Publications
324 results found
Thursz M, Lingford-Hughes A, 2023, Advances in the understanding and management of alcohol-related liver disease., BMJ, Vol: 383
Alcohol-related liver disease (ALD) is a major cause of liver-related morbidity and mortality. Epidemiological trends indicate recent and predicted increases in the burden of disease. Disease progression is driven by continued alcohol exposure on a background of genetic predisposition together with environmental cofactors. Most individuals present with advanced disease despite a long history of excessive alcohol consumption and multiple missed opportunities to intervene. Increasing evidence supports the use of non-invasive tests to screen for and identify disease at earlier stages. There is a definite role for public health measures to reduce the overall burden of disease. At an individual level, however, the ability to influence subsequent disease course by modifying alcohol consumption or the underlying pathogenic mechanisms remains limited due to a comparative lack of effective, disease-modifying medical interventions. Abstinence from alcohol is the key determinant of outcome in established ALD and the cornerstone of clinical management. In those with decompensated ALD, liver transplant has a clear role. There is consensus that abstinence from alcohol for an arbitrary period should not be the sole determinant in a decision to transplant. An increasing understanding of the mechanisms by which alcohol causes liver disease in susceptible individuals offers the prospect of new therapeutic targets for disease-modifying drugs. Successful translation will require significant public and private investment in a disease area which has traditionally been underfunded when compared to its overall prevalence.
Rodrigues R, Mehesz EZ, Lingford-Hughes A, et al., 2023, Approach-avoidance biases to self-harm cues in young people with self-harm, JOURNAL OF AFFECTIVE DISORDERS, Vol: 340, Pages: 435-441, ISSN: 0165-0327
Donoghue K, Boniface S, Brobbin E, et al., 2023, Adjunctive Medication Management and Contingency Management to enhance adherence to acamprosate for alcohol dependence: the ADAM trial RCT., Health Technol Assess, Vol: 27, Pages: 1-88
BACKGROUND: Acamprosate is an effective and cost-effective medication for alcohol relapse prevention but poor adherence can limit its full benefit. Effective interventions to support adherence to acamprosate are therefore needed. OBJECTIVES: To determine the effectiveness of Medication Management, with and without Contingency Management, compared to Standard Support alone in enhancing adherence to acamprosate and the impact of adherence to acamprosate on abstinence and reduced alcohol consumption. DESIGN: Multicentre, three-arm, parallel-group, randomised controlled clinical trial. SETTING: Specialist alcohol treatment services in five regions of England (South East London, Central and North West London, Wessex, Yorkshire and Humber and West Midlands). PARTICIPANTS: Adults (aged 18 years or more), an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis of alcohol dependence, abstinent from alcohol at baseline assessment, in receipt of a prescription for acamprosate. INTERVENTIONS: (1) Standard Support, (2) Standard Support with adjunctive Medication Management provided by pharmacists via a clinical contact centre (12 sessions over 6 months), (3) Standard Support with adjunctive Medication Management plus Contingency Management that consisted of vouchers (up to £120) to reinforce participation in Medication Management. Consenting participants were randomised in a 2 : 1 : 1 ratio to one of the three groups using a stratified random permuted block method using a remote system. Participants and researchers were not blind to treatment allocation. MAIN OUTCOME MEASURES: Primary outcome: self-reported percentage of medication taken in the previous 28 days at 6 months post randomisation. Economic outcome: EuroQol-5 Dimensions, a five-level version, used to calculate quality-adjusted life-years, with costs estimated using the Adult Service Use Schedule. RESULTS: Of the 1459 potential participants approached, 1019 (
Sinclair J, Barnes TRE, Lingford-Hughes A, et al., 2023, Management of medically assisted withdrawal from alcohol in acute adult mental health and specialist addictions in-patient services: UK clinical audit findings, BJPsych Open, Vol: 9, Pages: 1-8, ISSN: 2056-4724
BackgroundMedically assisted alcohol withdrawal (MAAW) is increasingly undertaken on acute adult psychiatric wards.AimsComparison of the quality of MAAW between acute adult wards and specialist addictions units in mental health services.MethodClinical audit conducted by the Prescribing Observatory for Mental Health (POMH). Information on MAAW was collected from clinical records using a bespoke data collection tool.ResultsForty-five National Health Service (NHS) mental health trusts/healthcare organisations submitted data relating to the treatment of 908 patients undergoing MAAW on an acute adult ward or psychiatric intensive care unit (PICU) and 347 admitted to a specialist NHS addictions unit. MAAW had been overseen by an addiction specialist in 33 (4%) of the patients on an acute adult ward/PICU. A comprehensive alcohol history, measurement of breath alcohol, full screening for Wernicke's encephalopathy, use of parenteral thiamine, prescription of medications for relapse prevention (such as acamprosate) and referral for specialist continuing care of alcohol-related problems following discharge were all more commonly documented when care was provided on a specialist unit or when there was specialist addictions management on an acute ward.ConclusionsThe findings suggest that the quality of care provided for medically assisted withdrawal from alcohol, including the use of evidence-based interventions, is better when clinicians with specialist addictions training are involved. This has implications for future quality improvement in the provision of MAAW in acute adult mental health settings.
Roussakis A, Gennaro M, Gordon MF, et al., 2023, A PET-CT study on neuroinflammation in Huntington’s patients participating in a randomised trial with laquinimod, Brain Communications, Vol: 5, Pages: 1-10, ISSN: 2632-1297
Microglia activation, an indicator of central nervous system inflammation, is believed to contribute to the pathology of Huntington’s disease. Laquinimod is capable of regulating microglia. By targeting the translocator protein, 11C-PBR28 PET-CT imaging can be used to assess the state of regional gliosis in vivo and explore the effects of laquinimod treatment. This study relates to the LEGATO-HD, multi-centre, double-blinded, Phase 2 clinical trial with laquinimod (US National Registration: NCT02215616). Fifteen patients of the UK LEGATO-HD cohort (mean age: 45.2 ± 7.4 years; disease duration: 5.6 ± 3.0 years) were treated with laquinimod (0.5 mg, N = 4; 1.0 mg, N = 6) or placebo (N = 5) daily. All participants had one 11C-PBR28 PET-CT and one brain MRI scan before laquinimod (or placebo) and at the end of treatment (12 months apart). PET imaging data were quantified to produce 11C-PBR28 distribution volume ratios. These ratios were calculated for the caudate and putamen using the reference Logan plot with the corpus callosum as the reference region. Partial volume effect corrections (Müller–Gartner algorithm) were applied. Differences were sought in Unified Huntington’s Disease Rating Scale scores and regional distribution volume ratios between baseline and follow-up and between the two treatment groups (laquinimod versus placebo). No significant change in 11C-PBR28 distribution volume ratios was found post treatment in the caudate and putamen for both those treated with laquinimod (N = 10) and those treated with placebo (N = 5). Over time, the patients treated with laquinimod did not show a significant clinical improvement. Data from the 11C-PBR28 PET-CT study indicate that laquinimod may not have affected regional translocator protein expression and clinical performance over the studied period.
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