Incisional negative pressure wound therapy may not protect against post-operative surgical site complications in bicondylar tibial plateau fractures.

PURPOSE: To determine if incisional negative pressure wound therapy is protective against post-operative surgical site complications following definitive fixation of bicondylar tibial plateau fractures. METHODS: A retrospective analysis of patients diagnosed with an acute bicondylar tibial plateau fracture (AO/OTA 41-C) undergoing ORIF from 2010 to 2020 was performed. Patients received either a standard sterile dressing (SD) or incisional negative pressure wound therapy (iNPWT). Primary outcomes included surgical site infection, osteomyelitis, and wound dehiscence. Secondary outcomes included non-union and return to the operating room. Multivariate logistic regression analyses were performed. RESULTS: 180 patients were included and 22% received iNPWT (n = 40) and 78% received standard dressings (n = 140). iNPWT was more common in active smokers (24.7% vs. 19.3%, p = 0.002) and the SD group was more likely to be lost to follow up (3.6% vs. 0%, p = 0.025). iNPWT was not protective against infection or surgical site complications, and in fact, was associated with higher odds of post-operative infection (OR: 8.96, p = 0.005) and surgical site complications (OR:4.874, p = 0.009) overall. Alcohol abuse (OR: 19, p = 0.005), tobacco use (OR: 4.67, p = 0.009), and time to definitive surgery (OR = 1.21, p = 0.033) were all independent risk factors for post-operative infection. CONCLUSION: In this series of operatively treated bicondylar tibial plateau fractures, iNPWT did not protect against post-operative surgical site complications compared to conventional dressings. Tobacco use, alcohol abuse, and time to definitive surgery, were independent risk factors for post-operative infection. Further studies are needed to determine if iNPWT offers a protective benefit in exclusively high-risk patients with relevant medical and social history.

Grandparent alcohol use disorder and grandparent-grandchild relationships.

Involvement of grandparents in grandchildren's lives is important for grandchild well-being. Studies suggest that the quality of relationships between grandparents and their adult children may "spill over" to the quality of their relationships with their grandchildren. However, no research has tested whether grandparent alcohol use disorder (AUD) disrupts intergenerational relationships. This is important because grandchildren may not benefit from closeness with grandparents with AUD. In a sample of 295 parents and their children (N = 604) from a larger longitudinal study oversampled for familial AUD, this study tested whether grandparents (G1, "Generation 1") with AUD had poorer relationships with their adult children (G2 "Generation 2") in terms of greater stress and less support provided and less closeness with their grandchildren (G3, "Generation 3"). We also tested whether poorer G1-G2 relationship quality predicted less G1-G3 closeness. Finally, we tested whether effects of G1 AUD on G1-G3 closeness were explained by G1-G2 relationship quality. Separate models were estimated for maternal and paternal grandparents. We found evidence for three indirect effects. First, G1 maternal grandparent AUD predicted greater stress in the G1 grandmother-G2 mother relationship, which was associated with greater closeness between maternal grandmothers and grandchildren. This indirect effect was replicated in G1 paternal grandfathers and G2 fathers. Additionally, G1 paternal grandparent AUD was associated with lower levels of support provided from G1 grandfathers to G2 fathers, which predicted less closeness between paternal grandfathers and grandchildren. The results demonstrate complex intergenerational effects of AUD on family relationships and consistent with the hypothesized "spillover" effect of intergenerational relationships. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Negative modulation of AMPA receptors bound to transmembrane AMPA receptor regulatory protein γ-8 blunts the positive reinforcing properties of alcohol and sucrose in a brain region-dependent manner in male mice.

