Prehospital needle thoracostomy: What are the indications and is a post-trauma center arrival chest tube required?

OBJECTIVE: This study examined the indications for prehospital needle thoracostomy (pNT), the need for tube thoracostomy (TT) following pNT, and the outcomes of patients who underwent pNT. METHODS: This study is a retrospective chart review of patients who underwent pNT prior to trauma center arrival. Patients were identified from the trauma registry and a quality improvement (QI) database from 9/2014-9/2018. RESULTS: 59 patients underwent 63 pNTs during the time period. The indication for pNT was "hypotension" in only 5 patients (7.9%). A CT chest was obtained on 51 NT attempts with the catheter in place. In 48 (94.1%) NT attempts, the catheter was not in the pleural space. 44 (69.4%) TTs were placed on admission date. CONCLUSION: In patients undergoing pNT, hypotension was rarely the indication. Additionally, CT identified the catheter within the pleural space in only 3 (5.8%) NT attempts. TT placement was performed in 79.3% of NT attempts.

Variation and comparative effectiveness of patent ductus arteriosus pharmacotherapy in extremely low birth weight infants.

BACKGROUND: Patent ductus arteriosus (PDA) occurs in 70% of extremely low birth weight (ELBW, birth weight <1000 g) infants. Approximately 34% of ELBW infants with a PDA have spontaneous closure. Failure of the ductus arteriosus to close has been associated with multiple morbidities. OBJECTIVE: To examine variability over time and across hospitals in early therapeutic (2-7 day) use of indomethacin (INDO) vs ibuprofen (IBU) for PDA treatment in outborn ELBW infants and examine the outcomes and side effects of both pharmacological agents in this population. METHODS: Data were extracted from the Pediatric Health Information System. ELBW infants born between January 1, 2007 and December 31, 2010 and admitted on day of life 0 were eligible for inclusion. 732 infants had a PDA diagnosis and met inclusion criteria. We explored the variability in PDA pharmacotherapy over time and across hospitals. We compared outcomes of both agents for in-hospital mortality, need for surgical ligation, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, periventricular leukomalacia, renal failure, and persistent pulmonary hypertension. Statistical methods included chi square and multivariable regression analysis. Instrumental variable analysis was used to control for selection bias and omitted variables. RESULTS: There was large variability in PDA pharmacotherapy over time and across hospitals. INDO use declined as IBU use grew from 12.8 to 38.9%. There was no difference in hospital or NICU characteristics between high and low IBU using NICUs. Renal failure was more common in infants receiving INDO compared to IBU. CONCLUSION: We noted large variability in PDA pharmacotherapy. Renal failure was more common with INDO use. Until further studies to compare the long-term effects of both drugs, our data support IBU as the preferred medication for PDA pharmacotherapy in ELBW infants.

Domain wall motion in magnetic nanowires: an asymptotic approach.

We develop a systematic asymptotic description for domain wall motion in one-dimensional magnetic nanowires under the influence of small applied magnetic fields and currents and small material anisotropy. The magnetization dynamics, as governed by the Landau-Lifshitz-Gilbert equation, is investigated via a perturbation expansion. We compute leading-order behaviour, propagation velocities and first-order corrections of both travelling waves and oscillatory solutions, and find bifurcations between these two types of solutions. This treatment provides a sound mathematical foundation for numerous results in the literature obtained through more ad hoc arguments.

Toca 511 gene transfer and 5-fluorocytosine in combination with temozolomide demonstrates synergistic therapeutic efficacy in a temozolomide-sensitive glioblastoma model.

