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Illicit substance use is dangerous in both acute and chronic forms, frequently resulting in lethal poisoning, addiction, and other negative consequences. Similar to research in other psychiatric conditions, whose ultimate goal is to enable effective prevention and treatment, studies in substance use are focused on factors elevating the risk for the disorder. The rapid growth of the substance use problem despite the effort invested in fighting it, however, suggests the need in changing the research approach. Instead of attempting to identify risk factors, whose neutralization is often infeasible if not impossible, it may be more promising to systematically reverse the perspective to the factors enhancing the aspect of liability to disorder that shares the same dimension but is opposite to risk, that is, resistance to substance use. Resistance factors, which enable the majority of the population to remain unaffected despite the ubiquity of psychoactive substances, may be more amenable to translation. While the resistance aspect of liability is symmetric to risk, the resistance approach requires substantial changes in sampling (high-resistance rather than high-risk) and using quantitative indices of liability. This article provides an overview and a practical approach to research in resistance to substance use/addiction, currently implemented in a NIH-funded project. The project benefits from unique opportunities afforded by the data originating from two longitudinal twin studies, the Virginia Twin Study of Adolescent and Behavioral Development and the Minnesota Twin Family Study. The methodology described is also applicable to other psychiatric disorders. more...

Introduction: Prediction of high-risk events amongst patients with mental disorders is critical for personalized interventions. In our previous study, we developed a deep learning-based model, DeepBiomarker by utilizing electronic medical records (EMR) to predict the outcomes of patients with suicide-related events in post-traumatic stress disorder (PTSD) patients. Methods We improved our deep learning model to develop DeepBiomarker2 through data integration of multimodal information: lab tests, medication use, diagnosis, and social determinants of health (SDoH) parameters (both individual and neighborhood level) from EMR data for outcome prediction. We further refined our contribution analysis for identifying key factors. We applied DeepBiomarker2 to analyze EMR data of 38,807 patients from University of Pittsburgh Medical Center diagnosed with PTSD to determine their risk of developing alcohol and substance use disorder (ASUD). Results DeepBiomarker2 predicted whether a PTSD patient will have a diagnosis of ASUD within the following 3 months with a c-statistic (receiver operating characteristic AUC) of 0·93. We used contribution analysis technology to identify key lab tests, medication use and diagnosis for ASUD prediction. These identified factors imply that the regulation of the energy metabolism, blood circulation, inflammation, and microbiome is involved in shaping the pathophysiological pathways promoting ASUD risks in PTSD patients. Our study found protective medications such as oxybutynin, magnesium oxide, clindamycin, cetirizine, montelukast and venlafaxine all have a potential to reduce risk of ASUDs. Discussion DeepBiomarker2 can predict ASUD risk with high accuracy and can further identify potential risk factors along with medications with beneficial effects. We believe that our approach will help in personalized interventions of PTSD for a variety of clinical scenarios. more...

Because the construct of psychopathy is of chief interest across different disciplines, spanning developmental, clinical, and forensic psychology, its assessment bears far-reaching implications. One prominent contemporary conceptualization of psychopathy, the Triarchic Model, posits that a psychopathic personality encompasses three phenotypic constructs: boldness, meanness, and disinhibition. Recently, triarchic scales have been derived based on items from the Multidimensional Personality Questionnaire (MPQ), and the psychometric characteristics of this approach (MPQ-triarchic [MPQ-Tri]) are promising. The present study examined the longitudinal measurement invariance and the construct validity of the MPQ-Tri scales in a large and diverse high-risk sample (N = 716) across four time points from age 16-25. First, we report and discuss implications of confirmatory and exploratory factor analyses of the MPQ-Tri scales. Next, we report evidence for longitudinal configural and partial scalar invariance. In addition, in line with previous studies, MPQ-Boldness showed relatively higher levels of rank-order and mean-level stability compared to MPQ-Meanness and Disinhibition. Finally, in terms of construct validity, the MPQ-Tri scales showed a pattern of association with external correlates across internalizing and externalizing domains that were largely in line with theoretical expectations. One partial exception concerned the limited discriminant validity of the MPQ-Meanness and Disinhibition scales. On balance, the present findings suggest that the MPQ-Tri scales fulfill their intended purpose, with some noted limitation, and provide grounds for the use of the MPQ-Tri scales in developmentally-informed studies on the etiology and consequences of psychopathy. (PsycInfo Database Record (c) 2021 APA, all rights reserved). more...

The association between physical inactivity and substance use throughout adolescence was prospectively investigated in relation to developing cannabis use disorder (CUD). Physical inactivity and substance use in males (N = 462) and females (N = 178) were measured at 12-14, 16, 19, and 22 years of age in a repeated measures design. A structured diagnostic interview was administered to formulate current CUD diagnosis at 22 years of age. Mixture modeling path analysis evaluated the association between physical inactivity, substance use, and CUD. Males: Slope of physical inactivity increase spanning 12-22 years of age mediates the association between number of parents with substance use disorder (SUD) and rate of increase in substance use frequency (prodrome) which mediates the association between physical inactivity (hypothesized vulnerability) and CUD. Females: Number of SUD parents predicts slope of physical inactivity increase in daughters throughout adolescence which covaries with slope of increasing substance use frequency culminating in CUD. The association between parental SUD load (number of SUD affected parents) and CUD was found to not be mediated by physical inactivity. Rate of increase in physical inactivity during adolescence in males and females is a facet of the vulnerability for CUD. These results have ramifications for prevention considering that numerous cognitive, behavior, and emotion features of CUD vulnerability are attenuated by exercise. (PsycInfo Database Record (c) 2022 APA, all rights reserved). more...

