Is the Gap Closing? Comparison of Sociodemographic Disparities in COVID-19 Hospitalizations and Outcomes Between Two Temporal Waves of Admissions.

OBJECTIVE: The COVID-19 pandemic has disproportionately impacted minority communities, yet little data exists regarding whether disparities have improved at a health system level. This study examined whether sociodemographic disparities in hospitalization and clinical outcomes changed between two temporal waves of hospitalized COVID-19 patients. METHODS: This is a retrospective cohort study of primary care patients at Mass General Brigham (a large northeastern health system serving 1.27 million primary care patients) hospitalized in-system with COVID-19 between March 1, 2020, and March 1, 2021, categorized into two 6-month "wave" periods. We used chi-square tests to compare demographics between waves, and regression analysis to characterize the association of race/ethnicity and language with in-hospital severe outcomes (death, hospice discharge, intensive unit care need). RESULTS: Hispanic/Latino, Black, and non-English-speaking patients constituted 30.3%, 12.5%, and 29.7% of COVID-19 admissions in wave 1 (N = 5844) and 22.2%, 9.0%, and 22.7% in wave 2 (N = 4007), compared to 2019 general admission proportions of 8.8%, 6.3%, and 7.7%, respectively. Admissions from highly socially vulnerable census tracts decreased between waves. Non-English speakers had significantly higher odds of severe illness during wave 1 (OR 1.35; 95% CI: 1.10, 1.66) compared to English speakers; this association was non-significant during wave 2 (OR 1.01; 95% CI: 0.76, 1.36). CONCLUSIONS: Comparing two COVID-19 temporal waves, significant sociodemographic disparities in COVID-19 admissions improved between waves but continued to persist over a year, demonstrating the need for ongoing interventions to truly close equity gaps. Non-English-speaking language status independently predicted worse hospitalization outcomes in wave 1, underscoring the importance of targeted and effective in-hospital supports for non-English speakers.

The essential role of population health during and beyond COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has fundamentally changed how health care systems deliver services and revealed the tenuousness of care delivery based on face-to-face office visits and fee-for-service reimbursement models. Robust population health management, fostered by value-based contract participation, integrates analytics and agile clinical programs and is adaptable to optimize outcomes and reduce risk during population-level crises. In this article, we describe how mature population health programs in a learning health system have been rapidly leveraged to address the challenges of the pandemic. Population-level data and care management have facilitated identification of demographic-based disparities and community outreach. Telemedicine and integrated behavioral health have ensured critical primary care and specialty access, and mobile health and postacute interventions have shifted site of care and optimized hospital utilization. Beyond the pandemic, population health can lead as a cornerstone of a resilient health system, better prepared to improve public health and mitigate risk in a value-based paradigm.

Comparing neighborhood-based indices of socioeconomic risk factors and potentially preventable emergency department utilization.

BACKGROUND: Neighborhood stress score (NSS) and area deprivation index (ADI) are two neighborhood-based composite measures used to quantify an individual's socioeconomic risk based on home location. In this analysis, we compare the relationships between an individual's socioeconomic risk, based on each of these measures, and potentially preventable acute care utilization. METHODS: Using emergency department (ED) visit data from two academic medical centers in Boston, Massachusetts, we conducted adjusted Poisson regressions of ADI decile and NSS decile with counts of low acuity ED visits, admissions for ambulatory care sensitive conditions (ACSCs), and patients with high frequency ED utilization at the census block group (CBG) level within the greater Boston area. RESULTS: Both NSS and ADI decile were associated with elevated rates of utilization, although the associated incidence rate ratios (IRRs) for NSS were higher than those for ADI across all three measures. NSS decile was associated with IRRs of 1.11 [95% CI: 1.10-1.12], 1.16 [1.14-1.17], and 1.22 [1.19-1.25] for ACSC admissions, low acuity ED visits, and patients with high frequency ED utilization, respectively; compared with 1.04 [1.04-1.05], 1.11 [1.10-1.11], and 1.10 [1.08-1.12] for ADI decile. CONCLUSION: ADI and NSS both represent effective tools to assess the potential impact of geographically-linked socioeconomic drivers of health on potentially preventable acute care utilization. NSS decile was associated with a greater effect size for each measure of utilization suggesting that this may be a stronger predictor, however, additional research is necessary to evaluate these findings in other contexts.

