Alcohol Use Disorder and Chronic Pain: An Overlooked Epidemic.

Alcohol use disorder (AUD) and chronic pain disorders are pervasive, multifaceted medical conditions that often co-occur. However, their comorbidity is often overlooked, despite its prevalence and clinical relevance. Individuals with AUD are more likely to experience chronic pain than the general population. Conversely, individuals with chronic pain commonly alleviate their pain with alcohol, which may escalate into AUD. This narrative review discusses the intricate relationship between AUD and chronic pain. Based on the literature available, the authors present a theoretical model explaining the reciprocal relationship between AUD and chronic pain across alcohol intoxication and withdrawal. They propose that the use of alcohol for analgesia rapidly gives way to acute tolerance, triggering the need for higher levels of alcohol consumption. Attempts at abstinence lead to alcohol withdrawal syndrome and hyperalgesia, increasing the risk of relapse. Chronic neurobiological changes lead to preoccupation with pain and cravings for alcohol, further entrenching both conditions. To stimulate research in this area, the authors review methodologies to improve the assessment of pain in AUD studies, including self-report and psychophysical methods. Further, they discuss pharmacotherapies and psychotherapies that may target both conditions, potentially improving both AUD and chronic pain outcomes simultaneously. Finally, the authors emphasize the need to manage both conditions concurrently, and encourage both the scientific community and clinicians to ensure that these intertwined conditions are not overlooked given their clinical significance.

Neuromodulation for Cannabis Use: A Scoping Review.

This scoping review explores the use of neuromodulation techniques in individuals with cannabis use. Our goal was to determine whether cannabis use alters cortical excitation and inhibition in the context of neuromodulation and to determine whether neuromodulation affects craving and cannabis use patterns. A systematic search was conducted using PubMed, OVID Medline, and PsycINFO from inception to 20 December 2022. Our review identified ten relevant studies, eight of which used Transcranial Magnetic Stimulation (TMS), while two employed Transcranial Direct Current Stimulation (tDCS). Findings from TMS studies suggest that cannabis users exhibit altered cortical inhibition, with decreased short interval intracortical inhibition (SICI) compared to non-users. Single sessions of rTMS did not have any impact on cannabis craving. By contrast, two studies found that multiple sessions of rTMS reduced cannabis use, but these changes did not meet the threshold for statistical significance and both studies were limited by small sample sizes. The two included tDCS studies found contradictory results, with one showing reduced cannabis craving with active treatment and another showing no effect of active treatment on craving compared to sham. Future studies should further explore the effects of multiple treatment sessions and different neuromodulation modalities.

Rethinking Substance Use as Social History: Charting a Way Forward.

Physicians have traditionally asked about substance use within the Social History section of the consultation note. Drawing on social science theory and using the authors' own experiences as generalists and addiction scholars, we consider the possible unintended harms associated with this approach. The inclusion of the substance use history within the Social History reproduces the discourse of substance use disorders as "life-style choices" rather than medical conditions, and reinforces stigma among healthcare workers through the attribution of personal responsibility for complications associated with problematic substance use. The ongoing placement of the substance use history within the Social History may lead to a failure to diagnose and make appropriate management plans for clients with substance use disorders. These missed opportunities may include inadequate withdrawal management leading to discharge before medically advised, insufficient use of evidence-based pharmacotherapy and psychotherapy, polypharmacy, medical complications, and repeated admissions to hospital. We argue instead that the Substance Use History should be a stand-alone section within the consultation note. This new section would reduce the invisibility of substance use disorders within our medical systems and model that these chronic medical conditions are amenable to prevention, treatment and harm reduction through the application of evidence-based practices.

Patients With Significant Medical Comorbidities May Benefit from Unicompartmental Knee Arthroplasty Over Total Knee Arthroplasty.

Many studies have compared outcomes in total knee arthroplasty (TKA) versus unicompartmental knee arthroplasty (UKA); however, to the authors' knowledge, there is no study evaluating complication rates in patients with significant comorbidities. The purpose of this retrospective study was to compare the incidence of postoperative complications, readmission and reoperation rates, length of stay (LOS), and discharge location for patients with significant medical comorbidities undergoing TKA versus UKA. Using the NSQIP database from 2008 to 2018, patients were identified by CPT code (27447 or 27446) and admission diagnostic code of primary osteoarthritis and included in the study if they had an American Society of Anesthesia score greater than or equal to 3. Chi-square test was used to compare categorical variables and t-test for continuous variables. Multivariate regression was used to compare outcomes of interest between groups. A total of 167,054 patients were analyzed with 97.3% undergoing TKA. TKA patients had a greater overall complication rate than those undergoing UKA (p < 0.001). Readmission rates were approximately 1.5 times higher in TKA compared with UKA (p = 0.002), while no statistically significant difference was discovered in reoperation rates (p = 0.868). TKA was also associated with decreased rates of same day discharge, discharge within 24 hours of surgery, and discharge home (p < 0.001, <0.001, and <0.001, respectively). This study found an increase in complication rates, readmission rates, and LOS, along with a lower likelihood of discharge home when undergoing a TKA. These findings suggest that patients with significant medical comorbidities at baseline may benefit from UKA over TKA when anatomically indicated.

