Optimizing Contingency Management with Reinforcement Learning.

Contingency Management (CM) is a psychological treatment that aims to change behavior with financial incentives. In substance use disorders (SUDs), deployment of CM has been enriched by longstanding discussions around the cost-effectiveness of prized-based and voucher-based approaches. In prize-based CM, participants earn draws to win prizes, including small incentives to reduce costs, and the number of draws escalates depending on the duration of maintenance of abstinence. In voucher-based CM, participants receive a predetermined voucher amount based on specific substance test results. While both types have enhanced treatment outcomes, there is room for improvement in their cost-effectiveness: the voucher-based system requires enduring financial investment; the prize-based system might sacrifice efficacy. Previous work in computational psychiatry of SUDs typically employs frameworks wherein participants make decisions to maximize their expected compensation. In contrast, we developed new frameworks that clinical decision-makers choose actions, CM structures, to reinforce the substance abstinence behavior of participants. We consider the choice of the voucher or prize to be a sequential decision, where there are two pivotal parameters: the prize probability for each draw and the escalation rule determining the number of draws. Recent advancements in Reinforcement Learning, more specifically, in off-policy evaluation, afforded techniques to estimate outcomes for different CM decision scenarios from observed clinical trial data. We searched CM schemas that maximized treatment outcomes with budget constraints. Using this framework, we analyzed data from the Clinical Trials Network to construct unbiased estimators on the effects of new CM schemas. Our results indicated that the optimal CM schema would be to strengthen reinforcement rapidly in the middle of the treatment course. Our estimated optimal CM policy improved treatment outcomes by 32% while maintaining costs. Our methods and results have broad applications in future clinical trial planning and translational investigations on the neurobiological basis of SUDs.

Associations between stimulant use and return to illicit opioid use following initiation onto medication for opioid use disorder.

AIM: The aim of this study was to estimate how ongoing stimulant use affects return to illicit opioid use after initiation onto medication for opioid use disorder (MOUD). DESIGN: This was a secondary analysis of pooled data from two clinical trials comparing buprenorphine (BUP-NX) and extended-release naltrexone (XR-NTX). SETTING: Thirteen opioid treatment programs and HIV clinics across 10 states in the United States from 2014 to 2019 took part in this study. PARTICIPANTS: A total of 528 participants who initiated MOUD as part of trial participation were included. Nearly half (49%) were between 30 and 49 years of age, 69% were male and 66% were non-Hispanic White. MEASUREMENTS: The primary outcome was first self-reported day of non-prescribed opioid use following MOUD initiation, and the exposure of interest was daily stimulant use (methamphetamine, amphetamines or cocaine). Both were defined using time-line follow-back. Among participants reporting at least 1 day of illicit opioid use, we also examined relapse to ongoing use, defined as (1) 7 days of continuous opioid use or (2) 4 consecutive weeks with self-reported opioid use, one or more positive urine drug screens (UDS) for opioids or one or more missing UDS. FINDINGS: Forty-seven per cent of participants reported stimulant use following MOUD initiation, 58% returned to illicit opioid use and 66% of those relapsed to ongoing use. Stimulant use was strongly associated with increased risk of misusing opioids after MOUD initiation when measured daily [adjusted hazard ratio (aHR) = 9.23, 95% confidence interval (CI) = 6.80-12.50, P < 0.001] and over a 7-day period (aHR = 1.27 for each additional day, CI = 1.18-1.37, P < 0.001). Using stimulants weekly or more often was associated with increased likelihood of relapse to ongoing opioid use compared with less than weekly or no stimulant use (adjusted odds ratio = 2.30, CI = 1.05-5.39, P = 0.044). CONCLUSIONS: People initiated on medication for opioid use disorder who subsequently use stimulants appear to be more likely to return to and continue using non-prescribed opioids compared with those without stimulant use. The association appears to be stronger among patients who initiate buprenorphine compared with those who initiate extended-release naltrexone.

