442 research outputs found

    Household food insecurity positively associated with increased hospital charges for infants

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    Objective: To test whether household food insecurity (HFI) was associated with total annual hospitalization charges, annual days hospitalized, and charges per day, among low-income infants (months) with any non-neonatal hospital stays. Methods: Administrative inpatient hospital charge data were matched to survey data from infants\u27 caregivers interviewed 1998-2005 in emergency departments in Boston and Little Rock. All study infants had been hospitalized at least once since birth; infants whose diagnoses were not plausibly related to nutrition were excluded from both groups. Log-transformed hospitalization charges were analyzed, controlling for site fixed effects. Results: 24% of infants from food-insecure households and 16% from food-secure households were hospitalized \u3e2 times (P=0.02). Mean annual inpatient hospital charges (6,707vs6,707 vs 5,735; P Conclusion: HFI was positively associated with annual inpatient charges among hospitalized low income infants. Average annual inpatient charges were almost $2,000 higher (inflation adjusted) for infants living in food-insecure households. Reducing or eliminating food insecurity could reduce health services utilization and expenditures for infants in low-income families, most of whom are covered by public health insurance

    Dermal and muscle fibroblasts and skeletal myofibers survive chikungunya virus infection and harbor persistent RNA

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    Chikungunya virus (CHIKV) is an arthritogenic alphavirus that acutely causes fever as well as severe joint and muscle pain. Chronic musculoskeletal pain persists in a substantial fraction of patients for months to years after the initial infection, yet we still have a poor understanding of what promotes chronic disease. While replicating virus has not been detected in joint-associated tissues of patients with persistent arthritis nor in various animal models at convalescent time points, viral RNA is detected months after acute infection. To identify the cells that might contribute to pathogenesis during this chronic phase, we developed a recombinant CHIKV that expresses Cre recombinase (CHIKV-3'-Cre). CHIKV-3'-Cre replicated in myoblasts and fibroblasts, and it induced arthritis during the acute phase in mice. Importantly, it also induced chronic disease, including persistent viral RNA and chronic myositis and synovitis similar to wild-type virus. CHIKV-3'-Cre infection of tdTomato reporter mice resulted in a population of tdTomato+ cells that persisted for at least 112 days. Immunofluorescence and flow cytometric profiling revealed that these tdTomato+ cells predominantly were myofibers and dermal and muscle fibroblasts. Treatment with an antibody against Mxra8, a recently defined host receptor for CHIKV, reduced the number of tdTomato+ cells in the chronic phase and diminished the levels of chronic viral RNA, implicating these tdTomato+ cells as the reservoir of chronic viral RNA. Finally, isolation and flow cytometry-based sorting of the tdTomato+ fibroblasts from the skin and ankle and analysis for viral RNA revealed that the tdTomato+ cells harbor most of the persistent CHIKV RNA at chronic time points. Therefore, this CHIKV-3'-Cre and tdTomato reporter mouse system identifies the cells that survive CHIKV infection in vivo and are enriched for persistent CHIKV RNA. This model represents a useful tool for studying CHIKV pathogenesis in the acute and chronic stages of disease

    Distinct roles of interferon alpha and beta in controlling chikungunya virus replication and modulating neutrophil-mediated inflammation

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    Type I interferons (IFNs) are key mediators of the innate immune response. Although members of this family of cytokines signal through a single shared receptor, biochemical and functional variation exists in response to different IFN subtypes. While previous work has demonstrated that type I IFNs are essential to control infection by chikungunya virus (CHIKV), a globally emerging alphavirus, the contributions of individual IFN subtypes remain undefined. To address this question, we evaluated CHIKV pathogenesis in mice lacking IFN-β (IFN-β knockout [IFN-β-KO] mice or mice treated with an IFN-β-blocking antibody) or IFN-α (IFN regulatory factor 7 knockout [IRF7-KO] mice or mice treated with a pan-IFN-α-blocking antibody). Mice lacking either IFN-α or IFN-β developed severe clinical disease following infection with CHIKV, with a marked increase in foot swelling compared to wild-type mice. Virological analysis revealed that mice lacking IFN-α sustained elevated infection in the infected ankle and in distant tissues. In contrast, IFN-β-KO mice displayed minimal differences in viral burdens within the ankle or at distal sites and instead had an altered cellular immune response. Mice lacking IFN-β had increased neutrophil infiltration into musculoskeletal tissues, and depletion of neutrophils in IFN-β-KO but not IRF7-KO mice mitigated musculoskeletal disease caused by CHIKV. Our findings suggest disparate roles for the IFN subtypes during CHIKV infection, with IFN-α limiting early viral replication and dissemination and IFN-β modulating neutrophil-mediated inflammation

