Racial, Ethnic, and Rural Disparities in US Veteran COVID-19 Vaccine Rates.

Background: Race, ethnicity, and rurality-related disparities in coronavirus disease 2019 (COVID-19) vaccine uptake have been documented in the United States (US). Objective: We determined whether these disparities existed among patients at the Department of Veterans Affairs (VA), the largest healthcare system in the US. Design Settings Participants Measurements: Using VA Corporate Data Warehouse data, we included 5,871,438 patients (9.4% women) with at least one primary care visit in 2019 in a retrospective cohort study. Each patient was assigned a single race/ethnicity, which were mutually exclusive, self-reported categories. Rurality was based on 2019 home address at the zip code level. Our primary outcome was time-to-first COVID-19 vaccination between December 15, 2020-June 15, 2021. Additional covariates included age (in years), sex, geographic region (North Atlantic, Midwest, Southeast, Pacific, Continental), smoking status (current, former, never), Charlson Comorbidity Index (based on ≥1 inpatient or two outpatient ICD codes), service connection (any/none, using standardized VA-cutoffs for disability compensation), and influenza vaccination in 2019-2020 (yes/no). Results: Compared with unvaccinated patients, those vaccinated (n=3,238,532; 55.2%) were older (mean age in years vaccinated=66.3, (standard deviation=14.4) vs. unvaccinated=57.7, (18.0), p<.0001)). They were more likely to identify as Black (18.2% vs. 16.1%, p<.0001), Hispanic (7.0% vs. 6.6% p<.0001), or Asian American/Pacific Islander (AA/PI) (2.0% vs. 1.7%, P<.0001). In addition, they were more likely to reside in urban settings (68.0% vs. 62.8, p<.0001). Relative to non-Hispanic White urban Veterans, the reference group for race/ethnicity-urban/rural hazard ratios reported, all urban race/ethnicity groups were associated with increased likelihood for vaccination except American Indian/Alaskan Native (AI/AN) groups. Urban Black groups were 12% more likely (Hazard Ratio (HR)=1.12 [CI 1.12-1.13]) and rural Black groups were 6% more likely to receive a first vaccination (HR=1.06 [1.05-1.06]) relative to white urban groups. Urban Hispanic, AA/PI and Mixed groups were more likely to receive vaccination while rural members of these groups were less likely (Hispanic: Urban HR=1.17 [1.16-1.18], Rural HR=0.98 [0.97-0.99]; AA/PI: Urban HR=1.22 [1.21-1.23], Rural HR=0.86 [0.84-0.88]). Rural White Veterans were 21% less likely to receive an initial vaccine compared with urban White Veterans (HR=0.79 [0.78-0.79]). AI/AN groups were less likely to receive vaccination regardless of rurality: Urban HR=0.93 [0.91-0.95]; AI/AN-Rural HR=0.76 [0.74-0.78]. Conclusions: Urban Black, Hispanic, and AA/PI Veterans were more likely than their urban White counterparts to receive a first vaccination; all rural race/ethnicity groups except Black patients had lower likelihood for vaccination compared with urban White patients. A better understanding of disparities and rural outreach will inform equitable vaccine distribution.

Embracing the Diversity of Latinx Communities to Promote Vaccinations.

While vaccine hesitancy is well documented in the literature among the Latinx community, little attention or effort is given to the nuances among the members of individual communities, such as country of origin, immigration status, generational status, primary language, race, age, sex, gender, or rural residence and how these complexities affect vaccine messaging and uptake. We have evidence that this heterogeneity causes differences in access to healthcare, attitudes towards vaccines, and degree of health disparities. In this review we will describe their impact on vaccination rates in the Latinx community, highlighting missed opportunities for public health outreach, and how targeted messaging could improve vaccine uptake.

Sex differences and altered mitophagy in experimental pulmonary hypertension.

