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BACKGROUND Despite advances in the development of pharmacotherapy for alcohol use disorder (AUD), there remains a need for medications that can be administered to actively drinking outpatients to promote a reduction in harmful alcohol consumption. The primary aim of this pilot study was to determine whether high-dose gabapentin (3600 mg/daily) is more effective than placebo in reducing harmful alcohol consumption in outpatients with AUD. METHODS Forty patients (27 men) who met DSM-IV-TR criteria for alcohol dependence and reporting at least 4 heavy drinking days (HDD) per week were recruited at a single site. Participants were actively drinking at study entry and received double-blind gabapentin (3600 mg/day; n = 19) or placebo (n = 20) for 8 weeks. Study medication was titrated over 5 days and administered in three divided doses (1200 mg three times per day). The proportion of HDD (primary outcome) and percent days abstinent (PDA; secondary outcome) were analyzed using generalized longitudinal mixed models with the predictors being study arm, week, study arm by week interaction, and corresponding baseline drinking measure. RESULTS There was a significant interaction between study arm and week for the proportion of HDD per week, F (7, 215) = 3.33, p = 0.002 . There was also a significant interaction between study arm and week for PDA per week, F (7, 215) = 3.11, p = 0.004. The overall retention rate was 67.5% with no significant difference in time-to-dropout between treatment groups. There were no serious adverse events. No participants were removed from the trial due to the development of moderate-to-severe alcohol withdrawal (CIWA-Ar ≥ 13). CONCLUSIONS Gabapentin treatment rapidly titrated to a dosage of 3600 mg/day is associated with a reduction in the proportion of HDD per week and an increase in PDA per week in actively drinking outpatients with AUD. High-dose gabapentin is potentially a feasible approach to treating AUD and deserving of further study.

Individuals with opioid use disorder (OUD) suffer disproportionately from COVID-19. To inform clinical management of OUD patients, research is needed to identify characteristics associated with COVID-19 progression and death among this population. We aimed to investigate the role of OUD and specific comorbidities on COVID-19 progression among hospitalized OUD patients.Retrospective cohort study of merged electronic health records (EHR) from five large private health systems SETTING: New York City, New York, USA, 2011-2021 PARTICIPANTS: Adults with a COVID-19 encounter and OUD or opioid overdose diagnosis between March 2020-February 2021 MEASUREMENTS: Primary exposure included diagnosis of OUD/opioid overdose. Risk factors included age, sex, race/ethnicity and common medical, substance use and psychiatric co-morbidities known to be associated with COVID-19 severity. Outcomes included COVID-19 hospitalization and subsequent intubation, acute kidney failure, severe sepsis and death.Of 110,917 COVID-19+ adults, 1.17% were ever diagnosed with OUD/opioid overdose. OUD patients had higher risk of COVID-19 hospitalization (adjusted risk ratio [aRR]: 1.40 [95% confidence interval (CI) 1.33, 1.47]), intubation (adjusted aood ratio [aOR]: 2.05 [95% CI 1.74, 2.42]), kidney failure (aRR: 1.51 [95% CI 1.34, 1.70)), sepsis (aRR: 2.30 [95% CI 1.88, 2.81]), and death (aRR: 2.10 [95% CI 1.84, 2.40)]. Among hospitalized OUD patients, risks for COVID-19 outcomes included being male; older; of a race/ethnicity other than white, Black or Hispanic; and having co-morbid chronic kidney disease, diabetes, obesity or cancer. Protective factors included having asthma, hepatitis-C, and chronic pain.Opioid use disorder patients appears to have a substantial risk for COVID-19-associated morbidity and mortality, with particular comorbidities and treatments potentially moderating this risk.