Individual-Level Risk Prediction of Return to Use During Opioid Use Disorder Treatment.

Importance: No existing model allows clinicians to predict whether patients might return to opioid use in the early stages of treatment for opioid use disorder. Objective: To develop an individual-level prediction tool for risk of return to use in opioid use disorder. Design, Setting, and Participants: This decision analytical model used predictive modeling with individual-level data harmonized in June 1, 2019, to October 1, 2022, from 3 multicenter, pragmatic, randomized clinical trials of at least 12 weeks' duration within the National Institute on Drug Abuse Clinical Trials Network (CTN) performed between 2006 and 2016. The clinical trials covered a variety of treatment settings, including federally licensed treatment sites, physician practices, and inpatient treatment facilities. All 3 trials enrolled adult participants older than 18 years, with broad pragmatic inclusion and few exclusion criteria except for major medical and unstable psychiatric comorbidities. Intervention: All participants received 1 of 3 medications for opioid use disorder: methadone, buprenorphine, or extended-release naltrexone. Main Outcomes and Measures: Predictive models were developed for return to use, which was defined as 4 consecutive weeks of urine drug screen (UDS) results either missing or positive for nonprescribed opioids by week 12 of treatment. Results: The overall sample included 2199 trial participants (mean [SD] age, 35.3 [10.7] years; 728 women [33.1%] and 1471 men [66.9%]). The final model based on 4 predictors at treatment entry (heroin use days, morphine- and cocaine-positive UDS results, and heroin injection in the past 30 days) yielded an area under the receiver operating characteristic curve (AUROC) of 0.67 (95% CI, 0.62-0.71). Adding UDS in the first 3 treatment weeks improved model performance (AUROC, 0.82; 95% CI, 0.78-0.85). A simplified score (CTN-0094 OUD Return-to-Use Risk Score) provided good clinical risk stratification wherein patients with weekly opioid-negative UDS results in the 3 weeks after treatment initiation had a 13% risk of return to use compared with 85% for those with 3 weeks of opioid-positive or missing UDS results (AUROC, 0.80; 95% CI, 0.76-0.84). Conclusions and Relevance: The prediction model described in this study may be a universal risk measure for return to opioid use by treatment week 3. Interventions to prevent return to regular use should focus on this critical early treatment period.

Capturing drug use patterns at a glance: An n-ary word sufficient statistic for repeated univariate categorical values.

INTRODUCTION: The efficacy of treatments for substance use disorders (SUD) is tested in clinical trials in which participants typically provide urine samples to detect whether the person has used certain substances via urine drug screenings (UDS). UDS data form the foundation of treatment outcome assessment in the vast majority of SUD clinical trials. However, existing methods to calculate treatment outcomes are not standardized, impeding comparability between studies and prohibiting reproducibility of results. METHODS: We extended the concept of a binary UDS variable to multiple categories: "+" [positive for substance(s) of interest], "-" [negative for substance(s)], "o" [patient failed to provide sample], "*" [inconclusive or mixed results], and "_" [no specimens required per study design]. This construct can be used to create a standardized and sufficient representation of UDS datastreams and sufficiently collapses longitudinal records into a single, compact "word", which preserves all information contained in the original data. RESULTS: We developed the R software package CTNote (available on CRAN) as a tool to enable computers to parse these "words". The software package contains five groups of routines: detect a substance use pattern, account for a specific trial protocol, handle missing UDS data, measure the longest period of consecutive behavior, and count substance use events. Executing permutations of these routines result in algorithms which can define SUD clinical trial endpoints. As examples, we provide three algorithms to define primary endpoints from seminal SUD clinical trials. DISCUSSION: Representing substance use patterns as a "word" allows researchers and clinicians an "at a glance" assessment of participants' responses to treatment over time. Further, machine readable use pattern summaries are a standardized method to calculate treatment outcomes and are therefore useful to all future SUD clinical trials. We discuss some caveats when applying this data summarization technique in practice and areas of future study.

