Vital Directions For Health And Health Care: Priorities For 2021.

In 2016, in anticipation of the US presidential election and forthcoming new administration, the National Academy of Medicine launched a strategic initiative to marshal expert guidance on pressing health and health care priorities. Published as Vital Directions for Health and Health Care, the products of the initiative provide trusted, nonpartisan, evidence-based analysis of critical issues in health, health care, and biomedical science. The current collection of articles published in Health Affairs builds on the initial Vital Directions series by addressing a set of issues that have a particularly compelling need for attention from the next administration: health costs and financing, early childhood and maternal health, mental health and addiction, better health and health care for older adults, and infectious disease threats. The articles also reflect the current experience with both the coronavirus disease 2019 (COVID-19) pandemic and the health inequities that have been drawn out sharply by COVID-19, as well as the implications going forward for action.

Vital Directions for Health & Health Care: The North Carolina Experience.

In 2019, the National Academy of Medicine (NAM) turned to the all-important state level to draw insights on the status of health and health care within the context of the NAM Vital Directions for Health and Health Care initiative. The NAM held a two-day symposium in the Research Triangle to bring together various stakeholders to better understand actions that states and localities are taking to achieve-and the barriers they face in pursuing-more affordable, value-driven quality care and health outcomes. The NAM purposefully chose to pivot to the state level with North Carolina given that it has been at the forefront of health care transformation and illustrates the promise but also the challenges facing US health and health care nationally. A 19-member planning committee, cochaired by NAM President Victor Dzau and Secretary Mandy Cohen of the North Carolina Department of Health and Human Services, selected topics that resonate with the state's activities within the context of the Vital Directions framework, ranging from empowering people and connecting care through the integration of social, physical, and behavioral health to payer alignment though the advancement of new payment models (Figure 1). The priorities discussed during the symposium continue to be central to health reform in North Carolina and are further explored in the commentaries in this issue.

Safety, Efficacy, and Cost-Analysis of Percutaneous Endoscopic Gastrostomy and Ventriculoperitoneal Shunt Placement in a Simultaneous Surgery.

BACKGROUND: Limited historical data suggest that concomitant placement of both a ventriculoperitoneal (VP) shunt and percutaneous endoscopic gastrostomy (PEG) tube is associated with an increased risk of complications, including VP shunt infections. Here we compare the outcomes and cost difference between 2 groups of patients, one in which a VP shunt and PEG tube were placed in the same operation and the other in which separate operations were performed. METHODS: A total of 10 patients underwent simultaneous placement of a VP shunt and PEG tube. This group was compared with a group of 18 patients that underwent separate placements. Hospital billing charges were used to compare the total cost of the procedures in the 2 groups. RESULTS: Eight of the 10 patients presented with aneurysmal subarachnoid hemorrhage. The average length of stay was 25 ± 2 days for the simultaneous procedure group and 43 ± 7 days for the separate procedures group. The average duration of follow-up was 12 ± 3 months after simultaneous placement. No patient in the simultaneous surgery group had signs of infection or shunt malfunction at last follow-up. The overall complication rate was significantly lower in the simultaneous surgery group. A cost analysis demonstrated significant cost savings by completing both procedures in the same surgical procedure. CONCLUSIONS: Simultaneous placement of a PEG tube and VP shunt is safe, efficacious, and cost-effective. Thus, in patients requiring both a VP shunt and PEG tube, placement of both devices in a single surgical procedure should be considered.

Translational Control by Prion-like Proteins.

Prion-like proteins overlap with intrinsically disordered and low-complexity sequence families. These proteins are widespread, especially among mRNA-binding proteins. A salient feature of these proteins is the ability to form protein assemblies with distinct biophysical and functional properties. While prion-like proteins are involved in myriad of cellular processes, we propose potential roles for protein assemblies in regulated protein synthesis. Since proteins are the ultimate functional output of gene expression, when, where, and how much of a particular protein is made dictates the functional state of a cell. Recent finding suggests that the prion-like proteins offer unique advantages in translation regulation and also raises questions regarding formation and regulation of protein assemblies.