OBJECTIVE: Although specialized early intervention services (EISs) for psychosis promote engagement in care, a substantial number of individuals who receive these services are discharged from care earlier than expected. The main goal of this study was to examine predictors of early discharge in a large sample of individuals enrolled in an EIS program in the United States.METHODS: This cohort study (N=1,349) used programmatic data from OnTrackNY, an EIS program that delivers evidence-based interventions to youths across New York State experiencing a first episode of nonaffective psychosis. The main outcome was "early discharge," which was operationalized as discharge prior to completing 12 months of treatment. Cox proportional hazard regression models were used to assess the association between sociodemographic, clinical, and support system predictors and early discharge.RESULTS: The estimated probability of discharge before 1 year was 32%. Participants who at baseline had poor medication adherence, had no health insurance, were living alone or with nonparental family, or were using cannabis were at higher risk of leaving services within the first 12 months after enrollment. Individuals with higher social functioning were at lower risk of being discharged early from OnTrackNY, but those with higher occupational functioning were at a higher risk.CONCLUSIONS: Predictors of early discharge from EISs largely overlapped with previously identified predictors of poor prognosis in early psychosis. However, the association between early discharge and high occupational functioning indicates that trajectories leading up to discharge are heterogeneous.

Worldwide, early intervention services for young people with recent-onset psychosis have been associated with improvements in outcomes, including reductions in hospitalization, symptoms, and improvements in treatment engagement and work/school participation. States have received federal mental health block grant funding to implement team-based, multi-element, evidence-based early intervention services, now called coordinated specialty care (CSC) in the USA. New York State’s CSC program, OnTrackNY, has grown into a 23-site, statewide network, serving over 1800 individuals since its 2013 inception. A state-supported intermediary organization, OnTrackCentral, has overseen the growth of OnTrackNY. OnTrackNY has been committed to quality improvement since its inception. In 2019, OnTrackNY was awarded a regional hub within the National Institute of Mental Health-sponsored Early Psychosis Intervention Network (EPINET). The participation in the national EPINET initiative reframes and expands OnTrackNY’s quality improvement activities. The national EPINET initiative aims to develop a learning healthcare system (LHS); OnTrackNY’s participation will facilitate the development of infrastructure, including a systematic approach to facilitating stakeholder input and enhancing the data and informatics infrastructure to promote quality improvement. Additionally, this infrastructure will support practice-based research to improve care. The investment of the EPINET network to build regional and national LHSs will accelerate innovations to improve quality of care.

(1) Background: In the “post-COVID-19 era”, there is a need to focus on properly assessing and addressing the extent of its well-established mental health collateral damage. The “Electronic Mental Wellness Tool” (E-mwTool) is a 13-item validated stepped-care or stratified management instrument that aims at the high-sensitivity captures of individuals with mental health disorders to determine the need for mental health care. This study validated the E-mwTool in a Spanish-speaking population. (2) Methods: It is a cross-sectional validation study using the Mini International Neuropsychiatric Interview as a criterion standard in a sample of 433 participants. (3) Results: About 72% of the sample had a psychiatric disorder, and 67% had a common mental disorder. Severe mental disorders, alcohol use disorders, substance use disorders, and suicide risk had a much lower prevalence rate (6.7%, 6.2%, 3.2%, and 6.2%, respectively). The first three items performed excellently in identifying any mental health disorder with 0.97 sensitivity. Ten additional items classified participants with common mental disorders, severe mental disorders, substance use disorders, and suicide risk. (4) Conclusions: The E-mwTool had high sensitivity in identifying common mental disorders, alcohol and substance use disorders, and suicidal risk. However, the tool’s sensitivity in detecting low-prevalence disorders in the sample was low. This Spanish version may be useful to detect patients at risk of mental health burden at the front line of primary and secondary care in facilitating help-seeking and referral by their physicians.