Evaluation of Hospitalizations Preventable with Idealized Outpatient Care and Continuity of Care.

BACKGROUND: Unnecessary hospitalizations may pose the risk of iatrogenic complications, suboptimal patient experience, and increased cost. Administrative data lack granularity to understand the proportion and causes of hospitalizations preventable through optimizing care continuum (HPOCC). We aim to identify the incidence and causes of HPOCC through clinician-adjudicated chart review. METHODS: A retrospective review was performed for inpatient admissions from the emergency department (ED) over 1 week. Each admission was reviewed by a clinician to determine whether it is an HPOCC defined as not requiring inpatient care with the assumption of idealized outpatient care and social support. RESULTS: Of the 515 patients admitted from the ED, 31 (6.0%) patients were judged to have had an HPOCC. Causes of HPOCC include urgent diagnostics (9, 29.0%), unnecessary transfer from a long-term facility (7, 23.0%), needing IV therapy (5, 16.0%), benign incidental finding (5, 16.0%), diagnostic uncertainty in complex chronic illness (3, 10.0%), and lack of access to care for disposition (2, 6.0%). CONCLUSION: Hospitalizations preventable through optimizing care continuum account for about 1 in every 15 hospitalizations in an urban academic medical center. The need for urgent diagnostics accounts for a plurality of HPOCC and could be an important target for quality improvement.

RNA editing genes associated with extreme old age in humans and with lifespan in C. elegans.

BACKGROUND: The strong familiality of living to extreme ages suggests that human longevity is genetically regulated. The majority of genes found thus far to be associated with longevity primarily function in lipoprotein metabolism and insulin/IGF-1 signaling. There are likely many more genetic modifiers of human longevity that remain to be discovered. METHODOLOGY/PRINCIPAL FINDINGS: Here, we first show that 18 single nucleotide polymorphisms (SNPs) in the RNA editing genes ADARB1 and ADARB2 are associated with extreme old age in a U.S. based study of centenarians, the New England Centenarian Study. We describe replications of these findings in three independently conducted centenarian studies with different genetic backgrounds (Italian, Ashkenazi Jewish and Japanese) that collectively support an association of ADARB1 and ADARB2 with longevity. Some SNPs in ADARB2 replicate consistently in the four populations and suggest a strong effect that is independent of the different genetic backgrounds and environments. To evaluate the functional association of these genes with lifespan, we demonstrate that inactivation of their orthologues adr-1 and adr-2 in C. elegans reduces median survival by 50%. We further demonstrate that inactivation of the argonaute gene, rde-1, a critical regulator of RNA interference, completely restores lifespan to normal levels in the context of adr-1 and adr-2 loss of function. CONCLUSIONS/SIGNIFICANCE: Our results suggest that RNA editors may be an important regulator of aging in humans and that, when evaluated in C. elegans, this pathway may interact with the RNA interference machinery to regulate lifespan.

Personality traits of centenarians' offspring.

OBJECTIVES: To determine whether the offspring of centenarians have personality characteristics that are distinct from the general population. DESIGN: Case-control. SETTING: Nationwide U.S. sample. PARTICIPANTS: Unrelated offspring of centenarians (n=246, mean age 75) were compared with published norms. MEASUREMENTS: Using the NEO-Five-Factor Inventory (NEO-FFI) questionnaire, measures of the personality traits neuroticism, extraversion, openness, agreeableness, and conscientiousness were obtained. T-scores and percentiles were calculated according to sex and used to interpret the results. RESULTS: Male and female offspring of centenarians scored in the low range of published norms for neuroticism and in the high range for extraversion. The women also scored comparatively high in agreeableness. Otherwise, both sexes scored within normal range for conscientiousness and openness, and the men scored within normal range for agreeableness. CONCLUSION: Specific personality traits may be important to the relative successful aging demonstrated by the offspring of centenarians. Similarities across four of the five domains between male and female offspring is noteworthy and may relate to their successful aging. Measures of personality are an important phenotype to include in studies that assess genetic and environmental influences of longevity and successful aging.

The brachial artery remodels to maintain local shear stress despite the presence of cardiovascular risk factors.

