National Heart, Lung, And Blood Institute Research Articles

Machine learning with electrocardiograms to optimize mortality risk stratification in patients with suspected acute coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart, Lung, and Blood Institute (NHLBI) and National Center for Advancing Translational Sciences (NCATS). Background The importance of risk stratification in patients with suspected acute coronary syndrome (ACS) extends beyond diagnosis and immediate treatment. It influences the precision of care delivery and the allocation of resources to those at highest risk of adverse events. Purpose We sought to evaluate the prognostic value of electrocardiogram (ECG) feature-based machine learning models to risk-stratify long-term mortality in those with suspected ACS. Methods This was a multicenter prospective observational cohort study of consecutive, non-traumatic patients evaluated at the emergency department for suspected ACS. The derivation cohort included 4,015 patients from a University Medical Center (age 59±16 years, 47% women, 80% training with 10-fold cross-validation and 20% testing). Ascertainment of all-cause death was based on numerous data sources, including the Centers for Disease Control and Prevention’s National Death Index registry. We trained six machine learning methods for survival analysis using 73 morphological ECG features from presenting prehospital 10-second 12-lead ECGs. We used predicted risk scores in a variational Bayesian Gaussian mixture model to define three risk groups corresponding to low, moderate, and high-risk and compared the resulting classification performance against the HEART score. The external testing cohort included 3,095 patients from a University (age 59±15 years, 44% women). Results The mortality rate was 20.3% in the derivation cohort after an average follow-up period of 3.53 years (IQR 1.75 - 5.32). Extra Survival Trees outperformed other forecasting models during cross-validation. In the internal testing cohort, the derived risk groups were significantly predictive of survival (Kaplan-Meier log-rank test statistic = 121.14, p<0.001), outperforming the classification performance using the HEART score (Figure 1). Our machine learning-based risk stratification model detected >90% of death events missed by low-risk HEART score (Figure 2). Ruling-out the low-risk group, it achieved a negative predictive value of 93.4% with a sensitivity of 85.9% (compared to 89.0% and 75.0%, respectively, for the HEART score). This classification performance generalized well to our external testing cohort. Compared to those in the low-risk group, patients at moderate (OR = 3.62 [1.35-9.74]) and high (OR = 6.12 [2.38-15.75]) risk had significantly higher odds of 30-day cardiovascular death (n=109, 3.5%). Conclusions Using only features from the 10-second 12-lead ECG, we derived and externally validated a machine learning model that stratifies the mortality risk of patients during long-term follow up. This model outperformed current standard of care based on the HEART score. Future work should validate the potential of this decision-support tool in influencing treatment plans and resource allocation.Figure 1.Clustering performanceFigure 2.Sankey diagram

Clinical epidemiology and outcomes of emergency department-acute kidney injury: A systematic review

BackgroundOver half of all community-acquired acute kidney injury (CA-AKI) initially presented to emergency department (ED), but emergency department acute kidney injury (ED-AKI) is poorly characterised, poorly understood with no systematic review, often under-recognized and under-managed. ObjectiveTo review the incidence, risk factors, and outcomes of ED-AKI, and risk factors of post-ED-AKI mortality globally. MethodsWe included published prospective or retrospective observational studies, controlled trials, and systematic reviews reporting AKI in adult ED attendees within 24 h of ED admission. Iatrogenic causes of AKI from medical interventions were excluded. We used PubMed to identify articles from 1996 to August 14, 2021, and adopted the National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies to assess risk of bias. We used a Forest plot to present pooled ED-AKI incidence rates and I2 statistics. Other parameters were summarized narratively. ResultsUsing 24 h from ED admission as the definition for ED-AKI we identified six articles from 2005 to 2018 in high-income settings and one article with a 48-h timeframe. The pooled incidence of ED-AKI was 20 per 1000 adult ED attendances. Risk factors for ED-AKI included increasing age, nursing home residence, previous hospital admission within 30 days, discharge diagnosis of diabetes, obstructive uropathy, sepsis, gastrointestinal medical conditions, high serum creatinine, bilirubin, C-reactive protein, white blood cell, alanine aminotransferase, low serum sodium or albumin on admission, poor premorbid renal function, antibiotic use, active malignancy, lung disease, hyperlipidaemia, and infection. Crude, all-cause 24-h mortality rate was 4.56 % and the one-year mortality rate was 35.04 %. Increasing age and comorbidities including cardiovascular disease and malignancy were associated with higher mortality rates. ConclusionThe review reveals a paucity of relevant literature which calls for further research, increased vigilance, red flag identification, and standardized management protocols for ED-AKI.