A computer-assisted telephone collaborative care intervention provided by lay providers for the treatment of comorbid depression and at-risk drinking: Analysis of a randomized controlled trial.

INTRODUCTION: Virtual collaborative care for people with comorbid depression and at-risk drinking lacks strong evidence. Our aim was to assess the impact of 12 months of telephone collaborative care (tCC) versus enhanced usual care (eUC) on depression and drinking. METHODS: We performed a secondary analysis of the Primary care Assessment and Research of a Telephone intervention for Neuropsychiatric conditions with Education and Resources study (PARTNERs), a blinded randomized controlled trial. We examined 144 participants with comorbid depression and at-risk drinking, of which 129 were from the original sample whose data have been published, and 15 were studied since the original report had been published. PARTNERs compared eUC consisting of usual care plus assessment of symptoms at baseline, and 4, 8, and 12 months later vs. tCC consisting of eUC plus telephone-based coaching and symptom monitoring provided by a lay mental health technician to patients supervised by a psychiatrist. The study assessed depression response and remission using logistic regression; we assessed trajectory of drinking using Generalized-estimating equations (GEE). Baseline factors associated with likelihood of not exceeding number of drinks at 12 months were identified using decision trees. RESULTS: tCC produced a faster decline in the number of drinks than eUC (Wald Χ2 = 9.47, p = 0.02). However, drinking and depression outcomes did not differ significantly between the two groups at the end of treatment. Higher alcohol consumption at baseline (≥18 standard drinks per week in the tCC group and ≥11 standard drinks per week in the eUC group) was associated with a higher likelihood of having at-risk drinking after 12 months of treatment. CONCLUSIONS: Our findings suggest that, compared to eUC, tCC may accelerate drinking reductions in patients with comorbid depression and at-risk drinking. Both treatments were equally effective at the end of treatment for both depression and drinking outcomes.

Delay discounting and family history of psychopathology in children ages 9-11.

Delay discounting is a tendency to devalue delayed rewards compared to immediate rewards. Evidence suggests that steeper delay discounting is associated with psychiatric disorders across diagnostic categories, but it is unclear whether steeper delay discounting is a risk factor for these disorders. We examined whether children at higher risk for psychiatric disorders, based on family history, would demonstrate steeper delay discounting behavior using data from the Adolescent Brain Cognitive Development (ABCD) study, a nationally representative sample of 11,878 children. We looked at associations between delay discounting behavior and family history of alcohol problems, drug problems, depression, mania, schizophrenia, and suicidal behavior. Correlations between family history of psychopathology and delay discounting behavior were small, ranging from ρ = - 0.02 to 0.04. In mixed effects models controlled for sociodemographic factors, family history of psychopathology was not associated with steeper delay discounting behavior. Sociodemographic factors played a larger role in predicting delay discounting behavior than family history of psychopathology. These results do not support the hypothesis that children with greater risk for psychopathology display steeper delay discounting behavior.

Pilot study of machine learning in the task of distinguishing high and low-grade pediatric hydronephrosis on ultrasound.

PURPOSE: Hydronephrosis is a common pediatric urological condition, characterized by dilation of the renal collecting system. Accurate identification of the severity of hydronephrosis is crucial in clinical management, as high-grade hydronephrosis can cause significant damage to the kidney. In this pilot study, we demonstrate the feasibility of machine learning in differentiating between high and low-grade hydronephrosis in pediatric patients. MATERIALS AND METHODS: We retrospectively reviewed 592 images from 90 unique patients ages 0-8 years diagnosed with hydronephrosis at the University of Chicago's Pediatric Urology Clinic. The study included 74 high-grade hydronephrosis (145 images) and 227 low-grade hydronephrosis (447 images). Patients were excluded if they had less than 2 studies prior to surgical intervention or had structural abnormalities. We developed a radiomic-based artificial intelligence algorithm incorporating computerized texture analysis and machine learning (support-vector machine) to yield a predictor of hydronephrosis grade. RESULTS: Receiver operating characteristic analysis of the classifier output yielded an area under the curve value of 0.86 (95% CI 0.81-0.92) in the task of distinguishing between low and high-grade hydronephrosis using a five-fold cross-validation by kidney. In addition, a Mann-Kendall trend test between computer output and clinical hydronephrosis grade yielded a statistically significant upward trend (p<0.001). CONCLUSIONS: Our findings demonstrate the potential of machine learning in the differentiation between low and high-grade hydronephrosis. Further studies are warranted to validate our findings and their generalizability for use in clinical practice as a means to predict clinical outcomes and the resolution of hydronephrosis.

