A video intervention to improve patient understanding of tumor genomic testing in patients with cancer.

Introduction: Tumor genomic testing (TGT) is standard-of-care for most patients with advanced/metastatic cancer. Despite established guidelines, patient education prior to TGT is frequently omitted. The purpose of this study was to evaluate the impact of a concise 4 min video for patient education prior to TGT.

Postoperative risks associated with alcohol screening depend on documented drinking at the time of surgery.

Background: Both AUDIT-C alcohol screening scores up to a year before surgery and clinical documentation of drinking over 2 drinks per day immediately prior to surgery ("documented drinking >2d/d") are associated with increased postoperative complications and health care utilization. The purpose of this study was to evaluate whether documented drinking >2d/d contributed additional information about postoperative risk beyond past-year AUDIT-C screening results.

Method: Male Veterans Affairs (VA) patients who had a non-emergent, non-cardiac, major surgery assessed by the VA's Surgical Quality Improvement Program 10/2003-9/2006 and completed the AUDIT-C by mailed survey in the prior year were eligible for this study.

Discovery of a highly potent, nonabsorbable apical sodium-dependent bile acid transporter inhibitor (GSK2330672) for treatment of type 2 diabetes.

The apical sodium-dependent bile acid transporter (ASBT) transports bile salts from the lumen of the gastrointestinal (GI) tract to the liver via the portal vein. Multiple pharmaceutical companies have exploited the physiological link between ASBT and hepatic cholesterol metabolism, which led to the clinical investigation of ASBT inhibitors as lipid-lowering agents. While modest lipid effects were demonstrated, the potential utility of ASBT inhibitors for treatment of type 2 diabetes has been relatively unexplored.

Ultrasound-guided root/trunk (interscalene) block for hand and forearm anesthesia.

Background: Historically, the anterolateral interscalene block--deposition of local anesthetic adjacent to the brachial plexus roots/trunks--has been used for surgical procedures involving the shoulder. The resulting block frequently failed to provide surgical anesthesia of the hand and forearm, even though the brachial plexus at this level included all of the axons of the upper-extremity terminal nerves. However, it remains unknown whether deposition of local anesthetic adjacent to the seventh cervical root or inferior trunk results in anesthesia of the hand and forearm.

Continuous femoral nerve blocks: the impact of catheter tip location relative to the femoral nerve (anterior versus posterior) on quadriceps weakness and cutaneous sensory block.

Background: During a continuous femoral nerve block, the influence of catheter tip position relative to the femoral nerve on infusion characteristics remains unknown.

Methods: We inserted bilateral femoral perineural catheters in volunteers (ultrasound-guided, needle in-plane). Subjects' dominant side was randomized to have the catheter tip placed either anterior or posterior to the femoral nerve.

Prevalence of alcohol misuse among men and women undergoing major noncardiac surgery in the Veterans Affairs health care system.

Background: Patients who screen positive for alcohol misuse on the Alcohol Use Disorder Identification Test Consumption Questionnaire (AUDIT-C ≥5 points) have significantly increased postoperative complications. Severe alcohol misuse (AUDIT-C ≥9 points) is associated with increased postoperative health care use; however, little is known about the prevalence of alcohol misuse in demographic and clinical subgroups of surgical patients.

Methods: The prevalence of alcohol misuse was evaluated among 10,284 patients (9,771 men and 513 women) who underwent major noncardiac surgery in Veterans Affairs (VA) hospitals during the fiscal years 2004 to 2006 and completed the AUDIT-C.

AUDIT-C alcohol screening results and postoperative inpatient health care use.

Background: Alcohol screening scores ≥5 on the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) up to a year before surgery have been associated with postoperative complications, but the association with postoperative health care use is unknown. This study evaluated whether AUDIT-C scores in the year before surgery were associated with postoperative hospital length of stay, total ICU days, return to the operating room, and hospital readmission.

Study Design: This cohort study included male Veterans Affairs patients who completed the AUDIT-C on mailed surveys (October 2003 through September 2006) and were hospitalized for nonemergent noncardiac major operations in the following year.

Smoking as a risk factor for short-term outcomes following primary total hip and total knee replacement in veterans.