Epigenetics of conotruncal congenital heart disease: Protocol for a systematic review and meta-analysis.

Conotruncal congenital heart defects (CTD) are a subset of congenital heart diseases (CHD) that involve structural anomalies of the right, left, or both cardiac outflow tracts. CHD is caused by multifactorial inheritance and changes in the genes or chromosomes. Recently, CHD was found to be due to epigenetic alterations, which are a combination of genetic and other environmental factors. Epigenetics is the study of how a gene's function changes as a result of environmental and behavioral influences. These causative factors can indirectly cause CHD by altering the DNA through epigenetic modifications. This is a protocol for a systematic review and meta-analysis that aims to explore whether the strength of association between various epigenetic changes and CTD types varies by race. Furthermore, to determine and compare the changes in gene expression of each mutation. Our protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) guidelines. A comprehensive pre-search has been developed in PubMed and PubMed's Medical Subject Headings (MeSH). The final search will be performed in June 2023 in PubMed, Embase, Scopus, Web of Science, Cochrane Library, CIANHL, and PsycInfo, without restrictions on publication years. The Covidence systematic review software will be used for blinded screening and selection. Conflicts will be resolved by a third, independent reviewer. The risk of bias in selected studies will be assessed using the National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The data to be extracted will cover basic information on the included studies, study sample size, number of patients with various types of epigenetic changes, number of patients with various CTD types, measures of association and their 95% confidence interval between each epigenetic change and each CTD. The protocol has been registered with the International Prospero Register of Systematic Review (PROSPERO) [CRD42023377597]. To the best of our knowledge, this protocol outlines the first systematic review and meta-analysis of the epigenetics of CTD. There is a growing body of evidence on epigenetics and its indirect involvement in disease by altering the DNA through epigenetic modifications in the genes associated with the causative factors for CHD. We will conduct a comprehensive and systematic search for literature in the above-mentioned seven core biomedical databases. It is very important to identify population-specific risk factors for CHD, which will have significant creative, custom-made, and effective prevention programs for the future generation.

Effectiveness of immunoglobulin replacement therapy in preventing infections in patients with chronic obstructive pulmonary disease: a systematic review

PurposeImmunoglobulin replacement therapy is a standard treatment for patients with antibody production deficiencies, which is of interest in patients with chronic obstructive pulmonary disease (COPD). This systematic review, registered with PROSPERO (CRD42021281118), assessed the current literature regarding immunoglobulin replacement therapy on COPD clinical outcomes in patients with low immunoglobulin G (IgG) serum concentrations.MethodsLiterature searches conducted from inception to August 23, 2021, in databases including MEDLINE, EMBASE, and CINAHL. Population (sex, age, comorbidities), baseline clinical characteristics (pulmonary function testing results, IgG levels), and outcome (hospitalizations, emergency department visits) were extracted after title/abstract and full text screening. The Cochrane risk of bias assessment form was used for risk of bias assessment of randomized controlled trials and the National Heart, Lung, and Blood Institute (NHLBI) assessment was used for pre and post studies.ResultsA total of 1381 studies were identified in the preliminary search, and 874 records were screened after duplicates were removed. Screening 77 full texts yielded four studies that were included in the review.ConclusionIt is unclear whether immune globulin replacement therapy reduces acute exacerbation frequency and severity in COPD. Current evidence suggests that it is worth considering, but better developed protocols for administration of immune globulin supplementation is required for future randomized controlled trials.

The Efficacy of Physical Therapy to Alleviate Symptomatic Thoracic Radiculopathy: A Systematic Review and Meta-Narrative Analysis.

To evaluate the efficacy of physical therapy (PT) to alleviate symptomatic thoracic radiculopathy (TR) without the use of invasive procedures. Database search was conducted by an experienced medical librarian from inception until January 27, 2023, in EBSCO CINAHL with Full Text, Ovid Cochrane Central Register of Controlled Trials, Ovid Embase, Ovid MEDLINE, Scopus, and Web of Science Core Collection. Inclusion criteria included studies that involved adult patients (age≥18) who had a magnetic resonance imaging-confirmed TR and underwent a structured, supervised PT program of any length. All types of studies were included. Study quality and risk of bias were assessed using the National Heart, Lung, and Blood Institute (NHLBI) Study Quality of Assessment Tool. Certainty in evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. A meta-analysis was not performed. A total of 1,491 studies were screened and 7 studies met inclusion criteria, 5 case studies and 2 cohort studies. All studies showed improvement or resolution of the TR with PT. Quantitative improvements were not noted in most studies and PT regimens were sparsely described. Overall quality assessment demonstrated 3 studies had "good," 1 "fair," and 3 "poor" quality evidence. Certainty of evidence was "low" due to risk of bias. A dedicated PT program may help to alleviate symptomatic TR; however due to limited evidence, risk of bias, and low certainty in evidence, the data is too weak to support a definite conclusion.

