Socioeconomic factors differentiating maternal and child health-seeking behavior in rural Bangladesh: A cross-sectional analysis

BACKGROUND: There has been an increasing availability and accessibility of modern health services in rural Bangladesh over the past decades. However, previous studies on the socioeconomic differentials in the utilization of these services were based on a limited number of factors, focusing either on preventive or on curative modern health services. These studies failed to collect data from remote rural areas of the different regions to examine the socioeconomic differentials in health-seeking behavior. METHODS: Data from 3,498 randomly selected currently married women from three strata of households within 128 purposively chosen remote villages in three divisions of Bangladesh were collected in 2006. This study used bivariate and multivariate logistic analyses to examine both curative and preventive health-seeking behaviors in seven areas of maternal and child health care: antenatal care, postnatal care, child delivery care, mother's receipt of Vitamin A postpartum, newborn baby care, care during recent child fever/cough episodes, and maternal coverageby tetanus toxoid (TT). RESULTS: A principal finding was that a household's relative poverty status, as reflected by wealth quintiles, was a major determinant in health-seeking behavior. Mothers in the highest wealth quintile were significantly more likely to use modern trained providers for antenatal care, birth attendance, post natal care and child health care than those in the poorest quintile (χ(2), p < 0.01). The differentials were less pronounced for other factors examined, such as education, age, and the relative decision-making power of a woman, in both bivariate and multivariate analyses. CONCLUSION: Within rural areas of Bangladesh, where overall poverty is greater and access to health care more difficult, wealth differentials in utilization remain pronounced. Those programs with high international visibility and dedicated funding (e.g., Immunization and Vitamin A delivery) have higher overall prevalence and a more equitable distribution of beneficiaries than the use of modern trained providers for basic essential health care services. Implications of these findings and recommendations are provided

The Alzheimer's Disease Neuroimaging Initiative 2 Biomarker Core: A review of progress and plans

INTRODUCTION: We describe Alzheimer's Disease Neuroimaging Initiative (ADNI) Biomarker Core progress including: the Biobank; cerebrospinal fluid (CSF) amyloid beta (Aβ1-42), t-tau, and p-tau181 analytical performance, definition of Alzheimer's disease (AD) profile for plaque, and tangle burden detection and increased risk for progression to AD; AD disease heterogeneity; progress in standardization; and new studies using ADNI biofluids. METHODS: Review publications authored or coauthored by ADNI Biomarker core faculty and selected non-ADNI studies to deepen the understanding and interpretation of CSF Aβ1-42, t-tau, and p-tau181 data. RESULTS: CSF AD biomarker measurements with the qualified AlzBio3 immunoassay detects neuropathologic AD hallmarks in preclinical and prodromal disease stages, based on CSF studies in non-ADNI living subjects followed by the autopsy confirmation of AD. Collaboration across ADNI cores generated the temporal ordering model of AD biomarkers varying across individuals because of genetic/environmental factors that increase/decrease resilience to AD pathologies. DISCUSSION: Further studies will refine this model and enable the use of biomarkers studied in ADNI clinically and in disease-modifying therapeutic trials

Replication competent retrovirus testing (RCR) in the National Gene Vector Biorepository: No evidence of RCR in 1,595 post-treatment peripheral blood samples obtained from 60 clinical trials

The clinical impact of any therapy requires the product be safe and effective. Gammaretroviral vectors pose several unique risks, including inadvertent exposure to replication competent retrovirus (RCR) that can arise during vector manufacture. The US FDA has required patient monitoring for RCR, and the National Gene Vector Biorepository is an NIH resource that has assisted eligible investigators in meeting this requirement. To date, we have found no evidence of RCR in 338 pre-treatment and 1,595 post-treatment blood samples from 737 patients associated with 60 clinical trials. Most samples (75%) were obtained within 1 year of treatment, and samples as far out as 9 years after treatment were analyzed. The majority of trials (93%) were cancer immunotherapy, and 90% of the trials used vector products produced with the PG13 packaging cell line. The data presented here provide further evidence that current manufacturing methods generate RCR-free products and support the overall safety profile of retroviral gene therapy

Significant Improvements in the Practice Patterns of Adult Related Donor Care in US Transplantation Centers

Recent investigations have found a higher incidence of adverse events associated with hematopoietic cell donation in related donors (RDs) who have morbidities that if present in an unrelated donor (UD) would preclude donation. In the UD setting, regulatory standards ensure independent assessment of donors, one of several crucial measures to safeguard donor health and safety. A survey conducted by the Center for International Blood and Marrow Transplant Research (CIBMTR) Donor Health and Safety Working Committee in 2007 reported a potential conflict of interest in >70% US centers, where physicians had simultaneous responsibility for RDs and their recipients. Consequently, several international organizations have endeavored to improve practice through regulations and consensus recommendations. We hypothesized that the changes in the 2012 FACT-JACIE Standards, resulting from the CIBMTR study, will have significantly impacted practice. Accordingly, a follow-up survey of US transplant centers was conducted to assess practice changes since 2007, and investigate additional areas where RD care was predicted to differ from UD care. 73 centers (53%), performing 79% of US RD transplants responded. Significant improvements were observed since the earlier survey; 62% centers now ensure separation of RD and recipient care (P<0.0001). However, this study identifies several areas where RD management does not meet international donor care standards. Particular concerns include counseling and assessment of donors before HLA typing, with 61% centers first disclosing donor HLA results to an individual other than the donor, the use of unlicensed mobilization agents, and the absence of long-term donor follow-up. Recommendations for improvement are described

