Differences in COVID-19 Hospitalizations by Self-Reported Race and Ethnicity in a Hospital in Honolulu, Hawaii.

INTRODUCTION: The true extent of racial and ethnic disparities in COVID-19 hospitalizations may be hidden by misclassification of race and ethnicity. This study aimed to quantify this inaccuracy in a hospital's electronic medical record (EMR) against the gold standard of self-identification and then project data onto state-level COVID-19 hospitalizations by self-identified race and ethnicity. METHODS: To identify misclassification of race and ethnicity in the EMRs of a hospital in Honolulu, Hawaii, research and quality improvement staff members surveyed all available patients (N = 847) in 5 cohorts in 2007, 2008, 2010, 2013, and 2020 at randomly selected hospital and ambulatory units. The survey asked patients to self-identify up to 12 races and ethnicities. We compared these data with data from EMRs. We then estimated the number of COVID-19 hospitalizations by projecting racial misclassifications onto publicly available data. We determined significant differences via simulation-constructed medians and 95% CIs. RESULTS: EMR-based and self-identified race and ethnicity were the same in 86.5% of the sample. Native Hawaiians (79.2%) were significantly less likely than non-Native Hawaiians (89.4%) to be correctly classified on initial analysis; this difference was driven by Native Hawaiians being more likely than non-Native Hawaiians to be multiracial (93.4% vs 30.3%). When restricted to multiracial patients only, we found no significant difference in accuracy (P = .32). The number of COVID-19-related hospitalizations was 8.7% higher among Native Hawaiians and 3.9% higher among Pacific Islanders when we projected self-identified race and ethnicity rather than using EMR data. CONCLUSION: Using self-identified rather than hospital EMR data on race and ethnicity may uncover further disparities in COVID-19 hospitalizations.

A Cultural Dance Program Improves Hypertension Control and Cardiovascular Disease Risk in Native Hawaiians: A Randomized Controlled Trial.

BACKGROUND: Native Hawaiians have higher hypertension (HTN) and cardiovascular disease (CVD) rates than non-Hispanic whites, calling for culturally responsive interventions to close this gap. PURPOSE: We tested the effects of a 6-month behavioral intervention, a cultural dance program based on hula (the customary dance of Hawai'i), for improving blood pressure (BP) and CVD risk among Native Hawaiians with uncontrolled HTN. METHODS: In a randomized controlled trial, we tested the effects of the hula-based intervention among 263 Native Hawaiians with uncontrolled HTN (systolic ≥ 140 or ≥ 130 mmHg if diabetes) and no CVD at enrollment. All participants received a brief culturally tailored heart health education before random assignment to the hula-based intervention (n = 131) or the education-only waitlist control (n = 132). Intervention received hula lessons and group-based activities for 6 months. Control received only 1-week education through 6 months. RESULTS: Intervention yielded greater reductions in systolic (-15.3 mmHg) and diastolic (-6.4 mmHg) BP than control (-11.8 and -2.6 mmHg, respectively) from baseline to 6 months (p < .05). At 6 months, 43% of intervention participants compared to 21% of controls achieved a HTN stage <130/80 mmHg (p < .001). The 10-year CVD risk reduction was two times greater for the intervention group than the control group based on the Framingham Risk Score calculator. All improvements for intervention participants were maintained at 12 months. CONCLUSIONS: This trial represents one of the few rigorously conducted examinations of an Indigenous practice leveraged for health promotion, with implications for other ethnic populations.

Ka-HOLO Project: a protocol for a randomized controlled trial of a native cultural dance program for cardiovascular disease prevention in Native Hawaiians.