Potential effect of antidepressants on remission from cocaine use disorder - A nationwide matched retrospective cohort study.

BACKGROUND: Cocaine use disorder (CUD) is a significant public health issue for which there is no Food and Drug Administration-approved pharmacotherapy. Depressive disorders are common psychiatric comorbidity amongst individuals with CUD. METHODS: A retrospective cohort study was conducted among 161,544 patients diagnosed with CUD and depression to evaluate the effectiveness of 13 antidepressants on CUD remission. For any antidepressant found to be associated with CUD remission that had an additional indication, we conducted an additional analysis to evaluate the effectiveness of the candidate drug in patients with CUD with that indication. We then analyzed publicly genomic and functional databases to identify potential explanatory mechanisms of action of the candidate drug in the treatment of CUD. RESULTS: Among these antidepressants, bupropion was associated with higher rates of CUD remission compared to propensity-score matched patients prescribed other antidepressants: hazard ratio (HR) and 95% confidence interval (CI) 1.57 (95% CI: 1.27-1.94). Bupropion is also approved for smoking cessation. We identified CUD patients with co-occurring nicotine dependence and observed that patients prescribed bupropion displayed a higher rate of CUD remission compared to matched individuals prescribed other drugs for nicotine dependence: 1.38 (95% CI: 1.11-1.71). Genetic and functional analyses revealed that bupropion interacts with four protein-encoding genes (COMT, DRD2, SLC6A3, and SLC6A4) which are also associated with CUD and targets CUD-associated pathways including serotonergic synapses, cocaine addiction, and dopaminergic synapses. CONCLUSIONS: Our findings suggest that bupropion might be considered a treatment for improving CUD remission in patients with CUD and co-occurring depression or nicotine dependence.

Risks of returning to opioid use at treatment entry and early in opioid use disorder treatment: Role of non-opioid substances.

OBJECTIVE: Patients in treatment with medications for opioid use disorder (MOUD) often report use of other substances in addition to opioids. Few studies exist that examine the relationship between use at treatment entry and early non-opioid use in opioid treatment outcome. METHODOLOGY: We combined and harmonized three randomized, controlled MOUD clinical trials from the National Institutes of Drug Abuse (NIDA) Clinical Trials Network (CTN) (N=2197) and investigated the association of non-opioid substance use at treatment entry and during early treatment with a return to opioid use. The trials compared MOUD treatment (buprenorphine, methadone, extended-release naltrexone) in populations with opioid use disorder (OUD). Non-opioid substances were identified through harmonizing self-reported use. The primary outcomes were markers of return to opioid use by 12 weeks. RESULTS: When treatment cohorts were adjusted, no association between self-reported treatment entry use of non-opioid substances and week-12 opioid use was detected. During the first month of treatment, higher use of cocaine (OR 1.41 [1.18-1.69]) and amphetamine (OR 1.70 [1.27-2.26]) was found to be associated with higher likelihood of illicit opioid use by week 12. Exploratory analyses of potential treatment cohort-by-predictor interactions showed that those with heavier cocaine use had a lower rate of returning to opioid use in the extended-release naltrexone group than in the methadone group. CONCLUSION: Substance use other than opioids at treatment entry is not associated with relapse. Use of cocaine or amphetamines during the first few weeks of MOUD treatment may signal a worse outcome, suggesting a need for additional interventions.

Clinical effect of endovascular repair of complex aortic lesions using optimized Octopus surgery.

