Anorexia nervosa (AN) is a psychiatric disorder with complex etiology, with a significant portion of disease risk imparted by genetics. Traditional genome-wide association studies (GWAS) produce principal evidence for the association of genetic variants with disease. Transcriptomic imputation (TI) allows for the translation of those variants into regulatory mechanisms, which can then be used to assess the functional outcome of genetically regulated gene expression (GReX) in a broader setting through the use of phenome-wide association studies (pheWASs) in large and diverse clinical biobank populations with electronic health record phenotypes.

Here, we applied TI using S-PrediXcan to translate the most recent PGC-ED AN GWAS findings into AN-GReX. For significant genes, we imputed AN-GReX in the Mount Sinai BioMe™ Biobank and performed pheWASs on over 2000 outcomes to test the clinical consequences of aberrant expression of these genes. We performed a secondary analysis to assess the impact of body mass index (BMI) and sex on AN-GReX clinical associations.

Our S-PrediXcan analysis identified 53 genes associated with AN, including what is, to our knowledge, the first-genetic association of AN with the major histocompatibility complex. AN-GReX was associated with autoimmune, metabolic, and gastrointestinal diagnoses in our biobank cohort, as well as measures of cholesterol, medications, substance use, and pain. Additionally, our analyses showed moderation of AN-GReX associations with measures of cholesterol and substance use by BMI, and moderation of AN-GReX associations with celiac disease by sex.

Our BMI-stratified results provide potential avenues of functional mechanism for AN-genes to investigate further.

To estimate prior severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among skilled nursing facility (SNF) staff in the state of Georgia and to identify risk factors for seropositivity as of fall 2020.

Baseline survey and seroprevalence of the ongoing longitudinal Coronavirus 2019 (COVID-19) Prevention in Nursing Homes study.

The study included 14 SNFs in the state of Georgia.

In total, 792 SNF staff employed or contracted with participating SNFs were included in this study. The analysis included 749 participants with SARS-CoV-2 serostatus results who provided age, sex, and complete survey information.

We estimated unadjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for potential risk factors and SARS-CoV-2 serostatus. We estimated adjusted ORs using a logistic regression model including age, sex, community case rate, SNF resident infection rate, working at other facilities, and job role.

Staff working in high-infection SNFs were twice as likely (unadjusted OR, 2.08; 95% CI, 1.45–3.00) to be seropositive as those in low-infection SNFs. Certified nursing assistants and nurses were 3 times more likely to be seropositive than administrative, pharmacy, or nonresident care staff: unadjusted OR, 2.93 (95% CI, 1.58–5.78) and unadjusted OR, 3.08 (95% CI, 1.66–6.07). Logistic regression yielded similar adjusted ORs.

Working at high-infection SNFs was a risk factor for SARS-CoV-2 seropositivity. Even after accounting for resident infections, certified nursing assistants and nurses had a 3-fold higher risk of SARS-CoV-2 seropositivity than nonclinical staff. This knowledge can guide prioritized implementation of safer ways for caregivers to provide necessary care to SNF residents.

Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.

We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.

We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).

Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.

To conduct a pilot study implementing combined genomic and epidemiologic surveillance for hospital-acquired multidrug-resistant organisms (MDROs) to predict transmission between patients and to estimate the local burden of MDRO transmission.

Pilot prospective multicenter surveillance study.

The study was conducted in 8 university hospitals (2,800 beds total) in Melbourne, Australia (population 4.8 million), including 4 acute-care, 1 specialist cancer care, and 3 subacute-care hospitals.

All clinical and screening isolates from hospital inpatients (April 24 to June 18, 2017) were collected for 6 MDROs: vanA VRE, MRSA, ESBL Escherichia coli (ESBL-Ec) and Klebsiella pneumoniae (ESBL-Kp), and carbapenem-resistant Pseudomonas aeruginosa (CRPa) and Acinetobacter baumannii (CRAb). Isolates were analyzed and reported as routine by hospital laboratories, underwent whole-genome sequencing at the central laboratory, and were analyzed using open-source bioinformatic tools. MDRO burden and transmission were assessed using combined genomic and epidemiologic data.

