National Heart, Lung, And Blood Institute Research Articles

A New Phen X Collection: Sickle Cell Disease Psychosocial and Social Determinants of Health Protocols

Background: The PhenX (Phenotypes and eXposures) Toolkit (https://www.phenxtoolkit.org) is a web-based catalog of recommended measurement protocols and associated bioinformatics tools to assist with study design and facilitate cross-study data integration and analyses. The PhenX Toolkit currently includes measurement protocols from 29 research domains (e.g., Rare Genetic Conditions) and six collections that add depth to the Toolkit (e.g., Blood Sciences Research) and has over 4,200 registered users. Although an established resource that continues to expand content for investigators, the PhenX Toolkit does not currently contain measurement protocols specific to Sickle Cell Disease (SCD) Psychosocial or Social Determinants of Health (SDoH) outcomes. These outcomes were identified as key indicators by the National Academies of Sciences, Engineering and Medicine 2020 Report "Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action.” This effort is supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) through co-funding to the "PhenX Toolkit-Expansion and Sustainability” project award. Methods: PhenX protocols are recommended by domain experts using a consensus-based process that includes scientific community input. To identify protocols for the new collection, the PhenX SCD Research and Scientific Panel (SRSP) provided a list of scope elements for consideration and selected investigators with relevant expertise in psychology, behavioral science, hematology, and nursing to form a Psychosocial and SDoH Working Group (WG). A modified Delphi process was used to develop consensus on the topics and protocols. A set of 18 scope elements was initially developed and distributed to the WG (round 1). In round 2, preliminary consensus was reached on 12 topics via a virtual WG meeting. In round 3, WG members virtually presented background and recommendations for measurement protocols for the 12 topics and discussed these and other related protocols already included in the PhenX Toolkit. Consensus was reached on 12 primary protocols to move to the next phase, community outreach. Preliminary protocols will be shared with the scientific community for a 2-week period in which the community will have the opportunity to review and comment on the proposed protocols. The Psychosocial and SDoH WG will consider the outreach feedback in selecting final protocols to include in the SCD Research Collections. Results: The 12 measurement protocols recommended to-date include transition readiness (e.g., Sickle Cell Transition Intervention Program - Readiness for Transition (TIP-RFT)), self-management, impact of early aging (e.g., reactions to loss), stigma, trust in medical care and research, resilience, spirituality, and responses to stress. Some measures include multiple versions (e.g., parent/caregiver, child, adolescent, adult). Another 7 protocols were suggested as appropriate for supplemental information for this collection (e.g., American Society of Hematology Sickle Cell Disease Transition Readiness Assessment). Conclusion: This presentation will review the outreach data and the final recommendations of the WG and SRSP. These additional protocols will enhance the existing SCD Research Collections and the individual and structural SDoH protocols in the PhenX Toolkit. Furthermore, these recommendations will promote the use of valid and reliable measurement tools to investigate psychosocial constructs and social determinants of health in SCD. Funding was provided by a Genomic Research Grant (U41HG007050) from NHGRI, with current or prior funding support from the National Institute on Drug Abuse (NIDA); Office of Behavioral and Social Sciences Research (OBSSR); National Institute of Mental Health (NIMH); National Heart, Lung, and Blood Institute (NHLBI); National Institute on Minority Health and Health Disparities (NIMHD); and Tobacco Regulatory Science Program (TRSP).

Exploration of Menarche, Dietary Iron, and Additional Risk Factors on the Development of Iron Deficiency in Adolescent Girls

Background: Iron deficiency (ID) is estimated to affect between 9 and 16% of adolescent girls in the United States. It occurs during a critical time of increased iron demands related to blood volume expansion, muscle mass increase, and menstrual blood loss. Black girls are disproportionately affected, likely due to social determinants of health. ID is associated with decreased cognitive function, exercise capacity, and fatigue. Unrecognized ID can progress to complications of severe anemia. Despite readily available therapies including both oral and intravenous iron, no universal screening recommendations or evidence-based prediction tools exist to identify adolescent girls at risk for ID. Our objective was to determine the prevalence of, timing of, and clinical risk factors for ID in a large, biracial cohort of adolescent girls. Methods: Existing clinical data and stored serum specimens were obtained from the National Heart Lung and Blood Institute (NHLBI) Growth and Health Study (NGHS). The NGHS was a 10-year longitudinal study initiated in 1985 that enrolled 2,379 girls (51% Black, 49% White) from three cities (San Francisco, Cincinnati, Washington DC). Subjects participated in annual visits with serum samples obtained at Years 1, 3, 5, 7, and 10 with a retention rate of 89% at the 10th annual visit. Clinical data included socioeconomic data, body mass index (BMI), age at menarche, menstrual and pregnancy history, use of oral contraceptive medications, and dietary iron intake. We hypothesized that >10% of NGHS subjects would meet criteria for ID. We further hypothesized that longer duration from onset of menarche, low dietary iron intake, history of pregnancy, and obesity (defined as BMI >30) would be associated with ID. Available serum samples at Year 10 (n=692) were analyzed with Q-Plex Human Micronutrient Array ELISA kits (Quansys Biosciences) to measure iron-related parameters including serum ferritin, soluble transferrin receptor (sTfR1), sTfR1:ferritin index, and C-reactive protein. Subjects with ferritin >150 ng/mL and CRP >5 mg/L were excluded. ID was defined as serum ferritin <15 ng/mL, sTfR1 >5 mg/L, and sTfR1:ferritin index >2. Univariate logistic regression models assessed for the association of ID with established clinical risk factors. Results: Clinical and laboratory data from 510 subjects were included in the final analysis (median age 19 years, 51.4% Black). Of those, 83 (n=16.3%) were found to be iron deficient. ID was not associated with racial group, poverty threshold, BMI, age at menarche, history of pregnancy, oral contraceptive pill use, or average daily iron intake (TABLE). Subjects with later onset of menarche tended to have lower ferritin (OR 1.27 [1.05-1.54], p<0.015, FIGURE). Conclusion: The prevalence of ID in subjects 18 to 19 years of age enrolled in the NGHS was consistent with higher values of previously published prevalence estimates in adolescent girls. Established risk factors for the development of ID, such as earlier onset of menarche, were not clearly associated with ID in this cohort. These findings suggest that universal screening, rather than targeted screening, may be important for the early identification of all girls with ID. Additional clinical data and serum samples from Years 5 and 7 of the NGHS will be obtained to determine the prevalence of ID in the same cohort of subjects at earlier ages and determine changes in iron status over time. The results from this study will inform the development of a risk prediction tool as well as evidenced-based screening recommendations for ID in adolescent girls. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Dissemination and Implementation Looking at the Care Environment (DISPLACE) Study Evaluates Novel Interventions to Improve TCD (Sickle Stroke Screening) Implementation

