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In the United States, Black and Hispanic children have higher rates of asthma and asthma-related morbidity compared with White children and disproportionately reside in communities with economic deprivation.To determine the extent to which neighborhood-level socioeconomic indicators explain racial and ethnic disparities in childhood wheezing and asthma.The study population comprised children in birth cohorts located throughout the United States that are part of the Children's Respiratory and Environmental Workgroup consortium. Cox proportional hazard models were used to estimate hazard ratios (HRs) of asthma incidence, and logistic regression was used to estimate odds ratios of early and persistent wheeze prevalence accounting for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, and region and decade of birth.Neighborhood-level socioeconomic indicators defined by US census tracts calculated as z scores for multiple tract-level variables relative to the US average linked to participants' birth record address and decade of birth. The parent or caregiver reported the child's race and ethnicity.Prevalence of early and persistent childhood wheeze and asthma incidence.Of 5809 children, 46% reported wheezing before age 2 years, and 26% reported persistent wheeze through age 11 years. Asthma prevalence by age 11 years varied by cohort, with an overall median prevalence of 25%. Black children (HR, 1.47; 95% CI, 1.26-1.73) and Hispanic children (HR, 1.29; 95% CI, 1.09-1.53) were at significantly increased risk for asthma incidence compared with White children, with onset occurring earlier in childhood. Children born in tracts with a greater proportion of low-income households, population density, and poverty had increased asthma incidence. Results for early and persistent wheeze were similar. In effect modification analysis, census variables did not significantly modify the association between race and ethnicity and risk for asthma incidence; Black and Hispanic children remained at higher risk for asthma compared with White children across census tracts socioeconomic levels.Adjusting for individual-level characteristics, we observed neighborhood socioeconomic disparities in childhood wheeze and asthma. Black and Hispanic children had more asthma in neighborhoods of all income levels. Neighborhood- and individual-level characteristics and their root causes should be considered as sources of respiratory health inequities.

Background: Digital cognitive tests offer several potential advantages over established paper-pencil tests but have not yet been fully evaluated for the clinical evaluation of mild cognitive impairment. Objective: The NeuroCognitive Performance Test (NCPT) is a web-based, self-directed, modular battery intended for repeated assessments of multiple cognitive domains. Our objective was to examine its relationship with the Alzheimer’s Disease Assessment Scale-Cognition Subscale (ADAS-Cog) and Mini-Mental State Examination (MMSE) as well as with established paper-pencil tests of cognition and daily functioning in mild cognitive impairment (MCI). Methods: We used Spearman correlations, regressions and principal components analysis followed by a factor analysis (varimax rotated) to examine our objectives. Results: In MCI subjects, the NCPT composite is significantly correlated with both a composite measure of established tests (r = 0.78, p

Objectives: Brain arterial dilation is an increasingly recognized cerebrovascular disease marker. However, demographic and anatomical factors may influence brain arterial diameters within the normal spectrum. We hypothesize that age, sex, height, total cranial volume (TCV) and fetal posterior cerebral arteries (fPCA) presence correlate with brain arterial diameters across diverse populations. Methods: We included participants with available time-of-flight MRA from 9 cohort studies across the United States (4), Ecuador (1), Venezuela (1), South Africa (1) and Singapore (2). Arterial diameters of the basilar artery (BA), cavernous internal carotid arteries (ICAs) and middle cerebral arteries (MCAs) were measured using LKEB Automated Vessel Analysis (LAVA) software. Linear regression models were fitted to assess the association between brain arterial diameters and exposures. The R-squared was calculated to assess the extent of brain arterial diameter variation explained by the variables studied. Results: The sample included 6,269 participants (mean age 68 years; 42% men). Unilateral fPCA was found in 12.6% and bilateral fPCAs in 3.0%. Older age, male sex and TCV were uniformly correlated with larger BA, ICA and MCA diameters (Table). Unilateral and bilateral fPCAs showed a negative correlation with BA diameter and a positive correlation with ICA diameters in a dose-dependent manner. Models fitted for age, sex, TCV, and fPCA presence explained on average 24, 16 and 12 % of the BA, ICAs and MCA diameter interindividual variation, respectively. Using height instead of TCV decreased the R-squared by 2% on average. Conclusions: In this pooled analysis of cohort studies, we found brain arterial diameters consistently correlate with age, sex, TCV and fPCA presence. These factors should be considered to define abnormal arterial diameter cut-offs across populations. If resources are limited or if bedside applicability is desired, height could be used instead of TCV.

BACKGROUND: A case series suggested efficacy for lithium to treat agitation in dementia, but no placebo-controlled trials have been conducted. OBJECTIVES: To evaluate low-dose lithium treatment of agitation in Alzheimer’s disease (AD). METHOD: In a four-site trial, patients with AD and agitation/aggression score ≥ 4 on the Neuropsychiatric Inventory (NPI) were randomized, double-blind, to lithium carbonate 150–600 mg daily or placebo for 12 weeks. Primary efficacy outcome was change in NPI agitation/aggression; secondary efficacy outcome was treatment response (30% reduction in NPI score for agitation/aggression plus psychosis and a Clinical Global Impression (CGI) score of much or very much improved). Safety profile of lithium was assessed. RESULTS: Fifty-eight of 77 patients (75.3%) completed the trial. In linear mixed effects model analyses, lithium was not significantly superior to placebo for agitation/aggression. Proportion of responders was 31.6% on lithium and 17.9% on placebo (χ(2)=1.26, p=0.26). Moderate or marked improvement (CGI) was greater on lithium (10/38=36.8%) than placebo (0/39=0%, Fisher’s exact test p

