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Acamprosate is an anti-craving drug used for the pharmacotherapy of alcohol use disorder (AUD). However, only some patients achieve optimal therapeutic outcomes. This study was designed to explore differences in metabolomic profiles between patients who maintained sobriety and those who relapsed, to determine whether those differences provide insight into variation in acamprosate treatment response phenotypes.We previously conducted an acamprosate trial involving 442 AUD patients, and 267 of these subjects presented themselves for a 3-month follow-up. The primary outcome was abstinence. Clinical information, genomic data and metabolomics data were collected. Baseline plasma samples were assayed using targeted metabolomics.Baseline plasma arginine, threonine, α-aminoadipic acid and ethanolamine concentrations were associated with acamprosate treatment outcomes and baseline craving intensity, a measure that has been associated with acamprosate treatment response. We next applied a pharmacometabolomics-informed genome-wide association study (GWAS) strategy to identify genetic variants that might contribute to variations in plasma metabolomic profiles that were associated with craving and/or acamprosate treatment outcome. Gene expression data for induced pluripotent stem cell-derived forebrain astrocytes showed that a series of genes identified during the metabolomics-informed GWAS were ethanol responsive. Furthermore, a large number of those genes could be regulated by acamprosate. Finally, we identified a series of single nucleotide polymorphisms that were associated with acamprosate treatment outcomes.These results serve as an important step towards advancing our understanding of disease pathophysiology and drug action responsible for variation in acamprosate response and alcohol craving in AUD patients.

Background Decreasing pain catastrophizing and improving self-efficacy to self-manage chronic pain symptoms are important treatment targets in the context of interdisciplinary pain rehabilitation. Greater pain catastrophizing has been shown to be associated with greater impact of pain symptoms on functioning; conversely, greater pain self-efficacy has been associated with lower pain intensity and lower levels of disability. Objective To prospectively evaluate interdisciplinary pain rehabilitation outcomes, as well as to evaluate the mediating effects of both pain catastrophizing and pain self-efficacy on outcome. Methods Participants were 315 patients with chronic pain between April 2017 and April 2018 who completed a 3-week interdisciplinary pain rehabilitation program. Pain severity, pain interference, pain catastrophizing, pain self-efficacy, quality of life, depressive symptom questionnaires, and measures of physical performance were assessed before and after treatment. Follow-up questionnaires were returned by 163 participants. Effect size and reliable change analyses were conducted from pre- to posttreatment and from pretreatment to 6-month follow-up. Mediation analyses were conducted to determine the mediating effect of pain catastrophizing and pain self-efficacy on pain outcome. Results Significant improvements from pre- to posttreatment in pain outcomes were observed, and more than 80% evidenced a reliable change in at least one pain-relevant measure. Pain catastrophizing and pain self-efficacy mediated the relationship between changes in pain outcomes. Conclusions Interdisciplinary pain rehabilitation is an effective treatment, and decreasing pain catastrophizing and increasing pain self-efficacy can influence maintenance of treatment gains.

Naltrexone can aid in reducing alcohol consumption, while acamprosate supports abstinence; however, not all patients with alcohol use disorder (AUD) benefit from these treatments. Here we present the first genome-wide association study of AUD treatment outcomes based on data from the COMBINE and PREDICT studies of acamprosate and naltrexone, and the Mayo Clinic CITA study of acamprosate. Primary analyses focused on treatment outcomes regardless of pharmacological intervention and were followed by drug-stratified analyses to identify treatment-specific pharmacogenomic predictors of acamprosate and naltrexone response. Treatment outcomes were defined as: (1) time until relapse to any drinking (TR) and (2) time until relapse to heavy drinking (THR; ≥ 5 drinks for men, ≥4 drinks for women in a day), during the first 3 months of treatment. Analyses were performed within each dataset, followed by meta-analysis across the studies (N = 1083 European ancestry participants). Single nucleotide polymorphisms (SNPs) in the BRE gene were associated with THR (min p = 1.6E−8) in the entire sample, while two intergenic SNPs were associated with medication-specific outcomes (naltrexone THR: rs12749274, p = 3.9E−8; acamprosate TR: rs77583603, p = 3.1E−9). The top association signal for TR (p = 7.7E−8) and second strongest signal in the THR (p = 6.1E−8) analysis of naltrexone-treated patients maps to PTPRD, a gene previously implicated in addiction phenotypes in human and animal studies. Leave-one-out polygenic risk score analyses showed significant associations with TR (p = 3.7E−4) and THR (p = 2.6E−4). This study provides the first evidence of a polygenic effect on AUD treatment response, and identifies genetic variants associated with potentially medication-specific effects on AUD treatment response.

BACKGROUND. Background parenchymal uptake (BPU) on molecular breast imaging (MBI) was identified in a case-control study as a breast cancer risk factor beyond mammographic density. To our knowledge, this finding has not yet been confirmed in a cohort study. OBJECTIVE. The objectives of this study were to examine the association of BPU with breast cancer and to estimate the absolute risk and discriminatory accuracy of BPU in a cohort study. METHODS. A retrospective cohort was established that included women without a history of breast cancer who underwent MBI from 2004 to 2015. Radiologists who were blinded to future breast cancer diagnoses assessed BPU on baseline MBI examinations as low (photopenic or minimal) or elevated (mild, moderate, or marked). Associations of BPU with breast cancer were estimated using multivariable Cox proportional hazards models of the time to diagnosis. The 5-year absolute risk was calculated for study subgroups. The discriminatory accuracy of BPU was also assessed. RESULTS. Among 2992 women (mean age, 56.3 years; SD, 10.6 years) who underwent MBI, breast cancer events occurred in 144 women (median follow-up, 7.3 years). Median time to diagnosis after MBI was 4.2 years (range, 0.5-11.6 years). Elevated BPU was associated with a greater breast cancer risk (hazard ratio [HR], 2.39; 95% CI, 1.68-3.41; p ≤ .001). This association remained in postmenopausal women (HR, 3.50; 95% CI, 2.31-5.31; p < .001) but was not significant in premenopausal women (HR, 1.29; 95% CI, 0.72-2.32; p = .39). The 5-year absolute risk of breast cancer was 4.3% (95% CI, 2.9-5.7%) for women with elevated BPU versus 2.5% (95% CI, 1.8-3.1%) for those with low BPU. Postmenopausal women with dense breasts and elevated BPU had a 5-year absolute risk of 8.1% (95% CI, 4.3-11.8%) versus 2.8% (1.8-3.8%) for those with low BPU. Among postmenopausal women, discriminatory accuracy for invasive cancer was improved with the addition of BPU versus use of the Gail risk score alone (C statistic, 65.1 vs 59.1; p = .04) or use of the Breast Cancer Surveillance Consortium risk score alone (C statistic, 66.4 vs 60.4; p = .04). CONCLUSION. BPU on MBI is an independent risk factor for breast cancer, with the strongest association observed among postmenopausal women with dense breasts. In postmenopausal women, BPU provides incremental discrimination in predicting breast cancer when combined with either the Gail model or the Breast Cancer Surveillance Consortium model. CLINICAL IMPACT. Observation of elevated BPU on MBI may identify a subset of women with dense breasts who would benefit most from supplemental screening or preventive options.