Self-regulation is considered a major predictor of crime and deviant behavior. However, longitudinal research investigating these associations, frequently looked only at the effect of self-regulation on deviant behavior, but not the other way around. The current study argued that deviance may contribute to later problems in self-regulation, and examined bidirectional associations, comparing a unidirectional and bidirectional model of associations between these variables. A Random Intercept Cross-Lagged Panel Model and eight data waves from 772 participants, aged 10–12 years to 30 years were used. Results showed that a bidirectional model fit the data better than a unidirectional model. The final model revealed an influence of deviance on self-regulation mainly in adolescence, whereas self-regulation influenced deviance only over two time points in adulthood. The results suggest that, in adolescence, problems in self-regulation may follow, rather than precede deviant behavior. Thus, decreasing deviant behavior or intervening in the aftermaths of deviant behavior in adolescence might have a positive effect on self-regulation in young adulthood, lowering the chance of adult deviant behavior. The current study shows that the long-presumed directionality of self-regulation to deviance can lead to bias, and more rigorous longitudinal research is needed in order to further inform theory and practice. more...

Background Patient-reported outcomes are essential to understand the relationship between patients’ perception of sedation and clinicians’ assessments of sedation. Objectives To evaluate the association between sedation and agitation indexes and patient-reported outcomes of sedation and analgesia. Methods This prospective, single-center, observational study included adult patients who were continuously sedated for at least 24 hours in a medical or surgical/ trauma intensive care unit. Patients were interviewed after sedation was discontinued regarding their satisfaction with the quality of sedation and potentially related factors. The primary outcome was the correlation between sedation and agitation indexes and patient-reported outcomes. Results A total of 68 patients were interviewed after sedation. Of these, 29 (42.6%) described their overall feelings about their experience while receiving mechanical ventilation in the intensive care unit as "pleasant". When asked about their desires if they were to experience the situation again, 29 patients (42.6%) reported that they would want more sedation. Agitation index was statistically significantly correlated with several patient-reported outcomes. Receiving mechanical ventilation (r = 0.41, P = .002), the amount of noise (r = 0.34, P = .01), suctioning (r = 0.32, P = .02), difficulty resting or sleeping (r = 0.39, P = .003), inability to communicate by talking (r = 0.36, P = .008), anxiety (r = 0.29, P = .03), panic (r = 0.3, P = .02), and frustration (r = 0.47, P < .001) were associated with a higher agitation index. Conclusion Agitation index was significantly associated with several patient-reported outcomes and thus seems to be a promising descriptor of patients’ experience. more...

Text messaging (SMS) interventions incorporating a combination of behavior change techniques can assist reductions in alcohol consumption among young adult hazardous drinkers, but mechanisms of action remain unknown. In this secondary analysis, we test the hypothesis that desire to get drunk (DD) recorded prior to drinking episodes would mediate SMS intervention effects on the likelihood of event-level heavy drinking (4 +/5 + drinks for women/men). We recruited young adult hazardous drinkers to a trial where they were randomized to 1 of 5 SMS interventions: TRACK (self-monitoring of alcohol use), PLAN (feedback on drinking plans and DD), USE (postdrinking feedback on alcohol consumed), GOAL (goal prompts/support), and COMBO (i.e., 4 interventions combined). Up to 3 days per week for 14 weeks, when participants reported a plan to drink, they were asked to report DD on a scale from 0 (none) to 8 (completely) and next day asked to recall drink quantity. Multilevel structural equation models showed that DD mediated the treatment effect of GOAL on heavy drinking. This work illustrates the importance of goal support features in digital alcohol interventions and the utility of measuring desire to get drunk as a key mediator in alcohol studies. (PsycINFO Database Record (c) 2020 APA, all rights reserved). more...

Background: Severity of substance use disorder (SUD) is typically evaluated by tabulating the number of symptoms. The resulting estimate of disorder severity is, however, biased due to intercorrelations among symptoms and their unequal salience. Objective. Employing item response theory (IRT) methodology, opioid use disorder symptoms were calibrated to derive the Opioid Use Disorder Severity Scale (OUDSS) and assess its predictive ability in men and women separately. Methods: A two-parameter IRT model was utilized to derive the OUDSS from DSM-IV symptoms recorded on the Structured Clinical Interview for DSM-IV (SCID) in 438 men and 429 women who reported at least one lifetime opioid consumption event. The predictive ability of the OUDSS was evaluated using the 10 health, psychological, and social adjustment domains of the revised Drug Use Screening Inventory (DUSI-R) assessed 2 years later. Results: The OUDSS score predicted the severity of problems in all 10 DUSI-R domains in men and women. The OUDSS also predicted the DUSI-R diagnostic cutoff score of overall problem density score in men and women (OR = 2.21 and OR = 4.83, respectively). Withdrawal was the most frequently endorsed symptom in this sample of opioid users. The other symptoms' frequencies, while somewhat lower than withdrawal's, did not differ from it substantially, indicating a similar severity threshold. Conclusions: OUDSS enables dimensional measurement of opioid use severity on an interval scale. The OUDSS and DUSI-R together can identify problem areas requiring prevention or treatment. more...

Overdose of acetaminophen (APAP) is the leading cause of acute liver failure (ALF) in the United States. The sulfotransferase-mediated sulfation of APAP is widely believed to be a protective mechanism to attenuate the hepatotoxicity of APAP. The cholesterol sulfotransferase SULT2B1b is best known for its activity in catalyzing the sulfoconjugation of cholesterol to synthesize cholesterol sulfate. SULT2B1b can be transcriptionally and positively regulated by the hepatic nuclear factor 4α (HNF4α). In this study, we uncovered an unexpected role for SULT2B1b in APAP toxicity. Hepatic overexpression of SULT2B1b sensitized mice to APAP-induced liver injury, whereas ablation of the Sult2B1b gene in mice conferred resistance to the APAP hepatotoxicity. Consistent with the notion that Sult2B1b is a transcriptional target of HNF4α, overexpression of HNF4α sensitized mice or primary hepatocytes to APAP-induced hepatotoxicity in a Sult2B1b-dependent manner. We conclude that the HNF4α-SULT2B1b axis has a unique role in APAP-induced acute liver injury, and SULT2B1b induction might be a risk factor for APAP hepatotoxicity. more...

