Interval analysis of blood filtration efficacy in novel device for autotransfusion in postpartum hemorrhage.

Postpartum haemorrhage (PPH), the leading cause of maternal mortality, is particularly problematic in low resource settings where access to safe blood supplies and definitive medical treatment is limited. We describe the continued development of an autotransfusion device designed to treat PPH by collection, filtration and infusion of maternal blood. Previous study has demonstrated that the device effectively moves blood through a filtration apparatus and removes up to 97% of aerobic bacteria but had poor anaerobic bacteria reduction. In this study, we investigate the filtration efficacy of the device using configurations comprised of three different leukocyte depletion filter designs: the Pall Leukoguard RS leukocyte reduction filter (PLRF), the Haemonetics BPF4™ (BPF4) leukocyte reduction filter, and the Haemonetics SCRC Leukotrap® (SCRC) filter. All configurations performed well with reductions ranging from 49 to 98%. Configurations containing 2 Haemonetics SCRC Leukotrap®filters (configuration 5 and 6) consistently reduced anaerobic bacteria by at least 73%. These results indicate that utilising a combination of SCRC and PLRF filters confers a high level of microbial filtration with improved removal of anaerobic organisms.

Occupational Exposures and Computed Tomographic Imaging Characteristics in the SPIROMICS Cohort.

RATIONALE: Quantitative computed tomographic (CT) imaging can aid in chronic obstructive pulmonary disease (COPD) phenotyping. Few studies have identified whether occupational exposures are associated with distinct CT imaging characteristics. OBJECTIVES: To examine the association between occupational exposures and CT-measured patterns of disease in the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study). METHODS: Participants underwent whole-lung multidetector helical CT at full inspiration and expiration. The association between occupational exposures (self-report of exposure to vapors, gas, dust, or fumes [VGDF] at the longest job) and CT metrics of emphysema (percentage of total voxels < -950 Hounsfield units at total lung capacity), large airways (wall area percent [WAP] and square-root wall area of a single hypothetical airway with an internal perimeter of 10 mm [Pi10]), and small airways (percent air trapping [percent total voxels < -856 Hounsfield units at residual volume] and parametric response mapping of functional small-airway abnormality [PRM fSAD]) were explored by multivariate linear regression, and for central airway measures by generalized estimating equations to account for multiple measurements per individual. Models were adjusted for age, sex, race, current smoking status, pack-years of smoking, body mass index, and site. Airway measurements were additionally adjusted for total lung volume. RESULTS: A total of 2,736 participants with available occupational exposure data (n = 927 without airflow obstruction and 1,809 with COPD) were included. The mean age was 64 years, 78% were white, and 54% were male. Forty percent reported current smoking, and mean (SD) pack-years was 49.3 (26.9). Mean (SD) post-bronchodilator forced expiratory volume in 1 second (FEV1) was 73 (27) % predicted. Forty-nine percent reported VGDF exposure. VGDF exposure was associated with higher emphysema (ß = 1.17; 95% confidence interval [CI], 0.44-1.89), greater large-airway disease as measured by WAP (segmental ß = 0.487 [95% CI, 0.320-0.654]; subsegmental ß = 0.400 [95% CI, 0.275-0.527]) and Pi10 (ß = 0.008; 95% CI, 0.002-0.014), and greater small-airway disease was measured by air trapping (ß = 2.60; 95% CI, 1.11-4.09) and was nominally associated with an increase in PRM fSAD (ß = 1.45; 95% CI, 0.31-2.60). These findings correspond to higher odds of percent emphysema, WAP, and air trapping above the 95th percentile of measurements in nonsmoking control subjects in individuals reporting VGDF exposure. CONCLUSIONS: In an analysis of SPIROMICS participants, we found that VGDF exposure in the longest job was associated with an increase in emphysema, and in large- and small-airway disease, as measured by quantitative CT imaging.

Effects of Essential Oil from Thymus vulgaris on Viability and Inflammation in Zebrafish Embryos.

