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This study assessed the 2014 clinical productivity of 5,959 physician assistants (PAs) and nurse practitioners (NPs) in the US Department of Veterans Affairs' Veterans Health Administration (VHA). Total work relative value units divided by the direct clinical full-time equivalent measured annual productivity, and correlated factors were examined using weighted analysis of variance. PAs and NPs in adult primary care roles were more productive than those in other specialties. Both providers were more productive in rural than in nonrural settings and less productive in teaching than nonteaching hospitals. Men were slightly more productive than women but age and years of VHA employment were not correlates of productivity. PAs were more productive when their scope of practice allowed significant autonomy; NP productivity was unaffected by supervisory requirements. PAs and NPs are an important component of the VHA provider workforce, and their productivity correlates with a number of factors. More organizational research is necessary to better understand the contributing roles PAs and NPs provide in a rapidly evolving, vertically integrated, national health delivery system.

IMPORTANCE: The use of perioperative pharmacologic β-blockade in patients at low risk of myocardial ischemic events undergoing noncardiac surgery (NCS) is controversial because of the risk of stroke and hypotension. Published studies have not found a consistent benefit in this cohort. OBJECTIVE: To determine the effect of perioperative β-blockade on patients undergoing NCS, particularly those with no risk factors. DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective observational analysis of patients undergoing surgery in Veterans Affairs hospitals from October 1, 2008, through September 31, 2013. METHODS: β-Blocker use was determined if a dose was ordered at any time between 8 hours before surgery and 24 hours postoperatively. Data from the Veterans Affairs electronic database included demographics, diagnosis and procedural codes, medications, perioperative laboratory values, and date of death. A 4-point cardiac risk score was calculated by assigning 1 point each for renal failure, coronary artery disease, diabetes mellitus, and surgery in a major body cavity. Previously validated linear regression models for all hospitalized acute care medical or surgical patients were used to calculate predicted mortality and then to calculate odds ratios (ORs). MAIN OUTCOMES AND MEASURES: The end point was 30-day surgical mortality. RESULTS: There were 326 489 patients in this cohort: 314 114 underwent NCS and 12 375 underwent cardiac surgery. β-Blockade lowered the OR for mortality significantly in patients with 3 to 4 cardiac risk factors undergoing NCS (OR, 0.63; 95% CI, 0.43-0.93). It had no effect on patients with 1 to 2 risk factors. However, β-blockade resulted in a significantly higher chance of death in patients (OR, 1.19; 95% CI, 1.06-1.35) with no risk factors undergoing NCS. CONCLUSIONS AND RELEVANCE: In this large series, β-blockade appears to be beneficial perioperatively in patients with high cardiac risk undergoing NCS. However, the use of β-blockers in patients with no cardiac risk factors undergoing NCS increased risk of death in this patient cohort.

OBJECTIVETo examine the impact on infection rates and hospital rank for catheter-associated urinary tract infection (CAUTI), central line-associated bloodstream infection (CLABSI), and ventilator-associated pneumonia (VAP) using device days and bed days as the denominatorDESIGNRetrospective survey from October 2010 to July 2013SETTINGVeterans Health Administration medical centers providing acute medical and surgical carePATIENTSPatients admitted to 120 Veterans Health Administration medical centers reporting healthcare-associated infectionsMETHODSWe examined the importance of using device days and bed days as the denominator between infection rates and hospital rank for CAUTI, CLABSI, and VAP for each medical center. The relationship between device days and bed days as the denominator was assessed using a Pearson correlation, and changes in infection rates and device utilization were evaluated by an analysis of variance.RESULTSA total of 7.9 million bed days were included. From 2011 to 2013, CAUTI decreased whether measured by device days (2.32 to 1.64, P=.001) or bed days (4.21 to 3.02, P=.006). CLABSI decreased when measured by bed days (1.67 to 1.19, P=.04). VAP rates and device utilization ratios for CAUTI, CLABSI, and VAP were not statistically different across time. Infection rates calculated with device days were strongly correlated with infection rates calculated with bed days (r=0.79–0.94, P<.001). Hospital relative performance measured by ordered rank was also strongly correlated for both denominators (r=0.82–0.96, P<.001).CONCLUSIONSThese findings suggest that device days and bed days are equally effective adjustment metrics for comparing healthcare-associated infection rates between hospitals in the setting of stable device utilization.Infect Control Hosp Epidemiol2015;00(0): 1–7

Hospitalizations due to ambulatory care sensitive conditions (ACSCs) are widely accepted as an indicator of primary care access and effectiveness. However, broad early intervention to all patients in a health care system may be deemed infeasible due to limited resources.