Increasing the use of exposure by community therapists during the treatment of childhood anxiety disorders is critical to improving the quality of available treatment. The aim of the current study was to investigate whether a brief training in the delivery of an exposure-focused and technology-assisted treatment protocol increased community therapist openness to exposure therapy, use of exposure in treatment, and improvement in patient symptoms. Participants were 17 therapists recruited from a large health system to provide outpatient therapy to 32 youth ages 8 to 18 (M = 12.13, 78.1% girls) with treatment as usual (TAU) or with the Anxiety Coach application (AC-app). Consistent with two of three hypotheses, therapists in the AC-app coach condition increased their openness to, and use of, exposure; however, these changes did not translate into improved therapeutic outcomes. Comparisons to benchmark studies suggest that the community therapists did not implement enough in vivo exposure of sufficient intensity or include parents enough to improve outcome. Results support the ability of exposure-focused treatment protocols to increase community therapists use of evidence-based treatment and suggest that future efforts should focus on improving the quality, in addition to quantity, of therapist-delivered exposure.

Lifetime history of major depressive disorder (MDD) has a sex-specific association with pretreatment alcohol consumption in patients with alcohol dependence. Here, we investigated the association of genetic load for MDD estimated using a polygenic risk score (PRS) with pretreatment alcohol consumption assessed with Timeline Follow Back in a sample of 287 men and 156 women meeting DSM-IV-TR criteria for alcohol dependence. Preferred drinking situations were assessed using the Inventory of Drug Taking Situations (IDTS). Linear models were used to test for association of normalized alcohol consumption measures with the MDD-PRS, adjusting for ancestry, age, sex, and number of days sober at baseline. We fit models both with and without adjustment for MDD history and alcohol-use-related PRSs as covariates. Higher MDD-PRS was associated with lower 90-day total alcohol consumption in men (β = -0.16, p = 0.0012) but not in women (β = 0.11, p = 0.18). The association of MDD-PRS with IDTS measures was also sex-specific: higher MDD-PRS was associated with higher propensity to drink in temptation-related situations in women, while the opposite (negative association)was found in men. MDD-PRS was not associated with lifetime MDD history in our sample, and adjustment for lifetime MDD and alcohol-related PRSs did not impact the results. Our results suggest that genetic load for MDD impacts pretreatment alcohol consumption in a sex-specific manner, which is similar to, but independent from, the effect of history of MDD. The clinical implications of these findings and contributing biological and psychological factors should be investigated in future studies.

This study established the psychometric properties and preliminary validity of the Stricker Learning Span (SLS), a novel computer adaptive word list memory test designed for remote assessment and optimized for smartphone use.Women enrolled in the Mayo Clinic Specialized Center of Research Excellence (SCORE) were recruited via e-mail or phone to complete two remote cognitive testing sessions. Convergent validity was assessed through correlation with previously administered in-person neuropsychological tests (n = 96, ages 55-79) and criterion validity through associations with magnetic resonance imaging measures of neurodegeneration sensitive to Alzheimer's disease (n = 47).SLS performance significantly correlated with the Auditory Verbal Learning Test and measures of neurodegeneration (temporal meta-regions of interest and entorhinal cortical thickness, adjusting for age and education). Test-retest reliabilities across two sessions were 0.71-0.76 (two-way mixed intraclass correlation coefficients).The SLS is a valid and reliable self-administered memory test that shows promise for remote assessment of aging and neurodegenerative disorders.

Item does not contain fulltext Excursion of the median nerve and the surrounding subsynovial connective tissue (SSCT) is diminished in patients with carpal tunnel syndrome (CTS). This study sought to determine if SSCT excursion could be utilized to predict surgical outcome. Idiopathic CTS patients were reviewed with ultrasound and electrodiagnostic tests at baseline. A speckle tracking algorithm was used to determine SSCT relative to tendon motion (shear index). Analysis of variance tests were used to compare SSCT motion with disease severity at baseline. Adjusted linear regressions were used to test the association with patient-reported outcome. A total of 90 CTS patients were analyzed and found to have an average shear index of 79% (95% confidence interval: 76.3%-81.6%). SSCT motion was lower in CTS patients with increasing electrophysiological severity (p=0.0475). There was no significant association of pre-operative SSCT motion with symptomatic improvement (p=0.268). Overall, SSCT motion is decreased in CTS patients, but exhibits limited correlation with clinical severity.

PURPOSE Background parenchymal uptake (BPU), which describes the level of radiotracer uptake in normal fibroglandular tissue on molecular breast imaging (MBI), has been identified as a breast cancer risk factor. Our objective was to develop and validate a deep learning model using image convolution to automatically categorize BPU on MBI. METHODS MBI examinations obtained for clinical and research purposes from 2004 to 2015 were reviewed to classify the BPU pattern using a standardized five-category scale. Two expert radiologists provided interpretations that were used as the reference standard for modeling. The modeling consisted of training and validating a convolutional neural network to predict BPU. Model performance was summarized in data reserved to test the performance of the algorithm at the per-image and per-breast levels. RESULTS Training was performed on 24,639 images from 3,133 unique patients. The model performance on the withheld testing data (6,172 images; 786 patients) was evaluated. Using direct matching on the predicted classification resulted in an accuracy of 69.4% (95% CI, 67.4% to 71.3%), and if prediction within one category was considered, accuracy increased to 96.0% (95% CI, 95.2% to 96.7%). When considering the breast-level prediction of BPU, the accuracy remained strong, with 70.3% (95% CI, 68.0% to 72.6%) and 96.2% (95% CI, 95.3% to 97.2%) for the direct match and allowance for one category, respectively. CONCLUSION BPU provided a robust target for training a convolutional neural network. A validated computer algorithm will allow for objective, reproducible encoding of BPU to foster its integration into risk-stratification algorithms.

