Search

Author(s): Darren M. Lipnicki 1,*, Steve R. Makkar 1, John D. Crawford 1, Anbupalam Thalamuthu 1, Nicole A. Kochan 1, Maria Fernanda Lima-Costa 2, Erico Castro-Costa 2, Cleusa Pinheiro Ferri [...], Background With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. Methods and findings We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E [epsilon]4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. Conclusions These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.

Background: Poor immune function is associated with increased risk for a number of age-related diseases, however, little is known about the impact of early life trauma on immune function in late-life. Methods: Using nationally representative data from the Health and Retirement Study (n = 5,823), we examined the association between experiencing parental/caregiver death or separation before age 16 and four indicators of immune function in late-life: C-reactive Protein (CRP), Interleukin-6 (IL-6), soluble Tumor Necrosis Factor (sTNFR), and Immunoglobulin G (IgG) response to cytomegalovirus (CMV). We also examined racial/ethnic differences. Findings: Individuals that identified as racial/ethnic minorities were more likely to experience parental/caregiver loss and parental separation in early life compared to Non-Hispanic Whites, and had poorer immune function in late-life. We found consistent associations between experiencing parental/caregiver loss and separation and poor immune function measured by CMV IgG levels and IL-6 across all racial/ethnic subgroups. For example, among Non-Hispanic Blacks, those that experienced parental/caregiver death before age 16 had a 26% increase in CMV IgG antibodies in late-life (β = 1.26; 95% CI: 1.17, 1.34) compared to a 3% increase in CMV antibodies among Non-Hispanic Whites (β = 1.03; 95% CI: 0.99, 1.07) controlling for age, gender, and parental education. Interpretation: Our results suggest a durable association between experiencing early life trauma and immune health in late-life, and that structural forces may shape the ways in which these relationships unfold over the life course. [ABSTRACT FROM AUTHOR]

Purpose: While mental health stigma research is sparse in Malawi, research in other settings suggests that stigma represents a barrier to mental health treatment and recovery. Accordingly, we conducted an analysis to understand the role of treatment-related stigma in depression care in Malawi by estimating the effect of patients' baseline anticipated treatment-related stigma on their 3-month probability of depression remission when newly identified with depression. Methods: We conducted depression screening and treatment at 10 noncommunicable disease (NCD) clinics across Malawi from April 2019 through December 2021. Eligible cohort participants were 18–65 years with depressive symptoms indicated by a PHQ-9 score ≥5. Questionnaires at the baseline and 3-month interviews included a vignette-based quantitative stigma instrument that measured treatment-related stigma, i.e., concerns about external stigma because of receiving depression treatment. Using inverse probability weighting to adjust for confounding and multiple imputation to account for missing data, this analysis relates participants' baseline levels of anticipated treatment stigma to the 3-month probability of achieving depression remission (i.e., PHQ-9 score < 5). Results: Of 743 included participants, 273 (37%) achieved depression remission by their 3-month interview. The probability of achieving depression remission at the 3-month interview among participants with high anticipated treatment stigma (0.31; 95% Confidence Interval [CI]: 0.23, 0.39)) was 10 percentage points lower than among the low/neutral stigma group (risk: 0.41; 95% CI: 0.36, 0.45; RD: -0.10; 95% CI: -0.19, -0.003). Conclusion: In Malawi, a reduction in anticipated depression treatment-related stigma among NCD patients initiating depression treatment could improve depression outcomes. Further investigation is necessary to understand the modes by which stigma can be successfully reduced to improve mental health outcomes and quality of life among people living with depression. [ABSTRACT FROM AUTHOR]