The Intersection of Cardiovascular Health and Maternal Health: Portfolio Analysis of Federal Grant Funding 2016-2021.

Background: The United States has high and increasing rates of maternal morbidity and mortality, large proportions of which are related to cardiovascular health (CVH). Methods: We searched for National Institutes of Health (NIH) supported research as well as that of two other Agencies in the U.S. Department of Health and Human Services (DHHS) for fiscal years (FY) 2016-2021. Grants included maternal health conditions or exposures across all pregnancy stages, but excluded grants that focused entirely on birth, neonatal, infant/childhood outcomes. Results were manually curated by reviewing the abstract and specific aims. Grants deemed to be relevant were grouped by category. Results: Between FY 2016-2021, overall Maternal Health grants remained unchanged at an average of 1.4% of total DHHS grant funding. Maternal CVH-specific (MCVH) funding amounted to $278,926,105 for 755 grants, $191,344,649 was for 534 Type-1 grants, representing a twofold increase. Non-NIH DHHS agencies most commonly funded general Maternal Health related to CVH; NIH focused funding classified as hypertensive disorders of pregnancy, maternal morbidity and mortality, obesity, and diabetes. Non-NIH DHSS Agencies most commonly funded clinical applied research. In addition to clinical applied grants, NIH funded substantial proportions of grants classified as basic research, clinical trials, and/or translational. National Heart, Lung, and Blood Institute (NHLBI) MCVH grants studied participants in the pre-partum period (78.5%), followed by the post-partum period (50.5%), with relatively few in pre-pregnancy and peri-partum periods (10.8% and 9.7%, respectively); at the NIH level, the peri-partum period had better representation at 20.3%, whereas the pre-pregnancy period remained low at 9.9%. Conclusions: Federal grant funding for maternal health including MCVH increased at the same rate as its funding for overall research, and represented only 1.4% of overall total funding. The pre-pregnancy period was understudied in overall NIH funding and represents a gap area whereby funding agencies could further foster research advances.

Prospective bidirectional relations between depression and metabolic health: 30-year follow-up from the National Heart, Lung, and Blood Institute (NHLBI) Coronary Artery Disease in Young Adults (CARDIA) study.

This study investigated prospective bidirectional relationships between depressive symptoms and metabolic syndrome (MetS) and the moderating effects of race, sex, and health behaviors in a diverse cohort followed for 30 years. Data were analyzed from the National Heart, Lung, and Blood Institute (NHLBI) Coronary Artery Disease in Young Adults (CARDIA) study, a 30-year prospective study of young adults (N = 5,113; Mage = 24.76 [SD = 3.63] at baseline; 45% male) who were tested every 5 years between 1985 and 2015. Measures included biological assessments of MetS components and self-reported depressive symptoms based on the Center for Epidemiologic Studies Depression (CESD) scale. Data analyses included bidirectional general estimating equations analyses of time-lagged associations between depressive symptoms and MetS. There was a consistent, bidirectional relationship between depressive symptoms and MetS over time. Individuals with more CESD depressive symptoms were more likely to develop MetS over time compared to those reporting fewer symptoms, Wald χ²(1) = 7.09, p < .008, and MetS was similarly predictive of CESD. MetS more consistently predicted CESD scores at each 5-year exam than CESD predicted MetS. Race and sex moderated these relationships, with White females, White individuals overall, and females overall demonstrating significant relationships between CESD depressive symptoms and MetS. Health behaviors were not related to associations between CESD and MetS. In a diverse young adult population prospectively followed into late middle age, MetS more consistently predicted depressive symptoms over time than depressive symptoms predicted MetS. The relation between MetS and depressive symptoms was moderated by race and sex, but not health behaviors. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Metabolite signatures associated with microRNA miR-143-3p serve as drivers of poor lung function trajectories in childhood asthma