Background: Health anxiety may exist with or without prominent somatic symptoms, but the impact of somatic symptoms on treatment response is unclear. The study objective was to examine this question further as symptom burden may impact choice of type of treatment.Methods: This exploratory study used a unique database from a prior trial of 193 individuals with DSM-IV hypochondriasis who had been randomly assigned to either cognitive behavioral therapy, fluoxetine, combined therapy, or placebo. Two subgroups were newly defined—no/low somatic burden (n = 42) and prominent somatic burden (n = 151). Response was defined by ≥30% improvement in hypochondriasis.Results: Among high somatic hypochondriacal participants, compared to placebo, the odds of being a responder were significantly greater among those who received fluoxetine, either alone (OR = 4.46; 95% CI: 1.38, 14.41) or with cognitive behavioral therapy (OR = 3.56; 95% CI: 1.19, 10.68); the estimated odds were not significantly different for those receiving cognitive behavioral therapy alone (OR = 1.81; 95% CI: 0.59, 5.54). In contrast, among low somatic hypochondriacal participants, compared to placebo, the observed odds of being a responder were similar in magnitude and direction for those who received cognitive behavioral therapy, either alone (OR = 3.00; 95% CI: 0.38, 23.68) or in combination with fluoxetine (OR = 3.60; 95% CI: 0.62, 21.03), compared to the odds for those receiving fluoxetine alone (OR = 0.90; 95% CI: 0.14, 5.65). High somatic hypochondriacal individuals assigned to any fluoxetine group had significantly greater odds of being a responder than those who had not received fluoxetine (OR = 2.70; 95% CI: 1.33, 5.48). Low somatic hypochondriacal individuals assigned to any cognitive behavioral therapy group had significantly greater odds of being a responder than those who had not received cognitive behavioral therapy (OR = 8.03; 95% CI: 1.41, 45.67).Conclusion: These findings indicate that somatic symptom burden may be important in guiding treatment selection among individuals with marked health anxiety, as hypochondriacal individuals with high somatic burden responded more often to fluoxetine while those with low somatic burden responded more often to cognitive behavioral therapy. Systematic replication with larger studies is needed.

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: β = 0.182, p < .001; partner: β = .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, β = .15, p = .034, and men's, β = .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, β = .669, p < .001, or positive, β = 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.

Despite considerable global surveillance of antimicrobial resistance (AMR), data on the global emergence of new resistance genotypes in bacteria has not been systematically compiled. We conducted a study of English-language scientific literature (2006-2017) and ProMED-mail disease surveillance reports (1994-2017) to identify global events of novel AMR emergence (first clinical reports of unique drug-bacteria resistance combinations). We screened 24,966 abstracts and reports, ultimately identifying 1,757 novel AMR emergence events from 268 peer-reviewed studies and 26 disease surveillance reports (294 total). Events were reported in 66 countries, with most events in the United States (152), China (128), and India (127). The most common bacteria demonstrating new resistance were Klebsiella pneumoniae (344) and Escherichia coli (218). Resistance was most common against antibiotic drugs imipenem (89 events), ciprofloxacin (84) and ceftazidime (83). We provide an open-access database of emergence events with standardized fields for bacterial species, drugs, location, and date. We discuss the impact of reporting and surveillance bias on database coverage, and we suggest guidelines for data analysis. This database may be broadly useful for understanding rates and patterns of AMR evolution, identifying global drivers and correlates, and targeting surveillance and interventions.

Little is known about clients' preferences for family involvement and subsequent family contact in naturalistic, community-based coordinated specialty care (CSC) settings. The study's primary goal was to characterize clients' preferences and longitudinal patterns of family contact with providers across the OnTrackNY network in New York.Clinical administrative data collected at 3-month intervals and spanning 21 OnTrackNY CSC sites were used to analyze the preferences of 761 clients at baseline (unconditional involvement, conditional involvement, or no involvement) and patterns of family contact with program staff (always, sometimes, never, or early discharge) and their correlates during the initial 12-month service period. Data from clients discharged before 12 months were included for comparison.At baseline, most clients requested some form of family involvement (unconditional, 59%; conditional, 35%; and none, 6%). Within each 3-month assessment period, rates of family contact ranged from 73% to 84%. Variables associated with both client preferences and contact patterns included baseline insurance status, housing status, race, frequency of family contact, and employment. Clients' preferences for no or conditional family involvement were associated with higher rates of early discharge (i.e., before 1 year).Structuring family involvement around clients' preferences did not appear to negatively affect family contact, and for some clients, it seemed to bolster such contact. Additional mixed-methods research is needed to deepen the understanding of the contexts and reasoning underlying both client preferences for family involvement and subsequent levels of family contact.