Fistulous Complications following Radical Cystectomy for Bladder Cancer: Analysis of a Large Modern Cohort.

PURPOSE: Fistula formation is a rare and poorly described complication following radical cystectomy with urinary diversion. We sought to identify patients who experienced any type of fistulous complication and we analyzed risk factors for formation as well as management outcomes. MATERIALS AND METHODS: We retrospectively reviewed the records of patients who underwent radical cystectomy for bladder cancer at our institution. Patients who experienced any fistula were identified. Risk factors, management strategies and outcomes were analyzed. Patients underwent initial conservative treatment and those in whom this treatment failed underwent surgical repair. Univariable and multivariable analyses were performed to identify predictors of fistula formation as well as the need for surgical repair. RESULTS: Of the 1,041 patients 31 (3.0%) experienced fistula formation. Median time to fistula presentation was 31 days. Enterodiversion was the most common fistula type, noted in 54.8% of patients, followed by enterocutaneous and diversion cutaneous treatment in 29.0% and 12.9%, respectively. On multivariable analyses a history of radiation therapy (OR 3.1, p = 0.03) and an orthotopic neobladder (OR 3.1, p = 0.04) were predictors of fistula formation. Conservative management was successful in 41.9% of cases. There were no predictors of failed conservative management. Of patients who required surgical repair success was achieved in 94.4% at a single operation. CONCLUSIONS: Fistulas are rare after radical cystectomy and they are most common between the urinary diversion and the small bowel. A history of radiation therapy and a orthotopic neobladder are risk factors for formation. When required, surgical repair is generally successful at a single operation.

Regulated Intron Removal Integrates Motivational State and Experience.

Myriad experiences produce transient memory, yet, contingent on the internal state of the organism and the saliency of the experience, only some memories persist over time. How experience and internal state influence the duration of memory at the molecular level remains unknown. A self-assembled aggregated state of Drosophila Orb2A protein is required specifically for long-lasting memory. We report that in the adult fly brain the mRNA encoding Orb2A protein exists in an unspliced non-protein-coding form. The convergence of experience and internal drive transiently increases the spliced protein-coding Orb2A mRNA. A screen identified pasilla, the fly ortholog of mammalian Nova-1/2, as a mediator of Orb2A mRNA processing. A single-nucleotide substitution in the intronic region that reduces Pasilla binding and intron removal selectively impairs long-term memory. We posit that pasilla-mediated processing of unspliced Orb2A mRNA integrates experience and internal state to control Orb2A protein abundance and long-term memory formation.

Vital Directions for Health and Health Care: Priorities From a National Academy of Medicine Initiative.

Importance: Recent discussion has focused on questions related to the repeal and replacement of portions of the Affordable Care Act (ACA). However, issues central to the future of health and health care in the United States transcend the ACA provisions receiving the greatest attention. Initiatives directed to certain strategic and infrastructure priorities are vital to achieve better health at lower cost. Objectives: To review the most salient health challenges and opportunities facing the United States, to identify practical and achievable priorities essential to health progress, and to present policy initiatives critical to the nation's health and fiscal integrity. Evidence Review: Qualitative synthesis of 19 National Academy of Medicine-commissioned white papers, with supplemental review and analysis of publicly available data and published research findings. Findings: The US health system faces major challenges. Health care costs remain high at $3.2 trillion spent annually, of which an estimated 30% is related to waste, inefficiencies, and excessive prices; health disparities are persistent and worsening; and the health and financial burdens of chronic illness and disability are straining families and communities. Concurrently, promising opportunities and knowledge to achieve change exist. Across the 19 discussion papers examined, 8 crosscutting policy directions were identified as vital to the nation's health and fiscal future, including 4 action priorities and 4 essential infrastructure needs. The action priorities-pay for value, empower people, activate communities, and connect care-recurred across the articles as direct and strategic opportunities to advance a more efficient, equitable, and patient- and community-focused health system. The essential infrastructure needs-measure what matters most, modernize skills, accelerate real-world evidence, and advance science-were the most commonly cited foundational elements to ensure progress. Conclusions and Relevance: The action priorities and essential infrastructure needs represent major opportunities to improve health outcomes and increase efficiency and value in the health system. As the new US administration and Congress chart the future of health and health care for the United States, and as health leaders across the country contemplate future directions for their programs and initiatives, their leadership and strategic investment in these priorities will be essential for achieving significant progress.