GABAergic signaling in alcohol use disorder and withdrawal: pathological involvement and therapeutic potential.

Alcohol is one of the most widely used substances. Alcohol use accounts for 5.1% of the global disease burden, contributes substantially to societal and economic costs, and leads to approximately 3 million global deaths yearly. Alcohol use disorder (AUD) includes various drinking behavior patterns that lead to short-term or long-lasting effects on health. Ethanol, the main psychoactive molecule acting in alcoholic beverages, directly impacts the GABAergic system, contributing to GABAergic dysregulations that vary depending on the intensity and duration of alcohol consumption. A small number of interventions have been developed that target the GABAergic system, but there are promising future therapeutic avenues to explore. This review provides an overview of the impact of alcohol on the GABAergic system, the current interventions available for AUD that target the GABAergic system, and the novel interventions being explored that in the future could be included among first-line therapies for the treatment of AUD.

The LUAA Gundeti Technique for Bilateral Robotic Ureteral Reimplantation: Lessons Learned over a Decade for Optimal (Resolution, Urinary Retention, and Perioperative Complications) Trifecta Outcomes.

Background: Ureteral reimplantation is the gold standard treatment for high-grade vesicoureteral reflux (VUR) in pediatric patients. Robot-assisted laparoscopic extravesical ureteral reimplantation (RALUR-EV) using the LUAA technique has emerged as a viable alternative to traditional open and laparoscopic surgical correction. Objective: To evaluate the outcomes, reflux resolution, urinary retention, and complications associated with bilateral RALUR-EV for primary VUR using the LUAA Gundeti technique in pediatric patients. Design setting and participants: A retrospective study was conducted at a single academic center, involving 34 consecutive pediatric patients who underwent RALUR-EV for bilateral VUR management between December 2008 and December 2022. The study included only patients who were evaluated with postoperative voiding cystourethrogram (VCUG). Surgical procedure: The LUAA extravesical ureteral reimplantation technique was performed, involving the identification and mobilization of the ureter, creation of a peritoneal window, dissection close to the neurovascular bundle, Y dissection at the ureterovesical junction, detrusorotomy, detrusorrhaphy with advential inclusion, and apical alignment suture. Measurements: The primary outcome was radiographic resolution of VUR on VCUG. The secondary outcomes included urinary retention and Clavien-Dindo grade III complications. Results and limitations: The overall radiographic resolution rate was 85.2%, with success rates of 76.7%, 75%, and 96.7% across the three distinct patient cohorts. The overall Clavien-Dindo grade III complication rate was 5.8%, and transient urinary retention was 8.8%. Resolution of urinary retention occurred within 7-28 d. The study's limitations include the small sample size, single-center design, and retrospective nature. Conclusions: The LUAA technique demonstrates sustainable outcomes for VUR resolution with a low incidence of transient urinary retention and complications. A thorough understanding of pelvic anatomy is essential for successful dissection and minimization of the risk of complications. Further studies are needed to evaluate the effectiveness of different approaches in reducing the incidence of transient urinary retention following bilateral extravesical reimplantation. Patient summary: In this study, we examined the results of the Gundeti LUAA surgical technique for treating primary vesicoureteral reflux in children. We identified various essential modifications that increase the likelihood of achieving favorable outcomes.

Opioid receptor antagonism and neural response to monetary rewards: Pilot studies in light and heavy alcohol users.