Objective The quality of all clinical MRI is dependent on B0 homogeneity, which is optimized during the shimming part of a prescan or preparatory phase before image acquisition. The purpose of this study was to assess shimming techniques clinically employed for breast MRI across our practice, and to determine factors that correlate with higher image quality for contrast-enhanced breast MRI at 1.5T. Methods One hundred consecutive female patients were retrospectively collected with Institutional Review Board approval. Shimming-related parameters, including shim-box placement and shimming gradient offsets were extracted from prior contrast-enhanced 3D fat-suppressed T1-weighted gradient echo image acquisitions. Three breast radiologists evaluated these images for fat saturation, breast density, overall image quality, and artifacts. Technologist experience was also evaluated for variability of shimming. Generalized linear mixed models were used to compare acquisition parameters between fat saturation. P < 0.05 was considered as statistical significance. Results The percentage of soft tissue inside the field of view (FOV) (ie, Tissue/FOV) in the good fat-saturation group (0.37 ± 0.06) was significantly lower (P < 0.01) than that in the poor fat-saturation group (0.39 ± 0.06). Other shimming-related parameters were found not significantly affecting the fat-saturation outcomes. Technologists with more experience tended to have less variable shimming performance than junior technologists did. Conclusions The quality of clinical MRI and especially breast MRI is highly dependent on shimming. Decreasing Tissue/FOV was associated with good image quality (good fat saturation). Optimization of shimming may require manual shimming or higher-order field-correction strategies.

Objective The objective of this retrospective study is to characterize challenges with ultrasound (US)-guided localization of clipped metastatic axillary lymph nodes after neoadjuvant chemotherapy. Methods After institutional review board approval, our radiology database was searched for all radioactive seed localizations (RSLs), which use a low-dose radioactive isotope, Iodine-125, performed for clipped axillary lymph nodes between January 1, 2016, and December 31, 2018. The details of each procedure were reviewed. RSL was defined to be successful if US-guidance was used, and postlocalization imaging showed the seed was no more than 1 cm away from the target. Cause and subsequent management of unsuccessful localizations were documented. Results During the study period, 139 clipped axillary lymph nodes (in 138 women and 1 man) were scheduled for preoperative RSL. The overall success rate of RSL was 106/139 (76%). The number of unsuccessful localizations was 10/37 (27%) in 2016, 7/39 (18%) in 2017, and 16/63 (25%) in 2018, with a total unsuccessful case frequency of 33/139 (24%) over the entire study period. The mean time interval between marker placement and localization was 6.0 months (range 0.4–18.1 months). The coil biopsy marker was the most frequently used marker. Conclusions Preoperative US-guided I-125 seed localization of clipped metastatic axillary lymph nodes is suboptimal or unsuccessful 24% of the time. Other options for non-US imaging-guided localizations, such as tomosynthesis, are available for consideration when US detection is unsuccessful.

Background Bipolar disorder (BD) and borderline personality disorder (BPD) share overlapping phenomenology and are frequently misdiagnosed. This study investigated the diagnostic accuracy of the Mood Disorder Questionnaire (MDQ) and McLean Screening Instrument for Borderline Personality Disorder (MSI) in a clinical inpatient setting and whether individual screening items could differentiate BD from BPD. Methods 757 sequential inpatients admitted to a Mood Disorder Unit completed both the MDQ and MSI. Screen positive for the MDQ was defined as ≥7/13 symptoms endorsed with concurrence and at least moderate impact. Screen positive for the MSI was defined as a score of ≥7. The clinical discharge summary diagnosis completed by a board‐certified psychiatrist was used as the reference standard to identify concordance rates of a positive screen with clinical diagnosis. Individual items predicting one disorder and simultaneously predicting absence of other disorder by odds ratio (OR>and, 1. Clinical differentiation between bipolar disorder and borderline personality disorder can be challenging as both disorders share certain features like impulsivity, mood lability, and affective instability.2. The results from this study offer practical and useful clinical guidance for focusing on specific sub‐items from the Mood Disorder Questionnaire (MDQ) and McLean Screening Instrument for borderline personality disorder (MSI) that can help distinguish bipolar disorder and borderline personality disorder.

Objective: To compare outcomes among newborns of opioid-using and nonopioid drug-using mothers with those of control mothers who did not report substance use.Methods: Using the Rochester Epidemiology Project, newborns diagnosed with drug withdrawal syndrome (per ICD-9 or ICD-10 codes) from January 2010 through June 2017 were identified. For mothers, data collected included age, race, drug use, number of prenatal visits, and results of the urinary drug abuse survey, meconium test, and self-report survey. Demographic and perinatal data collected for newborns included birth date; sex; Apgar scores at 1, 5, and 10 minutes; neonatal intensive care stay; and vital status. Controls (n = 771) were similarly selected in regard to sex, birth date, and county.Results: Of 328 infants identified, 168 were born with opioid neonatal abstinence syndrome and 160 with a nonopioid withdrawal syndrome. Control mothers had more prenatal visits than mothers in the nonopioid and opioid groups. Newborns of control mothers had higher Apgar scores at 1 and 5 minutes than both substance-using groups. Opioid-using mothers were almost twice as likely to have newborns requiring intensive care and 3 times as likely to use benzodiazepines compared to the other substance-using mothers. Substance-using mothers had more premature babies than controls.Conclusions: Prenatal opioid use is a substantial risk factor for prematurity. Newborns diagnosed with neonatal abstinence syndrome are at risk of perinatal complications. Mothers using opioids during pregnancy also tend to use other substances. Longitudinal research should clarify how prenatal substance use interacts with other risk factors during a child's first years.

Objective Numerous commercial pharmacogenetics panels are now widely available for clinical use in psychiatric practice. However, there is a paucity of literature evaluating the use of combinatorial pharmacogenetics panels to enhance outcomes in the treatment of adolescents with depression. This study sought to prospectively evaluate the clinical impact of combinatorial pharmacogenetics testing in a double-blind, randomized, controlled effectiveness study for the pharmacologic treatment of adolescents with depression. Method Adolescents aged 13 to 18 years (N = 176) with moderate to severe major depressive disorder (MDD) were randomized to treatment arm guided by testing in which pharmacogenetic testing results were available at the baseline visit (GENE arm, n = 84) or a treatment-as-usual arm (TAU arm, n = 92) in which testing results were not available until an 8-week visit. Raters, participants, and families were blinded to group allocation. Symptom improvement, side effects, and satisfaction were assessed throughout the study at 4 weeks, 8 weeks, and 6 months. Results There were no differences between the GENE and TAU arms at 8 weeks or 6 months for symptom improvement, side effect burden, or satisfaction. Selective serotonin reuptake inhibitors were prescribed at higher rates in the TAU arm compared to the GENE arm (p = .024). Conclusion Combinatorial pharmacogenetics−guided treatment did not demonstrate improved outcomes compared to TAU in adolescents with MDD. Future research should examine how specific medication−gene pairs may affect clinical outcomes in the treatment of adolescents with depression and how best to integrate pharmacogenetics into clinical practice. Clinical trial registration information A PK/PD Genetic Variation Treatment Algorithm Versus Treatment As Usual for Adolescent Management Of Depression; https://www.clinicaltrials.gov ; NCT02286440.