Background: Stroke is a devastating complication of sickle cell anemia (SCA). The STOP (Stroke Prevention Trial in Sickle Cell Anemia) protocol was adopted in 2014 by the National Heart Lung and Blood Institute (NHLBI) guidelines for stroke-risk screening using transcranial Doppler ultrasound (TCD) and prevention with chronic red cell transfusion therapy (CRCT). These guidelines were upheld in the recent American Society of Hematology guidelines. Despite strong evidence supporting TCD screening (and CRCT initiation) in stroke prevention, wide scale implementation has not been achieved 4. DISPLACE (Dissemination and Implementation Looking at the Care Environment) is a multicenter, NHLBI-funded study conducted to identify barriers to TCD implementation and test novel methods for improving outcomes. DISPLACE is a 3-part study: 1) Retrospective assessment of current practice; 2) Assessment of barriers and facilitators; and 3) Implementation trial to improve TCD screening. This report focuses on Part 3. Methods: DISPLACE is a 28-center consortium across the US representing a range of: region (urban vs rural), size, and institution type (academic vs community). During Part 1, sites performed a rigorous retrospective chart review of children with SCA aged 2-16 years from 2012-2016 to collect baseline TCD rates. Part 2 included a rigorous mixed methods of the barriers and facilitators assessment to TCD screening was performed that resulted in 3 main interventions: 1.Re-branding TCD as Sickle Stroke Screen, a meaningful name selected by patients/families with SCD; 2. A Single Coordinator (SC) for each site's TCD screening, scheduling, and follow-up; 3. A newly designed application, Provider Minder (trademarked; PM). PMwas created to remind providers of patient appointments (versus reminders only sent to patients/families). Data entry in PM included birth date (to calculate age), city/state of residence, distance from SCD clinic and insurance. Date of last TCD was recorded to calculate date of next screen. When the TCD was due, the system alerted the provider to enter appointment completion or reason(s) why it was missed. TCD results were entered for PM to prompt for the next TCD date in a 10-14 month window (normal screens), 2-6 weeks (conditional screens), and intervention plan (abnormal screens): repeat scan in <2 weeks or other. If the provider failed to enter a patient's result, PM alerted the provider q3 days until the TCD was recorded as completed/rescheduled. Part 3 included 16 sites who successfully completed data entry in Part 1 and had the lowest TCD implementation rates. Part 3 inclusion criteria were the same as Part 1 except to specifically select children with SCA now aged 2-7 (the highest risk group to have an abnormal TCD in Part 1). All 28 sites received re-branding educational material (also disseminated to non-study sites). Cluster randomization was used to allocate sites to PM (8 sites) or PM + SC (8 sites). The primary outcome is which intervention results in the best TCD rates. Secondary outcomes include Part 3 sites’ improvement in TCD rates (compared to historical rates) and impact of the educational/rebranding of TCD to "Sickle Stroke Screen” in sites (4) that did not participate in Part 3. Stroke status, presence of CRCT after an abnormal TCD, missed TCD appointments, and medical decisions following TCD were also recorded. Results: Part 1 included 28 centers with 5223 individuals with SCA in the database. Of the 16 Part 3 sites, three could not implement the interventions due to a simultaneous change in hospital administration and site PI (1), inability to use PM due to institutional firewall (1) and inability to implement due to site specific issues (1). These 3 sites remained in the study as "control sites” and a fourth control site was added. Thus, 13 sites implemented the interventions with 877 patients; 520 were in sites using PM and 357 were in sites using PM+SC. Demographic data for the 877 children with SCA are in Table 1. The study ended on May 31, 2022. Calculations of TCD rates at all sites are in process and will be presented. Conclusions: Despite the benefit of TCD screening in children with SCA, guideline-based implementation remains poor. The range of barriers to screening has been previously reported by the DISPLACE study team and were used to design the study interventions. Results from this study will guide optimization of the intervention protocol proven to enhance TCD implementation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Optimizing Shared Decision Making about Hydroxyurea in Young Children with Sickle Cell Anemia

