Mid- and later-life risk factors for predicting neuropathological brain changes associated with Alzheimer's and vascular dementia: The Honolulu Asia Aging Study and the Age, Gene/Environment Susceptibility-Reykjavik Study.

INTRODUCTION: Dementia prediction models are necessary to inform the development of dementia risk reduction strategies. Here, we examine the utility of neuropathological-based risk scores to predict clinical dementia. METHODS: Models were developed for predicting Alzheimer's disease (AD) and non-AD neuropathologies using the Honolulu Asia Aging neuropathological sub-study (HAAS; n = 852). Model accuracy for predicting clinical dementia, over 30 years, was tested in the non-autopsied HAAS sample (n = 2960) and the Age, Gene/Environment Susceptibility-Reykjavik Study (n = 4614). RESULTS: Different models were identified for predicting neurodegenerative and vascular neuropathology (c-statistic range: 0.62 to 0.72). These typically included age, APOE, and a blood pressure-related measure. The neurofibrillary tangle and micro-vascular lesion models showed good accuracy for predicting clinical vascular dementia. DISCUSSION: There may be shared risk factors across dementia-related lesions, suggesting common pathways. Strategies targeting these models may reduce risk or postpone clinical symptoms of dementia as well as reduce neuropathological burden associated with AD and vascular lesions.

Decreases in COVID-19 Cases, Emergency Department Visits, Hospital Admissions, and Deaths Among Older Adults Following the Introduction of COVID-19 Vaccine - United States, September 6, 2020-May 1, 2021.

Throughout the COVID-19 pandemic, older U.S. adults have been at increased risk for severe COVID-19-associated illness and death (1). On December 14, 2020, the United States began a nationwide vaccination campaign after the Food and Drug Administration's Emergency Use Authorization of Pfizer-BioNTech COVID-19 vaccine. The Advisory Committee on Immunization Practices (ACIP) recommended prioritizing health care personnel and residents of long-term care facilities, followed by essential workers and persons at risk for severe illness, including adults aged ≥65 years, in the early phases of the vaccination program (2). By May 1, 2021, 82%, 63%, and 42% of persons aged ≥65, 50-64, and 18-49 years, respectively, had received ≥1 COVID-19 vaccine dose. CDC calculated the rates of COVID-19 cases, emergency department (ED) visits, hospital admissions, and deaths by age group during November 29-December 12, 2020 (prevaccine) and April 18-May 1, 2021. The rate ratios comparing the oldest age groups (≥70 years for hospital admissions; ≥65 years for other measures) with adults aged 18-49 years were 40%, 59%, 65%, and 66% lower, respectively, in the latter period. These differential declines are likely due, in part, to higher COVID-19 vaccination coverage among older adults, highlighting the potential benefits of rapidly increasing vaccination coverage.

Chronic kidney diseases in agricultural communities: report from a workshop.

In June 2018, the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Environmental Health Sciences sponsored a workshop to identify research gaps in an increasingly common form of chronic kidney disease in agricultural communities, often termed "CKDu." The organizers invited a broad range of experts who provided diverse expertise and perspectives, many of whom had never addressed this particular epidemic. Discussion was focused around selected topics, including identifying and mitigating barriers to research in CKDu, creating a case definition, and defining common data elements. All hypotheses regarding etiology were entertained, and meeting participants discussed potential research strategies, choices in study design, and novel tools that may prove useful in this disease. Achievements of the workshop included robust cross-disciplinary discussion and preliminary planning of research goals and design. Specific challenges in implementing basic and clinical research and interventions in low- and middle-income countries were recognized. A balanced approach to leveraging local resources and capacity building without overreaching was emphasized.

High hsCRP is associated with reduced lung function in structural firefighters.

BACKGROUND: To assess the association between markers of systemic inflammation and pulmonary function in a population of structural firefighters. METHODS: We studied male career members of a large Midwestern fire department with questionnaires, spirometry, and high-sensitivity C-reactive protein (hsCRP) as a biomarker of systemic inflammation. We examined percent predicted forced expiratory volume in 1 s (FEV1 %-predicted) and forced vital capacity (FVC%-predicted). RESULTS: Complete data were available for 401 firefighters. Higher hsCRP levels were associated with lower lung function values, after adjusting for confounding variables. Specifically, for every twofold increase in log10-hsCRP, FEV1 %-predicted decreased by a mean 1.5% (95% CI: 0.4, 2.6%) and FVC%-predicted decreased by a mean 1.4% (95% CI: 0.4, 2.3%). CONCLUSION: hsCRP as a biomarker of systemic inflammation may indicate reduced lung function in structural firefighters.

