Search

Social and occupational functioning deficits contribute to overall disability in hoarding disorder (HD), and psychiatric symptoms are likely strong contributors. In turn, social/occupational impairment and psychiatric illness are known to contribute to suicidality. However, few studies have examined the relationship between these factors. We examined these relationships in 313 treatment seeking individuals with HD, measuring hoarding severity with the Saving Inventory, Revised and functional impairment with the Activities of Daily Living for Hoarding Disorder (ADL-H). We created a composite social/occupational function variable assessing employment, cohabitation, and marriage. A path analysis was used to assess the relationship between social functioning, occupational functioning, hoarding related functional impairment in activities of daily living, hoarding severity, psychiatric burden, and suicidality in HD. At least one lifetime psychiatric comorbidity was noted in 61% of participants. High rates of unemployment, living alone, never marrying or being divorced/separated, and lifetime suicide attempts were present. Hoarding severity and hoarding-related functional impairment were associated with social/occupational impairment, and, along with psychiatric burden, with suicidality in this population. These findings suggest that thorough psychiatric evaluation and assessment of suicidality is warranted for those with HD, and that hoarding-related functional impairment is closely related to measures of real-world social functioning.

BackgroundThe unique phenotypic and genetic aspects of obsessive-compulsive (OCD) and attention-deficit/hyperactivity disorder (ADHD) among individuals with Tourette syndrome (TS) are not well characterized. Here, we examine symptom patterns and heritability of OCD and ADHD in TS families.MethodOCD and ADHD symptom patterns were examined in TS patients and their family members (N = 3494) using exploratory factor analyses (EFA) for OCD and ADHD symptoms separately, followed by latent class analyses (LCA) of the resulting OCD and ADHD factor sum scores jointly; heritability and clinical relevance of the resulting factors and classes were assessed.ResultsEFA yielded a 2-factor model for ADHD and an 8-factor model for OCD. Both ADHD factors (inattentive and hyperactive/impulsive symptoms) were genetically related to TS, ADHD, and OCD. The doubts, contamination, need for sameness, and superstitions factors were genetically related to OCD, but not ADHD or TS; symmetry/exactness and fear-of-harm were associated with TS and OCD while hoarding was associated with ADHD and OCD. In contrast, aggressive urges were genetically associated with TS, OCD, and ADHD. LCA revealed a three-class solution: few OCD/ADHD symptoms (LC1), OCD & ADHD symptoms (LC2), and symmetry/exactness, hoarding, and ADHD symptoms (LC3). LC2 had the highest psychiatric comorbidity rates (⩾50% for all disorders).ConclusionsSymmetry/exactness, aggressive urges, fear-of-harm, and hoarding show complex genetic relationships with TS, OCD, and ADHD, and, rather than being specific subtypes of OCD, transcend traditional diagnostic boundaries, perhaps representing an underlying vulnerability (e.g. failure of top-down cognitive control) common to all three disorders.

BackgroundWomen who terminate pregnancies drink more subsequent to the pregnancy than women who give birth, including women who give birth after seeking to terminate a pregnancy.MethodsData are from the Turnaway Study, a prospective, longitudinal study of 956 women who sought to terminate pregnancies at 30 U.S. facilities. This paper focuses on the 452 women who received terminations just below facility gestational limits and 231 who were denied terminations because they presented just beyond facility gestational limits. This study examined whether baseline characteristics moderate the relationship between termination and subsequent binge drinking and whether stress, feelings about the pregnancy, and number of social roles mediate the relationship.ResultsOnly having had a previous live birth modified the termination-binge drinking relationship. Among women with previous live births, binge drinking was reduced among women carrying to term compared to terminating the pregnancy. Among women who had not had a previous live birth, however, the reduction in binge drinking among those denied termination was not sustained over time, and binge drinking of those who had and had not had terminations converged by 2.5 years. Neither stress, negative emotions, nor social roles mediated effects on binge drinking. Positive emotions at one week mediated effects on binge drinking at six months, although positive emotions at two years did not mediate effects on binge drinking at 2.5 years.ConclusionsHigher levels of binge drinking among those who terminate pregnancies do not appear due to stress or to negative emotions. Only parous women - and not nulliparous women - denied terminations experienced sustained reductions in binge drinking over time.

© 2015 Ramo et al.Background: Tobacco use remains the leading cause of premature morbidity and mortality in the United States. Young adults are less successful at quitting, use cessation treatment less often than smokers of other ages, and can be a challen

© 2014 Jiang et al.; licensee BioMed Central Ltd.Background: Without effective treatment, PTSD and depression can cause persistent disability in disaster-affected populations. Methods: Our objective was to test the efficacy of Interpersonal Psychotherapy (

I reviewed sample estimation methods for research designs involving nonindependent data and a dichotomous response variable to examine the importance of proper sample size estimation and the need to align methods of sample size estimation with planned methods of statistical analysis. Examples and references to published literature are provided in this article. When the method of sample size estimation is not in concert with the method of planned analysis, poor estimates may result. The effects of multiple measures over time also need to be considered. Proper sample size estimation is often overlooked. Alignment of the sample size estimation method with the planned analysis method, especially in studies involving nonindependent data, will produce appropriate estimates. [ABSTRACT FROM AUTHOR]

Background: Automated analysis of lung computed tomography (CT) scans may help characterize subphenotypes of acute respiratory illness. We integrated lung CT features measured via deep learning with clinical and laboratory data in spontaneously breathing subjects to enhance the identification of COVID-19 subphenotypes., Methods: This is a multicenter observational cohort study in spontaneously breathing patients with COVID-19 respiratory failure exposed to early lung CT within 7 days of admission. We explored lung CT images using deep learning approaches to quantitative and qualitative analyses; latent class analysis (LCA) by using clinical, laboratory and lung CT variables; regional differences between subphenotypes following 3D spatial trajectories., Results: Complete datasets were available in 559 patients. LCA identified two subphenotypes (subphenotype 1 and 2). As compared with subphenotype 2 (n = 403), subphenotype 1 patients (n = 156) were older, had higher inflammatory biomarkers, and were more hypoxemic. Lungs in subphenotype 1 had a higher density gravitational gradient with a greater proportion of consolidated lungs as compared with subphenotype 2. In contrast, subphenotype 2 had a higher density submantellar-hilar gradient with a greater proportion of ground glass opacities as compared with subphenotype 1. Subphenotype 1 showed higher prevalence of comorbidities associated with endothelial dysfunction and higher 90-day mortality than subphenotype 2, even after adjustment for clinically meaningful variables., Conclusions: Integrating lung-CT data in a LCA allowed us to identify two subphenotypes of COVID-19, with different clinical trajectories. These exploratory findings suggest a role of automated imaging characterization guided by machine learning in subphenotyping patients with respiratory failure., Trial Registration: ClinicalTrials.gov Identifier: NCT04395482. Registration date: 19/05/2020., (© 2024. The Author(s).)

