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.
MacKillop J, Agabio R, Ewing SWFW, et al., 2022, Hazardous drinking and alcohol use disorders, NATURE REVIEWS DISEASE PRIMERS, Vol: 8, ISSN: 2056-676X
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- Citations: 9
Padmanathan P, Hall K, Moran P, et al., 2022, Corrigendum to "Prevention of suicide and reduction of self-harm among people with substance use disorder: A systematic review and meta-analysis of randomised controlled trials " [Comprehensive Psychiatry, volume 96 (2020)], COMPREHENSIVE PSYCHIATRY, Vol: 119, ISSN: 0010-440X
Vamvakopoulou IA, Fonville L, Hayes A, et al., 2022, Selective D3 receptor antagonism modulates neural response during negative emotional processing in substance dependence, Frontiers in Psychiatry, Vol: 13, Pages: 1-20, ISSN: 1664-0640
Introduction: Negative affective states contribute to the chronic-relapsingnature of addiction. Mesolimbic dopamine D3 receptors are well placed to modulate emotion and are dysregulated in substance dependence. Selective antagonists might restore dopaminergic hypofunction, thus representing a potential treatment target. We investigated the effects of selective D3 antagonist, GSK598809, on the neural response to negativeemotional processing in substance dependent individuals and healthy controls.Methodology: Functional MRI BOLD response was assessed during an evocative image task, 2h following acute administration of GSK598809 (60mg) or placebo in a multi-site, double-blind, pseudo-randomised, cross-over design. Abstinent drug dependent individuals (DD, n=36) comprising alcohol-only (AO, n=19) and cocaine-alcohol polydrug (PD, n=17) groups, and matched controls (n=32) were presented with aversive and neutral images in a block design (contrast of interest: aversive>neutral). Whole-brain mixed-effects and a priori ROI analyses tested for group and drug effects, with identical models exploring subgroup effects.Results: No group differences in task-related BOLD signal were identified between DD and controls. However, subgroup analysis revealed greater amygdala/insular BOLD signal in PD compared with AO groups. Following drug administration, GSK598809 increased BOLD response across HC and DD groups in thalamus, caudate, putamen, and pallidum, andreduced BOLD response in insular and opercular cortices relative to placebo. Multivariate analyses in a priori ROIs revealed differential effects of D3 antagonism according to subgroup in substantia nigra; GSK598809 increased BOLD response in AO and decreased response in PD groups.Conclusion: Acute GSK598809 modulates the BOLD response to aversive image processing, providing evidence that D3 antagonism may impact emotional regulation. Enhanced BOLD response within D3-rich mesolimbic regions is consistent with its pharmacology a
Paterson L, Lingford-Hughes A, Cro S, et al., 2022, FORWARDS-1; An adaptive, single-blind, placebo-controlled ascending dose study of acute baclofen on safety parameters in opioid dependence during methadone-maintenance treatment; a pharmacokinetic-pharmacodynamic study, Trials, Vol: 23, ISSN: 1745-6215
Background:Treatment of opiate addiction with opiate substitution treatment (e.g. methadone) is beneficial. However, some individuals desire or would benefit from abstinence but there are limited options to attenuate problems with opiate withdrawal. Preclinical and preliminary clinical evidence suggests that the GABA-B agonist, baclofen, has the desired properties to facilitate opiate detoxification and prevent relapse. This study aims to understand whether there are any safety issues in administering baclofen to opioid-dependent individuals receiving methadone.Methods:Opiate-dependent individuals (DSM-5 severe opioid use disorder) maintained on methadone will be recruited from addiction services in northwest London (NHS and third sector providers). Participants will be medically healthy with no severe chronic obstructive pulmonary disease or type 2 respiratory failure, no current dependence on other substances (excluding nicotine), no current severe DSM-5 psychiatric disorders, and no contraindications for baclofen or 4800 IU vitamin D (placebo). Eligible participants will be randomised in a 3:1 ratio to receive baclofen or placebo in an adaptive, single-blind, ascending dose design. A Bayesian dose-escalation model will inform the baclofen dose (10, 30, 60, or 90 mg) based on the incidence of ‘dose-limiting toxicity’ (DLT) events and participant-specific methadone dose. A range of respiratory, cardiovascular, and sedative measures including the National Early Warning Score (NEWS2) and Glasgow Coma Scale will determine DLT. On the experimental day, participants will consume their usual daily dose of methadone followed by an acute dose of baclofen or placebo (vitamin D3) ~ 1 h later. Measures including oxygen saturation, transcutaneous CO2, respiratory rate, QTc interval, subjective effects (sedation, drug liking, craving), plasma levels (baclofen, methadone), and adverse events will be obtained using validated questionnaires and examinations periodicall
Dhital R, Coleman R, Day E, et al., 2022, Service Users' Views and Experiences of Alcohol Relapse Prevention Treatment and Adherence: New Role for Pharmacists?, ALCOHOL AND ALCOHOLISM, Vol: 57, Pages: 602-608, ISSN: 0735-0414