Objective: Complex aortic lesions, especially those involving branches of the visceral artery, remain a challenge to treat. A single-center study using the Octopus technique to evaluate the safety and short-term effects of endovascular repair of complex aortic lesions was reported and documented. Methods: The data of six cases who underwent optimized Octopus surgery in our center from August 2020 to February 2022 were analyzed retrospectively. The choice of operation scheme, operation time, operation complications, and follow-up data were analyzed among them. Results: The average age of the six patients undergoing optimized Octopus surgery was 55.1 ± 17.2 years. Two cases were diagnosed as pararenal aortic aneurysms; four cases were aortic dissection involving the visceral artery. All cases achieved technical success; all visceral arteries were reconstructed as planned. A total of 17 visceral arteries were planned to be reconstructed; five celiac arteries were embolized. Three cases of gutter endoleak were found during the operation without embolization but with follow-up observation. There were two cases of slight damage to renal function and two cases of perioperative death. Other complications, such as intestinal ischemia and spinal cord ischemia, did not occur. Follow-up ranged from 6 months to 30 months. One patient died of gastrointestinal bleeding 6 months after the operation. At the 6 months follow-up, computed tomographic angiography showed that all internal leaks had disappeared. The patency rate of the visceral artery was 100%, and no complications, such as stent displacement and occlusion, occurred during the follow-up period. Conclusion: With fenestrated and branched stent grafts technology not widely available, and off label use not a viable option, Octopus technology for treating complex aortic lesions should be considered. The Octopus technique is an up-and-coming surgical method, but we should recognize its operation difficulty, operation-related complications, and long-term prognosis. We should pay attention to and continue to optimize Octopus technology.

Human descending aorta injury caused by brucellosis: A case report.

BACKGROUND: Brucellosis is one of the most common zoonotic diseases in the world. Although cardiovascular complications of human brucellosis account for only 3% of morbidity, they are the leading cause of death. Peripheral vascular disease due to brucellosis is rare and under-reported in the literature. CASE PRESENTATION: Two patients with previous brucellosis, both of whom had been treated with anti-brucellosis, were admitted to vascular surgery for thoracic aortic ulcer and abdominal aortic pseudoaneurysm, respectively, with positive IgG antibody to brucellosis and negative IgM antibody to brucellosis, tube agglutination test, and blood culture. These 2 patients were successfully treated with aortic stent-graft implantation and followed up for 8 and 10 weeks without complications. CONCLUSIONS: Chronic damage to human blood vessels by brucellosis may not disappear with brucellosis treatment, and peripheral blood vessels should be examined annually in people previously diagnosed with brucellosis. Clinicians in related departments should pay attention to peripheral vascular complications of brucellosis.

Immune checkpoint inhibitors related respiratory disorders in patients with lung cancer: A meta-analysis of randomized controlled trials.

Background: In recent years, immune checkpoint inhibitors (ICIs) had extremely rapid growth in anti-cancer and improved outcomes of many malignancies, specifically lung cancer. However, the incidence of ICIs-related adverse events also raised. Using this meta-analysis, ICIs-related respiratory disorders were investigated in lung cancer patients. Methods: Using Cochrane Library, Embase, and PubMed databases, we performed an integrated search for randomized controlled trials (RCTs) to compare respiratory disorders among different regimens. The data was prepared with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline, and the quality of included studies was evaluated based on the Cochrane manual. Results: In total, 22 RCTs were involved in this meta-analysis. Compared with ICIs, chemotherapy reduced the risk of interstitial lung disease (p = 0.03; SMD: 2.81; 95% CI: 1.08, 7.27), pleural effusion (p = 0.002; SMD: 2.12; 95% CI: 1.32, 3.42), and pneumonitis (p < 0.00001; SMD: 9.23; 95% CI: 4.57, 18.64). ICIs plus chemotherapy could provide a higher probability for patients to suffer pneumonitis than chemotherapy (p = 0.01; SMD: 1.96; 95% CI: 1.17, 3.28). In addition, single ICI brought a lower likelihood for patients suffering pneumonitis than double ICIs (p = 0.004; SMD: 2.17; 95% CI: 1.27, 3.69). Conclusion: ICIs-based treatment, such as ICIs alone, ICIs plus chemotherapy and double ICIs, can raise the incidences of some respiratory disorders in patients with lung cancer. It suggests that ICIs should be conducted based on a comprehensive consideration to prevent ICIs-related respiratory disorders. To a certain degree, this study might be provided to the clinician as a reference for ICIs practice. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022378901, identifier (CRD42022378901).

