Blood Institute Guidelines Research Articles

Periconceptional Dietary Quality and Metabolic Syndrome at 3 Years Postpartum.

The period around pregnancy is a critical window in the primordial prevention of cardiovascular disease, but little is known about the role of dietary patterns in cardiometabolic health. Our objective was to determine the association between alignment of periconceptional diet with the 2020 to 2025 Dietary Guidelines for Americans and the risk of metabolic syndrome. We used data from the Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-Be Heart Health Study, a pregnancy cohort study that followed pregnant participants to a median of 3 years postpartum (n=4423). Usual dietary intake in the 3 months around conception was estimated from a Food Frequency Questionnaire. Alignment with the Dietary Guidelines was measured using the Healthy Eating Index-2020, where higher scores represent greater alignment. Postpartum metabolic syndrome was defined using the American Heart Association/National Heart, Lung, and Blood Institute guideline. The prevalence of metabolic syndrome at 3 years postpartum was 20%. After adjusting for confounders, the prevalence of metabolic syndrome was flat up to a periconceptional Healthy Eating Index-2020 total score of ≈60, and then declined steeply as scores increased. Compared with a Healthy Eating Index-2020 score of 60, having scores of 70, 80, and 90 were associated with 2, 4, and 7 fewer cases of metabolic syndrome per 100 individuals, respectively (prevalence differences: -0.02 [95% CI, -0.03, 0]; -0.04 [-0.08, -0.1]; -0.07 [-0.13, -0.02]). Dietary interventions around conception and systems-level changes to support high diet quality may be important for improving postpartum cardiometabolic health, and helping to reverse or slow the decline in women's cardiometabolic health.

Association of metformin use and cancer incidence: a systematic review and meta-analysis.

Metformin is among the most widely used antidiabetics medications because of its minimal toxicity, favorable safety profile, availability, and low cost. In addition to its role in diabetes management, metformin may reduce cancer risk. We conducted a comprehensive systematic review and meta-analysis to investigate the association between metformin use and cancer risk, with evaluation by specific cancer type when possible. Applicable studies were identified in PubMed/MEDLINE, Embase, Cochrane Library, Web of Science, and Scopus from inception through March 7, 2023, with metformin use categorized as "ever" or "yes" and a cancer diagnosis as the outcome. Article quality was evaluated using National Heart, Lung, and Blood Institute guidelines, and publication bias was evaluated using the Egger test, Begg test, and funnel plots. Pooled relative risk (RR) estimates were calculated using random-effects models, and sensitivity analysis was completed through leave-one-out cross-validation. We included 166 studies with cancer incidence information in the meta-analysis. Reduced risk for overall cancer was observed in case-control studies (RR = 0.55, 95% confidence interval [CI] = 0.30 to 0.80) and prospective cohort studies (RR = 0.65, 95% CI = 0.37 to 0.93). Metformin use was associated with reduced gastrointestinal (RR = 0.79, 95% CI = 0.73 to 0.85), urologic (RR = 0.88, 95% CI = 0.78 to 0.99), and hematologic (RR = 0.87, 95% CI = 0.75 to 0.99) cancer risk. Statistically significant publication bias was observed within the studies (Egger P < .001). Metformin may be associated with a decreased risk of many cancer types, but high heterogeneity and risk of publication bias limit confidence in these results. Additional studies in populations without diabetes are needed to better understand the utility of metformin in cancer prevention.

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.

Successful Implementation Trial to Improve Stroke Risk (TCD) Screening in Children with Sickle Cell Anemia: A Roadmap to Care Enhancement