Post-traumatic stress disorder (PTSD) is a prevalent mental disorder marked by psychological and behavioral changes. Currently, there is no consensus of preferred antipsychotics to be used for the treatment of PTSD. We aim to discover whether certain antipsychotics have decreased suicide risk in the PTSD population, as these patients may be at higher risk. A total of 38,807 patients were identified with a diagnosis of PTSD through the ICD9 or ICD10 codes from January 2004 to October 2019. An emulation of randomized clinical trials was conducted to compare the outcomes of suicide-related events (SREs) among PTSD patients who ever used one of eight individual antipsychotics after the diagnosis of PTSD. Exclusion criteria included patients with a history of SREs and a previous history of antipsychotic use within one year before enrollment. Eligible individuals were assigned to a treatment group according to the antipsychotic initiated and followed until stopping current treatment, switching to another same class of drugs, death, or loss to follow up. The primary outcome was to identify the frequency of SREs associated with each antipsychotic. SREs were defined as ideation, attempts, and death by suicide. Pooled logistic regression methods with the Firth option were conducted to compare two drugs for their outcomes using SAS version 9.4 (SAS Institute, Cary, NC, USA). The results were adjusted for baseline characteristics and post-baseline, time-varying confounders. A total of 5294 patients were eligible for enrollment with an average follow up of 7.86 months. A total of 157 SREs were recorded throughout this study. Lurasidone showed a statistically significant decrease in SREs when compared head to head to almost all the other antipsychotics: aripiprazole, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone (p &lt, 0.0001 and false discovery rate-adjusted p value &lt, 0.0004). In addition, olanzapine was associated with higher SREs than quetiapine and risperidone, and ziprasidone was associated with higher SREs than risperidone. The results of this study suggest that certain antipsychotics may put individuals within the PTSD population at an increased risk of SREs, and that careful consideration may need to be taken when prescribed. more...

A gene expression signature (GES) is a group of genes that shows a unique expression profile as a result of perturbations by drugs, genetic modification or diseases on the transcriptional machinery. The comparisons between GES profiles have been used to investigate the relationships between drugs, their targets and diseases with quite a few successful cases reported. Especially in the study of GES-guided drugs&ndash, disease associations, researchers believe that if a GES induced by a drug is opposite to a GES induced by a disease, the drug may have potential as a treatment of that disease. In this study, we data-mined the crowd extracted expression of differential signatures (CREEDS) database to evaluate the similarity between GES profiles from drugs and their indicated diseases. Our study aims to explore the application domains of GES-guided drug&ndash, disease associations through the analysis of the similarity of GES profiles on known pairs of drug&ndash, disease associations, thereby identifying subgroups of drugs/diseases that are suitable for GES-guided drug repositioning approaches. Our results supported our hypothesis that the GES-guided drug&ndash, disease association method is better suited for some subgroups or pathways such as drugs and diseases associated with the immune system, diseases of the nervous system, non-chemotherapy drugs or the mTOR signaling pathway. more...

Introduction We investigated the effect of antihypertensive (aHTN) medications and cholinesterase inhibitors (ChEIs) on the cognitive decline in patients with Alzheimer's disease (AD) and analyzed synergism by chemogenomics systems pharmacology mapping. Methods We compared the effect of aHTN drugs on Mini-Mental State Examination scores in 617 AD patients with hypertension, and studied the synergistic effects. Results The combination of diuretics, calcium channel blockers, and renin-angiotensin-aldosterone system blockers showed slower cognitive decline compared with other aHTN groups (Δβ = +1.46, P, Highlights • Combination of three antihypertensive drug classes slowed down cognitive decline. • Antihypertensives and cholinesterase inhibitor showed synergistic cognitive benefit. • Computational systems pharmacology revealed molecular mechanisms for synergism. more...

Decreased cerebral blood flow (CBF) after cardiac arrest (CA) contributes to secondary ischemic injury in infants and children. We previously reported cortical hypoperfusion with tissue hypoxia early in a pediatric rat model of asphyxial CA. In order to identify specific alterations as potential therapeutic targets to improve cortical hypoperfusion post-CA, we characterize the CBF alterations at the cortical microvascular level in vivo using multiphoton microscopy. We hypothesize that microvascular constriction and disturbances of capillary red blood cell (RBC) flow contribute to cortical hypoperfusion post-CA. After resuscitation from 9 min asphyxial CA, transient dilation of capillaries and venules at 5 min was followed by pial arteriolar constriction at 30 and 60 min (19.6 ± 1.3, 19.3 ± 1.2 µm at 30, 60 min vs. 22.0 ± 1.2 µm at baseline, p more...

Conflicting data exists on the efficacy of antipsychotics for treatment of intensive care unit (ICU) delirium. The purpose of this study was to compare time to delirium resolution for ICU patients who were managed with and without antipsychotics.This retrospective cohort evaluation included patients admitted to 12 ICUs at 5 sites over 5 weeks diagnosed with delirium. The primary outcome was time to delirium resolution. Secondary outcomes included ICU length of stay (LOS), mortality, discharge disposition and delirium redevelopment. A Cox proportional hazards model explored the relationship between covariates including antipsychotics and time to delirium resolution.A total of 255 patients met inclusion criteria; 69 (27%) received antipsychotics. In the antipsychotic group, time to resolution of delirium was longer (Median: 36hours vs. 13hours, p0.001) and ICU LOS was longer (Median: 5.9days vs. 3.8days, p=0.005), but there were no differences in mortality or discharge disposition. Patients who used antipsychotics (HR=0.512; 95% CI: 0.276-0.952) and received mechanical ventilation (HR=0.381; 95% CI: 0.217-0.669) had slower rate for time to delirium resolution.While the treatment of delirium with antipsychotics remains common, antipsychotics were not associated with a shorter time to resolution of delirium. more...

