Palliative Therapies in Metastatic Pancreatic Cancer: Does Medicaid Expansion Make a Difference?

BACKGROUND: The aim of this study was to evaluate the impact of medicaid expansion (ME) on receipt of palliative therapies in metastatic pancreatic cancer patients. PATIENTS AND METHODS: A difference-in-differences (DID) approach was used to analyze patients with metastatic pancreatic cancer identified from the National Cancer Database diagnosed during two time periods: pre-expansion (2010-2012) and post-expansion (2014-2016). Patients diagnosed while residing in ME states were compared with those in non-ME states. Multivariable logistic regression was used to identify predictors of receipt of palliative therapies. RESULTS: Of 87,738 patients overall, 7483(18.1%) received palliative therapies in the pre-expansion, while 10,211(21.5%) received palliative therapies in the post-expansion period. In the pre-expansion period, treatment at a high-volume facility (HVF) (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.02-1.18) and non-west geographic location were predictive of increased palliative therapies. In the post-expansion period, treatment at an HVF (OR 1.09, 95% CI 1.02-1.16), geographic location, and living in an ME state at the time of diagnosis (OR 1.14, 95% CI 1.06-1.22) were predictive of increased palliative therapies. Older age, highest quartile median income (zip-code based), and treatment at a nonacademic facility were independently associated with decreased palliative therapies in both periods. DID analysis demonstrated that patients with metastatic pancreatic cancer living in ME states had increased receipt of palliative therapies relative to those in non-ME states (DID = 2.68, p < 0.001). CONCLUSIONS: The overall utilization of palliative therapies in metastatic pancreatic cancer is low. Multiple sociodemographic disparities exist in the receipt of palliative therapies. ME is associated with increased receipt of palliative therapies in patients with metastatic pancreatic cancer.

All-cause unplanned readmissions in the United States: insights from the Nationwide Readmission Database.

BACKGROUND: There are few studies looking into adult, all-cause and age-group-specific unplanned readmissions. The predictors of such unplanned readmissions for all inpatient encounters remain obscure. AIMS: To describe the incidence and factors associated with unplanned readmissions in all inpatient encounters in the United States. METHODS: The US Nationwide Readmission Database (NRD) is a representative sample of hospitalisations in the United States (from approximately 28 states) accounting for approximately 60% of the US population. All inpatient encounters during January-November 2017 in the NRD were evaluated for the rates, predictors and costs of unplanned 30 days readmissions for age groups 18-44 years, 45-64 years, 65-75 years and ≥75 years. Elective readmissions and those patients who died on their index hospitalisations were excluded. Weighted analysis was performed to obtain nationally representative data. RESULTS: We identified 28 942 224 inpatient encounters with a total of 3 051 189 (10.5%) unplanned readmissions within 30 days. The age groups 18-44 years, 45-64 years, 65-74 years and ≥75 years had 7.0%, 12.0%, 11.7% and 12.3% readmissions respectively. Female gender, private insurance and elective admissions were negative predictors for readmissions. For the group aged 18-44 years, schizophrenia and diabetes mellitus complications were the most frequent primary diagnosis for readmissions, while in all older age groups septicaemia and heart failure were the most frequent primary diagnosis for readmissions. CONCLUSIONS: Thirty-day unplanned readmissions are common in patients over age 45 years, leading to significant morbidity. Effective strategies for reducing unplanned readmission may help to improve quality of care, outcomes and higher value care.

Obesity Stigma and Bias.

Overweight and obesity are escalating in epidemic proportions in the United States. Individuals with overweight and obesity are often reluctant to seek medical help, not only for weight reduction but also for any health issue because of perceived provider discrimination. Providers who are biased against individuals with obesity can hinder our nation's effort to effectively fight the obesity epidemic. By addressing weight bias in the provider setting, individuals affected by obesity may be more likely to engage in a meaningful and productive discussion of weight. Providers need to be the go-to source for obesity-focused information on new and emerging treatments.

Large-scale gene-centric meta-analysis across 39 studies identifies type 2 diabetes loci.

To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with ∼2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 × 10(-9)) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p < 2.4 × 10(-6)). Second, meta-analyses of 1,986 cases and 7,695 controls from eight African-American studies identified study-wide-significant (p = 2.4 × 10(-7)) variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 × 10(-15)). Third, conditional analysis revealed multiple known and novel independent signals within five T2D-associated genes in samples of European ancestry and within HMGA2 in African-American samples. Fourth, a multiethnic meta-analysis of all 39 studies identified T2D-associated variants in BCL2 (p = 2.1 × 10(-8)). Finally, a composite genetic score of SNPs from new and established T2D signals was significantly associated with increased risk of diabetes in African-American, Hispanic, and Asian populations. In summary, large-scale meta-analysis involving a dense gene-centric approach has uncovered additional loci and variants that contribute to T2D risk and suggests substantial overlap of T2D association signals across multiple ethnic groups.