Toca 511 (vocimagene amiretrorepvec), an amphotropic retroviral replicating vector (RRV), can successfully and safely deliver a functional, optimized cytosine deaminase (CD) gene to tumors in orthotopic glioma models. This agent, in conjunction with subsequent oral extended-release 5-fluorocytosine (5-FC) (Toca FC), is currently under investigation in patients with recurrent high-grade glioma . Temozolomide (TMZ) with radiation is the most frequently used first-line treatment for patients with glioblastoma, the most common and aggressive form of primary brain cancer in adults. However, subsets of patients with certain genetic alterations do not respond well to TMZ treatment and the overall median survival for patients who respond remains modest, suggesting that combinatorial approaches may be necessary to significantly improve outcomes. We show that in vitro TMZ delays but does not prevent RRV spread, nor interfere with Toca 511+5-FC-mediated cell killing in glioma tumor cells, and in vivo there is no significant hematologic effect from the combination of 5-FC and the clinically relevant dose of TMZ. A synergistic long-term survival advantage is observed in mice bearing an orthotopic TMZ-sensitive glioma after Toca 511 administration followed by coadministration of TMZ and 5-FC. These results provide support for the investigation of this novel combination treatment strategy in patients with newly diagnosed malignant glioma.

Convection-enhanced delivery improves distribution and efficacy of tumor-selective retroviral replicating vectors in a rodent brain tumor model.

In the present study, we compared the therapeutic effect of tumor-selective retroviral replicating vectors (RRV) expressing the yeast cytosine deaminase (CD) delivered by convection-enhanced delivery (CED) or simple injection, followed by systemic administration of the pro-drug, 5-fluorocytosine (5-FC). Treatment with RRV-CD and systemic 5-FC significantly increased survival in rodent U87MG glioma model in comparison with controls (P<0.01). Interestingly, CED of RRV-CD followed by 5-FC further enhanced survival in this animal model in comparison with intra-tumoral injection of RRV-CD, followed by systemic 5-FC (P<0.05). High expression levels of Ki-67 were found in untreated tumors compared with treated. Untreated tumors were also much larger than treated. CED resulted in excellent distribution of RRV while only partial distribution of RRV was obtained after injection. Furthermore, RRV-CD and CD were also found in tumors from treated rats at study end points. These results demonstrated that RRV vectors may efficiently transduce and stably propagate in malignant human glioma, thereby achieving a significant in situ amplification effect after initial administration. We conclude that delivery of RRV into the glioma by CED provides much wider vector distribution than simple injection, and this correlated with better therapeutic outcomes.

Domain-wall motion in ferromagnetic nanowires driven by arbitrary time-dependent fields: an exact result.

We address the dynamics of magnetic domain walls in ferromagnetic nanowires under the influence of external time-dependent magnetic fields. We report a new exact spatiotemporal solution of the Landau-Lifshitz-Gilbert equation for the case of soft ferromagnetic wires and nanostructures with uniaxial anisotropy. The solution holds for applied fields with arbitrary strength and time dependence. We further extend this solution to applied fields slowly varying in space and to multiple domain walls.

Topology and bistability in liquid crystal devices.

We study nematic liquid crystal configurations in a prototype bistable device -- the post aligned bistable nematic (PABN) cell. Working within the Oseen-Frank continuum model, we describe the liquid crystal configuration by a unit-vector field n , in a model version of the PABN cell. First, we identify four distinct topologies in this geometry. We explicitly construct trial configurations with these topologies which are used as initial conditions for a numerical solver, based on the finite-element method. The morphologies and energetics of the corresponding numerical solutions qualitatively agree with experimental observations and suggest a topological mechanism for bistability in the PABN cell geometry.

Inpatient care for uncomplicated bronchiolitis: comparison with Milliman and Robertson guidelines.