BACKGROUND: As a major risk factor for cardiovascular and cerebrovascular disease (CVD), hypertension affects 33% of U.S. adults. Relative to other US races and ethnicities, Native Hawaiians have a high prevalence of hypertension and are 3 to 4 times more likely to have CVD. Effective, culturally-relevant interventions are needed to address CVD risk in this population. Investigators of the Ka-HOLO Project developed a study design to test the efficacy of an intervention that uses hula, a traditional Hawaiian dance, to increase physical activity and reduce CVD risk. METHODS: A 2-arm randomized controlled trial with a wait-list control design will be implemented to test a 6-month intervention based on hula to manage blood pressure and reduce CVD risk in 250 adult Native Hawaiians with diagnosed hypertension. Half of the sample will be randomized to each arm, stratified across multiple study sites. Primary outcomes are reduction in systolic blood pressure and improvement in CVD risk as measured by the Framingham Risk Score. Other psychosocial and sociocultural measures will be included to determine mediators of intervention effects on primary outcomes. Assessments will be conducted at baseline, 3 months, and 6 months for all participants, and at 12 months for intervention participants only. DISCUSSION: This trial will elucidate the efficacy of a novel hypertension management program designed to reduce CVD risk in an indigenous population by using a cultural dance form as its physical activity component. The results of this culturally-based intervention will have implications for other indigenous populations globally and will offer a sustainable, culturally-relevant means of addressing CVD disparities. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02620709 , registration date November 23, 2015.

B-type natriuretic peptide and echocardiography reflect volume changes during pregnancy.

OBJECTIVE: To evaluate B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac structure and function in normal women through pregnancy and the postpartum. METHODS: In this prospective observational study, we obtained serial transthoracic echocardiograms, BNP, and NT-proBNP at seven intervals from 6 weeks' gestation through 12 months postpartum. Women with hypertension or cardiac disease were excluded. Using 6-12 months postpartum as reference for non-pregnant levels, echocardiogram measurements and BNP/NT-proBNP were compared over time using linear mixed models with Tukey-Kramer adjustment for multiple comparisons. RESULTS: Of 116 patients, data was available for 78-114 healthy pregnant or postpartum women within each time interval, and 102 patients provided data for ≥4 intervals. Compared to 6-12 months postpartum, BNP and NT-proBNP remained stable through pregnancy and delivery, increased within 48 h postpartum (P<0.0001), then returned to baseline. Left ventricular volume increased within 48 h postpartum (P=0.021) while left atrial volume increased at 18-24 weeks (P=0.0002), 30-36 weeks (P<0.0001) and within 48 h postpartum (P=0.002). The transmitral early/late diastolic velocity (E/A) ratio, transmitral early/peak mitral annulus diastolic velocity (E/E') ratio, isovolumic relaxation times, and mitral valve deceleration times were similar within 48 h and 6-12 months postpartum. CONCLUSION: In normal women, BNP/NT-proBNP, left atrial, and left ventricular volumes increase within 48 h postpartum without indications of altered diastolic function.

Pathways to potentially preventable hospitalizations for diabetes and heart failure: a qualitative analysis of patient perspectives.

BACKGROUND: Potentially preventable hospitalizations (PPH) for heart failure (HF) and diabetes mellitus (DM) cost the United States over $14 billion annually. Studies about PPH typically lack patient perspectives, especially across diverse racial/ethnic groups with known PPH health disparities. METHODS: English-speaking individuals with a HF or DM-related PPH (n = 90) at the largest hospital in Hawai'i completed an in-person interview, including open-ended questions on precipitating factors to their PPH. Using the framework approach, two independent coders identified patient-reported factors and pathways to their PPH. RESULTS: Seventy-two percent of respondents were under 65 years, 30 % were female, 90 % had health insurance, and 66 % had previously been hospitalized for the same problem. Patients' stories identified immediate, precipitating, and underlying reasons for the admission. Underlying background factors were critical to understanding why patients had the acute problems necessitating their hospitalizations. Six, non-exclusive, underlying factors included: extreme social vulnerability (e.g., homeless, poverty, no social support, reported by 54 % of respondents); health system interaction issues (e.g., poor communication with providers, 44 %); limited health-related knowledge (42 %); behavioral health issues (e.g., substance abuse, mental illness, 36 %); denial of illness (27 %); and practical problems (e.g., too busy, 6 %). From these findings, we developed a model to understand an individual's pathways to a PPH through immediate, precipitating, and underlying factors, which could help identify potential intervention foci. We demonstrate the model's utility using five examples. CONCLUSIONS: In a young, predominately insured population, factors well outside the traditional purview of the hospital, or even clinical medicine, critically influenced many PPH. Patient perspectives were vital to understanding this issue. Innovative partnerships and policies should address these issues, including linkages to social services and behavioral health.

Hawaii state legislator views on e-cigarettes and likelihood of legislative action.

