Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:Surgery in NF2-related schwannomatosis (NF2-SWN) vestibular schwannoma (VS) carries a higher risk of facial nerve damage, hearing loss, and partial resection, than in sporadic cases. Radiosurgery is also associated with higher failure compared with sporadic schwannomas. Nowadays, bevacizumab (BEV) is frequently considered in the NF2-SWN population. However, some patients experience progression despite treatment. Among other surgical risks, in BEV-treated patients, hemorrhage and impaired healing are specific considerations. These concerns have led manufacturers to recommend stopping BEV 6 to 8 weeks preoperatively. The aim of our multicentric study was to assess the perioperative bleeding risk and postoperative outcomes in NF2-SWN patients undergoing VS surgery after preoperative BEV treatment. METHODS:Our retrospective analysis included medical and surgical records along with imaging reviews from 4 high-volume tertiary academic referral centers for NF2-SWN and VS. RESULTS:A total of 21 patients met the inclusion criteria. VS had a mean volume of 13.2 ±7.6 cm3 corresponding to 1 KOOS III and 20 KOOS IV. BEV was stopped at a mean of 5.8 ± 4.0 months before surgery with a total mean treatment duration of 33.7 ± 20.7 months and a monthly dose of 10.2 ± 4.1 mg/kg. Intraoperatively, the tumor was assessed to be bloody by the operating surgeons in 7 patients. Late BEV discontinuation and high cumulative dose independently predicted perioperative bleeding and longer surgery duration. No other complication such as wound dehiscence was reported. CONCLUSION/CONCLUSIONS:Our findings suggest that a higher cumulative BEV dose (∼600 mg/kg) and a longer interval between BEV discontinuation and surgery (∼8 months) are associated with a modest but statistically significant increase in intraoperative bleeding risk. Based on these observations, a BEV-free window between 6 weeks and 6 months (depending on the clinical scenario) before tumor resection seems optimal, particularly for patients with high cumulative exposure.

INTRODUCTION/BACKGROUND:Although an open-group model is often used in substance use treatment, there are no evidence-based open-group treatment protocols. A large federal substance treatment agency (the Alcohol and Drug Abuse Prevention and Treatment Program within the Department of the Air Force) requested an evidence-informed open-group treatment protocol to treat alcohol misuse to implement throughout their clinics. MATERIALS AND METHODS/METHODS:The research team: (a) compiled and reviewed manuals for empirically supported closed groups, general literature, and best practices; (b) developed an overarching and unifying framework; (c) drafted preliminary pilot materials; (d) implemented and refined groups with providers via ongoing feedback; and (e) evaluated feasibility and usability of, and participant engagement in, the program. Providers gave detailed weekly feedback in meetings on program content and process. RESULTS:The feedback was positive in both phases. With the addition of new installations, program content and delivery continued to be perceived as useful in meeting patient and provider needs. CONCLUSIONS:Effective delivery of an evidence-based open-group treatment can be achieved with basic training of providers in the protocol.

INTRODUCTION/BACKGROUND:Understanding which theories have been effectively applied in tobacco control efforts for sexual and gender minority (SGM) individuals will help identify constructs to incorporate into future tobacco control efforts aimed at reducing SGM tobacco disparities. This scoping review summarizes the use of theory in SGM-focused tobacco control efforts. METHODS:We searched four databases using SGM- and tobacco-focused terms in November 2023. Two trained coders independently screened each title and abstract, reviewed the full text, and extracted data about theories used and which tobacco control measures from the World Health Organization Framework Convention on Tobacco Control were included. RESULTS:The final analytic sample included 86 papers. Of those, 11 (12.9%) discussed price/tax manipulations, 15 (17.7%) discussed secondhand smoke and smoke-free policies, 11 (12.9%) discussed product characteristics (e.g., flavors), 5 (5.9%) discussed product disclosures (e.g., warning labels), 7 (8.1%) discussed packaging, 23 (27.1%) discussed education, communication and public awareness, 15 (17.7%) discussed tobacco advertising and promotion, 49 (57.7%) discussed tobacco prevention/cessation interventions, and 1 discussed Tobacco 21 (1%). Under half (31 articles, 36.0%) explicitly presented theoretical models. CONCLUSIONS:This review found a relative lack of theoretical models applied in tobacco control initiatives for SGM people. Of the 31 studies that did, most used theory to help clarify the etiology and associated factors of tobacco use (e.g., minority stress, increased exposure to marketing) or tailor prevention/cessation interventions focused on SGM individuals. Future studies should be grounded in theory to increase the effectiveness of these activities while preventing potential unintended consequences.

