Prediction Tool for Individual Outcome Trajectories Across the Next Year in First-Episode Psychosis in Coordinated Specialty Care.

Importance: In coordinated specialty care (CSC) settings for people with a first episode of psychosis, the development of reliable, validated individual-level prediction tools for key outcomes may be informative for shared clinician and client decision-making. Objective: To develop an individual-level prediction tool using machine-learning methods that predicts a trajectory of education/work status or psychiatric hospitalization outcomes over a client's next year of quarterly follow-up assessments. Additionally, to visualize these predictions in a way that is informative to clinicians and clients. Design, Setting, and Participants: Individual-level data were collected for all patients enrolled in the OnTrackNY program at enrollment and at quarterly follow-ups using standardized forms. The OnTrackNY program, a network of CSC sites in New York State, provides person-centered, recovery-oriented, and evidence-based psychosocial and pharmaceutical interventions to individuals aged 16 to 30 years with recent-onset (<2 years) nonaffective psychosis. Although data collection is ongoing, data for this study were collected from October 2013 to December 2018, and the time frame for analysis was July 2020 to May 2021. Data were separated into a training/cross-validation set to perform internally validated model development and a separate holdout test set (~20% of the sample) for external validation. Random probability forest models were developed to predict individual-level trajectories of outcomes. Exposures: Forty-three individual-level demographic and clinical features collected at enrollment in OnTrackNY, 25 of which were time-varying and updated at quarterly follow-up assessments, and 13 site-level demographic and economic census variables. Main Outcomes and Measures: Individual-level education and/or employment status and psychiatric hospitalization trajectories at quarterly follow-up periods across the first 2 years of CSC. Results: The total study sample consists of 1298 individuals aged 16 to 30 years and included 341 women (26.3%), 949 men (73.1%), and 8 (<1%) with another gender. Prediction models performed well for 1-year trajectories of education/work across all validation sets, with areas under the receiver operating characteristic curve (AUCs) ranging from 0.68 (95% CI, 0.63-0.74) to 0.88 (95% CI, 0.81-0.96). Predictive accuracy for psychiatric hospitalization 3 months ahead reached AUC above 0.70; moreover, predictions of future psychiatric hospitalizations at 6 months and beyond were consistently poor, with AUCs below 0.60. Given the good externally validated performance for predicting education/work, a prototype interactive visualization tool displaying individual-level education/work trajectories and related features was developed. Conclusions and Relevance: This study suggests that accurate prediction tools can be developed for outcomes in people with first-episode psychosis, which may help inform shared clinician/client decision-making. Future work should study the effectiveness of its deployment, including proper communication to inform shared clinician/client decision-making in the context of a learning health care system. At present, more work is needed to develop better performing prediction models for future psychiatric hospitalizations before any tool is recommended for this outcome.

Preliminary attitudes on medications for opioid use disorders (MOUDs) in Southeastern Switzerland and New York City.

The United States (US) and Switzerland are affluent countries with different responses to surges in opioid use disorder (OUD) cases over the last thirty years. The Swiss "PROVE" trail implemented heroin-assisted treatment (HAT) for OUD alongside other medications for opioid use disorder (MOUD). In contrast, heroin remains highly controlled, HAT is inaccessible, and MOUD programs are generally more restrictive in the US than in Switzerland. We conducted a survey to compare practitioners' attitudes toward HAT across sites in both countries. Surveys were distributed electronically for voluntary, uncompensated completion (N = 120) at two mental health delivery sites, Psychiatrische Dienste Graubünden (PDGR) in Graubünden, Switzerland and Montefiore Medical Center (MMC) in the Bronx, NY. The survey instrument included 10 demographic and 19 "beliefs" questions measuring agreement level with a statement on a 5-point scale. Analysis included 79 PDGR respondents (mean age = 43.2, 59.5% women) and 41 MMC respondents (mean age = 44.7, 63.4% women), and did not show differences in confidence to treat OUD, addictions, and psychiatric disorders. For belief in HAT, Swiss respondents had a significantly more favorable view (b = 0.62) than those in New York (p = 0.00027). This study shows a difference in attitudes toward HAT among demographically similar staff treating OUD patients across sites. The cohorts demonstrate an overall positive attitude toward HAT but a more robust positive attitude was evident in Switzerland. Previously unreported attitude comparisons across sites with dissimilar OUD treatment availability may explain differences in practices and success in reducing harm from this disorder.

Does It Matter What Screener We Use? A Comparison of Ultra-brief PHQ-4 and E-mwTool-3 Screeners for Anxiety and Depression Among People With and Without HIV.