Public health surveillance systems likely underestimate the true prevalence and incidence of SARS-CoV-2 infection due to limited access to testing and the high proportion of subclinical infections in community-based settings. This ongoing prospective, observational study aimed to generate accurate estimates of the prevalence and incidence of, and risk factors for, SARS-CoV-2 infection among residents of a central North Carolina county. From this cohort, we collected survey data and nasal swabs every two weeks and venous blood specimens every month. Nasal swabs were tested for the presence of SARS-CoV-2 virus (evidence of active infection), and serum specimens for SARS-CoV-2-specific antibodies (evidence of prior infection). As of June 23, 2021, we have enrolled a total of 153 participants from a county with an estimated 76,285 total residents. The anticipated study duration is at least 24 months, pending the evolution of the pandemic. Study data are being shared on a monthly basis with North Carolina state health authorities and future analyses aim to compare study data to state-wide metrics over time. Overall, the use of a probability-based sampling design and a well-characterized cohort will enable collection of critical data that can be used in planning and policy decisions for North Carolina and may be informative for other states with similar demographic characteristics. [ABSTRACT FROM AUTHOR]

Office-based workplaces are an important but understudied context for infectious disease transmission. We examined the feasibility of two different sensors (Opos and Bluetooth beacons) for collecting person-to-person contacts and hand hygiene in office-based workplaces. Opo is an interaction sensor that captures sensor-to-sensor interactions through ultrasonic frequencies, which correspond to face-to-face contacts between study participants. Opos were additionally used to measure hand hygiene events by affixing sensors to soap and alcohol-based hand sanitizer dispensers. Bluetooth beacons were used in conjunction with a smartphone application and recorded proximity contacts between study participants. Participants in two office sites were followed for one-week in their workplace in March 2018. Contact patterns varied by time of day and day of the week. Face-to-face contacts were of shorter mean duration than proximity contacts. Supervisors had fewer proximity contacts but more face-to-face contacts than non-supervisors. Self-reported hand hygiene was substantively higher than sensor-collected hand hygiene events and duration of hand washing events was short (median: 9 seconds, range: 2.5–33 seconds). Given that office settings are key environments in which working age populations spend a large proportion of their time and interactions, a better characterization of empirical social networks and hand hygiene behaviors for workplace interactions are needed to mitigate outbreaks and prepare for pandemics. Our study demonstrates that implementing sensor technologies for tracking interactions and behaviors in offices is feasible and can provide new insights into real-world social networks and hygiene practices. We identified key social interactions, variability in hand hygiene, and differences in interactions by workplace roles. High-resolution network data will be essential for identifying the most effective ways to mitigate infectious disease transmission and develop pandemic preparedness plans for the workplace setting. [ABSTRACT FROM AUTHOR]

Human herpesviruses (HHV) cause a variety of clinically relevant conditions upon primary infection of typically young and immunocompetent hosts. Both primary infection and reactivation after latency can lead to more severe disease, such as encephalitis, congenital defects and cancer. Infections with HHV are also associated with cardiovascular and neurodegenerative disease. However, most of the associations are based on retrospective case-control analyses and well-powered prospective cohort studies are needed for assessing temporality and causality. To enable comprehensive investigations of HHV-related disease etiology in large prospective population-based cohort studies, we developed HHV Multiplex Serology. This methodology represents a low-cost, high-throughput technology that allows simultaneous measurement of specific antibodies against five HHV species: Herpes simplex viruses 1 and 2, Varicella zoster virus, Epstein-Barr virus, and Cytomegalovirus. The newly developed HHV species-specific (‘Monoplex’) assays were validated against established gold-standard reference assays. The specificity and sensitivity of the HHV species-specific Monoplex Serology assays ranged from 92.3% to 100.0% (median 97.4%) and 91.8% to 98.7% (median 96.6%), respectively. Concordance with reference assays was very high with kappa values ranging from 0.86 to 0.96 (median kappa 0.93). Multiplexing the Monoplex Serology assays resulted in no loss of performance and allows simultaneous detection of antibodies against the 5 HHV species in a high-throughput manner. [ABSTRACT FROM AUTHOR]