Pulmonary hypertension (PH) is a debilitating condition characterized by increased pulmonary arterial pressures and remodeling of pulmonary arteries, leading to right heart failure. Women have a higher prevalence of PH, whereas men have more severe disease and poorer outcomes. Animal models also show female-predominant disease. Despite the known sex differences in PH, little is known about how pathogenesis differs between the sexes. There is growing evidence of mitochondrial dysfunction, as well as altered mitophagy in PH. We hypothesized that sexual dimorphism contributes to mitochondrial dysfunction and altered mitophagy in PH. Using mouse lung endothelial cells, we exposed both wild-type and Parkin-/- cells to hypoxia and measured the effects on mitochondrial function and mitophagy-associated proteins. Our results show that females have more Parkin expression at baseline as well as increased mitochondrial respiratory capacity when exposed to oxidative stress. Inhibition of Parkin increased metabolic activity but reduced cell proliferation but to different degrees depending on sex, with results differing by sex. Our findings demonstrate sexual dimorphism in mitophagy-associated proteins and in mitochondrial respiration, which may help shed light on how the pathogenesis of PH may differ between the sexes.

COVID-19 Healthcare Inequity: Lessons Learned from Annual Influenza Vaccination Rates to Mitigate COVID-19 Vaccine Disparities.

The COVID-19 pandemic has infected 33 million Americans and resulted in more than 600,000 deaths as of late Spring 2021. Black, Indigenous, and Latinx (BIL) people are disproportionately infected, hospitalized, and dying. Effective vaccines were rapidly developed and have been widely available in the United States since their initial rollout in late 2020-early 2021 but vaccination rates in BIL communities have remained low compared with non-BIL communities. Limited access to the vaccine, lack of customized information, and mistrust of the medical system, all contribute to vaccine hesitancy and low vaccination rates. Regrettably, COVID-19 is not the only vaccine-preventable illness with racial/ethnic inequities. Similar inequities are seen with the seasonal influenza vaccine. We review the racial/ethnic health disparities in COVID-19 illness and vaccination rates and what inequities contribute to these disparities. We use evidence from the seasonal influenza vaccination efforts to inform potential strategies to attenuate these inequities. The development of effective and sustainable strategies to improve vaccination rates and reduce factors that result in health inequities is essential in managing current and future pandemics and promoting improved health for all communities.

Pulmonary artery pseudoaneurysm causing massive hemoptysis in hyperimmunoglobulin E syndrome: a case report.

BACKGROUND: Hyperimmunoglobulin E syndrome (HIES) is a rare primary immunodeficiency disorder defined by high serum immunoglobulin E titers that is associated with recurrent respiratory infections, formation of pneumoatoceles, recurrent skin abscesses, and characteristic dental and skeletal abnormalities. CASE PRESENTATION: We report a case of a 56-year-old male with a history of HIES, cavitary mycetomas, and allergic bronchopulmonary aspergillosis who presented with recurrent massive hemoptysis. Bronchial artery angiography and bronchoscopy failed to identify active hemorrhage, and two embolizations of the bronchial artery did not resolve the bleeding. Subsequently, selective pulmonary artery angiography was conducted that demonstrated a subsegmental pulmonary artery branch pseudoaneurysm with extravasation into an adjacent lung cavity. This was treated successfully with transcatheter embolization. CONCLUSIONS: To our knowledge, this is the first case reported of pulmonary artery pseudoaneurysm in HIES in the medical literature. Pulmonary artery pseudoaneurysm should be considered in the differential diagnosis in patients with HIES and massive hemoptysis.

Cell Death in the Lung: The Apoptosis-Necroptosis Axis.

Regulated cell death is a major mechanism to eliminate damaged, infected, or superfluous cells. Previously, apoptosis was thought to be the only regulated cell death mechanism; however, new modalities of caspase-independent regulated cell death have been identified, including necroptosis, pyroptosis, and autophagic cell death. As an understanding of the cellular mechanisms that mediate regulated cell death continues to grow, there is increasing evidence that these pathways are implicated in the pathogenesis of many pulmonary disorders. This review summarizes our understanding of regulated cell death as it pertains to the pathogenesis of chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis, acute respiratory distress syndrome, and pulmonary arterial hypertension.

Hypercoagulability in Pulmonary Hypertension.