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- Citations: 1
Dhital R, Coleman R, Day E, et al., 2022, Service Users' Views and Experiences of Alcohol Relapse Prevention Treatment and Adherence: New Role for Pharmacists? (Mar, 10.1093/alcalc/agac011, 2022), ALCOHOL AND ALCOHOLISM, Vol: 57, Pages: 642-642, ISSN: 0735-0414
Goldstone AP, Ling YY, Nestor LJ, et al., 2022, Effect of acute desacyl ghrelin administration on eating and addictive behaviours: The gut hormone in addiction study, 2nd World Congress on Alcohol and Alcoholism Joint meeting of ISBRA and ESBRA, Publisher: Wiley, Pages: 72-73, ISSN: 0145-6008
Agunbiade K, Fonville L, McGonigle J, et al., 2022, Alterations in white matter microstructure in alcohol and alcohol-polydrug dependence: Associations with lifetime alcohol and nicotine exposure, ADDICTION BIOLOGY, Vol: 27, ISSN: 1355-6215
Venkataraman A, Mansur A, Rizzo G, et al., 2022, Widespread cell stress and mitochondrial dysfunction occur in patients with early Alzheimer’s Disease, Science Translational Medicine, Vol: 14, Pages: 1-11, ISSN: 1946-6234
Cell stress and impaired oxidative phosphorylation are central to mechanisms of synaptic loss and neurodegeneration in the cellular pathology of Alzheimer’s disease (AD). In this study, we quantified the in vivo expression of the endoplasmic reticulum stress marker, sigma 1 receptor (S1R), using [11C]SA4503 PET, the mitochondrial complex I (MC1) with [18F]BCPP-EF and the pre-synaptic vesicular protein SV2A with [11C]UCB-J in 12 patients with early AD and in 16 cognitively normal controls. We integrated these molecular measures with assessments of regional brain volumes and cerebral blood flow (CBF) measured with magnetic resonance imaging (MRI) arterial spin labelling. Eight patients with AD were followed longitudinally to estimate the rate of change of the physiological and structural pathology markers with disease progression. The patients showed widespread increases in S1R (≤ 27%) and regional reduction in MC1 (≥ -28%) and SV2A (≥ -25%) radioligand binding, brain volume (≥ -23%), and CBF (≥ -26%). [18F]BCPP-EF PET MC1 binding (≥ -12%) and brain volumes (≥ -5%) showed progressive reductions over 12-18 months, suggesting that they both could be used as pharmacodynamic indicators in early-stage therapeutics trials. Associations of reduced MC1 and SV2A and increased S1R radioligand binding with reduced cognitive performance in AD, although exploratory, suggested a loss of metabolic functional reserve with disease. Our study thus provides in vivo evidence for widespread, clinically relevant cellular stress and bioenergetic abnormalities in early AD.
Evans RA, Leavy OC, Richardson M, et al., 2022, Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study, The Lancet Respiratory Medicine, Vol: 10, Pages: 761-775, ISSN: 2213-2600
BackgroundNo effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge.MethodsThe Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing.Findings2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46–0·99]), obes
Hayes A, McGonigle J, Elliott R, et al., 2022, The Relationship Between Reward and Impulsivity in Substance Dependence: An fMRI Study, Publisher: ELSEVIER SCIENCE INC, Pages: S103-S103, ISSN: 0006-3223
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- Citations: 1
Sparasci O, Bhui K, Biswas A, et al., 2022, Impact of COVID-19 on mental health research: is this the breaking point?, BRITISH JOURNAL OF PSYCHIATRY, Vol: 220, Pages: 254-256, ISSN: 0007-1250
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- Citations: 4
Ostinelli EG, Smith K, Zangani C, et al., 2022, COVID-19 and substance use disorders: a review of international guidelines for frontline healthcare workers of addiction services, BMC PSYCHIATRY, Vol: 22
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- Citations: 2
Mozgunov P, Cro S, Lingford-Hughes A, et al., 2022, A dose-finding design for dual-agent trials with patient-specific doses for one agent with application to an opiate detoxification trial, Pharmaceutical Statistics: the journal of applied statistics in the pharmaceutical industry, Vol: 21, Pages: 476-495, ISSN: 1539-1604
There is a growing interest in early phase dose-finding clinical trials studying combinations of several treatments. While the majority of dose finding designs for such setting were proposed for oncology trials, the corresponding designs are also essential in other therapeutic areas. Furthermore, there is increased recognition of recommending the patient-specific doses/combinations, rather than a single target one that would be recommended to all patients in later phases regardless of their characteristics. In this paper, we propose a dose-finding design for a dual-agent combination trial motivated by an opiate detoxification trial. The distinguishing feature of the trial is that the (continuous) dose of one compound is defined externally by the clinicians and is individual for every patient. The objective of the trial is to define the dosing function that for each patient would recommend the optimal dosage of the second compound. Via a simulation study, we have found that the proposed design results in high accuracy of individual dose recommendation and is robust to the model misspecification and assumptions on the distribution of externally defined doses.
