Search

Cholecystokinin (CCK) has been suggested to be both pro-nociceptive and "anti-opioid" by actions on pain-modulatory cells within the rostral ventromedial medulla (RVM). One consequence of activation of RVM CCK₂ receptors may be enhanced spinal nociceptive transmission; but how this might occur, especially in states of pathological pain, is unknown. Here, in vivo microdialysis was used to demonstrate that levels of RVM CCK increased by approximately 2-fold after ligation of L₅/L₆ spinal nerves (SNL). Microinjection of CCK into the RVM of naïve rats elicited hypersensitivity to tactile stimulation of the hindpaw. In addition, RVM CCK elicited a time-related increase in (prostaglandin-E₂) PGE₂ measured in cerebrospinal fluid from the lumbar spinal cord. The peak increase in spinal PGE₂ was approximately 5-fold and was observed at approximately 80 minutes post-RVM CCK, a time coincident with maximal RVM CCK-induced mechanical hypersensitivity. Spinal administration of naproxen, a nonselective COX-inhibitor, significantly attenuated RVM CCK-induced hindpaw tactile hypersensitivity. RVM-CCK also resulted in a 2-fold increase in spinal 5-hydroxyindoleacetic acid (5-HIAA), a 5-hydoxytryptophan (5-HT) metabolite, as compared with controls, and mechanical hypersensitivity that was attenuated by spinal application of ondansetron, a 5-HT₃ antagonist. The present studies suggest that chronic nerve injury can result in activation of descending facilitatory mechanisms that may promote hyperalgesia via ultimate release of PGE₂ and 5-HT in the spinal cord. [ABSTRACT FROM AUTHOR]

BACKGROUND: This study was undertaken to determine if alcohol use is associated with sexual risk taking among human immunodeficiency virus (HIV)-infected persons. METHODS: Cross-sectional interviews of 262 HIV-infected patients in the Brown University AIDS Program were performed. Factors associated with any sexual activity, unsafe sexual activity, and a 4-fold typology of sexual risk were examined. Alcohol measures included drinking days, drinks per drinking day, binge drinking, and hazardous alcohol use. RESULTS: The sample was 58% male and 40% white; 67% of patients were self-identified as heterosexual, and 48% drank alcohol. Nearly two thirds of patients reported sexual activity in the past 6 months, with 38% reporting unprotected sex during that period. All measures of alcohol use were significantly associated with any sexual activity and with unsafe sexual behavior. As an example, controlling for age, HIV transmission risk, marital status, and HIV clinical indicators, hazardous drinkers were 5.64 times more likely to report unprotected sex and have multiple partners (p < 0.01) than were those not drinking at hazardous levels. CONCLUSIONS: A high proportion of HIV-infected persons were sexually active and having unsafe sex. Alcohol, at all levels of use, was associated with increased sexual risk taking. [ABSTRACT FROM AUTHOR]

Sleep disturbance is common among patients in recovery from alcoholism and can precipitate relapse. Though sleep complaints are commonly managed with medication, little is known about their management among recovering alcoholic patients. We performed a postal survey of a self-weighted, random systematic sample of 503 members of the American Society of Addiction Medicine (ASAM) to examine addiction medicine physicians' medical management of sleep disturbance among patients in early recovery from alcoholism. After 3 mailings, 311 (62%) responded. Of responents, 64% have offered pharmacological treatment to an insomniac, alcoholic patient in the first 3 months after detoxification, but only 22% offered medication to more than half of such patients. Trazodone was the preferred therapy, chosen first by 38% of respondents, followed by other sedating antidepressants (12%), and antihistamines (12%). The mean duration of therapy for trazodone and other sedating antidepressants exceeded one month. Experts in addiction medicine appear reluctant to prescribe medication to sleep-disturbed patients in early recovery from alcoholism. When they do prescribe, trazodone, other sedating antidepressants and antihistamines are favored, despite limited evidence for or against this indication. Although the treatment of disordered sleep among alcoholic patients in early recovery may have merit to prevent relapse, controlled studies of these sleep agents are needed. [ABSTRACT FROM AUTHOR]

Background: Chronic pain and non-prescribed substance use are associated with lower retention in opioid use disorder (OUD) treatment. We examined the associations of perceived capacity to tolerate uncomfortable physical sensations (discomfort intolerance and discomfort avoidance) and cannabis and alcohol use among persons with chronic pain receiving prescription buprenorphine for OUD., Methods: This study utilizes baseline data from 163 persons with chronic pain receiving prescription buprenorphine for OUD enrolled in the Treating Opioid use, Persistent Pain, and Sadness (TOPPS) intervention trial. We used negative-binomial regression models, adjusted for age, education, gender, race/ethnicity, pain interference, depression, generalized anxiety disorder, and average cigarettes smoked/day to estimate the associations of discomfort tolerance and discomfort avoidance with frequency of cannabis and alcohol use., Results: Participants (n=163) were on average 45 years old (standard deviation=10.6) and predominantly White (86 %, n=141). Forty-one percent (n=66) used cannabis and 24 % (n=30) used alcohol use in the past 30 days. In adjusted models, discomfort intolerance was positively associated with days of cannabis use (IRR = 1.11, p =.016) and days of alcohol use (IRR = 1.14, p =.022). Discomfort avoidance was not associated with cannabis or alcohol use., Conclusion: Individuals with chronic pain receiving prescribed buprenorphine for treatment of OUD with lower tolerance for physical discomfort may augment pain management with cannabis and alcohol. Given the intersections between substance use and retention in care for OUD, future work should extend this preliminary work by exploring these relationships over time and in experimental settings. Clinical Trial # NCT03698669., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Risa B. Weisberg reports a relationship with RealizedCare that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Primary aldosteronism (PA) is the most common cause of secondary hypertension, yet screening remains startlingly infrequent. We describe: 1) PA screening practices in a large, diverse health system, 2) the development of a computable phenotype for PA screening, and 3) the design and pilot deployment of an electronic health record (EHR)-based active choice nudge to recommend PA screening., Study Design: A multidisciplinary team developed a multi-pronged intervention to improve PA screening informed by guidelines, expertise, and multivariable analyses of factors associated with screening. The intervention included EHR-based tools to automatically identify screen-eligible patients, an active choice nudge recommending screening for these patients, and screening result interpretation. The intervention was piloted across two primary care practices for seven months. Screening frequencies were compared to clinics not receiving the intervention., Results: The baseline frequency of screening of eligible patients within one year was 1.4%. Higher mean systolic blood pressure (OR=1.4; p<0.001), more antihypertensive medications (OR=1.3; p=0.002), lower minimum serum potassium (OR=2.0; p=0.001), specialist care (OR=3.0; p<0.001), and Black race (OR=1.5; p=0.001) were associated with a higher likelihood of screening. The refined computable phenotype identified a subcohort with a higher frequency of positive screening (8.6% versus 4.1%; p=0.03). In a pilot study of an active choice nudge, a greater proportion of eligible patients were screened in the intervention clinics (16.4%) than in the non-intervention clinics (1.8%; p<0.001)., Conclusion: PA screening rates are low. This pilot study suggests an EHR-based nudge leveraging a precise computable phenotype can dramatically increase appropriate PA screening., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Persons receiving prescription buprenorphine for opioid use disorder experience high rates of comorbid conditions such as chronic pain and depression, which present barriers to buprenorphine care retention. This paper describes the protocol of the TOPPS (Treating Opioid Patients' Pain and Sadness) study, which compares a values-based, behavioral activation intervention with a health education contact-control condition, with the aim of decreasing chronic pain and depression, and increasing buprenorphine care retention for persons with opioid use disorder., Methods: This randomized controlled trial (RCT) enrolls and randomizes up to 250 participants currently being treated with buprenorphine to receive three months of either TOPPS, a six-session phone-based behavioral intervention, or a health education (HE) control condition. We compare the TOPPS intervention to HE on the following outcomes: 1) pain interference and pain severity over the 3-month treatment phrase; 2) depressive symptoms over the 3-month treatment phase; and 3) sustained improvements in pain interference, depressive symptoms, and buprenorphine treatment retention over the 12-month study period. We also examine mechanisms by which the intervention may reduce pain interference., Discussion: This RCT explores a novel intervention to address chronic pain and depression for individuals receiving buprenorphine in office-based settings. TOPPS may lead to improved pain, depression, and substance use outcomes, and can utilize providers available within buprenorphine programs, broadening the disseminability of this intervention and heightening its public health impact., Clinical Trial: #NCT03698669., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Risa Weisberg is currently the Chief Clinical Officer for RealizedCare, a digital therapeutics-based healthcare company. RealizedCare manufactures and sells behavioral health products including those for chronic pain and opioid use., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Machine learning (ML) models trained for triggering clinical decision support (CDS) are typically either accurate or interpretable but not both. Scaling CDS to the panoply of clinical use cases while mitigating risks to patients will require many ML models be intuitively interpretable for clinicians. To this end, we adapted a symbolic regression method, coined the feature engineering automation tool (FEAT), to train concise and accurate models from high-dimensional electronic health record (EHR) data. We first present an in-depth application of FEAT to classify hypertension, hypertension with unexplained hypokalemia, and apparent treatment-resistant hypertension (aTRH) using EHR data for 1200 subjects receiving longitudinal care in a large healthcare system. FEAT models trained to predict phenotypes adjudicated by chart review had equivalent or higher discriminative performance (p < 0.001) and were at least three times smaller (p < 1 × 10 -6 ) than other potentially interpretable models. For aTRH, FEAT generated a six-feature, highly discriminative (positive predictive value = 0.70, sensitivity = 0.62), and clinically intuitive model. To assess the generalizability of the approach, we tested FEAT on 25 benchmark clinical phenotyping tasks using the MIMIC-III critical care database. Under comparable dimensionality constraints, FEAT's models exhibited higher area under the receiver-operating curve scores than penalized linear models across tasks (p < 6 × 10 -6 ). In summary, FEAT can train EHR prediction models that are both intuitively interpretable and accurate, which should facilitate safe and effective scaling of ML-triggered CDS to the panoply of potential clinical use cases and healthcare practices., (© 2023. The Author(s).)