A phase 2 study of MK-5442, a calcium-sensing receptor antagonist, in postmenopausal women with osteoporosis after long-term use of oral bisphosphonates.

UNLABELLED: In women with osteoporosis treated with alendronate for >12 months and oral bisphosphonates for >3 of the last 4 years, switching to MK-5442, a calcium receptor antagonist, stimulated endogenous parathyroid hormone (PTH) secretion and increased bone turnover marker levels, but produced a decline in bone mineral density (BMD) at all sites. INTRODUCTION: This study assessed the effects of switching from long-term oral bisphosphonate therapy to the calcium-sensing receptor antagonist MK-5442 on BMD and bone turnover markers (BTMs) in post-menopausal women with osteoporosis. METHODS: This randomized, active and placebo-controlled, dose-ranging study enrolled 526 postmenopausal women, who had taken alendronate (ALN) for ≥12 months preceding the trial and any oral bisphosphonate for ≥3 of the preceding 4 years and had spine or hip BMD T-scores ≤-2.5 or ≤-1.5 with ≥1 prior fragility fracture. Women were randomized to continue ALN 70 mg weekly or switch to MK-5442 (5, 7.5, 10, or 15 mg daily) or placebo. RESULTS: Switching from ALN to MK-5442 produced a dose-dependent parathyroid hormone (PTH) pulse of threefold to sixfold above baseline at 1 h, with PTH levels that remained twofold to threefold above baseline at 4 h and returned to baseline by 24 h. Switching to MK-5442 or placebo increased BTM levels compared to baseline within 3 months and MK-5442 10 mg increased BTM levels compared to placebo by 6 months. With all MK-5442 doses and placebo, spine and hip BMD declined from baseline, and at 12 months, BMD levels were below those who continued ALN (all groups P < 0.05 vs ALN). There was also a dose-dependent increase in the incidence of hypercalcemia with MK-5442. CONCLUSION: Switching from ALN to MK-5442 resulted in a pulsatile increase in PTH and increases in BTMs, but a decline in BMD compared with continued ALN. MK-5442 is not a viable option for the treatment of osteoporosis.

IOM and DHHS meeting on making clinical practice guidelines appropriate for patients with multiple chronic conditions.

BACKGROUND: The increasing prevalence of Americans with multiple (2 or more) chronic conditions raises concerns about the appropriateness and applicability of clinical practice guidelines for patient management. Most guidelines clinicians currently rely on have been designed with a single chronic condition in mind, and many such guidelines are inattentive to issues related to comorbidities. PURPOSE: In response to the need for guideline developers to address comorbidities in guidelines, the Department of Health and Human Services convened a meeting in May 2012 in partnership with the Institute of Medicine to identify principles and action options. RESULTS: Eleven principles to improve guidelines' attentiveness to the population with multiple chronic conditions were identified during the meeting. They are grouped into 3 interrelated categories: (1) principles intended to improve the stakeholder technical process for developing guidelines; (2) principles intended to strengthen content of guidelines in terms of multiple chronic conditions; and (3) principles intended to increase focus on patient-centered care. CONCLUSION: This meeting built upon previously recommended actions by identifying additional principles and options for government, guideline developers, and others to use in strengthening the applicability of clinical practice guidelines to the growing population of people with multiple chronic conditions. The suggested principles are helping professional societies to improve guidelines' attentiveness to persons with multiple chronic conditions.