Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Mechanisms and Risk Factors of Cognitive Aging

This dissertation explores the role of biologic factors and a novel method of measuring cognitive function in investigating mechanisms and risk factors of cognitive aging. With a rapidly increasing aging population, the public health burden of dementia is expected to rise in the future. Therefore, it is important to both better understand the etiology and identify novel risk factors, in order to reduce the incidence of new cases and develop effective treatments. Blood-based biomarkers, such as amyloid-beta and sex hormones, can provide an objective measure of factors likely associated with dementia risk. Additionally, computerized cognitive testing can provide efficient and accurate measurement of cognitive function, yet is seldom used in epidemiologic studies. Our first chapter involves the first systematic review and meta-analysis of prospective studies exploring the association between plasma amyloid-beta and incident Alzheimer’s disease or dementia. While preclinical prediction of Alzheimer’s disease is important for effective intervention, studies have considerably varied in design, assays and sample size, making it difficult to interpret the overall data and thus necessitating a systematic review and meta-analysis. The second chapter explores the association between endogenous hormone levels and cognitive function in a population of older women. While many studies have investigated the role of hormone therapy in cognitive aging, fewer studies have investigated endogenous hormones, which may provide a more objective measure of hormonal status. We therefore present a prospective cohort study investigating the association between several endogenous sex hormones and their prohormones at baseline, and cognitive function over 20 years later. The third chapter evaluates the feasibility and performance of a self-administered computerized cognitive battery. Although most epidemiologic studies of cognitive aging rely on traditional neuropsychological testing to measure cognitive outcomes, such methods can be prone to error, interviewer bias, and demand substantial time and cost. Therefore, we present results demonstrating for the first time the feasibility and performance of an unsupervised self-administered computerized cognitive battery in a population of older men.Epidemiolog

Role of Anemia in Dementia Risk Among Veterans With Incident CKD

RATIONALE & OBJECTIVE: Although some evidence exists of increased dementia risk from anemia, it is unclear whether this association persists among adults with CKD. Anemia may be a key marker for dementia among adults with CKD, so we evaluated whether anemia is associated with an increased risk of dementia among adults with CKD. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: The study included 620,095 veterans aged≥45 years with incident stage 3 CKD (estimated glomerular filtration rate [eGFR]\u3c60mL/min/1.73m) between January 2005 and December 2016 in the US Veterans Health Administration system and followed through December 31, 2018, for incident dementia, kidney failure, or death. EXPOSURE: Anemia was assessed based on the average of hemoglobin levels (g/L) during the 2 years before the date of incident CKD and categorized as normal, mild, or moderate/severe anemia (≥12.0, 11.0-11.9,\u3c11.0g/dL, respectively, for women, and≥13.0, 11.0-12.9,\u3c11.0g/dL for men). OUTCOME: Dementia and the composite outcome of kidney failure or death. ANALYTICAL APPROACH: Adjusted cause-specific hazard ratios were estimated for each outcome. RESULTS: At the time of incident CKD, the mean age of the participants was 72 years, 97% were male, and their mean eGFR was 51mL/min per 1.73m. Over a median 4.1 years of follow-up, 92,306 veterans (15%) developed dementia before kidney failure or death. Compared with the veterans with CKD without anemia, the multivariable-adjusted models showed a 16% (95% CI, 14%-17%) significantly higher risk of dementia for those with mild anemia and a 27% (95% CI, 23%-31%) higher risk with moderate/severe anemia. Combined risk of kidney failure or death was higher at 39% (95% CI, 37%-40%) and 115% (95% CI, 112%-119%) for mild and moderate/severe anemia, respectively, compared with no anemia. LIMITATIONS: Residual confounding from the observational study design. Findings may not be generalizable to the broader US population. CONCLUSIONS: Anemia was significantly associated with an increased risk of dementia among veterans with incident CKD, underscoring the role of anemia as a predictor of dementia risk. PLAIN-LANGUAGE SUMMARY: Adults with chronic kidney disease (CKD) often have anemia. Prior studies among adults in the general population suggest anemia is a risk factor for dementia, though it is unclear whether this association persists among adults with CKD. In this large study of veterans in the United States, we studied the association between anemia and the risk of 2 important outcomes in this population: (1) dementia and (2) kidney failure or death. We found that anemia was associated with a greater risk of dementia as well as risk of kidney failure or death. The study findings therefore emphasize the role of anemia as a key predictor of dementia risk among adults with CKD

Age-Related Association between Multimorbidity and Mortality in US Veterans with Incident Chronic Kidney Disease