In total, 408 isolates were collected from 358 patients; 47.5% were screening isolates. ESBL-Ec was most common (52.5%), then MRSA (21.6%), vanA VRE (15.7%), and ESBL-Kp (7.6%). Most MDROs (88.3%) were isolated from patients with recent healthcare exposure.

Combining genomics and epidemiology identified that at least 27.1% of MDROs were likely acquired in a hospital; most of these transmission events would not have been detected without genomics. The highest proportion of transmission occurred with vanA VRE (88.4% of patients).

Genomic and epidemiologic data from multiple institutions can feasibly be combined prospectively, providing substantial insights into the burden and distribution of MDROs, including in-hospital transmission. This analysis enables infection control teams to target interventions more effectively.

This study investigated the latent factor structure of the NIH Toolbox Cognition Battery (NIHTB-CB) and its measurement invariance across clinical diagnosis and key demographic variables including sex, race/ethnicity, age, and education for a typical Alzheimer’s disease (AD) research sample.

The NIHTB-CB iPad English version, consisting of 7 tests, was administered to 411 participants aged 45–94 with clinical diagnosis of cognitively unimpaired, dementia, mild cognitive impairment (MCI), or impaired not MCI. The factor structure of the whole sample was first examined with exploratory factor analysis (EFA) and further refined using confirmatory factor analysis (CFA). Two groups were classified for each variable (diagnosis or demographic factors). The confirmed factor model was next tested for each group with CFA. If the factor structure was the same between the groups, measurement invariance was then tested using a hierarchical series of nested two-group CFA models.

A two-factor model capturing fluid cognition (executive function, processing speed, and memory) versus crystalized cognition (language) fit well for the whole sample and each group except for those with age < 65. This model generally had measurement invariance across sex, race/ethnicity, and education, and partial invariance across diagnosis. For individuals with age < 65, the language factor remained intact while the fluid cognition was separated into two factors: (1) executive function/processing speed and (2) memory.

The findings mostly supported the utility of the battery in AD research, yet revealed challenges in measuring memory for AD participants and longitudinal change in fluid cognition.

Cognitive behavior therapy (CBT) is effective for most patients with a social anxiety disorder (SAD) but a substantial proportion fails to remit. Experimental and clinical research suggests that enhancing CBT using imagery-based techniques could improve outcomes. It was hypothesized that imagery-enhanced CBT (IE-CBT) would be superior to verbally-based CBT (VB-CBT) on pre-registered outcomes.

A randomized controlled trial of IE-CBT v. VB-CBT for social anxiety was completed in a community mental health clinic setting. Participants were randomized to IE (n = 53) or VB (n = 54) CBT, with 1-month (primary end point) and 6-month follow-up assessments. Participants completed 12, 2-hour, weekly sessions of IE-CBT or VB-CBT plus 1-month follow-up.

Intention to treat analyses showed very large within-treatment effect sizes on the social interaction anxiety at all time points (ds = 2.09–2.62), with no between-treatment differences on this outcome or clinician-rated severity [1-month OR = 1.45 (0.45, 4.62), p = 0.53; 6-month OR = 1.31 (0.42, 4.08), p = 0.65], SAD remission (1-month: IE = 61.04%, VB = 55.09%, p = 0.59); 6-month: IE = 58.73%, VB = 61.89%, p = 0.77), or secondary outcomes. Three adverse events were noted (substance abuse, n = 1 in IE-CBT; temporary increase in suicide risk, n = 1 in each condition, with one being withdrawn at 1-month follow-up).

Group IE-CBT and VB-CBT were safe and there were no significant differences in outcomes. Both treatments were associated with very large within-group effect sizes and the majority of patients remitted following treatment.

Optimal management of schizophrenia in adolescents is limited by the lack of available therapies. The efficacy and tolerability of aripiprazole was investigated in this patient population.

This 6-week, randomized, double-blind, placebo controlled trial was conducted at 101 international centers, with a safety monitoring board. 13-17 year-olds with a DSM-IV diagnosis of schizophrenia were randomized to placebo, or a fixed dose of aripiprazole 10 mg or 30 mg reached after a 5 or 11 day titration, respectively. The primary endpoint was mean change from baseline on the PANSS Total score at week 6. Secondary endpoints included the PANSS Positive and Negative subscales, and CGI Improvement score. Tolerabilility assessements included frequency and severity of adverse events, as well as blood chemistries, metabolic parameters and weight gain.