Pulmonary hypertension (PH) is divided into varied pathophysiological and etiologic groupings, as classified by the World Health Organization (WHO). Pulmonary arterial hypertension (PAH), which falls under WHO group 1 PH, is a progressive and potentially fatal disease characterized by a vasoconstrictive, proliferative, and thrombotic phenotype, which leads to increased pulmonary artery pressure, right heart failure, and death. Pathologically, in situ thromboses are found in the small distal pulmonary arteries. Dysregulation of coagulation, platelet function, and endothelial cells may contribute to a prothrombotic state. There is mixed evidence for the use of anticoagulation or antiplatelet therapy in PAH patients.

Pulmonary arterial hypertension in the setting of scleroderma is different than in the setting of lupus: A review.

Pulmonary hypertension (PH) is a clinical syndrome that is subdivided into five groups per the World Health Organization (WHO) classification, based largely on hemodynamic and pathophysiologic criteria. WHO Group 1 PH, termed pulmonary arterial hypertension (PAH), is a clinically progressive disease that can eventually lead to right heart failure and death, and it is hemodynamically characterized by pre-capillary PH and increased pulmonary vascular resistance in the absence of elevated left ventricular filling pressures. PAH can be idiopathic, heritable, or associated with a variety of conditions. Connective tissue diseases make up the largest portion of these associated conditions, most commonly systemic sclerosis (SSc), followed by mixed connective tissue disease and systemic lupus erythematous. These etiologies (namely SSc and Lupus) have been grouped together as connective tissue disease-associated PAH, however emerging evidence suggests they differ in pathogenesis, clinical course, prognosis, and treatment response. This review highlights the differences between SSc-PAH and Lupus-PAH. After introducing the diagnosis, screening, and pathobiology of PAH, we discuss connective tissue disease-associated PAH as a group, and then explore SSc-PAH and SLE-PAH separately, comparing these 2 PAH etiologies.

Review of the Ongoing Story of Appetite Suppressants, Serotonin Pathway, and Pulmonary Vascular Disease.

Obesity is pandemic in the Western Hemisphere, especially in the United States (US) and is associated with morbidity and mortality. Recent data show that a large proportion of the US population is at least overweight and almost 2 in 5 Americans are obese. This ongoing trend of increasing obesity rates has led to a thriving market for anorexigens. Despite the health benefits of weight loss, several anorexigens had devastating side effects including pulmonary vascular disease which manifests as the clinical syndrome of pulmonary arterial hypertension (PAH). PAH is an incurable and fatal disease and is characterized by vascular constriction, hypertrophy, and proliferation that over time lead to right-sided cardiac failure. Over the past few decades, several weight loss medications have been associated with the development of PAH, possibly caused by an increase in systemic serotonin levels, resulting in vasoconstriction of the pulmonary arteries and initiating a cascade of pathologic vascular remodeling leading to vascular fibrosis. Once sufficient evidence for the association of these drugs with PAH or other related pathologies was found, many were removed from the market. However, there are other appetite suppressants still currently on the market (whether Food and Drug Administration-approved or "dietary supplements") that have to some extent similar mechanisms of action to those associated with PAH but lack robust enough data to prove or disprove an association. The serotonin pathway seems to be repeatedly implicated. In conclusion, given that PAH is a progressive and debilitating disease, it is important to highlight possible risk factors that could be avoided.

Pulmonary hypertension: diagnostic and therapeutic challenges.

Pulmonary hypertension (PH) is a hemodynamic and pathophysiologic state that can be found in multiple conditions with associated symptoms of dyspnea, decreased exercise tolerance, and progression to right heart failure. The World Health Organization has classified PH into five groups. The first group is pulmonary arterial hypertension (PAH), which can be idiopathic, heritable, due to drugs and toxins, or associated with conditions such as connective tissue diseases, congenital heart disease, portal hypertension, and others. The development of PAH is believed to result from smooth muscle cells and endothelial dysfunction that impairs production of vasodilators, including nitric oxide and prostacyclin. The importance of distinguishing this group from the other groups of PH is that there are PAH-specific drugs that target the molecular pathways that are pathogenic in the vascular derangements, leading to arterial hypertension, which should not be used in the other forms of PH. Other groups of PH include PH due to left heart disease, lung disease, chronic thromboembolic disease, as well as a miscellaneous category. Echocardiography is used to screen for PH and has varying sensitivity and specificity in detecting PH. Additionally, the right heart pressures estimated during echocardiogram often differ from those obtained during confirmatory testing with right heart catheterization. The most challenging PH diagnosis is in a case that does not fit one group of PH, but meets criteria that overlap between several groups. This also makes the treatment challenging because each group of PH is managed differently. This review provides an overview of the five groups of PH and discusses the diagnostic and therapeutic challenges of each.

