Comorbid Alcohol Research Articles

Abstract 17236: Risk of Incident Atrial Fibrillation Associated With Recreational Cannabis Use

Background: Cannabis use is increasing worldwide as legalization becomes more common. Prior studies have reported an association between cannabis use and increased risk of atrial fibrillation (AF). However, these have been cross-sectional and generally relied on diagnostic coding to identify cannabis users, which may not be representative of the typical recreational cannabis user. Goals: To examine the association between recreational cannabis use and AF risk. Methods: We utilized the UK Biobank, a prospective cohort study with serial assessments of lifestyle and medical diagnoses. Those who completed the cannabis use questionnaire and without prevalent AF were analyzed. Cannabis exposure was ascertained by self-reported lifetime use. AF events were identified using healthcare coding. Cox proportional hazard regression models were used to estimate the hazard ratios between the cannabis use groups and incident AF. Models were adjusted for age, sex, race, alcohol, coffee, smoking, education, and baseline cardiovascular comorbidities. Results: 157,305 participants (mean age 55.9 ± 7.7 years, 57.0% female, and 22.1% having used cannabis at least once) were followed for a mean 13.5 ± 1.7 years. Before multivariable adjustment, AF risk was found to be lower among occasional cannabis users (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.66 to 0.75, p < 0.001) and frequent cannabis users (HR 0.63, 95% CI 0.53 to 0.75, p < 0.001) compared to never users. However, after multivariable adjustment and compared to no cannabis use, neither occasional nor frequent cannabis use was associated with statistically significant differences in incident AF (HR 0.98, 95% CI 0.91 to 1.05, p = 0.58 and HR 0.98, 95% CI 0.82 to 1.18, p = 0.86 respectively) (Figure). Conclusions: Contrary to previous evidence relying on healthcare coding of cannabis use, this large prospective cohort study failed to reveal any evidence that cannabis use was associated with an increased risk of AF.

Polysubstance use and post-discharge mortality risk among hospitalized patients with opioid use disorder

Polysubstance use is becoming increasingly common and presents several harms. This study aimed to examine the association of comorbid cocaine, alcohol (binge drinking), and sedative use with mortality among hospitalized patients with opioid use disorder (OUD).A subsample of adult medical/surgical hospital patients with OUD who were seen by a hospital addiction consultation service in Baltimore City and enrolled in a randomized trial of a patient navigation intervention were included in this study (N = 314; 45 % female; 48 % White; mean age = 44). Death certificate data from the Maryland Division of Vital Records was used, covering 3.3–5.5 years post-discharge. Multivariable proportional hazards Cox regression and competing risks regression were used to estimate all-cause mortality and overdose mortality, respectively, as a function of concurrent use of cocaine, alcohol (binge drinking), and non-prescribed sedatives at baseline.In the 30 days prior to hospital admission, 230 (73 %) participants used cocaine, 64 (20 %) binge drank, and 45 (14 %) used non-prescribed sedatives. Nearly one-third (N = 98; 31 %) died during the observation period. Drug overdose caused 53 % (N = 52) of deaths. Older age (HR = 1.03 [1.01,1.05]; P = 0.001), less than high school education (HR = 0.36 [0.24,0.54]; P < 0.001), and past 30-day sedative use (HR = 2.05 [1.20,3.50]; P = 0.008) were significantly associated with all-cause mortality. The risk of overdose mortality was 62 % lower (HR = 0.38 [0.22,0.66]; P = 0.001) for those who completed high school. No other characteristics were significantly associated with overdose mortality.The concurrent use of opioids and sedatives increases the post-discharge mortality risk among hospitalized patients with OUD. Interventions are needed to prevent mortality among this high-risk population.

Update on Pharmacological Treatment for Comorbid Major Depressive and Alcohol Use Disorders: The Role of Extended-release Trazodone.

Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD) are major public health concerns because of their high prevalence and clinical and functional severity. MDD and AUD commonly co-occur, but effective therapeutic approaches for comorbidity are still scarce. Available evidence on selective serotonin reuptake inhibitors and tricyclic antidepressants held mixed results, and further pharmacological categories have been less investigated. Trazodone is an approved antidepressant drug for adults and has shown efficacy on symptoms like anxiety and insomnia observed in AUD patients as well. Thus, this study aims to evaluate the effect of extended-release trazodone on clinical and functional features in MDD + AUD subjects. One hundred MDD + AUD outpatients were retrospectively evaluated at 1, 3, and 6 months of treatment with extended-release trazodone (150-300 mg/day, flexibly dosed). Improvement in depressive symptoms was the primary outcome measure. Changes in anxiety, sleep, functioning, quality of life, clinical global severity, and alcohol craving were also investigated. Trazodone reduced depressive symptoms (p < 0.001) with 54.5% remission at the endpoint. Similar improvements were observed in all secondary outcomes, including anxiety, sleep alterations, and craving (p < 0.001). Only mild side effects were reported and disappeared over time. Extended-release trazodone displayed good antidepressant properties in MDD + AUD patients, ameliorating overall symptomatology, functioning, and quality of life, with a good safety/ tolerability profile. Further, it significantly improved sleep disturbances and craving symptoms, which are associated with drinking relapse and worse outcomes. Therefore, trazodone might represent a promising pharmacological option for MDD + AUD patients.

Anxiety, distress tolerance, and the relationship between complex posttraumatic stress disorder symptoms and alcohol use in veterans.

Little is known about whether distress tolerance and anxiety mediate the relationship between comorbid complex posttraumatic stress disorder (CPTSD) and alcohol use among military veterans. Here, we investigated the contribution of distress tolerance and anxiety on the strength of the CPTSD and alcohol use association. We hypothesized that the impact of a two-factor model of CPTSD derived from subscale scores on the International Trauma Questionnaire (ITQ)-namely ITQ PTSD and ITQ Disturbances in Self Organization (DSO; e.g., issues with affective regulation/self-belief and shame)-on alcohol use severity would be mediated by anxiety but not by distress tolerance. Participants included 403 community-dwelling United Kingdom (UK) veterans (91.64% male, Mage = 51.15 years, SD = 12.48) recruited as part of a larger, online study. Findings indicated that the influence of CPTSD symptoms on alcohol use severity was mediated by anxiety, not by distress tolerance, with greater relative impact due to ITQ DSO status than ITQ PTSD status. We identified the mediational influence of anxiety and distress tolerance on the association between CPTSD subscales and alcohol use in UK veterans. Interventions for anxiety may be adapted for reducing problematic alcohol use and the impact of CPTSD symptoms in veterans with comorbid PTSD and alcohol use disorder.

Internalized Stigma and its Correlates Among Opioid Agonist Treatment Service Users in Nepal

Opioid use disorder is associated with high levels of stigma and discrimination, which impact treatment seeking and compliance. Despite extensive evidence as an optimal intervention for opioid use disorder, enrollment in Opioid Agonist Treatment (OAT) in settings like Nepal, is accompanied by moral judgements and stigma with a broad narrative of it being merely a replacement of ‘one addiction with another’. Stigma is eventually internalized by many service users impacting enrollment and maintenance in OAT, and quality of life. This study aimed to assess internalized stigma among OAT service users in Nepal and to explore its association with sociodemographic characteristics, lifetime mental disorders and quality of life. A cross-sectional study was conducted among 231 OAT service users, the survey instrument included the Mini-International Neuropsychiatric Interview for DSM-5, Internalized Stigma of Mental Illness Inventory (ISMI) and the World Health Organization Quality of Life –BREF. Factors associated with quality of life and internalized stigma were investigated using bivariate and multivariate analyses. More than half (56.28%) of respondents reported having high internalized stigma with a mean ISMI score of 2.71 ± 0.64. All 29 ISMI items were found to have a mean score greater than 2.5 indicating a high burden of internalized stigma. Service users reporting higher internalized stigma had significantly lower quality of life across all domains, greater medical co-morbidity, lifetime anxiety and depressive disorder and alcohol use disorder. To lessen stigma and its impacts, our findings recommend a national initiative targeting stigma reduction interventions for existing OAT services and beneficiaries.