Arterial stiffness, oxidative stress, and smoke exposure in wildland firefighters.

OBJECTIVES: To assess the association between exposure, oxidative stress, symptoms, and cardiorespiratory function in wildland firefighters. METHODS: We studied two Interagency Hotshot Crews with questionnaires, pulse wave analysis for arterial stiffness, spirometry, urinary 8-iso-prostaglandin F2α (8-isoprostane) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), and the smoke exposure marker (urinary levoglucosan). Arterial stiffness was assessed by examining levels of the aortic augmentation index, expressed as a percentage. An oxidative stress score comprising the average of z-scores created for 8-OHdG and 8-isoprostane was calculated. RESULTS: Mean augmentation index % was higher for participants with higher oxidative stress scores after adjusting for smoking status. Specifically for every one unit increase in oxidative stress score the augmentation index % increased 10.5% (95% CI: 2.5, 18.5%). Higher mean lower respiratory symptom score was associated with lower percent predicted forced expiratory volume in one second/forced vital capacity. CONCLUSIONS: Biomarkers of oxidative stress may serve as indicators of arterial stiffness in wildland firefighters.

Exposures and cross-shift lung function declines in wildland firefighters.

Respiratory problems are common among wildland firefighters. However, there are few studies directly linking occupational exposures to respiratory effects in this population. Our objective was to characterize wildland fire fighting occupational exposures and assess their associations with cross-shift changes in lung function. We studied 17 members of the Alpine Interagency Hotshot Crew with environmental sampling and pulmonary function testing during a large wildfire. We characterized particles by examining size distribution and mass concentration, and conducting elemental and morphological analyses. We examined associations between cross-shift lung function change and various analytes, including levoglucosan, an indicator of wood smoke from burning biomass. The levoglucosan component of the wildfire aerosol showed a predominantly bimodal size distribution: a coarse particle mode with a mass median aerodynamic diameter about 12 µm and a fine particle mode with a mass median aerodynamic diameter < 0.5 µm. Levoglucosan was found mainly in the respirable fraction and its concentration was higher for fire line construction operations than for mop-up operations. Larger cross-shift declines in forced expiratory volume in one second were associated with exposure to higher concentrations of respirable levoglucosan (p < 0.05). Paired analyses of real-time personal air sampling measurements indicated that higher carbon monoxide (CO) concentrations were correlated with higher particulate concentrations when examined by mean values, but not by individual data points. However, low CO concentrations did not provide reliable assurance of concomitantly low particulate concentrations. We conclude that inhalation of fine smoke particles is associated with acute lung function decline in some wildland firefighters. Based on short-term findings, it appears important to address possible long-term respiratory health issues for wildland firefighters. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resources: a file containing additional information on historical studies of wildland fire exposures, a file containing the daily-exposure-severity questionnaire completed by wildland firefighter participants at the end of each day, and a file containing additional details of the investigation of correlations between carbon monoxide concentrations and other measured exposure factors in the current study.].

Tracking COVID-19 in the United States With Surveillance of Aggregate Cases and Deaths.

Early during the COVID-19 pandemic, the Centers for Disease Control and Prevention (CDC) leveraged an existing surveillance system infrastructure to monitor COVID-19 cases and deaths in the United States. Given the time needed to report individual-level (also called line-level) COVID-19 case and death data containing detailed information from individual case reports, CDC designed and implemented a new aggregate case surveillance system to inform emergency response decisions more efficiently, with timelier indicators of emerging areas of concern. We describe the processes implemented by CDC to operationalize this novel, multifaceted aggregate surveillance system for collecting COVID-19 case and death data to track the spread and impact of the SARS-CoV-2 virus at national, state, and county levels. We also review the processes established to acquire, process, and validate the aggregate number of cases and deaths due to COVID-19 in the United States at the county and jurisdiction levels during the pandemic. These processes include time-saving tools and strategies implemented to collect and validate authoritative COVID-19 case and death data from jurisdictions, such as web scraping to automate data collection and algorithms to identify and correct data anomalies. This topical review highlights the need to prepare for future emergencies, such as novel disease outbreaks, by having an event-agnostic aggregate surveillance system infrastructure in place to supplement line-level case reporting for near-real-time situational awareness and timely data.

