Faculty Bibliography

In this issue of Cell Host & Microbe, Liang et al. demonstrate through genomic analysis of the sputum microbiome from COPD patients and preclinical models that Staphylococcus aureus promotes lung function decline via regulation of homocysteine levels. Homocysteine can promote lung injury by promoting neutrophil apoptosis-to-NETosis shift via AKT1-S100A8/A9 axis.

BACKGROUND:Very elderly patients (age ≥ 85 years) are a rapidly increasing segment of the population. As a group, they experience high rates of in-hospital mortality and bleeding complications following percutaneous coronary intervention (PCI). However, the relationship between bleeding and mortality in the very elderly is unknown. METHODS:Retrospective review was performed on 17,378 consecutive PCI procedures from 2000 to 2015 at Dartmouth-Hitchcock Medical Center. Incidence of bleeding during the index PCI admission (bleeding requiring transfusion, access site hematoma > 5 cm, pseudoaneurysm, and retroperitoneal bleed) and in-hospital mortality were reported for four age groups (< 65 years, 65-74 years, 75-84 years, and ≥ 85 years). The mortality of patients who suffered bleeding complications and those who did not was calculated and multivariate analysis was performed for in-hospital mortality. Lastly, known predictors of bleeding were compared between patients age < 85 years and age ≥ 85 years. RESULTS:Of 17,378 patients studied, 1019 (5.9%) experienced bleeding and 369 (2.1%) died in-hospital following PCI. Incidence of bleeding and in-hospital mortality increased monotonically with increasing age (mortality: 0.94%, 2.27%, 4.24% and 4.58%; bleeding: 3.96%, 6.62%, 10.68% and 13.99% for ages < 65, 65-74, 75-84 and ≥ 85 years, respectively). On multivariate analysis, bleeding was associated with increased mortality for all age groups except patients age ≥ 85 years [odds ratio (95% CI): age < 65 years, 3.65 (1.99-6.74); age 65-74 years, 2.83 (1.62-4.94); age 75-84 years, 3.86 (2.56-5.82), age ≥ 85 years: 1.39 (0.49-3.95)]. CONCLUSIONS:Bleeding and mortality following PCI increase with increasing age. For the very elderly, despite high rates of bleeding, bleeding is no longer predictive of in-hospital mortality following PCI.

IMPORTANCE:Physicians often must decide whether to treat patients with acute stroke locally or refer them to a more distant Primary Stroke Center (PSC). There is little evidence on how much the increased risk of prolonged travel time offsets benefits of a specialized PSC care. OBJECTIVES:To examine the association of case fatality with receiving care in PSCs vs other hospitals for patients with stroke and to identify whether prolonged travel time offsets the effect of PSCs. DESIGN, SETTING, AND PARTICIPANTS:Retrospective cohort study of Medicare beneficiaries with stroke admitted to a hospital between January 1, 2010, and December 31, 2013. Drive times were calculated based on zip code centroids and street-level road network data. We used an instrumental variable analysis based on the differential travel time to PSCs to control for unmeasured confounding. The setting was a 100% sample of Medicare fee-for-service claims. EXPOSURES:Admission to a PSC. MAIN OUTCOMES AND MEASURES:Seven-day and 30-day postadmission case-fatality rates. RESULTS:Among 865 184 elderly patients with stroke (mean age, 78.9 years; 55.5% female), 53.9% were treated in PSCs. We found that admission to PSCs was associated with 1.8% (95% CI, -2.1% to -1.4%) lower 7-day and 1.8% (95% CI, -2.3% to -1.4%) lower 30-day case fatality. Fifty-six patients with stroke needed to be treated in PSCs to save one life at 30 days. Receiving treatment in PSCs was associated with a 30-day survival benefit for patients traveling less than 90 minutes, but traveling at least 90 minutes offset any benefit of PSC care. CONCLUSIONS AND RELEVANCE:Hospitalization of patients with stroke in PSCs was associated with decreased 7-day and 30-day case fatality compared with noncertified hospitals. Traveling at least 90 minutes to receive care offset the 30-day survival benefit of PSC admission.

OBJECT/OBJECTIVE:The potential imbalance between malpractice liability cost and quality of care has been an issue of debate. We investigated the association of malpractice liability with unfavorable outcomes and increased hospitalization charges in cranial neurosurgery. METHODS:We performed a retrospective cohort study involving patients who underwent cranial neurosurgical procedures from 2005-2010, and were registered in the National Inpatient Sample (NIS) database. We used data from the National Practitioner Data Bank (NPDB) from 2005 to 2010 to create measures of volume and size of malpractice claim payments. The association of the latter with the state-level mortality, length of stay (LOS), unfavorable discharge, and hospitalization charges for cranial neurosurgery was investigated. RESULTS:During the study period, there were 189,103 patients (mean age 46.4 years, with 48.3% females) who underwent cranial neurosurgical procedures, and were registered in NIS. In a multivariable regression, higher number of claims per physician in a state was associated with increased ln-transformed hospitalization charges (beta 0.18; 95% CI, 0.17 to 0.19). On the contrary, there was no association with mortality (OR 1.00; 95% CI, 0.94 to 1.06). We observed a small association with unfavorable discharge (OR 1.09; 95% CI, 1.06 to 1.13), and LOS (beta 0.01; 95% CI, 0.002 to 0.03). The size of the awarded claims demonstrated similar relationships. The average claims payment size (ln-transformed) (Pearson's rho=0.435, P=0.01) demonstrated a positive correlation with the risk-adjusted hospitalization charges but did not demonstrate a correlation with mortality, unfavorable discharge, or LOS. CONCLUSIONS:In the present national study, aggressive malpractice environment was not correlated with mortality but was associated with higher hospitalization charges after cranial neurosurgery. In view of the association of malpractice with the economics of healthcare, further research on its impact is necessary.