RATIONALE: The development and progression of alcohol use disorder (AUD) are widely viewed as maladaptive neuroplasticity. The transmembrane alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) regulatory protein γ8 (TARP γ-8) is a molecular mechanism of neuroplasticity that has not been evaluated in AUD or other addictions. OBJECTIVE: To address this gap in knowledge, we evaluated the mechanistic role of TARP γ-8 bound AMPAR activity in the basolateral amygdala (BLA) and ventral hippocampus (vHPC) in the positive reinforcing effects of alcohol, which drive repetitive alcohol use throughout the course of AUD, in male C57BL/6 J mice. These brain regions were selected because they exhibit high levels of TARP γ-8 expression and send glutamate projections to the nucleus accumbens (NAc), which is a key nucleus in the brain reward pathway. METHODS AND RESULTS: Site-specific pharmacological inhibition of AMPARs bound to TARP γ-8 in the BLA via bilateral infusion of the selective negative modulator JNJ-55511118 (0-2 µg/µl/side) significantly decreased operant alcohol self-administration with no effect on sucrose self-administration in behavior-matched controls. Temporal analysis showed that reductions in alcohol-reinforced response rate occurred > 25 min after the onset of responding, consistent with a blunting of the positive reinforcing effects of alcohol in the absence of nonspecific behavioral effects. In contrast, inhibition of TARP γ-8 bound AMPARs in the vHPC selectively decreased sucrose self-administration with no effect on alcohol. CONCLUSIONS: This study reveals a novel brain region-specific role of TARP γ-8 bound AMPARs as a molecular mechanism of the positive reinforcing effects of alcohol and non-drug rewards.

Impact of comorbidity scores and lifestyle factors in curative radiotherapy in laryngeal cancer.

PURPOSE: The principal goal of treatment of laryngeal cancer is to eliminate a tumour while preserving laryngeal function with radio(chemo)therapy being the mainstay of treatment. The aim of this report is to present the influence of comorbidities and lifestyle factors on treatment outcomes in our cohort of patients. METHODS: During the period 2009-2018, curative radio(chemo)therapy for laryngeal cancer was performed on 189 patients. RESULTS: The median OS was 50.8 months, with a mean PFS of 96.5 months, mean LC of 101.4 months and a median follow-up of 38.1 months. Acute and late treatment toxicity grade 3-4 was observed in 39.2% patients and 10.1% patients, respectively. A significant effect on overall survival was confirmed for the baseline PS (performance status), severity of weight loss, baseline haemoglobin values, history of alcohol abuse, marital status and comorbidities according to the Charlson Comorbidity Index, as well as the ACE-27 and ASA scores. CONCLUSIONS: In our cohort of patients treated with radio(chemo)therapy for laryngeal cancer, we found good therapeutic results and an acceptable side-effect profile. Statistically significant predictors of overall survival were the baseline PS, weight loss, anaemia, associated comorbidities, history of alcohol abuse and marital status.

Cross-sectional survey of a convenience sample of Australians who use alcohol home delivery services.

INTRODUCTION: Online alcohol purchasing and home delivery has increased in recent years, accelerated by the onset of the coronavirus disease 2019 pandemic. This article aims to investigate the purchasing and drinking behaviour of Australians who use online alcohol delivery services. METHOD: A cross-sectional self-report survey with a convenience sample of 1158 Australians ≥18 years (49.3% female) who used an online alcohol delivery service in the past 3 months, recruited through paid social media advertisements from September to November 2021. Quota sampling was used to obtain a sample with age and gender strata proportional to the Australian adult population. Descriptive statistics were generated and logistic regression used to explore variables that predict hazardous/harmful drinking (Alcohol Use Disorders Identification Test score ≥8). RESULTS: One-in-five (20.1%, 95% confidence interval [CI] 17.8-22.5) participants had used an alcohol delivery service to extend a home drinking session because they had run out of alcohol and wanted to continue drinking and, of these, one-third (33.9%, 95% CI 27.9-40.4) indicated that if the service was not available they would have stopped drinking. Using delivery services in this way was associated with six times higher odds of drinking at hazardous/harmful levels (odds ratio 6.26, 95% CI 3.78-10.36). Participants ≤25 years were significantly more likely to report never having their identification verified when receiving their alcohol delivery at the door compared with purchasing takeaway alcohol in-person at a bottle shop (p < 0.001, McNemar). DISCUSSION AND CONCLUSION: Given the risks associated with alcohol delivery, regulation of these services should be improved to meet the same standards as bricks-and-mortar bottle shops.

