Older adults with treatment-resistant depression (TRD) benefit more from treatment augmentation than switching. It is useful to identify moderators that influence these treatment strategies for personalised medicine.

Our objective was to test whether age, executive dysfunction, comorbid medical burden, comorbid anxiety or the number of previous adequate antidepressant trials could moderate the superiority of augmentation over switching. A significant moderator would influence the differential effect of augmentation versus switching on treatment outcomes.

We performed a preplanned moderation analysis of data from the Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM) randomised controlled trial (N = 742). Participants were 60 years old or older with TRD. Participants were either (a) randomised to antidepressant augmentation with aripiprazole (2.5–15 mg), bupropion (150–450 mg) or lithium (target serum drug level 0.6 mmol/L) or (b) switched to bupropion (150–450 mg) or nortriptyline (target serum drug level 80–120 ng/mL). Treatment duration was 10 weeks. The two main outcomes of this analysis were (a) symptom improvement, defined as change in Montgomery–Asberg Depression Rating Scale (MADRS) scores from baseline to week 10 and (b) remission, defined as MADRS score of 10 or less at week 10.

Of the 742 participants, 480 were randomised to augmentation and 262 to switching. The number of adequate previous antidepressant trials was a significant moderator of depression symptom improvement (b = −1.6, t = −2.1, P = 0.033, 95% CI [−3.0, −0.1], where b is the coefficient of the relationship (i.e. effect size), and t is the t-statistic for that coefficient associated with the P-value). The effect was similar across all augmentation strategies. No other putative moderators were significant.

Augmenting was superior to switching antidepressants only in older patients with fewer than three previous antidepressant trials. This suggests that other intervention strategies should be considered following three or more trials.

Former professional American football players have a high relative risk for neurodegenerative diseases like chronic traumatic encephalopathy (CTE). Interpreting low cognitive test scores in this population occasionally is complicated by performance on validity testing. Neuroimaging biomarkers may help inform whether a neurodegenerative disease is present in these situations. We report three cases of retired professional American football players who completed comprehensive neuropsychological testing, but “failed” performance validity tests, and underwent multimodal neuroimaging (structural MRI, Aß-PET, and tau-PET).

Three cases were identified from the Focused Neuroimaging for the Neurodegenerative Disease Chronic Traumatic Encephalopathy (FIND-CTE) study, an ongoing multimodal imaging study of retired National Football League players with complaints of progressive cognitive decline conducted at Boston University and the UCSF Memory and Aging Center. Participants were relatively young (age range 55-65), had 16 or more years of education, and two identified as Black/African American. Raw neuropsychological test scores were converted to demographically-adjusted z-scores. Testing included standalone (Test of Memory Malingering; TOMM) and embedded (reliable digit span, RDS) performance validity measures. Validity cutoffs were TOMM Trial 2 < 45 and RDS < 7. Structural MRIs were interpreted by trained neurologists. Aß-PET with Florbetapir was used to quantify cortical Aß deposition as global Centiloids (0 = mean cortical signal for a young, cognitively normal, Aß negative individual in their 20s, 100 = mean cortical signal for a patient with mild-to-moderate Alzheimer’s disease dementia). Tau-PET was performed with MK-6240 and first quantified as standardized uptake value ratio (SUVR) map. The SUVR map was then converted to a w-score map representing signal intensity relative to a sample of demographically-matched healthy controls.

All performed in the average range on a word reading-based estimate of premorbid intellect. Contribution of Alzheimer’s disease pathology was ruled out in each case based on Centiloids quantifications < 0. All cases scored below cutoff on TOMM Trial 2 (Case #1=43, Case #2=42, Case #3=19) and Case #3 also scored well below RDS cutoff (2). Each case had multiple cognitive scores below expectations (z < -2.0) most consistently in memory, executive function, processing speed domains. For Case #1, MRI revealed mild atrophy in dorsal fronto-parietal and medial temporal lobe (MTL) regions and mild periventricular white matter disease. Tau-PET showed MTL tau burden modestly elevated relative to controls (regional w-score=0.59, 72nd%ile). For Case #2, MRI revealed cortical atrophy, mild hippocampal atrophy, and a microhemorrhage, with no evidence of meaningful tau-PET signal. For Case #3, MRI showed cortical atrophy and severe white matter disease, and tau-PET revealed significantly elevated MTL tau burden relative to controls (w-score=1.90, 97th%ile) as well as focal high signal in the dorsal frontal lobe (overall frontal region w-score=0.64, 74th%ile).

