Faculty Bibliography

BACKGROUND:We sought to describe neuropsychiatric symptoms (NPS) among people living with dementia (PLWD) from diverse racial and ethnic groups receiving home health services while accounting for dementia severity, individual symptom prevalence, and neighborhood disadvantage. METHODS:A prospective study using cross-sectional data from n = 192 PLWD receiving skilled home healthcare in New Jersey enrolled in the Dementia Symptom Management at Home Program trial. We prospectively measured symptom prevalence with the Neuropsychiatric Inventory Questionnaire and dementia severity using the Quick Dementia Rating System. A one-way ANOVA determined NPS prevalence by dementia severity (mild, moderate, severe). Fisher's exact tests were used to assess the association of individual symptom prevalence with race and ethnicity and cross tabs to descriptively stratify individual symptom prevalence by dementia severity among groups. A Pearson correlation was performed to determine if a correlation existed among neighborhood disadvantages measured by the Area Deprivation Index (ADI) state decile scores and NPS prevalence and severity. RESULTS:Participants identified as non-Hispanic White (50%), non-Hispanic Black (30%), or Hispanic (13%). NPS were prevalent in 97% of participants who experienced 5.4 ± 2.6 symptoms with increased severity (10.8 ± 6.6) and care partner distress (13.8 ± 10.8). NPS increased with dementia severity (p = 0.004) with the greatest difference seen between individuals with mild dementia (4.3 ± 2.3) versus severe dementia (5.9 ± 2.3; p = 0.002). Few differences were found in symptom prevalence by racial and ethnic sub-groups. Nighttime behaviors were higher in non-Hispanic Black (78%), compared with non-Hispanic Whites (46%) with moderate dementia, p = 0.042. State ADI scores were not correlated with the number of NPS reported, or severity. CONCLUSIONS:NPS were prevalent and increased with dementia severity with commonalities among racial and ethnic groups with varying levels of neighborhood disadvantage. There is a need for effective methods for improving NPS identification, assessment, and management broadly for homebound PLWD.

BACKGROUND/UNASSIGNED:Nightclub/festival attendees are a population with high rates of party drug use, but research is needed to determine whether there have been shifts in unintended drug exposure in this population (e.g., via adulterants) to inform prevention and harm reduction efforts. METHODS/UNASSIGNED:Adults entering nightclubs and festivals in New York City were asked about past-year drug use in 2016 through 2022, with a subset providing a hair sample for testing. We focused on the 1943 who reported ecstasy use (of which 247 had a hair sample analyzed) and compared trends in self-reported drug use, drug positivity, and adjusted prevalence (adjusting for unreported use). RESULTS/UNASSIGNED:MDMA positivity decreased from 74.4 % to 42.3 %, and decreases occurred regarding detection of synthetic cathinones ("bath salts"; a 100.0 % decrease), MDA (a 76.9 % decrease), amphetamine (an 81.3 % decrease), methamphetamine (a 64.2 % decrease), and ketamine (a 33.4 % decrease) (ps < .05). Although prevalence of MDA and synthetic cathinone use was comparable between self-report and adjusted report in 2022, gaps in prevalence were wider in 2016 (ps < .01). Adjusted prevalence of synthetic cathinone use decreased more across time than prevalence based on self-report (a 79.4 % vs. 69.1 % decrease) and adjusted report for MDA use decreased more than prevalence based on self-report (a 50.6 % vs. 38.9 % decrease). CONCLUSIONS/UNASSIGNED:Combining self-report and toxicology tests helped us determine that decreases in drug use/exposure were steeper regarding adjusted prevalence. Underreported drug exposure-possibly due to exposure to adulterants-appears to have had less of an effect on prevalence in 2022 than it did in 2016.

Brain iron is vital for core neurodevelopmental processes including myelination and neurotransmitter synthesis and, accordingly, iron accumulates in the brain with age. However, little is known about the association between brain iron and neural functioning and how they evolve with age in early infancy. This study investigated brain iron in 48 healthy infants (22 females) aged 64.00 ± 33.28 days by estimating R2 * relaxometry from multi-echo functional MRI (fMRI). Linked independent component analysis was performed to examine the association between iron deposition and spontaneous neural activity, as measured by the amplitude of low frequency fluctuations (ALFF) by interrogating shared component loadings across modalities. Further, findings were validated in an independent dataset (n = 45, 24 females, 77.93 ± 26.18 days). The analysis revealed developmental coupling between the global R2 * and ALFF within the default mode network (DMN). Furthermore, we observed that this coupling effect significantly increased with age (r = 0.78, p = 9.2e-11). Our results highlight the importance of iron-neural coupling during early development and suggest that the neural maturation of the DMN may correspond to growth in distributed brain iron.