Background Opioid Use Disorder (OUD) is a significant public health problem associated with severe morbidity and mortality. While effective pharmacotherapies are available, limitations exist with each. Induction onto extended-release naltrexone (XR-NTX) is more difficult than initiation of buprenorphine or methadone, even in inpatient settings, as it is recommended that patients remain abstinent for at least 7 days prior to initiating XR-NTX. The purpose of this trial was to determine if lorcaserin, a 5HT2c agonist, improves outpatient XR-NTX induction rates. Methods An 8-week trial beginning with a brief detoxification period and induction onto XR-NTX. Sixty participants with OUD were enrolled in the trial, with 49 participants at the initiation of detoxification randomized to lorcaserin or placebo for 39 days. Additionally, ancillary medications were provided. The primary outcome was the proportion of participants inducted onto the first XR-NTX injection. Secondary outcomes were withdrawal severity (measured by COWS and SOWS) prior to the first injection and the proportion of participants receiving the second XR-NTX injection. Results The proportion of participants inducted onto the first (lorcaserin: 36 %; placebo: 44 %; p = .67) and the second XR-NTX injection (lorcaserin: 27 %; placebo: 31 %; p = .77) was not significantly different between treatment arms. Prior to the first injection, withdrawal scores did not significantly differ between treatment arms over time (treatment*time interaction COWS: p = .11; SOWS: p = .39). Conclusions Lorcaserin failed to improve outpatient XR-NTX induction rates. Although this study is small, the findings do not support the use of lorcaserin in promoting induction onto XR-NTX or in mitigating withdrawal symptoms.

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 (&lt, 4 days, 41%, 4–8 days, 31%, &gt, 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 &lt, 4, 4–8, and &gt, 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.

Pharmacotherapy and behavioral treatments for alcohol use disorder are limited in their effectiveness, and new treatments with innovative mechanisms would be valuable. In this pilot study, the authors tested whether a single subanesthetic infusion of ketamine administered to adults with alcohol dependence and engaged in motivational enhancement therapy affects drinking outcomes.Participants were randomly assigned to a 52-minute intravenous administration of ketamine (0.71 mg/kg, N=17) or the active control midazolam (0.025 mg/kg, N=23), provided during the second week of a 5-week outpatient regimen of motivational enhancement therapy. Alcohol use following the infusion was assessed with timeline followback method, with abstinence confirmed by urine ethyl glucuronide testing. A longitudinal logistic mixed-effects model was used to model daily abstinence from alcohol over the 21 days after ketamine infusion.Participants (N=40) were mostly middle-aged (mean age=53 years [SD=9.8]), predominantly white (70.3%), and largely employed (71.8%) and consumed an average of five drinks per day prior to entering the study. Ketamine significantly increased the likelihood of abstinence, delayed the time to relapse, and reduced the likelihood of heavy drinking days compared with midazolam. Infusions were well tolerated, with no participants removed from the study as a result of adverse events.A single ketamine infusion was found to improve measures of drinking in persons with alcohol dependence engaged in motivational enhancement therapy. These preliminary data suggest new directions in integrated pharmacotherapy-behavioral treatments for alcohol use disorder. Further research is needed to replicate these promising results in a larger sample.

Many individuals with obsessive-compulsive disorder (OCD) do not receive evidence-based care (specifically exposure and ritual prevention; EX/RP) due to barriers such as a lack of EX/RP-trained clinicians, geographic obstacles, and the cost and time associated with the treatment. Offering an integrated treatment model consisting of brief in-person therapy coupled with a mobile application (app) might be one way to increase access to and reduce the time burden (to clinicians and patients) of EX/RP. This pilot trial evaluated the feasibility, acceptability, and clinical effects of such a treatment program for adults with OCD. Thirty-three participants enrolled in the 8-week open trial. The integrated treatment program consisted of 3 to 5 in-person sessions followed by weekly phone calls supported by a mobile app (nOCD). Participants were evaluated by trained raters and completed self-report measures at baseline, midtreatment, posttreatment and 2-month follow-up; the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was the primary outcome. This integrated treatment program was feasible and acceptable to participants. Of the 33 study entrants, 14 (42%) responded to treatment (Y-BOCS decrease ≥ 35% with CGI- of 1 or 2), and 8 (24%) achieved minimal symptoms (i.e., Y-BOCS ≤ 12). At 2-month follow-up (n = 20), 7/20 (35%) met criteria for treatment response, and 3/20 (15.0%) met criteria for treatment remission. Although preliminary, this model warrants further study as an efficacious and resource-efficient way to deliver EX/RP for some patients with OCD.