Reported exposure trends among healthcare personnel COVID-19 cases, USA, March 2020-March 2021.

BACKGROUND: Health care personnel (HCP) have experienced significant SARS-CoV-2 risk, but exposure settings among HCP COVID-19 cases are poorly characterized. METHODS: We assessed exposure settings among HCP COVID-19 cases in the United States from March 2020 to March 2021 with reported exposures (n = 83,775) using national COVID-19 surveillance data. Exposure setting and reported community incidence temporal trends were described using breakpoint estimation. Among cases identified before initiation of COVID-19 vaccination programs (n = 65,650), we used separate multivariable regression models to estimate adjusted prevalence ratios (aPR) for associations of community incidence with health care and household and/or community exposures. RESULTS: Health care exposures were the most reported (52.0%), followed by household (30.8%) and community exposures (25.6%). Health care exposures and community COVID-19 incidence showed similar temporal trends. In adjusted analyses, HCP cases were more likely to report health care exposures (aPR = 1.31; 95% CI:1.26-1.36) and less likely to report household and/or community exposures (aPR = 0.73; 95% CI:0.70-0.76) under the highest vs lowest community incidence levels. DISCUSSION: These findings highlight HCP exposure setting temporal trends and workplace exposure hazards under high community incidence. Findings also underscore the need for robust collection of work-related data in infectious disease surveillance. CONCLUSIONS: Many reported HCP cases experienced occupational COVID-19 exposures, particularly during periods of higher community COVID-19 incidence.

Particle size-dependent radical generation from wildland fire smoke.

Firefighting, along with construction, mining and agriculture, ranks among the most dangerous occupations. In addition, the work environment of firefighters is unlike that of any other occupation, not only because of the obvious physical hazards but also due to the respiratory and systemic health hazards of smoke inhalation resulting from combustion. A significant amount of research has been devoted to studying municipal firefighters; however, these studies may not be useful in wildland firefighter exposures, because the two work environments are so different. Not only are wildland firefighters exposed to different combustion products, but their exposure profiles are different. The combustion products wildland firefighters are exposed to can vary greatly in characteristics due to the type and amount of material being burned, soil conditions, temperature and exposure time. Smoke inhalation is one of the greatest concerns for firefighter health and it has been shown that the smoke consists of a large number of particles. These smoke particles contain intermediates of hydrogen, carbon and oxygen free radicals, which may pose a potential health risk. Our investigation looked into the involvement of free radicals in smoke toxicity and the relationship between particle size and radical generation. Samples were collected in discrete aerodynamic particle sizes from a wildfire in Alaska, preserved and then shipped to our laboratory for analysis. Electron spin resonance was used to measure carbon-centered as well as hydroxyl radicals produced by a Fenton-like reaction with wildfire smoke. Further study of reactive oxygen species was conducted using analysis of cellular H(2)O(2) generation, lipid peroxidation of cellular membranes and DNA damage. Results demonstrate that coarse size-range particles contained more carbon radicals per unit mass than the ultrafine particles; however, the ultrafine particles generated more *OH radicals in the acellular Fenton-like reaction. The ultrafine particles also caused significant increases in H(2)O(2) production by monocytes and lipid peroxidation. All particle sizes showed the ability to cause DNA damage. These results indicate that the radical generation and the damage caused by them is not only a function of surface area but is also influenced by changing chemical and other characteristics due to particle size.

Acute upper and lower respiratory effects in wildland firefighters.

