Integration of genetic fine-mapping and multi-omics data reveals candidate effector genes for hypertension.

Genome-wide association studies of blood pressure (BP) have identified >1,000 loci, but the effector genes and biological pathways at these loci are mostly unknown. Using published association summary statistics, we conducted annotation-informed fine-mapping incorporating tissue-specific chromatin segmentation and colocalization to identify causal variants and candidate effector genes for systolic BP, diastolic BP, and pulse pressure. We observed 532 distinct signals associated with ≥2 BP traits and 84 with all three. For >20% of signals, a single variant accounted for >75% posterior probability, 65 were missense variants in known (SLC39A8, ADRB2, and DBH) and previously unreported BP candidate genes (NRIP1 and MMP14). In disease-relevant tissues, we colocalized >80 and >400 distinct signals for each BP trait with cis-eQTLs and regulatory regions from promoter capture Hi-C, respectively. Integrating mouse, human disorder, gene expression and tissue abundance data, and literature review, we provide consolidated evidence for 436 BP candidate genes for future functional validation and discover several potential drug targets.

Prognostic Significance of Different Ventricular Ectopic Burdens During Submaximal Exercise in Asymptomatic UK Biobank Subjects.

BACKGROUND: The consequences of exercise-induced premature ventricular contractions (PVCs) in asymptomatic individuals remain unclear. This study aimed to assess the association between PVC burdens during submaximal exercise and major adverse cardiovascular events (MI/HF/LTVA: myocardial infarction [MI], heart failure [HF], and life-threatening ventricular arrhythmia [LTVA]), and all-cause mortality. Additional end points were MI, LTVA, HF, and cardiovascular mortality. METHODS: A neural network was developed to count PVCs from ECGs recorded during exercise (6 minutes) and recovery (1 minute) in 48 315 asymptomatic participants from UK Biobank. Associations were estimated using multivariable Cox proportional hazard models. Explorative studies were conducted in subgroups with cardiovascular magnetic resonance imaging data (n=6290) and NT-proBNP (N-terminal Pro-B-type natriuretic peptide) levels (n=4607) to examine whether PVC burden was associated with subclinical cardiomyopathy. RESULTS: Mean age was 56.8±8.2 years; 51.1% of the participants were female; and median follow-up was 12.6 years. Low PVC counts during exercise and recovery were both associated with MI/HF/LTVA risk, independently of clinical factors: adjusted hazard ratio (HR), 1.2 (1-5 exercise PVCs, P<0.001) and HR, 1.3 (1-5 recovery PVCs, P<0.001). Risks were higher with increasing PVC count: HR, 1.8 (>20 exercise PVCs, P<0.001) and HR, 1.6 (>5 recovery PVCs, P<0.001). A similar trend was observed for all-cause mortality, although associations were only significant for high PVC burdens: HRs, 1.6 (>20 exercise PVCs, P<0.001) and 1.5 (>5 recovery PVCs, P<0.001). Complex PVC rhythms were associated with higher risk compared with PVC count alone. PVCs were also associated with incident HF, LTVA, and cardiovascular mortality, but not MI. In the explorative studies, high PVC burden was associated with larger left ventricular volumes, lower ejection fraction, and higher levels of NT-proBNP compared with participants without PVCs. CONCLUSIONS: In this cohort of middle-aged and older adults, PVC count during submaximal exercise and recovery were both associated with MI/HF/LTVA, all-cause mortality, HF, LTVAs, and cardiovascular mortality, independent of clinical and exercise test factors, indicating an incremental increase in risk as PVC count rises. Complex PVC rhythms were associated with higher risk compared with PVC count alone. Underlying mechanisms may include the presence of subclinical cardiomyopathy.

Fine mapping of candidate effector genes for heart rate.