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.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).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.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.

Despite considerable global surveillance of antimicrobial resistance (AMR), data on the global emergence of new resistance genotypes in bacteria has not been systematically compiled. We conducted a study of English-language scientific literature (2006-2017) and ProMED-mail disease surveillance reports (1994-2017) to identify global events of novel AMR emergence (first clinical reports of unique drug-bacteria resistance combinations). We screened 24,966 abstracts and reports, ultimately identifying 1,757 novel AMR emergence events from 268 peer-reviewed studies and 26 disease surveillance reports (294 total). Events were reported in 66 countries, with most events in the United States (152), China (128), and India (127). The most common bacteria demonstrating new resistance were Klebsiella pneumoniae (344) and Escherichia coli (218). Resistance was most common against antibiotic drugs imipenem (89 events), ciprofloxacin (84) and ceftazidime (83). We provide an open-access database of emergence events with standardized fields for bacterial species, drugs, location, and date. We discuss the impact of reporting and surveillance bias on database coverage, and we suggest guidelines for data analysis. This database may be broadly useful for understanding rates and patterns of AMR evolution, identifying global drivers and correlates, and targeting surveillance and interventions.

Backround Pharmacotherapy for cannabis use disorder (CUD) is an important unmet public health need. Methods In a 12-week randomized double-blind placebo-controlled trial, the efficacy of quetiapine (300 mg nightly) for the treatment of CUD was tested in 130 outpatients. Weekly cannabis use was categorized into three groups: heavy use (5−7 days), moderate use (2–4 days) and light use (0–1 days). Results At baseline both groups were considered heavy users (using days per week: median = 7.0; interquartile range (IQR): 6.5−7.0; daily dollar value: median = $121.4; IQR: 73.8–206.3). The week-by-treatment interaction was marginally significant (χ2(2) = 5.56, P = .06). With each week, the odds of moderate compared to heavy use significantly increased in the quetiapine group (OR=1.17, P Conclusions The use of quetiapine to treat CUD was associated with an increased likelihood of heavy frequency use transitioning to moderate use, but not light use. The clinical significance of reductions in cannabis use, short of abstinence warrants further study.

Despite considerable global surveillance of antimicrobial resistance (AMR), data on the global emergence of new resistance genotypes in bacteria has not been systematically compiled. We conducted a study of English-language scientific literature (2006-2017) and ProMED-mail disease surveillance reports (1994-2017) to identify global events of novel AMR emergence (first clinical reports of unique drug-bacteria resistance combinations). We screened 24,966 abstracts and reports, ultimately identifying 1,757 novel AMR emergence events from 268 peer-reviewed studies and 26 disease surveillance reports (294 total). Events were reported in 66 countries, with most events in the United States (152), China (128), and India (127). The most common bacteria demonstrating new resistance were Klebsiella pneumoniae (344) and Escherichia coli (218). Resistance was most common against antibiotic drugs imipenem (89 events), ciprofloxacin (84) and ceftazidime (83). We provide an open-access database of emergence events with standardized fields for bacterial species, drugs, location, and date. We discuss the impact of reporting and surveillance bias on database coverage, and we suggest guidelines for data analysis. This database may be broadly useful for understanding rates and patterns of AMR evolution, identifying global drivers and correlates, and targeting surveillance and interventions.