    Psychosocial correlates of patient–provider family planning discussions among HIV-infected pregnant women in South Africa

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    Patient-provider family planning discussions and preconception counseling can reduce maternal and neonatal risks by increasing adherence to provider recommendations and antiretroviral medication. However, HIV-infected women may not discuss reproductive intentions with providers due to anticipation of negative reactions and stigma. This study aimed to identify correlates of patient-provider family planning discussions among HIV-infected women in rural South Africa, an area with high rates of antenatal HIV and suboptimal rates of prevention of mother-to-child transmission (PMTCT) of HIV. Participants were N=673 pregnant HIV-infected women who completed measures of family planning discussions and knowledge, depression, stigma, intimate partner violence, and male involvement. Participants were, on average, 28 ± 6 years old, and half of them had completed at least 10-11 years of education. Most women were unemployed and had a monthly income of less than ~US$76. Fewer than half of the women reported having family planning discussions with providers. Correlates of patient-provider family planning discussions included younger age, discussions about PMTCT of HIV, male involvement, and decreased stigma ( < 0.05). Depression was indirectly associated with patient-provider family planning discussions through male involvement ( = -0.010, bias-corrected 95% confidence interval [bCI] [-0.019, -0.005]). That is, depression decreased male involvement, and in turn, male involvement increased patient-provider family planning discussions. Therefore, by decreasing male involvement, depression indirectly decreased family planning discussions. Study findings point to the importance of family planning strategies that address depression and facilitate male involvement to enhance communication between patients and providers and optimize maternal and neonatal health outcomes. This study underscores the need for longitudinal assessment of men's impact on family planning discussions both pre- and postpartum. Increasing support for provision of mental health services during pregnancy is merited to ensure the health of pregnant women living with HIV and their infants

    Trends in Household and Child Food Insecurity Among Families with Young Children from 2007 to 2013

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    Background: 2007-2013 spanned an economic downturn with rising food costs. While Supplemental Nutrition Assistance Program (SNAP) benefits increased during those years by 13.6% from the 2009 American Recovery Reinvestment Act (ARRA), the impact of these competing conditions on household food insecurity (HFI, household food insecure but child food secure) and child food insecurity (CFI, household and child food insecure) in households with infants and toddlers has not been investigated. Objective: To describe HFI and CFI in households participating in SNAP vs. households likely eligible but not participating (No SNAP). Design: Repeat cross-sectional Participants/Setting: 19,999 caregivers of childrenChildren’s HealthWatch survey in emergency and primary care departments in 5 US cities. Main Outcome Measures: The 18-item U.S. Household Food Security Survey (HFSS) measured HFI (≥3 affirmative responses on non-child-specific questions) and CFI (≥2 affirmative responses to eight child-specific questions). Statistical analyses performed: The sample was stratified by SNAP/ No SNAP. Multinomial logistic regression analyses examined the association between SNAP receipt and HFI and CFI. Results: Across the study period, controlling for confounders including year, households with SNAP were 17% less likely to experience HFI (AOR 0.83; 95% CI,0 .75, 0.91; p Conclusions: Receipt of SNAP vs. No SNAP was associated with decreased prevalence of HFI and CFI during much of the economic downturn; this impact waned as the buying power of the boost in benefit amounts during the ARRA period eroded

    Efficient Foreign Gene Expression in Epstein-Barr Virus-Transformed Human B-Cells