Introduction: The National Heart, Lung, and Blood Institute (NHLBI) recommends hydroxyurea (HU) be offered to all children with sickle cell anemia (SCA) age >9 months via shared decision-making (SDM). However, HU remains underutilized, largely due to parental concerns about safety and potential long-term effects. SDM was recommended because it can decrease parental uncertainty as families clarify their values/preferences and understand scientific evidence about HU. Funded by the Patient-Centered Outcomes Research Institute (PCORI), the Engage HU study (NCT03442114) compared two methods for optimizing SDM for HU in young children with SCA: the American Society of Hematology's (ASH) HU clinician pocket guide (usual care condition) and a HU SDM toolkit (toolkit condition) created by the research team. This study aimed to compare the impact of these on caregiver decisional uncertainty and caregiver perception of clinician use of SDM. Methods: Engage HU was a prospective, multi-site intervention trial with a unidirectional crossover design in which each clinic began enrolling in the usual care condition and then one-by-one crossed over to the toolkit condition. Inclusion criteria included children ages 0-5 years followed at 12 SCA centers in the US who were candidates for HU and whose caregivers had not decided about HU therapy within 3 months prior to enrollment. After receiving a flyer/letter, eligible caregivers were approached in clinic or by phone. Caregivers completed an e-consent form. Study visits were conducted in-person or via telehealth. Primary endpoints were caregiver decisional uncertainty (Decisional Conflict Scale-DCS) and caregiver perception of clinician use of SDM (Dyadic OPTION scale-OPTION). Lower scores on the DCS indicate less decisional uncertainty and higher scores on the OPTION indicate that the clinician demonstrated more SDM behaviors (e.g., asked about caregiver preferences/values). All survey data were collected using paper surveys or electronically via REDCap™. Data were analyzed using linear regression models in Stata version 17 for each main outcome of interest (DCS and OPTION Total Scores). Our primary predictor was group (toolkit versus usual care). The model was estimated using full information maximum likelihood estimation on the full analysis sample (N=132) to account for missing data. We also accounted for site-level variation, when the sites crossed from usual care to toolkit (i.e., the cluster), when data were collected (0=pre-COVID, 1=during COVID), and the impact of COVID-19 on caregivers (assessed using the COVID-19 Exposure and Family Impact Survey [CEFIS]). Results: A total of 176 caregivers of eligible children consented. Twelve SCA clinical sites participated; however, four sites were terminated early due to staff turnover or low accrual. Mean caregiver age was 30.19 (SD=6.97); most identified as female (93.1%), Black/African American (89.3%), or Mixed race (6.1%), and mothers (90.8%). Most children had HbSS (94.7%). Preliminary analyses were conducted on 132 caregivers with complete data (n=85 Usual Care; n=47 Toolkit). Regression analyses showed that participants in the toolkit condition had significantly lower DCS Total scores (i.e., lower decisional conflict) than those in usual care condition (b=-7.33, 95% CI=-13.3 to 1.31, p=.017). In addition, significant differences were found on the DCS subscales (see Table 1). Similarly, participants in the toolkit condition had significantly higher OPTION Total scores (i.e., parents reported that the clinician exhibited more SDM behaviors) than those in usual care (b=2.38, 95% CI=0.44 to 4.34, p=.016). Conclusions: Use of the HU toolkit compared to the usual care approach significantly improved SDM between providers and caregivers of children with SCA; however, given site team turnover, lower than expected accrual, and study interruption due to the COVID-19 pandemic, additional research is needed to confirm these preliminary findings. Future studies should also seek to identify context-specific factors (e.g., clinic processes) that are key to successful implementation of SDM with both younger and older children with SCA. This project was supported by an award fromPCORI contract number CDR-1609-36055 (PI: Crosby).Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Mortality in Adults with Sickle Cell Disease: Results from the Sickle Cell Disease Implementation Consortium (SCDIC) Registry