IntroductionMortality is an important long-term indicator of the public health impact of chronic kidney disease (CKD). We investigated the role of individual comorbidities and multimorbidity on age-specific mortality risk among US veterans with new-onset CKD.MethodsThe cohort included 892,005 veterans aged ≥18 years with incident CKD stage 3 between January 2004 and April 2018 in the US Veterans Health Administration (VHA) system and followed until death, December 2018, or up to 10 years. Incident CKD was defined as the first-time estimated glomerular filtration rate (eGFR) was &lt;60 mL/min/1.73 m2 for &gt;3 months. Comorbidities were ascertained using inpatient and outpatient clinical records in the VHA system and Medicare claims. We estimated death rates for any cardiovascular disease (CVD, a composite of 6 CVD conditions) and 15 non-CVD comorbidities, and adjusted risks of death (hazard ratio [HR], 95% confidence interval [CI]) overall and by age group at CKD incidence.ResultsAt CKD incidence, the mean age was 72 years, and 97% were male; the mean eGFR was 52 mL/min/1.73 m2, and 95% had ≥2 comorbidities (median, 4) in addition to CKD. During a median follow-up of 4.5 years, among the 16 comorbidities, CVD was associated with the highest relative risk of death in younger veterans (HR 1.96 [95% CI: 1.61-2.37] in ages 18-44 years and HR 1.66 [1.63-1.70] in ages 45-64 years). Dementia was associated with the highest relative risk of death among older veterans (HR 1.71 [1.68-1.74] in ages 65-84 years and HR 1.69 [1.65-1.73] in ages 85-100 years). The additive effect of multimorbidity on risk of death was stronger in younger than older veterans. Compared to having 1 or no comorbidity at CKD onset, the risk of death with ≥5 comorbidities was &gt;7-fold higher among veterans aged 18-44 years and &gt;2-fold higher among veterans aged 85-100 years.ConclusionThe large burden of comorbidities in US veterans with newly identified CKD places them at the risk of premature death. Compared with older veterans, younger veterans with multiple comorbidities, particularly with CVD, at CKD onset are at an even higher relative risk of death

Trends in lifetime risk and years of potential life lost from diabetes in the United States, 1997-2018

Koyama AK, Cheng YJ, Brinks R, et al. Trends in lifetime risk and years of potential life lost from diabetes in the United States, 1997-2018. PLoS ONE . 2022;17(5): e0268805.BACKGROUND: Both incidence and mortality of diagnosed diabetes have decreased over the past decade. However, the impact of these changes on key metrics of diabetes burden-lifetime risk (LR), years of potential life lost (YPLL), and years spent with diabetes-is unknown.; METHODS: We used data from 653,811 adults aged ≥18 years from the National Health Interview Survey, a cross-sectional sample of the civilian non-institutionalized population in the United States. LR, YPLL, and years spent with diabetes were estimated from age 18 to 84 by survey period (1997-1999, 2000-2004, 2005-2009, 2010-2014, 2015-2018). The age-specific incidence of diagnosed diabetes and mortality were estimated using Poisson regression. A multistate difference equation accounting for competing risks was used to model each metric.; RESULTS: LR and years spent with diabetes initially increased then decreased over the most recent time periods. LR for adults at age 20 increased from 31.7% (95% CI: 31.2-32.1%) in 1997-1999 to 40.7% (40.2-41.1%) in 2005-2009, then decreased to 32.8% (32.4-33.2%) in 2015-2018. Both LR and years spent with diabetes were markedly higher among adults of non-Hispanic Black, Hispanic, and other races compared to non-Hispanic Whites. YPLL significantly decreased over the study period, with the estimated YPLL due to diabetes for an adult aged 20 decreasing from 8.9 (8.7-9.1) in 1997-1999 to 6.2 (6.1-6.4) in 2015-2018 (p = 0.02).; CONCLUSION: In the United States, diabetes burden is declining, but disparities by race/ethnicity remain. LR remains high with approximately one-third of adults estimated to develop diabetes during their lifetime

Endogenous sex hormones and cognitive function in older women

IntroductionWe examined the association between endogenous sex hormones and both objective and subjective measures of cognitive function.MethodsWe followed 3044 women up to 23&nbsp;years in a prospective cohort study. We measured plasma levels of estrone, estrone sulfate, estradiol, androstenedione, testosterone, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEA-S) in 1989-1990, conducted neuropsychologic testing in 1999-2008, and inquired about subjective cognition in&nbsp;2012.ResultsOverall, we observed little relation between plasma levels of hormones and either neuropsychologic test performance or subjective cognition. However, after adjustment for age and education, we observed a borderline significant association of higher levels of plasma estrone with higher scores for both overall cognition (P trend&nbsp;=&nbsp;.10) and verbal memory (P trend&nbsp;=&nbsp;.08).DiscussionThere were no clear associations of endogenous hormone levels at midlife and cognition in later life, although a suggested finding of higher levels of plasma estrone associated with better cognitive function merits further research

Association Between the Mediterranean Diet and Cognitive Decline in a Biracial Population