IntroductionThe onslaught of the COVID-19 pandemic has placed severe demands on US health systems and the health care workforce. In New York State (NYS) and New York City (NYC), the early American epicenter, hospitals ran the risk of exhausting supplies of ventilators, ICU beds, and personal protective equipment (PPE); the capacity of the healthcare workforce to meet the added demand was equally strained. The COVID-19 Healthcare Personnel Study (CHPS) was designed to assess adverse short and long-term physical and mental health impacts of the COVID-19 pandemic on New York’s physicians, nurse practitioners, and physician assistants.MethodsPopulation-based online survey of physicians, nurse practitioners and physician assistants registered with the New York State Department of Health. Survey-weighted descriptive results were analyzed using frequencies, proportions, and means, with 95% confidence intervals. Odds ratios were calculated for association using survey-weighted logistic regression.ResultsOver half (51.5%; 95% CI 49.1, 54.0) of respondents worked directly with COVID-19 patients. Among those tested, 27.3% (95% CI 22.5, 32.2) were positive. The majority (57.6%; 95% CI 55.2, 60.0) of respondents reported that the COVID-19 pandemic had a negative impact on their mental health. Negative mental health was associated with experiencing symptoms of COVID-19 (OR=1.7, 95% CI 1.3, 2.1) and redeployment to unfamiliar functions. (OR=1.3, 95% CI 1.1, 1.6).ConclusionsA majority of New York healthcare providers were involved in treating COVID-19 patients and reported that the pandemic had a negative impact on their mental health.

Objective: To identify occupational risk factors for ALS using well-characterized participants with ALS (P-ALS), sibling controls (S-controls), and matched population controls (P-controls) within the National ALS Registry. We also compared oxidative stress (OS) biomarkers between groups. Methods: P-ALS were recruited over 4 years. Demographic, socioeconomic, and medical data were ascertained from medical records and structured interviews. P-ALS were followed prospectively for 2 years or until death, whichever came sooner. S-controls and age-, sex-, race/ethnicity-, and residential location-matched P-controls were recruited over 3 years. Occupational exposure to lead and agricultural chemicals (ACs) were assigned by an occupational hygienist, blinded to case status. OS biomarkers in urine were measured. Results: P-ALS (mean age 62.8 years; 63% males) resided across the United States. Demographic and socioeconomic variables did not differ among P-ALS, S-controls, and P-controls. P-ALS were more likely to report occupations with exposure to lead (adjusted OR (aOR)=2.3, 95% CI 1.1, 4.6) and ACs (aOR = 2.4, 95% CI 1.2, 4.6) compared to pooled controls. Among those with occupations with exposure to both lead and ACs, aOR was 7.2 (95% CI 2.0, 26.1). Urinary 8-oxo-dG was significantly elevated among P-ALS (11.07 ± 5.42 ng/mL) compared to S-controls, P-controls, or pooled controls (pooled 7.43 ± 5.42 ng/mL; p Conclusions: Findings reveal increased risk of ALS diagnosis among those with occupational exposure to lead and ACs and increased OS biomarkers among cases compared to controls. OS may be an important pathogenic mechanism in ALS.

Objective:The aim of this study was to identify factors associated with distress experienced by physicians during their first coronavirus disease 2019 (COVID-19) triage decisions.Methods:An online survey was administered to physicians licensed in New York State.Results:Of the 164 physicians studied, 20.7% experienced severe distress during their first COVID-19 triage decisions. The mean distress score was not significantly different between physicians who received just-in-time training and those who did not (6.0 ± 2.7 vs 6.2 ± 2.8; P = 0.550) and between physicians who received clinical guidelines and those who did not (6.0 ± 2.9 vs 6.2 ± 2.7; P = 0.820). Substantially increased odds of severe distress were found in physicians who reported that their first COVID-19 triage decisions were inconsistent with their core values (adjusted odds ratio, 6.33; 95% confidence interval, 2.03-19.76) and who reported having insufficient skills and expertise (adjusted odds ratio 2.99, 95% confidence interval 0.91-9.87).Conclusion:Approximately 1 in 5 physicians in New York experienced severe distress during their first COVID-19 triage decisions. Physicians with insufficient skills and expertise, and core values misaligned to triage decisions are at heightened risk of experiencing severe distress. Just-in-time training and clinical guidelines do not appear to alleviate distress experienced by physicians during their first COVID-19 triage decisions.

BACKGROUND: Overdose education and naloxone distribution (OEND) trains people who use opioids (PWUO) in how to intervene in cases of opioid overdose but best practices have not been assessed empirically. METHODS: PWUO along with a significant other (SO) were randomized to one of three training conditions. In the Treatment-as-Usual (TAU) condition, participants were randomized to receive minimal overdose-related education. In the extended training (ET) condition, PWUO received an extended training, while their SO received no overdose training. In the final condition, both the participant and SO received the extended overdose training (ETwSO). Outcome measures were naloxone use and overdose knowledge and competency assessed immediately before and after training, and at 1-, 3-, 6-, and 12-month timepoints following training. RESULTS: Three hundred and twenty-one PWUO (w/ a SO) were randomized. All intensities of OD training were associated with sustained increases in OD knowledge/ competency (versus pre-training baseline p’s < 0.01). PWUO intervened in 166 ODs. The 12-month incidence of naloxone use did not significantly differ between groups. Extended training (ET + ETwSO) compared to TAU resulted in significantly greater naloxone utilization by: 30 days (10.1% vs 4.1%, p = 0.041), 60 days (16.4% vs 5.2%, p