Reliance on administrative data sources and a cohort with restricted age range (Medicare 65 y and above) may limit conclusions drawn from public reporting of 30-day mortality rates in 3 diagnoses acute myocardial infarction (AMI), congestive heart failure (CHF), pneumonia (PNA) from Center for Medicaid and Medicare Services.

ABSTRACTJNJ-Q2 is a fluoroquinolone with broad coverage including methicillin-resistant Staphylococcus aureus(MRSA). A double-blind, multicenter, phase II noninferiority study treated 161 patients for 7 to 14 days, testing the efficacy of JNJ-Q2 (250 mg, twice a day [BID]) versus linezolid (600 mg, BID) in patients with acute bacterial skin and skin structure infections (ABSSSI). The prespecified criterion for noninferiority was 15%. Primary intent-to-treat analysis was unable to declare noninferiority, as the risk difference lower bound of the 95% confidence interval between treatments was 19% at 36 to 84 h postrandomization for the composite end point of lesion assessment and temperature. Prespecified clinical cure rates 2 to 14 days after completion of therapy were similar (83.1% for JNJ-Q2 versus 82.1% for linezolid). Post hocanalyses revealed that JNJ-Q2 was statistically noninferior to linezolid (61.4% versus 57.7%, respectively; P= 0.024) based on the 2010 FDA guidance, which defines treatment success as lack of lesion spread and afebrile status within 48 to 72 h postrandomization. Despite evidence of systemic disease, <5% of patients presented with fever, suggesting fever is not a compelling surrogate measure of systemic disease resolution for this indication. Nausea and vomiting were the most common adverse events. Of the patients, 86% (104/121) had S. aureusisolated from the infection site; 63% of these were MRSA. The results suggest JNJ-Q2 shows promise as an effective treatment for ABSSSI, demonstrating (i) efficacy for early clinical response (i.e., lack of spread of lesions and absence of fever at 48 to 72 h), and (ii) cure rates for ABSSSI pathogens (especially MRSA) consistent with the historical literature.

Historically, the prevalence of smoking and smoking-related illnesses has been higher among veteran patients in the Veterans Health Administration (VHA) in comparison to that of the general population. Although rates of tobacco use have remained high, smoking cessation interventions continued to be greatly underutilized in VHA clinical settings just as they have been nationally. To address tobacco use as a public health priority, VHA has implemented a number of evidence-based national initiatives in recent years. This paper describes these initiatives, including: adoption of a population-health approach to smoking cessation; increased access to nicotine replacement therapy and/or smoking cessation medications; elimination of outpatient copayments for smoking cessation counseling; clinical practice guidelines; and collaboration with mental health and substance use disorder health care providers to promote integration of smoking cessation into routine treatment of psychiatric populations. The context of tobacco use among the newest veteran populations is also discussed, as well as recent efforts to evaluate the current state of smoking cessation care in VHA.

We describe the national organization and distribution of intensive care services within the Veterans Health Administration (VHA), the largest single integrated health-care system in the United States.

All medicines have adverse effects as well as benefits. The aim of pharmacovigilance is to protect public health by monitoring medicines to identify and evaluate issues and ensure that the overall benefits outweigh the potential risks. The tools and processes used in pharmacovigilance are continually evolving. Increasingly sophisticated tools are being designed to evaluate safety data from clinical trials to enhance the likelihood of detecting safety signals ahead of product registration. Methods include integration of safety data throughout development, meta-analytical techniques, quantitative and qualitative methods for evaluation of adverse event data and graphical tools to explore laboratory and biometric data. Electronic data capture facilitates monitoring of ongoing studies so that it is possible to promptly identify potential issues and manage patient safety. In addition, GSK employs a number of proactive methods for post-marketing signal detection and knowledge management using state-of-the-art statistical and analytical tools. Using these tools, together with safety data collected through pharmacoepidemiologic studies, literature and spontaneous reporting, potential adverse drug reactions can be better identified in marketed products. In summary, the information outlined in this paper provides a valuable benchmark for risk management and pharmacovigilance in pharmaceutical development.