Objective: This study aimed to determine whether HIV-Pain and Sadness Support (HIV-PASS), a collaborative behavioral health intervention based on behavioral activation, is associated with decreased pain-related interference with daily activities, depression, and other outcomes in people living with HIV., Methods: We conducted a three-site clinical trial ( n = 187) in which we randomly assigned participants to receive either HIV-PASS or health education control condition. In both conditions, participants received seven intervention sessions, comprising an initial in-person joint meeting with the participant, their HIV primary care provider and a behavioral health specialist, and six, primarily telephone-based, meetings with the behavioral health specialist and participant. The intervention period lasted 3 months, and follow-up assessments were conducted for an additional 9 months., Results: Compared with health education, HIV-PASS was associated with significantly lower pain-related interference with daily activities at the end of month 3 (our primary outcome; b = -1.31, 95% confidence interval = -2.28 to -0.34). We did not observe other differences between groups at 3 months in secondary outcomes that included worst or average pain in the past week, depression symptoms, anxiety, and perceived overall mental and physical health. There were no differences between groups on any outcomes at 12 months after enrollment., Conclusions: A targeted intervention can have positive effects on pain interference. At the end of intervention, effects we found were in a clinically significant range. However, effects diminished once the intervention period ended., Trial Registration: ClinicalTrials.gov NCT02766751., (Copyright © 2023 by the American Psychosomatic Society.)