Stroke remains a devastating complication of sickle cell anemia (SCA). The STOP (Stroke Prevention Trial in Sickle Cell Anemia) protocol adopted in 2014 by the National Heart Lung and Blood Institute (NHLBI) guidelines includes stroke-risk screening using transcranial Doppler ultrasound (TCD) and prevention with chronic red cell transfusion therapy (CRCT). Theserecommendations were reinforced by the American Society of Hematology guidelines.However, despite the evidence supporting TCD screening in stroke prevention, the DISPLACE study (Dissemination and Implementation of Stroke Prevention Looking at the Care Environment) showed that real-world implementation was insufficient. To evaluate and improve sickle stroke screening, we conducted the NHLBI-funded multi-center DISPLACE study to identify barriers to TCD implementation and test novel methods for improving outcomes. DISPLACE is a 4-part study: 1) Retrospective calculation of TCD screening rates; 2) Assessment of barriers and facilitators; 3) Implementation trial to improve TCD screening and 4) Comparison of implementation sites to controls. Importantly, DISPLACE is the largest prospective study of children with SCA. This study employed a multi-level, multi-faceted cluster-randomized study of interventions to improve implementation rates of TCD. Methods: DISPLACE is a 28-center US consortium representing a range of: regions (urban vs rural), size (patient number), and institution type (academic vs community). In Part 1, sites performed a rigorous retrospective review of TCD screening from 2012-2016 to collect baseline rates. Part 2 included a barriers and facilitators assessment to TCD screening to inform the trial interventions: 1) Re-branding TCD as Sickle Stroke Screen, a meaningful name for SCD stakeholders; 2) Using a Single Coordinator (SC) for each site's TCD scheduling, and follow-up; 3) A custom designed provider-focused application, ProviderMinder TM (PM) created to remind providers to track TCD appointments and follow-up on results. When a TCD was due, PM alerted the provider to enter scan results or reason(s) missed. Once the TCD results (normal/conditional/abnormal) were entered in PM, providers were prompted to enter the next TCD date and/or intervention plan (if not normal). If a result was not entered, PM alerted the provider q3 days until the TCD was recorded as completed or rescheduled. The implementation trial (parts 3 and 4 of DISPLACE) included 16 sites that had the lowest TCD rates in part 1. The implementation trial included children with SCA aged 2-7 years (the group at highest risk for an abnormal TCD). Cluster randomization was used to allocate sites to PM alone (8 sites) or PM + SC (8 sites). The primary outcome was comparison of TCD rates between PM and PM+SC sites. Secondary outcomes included comparisons between 1) Part 3 sites' TCD rates and Part 1 baseline rates 2) Part 3 sites and control sites (to assess the impact of the educational rebranding of TCD). Results: Part 1 included 28 centers with 5246 children with SCA. Of the 16 intervention sites, 3 sites could not implement the interventions due to administrative issues but remained in the study and were re-designated as “control sites” and a 4th control site was added (they were not informed prospectively to avoid bias). Thus, there were 13 evaluable sites for the primary endpoint including 776 patients; 484 in sites using PM and 292 in sites using PM+SC. Control sites included 185 patients. The trial demonstrated superiority of the PM arm compared to the PM + SC arm (P&amp;lt;.0001 year 1 and p=0.002 year 2) in both years of implementation and in comparison, to the control sites (P&amp;lt;.0001 year 1, p=.009 year 2) with an overall improvement in mean TCD screening from part 1 by 25% (table 1). Conclusions: This was a highly successful implementation study in SCA. This study emphasizes the importance of performing barrier and facilitator assessments when introducing new guideline-recommended screenings into clinical practice. These findings also highlight the importance of ongoing quality assurance in SCA to ensure prevention practices are maintained. Despite the benefit of TCD (sickle stroke screening) in children with SCA, implementation was poor prior to these interventions. Results from this study will guide ongoing optimization of TCD screening and demonstrate the importance of adopting these interventions in the real world.

Metabolic Profile of Liver Transplant Recipients and Determinants of their Body Fat Distribution

Obesity and diabetes mellitus epidemics exert a measurable impact on the liver transplant (Ltx) population. This study aimed to investigate the metabolic profile of Ltx recipients and its association with body fat distribution. Adults who underwent de novo elective cadaveric-donor Ltx were eligible. Metabolic syndrome (MS) was diagnosed based on the adapted International Diabetes Federation, the American Heart Association, and the National Heart, Lung, and Blood Institute guidelines. We recruited 100 patients with a mean age of 54 years, of whom 70% were men. Overall, 54% met the criteria for MS, most of which comprised new-onset cases. Excessive fat accumulation in liver donors was found to be associated with an increased metabolic risk in liver recipients. Haemoglobin A1C (OR: 8.962, 95% CI: 2.188–84.545, p = 0.013), ferritin (OR: 1.024, 95% CI: 1.005–1.054, p = 0.038), and de novo hypertriglycaeridemia (OR 27.957, 95% CI: 2.626–752.121, p = 0.014) were found to be independently associated with de novo MS. After a step-wise multivariate analysis, only the anthropometric obesity indices were significantly associated with abdominal fat distribution in Ltx recipients. Metabolic complications were common in liver recipients. Both pre- and post-Ltx factors impacted MS development in liver recipients and determined abdominal fat distribution.

