The frequency of inappropriate nonformulary medication alert overrides in the inpatient setting

BACKGROUND: Experts suggest that formulary alerts at the time of medication order entry are the most effective form of clinical decision support to automate formulary management. OBJECTIVE: Our objectives were to quantify the frequency of inappropriate nonformulary medication (NFM) alert overrides in the inpatient setting and provide insight on how the design of formulary alerts could be improved. METHODS: Alert overrides of the top 11 (n = 206) most-utilized and highest-costing NFMs, from January 1 to December 31, 2012, were randomly selected for appropriateness evaluation. Using an empirically developed appropriateness algorithm, appropriateness of NFM alert overrides was assessed by 2 pharmacists via chart review. Appropriateness agreement of overrides was assessed with a Cohen's kappa. We also assessed which types of NFMs were most likely to be inappropriately overridden, the override reasons that were disproportionately provided in the inappropriate overrides, and the specific reasons the overrides were considered inappropriate. RESULTS: Approximately 17.2% (n = 35.4/206) of NFM alerts were inappropriately overridden. Non-oral NFM alerts were more likely to be inappropriately overridden compared to orals. Alerts overridden with "blank" reasons were more likely to be inappropriate. The failure to first try a formulary alternative was the most common reason for alerts being overridden inappropriately. CONCLUSION: Approximately 1 in 5 NFM alert overrides are overridden inappropriately. Future research should evaluate the impact of mandating a valid override reason and adding a list of formulary alternatives to each NFM alert; we speculate these NFM alert features may decrease the frequency of inappropriate overrides

Development of an Automated Microfluidic Reaction Platform for Multidimensional Screening: Reaction Discovery Employing Bicyclo[3.2.1]octanoid Scaffolds

An automated, silicon-based microreactor system has been developed for rapid, low-volume, multidimensional reaction screening. Use of the microfluidic platform to identify transformations of densely functionalized bicyclo [3.2.1] octanoid scaffolds will be described.National Institute of General Medical Sciences (U.S.) (CMLD Initiative (P50 GM067041))Pfizer Inc.Merck Research LaboratoriesNational Science Foundation (U.S.) (NSF-REU program (CHE-0649114)

Thinking through transition: USAF doctrine, technology and the F-111A

The dynamic created in the USAF between technological advances and strategic bombardment doctrine dates from the earliest systematic attempts to codify air doctrine after World War I. These ideas seemed to be validated by the advent of atomic weapons and long range bombers during World War II. By the 1950s, strategic bombardment and technologically advanced aircraft had become the lens through which airmen viewed modern warfare. Airmen were generally persuaded that war was total, and would be fought with nuclear weapons, despite a growing body of evidence that the geostrategic environment had changed since World War II. This dissertation uses the F-111A as a case study to demonstrate the consistency of USAF thinking concerning doctrine and technology, which ultimately affected procurement decisions. As envisioned in 1959, the F-111A was the product of not only the latest aircraft technology available, but also a persistent preference for strategic bombardment doctrine within the USAF. Acquired as a long-range high-speed tactical nuclear fighter-bomber to counter the Soviet nuclear threat in a general war, the F-111A was sent to Southeast Asia in 1968, and again in 1972, to face an insurgent threat in a limited war. Enamored with technology, airmen believed that the F-111A, with its advanced systems, could solve the tactical problems encountered in Southeast Asia that were unforeseen in institutional doctrine. The complicated history of the F-111A serves to illustrate the pitfalls of static doctrine in an ever-changing strategic environment. This study addresses why the USAF arrived in Southeast Asia equipped for a general war in Europe, and illuminates the continuing challenge of matching technology and doctrine. (Published By University of Alabama Libraries

New Technologies to Image Tumors.

The premise of this book is the importance of the tumor microenvironment (TME). Until recently, most research on and clinical attention to cancer biology, diagnosis, and prognosis were focused on the malignant (or premalignant) cellular compartment that could be readily appreciated using standard morphology-based imaging

Targeted sequencing of plasma cell-free DNA to predict response to PD1 inhibitors in advanced non-small cell lung cancer

International audienceObjectives: Tumor mutational burden is an emerging biomarker of response to immune checkpoint inhibitors (ICI), whose clinical adoption is challenging. We hypothesized that targeting limited but relevant genetic alterations in plasma cell-free DNA along with early monitoring may non-invasively predict response to ICI in advanced non-small cell lung cancer (NSCLC).Material and methods: Plasma samples from patients with progressive NSCLC collected before ICI initiation and at 1 month were profiled from responders (R: PFS > 6 months) and non-responders (NR: progressive disease at first evaluation) using amplicon sequencing of hotspots and coding regions from 36 genes. The molecular profile of ctDNA, and its early kinetics were analyzed.Results: 97 patients were analyzed, of which 86 (39 R, 47 NR) were evaluable. Alterations in ctDNA were detectable in 67/86 baseline samples (78%). The detection of a targetable oncogenic driver was associated with a 2 months PFS. The presence of a PTEN or STK11 mutation was correlated with early progression (HR 8.9, p = 0.09 for PTEN, HR 4.7, p = 0.003 for STK11), while transversion mutations (Tv) in KRAS and TP53 predicted better outcomes (HR 0.36, p = 0.011 for TP53 Tv; HR 0.46, p = 0.11 for KRAS Tv). Patients with a low "immune score" (driver and/or PTEN or STK11 mutation and/or without KRAS or TP53 Tv) derived poor outcomes (median PFS 2 months), compared with patients with a high immune score (no driver, no PTEN or STK11 and with KRAS or TP53 Tv (median PFS 14 months, p = 0.0001, HR 2.96). Early changes in the ctDNA allele fraction (AF) of 65 specimens were correlated with clinical outcomes (14 months PFS if AF decreases vs. 2 months if AF increases, p < 0.0001).Conclusion: Targeted sequencing of plasma ctDNA and monitoring its early variations can predict response to ICI