Advances in drug and alcohol research最新文献

At-risk alcohol and illicit drug use are risk factors for disease and in-hospital complications. This study investigated whether clinicians document substance use in the electronic records of acutely hospitalized internal medicine patients. Alcohol and illicit drug positive patients were identified using prospectively gathered substance use data from a study sample comprising 2,872 patients included from November 2016 to December 2017 at an internal medicine hospital in Oslo, Norway. These data were unknown to hospital staff. Whether physicians recorded quantitative substance use assessments and interventions was examined in patients with study-verified alcohol use in excess of low-risk guidelines (Alcohol Use Disorder Identification Test-4 scores [AUDIT-4] of ≥5 for women and ≥7 for men) and/or illicit drug use (one or more illicit drug detected by liquid chromatography-mass spectrometry [LC-MS] analysis). Among 548 study-verified alcohol-positive patients, physicians documented quantity and frequency (QF) of use in 43.2% (n = 237) and interventions in 22.0% (n = 121). Alcohol interventions were associated with harmful drinking (AUDIT-4 ≥9 points; adjusted odds ratio [AOR] = 4.87; 95% CI: 2.54-9.31; p < 0.001) and QF assessments (AOR = 3.66; 95% CI: 1.13-11.84; p = 0.02). Among 157 illicit-positive patients, drug use was described quantitatively in 34.4% (n = 54) and interventions in 26.0% (n = 40). The rate of quantitative alcohol and illicit drug use assessment by hospital physicians is poor, with a correspondingly low intervention rate. Important opportunities for attenuating or intervening in at-risk alcohol and illicit drug use are missed.

As part of a broader qualitative study aimed at understanding the experiences and opinions of adolescents and young adults (AYA) who do not drink alcohol in Switzerland, participants were questioned about their perceptions of the term "abstinence" in the context of alcohol non-consumption. Twelve focus groups were conducted with 63 participants (36 females, 27 males), aged between 14 years and 20 years. Participants were grouped by gender, age (based on Swiss alcohol laws), and drinking status (non-drinker or drinker). The discussions were recorded and transcribed, and thematic content analysis was used to identify and categorize key themes. The terms "abstinence," "abstainer," and "abstention" were generally considered unsuitable when describing young people who do not consume alcohol regardless of the drinking status of the participants. The connotation carried by the terms was mostly perceived as religious, sexual, negative and stigmatizing. "Abstinence" was considered more appropriate for adults who have stopped drinking due to alcohol-related issues. When referring to youths, terms such as "non-drinking," "non-drinkers" or "alcohol non-consumption" were preferred, especially to better integrate non-drinking youths and positively highlight their choices in preventive and educational initiatives.

Aims: The objective of this study is to illustrate the application of a machine learning algorithm, K Nearest Neighbor (k-NN) to impute missing alcohol data in a prospective study among pregnant women.

Methods: We used data from the Safe Passage study (n = 11,083). Daily alcohol consumption for the last reported drinking day and 30 days prior was recorded using the Timeline Follow back method, which generated a variable amount of missing data per participants. Of the 3.2 million person-days of observation, data were missing for 0.36 million (11.4%). Using the k-NN imputed values were weighted for the distances and matched for the day of the week. Since participants with no missing days were not comparable to those with missing data, segments of non-missing data from all participants were included as a reference. Validation was done after randomly deleting data for 5-15 consecutive days from the first trimester.

Results: We found that data from 5 nearest neighbors (i.e., K = 5) and segments of 55 days provided imputed values with least imputation error. After deleting data segments from the first trimester data set with no missing days, there was no difference between actual and predicted values for 64% of deleted segments. For 31% of the segments, imputed data were within +/-1 drink/day of the actual. Imputation accuracy varied by study site because of the differences in the magnitude of drinking and proportion of missing data.

Conclusion: k-NN can be used to impute missing data from longitudinal studies of alcohol during pregnancy with high accuracy.