OBJECTIVE: Under physiological conditions, arteries remodel in response to changes in blood flow to maintain local shear stress. Risk factors and developing atherosclerosis may be associated with maladaptive remodeling that produces relatively large arteries with low levels of shear stress. Recent studies have shown that the brachial artery and other peripheral arteries are enlarged in patients with risk factors and cardiovascular disease, and we tested the hypothesis that this finding represents maladaptive remodeling. METHODS AND RESULTS: We measured brachial artery diameter and flow by ultrasound and calculated shear stress in a diverse cohort of 1583 subjects (age 53+/-17 years, 62% male, and 51% with coronary artery disease and/or peripheral arterial disease). In a stepwise linear regression model, age (P<0.001), gender (P<0.001), body mass index (P<0.001), hypertension (P=0.005), and hypercholesterolemia (P=0.02) were associated with larger brachial diameter. Older age was associated with lower shear stress (P<0.01), consistent with maladaptive remodeling. However, body mass index, hypertension, hypercholesterolemia, and prevalent atherosclerosis were associated with proportionate changes in blood flow and no difference in shear stress compared to reference groups, suggesting adaptive remodeling. CONCLUSIONS: These findings suggest that enlargement of the brachial artery in the setting of obesity, hypertension, hypercholesterolemia, and atherosclerosis reflects adaptive remodeling. The results provide further support for the concept that arterial remodeling is an important homeostatic response that is maintained despite the presence of risk factors and developing atherosclerosis.

Centenarian offspring: start healthier and stay healthier.

OBJECTIVES: To assess the relative incidence of age-related diseases in a group of centenarian offspring who have thus far been considered to be predisposed to "healthy" aging. DESIGN: Longitudinal study. SETTING: Nationwide sample. PARTICIPANTS: Four hundred forty centenarian offspring and 192 referent cohort subjects who met inclusion criteria of having initial and follow-up health questionnaire data available. Median age of both cohorts was 72 at the initial health questionnaire. MEASUREMENTS: Initial health questionnaires were collected from 1997 to 2006. Follow-up questionnaires were collected from 2004 to 2007. The mean period of follow-up was 3.5+/-1.7 years for the centenarian offspring and 3.9+/-2.2 years for the referent cohort. RESULTS: During the follow-up period, centenarian offspring had a 78% lower risk of myocardial infarction (P<.04), 83% lower risk of stroke (P<.004), and 86% lower risk of developing diabetes mellitus (P<.005) than the referent cohort. There were no significant differences in new onset of other age-related diseases. Additionally, centenarian offspring were 81% less likely to die (P<.01) than the referent cohort during the follow-up. CONCLUSION: These findings suggest that centenarian offspring retain some important cardiovascular advantages over time over similarly aged referent cohort subjects. These findings reinforce the notion that there may be physiological reasons that longevity runs in families and that centenarian offspring are more likely to age in better cardiovascular health and with a lower mortality than their peers.

Association of longer telomeres with better health in centenarians.

Prior animal model studies have demonstrated an association between telomere length and longevity. Our study examines telomere length in centenarians in good health versus poor health. Using DNA from blood lymphocytes, telomere length was measured by quantitative polymerase chain reaction in 38 sex- and age-matched centenarians (ages 97-108). "Healthy" centenarians (n = 19) with physical function in the independent range and the absence of hypertension, congestive heart failure, myocardial infarction, peripheral vascular disease, dementia, cancer, stroke, chronic obstructive pulmonary disease, and diabetes were compared to centenarians with physical function limitations and > or =2 of the above conditions (n = 19). Healthy centenarians had significantly longer telomeres than did unhealthy centenarians (p =.0475). Our study demonstrated that investigations of the association between telomere length and exceptional longevity must take into account the health status of the individuals. This raises the possibility that perhaps it is not exceptional longevity but one's function and health that may be associated with telomere length.

Disentangling the roles of disability and morbidity in survival to exceptional old age.