Objective: To assess the effect of smoking on postoperative complications following elective primary total hip replacement (THR) or primary total knee replacement (TKR).

Methods: We used data from the national Veterans Affairs Surgical Quality Improvement Program to examine the association of smoking status at surgery with 30-day postoperative complication rates (including surgical site and other infections, pneumonia, stroke, myocardial infarction, mortality, and other complications) in veterans undergoing primary elective THR or TKR. Multilevel multivariable-adjusted logistic regression models, adjusted for age, race/ethnicity, work relative value units, American Society of Anesthesiology classification, and year of surgery, with additional adjustment for wound classification for surgical site infections, were used.

Tetrahydroquinoline derivatives as opioid receptor antagonists.

Opioid receptors play an important role in both behavioral and homeostatic functions. We herein report tetrahydroquinoline derivatives as opioid receptor antagonists. SAR studies led to the identification of the potent antagonist 2v, endowed with 1.

Alcohol screening and risk of postoperative complications in male VA patients undergoing major non-cardiac surgery.

Background: Patients who misuse alcohol are at increased risk for surgical complications. Four weeks of preoperative abstinence decreases the risk of complications, but practical approaches for early preoperative identification of alcohol misuse are needed.

Objective: To evaluate whether results of alcohol screening with the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) questionnaire-up to a year before surgery-were associated with the risk of postoperative complications.

Elective surgical case cancellation in the Veterans Health Administration system: identifying areas for improvement.

Background: This study evaluated elective surgical case cancellation (CC) rates, reasons for these cancellations, and identified areas for improvement within the Veterans Health Administration (VA) system.

Methods: CC data for 2006 were collected from the scheduling software for 123 VA facilities. Surveys were distributed to 40 facilities (10 highest and 10 lowest CC rates for high- and low-volume facilities).

Rapid quantitative determination of fat-soluble vitamins and coenzyme Q-10 in human serum by reversed phase ultra-high pressure liquid chromatography with UV detection.

We are presenting the first ultra-high pressure LC (UHPLC) method for rapid quantitative measurement of vitamin A, E (alpha- and gamma-tocopherol), beta-carotene and CoQ(10) from human serum. The chromatography was performed on Shield RP(18) UHPLC column with UV detection. The method was validated based on linearity, accuracy, matrix effects study, precision and stability.

Factors associated with unanticipated day of surgery deaths in Department of Veterans Affairs hospitals.

Background: Patients of ASA physical status 1, 2, and 3 undergoing elective surgery do not have underlying conditions that are a constant threat to life, and hence should not be expected to be at significant risk for death on the day of surgery.

Methods: We analyzed 815,077 ASA physical status 1, 2, and 3 elective surgery patients in the Department of Veterans Affairs National Surgical Quality Improvement Program database to identify patients who died on the day of surgery. We then attempted to identify factors predictive of unexpected death and to identify potential areas for improvement in care.

The relationship between repeated epidural steroid injections and subsequent opioid use and lumbar surgery.

Objectives: To evaluate whether the use of epidural steroid injections (ESIs) is associated with decreased subsequent opioid use in patients in the Department of Veteran's Affairs (VA) and to determine whether treatment with multiple injections are associated with decreased opioid use and lumbar surgery after ESIs.

Design: VA patients undergoing ESIs during the study period for specific low back pain (LBP) diagnoses were identified, and lumbar surgery and opioid use were examined for 6 months before and after ESI.

Setting: National VA administrative data.

Direct analysis of un-derivatized asymmetric dimethylarginine (ADMA) and L-arginine from plasma using mixed-mode ion-exchange liquid chromatography-tandem mass spectrometry.

A high-throughput analytical method was developed for the measurement of asymmetric dimethylarginine (ADMA) and L-arginine (ARG) from plasma using LC/MS/MS. The sample preparation was simple and only required microfiltration prior to analysis. ADMA and ARG were assayed using mixed-mode ion-exchange chromatography which allowed for the retention of the un-derivatized compounds.

Awareness and use of a cognitive aid for anesthesiology.