An elevated resting heart rate (RHR) is associated with increased cardiovascular mortality. Genome-wide association studies (GWAS) have identified > 350 loci. Uniquely, in this study we applied genetic fine-mapping leveraging tissue specific chromatin segmentation and colocalization analyses to identify causal variants and candidate effector genes for RHR. We used RHR GWAS summary statistics from 388,237 individuals of European ancestry from UK Biobank and performed fine mapping using publicly available genomic annotation datasets. High-confidence causal variants (accounting for > 75% posterior probability) were identified, and we collated candidate effector genes using a multi-omics approach that combined evidence from colocalisation with molecular quantitative trait loci (QTLs), and long-range chromatin interaction analyses. Finally, we performed druggability analyses to investigate drug repurposing opportunities. The fine mapping pipeline indicated 442 distinct RHR signals. For 90 signals, a single variant was identified as a high-confidence causal variant, of which 22 were annotated as missense. In trait-relevant tissues, 39 signals colocalised with cis-expression QTLs (eQTLs), 3 with cis-protein QTLs (pQTLs), and 75 had promoter interactions via Hi-C. In total, 262 candidate genes were highlighted (79% had promoter interactions, 15% had a colocalised eQTL, 8% had a missense variant and 1% had a colocalised pQTL), and, for the first time, enrichment in nervous system pathways. Druggability analyses highlighted ACHE, CALCRL, MYT1 and TDP1 as potential targets. Our genetic fine-mapping pipeline prioritised 262 candidate genes for RHR that warrant further investigation in functional studies, and we provide potential therapeutic targets to reduce RHR and cardiovascular mortality.

Genomic and pleiotropic analyses of resting QT interval identifies novel loci and overlap with atrial electrical disorders.

The resting QT interval, an electrocardiographic (ECG) measure of ventricular myocardial repolarization, is a heritable risk marker of cardiovascular mortality, but the mechanisms remain incompletely understood. Previously reported candidate genes have provided insights into the regulatory mechanisms of the QT interval. However, there are still important knowledge gaps. We aimed to gain new insights by (i) providing new candidate genes, (ii) identifying pleiotropic associations with other cardiovascular traits, and (iii) scanning for sexually dimorphic genetic effects. We conducted a genome-wide association analysis for resting QT interval with ~9.8 million variants in 52 107 individuals of European ancestry without known cardiovascular disease from the UK Biobank. We identified 40 loci, 13 of which were novel, including 2 potential sex-specific loci, explaining ~11% of the trait variance. Candidate genes at novel loci were involved in myocardial structure and arrhythmogenic cardiomyopathy. Investigation of pleiotropic effects of QT interval variants using phenome-wide association analyses in 302 000 unrelated individuals from the UK Biobank and pairwise genome-wide comparisons with other ECG and cardiac imaging traits revealed genetic overlap with atrial electrical pathology. These findings provide novel insights into how abnormal myocardial repolarization and increased cardiovascular mortality may be linked.

Common Genetic Variants Modulate the Electrocardiographic Tpeak-to-Tend Interval.

Sudden cardiac death is responsible for half of all deaths from cardiovascular disease. The analysis of the electrophysiological substrate for arrhythmias is crucial for optimal risk stratification. A prolonged T-peak-to-Tend (Tpe) interval on the electrocardiogram is an independent predictor of increased arrhythmic risk, and Tpe changes with heart rate are even stronger predictors. However, our understanding of the electrophysiological mechanisms supporting these risk factors is limited. We conducted genome-wide association studies (GWASs) for resting Tpe and Tpe response to exercise and recovery in ∼30,000 individuals, followed by replication in independent samples (∼42,000 for resting Tpe and ∼22,000 for Tpe response to exercise and recovery), all from UK Biobank. Fifteen and one single-nucleotide variants for resting Tpe and Tpe response to exercise, respectively, were formally replicated. In a full dataset GWAS, 13 further loci for resting Tpe, 1 for Tpe response to exercise and 1 for Tpe response to exercise were genome-wide significant (p ≤ 5 × 10-8). Sex-specific analyses indicated seven additional loci. In total, we identify 32 loci for resting Tpe, 3 for Tpe response to exercise and 3 for Tpe response to recovery modulating ventricular repolarization, as well as cardiac conduction and contraction. Our findings shed light on the genetic basis of resting Tpe and Tpe response to exercise and recovery, unveiling plausible candidate genes and biological mechanisms underlying ventricular excitability.