AIMS/OBJECTIVE:To estimate the effectiveness of different thresholds for administering opioid withdrawal medications (clonidine and clonazepam) on the probability of successfully initiating extended-release naltrexone (XR-NTX) among participants with opioid use disorder (OUD) during medically managed withdrawal. DESIGN/METHODS:Secondary analysis of a multisite clinical trial comparing a rapid vs. standard approach for XR-NTX initiation, 2021-2022. SETTING/METHODS:Six community inpatient addiction treatment units in the United States. PARTICIPANTS/METHODS:English-speaking adults seeking treatment for DSM-5 OUD and expressing interest in XR-NTX treatment (n = 415). MEASUREMENTS/METHODS:We estimated the extent to which the following thresholds for adjunctive medication administration would affect the probability of initiating XR-NTX over time: 1) where adjunctive medications were given in response to at mild-to-moderate withdrawal symptoms or greater [Clinical Opiate Withdrawal Scale (COWS) score ≥ 5), 2) where adjunctive medications were given in response to minimal withdrawal symptoms or greater (COWS score ≥ 3) and 3) where adjunctive medications were given regardless of withdrawal symptoms. Using a longitudinal sequentially doubly robust estimator, we estimated the cumulative probability of XR-NTX initiation under each of these three treatment regimes while accounting for dropout and initiation of other medications as competing events. FINDINGS/RESULTS:The estimated probability of initiating XR-NTX by day 14 was 50.4% [95% confidence interval (CI) = 41.8-58.9) under the no-threshold regime, 43.9% (95% CI = 39.1-48.7) under the regime of waiting for minimal withdrawal symptoms and 38.5% (95% CI = 34.3-42.6) under the regime of waiting for mild-to-moderate withdrawal symptoms. Probability of XR-NTX initiation was a statistically significant 11.9 percentage points higher (95% CI = 3.6-20.2) under the no-threshold regime versus the mild-to-moderate threshold regime, and a non-statistically significant 6.4 percentage points (95% CI = -0.8 to 13.7) higher under the no-threshold regime versus the minimal threshold regime. CONCLUSIONS:Providing clonidine and clonazepam daily during the first five days of medically managed opioid withdrawal appears to statistically significantly increase the likelihood of initiating extended-release naltrexone treatment compared with waiting for mild-to-moderate withdrawal symptoms to administer adjunctive medications. To improve initiation rates, providers may consider lowering the threshold at which they provide adjunctive medications, giving these medications preemptively or to manage even minimal withdrawal symptoms.

Liver transplant (LT) recipients experience a wide range of comorbidities, leading to frequent healthcare encounters. Until now, national registries, which have limited exposures and outcomes, and laborious small cohort studies have been the main data sources for LT research. Cosmos database offers electronic health record (EHR)-based insights into LT recipients at the national level with granular data. We evaluated if Cosmos data is representative of the entire US LT recipient population. Using Cosmos (N=20,235) and the national Scientific Registry of Transplant Recipients (SRTR) (N=51,281), we identified adult, first-time LT recipients between 7/2016-12/2022. We compared demographics, clinical data, and mortality across datasets, calculating Kaplan-Meier survival estimates and multi-variable Cox regressions. Recipient characteristics were highly comparable (e.g., female: Cosmos=36.5% vs. SRTR=36.4%, Black: 6.8% vs. 7.2%; BMI: 28.5 kg/m2 [24.8-32.9] vs. 28.2 [24.6-32.4]). Lab values were similar across cohorts, including MELD (24 [17-30] vs. 23 [16-30]). Transplant indications, donor characteristics, and 5-year survival (Cosmos 83.1% [82.3-83.8) vs. SRTR 80.9% [80.4-81.3]) were similar. The associations of clinical factors with survival were similar across both groups. Cosmos database demonstrated acceptable generalizability to the general US LT recipient population, which may advance LT research through a better understanding about LT recipients' experiences and outcomes.