Adolescence and emerging adulthood are developmental periods associated with increased risk taking, including alcohol and substance use and antisocial behaviors. Typical psychological growth from adolescence into early adulthood reflects increases in traits related to psychological regulation (e.g., greater emotional stability and less impulsivity), which are typically considered protective factors against risk behaviors. However, individuals may vary greatly in their development of these characteristics. This study examines the degree to which heterogeneity in developmental trajectories of psychological regulation are associated with later performance on decision-making skills battery. In this study, psychological regulation was assessed at age 10–12, with follow-up assessments at 14, 16, and 19 years. At age 19, we administered the Youth Decision-Making Competence (DMC; Parker & Fischhoff, 2005) measure. Correlational analyses revealed that lower psychological regulation, as early as age 10, was associated with lower DMC scores. A latent class growth mixture model yielded three distinct developmental trajectory classes of psychological dysregulation: (a) a Moderate-Stable group, a modal class that demonstrated stable and average regulative tendencies throughout adolescence, (b) a Low-Decreasing group, which demonstrated greater self-regulation throughout childhood, and a (c) High-Increasing group, which demonstrated low self-regulative tendencies (higher dysregulation) at age 10 that became increasingly dysregulated throughout adolescence. Individuals in the High-Increasing group demonstrated lower DMC performance than those in the Moderate-Stable and Low-Decreasing groups. Our findings also reinforce past work that indicates considerable individual differences in intra-individual change across adolescence, and that early patterns of psychological dysregulation development can impact later decision-making tendencies. more...

Background: The development of person-centered medical education is inscribed within an international programmatic movement toward a medicine focused on the totality of the person. This movement, with broad historical bases, has been maturing since 2008 through conferences with global health institutions, research projects, and academic publications. A key challenge in the application of person-centered medicine (PCM) to the practice of medicine has been the elucidation of its core principles and the development of operationalized measures that allows for assessment of the degree of person-centeredness in clinical care and medical education. more...

Objectives To examine the differential impact of depressive and manic mood states on alcohol craving in patients with bipolar disorder and comorbid alcoholism. Methods Forty-four men and women, ages 18-65, with DSM-IV-TR comorbid diagnoses of bipolar I disorder and alcohol dependence were assessed over a three-month period to examine the extent to which their depressive and manic symptoms were associated with alcohol cravings (i.e., desire to use and not to use alcohol) at each assessment point, controlling for age, ethnicity, socio-economic status, baseline alcohol use, and number of assessments. Results Both manic and depressive symptoms were associated with greater desire to use alcohol. Only depressive symptomatology was associated with reduced desire not to use alcohol, and desire not to use alcohol declined over the course of the three-month treatment period. Conclusion Whereas enhanced desire to drink alcohol may be a conditioned reaction to both manic and depressed mood states, desire not to drink alcohol may be more of an indicator of treatment motivation, which is negatively affected by depressed mood. Depressive symptoms may warrant prioritization and aggressive targeting early in treatment given that desire to refrain from alcohol use was only influenced by depressive symptoms and declined over the course of treatment. more...

This was a first double-blind, placebo-controlled pilot study to evaluate the efficacy of the novel antidepressant medication mirtazapine for treating both the depressive symptoms and the level of alcohol consumption of subjects with comorbid major depressive disorder and an alcohol use disorder (MDD/AUD). The results of two previous studies of mirtazapine in MDD/AUD subjects had suggested efficacy for mirtazapine for decreasing their level of depressive symptoms, but level of alcohol consumption had not been assessed in those studies. All subjects in this 12-week pilot study were randomized to either mirtazapine or placebo, and also received motivational enhancement therapy. Between-group analyses involving the outcome measures of depressive symptoms, level of alcohol consumption, and level of alcohol craving indicated no significant differences between groups, possibly because of limited sample size. However, within-group t tests in the mirtazapine group showed a significant decrease in depressive symptoms by week 2, also noted at all subsequent assessments (weeks 3, 4, 6, 8, 10, and 12) during the 12-week study. In contrast, no significant decrease in depressive symptoms was noted in the placebo group until week 8. No evidence of efficacy was found for mirtazapine for decreasing level of alcohol consumption in MDD /AUD subjects. more...

OBJECTIVE: Limited prospective data indicate that premorbid sleep disturbances elevate the risk for subsequent alcohol and other drug problems, yet the implications for subsequent substance involvement trajectories remain unclear. In the present analyses, we examined risk associations between sleep characteristics during late childhood and the onset of substance use and substance use disorders into adulthood. METHOD: A sample of 707 children was recruited at ages 9-13 years and followed over seven additional visits through age 30 years. In 304 participants, fathers had a history of substance use disorder involving illicit drugs. Self-reported baseline sleep characteristics (restless sleep and variable sleep timing) were assessed at approximately ages 9-13 years. Assessment of alcohol, cannabis, and cocaine involvement occurred at follow-up visits. Cox proportional hazard models tested sleep characteristics as predictors of two substance-related outcomes (age at first use or diagnosis of disorder), as well as the onset of major depressive disorder. RESULTS: Restless sleep at baseline significantly predicted an earlier onset age for trying alcohol and cannabis and showed a trend toward predicting early onset of cannabis use disorder. Restless sleep also predicted an earlier onset of depression. Irregular sleep timing at baseline significantly predicted an earlier onset age for alcohol use disorder and showed trends toward predicting early onsets of disorders of cannabis and cocaine use. CONCLUSIONS: Disturbed sleep during late childhood appears to accelerate the onset of not only initial substance use but also the development of clinically defined substance use disorder. Sleep-focused preventative efforts during late childhood may reduce the incidence of mood and substance use disorders. Language: en more...