CONTEXT: Bronchiolitis is the most common lower respiratory tract infection in infancy. A recent Centers for Disease Control and Prevention report confirmed that hospitalization rates for bronchiolitis have increased 2.4-fold from 1980 to 1996. Controversies exist about optimal treatment plans. Milliman and Robertson recommend ambulatory care management; in case of hospitalization, the recommended length of stay is 1 day. OBJECTIVES: To relate actual practice variation for infants admitted with uncomplicated bronchiolitis to Milliman and Robertson's recommendations. DESIGN: Prospective observational study. SETTING: General care wards of 8 pediatric hospitals of the Child Health Accountability Initiative during the winter of 1998-1999. PATIENTS: First-time admissions for uncomplicated bronchiolitis in patients not previously diagnosed as having asthma and who were younger than 1 year. MAIN OUTCOME MEASURES: Respiratory rate, monitored interventions, attainment of discharge criteria goals, and length of stay. RESULTS: Eight hundred forty-six patients were included in the final analysis: 85.7% were younger than 6 months, 48.5% were nonwhite, and 64.1% were Medicaid recipients or self-pay. On admission to the hospital, 18.3% of the infants had respiratory rates higher than higher than 80 breaths per minute, 53.8% received supplemental oxygen therapy, and 52.6% received intravenous fluids. These proportions decreased to 1.9%, 33.8%, and 20.3%, respectively, 1 day after admission, and to 0.7%, 20.1%, and 8.6%, respectively, 2 days after admission. The average length of stay was 2.8 days (SD, 2.3 days). CONCLUSIONS: Milliman and Robertson's recommendations do not correspond to practice patterns observed at the hospitals participating in this study; no hospital met the Milliman and Robertson recommended 1-day goal length of stay. Administration of monitored intervention persisted past the second day of hospitalization.

Improving estimates of caregiver time cost and family impact associated with birth defects.

BACKGROUND: Birth defects impose substantial costs on both families and society because of medical, developmental, and special education needs. Caring for children with birth defects also may influence caregiver time and impact the family. However, the economic cost of caregiver time and other impacts on the family has received far less attention than traditional healthcare costs. METHODS: This study reviews the literature on measuring caregiver time costs and family impact in an economic framework. The economic framework involves translating caregiver time or difficulties into appropriate units such as cost or quality adjusted life years (QALYs). RESULTS: Despite the potential important contribution of caregiver time costs to the total cost estimate of birth defects, few studies estimate caregiver time costs related specifically to birth defects. Only two studies provide estimates of these costs. Recent work has investigated the impact of chronic illness on caregivers in QALY terms, but birth defects have not been studied. Several issues need to be addressed in both the estimation of caregiver time costs and family impact to improve cost estimates. CONCLUSIONS: Improved estimates of caregiver time costs and impact on the family will assist policy makers in allocating resources for the prevention and treatment of birth defects. Future research should investigate the economic costs of caregiver time and family impact associated with caring for children with birth defects.

Measuring outcomes of care for adolescents with emotional and behavioral problems.

OBJECTIVES: To validate the prototype Adolescent Treatment Outcomes Module (ATOM), examine its sensitivity to clinical change, and determine its feasibility for administration in routine clinical settings. METHOD: A sample of 67 adolescents, aged 11 through 18, was selected from new patients at two inpatient and two outpatient mental health programs. Adolescents and parents completed the ATOM and validating instruments at intake, 1 week postintake, and again at 6 months. RESULTS: Nine self-report symptoms predicted positive diagnoses of oppositional defiant, conduct, anxiety, and depressive disorders on the basis of structured diagnoses, with sensitivities of 0.7 to 0.8. Test-retest correlations for outcome scales were largely excellent (>0.70). Scales that measured functioning at home, in school, and in the community were moderately correlated in the expected direction with global functioning. Decreases in symptom severity and functional impairment were generally associated with decreases in validating instruments. Administration time averaged 25 minutes for adolescents and 28 minutes for parents. CONCLUSIONS: Both parents and adolescents readily completed the ATOM. Module scales demonstrated excellent reliability and good to fair concurrent validity. The ATOM was able to detect change and its absence.

Socioeconomic status and type 2 diabetes in African American and non-Hispanic white women and men: evidence from the Third National Health and Nutrition Examination Survey.

