National Institutes of Health Advancing Multimorbidity Research.

BACKGROUND: Multimorbidity, the co-occurrence of 2 or more chronic diseases, is more common than having a single chronic disease, especially among persons age 65 years and older. The routine measurement of multimorbidity can facilitate a better understanding of potential causes and interactions and promote more effective treatment and improved outcomes. OBJECTIVES: To present a multimorbidity research framework and identify gaps in the research literature related to multimorbidity. DESIGN: In preparation for an expert panel workshop convened in September 2018, planning committee members reviewed the literature and developed a guiding framework that informed the selection of topics and speakers. RESULTS: The framework, grounded in a patient-centered approach, incorporates the concept of concordant and discordant comorbidity, and includes potential causes, interactions, and outcomes. This work informed workshop presentations and discussion related to identifying and selecting the best available multimorbidity instruments and determining future research needs. CONCLUSIONS: Multimorbidity research can be advanced by addressing gaps in study design and target populations, and by increasing attention to universal outcome measurement.

Understanding the context of health for persons with multiple chronic conditions: moving from what is the matter to what matters.

PURPOSE: An isolated focus on 1 disease at a time is insufficient to generate the scientific evidence needed to improve the health of persons living with more than 1 chronic condition. This article explores how to bring context into research efforts to improve the health of persons living with multiple chronic conditions (MCC). METHODS: Forty-five experts, including persons with MCC, family and friend caregivers, researchers, policy makers, funders, and clinicians met to critically consider 4 aspects of incorporating context into research on MCC: key contextual factors, needed research, essential research methods for understanding important contextual factors, and necessary partnerships for catalyzing collaborative action in conducting and applying research. RESULTS: Key contextual factors involve complementary perspectives across multiple levels: public policy, community, health care systems, family, and person, as well as the cellular and molecular levels where most research currently is focused. Needed research involves moving from a disease focus toward a person-driven, goal-directed research agenda. Relevant research methods are participatory, flexible, multilevel, quantitative and qualitative, conducive to longitudinal dynamic measurement from diverse data sources, sufficiently detailed to consider what works for whom in which situation, and generative of ongoing communities of learning, living and practice. Important partnerships for collaborative action include cooperation among members of the research enterprise, health care providers, community-based support, persons with MCC and their family and friend caregivers, policy makers, and payers, including government, public health, philanthropic organizations, and the business community. CONCLUSION: Consistent attention to contextual factors is needed to enhance health research for persons with MCC. Rigorous, integrated, participatory, multimethod approaches to generate new knowledge and diverse partnerships can be used to increase the relevance of research to make health care more sustainable, safe, equitable and effective, to reduce suffering, and to improve quality of life.

Multimorbidity in older adults.

Multimorbidity, the coexistence of 2 or more chronic conditions, has become prevalent among older adults as mortality rates have declined and the population has aged. We examined population-based administrative claims data indicating specific health service delivery to nearly 31 million Medicare fee-for-service beneficiaries for 15 prevalent chronic conditions. A total of 67% had multimorbidity, which increased with age, from 50% for persons under age 65 years to 62% for those aged 65-74 years and 81.5% for those aged ≥85 years. A systematic review identified 16 other prevalence studies conducted in community samples that included older adults, with median prevalence of 63% and a mode of 67%. Prevalence differences between studies are probably due to methodological biases; no studies were comparable. Key methodological issues arise from elements of the case definition, including type and number of chronic conditions included, ascertainment methods, and source population. Standardized methods for measuring multimorbidity are needed to enable public health surveillance and prevention. Multimorbidity is associated with elevated risk of death, disability, poor functional status, poor quality of life, and adverse drug events. Additional research is needed to develop an understanding of causal pathways and to further develop and test potential clinical and population interventions targeting multimorbidity.

Emerging approaches to multiple chronic condition assessment.