Risk of Experiencing an Overdose Event for Patients Undergoing Treatment With Medication for Opioid Use Disorder.

OBJECTIVE: Overdose risk during a course of treatment with medication for opioid use disorder (MOUD) has not been clearly delineated. The authors sought to address this gap by leveraging a new data set from three large pragmatic clinical trials of MOUD. METHODS: Adverse event logs, including overdose events, from the three trials (N=2,199) were harmonized, and the overall risk of having an overdose event in the 24 weeks after randomization was compared for each study arm (one methadone, one naltrexone, and three buprenorphine groups), using survival analysis with time-dependent Cox proportional hazard models. RESULTS: By week 24, 39 participants had ≥1 overdose event. The observed frequency of having an overdose event was 15 (5.30%) among 283 patients assigned to naltrexone, eight (1.51%) among 529 patients assigned to methadone, and 16 (1.15%) among 1,387 patients assigned to buprenorphine. Notably, 27.9% of patients assigned to extended-release naltrexone never initiated the medication, and their overdose rate was 8.9% (7/79), compared with 3.9% (8/204) among those who initiated naltrexone. Controlling for sociodemographic and time-varying medication adherence variables and baseline substance use, a proportional hazard model did not show a significant effect of naltrexone assignment. Significantly higher probabilities of experiencing an overdose event were observed among patients with baseline benzodiazepine use (hazard ratio=3.36, 95% CI=1.76, 6.42) and those who either were never inducted on their assigned study medication (hazard ratio=6.64, 95% CI=2.12, 19.54) or stopped their medication after initial induction (hazard ratio=4.04, 95% CI=1.54, 10.65). CONCLUSIONS: Among patients with opioid use disorder seeking medication treatment, the risk of overdose events over the next 24 weeks is elevated among those who fail to initiate or discontinue medication and those who report benzodiazepine use at baseline.

Treatment of abdominal aortic pseudoaneurysm caused by brucellosis with endovascular aneurysm repair.

Peripheral vascular disease caused by brucellosis is rarely seen around the world; thus, it is easily ignored by patients and doctors, leading to a lack of corresponding screening and delayed comprehensive treatment. Currently, there is no standard or guideline for diagnosing and treating peripheral arterial disease caused by brucellosis. From June 2021 to December 2022, four cases of abdominal aortic pseudoaneurysm caused by brucellosis disease were treated with endovascular aneurysm repair This study reported treatment results as follows and reviewed the incidence, treatment, and prognosis of abdominal aortic pseudoaneurysm caused by brucellosis.

Optimally Choosing Medication Type for Patients With Opioid Use Disorder.

Patients with opioid use disorder (OUD) tend to get assigned to one of 3 medications based on the treatment program to which the patient presents (e.g., opioid treatment programs tend to treat patients with methadone, while office-based practices tend to prescribe buprenorphine). It is possible that optimally matching patients with treatment type would reduce the risk of return to regular opioid use (RROU). We analyzed data from 3 comparative effectiveness trials from the US National Institute on Drug Abuse Clinical Trials Network (CTN0027, 2006-2010; CTN0030, 2006-2009; and CTN0051 2014-2017), in which patients with OUD (n = 1,459) were assigned to treatment with either injection extended-release naltrexone (XR-NTX), sublingual buprenorphine-naloxone (BUP-NX), or oral methadone. We learned an individualized rule by which to assign medication type such that risk of RROU during 12 weeks of treatment would be minimized, and then estimated the amount by which RROU risk could be reduced if the rule were applied. Applying our estimated treatment rule would reduce risk of RROU compared with treating everyone with methadone (relative risk (RR) = 0.79, 95% confidence interval (CI): 0.60, 0.97) or treating everyone with XR-NTX (RR = 0.71, 95% CI: 0.47, 0.96). Applying the estimated treatment rule would have resulted in a similar risk of RROU to that of with treating everyone with BUP-NX (RR = 0.92, 95% CI: 0.73, 1.11).