OBJECTIVES: This study examined the associations of poverty income ratio (PIR), education, and occupational status with type 2 diabetes prevalence among African American and non-Hispanic White (White) women and men aged 40 to 74 years. METHODS: We analyzed cross-sectional data from the Third National Health and Nutrition Examination Survey, controlling for age and examination-related variables. RESULTS: Among African American women, there was a strong, graded association between PIR and diabetes, which remained significant after other risk factors were adjusted for. All 3 variables were significantly associated with diabetes among White women. Among White men, only PIR was significantly associated with diabetes. Controlling for risk factors substantially attenuated these associations among White women. There were no significant associations for African American men. CONCLUSIONS: Socioeconomic status is associated with type 2 diabetes prevalence among women, but not consistently among men. Diabetes prevalence is more strongly associated with PIR than with education or occupational status. These associations are largely independent of other risk factors, especially among African American women. Economic resources should be addressed in efforts to explain and reverse the increasing prevalence of diabetes in the United States.

Identification of Id4 as a regulator of BRCA1 expression by using a ribozyme-library-based inverse genomics approach.

Expression of the breast and ovarian cancer susceptibility gene BRCA1 is down-regulated in sporadic breast and ovarian cancer cases. Therefore, the identification of genes involved in the regulation of BRCA1 expression might lead to new insights into the pathogenesis and treatment of these tumors. In the present study, an "inverse genomics" approach based on a randomized ribozyme gene library was applied to identify cellular genes regulating BRCA1 expression. A ribozyme gene library with randomized target recognition sequences was introduced into human ovarian cancer-derived cells stably expressing a selectable marker [enhanced green fluorescence protein (EGFP)] under the control of the BRCA1 promoter. Cells in which BRCA1 expression was upregulated by particular ribozymes were selected through their concomitant increase in EGFP expression. The cellular target gene of one ribozyme was identified to be the dominant negative transcriptional regulator Id4. Modulation of Id4 expression resulted in inversely regulated expression of BRCA1. In addition, increase in Id4 expression was associated with the ability of cells to exhibit anchorage-independent growth, demonstrating the biological relevance of this gene. Our data suggest that Id4 is a crucial gene regulating BRCA1 expression and might therefore be important for the BRCA1 regulatory pathway involved in the pathogenesis of sporadic breast and ovarian cancer.

Toward a level playing field: predictive factors for the outcomes of mental health treatment for adolescents.

OBJECTIVE: To understand better the effectiveness of routine treatment for emotional and behavioral problems experienced by adolescents, methods are needed to control for between-provider differences in the distribution of factors that adversely affect treatment success. Such methods are necessary to fairly compare providers' outcomes and to aid clinicians in identifying adolescents for whom routine care may need to be altered. As a preliminary step toward developing a model to adjust treatment outcomes to account for predictive factors, findings from studies of treated samples of adolescents were reviewed to identify the factors that influence the likelihood of treatment success for this population. METHOD: Medline and PSYCInfo databases were searched for studies of treated adolescents that reported the association between expert-nominated predictive factors and outcomes. Thirty-four studies met inclusion criteria. RESULTS: Significant predictors identified in these studies include diagnosis, baseline severity of symptoms and functional impairment, family dysfunction, and previous treatment. Several expert-nominated factors have not been adequately studied in treated samples. CONCLUSIONS: Much basic work is needed before a convincing body of empirical evidence can explain predictive factors for adolescent mental health treatment outcomes. Future efforts should determine a reduced set of predictive factors that can be measured with minimal burden to providers.

Excess type 2 diabetes in African-American women and men aged 40-74 and socioeconomic status: evidence from the Third National Health and Nutrition Examination Survey.