Introduction: In the current overdose epidemic, effective treatments for opioid use disorders (OUD), including innovations in medication delivery such as extended-release formulations, have the potential to improve treatment access and reduce treatment discontinuation. This study assessed treatment retention in a primary care-based, extended-release buprenorphine program., Methods: The study recruited individuals (n = 92) who transitioned from sublingual buprenorphine to extended-release buprenorphine (BUP-XR) in 2018-2019. The study defined the primary outcome, treatment retention, as three or more consecutive, monthly BUP-XR injections following the transition to BUP-XR in this retrospective chart review., Results: Participants' mean age was 38 years old and 67% were male. The average duration of sublingual buprenorphine prior to transition was 17.1 (±28.1) months. Three months after transition, 48% of extended-release buprenorphine patients had discontinued BUP-XR treatment. Persons with chronic pain were more likely, and those who had used heroin in the past month less likely to continue BUP-XR. Mean months on sublingual buprenorphine prior to BUP-XR initiation was 24.3 (±32.5) months for people who received 3+ post-induction injections compared to only 8.9 (±19.5) months for those who did not (p = .009)., Conclusions: Extended-release buprenorphine discontinuation was high in a real-world setting. Retention continues to represent a major obstacle to treatment effectiveness, and programs need interventions with even newer MOUD formulations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Modern artificial intelligence (AI) and machine learning (ML) methods are now capable of completing tasks with performance characteristics that are comparable to those of expert human operators. As a result, many areas throughout healthcare are incorporating these technologies, including in vitro diagnostics and, more broadly, laboratory medicine. However, there are limited literature reviews of the landscape, likely future, and challenges of the application of AI/ML in laboratory medicine., Content: In this review, we begin with a brief introduction to AI and its subfield of ML. The ensuing sections describe ML systems that are currently in clinical laboratory practice or are being proposed for such use in recent literature, ML systems that use laboratory data outside the clinical laboratory, challenges to the adoption of ML, and future opportunities for ML in laboratory medicine., Summary: AI and ML have and will continue to influence the practice and scope of laboratory medicine dramatically. This has been made possible by advancements in modern computing and the widespread digitization of health information. These technologies are being rapidly developed and described, but in comparison, their implementation thus far has been modest. To spur the implementation of reliable and sophisticated ML-based technologies, we need to establish best practices further and improve our information system and communication infrastructure. The participation of the clinical laboratory community is essential to ensure that laboratory data are sufficiently available and incorporated conscientiously into robust, safe, and clinically effective ML-supported clinical diagnostics., (© American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: People with HIV (PWH) who are not consistently retained in medical care, particularly when they are first diagnosed, are at risk for: delayed antiretroviral therapy (ART) initiation, suboptimal ART adherence, unsuppressed viremia, and mortality. Suboptimal retention means effective ART cannot be leveraged to prevent onward HIV transmission. To address this, we developed and previously pilot tested the HIV Engage intervention-a novel behavioral approach to enhance retention in HIV care using acceptance-based behavioral therapy (ABBT)-and established feasibility and acceptability of this approach. In the current study, we investigate the efficacy of ABBT compared to an attention-matched control condition in a full-scale randomized controlled efficacy trial., Methods: Two hundred seventy HIV care naïve patients from geographically diverse clinics will be recruited and equally randomized to receive (a) the HIV Engage intervention, consisting of two 20-30 min ABBT sessions delivered in-person or remotely, or (b) an attention-matched HIV education control condition. Primary outcomes are number of HIV care appointments kept and HIV viral load suppression. Secondary outcomes are higher self-reported ART adherence, HIV status disclosure, increased social support, and reductions in perceived HIV stigma. Hypothesized mediators include acceptance of one's HIV diagnosis and willingness to disclose serostatus. We will also assess for epidemiologically-linked moderators of the treatment effect., Conclusions: ABBT represents a novel, potentially promising approach to enhance retention in ongoing HIV care among treatment naïve PWH. This study will contribute significant actionable data establishing the impact, mediational mechanisms, and effect modifiers of ABBT., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The coronavirus disease 2019 (COVID-19) pandemic caused a halt to in-person ambulatory care. We evaluated how the reduction in access to care affected HbA1c testing and patient HbA1c levels., Methods: HbA1c data from 11 institutions were extracted to compare testing volume and the percentage of abnormal results between a pre-pandemic period (January-June 2019, period 1) and a portion of the COVID-19 pandemic period (Jan-June 2020, period 2). HbA1c results greater than 6.4% were categorized as abnormal., Results: HbA1C testing volumes decreased in March, April and May by 23, 61 and 40% relative to the corresponding months in 2019. The percentage of abnormal results increased in April, May and June (25, 23, 9%). On average, we found that the frequency of abnormal results increased by 0.31% for every 1% decrease in testing volume (p < 0.0005)., Conclusion: HbA1c testing volume for outpatients decreased by up to 70% during the early months of the pandemic. The decrease in testing was associated with an increase in abnormal HbA1c results., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Numerous studies have documented reduced access to patient care due to the COVID-19 pandemic, including access to diagnostic or screening tests, prescription medications, and treatment for an ongoing condition. In the context of clinical management for venous thromboembolism, this could result in suboptimal therapy with warfarin. We aimed to determine the impact of the pandemic on utilization of International Normalized Ratio (INR) testing and the percentage of high and low results., Methods: INR data from 11 institutions were extracted to compare testing volume and the percentage of INR results ≥3.5 and ≤1.5 between a pre-pandemic period (January-June 2019, period 1) and a portion of the COVID-19 pandemic period (January-June 2020, period 2). The analysis was performed for inpatient and outpatient cohorts., Results: Testing volumes showed relatively little change in January and February, followed by a significant decrease in March, April, and May, and then returned to baseline in June. Outpatient testing showed a larger percentage decrease in testing volume compared to inpatient testing. At 10 of the 11 study sites, we observed an increase in the percentage of abnormal high INR results as test volumes decreased, primarily among outpatients., Conclusion: The COVID-19 pandemic impacted INR testing among outpatients which may be attributable to several factors. Increased supratherapeutic INR results during the pandemic period when there was reduced laboratory utilization and access to care is concerning because of the risk of adverse bleeding events in this group of patients. This could be mitigated in the future by offering drive-through testing and/or widespread implementation of home INR monitoring., (© American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Persons with opioid use disorder (OUD) are prone to frequent relapse following brief inpatient medically managed withdrawal. This longitudinal, naturalistic study examines associations among illicit opioid use, use of medication for opioid use disorder (MOUD), and one's confidence in the ability to resist drug use in the face of negative emotions (i.e., negative affect-associated drug refusal self-efficacy)., Method: Participants were 220 adults with OUD who recently completed a short-term inpatient program and the study followed for 6 months. At baseline, participants reported demographics, illicit opioid use, recent engagement with MOUD, and negative affect-associated drug refusal self-efficacy. At follow-up (1 week and 1-, 3-, and 6-months following discharge), participants reported illicit opioid use and MOUD., Results: Participants averaged 30.7 years of age, 63.2% were male, and 84.1% were white. Both illicit opioid use and rates of MOUD increased during the 6-month follow-up period, although only 34.1% received MOUD. At baseline, participants reported less than 50% self-confidence to resist using opioids during negative emotional states. Baseline negative affect-associated drug refusal self-efficacy inversely predicted illicit opioid use (p = .01) at follow-up but was not associated with follow-up MOUD., Conclusion: Among persons with OUD, lower confidence to resist using opioids in negative emotional states predicts greater use of illicit opioids in the months following medically managed withdrawal, even with receipt of MOUD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: To test the hypothesis that among hospitalized people who inject drugs (PWID), a brief intervention in skin-cleaning would result in greater reductions in follow-up emergency department (ED) or hospitalization rates compared with a usual care condition., Design: Randomized, two-group (intervention, n = 128; usual care, n = 124), single-site clinical trial with12-month follow-up., Setting: Hospital inpatient services in Boston, Massachusetts, United States., Participants: People who injected drugs on at least 3 days each week prior to hospital admission (n = 252). Participants averaged 37.9 (± 10.7) years of age; 58.5% were male, 59.3% were white and 61.1% had a diagnosis related to skin infection at enrollment., Intervention and Comparator: Intervention was a skin hygiene education and skills-training behavioral intervention [short-term efficacy data on a behavioral intervention (SKIN)] consisting of two education- and skills-based skin-cleaning sessions, one during hospitalization and another 4 weeks later. The comparator was treatment as usual: an informational brochure about substance use treatment options and needle exchange programs in the area and follow-up clinical appointments as arranged by the inpatient medical staff., Measurements: Electronic medical records were reviewed and discharge diagnoses for each ED visit and hospital admission were categorized into injection-related bacterial events (e.g. cellulitis) and non-injection-related events. Negative binomial regression was used to test the intervention effects for the primary outcome and total ED visits, as well as the secondary outcomes, total number of hospitalizations, injection drug use-related (IDU-related) ED visits and IDU-related hospitalizations. We also tested whether the outcomes were moderated by whether the initial hospitalization was IDU-related., Findings: Of people assigned to SKIN, 66 completed two sessions, 55 completed one session and seven completed zero sessions. Adjusting for baseline covariates, the mean rate of total ED visits in the next 12 months was non-significantly higher [incidence rate ratio (IRR) = 1.13, 95% confidence interval (CI) = 0.96, 1.33, P = 0.152] compared with usual treatment. The intervention did not significantly reduce total hospitalizations or IDU-related hospitalizations. Adjusting for baseline covariates, the mean rate of injection drug use-related ED visits in the next 12 months was lower (IRR = 0.57, 95% CI = 0.35, 0.91, P = 0.019) compared with treatment as usual., Conclusions: A skin-cleaning intervention for people who inject drugs delivered during a hospitalization did not significantly reduce either overall emergency department use or hospitalization. There was some evidence that it may have reduced injection drug use-related emergency department visits., (© 2020 Society for the Study of Addiction.)