Objective To evaluate the accuracy of detecting 16-year-old male (n = 465) and female (n = 162) youths who subsequently manifest opioid use disorder (OUD) at 25 years of age. We hypothesized that the combined measures of 2 components of etiology, heritable risk, and substance use, accurately detect youths who develop OUD. Study design Heritable risk was measured by the transmissible liability index (TLI). Severity of the prodrome presaging OUD was quantified by the revised Drug Use Screening Inventory containing the consumption frequency index (CFI) documenting substance use events during the past month and the overall problem density (OPD) score indicating co-occurring biopsychosocial problems. Diagnosis of OUD was formulated by a clinical committee based on results of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition in conjunction with medical and social history records. Results Bivariate analysis shows that the TLI, CFI, and OPD scores at 16 years of age predict OUD at 25 years. Multivariate modeling indicates that the TLI combined with the CFI predict OUD with 86% accuracy (sensitivity = 87%; specificity = 62%). The TLI and CFI at 16 years of age mediate the association between parental substance use disorder and OUD in offspring at 25 years of age, indicating that these measures respectively evaluate risk and prodrome. Conclusions These results demonstrate the feasibility of identifying youths requiring intervention to prevent OUD. more...

BACKGROUND: This longitudinal study explored the utility of machine learning (ML) methodology in predicting the trajectory of severity of substance use from childhood to thirty years of age using a set of psychological and health characteristics. DESIGN: Boys (N=494) and girls (N=206) were recruited using a high-risk paradigm at 10–12 years of age and followed up at 12–14, 16, 19, 22, 25 and 30 years of age. MEASUREMENTS: At each visit, the subjects were administered a comprehensive battery to measure psychological makeup, health status, substance use and psychiatric disorder, and their overall harmfulness of substance consumption was quantified according to the multidimensional criteria (physical, dependence, and social) developed by Nutt et al. (2007). Next, high- and low- substance use severity trajectories were derived differentially associated with probability of segueing to substance use disorder (SUD). ML methodology was employed to predict trajectory membership. FINDINGS: The high-severity trajectory group had a higher probability of leading to SUD than the low-severity trajectory (89.0% vs 32.4%; odds ratio=16.88, p more...

Background: Interest in person-centered medicine is growing in response to serious contemporary limitations and distortions in medicine and health care across the world. The development of generic instruments with substantial metric features to appraise progress toward person-centered care is providing instrumentation to advance the emerging field. more...

Text message (SMS) interventions can reduce binge drinking in young adults, but optimal behavior change techniques (BCTs) remain unknown. The present study tests the acceptability and preliminary efficacy of different combinations of SMS-delivered BCTs. 149 young adults who screened positive for hazardous drinking completed a baseline survey in the Emergency Department. For the following 2-weeks, on days they typically drank (1 to 3 days per week), participants received ecological momentary assessments (EMA) of drinking plans and desire to get drunk; the next day they were prompted to report recall of number of drinks consumed the prior day. Participants who responded to at least 50% these EMA (N = 127) were randomized to one of five 12-week interventions: Cued Self-Monitoring (TRACK); Drinking Intentions Feedback (PLAN); Drinking Performance Feedback (USE); Adaptive Goal Support (GOAL); and a combination of BCTs (COMBO). 79% of all EMA were completed over 12 weeks, which decreased from around 93% on week 1 to 65% by week 12. Using EMA data, relative to TRACK, only COMBO showed significant reductions in binge drinking and max drinks per drinking episode over time. Using TLFB data, there were no significant differences between groups from baseline to 14- and 28-weeks follow-up. Results lay the groundwork for a larger trial testing the effects of BCTs on binge drinking for young adults. more...

This study examined correspondence between timing (onset) and tempo (rate) of sexual maturation prospectively (average ages 11-16 years) measured by gonadal hormones and secondary sex characteristics (Tanner stage) using dual-process models, and associations of these measures with substance use (SU) involvement in boys at age 16 years (N = 534, 77.5% White/22.5% Non-White). All measures of timing were highly associated. Early Tanner stage timing often predicted slower increases in gonadal steroids, but not the reverse; patterns varied by ethnicity. Hormone and Tanner stage measures were similar earlier in development but diverged later in development. In White boys only, early timing of the pubertal rise in testosterone was associated with increased SU involvement, suggesting a physiological rather than psychosocial mechanism of association. [ABSTRACT FROM AUTHOR] more...

Background: The measurement of quality of life as estimate of well being is assuming increasing importance in the evaluation of health and treatment efficacy. Objectives: The aim of this study is to evaluate the applicability, internal structure and clinical patterns of the Multicultural Quality of Life Index (MQLI), a brief, self-rated, culturally informed, quality of life scale, in patients experiencing comorbid psychiatric and substance use disorders. Methods: Sixty-two consecutively admitted outpatients completed the MQLI. With this data, the applicability, internal consistency, factorial structure, and prediction of treatment adherence over a three-month period were assessed. Results: It was found that the MQLI was easy to administer. It had good internal consistency (Cronbach’s alpha 0.89). Factor analysis revealed that the first factor explained 53% of the variance, indicating the unidimensionality of the instrument around quality of life. Two MQLI items, interpersonal functioning and the availability of supports, significantly predicted treatment adherence. Conclusions: The MQLI is easy to use, it has a coherent structure, and is clinically useful in psychiatric patients with comorbid substance use disorders. more...

