Oscillatory Coupling Between Neural and Cardiac Rhythms.

Oscillations serve a critical role in organizing biological systems. In the brain, oscillatory coupling is a fundamental mechanism of communication. The possibility that neural oscillations interact directly with slower physiological rhythms (e.g., heart rate, respiration) is largely unexplored and may have important implications for psychological functioning. Oscillations in heart rate, an aspect of heart rate variability (HRV), show remarkably robust associations with psychological health. Mather and Thayer proposed coupling between high-frequency HRV (HF-HRV) and neural oscillations as a mechanism that partially accounts for such relationships. We tested this hypothesis by measuring phase-amplitude coupling between HF-HRV and neural oscillations in 37 healthy adults at rest. Robust coupling was detected in all frequency bands. Granger causality analyses indicated stronger heart-to-brain than brain-to-heart effects in all frequency bands except gamma. These findings suggest that cardiac rhythms play a causal role in modulating neural oscillations, which may have important implications for mental health.

Awareness of Racial and Ethnic Bias and Potential Solutions to Address Bias With Use of Health Care Algorithms.

Importance: Algorithms are commonly incorporated into health care decision tools used by health systems and payers and thus affect quality of care, access, and health outcomes. Some algorithms include a patient's race or ethnicity among their inputs and can lead clinicians and decision-makers to make choices that vary by race and potentially affect inequities. Objective: To inform an evidence review on the use of race- and ethnicity-based algorithms in health care by gathering public and stakeholder perspectives about the repercussions of and efforts to address algorithm-related bias. Design, Setting, and Participants: Qualitative methods were used to analyze responses. Responses were initially open coded and then consolidated to create a codebook, with themes and subthemes identified and finalized by consensus. This qualitative study was conducted from May 4, 2021, through December 7, 2022. Forty-two organization representatives (eg, clinical professional societies, universities, government agencies, payers, and health technology organizations) and individuals responded to the request for information. Main Outcomes and Measures: Identification of algorithms with the potential for race- and ethnicity-based biases and qualitative themes. Results: Forty-two respondents identified 18 algorithms currently in use with the potential for bias, including, for example, the Simple Calculated Osteoporosis Risk Estimation risk prediction tool and the risk calculator for vaginal birth after cesarean section. The 7 qualitative themes, with 31 subthemes, included the following: (1) algorithms are in widespread use and have significant repercussions, (2) bias can result from algorithms whether or not they explicitly include race, (3) clinicians and patients are often unaware of the use of algorithms and potential for bias, (4) race is a social construct used as a proxy for clinical variables, (5) there is a lack of standardization in how race and social determinants of health are collected and defined, (6) bias can be introduced at all stages of algorithm development, and (7) algorithms should be discussed as part of shared decision-making between the patient and clinician. Conclusions and Relevance: This qualitative study found that participants perceived widespread and increasing use of algorithms in health care and lack of oversight, potentially exacerbating racial and ethnic inequities. Increasing awareness for clinicians and patients and standardized, transparent approaches for algorithm development and implementation may be needed to address racial and ethnic biases related to algorithms.

Prioritizing Evidence-based Interventions for Dissemination and Implementation Investments: AHRQ's Model and Experience.

BACKGROUND: The Agency for Healthcare Research and Quality (AHRQ) is mandated to implement patient-centered outcomes research (PCOR) to promote safer, higher quality care. With this goal, we developed a process to identify which evidence-based PCOR interventions merit investment in implementation. We present our process and experience to date. MATERIALS AND METHODS: AHRQ developed and applied a systematic, transparent, and stakeholder-driven process to identify, evaluate, and prioritize PCOR interventions for broad dissemination and implementation. AHRQ encouraged public nominations, and assessed them against criteria for quality of evidence, potential impact, and feasibility of successful implementation. Nominations with sufficient evidence, impact, and feasibility were considered for funding. RESULTS: Between June 2016 and June 2018, AHRQ received 35 nominations from researchers, nonprofit corporations, and federal agencies. Topics covered diverse settings, populations, and clinical areas. Twenty-eight unique PCOR interventions met minimum criteria; 16 of those had moderate to high evidence/impact and were assessed for feasibility. Fourteen topics either duplicated other efforts or lacked evidence on implementation feasibility. Two topics were prioritized for funding (cardiac rehabilitation after myocardial infarction and screening/treatment for unhealthy alcohol use). CONCLUSIONS: AHRQ developed replicable criteria, and a transparent and stakeholder-driven framework that attracted a diverse array of nominations. We identified 2 evidence-based practice interventions to improve care with sufficient evidence, impact, and feasibility to justify an AHRQ investment to scale up practice. Other funders, health systems or institutions could use or modify this process to guide prioritization for implementation.