Objectives: The COVID-19 Healthcare Personnel Study is a longitudinal survey to assess the changing impact of the COVID-19 pandemic on the New York State health care workforce. We analyzed results from a follow-up survey of physicians, nurse practitioners, and physician assistants on the availability of equipment and personnel, work conditions, physical and mental health of participants, and impact of the pandemic on commitment to their profession. Methods: We conducted an online survey of all licensed New York State physicians, nurse practitioners, and physician assistants in April 2020 (N = 2105) and a follow-up survey in February 2021 (N = 978). We analyzed changes in item responses from baseline to follow-up. We calculated survey-adjusted paired t tests and odds ratios (ORs) using survey-adjusted generalized linear models controlling for age, sex, region of practice, and hospital versus non–hospital-based practice. Results: Twenty percent of respondents expressed continuing concern about personnel shortages at both baseline and follow-up. Respondents reported working approximately 5 more hours on average during a 2-week period at follow-up compared with baseline (78.1 vs 72.6 hours; P = .008). For 20.4% (95% CI, 17.2%-23.5%) of respondents, mental health issues had become persistent. More than one-third (35.6%; 95% CI, 31.9%-39.4%) of respondents reported that they thought about leaving their profession more often than once per month. The association between persistent mental and behavioral health issues and contemplating leaving one’s profession was significant (OR = 2.7; 95% CI, 1.8-4.1; P < .001). Conclusions: Interventions such as decreasing the number of hours worked, ensuring health care professionals do not work directly with patients while ill, and addressing shortages of personal protective equipment can help address concerns of the health care workforce.

Objective: The Aberrant Behavior Checklist (ABC) is a standardized rating scale used for assessing problematic behavior of individuals with developmental disabilities. It has five subscales: Irritability, Social Withdrawal, Stereotypic Behavior, Hyperactivity, and Inappropriate Speech. A previous study in individuals with fragile X syndrome (FXS) reported six factors, with the Social Withdrawal factor bifurcating into Socially Unresponsive and Social Avoidance factors, suggesting a different factor structure in people with FXS. Methods: We assessed the ABC's factor structure (with both exploratory and confirmatory analyses) in 797 people with FXS and we compared these findings with exploratory factors derived from an independent sample of 357 individuals with FXS. In an ancillary analysis, we compared the overlap of the traditional ABC's Social Withdrawal scores with the Social Avoidance scores from the FXS-derived newer scale to determine whether overlap between these was very high and essentially redundant. Finally, we computed norms using both the traditional and the FXS-specific algorithms. Results: In confirmatory factor analyses, the FXS-specific algorithm produced the most consistent factor structure for the sample of 797 participants, but model fit was only marginally better than that derived by the original ABC scoring algorithm. Comparisons of factor structures from separate exploratory analyses revealed no consistent advantage of the FXS algorithm over the traditional algorithm. While a Social Avoidance subscale did emerge in some analyses, in other analyses, this was accompanied by loss of coherence on other domains of interest, such as the Socially Unresponsive/Social Withdrawal subscale. Conclusion: We question whether the newer FXS scoring algorithm contributes data that are consistently helpful in evaluating behavior of people with FXS. In general, we recommend continued use of the original ABC algorithm for scoring behavior of clients with FXS. However, we acknowledge that there may be circumscribed times when the new algorithm may be appropriate for scoring, namely when anxiety and/or social avoidance constructs are the central and unequivocal domains of interest.

Cerebrovascular disease is associated with symptoms and pathogenesis of Alzheimer's disease (AD) among adults with Down syndrome (DS). The cause of increased dementia-related cerebrovascular disease in DS is unknown. We explored whether protein markers of neuroinflammation are associated with markers of cerebrovascular disease among adults with DS. Participants from the Alzheimer's disease in Down syndrome (ADDS) study with magnetic resonance imaging (MRI) scans and blood biomarker data were included. Support vector machine (SVM) analyses examined the relationship of blood-based proteomic biomarkers with MRI-defined cerebrovascular disease among participants characterized as having cognitive decline (n = 36, mean age ± SD = 53 ± 6.2) and as being cognitively stable (n = 78, mean age = 49 ± 6.4). Inflammatory and AD markers were associated with cerebrovascular disease, particularly among symptomatic individuals. The pattern suggested relatively greater inflammatory involvement among cognitively stable individuals and greater AD involvement among those with cognitively decline. The findings help to generate hypotheses that both inflammatory and AD markers are implicated in cerebrovascular disease among those with DS and point to potential mechanistic pathways for further examination.

We determined the extent to which obstructive sleep apnea (OSA) is associated with increased cerebrovascular disease and amyloid burden, and the relation of the two processes across clinical Alzheimer’s disease (AD) diagnostic groups in adults with Down syndrome (DS). Adults with DS from the Biomarkers of Alzheimer’s Disease in Down Syndrome (ADDS) study were included given available research MRI (n = 116; 50 ± 8 years; 42% women) and amyloid PET scans (n = 71; 50 ± 7 years; 39% women) at the time of analysis. Participants were characterized as cognitively stable (CS; 64%), with mild cognitive impairment-DS (MCI-DS; 23%), with possible AD dementia (5%), or with definite AD dementia (8%). OSA was determined via medical records and interviews. Models tested the effect of OSA on MRI-derived cerebrovascular biomarkers and PET-derived amyloid burden, and the moderating effect of OSA and AD diagnosis on biomarkers. OSA was reported in 39% of participants, which did not differ by clinical AD diagnostic group. OSA was not associated with cerebrovascular biomarkers but was associated with greater cortical amyloid burden. White matter hyperintensity (WMH) volume (primarily in the parietal lobe), enlarged perivascular spaces, and cortical and striatal amyloid burden were greater across clinical AD diagnostic groups (CS

