Viral Suppression in HIV Studies: Combining Times to Suppression and Rebound

In HIV-1 clinical trials the interest is often to compare how well treatments suppress the HIV-1 RNA viral load. The current practice in statistical analysis of such trials is to define a single ad hoc composite event which combines information about both the viral load suppression and the subsequent viral rebound, and then analyze the data using standard univariate survival analysis techniques. The main weakness of this approach is that the results of the analysis can be easily influenced by minor details in the definition of the composite event. We propose a straightforward alternative endpoint based on the probability of being suppressed over time, and suggest that treatment differences be summarized using the restricted mean time a patient spends in the state of viral suppression. A nonparametric analysis is based on methods for multiple endpoint studies. We demonstrate the utility of our analytic strategy using a recent therapeutic trial, in which the protocol specified a primary analysis using a composite endpoint approach

Self-Reported Head Trauma Predicts Poor Dual Task Gait in Retired National Football League Players

Symptomatic head trauma associated with American-style football (ASF) has been linked to brain pathology, along with physical and mental distress in later life. However, the longer-term effects of such trauma on objective metrics of cognitive-motor function remain poorly understood. We hypothesized that ASF-related symptomatic head trauma would predict worse gait performance, particularly during dual task conditions (ie, walking while performing an additional cognitive task), in later life. Sixty-six retired professional ASF players aged 29 to 75 years completed a health and wellness questionnaire. They also completed a validated smartphone-based assessment in their own homes, during which gait was monitored while they walked normally and while they performed a verbalized serial-subtraction cognitive task. Participants who reported more symptomatic head trauma, defined as the total number of impacts to the head or neck followed by concussion-related symptoms, exhibited greater dual task cost (ie, percentage increase) to stride time variability (ie, the coefficient of variation of mean stride time). Those who reported ≥1 hit followed by loss of consciousness, compared to those who did not, also exhibited greater dual task costs to this metric. Relationships between reported trauma and dual task costs were independent of age, body mass index, National Football League career duration, and history of musculoskeletal surgery. Symptomatic head trauma was not correlated with average stride times in either walking condition. Remote, smartphone-based assessments of dual task walking may be utilized to capture meaningful data sensitive to the long-term impact of symptomatic head trauma in former professional ASF players and other contact sport athletes. ANN NEUROL 2020;87:75-8

The age-related contribution of cognitive function to dual-task gait in middle-aged adults in Spain : observations from a population-based study

Poor dual-task gait performance is associated with a risk of falls and cognitive decline in adults aged 65 years or older. When and why dual-task gait performance begins to deteriorate is unknown. This study aimed to characterise the relationships between age, dual-task gait, and cognitive function in middle age (ie, aged 40-64 years). We conducted a secondary analysis of data from community-dwelling adults aged 40-64 years that took part in the Barcelona Brain Health Initiative (BBHI) study, an ongoing longitudinal cohort study in Barcelona, Spain. Participants were eligible for inclusion if they were able to walk independently without assistance and had completed assessments of both gait and cognition at the time of analysis and ineligble if they could not understand the study protocol, had any clinically diagnosed neurological or psychiatric diseases, were cognitively impaired, or had lower-extremity pain, osteoarthritis, or rheumatoid arthritis that could cause abnormal gait. Stride time and stride time variability were measured under single-task (ie, walking only) and dual-task (ie, walking while performing serial subtractions) conditions. Dual-task cost (DTC; the percentage increase in the gait outcomes from single-task to dual-task conditions) to each gait outcome was calculated and used as the primary measure in analyses. Global cognitive function and composite scores of five cognitive domains were derived from neuropsychological testing. We used locally estimated scatterplot smoothing to characterise the relationship between age and dual-task gait, and structural equation modelling to establish whether cognitive function mediated the association between observed biological age and dual tasks. 996 people were recruited to the BBHI study between May 5, 2018, and July 7, 2020, of which 640 participants completed gait and cognitive assessments during this time (mean 24 days [SD 34] between first and second visit) and were included in our analysis (342 men and 298 women). Non-linear associations were observed between age and dual-task performance. Starting at 54 years, the DTC to stride time (β=0·27 [95% CI 0·11 to 0·36]; p<0·0001) and stride time variability (0·24 [0·08 to 0·32]; p=0·0006) increased with advancing age. In individuals aged 54 years or older, decreased global cognitive function correlated with increased DTC to stride time (β=−0·27 [−0·38 to −0·11]; p=0·0006) and increased DTC to stride time variability (β=−0·19 [−0·28 to −0·08]; p=0·0002). Dual-task gait performance begins to deteriorate in the sixth decade of life and, after this point, interindividual variance in cognition explains a substantial portion of dual-task performance

Association of Childhood Economic Hardship with Adult Height and Adult Adiposity among Hispanics/Latinos. The HCHS/SOL Socio-Cultural Ancillary Study