We conducted a cross-sectional oral cancer screening study in Northeast India to develop and validate an oral precancer/cancer risk prediction model. We compared epidemiologic profiles between tobacco pouch keratosis and oral precancer/cancer. During 2018-2022, we recruited 14,749 participants who underwent an interviewer-administered questionnaire and oral examination (visual inspection and autofluorescence). Logistic regression was used to compare risk factors between tobacco pouch keratosis and precancer/cancer and risk model development for prevalent lesions (keratosis and oral precancer/cancer, combined). Model validation was conducted internally and externally (Kerala oral cancer screening trial). Among the 14,749 participants, as per dentists' diagnosis, 1365 lesions were identified. These included 249 benign lesions (prevalence = 1.6%), 795 tobacco pouch keratosis (prevalence = 5.4%), and 321 precancers/cancers (prevalence = 2.2%). Agreement between dentists and health workers was high for visual diagnosis of prevalent lesions (keratotic/precancer/cancer; positive-agreement = 87.5%; kappa = 0.77; 95% confidence interval [CI] = 0.75-0.78). Risk factor profiles were similar between tobacco pouch keratosis and oral precancer/cancer. The risk prediction model (based on age, sex, education, income, chewing duration, chewing type, smoking duration and intensity, alcohol duration and intensity) had good discrimination (area under the curve [AUC] = 0.83) and calibration (E/O ratio = 1.00) internally. Further, 30% of individuals at the highest model-predicted risk accounted for 81.8% of prevalent lesions. However, in external validation, the risk model had modest discrimination (AUC = 0.67; 95% CI = 0.66-0.68) and poor calibration (E/O ratio = 0.52; 95% CI = 0.50-0.54). Our results suggest tobacco pouch keratosis as an early carcinogenic event amenable for behavioral interception. Poor transportability of our risk model reflects the need for prediction models that account for geographic differences in risk factors within regions in India.

BACKGROUND:Immunosuppression is associated with a higher risk of developing cutaneous squamous cell carcinoma and more aggressive tumors, but its role as an independent predictor of poor outcomes remains unclear. OBJECTIVE:To determine whether immunosuppression independently predicts poor outcomes in cutaneous squamous cell carcinoma. METHODS:This was a retrospective cohort study with pooled data from 12 international centers. Demographics, immunosuppression status, tumor characteristics, treatment, and outcomes were collected. Univariable and multivariable marginal Fine and Gray competing risk analyses were performed. Subgroup multivariable analyses were performed on the organ transplant and chronic lymphocytic leukemia cohorts. RESULTS:A total of 11,930 patients with 18,760 tumors (14,766 in immunocompetent and 3,994 in immunosuppressed) were included. Immunosuppressed patients had a higher prevalence of high-risk tumor features and poor disease outcomes. On multivariable analysis, immunosuppression was independently associated with local recurrence, distant metastasis, disease-specific death, and major poor outcomes. Organ transplantation was predictive of local recurrence, distant metastasis, and disease-specific death, whereas chronic lymphocytic leukemia independently predicted local recurrence, disease-specific death, and major poor outcomes. LIMITATIONS/CONCLUSIONS:Retrospective design, potential for data heterogeneity. CONCLUSIONS:Immunosuppression is an independent risk factor for major poor outcomes in cutaneous squamous cell carcinoma and should be included in risk nomograms.