Male rhesus monkeys (n = 24) had a biopsy of prefrontal cortical area 46 prior to chronic ethanol self-administration (n = 17) or caloric control (n = 7). Fourteen months of daily self-administration (water vs. 4% alcohol, 22 h access/day termed "open-access") was followed by two cycles of prolonged abstinence (5 weeks) each followed by 3 months of open-access alcohol and a final abstinence followed by necropsy. At necropsy, a biopsy of Area 46, contralateral to the original biopsy, was obtained. Gene expression data (RNA-Seq) were collected comparing biopsy/necropsy samples. Monkeys were categorized by drinking status during the final post-abstinent drinking phase as light (LD), binge (BD), heavy (HD) and very heavy (VHD drinkers). Comparing pre-ethanol to post-abstinent biopsies, four animals that converted from HD to VHD status had significant ontology enrichments in downregulated genes (necropsy minus biopsy n = 286) that included immune response (FDR < 9 × 10^-7) and plasma membrane changes (FDR < 1 × 10^-7). Genes in the immune response category included IL16 and 18, CCR1, B2M, TLR3, 6 and 7, SP2 and CX3CR1. Upregulated genes (N = 388) were particularly enriched in genes associated with the negative regulation of MAP kinase activity (FDR < 3 × 10^-5), including DUSP 1, 4, 5, 6 and 18, SPRY 2, 3, and 4, SPRED2, BMP4 and RGS2. Overall, these data illustrate the power of the NHP model and the within-subject design of genomic changes due to alcohol and suggest new targets for treating severe escalated drinking following repeated alcohol abstinence attempts.

Adolescent alcohol drinking is linked to high rates of adult alcohol problems and alcohol use disorder (AUD). The Neurobiology of Alcohol Drinking in Adulthood (NADIA) consortium adolescent intermittent ethanol (AIE) models adolescent binge drinking, followed by abstinent maturation to adulthood to determine the persistent AIE changes in neurobiology and behavior. AIE increases adult alcohol drinking and preference, increases anxiety and reward seeking, and disrupts sleep and cognition, all risks for AUD. In addition, AIE induces changes in neuroimmune gene expression in neurons and glia that alter neurocircuitry and behavior. HMGB1 is a unique neuroimmune signal released from neurons and glia by ethanol that activates multiple proinflammatory receptors, including Toll-like receptors (TLRs), that spread proinflammatory gene induction. HMGB1 expression is increased by AIE in rat brain and in post-mortem human AUD brain, where it correlates with lifetime alcohol consumption. HMGB1 activation of TLR increase TLR expression. Human AUD brain and rat brain following AIE show increases in multiple TLRs. Brain regional differences in neurotransmitters and cell types impact ethanol responses and neuroimmune gene induction. Microglia are monocyte-like cells that provide trophic and synaptic functions, that ethanol proinflammatory signals sensitize or "prime" during repeated drinking cycles, impacting neurocircuitry. Neurocircuits are differently impacted dependent upon neuronal-glial signaling. Acetylcholine is an anti-inflammatory neurotransmitter. AIE increases HMGB1-TLR4 signaling in forebrain, reducing cholinergic neurons by silencing multiple cholinergic defining genes through upregulation of RE-1 silencing factor (REST), a transcription inhibitor known to regulate neuronal differentiation. HMGB1 REST induction reduces cholinergic neurons in basal forebrain and cholinergic innervation of hippocampus. Adult brain hippocampal neurogenesis is regulated by a neurogenic niche formed from multiple cells. In vivo AIE and in vitro studies find ethanol increases HMGB1-TLR4 signaling and other proinflammatory signaling as well as reducing trophic factors, NGF, and BDNF, coincident with loss of the cholinergic synapse marker vChAT. These changes in gene expression-transcriptomes result in reduced adult neurogenesis. Excitingly, HMGB1 antagonists, anti-inflammatories, and epigenetic modifiers like histone deacetylase inhibitors restore trophic the neurogenesis. These findings suggest anti-inflammatory and epigenetic drugs should be considered for AUD therapy and may provide long-lasting reversal of psychopathology.