Lung function trajectories (LFTs) have been shown to be an important measure of long-term health in asthma. While there is a growing body of metabolomic studies on asthma status and other phenotypes, there are no prospective studies of the relationship between metabolomics and LFTs or their genomic determinants. We utilized ordinal logistic regression to identify plasma metabolite principal components associated with four previously-published LFTs in children from the Childhood Asthma Management Program (CAMP) (n=660). The top significant metabolite principal component (PCLF) was evaluated in an independent cross-sectional child cohort, the Genetic Epidemiology of Asthma in Costa Rica Study (GACRS) (n=1151) and evaluated for association with spirometric measures. Using meta-analysis of CAMP and GACRS, we identified associations between PCLF and microRNA, and SNPs in their target genes. Statistical significance was determined using an false discovery rate-adjusted Q-value. The top metabolite principal component, PCLF, was significantly associated with better LFTs after multiple-testing correction (Q-value=0.03). PCLF is composed of the urea cycle, caffeine, corticosteroid, carnitine, and potential microbial (secondary bile acid, tryptophan, linoleate, histidine metabolism) metabolites. Higher levels of PCLF were also associated with increases in lung function measures and decreased circulating neutrophil percentage in both CAMP and GACRS. PCLF was also significantly associated with microRNA miR-143-3p, and SNPs in three miR-143-3p target genes; CCZ1 (P-value=2.6×10-5), SLC8A1 (P-value=3.9×10-5); and TENM4 (P-value=4.9×10-5). This study reveals associations between metabolites, miR-143-3p and LFTs in children with asthma, offering insights into asthma physiology and possible interventions to enhance lung function and long-term health. Molecular data for CAMP and GACRS via the Trans-Omics in Precision Medicine (TOPMed) program was supported by the National Heart, Lung, and Blood Institute (NHLBI).

Evaluation of adherence to guideline-directed therapy and risk factors for exacerbation in mild asthma: a retrospective chart review

BackgroundA significant update was made to both the Global Initiative for Asthma (GINA) in 2019 and the National Heart Lung and Blood Institute (NHLBI) asthma guidelines in 2020 for mild asthma. These groups no longer recommend short-acting beta-agonists (SABA) as monotherapy for mild (GINA) or mild-persistent (NHLBI) asthma. With the lag that can occur between guideline or evidence updates and changes in practice, this study sought to evaluate whether guideline adoption had occurred.MethodsIn this retrospective chart review, patient electronic medical records from a large healthcare system were evaluated from July 1 of 2021 to July 1 of 2022 to determine how many patients with mild asthma were prescribed as needed or daily inhaled corticosteroids (ICS) in addition to as needed SABA. The secondary outcome was to evaluate the incidence of exacerbations in patients with mild asthma, comparing those on guideline-directed therapy or not. In addition, we evaluated other patient factors increasing exacerbation risk in mild asthma.ResultsFor the primary outcome, of the 1,107 patients meeting inclusion criteria, 284 patients (26%) did not have documentation of guideline-directed therapy for mild asthma during the study period, while 823 (74%) were on guideline-directed therapy (Diff:48.7%; 95% CI:45.1 to 52.3%, p < 0.001). For the secondary objective, 161 patients had an exacerbation (12% on guideline-directed therapy, 15.4% not on guideline-directed therapy). This difference in incidence of exacerbation between the two treatment groups was not statistically significant (Diff: -3.4%; 95% CI: -8 to 1.1%; p = 0.133). In addition, being female, having GERD, and being obese were all statistically significant factors associated with having asthma exacerbations among our patient population.ConclusionsNearly one-fourth of patients with mild persistent asthma were not on guideline-directed therapy, despite updates in asthma guidelines (GINA 2019, NHLBI 2020). Factors such as being female, having GERD, and being obese were all statistically significant factors associated with having asthma exacerbations among patients with mild persistent asthma.

Tackling Brain and Muscle Dysfunction in Acute Respiratory Distress Syndrome Survivors: National Heart, Lung, and Blood Institute Workshop Report.

Acute respiratory distress syndrome (ARDS) is associated with long-term impairments in brain and muscle function that significantly impact the quality of life of those who survive the acute illness. The mechanisms underlying these impairments are not yet well understood, and evidence-based interventions to minimize the burden on patients remain unproven. The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health assembled a workshop in April 2023 to review the state of the science regarding ARDS-associated brain and muscle dysfunction, to identify gaps in current knowledge, and to determine priorities for future investigation. The workshop included presentations by scientific leaders across the translational science spectrum and was open to the public as well as the scientific community. This report describes the themes discussed at the workshop as well as recommendations to advance the field toward the goal of improving the health and wellbeing of ARDS survivors.

A systematic review of interventions to improve medication adherence in adults with mental-physical multimorbidity in primary care.