Background Family-Based Treatment (FBT) is considered the first-line intervention for adolescent anorexia nervosa. However, access to this treatment is limited. Treatment programs for other pediatric mental health conditions have successfully overcome barriers to accessing evidence-based intervention by integrating mental health services into primary care. This study evaluated the proof-of-concept of a novel modification of FBT, Family-Based Treatment for Primary Care (FBT-PC) for adolescent restrictive eating disorders designed for delivery by primary care providers in their practices. Methods This retrospective clinical cohort study evaluated 15 adolescents with restrictive eating disorders receiving FBT-PC and 15 adolescents receiving standard FBT. We examined improvement in BMI percentile, reduction in weight suppression, and clinical benchmarks of eating disorder recovery including weight restoration to > 95% of expected body weight (EBW) and resolution of DSM-5 criteria for eating disorders. Results In both groups, effect sizes for increased BMI percentile exceeded Cohen’s convention for a large effect (FBT-PC: d = .94; standard FBT: d = 1.15) as did effect sizes for reduction in weight suppression (FBT-PC: d = 1.83; standard FBT: d = 1.21). At the end of treatment, 80% of the FBT-PC cohort and 87% in the standard FBT group achieved > 95%EBW and 67% in the FBT-PC group and 60% in the standard FBT group no longer met DSM-5 criteria for an eating disorder. There were no cohort differences in the number of treatment drop-outs or referrals to a more intensive level of eating disorder treatment. Conclusions Findings suggest that primary care providers have potential to improve weight and clinical status in adolescents with restrictive eating disorders. Based on these results, more rigorous testing of the FBT-PC model is warranted., Plain English summary Family-Based Treatment (FBT) is considered the first-choice intervention for adolescent anorexia nervosa. However, finding a qualified provider in this modality is difficult. Treatment programs for other pediatric mental health conditions have successfully overcome barriers to accessing quality treatment by integrating mental health services into primary care. This study evaluated the proof-of-concept of a novel modification of FBT, Family-Based Treatment for Primary Care (FBT-PC) for adolescent restrictive eating disorders designed for delivery by primary care providers in their practices. This study examined weight gain in 15 adolescents with restrictive eating disorders receiving FBT-PC and 15 adolescents receiving standard FBT. At the end of treatment, both groups showed large improvements in BMI percentile and large decreases in weight suppression. Each group had the same number of drop-outs and referrals to more intensive eating disorder treatment. Findings suggest that primary care providers have potential to improve weight and clinical status in adolescents with restrictive eating disorders. Based on these preliminary results, more rigorous testing of the FBT-PC model is indicated.

Purpose Understanding all factors that may impact radiation dose and procedural time is crucial to safe and efficient image-guided interventions, such as fluoroscopically guided sacroiliac (SI) joint injections. The purpose of this study was to evaluate the effect of flow pattern (intra- vs. periarticular), patient age, and body mass index (BMI) on radiation dose and fluoroscopy time. Methods A total of 134 SI joint injections were reviewed. Injectate flow pattern, age, and BMI were analyzed in respect to fluoroscopy time (minutes), radiation dose (kerma area product (KAP); µGy m2), and estimated skin dose (mGy). Results BMI did not affect fluoroscopy time, but increased BMI resulted in significantly higher skin and fluoroscopy doses ( p Conclusion Increased BMI had the largest impact on procedural radiation dose and skin dose. Flow pattern also showed a statistically significant association with radiation dose and skin dose, but the clinical difference was small. Proceduralists should be aware that BMI has the greatest impact on fluoroscopy dose and skin dose during SI joint injections compared to other factors.

Alcohol misuse is a major public health problem originating from genetic and environmental risk factors. Alterations in the brain epigenome may orchestrate changes in gene expression that lead to alcohol misuse and dependence. Through epigenome-wide association analysis of DNA methylation from human brain tissues, we identified a differentially methylated region, DMR-DLGAP2, associated with alcohol dependence. Methylation within DMR-DLGAP2 was found to be genotype-dependent, allele-specific and associated with reward processing in brain. Methylation at the DMR-DLGAP2 regulated expression of DLGAP2 in vitro, and Dlgap2-deficient mice showed reduced alcohol consumption compared with wild-type controls. These results suggest that DLGAP2 may be an interface for genetic and epigenetic factors controlling alcohol use and dependence.

BACKGROUND In the context of the COVID-19 pandemic, many behavioral health services have transitioned to teletherapy to continue delivering care for patients with mental illness. Studies that evaluate the outcome of this rapid teletherapy adoption and implementation are pertinent. OBJECTIVE This single-arm, nonrandomized pilot study aimed to assess the feasibility and initial patient-level outcomes of a psychiatric transitional day program that switched from an in-person group to a video teletherapy group during the COVID-19 pandemic. METHODS Patients with transdiagnostic conditions who were at risk of psychiatric hospitalization were referred to the Adult Transitions Program (ATP) at a large academic medical center in the United States. ATP was a 3-week intensive outpatient program that implemented group teletherapy guided by cognitive and behavioral principles delivered daily for 3 hours per day. Feasibility was assessed via retention, attendance rate, and rate of securing aftercare appointments prior to ATP discharge. Patients completed standardized patient-reported outcome measures at admission and discharge to assess the effectiveness of the program for improving quality of mental health, depression, anxiety, and suicide risk. RESULTS Patients (N=76) started the program between March and August of 2020. Feasibility was established, with 70 of the 76 patients (92%) completing the program and a mean attendance of 14.43 days (SD 1.22); also, 71 patients (95%) scheduled at least one behavioral health aftercare service prior to ATP discharge. All patient-level reported outcomes demonstrated significant improvements in depression (95% CI –3.6 to –6.2; Cohen d=0.77; Pd=0.74; Pd=0.41; P=.02), wish to live (95% CI 0.3 to 1.0; Cohen d=0.39; Pd=0.52; P=.01), and overall mental health (95% CI 1.5 to 4.5; Cohen d=0.39; P CONCLUSIONS Rapid adoption and implementation of a group-based teletherapy day program for adults at risk of psychiatric hospitalization appeared to be feasible and effective. Patients demonstrated high completion and attendance rates and reported significant improvements in psychosocial outcomes. Larger trials should be conducted to further evaluate the efficacy and effectiveness of the program through randomized controlled trials.

Diagnostic thoracentesis results rarely yield a microorganism or result in management change in children and should not be routinely performed in most children with known or suspected pulmonary inf...