Socioeconomic factors differentiating maternal and child health-seeking behavior in rural Bangladesh: A cross-sectional analysis

Abstract Background There has been an increasing availability and accessibility of modern health services in rural Bangladesh over the past decades. However, previous studies on the socioeconomic differentials in the utilization of these services were based on a limited number of factors, focusing either on preventive or on curative modern health services. These studies failed to collect data from remote rural areas of the different regions to examine the socioeconomic differentials in health-seeking behavior. Methods Data from 3,498 randomly selected currently married women from three strata of households within 128 purposively chosen remote villages in three divisions of Bangladesh were collected in 2006. This study used bivariate and multivariate logistic analyses to examine both curative and preventive health-seeking behaviors in seven areas of maternal and child health care: antenatal care, postnatal care, child delivery care, mother's receipt of Vitamin A postpartum, newborn baby care, care during recent child fever/cough episodes, and maternal coverageby tetanus toxoid (TT). Results A principal finding was that a household's relative poverty status, as reflected by wealth quintiles, was a major determinant in health-seeking behavior. Mothers in the highest wealth quintile were significantly more likely to use modern trained providers for antenatal care, birth attendance, post natal care and child health care than those in the poorest quintile (χ2, p Conclusion Within rural areas of Bangladesh, where overall poverty is greater and access to health care more difficult, wealth differentials in utilization remain pronounced. Those programs with high international visibility and dedicated funding (e.g., Immunization and Vitamin A delivery) have higher overall prevalence and a more equitable distribution of beneficiaries than the use of modern trained providers for basic essential health care services. Implications of these findings and recommendations are provided.</p

CAR T-cell detection scoping review: an essential biomarker in critical need of standardization

The expansion and persistence of chimeric antigen receptor (CAR) T-cells in patients are associated with response, toxicity, and long-term efficacy. As such, the tools used to detect CAR T-cells following infusion are fundamental for optimizing this therapeutic approach. Nevertheless, despite the critical value of this essential biomarker, there is significant variability in CAR T-cell detection methods as well as the frequency and intervals of testing. Furthermore, heterogeneity in the reporting of quantitative data adds layers of complexity that limit intertrial and interconstruct comparisons. We sought to assess the heterogeneity of CAR T-cell expansion and persistence data in a scoping review using the PRISMA-ScR checklist. Focusing on 21 clinical trials from the USA, featuring a Food and Drug Administration-approved CAR T-cell construct or one of its predecessors, 105 manuscripts were screened and 60 were selected for analysis, based on the inclusion of CAR T-cell expansion and persistence data. Across the array of CAR T-cell constructs, flow cytometry and quantitative PCR were identified as the two primary techniques for detecting CAR T-cells. However, despite apparent uniformity in detection techniques, the specific methods used were highly variable. Detection time points and the number of evaluated time points also ranged markedly and quantitative data were often not reported. To evaluate whether subsequent manuscripts from a trial resolved these issues, we analyzed all subsequent manuscripts reporting on the 21 clinical trials, recording all expansion and persistence data. While additional detection techniques–including droplet digital PCR, NanoString, and single-cell RNA sequencing–were reported in follow-up publications, inconsistencies with respect to detection time points and frequency remained, with a significant amount of quantitative data still not readily available. Our findings highlight the critical need to establish universal standards for reporting on CAR T-cell detection, especially in early phase studies. The current reporting of non-interconvertible metrics and limited provision of quantitative data make cross-trial and cross-CAR T-cell construct comparisons extremely challenging. Establishing a standardized approach for collecting and reporting data is urgently needed and would represent a substantial advancement in the ability to improve outcomes for patients receiving CAR T-cell therapies

DOCK 8 Deficiency, EBV+ Lymphomatoid Granulomatosis, and Intrafamilial Variation in Presentation

Dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal recessive, combined immunodeficiency within the spectrum of hyper-IgE syndromes. Epstein-Barr virus-positive lymphomatoid granulomatosis (LYG) (EBV + LYG) is a rare diagnosis and a previously unreported presentation of DOCK8 deficiency. A 10-year-old girl was initially evaluated for mild eczema and recurrent sinopulmonary infections. She had normal immunoglobulins with elevated IgE, poor polysaccharide response with low switched memory B cells, low CD4 count, and normal mitogen and antigen responses. Despite clinical improvement following immunoglobulin replacement, a prolonged cough prompted a CT scan, which showed nodules. Biopsy identified a Grade 2 EBV + LYG. Due to an inadequate response with chemotherapy, further workup for primary immunodeficiency was performed. With her symptoms of eczema and IgE elevation, along with her brother's history of recurrent sinopulmonary infections and warts, targeted sequencing of DOCK8 was performed revealing compound heterozygous mutations for the two siblings. Both patients were successfully transplanted with resolution of the LYG and warts, respectively. This is the first reported case of LYG in DOCK8 deficiency. The EBV-driven lymphoproliferative disease along with the infection history in the brother led to the diagnosis of DOCK8 deficiency and curative hematopoietic stem cell transplants