Patient perceptions regarding alcohol use after bariatric surgery.

INTRODUCTION: Patients who have undergone bariatric surgery are at increased risk of an alcohol use disorder. Though patients understand this risk, the majority engage in post-surgical alcohol use. This suggests that education alone is not sufficient to reduce post-surgical drinking. To prevent development of post-surgical alcohol use disorders, we need better understanding of the reasons patients use alcohol following surgery. The purpose of this study was to identify factors associated with post-surgical alcohol use. METHOD: Patients (N = 20) who were 1-3 years post-bariatric surgery and were consuming alcohol at least twice monthly participated in a 60-min interview. Participants responded about their knowledge regarding risk of post-surgical alcohol use and reasons why patients may start drinking. Deductive and inductive coding were completed by two independent raters. RESULTS: Although nearly all participants were aware of the risks associated with post-surgical alcohol use, most believed that lifelong abstinence from alcohol was unrealistic. Common reasons identified for using alcohol after bariatric surgery included social gatherings, resuming pre-surgical use, and addiction transfer. Inductive coding identified three themes: participants consumed alcohol in different ways compared to prior to surgery; the effect of alcohol was substantially stronger than pre-surgery; and beliefs about why patients develop problematic alcohol use following surgery. CONCLUSION: Patients consume alcohol after bariatric surgery for a variety of reasons and they do not believe recommending abstinence is useful. Understanding patient perceptions can inform interventions to minimize alcohol use after bariatric surgery. Modifications to traditional alcohol relapse prevention strategies may provide a more robust solution to decreasing negative outcomes experienced by individuals undergoing bariatric surgery.

Disparities in Elective and Nonelective Total Hip Arthroplasty.

BACKGROUND: Prior studies have shown disparities in utilization of primary and revision total hip arthroplasty (THA). However, little is known about patient population differences associated with elective and nonelective surgery. Therefore, the aim of this study was to explore factors that influence primary utilization and revision risk of THA based on surgery indication. METHODS: Data were obtained from 7,543 patients who had a primary THA from 2014 to 2020 in a database, which consists of multiple health partner systems in Louisiana and Texas. Of these patients, 602 patients (8%) underwent nonelective THA. THA was classified as "elective" or "nonelective" if the patient had a diagnosis of hip osteoarthritis or femoral neck fracture, respectively. RESULTS: After multivariable logistic regression, nonelective THA was associated with alcohol dependence, lower body mass index (BMI), women, and increased age and number of comorbid conditions. No racial or ethnic differences were observed for the utilization of primary THA. Of the 262 patients who underwent revision surgery, patients who underwent THA for nonelective etiologies had an increased odds of revision within 3 years of primary THA (odds ratio (OR) = 1.66, 95% Confidence Interval (CI) = 1.06-2.58, P-value = .025). After multivariable logistic regression, patients who had tobacco usage (adjusted odds ratio (aOR) = 1.36, 95% CI = 1.04-1.78, P-value = .024), alcohol dependence (aOR = 2.46, 95% CI = 1.45-4.15, P-value = .001), and public insurance (OR = 2.08, 95% CI = 1.18-3.70, P-value = .026) had an increased risk of reoperation. CONCLUSION: Demographic and social factors impact the utilization of elective and nonelective primary THA and subsequent revision surgery. Orthopaedic surgeons should focus on preoperative counseling for tobacco and alcohol cessation as these are modifiable risk factors to directly decrease reoperation risk.

A Prospective Cohort of Alcohol Use and Alcohol-related Problems Before and After Metabolic and Bariatric Surgery in Adolescents.