Background: Rapidly improving acute respiratory distress syndrome (RIARDS) is an increasingly appreciated subgroup of ARDS in which hypoxemia improves within 24 h after initiation of mechanical ventilation. Detailed clinical and biological features of RIARDS have not been clearly defined, and it is unknown whether RIARDS is associated with the hypoinflammatory or hyperinflammatory phenotype of ARDS. The purpose of this study was to define the clinical and biological features of RIARDS and its association with inflammatory subphenotypes., Methods: We analyzed data from 215 patients who met Berlin criteria for ARDS (endotracheally intubated) and were enrolled in a prospective observational cohort conducted at two sites, one tertiary care center and one urban safety net hospital. RIARDS was defined according to previous studies as improvement of hypoxemia defined as (i) PaO 2 :FiO 2  > 300 or (ii) SpO2: FiO 2  > 315 on the day following diagnosis of ARDS (day 2) or (iii) unassisted breathing by day 2 and for the next 48 h (defined as absence of endotracheal intubation on day 2 through day 4). Plasma biomarkers were measured on samples collected on the day of study enrollment, and ARDS phenotypes were allocated as previously described., Results: RIARDS accounted for 21% of all ARDS participants. Patients with RIARDS had better clinical outcomes compared to those with persistent ARDS, with lower hospital mortality (13% vs. 57%; p value < 0.001) and more ICU-free days (median 24 vs. 0; p value < 0.001). Plasma levels of interleukin-6, interleukin-8, and plasminogen activator inhibitor-1 were significantly lower among patients with RIARDS. The hypoinflammatory phenotype of ARDS was more common among patients with RIARDS (78% vs. 51% in persistent ARDS; p value = 0.001)., Conclusions: This study identifies a high prevalence of RIARDS in a multicenter observational cohort and confirms the more benign clinical course of these patients. We report the novel finding that RIARDS is characterized by lower concentrations of plasma biomarkers of inflammation compared to persistent ARDS, and that hypoinflammatory ARDS is more prevalent among patients with RIARDS. Identification and exclusion of RIARDS could potentially improve prognostic and predictive enrichment in clinical trials., (© 2024. The Author(s).)

Background: The ventilatory ratio (VR, [minute ventilation × PaCO 2 ]/[predicted body weight × 100 × 37.5]) is associated with mortality in ARDS. The aims of this study were to test whether baseline disease severity or neuromuscular blockade (NMB) modified the relationship between VR and mortality., Methods: This was a post hoc analysis of the PETAL-ROSE trial, which randomized moderate-to-severe ARDS patients to NMB or control. Survival among patients with different VR trajectories or VR cutoff above and below the median was assessed by Kaplan-Meier analysis. The relationships between single-day or 48-h VR trajectories with 28- or 90-day mortality were tested by logistic regression. Randomization allocation to NMB and markers of disease severity were tested as confounders by multivariable regression and interaction term analyses., Results: Patients with worsening VR trajectories had significantly lower survival compared to those with improving VR (n = 602, p < 0.05). Patients with VR > 2 (median) at day 1 had a significantly lower 90-day survival compared to patients with VR ≤ 2 (HR 1.36, 95% CI 1.10-1.69). VR at day 1 was significantly associated with 28-day mortality (OR = 1.40, 95% CI 1.15-1.72). There was no interaction between NMB and VR for 28-day mortality. APACHE-III had a significant interaction with VR at baseline for the outcome of 28-day mortality, such that the relationship between VR and mortality was stronger among patients with lower APACHE-III. There was a significant association between rising VR trajectory and mortality that was independent of NMB, baseline PaO 2 /FiO 2 ratio and generalized markers of disease severity (Adjusted OR 1.81, 95% CI 1.28-2.84 for 28-day and OR 2.07 95% CI 1.41-3.10 for 90-day mortality). APACHE-III and NMB were not effect modifiers in the relationship between VR trajectory and mortality., Conclusions: Elevated baseline and day 1 VR were associated with higher 28-day mortality. The relationship between baseline VR and mortality was stronger among patients with lower APACHE-III. APACHE-III was not an effect modifier for the relationship between VR trajectory and mortality, so that the VR trajectory may be optimally suited for prognostication and predictive enrichment. VR was not different between patients randomized to NMB or control, indicating that VR can be utilized without correcting for NMB., (© 2022. The Author(s).)