OBJECTIVE: To examine perspectives on e-cigarette use and regulations in Hawaii through key informant interviews with state legislators. BACKGROUND: E-cigarette use is rapidly increasing, with sales in 2013 topping $1 billion in the United States, but e-cigarettes are still a largely unregulated industry. Although e-cigarettes are thought by most to be a healthier alternative to traditional cigarettes, long-term health effects are not yet known. METHODS: Semistructured key informant interviews were conducted with Hawaii state legislators (n = 15). RESULTS: We found a lack of consensus among legislators, which suggests that substantial legislative action is unlikely in the upcoming session. However, most legislators believe that some type of incremental legislation will pass, such as enactment of a small tax, limitations on advertising to protect adolescents, or regulations concerning where people can use e-cigarettes. CONCLUSION: Legislators eagerly await further research to clarify the overall benefits and harms of e-cigarettes at both the individual and population levels.

Patient perspectives on the Hula Empowering Lifestyle Adaptation Study: benefits of dancing hula for cardiac rehabilitation.

BACKGROUND: The Hula Empowering Lifestyle Adaption Study, funded by the National Institute on Minority Health and Health Disparities, was a 5-year research trial evaluating the impact of the traditional Native Hawaiian dance form, hula, as an exercise modality for cardiac rehabilitation, compared with usual care, on individuals recently hospitalized for a cardiac event or who had recently undergone coronary artery bypass surgery. METHOD AND RESULTS: Seeking to learn what physical, mental, spiritual, and social effects the intervention may have had for participants, we interviewed 20 of a total of 35 patients who were enrolled in the dance arm of the study. Classical thematic triangulation analysis was used. Participants recognized that hula's coordination of body, mind, and spirit as a group activity deepened their appreciation of and connections to Hawaiian culture. This was true for those who were Native Hawaiian, connecting to their own cultural heritage, as well as for non-Native Hawaiians, who found that it improved their appreciation of the surrounding cultural traditions of the host culture where they now live. CONCLUSIONS: Not only was hula a safe activity that improved functional capacity, participants also regarded its significant sociocultural aspects-even for participants who are not Native Hawaiian -as enhancing its value and meaningfulness. Learning the words of well-known Hawaiian songs provided additional long-term cues that encouraged "ownership" of the therapy and acted as practical reminders of the importance of exercise and lifestyle moderation while also offering new spiritual connections to the surrounding social environment.

Regional pulse wave velocities and their cardiovascular risk factors among healthy middle-aged men: a cross-sectional population-based study.

BACKGROUND: Both carotid-femoral (cf) pulse wave velocity (PWV) and brachial-ankle (ba) PWV employ arterial sites that are not consistent with the path of blood flow. Few previous studies have reported the differential characteristics between cfPWV and baPWV by simultaneously comparing these with measures of pure central (aorta) and peripheral (leg) arterial stiffness, i.e., heart-femoral (hf) PWV and femoral-ankle (fa) PWV in healthy populations. We aimed to identify the degree to which these commonly used measures of cfPWV and baPWV correlate with hfPWV and faPWV, respectively, and to evaluate whether both cfPWV and baPWV are consistent with either hfPWV or faPWV in their associations with cardiovascular (CV) risk factors. METHODS: A population-based sample of healthy 784 men aged 40-49 (202 white Americans, 68 African Americans, 202 Japanese-Americans, and 282 Koreans) was examined in this cross-sectional study. Four regional PWVs were simultaneously measured by an automated tonometry/plethysmography system. RESULTS: cfPWV correlated strongly with hfPWV (r = .81, P < .001), but weakly with faPWV (r = .12, P = .001). baPWV correlated moderately with both hfPWV (r = .47, P < .001) and faPWV (r = .62, P < .001). After stepwise regression analyses with adjustments for race, cfPWV shared common significant correlates with both hfPWV and faPWV: systolic blood pressure (BP) and body mass index (BMI). However, BMI was positively associated with hfPWV and cfPWV, and negatively associated with faPWV. baPWV shared common significant correlates with hfPWV: age and systolic BP. baPWV also shared the following correlates with faPWV: systolic BP, triglycerides, and current smoking. CONCLUSIONS: Among healthy men aged 40 - 49, cfPWV correlated strongly with central PWV, and baPWV correlated with both central and peripheral PWVs. Of the CV risk factors, systolic BP was uniformly associated with all the regional PWVs. In the associations with factors other than systolic BP, cfPWV was consistent with central PWV, while baPWV was consistent with both central and peripheral PWVs.