Medication non-adherence is a significant contributor to healthcare inefficiency, resulting in poor medication management, impaired patient outcomes and ineffective symptom control. This review summarises interventions targeting medication adherence for adults with mental-physical multimorbidity, in primary healthcare settings. A systematic review of literature was conducted using Medline, Embase, PsycInfo, Web of Science, Cochrane Library, and CINAHL were searched for relevant studies. Data were extracted and synthesized using narrative synthesis. The Cochrane Effective Practice and Organisation of Care (EPOC) was used to classify intervention types. Risk of bias was assessed using the National Heart, Lung, and Blood Institute (NHLBI) quality assessment tool. Eleven studies representing 2,279 patients were included. All interventions examined were classified into one EPOC domain, which was delivery arrangements. All included studies examined patients with a physical condition, alongside depression. Seven studies examining coordination of care and management of care processes interventions reported significant improvements in medication adherence attributed to the intervention. Four studies considering the use of information and communication technology observed no changes in medication adherence. Interventions that coordinate and manage healthcare processes may help improve how patients adhere to their medication regimes, particularly in patients with mental-physical multimorbidity. However, we still need to better understand how digital health technology can support patients in following their medication regimes. As we face the growing challenges of treating multimorbidity, everyone involved in health services - from providers to policymakers - must be receptive to a more integrated approach to the delivery of healthcare.

Health Literacy Assessment of NHLBI COPD Education Playlist on YouTube

ABSTRACT Background The National Heart, Lung, and Blood Institute (NHLBI) Learn About Chronic Obstructive Pulmonary Disease (COPD) YouTube playlist educates the public on diagnosing, treating, and managing COPD. Despite its potential benefits, it is unknown if users with inadequate health literacy will likely understand and apply the information described in these videos. Purpose Assess the Learn About COPD playlist’s readability, actionability, and understandability. Methods Central tendency statistics were computed to describe the meta-data of 28 videos available as of April 2023. Assessments included the Patient Education Materials Assessment Tool for Audiovisual Materials (PEMAT-AV), Accessible Health IT for Limited-Literacy Populations Checklist (LLPC), and the Modified Centers for Disease Control and Prevention (CDC)-Clear Communication Index (CCI) for audiovisual materials. Results Playlist videos received an average of over 2,000 views (Mdn = 2,220, IQR = 496–8336), with very few “likes” (Mdn = 13, IQR = 1–48 “likes”). PEMAT-understandability (Mdn = 81.81%, IQR = 80–97.72%) and LLPC (Mdn = 87.50%, IQR = 75–93.75%) scores were high (above 80%). However, the modified CDC-CCI median score was 57.14% (IQR = 42.86–75%), and the median PEMAT-actionability score was 50% (IQR = 0–66.67%). Discussion The playlist earned passing understandability, acceptability, and usability scores but scored poorly on actionability and communication clarity. Translation to Health Education Practice Findings could inform enhancements to NHLBI’s Learn About COPD YouTube playlist.

Factors associated with mortality of elderly people due to COVID-19: Protocol for systematic review and meta-analysis.

The COVID-19 pandemic has become a significant health crisis, marked by high mortality rates on a global scale, with mortality from the disease being notably concentrated among the elderly due to various factors. This study aims to investigate the biological and non-biological factors associated with COVID-19 mortality rates among the elderly worldwide. The following databases will be consulted: PubMed, Scopus, EMBASE, Web of Science and ScienceDirect. Longitudinal observational studies (cohort and case-control-risk factors) will be included. The risk of bias, defined as low, moderate, high, will be assessed using the National Heart, Lung and Blood Institute (NHLBI) Quality Assessment Tool for observational cohort and cross-sectional studies. Two independent authors will conduct the searches, and any possible disagreements will be resolved by a third author. Heterogeneity between study results will be assessed using a standard X2 test with a significance level of 0.05, and an I2 value will be calculated to further assess heterogeneity. The random effects model for meta-analyses will be adopted to distribute the weight between the studies and standardize their contributions. The meta-analyses will be conducted using RevMan software. Despite the numerous publications on COVID-19 mortality among the elderly, there is still a gap in knowledge, as there is no systematic review and meta-analysis that summarizes the main biological and non-biological associated factors globally. The results of this study will consolidate the latest evidence and address gaps in the overall understanding of biological or non-biological associated factors. This knowledge will facilitate the development of appropriate health strategies for this demographic group and pave the way for further research. PROSPERO (CRD42023400873).

Gonadotropins for pubertal induction in males with hypogonadotropic hypogonadism: systematic review and meta-analysis.