During late April 2009, the first cases of 2009 pandemic influenza A (H1N1) (pH1N1) in Illinois were reported. On-going, sustained local transmission resulted in an estimated 500,000 infected persons. We conducted a mixed method analysis using both quantitative (surveillance) and qualitative (interview) data; surveillance data was used to analyze demographic distribution of hospitalized cases and follow-up interview data was used to assess health seeking behavior. Invitations to participate in a telephone interview were sent to 120 randomly selected Illinois residents that were hospitalized during April–December 2009. During April–December 2009, 2,824 pH1N1 hospitalizations occurred in Illinois hospitals; median age (interquartile range) at admission was 24 (range: 6–49) years. Hospitalization rates/100,000 persons for blacks and Hispanics, regardless of age or sex were 2–3 times greater than for whites (blacks, 36/100,000 (95% Confidence Interval ([95% CI], 33–39)); Hispanics, 35/100,000 [95%CI,32–37] (; whites, 13/100,000[95%CI, 12–14); p<0.001). Mortality rates were higher for blacks (0.9/100,000; p<0.09) and Hispanics (1/100,000; p<0.04) when compared with the mortality rates for whites (0.6/100,000). Of 33 interview respondents, 31 (94%) stated that they had heard of pH1N1 before being hospitalized, and 24 (73%) did not believed they were at risk for pH1N1. On average, respondents reported experiencing symptoms for 2 days (range: 1–7) before seeking medical care. When asked how to prevent pH1N1 infection in the future, the most common responses were getting vaccinated and practicing hand hygiene. Blacks and Hispanics in Illinois experienced disproportionate pH1N1 hospitalization and mortality rates. Public health education and outreach efforts in preparation for future influenza pandemics should include prevention messaging focused on perception of risk, and ensure community wide access to prevention messages and practices. [ABSTRACT FROM AUTHOR]

We assessed the dynamics of hand microbial community structure of 34 healthcare workers from a single surgical intensive care unit over a short (3 week) time period, whilst taking into account the technical sources of variability introduced by specimen collection, DNA extraction, and sequencing. Sample collection took place at 3 different time points. Only the sampling collection method appeared to have a significant impact on the observed hand microbial community structure among the healthcare workers. Analysis of samples collected using glove-juice showed a slightly more similar microbial composition within individual hand samples over time than between the hands of different individuals over time. This was not true for samples collected using a swab, where samples from a single individual were no more similar to each other over time than those among other individuals over time, suggesting they were essentially independent. DNA extraction techniques (lysozyme only versus enzyme cocktail) and sequencing (replicate set 1 versus 2) using Ion Torrent Personal Genome Machine, were not influential to the microbial community structures. Glove-juice sample collection may likely be the method of choice in hand hygiene studies in the healthcare setting. [ABSTRACT FROM AUTHOR]

Background: Persistent pathogens have been proposed as risk factors for stroke; however, the evidence remains inconclusive. Mexican Americans have an increased risk of stroke especially at younger ages, as well as a higher prevalence of infections caused by several persistent pathogens. Methodology/Principal: Findings Using data from the Sacramento Area Latino Study on Aging (n = 1621), the authors used discrete-time regression to examine associations between stroke risk and (1) immunoglobulin G antibody levels to Helicobacter pylori (H. pylori), Cytomegalovirus, Varicella Zoster Virus, Toxoplasma gondii and Herpes simplex virus 1, and (2) concurrent exposure to several pathogens (pathogen burden), defined as: (a) summed sero-positivity, (b) number of pathogens eliciting high antibody levels, and (c) average antibody level. Models were adjusted for socio-demographics and stroke risk factors. Antibody levels to H. pylori predicted incident stroke in fully adjusted models (Odds Ratio: 1.58; 95% Confidence Interval: 1.09, 2.28). No significant associations were found between stroke risk and antibody levels to the other four pathogens. No associations were found for pathogen burden and incident stroke in fully adjusted models. Conclusions/Significance: Our results suggest that exposure to H. pylori may be a stroke risk factor in Mexican Americans and may contribute to ethnic differences in stroke risk given the increased prevalence of exposure to H. pylori in this population. Future studies are needed to confirm this association. [ABSTRACT FROM AUTHOR]