Innate immunity provides the initial response against pathogens and includes the inflammatory response. Regulation of the initiation and duration of neutrophil and mononuclear cell influx during inflammation determines both the successfulness of pathogen elimination and the level of resulting tissue damage. Zebrafish embryos provide excellent opportunities to visualize the inflammatory response. Neutrophil granules may be stained with Sudan black, and variation in neutrophil counts may be used to monitor the level of the response. Inflammation may be triggered by injuring the caudal fin, providing an opportunity for testing possible anti-inflammatory compounds in a whole-animal system. The use of homeopathic compounds as anti-inflammatory treatments is common in alternative medicine. Effects of unfractionated essential oil from Thymus vulgaris and its specific component, carvacrol, have been examined in cells in culture and in rodents. Our work extends this research to zebrafish, and includes toxicity and morphological studies as well as examination of anti-inflammatory effects following tail fin injury. Our results show that zebrafish are more sensitive to thyme oil compared to cells in culture, that cardiac defects arise due to thyme oil treatment, and that thyme oil reduces neutrophil infiltration during an inflammatory response.

Outcomes and changes in code status of patients with acute myeloid leukemia undergoing induction chemotherapy who were transferred to the intensive care unit.

Patients with Acute Myeloid Leukemia (AML) have compromised marrow function and chemotherapy causes further suppression. As a result complications are frequent, and patients may require admission to the intensive care unit (ICU). How codes status changes when these events occur and how those changes influence outcome are largely unknown. Outcomes for adult patients with AML, undergoing induction chemotherapy, and transferred to the ICU between January 2000 and December 2013 were analyzed. 94 patients were included. Median survival was 1.3 months. At 3 and 6 months overall survival (OS) was 27% and 18% respectively. Respiratory failure was the most common reason for transfer to ICU (88%), with 63% requiring mechanical ventilation at transfer. Other reasons included: cardiac arrest (18%), septic shock (17%), hypotension (9%), and acute renal failure (9%). The most frequent interventions were mechanical ventilation in 85%, vasopressors in 62%, and hemodialysis in 30%. Following transfer 55 patients (58%) had a change in code status. Overall, 46 patients (49%) changed from Full Code (FC) to Comfort Care (CC), 7 (7%) from FC to Do Not Resuscitate (DNR), and 2 (2%) from DNR to CC. For the entire cohort, ICU mortality (IM) was 61% and hospital mortality (HM) was 71%. For FC or DNR patients, IM was 30% and HM was 41%. For CC patients, IM was 90% and HM was 100%. Overall, 27 patients (29%) survived to discharge. Of those discharged, 22 (81%) were alive at 3 months and 17 (63%) were alive at 6 months. In conclusion, patients that required ICU admission during induction chemotherapy have a poor prognosis. Code status changed during the ICU stay for the majority of patients and always to a less aggressive status.

Do hospitals need oncological critical care units?

Since the inception of critical care as a formal discipline in the late 1950s, we have seen rapid specialization to many types of intensive care units (ICUs) to accommodate evolving life support technologies and novel therapies in various disciplines of medicine. Indeed, the field has expanded such that specialized ICUs currently exist to address critical care problems in medicine, cardiology, neurology and neurosurgery, trauma, burns, organ transplant and cardiothoracic surgeries. Specialization does not only need new infrastructure, but also training and staffing of health care providers, ancillary staff, and development and implementation of processes of care. Oncology is another branch of medicine with growing ICU needs. Given the rise in cancer incidence worldwide and better survival rates alongside advances in chemotherapeutic and surgical options, more cancer patients are nowadays requiring advanced life support for cancer-related complications, treatment-related toxicities and severe infections. Here we provide a brief summary of the current evidence supporting the specialization of critical care and explore three different models of care for critically ill cancer patients, including the development of a specialized oncological ICU. Finally, we also discuss recently published and future research related to the care of critically ill cancer patients.

Quantitative DNA methylation analysis of candidate genes in cervical cancer.