Hypogonadotropic hypogonadism is characterized by inadequate secretion of pituitary gonadotropins, leading to absent, partial, or arrested puberty. In males, classical treatment with testosterone promotes virilization but not testicular growth or spermatogenesis. To quantify treatment practices and efficacy, we systematically reviewed all studies investigating gonadotropins for the achievement of pubertal outcomes in males with hypogonadotropic hypogonadism. Systematic review and meta-analysis. A systematic review of Medline, Embase, Global Health, and PsycINFO databases in December 2022. Risk of Bias 2.0/Risk Of Bias In Non-randomized Studies of Interventions/National Heart, Lung, and Blood Institute tools for quality appraisal. Protocol registered on PROSPERO (CRD42022381713). After screening 3925 abstracts, 103 studies were identified including 5328 patients from 21 countries. The average age of participants was <25 years in 45.6% (n = 47) of studies. Studies utilized human chorionic gonadotropin (hCG) (n = 93, 90.3% of studies), human menopausal gonadotropin (n = 42, 40.8%), follicle-stimulating hormone (FSH) (n = 37, 35.9%), and gonadotropin-releasing hormone (28.2% n = 29). The median reported duration of treatment/follow-up was 18 months (interquartile range 10.5-24 months). Gonadotropins induced significant increases in testicular volume, penile size, and testosterone in over 98% of analyses. Spermatogenesis rates were higher with hCG + FSH (86%, 95% confidence interval [CI] 82%-91%) as compared with hCG alone (40%, 95% CI 25%-56%). However, study heterogeneity and treatment variability were high. This systematic review provides convincing evidence of the efficacy of gonadotropins for pubertal induction. However, there remains substantial heterogeneity in treatment choice, dose, duration, and outcomes assessed. Formal guidelines and randomized studies are needed.

Supplemental Material for Prospective Bidirectional Relations Between Depression and Metabolic Health: 30-Year Follow-Up From the National Heart, Lung, and Blood Institute (NHLBI) Coronary Artery Disease in Young Adults (CARDIA) Study

Supplemental Material for Prospective Bidirectional Relations Between Depression and Metabolic Health: 30-Year Follow-Up From the National Heart, Lung, and Blood Institute (NHLBI) Coronary Artery Disease in Young Adults (CARDIA) Study

Deciphering Disparities: The NHLBI Program on Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease Risk (DECIPHeR)

Despite several ambitious national health initiatives to eliminate health disparities, spanning more than 4 decades, health disparities remain pervasive in the United States. In an attempt to bend the curve in disparities elimination, the National Heart, Lung, and Blood Institute (NHLBI) issued a funding opportunity on Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease Risk (DECIPHeR) in March 2019. Seven implementation research centers and 1 research coordinating center were funded in September 2020 to plan, develop, and test effective implementation strategies for eliminating disparities in heart and lung disease risk. In the 16 articles presented in this issue of Ethnicity &amp; Disease, the DECIPHeR Alliance investigators and their NHLBI program staff address the work accomplished in the first phase of this biphasic research endeavor. Included in the collection are an article on important lessons learned during technical assistance sessions designed to ensure scientific rigor in clinical study designs, and 2 examples of clinical study process articles. Several articles show the diversity of clinical and public health settings addressed including schools, faith-based settings, federally qualified health centers, and other safety net clinics. All strategies for eliminating disparities tackle a cardiovascular or pulmonary disease and related risk factors. In an additional article, NHLBI program staff address expectations in phase 2 of the DECIPHeR program, strategies to ensure feasibility of scaling and spreading promising strategies identified, and opportunities for translating the DECIPHeR research model to other chronic diseases for the elimination of related health disparities.

Charting the Future of Health Equity Research: Lessons Learned and Future Aspirations for NHLBI’s DECIPHeR Alliance

The Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease Risk (DECIPHeR) research program, supported by the National Heart, Lung, and Blood Institute (NHLBI), focuses on developing and testing sustainable interventions to reduce heart and lung disease disparities. This perspective piece reflects on lessons learned during the planning phase (UG3) and outlines the accomplishments of the DECIPHeR Alliance. The article emphasizes the importance of a biphasic (UG3/UH3) funding mechanism, technical assistance, and collaborative subcommittees in achieving success. As DECIPHeR enters phase 2 (UH3), the article anticipates rigorously planned studies addressing social determinants of health and emphasizes the need for effective implementation strategies and equitable research frameworks. The Alliance’s contributions, such as the IM4Equity framework, offer novel approaches to community-engaged health equity and implementation science research. The article explores future opportunities, including dissemination strategies, community engagement, and collaboration with diverse partners, to maximize DECIPHeR’s impact on health disparities beyond cardiovascular and pulmonary health.