Older adults experience a higher prevalence of multiple chronic conditions (MCCs). Establishing the presence and pattern of MCCs in individuals or populations is important for healthcare delivery, research, and policy. This report describes four emerging approaches and discusses their potential applications for enhancing assessment, treatment, and policy for the aging population. The National Institutes of Health convened a 2-day panel workshop of experts in 2018. Four emerging models were identified by the panel, including classification and regression tree (CART), qualifying comorbidity sets (QCS), the multimorbidity index (MMI), and the application of omics to network medicine. Future research into models of multiple chronic condition assessment may improve understanding of the epidemiology, diagnosis, and treatment of older persons.

NAMS 2021 Utian Translational Science SymposiumSeptember 2021, Washington, DCCharting the path to health in midlife and beyond: the biology and practice of wellness.

ABSTRACT: Charting the Path to Health in Midlife and Beyond: The Biology and Practice of Wellness was a Translational Science Symposium held on Tuesday, September 21, 2021. Foundational psychosocial and behavioral approaches to promote healthy aging and strategies to disseminate this information were discussed. The following synopsis documents the conversation, describes the state of the science, and outlines a path forward for clinical practice. Wellness, in its broadest sense, prioritizes an orientation toward health, and an embrace of behaviors that will promote it. It involves a journey to improve and maintain physical and mental health and overall well-being to fully engage and live one's best life. It is more about recognizing and optimizing what one can do than what one cannot do and emphasizes the individual's agency over changing what they are able to change. Wellness is therefore not a passive state but rather an active goal to be sought continually. When viewed in this fashion, wellness is accessible to all. The conference addressed multiple aspects of wellness and embraced this philosophy throughout.

Cardiovascular Biomarkers and Imaging in Older Adults: JACC Council Perspectives.

Whereas the burgeoning population of older adults is intrinsically vulnerable to cardiovascular disease, the utility of many management precepts that were validated in younger adults is often unclear. Whereas biomarker- and imaging-based tests are a major part of cardiovascular disease care, basic assumptions about their use and efficacy cannot be simply extrapolated to many older adults. Biology, physiology, and body composition change with aging, with important influences on cardiovascular disease testing procedures and their interpretation. Furthermore, clinical priorities of older adults are more heterogeneous, potentially undercutting the utility of testing data that are collected. The American College of Cardiology and the National Institutes on Aging, in collaboration with the American Geriatrics Society, convened, at the American College of Cardiology Heart House, a 2-day multidisciplinary workshop, "Diagnostic Testing in Older Adults with Cardiovascular Disease," to address these issues. This review summarizes key concepts, clinical limitations, and important opportunities for research.

Accelerating the Search for Interventions Aimed at Expanding the Health Span in Humans: The Role of Epidemiology.

BACKGROUND: Extensive work in basic and clinical science suggests that biological mechanisms of aging are causally related to the development of disease and disability in late life. Modulation of the biological mechanisms of aging can extend both life span and health span in animal models, but translation to humans has been slow. METHODS: Summary of workshop proceedings from the 2018-2019 Epidemiology of Aging Workshop hosted by the Intramural Research Program at the National Institute on Aging. RESULTS: Epidemiologic studies play a vital role to progress in this field, particularly in evaluating new risk factors and measures of biologic aging that may influence health span, as well as developing relevant outcome measures that are robust and relevant for older individuals. CONCLUSIONS: Appropriately designed epidemiological studies are needed to identify targets for intervention and to inform study design and sample size estimates for future clinical trials designed to promote health span.

Prioritized Research for the Prevention, Treatment, and Reversal of Chronic Disease: Recommendations From the Lifestyle Medicine Research Summit.