Background. The Sickle Cell Disease Implementation Consortium (SCDIC) was funded at eight sites in the United States by the National Heart Lung and Blood Institute (NHLBI) in 2016 to use implementation science to identify and address barriers to quality care in adolescents and adults with Sickle Cell Disease (SCD). As part of the SCDIC, the centers developed a SCD registry including 2444 persons (~300/site) ages 15-45 years at time of consent. To better understand the cause of death in adults living with SCD, this project assessed clinical co-morbidities among the enrolled adolescents and adults to identify causes of mortality and evaluate whether there are any identifiable clinical phenotypes at enrollment that would predict decreased survival. Methods. At enrollment, data were collected, including patient reported demographics, and from the medical record: SCD phenotype, baseline laboratory values, comorbidities, and medication usage. Patient reported outcome (PRO) data were also collected regarding pain and quality of life. Mortality data were obtained for 84 adults who were enrolled since 2016 in the SCDIC registry. Subjects were followed for a median of 1.76 years. The relationship of clinical co-morbidities to mortality was determined using logistic regression after adjusting for SCD phenotype and age group. Specifically, a separate model was run for each co-morbidity, with SCD phenotype, age group, and the co-morbidity being retained in the model, regardless of significance. Summary statistics were calculated, including frequency and percentage for categorical variables and mean, standard deviation, median, and interquartile range (IQR) for continuous variables. Age was evaluated as a continuous and as a categorical variable (15-24, 25-34, 35-45 years). Results. A total of 2,444 registry participants were included for analysis. Eighty-four patients died over the course of the registry data collection (2017-2022), but six deaths were caused by trauma and were removed from further analysis. Baseline characteristics of the other 78 individuals who died (n=78, 3.2%) and those who are last known to be alive (n=2,360, 96.8%) are presented in Table 1. Several co-morbidities increase the odds of death, after adjusting for genotype and age group Table 2. These include, avascular necrosis in any joint (OR [95% CI], 1.87 [1.101-3.197]), chronic kidney disease (OR [95% CI], 2.14 [1.142-3.867]), end stage renal disease (OR [95% CI], 5.95 [1.856-16.249]), pulmonary arterial hypertension (OR [95% CI], 2.41 [1.385-4.124]), sarcoidosis (OR [95% CI], 18.61 [4.191-82.986]), iron overload (OR [95% CI], 2.95 [1.691-5.348]), chronic refractory pain (OR [95% CI], 2.07 [1.183-3.661]), anxiety (OR [95% CI], 2.05 [1.162-3.523]), depression (OR [95% CI], 2.02 [1.179-3.449]), and increased acute care utilization >10 hospitalizations in year prior to enrollment: 6.48 [2.400-16.998]; >10 visits to day-hospital/infusion center in year prior to enrollment: 5.11 [2.287-12.527]). Importantly, chronic pain, anxiety and depression were reported from the patient's past medical history and not abstracted from the PRO. Current use of hydroxyurea was not significant for the total study population (deaths vs survivors, p=0.0948). Among those who died, use of hydroxyurea was also non-significant for SCD phenotype [Hb SS vs Hb SC: p=0.0758 (current use), 1.000 (use within a year of death)]. Conclusion. SCD continues to reduce life expectancy for affected individuals. These findings support that clinicians and researchers still have much work to do in providing comprehensive and supportive care to prevent end-organ damage, comorbidities and SCD complications that are associated with decreased survival. These data also continue to demonstrate the need for improved mental health resources for this population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinical response to lifestyle counseling for dyslipidemia and elevated blood pressure in childhood cancer survivors.

Childhood cancer survivors (CCS) have increased risk of premature cardiovascular disease. Whether they respond similarly to lifestyle changes for elevated blood pressure (BP), body mass index (BMI), and dyslipidemia to those without history of childhood cancer is unknown. This retrospective cohort study included CCS and 3:1 age- and sex-matched controls treated at Boston Children's Hospital Preventive Cardiology (2010-2019) using lifestyle management based on National Heart, Lung, and Blood Institute (NHLBI) guidelines. Change in BMI, BP, and lipids were analyzed. We included 52 CCS and 162 controls with a median age of approximately 16years. More CCS (84.3%) had elevated baseline fasting triglycerides (TG) than controls (49.4%) (p < .001). More CCS (62.5%) also had abnormal baseline high-density lipoprotein cholesterol (HDL-C) compared to controls (35.2%) (p = .001). Baseline BMI, BP, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were similar between groups. Over 15weeks [IQR: 10.5-26], CCS had greater decrease in TG than controls (72.5 vs. 17mg/dl decrease, p = .095). BP improved in 5% of CCS versus 38% of controls (p = .008). For both, BMI, TC, LDL-C, and HDL-C remained stable. CCS with stem cell transplantation (SCT) had a TC increase of 5% (6mg/dl) compared to a decrease of 9% (19mg/dl) among CCS without SCT (p = .02). CCS demonstrated similar improvement in lipids, but impaired BP lowering in response to lifestyle management compared to controls. Further prospective studies are needed to determine if earlier pharmaceutical treatment is warranted in this higher risk population and for the long-term risk reductions of these approaches.

Application of machine learning to identify top determinants of fibrofatty plaque burden by CCTA in humans with psoriasis

