Clustering of Social Determinants of Health as an Indicator of Meaningful Subgroups within an African American Population: Application of Latent Class Analysis.

BACKGROUND: Health disparities between people who are African American (AA) versus their White counterparts have been well established, but disparities among AA people have not. The current study introduces a systematic method to determine subgroups within a sample of AA people based on their social determinants of health. METHODS: Health screening data collected in the West Side of Chicago, an underserved predominantly AA area, in 2018 were used. Exploratory latent class analysis was used to determine subgroups of participants based on their responses to 16 variables, each pertaining to a specific social determinant of health. RESULTS: Four unique clusters of participants were found, corresponding to those with "many unmet needs", "basic unmet needs", "unmet healthcare needs", and "few unmet needs". CONCLUSION: The findings support the utility of analytically determining meaningful subgroups among a sample of AA people and their social determinants of health. Understanding the differences within an underserved population may contribute to future interventions to eliminate health disparities.

Equity in Cardio-Oncology Care and Research: A Scientific Statement From the American Heart Association.

Advances in cancer therapeutics have revolutionized survival outcomes in patients with cancer. However, cardiovascular toxicities associated with specific cancer therapeutics adversely affect the outcomes of patients with cancer. Recent studies have uncovered excess risks of these cardiotoxic events, especially in traditionally underrepresented populations. Despite advances in strategies to limit the risks of cardiovascular events among cancer survivors, relatively limited guidance is available to address the rapidly growing problem of disparate cardiotoxic risks among women and underrepresented patient populations. Previously decentralized and sporadic evaluations have led to a lack of consensus on the definitions, investigation, and potential optimal strategies to address disparate cardiotoxicity in contemporary cancer care (eg, with immunotherapy, biologic, or cytotoxic therapies) settings. This scientific statement aims to define the current state of evidence for disparate cardiotoxicity while proposing uniform and novel methodological approaches to inform the identification and mitigation of disparate cardio-oncology outcomes in future clinical trials, registries, and daily clinical care settings. We also propose an evidence-based integrated approach to identify and mitigate disparities in the routine clinical setting. This consensus scientific statement summarizes and clarifies available evidence while providing guidance on addressing inequities in the era of emerging anticancer therapies.

Rapid Deployment of Whole Slide Imaging for Primary Diagnosis in Surgical Pathology at Stanford Medicine: Responding to Challenges of the COVID-19 Pandemic.

CONTEXT.­: Stanford Pathology began stepwise subspecialty implementation of whole slide imaging (WSI) in 2018 soon after the first US Food and Drug Administration approval. In 2020, during the COVID-19 pandemic, the Centers for Medicare & Medicaid Services waived the requirement for pathologists to perform diagnostic tests in Clinical Laboratory Improvement Amendments (CLIA)-licensed facilities. This encouraged rapid implementation of WSI across all surgical pathology subspecialties. OBJECTIVE.­: To present our experience with validation and implementation of WSI at a large academic medical center encompassing a caseload of more than 50 000 cases per year. DESIGN.­: Validation was performed independently for 3 subspecialty services with a diagnostic concordance threshold above 95%. Analysis of user experience, staffing, infrastructure, and information technology was performed after department-wide expansion. RESULTS.­: Diagnostic concordance was achieved in 96% of neuropathology cases, 100% of gynecologic pathology cases, and 98% of immunohistochemistry cases. After full implementation, 8 high-capacity scanners were operational, with whole slide images generated on greater than 2000 slides per weekday, accounting for approximately 80% of histologic slides at Stanford Medicine. Multiple modifications in workflow and information technology were needed to improve performance. Within months of full implementation, most attending pathologists and trainees had adopted WSI for primary diagnosis. CONCLUSIONS.­: WSI across all surgical subspecialities is achievable at scale at an academic medical center; however, adoption required flexibility to adjust workflows and develop tailored solutions. WSI at scale supported the health and safety of medical staff while facilitating high-quality patient care and education during COVID-19 restrictions.

Changes in Drug List Prices and Amounts Paid by Patients and Insurers.