Declining life expectancy and increasing all-cause mortality in the United States have been associated with unhealthy behaviors, socioecological factors, and preventable disease. A growing body of basic science, clinical research, and population health evidence points to the benefits of healthy behaviors, environments and policies to maintain health and prevent, treat, and reverse the root causes of common chronic diseases. Similarly, innovations in research methodologies, standards of evidence, emergence of unique study cohorts, and breakthroughs in data analytics and modeling create new possibilities for producing biomedical knowledge and clinical translation. To understand these advances and inform future directions research, The Lifestyle Medicine Research Summit was convened at the University of Pittsburgh on December 4-5, 2019. The Summit's goal was to review current status and define research priorities in the six core areas of lifestyle medicine: plant-predominant nutrition, physical activity, sleep, stress, addictive behaviors, and positive psychology/social connection. Forty invited subject matter experts (1) reviewed existing knowledge and gaps relating lifestyle behaviors to common chronic diseases, such as cardiovascular disease, diabetes, many cancers, inflammatory- and immune-related disorders and other conditions; and (2) discussed the potential for applying cutting-edge molecular, cellular, epigenetic and emerging science knowledge and computational methodologies, research designs, and study cohorts to accelerate clinical applications across all six domains of lifestyle medicine. Notably, federal health agencies, such as the Department of Defense and Veterans Administration have begun to adopt "whole-person health and performance" models that address these lifestyle and environmental root causes of chronic disease and associated morbidity, mortality, and cost. Recommendations strongly support leveraging emerging research methodologies, systems biology, and computational modeling in order to accelerate effective clinical and population solutions to improve health and reduce societal costs. New and alternative hierarchies of evidence are also be needed in order to assess the quality of evidence and develop evidence-based guidelines on lifestyle medicine. Children and underserved populations were identified as prioritized groups to study. The COVID-19 pandemic, which disproportionately impacts people with chronic diseases that are amenable to effective lifestyle medicine interventions, makes the Summit's findings and recommendations for future research particularly timely and relevant.

Advancing Nutrition Education, Training, and Research for Medical Students, Residents, Fellows, Attending Physicians, and Other Clinicians: Building Competencies and Interdisciplinary Coordination.

Nutrition plays an important role in health promotion and disease prevention and treatment across the lifespan. Physicians and other healthcare professionals are expected to counsel patients about nutrition, but recent surveys report minimal to no improvements in medical nutrition education in US medical schools. A workshop sponsored by the National Heart, Lung, and Blood Institute addressed this gap in knowledge by convening experts in clinical and academic health professional schools. Representatives from the National Board of Medical Examiners, the Accreditation Council for Graduate Medical Education, the Liaison Committee on Medical Education, and the American Society for Nutrition provided relevant presentations. Reported is an overview of lessons learned from nutrition education efforts in medical schools and health professional schools including interprofessional domains and competency-based nutrition education. Proposed is a framework for coordinating activities of various entities using a public-private partnership platform. Recommendations for nutrition research and accreditation are provided.

Preventing tomorrow's sudden cardiac death today: dissemination of effective therapies for sudden cardiac death prevention.

Because the burden of sudden cardiac death (SCD) is substantial, it is important to use all guideline-driven therapies to prevent SCD. Among those therapies is the implantable cardioverter defibrillator (ICD). When indicated, ICD use is beneficial and cost-effective. Unfortunately, studies suggest that most patients who have indications for this therapy for primary or secondary prevention of SCD are not receiving it. To explore potential reasons for this underuse and to propose potential facilitators for ICD dissemination, the Duke Center for the Prevention of SCD at the Duke Clinical Research Institute (Durham, NC) organized a think tank meeting of experts on this issue. The meeting took place on December 12 and 13, 2007, and it included representatives of clinical cardiology, cardiac electrophysiology, general internal medicine, economics, health policy, the US Food and Drug Administration, the Centers for Medicare and Medicaid Services, the Agency for Health care Research and Quality, and the device and pharmaceutical industry. Although the meeting was funded by industry participants, this article summarizing the presentations and discussions that occurred at the meeting presents the expert opinion of the authors.

Rationale and design of the Home Automatic External Defibrillator Trial (HAT).