BACKGROUND: Although it is commonly held that survival to age 100 years entails markedly delaying or escaping age-related morbidities, nearly one-third of centenarians have age-related morbidities for 15 or more years. Yet, we have previously observed that many centenarians compress disability toward the end of their lives. Therefore, we hypothesize that for some centenarians, compression of disability rather than morbidity is a key feature for survival to old age. METHODS: This cross-sectional, nationwide study included 523 women and 216 men 97 years or older. The participants were stratified by sex and age at onset (age <85 years [termed survivors] and age >or=85 years [termed delayers]) of chronic obstructive pulmonary disease, dementia, diabetes, heart disease, hypertension, osteoporosis, Parkinson disease, and stroke. Dependent variables were the Barthel Activities of Daily Living Index (Barthel Index) and the Information-Memory-Concentration test of the Blessed Dementia Scale. RESULTS: Thirty-two percent of the participants were survivors. For men with hypertension and/or heart disease for 15 or more years, the median Barthel Index score was 90 (independence range, 80-100). For female survivors with hypertension, heart disease, and/or osteoporosis, the median Barthel Index score was 65 (minimal assistance range, 60-79). Generally, men had better function than women: 60% of male survivors had Barthel Index scores of 90 or higher compared with 18% of female survivors (P < .001) and 50% of male delayers had Barthel Index scores of 90 or higher compared with 27% of females delayers (P < .001). CONCLUSIONS: Whereas the compression of both morbidity and disability are essential features of survival to old age for some centenarians, for others, the compression of disability alone may be the key prerequisite. Though far fewer in number, male centenarians tend to have significantly better cognition and physical function than their female counterparts.

Characteristics of Framingham offspring participants with long-lived parents.

BACKGROUND: Prior research has suggested that delay or avoidance of cardiovascular disease and cardiovascular disease risk factors plays an important role in longevity. METHODS: We studied 1697 Framingham Heart Study (FHS) offspring members 30 years or older, whose parents (1) participated in the original FHS cohort and (2) achieved age 85 years or died before January 1, 2005. Offspring participants (mean +/- SD age, 40 +/- 7 years; 51% women) were grouped according to whether neither (n = 705), one (n = 804), or both parents (n = 188) survived to 85 years or older. We examined offspring risk factors at examination cycle 1 (1971-1975) including age, sex, education, cigarette smoking, systolic and diastolic blood pressures, total-high-density lipoprotein cholesterol ratio, body mass index, and Framingham Risk Score. Participants returning for examination cycle 3 (1983-1987; n = 1319) were eligible for inclusion in longitudinal analyses evaluating risk factor progression from baseline to a higher follow-up risk category. RESULTS: For all factors studied, except body mass index, we observed statistically significant linear trends for lower offspring examination 1 risk factor levels with increasing parental survival category. The mean Framingham Risk Score was most favorable in offspring with both parents surviving to 85 years or older and was progressively worse in those with one or no long-lived parent (0.55, 1.08, and 1.71, respectively; P value for trend, <.001). Longitudinally, offspring of parents who lived longer had lower risk of blood pressure and Framingham Risk Score progression. CONCLUSIONS: Our findings suggest that individuals with long-lived parents have advantageous cardiovascular risk profiles in middle age compared with those whose parents died younger. The risk factor advantage persists over time.

Serum heat shock protein 70 level as a biomarker of exceptional longevity.

Heat shock proteins are highly conserved proteins that, when produced intracellularly, protect stress exposed cells. In contrast, extracellular heat shock protein 70 (Hsp70) has been shown to have both protective and deleterious effects. In this study, we assessed heat shock protein 70 for its potential role in human longevity. Because of the importance of HSP to disease processes, cellular protection, and inflammation, we hypothesized that: (1) Hsp70 levels in centenarians and centenarian offspring are different from controls and (2) alleles in genes associated with Hsp70 explain these differences. In this cross-sectional study, we assessed serum Hsp70 levels from participants enrolled in either the New England Centenarian Study (NECS) or the Longevity Genes Project (LGP): 87 centenarians (from LGP), 93 centenarian offspring (from NECS), and 126 controls (43 from NECS, 83 from LGP). We also examined genotypic and allelic frequencies of polymorphisms in HSP70-A1A and HSP70-A1B in 347 centenarians (266 from the NECS, 81 from the LGP), 260 NECS centenarian offspring, and 238 controls (NECS: 53 spousal controls and 106 septuagenarian offspring controls; LGP: 79 spousal controls). The adjusted mean serum Hsp70 levels (ng/mL) for the NECS centenarian offspring, LGP centenarians, LGP spousal controls, and NECS controls were 1.05, 1.13, 3.07, 6.93, respectively, suggesting that a low serum Hsp70 level is associated with longevity; however, no genetic associations were found with two SNPs within two hsp70 genes.