The burden of depression and anxiety disorders is high in sub-Saharan Africa, especially for people with HIV (PWH). The Patient Health Questionnaire-4 (PHQ-4) and Electronic Mental Wellness Tool-3 (E-mwTool-3) are ultra-brief screening tools for these disorders. We compared the performance of PHQ-4 and E-mwTool-3 for screening MINI-International Neuropsychiatric Interview diagnoses of depression and anxiety among a sample of individuals with and without HIV in two primary care clinics and one general hospital in Maputo City, Mozambique. Areas-under-the-curve (AUC) were calculated along with sensitivities and specificities at a range of cutoffs. For PWH, at a sum score cutoff of ≥ 1, sensitivities were strong: PHQ-4:Depression = 0.843; PHQ-4:Anxiety = 0.786; E-mwTool-3:Depression = 0.843; E-mwTool-3:Anxiety = 0.929. E-mwTool-3 performance was comparable to PHQ-4 among people with and without HIV.

Armed conflict, HIV, and syndemic risk markers of mental distress, alcohol misuse, and intimate partner violence among couples in Uganda.

Northeastern Uganda has suffered from protracted armed conflict and HIV/AIDS and has some of the highest rates of intimate partner violence (IPV) globally. Little is known about how exposure to conflict and HIV influence individuals' syndemic risk markers or those of their partners. We conducted a population-based study using multistage sampling across three districts in Northeastern Uganda. We randomly surveyed 605 women aged 13-49 years and estimated syndemic problems for currently partnered women (N = 561) who reported for their male partners. Syndemic problems were lower in the low-conflict district than the high-conflict district, p = .009. Conflict exposure was associated with couples' syndemic scores, respondent: ß = 0.182, p < .001; partner: ß = .181, p < .001. Problem scores were significantly higher among women whose partner was either HIV positive, p = .031, or had an unknown HIV status, p = .016, compared with those whose partner was HIV negative. The total effects of women's, ß = .15, p = .034, and men's, ß = .137, p = .038, armed conflict exposure on male-to-female IPV were significant. For male partners, there were significant total effects of having an unknown, ß = .669, p < .001, or positive, ß = 1.143, p < .001, HIV status on experiencing female-to-male IPV. These results suggest that syndemic problems and corresponding treatments should consider couple influences. Addressing mediating problems of mental distress and alcohol misuse may reduce the risk of male-to-female IPV. Providing couple-based HIV psychosocial interventions could reduce men's exposure to IPV.

Supervised Machine Learning Approach to Identify Early Predictors of Poor Outcome in Patients with COVID-19 Presenting to a Large Quaternary Care Hospital in New York City.

BACKGROUND: The progression of clinical manifestations in patients with coronavirus disease 2019 (COVID-19) highlights the need to account for symptom duration at the time of hospital presentation in decision-making algorithms. METHODS: We performed a nested case-control analysis of 4103 adult patients with COVID-19 and at least 28 days of follow-up who presented to a New York City medical center. Multivariable logistic regression and classification and regression tree (CART) analysis were used to identify predictors of poor outcome. RESULTS: Patients presenting to the hospital earlier in their disease course were older, had more comorbidities, and a greater proportion decompensated (<4 days, 41%; 4-8 days, 31%; >8 days, 26%). The first recorded oxygen delivery method was the most important predictor of decompensation overall in CART analysis. In patients with symptoms for <4, 4-8, and >8 days, requiring at least non-rebreather, age ≥ 63 years, and neutrophil/lymphocyte ratio ≥ 5.1; requiring at least non-rebreather, IL-6 ≥ 24.7 pg/mL, and D-dimer ≥ 2.4 µg/mL; and IL-6 ≥ 64.3 pg/mL, requiring non-rebreather, and CRP ≥ 152.5 mg/mL in predictive models were independently associated with poor outcome, respectively. CONCLUSION: Symptom duration in tandem with initial clinical and laboratory markers can be used to identify patients with COVID-19 at increased risk for poor outcomes.

A Single Ketamine Infusion Combined With Mindfulness-Based Behavioral Modification to Treat Cocaine Dependence: A Randomized Clinical Trial.

OBJECTIVE: Research has suggested that subanesthetic doses of ketamine may work to improve cocaine-related vulnerabilities and facilitate efforts at behavioral modification. The purpose of this trial was to test whether a single ketamine infusion improved treatment outcomes in cocaine-dependent adults engaged in mindfulness-based relapse prevention. METHODS: Fifty-five cocaine-dependent individuals were randomly assigned to receive a 40-minute intravenous infusion of ketamine (0.5 mg/kg) or midazolam (the control condition) during a 5-day inpatient stay, during which they also initiated a 5-week course of mindfulness-based relapse prevention. Cocaine use was assessed through self-report and urine toxicology. The primary outcomes were end-of-study abstinence and time to relapse (defined as first use or dropout). RESULTS: Overall, 48.2% of individuals in the ketamine group maintained abstinence over the last 2 weeks of the trial, compared with 10.7% in the midazolam group (intent-to-treat analysis). The ketamine group was 53% less likely (hazard ratio=0.47; 95% CI=0.24, 0.92) to relapse (dropout or use cocaine) compared with the midazolam group, and craving scores were 58.1% lower in the ketamine group throughout the trial (95% CI=18.6, 78.6); both differences were statistically significant. Infusions were well tolerated, and no participants were removed from the study as a result of adverse events. CONCLUSIONS: A single ketamine infusion improved a range of important treatment outcomes in cocaine-dependent adults engaged in mindfulness-based behavioral modification, including promoting abstinence, diminishing craving, and reducing risk of relapse. Further research is needed to replicate these promising results in a larger sample.