Background:  The electronic health record (EHR) has become increasingly ubiquitous. At the same time, health professionals have been turning to this resource for access to data that is needed for the delivery of health care and for clinical research. There is little doubt that the EHR has made both of these functions easier than earlier days when we relied on paper-based clinical records. Coupled with modern database and data warehouse systems, high-speed networks, and the ability to share clinical data with others are large number of challenges that arguably limit the optimal use of the EHR OBJECTIVES:  Our goal was to provide an exhaustive reference for those who use the EHR in clinical and research contexts, but also for health information systems professionals as they design, implement, and maintain EHR systems., Methods:  This study includes a panel of 24 biomedical informatics researchers, information technology professionals, and clinicians, all of whom have extensive experience in design, implementation, and maintenance of EHR systems, or in using the EHR as clinicians or researchers. All members of the panel are affiliated with Penn Medicine at the University of Pennsylvania and have experience with a variety of different EHR platforms and systems and how they have evolved over time., Results:  Each of the authors has shared their knowledge and experience in using the EHR in a suite of 20 short essays, each representing a specific challenge and classified according to a functional hierarchy of interlocking facets such as usability and usefulness, data quality, standards, governance, data integration, clinical care, and clinical research., Conclusion:  We provide here a set of perspectives on the challenges posed by the EHR to clinical and research users., Competing Interests: T.S.C. reports grants from ACRIN, NIH, ACR, and RSNA, as well as royalties from the Osler Institute for lectures in 2013, outside the submitted work. D.S.H. reports grants and nonfinancial support from Roche Diagnostics, outside the submitted work. R.A.H. reports grants from Johnson & Johnson, Merck, and Pfizer, outside the submitted work. Q.L. reports grants from NIH, during the conduct of the study; grants from Pfizer and Bayer, outside the submitted work., (Thieme. All rights reserved.)

For persons diagnosed with HIV and who are coinfected with hepatitis C virus (HCV), chronic liver disease is a leading cause of death and excessive consumption of alcohol can be a contributing factor. Little is known about the factors these individuals identify as key to achieving sustained sobriety. In this qualitative study, fourteen HIV/HCV coinfected persons who endorsed past problematic drinking were interviewed about their path to sustained sobriety. In open-ended interviews, participants often described their drinking in the context of polysubstance use and their decision to become sober as a singular response to a transcendent moment or a traumatic event. All articulated specific, concrete strategies for maintaining sobriety. The perceived effect of the HIV or HCV diagnosis on sobriety was inconsistent, and medical care as an influence on sobriety was rarely mentioned. Qualitative interviews may offer new insights on interventions and support strategies for heavy-drinking persons with HIV/HCV coinfection.

Background: People who inject drugs (PWID) are at high risk for skin and soft tissue infections (SSTIs), but few interventions have targeted their reduction. The goal of the current study was to test the effects of a brief skin and needle hygiene behavioral intervention (SKIN) in a two-group randomized controlled trial with 12-month follow-up., Method: PWID (N = 252) were recruited from inpatient hospital units at a single urban medical center site and randomly assigned to an assessment-only (AO) condition or SKIN, which was a two-session intervention that included psychoeducation, behavioral skills demonstrations, and motivational interviewing. Mixed effects generalized linear models assessed the impact of the intervention on frequency of: 1) self-reported SSTIs, 2) uncleaned skin injections, and 3) injection., Results: Participants were 58.3 % male, 59.5 % White, and averaged 38 years of age. SKIN participants had 35 % fewer SSTIs compared to AO (p = .179), a difference of nearly one infection per year. The mean rate of uncleaned skin injections was about 66 % lower (IRR = 0.34, 95 % CI 0.20; 0.59, p < .001) among SKIN participants compared to AO. Almost one-third of participants reported no injection over follow-up and the mean rate of injection during follow-up was about 39 % lower (IRR = 0.61; 95 % CI 0.36; 1.02, p = .058) among persons randomized to SKIN than AO., Conclusions: The SKIN intervention reduced uncleaned skin injections but did not reduce SSTIs significantly more than a control condition. Brief interventions can improve high-risk practices among PWID and lead to clinically meaningful outcomes., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Alcohol use contributes to the progression of liver disease in HIV-HCV co-infected persons, but alcohol interventions have never addressed low levels of alcohol use in this population. We enrolled 110 persons consuming at least 4 alcoholic drinks weekly in a clinical trial comparing two active 18-month long interventions, delivered every 3 months by phone, brief advice about drinking versus a motivational intervention. Final assessment was at 24 months. MI had larger reductions in alcohol use days than the BA arm at all follow-up assessments. The treatment by time effect was not significant for days of drinking (p = 0.470), mean drinks per day (p = 0.155), or for the continuous FIB-4 index (p = 0.175). Drinking declined in both conditions from baseline, but given the small sample, we do not have sufficient data to make any conclusion that one treatment is superior to the other.Trial Registry Trial registered at clinicaltrials.gov; Clinical Trial NCT02316184.

Background: Primary aldosteronism is a common cause of treatment-resistant hypertension. However, evidence from local health systems suggests low rates of testing for primary aldosteronism., Objective: To evaluate testing rates for primary aldosteronism and evidence-based hypertension management in patients with treatment-resistant hypertension., Design: Retrospective cohort study., Setting: U.S. Veterans Health Administration., Participants: Veterans with apparent treatment-resistant hypertension ( n  = 269 010) from 2000 to 2017, defined as either 2 blood pressures (BPs) of at least 140 mm Hg (systolic) or 90 mm Hg (diastolic) at least 1 month apart during use of 3 antihypertensive agents (including a diuretic), or hypertension requiring 4 antihypertensive classes., Measurements: Rates of primary aldosteronism testing (plasma aldosterone-renin) and the association of testing with evidence-based treatment using a mineralocorticoid receptor antagonist (MRA) and with longitudinal systolic BP., Results: 4277 (1.6%) patients who were tested for primary aldosteronism were identified. An index visit with a nephrologist (hazard ratio [HR], 2.05 [95% CI, 1.66 to 2.52]) or an endocrinologist (HR, 2.48 [CI, 1.69 to 3.63]) was associated with a higher likelihood of testing compared with primary care. Testing was associated with a 4-fold higher likelihood of initiating MRA therapy (HR, 4.10 [CI, 3.68 to 4.55]) and with better BP control over time., Limitations: Predominantly male cohort, retrospective design, susceptibility of office BPs to misclassification, and lack of confirmatory testing for primary aldosteronism., Conclusion: In a nationally distributed cohort of veterans with apparent treatment-resistant hypertension, testing for primary aldosteronism was rare and was associated with higher rates of evidence-based treatment with MRAs and better longitudinal BP control. The findings reinforce prior observations of low adherence to guideline-recommended practices in smaller health systems and underscore the urgent need for improved management of patients with treatment-resistant hypertension., Primary Funding Source: National Institutes of Health.

