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We investigated whether early enteral nutrition alone may be sufficient prophylaxis against stress-related gastrointestinal (GI) bleeding in mechanically ventilated patients. Prospective, double blind, randomized, placebo-controlled, exploratory study that included mechanically ventilated patients in medical ICUs of two academic hospitals. Intravenous pantoprazole and early enteral nutrition were compared to placebo and early enteral nutrition as stress-ulcer prophylaxis. The incidences of clinically significant and overt GI bleeding were compared in the two groups. 124 patients were enrolled in the study. After exclusion of 22 patients, 102 patients were included in analysis: 55 patients in the treatment group and 47 patients in the placebo group. Two patients (one from each group) showed signs of overt GI bleeding (overall incidence 1.96%), and both patients experienced a drop of >3 points in hematocrit in a 24-hour period indicating a clinically significant GI bleed. There was no statistical significant difference in the incidence of overt or significant GI bleeding between groups (p=0.99). We found no benefit when pantoprazole is added to early enteral nutrition in mechanically ventilated critically ill patients. The routine prescription of acid-suppressive therapy in critically ill patients who tolerate early enteral nutrition warrants further evaluation. •GI bleeding has low incidence in the critically ill mechanically ventilated patients.•Adding PPI to enteral nutrition may not offer an added prophylaxis against stress-related GI bleeding.•Our study supports the protective role of enteral nutrition in ICU.

Understanding the burden of community-acquired pneumonia (CAP) is critical to allocate resources for prevention, management, and research. The objectives of this study were to define incidence, epidemiology, and mortality of adult patients hospitalized with CAP in the city of Louisville, and to estimate burden of CAP in the US adult population. This was a prospective population-based cohort study of adult residents in Louisville, Kentucky, from 1 June 2014 to 31 May 2016. Consecutive hospitalized patients with CAP were enrolled at all adult hospitals in Louisville. The annual population-based CAP incidence was calculated. Geospatial epidemiology was used to define ecological associations among CAP and income level, race, and age. Mortality was evaluated during hospitalization and at 30 days, 6 months, and 1 year after hospitalization. During the 2-year study, from a Louisville population of 587499 adults, 186384 hospitalizations occurred. A total of 7449 unique patients hospitalized with CAP were documented. The annual age-adjusted incidence was 649 patients hospitalized with CAP per 100000 adults (95% confidence interval, 628.2-669.8), corresponding to 1591825 annual adult CAP hospitalizations in the United States. Clusters of CAP cases were found in areas with low-income and black/African American populations. Mortality during hospitalization was 6.5%, corresponding to 102821 annual deaths in the United States. Mortality at 30 days, 6 months, and 1 year was 13.0%, 23.4%, and 30.6%, respectively. The estimated US burden of CAP is substantial, with >1.5 million unique adults being hospitalized annually, 100000 deaths occurring during hospitalization, and approximately 1 of 3 patients hospitalized with CAP dying within 1 year.

Objectives The influence of socioeconomic disparities on adults with pneumonia is not well understood. The objective of our study was to evaluate the relationship between community-level socioeconomic position, as measured by an area deprivation index, and the incidence, severity, and outcomes among adults with community-acquired pneumonia (CAP). Methods This was an ancillary study of a population-based, prospective cohort study of patients hospitalized with CAP in Louisville, Kentucky, from June 1, 2013, through May 31, 2015. We used a race-specific, block group–level area deprivation index as a proxy for community-level socioeconomic position and evaluated it as a predictor of CAP incidence, CAP severity, early clinical improvement, 30-day mortality, and 1-year mortality. Results The cohort comprised 6349 unique adults hospitalized with CAP. CAP incidence per 100 000 population increased significantly with increasing levels of area deprivation, from 303 in tertile 1 (low deprivation), to 467 in tertile 2 (medium deprivation), and 553 in tertile 3 (high deprivation) (P < .001). Adults in medium- and high-deprivation areas had significantly higher odds of severe CAP (tertile 2 odds ratio [OR] = 1.2 [95% confidence interval (CI), 1.06-1.39]; tertile 3 OR = 1.4 [95% CI, 1.18-1.64] and 1-year mortality (tertile 2 OR = 1.3 [95% CI, 1.11-1.54], tertile 3 OR = 1.3 [95% CI, 1.10-1.64]) than adults in low-deprivation areas. Conclusions Compared with adults residing in low-deprivation areas, adults residing in high-deprivation areas had an increased incidence of CAP, and they were more likely to have severe CAP. Beyond 30 days of care, we identified an increased long-term mortality for persons in high-deprivation areas. Community-level socioeconomic position should be considered an important factor for research in CAP and policy decisions.

