American College of Lifestyle Medicine Expert Consensus Statement: Lifestyle Medicine for Optimal Outcomes in Primary Care.

OBJECTIVE: Identify areas of consensus on integrating lifestyle medicine (LM) into primary care to achieve optimal outcomes. METHODS: Experts in both LM and primary care followed an a priori protocol for developing consensus statements. Using an iterative, online process, panel members expressed levels of agreement with statements, resulting in classification as consensus, near consensus, or no consensus. RESULTS: The panel identified 124 candidate statements addressing: (1) Integration into Primary Care, (2) Delivery Models, (3) Provider Education, (4) Evidence-base for LM, (5) Vital Signs, (6) Treatment, (7) Resource Referral and Reimbursement, (8) Patient, Family, and Community Involvement; Shared Decision-Making, (9) Social Determinants of Health and Health Equity, and (10) Barriers to LM. After three iterations of an online Delphi survey, statement revisions, and removal of duplicative statements, 65 statements met criteria for consensus, 24 for near consensus, and 35 for no consensus. Consensus was reached on key topics that included LM being recognized as an essential component of primary care in patients of all ages, including LM as a foundational element of health professional education. CONCLUSION: The practice of LM in primary care can be strengthened by applying these statements to improve quality of care, inform policy, and identify areas for future research.

Lifestyle Medicine: Prevention, Treatment, and Reversal of Disease.

Lifestyle medicine (LM) expands the scope of preventive medicine by focusing on the promotion of healthy lifestyles while preventing, treating, and reversing the vast majority of chronic diseases caused by behaviors and environmental factors. LM focuses on six pillars-a plant-predominant eating pattern; physical movement; restorative sleep; management of stress; avoidance of risky substances; and positive social connections. Advances in LM competencies, education, certification, resources, and practice models are accelerating with a particular need and focus on underserved and most seriously impacted patients and communities. A comprehensive and integrated strategy addressing "whole person health" is emerging as a compelling framework for providers and health systems which combines a foundational commitment to prevention with a systematic approach to the actual and root causes of premature disease, disability, and death.

A Career Life-Cycle Perspective on Women's Health and Safety: Insights From the Defense Health Board Report on Military Women's Health.

OBJECTIVE: Women's health has demanded more attention from employers as women integrated into the workforce. Traditionally male-dominant fields and occupations require special attention to workplace design, physical standards for entry, employment practices, equipment, and health monitoring. This editorial summarizes the Defense Health Board's (DHB) review of Active Duty Women's Health and its recommendations grounded in a woman's career life-cycle. METHODS: The DHB reviewed the Department of Defense and foreign militaries' current women's health services, relevant policies and practices, peer-reviewed scientific literature, and subject matter expert interviews. RESULTS: The DHB's recommendations centered on a comprehensive approach to education, health care access and treatment, professional workforce development, workplace standards and equipment, and accountable outcomes metrics to guide improvement. CONCLUSIONS: Employers can learn how to reduce morbidity, leading to a healthier and more productive female workforce.

Mobilizing the U.S. Military's TRICARE Program for Value-Based Care: A Report From the Defense Health Board.

The U.S. Military Health System spends about $50 billion annually to provide care to 9.6 million active duty service members, retirees, and their families through its TRICARE health plans. TRICARE follows the predominant payment model in the USA-fee-for-service-although the Department of Defense (DoD) and Congress encourage and mandate a move toward alternative payment models-mainly, fee-for-value. For the next TRICARE contracts which will begin in 2023, the DoD asked its health-focused federal advisory committee, the Defense Health Board (DHB), to recommend how best to assess and prioritize leading value-based healthcare initiatives identified from private, public, and employer-based health plans. The November 2020 report, 'Modernization of the TRICARE Benefit', specifies a rubric to evaluate these value-based care initiatives not only in traditional measures of effectiveness but also in terms of the Defense Health Agency's Quadruple Aim with its focus on readiness. The goal of TRICARE's move toward value-based care is to leverage its size and focus on prevention of disease and injury to maintain the readiness of the U.S. Armed Forces in addition to delivering great outcomes and value to the DoD's nearly 10 million beneficiaries. The DHB emphasizes that TRICARE's size and focus on providing quality care at lower cost will incentivize providers to participate in the shift toward value-based care despite the potential challenges in transitioning to this system. This shift also aims to motivate other large government and private payors to accelerate the adoption of value-based care through TRICARE's example.