Food Insecurity among Cancer Patients Enrolled in the Supplemental Nutrition Assistance Program (SNAP).

Purpose: Food insecurity, which leads to adverse health outcomes, has even more severe implications for cancer patients. Yet medically underserved cancer patients are more likely to be food insecure than the general population.Methods: This study is a cross-sectional analysis of intake data from patients who participated in the Integrated Cancer Care Access Network (ICCAN). ICCAN is a specialized program that addresses socioeconomic barriers to cancer care among underserved cancer patients in NYC. This study utilized ICCAN data from 2011 to 2017. The USDA food insecurity score, self-reported SNAP receipt, and SNAP eligibility based on household income were compared between SNAP and non-SNAP recipients.Results: 681 patients were assessed for food insecurity. Sixty-nine percent of participants lived in food insecure households. Despite SNAP assistance, most SNAP recipients (68%) were food insecure; 69% of respondents who did not receive SNAP were also food insecure.Conclusions: Underserved cancer patients who receive SNAP are still food insecure, hence at more significant risk for its associated negative outcomes. Supplemental programs for patients with chronic diseases are needed in clinics with large low income populations. SNAP benefits should account for the additional financial burden posed by treatment costs and exceptional circumstances faced by cancer patients.

The association between housing and food insecurity among medically underserved cancer patients.

PURPOSE: To assess the prevalence of socioeconomic needs and associations between housing characteristics and food insecurity among low-income cancer patients, among whom housing and food insecurity are particularly prevalent. METHODS: Low-income cancer patients in active treatment (N = 1618) were enrolled in a comprehensive patient navigation program. Food insecurity was assessed using the 18-item US Department of Agriculture US Household Food Security Survey Module. Participants self-reported their need for assistance with housing issues/type of assistance needed, perception of overcrowding, satisfaction with living situation, and household density via a cross-sectional survey. Descriptive analyses, cross-tabulations and tests of proportions, and binary logistic regression were used in data analyses. RESULTS: Seventy percent of patients were food insecure. Housing characteristics associated with food insecurity were homelessness or living in sheltered/supportive housing (83.3% food insecure), renting (71.9%), and homeownership (58.1%; p < .001); living situation satisfaction (not satisfied, 79.4%; somewhat satisfied, 25.6%; very satisfied, 66%; p < .001); need of housing assistance (79.2%; p < .001), and feeling crowded in their living unit (77.6%; p < .05). Associations of living unit type with food insecurity were significant in the binary logistic regression model (renters 1.68 OR, homeless/sheltered housing 2.80 OR vs homeowners). CONCLUSION: The vulnerability to food insecurity of patients in this low-income sample was underlined by the high rates found, and clear associations with housing characteristics of homelessness, housing assistance needs, and feeling overcrowded were identified. These results could help shape priorities around screening patients for nutrition and housing needs and developing interventions to address them.

A Case Study in Academic-Community Partnerships: A Community-Based Nutrition Education Program for Mexican Immigrants.

Hispanics are the largest U.S. immigrant group and Mexican Americans are the largest U.S. Hispanic population. Hispanics, particularly Mexican Americans, are among the highest risk groups for obesity, placing them at increased risk for cardiovascular disease and certain types of cancer. Obesity lifestyle interventions incorporating Motivational Interviewing techniques and specific adaptations for the population of interest can have a significant impact on reducing health risks. This paper presents a community-engaged, culturally-sensitive nutrition and dietary counseling intervention conducted between 2016 and 2018 at the Consulate General of Mexico in New York City and reports preliminary findings regarding participant satisfaction and self-reported changes in eating and exercise habits. In addition, it describes the community and academic partners' roles and processes in program development, discusses strengths and challenges posed by a multi-sector partnership and describes adaptations made using the Behavioral Model for Vulnerable Populations to increase the program's sustainability and potential for scalability.

Nonlinear T-Wave Time Warping-Based Sensing Model for Non-Invasive Personalised Blood Potassium Monitoring in Hemodialysis Patients: A Pilot Study.