The Prevalence of Hospitalized Parkinson's Disease Patients in All Case Hospitalization among Different Race/Ethnic Subgroups in Hawaii.

Background: Little is known about the epidemiology of Parkinson's disease (PD) patients in Native Hawaiian Or Other Pacific Islander (NHPI) and Asian American (AA) subgroups. Objective: To determine if the prevalence of hospitalized PD patients is different across age groups and racial/ethnic subgroups in Hawaii. Methods: We conducted a retrospective analysis of Hawaii statewide registry (2016-2020) hospitalization data for patients who were 50 years or older. PD patients were identified using an ICD 10 code: Parkinson's Disease (G20) as their primary/secondary hospitalization discharge diagnosis code. Demographic and clinical characteristics among racial/ethnic subgroups (White, Japanese, Filipino, Chinese, NHPI, or Other) were compared. Results: Of 146,844 total hospitalized patients (n = 429,879 records), 1.6% (n = 2,401) had a PD diagnosis. The prevalence of hospitalized PD patients was 2.3% among Japanese and Chinese, followed by 1.7% for Whites, 1.2% for Filipinos and was lowest for NHPI with 0.9% (p < 0.001). As patient's age increased, the prevalence of hospitalized PD patients increased, with 80-84 years old for the highest age range (3.4%). The prevalence of hospitalized PD patients at 80-84 years old varied across the race/ethnic subgroups (Chinese 4.3%, Japanese 4.0%, Whites 3.7%, Filipinos 2.5%, NHPI 2.3%). Conclusions: The prevalence of hospitalized PD patients among all case hospitalizations were lower for NHPI and Filipino compared to that of Japanese, Chinese, and Whites. As patients' age increased, the prevalence of hospitalized patients with PD increased, but less so in NHPI and Filipino groups. Further research is warranted to understand the reason for these observed differences among racial/ethnic subgroups.

Prevalence Study of MASLD in Adolescent and Young Adult Pacific Islanders and Asians Living in Hawai'i.

Context: Nonalcoholic fatty liver disease, renamed metabolic dysfunction-associated steatotic liver disease (MASLD), is the most common cause of chronic liver disease with an estimated worldwide prevalence of 30.1% while clinical practice observations reflect a disproportionately lower prevalence of 1.9%, indicating a condition that is underrecognized in clinical care settings. Screening for MASLD is rarely performed, and little is known about the prevalence in Hawai'i. Objective: This pilot aims to develop an understanding of the prevalence and factors associated with MASLD in Hawai'i's adolescent and young adult (AYA) population. Design/Methods: Cross-sectional observational pilot study: We used Fibroscan®-liver ultrasonographic vibration-controlled transient elastography (VCTE) to identify MASLD based on controlled attenuation parameter (CAP) scores ≥238 (dB/m) and collected biometric, anthropometric, and Beverage Intake Questionnaire (sugar-sweetened beverage) survey data. Setting: The study took place at community clinics in Hawai'i on the island of O'ahu. Participants: One hundred individuals were evaluated, age 14 to 34 years. Main Outcome Measures: We used VCTE Fibroscan® with CAP scoring to identify the presence of hepatocyte steatosis (fatty liver). Results: Overall MASLD prevalence in the sample was 44% (95% confidence interval: 34.1%-54.3%). In participants with MASLD, obese Native Hawaiian and other Pacific Islanders (62%) and nonobese Asians (43%) had the highest rates of MASLD. Conclusion: This pilot evaluation of the AYA NHOPI and Asian MASLD population in Hawai'i shows a higher rate of MASLD than those reported in other parts of the United States. Larger population health studies are indicated to expand our knowledge of MASLD in the Hawaiian Islands.

Racial disparities in hospitalization characteristics among Native Hawaiians, Pacific Islanders and Asian American subgroups with Parkinson's disease.