S1504 Mortality Differences in Those Admitted for Sepsis With Comorbid Alcohol Associated Cirrhosis vs Non-Alcohol Associated Cirrhosis

S1504 Mortality Differences in Those Admitted for Sepsis With Comorbid Alcohol Associated Cirrhosis vs Non-Alcohol Associated Cirrhosis

Olfactory decline develops in parallel with frailty in older US adults with obstructive lung diseases.

Frailty is prevalent among older adults with asthma or chronic obstructive pulmonary disease (obstructive lung diseases [OLDs]). Frailty and OLD's co-occurrence is associated with increased hospitalization/mortality. Chemosensory dysfunction is closely connected to both OLD and frailty. We evaluated the utility of olfactory decline as a biomarker of frailty in the setting of OLD. We performed a prospective, longitudinal, nationally representative study of community-dwelling older US adults in the National Social Life, Health and Aging Project, an omnibus in-home survey. Respondents reported a physician's diagnosis of OLD. Decline in odor identification and sensitivity over 5 years and frailty (adapted fried frailty phenotype criteria) were measured using standard tools. Multivariate logistic regressions evaluated the association between OLD status, olfactory decline, and frailty. We compared individuals with OLD (n=98; mean age 71.2 years, 59.2% women) and those without OLD (n=1036; mean age 69.5 years, 58.9% women). Olfactory identification decline was associated with developing frailty over the 5-year follow-up period in individuals with OLD (odds ratio [OR]=9.1, 95% confidence interval [CI]=2.1-38.6, p=0.003). Olfactory decline predicted incidence of frailty in individuals with OLD (identification: OR=4.8, 95% CI=1.3-17.5, P=0.018; sensitivity: OR=6.1, 95%CI=1.2-31.0, p=0.030) but not in those without OLD adjusting for demographics, heavy alcohol use, current smoking, and comorbidity. Results were robust to different thresholds for olfactory decline and frailty development. Older adults with OLD who experience olfactory decline face higher odds of developing frailty. Use of olfactory decline as a biomarker to identify frailty could allow earlier intervention and decrease adverse outcomes for high-risk older adults with OLD.

Epidemiology of social phobia in Andalusia

IntroductionPopulation studies on social anxiety disorder (SAD) are relatively scarce and there is no previous reported evidence on prevalence or correlates of SAD in an Andalusian general population sample. Material and methodsWe used a random representative sample previously identified via standard stratification procedures. Thus, a final sample of 4507 participants were included (response rate 83.7%). Interviewees were thoroughly assessed on sociodemographic, clinical and psychosocial factors, including: exposures to threatening life events (TLEs), childhood abuse, personality disorder and traits (neuroticism, impulsivity, paranoia), global functioning, physical health and toxics consumption. SAD diagnosis was ascertained using the Mini International Neuropsychiatric Interview. Both, pooled prevalences (with 95% confidence intervals) and risk correlates for SAD were estimated using binary logistic regression. ResultsEstimated prevalence for SAD was 1.1% (95% CI=0.8-1.4). Having a SAD diagnosis was independently and significantly associated with younger age, poorer global functioning, higher neuroticism and paranoia personality traits, having suffered childhood abuse and exposure to previous TLEs. Furthermore, SAD was significantly associated with comorbid personality disorder, major depression, panic disorder and alcohol abuse. ConclusionsAmong this large Andalusian population sample, the prevalence of SAD and its associated factors are relatively similar to previously reported international studies, although no population study had previously reported such a strong association with paranoia.