Abstract Introduction Fibrofatty plaque burden (FFB) is a high-risk, vulnerable plaque feature comprised of an atheromatous core and fibrous cap with increased risk of coronary artery disease (CAD) [1]. Psoriasis (PSO) is a chronic inflammatory disease linked with atherosclerotic risk and premature cardiovascular disease, driven in part by vulnerable plaque rupture [2,3]. Machine learning (ML) previously showed the prognostic value of FFB in predicting 5-year risk of cardiac-related mortality in patients with CAD [4]. Whether ML can predict FFB in psoriasis is understudied. Purpose To use ML to identify top determinants of FFB by CCTA in PSO. Methods 320 consecutive participants with psoriasis were recruited as part of an ongoing cohort study, of whom 307 had FFB analyzed with coronary computed tomography angiography (CCTA) and quantified by QAngio CT (Medis, The Netherlands). 140 out of 182 potential determinants were subjected to ML algorithms analyzed by random forest and validated by 5-fold cross validation to select the top determinants based on R-square criteria. Lipid concentration and size were measured by nuclear magnetic resonance (NMR) and sdLDL-C was calculated by Sampson's formula. Results The top 21 determinants of FFB at baseline were grouped into 3 categories: cardiometabolic risk factors (BMI, sex, DBP, mean arterial pressure, exercise, heart rate, glucose, anxiety, psoriasis disease duration), clinical measurements (basophils, platelets, hemoglobin, RBC, alkaline phosphatase, ALT, creatinine, neutrophil-to-lymphocyte ratio), and lipoproteins (LDL particle size, apolipoprotein A1, apolipoprotein B-to-A1 ratio, calculated sdLDL-C). Conclusion ML confirmed that FFB strongly correlates with cardiometabolic risk factors, clinical measurements, and lipoproteins. Further investigations into these top determinants of FFB over time may provide insight into potential therapeutic interventions that decrease cardiovascular risk in patients with chronic inflammatory diseases and should be validated in larger studies. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): This study was supported by the National Heart, Lung and Blood Institute (NHLBI) IntramuralResearch Program (ZIA-HL-06193). This research was made possible through the NIH MedicalResearch Scholars Program, a public-private partnership supported jointly by the NIH andcontributions to the Foundation for the NIH from the Doris Duke Charitable Foundation,Genentech, the American Association for Dental Research, the Colgate-Palmolive Company, andother private donors.

Editorial introductions.

Editorial introductions.

Meeting the Challenges of Myocarditis: New Opportunities for Prevention, Detection, and Intervention-A Report from the 2021 National Heart, Lung, and Blood Institute Workshop.

The National Heart, Lung, and Blood Institute (NHLBI) convened a workshop of international experts to discuss new research opportunities for the prevention, detection, and intervention of myocarditis in May 2021. These experts reviewed the current state of science and identified key gaps and opportunities in basic, diagnostic, translational, and therapeutic frontiers to guide future research in myocarditis. In addition to addressing community-acquired myocarditis, the workshop also focused on emerging causes of myocarditis including immune checkpoint inhibitors and SARS-CoV-2 related myocardial injuries and considered the use of systems biology and artificial intelligence methodologies to define workflows to identify novel mechanisms of disease and new therapeutic targets. A new priority is the investigation of the relationship between social determinants of health (SDoH), including race and economic status, and inflammatory response and outcomes in myocarditis. The result is a proposal for the reclassification of myocarditis that integrates the latest knowledge of immunological pathogenesis to refine estimates of prognosis and target pathway-specific treatments.

A Quality Improvement Initiative to Decrease Time to Analgesia in Patients With Sickle Cell and Vaso-Occlusive Crisis: A Population With Disparities in Treatment.

Introduction: Vaso-occlusive crises (VOCs) are the leading cause of emergency department (ED) visits and hospitalizations in patients with sickle cell disease (SCD). Timely administration of analgesia, within 60 minutes of patient registration, is the standard of care for SCD patients with VOCs. Patients with VOCs have longer times to initial analgesia compared to similar painful conditions. The primary aim of the project is to have 75% of patients with VOCs receive initial analgesia within 60 minutes of being registered, the current recommended time frame from the National Heart, Lung, and Blood Institute (NHLBI).Methods: A multi-disciplinary team used quality improvement (QI) methodology to develop a plan involving multiple Plan-Do-Study-Act (PDSA) cycles. A rapid evaluation process was employed which included notification of a patient with a VOC being placed in a room, rapid evaluation by all team members and use of an electronic order set.Results: The aim was met 72% of the time during our intervention period, compared to 17% pre-intervention. Average time to initial analgesia was decreased from 61 minutes to 42 minutes (p-value < 0.001), while time to disposition was also decreased when time goals were achieved.Conclusion: Using a rapid evaluation process we were able to decrease time to initial analgesia in a patient population that has previously experienced delays in care and decrease overall time to disposition.

Functional, imaging, and respiratory evaluation (FIRE) of patients post-hospitalization for COVID-19: protocol for a pilot observational study

IntroductionWe describe a protocol for FIRE CORAL, an observational cohort study that examines the recovery from COVID-19 disease following acute hospitalization with an emphasis on functional, imaging, and respiratory evaluation.Methods and analysisFIRE CORAL is a multicenter prospective cohort study of participants recovering from COVID-19 disease with in-person follow-up for functional and pulmonary phenotyping conducted by the National Heart, Lung and Blood Institute (NHLBI) Prevention and Early Treatment of Acute Lung Injury (PETAL) Network. FIRE CORAL will include a subset of participants enrolled in Biology and Longitudinal Epidemiology of PETAL COVID-19 Observational Study (BLUE CORAL), an NHLBI-funded prospective cohort study describing the clinical characteristics, treatments, biology, and outcomes of hospitalized patients with COVID-19 across the PETAL Network. FIRE CORAL consists of a battery of in-person assessments objectively measuring pulmonary function, abnormalities on lung imaging, physical functional status, and biospecimen analyses. Participants will attend and perform initial in-person testing at 3 to 9 months after hospitalization. The primary objective of the study is to determine the feasibility of longitudinal assessments investigating multiple domains of recovery from COVID-19. Secondarily, we will perform descriptive statistics, including the prevalence and characterization of abnormalities on pulmonary function, chest imaging, and functional status. We will also identify potential clinical and biologic factors that predict recovery or the occurrence of persistent impairment of pulmonary function, chest imaging, and functional status.Ethics and disseminationFIRE CORAL is approved via the Vanderbilt University central institutional review board (IRB) and via reliance agreement with the site IRBs. Results will be disseminated via the writing group for the protocol committee and reviewed by the PETAL Network publications committee prior to publication. Data obtained via the study will subsequently be made publicly available via NHLBI’s biorepository.Strengths and limitations of the studyStrengths:First US-based multicenter cohort of pulmonary and functional outcomes in patients previously hospitalized for COVID-19 infectionLongitudinal biospecimen measurement allowing for biologic phenotyping of abnormalitiesGeographically diverse cohort allowing for a more generalizable understanding of post-COVID pulmonary sequelaLimitations:Selected cohort given proximity to a participating centerSmall cohort which may be underpowered to identify small changes in pulmonary function

