Harnessing innate lung anti-cancer effector functions with a novel bacterial-derived immunotherapy.

Acute infection is known to induce strong anti-tumor immune responses, but clinical translation has been hindered by the lack of an effective strategy to safely and consistently provoke a therapeutic response. These limitations are overcome with a novel treatment approach involving repeated subcutaneous delivery of a Klebsiella-derived investigational immunotherapeutic, QBKPN. In preclinical models of lung cancer, QBKPN administration consistently showed anti-cancer efficacy, which was dependent on Klebsiella pre-exposure, but was independent of adaptive immunity. Rather, QBKPN induced anti-tumor innate immunity that required NK cells and NKG2D engagement. QBKPN increased NK cells and macrophages in the lungs, altered macrophage polarization, and augmented the production of cytotoxic molecules. An exploratory trial in patients with non-small cell lung cancer demonstrated QBKPN was well tolerated, safe, and induced peripheral immune changes suggestive of macrophage polarization and reduction of PD-1 and PD-L1 expression on leukocytes. These data demonstrate preclinical efficacy, and clinical safety and tolerability, for this cancer immunotherapy strategy that exploits innate anti-tumor immune mechanisms.

Is the OSA-18 predictive of obstructive sleep apnea: comparison to polysomnography.

OBJECTIVES/HYPOTHESIS: To examine the ability of the OSA-18 to predict Obstructive Sleep Apnea (OSA) in a racially diverse population when compared to overnight polysomnography (PSG). STUDY DESIGN: Cross-sectional retrospective. METHODS: Children 2 to 12 years of age diagnosed with OSA who were treated at a tertiary care institution between 2008 and 2013 and had complete PSG and OSA-18 data were included. We performed logistic regression with OSA as the dependent variable and the OSA-18 total symptom score (TSS), age, gender, race, asthma, and body mass index (BMI) as independent variables. RESULTS: Seventy-nine children (32 females) were included (mean age 5.2 ± 2.4 years). The positive predictive value (PPV) was greater than 90 for an obstructive apnea-hypopnea index (oAHI) ≥ 1. The PPV and specificity were higher for white than for nonwhite children; however, sensitivity and negative predictive value (NPV) of OSA-18 TSS were low for mild, moderate, and severe OSA regardless of race. Age, race, and BMI were not significantly associated with oAHI. CONCLUSIONS: This study, conducted in a racially diverse cohort, examined the ability of the OSA-18 to predict OSA when compared to PSG-the gold standard-and found that sensitivity and NPV were extremely low for both white and nonwhite children. This suggests that the OSA-18 is not sufficiently sensitive to detect OSA nor sufficiently specific to determine the absence of OSA. The OSA-18 should be used as a quality-of-life indicator and is not a reliable substitute for PSG. LEVEL OF EVIDENCE: 4.

Achieving a safety culture in obstetrics.

Preventable maternal and neonatal mortalities still occur, despite the wonders of today's technologically advanced healthcare system. Delivering high-quality, consistent care is the goal of every provider. Yet, obstetrical practice, in which unpredictable events and high-risk situations are the norm, is particularly vulnerable to medical errors. Obstetrics departments should be striving for a climate of patient safety, one that includes a just, reporting, and learning culture. This article discusses the various components of a safety culture as well as some of the advances that are being made in the field to improve the quality of care in obstetrics.

What affects time to care in emergency room appendicitis patients?

BACKGROUND: Emergency departments (EDs) provide a safety net for seriously ill individuals. Little is known about factors that affect time to diagnosis and treatment of patients with time-sensitive conditions within the ED. METHODS: Retrospective observational study of 236 appendicitis patients examining patient factors and ED characteristics with time to a surgeon's diagnosis of appendicitis and ED length of stay (LOS). RESULTS: Time to surgeon's diagnosis and ED LOS were slower for nonwhite patients without private insurance (parameter estimate = 0.38, P = 0.002 and 0.31, P < 0.001, respectively) and quicker for patients for whom the ED physician's diagnostic first impression was appendicitis (parameter estimate = -0.29, P = 0.003 and -0.14, P = 0.04, respectively). Greater numbers of physicians staffing the ED had a modest effect on time to surgeon diagnosis and ED LOS (parameter estimate = -0.04, P = 0.01 and -0.04, P = 0.01, respectively), whereas greater numbers of patients had little impact (parameter estimate = -0.005, P = 0.04 and -0.002, P = 0.28, respectively). CONCLUSIONS: Minority patients without private insurance had slower times to specialist consultation and treatment; ED staffing and census had a small effect. To maximize patient safety and ED quality of care, administrators should ensure timely specialist consultation and determine additional mechanisms facilitating white privately insured patients' quicker care.

Quality of care and racial health disparities: a strategic overview.

Substantial racial and ethnic disparities in health and health care exist in the United States. The Department of Health Policy at the Mount Sinai School of Medicine has developed a strategy for reducing those disparities that builds upon its quality improvement experience. This article discusses the utility of applying quality improvement principles to the development of interventions to eliminate underuse of effective treatments and reduce the disparities that may arise from this quality problem. We present a conceptual model of racial disparities in health and our underuse hypothesis. Parallels between our disparities research strategy and six sigma quality improvement methods are described. Finally, the article provides an example of how we have been able to successfully implement proven-effective health improvement programs in the Harlem community even after grant funding has ended.

Time and the risk of ruptured tubal pregnancy.

OBJECTIVE: Tubal pregnancy remains an important cause of maternal morbidity and mortality. We sought to quantify the relationship of time between symptom onset and treatment and the risk of tubal rupture. METHODS: We reviewed inpatient, clinic, and physician office charts of 221 women with tubal pregnancy. We assessed the conditional risk of rupture with passing time and other factors related to rupture. RESULTS: Time between symptom onset and treatment varied from 3 hours to 66 days with an average of 7 days. There was a 32% rupture rate. The conditional risk of rupture was highest within the first 48 hours of symptom onset (5-7%). The risk dropped, leveled off, and remained fairly steady at approximately 2.5% per 24 hours of untreated symptoms. Classic tubal pregnancy signs, symptoms, and tests were not helpful in predicting rupture. CONCLUSION: The rate of rupture is highest in women with the shortest times between symptom onset and treatment. With passing time, the risk declines, but remains steady despite women's getting into care. LEVEL OF EVIDENCE: II-2