Low scores on performance validity tests complicate the interpretation of the severity of cognitive deficits, but do not negate the presence of true cognitive impairment or an underlying neurodegenerative disease. In the rapidly developing era of biomarkers, neuroimaging tools can supplement neuropsychological testing to help inform whether cognitive or behavioral changes are related to a neurodegenerative disease.

Individuals living with HIV may experience cognitive difficulties or marked declines known as HIV-Associated Neurocognitive Disorder (HAND). Cognitive difficulties have been associated with worse outcomes for people living with HIV, therefore, accurate cognitive screening and identification is critical. One potentially sensitive marker of cognitive impairment which has been underutilized, is intra-individual variability (IIV). Cognitive IIV is the dispersion of scores across tasks in neuropsychological assessment. In individuals living with HIV, greater cognitive IIV has been associated with cortical atrophy, poorer cognitive functioning, with more rapid declines, and greater difficulties in daily functioning. Studies examining the use of IIV in clinical neuropsychological testing are limited, and few have examined IIV in the context of a single neuropsychological battery designed for culturally diverse or at-risk populations. To address these gaps, this study aimed to examine IIV profiles of individuals living with HIV and who inject drugs, utilizing the Neuropsi, a standardized neuropsychological instrument for Spanish speaking populations.

Spanish speaking adults residing in Puerto Rico (n=90) who are HIV positive and who inject drugs (HIV+I), HIV negative and who inject drugs (HIV-I), HIV positive who do not inject drugs (HIV+), or healthy controls (HC) completed the Neuropsi battery as part of a larger research protocol. The Neuropsi produces 3 index scores representing cognitive domains of memory, attention/memory, and attention/executive functioning. Total battery and within index IIV were calculated by dividing the standard deviation of T-scores by mean performance, resulting in a coefficient of variance (CoV). Group differences on overall test battery mean CoV (OTBMCoV) were investigated. To examine unique profiles of index specific IIV, a cluster analysis was performed for each group.

Results of a one-way ANOVA indicated significant between group differences on OTBMCoV (F[3,86]=6.54, p<.001). Post-hoc analyses revealed that HIV+I (M=.55, SE=.07, p=.003), HIV-I (M=.50, SE=.03, p=.001), and HIV+ (M=.48, SE=.02, p=.002) had greater OTBMCoV than the HC group (M=.30, SE=.02). To better understand sources of IIV within each group, cluster analysis of index specific IIV was conducted. For the HIV+ group, 3 distinct clusters were extracted: 1. High IIV in attention/memory and attention/executive functioning (n=3, 8%); 2. Elevated memory IIV (n=21, 52%); 3. Low IIV across all indices (n=16, 40%). For the HIV-I group, 2 distinct clusters were extracted: 1. High IIV across all 3 indices (n=7, 24%) and 2. Low IIV across all 3 indices (n=22, 76%). For the HC group, 3 distinct clusters were extracted: 1. Very low IIV across all 3 indices (n=5, 36%); 2. Elevated memory IIV (n=6, 43%); 3. Elevated attention/executive functioning IIV with very low attention/memory and memory IIV (n=3, 21%). Sample size of the HIV+I group was insufficient to extract clusters.

Current findings support IIV in the Neuropsi test battery as clinically sensitive marker for cognitive impairment in Spanish speaking individuals living with HIV or who inject drugs. Furthermore, the distinct IIV cluster types identified between groups can help to better understand specific sources of variability. Implications for clinical assessment in prognosis and etiological considerations are discussed.

Injection drug use is a significant public health crisis with adverse health outcomes, including increased risk of human immunodeficiency virus (HIV) infection. Comorbidity of HIV and injection drug use is highly prevalent in the United States and disproportionately elevated in surrounding territories such as Puerto Rico. While both HIV status and injection drug use are independently known to be associated with cognitive deficits, the interaction of these effects remains largely unknown. The aim of this study was to determine how HIV status and injection drug use are related to cognitive functioning in a group of Puerto Rican participants. Additionally, we investigated the degree to which type and frequency of substance use predict cognitive abilities.

96 Puerto Rican adults completed the Neuropsi Attention and Memory-3rd Edition battery for Spanish-speaking participants. Injection substance use over the previous 12 months was also obtained via clinical interview. Participants were categorized into four groups based on HIV status and injection substance use in the last 30 days (HIV+/injector, HIV+/non-injector, HIV/injector, HIV-/non-injector). One-way analysis of variance (ANOVA) was conducted to determine differences between groups on each index of the Neuropsi battery (Attention and Executive Function; Memory; Attention and Memory). Multiple linear regression was used to determine whether type and frequency of substance use predicted performance on these indices while considering HIV status.