Cardiac Myeloid Sarcoma: A 1-kg Heart.

A 53-year-old man with a background of acute myelomonocytic leukemia in remission presented with pleurisy. Repeat transthoracic echocardiography over several weeks revealed thickening left ventricular walls and decreasing systolic function. He died of decompensated heart failure due to cardiac myeloid sarcoma, with autopsy revealing an enlarged heart weighing >1 kg. (Level of Difficulty: Intermediate.).

Organelle tethering, pore formation and SNARE compensation in the late endocytic pathway.

To provide insights into the kiss-and-run and full fusion events resulting in endocytic delivery to lysosomes, we investigated conditions causing increased tethering and pore formation between late endocytic organelles in HeLa cells. Knockout of the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) VAMP7 and VAMP8 showed, by electron microscopy, the accumulation of tethered lysosome-associated membrane protein (LAMP)-carrier vesicles around multivesicular bodies, as well as the appearance of 'hourglass' profiles of late endocytic organelles attached by filamentous tethers, but did not prevent endocytic delivery to lysosomal hydrolases. Subsequent depletion of the SNARE YKT6 reduced this delivery, consistent with it compensating for the absence of VAMP7 and VAMP8. We also investigated filamentous tethering between multivesicular bodies and enlarged endolysosomes following depletion of charged multi-vesicular body protein 6 (CHMP6), and provide the first evidence that pore formation commences at the edge of tether arrays, with pore expansion required for full membrane fusion.

Impact of Physician Referral to Health Coaching on Patient Engagement and Health Risks: An Observational Study of UPMC's Prescription for Wellness.

PURPOSE: Evaluate impact of physician referral to health coaching on patient engagement and health risk reduction. DESIGN: Four-year retrospective, observational cohort study with propensity-matched pair comparisons. SETTING: Integrated delivery and finance system in Pittsburgh, Pennsylvania. SAMPLE: 10 457 adult insured members referred to health coaching by their physician; 37 864 other members identified for health coaching through insurer-initiated outreach. INTERVENTION: Practice-based, technology-supported workflow and process for physician prescribing of health coaching during regular office visit, with follow-up on patient's progress and implementation supports. MEASURES: Patient engagement based on completion of pre-enrollment assessment, formal enrollment in health coaching, completion of required sessions, health risk levels, and number of health risks pre- and post-health coaching referral. ANALYSIS: Difference-in-difference analysis to assess change in health risk levels and number of health risks pre- and post-health coaching and probability weighting to control for potential confounding between groups. RESULTS: Members referred by a physician were significantly more likely to enroll in a health coaching program (21.0% vs 6.0%, P < .001) and complete the program requirements (8.5% vs 2.7%, P < .001) than when referred by insurer-initiated outreach; significant within group improvement in health risk levels from baseline (P < .001) was observed for both the groups. CONCLUSIONS: Patients are significantly more likely to engage in health coaching when a referral is made by a physician; engagement in health coaching significantly improves health risk levels.

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.

The impact of genetic counseling on patient engagement in a specialty cancer clinic.