Over 85% of 302 patients completed this study. Both 10 mg and 30 mg doses were superior to placebo on the primary endpoint (PANSS total), with significant differences observed as early as Week 1 (30mg). Both doses showed significant improvement on the PANSS Positive and CGI-I scales; and the 10 mg dose group was superior on PANSS Negative score. Approximately 5% of aripiprazole patients discontinued due to AEs. Weight gain and changes in prolactin were minimal.

10mg and 30mg doses of aripiprazole were superior to placebo in the treatment of adolescents with schizophrenia. Aripiprazole was well tolerated, in general, with few discontinuations due to AEs. EPS was the most common AE. Change in body weight was similar to placebo.

There is limited published data from long-term pediatric bipolar clinical trials with which to guide appropriate treatment decisions. Long-term efficacy and safety of aripiprazole was investigated in this patient population.

296 youths, ages 10-17 year-old with a DSM-IV diagnosis of bipolar I disorder were randomized to receive either placebo or aripiprazole (10mg or 30mg) in a 4-week double-blind trial. Completers continued assigned treatments for an additional 26 weeks (double-blind). Efficacy endpoints included mean change from baseline to week 4 and week 30 on the Young Mania Rating Scale; Children's Global Assessment Scale, Clinical Global Impressions-Bipolar version severity scale, General Behavior Inventory, Attention Deficit Hyperactivity Disorders Rating Scale, and time to discontinuation. Tolerability/safety assessments included incidence and severity of AEs, blood chemistries and metabolic parameters.

Over the 30-week course of double-blind treatment, aripiprazole (10 mg and 30 mg) was superior to placebo as early as week 1 (p< 0.002) and at all scheduled visits from week 2 through week 30 on mean change from baseline in the Y-MRS total score (p<.0001; all visits). Significant improvements were observed on multiple endpoints including the CGAS, GBI, CGI-BP, ADHD-RS-IV total score, time to discontinuation, and response and remission rates. The 3 most common AEs were somnolence, extrapyramidal disorder, and fatigue. Mean change in body weight z-scores over 30 weeks was not clinically significant.

Over 30-weeks of treatment, both doses of aripiprazole were superior to placebo in the long term treatment of pediatric bipolar patients. Aripiprazole was generally well tolerated.

Lisdexamfetamine dimesylate (LDX) is a long-acting prodrug stimulant for treatment of attention-deficit/hyperactivity disorder (ADHD).

Review efficacy and safety data from two double-blind, randomized trials (SPD489-325 and SPD489-326) in patients with ADHD aged 6–17 years.

In SPD489-325, patients received placebo or optimized doses of LDX or the reference treatment, osmotic-release oral system methylphenidate (OROS-MPH) for ≤7 weeks. The primary efficacy measure was ADHD Rating Scale IV (ADHD-RS-IV) total score. Statistical comparison of LDX versus OROS-MPH was not pre-specified. In SPD489-326, a ≥26-week open-label LDX period preceded a 6-week, placebo-controlled, randomized-withdrawal period (RWP). The primary endpoint was treatment failure (50% increase in ADHD-RS-IV total score and ≥2-point increase in Clinical Global Impressions-Severity score from RWP baseline). Efficacy was assessed in the full analysis sets.

In SPD489-325 (N=317), placebo-adjusted least-squares-mean changes in ADHD-RS-IV total score from baseline to endpoint were: LDX, –18.6 (95% confidence interval [CI]: –21.5, –15.7; p<0.001; effect size 1.80) and OROS MPH, –13.0 (–15.9, –10.2; p<0.001; 1.26). In SPD489-326 (N=262, open-label period; N=153, RWP), 15.8% and 67.5% of patients receiving LDX and placebo, respectively, met treatment failure criteria at RWP endpoint (differen –51.7%; 95% CI: –65.0%, –38.5%; p<0.001). The most common treatment-emergent adverse events in LDX-treated patients were decreased appetite, headache and decreased weight.

Short-term LDX treatment improved symptoms of ADHD in children and adolescents. Continued LDX treatment was associated with maintenance of efficacy compared with placebo. The safety profile of LDX was generally consistent with that of stimulant therapy.