Background: Heterogeneity in Acute Respiratory Distress Syndrome (ARDS), as a consequence of its non-specific definition, has led to a multitude of negative randomised controlled trials (RCTs). Investigators have sought to identify heterogeneity of treatment effect (HTE) in RCTs using clustering algorithms. We evaluated the proficiency of several commonly-used machine-learning algorithms to identify clusters where HTE may be detected., Methods: Five unsupervised: Latent class analysis (LCA), K-means, partition around medoids, hierarchical, and spectral clustering; and four supervised algorithms: model-based recursive partitioning, Causal Forest (CF), and X-learner with Random Forest (XL-RF) and Bayesian Additive Regression Trees were individually applied to three prior ARDS RCTs. Clinical data and research protein biomarkers were used as partitioning variables, with the latter excluded for secondary analyses. For a clustering schema, HTE was evaluated based on the interaction term of treatment group and cluster with day-90 mortality as the dependent variable., Findings: No single algorithm identified clusters with significant HTE in all three trials. LCA, XL-RF, and CF identified HTE most frequently (2/3 RCTs). Important partitioning variables in the unsupervised approaches were consistent across algorithms and RCTs. In supervised models, important partitioning variables varied between algorithms and across RCTs. In algorithms where clusters demonstrated HTE in the same trial, patients frequently interchanged clusters from treatment-benefit to treatment-harm clusters across algorithms. LCA aside, results from all other algorithms were subject to significant alteration in cluster composition and HTE with random seed change. Removing research biomarkers as partitioning variables greatly reduced the chances of detecting HTE across all algorithms., Interpretation: Machine-learning algorithms were inconsistent in their abilities to identify clusters with significant HTE. Protein biomarkers were essential in identifying clusters with HTE. Investigations using machine-learning approaches to identify clusters to seek HTE require cautious interpretation., Funding: NIGMS R35 GM142992 (PS), NHLBI R35 HL140026 (CSC); NIGMS R01 GM123193, Department of Defense W81XWH-21-1-0009, NIA R21 AG068720, NIDA R01 DA051464 (MMC)., Competing Interests: Declaration of Competing Interest Dr Sinha received institutional grants from the National Institute of Health (NIH), Ms Spicer received institutional grant funding from the NIH and Department of Defense. Prof Delucchi declares no relevant conflicts of interest. Prof McAuley received institutional grants from the NIHR, Innovate UK, MRC, Novavax, Northern Ireland HSC R&D Division, Wellcome Trust; royalties/licenses from Queen's University Belfast for a patent of novel treatment for inflammatory diseases (USB962032); consulting fees from Bayer, GlaxoSmithKline, Boehringer Ingelhelm, Novartis, Eli Lilly, SOBI; payment from GlaxoSmithKline as an educational seminary speaker; travel support from Vir Biotechnology Inc and Faron Pharmaceuticals as a member of Data Safety Monitoring Board. His spouse received consultancy fees from Insmed and payments for participation in grant review panel from California Institute for Regenerative Medicine. Prof Calfee received institutional grants from the NIH, Bayer, Roche-Genentech, Quantum Leap Healthcare Collaborative; and personal fees from Quark, Vasomune, and Gen1e Life Science. Dr Churpek received institutional grants from the NIH, Department of Defense, and EarlySense., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Alveolar epithelial-capillary barrier disruption is a hallmark of acute respiratory distress syndrome (ARDS). Contribution of mitochondrial dysfunction to the compromised alveolar-capillary barrier in ARDS remains unclear. Mesenchymal stromal cells-derived extracellular vesicles (MSC-EVs) are considered as a cell-free therapy for ARDS. Mitochondrial transfer was shown to be important for the therapeutic effects of MSCs and MSC-EVs. Here we investigated the contribution of mitochondrial dysfunction to the injury of alveolar epithelial and endothelial barriers in ARDS and the ability of MSC-EVs to modulate alveolar-capillary barrier integrity through mitochondrial transfer.Primary human small airway epithelial and pulmonary microvascular endothelial cells and human precision cut lung slices (PCLSs) were stimulated with endotoxin or plasma samples from patients with ARDS and treated with MSC-EVs, barrier properties and mitochondrial functions were evaluated. Lipopolysaccharide (LPS)-injured mice were treated with MSC-EVs and degree of lung injury and mitochondrial respiration of the lung tissue were assessed.Inflammatory stimulation resulted in increased permeability coupled with pronounced mitochondrial dysfunction in both types of primary cells and PCLSs. Extracellular vesicles derived from normal MSCs restored barrier integrity and normal levels of oxidative phosphorylation while an extracellular vesicles preparation which did not contain mitochondria was not effective. In vivo , presence of mitochondria was critical for extracellular vesicles ability to reduce lung injury and restore mitochondrial respiration in the lung tissue.In the ARDS environment, MSC-EVs improve alveolar-capillary barrier properties through restoration of mitochondrial functions at least partially via mitochondrial transfer., Competing Interests: Conflict of interest: J. Dutra Silva has nothing to disclose. Conflict of interest: Y. Su has nothing to disclose. Conflict of interest: C.S. Calfee reports grants from NIH, during the conduct of the study; grants and personal fees for consultancy from Roche/Genentech and Bayer, personal fees for advisory board work from Quark Pharmaceuticals and Prometic, personal fees for consultancy from Gen1e Life Sciences and Vasomune, outside the submitted work. Conflict of interest: K.L. Delucchi has nothing to disclose. Conflict of interest: D. Weiss has nothing to disclose. Conflict of interest: D.F. McAuley reports personal fees from consultancy for GlaxoSmithKline, Boehringer Ingelheim and Bayer, outside the submitted work; his institution has received grants from the UK NIHR, Wellcome Trust and others; has a patent issued to his institution for a treatment for ARDS; and is a Director of Research for the Intensive Care Society and NIHR EME Programme Director. Conflict of interest: C. O'Kane reports grants from Wellcome Trust, MRC and NI HSC R& D, outside the submitted work, and that her spouse has received consultancy fees from GlaxoSmithKline, Boehringer Ingelheim and Bayer. Conflict of interest: A.D. Krasnodembskaya reports grants from Medical Research Council, UK, during the conduct of the study., (Copyright ©ERS 2021.)

Importance: Physician well-being is a critical component of sustainable health care. There are few data on the effects of multilevel well-being programs nor a clear understanding of where and how to target resources., Objective: To inform the design of future well-being interventions by exploring individual and workplace factors associated with surgical trainees' well-being, differences by gender identity, and end-user perceptions of these initiatives., Design, Setting, and Participants: This mixed-methods study among surgical trainees within a single US academic surgical department included a questionnaire in January 2019 (98 participants, including general surgery residents and clinical fellows) and a focus group (9 participants, all clinical residents who recently completed their third postgraduate year [PGY 3]) in July 2019. Participants self-reported gender (man, woman, nonbinary)., Exposures: Individual and organizational-level initiatives, including mindfulness-based affective regulation training (via Enhanced Stress Resilience Training), advanced scheduling of time off, wellness half-days, and the creation of a resident-driven well-being committee., Main Outcomes and Measures: Well-being was explored using validated measures of psychosocial risk (emotional exhaustion, depersonalization, perceived stress, depressive symptoms, alcohol use, languishing, anxiety, high psychological demand) and resilience (mindfulness, social support, flourishing) factors. End-user perceptions were assessed through open-ended responses and a formal focus group., Results: Of 98 participants surveyed, 64 responded (response rate, 65%), of whom 35 (55%) were women. Women vs men trainees were significantly more likely to report high depersonalization (odds ratio [OR], 5.50; 95% CI, 1.38-21.85) and less likely to report high mindfulness tendencies (OR, 0.17; 95% CI, 0.05-0.53). Open-ended responses highlighted time and priorities as the greatest barriers to using well-being resources. Focus group findings reflected Job Demand-Resource theory tenets, revealing the value of individual-level interventions to provide coping skills, the benefit of advance scheduling of time off for maintaining personal support resources, the importance of work quality rather than quantity, and the demoralizing effect of inefficient or nonresponsive systems., Conclusions and Relevance: In this study, surgical trainees indicated that multilevel well-being programs would benefit them, but tailoring these initiatives to individual needs and specific workplace elements is critical to maximizing intervention effects.