Background Estrogen may inhibit cell senescence that contributes to age‐related disorders. This study determined the effects of menopausal hormone treatments on circulating levels of markers of cell senescence. Methods Growth differentiation factor 15 (GDF15), tumor necrosis factor receptor 1 (TNFR1), FAS, and macrophage inflammatory protein 1α (MIP1α) were measured in serum using multiplexed bead‐based assays and compared among menopausal women participating in the Kronos Early Estrogen Prevention Study randomized to either placebo (n = 38), oral conjugated equine estrogen (oCEE, n = 37), or transdermal 17β‐estradiol (tE2, n = 34). Serum levels of the senescent markers for each treatment were compared to placebo 36 months after randomization using the Wilcoxon rank sum test. Results Serum levels of GDF15, TNFR1, and FAS, but not MIP1α, were lower in both the oCEE and tE2 groups compared to placebo. The difference in levels between treatment and placebo for GDF15, TNFR1, and FAS were greater for oCEE [−108 pg/mL (p = .008), −234 pg/mL (p = .0006), and −1374 pg/mL (p, Hormonal treatments reduced the levels of selected markers of aging in the blood of recently menopausal women.

Aims Replicate the previously reported association of elevated alcohol craving, measured by Penn Alcohol Craving Scale (PACS) during residential treatment, with post-treatment relapse and explore whether elevated craving scores 3 months post-treatment are also associated with subsequent relapse. Methods Alcohol craving was assessed with the PACS on admission and at several time points post-treatment in 190 subjects with DSM-IV diagnosis of alcohol dependence admitted to residential treatment. Data about relapse to any drinking (primary outcome measure) was collected at 3, 6, 9 and 12 months after treatment. Cox regression models were used to determine whether PACS scores were associated with relapse. Statistical models were adjusted for meaningful demographic and clinical covariates. Results Follow-up data was available for 149/190 (78%) of subjects. Elevated PACS scores at discharge were associated with increased relapse risk within the first 3 and 12 months after discharge (P = 0.032 and P = 0.045, respectively). Elevated PACS scores at 3 months were associated with increased risk of subsequent relapse within 12 months after treatment in contacted subjects (P = 0.034) and in the intent-to-treat analysis (P = 0.0001). Conclusions Our findings indicate strong association of post-treatment relapse with elevated alcohol craving measured at treatment completion and at 3 months after treatment and justify the use of this measure to guide relapse-prevention efforts.

Left ventricular assist device (LVAD) is a life-saving therapy, but it poses a substantial infection risk. Current evaluation of LVAD infection with (18)F-FDG PET/CT is predominately subjective. We present qualitative and semi-quantitative (18)F-FDG PET/CT parameters for early detection of LVAD infection and site localization. We retrospectively reviewed all 25 LVAD patients at our institution who had undergone (18)F-FDG PET/CT imaging between 2014 and 2018. LVADs were subdivided into five assessed regions: driveline exit site, subcutaneous driveline, LVAD pump, LVAD inflow, and LVAD outflow cannulae. Ultimate diagnosis of LVAD infection was determined by a multidisciplinary primary care team. Qualitative and semi-quantitative analysis of PET/CT data were performed, including calculation of the standardized uptake value maximum, mean, and peak (SUV(max), SUV(mean), and SUV(peak), respectively), as well as metabolic tumor volume (MTV), and total lesion glycolysis (TLG). A total of 14 patients presented with symptoms of infection, and LVAD infection was ultimately diagnosed in 19 of the 25 cases. All cases were correctly identified on (18)F-FDG PET/CT with no false positive and no false negative cases, corresponding to a sensitivity and specificity of 100%. The mean SUV(max) range at noninfected sites was 2.5-3.4, and the range was 5.7-8.1 at infected sites, resulting in a significant difference (P < 0.01) at all LVAD regions. (18)F-FDG PET/CT is a useful adjunctive tool for assessment of LVAD infection and infection localization, which is crucial for clinical management. A cut-off SUV(max) 5 is recommended to help diagnose LVAD infection.

Objectives The S1 dorsal foramen is the route for 30% of lumbar transforaminal epidural injections; it is therefore important to identify structures impeding S1 foraminal access. The study objective was to characterize the imaging findings, prevalence, and anatomic origin of synovial cysts presenting within the S1 neural foramen. Methods A case series (N = 14) established imaging characteristics of S1 synovial cysts. Imaging studies of 400 patients undergoing epidural injections were reviewed for lesions compromising S1 foraminal access. Cadaveric dissections defined the relationship of the inferior recess of the L5-S1 facet to the S1 dorsal foramen. Results Elderly patients (mean age = 76) exhibited S1 synovial cysts. Synovial cysts were typically 1–2 cm in diameter, hyperintense on sagittal T2 weighted magnetic resonance images (MRIs), fluid-density on computed tomography, and dorsal to the S1 spinal nerve. Sixty percent of cysts exhibited complex MRI signal characteristics (thick wall, internal structure). Tarlov cysts, in contrast, were larger, lobular, and exhibited pure fluid intensity. Lesions impeded access to the S1 dorsal foramina in 5% of reviewed imaging studies (16 Tarlov cysts, three synovial cysts, one conjoint S1-S2 nerve root). The multifidus muscle was interposed between the L5-S1 facet inferior recess and the S1 dorsal foramen on dissection specimens; severe atrophy of the ipsilateral multifidus was noted on imaging in 17/18 synovial cysts. Conclusions The S1 neural foramina should be inspected on sagittal MRI, when available, for confounding lesions before performing S1 epidural injections. Tarlov cysts are more common than synovial cysts; the latter are seen in elderly patients with severe multifidus atrophy.

Background Concurrent liothyronine treatment has been shown to accelerate time to response in patients treated for major depression. However, the relationship between genetic variation in deiodinase and T3 treatment response has received little investigation. Methods This is a post-hoc analysis of a randomized, double-blind, placebo-controlled trial of concurrent liothyronine (T3-Cytomel®, n = 23; mean dose 46.3 ± 3.3 mcg) in patients with major depression where a clinical recommendation was made to pursue ECT. The primary outcome measure was time to 50% reduction in depressive symptoms. Multivariable linear models were used to examine effect of T3 and placebo and genetic variants as predictors of change in HAMD24 and number of ECT treatments. Results Survival analysis did not show a significant effect for the T3 + ECT group achieving a faster time to response compared to placebo + ECT (p + ECT). Survival analysis for RUL lead placement alone showed a significant effect for the T3 + ECT group achieving a faster time to response compared to p + ECT (p = 0.01) with significantly fewer ECT treatments (p = 0.03). Carriers of the functional SNP rs11206244 gene DI01-C785T minor allele (TT and CT) vs. non-carriers (CC), showed fewer ECT treatments in the T3 + ECT group, compared to p + ECT (5.3 ± 1.0 vs. 8.3 ± 2.1, p = 0.045). Conclusions These pilot data identify clinically relevant genetic variation in DI01- C785T contributing to an accelerated response time, but not an overall greater symptom reduction. Exogenous T3 supplementation may be therapeutic by attenuating a baseline DI01 relative functional deficit which functionally reduces peripheral conversion of T4 to biologically active T3. Further work is encouraged to assess genetic variation of thyroid deiodinase enzymes in larger samples of depressed patients to better optimize accelerating strategies to ECT and more broadly, thyroid augmentation strategies in major depressive and bipolar disorders.