OBJECTIVE: To describe alcohol use, alcohol-related harm, and alcohol-related problems preoperatively and up to 8 years following metabolic and bariatric surgery (MBS) in adolescents. BACKGROUND: Risk for alcohol use and alcohol use disorders (AUD) increases post-Roux-en-Y gastric bypass and vertical sleeve gastrectomy in adults. However, data are lacking in adolescents who undergo MBS. METHODS: This study includes 217 adolescents (aged 13-19 y) enrolled in a 5-center prospective cohort study who underwent Roux-en-Y gastric bypass or vertical sleeve gastrectomy (2007-2011) and reported alcohol use preoperatively and annually postoperatively for up to 8 years. Time to elevated Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) score, alcohol-related harm, and alcohol-related problems were analyzed with Kaplan-Meier estimates of cumulative incidence. RESULTS: Preoperatively, the median age was 17 years; the median body mass index was 51 kg/m 2 . Alcohol use frequency and average quantity of drinks per drinking day increased postoperatively (2% consumed alcohol 2-4 times/month 6 months versus 24% 8 years postoperatively, P <0.001; 2% consumed≥3 drinks per drinking day 6 months versus 35% 8 years postoperatively, P <0.001). Cumulative incidence of postoperative onset elevated AUDIT-C score, alcohol-related harm, and alcohol-related problems at year 8 were 45% (95% CI:37-53), 43% (95% CI:36-51), and 47% (95% CI:40-55), respectively. CONCLUSIONS: Nearly half of those who underwent MBS as adolescents screened positively for AUD, symptoms of alcohol-related harm, or alcohol-related problems 8 years post-MBS, highlighting the risk for alcohol use and AUD after MBS in adolescents. AUD evaluation and treatment should be integrated into routine long-term care for adolescents undergoing MBS.

Nicotine replacement therapy for vaping cessation among mono and dual users: A mixed methods preliminary study.

Many adults express interest in e-cigarette cessation; however, there are few empirically tested interventions for quitting vaping. This study seeks to (1) evaluate reasons for quitting e-cigarettes in treatment-seeking adults, and (2) assess the feasibility and acceptability of nicotine replacement therapy (NRT) for e-cigarette cessation. Adult daily e-cigarette users completed qualitative interviews about quitting e-cigarettes, then were randomized to either 28-day supply of combination NRT (21 mg patches, 4 mg lozenges) + supportive booklet or Quitline referral. Primary aims were feasibility (number who enrolled) and acceptability (NRT use, adverse side effects). Exploratory aims evaluated abstinence (7-day point-prevalence) at end of treatment. Of the 30 participants who were enrolled, 50 % (n = 15) were dual users, and 50 % (n = 15) were mono-vapers, 26.6 % (n = 8) of whom were former smokers. Participants reported seeking treatment due to health concerns, dependence, stigma, and cost. Anticipated challenges of quitting vaping were withdrawal, negative mood, sensorimotor habits, and convenience. Most completed the end of treatment survey (n = 24; 80 %). Participants who received NRT reported using the patch M = 10.89 days and lozenges M = 6.39 days, with few days of adverse effects (M = 2.67). At end of treatment, 6/18 (33.3 %; 6 mono and 0 dual users) in the intervention group reported abstinence from vaping, compared to 0 in the control group (Fisher = 5.00, p =.057). In conclusion, adults are interested in quitting e-cigarettes due to negative consequences of use and are willing to use pharmacotherapy. Future research should confirm these results in a larger trial, address cigarette smoking in dual users, and aim to disseminate treatments.

Complications following surgical treatment of posterior malleolar fractures: an analysis of 300 cases.