Background Statural growth impairment is more common in male patients with Crohn’s disease (CD). We identified clinical variables associated with height z score differences by sex in children participating in the Growth Study, a prospective multicenter longitudinal study examining sex differences in growth impairment in pediatric CD. Methods Patients with CD (female patients with bone age [BA] ≥4 years 2 months and ≤12 years; male patients with BA ≥5 years and ≤14 years at screening) who had completed study visit 1 qualified. The height z score difference was computed as height z score based on chronological age minus height z score based on BA. Results One hundred thirteen patients with CD (36% female) qualified. The mean chronological age was 12.0 ± 1.8 (SD) years. The magnitude of the mean height z score difference was significantly greater in female patients (–0.9 ± 0.8) than in male patients (–0.5 ± 0.9; P = 0.021). An initial classification of inflammatory bowel disease as CD (P = 0.038) and perianal disease behavior at diagnosis (P = 0.009) were associated with higher standardized height gain with BA progression, and arthralgia at symptom onset (P = 0.016), azathioprine/6-merpcaptopurine (P = 0.041), and probiotics (P ≤ 0.021) were associated with lower standardized height gain with BA progression in female patients. Patient-reported poor growth at symptom onset (P = 0.001), infliximab (P ≤ 0.025), biologics (P ≤ 0.015), methotrexate (P = 0.042), and vitamin D (P ≤ 0.010) were associated with higher standardized height gain with BA progression, and initial classification as CD (P = 0.025) and anorexia (P = 0.005) or mouth sores (P = 0.004) at symptom onset were associated with lower standardized height gain with BA progression in male patients. Conclusions Different clinical variables were associated with statural growth in male patients vs female patients, suggesting that sex-specific molecular pathways lead to statural growth impairment in CD.

Background: African ancestry is associated with a higher prevalence and greater severity of asthma than European ancestries, yet genetic studies of the most common locus associated with childhood-onset asthma, 17q12–21, in African Americans have been inconclusive. The aim of this study was to leverage both the phenotyping of the Children's Respiratory and Environmental Workgroup (CREW) birth cohort consortium, and the reduced linkage disequilibrium in African Americans, to fine map the 17q12–21 locus. Methods: We first did a genetic association study and meta-analysis using 17q12–21 tag single-nucleotide polymorphisms (SNPs) for childhood-onset asthma in 1613 European American and 870 African American children from the CREW consortium. Nine tag SNPs were selected based on linkage disequilibrium patterns at 17q12–21 and their association with asthma, considering the effect allele under an additive model (0, 1, or 2 effect alleles). Results were meta-analysed with publicly available summary data from the EVE consortium (on 4303 European American and 3034 African American individuals) for seven of the nine SNPs of interest. Subsequently, we tested for expression quantitative trait loci (eQTLs) among the SNPs associated with childhood-onset asthma and the expression of 17q12–21 genes in resting peripheral blood mononuclear cells (PBMCs) from 85 African American CREW children and in upper airway epithelial cells from 246 African American CREW children; and in lower airway epithelial cells from 44 European American and 72 African American adults from a case-control study of asthma genetic risk in Chicago (IL, USA). Findings: 17q12–21 SNPs were broadly associated with asthma in European Americans. Only two SNPs (rs2305480 in gasdermin-B [GSDMB] and rs8076131 in ORMDL sphingolipid biosynthesis regulator 3 [ORMDL3]) were associated with asthma in African Americans, at a Bonferroni-corrected threshold of p

Introduction Odor identification deficits characterize Alzheimer's disease and other dementias. We examined if intact performance on brief cognitive and odor identification tests predicts lack of transition to dementia. Methods In an urban community, 1037 older adults without dementia completed the 40-item University of Pennsylvania Smell Identification Test, which includes the 12-item Brief Smell Identification Test (B-SIT). Data from 749 participants followed up for 4 years were analyzed. Results In covariate-adjusted survival analyses, impairment on the Blessed Orientation Memory Concentration Test and B-SIT each predicted dementia (n = 109), primarily Alzheimer's disease (n = 101). Among participants with intact olfactory (B-SIT ≥ 11/12 correct) and cognitive (Blessed Orientation Memory Concentration Test ≤ 5/28 incorrect) ability, 3.4% (4/117) transitioned to dementia during follow-up with no transitions in the 70–75 and 81–83 years age group quartiles. Discussion Odor identification testing adds value to global cognitive testing, and together can identify individuals who rarely transition to dementia, thereby avoiding unnecessary diagnostic investigation.

Background This article reports the results of one of a series of global field studies implemented by the World Health Organization (WHO) to evaluate the accuracy, clinical utility, and global applicability of the new diagnostic guidelines for Mental, Behavioural and Neurological Disorders included in the next version of WHO's International Classification of Diseases (ICD-11). Aims of the study The purpose of this study was to compare the diagnostic accuracy and clinical utility ratings of global clinicians implementing the ICD-11 diagnostic guidelines for Anxiety and Fear-Related Disorders, relative to those applying ICD-10 guidelines. The study also aimed to identify elements of the guidelines that required further refinement or clarification. Methods 1840 global mental health professionals registered with WHO's Global Clinical Practice Network completed the study in one of six study languages. Participants were randomly assigned to apply either the ICD-11 or ICD-10 guidelines to diagnose standardized case vignettes, and to rate the clinical utility of their assigned guidelines. Results ICD-11's diagnostic accuracy and clinical utility were equivalent or superior to that of ICD-10. Global clinicians were significantly more accurate in diagnosing Generalized Anxiety Disorder, Specific Phobia and adult cases of Separation Anxiety Disorder when using ICD-11 and provided high clinical utility ratings for these disorders. Clinicians also found the ICD-11 guidelines easy to use, clear, and a good fit to patients they see in their clinical practice. However, clinicians had difficulty with distinguishing the boundary between disorder and normality for subthreshold cases of anxiety, and also with applying the new ICD-11 guidelines on panic attacks. Conclusions The new diagnostic guidelines for Anxiety Disorders in ICD-11 can be applied in an acceptably consistent manner by global clinicians and perform as well or better than the previous guidelines for ICD-10. Study findings also helped identify aspects of the ICD-11 guidelines that required refinement prior to their publication and areas that should be emphasized in training programs.