Pharmacokinetics of levonorgestrel and ulipristal acetate emergency contraception in women with normal and obese body mass index.

OBJECTIVE: This study compares the pharmacokinetics (PK) of levonorgestrel (LNG) emergency contraceptive (EC) and ulipristal acetate (UPA)-EC between normal-body mass index (BMI) and obese-BMI women. STUDY DESIGN: This prospective, randomized crossover study evaluates the PK of women after single doses of LNG-EC (1.5mg) and UPA-EC (30mg). Study procedures took place during clinical research unit admissions, where participants received a standardized meal and each study drug, in random order, during two separate 24-h admissions. Study staff collected 14 blood specimens (0, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24 and 48h). We evaluated serum concentrations of LNG and UPA using liquid chromatography-tandem mass spectroscopy and estimated the PK parameters of both drugs using noncompartmental analysis. The main outcome of this study was a comparison of between-group differences in AUC0-24. RESULTS: Thirty-two women completed the study (16 in each group). Among normal-BMI and obese-BMI participants, the mean BMIs were 22.0 (range 18.8-24.6) and 34.3 (range 30.6-39.9), respectively. After LNG-EC, mean AUC0-24 and maximum concentration (Cmax) were 50% lower among obese-BMI women than among normal-BMI women (AUC0-24 100.8 vs. 208.5ng*h/mL, IQRobese-BMI 35.8, IQRnormal-BMI 74.2, p≤.01; Cmax 10.8 vs. 18.2ng/mL, p=.01). After UPA-EC, AUC0-24 and Cmax were similar between obese-BMI and normal-BMI women (AUC0-24 362.5 vs. 293.5ng*h/mL, IQRobese-BMI 263.2, IQRnormal-BMI 112.5, p=.15; Cmax 95.6 vs. 89.3ng/mL, p=.70). CONCLUSION: After a single dose of EC, obese-BMI women are exposed to lower concentrations of LNG and similar concentrations of UPA, when compared to normal-BMI women. IMPLICATIONS: Differences in LNG-EC PK by BMI group may underlie and account for the lower LNG-EC efficacy reported among obese-BMI women, but modest differences in UPA-EC PK by BMI group provide less support for variable efficacy. A pharmacodynamic study may be able to clarify whether these PK differences account for observed differences in LNG-EC and UPA-EC efficacy.

Estimating systemic exposure to levonorgestrel from an oral contraceptive.

OBJECTIVE: The gold standard for measuring oral contraceptive (OC) pharmacokinetics is the 24-h steady-state area under the curve (AUC). We conducted this study to assess whether limited sampling at steady state or measurements following use of one or two OCs could provide an adequate proxy in epidemiological studies for the progestin 24-h steady-state AUC of a particular OC. STUDY DESIGN: We conducted a 13-sample, 24-h pharmacokinetic study on both day 1 and day 21 of the first cycle of a monophasic OC containing 30-mcg ethinyl estradiol and 150-mcg levonorgestrel (LNG) in 17 normal-weight healthy White women and a single-dose 9-sample study of the same OC after a 1-month washout. We compared the 13-sample steady-state results with several steady-state and single-dose results calculated using parsimonious sampling schemes. RESULTS: The 13-sample steady-state 24-h LNG AUC was highly correlated with the steady-state 24-h trough value [r=0.95; 95% confidence interval (0.85, 0.98)] and with the steady-state 6-, 8-, 12- and 16-h values (0.92≤r≤0.95). The trough values after one or two doses were moderately correlated with the steady-state 24-h AUC value [r=0.70; 95% CI (0.27, 0.90) and 0.77; 95% CI (0.40, 0.92), respectively]. CONCLUSIONS: Single time-point concentrations at steady state and after administration of one or two OCs gave highly to moderately correlated estimates of steady-state LNG AUC. Using such measures could facilitate prospective pharmaco-epidemiologic studies of the OC and its side effects. IMPLICATIONS: A single time-point LNG concentration at steady state is an excellent proxy for complete and resource-intensive steady-state AUC measurement. The trough level after two single doses is a fair proxy for steady-state AUC. These results provide practical tools to facilitate large studies to investigate the relationship between systemic LNG exposure and side effects in a real-life setting.