Perspectives: on Precision Nutrition Research in Heart, Lung, and Blood Diseases and Sleep Disorders

The release of the 2020-2030 Strategic Plan for NIH Nutrition Research (SPNR) and its emphasis on precision nutrition has provided an opportunity to identify future nutrition research that addresses individual variability in response to diet and nutrition across the life span-including those relevant to the Strategic Vision of the National Heart, Lung, and Blood Institute (NHLBI). The SPNR and the NHLBI's Strategic Vision were developed with extensive input from the extramural research community, and both have 4 overarching strategic goals within which are embedded several objectives for research. For the SPNR, these include 1) spur discovery science and normal biological functions (e.g., role of the microbiome in health and disease), 2) population science to understand individual differences (e.g., biomarkers including 'omics that predict disease status), 3) emerging scientific areas of investigation and their application (e.g., data science, artificial intelligence), and 4) cross-cutting themes (e.g., training the scientific workforce and minority health and health disparities). These strategic goals and objectives serve as blueprints for research and training. Nutrition remains important in the prevention and treatment of heart, lung, blood, and sleep (HLBS) disorders and diseases, and the NHLBI has played a pivotal role in supporting nutrition research. In this paper, we report important gaps in the scientific literature related to precision nutrition in HLBS diseases. Research opportunities that could stimulate precision nutrition and their alignment with the SPNR and the NHLBI Strategic Vision Objectives are provided. These opportunities include 1) exploring individual differences in response to varying dietary patterns and nutrients; 2) investigating genetic/epigenetic, biological (e.g., microbiome, biomarkers), social, psychosocial, and environmental underpinnings of individual variability in diet; 3) elucidating the role of circadian rhythm and chrononutrition; and 4) applying implementation science research methods in precision nutrition interventions relevant to HLBS diseases.

Development and Utilization of a Diagnostic Support Tool for Asthma within the Electronic Medical Record.

Asthma in childhood is a common and costly chronic disease. Quality asthma care can lead to better control of asthma thus decreasing use of health services. The gold standard for pediatric asthma diagnosis and management is the National Heart, Lung and Blood Institute (NHLBI) guidelines for Diagnosis and Management of Asthma which center on precisely establishing the severity of asthma, as this precise classification delineates appropriate therapy. However, navigating these guidelines is a challenge for primary care providers that creates a barrier to providing quality care. We aim to improve precision in asthma severity classification in the community healthcare setting through the development of an electronic asthma decision support tool (eADST) incorporating NHLBI guidelines embedded within the electronic health record system. We developed an algorithm for the eADST to guide the health care provider to the appropriate classification and subsequent therapy. We engaged our health system's electronic health record informatics team and together developed and revised the tool. We launched the tool in three academic community clinics and measured precision in asthma classification in the twelve months prior to the availability of the tool and the twelve months following the launch. We found a significant improvement in precision of asthma severity classification following the launch, a necessary first step in improvement of asthma care. The next step will be to evaluate the impact of the tool on asthma outcomes.

Implementation Of Hypertension Management Program In The Work Area Of The Ri Sidomulyo Puskesmas Pekanbaru City 2022

Hypertension is an increase in systolic blood pressure 140 mmHg and diastolic blood pressure ≧90 mmHg. In addition, in primary medical practice hypertension is one of the most common diseases found. The National Heart, Lung, and Blood Institute (NHLBI) believes that one in three patients has hypertension. This study aims to find out how the implementation of the hypertension management program in the working area of the RI Sidomulyo Public Health Center in 2022. This research was conducted using a qualitative descriptive research design with in-depth interviews, observation and document tracking methods, to 5 informants consisting of the Head of the Public Health Center, the Person in Charge of the PTM Program , Head of Administration, Doctors, and Nurses. This research was carried out in Mei 2022 at the Indonesian Health Center Sidomulyo Pekanbaru City. The results of this study indicate that human resources are adequate but the coordination and cross-programme are not running well. Facilities and infrastructure are still inadequate, such as the unavailability of a technical guidebook for the discovery and management of hypertension and no instructions for implementing the hypertension program. covid-19, in addition to the puskesmas itself, the visit, judging from the achievements, the SPM is not too good, because many people are lazy to seek treatment and do not care about their health and the implementation of the PTM Posbindu in the Implementation of the Hypertension Management Program in the Work Area of the Indonesian Health Center Sidomulyo was known before the pandemic Covid-19 activities at the Posbindu implementation have been going well, but during the pandemic the activities did not run and were not optimal, apart from the lack of Posbindu.