In this web-based field study, we compared the diagnostic accuracy and clinical utility of 10 selected mental disorders between the ICD-11 Clinical Descriptions and Diagnostic Guidelines (CDDG) and the ICD-10 CDDG using vignettes in a sample of 928 health professionals from all WHO regions. On average, the ICD-11 CDDG displayed significantly higher diagnostic accuracy (71.9% for ICD-11, 53.2% for ICD-10), higher ease of use, better goodness of fit, higher clarity, and lower time required for diagnosis compared to the ICD-10 CDDG. The advantages of the ICD-11 CDDG were largely limited to new diagnoses in ICD-11. After limiting analyses to diagnoses existing in ICD-11 and ICD-10, the ICD-11 CDDG were only superior in ease of use. The ICD-11 CDDG were not inferior in diagnostic accuracy or clinical utility compared to the ICD-10 CDDG for any of the vignettes. Diagnostic accuracy was consistent across WHO regions and independent of participants' clinical experience. There were no differences between medical doctors and psychologists in diagnostic accuracy, but members of other health professions had greater difficulties in determining correct diagnoses based on the ICD-11 CDDG. In sum, there were no differences in diagnostic accuracy for diagnoses existing in ICD-10 and ICD-11, but the introduction of new diagnoses in ICD-11 has improved the diagnostic classification of some clinical presentations. The favourable clinical utility ratings of the ICD-11 CDDG give reason to expect a positive evaluation by health professionals in the implementation phase of ICD-11. Yet, training in ICD-11 is needed to further enhance the diagnostic accuracy.

Previously reported data regarding growth parameters in individuals with fragile X syndrome (FXS) are inconsistent. A longitudinal analysis of height and BMI in a large number of individuals with FXS was conducted.Age- and sex-specific z scores for height and BMI of 1,223 individuals with FXS were calculated based on published normative data. Mixed-effect linear regression models were fit separately for males and females, and z scores for height and weight were regressed against age and adjusted for intellectual disability (ID) and psychotropic medication use.Mean height z score for both sexes decreased with age and was lower than normative data. Mean BMI z score was greater than normative data in both sexes, and this disparity increased with age. BMI z score in females was greater for those with moderate or severe ID than those with no or mild ID. Individuals taking antipsychotics had higher BMI z scores than those taking no or other medications; those taking anticonvulsants or stimulants had lower BMI z scores.Individuals with FXS are at elevated risk for overweight and obesity. The risk is higher in individuals taking antipsychotics and among females with severe ID. These findings warrant increased attention to obesity prevention for all individuals with FXS.

Objective: Psychiatric comorbidity is common in fragile X syndrome (FXS) and often addressed through pharmacological management. Here we examine data in the Fragile X Online Registry With Accessible Research Database (FORWARD) to characterize specific symptoms being treated with psychotropic medication, patterns of medication use, as well as the influence of gender, intellectual disability (ID), age, and autism spectrum disorder (ASD) diagnosis. Methods: Data were drawn from the 975 participants who have a completed clinician form. We explored the frequency of psychotropic medication use for the following symptom clusters: attention, hyperactivity, anxiety, hypersensitivity, obsessive-compulsive disorder (OCD), mood swings, irritability/agitation, aggression, and self-injury (IAAS). Results: A majority of participants (617 or 63.3%) were taking a psychotropic medication, including investigational drugs. Medications were often targeting multiple symptoms. Psychotropic medication use was more common in males, adolescents, and those with comorbid ID and ASD. Anxiety was the most frequently targeted symptom, followed by attention-deficit/hyperactivity disorder symptoms and IAAS. Selective serotonin reuptake inhibitors (SSRIs) were the most frequently prescribed medication class among all patients (n = 266, 43%), followed by stimulants (n = 235, 38%), each with no gender difference. Antipsychotics were the third most frequently prescribed medication class (n = 205, 33%), and were more frequently prescribed to males and those with ID and ASD. Conclusions: Anxiety, attention and hyperactivity were the most common symptom targets for psychopharmacologic intervention in FXS. Our results support clinical knowledge that males with comorbid ASD and ID have a more severe presentation requiring more intervention including medications. These results highlight the need for examination of symptom overlap and interaction.

Digital cognitive tests offer several potential advantages over established paper-pencil tests but have not yet been fully evaluated for the clinical evaluation of mild cognitive impairment. The NeuroCognitive Performance Test (NCPT) is a web-based, self-directed, modular battery intended for repeated assessments of multiple cognitive domains. Using a sample of 101 MCI subjects, we report in this study that the NCPT composite is significantly correlated with both a composite measure of established tests (r=0.77, p

To examine the underlying mechanisms that lead growth impairment to occur more commonly in males than females with Crohn's disease (CD).Children and adolescents with CD were enrolled in a prospective multicenter longitudinal cohort study. Height Z-score difference was computed as height Z-score based on chronological age (height chronological age-Z-score) minus height Z-score based on bone age (height bone age-Z-score) using longitudinal data. Specific serum cytokines were measured, hormone Z-scores were calculated based on bone age (bone age-Z), and their longitudinal associations were examined.There were 122 children with CD (63% male) who completed 594 visits. The mean ± SD chronological age was 11.70 ± 1.79 years. The mean ± SD height chronological age-Z-score was -0.03 ± 0.99 in males and -0.49 ± 0.87 in females. The mean ± SD height bone age-Z-score was 0.23 ± 0.93 in males and 0.37 ± 0.96 in females. The magnitude of the mean height Z-score difference was greater in females (-0.87 ± 0.94) than males (-0.27 ± 0.90; P = .005), indicating growth was better in females than males. The following negative associations were identified: in females, interleukin (IL)-8 (P .001) and IL-12p70 (P = .035) with gonadotropin-bone age-Z-scores; IL-8 (P = .010), IL-12p70 (P = .020), and interferon-γ (P = .004) with sex hormone-bone age-Z-scores, and IL-8 (P = .044) and interferon-γ (P .001) with insulin-like growth factor 1-bone age-Z-scores; in males, IL-1 beta (P = .019) and IL-6 (P = .025) with insulin-like growth factor 1-bone age-Z-scores.Our data suggest that sex-specific molecular pathways lead to growth impairment in children with CD (primarily growth hormone/insulin-like growth factor-1 axis in males and primarily hypothalamic-pituitary-gonadal axis in females). Mapping these sex-specific molecular pathways may help in the development of sex-specific treatment approaches targeting the underlying inflammation characteristic of CD.