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    Epstein-Barr virus (EBV) is a herpesvirus that transforms B-cells (B-LCL) and has undergone intense scrutiny owing to its association with Burkitt's lymphoma, nasopharyngeal carcinoma, and immunoblastic lymphomas. B-LCL have also proven useful in the study of human immunology. We describe a novel system for inducing efficient foreign gene expression in B-LCL using biotinylated adenovirus as an endosome-disrupting agent. Plasmid DNA is coupled to the exterior of viral particles by streptavidin-polylysine chimeric proteins. Up to 67% of B-LCL may be induced to express foreign genes in vitro in transient expression systems, and gene expression lasts for at least 17 days. We have expressed firefly luciferase, β-galactosidase (β-gal), chloramphenicol acetyltransferase, HIV gag, and env genes, as well as infectious HIV, and the EBV-specific BZLF gene in B-LCL with this system. In vivo delivery of a β-gal reporter gene to B-LCL was documented in a SCID mouse model. Potential applications include study of genetic regulation of EBV infection and transformation events, study of potential gene therapies for EBV-related B-cell tumors, and production of antigen-presenting cells for use in immunologic assays. Because of the high percentage of cells transformed and the length of foreign gene expression, the possibility of examining foreign gene expression in transient assays, without selection for clonal populations, exists

    Practical help for specifying the target difference in sample size calculations for RCTs: the DELTA2 five-stage study, including a workshop

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    BACKGROUND: The randomised controlled trial is widely considered to be the gold standard study for comparing the effectiveness of health interventions. Central to its design is a calculation of the number of participants needed (the sample size) for the trial. The sample size is typically calculated by specifying the magnitude of the difference in the primary outcome between the intervention effects for the population of interest. This difference is called the 'target difference' and should be appropriate for the principal estimand of interest and determined by the primary aim of the study. The target difference between treatments should be considered realistic and/or important by one or more key stakeholder groups. OBJECTIVE: The objective of the report is to provide practical help on the choice of target difference used in the sample size calculation for a randomised controlled trial for researchers and funder representatives. METHODS: The Difference ELicitation in TriAls2 (DELTA2) recommendations and advice were developed through a five-stage process, which included two literature reviews of existing funder guidance and recent methodological literature; a Delphi process to engage with a wider group of stakeholders; a 2-day workshop; and finalising the core document. RESULTS: Advice is provided for definitive trials (Phase III/IV studies). Methods for choosing the target difference are reviewed. To aid those new to the topic, and to encourage better practice, 10 recommendations are made regarding choosing the target difference and undertaking a sample size calculation. Recommended reporting items for trial proposal, protocols and results papers under the conventional approach are also provided. Case studies reflecting different trial designs and covering different conditions are provided. Alternative trial designs and methods for choosing the sample size are also briefly considered. CONCLUSIONS: Choosing an appropriate sample size is crucial if a study is to inform clinical practice. The number of patients recruited into the trial needs to be sufficient to answer the objectives; however, the number should not be higher than necessary to avoid unnecessary burden on patients and wasting precious resources. The choice of the target difference is a key part of this process under the conventional approach to sample size calculations. This document provides advice and recommendations to improve practice and reporting regarding this aspect of trial design. Future work could extend the work to address other less common approaches to the sample size calculations, particularly in terms of appropriate reporting items. FUNDING: Funded by the Medical Research Council (MRC) UK and the National Institute for Health Research as part of the MRC-National Institute for Health Research Methodology Research programme

    Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: subset analysis of randomized trial intergroup SWOG S9704

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    Double hit lymphoma (DHL) and double protein-expressing (MYC and BCL2) lymphomas (DPL) fare poorly with R-CHOP; consolidative autologous stem cell transplant (ASCT) may improve outcomes. S9704, a phase III randomized study of CHOP +/−R with or without ASCT allows evaluation of intensive consolidation. Immunohistochemical analysis identified 27 of 198 patients (13.6%) with MYC IHC overexpression and 20 (74%) harboring concurrent BCL2 overexpression. Four had DHL and 16 had DPL only. With median follow-up 127 months, there is a trend favoring outcomes after consolidative ASCT in DPL and MYC protein overexpressing patients, whereas all DHL patients have died irrespective of ASCT
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