Importance: High out-of-pocket drug costs can cause patients to skip treatment and worsen outcomes, and high insurer drug payments could increase premiums. Drug wholesale list prices have doubled in recent years. However, because of manufacturer discounts and rebates, the extent to which increases in wholesale list prices are associated with amounts paid by patients and insurers is poorly characterized. Objective: To determine whether increases in wholesale list prices are associated with increases in amounts paid by patients and insurers for branded medications. Design, Setting, and Participants: Cross-sectional retrospective study analyzing pharmacy claims for patients younger than 65 years in the IBM MarketScan Commercial Database and pricing data from SSR Health, LLC, between January 1, 2010, and December 31, 2016. Pharmacy claims analyzed represent claims of employees and dependents participating in employer health benefit programs belonging to large employers. Rebate data were estimated from sales data from publicly traded companies. Analysis focused on the top 5 patent-protected specialty and 9 traditional brand-name medications with the highest total drug expenditures by commercial insurers nationwide in 2014. Data were analyzed from July 2017 to July 2020. Exposures: Calendar year. Main Outcomes and Measures: Changes in inflation-adjusted amounts paid by patients and insurers for branded medications. Results: In this analysis of 14.4 million pharmacy claims made by 1.8 million patients from 2010-2016, median drug wholesale list price increased by 129% (interquartile range [IQR], 78%-133%), while median insurance payments increased by 64% (IQR, 28%-120%) and out-of-pocket costs increased by 53% (IQR, 42%-82%). The mean percentage of wholesale list price accounted for by discounts increased from 17% in 2010 to 21% in 2016, and the mean percentage of wholesale list price accounted for by rebates increased from 22% in 2010 to 24% in 2016. For specialty medications, median patient out-of-pocket costs increased by 85% (IQR, 73%-88%) from 2010 to 2016 after adjustment for inflation and 42% (IQR, 25%-53%) for nonspecialty medications. During that same period, insurer payments increased by 116% for specialty medications (IQR, 100%-127%) and 28% for nonspecialty medications (IQR, 5%-34%). Conclusions and Relevance: This study's findings suggest that drug list prices more than doubled over a 7-year study period. Despite rising manufacturer discounts and rebates, these price increases were associated with large increases in patient out-of-pocket costs and insurer payments.

Paravalvular Leak Assessment: Challenges in Assessing Severity and Interventional Approaches.

PURPOSE OF REVIEW: With increasing use of prosthetic valves to treat degenerative valvular heart disease (VHD) in an aging population, the incidence and adverse consequences of paravalvular leaks (PVL) are better recognized. The present work aims to provide a cohesive review of the available literature in order to better guide the evaluation and management of PVL. RECENT FINDINGS: Despite gains in operator experience and design innovation, significant PVL remains a significant complication that may present with congestive heart failure and/or hemolytic anemia. To date, clear consensus or guidelines on the evaluation and management of PVL remain lacking. Although the evolution of transcatheter valve therapies has had a tremendous impact on the management of patients with VHD, the limitations and complications of such techniques, including PVL, present further challenges. Incidence of PVL, graded as moderate or greater, ranges from 4 to 7.4% in surgical and transcatheter valve replacements, respectively. Improved imaging modalities and the advent of novel surgical and percutaneous therapies have undoubtedly yielded a better understanding of PVL including its anatomical location, mechanism, severity, and treatment options. Echocardiography, used in conjunction with cardiac computed tomography and cardiac magnetic resonance, provides essential details for diagnosis and management of PVL. Transcatheter intervention has become a favored approach in lieu of surgical intervention in select patients after previous surgical or percutaneous valve replacement. PVL treatment with vascular plugs, balloon post-dilation, and the valve-in-valve methods have shown technical success with promising clinical outcomes in appropriately selected patients.

Quantitative assessment of cardiovascular autonomic impairment in cancer survivors: a single center case series.

BACKGROUND: Cardiovascular autonomic dysfunction in cancer survivors is poorly understood. OBJECTIVES: To better characterize the clinical characteristics and types of autonomic dysfunction in this population. METHODS: A retrospective analysis of cancer survivors within an academic cardio-oncology program referred for suspected autonomic dysfunction was performed. Autonomic reflex testing of adrenergic, cardiovagal, and sudomotor function was done. Autonomic impairment was graded on severity based on the Composite Autonomic Severity Score system. Patients with pre-existing autonomic dysfunction prior to their cancer diagnosis were excluded. RESULTS: Of approximately 282 total patients in the UCLA Cardio-Oncology program, 24 were referred for suspected autonomic dysfunction and met the inclusion criteria. 22 had autonomic impairment on autonomic reflex testing. Eight patients were female, and the mean age at time of autonomic testing was 51.3 years. The average duration from cancer diagnosis to autonomic testing was 10.3 years. The reasons for referral included dizziness, tachycardia, palpitations, and syncope. The majority of patients (75%) had hematologic disorders. The most common chemotherapies administered were vinca alkaloids (54.2%), alkylating agents (66.7%), and anthracyclines (54.2%). Most patients received radiation to the thorax (66.7%) and neck (53.3%). Eleven patients had mild autonomic impairment, 7 had moderate, and 4 had severe autonomic impairment. Dysfunction was commonly present in the sympathetic and parasympathetic branches, but most pronounced in the sympathetic system. The majority of patients were diagnosed with orthostatic hypotension (50%), inappropriate sinus tachycardia (20.8%), and postural orthostatic tachycardia syndrome (12.5%) and had subjective improvement with treatment. CONCLUSION: Cardiovascular autonomic dysfunction occurs in cancer survivors, and commonly affects both the sympathetic and parasympathetic systems. Symptom recognition in patients should prompt autonomic testing and treatment where appropriate.