BACKGROUND: Differences among Native Hawaiians/Pacific Islanders (NHPI) and Asian American (AA) subgroups have not been adequately studied in Parkinson's disease (PD). OBJECTIVE: To determine differences in demographics, comorbidities, and healthcare utilization among NHPI, AA subgroups, and White hospitalized PD patients. METHODS: We conducted a retrospective cross-sectional analysis of Hawai'is statewide registry (2016-2020). Patients with PD were identified using ICD10 code G20 and categorized as White, Japanese, Filipino, Chinese, NHPI, or Other. Variables collected included: age, sex, residence (county), primary source of payment, discharge status, length of stay, in-hospital expiration, Charlson Comorbidity Index (CCI) and Deep Brain Stimulation (DBS) utilization. Bivariate analyses were performed: differences in age and CCI were further examined by multivariable linear regression and proportional odds models. RESULTS: Of 229,238 hospitalizations, 2428 had PD (Japanese: 31.3 %, White: 30.4 %, Filipino: 11.3 %, NHPI: 9.6 %, Chinese: 8.0 %). NHPI were younger compared to rest of the subgroups [estimate in years (95 % CI): Whites: 4.4 (3.0-5.8), Filipinos: 4.3 (2.7-5.9), Japanese: 7.7 (6.4-9.1), Chinese: 7.9 (6.1-9.7), p < 0.001)]. NHPI had a higher CCI compared to White, Japanese, and Chinese (p < 0.001). Among AA subgroups, Filipinos were younger and had a higher CCI compared to Japanese and Chinese (p < 0.001). There were no significant differences in DBS utilization among subgroups. CONCLUSIONS: NHPI and Filipinos with PD were hospitalized at a younger age and had a greater comorbidity burden compared to other AAs and Whites. Further research, ideally prospective studies, are needed to understand these racial disparities.

Progression of aortic calcification among Japanese in Japan and white and Japanese Americans: a prospective cohort study.

AIMS: Continued low mortality from coronary heart disease in Japan, despite deleterious changes in traditional risk factors, remains unexplained. Since aortic calcification (AC) was an early predictor of cardiovascular mortality, we compared the progression and incidence of AC between Japanese in Japan, white Americans, and third-generation Japanese Americans in the ERA JUMP cohort. We examined whether higher blood levels of marine-derived n-3 fatty acids (FAs) in Japanese than in Americans accounted for the difference. METHODS AND RESULTS: Men (n=700) aged 40-49 years (252 Japanese in Japan, 238 white, and 210 Japanese Americans) were examined at baseline and 4-7 years later. AC was evaluated from the aortic arch to the iliac bifurcation with computed tomography and quantified by the Agatston method. Robust linear regression and linear mixed models were used to compare the progression of AC. Multivariable logistic regression models were fitted to compare the incidence of AC (AC≥50 at follow-up) among those with baseline AC<50. Japanese in Japan had a significantly slower progression of AC than white and Japanese Americans after adjusting for age, baseline AC, follow-up time, and traditional risk factors. White Americans had a significantly higher incidence of AC than Japanese in Japan (OR=4.61 [95%CI, 1.27-16.82]). Additional adjustment for blood levels of n-3 FAs accounted for the difference in AC incidence but not progression. CONCLUSION: Japanese in Japan had a significantly slower progression and lower incidence of AC than white Americans. High levels of marine-derived n-3 FAs in Japanese in Japan partly accounted for the difference in incidence.

Sex differences in the use of early do-not-resuscitate orders after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Studies show that women are more likely to receive do-not-resuscitate (DNR) orders after acute medical illnesses than men. However, the sex differences in the use of DNR orders after acute intracerebral hemorrhage (ICH) have not been described. METHODS: We conducted a retrospective study of consecutive patients hospitalized for acute ICH at a tertiary stroke center between 2006 and 2010. Unadjusted and multivariable logistic regression analyses were performed to test for associations between female sex and early (<24 hours of presentation) DNR orders. RESULTS: A total of 372 consecutive ICH patients without preexisting DNR orders were studied. Overall, 82 (22%) patients had early DNR orders after being hospitalized with ICH. In the fully adjusted model, early DNR orders were more likely in women (odds ratio, 3.18; 95% confidence interval, 1.51-6.70), higher age (odds ratio, 1.09 per year; 95% confidence interval, 1.05-1.12), larger ICH volume (odds ratio, 1.01 per cm(3); 95% confidence interval, 1.01-1.02), and lower initial GCS score (odds ratio, 0.76 per point; 95% confidence interval, 0.69-0.84). Early DNR orders were less likely when the patients were transferred from another hospital (odds ratio, 0.28, 95% confidence interval, 0.11-0.76). CONCLUSIONS: Women are more likely to receive early DNR orders after ICH than men. Further prospective studies are needed to determine factors contributing to the sex variation in the use of early DNR order after ICH.