Objective: Cross-sectional research shows that coping-motivated marijuana use is associated with marijuana use and problems. However, limited research has examined how coping-motivated use might longitudinally relate to these outcomes. We examined the temporal relationship of coping-motivated marijuana use with severity of use and marijuana-related problems., Method: Participants were 226 emerging adults, aged 18-25 years old, who currently used marijuana. Multilevel generalized linear models were used to evaluate the association between change in coping motives with change in frequency of marijuana use and marijuana problem severity from baseline to 6- and 12-month follow-ups., Results: In the adjusted models, frequency of marijuana use was positively associated with between subject differences (IRR = 1.49; 95%CI: 1.30, 1.71; p < .001) but not within subject change over time (IRR = 1.09; 95%CI: 0.97, 1.22; p = .139) in use of marijuana to cope. Additionally, marijuana problem severity scores were associated positively with between subject differences (IRR = 1.45; 95%CI: 1.21, 1.75; p < .001) and within subject changes over time (IRR = 1.30; 95%CI: 1.07, 1.57; p < .01) in use of marijuana to cope., Conclusions: Changes in coping-motivated use of marijuana in emerging adults were directionally associated with changes in marijuana use and marijuana problems up to 12 months post-baseline. Results highlight the possible bi-directional relationship between coping motives and marijuana use and problems. Findings could be valuable in helping practitioners go beyond quantity and frequency as sufficient metrics of marijuana use problems. Motives for use may reflect additional problems and the clinical need to explore these possibilities., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background and Objectives: Internationally, supervised injection facilities (SIFs) have demonstrated efficacy in reducing rates of overdose and promoting entry into treatment among persons who inject drugs (PWID); however, they remain unavailable in the United States. Early findings examining American PWID illustrate high overall willingness to use SIFs. The current study expands upon this research by examining PWID's likelihood to use SIFs based on services offered (eg, provides clean needles, linkage to treatment programs) and whether known risk factors (prior overdose, homelessness) influence PWID's willingness to use a SIF., Methods: Participants (n = 184) were patients entering short-term inpatient opioid withdrawal management in Massachusetts between May 2018 and February 2019 who reported injection drug use in the prior 30 days. We examined PWID's likelihood to use a SIF if eight unique services were available, and compared if this differed by overdose history and homelessness status using ordered logistic regression and Pearson's χ 2 -tests of independence., Results: Participants (34.2 [±8.3 SD] years of age, 68.5% male, 85.9% white, 8.2% Hispanic) reported being most likely to use SIFs that provided safety from police intervention (86.7%), entry into withdrawal management (85.9%), or clean needles (83.2%). Drug works disposal and safety from police were particularly important for PWID with a history of overdose., Conclusion and Scientific Significance: Overall, treatment-seeking PWIDs reported greater willingness to utilize SIFs if particular services were provided. These findings point to features of SIFs that may enhance treatment-seeking PWID's amenability to utilizing these services if such sites open in the United States. (Am J Addict 2021;30:21-25)., (© 2020 American Academy of Addiction Psychiatry.)

Labeling patients in electronic health records with respect to their statuses of having a disease or condition, i.e. case or control statuses, has increasingly relied on prediction models using high-dimensional variables derived from structured and unstructured electronic health record data. A major hurdle currently is a lack of valid statistical inference methods for the case probability. In this paper, considering high-dimensional sparse logistic regression models for prediction, we propose a novel bias-corrected estimator for the case probability through the development of linearization and variance enhancement techniques. We establish asymptotic normality of the proposed estimator for any loading vector in high dimensions. We construct a confidence interval for the case probability and propose a hypothesis testing procedure for patient case-control labelling. We demonstrate the proposed method via extensive simulation studies and application to real-world electronic health record data.

Depression is common among people living with HIV (PLWH) and some likely turn to alcohol to cope with this emotional distress. Using alcohol to cope is associated with increased alcohol use, persistent longitudinal alcohol use, and alcohol-related problems. This association is particularly concerning among PLWH who are co-infected with Hepatitis C (HCV) because alcohol adds to the damage already caused by HCV. Despite data showing the associated risks of using alcohol to cope, scant research has examined factors that might contribute to coping-based alcohol use in HIV-HCV patients, such as limited social support. Baseline data from a randomized trial of strategies to reduce alcohol use in co-infected HIV and HCV adult patients (n=110) were analyzed. Multiple linear regression models were used to estimate the association between using alcohol to cope, depression, and four aspects of social support, controlling for demographic variables. Results showed that using alcohol to cope was not significantly correlated with social support but was significantly correlated with depressive symptoms. In fact, depressive symptoms and severity of alcohol consumption accounted for nearly 45% of the variance related to coping-based alcohol use. These data highlight the central role of depression in the coping motives-alcohol use relationship among co-infected patients.

Objectives: We examined how patient perceptions of alcohol risk, provider discussions about alcohol, and treatment of hepatitis C virus (HCV) differed among HIV-HCV coinfected patients in primary care., Methods: Between April, 2016 and April, 2017, we conducted a screening survey with patients in an HIV primary care clinic in Seattle, Washington, who had chronic HCV coinfection or a history of chronic HCV infection who had successfully cleared their infection with treatment., Results: Of 225 participants, 84 (37%) were active drinkers (drank ≥2-4 times/mo in past 3 months). Of those with little to no use for ≥3 months, 65 (29%) were former drinkers with a history of alcohol use and 76 were abstainers with no such history. Former drinkers and abstainers were more likely than active drinkers to perceive that any drinking was unsafe (69% vs 58% vs 31%; P < 0.001). Former drinkers were more likely to report a physician's recommendation to stop drinking than active drinkers (63% vs 47%; P = 0.05). The great majority (87%) of former drinkers decided to stop or reduce drinking on their own (most often in response to a nonhealth life event) and only 13% acknowledged doing so on their doctor's prompting. HCV treatment was not associated with former or active drinking status., Conclusions: Our findings underscore the importance of educating not only HIV-HCV patients about the effects of alcohol use but also HIV clinicians about delivering consistent counseling about alcohol avoidance. Understanding the reasons that HIV-HCV coinfected persons make changes in their alcohol use could drive novel interventions that reduce the negative consequences of drinking.

Objective: To explore the transcriptomic differences between patients with hypertrophic cardiomyopathy (HCM) and controls., Patients and Methods: RNA was extracted from cardiac tissue flash frozen at therapeutic surgical septal myectomy for 106 patients with HCM and 39 healthy donor hearts. Expression profiling of 37,846 genes was performed using the Illumina Human HT-12v3 Expression BeadChip. All patients with HCM were genotyped for pathogenic variants causing HCM. Technical validation was performed using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. This study was started on January 1, 1999, and final analysis was completed on April 20, 2020., Results: Overall, 22% of the transcriptome (8443 of 37,846 genes) was expressed differentially between HCM and control tissues. Analysis by genotype revealed that gene expression changes were similar among genotypic subgroups of HCM, with only 4% (1502 of 37,846) to 6% (2336 of 37,846) of the transcriptome exhibiting differential expression between genotypic subgroups. The qRT-PCR confirmed differential expression in 92% (11 of 12 genes) of tested transcripts. Notably, in the context of coronavirus disease 2019 (COVID-19), the transcript for angiotensin I converting enzyme 2 (ACE2), a negative regulator of the angiotensin system, was the single most up-regulated gene in HCM (fold-change, 3.53; q-value =1.30×10 -23 ), which was confirmed by qRT-PCR in triplicate (fold change, 3.78; P=5.22×10 -4 ), and Western blot confirmed greater than 5-fold overexpression of ACE2 protein (fold change, 5.34; P=1.66×10 -6 )., Conclusion: More than 20% of the transcriptome is expressed differentially between HCM and control tissues. Importantly, ACE2 was the most up-regulated gene in HCM, indicating perhaps the heart's compensatory effort to mount an antihypertrophic, antifibrotic response. However, given that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses ACE2 for viral entry, this 5-fold increase in ACE2 protein may confer increased risk for COVID-19 manifestations and outcomes in patients with increased ACE2 transcript expression and protein levels in the heart., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Alcohol consumption is common among individuals coinfected with HIV and hepatitis C (HCV) despite the uniquely harmful effects in this population. Limited research has examined factors that could influence drinking reduction or cessation among HIV/HCV coinfected persons; this study investigates motivation to quit. Participants were 110 alcohol-consuming HIV/HCV coinfected patients recruited from medical clinics. Participants self-reported 90-day drinking frequency and intensity; alcohol-related problems; reasons to quit drinking; reasons to drink; and motivation to quit drinking. Participants consumed alcohol on 54.1 (± 26.9) of the past 90 days. In a multivariate model that controlled for demographic variables, motivation to quit drinking was directly associated with alcohol-related problems (β y·x  = 0.35, p = .007) and reasons to quit drinking (β y·x  = 0.23, p = .021), and inversely associated with drinking for enhancement (β y·x  = - 0.36, p = .004). This study identified several factors associated with motivation to quit drinking in a sample of alcohol-consuming HIV/HCV patients.