Health behavior theorists and prevention researchers use a variety of measures of adolescent and young adult (AYA) risk and benefit perceptions to predict tobacco-use and marijuana-use behaviors. However, studies have not examined whether and how perception measures that ask about likelihood of more general outcomes such as "harm" versus ask about specific risk or benefit outcomes compare or whether they differentially predict AYA willingness to use if one of your best friends were to offer it and intentions to use in the next year; and if these measures have differential ability to predict actual use of tobacco and marijuana. We used data from a prospective cohort of California AYAs to create and test new scales to measure perceptions of specific health and social outcomes related to risks (e.g., smell bad) and benefits (e.g., look cool) related to tobacco and marijuana, and then addressed three questions: (1) Whether and how measures of perceptions of specific social and health risks and benefits (for our purposes "specific measures") and measures of perceived general harm are differentially associated with measures of willingness, social norms, and intentions to use? (2) Are specific versus general measures differentially associated with and predictive of tobacco and cannabis use behavior? (3) Are specific perceptions measures differentially predictive of behavior compared to measures of willingness, social norms, and behavioral intentions? Our results demonstrate that to better predict AYA tobacco and marijuana use, measures that address general outcomes, such as harmfulness, as well as willingness and behavioral intention should be used. We also found that measures of specific perceived risks (short-term, long-term, social) and benefits were unrelated and correlated differently with different products. For example, adolescents perceived both risks and benefits from using products like e-cigarettes, and perceived greater risk from smokeless tobacco compared to combustible cigarettes. These findings indicate that measures of specific perceived social and health outcomes can be useful to discern nuanced differences in motivation for using different substances. Study implications are important for survey dimension-reduction and assessing relationships among perceptions, motivations, and use of tobacco and marijuana products., Competing Interests: Competing interests The authors declare no competing interests.

Background: Loneliness is a widespread and significant problem on college campuses. Prolonged loneliness in young adulthood is a risk factor for concurrent and future mental health problems and attrition, making college a critical time for support. Cognitive and behavioral interventions show promise for decreasing loneliness and can be widely disseminated through technology., Objective: This pilot randomized controlled trial was conducted to examine the initial efficacy, feasibility, and desirability of a smartphone app, Nod, designed to deliver cognitive and behavioral skill-building exercises to reduce loneliness during the transition to college., Methods: First-year college students (N=221, mean age 18.7 years, 59% female) were recruited online during incoming student orientation, and randomized to either receive immediate access to Nod (experimental group, n=100) or access after 4 weeks (control group, n=121). The app delivered skills via fully automated (1) "social challenges," suggested activities designed to build social connections; (2) reflections, brief cognitive reframing exercises; and (3) student testimonials that encouraged a growth mindset toward social connection building. Main intention-to-treat analyses were used to compare the conditions on self-assessed loneliness, depressive symptoms, and other mental health and college adjustment outcomes at week 4, controlling for baseline values on those variables. Analyses were also performed to test the hypothesis that the treatment benefits would be particularly pronounced for participants with heightened psychological vulnerability at baseline (ie, higher baseline depressive symptoms and loneliness)., Results: Retention was 97% at week 4, and participants viewed an average 36.7 pages of app content. There were no significant condition differences in loneliness at week 4 (F 1, 211 =0.05, P=.82; η p 2 <.001). However, there was a significant condition-by-baseline depression interaction to predict week-4 loneliness (F 1,209 =9.65, P=.002; η p 2 =.04). Simple slope analyses indicated that baseline depression positively predicted week-4 loneliness among control participants (r=0.30, t 209 =3.81, P<.001), but not among experimental participants (r=-0.09, t 209 =-0.84, P=.40), suggesting that Nod buffered participants with high baseline depression scores from experiencing heightened midquarter loneliness. Similarly, there were no significant condition differences in other week-4 outcomes. However, moderation by baseline vulnerability was found for week-4 depressive symptoms, sleep quality, and indices of college adjustment (eg, perceived social support and campus belonging)., Conclusions: Although Nod exposure did not impact outcomes for the full sample, these results provide initial evidence of its benefit for vulnerable students. The results of this trial suggest that cognitive and behavioral skills delivered via a mobile app can buffer psychologically vulnerable college students against heightened loneliness and depressive symptoms, as well as other negative college adjustment outcomes. Future work will aim to improve upon app engagement, and to address loneliness among other key populations., Trial Registration: ClinicalTrials.gov NCT04164654; https://clinicaltrials.gov/ct2/show/NCT04164654., (©Emma Bruehlman-Senecal, Cayce J Hook, Jennifer H Pfeifer, Caroline FitzGerald, Brittany Davis, Kevin L Delucchi, Jana Haritatos, Danielle E Ramo. Originally published in JMIR Mental Health (http://mental.jmir.org), 20.10.2020.)

Importance: Mindfulness meditation training has been shown to be feasible in surgical trainees, but affective, cognitive, and performance benefits seen in other high-stress populations have yet to be evaluated., Objective: To explore potential benefits to stress, cognition, and performance in postgraduate year 1 (PGY-1) surgery residents receiving modified mindfulness-based stress reduction (modMBSR)., Design, Setting, and Participants: This follow-up study is an analysis of the Mindful Surgeon pilot randomized clinical trial of modMBSR (n = 12) vs an active control (n = 9), evaluated at baseline (T1), postintervention (T2), and 1 year (T3), took place at an academic medical center residency training program among PGY-1 surgery residents. Data were collected between June 2016 and June 2017 and analyzed from June 2017 to December 2017., Interventions: Weekly 2-hour modMBSR classes and 20 minutes of daily home practice during an 8-week period vs an active control (different content, same structure)., Main Outcomes and Measures: Preliminary evidence of efficacy was explored, primarily focusing on perceived stress and executive function and secondarily on burnout, depression, motor skill performance, and changes in blood oxygen level-dependent functional neuroimaging during an emotion regulation task. Group mean scores were calculated at T1, T2, and T3 and in linear mixed-effects multivariate analysis. Effect size for analysis of covariance is presented as partial η2 with the following cutoff points: small, less than 0.06; medium, 0.06 to 0.14; large, greater than 0.14., Results: Postgraduate year 1 surgery residents (N = 21; 8 [38%] women) were randomized to a modMBSR arm (n = 12) or an active control arm (n = 9). Linear mixed-effects modeling revealed differences at T2 and T3 in perceived stress (mean [SD] difference at T2: modMBSR, 1.42 [5.74]; control, 3.44 [6.71]; η2 = 0.07; mean [SD] difference at T3: modMBSR, 1.00 [4.18]; control, 1.33 [4.69]; η2 = 0.09) and in mindfulness (mean [SD] difference at T2: modMBSR, 3.08 [3.63]; control, 1.56 [4.28]; η2 = 0.13; mean [SD] difference at T3: modMBSR, 2.17 [3.66]; control, -0.11 [6.19]; η2 = 0.15). Burnout at T2 (mean [SD] difference: modMBSR, 4.50 [9.08]; control, 3.44 [6.71]; η2 = 0.01) and T3 (mean [SD] difference: modMBSR, 5.50 [9.96]; control, 5.56 [9.69]; η2 = 0.01) showed similar increase in both groups. Working memory increased more at T2 in the modMBSR arm (mean [SD] difference, 0.35 [0.60]) than in the control arm (mean [SD] difference, 0.21 [0.74]; η2 = 0.02) and at T3 (modMBSR, 0.68 [0.69]; control, 0.26 [0.58]; η2 = 0.20). Cognitive control decreased more in the control arm at T2 (mean [SD] difference at T2: modMBSR, 0.15 [0.40]; control, -0.07 [0.32]; η2 = 0.13) and at T3 (mean [SD] difference: modMBSR, 0.07 [0.59]; control, -0.26 [0.53]; η2 = 0.16). Mean (SD) circle-cutting time improved more at T2 in the modMBSR arm (-24.08 [63.00] seconds) than in the control arm (-4.22 [112.94] seconds; η2 = 0.23) and at T3 in the modMBSR arm (-4.83 [77.94] seconds) than in the control arm (11.67 [145.17] seconds; η2 = 0.13). Blood oxygen level-dependent functional neuroimaging during an emotional regulation task showed unique postintervention activity in the modMBSR arm in areas associated with executive function control (dorsolateral prefrontal cortex) and self-awareness (precuneus)., Conclusions and Relevance: In this pilot randomized clinical trial, modMBSR in PGY-1 surgery residents showed potential benefits to well-being and executive function, suggesting a powerful role for mindfulness-based cognitive training to support resident well-being and performance, as mandated by the Accreditation Council for Graduate Medical Education., Trial Registration: ClinicalTrials.gov identifier: NCT03141190.

