Comparative Performance of Pulmonary Ultrasound, Chest Radiograph, and CT Among Patients With Acute Respiratory Failure.

OBJECTIVES: The study goal was to concurrently evaluate agreement of a 9-point pulmonary ultrasound protocol and portable chest radiograph with chest CT for localization of pathology to the correct lung and also to specific anatomic lobes among a diverse group of intubated patients with acute respiratory failure. DESIGN: Prospective cohort study. SETTING: Medical, surgical, and neurologic ICUs at a 670-bed urban teaching hospital. PATIENTS: Intubated adults with acute respiratory failure having chest CT and portable chest radiograph performed within 24 hours of intubation. INTERVENTIONS: A 9-point pulmonary ultrasound examination performed at the time of intubation. MEASUREMENTS AND MAIN RESULTS: Sixty-seven patients had pulmonary ultrasound, portable chest radiograph, and chest CT performed within 24 hours of intubation. Overall agreement of pulmonary ultrasound and portable chest radiograph findings with correlating lobe ("lobe-specific" agreement) on CT was 87% versus 62% (p < 0.001), respectively. Relaxing the agreement definition to a matching CT finding being present anywhere within the correct lung ("lung-specific" agreement), not necessarily the specific mapped lobe, showed improved agreement for both pulmonary ultrasound and portable chest radiograph respectively (right lung: 92.5% vs 65.7%; p < 0.001 and left lung: 83.6% vs 71.6%; p = 0.097). The highest lobe-specific agreement was for the finding of atelectasis/consolidation for both pulmonary ultrasound and portable chest radiograph (96% and 73%, respectively). The lowest lobe-specific agreement for pulmonary ultrasound was normal lung (79%) and interstitial process for portable chest radiograph (29%). Lobe-specific agreement differed most between pulmonary ultrasound and portable chest radiograph for interstitial findings (86% vs 29%, respectively). Pulmonary ultrasound had the lowest agreement with CT for findings in the left lower lobe (82.1%). Pleural effusion agreement also differed between pulmonary ultrasound and portable chest radiograph (right: 99% vs 87%; p = 0.009 and left: 99% vs 85%; p = 0.004). CONCLUSIONS: A clinical, 9-point pulmonary ultrasound protocol strongly agreed with specific CT findings when analyzed by both lung- and lobe-specific location among a diverse population of mechanically ventilated patients with acute respiratory failure; in this regard, pulmonary ultrasound significantly outperformed portable chest radiograph.

Reduced annexin A6 expression promotes the degradation of activated epidermal growth factor receptor and sensitizes invasive breast cancer cells to EGFR-targeted tyrosine kinase inhibitors.

BACKGROUND: The expression of annexin A6 (AnxA6) in AnxA6-deficient non-invasive tumor cells has been shown to terminate epidermal growth factor receptor (EGFR) activation and downstream signaling. However, as a scaffolding protein, AnxA6 may stabilize activated cell-surface receptors to promote cellular processes such as tumor cell motility and invasiveness. In this study, we investigated the contribution of AnxA6 in the activity of EGFR in invasive breast cancer cells and examined whether the expression status of AnxA6 influences the response of these cells to EGFR-targeted tyrosine kinase inhibitors (TKIs) and/or patient survival. RESULTS: We demonstrate that in invasive BT-549 breast cancer cells AnxA6 expression is required for sustained membrane localization of activated (phosho-Y1068) EGFR and consequently, persistent activation of MAP kinase ERK1/2 and phosphoinositide 3-kinase/Akt pathways. Depletion of AnxA6 in these cells was accompanied by rapid degradation of activated EGFR, attenuated downstream signaling and as expected enhanced anchorage-independent growth. Besides inhibition of cell motility and invasiveness, AnxA6-depleted cells were also more sensitive to the EGFR-targeted TKIs lapatinib and PD153035. We also provide evidence suggesting that reduced AnxA6 expression is associated with a better relapse-free survival but poorer distant metastasis-free and overall survival of basal-like breast cancer patients. CONCLUSIONS: Together this demonstrates that the rapid degradation of activated EGFR in AnxA6-depleted invasive tumor cells underlies their sensitivity to EGFR-targeted TKIs and reduced motility. These data also suggest that AnxA6 expression status may be useful for the prediction of the survival and likelihood of basal-like breast cancer patients to respond to EGFR-targeted therapies.