The identification of patient outcomes unique to the field of genetic counseling has become a recent priority of the profession. Current health-care efforts have targeted patient engagement as an outcome capable of improving population health and reducing health-care costs. This study analyzed patient engagement levels among 182 participants who underwent genetic counseling for gastrointestinal (GI) cancer risk assessment in an outpatient specialty clinic. Patients seen at the UPMC Hereditary GI Tumor Program completed a validated patient engagement measure, the Altarum Consumer Engagement (ACE), prior to undergoing genetic counseling and again three months after enrollment. Paired t test analysis was conducted to assess the changes in Total ACE scores, and within the following three domains: Navigation, Informed Choice, and Commitment. In the sample of 182 participants, Total ACE scores increased after genetic counseling (by 5.7%; p < .0001), as did all three domains (Commitment p = .0008; Navigation p = .0008; and Informed Choice p = .0016). This study is the first known report of patient engagement levels in individuals undergoing genetic counseling in a specialty cancer clinic and suggests that genetic counseling improves patient engagement levels.

An Evaluation of Lifestyle Health Coaching Programs Using Trained Health Coaches and Evidence-Based Curricula at 6 Months Over 6 Years.

PURPOSE: Describe health plan member-level participation, completion, and 6-month outcomes for 5 lifestyle health coaching programs offered by an integrated delivery and financing system (IDFS) over 6 years. DESIGN: Case series study of 5 lifestyle programs with 180-day follow-up. SETTING: Large Western PA integrated delivery and financing system (IDFS) deployed multiple coaching modalities for diverse insurance-member enrolled population. PARTICIPANTS: A total of 14 591 health plan members choosing a lifestyle health coaching program. INTERVENTION: Evidence- and curriculum-based lifestyle health coaching programs delivered by 1 of 4 interactive modalities. MEASURES: A single metric was used as an overall indicator of clinical success for each program. Success measures include a ≥5% reduction of self-reported baseline weight, meeting physical activity guidelines, and 7-day point prevalence abstinence from tobacco. For stress and nutrition, where no single target measure exists, a metric was created that represented a net improvement across all key outcomes measured. ANALYSIS: The proportion of members meeting target outcomes were calculated and described across all time points and modalities. RESULTS: At 180 days, 77% of enrolled members reported reduced stress, 7% quit tobacco, 50.5% met physical activity guidelines, 65.2% improved nutrition, and 44.2% lost 5% or more of baseline weight. CONCLUSION: This evaluation describes the real-world effectiveness of evidence- and curriculum-based lifestyle improvement programs delivered by trained health coaches to a diverse health plan member population.

The Healthy Health Care Workplace: a Competitive Advantage.

PURPOSE OF REVIEW: This review provides an evidence-based approach to improve health, reduce excessive medical costs, and optimize productivity for health care employees and their families. What opportunities and challenges are unique or specific to health care organizations particularly as aligned with value and competitive advantage in achieving the Quadruple Aim? RECENT FINDINGS: An integrated approach to improving health and performance is essential. The strategy includes the employer "environment" (broadly defined), health and medical care behaviors, care delivery modalities, benefits alignment, and a supportive, total health and productivity integrated data analytic capability. Epigenetics and lifestyle medicine represent a promising direction in accelerating the prevention, treatment, and reversal of common chronic disease. An integrated health and productivity approach, emerging science, and practices can accelerate health care systems' goal to improve employee health and organizational competitiveness. Additional published examples of health care specific employer experience will further advance refinement of existing models and tailoring to the medical care setting.

UPMC Prescription for Wellness: A Quality Improvement Case Study for Supporting Patient Engagement and Health Behavior Change.

Addressing patient health and care behaviors that underlie much of chronic disease continues to challenge providers, medical practices, health systems, and insurers. Improving health and care as described by the Quadruple Aim requires innovation at the front lines of clinical care: the doctor-patient interaction and office practice. This article describes the use of Lean Six Sigma in a quality improvement (QI) effort to design an effective and scalable method for physicians to prescribe health coaching for healthy behaviors in a primary care medical home within a large integrated delivery and financing system. Building on the national Agency for Healthcare Research and Quality and Robert Wood Johnson Foundation-funded Prescription for Health multisite demonstration, this QI case study provides important lessons for transforming patient-physician-practice support systems to better address lifestyle and care management challenges critical to producing better outcomes.