Prevalence and predictors of comorbid current alcohol, cannabis, and tobacco use among school adolescents in Liberia and Mauritius

This study aimed to provide estimates on current comorbid alcohol, cannabis, and tobacco use among school adolescents in Liberia and Mauritius. Secondary data were analysed from the 2017 national and cross-sectional school health surveys in Liberia and Mauritius which sampled 4 934 adolescents (median age 17 years). One in five students (20.6%) reported one type of current substance use, 6.2% two types of current substance use, and 3.8% three types of current substance use. Almost one in 10 (7.8%) students reported current alcohol and tobacco use, 4.6% current alcohol and cannabis use, and 5.2% current cannabis and tobacco use. Male sex, older age, parental tobacco use, passive smoking, psychological distress, soft drink intake, school truancy and low parental support were associated with a higher degree of comorbid substance. One in 10 students engaged in two or three types of current substance use, and several associated factors were identified. Interventions targeting comorbid substance use among adolescents should prioritise identified associated factors.

A comparison of the reinforcing strength of cocaethylene and cocaine in monkeys responding under progressive-ratio and concurrent choice schedules of reinforcement

BackgroundIndividuals who use cocaine have high rates of co-morbid alcohol use and when ethanol and cocaine are administered concurrently, the metabolite cocaethylene is formed. Cocaethylene is equipotent to cocaine in blocking dopamine reuptake and substitutes for cocaine in drug discrimination studies. However, no previous work has directly compared the reinforcing strength of cocaine to cocaethylene. MethodsIn Experiment 1, three individually-housed adult male rhesus macaques self-administer cocaine under a progressive-ratio (PR) schedule of reinforcement, during daily 4-hr sessions. Under this schedule, the primary dependent variable is the number of injections received, or the break point (BP). Saline, cocaine (0.001–0.3mg/kg/injection) and cocaethylene (0.0003–0.1mg/kg/injection) dose-response curves were determined. In Experiment 2, two female cynomolgus and one rhesus macaque responded under a concurrent schedule of drug (cocaine or cocaethylene) vs. 1.0-g banana-flavored food pellets, during daily 1-hr sessions. ResultsBoth cocaine and cocaethylene functioned as reinforcers under the PR and concurrent choice schedules of reinforcement. Under the PR schedule, peak BPs were not significantly different, nor were ED50 values on the ascending limb, suggesting that cocaethylene has equal reinforcing strength and potency to cocaine. Under the concurrent drug-food choice procedure, cocaethylene was also equally potent to cocaine. ConclusionsUnder two schedules of reinforcement designed to assess reinforcing strength, cocaethylene and cocaine were equipotent and of equal reinforcing strength. Because cocaethylene has a longer duration of action, it is important for studies designed to evaluate treatments for cocaine use to also consider the effects of these interventions on cocaethylene.

Comorbid alcohol use disorder and posttraumatic stress disorder: A proof-of-concept randomized placebo-controlled trial of buprenorphine and naltrexone combination treatment.

Effective pharmacologic treatments for comorbid alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) are lacking. Kappa (κ) opioid receptor antagonists may address this unmet need. Buprenorphine is a κ-opioid antagonist and a partial agonist of mu (μ) opioid receptors. Whereas naltrexone blocks all μ-mediated effects combining it with buprenorphine yields a pharmacologic net effect of opioid receptor antagonism. Because no κ-opioid receptor antagonist it available for clinical use, we tested this combination in a proof-of-concept study. Consenting participants were enrolled in a Phase II, multisite, double-blind, randomized, placebo-controlled trial evaluating the effectiveness of sublingual (SL) buprenorphine combined with extended-release (XR) injectable naltrexone for the treatment of comorbid AUD and PTSD. Eligible participants (n = 75) were randomized (1:1:1) to receive either buprenorphine 2 mg/day plus naltrexone-XR (n = 35), buprenorphine 8 mg/day plus naltrexone-XR (n = 6) or SL plus injectable placebo (n = 34) for 12 weeks. The buprenorphine 8 mg/day plus naltrexone-XR arm was dropped early in the trial due to the negative impact of COVID-19 on enrollment. A binary primary outcome of response at week 8 was defined as a decrease from baseline of ≥10 points on the past week Clinician-Administered PTSD Scale (CAPS-5) and a reduction of ≥1 of past month alcohol risk level, as defined by the World Health Organization (WHO) and measured by the Timeline Follow-Back. Based on the results of a futility analysis, enrollment was stopped prior to reaching the initial goal of 90 participants. At the week eight primary timepoint, there were no statistically significant differences between buprenorphine plus naltrexone-XR and placebo group for the primary composite outcome (OR = 0.63; p-value = 0.52), or the subcomponents of the PTSD outcome (OR = 0.76; p-value = 0.69) and AUD outcome (OR = 0.17; p-value = 0.08). The placebo arm had a significantly higher proportion of participants with ≥1 WHO risk level reduction than the buprenorphine plus naltrexone-XR arm (OR = 0.18, p value = 0.02). This is the first study to evaluate the potential of κ-opioid receptor antagonism for the treatment of comorbid AUD and PTSD. The combination of buprenorphine and naltrexone-XR showed no significant improvement over placebo for the composite, PTSD, or alcohol measures.