Prior research indicates that off-label use is common in the ICU; however, the safety of off-label use has not been assessed. The study objective was to determine the prevalence of adverse drug reactions associated with off-label use and evaluate off-label use as a risk factor for the development of adverse drug reactions in an adult ICU population.Multicenter, observational study: Medical ICUs at three academic medical centers.Adult patients (age ≥ 18 yr old) receiving medication therapy.All administered medications were evaluated for Food and Drug Administration-approved or off-label use. Patients were assessed daily for the development of an adverse drug reaction through active surveillance. Three adverse drug reaction assessment instruments were used to determine the probability of an adverse drug reaction resulting from drug therapy. Severity and harm of the adverse drug reaction were also assessed. Cox proportional hazard regression was used to identify a set of covariates that influenced the rate of adverse drug reactions.Overall, 1,654 patient-days (327 patients) and 16,391 medications were evaluated, with 43% of medications being used off-label. One hundred and sixteen adverse drug reactions were categorized dichotomously (Food and Drug Administration or off-label), with 56% and 44% being associated with Food and Drug Administration-approved and off-label use, respectively. The number of adverse drug reactions for medications administered and the number of harmful and severe adverse drug reactions did not differ for medications used for Food and Drug Administration-approved or off-label use (0.74% vs 0.67%; p = 0.336; 33 vs 31 events, p = 0.567; 24 vs 24 events, p = 0.276). Age, sex, number of high-risk medications, number of off-label medications, and severity of illness score were included in the Cox proportional hazard regression. It was found that the rate of adverse drug reactions increases by 8% for every one additional off-label medication (hazard ratio = 1.08; 95% CI, 1.018-1.154).Although adverse drug reactions do not occur more frequently with off-label use, adverse drug reaction risk increases with each additional off-label medication used. more...

Benzodiazepine-resistant alcohol withdrawal (RAW), defined by a requirement of ≥ 40 mg of diazepam in 1 h, represents a severe form of withdrawal without predictive parameters. This study was designed to identify risk factors associated with RAW versus withdrawal without benzodiazepine resistance (nRAW).A retrospective cohort of adults with severe alcohol withdrawal were screened. Demographic and clinical variables, collected through chart review, underwent logistic regression to select the subset that predicst RAW.736 patients (515 nRAW, 221 RAW) were analyzed. RAW patients were younger (P 0.001), male (P = 0.008) Caucasians (P = 0.037) with histories of psychiatric illness (P 0.001), higher serum ethanol concentrations (P 0.007), and abnormal liver enzymes (P = 0.01). RAW patients had significantly lower platelets (P 0.001), chloride (P = 0.02), and potassium (P = 0.01) levels; severity of illness (SAPSII) (P 0.001) and comorbidity scores (P 0.001). Caucasian race and male gender were found to be 3.6 and 2.6 times more likely to be RAW. For every 1-unit increase in comorbidity and severity of illness scores, patients were 22% [OR(95% CI) 0.78 (0.66-0.90)] and 4% [0.96 (0.93-0.98)] less likely to be RAW. Patients with a psychiatric history or thrombocytopenia were 2 times more likely [2.02 (1.24-3.30); 2.13 (1.31-3.50), respectively] to be RAW.These data demonstrate the predictive ability of a history of psychiatric illness, thrombocytopenia, gender, race, baseline severity of illness and comorbidity scores for developing RAW. Considering these characteristics in early withdrawal management may prevent progression to RAW outcomes. more...

Background Psychological items discriminating children of fathers diagnosed with an illicit drug-related substance use disorder and normal controls are indicators of a unidimensional construct termed transmissible liability index (TLI) (Vanyukov et al., 2009). TLI is a highly heritable (Vanyukov et al., 2009; Hicks, Iacono, McGue, 2012) and valid (Vanyukov et al., 2009; Hicks et al., 2009; Kirisci et al., 2013a) measure of childhood liability to substance use disorders (SUDs). Aims This longitudinal study determined whether TLI has incremental validity for predicting SUD beyond commonly measured psychological indicators of risk. Methods TLI and measures of executive cognitive capacity, emotion dysregulation and externalizing disturbance were administered to boys at ages 10–12 and 16. SUD outcome determined at age 22 was assessed as (1) any SUD, (2) the number of drug-specific SUDs, and (3) SUD severity. Results TLI predicted SUD beyond the contribution of measures of emotion dysregulation, executive cognitive capacity and externalizing disturbance. The association of emotion dysregulation and externalizing behavior at ages 10–12 and 16 with SUD at age 22 was also reduced to non-significance after controlling for transmissible risk measured by TLI. Conclusions TLI's incremental validity beyond these latter indicators of risk points to its utility for identifying vulnerable youths requiring intervention. more...

Item response theory (IRT) based studies conducted on diverse samples showed a single dominant factor for DSM-III-R and DSM-IV substance use disorder (SUD) abuse and dependence symptoms of alcohol, cannabis, sedative, cocaine, stimulants, and opiates use disorders. IRT provides the opportunity, within a person-centered framework, to accurately gauge each person's severity of disorder that, in turn, informs required intensiveness of treatment.The aim of this study was to determine whether the SUD symptoms indicate a unidimensional trait or instead need to be conceptualized and quantified as a multidimensional scale.The sample was composed of families of adult SUD+ men (n=349), and SUD+ women (n=173), who qualified for DSM-III-R diagnosis of substance use disorder (abuse or dependence) and families of adult men and women who did not qualify for a SUD diagnosis (SUD- men: n=190, SUD- women: n=133). An expanded version of the Structured Clinical Interview for DSM-III-R (SCID) was administered to characterize lifetime and current substance use disorders. Item response theory methodology was used to assess the dimensionality of DSM-III-R SUD abuse and dependence symptoms.A bi-factor model provided the optimal representation of the factor structure of SUD symptoms in males and females. SUD symptoms are scalable as indicators of a single common factor, corresponding to general (non-drug-specific, common) liability to addiction, combined with drug-specific liabilities.IRT methodology used to quantify the continuous general liability to addiction (GLA) latent trait in individuals having SUD symptoms was found effective for accurately measuring SUD severity in men and women. This may be helpful for person-centered medicine approaches to effectively address intensity of treatment. more...