Fragmentation of Care in Pancreatic Cancer: Effects on Receipt of Care and Survival.

BACKGROUND: The impact of fragmentation of care (FC), i.e., receipt of care at > 1 institution, on treatment of pancreatic cancer is unknown. The purpose of this study was to determine factors associated with FC in curative-intent treatment of pancreatic cancer (PDAC) patients and evaluate how FC affects survival outcomes. METHODS: Using the National Cancer Database (NCDB), data on stage I-III PDAC patients diagnosed 2006-2016 were extracted. Multiple logistic regression analyses were performed to identify factors predictive of FC and survival. RESULTS: Of the 20,013 patients identified, 24.1% had FC. Factors predictive of FC were stage-III tumors (odds ratio [OR] 1.36; p = 0.014), higher median-income [third quartile (OR 1.38; p = 0.006) and highest-quartile (OR 1.50; p = 0.003)], care at high-volume facility (OR 1.47; p < 0.001), and receipt of multi-modal therapy (OR 1.69; p < 0.001). In contrast, age > 80 years (OR 0.82; p = 0.018), Black (OR 0.85; p = 0.013) or Asian race (OR 0.76; p = 0.033), Charlson comorbidity-index 2 (OR 0.85; p = 0.033), treatment at non-academic facility (OR 0.87; p = 0.041), and non-private insurance were negatively predictive of FC. FC independently predicted decreased 30-day [OR 0.57; p < 0.001] and 90-day mortality [OR 0.61; p < 0.001] and improved overall survival [hazard ratio 0.91; p < 0.001]. DISCUSSION: Sociodemographic factors are significantly associated with FC in curative-intent treatment of PDAC patients. FC was found to predict improved 30-day, 90-day, and overall survival outcomes.

Neurovascular Dysfunction in Diverse Communities With Health Disparities-Contributions to Dementia and Alzheimer's Disease.

Alzheimer's disease and related dementias (ADRD) are an expanding worldwide crisis. In the absence of scientific breakthroughs, the global prevalence of ADRD will continue to increase as more people are living longer. Racial or ethnic minority groups have an increased risk and incidence of ADRD and have often been neglected by the scientific research community. There is mounting evidence that vascular insults in the brain can initiate a series of biological events leading to neurodegeneration, cognitive impairment, and ADRD. We are a group of researchers interested in developing and expanding ADRD research, with an emphasis on vascular contributions to dementia, to serve our local diverse community. Toward this goal, the primary objective of this review was to investigate and better understand health disparities in Alabama and the contributions of the social determinants of health to those disparities, particularly in the context of vascular dysfunction in ADRD. Here, we explain the neurovascular dysfunction associated with Alzheimer's disease (AD) as well as the intrinsic and extrinsic risk factors contributing to dysfunction of the neurovascular unit (NVU). Next, we ascertain ethnoregional health disparities of individuals living in Alabama, as well as relevant vascular risk factors linked to AD. We also discuss current pharmaceutical and non-pharmaceutical treatment options for neurovascular dysfunction, mild cognitive impairment (MCI) and AD, including relevant studies and ongoing clinical trials. Overall, individuals in Alabama are adversely affected by social and structural determinants of health leading to health disparities, driven by rurality, ethnic minority status, and lower socioeconomic status (SES). In general, these communities have limited access to healthcare and healthy food and other amenities resulting in decreased opportunities for early diagnosis of and pharmaceutical treatments for ADRD. Although this review is focused on the current state of health disparities of ADRD patients in Alabama, future studies must include diversity of race, ethnicity, and region to best be able to treat all individuals affected by ADRD.

Association of socioeconomic status and CKD among African Americans: the Jackson Heart Study.