Correlation of a self-report and direct measure of physical activity level in the electron-beam tomography and risk assessment among Japanese and US Men in the post World War II birth cohort (ERA JUMP) study.

BACKGROUND: Physical activity (PA) is complex and a difficult behavior to assess as there is no ideal assessment tool(s) that can capture all contexts of PA. Therefore, it is important to understand how different assessment tools rank individuals. We examined the extent to which self-report and direct assessment PA tools yielded the same ranking of PA levels. METHODS: PA levels were measured by the Modifiable Activity Questionnaire (MAQ) and pedometer at baseline among 855 white (W), African-American (AA), Japanese-American (JA), and Korean (K) men (mean age 45.3 years) in 3 geographic locations in the ERA JUMP study. RESULTS: Korean men were more active than W, AA, and JA men, according to both the MAQ and pedometer (MAQ total PA [mean ± SD]: 41.6 ± 17.8, 20.9 ± 9.9, 20.0 ± 9.1, and 29.4 ± 10.3 metabolic equivalent [MET] hours/week, respectively; pedometer: 9584.4 ± 449.4, 8363.8 ± 368.6, 8930.3 ± 285.6, 8335.7 ± 368.6 steps/day, respectively). Higher levels of total PA in Korean men, as shown by MAQ, were due to higher occupational PA. Spearman correlations between PA levels reported on the MAQ and pedometer indicated positive associations ranging from rho = 0.29 to 0.42 for total activity, rho = 0.13 to 0.35 for leisure activity, and rho = 0.10 to 0.26 for occupational activity. CONCLUSIONS: The 2 assessment methods correlated and were complementary rather than interchangeable. The MAQ revealed why Korean men were more active. In some subpopulations it may be necessary to assess PA domains other than leisure and to use more than 1 assessment tool to obtain a more representative picture of PA levels.

A Lethal Case of Pseudomonas putida Bacteremia Due to Soft Tissue Infection.

Pseudomonas putida is an uncommon cause of skin and soft tissue infections. It is often associated with trauma or immunocompromised state. We present the first lethal case of bacteremia due to skin and soft tissue infections, which had malnutrition, immobility, and peripheral vascular disease as risk factors.

Impact of More Detailed Measures of Disease Severity on Racial Disparities in Cardiac Surgery Mortality among Native Hawaiians and Pacific Islanders.

Studies that examine racial disparities in health outcomes often include analyses that account or adjust for baseline differences in co-morbid conditions. Often, these conditions are defined as dichotomous (Yes/No) variables, and few analyses include clinical and/or laboratory data that could allow for more nuanced estimates of disease severity. However, disease severity - not just prevalence - can differ substantially by race and is an underappreciated mechanism for health disparities. Thus, relying on dichotomous disease indicators may not fully describe health disparities. This study explores the effect of substituting continuous clinical and/or laboratory data for dichotomous disease indicators on racial disparities, using data from the Queen's Medical Center's (QMC) cardiac surgery database (a subset of the national Society of Thoracic Surgeon's cardiothoracic surgery database) as an example case. Two logistic regression models predicting in-hospital mortality were constructed: (I) a baseline model including race and dichotomous (Yes/No) indicators of disease (diabetes, heart failure, liver disease, kidney disease), and (II) a more detailed model with continuous laboratory values in place of the dichotomous indicators (eg, including Hemoglobin A1c level rather than just diabetes yes/no). When only dichotomous disease indicators were used in the model, Native Hawaiian and other Pacific Islander (NHPI) race was significantly associated with in-hospital mortality (OR: 1.57[1.29,2.47], P=.04). Yet when the more specific laboratory values were included, NHPI race was no longer associated with in-hospital mortality (OR: 1.67[0.92,2.28], P=.28). Thus, researchers should be thoughtful in their choice of independent variables and understand the potential impact of how clinical measures are operationalized in their research.

Target Trial Emulation: A Design Tool for Cancer Clinical Trials.