Prevalence of stunting among under-five children in refugee and internally displaced communities: a systematic review and meta-analysis.

A pooled estimate of stunting prevalence in refugee and internally displaced under-five children can help quantify the problem and focus on the nutritional needs of these marginalized groups. We aimed to assess the pooled prevalence of stunting in refugees and internally displaced under-five children from different parts of the globe. In this systematic review and meta-analysis, seven databases (Cochrane, EBSCOHost, EMBASE, ProQuest, PubMed, Scopus, and Web of Science) along with "preprint servers" were searched systematically from the earliest available date to 14 February 2023. Refugee and internally displaced (IDP) under-five children were included, and study quality was assessed using "National Heart, Lung, and Blood Institute (NHLBI)" tools. A total of 776 abstracts (PubMed = 208, Scopus = 192, Cochrane = 1, Web of Science = 27, Embase = 8, EBSCOHost = 123, ProQuest = 5, Google Scholar = 209, and Preprints = 3) were retrieved, duplicates removed, and screened, among which 30 studies were found eligible for qualitative and quantitative synthesis. The pooled prevalence of stunting was 26% [95% confidence interval (CI): 21-31]. Heterogeneity was high (I2 = 99%, p < 0.01). A subgroup analysis of the type of study subjects revealed a pooled stunting prevalence of 37% (95% CI: 23-53) in internally displaced populations and 22% (95% CI: 18-28) among refugee children. Based on geographical distribution, the stunting was 32% (95% CI: 24-40) in the African region, 34% (95% CI: 24-46) in the South-East Asian region, and 14% (95% CI: 11-19) in Eastern Mediterranean region. The stunting rate is more in the internally displaced population than the refugee population and more in the South-East Asian and African regions. Our recommendation is to conduct further research to evaluate the determinants of undernutrition among under-five children of refugees and internally displaced populations from different regions so that international organizations and responsible stakeholders of that region can take effective remedial actions. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=387156, PROSPERO [CRD42023387156].

Impact of the 2014 NHLBI Hydroxyurea Guidelines on Cerebrovascular Events in Sickle Cell Disease

Background: Cerebrovascular disease (CVD) is a common cause of morbidity in patients with sickle cell disease (SCD). An estimated 37% of children with SCD have silent cerebral infarcts (SCI) by age 14, leading to increased stroke risk and neurocognitive impairment. In the DISPLACE trial (Kanter et al, 2021), 2.9% of patients had abnormal cerebral blood flow as measured on transcranial Doppler ultrasound (TCD). The 2014 National Heart, Lung, and Blood Institute (NHLBI) guidelines recommend hydroxyurea (HU) for all patients with SCD-SS and SCD-Sβ 0 starting at age 9 months, a significant shift from prior practice. In patients who have already developed TCD abnormalities, HU is protective against stroke and CVD progression. The real-world impact of universal early HU on the development of CVD, particularly on SCI, is not well defined . We hypothesize that the 2014 guidelines led to an increase in HU use and a reduction in the initial development of CVD. Methods: We performed a single center, retrospective cohort study investigating trends in HU prescriptions and CVD before and after the publication of the 2014 NHLBI guidelines. Patients with SCD-SS and SCD-Sβ 0 who initiated hematology care at the Children's Hospital of Philadelphia between 2009 and 2023 were identified using an institutional registry. Incident HU was defined as the first outpatient HU prescription in patients with a minimum of two orders. Incident CVD was defined as a composite outcome consisting of the first documentation of: abnormal TCD, brain magnetic resonance imaging (MRI) with silent infarct, or overt ischemic stroke. Patients with known CVD before care initiation, prematurity &amp;lt; 28 weeks gestational age, or non-SCD neurologic disease were excluded. For time-to-HU analysis, patients with HU prescriptions before enrollment at our center also were excluded. Patients were followed from their first hematology visit until the outcome of interest or censoring. Censoring criteria included loss to follow up, transition of care, or bone marrow transplant. All brain MRI and TCD reports were manually reviewed. Ages at HU initiation pre- and post- guideline were compared using the Wilcoxon rank-sum test . Times to 1) HU and 2) CVD were summarized using Kaplan-Meier estimators, with the guideline publication date of September 1, 2014 incorporated as a time-varying exposure. Unadjusted associations were calculated using a Cox proportional hazard regression. Results: A total of 446 patients met inclusion criteria and contributed to analyses. Median age at baseline was 2.4 months, and median duration of follow-up was 5.0 years (IQR: 2.3-8.7). Most patients (430/446, 96%) had SCD SS, and 51% were male. The proportion of patients ever prescribed HU increased with time (Fig 1), with a peak prevalence of 82% in 2022. Of 385 patients not exposed to HU at baseline, 277 (72%) were prescribed HU during study follow-up. Incident HU prescriptions significantly increased after NHLBI guideline publication (HR 3.40, CI: 2.50 to 4.63, p &amp;lt; 0.001) with an older age at HU initiation before (median 4.0 y, IQR 2.5-7.7) than after (median 2.9 y, IQR 1.1-5.8) publication of the guideline (p = 0.002). Over a total of 2,395 person-years of follow-up, 66 incident CVD outcomes occurred in this longitudinal cohort, corresponding to a cumulative incidence of 14.8%. These events included 53 SCI, 10 abnormal TCD, and 3 overt ischemic strokes. CVD outcome occurrence was lower after guideline publication than before (HR 0.58, CI: 0.32-1.05), though the association did not reach statistical significance (p = 0.071, Fig. 2). Discussion: After the NHLBI guideline publication, HU prescriptions increased significantly at our center.Our data suggest that the 2014 guideline-directed care may have led to a greater than 40% reduction in CVD, though this reduction was not statistically significant in our small sample size. Despite guideline recommendations and strong evidence for the role of HU in reducing pain and acute chest syndrome, few patients across the United States are prescribed HU therapy. Adherence and care continuity challenges further lessen the number of patients benefitting from HU. Evidence of efficacy of early and universal HU in CVD prevention would strengthen guideline recommendations and improve clinical care in patients with SCD. Ongoing analysis includes an expanded cohort and adjustment for clinical covariates to better examine the direct impact of early HU on CVD.