The study examined the association of childhood and current economic hardship with anthropometric indices in Hispanic/Latino adults, using data from the HCHS/SOL Socio-cultural ancillary study (N = 5,084), a community-based study of Hispanic/Latinos living in four urban areas (Bronx, NY, Chicago, IL, Miami, FL, and San Diego, CA). Childhood economic hardship was defined as having experienced a period of time when one’s family had trouble paying for basic needs (e.g., food, housing), and when this economic hardship occurred: between 0–12, 13–18 years old, or throughout both of those times. Current economic hardship was defined as experiencing trouble paying for basic needs during the past 12 months. Anthropometry included height, body mass index (BMI), waist circumference (WC), and percentage body fat (%BF). Complex survey linear regression models were used to test the associations of childhood economic hardship with adult anthropometric indices, adjusting for potential confounders (e.g., age, sex, Hispanic background). Childhood economic hardship varied by Hispanic background, place of birth, and adult socio-economic status. Childhood economic hardship during both periods, childhood and adolescence, was associated with shorter height. Childhood economic hardship was associated with greater adiposity among US born individuals only. Current economic hardship was significantly associated with all three measures of adiposity (BMI, WC, %BF). These findings suggest that previous periods of childhood economic hardship appear to influence adult height more than adiposity, whereas current economic hardship may be a better determinant of adult adiposity in Hispanics

Clinical Significance of Symptoms in Smokers with Preserved Pulmonary Function

Currently, the diagnosis of chronic obstructive pulmonary disease (COPD) requires a ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) of less than 0.70 as assessed by spirometry after bronchodilator use. However, many smokers who do not meet this definition have respiratory symptoms

Prevalence of Suspected Nonalcoholic Fatty Liver Disease in Hispanic/Latino Individuals Differs by Heritage

Non-alcoholic fatty liver disease (NAFLD) was shown to disproportionally affect Hispanic persons. We examined the prevalence of suspected NAFLD in Hispanic/Latino persons with diverse backgrounds

Associations of structural and functional social support with diabetes prevalence in U.S. Hispanics/Latinos: Results from the HCHS/SOL Sociocultural Ancillary Study

Little research has examined associations of social support with diabetes (or other physical health outcomes) in Hispanics, who are at elevated risk

Prevalence of Major Cardiovascular Risk Factors and Cardiovascular Diseases Among Hispanic/Latino Individuals of Diverse Backgrounds in the United States

Major cardiovascular diseases (CVDs) are leading causes of mortality among US Hispanic and Latino individuals. Comprehensive data are limited regarding the prevalence of CVD risk factors in this population and relations of these traits to socioeconomic status (SES) and acculturation

Multiple Loci Are Associated with White Blood Cell Phenotypes

White blood cell (WBC) count is a common clinical measure from complete blood count assays, and it varies widely among healthy individuals. Total WBC count and its constituent subtypes have been shown to be moderately heritable, with the heritability estimates varying across cell types. We studied 19,509 subjects from seven cohorts in a discovery analysis, and 11,823 subjects from ten cohorts for replication analyses, to determine genetic factors influencing variability within the normal hematological range for total WBC count and five WBC subtype measures. Cohort specific data was supplied by the CHARGE, HeamGen, and INGI consortia, as well as independent collaborative studies. We identified and replicated ten associations with total WBC count and five WBC subtypes at seven different genomic loci (total WBC count—6p21 in the HLA region, 17q21 near ORMDL3, and CSF3; neutrophil count—17q21; basophil count- 3p21 near RPN1 and C3orf27; lymphocyte count—6p21, 19p13 at EPS15L1; monocyte count—2q31 at ITGA4, 3q21, 8q24 an intergenic region, 9q31 near EDG2), including three previously reported associations and seven novel associations. To investigate functional relationships among variants contributing to variability in the six WBC traits, we utilized gene expression- and pathways-based analyses. We implemented gene-clustering algorithms to evaluate functional connectivity among implicated loci and showed functional relationships across cell types. Gene expression data from whole blood was utilized to show that significant biological consequences can be extracted from our genome-wide analyses, with effect estimates for significant loci from the meta-analyses being highly corellated with the proximal gene expression. In addition, collaborative efforts between the groups contributing to this study and related studies conducted by the COGENT and RIKEN groups allowed for the examination of effect homogeneity for genome-wide significant associations across populations of diverse ancestral backgrounds

Multiple Loci Are Associated with White Blood Cell Phenotypes

White blood cell (WBC) count is a common clinical measure from complete blood count assays, and it varies widely among healthy individuals. Total WBC count and its constituent subtypes have been shown to be moderately heritable, with the heritability estimates varying across cell types. We studied 19,509 subjects from seven cohorts in a discovery analysis, and 11,823 subjects from ten cohorts for replication analyses, to determine genetic factors influencing variability within the normal hematological range for total WBC count and five WBC subtype measures. Cohort specific data was supplied by the CHARGE, HeamGen, and INGI consortia, as well as independent collaborative studies. We identified and replicated ten associations with total WBC count and five WBC subtypes at seven different genomic loci (total WBC count—6p21 in the HLA region, 17q21 near ORMDL3, and CSF3; neutrophil count—17q21; basophil count- 3p21 near RPN1 and C3orf27; lymphocyte count—6p21, 19p13 at EPS15L1; monocyte count—2q31 at ITGA4, 3q21, 8q24 an intergenic region, 9q31 near EDG2), including three previously reported associations and seven novel associations. To investigate functional relationships among variants contributing to variability in the six WBC traits, we utilized gene expression- and pathways-based analyses. We implemented gene-clustering algorithms to evaluate functional connectivity among implicated loci and showed functional relationships across cell types. Gene expression data from whole blood was utilized to show that significant biological consequences can be extracted from our genome-wide analyses, with effect estimates for significant loci from the meta-analyses being highly corellated with the proximal gene expression. In addition, collaborative efforts between the groups contributing to this study and related studies conducted by the COGENT and RIKEN groups allowed for the examination of effect homogeneity for genome-wide significant associations across populations of diverse ancestral backgrounds