Objective: Specialty addiction programs treat people who are addicted to alcohol, opioids, stimulants, and other drugs. This study identified the proportion of addiction program clients who received tobacco-related services and factors associated with receipt of such services., Methods: In 2015 and 2016, clients (N=2,119) in 24 programs were surveyed for receipt of services aligning with three of the five As of tobacco cessation: ask, advise, assist. Multivariate analyses examined factors associated with receipt of each service., Results: Most clients (76%) were asked about smoking. Among smokers (N=1,630), 53% were advised to quit, 41% received counseling, 26% received cessation medication, and 17% received counseling and medication. Clients were more likely to receive tobacco-related services if they wanted help quitting smoking or were enrolled in programs with tobacco-free grounds., Conclusions: These correlational findings suggest that increasing client motivation to quit and implementing tobacco-free policies on the grounds of treatment centers may increase tobacco-related services in addiction treatment.

Purpose: Alcohol use during pregnancy is a significant public health concern. Nearly all U.S. states have enacted policies targeting alcohol use during pregnancy, but there has been little research examining their impact, particularly across racial/ethnic groups. Methods: Using data from the Behavioral Risk Factor Surveillance System and about eight state-level, pregnancy-specific alcohol policies from 1985 to 2016, the aim of this study was to examine the differential effects of these policies on drinking among pregnant women by race/ethnicity. Results: We found evidence of differential effects for priority treatment, prohibitions on criminal prosecution, and civil commitment policies. In relation to priority treatment policies, effects benefited versus harmed different racial/ethnic groups depending on whether the priority treatment policies were for pregnant women only or if they gave priority to both pregnant women and pregnant women with children. Conclusions: Findings from this study suggest that benefits and harms from these policies do not appear to be equitably distributed across different racial/ethnic groups. Research considering the impact of alcohol/pregnancy policies should consider differential effects by race/ethnicity., Competing Interests: No competing financial interests exist.

This study compares the effectiveness of approaches used to recruit a diverse sample for a randomized clinical trial for Hoarding Disorder (HD) in the San Francisco Bay Area. Of the 632 individuals who inquired about the study, 313 were randomized and 231 completed treatment. Most participants heard about the study via flyering (N = 161), followed by advocacy groups (N = 113), word of mouth (N = 84), health care professionals (N = 78), online (N = 68), and media (N = 11). However, those that heard about the study via advertising methods, such as flyers, were less likely to complete the study, p = .01, while those recruited via advocacy groups were most likely to be randomized, p = .03. No source proved more effective in recruiting underrepresented groups such as men, p = .60; non-whites, p = .49; or Hispanics, p = .97. Advertising recruited the youngest individuals, p < 0.001, and word of mouth was most likely to recruit unemployed, disabled, or retired individuals, p = .01. Thus, results suggest an ongoing multimodal approach is likely to be most effective in both soliciting and retaining a diverse sample. Future studies should compare recruitment methods across greater geographical regions too, as well as in terms of financial and human costs.

The combined use of opioid and benzodiazepine medications increases the risk of hazardous effects, such as respiratory depression. Although recent increases in outpatient use of opioid prescriptions have been documented, there are limited data regarding rates and correlates of combined opioid and benzodiazepines among adults in outpatient settings. Our objective was to examine annual trends in outpatient visits including opioids, benzodiazepines, and their combination among adults as well as clinical and demographic correlates. We used data from the 1993-2014 National Ambulatory Medical Care Survey (NAMCS) among non-elderly (i.e., ages 18-64 years) adults to examine the probability of a visit including an opioid, benzodiazepine, or their combination, in addition to clinical and demographic correlates. From 1993 to 2014, benzodiazepines-with-opioids visits increased from 9.8 to 62.5 (OR = 9.23, 95% CI = 5.45-15.65) per 10,000 visits. Highest-represented groups among benzodiazepines-with-opioids visits were older (50-64 years) (49.1%), white (88.8%), commercially insured (58.0%) patients during their first visit (87.6%) to a primary-care physician (41.9%). We identified a significant increase in the outpatient co-prescription of opioids and benzodiazepines, notably among adults aged 50-64 years during primary-care visits. Educational and policy changes to provide alternatives to benzodiazepine-with-opioid co-prescription and limiting opioid prescription to pain specialists may reduce rates of this potentially hazardous combination.