A non-canonical ESCRT pathway, including histidine domain phosphotyrosine phosphatase (HD-PTP), is used for down-regulation of virally ubiquitinated MHC class I.

The Kaposi's sarcoma-associated herpes virus (KSHV) K3 viral gene product effectively down-regulates cell surface MHC class I. K3 is an E3 ubiquitin ligase that promotes Lys(63)-linked polyubiquitination of MHC class I, providing the signal for clathrin-mediated endocytosis. Endocytosis is followed by sorting into the intralumenal vesicles (ILVs) of multivesicular bodies (MVBs) and eventual delivery to lysosomes. The sorting of MHC class I into MVBs requires many individual proteins of the four endosomal sorting complexes required for transport (ESCRTs). In HeLa cells expressing the KSHV K3 ubiquitin ligase, the effect of RNAi-mediated depletion of individual proteins of the ESCRT-0 and ESCRT-I complexes and three ESCRT-III proteins showed that these are required to down-regulate MHC class I. However, depletion of proteins of the ESCRT-II complex or of the ESCRT-III protein, VPS20 (vacuolar protein sorting 20)/CHMP6 (charged MVB protein 6), failed to prevent the loss of MHC class I from the cell surface. Depletion of histidine domain phosphotyrosine phosphatase (HD-PTP) resulted in an increase in the cell surface concentration of MHC class I in HeLa cells expressing the KSHV K3 ubiquitin ligase. Rescue experiments with wild-type (WT) and mutant HD-PTP supported the conclusion that HD-PTP acts as an alternative to ESCRT-II and VPS20/CHMP6 as a link between the ESCRT-I and those ESCRT-III protein(s) necessary for ILV formation. Thus, the down-regulation of cell surface MHC class I, polyubiquitinated by the KSHV K3 ubiquitin ligase, does not employ the canonical ESCRT pathway, but instead utilizes an alternative pathway in which HD-PTP replaces ESCRT-II and VPS20/CHMP6.

UPMC MyHealth: managing the health and costs of U.S. healthcare workers.

BACKGROUND: Workplace wellness programs hold promise for managing the health and costs of the U.S. workforce. These programs have not been rigorously tested in healthcare worksites. PURPOSE: To evaluate the impact of MyHealth on the health and costs of UPMC healthcare workers. DESIGN: Five-year observational study conducted in 2013 with subgroup analyses and propensity-matched pair comparisons to more accurately interpret program effects. SETTING/PARTICIPANTS: UPMC, an integrated health care delivery and financing system headquartered in Pittsburgh, Pennsylvania. Participants included 13,627 UPMC employees who were continuously enrolled in UPMC-sponsored health insurance during the study period and demonstrated participation in MyHealth by completing a Health Risk Assessment in both 2007 and 2011, as well as 4,448 other healthcare workers employed outside of UPMC who did not participate in the program. INTERVENTION: A comprehensive wellness, prevention, and chronic disease management program that ties achievement of health and wellness requirements to receipt of an annual credit on participants' health insurance deductible. MAIN OUTCOME MEASURES: Health-risk levels, medical, pharmacy, and total healthcare costs, and Healthcare Effectiveness Data and Information Set performance rates for prevention and chronic disease management. RESULTS: Significant improvements in health-risk status and increases in use of preventive and chronic disease management services were observed in the intervention group. Although total healthcare costs increased significantly, reductions in costs were significant for those who moved from higher- to the lowest-risk levels. The contrast differences in costs between reduced- and maintained-risk groups was also significant. Matched pair comparisons provided further evidence of program effects on observed reductions in costs and improvements in prevention, but not improvements in chronic disease management. CONCLUSIONS: Incorporating incentivized health management strategies in employer-sponsored health insurance benefit designs can serve as a useful, though not sufficient, tool for managing the health and costs of the U.S. healthcare workforce.

Employer Health and Productivity Roadmap™ strategy.