BackgroundResults from numerous studies suggest protective effects of the Mediterranean diet for cardiovascular disease, cancer, and mortality. Evidence for an association with a decreased risk of cognitive decline is less consistent and studies are limited by a lack of diversity in their populations.MethodsWe followed 2,326 older adults (38.2% black, 51.3% female, aged 70-79 at baseline) over 8 years in a prospective cohort study in the United States (Health, Aging and Body Composition study). To measure adherence to a Mediterranean diet, we calculated race-specific tertiles of the MedDiet score (range: 0-55) using baseline food frequency questionnaires. Cognitive decline was assessed using repeated Modified Mini Mental State Examination scores over the study. We used linear mixed models to assess the association between MedDiet score and trajectory of cognitive decline.ResultsAmong blacks, participants with high MedDiet scores had a significantly lower mean rate of decline on the Modified Mini Mental State Examination score compared with participants with lower MedDiet scores (middle and bottom tertiles). The mean difference in points per year was 0.22 (95% confidence interval: 0.05-0.39; p = .01) after adjustment for age, sex, education, body mass index, current smoking, physical activity, depression, diabetes, total energy intake, and socioeconomic status. No association between MedDiet scores and change in Modified Mini Mental State Examination score was seen among white participants (p = .14).ConclusionsStronger adherence to the Mediterranean diet may reduce the rate of cognitive decline among black, but not white older adults. Further studies in diverse populations are needed to confirm this association and pinpoint mechanisms that may explain these results

Risk Factors Amenable to Primary Prevention of Type 2 Diabetes Among Disaggregated Racial and Ethnic Subgroups in the United States

Race and ethnicity data disaggregated into detailed subgroups may reveal pronounced heterogeneity in diabetes risk factors. We therefore used disaggregated data to examine the prevalence of type 2 diabetes risk factors related to lifestyle behaviors and barriers to preventive care, among adults in the United States. We conducted a pooled cross-sectional study of 3,437,640 adults aged ≥18 in the United States without diagnosed diabetes from the Behavioral Risk Factor Surveillance System (2013–2021). Self-reported race and ethnicity included: Hispanic (Cuban, Mexican, Puerto Rican, Other Hispanic), Non-Hispanic (NH) American Indian/Alaska Native, NH Asian (Chinese, Filipino, Indian, Japanese, Korean, Vietnamese, Other Asian), NH Black, NH Pacific Islander (Guamanian/Chamorro, Native Hawaiian, Samoan, Other Pacific Islander), NH White, NH Multiracial, NH Other. Risk factors included: current smoking, hypertension, overweight or obesity, physical inactivity, being uninsured, not having a primary care doctor, healthcare cost concerns, and no physical exam in the past 12 months. Prevalence of hypertension, lifestyle factors and barriers to preventive care showed substantial heterogeneity among both aggregated, self-identified racial and ethnic groups and disaggregated subgroups. For example, the prevalence of overweight or obesity ranged from 50.8% (95% confidence interval [CI], 49.1–52.5) among Chinese adults to 79.8% (73.5–84.9) among Samoan adults. Prevalence of being uninsured among Hispanic subgroups ranged from 11.4% (10.9–11.9) among Puerto Rican adults to 33.0% (32.5–33.5) among Mexican adults. These findings underscore the importance of using disaggregated race and ethnicity data to accurately characterize disparities in type 2 diabetes risk factors and access to care.</p

Risk of Cardiovascular Disease After COVID‐19 Diagnosis Among Adults With and Without Diabetes

Background Growing evidence suggests incident cardiovascular disease (CVD) may be a long‐term outcome of COVID‐19 infection, and chronic diseases, such as diabetes, may influence CVD risk associated with COVID‐19. We evaluated the postacute risk of CVD >30 days after a COVID‐19 diagnosis by diabetes status. Methods and Results We included adults ≥20 years old with a COVID‐19 diagnosis from March 1, 2020 through December 31, 2021 in a retrospective cohort study from the IQVIA PharMetrics Plus insurance claims database. A contemporaneous control group comprised adults without recorded diagnoses for COVID‐19 or other acute respiratory infections. Two historical control groups comprised patients with or without an acute respiratory infection. Cardiovascular outcomes included cerebrovascular disorders, dysrhythmia, inflammatory heart disease, ischemic heart disease, thrombotic disorders, other cardiac disorders, major adverse cardiovascular events, and any CVD. The total sample comprised 23 824 095 adults (mean age, 48.4 years [SD, 15.7 years]; 51.9% women; mean follow‐up, 8.5 months [SD, 5.8 months]). In multivariable Cox regression models, patients with a COVID‐19 diagnosis had a significantly greater risk of all cardiovascular outcomes compared with patients without a diagnosis of COVID‐19 (hazard ratio [HR], 1.66 [1.62–1.71], with diabetes; HR, 1.75 [1.73–1.78], without diabetes). Risk was attenuated but still significant for the majority of outcomes when comparing patients with COVID‐19 to both historical control groups. Conclusions In patients with COVID‐19 infection, postacute risk of incident cardiovascular outcomes is significantly higher than among controls without COVID‐19, regardless of diabetes status. Therefore, monitoring for incident CVD may be essential beyond the first 30 days after a COVID‐19 diagnosis