Grabski M, McAndrew A, Lawn W, et al., 2022, Adjunctive Ketamine With Relapse Prevention-Based Psychological Therapy in the Treatment of Alcohol Use Disorder, AMERICAN JOURNAL OF PSYCHIATRY, Vol: 179, Pages: 152-162, ISSN: 0002-953X
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- Citations: 33
Herlinger K, Lingford-Hughes A, 2022, Opioid use disorder and the brain: a clinical perspective, ADDICTION, Vol: 117, Pages: 495-505, ISSN: 0965-2140
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- Citations: 5
Notley C, Houghton B, Maskrey V, et al., 2022, An exploration of identity change in post-detoxification alcohol dependent individuals, DRUGS HABITS AND SOCIAL POLICY, Vol: 23, Pages: 48-61, ISSN: 2752-6739
Venkataraman AV, Bai W, Whittington A, et al., 2021, Boosting the diagnostic power of amyloid-β PET using a data-driven spatially informed classifier for decision support, Alzheimer's Research and Therapy, Vol: 13, Pages: 1-12, ISSN: 1758-9193
BackgroundAmyloid-β (Aβ) PET has emerged as clinically useful for more accurate diagnosis of patients with cognitive decline. Aβ deposition is a necessary cause or response to the cellular pathology of Alzheimer’s disease (AD). Usual clinical and research interpretation of amyloid PET does not fully utilise all information regarding the spatial distribution of signal. We present a data-driven, spatially informed classifier to boost the diagnostic power of amyloid PET in AD.MethodsVoxel-wise k-means clustering of amyloid-positive voxels was performed; clusters were mapped to brain anatomy and tested for their associations by diagnostic category and disease severity with 758 amyloid PET scans from volunteers in the AD continuum from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). A machine learning approach based on this spatially constrained model using an optimised quadratic support vector machine was developed for automatic classification of scans for AD vs non-AD pathology.ResultsThis classifier boosted the accuracy of classification of AD scans to 81% using the amyloid PET alone with an area under the curve (AUC) of 0.91 compared to other spatial methods. This increased sensitivity to detect AD by 15% and the AUC by 9% compared to the use of a composite region of interest SUVr.ConclusionsThe diagnostic classification accuracy of amyloid PET was improved using an automated data-driven spatial classifier. Our classifier highlights the importance of considering the spatial variation in Aβ PET signal for optimal interpretation of scans. The algorithm now is available to be evaluated prospectively as a tool for automated clinical decision support in research settings.
Venkataraman A, Bishop C, Mansur A, et al., 2021, Imaging synaptic microstructure and synaptic loss in vivo in early Alzheimer’s Disease, Publisher: Cold Spring Harbor Laboratory
Background Synaptic loss and neurite dystrophy are early events in Alzheimer’s Disease (AD). We aimed to characterise early synaptic microstructural changes in vivo.Methods MRI neurite orientation dispersion and density imaging (NODDI) and diffusion tensor imaging (DTI) were used to image cortical microstructure in both sporadic, late onset, amyloid PET positive AD patients and healthy controls (total n = 28). We derived NODDI measures of grey matter extracellular free water (FISO), neurite density (NDI) and orientation dispersion (ODI), which provides an index of neurite branching and orientation, as well as more conventional DTI measures of fractional anisotropy (FA), mean/axial/radial diffusivity (MD, AD, RD, respectively). We also performed [11C]UCB-J PET, which provides a specific measure of the density of pre-synaptic vesicular protein SV2A. Both sets of measures were compared to regional brain volumes.Results The AD patients showed expected relative decreases in regional brain volumes (range, -6 to - 23%) and regional [11C]UCB-J densities (range, -2 to -25%). Differences between AD and controls were greatest in the hippocampus. NODDI microstructural measures showed greater FISO (range, +26 to +44%) in AD, with little difference in NDI (range, -1 to +7%) and mild focal changes in ODI (range, -4 to +3%). Regionally greater FISO and lower [11C]UCB-J binding were correlated across grey matter in patients (most strongly in the caudate, r2 = 0.37, p = 0.001). FISO and DTI RD were strongly positively associated, particularly in the hippocampus (r2 = 0.98, p < 7.4 × 10−9). After 12-18 months we found a 5% increase in FISO in the temporal lobe, but little change across all ROIs in NDI and ODI. An exploratory analysis showed higher parietal lobe FISO was associated with lower language scores in people with AD.Conclusions We interpreted the increased extracellular free water as a possible consequence of glial activation. The dynamic range of disease