AIMS: The treatment of ankle fractures and fracture-dislocations involving the posterior malleolus (PM) has undergone considerable changes over the past decade. The aim of our study was to identify risk factors related to the occurrence of complications in surgically treated ankle fractures with PM involvement. PATIENTS AND METHODS: We retrospectively analyzed 300 patients at a mean age of 57 years with 300 ankle fractures involving the PM treated surgically at our institution over a 12-year period. The following relevant comorbidities were noted: arterial hypertension (43.7%; n = 131), diabetes mellitus (DM) (14.0%; n = 42), thereof insulin-dependent (3.7%; n = 11), peripheral vascular disease (0.7%; n = 2), osteoporosis (12.0%; n = 36), dementia (1.0%; n = 3), and rheumatoid arthritis (2.0%; n = 6). Furthermore, nicotine consumption was recorded in 7.3% (n = 22) and alcohol abuse in 4.0% (n = 12). RESULTS: Complications occurred in 41 patients (13.7%). A total of 20 (6.7%) revision surgeries had to be performed. Patients with DM (p < 0.001), peripheral vascular disease (p = 0.003) and arterial hypertension (p = 0.001) had a significantly increased risk of delayed wound healing. Alcohol abuse was associated with a significantly higher overall complication rate (OR 3.40; 95% CI 0.97-11.83; p = 0.043), increased rates of wound healing problems (OR 11.32; 95% CI 1.94-65.60; p = 0.001) and malalignment requiring revision (p = 0.033). The presence of an open fracture was associated with an increased rate of infection and wound necrosis requiring revision (OR 14.25; 95% CI 2.39-84.84; p < 0.001). Multivariate analysis identified BMI (p = 0.028), insulin-dependent DM (p = 0.003), and staged fixation (p = 0.043) as independent risk factors for delayed wound healing. Compared to the traditional lateral approach, using the posterolateral approach for fibular fixation did not lead to increased complication rates. CONCLUSIONS: Significant risk factors for the occurrence of complications following PM fracture treatment were identified. An individually tailored treatment regimen that incorporates all risk factors is important for a good outcome.

What are the Causes, Costs and Risk-Factors for Emergency Department Visits Following Primary Total Hip Arthroplasty? An Analysis of 1,018,772 Patients.

BACKGROUND: Well-powered studies analyzing the relationship and nature of emergency department (ED) visits following primary total hip arthroplasties (THAs) are limited. The aim of this study was to: 1) compare baseline demographics of patients with/without an ED visit; 2) determine leading causes of ED visits; 3) identify patient-related risk factors; and 4) quantify 90-day episode-of-care healthcare costs divided by final diagnosis. METHODS: Patients undergoing primary THA between January 1, 2010 and October 1, 2020 who presented to the ED within 90-days postoperatively were identified using the Mariner dataset of PearlDiver, yielding 1,018,772 patients. This included 3.9% (n = 39,439) patients who did and 96.1% (n = 979,333) who did not have an ED visit. Baseline demographics between the control/study cohorts, ED visit causes, risk-factors, and subsequent costs-of-care were analyzed. Using Bonferroni-correction, a P-value less than 0.002 was considered statistically significant. RESULTS: Patients who presented to the ED post-operatively were most often aged 65-74 years old (41.09%) or female sex (55.60%). Nonmusculoskeletal etiologies comprised 66.8% of all ED visits. Risk factors associated with increased ED visits included alcohol abuse, depressive disorders, congestive heart failure, coagulopathy, and electrolyte/fluid derangements (P < .001 for all). Pulmonary ($28,928.01) and cardiac ($28,574.69) visits attributed to the highest costs of care. CONCLUSION: Nonmusculoskeletal causes constituted the majority of ED visits. The top five risk factors associated with increased odds of ED visits were alcohol abuse, electrolyte/fluid derangements, congestive heart failure, coagulopathy, and depression. This study highlights potential areas of pre-operative medical optimization that may reduce ED visits following primary THA.

Predictive Factors for Aortic Graft Infection: A Case-Control Study.