Sickle Cell Disease Treatment with Arginine Therapy (STArT): study protocol for a phase 3 randomized controlled trial

BackgroundDespite substantial illness burden and healthcare utilization conferred by pain from vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD), disease-modifying therapies to effectively treat SCD-VOE are lacking. The aim of the Sickle Cell Disease Treatment with Arginine Therapy (STArT) Trial is to provide definitive evidence regarding the efficacy of intravenous arginine as a treatment for acute SCD-VOE among children, adolescents, and young adults.MethodsSTArT is a double-blind, placebo-controlled, randomized, phase 3, multicenter trial of intravenous arginine therapy in 360 children, adolescents, and young adults who present with SCD-VOE. The STArT Trial is being conducted at 10 sites in the USA through the Pediatric Emergency Care Applied Research Network (PECARN). Enrollment began in 2021 and will continue for 5 years. Within 12 h of receiving their first dose of intravenous opioids, enrolled participants are randomized 1:1 to receive either (1) a one-time loading dose of L-arginine (200 mg/kg with a maximum of 20 g) administered intravenously followed by a standard dose of 100 mg/kg (maximum 10 g) three times a day or (2) a one-time placebo loading dose of normal saline followed by normal saline three times per day at equivalent volumes and duration as the study drug. Participants, research staff, and investigators are blinded to the participant’s randomization. All clinical care is provided in accordance with the institution-specific standard of care for SCD-VOE based on the 2014 National Heart, Lung, and Blood Institute guidelines. The primary outcome is time to SCD-VOE pain crisis resolution, defined as the time (in hours) from study drug delivery to the last dose of parenteral opioid delivery. Secondary outcomes include total parental opioid use and patient-reported outcomes. In addition, the trial will characterize alterations in the arginine metabolome and mitochondrial function in children with SCD-VOE.DiscussionBuilding on the foundation of established relationships between emergency medicine providers and hematologists in a multicenter research network to ensure adequate participant accrual, the STArT Trial will provide definitive information about the efficacy of intravenous arginine for the treatment of SCD-VOE for children.Trial registrationThe STArT Trial was registered in ClinicalTrials.gov on April 9, 2021, and enrollment began on June 21, 2021 (NCT04839354).

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

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.

Prevalence and factors associated with dyslipidemia among adolescents in Saudi Arabia

Dyslipidemia is a major risk factor for atherosclerosis. Screening for dyslipidemia at an early age is essential to prevent and control its consequences. This study aimed to determine prevalence of dyslipidemia and its correlates among adolescents in Saudi Arabia. Data of 5854 adolescents aged 10–19 years from all 13 regions of Saudi Arabia were obtained from the Jeeluna study; a national cross-sectional, multistage stratified cluster sample survey. Dyslipidemia was defined based on the National Heart Lung and Blood Institute and National Cholesterol Education Program guidelines for adolescents. We found that a quarter of Saudi adolescents have dyslipidemia (males: 33.3%, females: 17.9%). Significant variation was observed by region (p < 0.001). Prevalence of abnormal Total Cholesterol was 6.7%, LDL-C 7.1%, HDL-C 12.8%, Non-HDL-C 8.3%, and Triglycerides 9.6%. Factors independently associated with dyslipidemia were male gender (OR = 2.19, 95% CI 1.78–2.70, p < 0.001), BMI (underweight OR = 0.80, 95% CI 0.69–0.94, overweight OR = 1.76, 95% CI 1.50–2.06, obese OR = 2.80, 95% CI 2.34–3.34, p < 0.001, vs. normal) and serum ferritin (high OR = 7.02, 95% CI 1.49–34.79, low OR = 0.82, 95% CI 0.67–1.01, p = 0.04 vs. normal) and ≥ 1 daily intake of carbonated beverage (OR = 1.10, 95% CI 1.00–1.20, p = 0.03 vs. no or not daily intake). Public health interventions for improving lipid profile of adolescents are urgently needed.