BACKGROUND: End-stage renal disease patients undergoing hemodialysis (ESRD-HD) therapy are highly susceptible to malignant ventricular arrhythmias caused by undetected potassium concentration ([K+]) variations (Δ[K+]) out of normal ranges. Therefore, a reliable method for continuous, noninvasive monitoring of [K+] is crucial. The morphology of the T-wave in the electrocardiogram (ECG) reflects Δ[K+] and two time-warping-based T-wave morphological parameters, dw and its heart-rate corrected version dw,c, have been shown to reliably track Δ[K+] from the ECG. The aim of this study is to derive polynomial models relating dw and dw,c with Δ[K+], and to test their ability to reliably sense and quantify Δ[K+] values. METHODS: 48-hour Holter ECGs and [K+] values from six blood samples were collected from 29 ESRD-HD patients. For every patient, dw and dw,c were computed, and linear, quadratic, and cubic fitting models were derived from them. Then, Spearman's (ρ) and Pearson's (r) correlation coefficients, and the estimation error (ed) between Δ[K+] and the corresponding model-estimated values (Δ^[K+]) were calculated. RESULTS AND DISCUSSIONS: Nonlinear models were the most suitable for Δ[K+] estimation, rendering higher Pearson's correlation (median 0.77 ≤r≤ 0.92) and smaller estimation error (median 0.20 ≤ed≤ 0.43) than the linear model (median 0.76 ≤r≤ 0.86 and 0.30 ≤ed≤ 0.40), even if similar Spearman's ρ were found across models (median 0.77 ≤ρ≤ 0.83). CONCLUSION: Results support the use of nonlinear T-wave-based models as Δ[K+] sensors in ESRD-HD patients.

Food Purchasing Behavior of Food Insecure Cancer Patients Receiving Supplemental Food Vouchers.

PURPOSE: Food insecure cancer patients experience worse health outcomes and poorer quality of life than food secure patients. There has been little research in programs to alleviate food insecurity in cancer patients. The objective of this paper is to report on the food purchasing behaviors of cancer patients enrolled in a supplemental food voucher program. METHODS: This paper utilized data from a three-arm randomized controlled trial investigating the impact of food interventions on alleviating food insecurity in cancer patients receiving chemotherapy and/or radiation therapy. In one arm, patients received a monthly $230 voucher with which to purchase food. Receipts were collected for items purchased with the voucher and were coded to analyze purchasing behaviors. RESULTS: Thirty-three patients provided receipts for more than 11,000 individual items. Patients spent 50% of voucher funds on animal protein, fruits, and vegetables. Patients spent, on average, 77% of voucher funds on items categorized as "healthy." CONCLUSIONS: Patients who received a food voucher purchased more fruits and vegetables than national averages would suggest. They also spent less on sweetened beverages than national samples. Patients who were born outside of the United States or who were limited English proficient purchased significantly more healthy foods than English-speaking and American-born study patients. Supplemental food vouchers for food insecure cancer patients resulted in the purchase of healthy food items.

Predictors of Health Insurance, Life Insurance, and Retirement Savings Among NYC's Immigrant Taxi and For-Hire Vehicle Drivers.

Taxi and for-hire vehicle (FHV) drivers are a predominantly immigrant population facing a range of occupational stressors, including lack of workplace benefits and increasing financial strain from tumultuous industry changes and now COVID-19's devastating impact. Bilingual research staff surveyed 422 New York City taxi/FHV drivers using a stratified sampling approach in driver-frequented locations to examine drivers' health and financial planning behaviors for the first time. Drivers lacked health insurance at double the NYC rate (20% vs. 10%). Life insurance and retirement savings rates were lower than U.S. averages (20% vs. 60%, 25% vs. 58%, respectively). Vehicle ownership was a significant predictor of health insurance, life insurance, and retirement savings. Compared to South Asian drivers, Sub-Saharan African drivers were significantly less likely to have health insurance and North African, and Middle Eastern drivers were significantly less likely to have retirement savings. Although most drivers indicated the importance of insurance and benefits, < 50% understood how to use them. Drivers felt primary care coverage to be most important followed by other health-related coverage, retirement benefits, and life insurance. Results reveal compelling addressable gaps in insurance and benefits coverage and the need to implement accessible financial literacy with navigation and advising services and programs.