Objectives: Skin and soft-tissue infections (SSTI) among people who inject drugs (PWID) are common and represent a significant public health burden. In the current study, we examined the relationship between perceived behavioral control and perceived barriers to cleaning skin before injecting drugs., Methods: Participants (n = 248; 37.9 [±10.7] years of age, 58.5% male, 59.3% white, 16.1% Hispanic) were patients seeking medical care at a large urban hospital in the northeastern United States. We used ordinary least squares regression to estimate the associations between perceived barriers to skin cleaning with background characteristics and perceived behavioral control., Results: Controlling for background and other study variables, greater number of past-year skin abscesses was associated with greater level of perceived barriers to skin cleaning (P < 0.001), whereas higher level of education and higher perceived behavioral control were associated with lower levels of perceived barriers to skin cleaning (P < 0.001)., Conclusions: Interventions aiming to reduce the likelihood for SSTI among people who inject drugs may benefit from strengthening individual's behavioral control and providing skin cleaning skills training.

Background and Aims: Persons who inject drugs (PWID) experience high rates of skin and soft tissue infections (SSTI) and often access emergency or inpatient treatment. However, many PWID do not seek care and self-treat some or all of their infections. The goal of the current study was to examine predictors of self-treatment of SSTI in a sample of hospitalized PWID, and describe methods of and reasons for self-treatment., Methods: PWID (N = 252) were recruited from inpatient medical units at an urban safety-net hospital to join a behavioral intervention trial. The baseline interview focused on past-year SSTI incidence and related treatment, including reasons for not accessing medical care and methods of self-treatment., Results: Of study participants, 162 (64%) reported having at least one SSTI in the past year. This subset was 59.9% White/Caucasian with a mean age of 38.0 (SD + 10.5). One-third of these participants (32.3%) reported ever self-treating SSTI in the past year. In a logistic regression model, number of past-year infections (OR = 1.81, p < .001) and positive outlook (OR = 2.46, p < .001) were associated with self-treatment of SSTI. Common methods of self-treatment included mechanically draining sores, applying heat/warm compress, and cleaning affected areas. Continued drug use and belief that infections were not serious and could be self-treated were two main reasons for not seeking professional medical care., Conclusions: Interventions targeting SSTI among PWID should include education on when to seek medical care and the risks of serious infection, and could be implemented at local clinics or harm reduction programs to increase access., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Phenotyping patients using electronic health record (EHR) data conventionally requires labeled cases and controls. Assigning labels requires manual medical chart review and therefore is labor intensive. For some phenotypes, identifying gold-standard controls is prohibitive. We developed an accurate EHR phenotyping approach that does not require labeled controls., Materials and Methods: Our framework relies on a random subset of cases, which can be specified using an anchor variable that has excellent positive predictive value and sensitivity independent of predictors. We proposed a maximum likelihood approach that efficiently leverages data from the specified cases and unlabeled patients to develop logistic regression phenotyping models, and compare model performance with existing algorithms., Results: Our method outperformed the existing algorithms on predictive accuracy in Monte Carlo simulation studies, application to identify hypertension patients with hypokalemia requiring oral supplementation using a simulated anchor, and application to identify primary aldosteronism patients using real-world cases and anchor variables. Our method additionally generated consistent estimates of 2 important parameters, phenotype prevalence and the proportion of true cases that are labeled., Discussion: Upon identification of an anchor variable that is scalable and transferable to different practices, our approach should facilitate development of scalable, transferable, and practice-specific phenotyping models., Conclusions: Our proposed approach enables accurate semiautomated EHR phenotyping with minimal manual labeling and therefore should greatly facilitate EHR clinical decision support and research., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Obese patients may have unrecognized primary aldosteronism due to high rates of concomitant hypertension. We hypothesized that obesity impacts the diagnosis and management of patients with primary aldosteronism., Methods: We conducted a retrospective analysis of all primary aldosteronism patients (n = 418) who underwent adrenal vein sampling (1997-2017). Patients were classified by body mass index as obese (body mass index ≥35) or nonobese (body mass index <35) and diagnostic evaluation was compared between groups. Within the operative cohort (n = 285), primary outcomes were changes in both blood pressure and antihypertensive medications after adrenalectomy. Secondary outcome was clinical resolution by Primary Aldosteronism Surgery Outcomes criteria., Results: Thirty-five percent of patients were obese. Obese patients were more likely to be male (67.8% vs 56.1%, P = .025), somewhat younger (51.5 vs 54.4 years old, P < .012), and require more preoperative antihypertensive medications (6.7 vs 5.7, P = .04) than nonobese patients. Obese patients had lesser rates of radiologic evidence of adrenal tumors (68.4 vs 77.9%, P = .038) despite similar rates of lateralization on adrenal vein sampling. In the operative subset, obese patients had somewhat smaller tumors on final pathology (1.1 vs 1.5 cm, P = .014) but similar rates of complete and partial clinical resolution (P = 1.000)., Conclusion: Obese primary aldosteronism patients have lesser rates of localization by imaging, likely due to smaller tumor size, however, experience similar benefit from adrenalectomy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Lactate dehydrogenase (LDH) is a nonspecific biomarker for diseases including lymphoma. Serum and plasma are generally considered interchangeable for LDH testing. Investigation into falsely increased plasma LDH concentration results led to the hypothesis that a workflow change that included pneumatic tube system (PTS) transportation caused the errors. The following study was conducted to test the hypothesis., Methods: Plasma and serum separator tube samples were each drawn in duplicate, centrifuged, transported either through the PTS or by hand courier, and evaluated by means of clinical chemistry and hematology assays. Smear slides were made out of the plasma and examined. Aggregate patient results before and after the PTS workflow change were compared., Results: In post-PTS plasma samples, LDH activity was 26%-149% higher. Similarly, white blood cells (WBCs) were 14- to 156-fold higher and platelets were 1- to 13-fold higher. Smear examination revealed dramatically more cells and cell fragments. No significant hemolysis was observed in plasma by chemistry hemolysis indices or hemoglobin testing. These effects were not observed in similarly transported serum samples in gel separator tubes. Aggregate LDH patient results, including moving medians, demonstrated dramatic changes following PTS workflow implementation., Conclusions: PTS transportation led to falsely increased LDH concentration in plasma. These LDH concentration elevations are not heralded by standard indicators of hemolysis. These errors can be prevented by restricting LDH concentration testing to serum collected in gel separator tubes. Moving patient statistics can effectively detect important testing process changes not revealed by external QC or indices., (© 2019 American Association for Clinical Chemistry.)