Aberrant DNA methylation has been observed in cervical cancer; however, most studies have used non-quantitative approaches to measure DNA methylation. The objective of this study was to quantify methylation within a select panel of genes previously identified as targets for epigenetic silencing in cervical cancer and to identify genes with elevated methylation that can distinguish cancer from normal cervical tissues. We identified 49 women with invasive squamous cell cancer of the cervix and 22 women with normal cytology specimens. Bisulfite-modified genomic DNA was amplified and quantitative pyrosequencing completed for 10 genes (APC, CCNA, CDH1, CDH13, WIF1, TIMP3, DAPK1, RARB, FHIT, and SLIT2). A Methylation Index was calculated as the mean percent methylation across all CpG sites analyzed per gene (~4-9 CpG site) per sequence. A binary cut-point was defined at >15% methylation. Sensitivity, specificity and area under ROC curve (AUC) of methylation in individual genes or a panel was examined. The median methylation index was significantly higher in cases compared to controls in 8 genes, whereas there was no difference in median methylation for 2 genes. Compared to HPV and age, the combination of DNA methylation level of DAPK1, SLIT2, WIF1 and RARB with HPV and age significantly improved the AUC from 0.79 to 0.99 (95% CI: 0.97-1.00, p-value = 0.003). Pyrosequencing analysis confirmed that several genes are common targets for aberrant methylation in cervical cancer and DNA methylation level of four genes appears to increase specificity to identify cancer compared to HPV detection alone. Alterations in DNA methylation of specific genes in cervical cancers, such as DAPK1, RARB, WIF1, and SLIT2, may also occur early in cervical carcinogenesis and should be evaluated.

Heart smart for women: a community-based lifestyle change intervention to reduce cardiovascular risk in rural women.

PURPOSE: Cardiovascular disease (CVD) is the leading cause of death for rural women in the United States. Lifestyle change interventions in group settings focused on increasing physical activity and improving nutrition have been shown to help reduce the risk for CVD. This paper describes the implementation and evaluation of Heart Smart for Women (HSFW), a 12-week lifestyle behavior change intervention to reduce CVD risk for women in the rural southernmost 7 counties (S7) of Illinois. METHODS: The HSFW evidence-based lifestyle intervention was delivered by a trained facilitator in 12 weekly 1-hour sessions to groups of women in the rural S7 region of Illinois. Dietary and physical activity assessments were collected at baseline, postintervention, and 1 year. Clinical measurements were taken at baseline, 6 months and 1 year. Data were analyzed for change in behavioral and clinical outcomes over time. FINDINGS: In total, 162 women completed HSFW in 13 communities across the S7 region. HSFW participants showed improvement in dietary and physical activity indicators at the end of the 12-week intervention, but only increases in vegetable consumption and physical activity were sustained over 1 year. A decrease in total cholesterol was observed at 6 months but not maintained at 1 year. CONCLUSIONS: HSFW led to short-term, moderate changes in nutrition and physical activity in rural women, but some health improvements were not sustained at 1 year. These findings suggest that more intensive follow-up maybe required to help maintain long-term behavior change, especially in rural areas where women are geographically dispersed.

The effect of midwifery care on rates of cesarean delivery.

OBJECTIVE: To examine whether changing to a midwifery-led maternity service model was associated with a lower national rate of cesarean delivery. METHODS: We analyzed trends in the rate of cesarean delivery per 1000 live births between 1996 and 2010 in New Zealand. Estimates of relative increases in rate were calculated via Poisson regression for several maternal age groups over the study period. RESULTS: Rates of cesarean delivery increased over the study period, from 156.9 per 1000 live births in 1996 to 235 per 1000 in 2010: a crude increase of 49.8%. Increasing trends were apparent in each age group, with the largest increases occurring before 2003 and relatively stable rates in the subsequent period. The smoothed estimate showed that the increase in cesarean rate across all age groups was 43.7% (95% confidence interval, 41.6-45.8) over the 15-year period. CONCLUSION: A national midwifery-led care model was not associated with a decreased rate of cesarean delivery but, instead, with an increase similar to that in other high-resource countries. This indicates that other factors may account for the increase. Further research is needed to examine maternity outcomes associated with different models of maternity care.