The one-way ANOVAs revealed significant differences (p’s < 0.01) between the healthy control group and all other groups across all indices. No significant differences were observed between the other groups. Injection drug use, regardless of the substance, was associated with lower combined attention and memory performance compared to those who inject less than monthly (Monthly: p = 0.04; 2-3x daily: p < 0.01; 4-7x daily: p = 0.02; 8+ times daily: p < 0.01). Both minimal and heavy daily use predicted poorer memory performance (p = 0.02 and p = 0.01, respectively). Heavy heroin use predicted poorer attention and executive functioning (p = 0.04). Heroin use also predicted lower performance on tests of memory when used monthly (p = 0.049), and daily or almost daily (2-6x weekly: p = 0.04; 4-7x daily: p = 0.04). Finally, moderate injection of heroin predicted lower scores on attention and memory (Weekly: p = 0.04; 2-6x weekly: p = 0.048). Heavy combined heroin and cocaine use predicted worse memory performance (p = 0.03) and combined attention and memory (p = 0.046). HIV status was not a moderating factor in any circumstance.

As predicted, residents of Puerto Rico who do not inject substances and are HIVnegative performed better in domains of memory, attention, and executive function than those living with HIV and/or inject substances. There was no significant difference among the affected groups in cognitive ability. As expected, daily injection of substances predicted worse performance on tasks of memory. Heavy heroin use predicted worse performance on executive function and memory tasks, while heroin-only and combined heroin and cocaine use predicted worse memory performance. Overall, the type and frequency of substance is more predictive of cognitive functioning than HIV status.

Sleep problems associated with poor mental health and academic outcomes may have been exacerbated by the COVID-19 pandemic.

To describe sleep in undergraduate students during the COVID-19 pandemic.

This longitudinal analysis included data from 9523 students over 4 years (2018–2022), associated with different pandemic phases. Students completed a biannual survey assessing risk factors, mental health symptoms and lifestyle, using validated measures. Sleep was assessed with the Sleep Condition Indicator (SCI-8). Propensity weights and multivariable log-binomial regressions were used to compare sleep in four successive first-year cohorts. Linear mixed-effects models were used to examine changes in sleep over academic semesters and years.

There was an overall decrease in average SCI-8 scores, indicating worsening sleep across academic years (average change −0.42 per year; P-trend < 0.001), and an increase in probable insomnia at university entry (range 18.1–29.7%; P-trend < 0.001) before and up to the peak of the pandemic. Sleep improved somewhat in autumn 2021, when restrictions loosened. Students commonly reported daytime sleep problems, including mood, energy, relationships (36–48%) and concentration, productivity, and daytime sleepiness (54–66%). There was a consistent pattern of worsening sleep over the academic year. Probable insomnia was associated with increased cannabis use and passive screen time, and reduced recreation and exercise.

Sleep difficulties are common and persistent in students, were amplified by the pandemic and worsen over the academic year. Given the importance of sleep for well-being and academic success, a preventive focus on sleep hygiene, healthy lifestyle and low-intensity sleep interventions seems justified.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen in neonatal intensive care units (NICU) that confers significant morbidity and mortality.

Improving our understanding of MRSA transmission dynamics, especially among high-risk patients, is an infection prevention priority.

We investigated a cluster of clinical MRSA cases in the NICU using a combination of epidemiologic review and whole-genome sequencing (WGS) of isolates from clinical and surveillance cultures obtained from patients and healthcare personnel (HCP).

Phylogenetic analysis identified 2 genetically distinct phylogenetic clades and revealed multiple silent-transmission events between HCP and infants. The predominant outbreak strain harbored multiple virulence factors. Epidemiologic investigation and genomic analysis identified a HCP colonized with the dominant MRSA outbreak strain who cared for most NICU patients who were infected or colonized with the same strain, including 1 NICU patient with severe infection 7 months before the described outbreak. These results guided implementation of infection prevention interventions that prevented further transmission events.

Silent transmission of MRSA between HCP and NICU patients likely contributed to a NICU outbreak involving a virulent MRSA strain. WGS enabled data-driven decision making to inform implementation of infection control policies that mitigated the outbreak. Prospective WGS coupled with epidemiologic analysis can be used to detect transmission events and prompt early implementation of control strategies.