Objective and self-reported sleep outcomes in people with comorbid alcohol and opioid use disorder: examining the role of gabapentin

ABSTRACT Background Chronic substance use contributes to reduced sleep time and REM sleep, and increased sleep latency and WASO. These effects are exacerbated by withdrawal, impact craving, and increase risk factors for relapse to substance use. Methods This secondary analysis examined objective and subjective sleep data in individuals with comorbid alcohol and opioid use disorders (AUD and OUD) in an 8-week randomized, double-blind inpatient trial on gabapentin’s subjective and physiological effects on oxycodone and alcohol alone, and their combination. Participants (n = 13; 8% female) were non-treatment-seeking individuals with OUD and AUD. Participants wore an ActiWatch Monitor nightly and completed daily sleep diaries. We examined the effects of gabapentin on sleep after nine laboratory sessions where oxycodone (0 mg, 15 mg, 30 mg), alcohol (placebo, 0.5 g/kg, 0.75 g/kg) and combined doses were administered and explored the relationship between baseline substance use and sleep. Results Active gabapentin dosing attenuated the relationship between laboratory-administered alcohol, oxycodone, and their combinations on some objective sleep measures, but not others. Self-reported heroin and alcohol use at baseline impacted sleep outcomes throughout the inpatient trial. Discussion and Conclusion Gabapentin may attenuate the negative effects of opioids and alcohol on sleep, though further work is needed to examine this relationship. Scientific Significance Subjective and objective sleep outcomes are impacted by laboratory-administered doses of alcohol, oxycodone, and their combination, though patterns of results were somewhat inconsistent. More work is needed to understand safe and effective treatments for sleep disruption in those with OUD and AUD.

Alcohol relapse prevention health care after alcohol withdrawal in New South Wales prisons, Australia: A patient file review.

People who enter custody have complex health issues and comorbidities may include alcohol use disorders. We investigated clinical service provision and comorbidities recorded among individuals with a likely alcohol withdrawal syndrome within prison in New South Wales, Australia. For this clinical case series review, electronic medical data were used to identify 50 people entering custody between August and November 2018 who likely had a treated alcohol withdrawal syndrome. We aimed for a 3:2 ratio of men and women, and a 1:1 ratio of Aboriginal and non-Aboriginal individuals. Data were extracted using a purposefully designed tool which included current alcohol withdrawal management, comorbidities and alcohol relapse prevention approaches used or recommended. Thirty-eight men and 12 women, of whom 22 were Aboriginal, were included. Twenty-nine individuals (58%) reported a history of medical comorbidities. Thirty-five (70%) reported using other substances and over half (60%) had a diagnosis of mental health disorders. Fourteen (28%) individuals had a record of receiving brief intervention and five (10%) of motivational interviewing. Twenty-three individuals (46%) were referred to and seen by drug and alcohol clinicians. Only seven (14%) of the sample had pre-release community care plans. Individuals treated for an alcohol withdrawal syndrome in New South Wales prisons have a high prevalence of medical comorbidities and other substance use. Clinical interventions focused on alcohol withdrawal management, and relapse prevention interventions were not recorded for most individuals. Service innovation and expansion are needed to increase the provision of post-withdrawal management.