AbstractObjective:The relationship of respiratory symptoms to pulmonary function parameters and smoking status was assessed in subjects with chronic (>1 year) spinal cord injury (SCI).Methods and Participants:As part of their annual physical examination, subjects were queried regarding respiratory symptoms and underwent pulmonary function studies. The 180 patients who successfully completed pulmonary function testing were evaluated, including 79 subjects with tetraplegia (56 nonsmokers and 23 smokers) and 101subjects with paraplegia (78 nonsmokers and 23 smokers).Findings:Logistic-regression analysis revealed the following independent predictors of breathlessness: level of injury (tetraplegia, paraplegia, odds ratio = 3.5, P < 0.0015), cough combined with phlegm and/or wheeze (CPWZ, odds ratio = 3.1, P < 0.015), total lung capacity percentage predicted (TLC < 60%, odds ratio = 3.9, P < 0.02), and expiratory reserve volume (ERV < 0.6 L, odds ratio = 2.5, P < 0.05). Independent predictors of CPWZ were current smoking (odds ratio = 3.3, P < 0.004), breathlessness (odds ratio = 2.9, P < 0.03), and forced expiratory volume in 1second (FEV1< 60%, odds ratio = 3.2, P < 0.01).Conclusion:Altered respiratory mechanics associated with tetraplegia contribute to breathlessness, restrictive ventilatory impairment (low TLC%), and reduced expiratory muscle strength (low ERV). These factors apparently overshadow adverse effects caused by smoking. Conversely, smoking and reduction of airflow (low FEV1%) were predictive of CPWZ, symptoms commonly associated with cigarette use.

Aerosolized ipratropium bromide or orally administered baclofen or oxybutynin chloride (Ditropan) block methacholine-associated airway hyperreactivity in subjects with chronic cervical spinal cord injury (SCI), whereas these agents do not inhibit airway hyperreactivity associated with the inhalation of histamine. The present study was performed to determine whether pretreatment with aβ 2-agonist attenuates airway hyperresponsiveness in these subjects.

The majority of otherwise healthy subjects with chronic cervical spinal cord injury (SCI) demonstrate airway hyperresponsiveness to aerosolized methacholine or histamine. The present study was performed to determine whether ultrasonically nebulized distilled water (UNDW) induces airway hyperresponsiveness and to further elucidate potential mechanisms in this population. Fifteen subjects with SCI, nine with tetraplegia (C4–7) and six with paraplegia (T9–L1), were initially exposed to UNDW for 30 s; spirometry was performed immediately and again 2 min after exposure. The challenge continued by progressively increasing exposure time until the forced expiratory volume in 1 s decreased 20% or more from baseline (PD20) or the maximal exposure time was reached. Five subjects responding to UNDW returned for a second challenge 30 min after inhalation of aerosolized ipratropium bromide (2.5 ml of a 0.6% solution). Eight of nine subjects with tetraplegia had significant bronchoconstrictor responses to UNDW (geometric mean PD20= 7.76 ± 7.67 ml), whereas none with paraplegia demonstrated a response (geometric mean PD20= 24 ml). Five of the subjects with tetraplegia who initially responded to distilled water (geometric mean PD20= 5.99 ± 4.47 ml) were not responsive after pretreatment with ipratropium bromide (geometric mean PD20= 24 ml). Findings that subjects with tetraplegia are hyperreactive to UNDW, a physicochemical agent, combined with previous observations of hyperreactivity to methacholine and histamine, suggest that overall airway hyperresponsiveness in these individuals is a nonspecific phenomenon similar to that observed in patients with asthma. The ability of ipratropium bromide to completely block UNDW-induced bronchoconstriction suggests that, in part, airway hyperresponsiveness in subjects with tetraplegia represents unopposed parasympathetic activity.

Cervical spinal cord injury results in interruption of sympathetic airway innervation, which originates from the upper thoracic spine, whereas parasympathetic nerve supply, arising in the vagal nuclei of the brainstem, remains intact. To assess the effect of such an altered neural environment on airway reactivity, bronchoprovocation testing was performed on eight subjects with nonacute traumatic lesions of the cervical spine, all of whom were lifetime nonsmokers without history of respiratory symptoms prior to their injury. Bronchial challenge was subsequently repeated after pretreatment with the anticholinergic agent, ipratropium bromide, an inhibitor of airway muscarinic receptors. All subjects demonstrated hyperresponsiveness to methacholine (the concentration of methacholine producing a fall in FEV1of 20 percent from baseline [PC20]= 1.42 ± 1.61 [SD] mg/ml). Airway hyperreactivity was completely blocked by pretreatment with inhaled ipratropium bromide (mean PC20 >25 mg/ml [p<0.0001]). The bronchial hyperresponsiveness observed in this population most likely reflects the loss of sympathetic airway innervation and resultant unopposed cholinergic bronchoconstrictor tone which results from transection of the cervical spine. Blockade of methacholine hyperresponsiveness with ipratropium bromide suggests a muscarinic receptor-mediated phenomenon.