Most cardiac arrests occur in the home, where emergency medical services (EMS) systems are challenged to provide timely care. Because a large proportion of sudden cardiac arrests (SCAs) are due to ventricular tachycardia or ventricular fibrillation, home use of an automated external defibrillator (AED) might offer an opportunity to decrease mortality in those at risk. Predicting who will have a cardiac arrest in the general population is difficult. Individuals at high risk are usually easily identified and may become candidates for implantable cardioverter defibrillators. It is within the population at lower risk where home AEDs may be most useful. The purpose of the Home Automatic External Defibrillator Trial (HAT) is to test whether providing home access to an AED can improve survival in patients at modest risk of SCA, such as those surviving an anterior myocardial infarction but in whom implantable cardioverter defibrillator therapy is not deemed necessary. Between January 23, 2003, and October 20, 2005, 7001 patients were enrolled, with completion of follow-up scheduled for September 30, 2007. Randomization was conducted in a 1:1 fashion between control therapy, comprising the standard lay response to SCA (calling the EMS and performing cardiopulmonary resuscitation), and the use of an AED first, followed by calling the EMS and performing cardiopulmonary resuscitation. The primary end point is all-cause mortality. Secondary outcomes include survival from SCA (witnessed and unwitnessed, in home and out of home), incremental cost-effectiveness, and quality of life measures for both the patient and the spouse/companion. The results of the trial should be available in mid 2008.

Multimorbidity in Older Adults With Cardiovascular Disease.

Multimorbidity occurs in adults of all ages, but the number and complexity of comorbid conditions commonly increase with advancing age such that cardiovascular disease (CVD) in older adults typically occurs in a context of multimorbidity. Current clinical practice and research mainly target single disease-specific care that does not embrace the complexities imposed by concurrent conditions. In this paper, emerging concepts regarding CVD in combination with multimorbidity are reviewed, including recommendations for incorporating multimorbidity into clinical decision making, critical knowledge gaps, and research priorities to optimize care of complex older patients.

Future Research Directions for Multimorbidity Involving Cardiovascular Diseases.

Multimorbidity, defined as the co-occurrence of two or more chronic conditions, increases with age and may be found in approximately two-thirds of older adults in population studies, commonly including a variety of cardiovascular risk factors and chronic diseases. This article offers a research agenda for cardiovascular disease from a patient-centered multimorbidity perspective. Definitional issues remain for multimorbidity, along with high interest in understanding the inter-relationships between aging, diseases, treatments, and organ dysfunction in the development and progression of multimorbidity. Clinical trials, practice-based and population-based observational studies, and linkages of big data can play a role in improving health outcomes among persons with multimorbidity.

Aging and Multimorbidity: New Tasks, Priorities, and Frontiers for Integrated Gerontological and Clinical Research.

Aging is characterized by rising susceptibility to development of multiple chronic diseases and, therefore, represents the major risk factor for multimorbidity. From a gerontological perspective, the progressive accumulation of multiple diseases, which significantly accelerates at older ages, is a milestone for progressive loss of resilience and age-related multisystem homeostatic dysregulation. Because it is most likely that the same mechanisms that drive aging also drive multiple age-related chronic diseases, addressing those mechanisms may reduce the development of multimorbidity. According to this vision, studying multimorbidity may help to understand the biology of aging and, at the same time, understanding the underpinnings of aging may help to develop strategies to prevent or delay the burden of multimorbidity. As a consequence, we believe that it is time to build connections and dialogue between the clinical experience of general practitioners and geriatricians and the scientists who study aging, so as to stimulate innovative research projects to improve the management and the treatment of older patients with multiple morbidities.

Microalbuminuria in the US population: third National Health and Nutrition Examination Survey.