320 Trends in Acute Care of Vaso-Occlusive Episodes in the Emergency Department Following the 2014 National Heart Lung Blood Institute Guidelines

Patients presenting to the Emergency Department (ED) with sickle cell disease (SCD) vaso-occlusive episodes (VOE) encounter variability in triage acuity level designation and pain management practices. Our study aims to describe national trends in Emergency Severity Index (ESI) level designation and the rate of narcotic administration for ED patients with SCD VOE. We additionally compare both of these variables before and after publication of the 2014 National Heart Lymph Blood Institute (NHLBI) guidelines for the management of patients with VOE.

Diagnostic Testing for von Willebrand Disease: Trends and Insights from North American Laboratories over the Last Decade.

Accurate diagnosis of von Willebrand disease (VWD) depends on the quality, precision, and variability of the laboratory assays. The North American Specialized Coagulation Laboratory Association (NASCOLA) is a provider of external quality assessment (EQA) for approximately 60 specialized coagulation laboratories in North America. In this report, NASCOLA EQA data from 2010 to 2021 are reviewed for trends in methodology and precision among various assays. In particular, recent ASH ISTH NHF WFH (American Society of Hematology, International Society on Thrombosis and Haemostasis, National Hemophilia Foundation, and World Hemophilia Federation) guidelines for diagnosis of VWD are reviewed in light of EQA data. In contrast to other geographic regions, laboratories in North America predominantly use three-assay screening panels (antigen, platelet-binding activity, and factor VIII [FVIII] activity) rather than four-assay panels (antigen, platelet-binding activity, FVIII activity, and collagen-binding activity). They also use latex immunoassays rather than chemiluminescence immunoassays, and the classic ristocetin cofactor (VWF:RCo) assay and monoclonal antibody (VWF:Ab) assay to assess VWF platelet-binding activity over newer recommended assays (VWF:GPIbM and VWF:GPIbR). Factors that may be influencing these North American practice patterns include lack of Food and Drug Administration approval of the VWF:GPIbM, VWF:GPIbR, collagen binding assays, and chemiluminescence methodologies, and the influence of the 2008 National Heart, Lung, and Blood Institute guidelines on laboratory practice. Lastly, systems-based solutions are urgently needed to improve the overall accuracy of laboratory testing for VWD by minimizing preanalytical variables and adopting assay standardization.

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.

Results From a National Survey of Asthma Provider Beliefs and Practices Regarding Exercise and Asthma: A Work Group Report of the AAAAI Committee on Sports, Exercise, and Fitness

National Heart, Lung, and Blood Institute guidelines recommend regular physical activity (PA) for patients with asthma. Health care provider (HCP) counseling represents an effective approach to optimizing patient PA. However, current exercise rates among asthma patients are suboptimal, which suggests that counseling may be improved. To understand PA counseling behaviors among HCPs who manage asthma. A voluntary 36-item survey assessing self-reported awareness of PA recommendations and current clinical practices was sent to 979 randomly selected HCP members of the American Academy of Allergy, Asthma & Immunology (AAAAI). The overall response rate was 9.3% (91 of 979). Respondents were physicians (100%) and allergists/immunologists (96%) who reported an average of 18.1 ± 12.3 years in independent practice. Over half (58%) reported personally engaging in 150 min/wk or more of moderate to strenuous PA. Eighty percent of participants were unaware of specific PA guidelines for patients with asthma, yet 66% acknowledged evidence for improved asthma outcomes with moderate exercise. A large majority of respondents believed that patients with asthma (97%) and severe asthma (84%) should pursue exercise. Whereas 90% of respondents support incorporating exercise counseling into asthma care, only 69% regularly counsel asthma patients about PA. Barriers cited included limited time, lack of knowledge regarding how and where to refer patients for exercise, and other medical priorities. Potential facilitators of PA included increasing practitioner education and patient-directed posters in waiting areas. Health care providers recognized PA as an important component of asthma care but were often unaware of specific guidelines. Promoting PA counseling may require using a time-efficient approach to implement counseling at each asthma patient encounter.