Electroencephalogram pattern association with drug-related cues in a long-duration virtual reality environment in patients with methamphetamine use disorder.

The cognitive processing of drug-related cues and the subsequent dysregulation of behaviour play a central role in the pathophysiology of substance use disorders. Prior studies are limited by small sample sizes and a lack of immersion in stimulus presentation. In the present study, we recruited patients with methamphetamine use disorder (MUD; N = 1099) from four compulsory isolated detoxification centres and healthy control participants (N = 305). With a 12-min-long virtual reality (VR) protocol stimulus, we discovered that patients showed a decrease in electroencephalogram (EEG) power across alpha to gamma bands in anterior scalp regions under methamphetamine-related VR stimuli (e.g. a glass pipe and medical tubing) compared with the control stimuli (e.g. balls and cubes). Analysis of variance (ANOVA) showed that the interaction effects of stimuli type and group were significant in five EEG bands. Using generalised linear models, we classified the stimuli type (i.e. drug-related vs. drug-unrelated cues) in MUD patients with an f1 score of 90% on an out-of-sample testing set. The decreases of EEG between drug-related cues and drug-unrelated cues in delta, theta and alpha frequency bands are more frequently seen in patients than in healthy controls, perhaps reflecting general arousal and attenuated impulsive control. Our results suggest that EEG responses elicited by long-duration methamphetamine-related VR cues showed a specific signature, which may have future clinical implications.

Under-representation of key demographic groups in opioid use disorder trials.

Background: The extent to which clinical trials of medications for opioid use disorder (MOUD) are representative or not is unknown. Some patient characteristics modify MOUD effectiveness; if these same characteristics differ in distribution between the trial population and usual-care population, this could contribute to lack of generalizability-a discrepancy between trial and usual-care effectiveness. Our objective was to identify interpretable, multidimensional subgroups who were prescribed MOUD in substance use treatment programs in the US but who were not represented or under-represented by clinical trial participants. Methods: This was a secondary descriptive analysis of trial and real-world data. The trial data included twenty-seven US opioid treatment programs in the National Drug Abuse Treatment Clinical Trials Network, N = 2,199 patients. The real-world data included US substance use treatment programs that receive public funding, N = 740,015 patients. We characterized real-world patient populations who were non-represented and under-represented in the trial data in terms of sociodemographic and clinical characteristics that could modify MOUD effectiveness. Results: We found that 10.7% of MOUD patients in TEDS-A were not represented in the three clinical trials. As expected, pregnant MOUD patients (n = 19,490) were not represented. Excluding pregnancy, education and marital status from the characteristics, 2.6% of MOUD patients were not represented. Patients aged 65 years and older (n = 11,204), and those 50-64 years who identified as other (non-White, non-Black, and non-Hispanic) race/ethnicity or multi-racial (n = 7,281) were under-represented. Conclusions: Quantifying and characterizing non- or under-represented subgroups in trials can provide the data necessary to improve representation in future trials and address research-to-practice gaps.

Efficacy of terpenoids in attenuating pulmonary edema in acute lung injury: A meta-analysis of animal studies.