New antibiotics are needed to combat rising levels of resistance, with new Mycobacterium tuberculosis (Mtb) drugs having the highest priority. However, conventional whole-cell and biochemical antibiotic screens have failed. Here we develop a strategy termed PROSPECT (primary screening of strains to prioritize expanded chemistry and targets), in which we screen compounds against pools of strains depleted of essential bacterial targets. We engineered strains that target 474 essential Mtb genes and screened pools of 100–150 strains against activity-enriched and unbiased compound libraries, probing more than 8.5 million chemical–genetic interactions. Primary screens identified over tenfold more hits than screening wild-type Mtb alone, with chemical–genetic interactions providing immediate, direct target insights. We identified over 40 compounds that target DNA gyrase, the cell wall, tryptophan, folate biosynthesis and RNA polymerase, as well as inhibitors that target EfpA. Chemical optimization yielded EfpA inhibitors with potent wild-type activity, thus demonstrating the ability of PROSPECT to yield inhibitors against targets that would have eluded conventional drug discovery. A high-throughput chemical–genetic screening approach for the discovery of targets and chemicals to treat Mycobacterium tuberculosis yields tenfold more hit compounds than conventional whole-cell screening methods.

Between 2000 and 2015 the proportion of US hospitals with more than fifty beds that had palliative care programs tripled, from 25 percent to 75 percent. The rapid adoption of this high-value program, which is voluntary and runs counter to the dominant culture in US hospitals, was catalyzed by tens of millions of dollars in philanthropic support for innovation, dissemination, and professionalization in the palliative care field. We describe the dissemination strategies of the Center to Advance Palliative Care in the context of the principles of social entrepreneurship, and we provide an in-depth look at its hallmark training initiative, Palliative Care Leadership Centers. Over 1,240 hospital palliative care teams have trained at the Leadership Centers to date, with 80 percent of them instituting palliative care services within two years. We conclude with lessons learned about the role of purposeful technical assistance in promoting the rapid diffusion of high-value health care innovation1.

New antibiotics are needed to combat rising resistance, with new Mycobacterium tuberculosis (Mtb) drugs of highest priority. Conventional whole-cell and biochemical antibiotic screens have failed. We developed a novel strategy termed PROSPECT (PRimary screening Of Strains to Prioritize Expanded Chemistry and Targets) in which we screen compounds against pools of strains depleted for essential bacterial targets. We engineered strains targeting 474 Mtb essential genes and screened pools of 100-150 strains against activity-enriched and unbiased compounds libraries, measuring > 8.5-million chemical-genetic interactions. Primary screens identified > 10-fold more hits than screening wild-type Mtb alone, with chemical-genetic interactions providing immediate, direct target insight. We identified > 40 novel compounds targeting DNA gyrase, cell wall, tryptophan, folate biosynthesis, and RNA polymerase, as well as inhibitors of a novel target EfpA. Chemical optimization yielded EfpA inhibitors with potent wild-type activity, thus demonstrating PROSPECT's ability to yield inhibitors against novel targets which would have eluded conventional drug discovery. Footnotes * Title updated; text and figures revised to be clearer and include new data; supplemental figures revised including new data.