National Outcomes in Hospitalized Patients With Cancer and Comorbid Heart Failure.

BACKGROUND: Heart failure (HF) and cancer are a significant cause of morbidity and mortality in the US. Due to overlapping risk factors, these two conditions often coexist. METHODS: We sought to describe the national burden of HF for hospitalized patients with cancer. We identified adults admitted with a primary oncologic diagnosis in 2014 included in the National Inpatient Sample (NIS). Patient hospitalizations were divided based on presence or absence of comorbid HF. Primary outcomes included cost, length of stay (LOS), and inpatient mortality. Logistic regression analysis with cluster adjustment was performed to determine predictors of inpatient mortality. RESULTS: There were 834,900 admissions for a primary oncologic diagnosis in patients without comorbid HF, and 64,740 (7.2%) admissions for patients with comorbid HF. Patients with HF were on average older and had more comorbidities. Patients with HF had significantly higher mean hospitalization cost ($22,571 vs $20,234, p-value <0.001), age-standardized LOS (12.7 vs 8.2 days, p-value <0.001), and age-standardized inpatient mortality (12.2% vs 4.5%, p-value <0.001). Presence of HF predicted inpatient mortality after adjusting for age, race, insurance payer, and comorbidity index (OR 1.12, 95% CI 1.04-20, p-value = 0.002). CONCLUSION: Patients with cancer hospitalized with comorbid HF represent a high-risk population with increased costs and high inpatient mortality rates. More data is needed to determine what screening and treatment measures may improve outcomes.

Association of left atrial volume index and all-cause mortality in patients referred for routine cardiovascular magnetic resonance: a multicenter study.

BACKGROUND: Routine cine cardiovascular magnetic resonance (CMR) allows for the measurement of left atrial (LA) volumes. Normal reference values for LA volumes have been published based on a group of European individuals without known cardiovascular disease (CVD) but not on one of similar United States (US) based volunteers. Furthermore, the association between grades of LA dilatation by CMR and outcomes has not been established. We aimed to assess the relationship between grades of LA dilatation measured on CMR based on US volunteers without known CVD and all-cause mortality in a large, multicenter cohort of patients referred for a clinically indicated CMR scan. METHOD: We identified 85 healthy US subjects to determine normal reference LA volumes using the biplane area-length method and indexed for body surface area (LAVi). Clinical CMR reports of patients with LA volume measures (n = 11,613) were obtained. Data analysis was performed on a cloud-based system for consecutive CMR exams performed at three geographically distinct US medical centers from August 2008 through August 2017. We identified 10,890 eligible cases. We categorized patients into 4 groups based on LAVi partitions derived from US normal reference values: Normal (21-52 ml/m2), Mild (52-62 ml/m2), Moderate (63-73 ml/m2) and Severe (> 73 ml/m2). Mortality data were ascertained for the patient group using electronic health records and social security death index. Cox proportional hazard risk models were used to derive hazard ratios for measuring association of LA enlargement and all-cause mortality. RESULTS: The distribution of LAVi from healthy subjects without known CVD was 36.3 ± 7.8 mL/m2. In clinical patients, enlarged LA was associated with older age, atrial fibrillation, hypertension, heart failure, inpatient status and biventricular dilatation. The median follow-up duration was 48.9 (IQR 32.1-71.2) months. On univariate analyses, mild [Hazard Ratio (HR) 1.35 (95% Confidence Interval [CI] 1.11 to 1.65], moderate [HR 1.51 (95% CI 1.22 to 1.88)] and severe LA enlargement [HR 2.14 (95% CI 1.81 to 2.53)] were significant predictors of death. After adjustment for significant covariates, moderate [HR 1.45 (95% CI 1.1 to 1.89)] and severe LA enlargement [HR 1.64 (95% CI 1.29 to 2.08)] remained independent predictors of death. CONCLUSION: LAVi determined on routine cine-CMR is independently associated with all-cause mortality in patients undergoing a clinically indicated CMR.