Background The racial and ethnic background of individuals with psychosis may shape their pathway to early intervention services and clinical presentation at admission. Studies from Europe and Canada demonstrate that black minority patients with first-episode psychosis experience a more adverse and coercive pathway to care. The extent to which these findings can be extrapolated to the US context is unknown. The aims of this study are (1) to compare baseline contextual and clinical characteristics, and (2) to examine care pathways by race and ethnicity among young people with psychosis in early intervention services. Methods This study included individuals with a recent-onset ( Results The sample included 767 individuals with a non-Hispanic white (n=209, 27.2%), non-Hispanic black (277, 36.1%), Hispanic (218, 28.4%), or Asian (63, 8.2%) racial/ethnic background. Compared to non-Hispanic white, minority individuals were more likely to have public or no insurance and, overall, had a lower level of completed education. In terms of pathway to care, a lower proportion of non-Hispanic black (65.7%) and Asian (58.7%) participants had previously used mental health services compared to the non-Hispanic white group (78.0%). In contrast, psychiatric hospital or emergency department admissions in the 90 days prior to program enrollment were more frequent among all minority groups in comparison to the non-Hispanic white group. There were no significant differences by race and ethnicity in the level of symptoms or social functioning at baseline. Discussion Our findings suggest a pattern of mental health service use among minority groups with psychosis characterized by less mental health contacts but more inpatient and emergency care prior to the initiation of early intervention services. This trend could be partly explained by racial and ethnic patterning at the contextual level, including financial barriers to care, less so by racial/ethnic differences in illness severity. Our findings are consistent with evidence demonstrating an overrepresentation of minority individuals, especially African-Americans, in psychiatric emergency services suggesting a gap in unmet mental health need among minority populations in the US.

BACKGROUND: Multicomponent programs for first-episode psychosis (FEP) offering coordinated specialty care (CSC) aim at maximizing opportunities for recovery by intervening early in the course of the illness. Two key components of recovery include social and occupational functioning. This study identified trajectories of social and occupational functioning in individuals enrolled in OnTrackNY, a statewide CSC program for treatment of early psychosis in community settings. METHODS: The sample in this naturalistic cohort design included 634 individuals between ages 16 and 30 with recent-onset, non-affective psychosis with at least one CSC follow-up assessment at 20 different sites across New York State. Clinicians collected demographic and clinical data at program entry and quarterly up to one year. Social and occupational functioning were assessed using the MIRECC Global Assessment of Functioning scales.3 Growth mixture models (GMM) were used to identify subgroups of clients with similar social and occupational functioning trajectories. The association between baseline demographic variables and trajectories were tested using chi-square tests and one-way ANOVAs. RESULTS: The GMM with four trajectory classes of social and occupational functioning best fit the data. The majority of the sample (59.1%) exhibited a greatly improving trajectory for occupational functioning from very low at baseline to moderate by 12 months with moderate and stable social functioning across the same period. A subgroup consisting of 14.9% of the sample had a similar moderate and stable trajectory for social functioning as the majority group, but were already exhibiting moderate occupational functioning at baseline and showed further improvement. Another subgroup (14.8%) entered the program high on both domains and remained stable or improved further. The most disabled group (11.4%) started low in both domains and improved across the year but remained at a dysfunctional occupational level. Female gender, higher education, adherence to antipsychotic medication and being employed or in school at enrollment were significantly associated with trajectories leading to more favorable social and occupational functioning. DISCUSSION: Four identified trajectories of FEP patients enrolled in CSC had improving or high-stable social and occupational functioning patterns. This is in contrast with the long-held view that most individuals with psychotic disorders have a deteriorating course of illness. Most variability in terms of trajectory patterns over 1-year follow-up is observed in occupational functioning, which suggests that this may be an important domain to target for intervention.

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.

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 (1.5 mg) and UPA-EC (30 mg). 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 48 h). 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 AUC 0–24 . 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 AUC 0–24 and maximum concentration ( C max ) were 50% lower among obese-BMI women than among normal-BMI women (AUC 0–24 100.8 vs. 208.5 ng*h/mL, IQR obese-BMI 35.8, IQR normal-BMI 74.2, p≤.01; C max 10.8 vs. 18.2 ng/mL, p=.01). After UPA-EC, AUC 0–24 and C max were similar between obese-BMI and normal-BMI women (AUC 0–24 362.5 vs. 293.5 ng*h/mL, IQR obese-BMI 263.2, IQR normal-BMI 112.5, p=.15; C max 95.6 vs. 89.3 ng/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.