Outcomes of Minnesota Detoxification Scale (MINDS) Assessment With High-Dose Front Loading Diazepam Treatment for Alcohol Withdrawal in Hospitalized Patients.

BACKGROUND: Benzodiazepines are the gold standard for alcohol withdrawal treatment but choice and dosing vary widely. In 2015, our institution implemented a Minnesota detoxification scale (MINDS) and single standardized high-dose diazepam based protocol for treatment of alcohol withdrawal to replace multiple Clinical Institute Withdrawal Assessment for Alcohol (CIWA) based protocols using lower dose benzodiazepines. We compared use of MINDS versus CIWA assessment protocols with high front loading diazepam treatment in care of patient experiencing alcohol withdrawal during hospitalization. METHODS: Retrospective cohort study of hospitalized patients experiencing alcohol withdrawal to statistically analyze difference in outcomes between CIWA based lower benzodiazepine dose protocols used in 2013-2015 versus the MINDS based high-dose front-loading diazepam protocol used in 2015-2017. RESULTS: Patients treated with MINDS based high dose diazepam protocol were less likely to have physical restraints used (AOR = 0.8, CI: 0.70-0.92), had a shorter hospital length of stay, and fewer days on benzodiazepines (p < 0.001). Patients were more likely to be readmitted to the hospital within 30 days (AOR = 1.13, CI: 1.03-1.26) in MINDS based diazepam treatment group. Total diazepam equivalent dosing was similar in both groups. Mortality rates and ICU use rates were similar between the groups. CONCLUSIONS: Higher dose front loading long acting benzodiazepine can be safely used with beneficial outcomes in hospitalized alcohol withdrawal patients.

Increased Black-White disparities in mortality after the introduction of lifesaving innovations: a possible consequence of US federal laws.

OBJECTIVES: We explored whether the introduction of 3 lifesaving innovations introduced between 1989 and 1996 increased, decreased, or had no effect on disparities in Black-White mortality in the United States through 2006. METHODS: Centers for Disease Control and Prevention data were used to assess disease-, age-, gender-, and race-specific changes in mortality after the introduction of highly active anti-retroviral therapy (HAART) for treatment of HIV, surfactants for neonatal respiratory distress syndrome, and Medicare reimbursement of mammography screening for breast cancer. RESULTS: Disparities in Black-White mortality from HIV significantly increased after the introduction of HAART, surfactant therapy, and reimbursement for screening mammography. Between 1989 and 2006, these circumstances may have accounted for an estimated 22,441 potentially avoidable deaths among Blacks. CONCLUSIONS: These descriptive data contribute to the formulation of the hypothesis that federal laws promote increased disparities in Black-White mortality by inadvertently favoring Whites with respect to access to lifesaving innovations. Failure of legislation to address known social factors is a plausible explanation, at least in part, for the observed findings. Further research is necessary to test this hypothesis, including analytic epidemiological studies designed a priori to do so.

United States black:white infant mortality disparities are not inevitable: identification of community resilience independent of socioeconomic status.

INTRODUCTION: U.S. disparities in Black:White infant mortality are persistent. National trends, however, may obscure local successes. METHODS: Zero-corrected, negative binomial multivariable modeling was used to predict Black infant mortality (1999-2003) in all U.S. counties with reliable rates. Independent variables included county population size, racial composition, educational attainment, poverty, income and geographic origin. Resilient counties were defined as those whose Black infant mortality rate residual score was < 2.0. Mortality data was accessed from the Compressed Mortality File compiled by the National Center for Health Statistics and found on the CDC WONDER website. Demographic information was obtained from the US Census. RESULTS: The final model included the percentage of Blacks, age 18 to 64 years, speaking little or no English (P < .008), a socioeconomic index comprising educational attainment, poverty, and per capita income (P < .001), and household income in 1990 (P < .001). After accounting for these factors, a stratum comprising Essex and Plymouth Counties, Mass.; Bronx, N.Y.; and Multnomah, Ore. was identified as unusually resilient. Percentage of Black poverty and educational attainment in Black women in the resilient stratum approximated the average for all 330 counties. In 1979, Black infant mortality in the resilient stratum (23.6 per 1000 live births) exceeded Black US infant mortality (22.6). By 2001, Black infant mortality in the resilient stratum (5.6) was below the corresponding value for Whites (5.7). Resilient county neonatal mortality declined both early and late in the observation period, while post-neonatal declines were most marked after 1996. CONCLUSIONS: Models for reduction/elimination of racial disparities in US infant mortality, independent from county-level contextual measures of socioeconomic status, may already exist.