Understanding place-based contributors to health requires geographically and culturally diverse study populations, but sharing location data is a significant challenge to multisite studies. Here, we describe a standardized and reproducible method to perform geospatial analyses for multisite studies. Using census tract-level information, we created software for geocoding and geospatial data linkage that was distributed to a consortium of birth cohorts located throughout the USA. Individual sites performed geospatial linkages and returned tract-level information for 8810 children to a central site for analyses. Our generalizable approach demonstrates the feasibility of geospatial analyses across study sites to promote collaborative translational research.

Background Substantial data from high-income countries support early interventions in the form of evidence-based Coordinated Specialty Care (CSC) for people experiencing First Episode Psychosis (FEP) to ameliorate symptoms and minimize disability. Chile is unique among Latin American countries in providing universal access to FEP services through a national FEP policy that mandates the identification of FEP individuals in primary care and guarantees delivery of community-based FEP treatments within a public health care system. Nonetheless, previous research has documented that FEP services currently provided at mental health clinics do not provide evidence-based approaches. This proposal aims to address this shortfall by first adapting OnTrackNY (OTNY), a CSC program currently being implemented across the USA, into OnTrackChile (OTCH), and then examine its effectiveness and implementation in Chile. Methods The Dynamic Adaptation Process will be used first to inform the adaptation and implementation of OTCH to the Chilean context. Then, a Hybrid Type 1 trial design will test its effectiveness and cost and evaluate its implementation using a cluster-randomized controlled trial (RCT) (N = 300 from 21 outpatient clinics). The OTCH program will be offered in half of these outpatient clinics to individuals ages 15-35. Usual care services will continue to be offered at the other clinics. Given the current COVID-19 pandemic, most research and intervention procedures will be conducted remotely. The study will engage participants over the course of 2 years, with assessments administered at enrollment, 12 months, and 24 months. Primary outcomes include implementation (fidelity, acceptability, and uptake) and service outcomes (person-centeredness, adherence, and retention). Secondary outcomes comprise participant-level outcomes such as symptoms, functioning, and recovery orientation. Over the course of the study, interviews and focus groups with stakeholders will be conducted to better understand the implementation of OTCH. Discussion Findings from this study will help determine the feasibility, effectiveness, and cost for delivering CSC services in Chile. Lessons learned about facilitators and barriers related to the implementation of the model could help inform the approach needed for these services to be further expanded throughout Latin America. Trial registration www.ClinicalTrials.govNCT04247711. Registered 30 January 2020. Trial status The OTCH trial is currently recruiting participants. Recruitment started on March 1, 2021, and is expected to be completed by December 1, 2022. This is the first version of this protocol (5/12/2021).

Objectives The main objective of this study was to estimate effects of dementia on Medicaid expenditures in an ethnically diverse community. Methods The sample included 1,211 Medicare beneficiaries who did not have any Medicaid coverage and 568 who additionally had full Medicaid coverage enrolled in the Washington Heights-Inwood Columbia Aging Project (WHICAP), a multiethnic, population-based, prospective study of cognitive aging in northern Manhattan (1999–2010). Individuals’ dementia status was determined using a rigorous clinical protocol. Relationship between dementia and Medicaid coverage and expenditures were estimated using a two-part model. Results In participants who had full Medicaid coverage, average annual Medicaid expenditures were substantially higher for those with dementia than those without dementia ($50,270 vs. $21,966, p < .001), but Medicare expenditures did not differ by dementia status ($8,458 vs. $9,324, p = .19). In participants who did not have any Medicaid coverage, average annual Medicare expenditures were substantially higher for those with dementia than those without dementia ($12,408 vs. $8,113, p = .02). In adjusted models, dementia was associated with a $6,278 increase in annual Medicaid spending per person after controlling for other characteristics. Discussion Results highlight Medicaid’s contribution to covering the cost of dementia care in addition to Medicare. Studies that do not include Medicaid are unlikely to accurately reflect the true cost of dementia.

Objective: This study examines the prevalence of self-reported driving while intoxicated (DWI) among drivers aged 65 and older. Method: This cross-sectional study was based on baseline data from the AAA Longitudinal Research on Aging Drivers (LongROAD) study, a multisite prospective cohort study of 2,990 older adult drivers. Alcohol-related variables from the baseline questionnaire were examined in relation to demographics, health status, and driving behaviors. A logistic regression model assessed variables associated with DWI. Results: Of the 2,990 participants, 72.7% reported consuming alcohol, 15.0% reported high-risk drinking, and 3.3% reported DWI. High-risk drinking (OR = 12.01) and risky driving behaviors (OR = 13.34) were significantly associated with at least occasional DWI. Avoidance of hazardous driving conditions (OR = 0.71) and higher level of comfort during challenging driving scenarios (OR = 0.65) were less likely to be associated with DWI. Conclusion: A large number of older adults engage in high-risk drinking and DWI. Public health education and DWI-related interventions should include older adults.