Use of a pictographic diagram to decrease parent dosing errors with infant acetaminophen: a health literacy perspective.

OBJECTIVE: Medication dosing errors by parents are frequent. We sought to whether a pictographic dosing diagram could improve parent ability to dose infant acetaminophen, and to determine whether pictogram benefit varies by health literacy level. METHODS: We conducted an experimental study of parents presenting with their children to an urban public hospital pediatric clinic. Caregivers were randomized to dose infant acetaminophen with a standard dropper using text-only or text-plus-pictogram instructions (pictographic diagram of dose). The primary outcome variable was dosing accuracy (error defined as >20% deviation above/below dose; large overdosing error defined as >1.5 times recommended dose). Caregiver health literacy was assessed by means of the Newest Vital Sign measure. RESULTS: A total of 299 parents were assessed (144 text-only instructions; 155 text plus pictogram); 77.9% had limited health literacy (Newest Vital Sign score 0-3). Text-plus-pictogram recipients were less likely to make an error compared to text-only recipients (43.9% vs 59.0%, P = .01; absolute risk reduction, 15.2% [95% confidence interval, 3.8-26.0]; number needed to treat, 7 [4-26]). Of text-plus-pictogram recipients, 0.6% made a large overdosing error compared to 5.6% of text-only recipients (absolute risk reduction, 4.9% [0.9-10.0]; number needed to treat, 20 [10-108]). Pictogram benefit varied by health literacy, with a statistically significant difference in dosing error evident in the text-plus-pictogram group compared to the text-only group among parents with low health literacy (50.4% vs 66.4%; P = .02), but not for parents with adequate health literacy (P = .7). CONCLUSIONS: Inclusion of pictographic dosing diagrams as part of written medication instructions for infant acetaminophen may help parents provide doses of medication more accurately, especially those with low health literacy. High error rates, even among parents with adequate health literacy, suggest that additional study of strategies to optimize dosing is needed.

Parents' medication administration errors: role of dosing instruments and health literacy.

OBJECTIVES: To assess parents' liquid medication administration errors by dosing instrument type and to examine the degree to which parents' health literacy influences dosing accuracy. DESIGN: Experimental study. SETTING: Interviews conducted in a public hospital pediatric clinic in New York, New York, between October 28, 2008, and December 24, 2008. PARTICIPANTS: Three hundred two parents of children presenting for care were enrolled. MAIN OUTCOME MEASURES: Parents were observed for dosing accuracy (5-mL dose) using a set of standardized instruments (2 dosing cups [one with printed calibration markings, the other with etched markings], dropper, dosing spoon, and 2 oral syringes [one with and the other without a bottle adapter]). RESULTS: The percentages of parents dosing accurately (within 20% of the recommended dose) were 30.5% using the cup with printed markings and 50.2% using the cup with etched markings, while more than 85% dosed accurately with the remaining instruments. Large dosing errors (>40% deviation) were made by 25.8% of parents using the cup with printed markings and 23.3% of parents using the cup with etched markings. In adjusted analyses, cups were associated with increased odds of making a dosing error (>20% deviation) compared with the oral syringe (cup with printed markings: adjusted odds ratio [AOR] = 26.7; 95% confidence interval [CI], 16.8-42.4; cup with etched markings: AOR = 11.0; 95% CI, 7.2-16.8). Compared with the oral syringe, cups were also associated with increased odds of making large dosing errors (cup with printed markings: AOR = 7.3; 95% CI, 4.1-13.2; cup with etched markings: AOR = 6.3; 95% CI, 3.5-11.2). Limited health literacy was associated with making a dosing error (AOR = 1.7; 95% CI, 1.1-2.8). CONCLUSIONS: Dosing errors by parents were highly prevalent with cups compared with droppers, spoons, or syringes. Strategies to reduce errors should address both accurate use of dosing instruments and health literacy.