Alcohol use disorder (AUD) is a prevalent condition associated with high degree of comorbidity and mortality. Among the few approved pharmacotherapies for AUD, two involve opioid receptor antagonism. Naltrexone and nalmefene are thought to act via opioid receptor blockage to reduce neural response to alcohol and drug-associated cues and consumption, but there have been limited efforts to characterize these effects in humans. In these studies, we sought to test the magnitude of opioid antagonism effects on neural response to monetary rewards in two groups: light drinkers (for the naltrexone study) and heavy drinkers (for the nalmefene study). We conducted double-blind, randomized, crossover pilot studies of reward activation in the brain following acute administration of opioid antagonist and placebo in 11 light and 9 heavy alcohol users. We used a monetary incentive delay task during functional MRI. We found a main effect of cue type on BOLD activation in the nucleus accumbens, demonstrating a neural reward response. The effect of opioid antagonism, relative to placebo, was small and nonsignificant for reward activation in the accumbens for both light and heavy alcohol users. Based on the results of two pilot studies, opioid antagonist medications do not appear to decrease neural activation to monetary rewards in the nucleus accumbens relative to placebo.

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

INTRODUCTION: Guidance 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. METHODS: STAR*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. RESULTS: Chi-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). LIMITATIONS: Open label study design and lack of alcohol use data. CONCLUSIONS: Comorbid 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.

Repetitive transcranial magnetic stimulation for smoking cessation: Next steps for translation and implementation into clinical practice.

Tobacco smoking is a significant determinant of preventable morbidity and mortality worldwide. It is now possible to modulate the activity of the neurocircuitry associated with nicotine dependence using repetitive Transcranial Magnetic Stimulation (rTMS), a non-invasive neurostimulation approach, which has recently demonstrated efficacy in clinical trials and received regulatory approval in the US and Canada. However there remains a paucity of replication studies and real-world patient effectiveness data as access to this intervention is extremely limited. There are a number of unique challenges related to the delivery of rTMS that need to be addressed prior to widespread adoption and implementation of this treatment modality for smoking cessation. In this paper, we review the accessibility, scientific, technological, economical, and social challenges that remain before this treatment can be translated into clinical practice. By addressing these remaining barriers and scientific challenges with rTMS for smoking cessation and delineating implementation strategies, we can greatly reduce the burden of tobacco-related disease worldwide.

Cannabis self-administration in the human laboratory: a scoping review of ad libitum studies.

Cannabis self-administration studies may be helpful for identifying factors that influence cannabis consumption and subjective response to cannabis. Additionally, these paradigms could be useful for testing novel pharmacotherapies for cannabis use disorder. This scoping review aims to summarize the findings from existing ad libitum cannabis self-administration studies to determine what has been learned from these studies as well as their limitations. We examined studies that specifically examined cannabis smoking, focusing on subjective response and self-administration behavior (e.g., smoking topography). A systematic search was conducted using PubMed and Embase from inception to October 22, 2022. Our search strategy identified 26 studies (total N = 662, 79% male) that met our eligibility criteria. We found that tetrahydrocannabinol (THC) concentration significantly affected subjective response to cannabis in some but not all studies. In general, cannabis self-administration tended to be most intense at the beginning of the laboratory session and decreased in later parts of the session. There was limited data on cannabis self-administration in adults older than 55. Data on external validity and test-retest reliability were also limited. Addressing these limitations in future ad libitum cannabis self-administration studies could lead to more valid and generalizable paradigms, which in turn could be used to improve our understanding of cannabis use patterns and to help guide medication development for cannabis use disorder.

Outcomes and Survivorships of Total Knee Arthroplasty Comparing Resurfaced and Unresurfaced Patellae.

BACKGROUND: The decision to resurface the patella in total knee arthroplasty (TKA) is controversial. While there is some consensus that leaving the patella unresurfaced increases risk of reoperation, there is conflicting evidence about patient reported outcomes or indications for resurfacing. This study sought to determine recent rates of patellar resurfacing, examine factors affecting rates of resurfacing, and analyze the associations between patellar resurfacing and both revision rates and patient-reported outcome measures (PROMs). METHODS: The American Joint Replacement Registry was used to identify primary TKAs performed for osteoarthritis between 2012 and 2021. Cases were classified as resurfaced patella and unresurfaced patella (URP). Outcomes analyzed included trends in patellar resurfacing, factors influencing rate of resurfacing, revision rates, operative time, and 2 PROMs. RESULTS: Rates of patellar resurfacing decreased and rates of URP increased significantly faster in ambulatory surgery centers and among high volume surgeons. Operative time was significantly lower in URP versus resurfaced patella (88.15 versus 89.90 minutes). The URP were significantly more likely to require revision surgery (odds ratio = 1.206 (1.078, 1.35), P = .0011). There was no significant difference in the likelihood of achieving the minimal clinically important difference in PROMs between resurfaced and nonresurfaced TKAs at 1 year (odds ratio = 1.060 (0.710, 1.581), P = .7755). CONCLUSION: There was no difference in minimal clinically important difference between resurfaced and URPs and no clinically relevant difference in operative time. However, URPs were more likely to require revision surgery. Therefore, the decision not to resurface should be made carefully considering the known risk of revision and the uncertain benefit.