Dual-specificity tyrosine phosphorylation-regulated kinase-1A (DYRK1A) is known to phosphorylate the microtubule-associated tau protein. Overexpression is correlated with tau hyperphosphorylation and neurofibrillary tangle (NFT) formation in Alzheimer's disease (AD). This study assessed the potential of SM07883, an oral DYRK1A inhibitor, to inhibit tau hyperphosphorylation, aggregation, NFT formation, and associated phenotypes in mouse models. Exploratory neuroinflammatory effects were also studied. SM07883 specificity was tested in a kinase panel screen and showed potent inhibition of DYRK1A (IC 50  = 1.6 nM) and GSK-3β (IC 50  = 10.8 nM) kinase activity. Tau phosphorylation measured in cell-based assays showed a reduction in phosphorylation of multiple tau epitopes, especially the threonine 212 site (EC 50  = 16 nM). SM07883 showed good oral bioavailability in multiple species and demonstrated a dose-dependent reduction of transient hypothermia-induced phosphorylated tau in the brains of wild-type mice compared to vehicle (47%, p < 0.001). Long-term efficacy assessed in aged JNPL3 mice overexpressing the P301L human tau mutation (3 mg/kg, QD, for 3 months) exhibited significant reductions in tau hyperphosphorylation, oligomeric and aggregated tau, and tau-positive inclusions compared to vehicle in brainstem and spinal cord samples. Reduced gliosis compared to vehicle was further confirmed by ELISA. SM07883 was well tolerated with improved general health, weight gain, and functional improvement in a wire-hang test compared to vehicle-treated mice (p = 0.048). SM07883, a potent, orally bioavailable, brain-penetrant DYRK1A inhibitor, significantly reduced effects of pathological tau overexpression and neuroinflammation, while functional endpoints were improved compared to vehicle in animal models. This small molecule has potential as a treatment for AD., (© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Background and Objectives: Despite the benefits of maintenance buprenorphine treatment for opioid use disorder (OUD), many individuals report an interest in discontinuing the medication, while also expressing worries about tapering. The purpose of this study was to develop a measure of worries about buprenorphine discontinuation ("Off Bupe") and determine the demographic and clinical characteristics associated with these worries., Methods: Between May 2017 and May 2018, we surveyed adults in an outpatient primary care buprenorphine program (n = 138). Reliability and validity of the Off Bupe measure were examined., Results: Participants averaged 39 years of age, 54% were male, average duration of buprenorphine was 189 weeks and 85.5% reported eventually wanting to discontinue buprenorphine, although fewer than 10% were actively tapering. We derived two scales, withdrawal symptom worry (10 items, ɑ = 0.94) and relapse worry (7 items, ɑ = 0.88). Worry about symptoms was positively associated with current buprenorphine dose (P = 0.016), physical discomfort avoidance (P < 0.001), and inversely associated with self-efficacy to quit buprenorphine (P < 0.001) and distress tolerance (P < 0.001). Worry about opioid relapse was associated positively with age (P = 0.019), current buprenorphine dose (P = 0.004), physical discomfort avoidance (P < 0.001), and impulsivity (P = 0.002), and inversely associated with self-efficacy to quit buprenorphine (P < 0.001)., Discussion and Conclusions: Psychometric evaluation of the "Off Bupe" scale demonstrated its content and construct validity and internal reliability., Scientific Significance: The scale might help individuals with OUD and their providers identify concerns about discontinuing buprenorphine. (Am J Addict 2019;28:270-276)., (© 2019 American Academy of Addiction Psychiatry.)

Emerging adulthood (ages 18-25) is a time of increased autonomy and associated with a high rate of risky substance use and sexual behavior. As emerging adults (EA) increasingly have more independence, they have the ability to make health decisions, including whether to see a provider (primary care (PCP) and/or gynecologist (GYN)) and whether to discuss substance use and sexual behavior. The current study aimed to determine: (1) factors associated with PCP and GYN health-care seeking by sexually active EA who use alcohol and/or marijuana; (2) gender differences in substance use and sexual risk topics initiated by providers; (3) whether PCPs compared to GYNs discuss different topics with women. Alcohol and/or marijuana-using, sexually active EA (n = 500) were recruited as part of a health behaviors study. Among participants, 39% did not see a PCP in the previous year. Women, White individuals, and EA with health insurance were most likely to attend a PCP appointment. Even among participants who saw a provider, many participants reported that providers did not initiate a discussion about substance use (approximately half discussed substance use) and sexual behavior (about half discussed STI history, two-thirds discussed condom use, and three-quarters discussed sexual partners). Among women with a PCP and GYN provider, discussions on substance use were more likely to be initiated by a PCP while sexual issues were more likely to be initiated by a GYN. Thus, even among sexually active, substance-using EA, central topics - specifically substance use and sexual behavior - are not routinely brought up by providers.

Purpose: We evaluated strategies for identifying disease-causing variants in genetic testing for dilated cardiomyopathy (DCM)., Methods: Cardiomyopathy gene panel testing was performed in 532 DCM patients and 527 healthy control subjects. Rare variants in 41 genes were stratified using variant-level and gene-level characteristics., Results: A majority of DCM cases and controls carried rare protein-altering cardiomyopathy gene variants. Variant-level characteristics alone had limited discriminative value. Differentiation between groups was substantially improved by addition of gene-level information that incorporated ranking of genes based on literature evidence for disease association. The odds of DCM were increased to nearly 9-fold for truncating variants or high-impact missense variants in the subset of 14 genes that had the strongest biological links to DCM (P <0.0001). For some of these genes, DCM-associated variants appeared to be clustered in key protein functional domains. Multiple rare variants were present in many family probands, however, there was generally only one "driver" pathogenic variant that cosegregated with disease., Conclusion: Rare variants in cardiomyopathy genes can be effectively stratified by combining variant-level and gene-level information. Prioritization of genes based on their a priori likelihood of disease causation is a key factor in identifying clinically actionable variants in cardiac genetic testing.

Background and Objectives: Emerging adulthood is a time of identity formation, and is also the most common time period for individuals to consume alcohol. Alcohol self-concept (or drinking identity) has been associated cross-sectionally with rates of alcohol use and use-related problems. Additionally, there is preliminary evidence that alcohol self-concept is related to negative affect and to alcohol use motives. However, less research has evaluated the longitudinal nature of these variables, particularly in a community sample. The current study evaluated relationships between self-concept, alcohol-related variables, and negative affect among emerging adults. Additionally, the study explored self-concept as a mediator between motives and alcohol use and problems., Methods: Community-recruited participants (n = 226, 55.3% male) involved in a health behaviors study were assessed over the course of 12 months., Results: Results substantiated both the cross-sectional and longitudinal relationships between these variables. Self-concept, rates of use, and problems decreased over the course of time. Decreases in motives for alcohol use (including coping and enhancement motives) were related to subsequent decreases in alcohol self-concept, which in turn were associated with decreases in use and use-related problems. Alcohol self-concept mediated the longitudinal relationship between coping motives and use as well as use-related problems., Discussion and Conclusions: Results from this study underscore the importance of motivation for alcohol use and internalization of alcohol identity in predicting changes in behavior across emerging adulthood and suggest future avenues of research., Scientific Significance: Alcohol self-concept may be a risk factor and intervention target. (Am J Addict 2018;27:501-508)., (© 2018 American Academy of Addiction Psychiatry.)