BACKGROUND: Graft infections are one of the most serious complications in vascular surgery, with high mortality rates. Few studies addressed risk factors associated with a higher susceptibility to infection. The aim of this study is to identify perioperative factors associated with aortic graft infections (AGI). METHODS: We designed a retrospective, case-control study from patients subjected to open aortic repair between 2013 and 2019. Cases of AGI were defined according to the management of aortic graft infection collaboration (MAGIC) criteria and matched to controls without proven infection. Demographics, hospital complications, and laboratory workups were assessed. Predictors of AGI were identified through univariate and multivariate analysis. RESULTS: Most graft infections occurred in a late period (n = 17; 85%), after a median interval of 13.5 months interquartile range (IQR 1.5-36). Gram-negative bacteria were most frequently isolated in infected grafts, namely Enterobacteriaceae (n = 12). Cases had significantly lower postoperative serum albumin levels (1.9 g/dL vs. 2.4 g/dL; P = 0.002). Alcohol abuse, malignancy, prolonged lengths of stay, wound infection and dehiscence, in-hospital infection, postoperative heart failure or bowel ischemia were significantly correlated to the onset of AGI. In the multivariate analysis, prolonged hospital stays odds ratio (OR 1.05; P = 0.03), malignancy (OR 5.82; P = 0.03) and alcohol abuse (OR 42.41; P = 0.002) maintained a significant association. CONCLUSIONS: The risk of AGI seems to be higher in patients with concurrent malignancy, alcohol abuse or prolonged hospital stays. Strategies to mitigate this complication in these patients are of utmost importance.

Reciprocal midbrain-extended amygdala circuit activity in preclinical models of alcohol use and misuse.

Alcohol dependence is characterized by a shift in motivation to consume alcohol from positive reinforcement (i.e., increased likelihood of future alcohol drinking based on its rewarding effects) to negative reinforcement (i.e., increased likelihood of future alcohol drinking based on alcohol-induced reductions in negative affective symptoms, including but not limited to those experienced during alcohol withdrawal). The neural adaptations that occur during this transition are not entirely understood. Mesolimbic reinforcement circuitry (i.e., ventral tegmental area [VTA] neurons) is activated during early stages of alcohol use, and may be involved in the recruitment of brain stress circuitry (i.e., extended amygdala) during the transition to alcohol dependence, after chronic periods of high-dose alcohol exposure. Here, we review the literature regarding the role of canonical brain reinforcement (VTA) and brain stress (extended amygdala) systems, and the connections between them, in acute, sub-chronic, and chronic alcohol response. Particular emphasis is placed on preclinical models of alcohol use.

The rewarding effects of alcohol after bariatric surgery: do they change and are they associated with pharmacokinetic changes?

BACKGROUND: Research shows that surgery patients who have undergone Roux-en-Y gastric bypass (RYGB) are at increased risk for an alcohol use disorder (AUD). However, the mechanisms through which this increased risk is incurred are poorly understood. A host of variables have been proposed as potentially causal in developing AUDs, but empirical examination of many of these variables in human samples is lacking. OBJECTIVES: Our objective was to examine the extent to which alcohol pharmacokinetics (PK), the rewarding effects of alcohol, and the relationship between these variables change from before to after weight loss surgery. SETTING: Large healthcare facility in the Midwest United States METHODS: Thirty-four participants completed assessments before and 1 year after RYGB. They completed laboratory sessions and provided data on the PK of alcohol and the extent to which alcohol was reinforcing to them at each timepoint. RESULTS: Findings show that the PK effects of alcohol (P < .01) and how rewarding alcohol was reported to be (P < .01) changed from before to 1 year after weight loss surgery. Further, statistically significant increases in the association between these variables were witnessed from before to 1 year after surgery (P < .01). CONCLUSION: These results implicate changes (from before surgery to one year after) in the reinforcing and PK effects of alcohol as possible mechanisms for increased risk of alcohol use disorder following Roux-en-Y gastric bypass surgery.

