173 research outputs found

    Severe sepsis: variation in resource and therapeutic modality use among academic centers

    Get PDF
    BACKGROUND: Treatment of severe sepsis is expensive, often encompassing a number of discretionary modalities. The objective of the present study was to assess intercenter variation in resource and therapeutic modality use in patients with severe sepsis. METHODS: We conducted a prospective cohort study of 1028 adult admissions with severe sepsis from a stratified random sample of patients admitted to eight academic tertiary care centers. The main outcome measures were length of stay (LOS; total LOS and LOS after onset of severe sepsis) and total hospital charges. RESULTS: The adjusted mean total hospital charges varied from 69429toUS69 429 to US237 898 across centers, whereas the adjusted LOS after onset varied from 15.9 days to 24.2 days per admission. Treatments used frequently after the first onset of sepsis among patients with severe sepsis were pulmonary artery catheters (19.4%), ventilator support (21.8%), pressor support (45.8%) and albumin infusion (14.4%). Pulmonary artery catheter use, ventilator support and albumin infusion had moderate variation profiles, varying 3.2-fold to 4.9-fold, whereas the rate of pressor support varied only 1.92-fold across centers. Even after adjusting for age, sex, Charlson comorbidity score, discharge diagnosis-relative group weight, organ dysfunction and service at onset, the odds for using these therapeutic modalities still varied significantly across centers. Failure to start antibiotics within 24 hours was strongly correlated with a higher probability of 28-day mortality (r(2 )= 0.72). CONCLUSION: These data demonstrate moderate but significant variation in resource use and use of technologies in treatment of severe sepsis among academic centers. Delay in antibiotic therapy was associated with worse outcome at the center level

    Longitudinal Homogenization of the Microbiome between Both Occupants and the Built Environment in a Cohort of United States Air Force Cadets

    Get PDF
    The microbiome of the built environment has important implications for human health and wellbeing; however, bidirectional exchange of microbes between occupants and surfaces can be confounded by lifestyle, architecture, and external environmental exposures. Here, we present a longitudinal study of United States Air Force Academy cadets (n = 34), which have substantial homogeneity in lifestyle, diet, and age, all factors that influence the human microbiome. We characterized bacterial communities associated with (1) skin and gut samples from roommate pairs, (2) four built environment sample locations inside the pairs’ dormitory rooms, (3) four built environment sample locations within shared spaces in the dormitory, and (4) room-matched outdoor samples from the window ledge of their rooms

    Effectiveness of a peer-delivered, psychosocial intervention on maternal depression and child development at 3 years postnatal: a cluster randomised trial in Pakistan

    Get PDF
    Maternal depression has a recurring course that can influence offspring outcomes. Evidence on how to treat maternal depression to improve longer-term maternal outcomes and reduce intergenerational transmission of psychopathology is scarce, particularly for task-shifted, low-intensity, and scalable psychosocial interventions. We evaluated the effects of a peer-delivered, psychosocial intervention on maternal depression and child development at 3 years postnatal

    The contribution of grandmother involvement to child growth and development: an observational study in rural Pakistan

    Get PDF
    INTRODUCTION: Early childhood interventions primarily focus on the mother-child relationship, but grandmothers are often critical in childcare in low-resource settings. Prior research is mixed on how grandmother involvement influences child outcomes and there is a paucity of research on grandmother caregiving in low-income and middle-income countries. We examined the role of grandmother involvement on child growth and development in the first 2 years of life cross sectionally and longitudinally in rural Pakistan. METHODS: We used data from the Bachpan Cohort, a longitudinal birth cohort in rural Pakistan. Maternally reported grandmother involvement in daily instrumental and non-instrumental caregiving was collected at 3 and 12 months. A summed score was created and categorised into non-involved, low and high. Outcomes included 12-month and 24-month child growth, 12-month Bayley Scales of Infant and Toddler Development and 24-month Ages and Stages Questionnaire-Socioemotional. We used multivariable generalised linear models to estimate mean differences (MD) at 12 months (n=727) and 24 months (n=712). Inverse probability weighting was used to account for missingness and sampling. RESULTS: In our sample, 68% of children lived with a grandmother, and most grandmothers were involved in caregiving. Greater 3-month grandmother involvement was positively associated with 12-month weight z-scores; however, greater involvement was associated with lower 24-month weight z-scores. High 12-month grandmother involvement was associated with improved 12-month cognitive (MD=0.38, 95% CI -0.01 to 0.76), fine motor skills (MD=0.45, 95% CI 0.08 to 0.83) and 24-month socioemotional development (MD=-17.83, 95% CI -31.47 to -4.19). No meaningful associations were found for length z-scores or language development. CONCLUSION: In rural Pakistan, grandmothers provide caregiving that influences early child development. Our findings highlight the complex relationship between grandmother involvement and child weight, and suggest that grandmothers may positively promote early child cognitive, fine motor and socioemotional development. Understanding how grandmother involvement affects child outcomes in early life is necessary to inform caregiving interventions

    Integrated RNA and DNA sequencing reveals early drivers of metastatic breast cancer

    Get PDF
    Breast cancer metastasis remains a clinical challenge, even within a single patient across multiple sites of the disease. Genome-wide comparisons of both the DNA and gene expression of primary tumors and metastases in multiple patients could help elucidate the underlying mechanisms that cause breast cancer metastasis. To address this issue, we performed DNA exome and RNA sequencing of matched primary tumors and multiple metastases from 16 patients, totaling 83 distinct specimens. We identified tumor-specific drivers by integrating known protein-protein network information with RNA expression and somatic DNA alterations and found that genetic drivers were predominantly established in the primary tumor and maintained through metastatic spreading. In addition, our analyses revealed that most genetic drivers were DNA copy number changes, the TP53 mutation was a recurrent founding mutation regardless of subtype, and that multiclonal seeding of metastases was frequent and occurred in multiple subtypes. Genetic drivers unique to metastasis were identified as somatic mutations in the estrogen and androgen receptor genes. These results highlight the complexity of metastatic spreading, be it monoclonal or multiclonal, and suggest that most metastatic drivers are established in the primary tumor, despite the substantial heterogeneity seen in the metastases

    Claudin 4 Is Differentially Expressed between Ovarian Cancer Subtypes and Plays a Role in Spheroid Formation

    Get PDF
    Claudin 4 is a cellular adhesion molecule that is frequently overexpressed in ovarian cancer and other epithelial cancers. In this study, we sought to determine whether the expression of claudin 4 is associated with outcome in ovarian cancer patients and may be involved in tumor progression. We examined claudin 4 expression in ovarian cancer tissues and cell lines, as well as by immunohistochemical staining of tissue microarrays (TMAs; n = 500), spheroids present in patients’ ascites, and spheroids formed in vitro. Claudin 4 was expressed in nearly 70% of the ovarian cancer tissues examined and was differentially expressed across ovarian cancer subtypes, with the lowest expression in clear cell subtype. No association was found between claudin 4 expression and disease-specific survival in any subtype. Claudin 4 expression was also observed in multicellular spheroids obtained from patients’ ascites. Using an in vitro spheroid formation assay, we found that NIH:OVCAR5 cells treated with shRNA against claudin 4 required a longer time to form compact spheroids compared to control NIH:OVCAR5 cells that expressed high levels of claudin 4. The inability of the NIH:OVCAR5 cells treated with claudin 4 shRNA to form compact spheroids was verified by FITC-dextran exclusion. These results demonstrate a role for claudin 4 and tight junctions in spheroid formation and integrity

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

    Get PDF
    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy
    • …
    corecore