architecture and concentration patterns ...therefore provide information about root water and solute uptake. We present the application of magnetic resonance imaging (MRI) to image and monitor root architecture and the distribution of a tracer, GdDTPA2− (Gadolinium‐diethylenetriaminepentacetate) noninvasively during an infiltration experiment in a soil column planted with white lupin. We show that inversion recovery preparation within the MRI imaging sequence can quantitatively map concentrations of a tracer in a complex root‐soil system. Instead of a simple T1 weighting, the procedure is extended by a wide range of inversion times to precisely map T1 and subsequently to cover a much broader concentration range of the solute. The derived concentrations patterns were consistent with mass balances and showed that the GdDTPA2− tracer represents a solute that is excluded by roots. Monitoring and imaging the accumulation of the tracer in the root zone therefore offers the potential to determine where and by which roots water is taken up.
Key Points
Longitudinal relaxation time maps allow the quantification of a contrast agent in natural porous media over a wide concentration range
GdDTPA is a convenient tracer for monitoring flow and for quantification of accumulation processes in a lupin root soil system
Active and less‐active roots can be discriminated
Abstract
Background
In 2019 daily liquid methadone and sublingual buprenorphine-naloxone were primary opioid agonist treatments for correctional centres in New South Wales, Australia. However, both ...had significant potential for diversion to other patients, and their daily administration was resource intensive. An alternative treatment in the form of subcutaneous depot buprenorphine became a viable option following a safety trial in 2020 – the UNLOC-T study. Depot preparation demonstrated advantages over current treatments as more difficult to divert and requiring fewer administrations. This paper reports the results of economic modelling of staffing costs in medication administration comparing depot buprenorphine, methadone, and sublingual buprenorphine provision in UNLOC-T trial facilities.
Methods
The costing study adopted a micro-costing approach involving the synthesis of cost data from the UNLOC-T clinical trial as well as data collected from Justice Health and Forensic Mental Health Network records. Labour and materials data were collected during site observations and interviews. Costs were calculated from two payer perspectives: a) the New South Wales (state) government which funds custodial and health services; and b) the Australian Commonwealth government, which pays for medications. The analysis compared the monthly-per-patient cost for each of the three medications in trial-site facilities during July 2019. This was followed by simulation of depot buprenorphine implementation across the study population. Costs associated with medical assessment and reviews were excluded.
Results
The monthly-per-patient New South Wales government service costs of depot buprenorphine, methadone and sublingual buprenorphine were: $151, $379 and $1,529 respectively while Commonwealth government medication costs were $434, $80 and $525. The implementation simulation found that service costs of depot buprenorphine declined as patients transitioned from weekly to monthly administration. Costs of treatment using the other medications increased as patient numbers decreased alongside fixed costs. At 12 months, monthly-per-patient service costs for depot buprenorphine, methadone and sublingual buprenorphine—which would be completely phased out by month 13—were $92, $530 and $2,162 respectively.
Conclusions
Depot buprenorphine was consistently the least costly of the treatment options. Future modelling could allow for dynamic patient populations and downstream impacts for participants and the state health system.
Trial registration
ACTRN12618000942257
. Registered 4 June 2018.
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