BACKGROUND: Socioeconomic status (SES) is recognized as a key social environmental factor because it has implications for access to resources that help individuals care for themselves and others. Few studies have examined the association of SES with chronic kidney disease (CKD) in high-risk populations. STUDY DESIGN: Single-site longitudinal population-based cohort. SETTING & PARTICIPANTS: Data for this study were drawn from the baseline examination of the Jackson Heart Study. The analytic cohort consisted of 3,430 African American men and women living in the tricounty region of the Jackson, MS, metropolitan area with complete data to determine CKD status. PREDICTOR: High SES (defined as having a family income at least 3.5 times the poverty level or having at least 1 undergraduate degree). OUTCOMES & MEASUREMENTS: CKD (defined as the presence of albuminuria or decreased estimated glomerular filtration rate [<60 mL/min/1.73 m(2)]). Associations were explored using bivariable analyses and multivariable logistic regression analyses adjusting for CKD and cardiovascular disease risk factors, as well as demographic factors. RESULTS: The prevalence of CKD in the Jackson Heart Study was 20% (865 of 3,430 participants). Proportions of the Jackson Heart Study cohort with albuminuria and decreased estimated glomerular filtration rate were 12.5% (429 of 3,430 participants) and 10.1% (347 of 3,430 participants), respectively. High SES was associated inversely with CKD. The odds of having CKD were 41% lower for affluent participants than their less affluent counterparts. There were no statistically significant interactions between sex and education or income, although subgroup analysis showed that high income was associated with CKD in men (OR, 0.47; 95% CI, 0.23-0.97), but not women (OR, 0.64; 95% CI, 0.40-1.03). LIMITATIONS: Models were estimated using cross-sectional data. CONCLUSION: CKD is associated with SES. Additional research is needed to elucidate the impact of wealth and social contexts in which individuals are embedded and the mediating effects of sociocultural factors.

Transcriptional Regulation of Transforming Growth Factor ß1 by Glucose: Investigation into the Role of the Hexosamine Biosynthesis Pathway.

BACKGROUND: The hexosamine biosynthesis pathway (HBP) is hypothesized to mediate many of the adverse effects of hyperglycemia. We have shown previously that increased flux through this pathway leads to induction of the growth factor transforming growth factor-α (TGF-α) and to insulin resistance in cultured cells and transgenic mice. TGF-ß is regulated by glucose and is involved in the development of diabetic nephropathy. We therefore hypothesized that the HBP was involved in the regulation of TGF-ß by glucose in rat vascular and kidney cells. METHODS: A plasmid containing the promoter region of TGF-ß1 cloned upstream of the firefly luciferase gene was electroporated into rat aortic smooth muscle, mesangial, and proximal tubule cells. Luciferase activity was measured in cellular extracts from cells cultured in varying concentrations of glucose and glucosamine. RESULTS: Glucose treatment of all cultured cells led to a time- and dose-dependent stimulation in TGF-ß1 transcriptional activity, with high (20 mM) glucose causing a 1.4- to 2.0-fold increase. Glucose stimulation did not occur until after 12 hours and disappeared after 72 hours of treatment. Glucosamine was more potent than glucose, with 3 mM stimulating up to a 4-fold increase in TGFß1-transcriptional activity. The stimulatory effect of glucosamine was also dose-dependent but was slower to develop and longer lasting than that of glucose. CONCLUSIONS: The metabolism of glucose through the HBP mediates extracellular matrix production, possibly via the stimulation of TGF-ß in kidney cells. Hexosamine metabolism therefore, may play a role in the development of diabetic nephropathy.

A review of interventions to reduce health disparities in cardiovascular disease in African Americans.

BACKGROUND: There is a wealth of first- (type or extent) and second- (causes) generation health disparities research. Literature on health disparities interventions (third-generation research) is emerging. In this study, we compiled and qualitatively evaluated interventions to eliminate health disparities in cardiovascular disease (CVD) among African Americans. METHODS: We reviewed articles published from 1996 through 2006. Inclusion criteria were focus on CVD, African American participants, and intervention, including evaluation data. Two readers evaluated each abstract for including in the full review, and a third reader resolved incongruence. Articles with abstracts that received at least 2 votes for inclusion were reviewed in their entirety by 2 readers. Data were recorded in a Microsoft Access database. RESULTS: Of 524 abstracts identified, 111 were selected for full review. Only 33 articles were considered third-generation health disparities research by 2 readers and 23 by 1 reader. Approximately half of the interventions were in high-risk populations (low income, low education, urban) and hypertension and nutrition and physical activity were the most common focuses. Of the 33 that received 2 votes, the interventions that received the most enthusiasm from the reviewers used community-based clinics with lay health volunteers. The intensity of the intervention was not correlated with outcome. CONCLUSIONS: While not widely published, third-generation health disparities research demonstrates interventions to reduce CVD among African Americans. More of this type of research is necessary, and those results must be disseminated.

Identifying and Overcoming Roadblocks that Limit the Translation of Research Findings to the Achievement of Health Equity.