OBJECTIVE In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder (BD). METHODS Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003 to 2008. Mayo Clinic Bipolar Biobank samples were collected from 2009 to 2013. Genotyping and analyses for the present study took place from 2013 to 2014. The diagnosis of BD was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Eight single-nucleotide polymorphisms (SNPs), previously reported in genome-wide association studies to be associated with BD, were chosen for GRS analysis in early-onset bipolar disease. These SNPs map to 3 genes: CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit), ANK3 (ankyrin-3, node of Ranvier [ankyrin G]), and ODZ4 (teneurin transmembrane protein 4 [formerly "odz, odd Oz/10-m homolog 4 {Drosophila}, ODZ4"]). The 8 candidate SNPs were genotyped in patients from the TEAM study (n = 69); adult patients with BD (n = 732), including a subset with early-onset illness (n = 192); and healthy controls (n = 776). GRS analyses were performed to compare early-onset cases with controls. In addition, associations of early-onset BD with individual SNPs and haplotypes were explored. RESULTS GRS analysis revealed associations of the risk score with early-onset BD (P = .01). Gene-level haplotype analysis comparing TEAM patients with controls suggested association of early-onset BD with a CACNA1C haplotype (global test, P = .01). At the level of individual SNPs, comparison of TEAM cases with healthy controls provided nominally significant evidence for association of SNP rs10848632 in CACNA1C with early-onset BD (P = .017), which did not remain significant after correction for multiple comparisons. CONCLUSIONS These preliminary analyses suggest that previously identified BD risk loci, especially CACNA1C, have a role in early-onset BD, possibly with stronger effects than for late-onset BD.

We previously reported that SNPs near TSPAN5 were associated with plasma serotonin (5-HT) concentrations which were themselves associated with selective serotonin reuptake inhibitor treatment outcomes in patients with major depressive disorder (MDD). TSPAN5 SNPs were also associated with alcohol consumption and alcohol use disorder (AUD) risk. The present study was designed to explore the biological function of TSPAN5 with a focus on 5-HT and kynurenine concentrations in the tryptophan pathway. Ethanol treatment resulted in decreased 5-HT concentrations in human induced pluripotent stem cell (iPSC)-derived neuron culture media, and the downregulation of gene expression of TSPAN5, DDC, MAOA, MAOB, TPH1, and TPH2 in those cells. Strikingly, similar observations were made when the cells were treated with acamprosate—an FDA approved drug for AUD therapy. These results were replicated in iPSC-derived astrocytes. Furthermore, TSPAN5 interacted physically with proteins related to clathrin and other vesicle-related proteins, raising the possibility that TSPAN5 might play a role in vesicular function in addition to regulating expression of genes associated with 5-HT biosynthesis and metabolism. Downregulation of TSPAN5 expression by ethanol or acamprosate treatment was also associated with decreased concentrations of kynurenine, a major metabolite of tryptophan that plays a role in neuroinflammation. Knockdown of TSPAN5 also influenced the expression of genes associated with interferon signaling pathways. Finally, we determined that TSPAN5 SNPs were associated with acamprosate treatment outcomes in AUD patients. In conclusion, TSPAN5 can modulate the concentrations of 5-HT and kynurenine. Our data also highlight a potentially novel pharmacogenomic mechanism related to response to acamprosate.

BACKGROUND AND PURPOSE: Temporal lobe encephaloceles are increasingly identified and treated as epileptogenic foci. However, there is relatively scant research on the prevalence of asymptomatic encephaloceles. This study set out to describe the frequency of incidental temporal lobe encephaloceles and middle cranial fossa pits. MATERIALS AND METHODS: A retrospective review was completed of high-resolution (≤0.5-mm section thickness) axial T2WI for internal auditory canal protocol imaging. The presence and laterality of middle cranial fossa pits (small bony defects containing CSF) and encephaloceles (brain parenchyma protrusion through osseous defects with or without bony remodeling) were recorded. Electronic medical records of patients with encephaloceles were searched for a history of seizure. RESULTS: A total of 203 patients were included in the final cohort; 106 (52.2%) women. Forty-five (22.2%) patients had middle cranial fossa pits: 14 (31.1%) unilateral on the right, 17 (37.8%) unilateral on the left, and 14 (31.1%) bilateral. Ten (5.0%) patients had ≥1 encephalocele, none of whom had a documented history of seizure in the electronic medical record. No significant difference was noted in the frequency of pits or encephaloceles based on sex (P = .332 and P = .383, respectively) or age (P = .497 and P = .914, respectively). CONCLUSIONS: Incidental middle cranial fossa pits are common findings, and their prevalence is not related to age or sex. Temporal lobe encephaloceles, though rarer, also exist occasionally among asymptomatic patients. Such findings have diagnostic implications for encephaloceles identified during imaging work-up for epilepsy.

Glutamatergic dysregulation is implicated in the neurobiology of mood disorders. This study investigated the relationship between the anterior cingulate cortex (AC) glutamate, as measured by proton magnetic resonance spectroscopy (1H-MRS), and single-nucleotide polymorphisms (SNPs) from four genes (GLUL, SLC1A3, SLC1A2, and SLC1A7) that regulate the extracellular glutamate in 26 depressed patients with major depressive disorder (MDD; n = 15) and bipolar disorder (BD; n = 11). Two SNPs (rs3812778 and rs3829280), in perfect linkage disequilibrium, in the 3′ untranslated region of the EAAT2 gene SLC1A2, were associated with AC glutamate, with minor allele carriers having significantly higher glutamate levels (p CD44 localized downstream of SLC1A2 on chromosome 11. Finally, we tested the disease relevance of these SNPs in a large group of depressed patients [MDD (n = 458); BD (n = 1473)] and found that minor allele carriers had a significantly higher risk for rapid cycling (p = 0.006). Further work is encouraged to delineate the functional impact of excitatory amino acid transporter genetic variation on CD44 associated physiology and glutamatergic neurotransmission, specifically glutamate–glutamine cycling, and its contribution to subphenotypes of mood disorders.