Global Predictors of COVID-19 Vaccine Hesitancy: A Systematic Review.

Background: vaccine hesitancy is defined as a delay in the acceptance or refusal of vaccination, even though immunisation is a determinant in reducing the mortality and morbidity associated with Coronavirus Disease 2019 (COVID-19). Aim: to identify and analyse the predictors of COVID-19 vaccine acceptance and/or hesitancy. Methods: a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Keywords: vaccine and (COVID or SARS) and (acceptance or acceptability or willingness or hesitancy or refusal) and (multivariate or regression) and (questionnaire or survey) and national. Databases/resources: PubMed, DOAJ, SciELO and b-on. Timeframe: March 2020–2022. Inclusion criteria: general population, questionnaire-based, calculation of a multivariate regression model and national studies. Quality assessment: application of the National Heart, Lung, and Blood institute (NHLBI) tool. Results: a total of 37 studies were selected, whose overall rate was fair. The most predominant predictors of vaccine hesitancy were a lower perceived risk of getting infected, a lower level of institutional trust, not being vaccinated against influenza, lower levels of perceived severity of COVID-19, or stronger beliefs that the vaccination would cause side effects or be unsafe. Discussion and conclusion: the identified predictors can be used to design tailored health policies and/or public health interventions, or to evaluate subjects’ vaccine hesitancy.

Outcomes of the National Heart, Lung, and Blood Institute K12 program in emergency care research: 7-year follow-up.

Long-term follow-up for clinician-scientist training programs is sparse. We describe the outcomes of clinician-scientist scholars in the National Heart Lung and Blood Institute (NHLBI) K12 program in emergency care research up to 8.7 years after matriculation in the program. This was a cohort study of faculty clinician-scientist scholars enrolled in a NHLBI K12 research training program at 6 sites across the US, with median follow-up 7.7 years (range 5.7-8.7 years) from the date of matriculation. Scholars completed electronic surveys in 2017 and 2019, with the 2019 survey collecting information for their current work setting, percent time for research, and grant funding from all sources. We used NIH RePorter and online resources to verify federal grants through March 2021. The primary outcome was a funded career development award (CDA) or research project grant (RPG) where the scholar was principal investigator. We included funding from all federal sources and national foundations. There were 43 scholars, including 16 (37%) women. Over the follow-up period, 32 (74%) received an individual CDA or RPG, with a median of 36 months (range 9-83 months) after entering the program. Of the 43 scholars, 23 (54%) received a CDA and 22 (51%) received an RPG, 7 (16%) of which were R01s. Of the 23 scholars who received a CDA, 13 (56%) subsequently had an RPG funded. Time to CDA or RPG did not differ by sex (women vs. men log-rank test p=0.27) or specialty training (emergency medicine versus other specialties, p=0.59). After 7 years of follow-up for this NHLBI K12 emergency care research training program, three quarters of clinician-scientist scholars had obtained CDA or RPG funding, with no notable differences by sex or clinical training.

Acute kidney injury following multisystem inflammatory syndrome associated with SARS-CoV-2 infection in children: a systematic review and meta-analysis.

IntroductionMultisystem inflammatory syndrome (MIS-C) is a rare paediatric hyper-inflammatory disorder that occurs following SARS-CoV-2 infection. Acute kidney injury (AKI) occurs in approximately one-quarter to one-third of the patients with MIS-C and is associated with poor prognosis in critically ill children. This systematic review is aimed to evaluate the incidence of AKI, mortality, and the need for kidney replacement therapy (KRT) in patients with MIS-C.MethodsWe searched databases from Medline, EMBASE, Cochrane Register, and Google Scholar from December 2019 to December 2021 with our search strategy. Studies meeting the following criteria were included in this systematic review: (1) articles on AKI in MIS-C; (2) studies providing AKI in MIS-C and COVID-19 infection separately; (3) studies reporting outcomes such as mortality, KRT, serum creatinine; length of hospital/ICU stay.Quality assessmentThe quality of the included studies was independently assessed by using the National Heart Lung and Blood Institute (NHLBI) quality assessment tool for cohort studies and case series.Statistical analysisOutcomes and their 95% confidence intervals (CI) were reported if a meta-analysis of these outcomes was conducted. Heterogeneity was reported using I2 statistics, and heterogeneity ≥ 50% was considered high. We used Baujat’s plot for the contribution of each study toward overall heterogeneity. In sensitivity analysis, the summary estimates were assessed by repeating meta-analysis after omitting one study at a time. Forest plots were used for reporting outcomes in each study and with their 95% CI. All statistical tests were performed using R software version 4.0.3.Results A total of 24 studies were included in this systematic review and of these, 11 were included in the meta-analysis. The pooled proportion of patients with MIS-C developing AKI was 20% (95% CI: 14–28%, I2 = 80%). Pooled proportion of death in children with MIS-C was 4% (95% CI: 1–14%; I2 = 93%). The odds of death in patients with AKI were 4.68 times higher than in patients without AKI (95% CI: 1.06–20.7%; I2 = 17%). The overall pooled proportion of MIS-C-induced AKI patients requiring KRT was 15% (95% CI: 4–42%; I2 = 91%).ConclusionApproximately one-fifth of children with MIS-C develop AKI which is associated with higher odds of death.PROSPERO registration: CRD42022306170Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary informationSupplementary InformationThe online version contains supplementary material available at 10.1007/s00467-022-05701-3.