The Nutrition Benefits Participation Gap: Barriers to Uptake of SNAP and WIC Among Latinx American Immigrant Families.

To examine nutrition benefit under-enrollment in Latinx American immigrant families, we administered a survey to 100 adults attending a NY Latinx American community serving organization. We used a logistic regression approach to analyze misinformation impact on enrollment, and examined non-enrollment explanations, among participants in whose families a child or pregnant or breastfeeding woman appeared SNAP- or WIC-eligible. Among households (N = 51) with ≥ 1 SNAP-eligible child, 49% had no child enrolled. Reasons included repercussion fears (e.g. payback obligation, military conscription, college aid ineligibility, child removal, non-citizen family member penalties), and logistical barriers. In multivariable regression models, having heard the rumor that SNAP/WIC participation makes unauthorized status family members vulnerable to being reported to the government was associated with an 85% lower enrollment rate (OR 0.15, CI 0.03, 0.94). Misinformation impedes nutrition benefit participation. A multi-level intervention is necessary to inform potential applicants and providers regarding eligibility criteria and erroneous rumors, along with an informed discussion of the risks versus benefits of using resources, especially as public charge criteria change.

Taxi Drivers at Risk: Tailoring Nutrition and Exercise Materials.

Cognitive interviewing was used to refine nutrition and exercise health education materials for use in the New York City taxi driver community. Cognitive interviews were conducted with taxi drivers at garages and community centers across New York City. Interviews were conducted in five rounds with approximately 10 interviews conducted in each round. Modifications were made to the education materials between rounds based on driver feedback. Interviews were transcribed, coded to identify areas needing improvement, and then used to modify materials. Areas that needed adaptation included colloquialisms, literacy level, complex jargon/terminology, vague/confusing phrasing, driver-specific and ethnic-specific preferences, visual aids, and mathematical calculations. These were organized into four key themes: linguistic responsiveness, occupational and cultural adaptation, visuals, and calculations. Cognitive interviewing is a useful method for refining health education materials in the diverse driver population. Cognitive interviewing revealed a need to reduce literacy level, avoid complex terminology, make further occupational and cultural adaptations, use clear visual aids, and avoid the use of complex calculations. Cognitive interviewing is an effective method for refining health education materials for immigrant and low literacy populations.

pH-Responsive Microencapsulation Systems for the Oral Delivery of Polyanhydride Nanoparticles.

Multicompartmental polymer carriers, referred to as Polyanhydride-Releasing Oral MicroParticle Technology (PROMPT), were formed by a pH-triggered antisolvent precipitation technique. Polyanhydride nanoparticles were encapsulated into anionic pH-responsive microparticle gels, allowing for nanoparticle encapsulation in acidic conditions and subsequent release in neutral pH conditions. The effects of varying the nanoparticle composition and feed ratio on the encapsulation efficiency were evaluated. Nanoparticle encapsulation was confirmed by confocal microscopy and infrared spectroscopy. pH-triggered protein delivery from PROMPT was explored using ovalbumin (ova) as a model drug. PROMPT microgels released ova in a pH-controlled manner. Increasing the feed ratio of nanoparticles into the microgels increased the total amount of ova delivered, as well as decreased the observed burst release. The cytocompatibility of the polymer materials were assessed using cells representative of the GI tract. Overall, these results suggest that pH-dependent microencapsulation is a viable platform to achieve targeted intestinal delivery of polyanhydride nanoparticles and their payload(s).

An Investigation of Unmet Socio-Economic Needs Among Arab American Breast Cancer Patients Compared with Other Immigrant and Migrant Patients.