Herlinger K, Lingford-Hughes A, 2021, Addressing unmet needs in opiate dependence: supporting detoxification and advances in relapse prevention, BJPSYCH ADVANCES, Vol: 27, Pages: 362-372, ISSN: 2056-4678
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- Citations: 5
Nutt D, Hayes A, Fonville L, et al., 2021, Alcohol and the Brain, NUTRIENTS, Vol: 13
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- Citations: 13
Evans RA, McAuley H, Harrison EM, et al., 2021, Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study, The Lancet Respiratory Medicine, Vol: 9, Pages: 1275-1287, ISSN: 2213-2600
BACKGROUND: The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. METHODS: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9-6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40-59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health bur
Palmer EOC, Trender W, Tyacke RJ, et al., 2021, Impact of COVID-19 restrictions on alcohol consumption behaviours, BJPsych Open, Vol: 7, Pages: 1-7, ISSN: 2056-4724
BackgroundWe aimed to evaluate how coronavirus (COVID-19) restrictions had altered individual's drinking behaviours, including consumption, hangover experiences, and motivations to drink, and changing levels of depression and anxiety.MethodWe conducted an online cross-sectional self-report survey. Whole group analysis compared pre- versus post-COVID restrictions. A correlation coefficient matrix evaluated the associations between all outcome scores. Self-report data was compared with Alcohol Use Disorders Identification Test (AUDIT) scores from the 2014 Adult Psychiatric Morbidity Survey. Multiple linear modelling (MLM) was calculated to identify factors associated with increasing AUDIT scores and post-restriction AUDIT scores.ResultsIn total, 346 individuals completed the survey, of which 336 reported drinking and were therefore analysed. After COVID-19 restrictions 23.2% of respondents reported an increased AUDIT score, and 60.1% a decreased score. AUDIT score change was positively correlated with change in depression (P < 0.01, r = 0.15), anxiety (P < 0.01, r = 0.15) and drinking to cope scores (P < 0.0001, r = 0.35). MLM revealed that higher AUDIT scores were associated with age, mental illness, lack of a garden, self-employed or furloughed individuals, a confirmed COVID-19 diagnosis and smoking status.ConclusionsCOVID-19 restrictions decreased alcohol consumption for the majority of individuals in this study. However, a small proportion increased their consumption; this related to drinking to cope and increased depression and anxiety.
Venkataraman A, Mansur A, Rizzo G, et al., 2021, Widespread cell stress and mitochondrial dysfunction in early Alzheimer’s Disease, Publisher: MedRxiv
Cell stress and impaired oxidative phosphorylation are central to mechanisms of synaptic loss and neurodegeneration in the cellular pathology of Alzheimer’s disease (AD). We quantified the in vivo density of the endoplasmic reticulum stress marker, the sigma 1 receptor (S1R) using [11C]SA4503 PET, as well as that of mitochondrial complex I (MC1) with [18F]BCPP-EF and the pre-synaptic vesicular protein SV2A with [11C]UCB-J in 12 patients with early AD and in 16 cognitively normal controls. We integrated these molecular measures with assessments of regional brain volumes and brain perfusion (CBF) measured with MRI arterial spin labelling. 8 AD patients were followed longitudinally to estimate rates of change with disease progression over 12-18 months. The AD patients showed widespread increases in S1R (≤ 27%) and regional decreases in MC1 (≥ -28%), SV2A (≥ -25%), brain volume (≥ -23%), and CBF (≥ -26%). [18F]BCPP-EF PET MC1 density (≥ -12%) and brain volumes (≥ -5%) were further reduced at follow up in brain regions consistent with the differences between AD patients and controls at baseline. Exploratory analyses showing associations of MC1, SV2A and S1R density with cognitive changes at baseline and longitudinally with AD, but not in controls, suggested a loss of metabolic functional reserve with disease. Our study thus provides novel in vivo evidence for widespread cellular stress and bioenergetic abnormalities in early AD and that they may be clinically meaningful.
Kouimtsidis C, Houghton B, Gage H, et al., 2021, A feasibility trial of an intervention in alcohol dependence for structured preparation before detoxification versus usual care: the SPADe trial results, PILOT AND FEASIBILITY STUDIES, Vol: 7
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