The National Institute for Occupational Safety and Health Total Worker Health™ Program defines essential elements of an integrated health protection and health promotion model to improve the health, safety, and performance of employers and employees. The lack of a clear strategy to address the core drivers of poor health, excessive medical costs, and lost productivity has deterred a comprehensive, integrated, and proactive approach to meet these challenges. The Employer Health and Productivity Roadmap™, comprising six interrelated and integrated core elements, creates a framework of shared accountability for both employers and their health and productivity partners to implement and monitor actionable measures that improve health, maximize productivity, and reduce excessive costs. The strategy is most effective when linked to a financially incentivized health management program or consumer-directed health plan insurance benefit design.

Advancing aspirin utilization: a review of clinical and systems-based interventions.

Underuse of clinical preventive services (CPS) such as low-dose aspirin therapy leads to tens of thousands of preventable deaths per year. The authors examined the current literature related to delivery of CPS and then provided the results to a preventive medicine expert panel who identified best practices to improve aspirin counseling and use. An exploratory literature search was conducted in PubMed using keywords associated with preventive health interventions. The review included articles published between January 2000 and March 2009. More than 200 articles were identified for review, and 35 met inclusion criteria. Interventions that increased patient-provider contact and physician interactive educational programs were most likely to improve delivery of CPS. The expert panel recommended a prevention systems cascade of reinforcing strategies and tools to maximize appropriate aspirin use. This model emphasizes important interrelationships of clinical practice settings and how they affect aspirin use.

The delivery of endocytosed cargo to lysosomes.

In mammalian cells, endocytosed cargo that is internalized through clathrin-coated pits/vesicles passes through early endosomes and then to late endosomes, before delivery to lysosomes for degradation by proteases. Late endosomes are MVBs (multivesicular bodies) with ubiquitinated membrane proteins destined for lysosomal degradation being sorted into their luminal vesicles by the ESCRT (endosomal sorting complex required for transport) machinery. Cargo is delivered from late endosomes to lysosomes by kissing and direct fusion. These processes have been studied in live cell experiments and a cell-free system. Late endosome-lysosome fusion is preceded by tethering that probably requires mammalian orthologues of the yeast HOPS (homotypic fusion and vacuole protein sorting) complex. Heterotypic late endosome-lysosome membrane fusion is mediated by a trans-SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) complex comprising Syntaxin7, Vti1b, Syntaxin8 and VAMP7 (vesicle-associated membrane protein 7). This differs from the trans-SNARE complex required for homotypic late endosome fusion in which VAMP8 replaces VAMP7. VAMP7 is also required for lysosome fusion with the plasma membrane and its retrieval from the plasma membrane to lysosomes is mediated by its folded N-terminal longin domain. Co-ordinated interaction of the ESCRT, HOPS and SNARE complexes is required for cargo delivery to lysosomes.

ESCRT proteins and the regulation of endocytic delivery to lysosomes.

In mammalian cells, there is evidence of cargo specificity in the requirement for particular ESCRT (endosomal sorting complex required for transport) proteins to sort cargo into the luminal vesicles of MVBs (multivesicular bodies). We have focussed on studying the ESCRT requirements for delivery of MHC class I to lysosomes following polyubiquitination by the Kaposi's sarcoma-associated herpesvirus protein K3. Down-regulation of polyubiquitinated cell-surface MHC class I in HeLa cells stably expressing K3 is achieved via clathrin-mediated endocytosis, followed by sorting into the luminal vesicles of MVBs and eventual delivery to lysosomes. Depletion of ESCRT-I and some ESCRT-III components interferes with this sorting and allows recycling of MHC class I to the cell surface. Depletion of ESCRT-II components has no effect on K3-mediated down-regulation of MHC class I and no gross morphological effect on endocytic compartments. Thus virally polyubiquitinated MHC class I does not require all of the ESCRT proteins in order to be sorted into the luminal vesicles of MVBs. However, there may be a further requirement for ESCRT-III proteins to ensure the efficient fusion of MVBs with lysosomes.