Background: Mental disorders are the leading global cause of years lived with disability; the majority of this burden exists in low and middle income countries (LMICs). Over half of mental illness is attributable to depression and anxiety disorders, both of which have known treatments. While the scarcity of mental health care providers is recognized as a major contributor to the magnitude of untreated disorders in LMICs, studies in LMICs find that evidence-based treatments for depression and anxiety disorders, such as brief, structured psychotherapies, are feasible, acceptable and have strong efficacy when delivered by local non-specialist personnel. However, most mental health treatment studies using non-specialist providers in LMICs deploy traditional efficacy designs (T1) without the benefit of integrated mental health treatment models shown to succeed over vertical interventions or methods derived from new implementation science to speed policy change. Here, we describe an effectiveness-implementation hybrid study that evaluates non-specialist delivery of mental health treatment within an HIV clinic for HIV-positive (HIV+) women affected by gender- based violence (GBV) (HIV+ GBV+) in the Nyanza region of Kenya., Methods/design: In this effectiveness-implementation hybrid type I design, 200 HIV+ women with major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) who are receiving care at a Family AIDS Care Education and Services (FACES)-supported clinic in Kisumu, Kenya will be randomized to: (1) interpersonal psychotherapy (IPT) + treatment as usual (TAU) or (2) TAU, both delivered within the HIV clinic. IPT will consist of 12 weekly 60-minute individual IPT sessions, delivered by non-specialists trained to provide IPT. Primary effectiveness outcomes will include MDD and PTSD diagnosis on the Mini International Diagnostic Interview (MINI). Primary implementation outcomes will include treatment cost-benefit, acceptability, appropriateness, feasibility and fidelity of the IPT delivery within an HIV clinic., Discussion: This trial leverages newly defined effectiveness-implementation hybrid designs to gather data on mental health treatment implementation within an HIV care clinic, while testing the effectiveness of an evidence-based treatment for use with a large underserved population (HIV+ GBV+ women) in Kenya., Clinical Trials Identifier: NCT02320799, registered on 9 September 2014.

Background: Young adult smokers are a challenging group to engage in smoking cessation interventions. With wide reach and engagement among users, Facebook offers opportunity to engage young people in socially supportive communities for quitting smoking and sustaining abstinence., Objective: We developed and tested initial efficacy, engagement, and acceptability of the Tobacco Status Project, a smoking cessation intervention for young adults delivered within Facebook., Methods: The intervention was based on the US Public Health Service Clinical Practice Guidelines and the Transtheoretical Model and enrolled participants into study-run 3-month secret Facebook groups matched on readiness to quit smoking. Cigarette smokers (N=79) aged 18-25, who used Facebook on most days, were recruited via Facebook. All participants received the intervention and were randomized to one of three monetary incentive groups tied to engagement (commenting in groups). Assessments were completed at baseline, 3-, 6-, and 12-months follow-up. Analyses examined retention, smoking outcomes over 12 months (7-day point prevalence abstinence, ≥50% reduction in cigarettes smoked, quit attempts and strategies used, readiness to quit), engagement, and satisfaction with the intervention., Results: Retention was 82% (65/79) at 6 months and 72% (57/79) at 12 months. From baseline to 12-months follow-up, there was a significant increase in the proportion prepared to quit (10/79, 13%; 36/79, 46%, P<.001). Over a third (28/79, 35%) reduced their cigarette consumption by 50% or greater, and 66% (52/79) made at least one 24-hour quit attempt during the study. In an intent-to-treat analysis, 13% (10/79) self-reported 7-day abstinence (6/79, 8% verified biochemically) at 12-months follow-up. In their quit attempts, 11% (9/79) used a nicotine replacement therapy approved by the Food and Drug Administration, while 18% (14/79) used an electronic nicotine delivery system to quit (eg, electronic cigarette). A majority (48/79, 61%) commented on at least one Facebook post, with more commenting among those with biochemically verified abstinence at 3 months (P=.036) and those randomized to receive a personal monetary incentive (P=.015). Over a third of participants (28/79, 35%) reported reading most or all of the Facebook posts. Highest acceptability ratings of the intervention were for post ease (57/79, 72%) and thinking about what they read (52/79, 66%); 71% (56/79) recommended the program to others. Only 5 participants attended the optional cognitive-behavioral counseling sessions, though their attendance was high (6/7 sessions overall) and the sessions were rated as easy to understand, useful, and helpful (all 90-100% agreed)., Conclusions: A Facebook quit smoking intervention is attractive and feasible to deliver, and early efficacy data are encouraging. However, the 1.5-fold greater use of electronic cigarettes over nicotine replacement products for quitting is concerning.

Background: Tobacco use remains the leading cause of premature morbidity and mortality in the United States. Young adults are less successful at quitting, use cessation treatment less often than smokers of other ages, and can be a challenge to retain in treatment. Social media, integrated into the lives of many young adults, represents a promising strategy to deliver evidence-based smoking cessation treatment to a large, diverse audience. The goal of this trial is to test the efficacy of a stage-based smoking cessation intervention on Facebook for young adults age 18 to 25 on smoking abstinence, reduction in cigarettes smoked, and thoughts about smoking abstinence., Methods/design: This is a randomized controlled trial. Young adult smokers throughout the United States are recruited online and randomized to either the 3 month Tobacco Status Project intervention on Facebook or a referral to a smoking cessation website. The intervention consists of assignment to a secret Facebook group tailored to readiness to quit smoking (precontemplation, contemplation, preparation), daily Facebook contacts tailored to readiness to quit smoking, weekly live counseling sessions, and for those in preparation, weekly Cognitive Behavioral Therapy counseling sessions on Facebook. Primary outcome measure is biochemically-verified 7-day point prevalence abstinence from smoking at posttreatment (3 months), 6, and 12 months. Secondary outcome measures are reduction of 50 % or more in cigarettes smoked, 24 h quit attempts, and commitment to abstinence at each time point. A secondary aim is to test, within the TSP condition, the effect of a monetary incentive at increasing engagement in the intervention., Discussion: This randomized controlled trial is testing a novel Facebook intervention for treating young adults' tobacco use. If efficacious, the social media intervention could be disseminated widely and expanded to address additional health risks., Trial Registration: ClinicalTrials.gov: NCT02207036 , May 13, 2014.

Objective: Although many mental health courts (MHCs) have been established to reduce criminal justice involvement of persons with mental disorders, research has not kept pace with the widespread implementation of these courts. Whereas early MHCs were restricted to persons charged with nonviolent misdemeanors, many MHCs now accept persons with more serious charges for whom ameliorating risk of violence is a greater concern. This study evaluated the relationship between MHC participation and risk of violence by using a prospective design. It was hypothesized that MHC participation would decrease the risk of violence during a one year follow-up compared with a matched comparison group., Methods: The sample included 169 jail detainees with a mental disorder who either entered an MHC (N=88) or received treatment as usual (N=81). Seventy-two percent had been charged with felonies. Participants were interviewed at baseline and during a one-year follow up, and their arrest records were reviewed. Propensity-adjusted logistic regression evaluated the relationship between MHC participation and risk of violence, controlling for potential confounders such as history of violence, demographic characteristics, baseline treatment motivation, and time at risk in the community., Results: MHC participation was associated with reduction in risk of violence (odds ratio=.39). During follow-up, 25% of the MHC group perpetrated violence, compared with 42% of the treatment-as-usual group., Conclusions: MHC participation can reduce the risk of violence among justice-involved persons with mental disorders. The findings support the conclusion that the MHC model can be extended beyond persons charged with nonviolent misdemeanors in a way that enhances public safety.