Although Arabs are a growing population in the United States, they are a hidden minority when compared to larger, more studied groups like Latinos and Caribbean immigrants of African descent (CIAD). There is limited research pertaining to patients' unmet socioeconomic and supportive care needs when undergoing breast cancer treatment, particularly among immigrants and migrants. This is a comparative study of a nested cohort of 36 Arabs, 145 Latinos and 128 CIAD breast cancer patients participating in the Integrated Cancer Care Access Network and their areas of needed assistance. The patients were recruited from eleven community cancer clinics in New York City and through community based organizations. Patients most commonly reported needing financial, transportation, and food assistance. Arabs were more likely than their CIAD and Latino counterparts to have health insurance and legal aid needs. Arabs also has the highest proportion of patients unaware of their own cancer stage, at odds with their report of lower information needs than the other groups. Additional culturally tailored Arabic language interventions are needed to educate Arabic speaking breast cancer patients to help facilitate access to available services.

Rational Design of Targeted Next-Generation Carriers for Drug and Vaccine Delivery.

Pattern recognition receptors on innate immune cells play an important role in guiding how cells interact with the rest of the organism and in determining the direction of the downstream immune response. Recent advances have elucidated the structure and function of these receptors, providing new opportunities for developing targeted drugs and vaccines to treat infections, cancers, and neurological disorders. C-type lectin receptors, Toll-like receptors, and folate receptors have attracted interest for their ability to endocytose their ligands or initiate signaling pathways that influence the immune response. Several novel technologies are being developed to engage these receptors, including recombinant antibodies, adoptive immunotherapy, and chemically modified antigens and drug delivery vehicles. These active targeting technologies will help address current challenges facing drug and vaccine delivery and lead to new tools to treat human diseases.

Neuronal protection against oxidative insult by polyanhydride nanoparticle-based mitochondria-targeted antioxidant therapy.

A progressive loss of neuronal structure and function is a signature of many neurodegenerative conditions including chronic traumatic encephalopathy, Parkinson's, Huntington's and Alzheimer's diseases. Mitochondrial dysfunction and oxidative and nitrative stress have been implicated as key pathological mechanisms underlying the neurodegenerative processes. However, current therapeutic approaches targeting oxidative damage are ineffective in preventing the progression of neurodegeneration. Mitochondria-targeted antioxidants were recently shown to alleviate oxidative damage. In this work, we investigated the delivery of biodegradable polyanhydride nanoparticles containing the mitochondria-targeted antioxidant apocynin to neuronal cells and the ability of the nano-formulation to protect cells against oxidative stress. The nano-formulated mitochondria-targeted apocynin provided excellent protection against oxidative stress-induced mitochondrial dysfunction and neuronal damage in a dopaminergic neuronal cell line, mouse primary cortical neurons, and a human mesencephalic cell line. Collectively, our results demonstrate that nano-formulated mitochondria-targeted apocynin may offer improved efficacy of mitochondria-targeted antioxidants to treat neurodegenerative disease.

Navigating Language Barriers: A Systematic Review of Patient Navigators' Impact on Cancer Screening for Limited English Proficient Patients.

OBJECTIVES: To systematically review the literature on the impact of patient navigators on cancer screening for limited English proficient (LEP) patients. DATA SOURCES: Electronic databases (PubMed, PsycINFO via OVID, Web of Science, Cochrane, EMBASE, and Scopus) through 8 May 2015. ELIGIBILITY CRITERIA: Articles in this review had: (1) a study population of LEP patients eligible for breast, cervical or colorectal cancer screenings, (2) a patient navigator intervention to provide services prior to or during cancer screening, (3) a comparison of the patient navigator intervention to either a control group or another intervention, and (4) language-specific outcomes related to the patient navigator intervention. STUDY APPRAISAL: We assessed the quality of the articles using the Downs and Black Scale. RESULTS: Fifteen studies met the inclusion criteria and evaluated the screening rates for breast, colorectal, and cervical cancer in 15 language populations. Fourteen studies resulted in improved screening rates for LEP patients between 7 and 60%. There was great variability in the patient navigation interventions evaluated. Training received by navigators was not reported in nine of the studies and no studies assessed the language skills of the patient navigators in English or the target language. LIMITATIONS: This study is limited by the variability in study designs and limited reporting on patient navigator interventions, which reduces the ability to draw conclusions on the full effect of patient navigators. CONCLUSIONS: Overall, we found evidence that navigators improved screening rates for breast, cervical and colorectal cancer screening for LEP patients. Future studies should systematically collect data on the training curricula for navigators and assess their English and non-English language skills in order to identify ways to reduce disparities for LEP patients.