The National Heart Lung and Blood Institute guidelines finally say “yes” to fractional exhaled nitric oxide

Exhaled nitric oxide levels were first discovered to be elevated in patients with asthma in 1993, only 2 years after the first National Heart Lung and Blood Institute (NHLBI) asthma guidelines were published. 1 Alving K Weitzberg E Lundberg JM. Increased amount of nitric oxide in exhaled air of asthmatics. Eur Respir J. 1993; 6: 1368-1370 PubMed Google Scholar Since then, more than 3600 articles have been published relating to the measurement of fractional exhaled nitric oxide (FeNO) in asthma, with an average of almost 20 articles per month being published over the past 10 years. Despite our growing understanding of the use of FeNO as a tool to assist in the evaluation and management of asthma, it has seen a particularly slow uptake among practitioners in the United States, especially in comparison to its wider acceptance and uses in other parts of the world including the United Kingdom and European Union. In 2011, the American Thoracic Society published evidence-based guidelines on the clinical use of FeNO 2 Dweik RA Boggs PB Erzurum SC Irvin CG Leigh MW Lundberg JO et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011; 184: 602-615 Crossref PubMed Scopus (1677) Google Scholar ; however, the regularly updated international Global Initiative for Asthma guidelines did not adopt or endorse these recommendations at that time. 3 Global Initiative for Asthma. Global strategy for asthma management and prevention. 2020. Available at: http://www.ginasthma.org. Accessed September 25, 2021. Google Scholar The lack of consensus guidelines has, in part, been responsible for the slow adoption of FeNO by practitioners as a unique, clinically meaningful, and important tool in the diagnosis and management of asthma, and this has also led to several third-party payers denying payment and citing its use as “experimental.”

A Pharmacist-Managed Hydroxyurea Prescribing Protocol Improves Uptake and Optimization Among Patients with Sickle Cell Disease within the Southern Alberta Rare Blood and Bleeding Disorders (SARBBD) Comprehensive Care Program

Introduction: Sickle cell disease (SCD) is associated with major morbidity and mortality and yet many of our patients are not using the available disease modifying medication, hydroxyurea (HU). Furthermore, dose-titration of HU is required in order to achieve the maximum therapeutic benefit. Certain challenges can limit HU acceptance, such as misconceptions about safety, frequency of monitoring, and ease of access (i.e. insurance). Incorporating a pharmacist-managed HU hydroxyurea prescribing protocol into the SARBBD Comprehensive Care Program will help to address many of the barriers responsible for poor HU uptake among SCD patients and improve HU utilization.Objectives: To improve the uptake and optimization of HU among patients with Sickle Cell Disease within the SARBBD Comprehensive Care Program.Methods: Commencing in January 2020, clinic pharmacist support of 0.2 full-time equivalents (FTEs) was made available to the SARBBD program, and a pharmacist-led comprehensive HU prescribing protocol was adapted from the current CanHaem and National Heart, Lung, and Blood Institute guidelines. The clinical pharmacist was available for all Sickle Cell Disease clinic appointments, and was responsible for all aspects of HU management, including educating, counselling, and prescribing (titrating and monitoring as outlined in the prescribing protocol). It is worth noting that independent pharmacist prescribing is permitted in Alberta (Alberta College of Pharmacists, 2021).Patients were initiated on HU at a low dose of 500 mg daily to limit gastrointestinal sensitivities, and then increased to 1000 mg daily after one week. Thereafter the dose was titrated every 2-4 weeks as permitted by the patient's tolerance and laboratory parameters (i.e., CBC, liver and renal function, reticulocyte count) up to their maximum tolerated dose (MTD), defined as the maximum dose that maintains neutrophils ≥ 1.5 x 10 9/L, platelets > 80 x 10 9/L, and hemoglobin > 50 x 10 9/L. Following HU initiation and after every laboratory visit, the clinical pharmacist followed-up with patients via telephone to discuss HU tolerance, adherence, and dosing. Perceived benefits (i.e., pain episodes), medication supply, drug access (insurance), and planning for future follow-ups were also addressed as necessary.Results: As of January 2020, the SARBBD program provided care to 119 patients with SCD. Of those patients, 7 patients were managed with a transfusion exchange protocol, and therefore were not considered HU candidates. Of the 112 eligible SCD patients, 39 (34.8%) were already on HU therapy, 15 of whom were at MTD (38.4% of HU patients, 13.4% of 112 eligible SCD population). By June 2021 (18 months of pharmacist managed HU), there were 123 eligible SCD patients, of whom 71 were on HU (57.7%), with 37 at MTD (52.1% of HU patients, 30.1% of total eligible SCD population). Every month on average the pharmacist; has 27 interactions (phone, email) with SCD patients, reviews 18 lab reports, initiates HU for 2 patients, and will make over 4 dose adjustments.A majority of patient interactions involved educating patients on HU, and addressing common misconceptions about HU adverse effects and risks. Further, a significant proportion of HU initiations required pharmacist assistance with insurance authorization. Overall, patient acceptance of the pharmacist-managed HU prescribing was positive. One patient commented, “Working with [the pharmacist] has been great as he diligently has been able to keep a close eye on my blood results while making adjustments to my dosage of HU, without requiring a visit to the doctor. This was great as it didn't tie the doctors up, but also I was able to communicate with [the pharmacist] and get the same information at a convenient time. [The pharmacist] has also been extremely supportive, open and positive while answering questions”.Conclusion: Incorporating a pharmacist into the SARBBD program, as well as implementing a pharmacist-managed HU prescribing protocol has led to improved HU uptake and optimization. In addition, a greater proportion of patients have been able to reach MTD. The most common barriers to HU utilization, such as miseducation, frequency of laboratory monitoring, and medication access, can be overcome with dedicated pharmacist involvement.Funding: Sickle Cell Disease Association of Canada (SCDAC) grant and Novo Nordisk Investigator Initiated Grant DisclosuresPoon: University of Calgary: Current Employment; Bayer: Honoraria, Research Funding; CSL-Behring: Honoraria, Research Funding; Bioverativ/Sanofi: Honoraria; Novo Nordisk: Honoraria; Pfizer: Honoraria; Roche: Honoraria; Takeda: Honoraria. Lee: Bayer: Research Funding, Speakers Bureau; Biovertiv/Sanofi: Honoraria, Research Funding; CSL Behring: Honoraria; Novo Nordisk: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Roche: Honoraria; Takeda: Honoraria.