Characteristics of 32 supercentenarians.

OBJECTIVES: To report phenotypic characteristics of 32 age-validated supercentenarians. DESIGN: Case series. SETTING: U.S.-based recruitment effort. PARTICIPANTS: Thirty-two supercentenarians. MEASUREMENTS: Multiple forms of proof were used to validate age claims. Sociodemographic, activities of daily living, and medical history data were collected. RESULTS: Age range was 110 to 119. Fifty-nine percent had Barthel Index scores in the partially to totally dependent range, whereas 41% required minimal assistance or were independent. Few subjects had a history of clinically evident vascular-related diseases, including myocardial infarction (n=2, 6%) and stroke (n=4, 13%). Twenty-two percent (n=7) were taking medications for hypertension. Twenty-five percent (n=8) had a history of cancer (all cured). Diabetes mellitus (n=1, 3%) and Parkinson's disease (n=1, 3%) were rare. Osteoporosis (n=14, 44%) and cataract history (n=28, 88%) were common. CONCLUSION: Data collected thus far suggest that supercentenarians markedly delay and even escape clinical expression of vascular disease toward the end of their exceptionally long lives. A surprisingly substantial proportion of these individuals were still functionally independent or required minimal assistance.

Cardiovascular risk factors predictive for survival and morbidity-free survival in the oldest-old Framingham Heart Study participants.

OBJECTIVES: To examine whether midlife cardiovascular risk factors predict survival and survival free of major comorbidities to the age of 85. DESIGN: Prospective community-based cohort study. SETTING: Framingham Heart Study, Massachusetts. PARTICIPANTS: Two thousand five hundred thirty-one individuals (1,422 women) who attended at least two examinations between the ages of 40 and 50. MEASUREMENTS: Risk factors were classified at routine examinations performed between the ages of 40 and 50. Stepwise sex-adjusted logistic regression models predicting the outcomes of survival and survival free of morbidity to age 85 were selected from the following risk factors: systolic and diastolic blood pressure, total serum cholesterol, glucose intolerance, cigarette smoking, education, body mass index, physical activity index, pulse pressure, antihypertensive medication, and electrocardiographic left ventricular hypertrophy. RESULTS: More than one-third of the study sample survived to age 85, and 22% of the original study sample survived free of morbidity. Lower midlife blood pressure and total cholesterol levels, absence of glucose intolerance, nonsmoking status, higher educational attainment, and female sex predicted overall and morbidity-free survival. The predicted probability of survival to age 85 fell in the presence of accumulating risk factors: 37% for men with no risk factors to 2% with all five risk factors and 65% for women with no risk factors to 14% with all five risk factors. CONCLUSION: Lower levels of key cardiovascular risk factors in middle age predicted overall survival and major morbidity-free survival to age 85. Recognizing and modifying these factors may delay, if not prevent, age-related morbidity and mortality.

Cancer in the oldest old.

Our previous work revealed that 88% of centenarians delay or escape the age-related lethal diseases cardiac disease, stroke and diabetes. In the cases of those having a history of cancer we have observed anecdotes of centenarians presenting with large primary tumors that would have otherwise been expected to have metastasized and to have been lethal. However, these tumors were removed without consequence. To better understand the relationship between cancer and exceptional longevity, we quantified age of cancer diagnoses, life-time clinically evident cancer prevalence, tobacco use and family histories through medical record review and interviews. One thousand one hundred and forty-three subjects were studied revealing 20% (N=152) of female and 22% (N=80) of male centenarians with a history of non-skin cancer. The most common cancers were prostate (11.7% of males), breast (8.2% of females), and colon (5.7%). The average age of diagnosis was 80.5 years compared to 63.2 years in the general population according to National Cancer Institute SEER data. Similar delays were noted when age of onset was examined according to specific type of cancer. In conclusion, the age of diagnosis of cancer is relatively delayed in those who live to 100 years. Some cancers are very rare among these individuals suggesting that there are certain cancers that may be incompatible with survival to extreme old age.