Effects of a Consensus-Based Pulmonary Embolism Treatment Algorithm and Response Team on Treatment Modality Choices, Outcomes, and Complications.

Pulmonary embolism (PE) treatment depends on disease severity and risk of complications. Physician and institutional expertise may influence the use of reperfusion therapy (RT) such as systemic thrombolysis (SL) and catheter-directed interventions (CDI). We aimed to investigate the effects of a consensus-based treatment algorithm (TA) and subsequent implementation of PE response team (PERT) on RT modality choices and patient outcomes. A cohort of PE patients admitted to a tertiary care hospital between 2012 and 2017 was retrospectively evaluated. Demographics, clinical variables, RT selections, and patient outcomes during 3 consecutive 2-year periods (baseline, with TA, and with TA+PERT) were compared. Descriptive statistics were used for data analysis. A total of 1105 PE patients were admitted, and 112 received RT. Use of RT increased from 4.7% at baseline to 8.2% and 16.1% during the TA and TA+PERT periods. The primary RT modality transitioned from CDI to SL, and reduced-dose SL became most common. Treatment selection patterns remained unchanged after PERT introduction. Hospital length of stay decreased from 4.78 to 2.96 and 2.81 days (P < .001). Most of the hemorrhagic complications were minor, and their rates were similar across all 3 periods and between SL and CDI. No major hemorrhages occurred in patients treated with reduced-dose SL. In conclusion, TA and PERT represent components of a decision support system facilitating treatment modality selection, contributing to improved outcomes, and limiting complications. Treatment algorithm emerged as a factor providing consistency to PERT recommendations.

Assessing patient and caregiver understanding of and satisfaction with the use of contact isolation.

BACKGROUND: Contact isolation is a method used for limiting the spread of antimicrobial-resistant organisms when caring for patients. This policy has been linked to several adverse outcomes and less patient satisfaction. We assessed patient and caregiver understanding and satisfaction with the use of contact isolation. METHODS: A prospective survey of >500 patients in contact isolation at our institution was performed during 2014. Participants responded to a series of statements relating to contact isolation, using a 5-point Likert scale. Responses were assessed for overall positivity or negativity and further compared according to floor type or designation. RESULTS: Of the patients, 48.7% responded to the survey; 70 caregivers also responded. Patient and caregiver responses were similar and were positive overall. Most respondents felt safer because of the use of contact isolation and because it prevented infections. A smaller majority of respondents also thought the policy was adequately explained to them and adhered to by staff. CONCLUSIONS: In the largest collection of respondents surveyed to date about contact isolation and its impact on them, the policy was viewed positively, both by patients and caregivers. There is still room for improvement in the area of patient education regarding the use of contact isolation.

The public health exposome: a population-based, exposure science approach to health disparities research.

The lack of progress in reducing health disparities suggests that new approaches are needed if we are to achieve meaningful, equitable, and lasting reductions. Current scientific paradigms do not adequately capture the complexity of the relationships between environment, personal health and population level disparities. The public health exposome is presented as a universal exposure tracking framework for integrating complex relationships between exogenous and endogenous exposures across the lifespan from conception to death. It uses a social-ecological framework that builds on the exposome paradigm for conceptualizing how exogenous exposures "get under the skin". The public health exposome approach has led our team to develop a taxonomy and bioinformatics infrastructure to integrate health outcomes data with thousands of sources of exogenous exposure, organized in four broad domains: natural, built, social, and policy environments. With the input of a transdisciplinary team, we have borrowed and applied the methods, tools and terms from various disciplines to measure the effects of environmental exposures on personal and population health outcomes and disparities, many of which may not manifest until many years later. As is customary with a paradigm shift, this approach has far reaching implications for research methods and design, analytics, community engagement strategies, and research training.