Benefit of Inpatient Pain Plan Utilization on Hospital Length of Stay in Adolescents and Young Adults with Sickle Cell Disease

Introduction Vaso-occlusive crisis (VOC) is the most common manifestation of sickle cell disease (SCD) and the most common cause for emergency department (ED) visits and hospital admissions. VOC accounts for approximately 230,000 annual admissions in children with SCD. Patients with SCD face inconsistent analgesic management, leading to high inpatient healthcare utilization and financial burden for healthcare institutions. Furthermore, patients describe their pain management as the area of their care in most need of improvement. A prospective longitudinal cohort study showed that implementation of individualized pain plans in adult patients with SCD significantly decreased the duration of VOC hospital stays by 1.2 days. A similar study in children showed no change in duration of hospital stay, however the study was limited by a small sample size. We hypothesized parallel results to the prior adult study in adolescent and young adult (AYA) SCD patients. Methods At UCSF Benioff Children's Hospital Oakland, we implemented inpatient pain plans for SCD patients with frequent VOC admissions (i.e., &amp;gt;1 VOC admission in the prior year or complicated VOC admission history). Pain plans are individualized and embedded into the patient's electronic health record. These plans include detailed daily analgesic recommendations with the general recommendation for discharge on day 5 of the pain plan. After IRB approval, we performed a retrospective chart review of SCD patients with individualized inpatient pain plans initiated between November 2017 and April 2022. We recorded baseline demographic information including age at pain plan initiation, SCD genotype and sex. We assessed length of inpatient hospitalization for VOC admissions in the year prior and the year after pain plan initiation for each individual patient. We also noted number of admissions secondary to VOC during this two year time period. Results Twenty-six patients with SCD and individualized pain plans were identified (Table 1). Average length of hospital stay for VOC was significantly decreased in the year after inpatient pain plan initiation (Table 2). There was a trend towards increased admissions due to VOC in the year after inpatient pain plan initiation (Table 2). Conclusions Similar to the prior adult study in SCD patients, we found significantly reduced inpatient length of hospitalization after initiation of an inpatient pain plan for AYA patients with SCD and VOC. Although there was a trend towards increased hospitalizations in the year after inpatient pain plan initiation, this was likely secondary to the average patient age with an expected increased in VOC year over year. The National Heart, Lung, and Blood Institute (NHLBI) SCD guidelines recommend an individualized prescribing and monitoring protocol be written by a SCD provider and used in patients withVOC to promote effective, timely, and safe analgesic management. We further demonstrate that individualized pain plans for AYA patients with SCD can decrease length of hospital stay due to VOC, likely secondary to more effective pain management recommendations that have been prior agreed upon by the patient/family and SCD provider. We currently are calculating morphine equivalents and hypothesize total opioid utilization will be concomitantly decreased due to this significantly decreased length of hospitalization.