Lower all-cause, cardiovascular, and cancer mortality in centenarians' offspring.

OBJECTIVES: To assess the cause of death for centenarians' offspring and controls. DESIGN: Cross-sectional study. SETTING: Community-based, nationwide sample. PARTICIPANTS: Family pedigree information was collected on 295 offspring of centenarians (from 106 families with a parent already enrolled in the nationwide New England Centenarian Study) and on 276 controls (from 82 control families) from 1997 to 2000. Controls were individuals whose parents were born in the same year as the centenarians but at least one of whom died at the average life expectancy. MEASUREMENTS: Age at death and cause of death. RESULTS: Centenarians' offspring had a 62% lower risk of all-cause mortality (P<.001), a 71% lower risk of cancer-specific mortality (P=.002), and an 85% lower risk of coronary heart disease-specific mortality (P<.001). Significant differences were not found for other causes of death. However of those who died centenarian offsprings dead at a significantly younger age than controls. CONCLUSION: These findings suggest that centenarians' offspring have lower all-cause mortality rates and cause-specific mortality rates for cancer and coronary heart disease. These results suggest that mechanisms for survival to exceptional old age may go beyond the avoidance or delay of cardiovascular disease and also include the avoidance or delay of cancer. Moreover survival advantage of centenarian offsprings may not be due to factors related to childhood mortality. Ultimately, survival to exceptional old age may involve lower susceptibility to a broad range of age-related diseases, perhaps secondary to inhibition of basic mechanisms of aging.

Cardiovascular disease delay in centenarian offspring: role of heat shock proteins.

Cardiovascular disease is a major cause of morbidity and mortality of older Americans. We have demonstrated recently that centenarian offspring, when compared with age-matched controls, avoid and/or delay cardiovascular disease and cardiovascular risk factors. Given recent evidence suggesting that higher circulating levels of HSP70 predict the future development of cardiovascular disease in established hypertensives and a recent study demonstrating a decrease in HSP60 and HSP70 with advancing age, we hypothesized that HSP70 levels would be lower in centenarian offspring compared with controls. The circulating serum concentration of HSP70 in 20 centenarian offspring and 9 spousal controls was analyzed using a modified HSP70 ELISA method. Centenarian offspring showed approximately 10-fold lower levels of circulating serum HSP70 compared with spousal controls (P <.001). The exact biological significance of the extremely low levels of circulating serum HSP70 observed in centenarian offspring thus far is not clear. However, circulating HSP has been shown to correlate in diseases or disorders in which there is destruction or damage to target tissues or organs, including cardiovascular diseases and numerous autoimmune disorders. We hypothesize that low levels of circulating serum HSP70 may be an indicator of a healthy state and point to longevity of the host; therefore, our results suggest that levels of circulating serum HSP70 may be a marker for longevity.

Cardiovascular disease delay in centenarian offspring.

BACKGROUND: Previously, the authors have shown that an important component of the ability to survive to exceptionally old age is family health history. This study assessed the age at onset of age-related diseases in centenarian offspring. METHODS: The health histories of 177 offspring of centenarians enrolled in the nationwide New England Centenarian Study, and 166 controls were assessed from 1997 to 2000. Controls were the offspring of parents born in the same years as the centenarians but at least one of whom died at average life expectancy. Ages at onset of heart disease, hypertension, diabetes, cancer, osteoporosis, cataracts, glaucoma, macular degeneration, depression, thyroid disease, and stroke were compared in the two groups. RESULTS: The median ages of onset for coronary heart disease (p <.001), hypertension (p <.001), diabetes (p =.002), and stroke (p =.017) were significantly delayed in the centenarian offspring by 5.0, 2.0, 8.5, and 8.5 years, respectively, compared with the age-matched controls. Adjusted hazard ratios were 0.388 (p =.0004), 0.39 (p <.0001), 0.302 (p =.008), and 0.328 (p =.06). No differences were found in the ages of onset for the other diseases investigated. CONCLUSIONS: The offspring of centenarians show a marked delay in the age of onset for cardiovascular disease, diabetes, hypertension, and stroke but not for other age-related diseases such as cancer, osteoporosis, and thyroid disease. These results suggest that the children of centenarians may be following in their parents' footsteps, markedly delaying the onset of lethal diseases that commonly affect older persons.