Practices and Attitudes Regarding Pediatric Cholesterol Screening Recommendations Differ Between Pediatricians and Family Medicine Clinicians

Pediatricians had higher rates of ordering pediatric cholesterol screening than family medicine (FM) clinicians. This study aims to compare knowledge, attitude, and practices of clinicians' pediatric cholesterol screening practices and attitudes between these two specialties. A 14-item electronic survey using Likert scales was sent to all clinicians in the institution's Departments of Pediatrics and FM between 2018 and 2019. Chi-square and t-tests were used to compare pediatricians and FM clinicians. 22 clinicians from Pediatrics and 111 from FM completed the survey. Compared to FM clinicians, pediatricians were more familiar with the National Heart, Lung, and Blood Institute guidelines, which are more vigorous in their recommendation of universal cholesterol screening. Pediatricians reported being more supportive of universal cholesterol screening in children (p < 0.05). In practice, pediatricians reported screening almost two thirds (64.8%) of eligible patients during the past year, while FM clinicians reported screening approximately one third (34.1%) of eligible patients (p < 0.001). Pediatricians were more likely to screen based on patient-specific risk factors and their practice decisions were more heavily influenced by published guidelines, institutional education, availability of non-fasting blood to be used for screening, and the availability of an institutional pediatric lipid clinic (p < 0.05). The differences in knowledge, attitudes, and practices of cholesterol screening may contribute to different screening rates among clinicians from FM and pediatrics. To improve patient care and reduce gaps, it is important to implement interventions at the institutional level as well as to adopt uniform guideline recommendations at the national level.

Quality of periprocedural care in patients with von Willebrand disease.

While it has been shown that haemophilia patients receiving care at Haemophilia Treatment Centres (HTCs) experience decreased morbidity and mortality, little research has been done on the outcomes of patients with von Willebrand disease (VWD). To compare the quality of periprocedural care received by patients with VWD at HTCs and non-HTCs. We performed a retrospective chart review on all adult VWD patients undergoing an invasive procedure from 2015 to 2017. Quality of periprocedural care was measured using the following surrogate outcomes: periprocedural VWD-specific therapy use per 2007 National Heart, Lung, and Blood Institute (NHLBI) guidelines, procedural estimated blood loss (EBL), and post-procedure bleeding. Comparisons were performed according to the setting of care at the time of the invasive procedure, HTC versus non-HTC. There were 668 invasive procedures performed on 305 patients, of which 8.2% were HTC cases. Non-type 1 VWD was more likely in HTC cases. VWD-specific therapy was used per NHLBI guidelines in 100% of HTC cases compared with 10.6% of non-HTC cases. Procedural EBL>=100ml was more likely to occur in HTC differences cases (OR=2.34; 95% CI, 1.05 to 5.25). There was no difference in post-procedure bleeding between the two groups (OR=1.26, 95% CI, .20- 7.86). Despite widespread periprocedural use of VWD-specific therapy outside established guidelines at non-HTCs, there was no difference in periprocedural bleeding. Possible explanations include diagnostic error, in disease severity and procedure types, and dataset limitations. Additional studies are needed to investigate this further and compare other patient care outcomes between HTCs and non-HTCs.