Endocannabinoid System Biomarkers in Alzheimer's Disease.

Background: Alterations in the endocannabinoid system (ES) have been described in Alzheimer's disease (AD) pathophysiology. In the past years, multiple ES biomarkers have been developed, promising to advance our understanding of ES changes in AD. Discussion: ES biomarkers, including positron emission tomography with cannabinoid receptors tracers and biofluid-based endocannabinoids, are associated with AD disease progression and pathological features. Conclusion: Although not specific enough for AD diagnosis, ES biomarkers hold promise for prognosis, drug-target engagement, and a better understanding of the disease. Here, we summarize currently available ES biomarker findings and discuss their potential applications in the AD research field.

Emotion regulation in substance use disorders: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The ability to regulate emotions effectively has been associated with resilience to psychopathology. Individuals with substance use disorders (SUDs) have been shown to have higher levels of negative emotionality, with some evidence suggesting impairment in emotion regulation compared with individuals without SUDs. However, no previous attempt has been made to systematically review the literature to assess the magnitude of this difference. We aimed to assess the association between SUD diagnosis and emotion regulation as measured by the Difficulties in Emotion Regulation Scale (DERS) and Emotion Regulation Questionnaire (ERQ) through a systematic review and meta-analysis of existing findings. METHODS: The systematic review was conducted using PubMed, PsycINFO and Embase. We examined cross-sectional studies that compared a SUD group with a control group and measured emotion regulation using the DERS or the ERQ. The primary analysis focused on papers using the DERS, as this was the predominant instrument in the literature. RESULTS: Twenty-two studies met our primary analysis criteria, representing 1936 individuals with a SUD and 1567 controls. Individuals with SUDs relative to controls had significantly greater DERS scores, with a mean difference of 21.44 [95% confidence interval (CI) = 16.49-26.40, P < 0.001] and Hedges' g = 1.05 (95% CI = 0.86-1.24, P < 0.001). The difference was robust, remaining significant after removing outliers and studies with high risk of bias. Individuals with SUDs demonstrated poorer emotion regulation on each subscale of the DERS, with the largest deficits in the Strategies and Impulse subscales. The ERQ analysis revealed greater use of expressive suppression in those with SUDs relative to controls (Hedges' g = 0.76, 95% CI = 0.25-1.28, P = 0.004). CONCLUSIONS: People with substance use disorders appear to have greater difficulties in emotion regulation than people without substance use disorders.

A Historical and Contemporary Review of Questionnaires Used in the Management of Post-Radical Prostatectomy Patients.

INTRODUCTION: Patients undergoing radical prostatectomy (RP) face obstacles to recovery spanning the domains of erectile and sexual function; urinary function; and health-related quality of life (HRQoL). Numerous patient-directed questionnaires exist that serve to assist in the care of these men. AIM: To describe patient-directed questionnaires of historical and contemporary relevance involving the evaluation and treatment of men after radical prostatectomy. METHODS: A comprehensive review of peer-reviewed publications on the topic was performed. Using PubMed, the search terms used were: "radical prostatectomy; erectile function; lower urinary tract symptoms; sexual dysfunction; urinary incontinence; and health-related quality of life. MAIN OUTCOME MEASURE: We aimed to summarize questionnaires and survey devices of historical and contemporary importance for the care of men after RP. RESULTS: Many questionnaires have been developed specifically for, or conscripted for use in, the care of men after RP. Some of the oldest questionnaires relating to sexual function, urinary function, and general and cancer-specific QoL are important and still utilized in the routine clinical care of post-RP patients. However, recent devices that may offer clinicians a more comprehensive understanding to aid in the evaluation and care of these men. CONCLUSIONS: Post-RP patients face numerous challenges that require a thoughtful approach, one that is broad enough to identify a variety of potential physical and emotional disturbances, yet granular enough to identify appropriate areas for intervention. While there is not a "best" questionnaire for this population, having an appropriate understanding of the current available instruments and what information they provide may help clinicians more thoroughly assess and treat these men. Castillo O, Chen IK, Amini E, et al. Male Sexual Health Related Complications Among Combat Veterans. Sex Med Rev 2022;10:681-690.