Almost two decades ago, the Institute of Medicine's Clinical Research Roundtable commented on the major challenges of moving health related basic science discovery to the clinical setting. The roadblocks identified included challenges in evaluating a discovery's application to human disease, and, if justified, getting that application out to the general population. The obstacles to achieving this translation of discovery to improvements in human health remain today and are most evident in populations at highest risk for inequitably poor health. We address four potential roadblocks which, if solved, will have a great impact on achieving health equity. They are expanding the definition of basic discovery to include all facets of health disparities science, understanding the daily factors that affect a community's well-being, including diverse populations in clinical trials, and training the right scientists to perform the community-engaged research required to move discovery to application in the community.

Health disparities in chronic diseases: where the money is.

Chronic diseases account for three-quarters of the U.S. health care expenditures and a majority of early deaths and lost of productive years of life. Health disparities exist among the common chronic diseases, such as hypertension, diabetes mellitus, HIV/AIDS, cancer, cardiovascular disease, and obesity, with ethnic minorities and the poor having higher incidence or worse outcomes. Strategies to eliminate these disparities in chronic diseases need to be multidisciplinary and focus on increasing access to all aspects of health care, including prevention. This article discusses the impact of health disparities on chronic diseases and offers some factors to consider for solutions to the problem.

Using zip code-level mortality data as a local health status indicator in Mobile, Alabama.

OBJECTIVE: Having local health data is critical to combat health disparities, and zip code-level data are an underutilized source of such information. We sought to use zip code-level mortality data to determine where health disparities existed in our local area. METHODS: The most heavily populated zip codes were aggregated into 2 groups: (1) study area population (SAP) where >or=20% of individuals lived in poverty in 1999; (2) comparison area population, <20% in poverty. Disease-specific mortality rates (per 100,000 population) were calculated and compared. The relative risk (RR) of death from specific causes was the ratio of the mortality rate experienced by the SAP compared with that experienced by the comparison area population. RESULTS: The SAP had higher percentages of African Americans and women and much lower levels of income, employment, and education. Some zip codes in SAP had over 40% living below the poverty level. The RR of death from all but 4 of the 22 causes examined was >or=40% higher in the SAP. Major disparities (RR >2.5) were seen for human immunodeficiency virus, homicide, hypertensive heart and renal disease, and kidney disease. Actual death rates were highest for major cardiovascular disease and cancer, and the level of disparities here (RR approximately 1.4) make them important areas for concentration. CONCLUSION: Using zip code-level data provides an accurate foundation from which to design local interventions to address health disparities.

Insuring continuity of care for chronic disease patients after a disaster: key preparedness elements.

BACKGROUND: Care for patients with chronic diseases is a challenge after a disaster. This is particularly true for individuals from health disparate populations as they are less likely to evacuate, have fewer financial resources and often depend on resource-strapped institutions for their care. The specific aim of the study presented here was to elicit challenges and solutions in the provision of health care to those with chronic diseases after Hurricane Katrina in coastal Alabama and Mississippi. METHODS: Focusing on agencies providing care to health disparate populations, a qualitative methodology was employed using in-depth interviews with health and social service providers. Participants identified key elements essential to disaster preparedness. RESULTS: Predisaster issues were patient education and preparedness, evacuation, special needs shelters, and health care provider preparedness. Postdisaster issues were communication, volunteer coordination, and donation management. CONCLUSIONS: Lessons learned from those on the ground administering health care during disasters should inform future disaster preparations. Furthermore, the methodological approach used in this study engendered collaboration between health care institutions and may enhance future interagency disaster preparedness.

Research Apprenticeship and Its Potential as a Distinct Model of Peer Research Practice.

BACKGROUND: Three models of peer research have emerged: advisory, employment, and partner. We propose a fourth model, the "research apprentice" prototype conceived as a postsecondary workforce development avenue for members of disadvantaged communities. OBJECTIVES: We introduce the research apprenticeship experience and its potential contributions to the fields of health equity and translational research. METHODS: Implementation of the research apprenticeship model within a survey research project. RESULTS: In this article, we 1) identify the model's distinctive qualities, 2) conceptualize an appropriate industry for graduates, 3) recognize its value for those with little access to postsecondary education, and 4) formulate a vision for contributing to health equity and translational research. CONCLUSIONS: The research apprenticeship holds potential to realize goals of capacity building, empowerment, and co-learning; generate educational progress and employment for participants; expand diversity in biomedical research; support two-directional co-learning between community and academia; and contribute to dismantling structural racism within the biomedical sciences.

Cardiovascular complications of respiratory diseases.