Liability to substance use disorder (SUD) is largely nonspecific to particular drugs and is related to behavior dysregulation, including reduced cognitive control. Recent data suggest that cognitive mechanisms may be influenced by exposure to neurotropic infections, such as human herpesviruses. In this study, serological evidence of exposure to human herpesvirus Herpes simplex virus Type 1 (HSV-1), cytomegalovirus (CMV), and Epstein–Barr virus (EBV) as well as Toxoplasma gondii was determined in childhood (age ~11 years) in 395 sons and 174 daughters of fathers with or without SUD. Its relationships with a cognitive characteristic (IQ) in childhood and with risk for SUD in adulthood were examined using correlation, regression, survival, and path analyses. Exposure to HSV-1, EBV, and T. gondii in males and females, and CMV in males, was associated with lower IQ. Independent of that relationship, EBV in females and possibly in males, and CMV and possibly HSV-1 in females were associated with elevated risk for SUD. Therefore, childhood neurotropic infections may influence cognitive development and risk for behavior disorders such as SUD. The results may point to new avenues for alleviating cognitive impairment and SUD risk. more...

Background Substance use disorder (SUD) exacts enormous societal costs in the United States, and it is important to detect high-risk youths for prevention. Machine learning (ML) is the method to find patterns and make prediction from data. We hypothesized that ML identifies the health, psychological, psychiatric, and contextual features to predict SUD, and the identified features predict high-risk individuals to develop SUD. Method Male (N = 494) and female (N = 206) participants and their informant parents were administered a battery of questionnaires across five waves of assessment conducted at 10–12, 12–14, 16, 19, and 22 years of age. Characteristics most strongly associated with SUD were identified using the random forest (RF)algorithm from approximately 1000 variables measured at each assessment. Next, the complement of features was validated, and the best models were selected for predicting SUD using seven ML algorithms. Lastly, area under the receiver operating characteristic curve (AUROC) evaluated accuracy of detecting individuals who develop SUD+/- up to thirty years of age. Results Approximately thirty variables strongly predict SUD. The predictors shift from psychological dysregulation and poor health behavior in late childhood to non-normative socialization in mid to late adolescence. In 10–12-year-old youths, the features predict SUD+/- with 74% accuracy, increasing to 86% at 22 years of age. The RF algorithm optimally detects individuals between 10–22 years of age who develop SUD compared to other ML algorithms. Conclusion These findings inform the items required for inclusion in instruments to accurately identify high risk youths and young adults requiring SUD prevention. more...

Background. Prevention of substance use disorder (SUD) is impeded by the large number, complexity and idiosyncratic configuration of etiological factors. Effective prevention of SUD is feasible however when intervention resources are prioritized to individuals who are objectively determined high risk and tailored to their specific characteristics and circumstances.Objective. This study had the aim of developing a rapid accurate screening instrument for determining current presence of and future risk for SUD. Methods. The sample consisted of 182 girls recruited when they were 10-12 years of age and tracked to 22 years of age. From a large item pool the Drug Use Screening Inventory Quick Screen for Females (DQS-F) was derived consisting of the Substance Involvement Index and the Problem Severity Index.Results. The DQS for Females (DQS-F) has high sensitivity for identifying girls who currently qualify for SUD diagnosis. Furthermore, accuracy of predicting future SUD with the DQS-F is in the good range at age 16 and in the very good range at age 19.Conclusions. Requiring only three minutes for administration on the Web the DQS-F is an efficient method for identifying girls requiring thorough assessment prior to implementing individualized intervention. more...

This prospective study tested the hypothesis that psychological dysregulation in mid-adolescence (age 16) mediates the association between parent-child attachment in late childhood (age 10-12) and development of substance use disorder (SUD) in adulthood (age 22).The Youth Attachment to Parents Scale (YAPS) was developed in 10-12-year-old boys and girls (N = 694) at baseline residing in western Pennsylvania. Psychological dysregulation was measured by the neurobehavior disinhibition trait. Substance use was assessed at ages 10-12, 12-14, 16 and 19. SUD was diagnosed at age 22 using the Structured Clinical Interview for DSM Disorders. The mediation of parent-child attachment and SUD by neurobehavior disinhibition was tested separately for mothers and fathers while controlling for baseline substance use.Psychological dysregulation mediates the association between attachment to mothers and SUD, and partially mediates the association between attachment to fathers and SUD. Significant mediation effects remains after controlling for baseline substance use.Optimal prevention of SUD should include ameliorating both psychological dysregulation predisposing to SUD and quality of the parent-child relationship. more...

Background This prospective study investigated pubertal timing and transmissible risk in relation to affiliation with deviant peers on the development of substance use disorder (SUD). Method Participants were boys (N = 500) ascertained through proband fathers with (N = 250), and without (N = 250) DSM-III-R lifetime diagnosis of SUD who were prospectively tracked from age 10–12 to 22. Transmissible liability index (TLI), Tanner stage, peer delinquency, and substance use were measured at ages 10–12 and 16. SUD diagnosis during early adulthood was determined. Results Structural equation modeling revealed two pathways in which transmissible risk and sexual maturation influenced development of SUD. In the first pathway, transmissible risk was correlated with and prospectively predicted affiliation with deviant peers and substance use presaging SUD. In the second pathway, advanced sexual maturation positively predicted affiliation with deviant peers and substance use, which in turn predicted SUD. However, transmissible risk was not associated with pubertal development. Conclusion These findings indicate that advanced sexual maturation and transmissible risk constitute unrelated facets of SUD liability; however, both factors bias development toward SUD via affiliation with deviant peers. Scientific Significance Youth with advanced sexual maturation and/or transmissible risk for SUD are at higher risk for developing SUD. Additional research is needed to determine if addressing these risk factors will contribute to advancements in SUD prevention. (Am J Addict 2013;22:474–480) more...