Purpose The purpose of this study was to assess when in the life-course race-by-sex disparities in body mass index (BMI) emerge. Methods Child Health and Development Studies participants, from whom height and weight data were collected at ages 5, 9–11, and 15–17 years, were followed up at the age of 50 years for anthropometric outcomes. Follow-up was completed for 605 subjects, 460 of whom were assessed for height and weight at the age of 50 years, had at least one available childhood BMI measure, and self-identified as either non-Hispanic black or non-Hispanic white. Linear regression analyses were conducted to determine whether interactions existed between race (black vs. white) and sex for predicting BMI at ages 5, 9–11, 15–17, and 50 years. Results At age 5 years, BMI was independent of sex for both blacks and whites, but by the age of 9–11 years, BMI was sex-dependent in blacks, with higher BMI observed among black females. This sex dependence for BMI among blacks persisted at ages 15–17 years and age 50 years. The race-by-sex interaction was significant at ages 9–11, 15–17, and 50 years (P for interaction = 0.001, 0.002, and 0.01, respectively). Conclusions Race-by-sex disparities in body size were observed by the age of 9–11 years and persisted until the age of 50 years.

Activities of daily living (ADLs) is an important measure of the quality of care provided in home healthcare (HHC), but few studies describe the ADLs of HHC patients. The objectives of this study were to (1) describe the types and levels of ADL dependency among patients receiving home care, (2) identify the risk factors for severe ADL dependency at admission, and (3) identify the predictors of ADL improvement during a HHC stay. This was a secondary data analysis of a 5% random sample (n=105,654) of the national Outcome and Assessment Information Set (OASIS-C) for the year 2013. The dependent variables were severe ADL dependency level at admission and ADL improvement from admission to discharge. About two-thirds (65%) of the patients (n = 99,991) had severe ADL dependency (dependence in 7 or more ADLs) at admission. Older age, female gender, and impaired decision-making were associated with severe ADL dependency on admission. Of the 105,654 patients, 58.1% (n = 89,997) experienced ADL improvement. ADL improvement was associated with increasing home health care length of stay, being female, and prior inpatient stay. Clinicians, policy makers and agencies could focus on modifiable characteristics to achieve the goal of ADL improvement.

Although preterm infants are at risk for social deficits, interventions to improve mother-infant interaction in the neonatal intensive care unit (NICU) are not part of standard care (SC). Study participants were a subset from a randomized controlled trial of a new intervention for premature infants, the Family Nurture Intervention (FNI), designed to help mothers and infants establish an emotional connection. At infants' 4 months corrected age, mother-infant face-to-face interaction was filmed and coded on a 1-s time base for mother touch, infant vocal affect, mother gaze, and infant gaze. Time-series models assessed self- and interactive contingency. Comparing FNI to SC dyads, FNI mothers showed more touch and calmer touch patterns, and FNI infants showed more angry-protest but less cry. In maternal touch self-contingency, FNI mothers were more likely to sustain positive touch and to repair moments of negative touch by transitioning to positive touch. In maternal touch interactive contingency, when infants looked at mothers, FNI mothers were likely to respond with more positive touch. In infant vocal affect self-contingency, FNI infants were more likely to sustain positive vocal affect and to transition from negative to positive vocal affect. In maternal gaze interactive contingency, following infants' looking at mother, FNI mothers of male infants were more likely to look at their sons. In maternal gaze self-contingency, following mothers' looking away, FNI mothers of male infants were more likely to look at their sons. Documentation of positive effects of the FNI for 4-month mother-infant face-to-face communication is useful clinically and has important implications for an improved developmental trajectory of these infants. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Objectives To examine how misidentification of dementia affects estimation of Medicare costs in a largely minority cohort of participants for whom accurate in‐person diagnoses are available. Design Prospective cohort study. Setting Washington Heights‐Inwood Columbia Aging Project, a multiethnic, population‐based, prospective study of cognitive aging of Medicare beneficiaries aged 65 and older. Participants Individuals clinically diagnosed with dementia (n=495) and individuals clinically diagnosed without dementia (n=1,701). Measurements Medicare claims‐identified dementia was defined according to the presence of any International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for Alzheimer's disease and related dementias in all available claims during the study period. Participant characteristics associated with claims misidentification of dementia were estimated using logistic regression. Effects of dementia misidentification on Medicare expenditures were estimated using generalized linear models. Results Medicare claims correctly identified 250 of the 495 (51%) dementia cases and 1,565 of the 1,701 (92%) nondementia cases. Sensitivity of claims‐identified dementia was 0.51, and specificity was 0.92. Average annual Medicare expenditures were $14,721 for a beneficiary with a clinical diagnosis of dementia, and $18,208 for a beneficiary with claim‐identified dementia, suggesting an overestimation of $3,487 per person per year when Medicare claims were used to identify dementia. Total annual expenditures for all beneficiaries with claims‐identified dementia were $258,707 lower than that for all those who were clinically diagnosed, suggesting an overall underestimation of total Medicare expenditures if Medicare claims were used to identify dementia. Different types of misidentification have different effects on dementia‐related cost estimates. Average annual expenditures per person were highest for false positives. Conclusion Misidentification of dementia in Medicare claims is common. Using claims to identify dementia may result in significantly biased estimates of the cost of dementia. J Am Geriatr Soc 67:269–276, 2019.

Potentially inappropriate medications (PIMs) identified by the American Geriatrics Society should generally be avoided by older adults because of ineffectiveness or excess risk of adverse effects. Few studies have examined the effects of PIMs on driving safety measured by prospectively and objectively collected driving data. Data for this study came from the Longitudinal Research on Aging Drivers study, a multisite naturalistic driving study of older adults. Multivariable negative binominal modeling was used to estimate incidence rate ratios and 95% confidence intervals of hard braking events (proxies for unsafe driving behavior defined as events with a deceleration rate ≥0.4 g) associated with PIM use among older drivers. The study sample consisted of 2932 drivers aged 65–79 years at baseline, including 542 (18.5%) who used at least one PIM. These drivers were followed through an in-vehicle recording device for up to 44 months. The overall incidence of hard braking events was 1.16 per 1000 miles. Use of PIMs was associated with a 10% increased risk of hard braking events. Compared to drivers who were not using PIMs, the risk of hard braking events increased 6% for those using one PIM, and 24% for those using two or more PIMs. Use of PIMs by older adult drivers is associated in a dose-response fashion with elevated risks of hard braking events. Reducing PIM use in older adults might help improve driving safety as well as health outcomes.