BACKGROUND AND PURPOSE: The prevalence of patent facial nerve canals and meningoceles along the facial nerve course is unknown. This study aimed to assess the frequency of such findings in asymptomatic patients. MATERIALS AND METHODS: A retrospective review was completed of patients with high-resolution MR imaging of the temporal bone whose clinical presentations were unrelated to facial nerve pathology. Facial nerve canals were assessed for the presence of fluid along each segment and meningoceles within either the labyrinthine segment (fluid-filled distention, ≥1.0-mm diameter) or geniculate ganglion fossa (fluid-filled distention, ≥2.0-mm diameter). If a meningocele was noted, images were assessed for signs of CSF leak. RESULTS: Of 204 patients, 36 (17.6%) had fluid in the labyrinthine segment of the facial nerve canal and 40 (19.6%) had fluid in the geniculate ganglion fossa. Five (2.5%) had meningoceles of the geniculate ganglion fossa; no meningoceles of the labyrinthine segment of the canal were observed. No significant difference was observed in the ages of patients with fluid in the labyrinthine segment of the canal or geniculate ganglion compared with those without fluid (P = .177 and P = .896, respectively). Of the patients with a meningocele, one had a partially empty sella and none had imaging evidence of CSF leak or intracranial hypotension. CONCLUSIONS: Fluid within the labyrinthine and geniculate segments of the facial nerve canal is relatively common. Geniculate ganglion meningoceles are also observed, though less frequently. Such findings should be considered of little clinical importance without radiologic evidence of CSF otorrhea, meningitis, or facial nerve palsy.

Background In the context of the COVID-19 pandemic, many behavioral health services have transitioned to teletherapy to continue delivering care for patients with mental illness. Studies that evaluate the outcome of this rapid teletherapy adoption and implementation are pertinent. Objective This single-arm, nonrandomized pilot study aimed to assess the feasibility and initial patient-level outcomes of a psychiatric transitional day program that switched from an in-person group to a video teletherapy group during the COVID-19 pandemic. Methods Patients with transdiagnostic conditions who were at risk of psychiatric hospitalization were referred to the Adult Transitions Program (ATP) at a large academic medical center in the United States. ATP was a 3-week intensive outpatient program that implemented group teletherapy guided by cognitive and behavioral principles delivered daily for 3 hours per day. Feasibility was assessed via retention, attendance rate, and rate of securing aftercare appointments prior to ATP discharge. Patients completed standardized patient-reported outcome measures at admission and discharge to assess the effectiveness of the program for improving quality of mental health, depression, anxiety, and suicide risk. Results Patients (N=76) started the program between March and August of 2020. Feasibility was established, with 70 of the 76 patients (92%) completing the program and a mean attendance of 14.43 days (SD 1.22); also, 71 patients (95%) scheduled at least one behavioral health aftercare service prior to ATP discharge. All patient-level reported outcomes demonstrated significant improvements in depression (95% CI –3.6 to –6.2; Cohen d=0.77; P Conclusions Rapid adoption and implementation of a group-based teletherapy day program for adults at risk of psychiatric hospitalization appeared to be feasible and effective. Patients demonstrated high completion and attendance rates and reported significant improvements in psychosocial outcomes. Larger trials should be conducted to further evaluate the efficacy and effectiveness of the program through randomized controlled trials.

Objective:While suicide attempt history is considered to robustly predict completed suicide, previous studies have limited generalizability because of using convenience samples of specific methods/treatment settings, disregarding previous attempts, or overlooking first-attempt deaths. Eliminating these biases should more accurately estimate suicide prevalence in attempters.Method:This observational retrospective-prospective cohort study using the Rochester Epidemiology Project identified 1,490 (males, N=555; females, N=935) Olmsted County residents making index suicide attempts (first lifetime attempts reaching medical attention) between January 1, 1986, and December 31, 2007. The National Death Index identified suicides between enrollment and December 31, 2010 (follow-up 3–25 years). Medical records were queried for sex, age, method, and follow-up care for index attempt survivors. Coroner records yielded data on index attempt deaths.Results:During the study period, 81/1,490 enrollees (5.4%) died by suici...

The United Network for Organ Sharing mandates a psychosocial assessment of transplant candidates before listing. A quantified measure for determining transplant candidacy is the Psychosocial Assessment of Candidates for Transplant (PACT) scale. This instrument's predictive value for survival has not been rigorously evaluated among lung transplantation recipients.We reviewed medical records of all patients who underwent lung transplantation at Mayo Clinic, Rochester from 2000-2012. A transplant psychiatrist had assessed lung transplant candidates for psychosocial risk with the PACT scale. Recipients were divided into high- and low psychosocial risk cohorts using a PACT score cutoff of 2. The main outcome variable was posttransplant survival. Mortality was analyzed using the Kaplan-Meier estimator and Cox proportional hazard models.This study included 110 lung recipients: 57 (51.8%) were females, 101 (91.8%) Whites, mean age: 56.4 years. Further, 7 (6.4%) recipients received an initial PACT score2 (poor or borderline candidates) and later achieved a higher score, allowing transplant listing; 103 (93.6%) received initial scores ≥2 (acceptable, good or great candidates). An initial PACT score2 was modestly associated with higher mortality (adjusted hazard ratio = 2.73, p = 0.04).Lung transplant recipients who initially received a low score on the PACT scale, reflecting poor or borderline psychosocial candidacy, experienced greater likelihood of mortality. This primary finding suggests that the psychosocial assessment, as measured by the PACT scale, may provide additional mortality risk stratification for lung transplant candidates.

Context: Early postprandial hyperglycemia and delayed hypoglycemia remain major problems in current management of type 1 diabetes (T1D). Objective: Our objective was to investigate the effects of pramlintide, known to suppress glucagon and delay gastric emptying, on postprandial glucose fluxes in T1D. Design: This was a single-center, inpatient, randomized, crossover study. Patients: Twelve patients with T1D who completed the study were analyzed. Interventions: Subjects were studied on two occasions with or without pramlintide. Triple tracer mixed-meal method and oral minimal model were used to estimate postprandial glucose turnover and insulin sensitivity (SI). Integrated liver insulin sensitivity was calculated based on glucose turnover. Plasma glucagon and insulin were measured. Main Outcome Measure: Glucose turnover and SI were the main outcome measures. Results: With pramlintide, 2-hour postprandial glucose, insulin, glucagon, glucose turnover, and SI indices showed: plasma glucose excursions were reduced (difference in incremental area under the curve [iAUC], 444.0 mMmin, P = .0003); plasma insulin concentrations were lower (difference in iAUC, 7642.0 pMmin; P = .0099); plasma glucagon excursions were lower (difference in iAUC, 1730.6 pg/mlmin; P = .0147); meal rate of glucose appearance was lower (difference in iAUC: 1196.2 μM/kg fat free mass [FFM]; P = .0316), endogenous glucose production was not different (difference in iAUC: −105.5 μM/kg FFM; P = .5842), rate of glucose disappearance was lower (difference in iAUC: 1494.2 μM/kg FFM; P = .0083). SI and liver insulin sensitivity were not different between study visits (P > .05). Conclusions: Inhibition of glucagon and gastric emptying delaying reduced 2-hour prandial glucose excursions in T1D by delaying meal rate of glucose appearance.