Objectives: In the United States, minimum standards for quality control (QC) are specified in federal law under the Clinical Laboratory Improvement Amendment and its revisions. Beyond meeting this required standard, laboratories have flexibility to determine their overall QC program., Methods: We surveyed chemistry and immunochemistry QC procedures at 21 clinical laboratories within leading academic medical centers to assess if standardized QC practices exist for chemistry and immunochemistry testing., Results: We observed significant variation and unexpected similarities in practice across laboratories, including QC frequency, cutoffs, number of levels analyzed, and other features., Conclusions: This variation in practice indicates an opportunity exists to establish an evidence-based approach to QC that can be generalized across institutions.

Detection of 3' PMS2 copy-number mutations that cause Lynch syndrome is difficult because of highly homologous pseudogenes. To improve the accuracy and efficiency of clinical screening for these mutations, we developed a new method to analyze standard capture-based, next-generation sequencing data to identify deletions and duplications in PMS2 exons 9 to 15. The approach captures sequences using PMS2 targets, maps sequences randomly among regions with equal mapping quality, counts reads aligned to homologous exons and introns, and flags read count ratios outside of empirically derived reference ranges. The method was trained on 1352 samples, including 8 known positives, and tested on 719 samples, including 17 known positives. Clinical implementation of the first version of this method detected new mutations in the training (N = 7) and test (N = 2) sets that had not been identified by our initial clinical testing pipeline. The described final method showed complete sensitivity in both sample sets and false-positive rates of 5% (training) and 7% (test), dramatically decreasing the number of cases needing additional mutation evaluation. This approach leveraged the differences between gene and pseudogene to distinguish between PMS2 and PMS2CL copy-number mutations. These methods enable efficient and sensitive Lynch syndrome screening for 3' PMS2 copy-number mutations and may be applied similarly to other genomic regions with highly homologous pseudogenes., (Copyright © 2018 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

Introduction: Cannabis use has become a more normative, socially-acceptable behavior in the United States, despite research indicating that frequent use may become problematic for some individuals. Emerging adulthood, a time of identity development, is the most common time for cannabis use. Cannabis self-concept, or one's identification with cannabis as part of their personality or identity, is one factor that may influence use behavior. This study extends previous research that reported a link between self-concept, motivational factors, and normative beliefs by evaluating relationships between cannabis self-concept, motives for use, motivation to change, perceived descriptive norms, as well as cannabis-related outcomes (use, using alone, and cannabis-related problems)., Methods: Emerging adults who used cannabis in the previous month (n=345, 53.9% male, mean age 21.0, 67.5% Non-Latino White) were recruited from a community sample for a health behaviors study. Participants were assessed for explicit cannabis self-concept, frequency of use, problems associated with use, motives for use, motivation to change, and normative beliefs about others' use., Results: Participants reported using cannabis on an average of 17.9 (SD=11.1) days of the previous month. Correlational analyses revealed that cannabis self-concept was positively associated with frequency of use, use-related problems, several motives for use, descriptive norms, and with using cannabis alone. Multivariate analyses revealed that rates of use, problems, and social and enhancement motives were independently and positively associated (p<0.05) with cannabis self-concept, while self-concept was negatively associated with desire to reduce cannabis use., Conclusions: Cannabis self-concept may be a marker for more problematic patterns of use., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aims: To test the hypothesis that among non-treatment-seeking emerging adults (EA) who both use marijuana and have alcohol binges, a brief, longitudinally delivered, developmentally based motivational intervention would show greater reductions in the use of these two substances compared with a health education control condition., Design: Parallel, two-group, randomized controlled trial with follow-up interventions conducted at 1, 3, 6 and 9 months and final assessments at 12 and 15 months., Setting: Hospital-based research unit in the United States., Participants: Community-based 18-25-year-olds who reported at least monthly binge drinking and at least weekly marijuana use., Intervention: Motivational intervention (EA-MI) focused primarily on themes of emerging adulthood (identity exploration, instability, self-focus, feeling in-between, a sense of possibilities) and the subjects' relationship to substance use (n = 110) compared with an attention-matched health education control condition (n = 116)., Measurements: The primary outcomes were days of binge alcohol, marijuana and dual use day as measured using the timeline follow-back method analysing the treatment by time interaction to determine relative differences in the rate of change between intervention arms., Findings: At baseline, the mean rate (days/30) of binge drinking was 5.23 (± 4.31) of marijuana use was 19.4 (± 10.0) and of dual (same day) use was 4.11 (± 4.13). Relative to baseline, there were reductions in the rate of binge alcohol use, marijuana use and days of combined binge alcohol and marijuana use (P < 0.001) at all follow-up assessments. However, the treatment × time interaction was not statistically significant for alcohol (P = 0.37), for marijuana (P = 0.07) or for dual use (P = 0.55). Averaged over all follow-ups, mean reductions in binge, marijuana and dual use days were 1.16, 1.45 and 1.08, respectively, in the health education arm, and 1.06, 1.69 and 0.96 in EA-MI. Bayes factors were < 0.01 for frequency of binge alcohol use and frequency of dual binge alcohol and marijuana and 0.016 for marijuana use., Conclusions: A brief, longitudinally delivered, developmentally based motivational intervention for young adults did not produce reductions in binge alcohol, marijuana use or dual use days relative to a control condition., (© 2017 Society for the Study of Addiction.)

Objectives: Skin and soft tissue infections (SSTIs) are common among people who inject drugs (PWID), and can lead to serious morbidity and costly emergency room and hospital utilization. A range of high-risk injection practices may contribute to these infections. The goal of the current study was to examine risk practices that were associated with SSTIs in a sample of hospitalized PWID., Methods: PWID (N = 143; 40.6% female) were recruited from inpatient medical units at a large urban hospital and completed a baseline interview that focused on infection risk. Measures included demographics, substances used/injected, and self-report of SSTIs (ie, abscesses, ulcers, or cellulitis) within the past year. The Bacterial Infections Risk Scale for Injectors-a 7-item index-assessed specific behaviors expected to increase the risk of acquiring SSTIs (eg, injection without skin cleaning, intramuscular injection)., Results: The sample was 58% Caucasian and averaged 38.7 (SD = 10.7) years of age. Ninety-three participants (65%) reported at least 1 SSTI within the past year. Using a logistic regression model, the Bacterial Infections Risk Scale for Injectors (odds ratio 1.87, P = 0.004) and total number of injections over the past 3 months (odds ratio 2.21, P = 0.002) were associated with past year SSTIs., Conclusions: In conclusion, rates of past-year SSTIs were high in this sample of hospitalized PWID. Results suggest that interventions should target specific injection practices to reduce infection risk.