OBJECTIVE: To examine whether socioeconomic status (SES) explains differences in the prevalence of type 2 diabetes between African-American and non-Hispanic white women and men. DESIGN: Cross sectional study of diabetes prevalence, SES, and other risk factors ascertained by physical examination and interview. SETTING: Interviews were conducted in subjects' homes; physical examinations were conducted in mobile examination centres. PARTICIPANTS: 961 African-American women, 1641 non-Hispanic white women, 839 African-American men and 1537 non-Hispanic white men, aged 40 to 74 years, examined in the Third National Health and Nutrition Examination Survey (NHANES III), a representative sample of the non-institutionalised civilian population of the United States, 1988-1994. MAIN RESULTS: Among women, African-American race/ethnicity was associated with an age adjusted odds ratio of 1.76 (95% confidence intervals 1.21, 2.57), which was reduced to 1.42 (95% confidence intervals 0.95, 2.13) when poverty income ratio was controlled. Controlling for education or occupational status had minimal effects on this association. When other risk factors were controlled, race/ethnicity was not significantly associated with type 2 diabetes prevalence. Among men, the age adjusted odds ratio associated with African-American race/ethnicity was 1.43 (95% confidence intervals 1.03, 1.99). Controlling for SES variables only modestly affected the odds ratio for African/American race/ethnicity among men, while adjusting for other risk factors increased the racial/ethnic differences. CONCLUSIONS: Economic disadvantage may explain much of the excess prevalence of type 2 diabetes among African-American women, but not among men.

Agreement between older subjects and proxy informants on history of surgery and childbirth.

OBJECTIVES: To assess the agreement between proxy informants' reports of history of surgery and childbirth and older index subjects' own recall. DESIGN: Interrater reliability study. SETTING: An outpatient family medicine clinic and a provincial electoral district in Montreal, Canada. PARTICIPANTS: Eighty-two subjects aged 65 years and older without cognitive impairment, identified from clinic and community settings, and each index subject's proxy respondent. MEASUREMENTS: Identical questionnaires were administered to index subjects and proxies. RESULTS: Proxies failed to report 39% of non-childbirth surgeries reported by index subjects, but failed to report only 10% of childbirths. Female proxies were significantly less likely than male proxies to underreport non-childbirth surgeries after controlling for age of index subject and interval since surgery. Longer interval since surgery was significantly associated with greater underreporting, whereas age of the index subject and relationship between proxy and index subject were not. Agreement between proxies and index subjects on date of surgery was much higher for childbirths than for non-childbirth surgeries. CONCLUSIONS: Our findings suggest that proxy respondents can provide reliable information on older women's history of childbirth but that use of proxy respondents for history of non-childbirth surgeries may result in substantial underreporting.

A novel functional genomics approach identifies mTERT as a suppressor of fibroblast transformation.

As a tool for functional genomics, a hairpin ribozyme gene library with randomized target recognition sequences was constructed in a retroviral vector. This library has the potential to target and cleave any possible RNA substrate. Mouse fibroblasts transduced with this ribozyme gene vector library were selected in a focus formation assay to isolate in vivo functional ribozymes that promote cell transformation in tissue culture. After two successive rounds of selection by focus formation assay, a transforming ribozyme (Rz007) was identified. The sequence of this ribozyme was used to identify the putative target genes responsible for the transformation. A candidate gene target for Rz007 encodes telomerase reverse transcriptase (mTERT). Both mRNA level and enzymatic activity of mTERT were down-regulated in Rz007-transformed cells. Furthermore, newly designed ribozymes, recognizing other potential ribozyme cleavage sites unique to the mTERT mRNA, also cause cell transformation, thus validating the role of mTERT in suppressing the transformation phenotype. These surprising results suggest that the commonly accepted role of telomerase in maintaining cellular immortalization is more complicated than previously thought. These studies also demonstrate the utility of this novel 'reverse' functional genomics approach, enabling the targeted discovery of genes, whether previously known or not, that are involved in any selectable phenotype.

Recognizing, treating, and preventing common foot problems.

The incidence, prevalence, and severity of foot conditions increase with age. Teaching patients simple preventive techniques is crucial. Recognition, treatment, and prevention of common foot complaints--i.e., toenail problems, infections, corns and calluses, injuries, flat feet, bunions, arthritis of the toes, and toe and joint deformities--are reviewed.