OBJECTIVES: To assess acute respiratory effects experienced by wildland firefighters. METHODS: We studied two Interagency Hotshot Crews with questionnaires, spirometry, and measurement of albumin, eosinophilic cationic protein (ECP), and myeloperoxidase (MPO) as indicators of inflammation in sputum and nasal lavage fluid. Assessments were made preseason, postfire, and postseason. RESULTS: Fifty-eight members of the two crews had at least two assessments. Mean upper and lower respiratory symptom scores were higher postfire compared to preseason (P < 0.001). The mean forced expiratory volume in 1 second was lower postfire compared to preseason (P < 0.001) and then recovered by postseason. Individual increases in sputum and nasal ECP and MPO from preseason to postfire were all significantly associated with postfire respiratory symptom scores. CONCLUSIONS: Wildland firefighting was associated with upper and lower respiratory symptoms and reduced forced expiratory volume in 1 second. Within individuals, symptoms were associated with increased ECP and MPO in sputum and nasal lavage fluid. The long-term respiratory health impact of wildland firefighting, especially over multiple fire seasons, remains an important concern.

Osteonecrosis of the hip (Legg-Calvé-Perthes disease) in human immunodeficiency virus-infected children.

OBJECTIVE: Osteonecrosis of the hip has been reported in human immunodeficiency virus (HIV)-infected adults; whether this is related to HIV infection or its treatment is unknown. There has been 1 report of osteonecrosis among HIV-infected children. Specifically, avascular necrosis of the hip consistent with Legg-Calvé-Perthes disease (LCPD) was reported in 3 HIV-infected children with AIDS from Spain in 1992. We evaluated the prevalence and incidence of LCPD, the pediatric equivalent of adult osteonecrosis of the hip, in HIV-infected children participating in a prospective cohort study of long-term outcomes in HIV-infected and HIV-exposed children-Pediatric AIDS Clinical Trials Group (PACTG) protocol 219. METHODS: PACTG 219 enrolled 2014 HIV-infected and 849 HIV-exposed, uninfected children between April 1993 and September 2000. Children had periodic examinations with collection of clinical and laboratory data. The database was reviewed for reports of LCPD and other bone disorders. A prevalent case was defined as LCPD diagnosis preceding PACTG 219 enrollment and an incident case had to have occurred between enrollment and September 2000. A case-control study (matching on age, gender, and race/ethnicity, which are known to be associated with risk of LCPD and HIV infection status) was performed to investigate factors possibly associated with LCPD. RESULTS: Six cases of LCPD (4 prevalent cases reported at study entry; 2 diagnosed during 5837 person-years of follow-up) were observed; LCPD was seen only in children with perinatal HIV infection. LCPD prevalence was 199 per 100 000 compared with an estimated general pediatric population prevalence of 23 per 100 000. Based on age-adjusted general population rates, the expected number of prevalent cases at PACTG 219 study entry would have been 0.44; the age-adjusted LCPD prevalence rate ratio was 9.0 (95% confidence interval [CI]: 8.3-9.7) for HIV-infected children compared with the general population. LCPD incidence was 34 per 100 000 person-years (95% CI: 0.42-124) compared with the estimated general population incidence of 6 per 100 000 person-years (95% CI: 5-7). Based on age-adjusted general population rates, the expected incidence of LCPD in PACTG 219 would have been 0.42; the age-adjusted relative risk of LCPD in HIV-infected PACTG 219 children was 4.8 (95% CI: 0.56-10.4). No cases were observed in uninfected children during 1919 person-years of follow-up on PACTG 219; the age-adjusted expected number of cases was 0.09. Median onset age was 7 years; 67% were of Hispanic or black race/ethnicity and 33% were female. Four of the 6 LCPD cases had received antiretroviral therapy before diagnosis; treatment was primarily with nucleoside reverse transcriptase inhibitors, and 2 had received protease inhibitors. Three of the LCPD cases had corticosteroid exposure before the diagnosis, but only 1 child had systemic exposure and the remaining 2 had topical exposure exclusively. In the case-control study, antiretroviral and corticosteroid therapy, CD4 cell percentage, birth weight, height for age and gender percentile, and triglyceride levels were not significantly associated with LCPD. However, the case-control study had limited power to evaluate possible associations. CONCLUSION: Similar to HIV-infected adults, children with perinatal HIV infection have an increased risk for osteonecrosis of the hip, and clinicians should be alert to this diagnosis when HIV-infected children present with limp or hip pain. Whether LCPD is attributable to HIV infection itself, HIV-associated complications that could predispose to hypercoagulopathy, HIV-related therapies, or to the growth abnormalities in HIV-infected children is unknown and deserves additional evaluation.