Recent work suggests that the 9-repeat (9R) allele located in the 39UTR VNTR of the SLC6A3 gene increases risk of posttraumatic stress disorder (PTSD). However, no study reporting this association to date has been based on populationbased samples. Furthermore, no study of which we are aware has assessed the joint action of genetic and DNA methylation variation at SLC6A3 on risk of PTSD. In this study, we assessed whether molecular variation at SLC6A3 locus influences risk of PTSD. Participants (n = 320; 62 cases/258 controls) were drawn from an urban, community-based sample of predominantly African American Detroit adult residents, and included those who had completed a baseline telephone survey, had provided blood specimens, and had a homozygous genotype for either the 9R or 10R allele or a heterozygous 9R/10R genotype. The influence of DNA methylation variation in the SLC6A3 promoter locus was also assessed in a subset of participants with available methylation data (n = 83; 16 cases/67 controls). In the full analytic sample, 9R allele carriers had almost double the risk of lifetime PTSD compared to 10R/10R genotype carriers (OR = 1.98, 95% CI = 1.02-3.86), controlling for age, sex, race, socioeconomic status, number of traumas, smoking, and lifetime depression. In the subsample of participants with available methylation data, a significant (p = 0.008) interaction was observed whereby 9R allele carriers showed an increased risk of lifetime PTSD only in conjunction with high methylation in the SLC6A3 promoter locus, controlling for the same covariates. Our results confirm previous reports supporting a role for the 9R allele in increasing susceptibility to PTSD. They further extend these findings by providing preliminary evidence that a "double hit" model, including both a putatively reducedfunction allele and high methylation in the promoter region, may more accurately capture molecular risk of PTSD at the SLC6A3 locus. [ABSTRACT FROM AUTHOR]

Limited vaccine availability and the potential for resistance to antiviral medications have led to calls for establishing the efficacy of non-pharmaceutical measures formitigating pandemic influenza. Our objectivewas to examine if the use of facemasks and hand hygiene reduced rates of influenza-like illness (ILI) and laboratory-confirmed influenza in the natural setting. A cluster-randomized intervention trial was designed involving 1,178 young adults living in 37 residence houses in 5 university residence halls during the 2007-2008 influenza season. Participants were assigned to face mask and hand hygiene, face mask only, or control group during the study. Discrete-time survivalmodels using generalized estimating equations to estimate intervention effects on ILI and confirmed influenza A/B infection over a 6-week study period were examined. A significant reduction in the rate of ILI was observed in weeks 3 through 6 of the study, with amaximumreduction of 75% during the final study week (rate ratio [RR] = 0.25, [95% CI, 0.07 to 0.87]). Both intervention groups compared to the control showed cumulative reductions in rates of influenza over the study period, although results did not reach statistical significance. Generalizability limited to similar settings and age groups. Face masks and hand hygiene combined may reduce the rate of ILI and confirmed influenza in community settings. These nonpharmaceutical measures should be recommended in crowded settings at the start of an influenza pandemic. [ABSTRACT FROM AUTHOR]

We introduce a method for estimating incidence curves of several co-circulating infectious pathogens, where each infection has its own probabilities of particular symptom profiles. Our deconvolution method utilizes weekly surveillance data on symptoms from a defined population as well as additional data on symptoms from a sample of virologically confirmed infectious episodes. We illustrate this method by numerical simulations and by using data from a survey conducted on the University of Michigan campus. Last, we describe the data needs to make such estimates accurate. [ABSTRACT FROM AUTHOR]

Background: Studies have suggested that CMV infection may influence cardiovascular disease (CVD) risk and mortality. However, there have been no large-scale examinations of these relationships among demographically diverse populations. The inflammatory marker C-reactive protein (CRP) is also linked with CVD outcomes and mortality and may play an important role in the pathway between CMV and mortality. We utilized a U.S. nationally representative study to examine whether CMV infection is associated with all-cause and CVD-related mortality. We also assessed whether CRP level mediated or modified these relationships. Methodology/Principal Findings: Data come from subjects ⩾25 years of age who were tested for CMV and CRP level and were eligible for mortality follow-up on December 31st, 2006 (N = 14153) in the National Health and Nutrition Examination Survey (NHANES) III (1988-1994). Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and CVD-related mortality by CMV serostatus. After adjusting for multiple confounders, CMV seropositivity remained statistically significantly associated with all-cause mortality (HR 1.19, 95% CI: 1.01, 1.41). The association between CMV and CVD-related mortality did not achieve statistical significance after confounder adjustment. CRP did not mediate these associations. However, CMV seropositive individuals with high CRP levels showed a 30.1% higher risk for all-cause mortality and 29.5% higher risk for CVD-related mortality compared to CMV seropositive individuals with low CRP levels. Conclusions/Significance: CMV was associated with a significant increased risk for all-cause mortality and CMV seropositive subjects who also had high CRP levels were at substantially higher risk for both for all-cause and CVD-related mortality than subjects with low CRP levels. Future work should target the mechanisms by which CMV infection and low-level inflammation interact to yield significant impact on mortality. [ABSTRACT FROM AUTHOR]