Sustaining capacity building and evidence-based NCD intervention implementation: Perspectives from the GRIT consortium.

Implementation science has been primarily focused on adoption of evidence-based interventions, and less so on sustainability, creating a gap in the field. The Global Research on Implementation and Translation Science (GRIT) Consortium is funded by the National Heart Lung and Blood Institute (NHBLI) to support the planning, implementation, and sustainability of Late-Stage Phase 4 Translational Research (T4TR) and capacity building for NCD prevention and control in eight low-and middle-income countries (LMICs). This paper highlights perspectives, including barriers, facilitators, opportunities, and motivators for sustaining capacity building and evidence-based hypertension interventions within LMICs. Guided by the Capacity, Opportunity, Motivation, Behavior (COM-B) Model, this study surveyed GRIT consortium members on the barriers, facilitators, key motivators, and opportunities for sustaining capacity building and evidence-based hypertension interventions in LMICs. Thematic analysis was used to identify themes and patterns across responses. Twenty-five consortium members across all eight sites and from various research levels responded to the survey. Overarching themes identifying facilitators, key motivators and opportunities for sustainability included: (1) access to structured and continuous training and mentorship; (2) project integration with existing systems (i.e., political systems and health systems); (3) adaption to the local context of studies (i.e., accounting for policies, resources, and utilizing stakeholder engagement); and (4) development of interventions with decision makers and implementers. Barriers to sustainability included local policies and lack of infrastructure, unreliable access to hypertension medications, and lack of sufficient staff, time, and funding. Sustainability is an important implementation outcome to address in public health interventions, particularly as it pertains to the success of these initiatives. This study provides perspectives on the sustainability of NCD interventions with a focus on mitigating their NCD burden in LMICs. Addressing multilevel factors that influence the sustainability of capacity building and interventions will have notable implications for other global NCD efforts going forward. Current and future studies, as well as consortium networks, should account for sustainability barriers outlined as it will strengthen program implementation, and long-term outcomes.

Understanding the Updates in the Asthma Guidelines.

Asthma is a chronic inflammatory lung disease that affects millions of Americans, with variable symptoms of bronchospasm and obstruction among individuals over time. The National Heart, Lung, and Blood Institute (NHLBI) published the 2020 Focused Updates to the Asthma Management Guidelines based on the latest research since the 2007 Expert Panel Report-3 (EPR-3). The following article reviews the 21 new recommendations on the six core topics in asthma: use of intermittent inhaled corticosteroids, long-acting muscarinic antagonist therapy, use of the fractional exhaled nitric oxide test in asthma diagnosis and monitoring, indoor allergen mitigation, immunotherapy, and bronchial thermoplasty. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate recommendations as strong or conditional based on the evidence. The recommendations were based on systematic reviews of the literature and focused on patient-centered critical outcomes of asthma exacerbations, asthma control, and asthma-related quality of life. Understanding the recommendations with consideration of individual values through shared decision-making may improve asthma outcomes.

A Portfolio Analysis of Nutritional Biomarkers in NIH- and NHLBI-funded Research, 2008–2020

ObjectivesNutrition biomarkers are important in elucidating disease risks and severity, as surrogate markers of nutritional status, and provide objective measures of dietary intake. This study analyzed grants that investigated nutritional biomarkers and were funded between 2008 and 2020 by the National Heart, Lung, and Blood Institute (NHLBI) and across the National Institutes of Health (NIH). MethodsData were extracted using the NIH iSearch portfolio analysis platform to curate grant applications to the NIH and NHLBI. Keywords included nutrition or diet, followed by omics, metabolomics, lipidomics, proteomics, transcriptomics, genomics, and epigenomics. Funded and unfunded nutri-omics grants were separated and examined for keywords for total expenditures, Research, Condition, and Disease Categorization (RCDC) categories, administering Institute, fiscal year, Early-Stage Investigator eligibility, and organization. Citation and publication data stemming from each awarded grant were collated using iCite. ResultsThe total number of NIH- and NHLBI-funded grants in nutri-omics biomarkers was 1,143 and 95, respectively from 2008–2020. Total dollar amount of NIH-funded grants in nutri-omics biomarkers increased from $15M in 2008 to $59.5M in 2019 and declined to $47M in 2020. NHLBI funded grants increased substantially during the same years from $1.8M in 2008 to $7.5M in 2020. During the 12-year period, the proportion of ESI grants among funded grants increased by about 10-fold across NIH and 2-fold for NHLBI. There was an increase in the number of NHLBI research publications (500%) and relative citation ratios (RCR) (150%). Funded grants were concentrated along the East and West coasts of the United States. Major foam tree topics from NHLBI-administered nutri-omics grants included cardiovascular disease, dietary patterns, obesity, human genome, risk factors, microbiome, TMAO (trimethyl amine oxide), and fatty acids. ConclusionsThe analysis indicated increased funding in nutri-omics biomarkers. However, major gaps remain in topics categorized as nutrition biomarkers in NHLBI- and NIH-funded grants. More research is needed to characterize and examine novel biomarkers in NIH-funded grants. Funding SourcesNot applicable.