Childhood abuse, posttraumatic stress symptoms, and alcohol misuse among African-American women.

The study explored associations among childhood abuse, post-traumatic stress symptoms (PTSS), and alcohol misuse in a sample of low-income African-American women (N = 172). Using bootstrapping techniques, a mediation effect was found of childhood physical and emotional abuse on alcohol misuse via PTSS symptom severity, avoidance, and hyperarousal, as well as for childhood sexual abuse on alcohol misuse via PTSS symptom severity and hyperarousal. Our results suggest that PTSS indicators, particularly symptom severity and hyperarousal, may be important mechanisms underlying the association of experiences of abuse during childhood and alcohol misuse in adulthood.

Occipital neural dynamics in cannabis and alcohol use: independent effects of addiction.

Alcohol and cannabis use disorder (AUD/CUD) are two of the most common addictive disorders. While studies are beginning to understand the neural changes related to acute and chronic use, few studies have examined the independent effects of AUD and CUD on neural oscillatory activity. We examined 45 adults who reported current use of both cannabis and alcohol. Participants underwent the SCID-V to determine whether they met criteria for AUD and/or CUD. Participants also completed a visual-spatial processing task while undergoing magnetoencephalography (MEG). ANCOVA with a 2 × 2 design was then used to identify the main effects of AUD and CUD on source-level oscillatory activity. Of the 45 adults, 17 met criteria for AUD, and 26 met criteria for CUD. All participants, including comparison groups, reported use of both cannabis and alcohol. Statistical analyses showed a main effect of AUD, such that participants with AUD displayed a blunted occipital alpha (8-16 Hz) response. Post-hoc testing showed this decreased alpha response was related to increased AUD symptoms, above and beyond amount of use. No effects of AUD or CUD were identified in visual theta or gamma activity. In conclusion, AUD was associated with reduced alpha responses and scaled with increasing severity, independent of CUD. These findings indicate that alpha oscillatory activity may play an integral part in networks affected by alcohol addiction.

Primed for addiction: A critical review of the role of microglia in the neurodevelopmental consequences of adolescent alcohol drinking.

Alcohol is one of the most widely used recreational substances worldwide, with drinking frequently initiated during adolescence. The developmental state of the adolescent brain makes it vulnerable to initiating alcohol use, often in high doses, and particularly susceptible to alcohol-induced brain changes. Microglia, the brain parenchymal macrophages, have been implicated in mediating some of these effects, though the role that these cells play in the progression from alcohol drinking to dependence remains unclear. Microglia are uniquely positioned to sense and respond to central nervous system insult, and are now understood to exhibit innate immune memory, or "priming," altering their future functional responses based on prior exposures. In alcohol use disorders (AUDs), the role of microglia is debated. Whereas microglial activation can be pathogenic, contributing to neuroinflammation, tissue damage, and behavioral changes, or protective, it can also engage protective functions, providing support and mediating the resolution of damage. Understanding the role of microglia in adolescent AUDs is complicated by the fact that microglia are thought to be involved in developmental processes such as synaptic refinement and myelination, which underlie the functional maturation of multiple brain systems in adolescence. Thus, the role microglia play in the impact of alcohol use in adolescence is likely multifaceted. Long-term sequelae may be due to a failure to recover from EtOH-induced tissue damage, altered neurodevelopmental trajectories, and/or persistent changes to microglial responsivity and function. Here, we review critically the literature surrounding the effects of alcohol on microglia in models of adolescent alcohol misuse. We attempt to disentangle what is known about microglia from other neuroimmune effectors, to which we apply recent discoveries on the role of microglia in development and plasticity. Considered altogether, these studies challenge assumptions that proinflammatory microglia drive addiction. Alcohol priming microglia and thereby perturbing their homeostatic roles in neurodevelopment, especially during critical periods of plasticity such as adolescence, may have more serious implications for the neuropathogenesis of AUDs in adolescents.