Background: Without effective treatment, PTSD and depression can cause persistent disability in disaster-affected populations., Methods: Our objective was to test the efficacy of Interpersonal Psychotherapy (IPT) delivered by trained local personnel compared with treatment as usual (TAU) for Posttraumatic Stress Disorder (PTSD) and Major Depressive Disorder (MDD) among adults affected by the Sichuan 2008 earthquake. A small randomized controlled trial of IPT + TAU versus TAU alone was delivered by local mental health personnel in Shifang, China. Between July 2011 and January 2012, 49 adults ≥ 18 years with PTSD, MDD or both were enrolled and randomized to 12 weekly sessions of IPT + TAU (27) or TAU (22) alone x 12 weeks. IPT was then offered to the TAU group. Unblinded follow up assessments were conducted at three and six months. IPT was a 12 session, weekly one hour treatment delivered by local personnel who were trained and supervised in IPT. TAU was continuation of prescribed psychotropic medication (if applicable) and crisis counseling, as needed. MAIN OUTCOME(S) AND MEASURES (S): Clinician Administered PTSD Scale (CAPS) PTSD diagnosis; Structured Clinical Interview for DSM-IV (SCID) for MDD diagnosis. Secondary measures included PTSD/depression symptoms, interpersonal conflict/anger, social support, self-efficacy and functioning., Results: Using an intent-to-treat analysis, 22 IPT + TAU and 19 TAU participants were compared at three months post-baseline. A significantly greater reduction of PTSD and MDD diagnoses was found in the IPT group (51.9%, 30.1%, respectively) versus the TAU group (3.4%, 3.4%, respectively). Despite the small sample, the estimates for time-by-condition analyses of target outcomes (2.37 for PTSD (p = .018) and 1.91 for MDD (p = .056)) indicate the improvement was better in the IPT + TAU condition versus the TAU group. Treatment gains were maintained at 6 months for the IPT group. A similar treatment response was observed in the TAU group upon receipt of IPT., Conclusions: This initial study shows that IPT is a promising treatment for reducing PTSD and depression, the two major mental health disorders affecting populations surviving natural disaster, using a design that builds local mental health care capacity., Trial Registration: ClinicalTrials.Gov number, NCT01624935.

Background: Despite advances in supportive care, moderate-severe acute respiratory distress syndrome (ARDS) is associated with high mortality rates, and novel therapies to treat this condition are needed. Compelling pre-clinical data from mouse, rat, sheep and ex vivo perfused human lung models support the use of human mesenchymal stem (stromal) cells (MSCs) as a novel intravenous therapy for the early treatment of ARDS., Methods: This article describes the study design and challenges encountered during the implementation and phase 1 component of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of bone marrow-derived human MSCs for moderate-severe ARDS. A trial enrolling 69 subjects is planned (9 subjects in phase 1, 60 subjects in phase 2 treated with MSCs or placebo in a 2:1 ratio)., Results: This report describes study design features that are unique to a phase 1 trial in critically ill subjects and the specific challenges of implementation of a cell-based therapy trial in the ICU., Conclusions: Experience gained during the design and implementation of the START study will be useful to investigators planning future phase 1 clinical trials based in the ICU, as well as trials of cell-based therapy for other acute illnesses., Clinical Trials Registration: NCT01775774 and NCT02097641.

Background: Major depressive disorder (MDD) is the leading cause of disability in the developed world, yet broadly effective treatments remain elusive. Up to 40% of patients with depression are unresponsive to at least two trials of antidepressant medication and thus have "treatment-resistant depression" (TRD). There is an urgent need for cost-effective, non-pharmacologic, evidence-based treatments for TRD. Mindfulness-Based Cognitive Therapy (MBCT) is an effective treatment for relapse prevention and residual depression in major depression, but has not been previously studied in patients with TRD in a large randomized trial., Methods/design: The purpose of this study was to evaluate whether MBCT is an effective augmentation of antidepressants for adults with MDD who failed to respond to standard pharmacotherapy. MBCT was compared to an active control condition, the Health-Enhancement Program (HEP), which incorporates physical activity, functional movement, music therapy and nutritional advice. HEP was designed as a comparator condition for mindfulness-based interventions to control for non-specific effects. Originally investigated in a non-clinical sample to promote stress reduction, HEP was adapted for a depressed population for this study. Individuals age 18 and older with moderate to severe TRD, who failed to respond to at least two trials of antidepressants in the current episode, were recruited to participate. All participants were taking antidepressants (Treatment as usual; TAU) at the time of enrollment. After signing an informed consent, participants were randomly assigned to either MBCT or HEP condition. Participants were followed for 1 year and assessed at weeks 1-7, 8, 24, 36, and 52. Change in depression severity, rate of treatment response and remission after 8 weeks were the primary outcomes measured by the clinician-rated Hamilton Depression Severity Rating (HAM-D) 17-item scale. The participant-rated Quick Inventory of Depression Symptomology (QIDS-SR) 16-item scale was the secondary outcome measure of depression severity, response, and remission., Discussion: Treatment-resistant depression entails significant morbidity and has few effective treatments. We studied the effect of augmenting antidepressant medication with MBCT, compared with a HEP control, for patients with TRD. Analyses will focus on clinician and patient assessment of depression, participants' clinical global impression change, employment and social functioning scores and quality of life and satisfaction ratings., Trial Registration: ClincalTrials.gov identifier: NCT01021254.

Objectives: We evaluated the efficacy of a hepatitis care coordination intervention to improve linkage to hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccination and clinical evaluation of hepatitis C virus (HCV) infection among methadone maintenance patients., Methods: We conducted a randomized controlled trial of 489 participants from methadone maintenance treatment programs in San Francisco, California, and New York City from February 2008 through June 2011. We randomized participants to a control arm (n = 245) and an intervention arm (n = 244), which included on-site screening, motivational-enhanced education and counseling, on-site vaccination, and case management services., Results: Compared with the control group, intervention group participants were significantly more likely (odds ratio [OR] = 41.8; 95% confidence interval [CI] = 19.4, 90.0) to receive their first vaccine dose within 30 days and to receive an HCV evaluation within 6 months (OR = 4.10; 95% CI = 2.35, 7.17). A combined intervention adherence outcome that measured adherence to HAV-HBV vaccination, HCV evaluation, or both strongly favored the intervention group (OR = 8.70; 95% CI = 5.56, 13.61)., Conclusions: Hepatitis care coordination was efficacious in increasing adherence to HAV-HBV vaccination and HCV clinical evaluation among methadone patients.