Background: The Veterans Health Administration's (VHA's) National Center for Patient Safety developed a cognitive aid to help anesthesiologists manage rare, high-mortality adverse events.

Methods: Six months after the aids were sent to VHA facilities with anesthesia machines, anesthesia providers were surveyed about their knowledge and use of the aid.

Results: Seven percent of respondents had used the cognitive aid in an emergency ("emergent users").

A simple and selective method for the measurement of leucine and isoleucine from plasma using electrospray ionization tandem mass spectrometry.

An analytical method was developed for the rapid and accurate quantification of leucine (LEU) and isoleucine (ILE) from plasma using electrospray ionization tandem mass spectrometry (ESI-MS/MS). The two isomeric amino acids were selectively detected using fragment ions unique to each compound. As a result, the need for chromatographic separation was avoided allowing for faster analysis (3 min).

Recent advances in the discovery of alpha1-adrenoceptor agonists.

The alpha(1) adrenoceptors are three of nine well-characterized receptors that are activated by epinephrine and norepinephrine. Agonists acting at the alpha(1) adrenoceptors produce numerous physiological effects, and are used therapeutically for several indications. Many known alpha(1) adrenoceptor agonists are alpha(1A) selective, but the discovery of highly selective alpha(1B) and alpha(1D) adrenoceptor agonists has proven to be an extremely difficult goal to achieve.

6-(4-chlorophenyl)-3-substituted-thieno[3,2-d]pyrimidin-4(3H)-one-based melanin-concentrating hormone receptor 1 antagonist.

Genetic manipulation studies in mice at both the MCH receptor 1 (MCHR1) as well as the MCH peptide levels have implicated MCHR1 as a key player in energy homeostasis. The phenotype exhibited by these studies, that is, increased metabolic rate, resistance to high fat diet, and subsequent weight loss, has spurred considerable efforts to develop antagonists of MCHR1. In continuation of efforts directed toward this goal, the present work capitalizes on the putative binding mode of an MCH antagonist, resulting in the identification of several novel chemotypes that are potent and selective MCHR1 antagonists.

Potent, selective, and orally efficacious antagonists of melanin-concentrating hormone receptor 1.

The high expression of MCH in the hypothalamus with the lean hypophagic phenotype coupled with increased resting metabolic rate and resistance to high fat diet-induced obesity of MCH KO mice has spurred considerable efforts to develop small molecule MCHR1 antagonists. Starting from a lead thienopyrimidinone series, structure-activity studies at the 3- and 6-positions of the thienopyrimidinone core afforded potent and selective MCHR1 antagonists with representative examples having suitable pharmacokinetic properties. Based on structure-activity relationships, a structural model for MCHR1 was constructed to explain the binding mode of these antagonists.

Quantification of urinary zwitterionic organic acids using weak-anion exchange chromatography with tandem MS detection.

A rapid and accurate quantitative method was developed and validated for the analysis of four urinary organic acids with nitrogen containing functional groups, formiminoglutamic acid (FIGLU), pyroglutamic acid (PYRGLU), 5-hydroxyindoleacetic acid (5-HIAA), and 2-methylhippuric acid (2-METHIP) by liquid chromatography tandem mass spectrometry (LC/MS/MS). The chromatography was developed using a weak anion-exchange amino column that provided mixed-mode retention of the analytes. The elution gradient relied on changes in mobile phase pH over a concave gradient, without the use of counter-ions or concentrated salt buffers.

Timely administration of prophylactic antibiotics for major surgical procedures.

Background: Prophylactic antibiotics (PA) given within 60 minutes before surgical incision decrease risk of subsequent surgical site infection. Nationwide quality improvement initiatives have focused on improving the proportion of patients who receive timely prophylactic antibiotics.

Study Design: This is a cohort study of major surgical procedures performed in 108 Veterans Affairs hospitals between January and December 2005.

Novel benzimidazole-based MCH R1 antagonists.

The identification of an MCH R1 antagonist screening hit led to the optimization of a class of benzimidazole-based MCH R1 antagonists. Structure-activity relationships and efforts to optimize pharmacokinetic properties are detailed along with the demonstration of the effectiveness of an MCH R1 antagonist in an animal model of obesity.