BACKGROUND:Maternal stress has negative consequences on infant behavioral development, and COVID-19 presented uniquely stressful situations to mothers of infants born during the pandemic. We hypothesized that mothers with higher levels of perceived stress during the pandemic would report higher levels of infant regulatory problems including crying and interrupted sleep patterns. METHODS:As part 6 sites of a longitudinal study, mothers of infants born during the pandemic completed the Perceived Stress Scale, the Brief Infant Sleep Questionnaire, and an Infant Crying survey at 6 (n = 433) and 12 (n = 344) months of infant age. RESULTS:Maternal perceived stress, which remained consistent at 6 and 12 months of infant age, was significantly positively correlated with time taken to settle infants. Although maternal perceived stress was not correlated with uninterrupted sleep length, time taken to put the infant to sleep was correlated. Perceived stress was also correlated with the amount of infant crying and fussiness reported at 6 months. CONCLUSIONS:Mothers who reported higher levels of perceived stress during the pandemic reported higher levels of regulatory problems, specifically at 6 months. Examining how varying levels of maternal stress and infant behaviors relate to overall infant developmental status over time is an important next step. IMPACT/CONCLUSIONS:Women giving birth during the COVID-19 pandemic who reported higher levels of stress on the Perceived Stress Scale also reported higher levels of infant fussiness and crying at 6 months old, and more disruptive sleep patterns in their infants at 6 months and 12 months old. Sleeping problems and excessive crying in infancy are two regulatory problems that are known risk factors for emotional and behavioral issues in later childhood. This paper is one of the first studies highlighting the associations between maternal stress and infant behaviors during the COVID-19 pandemic.

Hearing loss is associated with cognitive/physical health; less is known about mental health. We investigated associations between hearing loss severity, depression, and health-related quality of life among older adults with unaided hearing loss. Data (N = 948) were from the Aging and Cognitive Health Evaluation in Elders Study. Hearing was measured by pure-tone average (PTA), Quick Speech-in-Noise (QuickSIN) test, and the Hearing Handicap Inventory for the Elderly (HHIE-S). Outcomes were validated measures of depression and health-related quality of life. Associations were assessed by negative binomial regression. More severe hearing loss was associated with worse physical health-related quality of life (ratio: .98, 95% CI: .96, 1.00). Better QuickSIN was associated with higher mental health-related quality of life (1.01 [1.00, 1.02]). Worse HHIE-S was associated with depression (1.24 [1.16, 1.33]) and worse mental (.97 [.96, .98]) and physical (.95 [ .93, .96]) health-related quality of life. Further work will test effects of hearing intervention on mental health.

IMPORTANCE:Obesity affects approximately 42% of US adults and is associated with increased rates of type 2 diabetes, hypertension, cardiovascular disease, sleep disorders, osteoarthritis, and premature death. OBSERVATIONS:A body mass index (BMI) of 25 or greater is commonly used to define overweight, and a BMI of 30 or greater to define obesity, with lower thresholds for Asian populations (BMI ≥25-27.5), although use of BMI alone is not recommended to determine individual risk. Individuals with obesity have higher rates of incident cardiovascular disease. In men with a BMI of 30 to 39, cardiovascular event rates are 20.21 per 1000 person-years compared with 13.72 per 1000 person-years in men with a normal BMI. In women with a BMI of 30 to 39.9, cardiovascular event rates are 9.97 per 1000 person-years compared with 6.37 per 1000 person-years in women with a normal BMI. Among people with obesity, 5% to 10% weight loss improves systolic blood pressure by about 3 mm Hg for those with hypertension, and may decrease hemoglobin A1c by 0.6% to 1% for those with type 2 diabetes. Evidence-based obesity treatment includes interventions addressing 5 major categories: behavioral interventions, nutrition, physical activity, pharmacotherapy, and metabolic/bariatric procedures. Comprehensive obesity care plans combine appropriate interventions for individual patients. Multicomponent behavioral interventions, ideally consisting of at least 14 sessions in 6 months to promote lifestyle changes, including components such as weight self-monitoring, dietary and physical activity counseling, and problem solving, often produce 5% to 10% weight loss, although weight regain occurs in 25% or more of participants at 2-year follow-up. Effective nutritional approaches focus on reducing total caloric intake and dietary strategies based on patient preferences. Physical activity without calorie reduction typically causes less weight loss (2-3 kg) but is important for weight-loss maintenance. Commonly prescribed medications such as antidepressants (eg, mirtazapine, amitriptyline) and antihyperglycemics such as glyburide or insulin cause weight gain, and clinicians should review and consider alternatives. Antiobesity medications are recommended for nonpregnant patients with obesity or overweight and weight-related comorbidities in conjunction with lifestyle modifications. Six medications are currently approved by the US Food and Drug Administration for long-term use: glucagon-like peptide receptor 1 (GLP-1) agonists (semaglutide and liraglutide only), tirzepatide (a glucose-dependent insulinotropic polypeptide/GLP-1 agonist), phentermine-topiramate, naltrexone-bupropion, and orlistat. Of these, tirzepatide has the greatest effect, with mean weight loss of 21% at 72 weeks. Endoscopic procedures (ie, intragastric balloon and endoscopic sleeve gastroplasty) can attain 10% to 13% weight loss at 6 months. Weight loss from metabolic and bariatric surgeries (ie, laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass) ranges from 25% to 30% at 12 months. Maintaining long-term weight loss is difficult, and clinical guidelines support the use of long-term antiobesity medications when weight maintenance is inadequate with lifestyle interventions alone. CONCLUSION AND RELEVANCE:Obesity affects approximately 42% of adults in the US. Behavioral interventions can attain approximately 5% to 10% weight loss, GLP-1 agonists and glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonists can attain approximately 8% to 21% weight loss, and bariatric surgery can attain approximately 25% to 30% weight loss. Comprehensive, evidence-based obesity treatment combines behavioral interventions, nutrition, physical activity, pharmacotherapy, and metabolic/bariatric procedures as appropriate for individual patients.