The impact of air pollution on fetal growth remains controversial, in part, because studies have been limited to sub-regions of the United States with limited variability. No study has examined air pollution impacts on neonatal health care utilization. We performed descriptive, univariate and multivariable analyses on administrative hospital record data from 222,359 births in the 2000, 2003 and 2006 Kids Inpatient Database linked to air pollution data drawn from the US Environmental Protection Agency's Aerometric Information Retrieval System. In this study, air pollution exposure during the birth month was estimated based on birth hospital address. Although air pollutants were not individually associated with mean birth weight, a three-pollutant model controlling for hospital characteristics, demographics, and birth month identified 9.3% and 7.2% increases in odds of low birth weight and very low birth weight for each mug/m(3) increase in PM(2.5) (both P<0.0001). PM(2.5) and NO(2) were associated with -3.0% odds/p.p.m. and +2.5% odds/p.p.b. of preterm birth, respectively (both P<0.0001). A four-pollutant multivariable model indicated a 0.05 days/p.p.m. NO(2) decrease in length of the birth hospitalization (P=0.0061) and a 0.13 days increase/p.p.m. CO (P=0.0416). A $1166 increase in per child costs was estimated for the birth hospitalization per p.p.m. CO (P=0.0002) and $964 per unit increase in O(3) (P=0.0448). A reduction from the 75th to the 25th percentile in the highest CO quartile for births predicts annual savings of $134.7 million in direct health care costs. In a national, predominantly urban, sample, air pollutant exposures during the month of birth are associated with increased low birth weight and neonatal health care utilization. Further study of this database, with enhanced control for confounding, improved exposure assessment, examination of exposures across multiple time windows in pregnancy, and in the entire national sample, is supported by these initial investigations.Journal of Exposure Science and Environmental Epidemiology advance online publication, 23 January 2013; doi:10.1038/jes.2012.124.

BACKGROUND:: Acute exposure to outdoor air pollutants has been associated with increased pediatric asthma morbidity. However, the impact of subchronic exposures is largely unknown. OBJECTIVE:: To examine the association between subchronic exposure to 6 outdoor air pollutants (PM2.5, PM10, ozone, nitrogen oxides, sulfur oxides, carbon monoxide) and pediatric asthma hospitalization length of stay, charges, and costs. METHODS:: We linked pediatric asthma hospitalization discharge data from a nationally representative dataset, the 1999-2007 Nationwide Inpatient Sample, with outdoor air pollution data from the Environmental Protection Agency. Hospitals with no air quality data within 10 miles were excluded. Our predictor was the average concentration of 6 pollutants near the hospital during the month of admission. We conducted bivariate analyses using Spearman correlations and multivariable analyses using Poisson regression for length of stay and linear regression for log-transformed charges and costs, controlling for patient demographics, hospital characteristics, and month of admission. RESULTS:: In unadjusted analyses, all 6 pollutants had minimal correlation with the 3 outcomes ( rho<0.1, P<0.001). In multivariable analyses, a 1-unit (mug/m) increase in monthly PM2.5 led to a $123 increase in charges (95% confidence interval $40-249) and a $47 increase in costs (95% confidence interval $15-93). No other pollutants were significant predictors of charges or costs or length of stay. CONCLUSION:: Subchronic PM2.5 exposure is associated with increased costs for pediatric asthma hospitalizations. Policy changes to reduce outdoor subchronic pollutant exposure may lead to improved asthma outcomes and substantial savings in healthcare spending

There has been little research to date on the linkages between air pollution and infectious respiratory illness in children, and the resulting health care costs. In this study we used data on air pollutants and national hospitalizations to study the relationship between fine particulate air pollution and health care charges and costs for the treatment of bronchiolitis, an acute viral infection of the lungs. We found that as the average exposure to fine particulate matter over the lifetime of an infant increased, so did costs for the child's health care. If the United States were to reduce levels of fine particulate matter to 7 percent below the current annual standard, the nation could save $15 million annually in reduced health care costs from hospitalizations of children with bronchiolitis living in urban areas. These findings reinforce the need for ongoing efforts to reduce levels of air pollutants. They should trigger additional investigation to determine if the current standards for fine-particulate matter are sufficiently protective of children's health