PURPOSE: To apply target trial emulation to explore the potential impact of eligibility criteria on the primary outcome of a randomized controlled trial. METHODS: Simulations of a real-world explanatory trial of transarterial radioembolization for advanced unresectable hepatocellular carcinoma with portal vein invasion were performed to examine the effects of cohort specification on survival outcomes and patient sample size. Simulations comprised 24 different permutations of the trial varied on three disease nonspecific eligibility parameters. Treatment and control arms for these emulated trials were drawn from the National Cancer Database and matched by treatment propensity. Target trial emulation served as the causal framework for this analysis, allowing the architecture of a true controlled experiment to address forms of bias routinely encountered in comparative effectiveness studies involving real-world observational data. RESULTS: Twenty-four propensity score-matched cohorts comprising a wider clinical spectrum of patients than specified by the original target trial were successfully generated using the National Cancer Database. The arms for each of the emulated trials demonstrated exchangeability across all eligibility criteria and other clinical covariates. Significant treatment benefits were associated with only a narrow range of eligibility criteria, indicating that the original target trial was well specified. CONCLUSION: The impact of patient selection on treatment outcomes can be studied using target trial emulation. This analytical framework can furthermore serve to leverage existing real-world data to inform the task of cohort specification for a randomized controlled trial, facilitating a more data-driven approach for this important step in clinical trial design.

Food Insecurity and Blood Pressure in a Multiethnic Population.

Food insecurity is a social determinant of health and is increasingly recognized as a risk factor for hypertension. Native Hawaiians bear a disproportionate burden of hypertension and known risk factors. Despite this, the relative effects of food insecurity and financial instability on blood pressure have yet to be investigated in this population. This study examines the relative effects of food insecurity and financial instability on blood pressure, controlling for potential confounders in a multiethnic sample. Participants (n = 124) were recruited from a U.S. Department of Agriculture-funded study called the Children's Healthy Living Center of Excellence. Biometrics (i.e., blood pressure, weight, and height) were measured. Demographics, physical activity, diet, psychosocial variables, food insecurity, and financial instability were assessed via self-report questionnaires. Hierarchical linear regression models were conducted. Model 1, which included sociodemographic variables and known biological risk factors, explained a small but significant amount of variance in systolic blood pressure. Model 2 added physical activity and daily intake of fruit, fiber, and whole grains, significantly improving the model. Model 3 added financial instability and food insecurity, further improving the model (R2 = 0.37, F = 2.67, p = 0.031). Food insecurity, female sex, and BMI were significantly and independently associated with increased systolic blood pressure. These results suggest a direct relationship between food insecurity and systolic blood pressure, which persisted after controlling for physical activity, consumption of fruits, fiber, and whole grains, and BMI. Efforts to reduce food insecurity, particularly among Native Hawaiians, may help reduce hypertension in this high-risk population.

Low-density granulocytes display immature cells with enhanced NET formation in people living with HIV.

While the protective role of neutrophil extracellular traps (NETs) in limiting human immunodeficiency virus (HIV) spread to susceptible cells has been documented, there is comparatively little insight into whether NET formation is harmful in people living with HIV (PLWH). To gain insight into neutrophil dysregulation and the pathological role of NETs in HIV, we examined expressions of NET-associated markers [cell-free DNA (cfDNA) and citrullinated histone H3 (CitH3)] in the plasmas from a cohort of the Hawaii Aging with HIV-cardiovascular and HIV-seronegative (HIV-) individuals. In a subset of participants, circulating low-density granulocyte (LDG) levels and their maturation and activation status were analyzed via flow cytometry. We demonstrated higher plasma levels of CitH3 in PLWH compared to HIV- individuals. LDGs from PLWH had heightened CD66b, but reduced CD16 expression. The percentages and counts of CD10+ LDGs were significantly decreased in PLWH. In addition, the CD16Lo LDG subsets were enriched in PLWH, compared to HIV- group, indicating that immature LDGs are increased in PLWH. Moreover, LDGs from PLWH exhibited significantly higher NET forming capacity. In summary, our study presents evidence that LDGs from PLWH on ART display an immature and altered phenotype with increased NET formation. Among PLWH, plasma NET levels as well as LDG parameters correlated with blood markers for inflammation and coagulation, suggesting that neutrophil activation and NETs may exert proinflammatory and coagulation effects. Our data provide insights into the pathologic role of LDGs at least in part mediated through NET formation in PLWH.