Building the Women's Health Research Workforce: Fostering Interdisciplinary Research Approaches in Women's Health.

BACKGROUND: The Building Interdisciplinary Research Careers in Women's Health (BIRCWH) program is a mentored institutional research career development program developed to support and foster the interdisciplinary research careers of men and women junior faculty in women's health and sex/gender factors. The number of scholars who apply for and receive National Institutes of Health (NIH) research or career development grants is one proximate indicator of whether the BIRCWH program is being successful in achieving its goals. PRIMARY STUDY OBJECTIVE: To present descriptive data on one metric of scholar performance-NIH grant application and funding rates. METHODS/DESIGN: Grant applications were counted if the start date was 12 months or more after the scholar's BIRCWH start date. Two types of measures were used for the outcome of interest-person-based funding rates and application-based success rates. MAIN OUTCOME MEASURES: Grant application, person funding, and application success rates. RESULTS: Four hundred and ninety-three scholars had participated in BIRCWH as of November 1, 2012. Seventy-nine percent of BIRCWH scholars who completed training had applied for at least one competitive NIH grant, and 64% of those who applied had received at least one grant award. Approximately 68% of completed scholars applied for at least one research grant, and about half of those who applied were successful in obtaining at least one research award. Men and women had similar person funding rates, but women had higher application success rates for RoI grants. LIMITATIONS: Data were calculated for all scholars across a series of years; many variables can influence person funding and application success rates beyond the BIRCWH program; and lack of an appropriate comparison group is another substantial limitation to this analysis. CONCLUSION: Our results suggest that the BIRCWH program has been successful in bridging advanced training with establishing independent research careers for scholars.

Assessing preventability for obstetric hemorrhage.

We sought to determine preventability for cases of obstetric hemorrhage, identify preventable factors, and compare differences between levels of hospital. We retrospectively reviewed a 1-year cohort of severe and near-miss obstetric hemorrhage in an urban perinatal network. An expert panel, using a validated preventability model, reviewed all cases. Preventability and distribution of preventability factors were compared between levels of hospital care. Sixty-three severe and near-miss obstetric hemorrhage cases were identified from 11 hospitals; 54% were deemed potentially preventable. Overall preventability was not statistically different by level of hospital, and 88% were provider related. The only treatment-related preventability factors were significantly different between levels of hospital and significantly less common in level III hospitals (p < 0.01). The majority of obstetric hemorrhage was preventable. The most common potentially preventable factor was provider treatment error, and this was significantly more common in level II hospitals. New interventions should be focused on decreasing providers' treatment errors.

Inclusion, analysis, and reporting of sex and race/ethnicity in clinical trials: have we made progress?

BACKGROUND: The National Institutes of Health (NIH) Revitalization Act of 1993 requires that NIH-funded clinical trials include women and minorities as participants; other federal agencies have adopted similar guidelines. The objective of this study is to determine the current level of compliance with these guidelines for the inclusion, analysis, and reporting of sex and race/ethnicity in federally funded randomized controlled trials (RCTs) and to compare the current level of compliance with that from 2004, which was reported previously. METHODS: RCTs published in nine prominent medical journals in 2009 were identified by PubMed search. Studies where individuals were not the unit of analysis, those begun before 1994, and those not receiving federal funding were excluded. PubMed search located 512 published articles. After exclusion of ineligible articles, 86 (17%) remained for analysis. RESULTS: Thirty studies were sex specific. The median enrollment of women in the 56 studies that included both men and women was 37%. Seventy-five percent of the studies did not report any outcomes by sex, including 9 studies reporting <20% women enrolled. Among all 86 studies, 21% did not report sample sizes by racial and ethnic groups, and 64% did not provide any analysis by racial or ethnic groups. Only 3 studies indicated that the generalizability of their results may be limited by lack of diversity among those studied. There were no statistically significant changes in inclusion or reporting of sex or race/ethnicity when compared with 2004. CONCLUSIONS: Ensuring enhanced inclusion, analysis, and reporting of sex and race/ethnicity entails the efforts of NIH, journal editors, and the researchers themselves.