The aim of the study was to assess occupational health effects 1 month after responding to a natural gas pipeline explosion.

First responders to a pipeline explosion in Kentucky were interviewed about pre- and post-response health symptoms, post-response health care, and physical exertion and personal protective equipment (PPE) use during the response. Logistic regression was used to examine associations between several risk factors and development of post-response symptoms.

Among 173 first responders involved, 105 (firefighters [58%], emergency medical services [19%], law enforcement [10%], and others [12%]) were interviewed. Half (53%) reported at least 1 new or worsening symptom, including upper respiratory symptoms (39%), headache (18%), eye irritation (17%), and lower respiratory symptoms (16%). The majority (79%) of symptomatic responders did not seek post-response care. Compared with light-exertion responders, hard-exertion responders (48%) had significantly greater odds of upper respiratory symptoms (aOR: 2.99, 95% CI: 1.25–7.50). Forty-four percent of responders and 77% of non-firefighter responders reported not using any PPE.

Upper respiratory symptoms were common among first responders of a natural gas pipeline explosion and associated with hard-exertion activity. Emergency managers should ensure responders are trained in, equipped with, and properly use PPE during these incidents and encourage responders to seek post-response health care when needed.

To describe epidemiologic and genomic characteristics of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in a large skilled-nursing facility (SNF), and the strategies that controlled transmission.

This cohort study was conducted during March 22–May 4, 2020, among all staff and residents at a 780-bed SNF in San Francisco, California.

Contact tracing and symptom screening guided targeted testing of staff and residents; respiratory specimens were also collected through serial point prevalence surveys (PPSs) in units with confirmed cases. Cases were confirmed by real-time reverse transcription–polymerase chain reaction testing for SARS-CoV-2, and whole-genome sequencing (WGS) was used to characterize viral isolate lineages and relatedness. Infection prevention and control (IPC) interventions included restricting from work any staff who had close contact with a confirmed case; restricting movement between units; implementing surgical face masking facility-wide; and the use of recommended PPE (ie, isolation gown, gloves, N95 respirator and eye protection) for clinical interactions in units with confirmed cases.

Of 725 staff and residents tested through targeted testing and serial PPSs, 21 (3%) were SARS-CoV-2 positive: 16 (76%) staff and 5 (24%) residents. Fifteen cases (71%) were linked to a single unit. Targeted testing identified 17 cases (81%), and PPSs identified 4 cases (19%). Most cases (71%) were identified before IPC interventions could be implemented. WGS was performed on SARS-CoV-2 isolates from 4 staff and 4 residents: 5 were of Santa Clara County lineage and the 3 others were distinct lineages.

Early implementation of targeted testing, serial PPSs, and multimodal IPC interventions limited SARS-CoV-2 transmission within the SNF.

This is a cross-sectional study aiming to understand the early characteristics and background of bone health impairment in clinically well children with Fontan circulation.

We enrolled 10 clinically well children with Fontan palliation (operated >5 years before study entrance, Tanner stage ≤3, age 12.1 ± 1.77 years, 7 males) and 11 healthy controls (age 12.0 ± 1.45 years, 9 males) at two children’s hospitals. All patients underwent peripheral quantitative CT. For the Fontan group, we obtained clinical characteristics, NYHA class, cardiac index by MRI, dual x-ray absorptiometry, and biochemical studies. Linear regression was used to compare radius and tibia peripheral quantitative CT measures between Fontan patients and controls.

All Fontan patients were clinically well (NYHA class 1 or 2, cardiac index 4.85 ± 1.51 L/min/m2) and without significant comorbidities. Adjusted trabecular bone mineral density, cortical thickness, and bone strength index at the radius were significantly decreased in Fontan patients compared to controls with mean differences −30.13 mg/cm3 (p = 0.041), −0.31 mm (p = 0.043), and −6.65 mg2/mm4 (p = 0.036), respectively. No differences were found for tibial measures. In Fontan patients, the mean height-adjusted lumbar bone mineral density and total body less head z scores were −0.46 ± 1.1 and −0.63 ± 1.1, respectively, which are below the average, but within normal range for age and sex.

In a clinically well Fontan cohort, we found significant bone deficits by peripheral quantitative CT in the radius but not the tibia, suggesting non-weight-bearing bones may be more vulnerable to the unique haemodynamics of the Fontan circulation.