Alcohol Withdrawal Syndrome: Outpatient Management.

Approximately one-half of patients with alcohol use disorder who abruptly stop or reduce their alcohol use will develop signs or symptoms of alcohol withdrawal syndrome. The syndrome is due to overactivity of the central and autonomic nervous systems, leading to tremors, insomnia, nausea and vomiting, hallucinations, anxiety, and agitation. If untreated or inadequately treated, withdrawal can progress to generalized tonic-clonic seizures, delirium tremens, and death. The three-question Alcohol Use Disorders Identification Test-Consumption and the Single Alcohol Screening Question instrument have the best accuracy for assessing unhealthy alcohol use in adults 18 years and older. Two commonly used tools to assess withdrawal symptoms are the Clinical Institute Withdrawal Assessment for Alcohol Scale, Revised, and the Short Alcohol Withdrawal Scale. Patients with mild to moderate withdrawal symptoms without additional risk factors for developing severe or complicated withdrawal should be treated as outpatients when possible. Ambulatory withdrawal treatment should include supportive care and pharmacotherapy as appropriate. Mild symptoms can be treated with carbamazepine or gabapentin. Benzodiazepines are first-line therapy for moderate to severe symptoms, with carbamazepine and gabapentin as potential adjunctive or alternative therapies. Physicians should monitor outpatients with alcohol withdrawal syndrome daily for up to five days after their last drink to verify symptom improvement and to evaluate the need for additional treatment. Primary care physicians should offer to initiate long-term treatment for alcohol use disorder, including pharmacotherapy, in addition to withdrawal management.

Perceptions of Diseases of Despair by Members of Rural and Urban High-Prevalence Communities: A Qualitative Study.

Importance: Diseases of despair (ie, mortality or morbidity from suicidality, drug abuse, and alcoholism) were first characterized as increasing in rural White working-class populations in midlife with low educational attainment and associated with long-term economic decline. Excess mortality now appears to be associated with working-class citizens across demographic and geographic boundaries, but no known qualitative studies have engaged residents of rural and urban locales with high prevalence of diseases of despair to learn their perspectives. Objective: To explore perceptions about despair-related illness and potential intervention strategies among diverse community members residing in discrete rural and urban hotspots. Design, Setting, and Participants: In this qualitative study, high-prevalence hotspots for diseases of despair were identified from health insurance claims data in Central Pennsylvania. Four focus groups were conducted with 60 community members in organizations and coalitions from 3 census block group hotspot clusters in the health system between September 2019 and January 2020. Focus groups explored awareness and beliefs about causation and potential intervention strategies. Main Outcomes and Measures: A descriptive phenomenological approach was applied to thematic analysis, and a preliminary conceptual model was constructed to describe how various factors may be associated with perpetuating despair and with public health. Results: In total, 60 adult community members participated in 4 focus groups (44 women, 16 men; 40 White non-Hispanic, 17 Black, and 3 Hispanic/Latino members). Three focus groups with 43 members were held in rural areas with high prevalence of diseases of despair, and 1 focus group with 17 members in a high-prevalence urban area. Four themes emerged with respect to awareness and believed causation of despair-related illness, and participants identified common associated factors, including financial distress, lack of critical infrastructure and social services, deteriorating sense of community, and family fragmentation. Intervention strategies focused around 2 themes: (1) building resilience to despair through better community and organizational coordination and peer support at the local level and (2) encouraging broader state investments in social services and infrastructure to mitigate despair-related illness. Conclusions and Relevance: In this qualitative study, rural and urban community members identified common factors associated with diseases of despair, highlighting the association between long-term political and economic decline and public health and a need for both community- and state-level solutions to address despair. Health care systems participating in addressing community health needs may improve processes to screen for despair (eg, social history taking) and codesign primary, secondary, and tertiary interventions aimed at addressing factors associated with distress. Such actions have taken on greater urgency with the COVID-19 pandemic.