IntroductionAssessment of cognition and everyday function is essential in clinical trials for Alzheimer’s disease (AD). Two novel measures of cognition (No Practice Effects (NPE) cognitive battery and Miami Computerized Functional Assessment Scale (CFAS)) were designed to have robust psychometric properties and reduced practice and ceiling effects. This study aims to evaluate if the NPE and CFAS demonstrate stronger psychometric properties and reduced practice effects compared with established measures, including the Preclinical Alzheimer Cognitive Composite (PACC), Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Functional Activities Questionnaire (FAQ).MethodsThis parallel group, four-site study will randomize 320 cognitively intact adults aged 60 to 85 years to novel or well-established measures of cognition and function. All participants will receive assessments at baseline (week 0), week 12, and week 52, as well as a brain MRI scan and Apolipoprotein E genetic test at study entry. Analyses will determine psychometric properties of the NPE and CFAS, compare the sensitivity of measures to AD risk markers, and identify cognitive domains within the NPE.DiscussionPractice effects have been a major limitation of Alzheimer’s disease clinical trials that typically assess cognitive changes over serial assessments. Detection of functional impairment in cognitively normal individuals with biomarkers for Alzheimer’s disease requires instruments sensitive to very subtle functional changes. This study is intended to support the validation of two new composite measures, the NPE battery and the CFAS, which may advance clinical testing of interventions for individuals across the spectrum of early stage Alzheimer’s disease.Trial RegistrationNCT03900273

Introduction Assessment of cognition and everyday function is essential in clinical trials for Alzheimer's disease (AD). Two novel measures of cognition (No Practice Effects (NPE) cognitive battery and Miami Computerized Functional Assessment Scale (CFAS)) were designed to have robust psychometric properties and reduced practice and ceiling effects. This study aims to evaluate if the NPE and CFAS demonstrate stronger psychometric properties and reduced practice effects compared with established measures, including the Preclinical Alzheimer Cognitive Composite (PACC), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Functional Activities Questionnaire (FAQ). Methods This parallel group, four-site study will randomize 320 cognitively intact adults aged 60 to 85 years to novel or well-established measures of cognition and function. All participants will receive assessments at baseline (week 0), 3-months, and 12-months, as well as a brain MRI scan and Apolipoprotein E genetic test at study entry. Analyses will determine psychometric properties of the NPE and CFAS, compare the sensitivity of measures to AD risk markers, and identify cognitive domains within the NPE. Discussion Practice effects have been a major limitation of Alzheimer's disease clinical trials that typically assess cognitive changes over serial assessments. Detection of functional impairment in cognitively normal individuals with biomarkers for Alzheimer's disease requires instruments sensitive to very subtle functional changes. This study is intended to support the validation of two new composite measures, the NPE battery and the CFAS, which may advance clinical testing of interventions for individuals across the spectrum of early stage Alzheimer's disease. Trial Registration: NCT03900273

OBJECTIVE Adults with Down syndrome (DS) develop Alzheimer disease (AD) pathology by their 5th decade. Compared with the general population, traditional vascular risks in adults with DS are rare, allowing examination of cerebrovascular disease in this population and insight into its role in AD without the confound of vascular risk factors. We examined in vivo magnetic resonance imaging (MRI)-based biomarkers of cerebrovascular pathology in adults with DS, and determined their cross-sectional relationship with age, beta-amyloid pathology, and mild cognitive impairment or clinical AD diagnostic status. METHODS Participants from the Biomarkers of Alzheimer's Disease in Down Syndrome study (n = 138, 50 ± 7 years, 39% women) with MRI data and a subset (n = 90) with amyloid positron emission tomography (PET) were included. We derived MRI-based biomarkers of cerebrovascular pathology, including white matter hyperintensities (WMH), infarcts, cerebral microbleeds, and enlarged perivascular spaces (PVS), as well as PET-based biomarkers of amyloid burden. Participants were characterized as cognitively stable (CS), mild cognitive impairment-DS (MCI-DS), possible AD dementia, or definite AD dementia based on in-depth assessments of cognition, function, and health status. RESULTS There were detectable WMH, enlarged PVS, infarcts, and microbleeds as early as the 5th decade of life. There was a monotonic increase in WMH volume, enlarged PVS, and presence of infarcts across diagnostic groups (CS < MCI-DS < possible AD dementia < definite AD dementia). Higher amyloid burden was associated with a higher likelihood of an infarct. INTERPRETATION The findings highlight the prevalence of cerebrovascular disease in adults with DS and add to a growing body of evidence that implicates cerebrovascular disease as a core feature of AD and not simply a comorbidity. ANN NEUROL 2020;88:1165-1177.

Objective: To determine the associations between plasma creatinine (PCr), plasma uric acid (PUA), and urinary oxidative stress (OS) biomarkers with the ALSFRS-R at baseline and survival in a large epidemiological cohort study (ALS COSMOS) with a well-phenotyped patient population (N = 355).Methods: Fasting plasma and first void urine samples were obtained. PCr, PUA, urinary 8-oxo-deoxy guanosine (8-oxodG), and 15-F2t-isoprostane (IsoP) were analyzed at baseline, near the midpoint of follow-up, and at the final blood draw (before death or withdrawal from study). We estimated associations between these biomarkers and the ALSFRS-R at baseline and survival.Results: At baseline, PCr correlated with ALSFRS-R (Spearman r = 0.30), percent (%) FVC (r = 0.20), PUA (r = 0.37), and 8-oxodG (r = -0.13, all p