Psychiatric hospitalizations among children and youths with human immunodeficiency virus infection.

OBJECTIVE: Psychiatric manifestations of pediatric human immunodeficiency virus (HIV) infection have been described. However, data on severe sequelae requiring hospitalization among this population have not been reported. METHODS: The Pediatric Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group (PACTG) 219C is a prospective cohort study designed to examine long-term outcomes among HIV-infected children and HIV-uninfected infants born to HIV-infected women. Children with HIV infection who have enrolled in PACTG 219C are examined quarterly, with collection of clinical and laboratory data. Hospitalizations and diagnoses for all participants between September 2000 (when enrollment into PACTG 219C was started) and December 2002 were reviewed. RESULTS: Among 1808 HIV-infected participants who were <15 years of age at the last visit date, 25 children had been hospitalized for psychiatric manifestations, 8 before enrollment into PACTG 219C. Seventeen children were hospitalized during 2757 person-years of follow-up monitoring after entry into PACTG 219C, which represents an incidence of 6.17 cases per 1000 person-years (95% confidence interval: 3.59-9.87 cases per 1000 person-years). This was significantly higher than the incidence of 1.70 cases per 1000 person-years (95% confidence interval: 1.67-1.72 cases per 1000 person-years) in the general pediatric population <15 years of age, as reported in the 2000 National Hospital Discharge Survey, yielding a relative rate of 3.62 (95% confidence interval: 2.11-5.80). A total of 32 HIV-infected children, regardless of age, were hospitalized because of psychiatric illnesses. The majority of patients were admitted because of depression (n = 16) or behavioral disorders (n = 8). Fifteen (47%) underwent multiple psychiatric hospitalizations. The median age at the first psychiatric hospitalization was 11 years (range: 4-17 years); all patients had been perinatally infected. Knowledge of HIV seropositivity status and having experienced a significant life event were both significantly associated with an increased risk of psychiatric hospitalization (hazard ratios of 6.13 and 3.04, respectively). No psychiatric hospitalizations were observed among the 1021 HIV-uninfected members of the cohort. CONCLUSIONS: Children with HIV/AIDS are at increased risk for psychiatric hospitalizations during childhood and early adolescence, compared with the general pediatric population. Knowledge of HIV seropositivity status and recent significant life events were significantly associated with increased risks of admission in this population.

The prevalence of pain in pediatric human immunodeficiency virus/acquired immunodeficiency syndrome as reported by participants in the Pediatric Late Outcomes Study (PACTG 219).

OBJECTIVES: As the life expectancy of children with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) increases, quality-of-life outcomes are of increasing concern. The prevalence of pain in adults with AIDS ranges from 40% to 60%, depending on stage of illness. There is limited research concerning pain in HIV-infected children and youth. DESIGN: The General Health Assessment for Children was administered to caregivers of HIV-infected children and youth enrolled in the Pediatric Late Outcomes Study (PACTG 219), a prospective cohort study. Pain is assessed over the previous month with 7 questions. For the purpose of this analysis, we defined pain as the presence of pain of at least moderate intensity. Participants were observed from January 1, 1996, to December 31, 1999. RESULTS: A total of 985 HIV-positive participants had a baseline pain evaluation in 1995. The prevalence of pain remained relatively constant during each year of observation, averaging 20%. Lower CD4+ T-lymphocyte percentage, female gender, and an HIV/AIDS-related diagnosis were highly associated with an increased risk of reported pain. Pain was also independently associated with increased risk of death. After adjusting for CD4 percentage, use of combination therapy including protease inhibitors, comorbid diagnoses, and other sociodemographic characteristics, individuals reporting pain were over 5 times more likely to die than those not reporting pain (hazard ratio = 5.07; 95% confidence interval = 3.23-7.95). CONCLUSIONS: Pain is a frequently encountered symptom in children and youth with HIV disease and is also associated with increased mortality. These findings emphasize the importance of pain management in this population.