Associations Between Cumulative Social Adversities and Substance Use Comorbidity in a Statewide Sample of Individuals in Treatment for Mental Illnesses.

We sought to investigate associations of cumulative social adversities in four areas (low education, unemployment, homelessness, and criminal/legal involvement) with presence of comorbid alcohol and drug use disorders among individuals in treatment for mental illnesses. Using data from 103,416 adults in mental health treatment, generalized estimating equation modified Poisson models were used to estimate increased risk of having comorbid substance use disorders based on individual and/or cumulative number of social adversities present. Controlling for effects of sex, race/ethnicity, and region (New York City vs . the rest of the State), as well as for the other social adversities, each of four social adversities was associated with presence of substance use comorbidity. Relative to having none of the social adversities, the presence of one, two, three, or four was associated with an increased prevalence ratio (PR) of having substance use comorbidity: 1.44, 2.10, 2.66, and 2.92; all p 's < 0.0001. PRs were greater among female patients, and among Hispanics and those classified as other or multiracial compared with non-Hispanic Whites or non-Hispanic Blacks. Findings indicate substantial associations between four social adversities and presence of substance use comorbidity; the strength of association with the four social adversities is cumulative.

A Prospective Comparison of Bipolar I and II Subjects with and without Comorbid Cannabis Use Disorders from the COGA Dataset.

The comorbidity of alcohol and substance use disorders among persons with bipolar disorder is elevated, as indicated by epidemiological and clinical studies. Following alcohol use, cannabis is the most frequently used and abused illicit substance among bipolar individuals, and such use may lead to comorbid cannabis use disorders (CUD). Previous research indicated that CUDs were related to a more severe course of bipolar disorder and higher rates of other comorbid alcohol and substance use disorders. Few studies, however, have conducted longitudinal research on this comorbidity. The aim of this study is to investigate the influence of CUD on the course of bipolar I and II individuals during a 5-year follow-up. The characteristics of bipolar disorder, cannabis use disorders, and other alcohol and substance use disorders, as well as comorbid mental disorders, were assessed using a standardized semi-structured interview (SSAGA) at both baseline and the 5-year follow-up. N = 180 bipolar I and II patients were subdivided into groups of with and without comorbid cannabis use disorders (CUD). Of the 77 bipolar I and 103 bipolar II patients, n = 65 (36.1%) had a comorbid diagnosis of any CUD (DSM-IV cannabis abuse or dependence). Comorbid bipolar patients with CUD had higher rates of other substance use disorders and posttraumatic stress disorders, more affective symptoms, and less psychosocial functioning at baseline and at 5-year follow-up. In contrast to previously reported findings, higher rates of anxiety disorders and bipolar disorder complications (e.g., mixed episodes, rapid cycling, and manic or hypomanic episodes) were not found. The effect of CUD on other substance use disorders was confirmed using moderation analyses. A 5-year prospective evaluation of bipolar patients with and without CUD confirmed previous investigations, suggesting that the risk of other substance use disorders is significantly increased in comorbid individuals. CUD has a moderation effect, while no effect was found for other mental disorders. Findings from this study and previous research may be due to the examination of different phenotypes (Cannabis use vs. CUD) and sample variation (family study vs. clinical and epidemiological populations).

Comorbidity of schizophrenia and alcoholism in the modern paradigm of outpatient psychiatric care

The comorbidity of alcohol disorder and schizophrenia or schizoaffective disorder is a complex and multifaceted problem that has a significant impact on the quality of life of patients and the complexity of medical care. This article discusses the common neurobiological mechanisms that explain the high rates of co-occurrence of these disorders, as well as the consequences of such comorbidity for patients and the healthcare system. Additionally, potential ways to optimize the treatment of these patients are being considered.