Microalbuminuria (MA) is associated with adverse health outcomes in diabetic and hypertensive adults. The prevalence and clinical significance of MA in nondiabetic populations is less clear. The purpose of this study was to generate national estimates of the prevalence of MA in the US population. Untimed urinary albumin concentrations (UACs) and creatinine concentrations were evaluated in a nationally representative sample of 22,244 participants aged 6 years and older. Persons with hematuria and menstruating or pregnant women were excluded from analysis. The percent prevalence of clinical proteinuria (UAC > or = 300 mg/L) was similar for males and females. However, the prevalence of MA (urinary albumin-creatinine ratio [ACR], 30 to 299 mg/g) was significantly lower in males (6.1%) compared with females (9.7%). MA prevalence was greater in children than young adults and increased continuously starting at 40 years of age. MA prevalence was greater in non-Hispanic blacks and Mexican Americans aged 40 to 79 years compared with similar-aged non-Hispanic whites. MA prevalence was 28.8% in persons with previously diagnosed diabetes, 16.0% in those with hypertension, and 5.1% in those without diabetes, hypertension, cardiovascular disease, or elevated serum creatinine levels. In adults aged 40+ years, after excluding persons with clinical proteinuria, albuminuria (defined as ACR > or = 30 mg/g) was independently associated with older age, non-Hispanic black and Mexican American ethnicity, diabetes, hypertension, and elevated serum creatinine concentration. MA is common, even among persons without diabetes or hypertension. Age, sex, race/ethnicity, and concomitant disease contribute to the variability of MA prevalence estimates.

Development of case definitions for acute encephalopathy, encephalitis, and multiple sclerosis reports to the vaccine: Adverse Event Reporting System.

The Vaccine Adverse Event Reporting System (VAERS), administered by the FDA and CDC, is the U.S. system for surveillance of vaccine adverse events (AE). Acute encephalopathy age <18 months (EO < 18), age > or =18 months (EO > or = 18), encephalitis (EI), and multiple sclerosis (MS) after vaccination have been reported to VAERS, but reports often contain insufficient information to validate diagnoses. Standardized case definitions would enhance the utility of VAERS reports for AE surveillance. We developed practical case definitions for classification of VAERS reports, and three neurologists independently applied the definitions to reports submitted in 1993. Inter-observer agreement was assessed, and non-concordant classifications were reviewed in a follow-up conference call. Reports of EO < 18 (n = 8), EO > or = 18 (n = 20), EI (n = 15), and MS (n = 16) were classified as "definite" in 7% to 30% of the cases, while 26% to 51% of reports were thought to have insufficient information to make a classification. Agreement among reviewers was good to excellent, (kappa: 0.65 to 0.85) except for EO < 18 m for which it was marginal (kappa: 0.37). It is possible to develop reproducible case definitions for acute encephalopathy, encephalitis, and multiple sclerosis using a standardized approach. Application of standardized case definitions to VAERS reports documents the limited information in many reports, specifies data for supplemental collection, and indicates that VAERS reports should be cautiously interpreted. Development and application of case definitions for other adverse events reported after vaccination should enhance the value of vaccine safety databases. Published by Elsevier Science Inc.

Pediatric deaths reported after vaccination: the utility of information obtained from parents.

BACKGROUND: The federally administered Vaccine Adverse Event Reporting System (VAERS) is a passive reporting system that receives domestic and foreign reports of adverse events that occur following immunization. This investigation explored whether routinely interviewing parents for follow-up of VAERS pediatric deaths would provide additional information important to vaccine safety. METHODS: The study was designed to follow up 100 consecutive pediatric deaths reported to VAERS by interviewing a parent and a healthcare provider (HCP) for each case. Several strategies contributed to successful follow-up. A standardized questionnaire was utilized to interview HCPs and parents. Overall and specific group frequencies (HCPs and parents) were calculated for each variable. McNemar's statistical tests of exact inference were calculated to assess whether there were statistically significant differences between HCP and parent knowledge by case for various variables. RESULTS: The median age of the cases was 4 months. Approximately half of the deaths were attributed to sudden infant death syndrome. In many instances, the information was equivalent in quality. For certain variables, such as knowledge of the child's position when found in distress, more parents than HCPs indicated that they knew the answer. CONCLUSIONS: Conducting parental and HCP follow-up for pediatric deaths reported to VAERS was resource intensive. In some instances, parents were more likely than HCPs to provide information regarding some important variables about the nature of the death. None of the additional information obtained from parents, however, provided a signal or confirmation of a causal link between the vaccine and death.