Harms and risks to groups and third-parties can be significant in the context of research, particularly in data-centric studies involving genomic, artificial intelligence, and/or machine learning technologies. This article explores whether and how United States federal regulations should be adapted to better align with current ethical thinking and protect group interests. Three aspects of the Common Rule deserve attention and reconsideration with respect to group interests: institutional review board (IRB) assessment of the risks/benefits of research; disclosure requirements in the informed consent process; and criteria for waivers of informed consent. In accordance with respect for persons and communities, investigators and IRBs should systematically consider potential group harm when designing and reviewing protocols, respectively. Research participants should be informed about any potential group harm in the consent process. We call for additional public discussion, empirical research, and normative analysis on these issues to determine the right regulatory and policy path forward.

It is unclear whether cancers of the upper aerodigestive tract (UADT) and gastric cancer are related to air pollution, due to few studies with inconsistent results. The effects of particulate matter (PM) may vary across locations due to different source contributions and related PM compositions, and it is not clear which PM constituents/sources are most relevant from a consideration of overall mass concentration alone. We therefore investigated the association of UADT and gastric cancers with PM_2.5 elemental constituents and sources components indicative of different sources within a large multicentre population based epidemiological study. Cohorts with at least 10 cases per cohort led to ten and eight cohorts from five countries contributing to UADT- and gastric cancer analysis, respectively. Outcome ascertainment was based on cancer registry data or data of comparable quality. We assigned home address exposure to eight elemental constituents (Cu, Fe, K, Ni, S, Si, V and Zn) estimated from Europe-wide exposure models, and five source components identified by absolute principal component analysis (APCA). Cox regression models were run with age as time scale, stratified for sex and cohort and adjusted for relevant individual and neighbourhood level confounders. We observed 1139 UADT and 872 gastric cancer cases during a mean follow-up of 18.3 and 18.5 years, respectively. UADT cancer incidence was associated with all constituents except K in single element analyses. After adjustment for NO₂, only Ni and V remained associated with UADT. Residual oil combustion and traffic source components were associated with UADT cancer persisting in the multiple source model. No associations were found for any of the elements or source components and gastric cancer incidence. Our results indicate an association of several PM constituents indicative of different sources with UADT but not gastric cancer incidence with the most robust evidence for traffic and residual oil combustion.

BACKGROUND:Preventing progression to moderate or severe opioid use disorder (OUD) among people who exhibit risky opioid use behavior that does not meet criteria for treatment with opioid agonists or antagonists (subthreshold OUD) is poorly understood. The Subthreshold Opioid Use Disorder Prevention (STOP) Trial is designed to study the efficacy of a collaborative care intervention to reduce risky opioid use and to prevent progression to moderate or severe OUD in adult primary care patients with subthreshold OUD. METHODS:The STOP trial is a cluster randomized controlled trial, randomized at the PCP level, conducted in 5 distinct geographic sites. STOP tests the efficacy of the STOP intervention in comparison to enhanced usual care (EUC) in adult primary care patients with risky opioid use that does not meet criteria for moderate-severe OUD. The STOP intervention consists of (1) a practice-embedded nurse care manager (NCM) who provides patient participant education and supports primary care providers (PCPs) in engaging and monitoring patient-participants; (2) brief advice, delivered to patient participants by their PCP and/or prerecorded video message, about health risks of opioid misuse; and (3) up to 6 sessions of telephone health coaching to motivate and support behavior change. EUC consists of primary care treatment as usual, plus printed overdose prevention educational materials and an educational video on cancer screening. The primary outcome measure is self-reported number of days of risky (illicit or nonmedical) opioid use over 180 days, assessed monthly via text message using items from the Addiction Severity Index and the Current Opioid Misuse Measure. Secondary outcomes assess other substance use, mental health, quality of life, and healthcare utilization as well as PCP prescribing and monitoring behaviors. A mixed effects negative binomial model with a log link will be fit to estimate the difference in means between treatment and control groups using an intent-to-treat population. DISCUSSION:Given a growing interest in interventions for the management of patients with risky opioid use, and the need for primary care-based interventions, this study potentially offers a blueprint for a feasible and effective approach to improving outcomes in this population. TRIAL REGISTRATION:Clinicaltrials.gov, identifier NCT04218201, January 6, 2020.