A major burden of morbidity and mortality due to respiratory diseases can be directly related to the cardiovascular (CV) complications of these disorders. Evidence from cross-sectional and longitudinal studies link reduced lung function and cardiovascular diseases. However, the underlying pathogenic mechanisms are unclear. Hypoxia-induced increased sympathetic activity, blood viscosity, or inflammation, among other factors, may mediate the underlying pathogenesis. In addition, sleep-disordered breathing (SDB) has been implicated by association in multiple CV diseases including hypertension, ischemic heart disease, congestive heart failure, arrhythmias, and stroke. However, the exact contribution of SDB, including obstructive and central sleep apneas, to the development of cardiovascular diseases is not fully understood. In this context, the contribution of the new large, prospective, Jackson Heart Study could be significant in that it is designed to answer several of these questions, specifically in the African American population. This review examines the current evidence that links both reduced lung function and SDB to CV diseases.

The effects of blood pressure and lipid control on kidney allograft outcome.

Despite the improvement in short- and long-term kidney allograft survival in recent years, a significant number of grafts are lost because of chronic allograft nephropathy (CAN) or death secondary to cardiovascular disease (CVD). There is growing evidence that both hypertension and hyperlipidemia play important roles in the progression of CAN and CVD in kidney transplant recipients. Large, randomized, controlled studies to determine the optimal target levels for BP and serum lipids, as well as the choice of drug therapy, are lacking. However, based on the available data, we suggest that currently recommended target levels in non-transplant patients should also be used after transplantation. We believe that achieving these target levels for BP and serum lipids are of primary importance, and that the non-lipid-lowering effects of HMG-CoA reductase inhibitors might exert additional benefits in prolonging graft survival.

Thiazolidinediones and progression of renal disease in patients with diabetes.

OBJECTIVE: Thiazolidinediones (TZDs) are used in the treatment of type 2 diabetes mellitus (T2DM) and appear to have beneficial effects on markers of cardiovascular or renal risk that are independent of glycemic control. We examined the effects of TZDs on renal survival in a predominantly black population with T2DM. METHODS: We performed a retrospective case-control study in patients with T2DM seen in our nephrology clinic in 2001 to 2002. Cases had T2DM and were on a TZD at presentation or for >or= 6 months over follow-up. Controls were matched for sex, age, duration of T2DM, and initial creatinine. Reaching end-stage renal disease (ESRD) was the primary end point. RESULTS: From 387 records, 43 cases (34 blacks, 31 females) and 106 controls (96 blacks, 83 females) were identified. The baseline characteristics were similar for both groups. Both groups had moderate renal disease (estimated glomerular filtration rate approximately 40-45 mL/min). Cases had lower systolic blood pressure over follow-up (p=.02), but there was no difference in glycemic control or use of insulin. Renal survival was better among cases (age- and gender-adjusted odds ratio for reaching ESRD 0.17 [95% confidence interval 0.03-0.8]; p=.03). When adjusted for systolic blood pressure over follow-up, the tendency for improved renal survival in cases remained but was no longer significant. CONCLUSION: We conclude that TZDs may protect against the progression of renal disease in T2DM. Prospective studies are required to determine the effects of TZDs on renal survival in T2DM.

Glycemic control predicts diabetic extrarenal microvascular complications but not renal survival in patients with moderate to severe chronic kidney disease.

BACKGROUND: Control of blood pressure (BP) and blood glucose can slow the development of diabetic nephropathy (DN). However, BP control may be of relatively more importance than glycemic control on the progression of DN. OBJECTIVE: To determine the effects of glycemic control on renal survival in a predominantly African American diabetic population with moderate-to-severe renal disease. DESIGN: This was a retrospective chart review of all diabetic patients seen in an academic nephrology clinic in 2001 and 2002 for renal survival and its predictors and micro/macrovascular disease. The weighted mean glycosylated hemoglobin (GHb) over followup was determined. Mean GHb < or = 9 was defined as low, and GHb >9 was high. The effect of glycemic control on endpoints was determined by Cox proportional hazards and logistic regression. RESULTS: One hundred fifty-five diabetic patients (87.7% African American, mean creatinine =2.2 mg/dL) had sufficient GHb measurements. Compared to the high group (n=81), the low group (n=74) was significantly younger, had a shorter duration of diabetes, and worse renal function. No significant association of glycemic control with renal survival (ESRD) was seen. Glycemic control and the presence of DN were significantly related to extrarenal microvascular complications, independent of other factors. CONCLUSION: Glycosylated hemoglobin (GHb) is not a significant predictor of renal survival in patients with diabetes and moderate renal disease. However, glycemic control does predict extrarenal microvascular complications in this population. Therefore, good metabolic control remains important in patients with diabetes and renal disease.