Background: The clinical efficiency of terpenoids in treating human acute lung injury (ALI) is yet to be determined. The lipopolysaccharide-induced rat model of ALI is a well-established and widely used experimental model for studying terpenoids' effects on ALI. Using a systematic review and meta-analysis, the therapeutic efficiency of terpenoid administration on the lung wet-to-dry weight ratio in rats was investigated. Methods: Using the Cochrane Library, Embase, and PubMed databases, a comprehensive literature search for studies evaluating the therapeutic efficacy of terpenoids on ALI in rats was conducted. The lung wet-to-dry weight ratio was extracted as the main outcome. The quality of the included studies was assessed using the Systematic Review Center for Laboratory Animal Experimentation's risk of bias tool. Results: In total, 16 studies were included in this meta-analysis. In general, terpenoids significantly lowered the lung wet-to-dry weight ratio when compared with the control vehicle (p = 0.0002; standardized mean difference (SMD): -0.16; 95% confidence interval (CI): -0.24, -0.08). Subgroup analysis revealed that low dose (≤10 µmol/kg) (p < 0.0001; SMD: -0.68; 95% CI: -1.02, -0.34), intraperitoneal injection (p = 0.0002; SMD: -0.43; 95% CI: -0.66, -0.20), diterpenoid (p = 0.004; SMD: -0.13; 95% CI: -0.23, -0.04), and triterpenoid (p = 0.04; SMD: -0.28; 95% CI: -0.54, -0.01) significantly lowered the lung wet-to-dry weight ratio when compared with the control vehicle. Conclusion: A low dose of diterpenoid and triterpenoid administered intraperitoneally is effective in alleviating ALI. This systematic review and meta-analysis provides a valuable mirror for clinical research aiming at the advancement of terpenoids for preventive and therapeutic use. Systematic Review Registration: CRD42022326779.

Characteristics of the Severe Acute Respiratory Syndrome Coronavirus 2 Omicron BA.2 Subvariant in Jilin, China from March to May 2022.

Background and Objectives: In the midst of the pandemic, new coronavirus mutants continue to emerge; the most relevant variant worldwide is omicron. Here, patients who recovered from the disease living in Jilin Province were analyzed to identify factors affecting the severity of omicron infection and to provide insights into its spread and early indication. Methods: In this study, 311 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were divided into two groups. Data on the patients' demographic characteristics and laboratory tests, including platelet count (PLT), neutrophil count (NE), C-reactive protein (CRP), serum creatinine (SCR), and neutrophil-to-lymphocyte ratio (NLR), were collected. The biomarkers for moderate and severe coronavirus disease 2019 (COVID-19) and factors affecting the incubation period and time to subsequent negative nucleic acid amplification test (NAAT) were also investigated. Results: Age, gender, vaccination, hypertension, stroke, chronic obstructive pulmonary disease (COPD)/chronic bronchitis/asthma, and some laboratory tests were statistically different between the two groups. In the receiver operating characteristic (ROC) analysis, PLT and CRP had higher area under the ROC curve values. In the multivariate analysis, age, hypertension, COPD/chronic bronchitis/asthma, and CRP were correlated with moderate and severe COVID-19. Moreover, age was correlated with longer incubation. In the Kaplan-Meier curve analysis, gender (male), CRP, and NLR were associated with longer time to subsequent negative NAAT. Conclusions: Older patients with hypertension and lung diseases were likely to have moderate or severe COVID-19, and younger patients might have a shorter incubation. A male patient with high CRP and NLR levels might take more time to turn back negative in the NAAT.

Specific polysubstance use patterns predict relapse among patients entering opioid use disorder treatment.