The refinement of topics for systematic reviews: lessons and recommendations from the Effective Health Care Program.

OBJECTIVES: The Agency for Healthcare Research and Quality (AHRQ) Effective Health Care Program conducts systematic reviews of health-care topics nominated by stakeholders. Topics undergo refinement to ensure relevant questions of appropriate scope and useful reviews. Input from key informants, experts, and a literature scan informs changes in the nominated topic. AHRQ convened a work group to assess approaches and develop recommendations for topic refinement. STUDY DESIGN AND SETTING: Work group members experienced in topic refinement generated a list of questions and guiding principles relevant to the refinement process. They discussed each issue and reached agreement on recommendations. RESULTS: Topics should address important health-care questions or dilemmas, consider stakeholder priorities and values, reflect the state of the science, and be consistent with systematic review research methods. Guiding principles of topic refinement are fidelity to the nomination, relevance, research feasibility, responsiveness to stakeholder inputs, reduced investigator bias, transparency, and suitable scope. Suggestions for stakeholder engagement, synthesis of input, and reporting are discussed. Refinement decisions require judgment and balancing guiding principles. Variability in topics precludes a prescriptive approach. CONCLUSION: Accurate, rigorous, and useful systematic reviews require well-refined topics. These guiding principles and methodological recommendations may help investigators refine topics for reviews.

Phenylketonuria Scientific Review Conference: state of the science and future research needs.

New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360 µmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360 µmol/L. The use of genotype information in the newborn period may yield valuable insights about the severity of the condition for infants diagnosed before maximal Phe levels are achieved. While emerging and established genotype-phenotype correlations may transform our understanding of PKU, establishing correlations with intellectual outcomes is more challenging. Regarding the use of sapropterin in PKU, there are significant gaps in predicting response to treatment; at least half of those with PKU will have either minimal or no response. A coordinated approach to PKU treatment improves long-term outcomes for those with PKU and facilitates the conduct of research to improve diagnosis and treatment. New drugs that are safe, efficacious, and impact a larger proportion of individuals with PKU are needed. However, it is imperative that treatment guidelines and the decision processes for determining access to treatments be tied to a solid evidence base with rigorous standards for robust and consistent data collection. The process that preceded the PKU State-of-the-Science Conference, the conference itself, and the identification of a research agenda have facilitated the development of clinical practice guidelines by professional organizations and serve as a model for other inborn errors of metabolism.

Lung mast cell density defines a subpopulation of patients with idiopathic pulmonary fibrosis.

AIMS: The relationship of mast cells to the pathogenesis of lung fibrosis remains undefined despite recognition of their presence in the lungs of patients with pulmonary fibrosis. This study was performed to characterize the relationship of mast cells to fibrotic lung diseases. METHODS AND RESULTS: Lung tissues from patients with idiopathic pulmonary fibrosis (IPF), chronic hypersensitivity pneumonitis (HP), systemic sclerosis (SSc)-related interstitial lung disease (ILD) and normal individuals were subjected to chymase immunostaining and the mast cell density quantified. Eosinophils were quantified by immunostaining for eosinophil peroxidase. Changes in lung function were correlated with mast cell density. Lung tissue obtained from IPF patients had a higher density of chymase-immunoreactive mast cells than that from patients with HP, SSc-related ILD or normal lungs. IPF lung tissue had a higher density of eosinophils than normal lung. There was no correlation between mast cell density and eosinophil density in IPF lung. IPF patients with high mast cell density had a slower rate of decline in forced vital capacity (FVC) than IPF patients with low mast cell density. CONCLUSIONS: Mast cell density in IPF lungs is higher than in other fibrotic lung diseases and normal lungs. Increased mast cell density in IPF may predict slower disease progression.