Previously, we reported that a majority of subjects with chronic cervical spinal cord injury (SCI) demonstrated airway hyperreactivity in response to inhaled methacholine. To further investigate mechanisms of airway hyperreactivity, 15 male subjects with cervical SCI were challenged with aerosolized histamine, and on a separate day responders were rechallenged 30 min after the inhalation of 72 μg of ipratropium bromide. Twelve of 15 subjects demonstrated airway hyper-responsiveness to histamine (geometric mean PC20 of 1.27 mg/ml), which was not blocked by pretreatment with ipratropium bromide (geometric mean PC20 1.50 mg/ml). Baseline forced vital capacity and forced expiratory volume in 1 sec were not significantly different between responders and nonresponders (2.8 ± 0.6 vs. 3.0 ± 0.4 L and 2.3 ± 0.6 vs. 2.4 ± 0.2 L, respectively). Findings that subjects with cervical SCI are hyperresponsive to methacholine and histamine, chemical agents with direct action through distinct receptor systems, suggest that bronchial hyperreactivity in these subjects represents a nonspecific process similar to that observed in patients with asthma.

Previously, we found that never-smokers with quadriplegia were hyperresponsive to aerosolized methacholine. To further explore the phenomenon, we compared responsiveness to methacholine in never-smokers with that of smokers and ex-smokers. We also evaluated responsiveness in subjects with high paraplegia (lesions at T-1 to T-6) or low paraplegia (lesions at T-7 and below). We found that smokers and ex-smokers with quadriplegia were hyperresponsive to methacholine (provocative concentration causing a 20% fall in FEV1=1.9 mg/mL), and that the response was comparable to that found in never-smokers, revealing that hyperresponsiveness among never-smokers cannot be attributed to preinjury airway hyperreactivity that precluded cigarette use. In contrast, subjects with low paraplegia were not hyperresponsive to methacholine. Among subjects with high paraplegia, the three subjects demonstrating airway hyperresponsiveness had significantly lower FEV1(percent predicted). The findings support the hypothesis that airway hyperresponsiveness in subjects with quadriplegia represents loss of sympathetic innervation of the lung, thereby leaving intact unopposed bronchoconstrictor cholinergic activity. However, reduced lung volumes in these subjects also suggest the possibility that airway hyperresponsiveness is due to loss of ability to stretch airway smooth muscle by deep breathing.

To compare therapeutic outcome and perform a cost-benefit analysis of inpatients with community-acquired pneumonia (CAP) treated with a shortened course of IV antibiotic therapy.

Release of Ca2+ stored in endoplasmic reticulum is a ubiquitous mechanism involved in cellular signal transduction, proliferation, and apoptosis. Recently, sphingolipid metabolites have been recognized as mediators of intracellular Ca2+ release, through their action at a previously undescribed intracellular Ca2+ channel. Here we describe the molecular cloning and characterization of a protein that causes the expression of sphingosyl-phosphocholine-mediated Ca2+ release when its complementary RNA is injected into Xenopus oocytes. SCaMPER (for sphingolipid Ca2+ release-mediating protein of endoplasmic reticulum) is an 181 amino acid protein with two putative membrane-spanning domains. SCaMPER is incorporated into microsomes upon expression in SO cells or after translation in vitro. It mediates Ca2+ release at 4 degrees C as well as 22 degrees C, consistent with having ion channel function. The EC50 for Ca2+ release from Xenopus oocytes is 40 microM, similar to sphingosyl-phosphocholine-mediated Ca2+ release from permeabilized mammalian cells. Because Ca2+ release is not blocked by ryanodine or La3+, the activity described here is distinct from the Ca2+ release activity of the ryanodine receptor and the inositol 1,4,5-trisphosphate receptor. The properties of SCaMPER are identical to those of the sphingolipid-gated Ca2+ channel that we have previously described. These findings suggest that SCaMPER is a sphingolipid-gated Ca2+-permeable channel and support its role as a mediator of this pathway for intracellular Ca2+ signal transduction.

A reliable test that detects malignancy and indicates response to therapy is needed. Frequency-pulsed electron-capture gas-liquid chromatography (FPEC-GLC), a selective analytical technique that is sensitive to 15 fmol quantities of metabolites, was used to analyse derivatised acidic chloroform extracts of sera from patients with biopsy-proven cancer, non-malignant infectious and non-infectious disease, and healthy controls. Two peaks designated P1 and P10, not found in serum from healthy controls (n = 7) or patients with non-malignant disease (n = 85), were detected in biopsy-proven samples (n = 52) from cancer patients. P1 and P10 were later shown by chemical and mass spectral studies to be carboxylic acids. When one or both of these peaks were detected in the sera of non-treated patients they were always associated with malignancy. In patients responding to therapy, a reduction or disappearance of these peaks was observed. Further, it was noted that P10 persisted or increased in sera of patients with progressive cancer not responding to therapy. We conclude that this test has potential in diagnosis and for following the response of the disease to therapy.