The impact of pediatric atopic dermatitis on families: A review.

BACKGROUND: Atopic dermatitis (AD) is an extremely common childhood disease, with considerable impact on the quality of life of affected children and their families. While pruritus is the hallmark symptom of this disease, AD has been well-documented to impact patients beyond physical symptoms, resulting in behavior problems, mood disorders, and sleep disturbance. OBJECTIVE: This literature review outlines how atopic dermatitis impacts the quality of life of families of children affected by AD. METHODS: A total of 3436 articles were identified via an online search of the MEDLINE health literature database and were screened for relevance to quality of life impacts on families with children affected by AD. RESULTS: Caring for children affected by AD can be an extremely time-consuming task that can impair personal relationships, decrease psychosocial functioning, and cause sleep loss among family members of affected patients. Additionally, AD may result in work absence or decreased work productivity for caregivers. Special diets, irritant and allergen avoidance strategies, and alternative therapies are commonly used by patients to manage their disease and require large amounts of family involvement. CONCLUSIONS: Atopic dermatitis can greatly decrease quality of life of families of affected children in various domains, including sleep, finances, and relationships. Early intervention and psychotherapy may be needed in some patients to address these quality of life impairments.

Four-dimensional flow cardiovascular magnetic resonance in aortic dissection: Assessment in an ex vivo model and preliminary clinical experience.

OBJECTIVE: Four-dimensional flow cardiovascular magnetic resonance may improve assessment of hemodynamics in patients with aortic dissection. The purpose of this study was to evaluate the feasibility and accuracy of 4-dimensional flow cardiovascular magnetic resonance assessment of true and false lumens flow. METHODS: Thirteen ex vivo porcine aortic dissection models were mounted to a flow loop. Four-dimensional flow cardiovascular magnetic resonance and 2-dimensional phase-contrast cardiovascular magnetic resonance measurements were performed, assessed for intraobserver and interobserver variability, and compared with a reference standard of sonotransducer flow volume measurements. Intraobserver and interobserver variability of 4-dimensional flow cardiovascular magnetic resonance were also assessed in 14 patients with aortic dissection and compared with 2-dimensional phase-contrast cardiovascular magnetic resonance. RESULTS: In the ex vivo model, the intraobserver and interobserver measurements had Lin's correlation coefficients of 0.98 and 0.96 and mean differences of 0.17 (±3.65) mL/beat and -0.59 (±5.33) mL/beat, respectively; 4-dimensional and sonotransducer measurements had a Lin's concordance correlation coefficient of 0.95 with a mean difference of 0.35 (±4.92) mL/beat, respectively. In patients with aortic dissection, the intraobserver and interobserver measurements had Lin's concordance correlation coefficients of 0.98 and 0.97 and mean differences of -0.95 (±8.24) mL/beat and 0.62 (±10.05) mL/beat, respectively; 4-dimensional and 2-dimensional flow had a Lin's concordance correlation coefficient of 0.91 with a mean difference of -9.27 (±17.79) mL/beat because of consistently higher flow measured with 4-dimensional flow cardiovascular magnetic resonance in the ascending aorta. CONCLUSIONS: Four-dimensional flow cardiovascular magnetic resonance is feasible in patients with aortic dissection and can reliably assess flow in the true and false lumens of the aorta. This promotes potential future work on functional assessment of aortic dissection hemodynamics.

Community-Based Diabetes Community Health Worker Intervention in an Underserved Chicago Population.

The Community Health Worker (CHW) model has been used to combat disparities in healthcare access by utilizing community members as healthcare liaisons to promote improved community health. CHW interventions have been effective in improving diabetes management. This case study reports on a low-intensity CHW intervention in a predominantly Hispanic and non-Hispanic Black population in two Chicago neighborhoods: North Lawndale and South Lawndale. CHWs conducted door-to-door outreach and, for individuals with self-reported type 2 diabetes, offered home visits at baseline and one-year follow-up to provide diabetes education, create an individual management strategy, and refer to clinic-based support services. During 2012, 459 participants were enrolled, with 343 completing follow-up visits in 2013 (75 % retention). The mean HbA1c decrease was 0.5 %. At follow-up, participants were less likely to be depressed, to forget to take their diabetes medications, and were more likely to report higher social support and score higher on an assessment of diabetes knowledge. Patients who were younger, Hispanic, had uncontrolled diabetes, and had lower levels of diabetes self-care at baseline demonstrated increased odds of a significant HbA1c decrease with the intervention than patients without these characteristics. This study demonstrates the effectiveness of a home-based, low-intensity CHW intervention in medically underserved communities, and identifies population groups who might benefit the most from future similar CHW interventions.