Risk for substance use disorder is frequently transmitted across generations due to significant heritability.This longitudinal study tests the hypothesis that initial exposure to cannabis in youths having high transmissible risk is a signal event promoting development of cannabis use disorder (CUD).At age 22, 412 men were classified into three groups: (1) lifetime CUD, (2) cannabis use without CUD, and (3) no lifetime cannabis use. Transmissible risk, quantified on a continuous scale using the previously validated transmissible liability index (TLI), along with cannabis use and CUD were documented at 10-12, 12-14, 16, 19, and 22 years of age.The CUD group scored higher on the TLI before they began cannabis use compared to the other two groups. In addition, a progressive increase in TLI severity was evinced by the CUD group beginning at the time of initiation of cannabis use whereas cannabis users who did not subsequently develop CUD exhibited a decline in transmissible risk following first exposure.Initial use of cannabis potentiates development of CUD in youths who are at high transmissible risk but is inconsequential in youths having low risk. The practical ramifications of these results for prevention are discussed. more...

Background: A world-wide movement is emerging for person centered medicine and healthcare collaboratively developed by the International College of Person Centered Medicine and a number of global institutions through annual Geneva Conferences and International Congresses as well as scholarly publications. While frequently quoted definitional note have been advanced through this maturational process, efforts are needed to conceptualize and measure systematically person-centered care. Objectives: These included the elucidation of the core concepts of person centered medicine and healthcare, the design of a prototype measuring instrument, and the study of its metric structure, acceptability, reliability and validity. Methods: The following methodological approaches were employed: A systematic review of the literature, consultation exercises with broad international panels composed of health professionals and representatives of patient and family organizations, and quantitative and qualitative data analyses. Results: The following key concepts underlying person centered medicine were elucidated: 1) Ethical Commitment, 2) Cultural Sensitivity, 3) Holistic scope, 4) Relational Focus, 5) Individualized Care, 6) Common Ground for Collaborative Diagnosis and Care, 7) People-centered Systems of Care, and 8) Person-centered Education and Research. On this basis, a Person-centered Care Index was developed composed of 8 broad items and 33 sub-items, each measured on a 4-point scale. The study of its metric structure revealed high Cronbach internal consistency (0.95), scale unidimensionality through factor analysis (69 % of the variance accounted for by the first factor), and interesting inter-correlations such as the sub-item attaining the highest correlation with the global average score being “fulfillment of the person’s life project” (0.88). Validation studies in California, London and Lucknow (India) showed quite high levels of inter-rater reliability (above 0.80 intra-class correlations for most items) and substantial content validity. Discussion: The elucidated core concepts of person centered medicine appear to be consistent with those of international studies on the bases of person- and people-centeredness in primary care and on research and implementation of person centered care. The concepts are also consistent with the key domains of person-centered diagnostic approaches. Further validation studies with larger samples in diverse settings and cultures seem to be warranted. Conclusions. The emerging core concepts of person centered medicine appear to be solid. The Person-centered Care Index built on such concepts appears to have suitable metrics and promising acceptability, reliability and content validity. Further empirical research is recommended. more...

Background. Item response theory (IRT) based studies conducted on diverse samples showed a single dominant factor for DSM-III-R and DSM-IV substance use disorder (SUD) abuse and dependence symptoms of alcohol, cannabis, sedative, cocaine, stimulants, and opiates use disorders. IRT provides the opportunity, within a person-centered framework, to accurately gauge each person’s severity of disorder that, in turn, informs required intensiveness of treatment. Objectives. The aim of this study was to determine whether the SUD symptoms indicate a unidimensional trait or instead need to be conceptualized and quantified as a multidimensional scale. Methods. The sample was composed of families of adult SUD+ men (n=349), and SUD+ women (n=173), who qualified for DSM-III-R diagnosis of substance use disorder (abuse or dependence) and families of adult men and women who did not qualify for a SUD diagnosis (SUD- men: n=190, SUD- women: n=133). An expanded version of the Structured Clinical Interview for DSM-III-R (SCID) was administered to characterize lifetime and current substance use disorders. Item response theory methodology was used to assess the dimensionality of DSM-III-R SUD abuse and dependence symptoms.Results. A bi-factor model provided the optimal representation of the factor structure of SUD symptoms in males and females. SUD symptoms are scalable as indicators of a single common factor, corresponding to general (non-drug-specific, common) liability to addiction, combined with drug-specific liabilities. Conclusions. IRT methodology used to quantify the continuous general liability to addiction (GLA) latent trait in individuals having SUD symptoms was found effective for accurately measuring SUD severity in men and women. This may be helpful for person-centered medicine approaches to effectively address intensity of treatment. more...

Since the inception of Person Centered Medicine (PCM) as a programmatic movement, one could find the articulation of science and humanism as a core concept. This revealed a prominent concern for conceptual clarity, illustratively to formulate humanism as the essence of medicine as well as to engage the scientific method as an essential tool. An ongoing scientific effort in PCM involves systematic conceptualization. Another one, reflecting concern for precision in description and prediction, looks at metrics and measurement in its various forms and levels. These two lines of work are outlined below. more...