System Level Informatics to Improve Triage Practices for Sickle Cell Disease Vaso-Occlusive Crisis: A Cluster Randomized Controlled Trial

BackgroundNational Heart Lung and Blood Institute guidelines for the treatment of vaso-occlusive crisis among people with sickle cell disease in the emergency department recommend assigning an emergency severity index of 2 at triage. However, patients with sickle cell disease often do not receive guideline-concordant care at triage. To address this gap, a decision support tool was developed, in the form of a text banner on the triage page in the electronic health record system, visible to triage nurses. MethodsA prospective quality improvement initiative was designed where the emergency severity index clinical decision support tool was deployed to a stratified random sample of emergency department triage nurses to receive the banner (n = 24) or not to receive the banner (n = 27), reminding them to assign the patient to emergency severity index category 2. The acceptability of the emergency severity index clinical decision support tool was evaluated with the Ottawa Acceptability of Decision Rules Instrument. Descriptive and bivariate (chi-square test) statistics were used to characterize the study's primary outcome, proportion of visits assigned an emergency severity index of 2 or higher. A generalized linear mixed model with clustering at the level of the triage nurse was performed to test the association between the banner intervention and triage practices. ResultsA total of 384 ED visits were included for analysis. Before study initiation, the percentage of sickle cell disease patients’ visits with the proper emergency severity index assignment at triage was 37.04%. After initiation, the proportion of sickle cell disease patients’ visits with an emergency severity index of 2 or higher triaged by nurses in the intervention group was markedly higher in the intervention group than in the control group (64.95% vs 35.05%; χ2 = 8.79, P ≤ .003). Accounting for clustering by nurse, the odds ratio for proper triage emergency severity index assignment was 3.22 (95% confidence interval 1.17–8.85; P ≤ .02) for the intervention versus control. Surveyed triage nurses reported the emergency severity index clinical decision support tool to be moderately acceptable (nurses’ mean Ottawa Acceptability of Decision Rules Instrument scores ranged from 4.13 to 4.90 on the 6-point scale; n = 11). There were no differences in ED experience outcomes including time to first analgesic or length of stay between the control and intervention groups. ConclusionSubstantial improvements in triage guideline concordance were achieved and sustained without direct nursing education.

Use of an Emergency Department-Based Intranasal Fentanyl Protocol for Vaso-Occlusive Episodes in Sickle Cell Disease: The Unanticipated Consequences