Treatment outcomes in major depressive disorder in patients with comorbid alcohol use disorder: A STAR*D analysis

IntroductionGuidance on Major Depressive Disorder (MDD) treatment in those with comorbid Alcohol Use Disorder (AUD) is limited. We performed a secondary analysis on the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, examining the association between comorbid AUD and depression outcomes. MethodsSTAR*D was a real-world effectiveness trial starting with citalopram in level 1. Non-responding participants progressed through 3 other sequential treatment levels with different switch or augmentation options. Antidepressant outcomes were compared between MDD (n = 2826) and comorbid MDD and AUD (n = 864). Logistic regressions were performed to evaluate remission and response predictors in the total STAR*D sample and the AUD-comorbidity interaction. ResultsChi-squared tests showed no significant difference in response or remission rates from depression between groups across treatment levels. Higher Hamilton Rating Scale for Depression (HRSD) score was associated with overall lower odds of remission in treatment level 1 (OR = 0.93, p < 0.001) and 2 (OR = 0.95, p < 0.001), with no significant interaction with comorbid AUD. Higher baseline suicidality had overall lower odds of remission in level 1 (OR = 0.82, p < 0.001) and 2 (OR = 0.1, p < 0.001), but with comorbid AUD compared to no AUD, suicidality increased odds of level 1 remission (OR = 1.30, p = 0.012). In comorbid AUD in level 2, venlafaxine was associated with lower odds of remission (OR = 0.13, p = 0.013) and response (OR = 0.12, p = 0.006); bupropion with lower odds of response (OR = 0.22, p = 0.024). LimitationsOpen label study design and lack of alcohol use data. ConclusionsComorbid AUD may interact with predictors of antidepressant response in MDD and using venlafaxine or bupropion may be less effective. Addressing this comorbidity requires unique assessment and treatment approaches.

Oncologic Significance of Therapeutic Delays in Patients With Oral Cavity Cancer

Oral cavity cancer often requires multidisciplinary management, subjecting patients to complex therapeutic trajectories. Prolonged treatment intervals in oral cavity cancer have been associated with poor oncological outcomes, but there has yet to be a study investigating treatment times in Canada. To report treatment delays for patients with oral cavity cancer in Canada and evaluate the outcomes of treatment delays on overall survival. This multicenter cohort study was performed at 8 Canadian academic centers from 2005 to 2019. Participants were patients with oral cavity cancer who underwent surgery and adjuvant radiation therapy. Analysis was performed in January 2023. Treatment intervals evaluated were surgery to initiation of postoperative radiation therapy interval (S-PORT) and radiation therapy interval (RTI). The exposure variables were prolonged intervals, respectively defined as index S-PORT greater than 42 days and RTI greater than 46 days. Patient demographics, Charlson Comorbidity Index, smoking status, alcohol status, and cancer staging were also considered. Univariate (log rank and Kaplan-Meier) and multivariate (Cox regression) analyses were performed to determine associations with overall survival (OS). Overall, 1368 patients were included; median (IQR) age at diagnosis was 61 (54-70) years, and 896 (65%) were men. Median (IQR) S-PORT was 56 (46-68) days, with 1093 (80%) patients waiting greater than 42 days, and median (IQR) RTI was 43 (41-47) days, with 353 (26%) patients having treatment time interval greater than 46 days. There were variations in treatment time intervals between institutions for S-PORT (institution with longest vs shortest median S-PORT, 64 days vs 48 days; η2 = 0.023) and RTI (institution with longest vs shortest median RTI, 44 days vs 40 days; η2 = 0.022). Median follow-up was 34 months. The 3-year OS was 68%. In univariate analysis, patients with prolonged S-PORT had worse survival at 3 years (66% vs 77%; odds ratio 1.75; 95% CI, 1.27-2.42), whereas prolonged RTI (67% vs 69%; odds ratio 1.06; 95% CI, 0.81-1.38) was not associated with OS. Other factors associated with OS were age, Charlson Comorbidity Index, alcohol status, T category, N category, and institution. In the multivariate model, prolonged S-PORT remained independently associated with OS (hazard ratio, 1.39; 95% CI, 1.07-1.80). In this multicenter cohort study of patients with oral cavity cancer requiring multimodal therapy, initiation of radiation therapy within 42 days from surgery was associated with improved survival. However, in Canada, only a minority completed S-PORT within the recommended time, whereas most had an appropriate RTI. An interinstitution variation existed in terms of treatment time intervals. Institutions should aim to identify reasons for delays in their respective centers, and efforts and resources should be directed toward achieving timely completion of S-PORT.