Integrating internal and external bioanalytical support to deliver a diversified pharmaceutical portfolio.

The portfolios of pharmaceutical companies have diversified substantially over recent years in recognition that monotherapies and/or small molecules are less suitable for modulating many complex disease etiologies. Furthermore, there has been increased pressure on drug-development budgets over this same period. This has placed new challenges in the path of bioanalytical scientists, both within the industry and with contract research organizations (CROs). Large pharmaceutical, biotechnology and small-medium healthcare enterprises have had to make important decisions on what internal capabilities they wish to retain and where CROs offers a significant strategic benefit to their business model. Our journey has involved asking where we believe an internal bioanalytical facility offers the greatest benefit to progressing drug candidates through the drug-development cycle and where externalization can help free up internal resources, adding flexibility to our organization in order to deal with the inevitable peaks and troughs in workload.

Evaluation of valvular disease by cardiac computed tomography assessment.

Cardiac multidetector computed tomography (MDCT) angiography is emerging as a technique to evaluate cardiac valve structure and function. MDCT can provide insights into cardiac valve anatomy and pathologic states, including comparable efficacy in valve area and regurgitant orifice area assessment compared with echocardiography and magnetic resonance imaging. MDCT can also be useful when initial evaluation of valvular disease with echocardiography yields suboptimal images. MDCT provides concurrent visualization of coronary anatomy which may avoid the need for further invasive preoperative testing. Overall, more studies have shown the utility of MDCT in imaging of left-sided valves (aortic and mitral), whereas its ability in assessing right-sided valves (tricuspid and pulmonary) is somewhat limited. MDCT has shown promise as a valuable adjunctive imaging tool to conventional imaging modalities in providing essential anatomic and physiologic data on the sequelae of valvular dysfunction, with the potential of guiding both surgical and percutaneous management. MDCT technology continues to evolve, and more studies are indicated to further refine its precise role in the evaluation of patients with valvular pathology.

2012 white paper on recent issues in bioanalysis and alignment of multiple guidelines.

Over 400 professionals representing pharmaceutical companies, CROs, and multiple regulatory agencies participated in the 6th Workshop on Recent Issues in Bioanalysis (WRIB). Like the previous sessions, this event was in the format of a practical, focused, highly interactive and informative workshop aiming for high-quality, improved regulatory compliance and scientific excellence. Numerous 'hot' topics in bioanalysis of both small and large molecules were shared and discussed, leading to consensus and recommendations among panelists and attendees representing the bioanalytical community. The major outcome of this year's workshop was the noticeable alignment of multiple bioanalytical guidance/guidelines from different regulatory agencies. This represents a concrete step forward in the global harmonization of bioanalytical activities. The present 2012 White Paper acts as a practical and useful reference document that provides key information and solutions on several topics and issues in the constantly evolving world of bioanalysis.

Ultrasound imaging of carotid intima-media thickness: an office-based tool to assist physicians in cardiovascular risk assessment.

Traditional coronary heart disease risk prediction schemes such as the Framingham Risk Score, although useful, do not adequately identify all individuals who experience an adverse coronary heart disease event. Therefore, additional tools, including biomarkers, genetic markers, and imaging markers, are being evaluated for their value in improving cardiovascular risk assessment. Of the two accepted imaging markers of atherosclerosis, namely coronary artery calcium score (CACS) measured by CT scan and carotid intima-media thickness (CIMT) measured by ultrasound, CIMT has the potential to be widely adopted as a clinical tool for physician offices. Ultrasound-based CIMT measurement is safe but has several challenges, including reproducibility and operator-dependency. We review and present data with respect to the added value of CIMT and information about plaque presence or absence in improving coronary heart disease risk prediction and further provide information related to adequate scanning protocols. New developments in the area of automated CIMT measurement, three-dimensional, ultrasound-based plaque volume estimation are promising and have the potential to create a quantum leap in our ability to measure, characterize, and monitor carotid atherosclerosis and in turn prediction of cardiovascular disease risk.