Scalable combinatorial tools for health disparities research.

Despite staggering investments made in unraveling the human genome, current estimates suggest that as much as 90% of the variance in cancer and chronic diseases can be attributed to factors outside an individual's genetic endowment, particularly to environmental exposures experienced across his or her life course. New analytical approaches are clearly required as investigators turn to complicated systems theory and ecological, place-based and life-history perspectives in order to understand more clearly the relationships between social determinants, environmental exposures and health disparities. While traditional data analysis techniques remain foundational to health disparities research, they are easily overwhelmed by the ever-increasing size and heterogeneity of available data needed to illuminate latent gene x environment interactions. This has prompted the adaptation and application of scalable combinatorial methods, many from genome science research, to the study of population health. Most of these powerful tools are algorithmically sophisticated, highly automated and mathematically abstract. Their utility motivates the main theme of this paper, which is to describe real applications of innovative transdisciplinary models and analyses in an effort to help move the research community closer toward identifying the causal mechanisms and associated environmental contexts underlying health disparities. The public health exposome is used as a contemporary focus for addressing the complex nature of this subject.

Perinatal factors and breast cancer risk among Hispanics.

PURPOSE: This study assessed whether perinatal factors were associated with breast cancer among Hispanics, a group with fairly low incidence rates of breast cancer. METHODS: Data were used from a case-control study of breast cancer among Hispanics aged 30-79 conducted between 2003 and 2008 on the Texas-Mexico border. In-person interviews were completed with 188 incident breast cancer cases ascertained through surgeons and oncologists, and 974 controls (with respective response rates of 97% and 78%). RESULTS: Relative to birth weight 2500-3999g, there was no elevation in breast cancer risk for birth weight of ≥ 4000g (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.47-1.21). CONCLUSIONS: The results tended to differ slightly from previous studies of this topic perhaps owing to the different hormonal milieu among Hispanics relative to Caucasians, African Americans and Asians in whom all previous studies of this topic have been conducted. Confirmation of these findings in larger studies may assist in determining how hormonal mechanisms responsible for breast cancer differ by ethnicity.

Preterm labor: CD55 in maternal blood leukocytes.

PROBLEM: Intrauterine inflammation is a frequent and significant factor associated with the pathogenesis of preterm labor/birth (PTL/PTB). However, it remains unclear whether the intrauterine inflammatory responses activate the maternal peripheral circulation. We explored the association between PTL/PTB and the 'activation' of the peripheral circulatory system by determining whether CD55 mRNA expression within peripheral WBCs differed between PTL and control patients not in labor. METHOD OF STUDY: RNA was purified from white blood cells collected from pregnant women with preterm labor (n = 45), and from pregnant (n = 30) control women. CD55 gene expression was evaluated by quantitative PCR. RESULTS: The mean CD55 mRNA level within the PTL group (0.77 +/- 0.03) was 1.48-fold higher than that observed (0.52 +/- 0.02) within the control group (P < 0.0001); 71% of PTL patients and only 6.7% of control subjects expressed elevated CD55 mRNA. The receiver operating characteristics (with 95% CI) of CD55 as a marker for PTL were as follows: Sensitivity, 69% (53-82%); Specificity, 93% (78-99%); Positive Predictive Value, 94% (80-99%); and Negative Predictive Value, 67% (51-80%). In the patient population that delivered prematurely (before 37 weeks), 81% expressed elevated CD55 mRNA levels with a mean of 0.78 +/- 0.03 and 95% CI of 0.71-0.84. The receiver operating characteristics were as follows: Sensitivity, 73% (54-88%); Specificity, 86% (71-95%); Positive Predictive Value, 81.5% (62-94%); and Negative Predictive Value, 80% (64-91%). CONCLUSION: Here we report for the first time that CD55 mRNA expression was elevated in the peripheral WBCs of subjects with preterm labor compared with control gestationally-matched pregnant woman and that elevated leukocyte CD55 may be a useful predictor of subsequent PTB.