Recent work suggests that the 9-repeat (9R) allele located in the 3′UTR VNTR of the SLC6A3 gene increases risk of posttraumatic stress disorder (PTSD). However, no study reporting this association to date has been based on population-based samples. Furthermore, no study of which we are aware has assessed the joint action of genetic and DNA methylation variation at SLC6A3 on risk of PTSD. In this study, we assessed whether molecular variation at SLC6A3 locus influences risk of PTSD. Participants (n = 320; 62 cases/258 controls) were drawn from an urban, community-based sample of predominantly African American Detroit adult residents, and included those who had completed a baseline telephone survey, had provided blood specimens, and had a homozygous genotype for either the 9R or 10R allele or a heterozygous 9R/10R genotype. The influence of DNA methylation variation in the SLC6A3 promoter locus was also assessed in a subset of participants with available methylation data (n = 83; 16 cases/67 controls). In the full analytic sample, 9R allele carriers had almost double the risk of lifetime PTSD compared to 10R/10R genotype carriers (OR = 1.98, 95% CI = 1.02–3.86), controlling for age, sex, race, socioeconomic status, number of traumas, smoking, and lifetime depression. In the subsample of participants with available methylation data, a significant (p = 0.008) interaction was observed whereby 9R allele carriers showed an increased risk of lifetime PTSD only in conjunction with high methylation in the SLC6A3 promoter locus, controlling for the same covariates. Our results confirm previous reports supporting a role for the 9R allele in increasing susceptibility to PTSD. They further extend these findings by providing preliminary evidence that a “double hit” model, including both a putatively reduced-function allele and high methylation in the promoter region, may more accurately capture molecular risk of PTSD at the SLC6A3 locus.

Meat packing, produce processing, and farm workers are known to have an elevated risk of COVID-19, but occupational risk factors in this population are unclear. We performed an observational cohort study of meat packing, produce processing, and farm workers in North Carolina in fall 2020. Blood, saliva, and nasal turbinate samples were collected to assess for SARS-CoV-2 seropositivity. Risk factors for SARS-CoV-2 seropositivity were investigated using chi-square tests, two-sample t-tests, and adjusted risk ratio analyses. Among 118 enrolled workers, the baseline SARS-CoV-2 seroprevalence was 50.0%. Meat packing plant workers had the highest SARS-CoV-2 seroprevalence (64.6%), followed by farm workers (45.0%) and produce processing workers (10.0%), despite similar sociodemographic characteristics. Compared to SARS-CoV-2 seronegative workers, seropositive workers were more likely to work in loud environments that necessitated yelling to communicate (RR: 1.83, 95% CI: 1.25-2.69), work in cold environments (RR: 1.58, 95% CI: 1.12-2.24), or continue working despite developing symptoms at work (RR: 1.63, 95% CI: 1.14-2.32). After adjusting for age and working despite symptoms, high occupational noise levels were associated with a 1.72 times higher risk of SARS-CoV-2 seropositivity (95% CI: 1.16-2.55). Half of food processing workers showed evidence of past SARS-CoV-2 infection, a prevalence five times higher than most of the United States population at the time of the study. Work environments with loud ambient noise may pose elevated risks for SARS-CoV-2 transmission. Our findings also highlight the disproportionate burden of COVID-19 among underserved and economically disadvantaged Latinx communities in the United States., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Klein et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)