Introduction: While polysubstance use has consistently been associated with higher rates of relapse, few studies have examined subgroups with specific combinations and time course of polysubstance use (i.e., polysubstance use patterns). This study aimed to classify and compare polysubstance use patterns, and their associations with relapse to regular opioid use in 2637 participants in three large opioid use disorder (OUD) treatment trials. Methods: We explored the daily patterns of self-reported substance use in the 28 days prior to treatment entry. Market basket analysis (MBA) and repeated measure latent class analysis (RMLCA) were used to examine the subgroups of polysubstance use patterns, and multiple logistic regression was used to examine associations between identified classes and relapse. Results: MBA and RMLCA identified 34 "associations rules " and 6 classes, respectively. Specific combinations of polysubstance use and time course (high baseline use and rapid decrease of use prior to initiation) predicts a worse relapse outcome. MBA showed individuals who co-used cocaine, heroin, prescription opioids, and cannabis had a higher risk for relapse (OR = 2.82, 95%CI = 1.13, 7.03). In RMLCA, higher risk of relapse was observed in individuals who presented with high baseline prescription opioid (OR = 1.9, 95% CI = 1.3, 2.76) or heroin use (OR = 3.54, 95%CI = 1.86, 6.72), although use decreased in both cases prior to treatment initiation. Conclusions: Our analyses identified subgroups with distinct patterns of polysubstance use. Different patterns of polysubstance use differentially predict relapse outcomes. Interventions tailored to these individuals with specific polysubstance use patterns prior to treatment initiation may increase the effectiveness of relapse prevention.

Medication Use and Physical Assaults in the Psychiatric Emergency Department.

Objective: To evaluate the relationship between medications used to treat acute agitation (antipsychotics, mood stabilizers, and benzodiazepines) and subsequent assault incidence in the psychiatric emergency department.Methods: Medication orders and assault incident reports were obtained from electronic health records for 17,056 visits to an urban psychiatric emergency department from 2014 to 2019. Assault risk was modeled longitudinally using Poisson mixed-effects regression.Results: Assaults were reported during 0.5% of visits. Intramuscular (IM) medications were ordered in 23.3% of visits overall and predominantly were ordered within the first 4 hours of a visit. IM medication orders were correlated with assault (incident rate ratio [IRR] = 24.2; 95% CI, 5.33-110.0), often because IM medications were ordered immediately subsequent to reported assaults. Interacted with time, IM medications were not significantly associated with reduction in subsequent assaults (IRR = 0.700; 95% CI, 0.467-1.04). Neither benzodiazepines nor mood stabilizers were associated with subsequent changes to the risk of reported assault. By contrast, antipsychotic medications were associated with decreased assault risk across time (IRR = 0.583; 95% CI, 0.360-0.942).Conclusions: Although assault prevention is not the sole reason for ordering IM medications, IM medication order rates are high relative to overall assault incident risk. Of the 3 major categories of medications ordered commonly in the psychiatric emergency setting, only antipsychotic medications were associated with measurable decreases in subsequent assault risk. As antipsychotic medication can have a significant side effect burden, careful weighing of the risks and benefits of medications is encouraged.

Optimizing opioid use disorder treatment with naltrexone or buprenorphine.

BACKGROUND: Relapse rates during opioid use disorder (OUD) treatment remain unacceptably high. It is possible that optimally matching patients with medication type would reduce risk of relapse. Our objective was to learn a rule by which to assign type of medication for OUD to reduce risk of relapse, and to estimate the extent to which risk of relapse would be reduced if such a rule were used. METHODS: This was a secondary analysis of an open-label randomized controlled, 24-week comparative effectiveness trial of injection extended-release naltrexone (XR-NTX), delivered approximately every 28 days, or daily sublingual buprenorphine-naloxone (BUP-NX) for treating OUD, 2014-2017 (N = 570). Outcome was a binary indicator of relapse to regular opioid use during the 24 weeks of outpatient treatment. RESULTS: We found that applying an estimated individualized treatment rule-i.e., a rule that assigns patients with OUD to either XR-NTX or BUP-NX based on their individual characteristics in such a way that risk of relapse is minimized-would reduce risk of relapse by 24 weeks by 12% compared to randomly assigned treatment. CONCLUSIONS: The number-needed-to-treat with the estimated treatment rule to prevent a single relapse is 14. A simpler, alternative estimated rule in which homeless participants would be treated with XR-NTX and stably housed participants would be treated with BUP-NX performed similarly. These results provide an estimate of the amount by which a relatively simple change in clinical practice could be expected to improve prevention of OUD relapse.