Exposure to an enriched environment exerts anxiolytic effects in Sardinian alcohol-preferring rats

Exposure to an enriched environment (EE) has been reported to generate multiple beneficial effects in rodents, including – among the many – amelioration of anxiety-related behaviors. The present study investigated whether living in an EE produced anxiolytic effects also in selectively bred Sardinian alcohol-preferring (sP) rats. The relevance of this research question relied on two factors: sP rats displayed an inherent, high anxiety-like state under different experimental conditions; exposure to EE reduced operant, oral alcohol self-administration in sP rats. Starting from weaning, male sP rats were kept under 3 different housing conditions: impoverished environment (IE; single housing with no environmental enrichment); standard environment (SE; 3 rats/cage with no environmental enrichment); EE (6 rats/cage with various elements of environmental enrichment). At the age of approximately 80 days, rats were exposed to an elevated plus maze test for assessment of anxiety-related behaviors. Compared to IE and SE rats, EE rats displayed higher basal levels of exploratory activity (i.e., increased number of entries into closed arms). Compared to IE and SE rats, EE rats also displayed a less “anxious” profile, as suggested by the increase in percent number of entries into open arms (OAs), percent time spent in OAs, number of head dips, and number of end-arm explorations in OAs. These data extend the protective (anxiolytic) effects of EE to a proposed animal model of comorbid alcohol use disorder and anxiety disorders.

Alcohol Use Disorder Visits and Suicide Ideation Diagnosis: Racial/Ethnic Differences at Emergency Departments

Nationally, suicide ideation prevalence is comparable among White, American Indian/Alaska Native, Black, and Hispanic adults experiencing alcohol use disorder. This study examines whether such comparability extends to the probability of receiving a suicide ideation diagnosis when presenting with alcohol use disorder at emergency departments. The probability of hospitalization following such diagnosis is examined as well. National Emergency Department Sample (2019) data were used. Logistic and multilevel logistic regression analyses were performed in 2022-2023 with suicide ideation diagnosis and subsequent hospitalization as the outcome variables. Control variables included demographics, payor, alcohol use disorder level, comorbidities, and emergency department facility. Adjusted probabilities were computed. Age-adjusted probabilities of suicide ideation diagnoses for American Indian/Alaska Native, Black, and Hispanic patients with alcohol use disorder were 5.4%, 6.7%, and 4.9% (95% CIs=3.7, 7.1; 6.0, 7.4; 4.4, 5.4), respectively; all less than that for White counterparts (8.7%; 95% CI=8.2, 9.2). Among patients with alcohol use disorder plus suicide ideation diagnoses, the age-adjusted probability of hospitalization for American Indians/Alaska Natives (32.4%; 95% CI=20.9, 44.0) was less than that for Whites, Blacks, and Hispanics (49.8%, 52.3%, and 49.9%; 95% CIs=46.7, 52.8; 47.1, 57.5; and 43.9, 55.8, respectively). In regressions with multiple control variables, the racial/ethnic differences remained statistically significant (p<0.05). Diagnosis of suicide ideation, a key step in emergency department suicide prevention care, occurred significantly less often for patients of color with alcohol use disorder than for White counterparts. American Indians/Alaska Natives, the racial/ethnic group known to have the nation's highest suicide rate, had the lowest probability of being hospitalized after a diagnosis of alcohol use disorder plus suicide ideation.