Pretransplant angiotensin II type 1-receptor antibodies are a risk factor for earlier detection of de novo HLA donor-specific antibodies.

BACKGROUND: Angiotensin II type 1 receptor antibodies (AT1Rabs) have been associated with significantly reduced graft survival. Earlier graft loss has been observed in patients who had pretransplant AT1Rabs and posttransplant donor-specific antibodies (DSA). METHODS: The main goal of this retrospective cohort study was to examine the association between AT1Rabs and the time period to detection of de novo human leukocyte antigen (HLA-DSA) posttransplantation in living donor kidney transplant recipients (KTR). The analysis included 141 KTRs. Pretransplant frozen serum samples were tested for AT1Rabs by ELISA and HLA-DSA by SAB (Luminex) at both the pre- and post-KT time points. RESULTS: The median AT1Rab level was 9.13 U (interquartile range 5.22-14.33). After a mean follow-up period of 3.55 years, 48 patients were found to harbour de novo HLA-DSAs. The presence of AT1Rabs [hazard ratio (HR) 1.009, 95% confidence interval (CI) 1.002-1.01, P = 0.010], male-to-male transplantation (HR 2.57, 95% CI 1.42-4.67, P = 0.002) and antecedent borderline changes or acute cellular rejection (ACR) (HR 2.47, 95% CI 1.29-4.75, P = 0.006) were significantly associated with de novo DSA detection. A dose-dependent association between AT1Rab levels (<10 U, 10.1-16.9 U, 17-29.9 U and >30 U) and de novo DSA detection was observed (log-rank P = 0.0031). After multivariate analysis of AT1Rab levels (continuous variable), AT1Rabs >30 U, male-to-male transplantation, donor age, higher class I percentage of Panel Reactive Antibody and antecedent borderline changes or ACR remained as independent significant risk factors for the detection of de novo DSAs. CONCLUSIONS: The findings suggest that higher levels of pretransplant circulating antibodies against AT1R (>30 U) in kidney graft recipients constitute an independent risk factor for earlier de novo HLA-DSA detection during the posttransplant period.

Association of socioeconomic and practical unmet needs with self-reported nonadherence to cancer treatment appointments in low-income Latino and Black cancer patients.

OBJECTIVE: Treatment adherence, with minimal numbers of missed appointments, is an important determinant of survival among cancer patients. This study aims to determine if unmet financial, logistic, and supportive care needs predict self-reported adherence to cancer treatment appointments of chemotherapy and/or radiation among low-income ethnic minority patients. DESIGN: The sample included 1098 underserved Latino and Black patients recruited from cancer clinics in New York City through the Cancer Portal Project. Participants completed a survey which included sociodemographic, health-related questions and a needs assessment, in their preferred language. Patients' adherence to chemotherapy and/or radiation treatment appointments was assessed using a self-report. RESULTS: A sample of 1098 patients (581 Latino and 517 Black cancer patients) was recruited. Forty-two Latino cancer patients (7.4%) and 78 Black cancer patients (15.5%) reported missing treatment appointments. Patients, who experienced four or more unmet needs (odds ratios [OR] = 2.02-3.36), and those with unmet housing needs (OR = 3.10-3.31), were more likely to report missing cancer treatment appointments, regardless of their ethnicity/race. Black patients with unmet supportive care (OR = 2.27) and health insurance needs (OR = 3.80) were more likely to miss appointments. Amongst Latinos, legal health-related issues (OR = 2.51) was a significant predictor of missed appointments. CONCLUSIONS: Among ethnic minority cancer patients, unmet socioeconomic and supportive care needs, housing needs in particular, predicted patient-reported missed radiation, and/or chemotherapy appointments. Future research should focus on exploring the impact of practical and supportive unmet needs on adherence and development of interventions aiming to improve cancer treatment adherence.