Background: Acute management of pain associated with vaso-occlusive episodes (VOE) in patients with sickle cell disease (SCD) is an on-going challenge in the emergency department (ED) setting. The 2014 National Heart, Lung, and Blood Institute (NHLBI) guidelines recommend rapid evaluation and treatment for moderate-severe VOE, including administration of 1stparenteral opioid within 30 minutes (min) of triage or 60 min from registration, pain reassessment, and repeat opioid delivery within 15-30 min. Despite these recommendations, significant delays in providing optimal pain management is common for patients with SCD. Intranasal fentanyl (INF), a powerful parenteral analgesia with rapid onset is commonly used for pain in the ED, a practice that has recently been extended to treatment of VOE in some institutions. We and others have demonstrated that INF use is effective in helping with sickle-related pain management and achieving better adherence to NHLBI guidelines. However, the utilization of INF may have led to an unanticipated delay in administering intravenous (IV) opioids for this patient population.Objective: To evaluate the utilization of INF in the ED and its effect on the timeliness of 1st IV opioid administration for treatment of VOE in children with SCD.Methods: We conducted a retrospective review of electronic medical records in a single Pediatric ED from January 2017 to June 2017. We evaluated patients with SCD ages ≥ 2 years presenting with moderate-severe VOE (pain scores ≥6 on a severity scale of 0-10) after introduction of a nurse-initiated INF order (1.5 mcg/kg/dose; max 100 mcg/dose X2, 5 min apart) that was added to the standard institutional protocol for VOE treatment. Outcomes included: Time of ED arrival to 1st parenteral opioid, time to first IV opioid, and disposition. We also compared time to 1st IV opioid administration in patients who received INF with historical data of SCD patients treated at this ED with only IV opioids before INF use was standard practice (Jan-Dec 2012, n=231).Results: 250 patients met inclusion criteria. Mean age was 12.5 years, 52% female, and 66% had HbSS, 22% HbSC, 6% HbSB0 and 6% other. Admission rate was 60%. 183 (73%) patients received INF and 204 (82%) received an IV opioid, 141 of whom received both INF and IV opioids, while 42 (17%) patients received INF only. Mean time±standard deviation to first INF dose was 28.5±21 min; mean time to IV opioid delivery was 77±47 min compared to 35±18 min prior to initiation of the INF protocol (historical data, n=231, p<0.0001; Figure 1). In the current cohort, there was no statistically significant difference in time to IV opioid delivery in patients who received IV opioid after INF vs. IV opioid alone. However, only 52 (36%) of patients who received IV opioid after INF received IV opioid within 60 min of ED arrival compared to 36 (57%) who received IV opioids without INF (p<0.01). Of the 42 patients who received INF without any IV opioids, 39 patients (93%) were discharged home, while 5 (13%) of these discharged patients returned to the ED within 72 hours for VOE, similar to the 72 hour return rate in 7/39 (18%) patients discharged from the ED after receiving INF followed by IV opioids.Conclusion: Use of INF in the ED for pediatric patients with SCD and VOE is an excellent strategy to shorten time to administration of 1st dose of parenteral opioid and therefore improve adherence to the NHLBI guidelines recommending rapid administration of parenteral opioids within 60 min of ED arrival. Of interest, INF alone appeared to provide sufficient pain control without IV opioids for disposition home in one out of 6 children with VOE, an observation not previously reported. Whether this reflects adequate pain control or insufficient management requires further investigation. However, our experience also illustrates the potential pitfall of an ED-based INF protocol with respect to delays in delivery of IV opioids after initial administration of INF compared to our historical data prior to the INF protocol implementation. Although the significance of this delay is unknown, quality improvement efforts are underway to address this unanticipated consequence. [Display omitted] DisclosuresMorris:MAST Therapeutics: Research Funding; Calithera Biosciences: Consultancy; Nestle: Consultancy; Lifetrients: Patents & Royalties: I am inventor of IP owned by USCF-Benioff Children's Hospital Oakland, licensed to Lifetrients, generating royalties; Pfizer: Consultancy.

A structured review evaluating content validity of the Asthma Control Test, and its consistency with U.S. guidelines and patient expectations for asthma control

Objective To assess whether the content of the Asthma Control Test (ACT) served as a valid measure of asthma control (i.e., content validity) by mapping ACT items to the National Heart, Lung and Blood Institute (NHLBI) guideline asthma control definitions, and to language used by patients to describe their asthma. Data sources PubMed and EMBASE databases were used for a structured literature analysis. Study selections Full-text, English-language articles that reported findings from qualitative studies conducted in adults, focusing on patient descriptors of asthma symptoms, impacts, or severity, were included. Pediatric studies, studies conducted in patients without asthma, and studies that did not contain qualitative data were excluded. Results ACT items reflected all domains of asthma impairment described in the NHLBI guidelines, except pulmonary function. Following the literature review, 28 full-text publications were identified that included patient descriptors that could be mapped to ACT items. For example, per ACT Item 1, patients described having trouble at work, school, and completing household chores; and, per ACT Item 2, patients used the phrase “short of breath” to describe asthma-associated symptoms. Conclusion ACT item content corresponded well with the NHLBI guideline definitions of the impairment domain of asthma control (focused on asthma symptoms and impact), and we identified numerous examples in the literature indicating that ACT concepts and item content mirror the language patients use when discussing asthma symptoms and impact, and their degree of asthma control. This provides further evidence to support content validity of the ACT as a measure of asthma control.