To reduce the phenotypic heterogeneity of obsessive-compulsive disorder (OCD) for genetic, clinical and translational studies, numerous factor analyses of the Yale-Brown Obsessive Compulsive Scale checklist (YBOCS-CL) have been conducted. Results of these analyses have been inconsistent, likely as a consequence of small sample sizes and variable methodologies. Furthermore, data concerning the heritability of the factors are limited. Item and category-level factor analyses of YBOCS-CL items from 1224 OCD subjects were followed by heritability analyses in 52 OCD-affected multigenerational families. Item-level analyses indicated that a five factor model: (1) taboo, (2) contamination/cleaning, (3) doubts, (4) superstitions/rituals, and (5) symmetry/hoarding provided the best fit, followed by a one-factor solution. All 5 factors as well as the one-factor solution were found to be heritable. Bivariate analyses indicated that the taboo and doubts factor, and the contamination and symmetry/hoarding factor share genetic influences. Contamination and symmetry/hoarding show shared genetic variance with symptom severity. Nearly all factors showed shared environmental variance with each other and with symptom severity. These results support the utility of both OCD diagnosis and symptom dimensions in genetic research and clinical contexts. Both shared and unique genetic influences underlie susceptibility to OCD and its symptom dimensions.

This investigation is a secondary analysis of demographic, smoking, and depression information in a global sample of Spanish- and English-speaking smokers who participated in a series of randomized controlled smoking cessation trials conducted via the Internet. The final sample consisted of 17,579 smokers from 157 countries. Smoking profiles were similar across languages and world regions and consistent with characteristics of participants in traditional smoking cessation studies. Participants were predominantly Spanish-speakers, evenly divided between men and women and relatively few indicated using traditional smoking cessation methods (e.g., groups or medication). This study demonstrates that substantial numbers of smokers from numerous countries seek Web-based smoking cessation resources and adds to the growing support for Web-assisted tobacco interventions as an additional tool to address the need for global smoking cessation efforts.

Objective: The Patient Health Questionnaire depression scale (PHQ-9) is a well-validated, Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV) criterion-based measure for diagnosing depression, assessing severity and monitoring treatment response. The performance of most depression scales including the PHQ-9, however, has not been rigorously evaluated in different racial/ethnic populations. Therefore, we compared the factor structure of the PHQ-9 between different racial/ethnic groups as well as the rates of endorsement and differential item functioning (DIF) of the 9 items of the PHQ-9. The presence of DIF would indicate that responses to an individual item differ significantly between groups, controlling for the level of depression., Measurements: A combined dataset from 2 separate studies of 5,053 primary care patients including non-Hispanic white (n=2,520), African American (n=598), Chinese American (n=941), and Latino (n=974) patients was used for our analysis. Exploratory principal components factor analysis was used to derive the factor structure of the PHQ-9 in each of the 4 racial/ethnic groups. A generalized Mantel-Haenszel statistic was used to test for DIF., Results: One main factor that included all PHQ-9 items was found in each racial/ethnic group with alpha coefficients ranging from 0.79 to 0.89. Although endorsement rates of individual items were generally similar among the 4 groups, evidence of DIF was found for some items., Conclusions: Our analyses indicate that in African American, Chinese American, Latino, and non-Hispanic white patient groups the PHQ-9 measures a common concept of depression and can be effective for the detection and monitoring of depression in these diverse populations.

Objective: To analyze the relationship between perinatal drug/alcohol use and maternal, fetal, neonatal, and postneonatal mortality., Study Design: Linked California discharge, birth and death certificate data from 1991-1998 were used to identify drug/alcohol-diagnosed births. Mortality relative risk (RR) ratios were calculated and logistic models were generated for mortality outcomes., Results: Among 4,536,701 birth records, 1.20% contained drug/alcohol discharge diagnostic codes (n=54,290). The unadjusted RRs for maternal (RR=2.7), fetal (RR=1.3), neonatal (RR=2.4), and postneonatal (RR=4.3) mortality were increased for drug/alcohol-diagnosed births. After controlling for potential confounding, the odds of maternal death for cocaine use (OR=2.15) remained significant as did amphetamine (OR=1.77), cocaine (OR=1.43), polydrug (OR=2.01) and other drug/alcohol use (OR=1.79) for postneonatal mortality., Conclusions: The association of cocaine use with maternal mortality and any drug/alcohol use with postneonatal mortality supports screening and identifying women using illicit drugs and alcohol during pregnancy. Increased collaboration with drug treatment programs and closer follow-up for drug-using women and their children may improve mortality outcomes.

I reviewed sample estimation methods for research designs involving nonindependent data and a dichotomous response variable to examine the importance of proper sample size estimation and the need to align methods of sample size estimation with planned methods of statistical analysis. Examples and references to published literature are provided in this article. When the method of sample size estimation is not in concert with the method of planned analysis, poor estimates may result. The effects of multiple measures over time also need to be considered. Proper sample size estimation is often overlooked. Alignment of the sample size estimation method with the planned analysis method, especially in studies involving nonindependent data, will produce appropriate estimates.

We have previously shown that nicotine enhances cue-induced cocaine craving. In the present study, the effects of a nicotine antagonist, mecamylamine, on cue-induced cocaine craving were investigated. Twenty-three cocaine-dependent patients, all cigarette smokers, were randomly assigned to mecamylamine (2.5 mg tablet) or placebo in a single-dose, placebo-controlled, crossover, double-blind study. Craving and anxiety were measured before and after cocaine cues with visual analog scales for desire to use cocaine and mood. Skin conductance, skin temperature and heart rate were recorded before and during cocaine cues. Following exposure to cocaine cues, all patients reported an increase in cocaine craving and anxiety relative to the precue measures. Cue exposure also produced an increase in skin conductance and decrease in skin temperature. The cue-induced increase in cocaine craving was reduced, while the cue-induced skin conductance and temperature responses were unaffected, by mecamylamine. These findings show that cue-induced cocaine craving is attenuated by mecamylamine. Further study on the use of mecamylamine in relapse prevention programs are suggested.