Background Prior work suggests that adult bipolar disorder (BD) is associated with increased oxidative stress and inflammation. This exploratory study examined markers of lipid and protein oxidation and inflammation in adolescents with and at varying risk for BD type I (BD-I). Methods Blood was obtained from four groups of adolescents (9–20 years of age): (1) healthy comparison subjects with no personal or family history of psychiatric disorders (n=13), (2) subjects with no psychiatric diagnosis and at least one parent with BD-I (‘high-risk’, n=15), (3) subjects with at least one parent with BD-I and a diagnosis of depressive disorder not-otherwise-specified (‘ultra-high-risk’, n=20), and (4) first-episode patients exhibiting mixed or manic symptoms that received a diagnosis of BD-I (n=16). Plasma levels of lipid peroxidation (LPH, 4-HNE, 8-ISO), protein carbonyl, and inflammation (IL-1α-β, IL-6, IL-10, IFNγ, TNFα) were assessed using analysis of variance and covariance models. Results LPH was lower in adolescents with fully syndromal BD than controls, while LPH levels in the at-risk groups were between healthy controls and fully syndromal BD. Post-hoc analysis showed a non-significant increase in the (4-HNE+8-ISO)/LPH ratio suggesting a potential conversion of LPH into late-stage markers of lipid peroxidation. There were no significant differences among protein carbonyl content and inflammatory markers. Conclusions In adolescents, fully syndromal BD is associated with significant reductions in LPH levels, and LPH levels decrease along the spectrum of risk for BD-I. Quantifying lipid peroxidation in longitudinal studies may help clarify the role of LPH in BD risk progression.

Item does not contain fulltext Nerve movement is decreased in patients with carpal tunnel syndrome and can be assessed with ultrasound. In addition to morphologic features, this study describes a novel approach in which nerve movement and the association with short-term patient-reported outcome are assessed. Ultrasound images at the carpal tunnel inlet were acquired during finger and wrist flexion. Linear regression models were used with the Boston Carpal Tunnel Questionnaire as main outcome. Eighty-five patients were included; 93% completed the 3-mo follow-up. Pre-surgical mean nerve area was 14.5 +/- 4.2 mm(2) and decreased to 13.3 +/- 3.8 mm(2) (p < 0.001). Displacement in dorsal direction with wrist flexion increased from 1.9 +/- 1.3 to 2.4 +/- 1.3 mm (p < 0.01). A pre-surgical larger nerve area was associated with more functional improvement (beta=-0.024, p=0.02), but baseline mobility was not. Change in excursion with finger flexion was associated with symptomatic improvement, but with a small effect (beta=-0.05, p=0.01). This indicates that there is limited prognostic potential for dynamic transverse ultrasound in carpal tunnel syndrome.

The purpose of this study is to compare diagnostic outcomes of digital breast tomosynthesis screen-detected masses worked up with mammography first with those evaluated with diagnostic ultrasound initially. METHODS: All masses recalled from screening digital breast tomosynthesis between July 1, 2017 and December 31, 2017 that were sent either to diagnostic mammography or ultrasound were compared. Size, shape, margins, visibility on ultrasound, diagnostic assessment and pathology of all masses along with breast density were evaluated. RESULTS: 102/212 digital breast tomosynthesis screen-detected masses were worked up with diagnostic mammography initially and 110/212 were worked up with ultrasound directly. There was no significant difference in ultrasound visibility of masses sent to diagnostic mammography first with those sent to ultrasound first (p = 0.42). 4 (4%) masses sent to mammogram first and 2 (2%) masses sent to ultrasound first were not visualized. There was a significant difference in size between masses that were visualized under ultrasound versus those that were not (p = 0.01), when masses in both groups were assessed cumulatively. CONCLUSIONS: 98% of digital breast tomosynthesis screen-detected masses sent to ultrasound directly were adequately assessed without diagnostic mammography. ADVANCES IN KNOWLEDGE: There is potential for avoiding a diagnostic mammogram for evaluation of majority of digital breast tomosynthesis screen-detected masses.

Background Sex-related differences in the susceptibility, progression, and treatment response in alcohol-dependent subjects have been repeatedly reported. In this study, we aimed to investigate the associations of the sex-related hormone/protein levels with alcohol dependence (AD) and alcohol craving in male and female subjects. Methods Plasma sex-related hormones (estradiol, estrone, total testosterone, progesterone, follicle stimulated hormone [FSH], luteinizing hormone), and sex hormone binding globulin were measured by mass spectrometry or automated immunoassays from 44 recently-abstained subjects (29 males and 15 females; mean age = 45.9 ± 15.6) meeting DSM-IV-TR criteria for AD and 44 age-, sex- and race-matched non-AD controls. Conditional logistic regression was conducted to examine the association of sex-related hormone and protein levels with AD risk, accounting for matching variables. Their associations with alcohol craving scales (Penn Alcohol Craving Scale and Inventory of Drug-Taking Situations) were assessed in AD subjects. Results Plasma FSH level was significantly higher in AD males (10.3 ± 9.8 IU/L) than control males (8.0 ± 15.9 IU/L; p = 0.005, pcorrected = 0.035). We also found a significant inverse correlation of FSH level with propensity to drink in negative emotional situations (Spearman’s rho=-.540; p = 0.021) and positive correlations between progesterone level and craving intensity (Spearman’s rho=.464; p = 0.020) and between total testosterone level and propensity to drink under temptations (adjusted for no-drinking days; β=6.496; p = 0.041) in AD males. Conclusions These results suggest that FSH, progesterone, and testosterone levels may be associated with AD and alcohol craving in AD males. Future research is needed to replicate these findings and investigate the underlying biological mechanisms.

We assessed the impact of comorbid depression and anxiety disorders as well as positive and negative emotional states on alcohol consumption in alcohol dependent men and women.Per day alcohol consumption during 90 days before enrolment was assessed by the Time Line Follow Back (TLFB) in 287 men and 156 women meeting DSM-IV-TR criteria for alcohol dependence. Propensity to drink in negative/positive emotional states was assessed using the Inventory of Drug Taking Situations (IDTS). Psychiatric comorbidities, including major depressive disorder (MDD), substance-induced depression (SID), anxiety disorders (AnxD), or substance-induced anxiety (SIA) were identified by Psychiatric Research Interview of Substance and Mood Disorders (PRISM).In the combined group, increased number of drinks per day and number of heavy drinking days correlated with increased IDTS scores (all p 0.0001), while the lifetime history of MDD was associated with fewer drinking days (p = 0.045) but not average number of drinks per day. Male sex was associated with higher alcohol consumption per day (p 0.0001), but not with the number of drinking days (p 0.05). Lifetime MDD history was associated with less drinking days (p = 0.0084) and less heavy drinking days (p = 0.021) in alcohol dependent men, while current MDD was associated with higher alcohol use per day in alcohol dependent women (p = 0.044).Our findings suggest that emotional states and lifetime MDD history have sex-specific impact on alcohol use in alcohol dependent men and women. The mechanisms underlying these findings and their relevance to treatment outcomes need to be examined in future studies.