Comparative Effectiveness of Linezolid and Vancomycin Among a National Veterans Affairs Cohort with Methicillin-Resistant Staphylococcus aureus Pneumonia

Study Objective: As variability in vancomycin dosing, susceptibility, and tolerability has driven the need to compare newer agents with vancomycin in real-world clinical settings, we sought to quantify the effectiveness of linezolid compared with vancomycin on clinical outcomes for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Design: Retrospective cohort study. Data Source: Veterans Health Administration national databases. Patients: Adults admitted to Veterans Affairs hospitals between January 2002 and September 2010 with diagnosis codes for MRSA and pneumonia, and who initiated and received at least 3 days of continuous intravenous vancomycin therapy (4943 patients) or intravenous or oral linezolid therapy (328 patients) while in the hospital. Measurements and Main Results: Propensity score–adjusted Cox proportional hazards regression models quantified the effect of linezolid compared with vancomycin on time to 30-day mortality (primary outcome), therapy change, hospital discharge, discharge from intensive care, intubation, 30-day readmission, and 30-day MRSA reinfection. In addition, a composite outcome of clinical success was defined as discharge from the hospital or intensive care unit by day 14 after treatment initiation, in the absence of death, therapy change, or intubation by day 14. Subgroup analyses were performed in a validated microbiology-confirmed MRSA subgroup and clinical subgroup meeting clinical criteria for infection. Although a number of baseline variables differed significantly between the vancomycin and linezolid treatment groups, balance was achieved within propensity score quintiles. A significantly lower rate of therapy change was observed in the linezolid group (adjusted hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.48–0.96). The clinical success rate was significantly higher among patients treated with linezolid (adjusted HR 1.25, 95% CI 1.07–1.47). Comparable findings were observed in the subgroup analyses. Conclusion: Individual clinical outcomes were similar among patients treated for MRSA pneumonia with linezolid compared with vancomycin. A significantly higher rate of the composite outcome of clinical success was observed, however, among patients treated with linezolid compared with vancomycin

Predictors of Clinical Success Among a National Veterans Affairs Cohort With Methicillin-Resistant Staphylococcus aureus Pneumonia

Background: The treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is exceedingly complicated, which is concerning because of the high mortality rate associated with the infection. Identification of independent predictors of clinical success can optimize patient care by assisting clinicians in treatment decisions. Objectives: We sought to identify independent predictors of clinical success in a national Veterans Affairs (VA) cohort of MRSA pneumonia patients. Methods: A nested case-control study was conducted among a cohort of VA patients with MRSA pneumonia receiving linezolid or vancomycin between January 2002 and September 2010. Cases included those demonstrating clinical success, defined as discharge from the hospital or intensive care unit (ICU) by day 14 after treatment initiation, in the absence of death, therapy change, or intubation by day 14. Controls represented non-success, defined as therapy change, intubation, ICU admission, re-admission, or death between treatment initiation and day 14. The potential predictors assessed included treatment, patient demographics and admission characteristics, previous healthcare and medication exposures, comorbidities, and medical history. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from logistic regression. Results: Our study included 2442 cases of clinical success and 1290 controls. Demographics varied between the clinical success and non-success groups, including age, race, and region of facility. A current diagnosis of chronic respiratory disease (46% vs 42%) and diagnosis of pneumonia in the year prior to the MRSA pneumonia admission (37% vs 32%) were both more common in the clinical success group. Despite these significant differences, only two predictors of clinical success were identified in our study: previous complication of an implant or graft, including mechanical complications and infections, in the year prior to the MRSA pneumonia admission (OR, 1.55; 95% CI, 1.17–2.06) and treatment with linezolid (1.53; 1.12–2.10). Predictors of non-success included concomitant urinary tract infection diagnosis (OR, 0.82; 95% CI, 0.70–0.96), intravenous line (0.76; 0.66–0.89), previous coagulopathy (0.74; 0.56–0.96), previous amputation procedure (0.72; 0.53–0.98), current coagulopathy diagnosis (0.71; 0.53–0.96), dialysis (0.54; 0.38–0.76), multiple inpatient procedures (0.53; 0.45–0.62), inpatient surgery (0.48; 0.41–0.57), and previous endocarditis (0.24; 0.07–0.81). Discussion: MRSA pneumonia tends to affect complex patients, and identification of the predictors of clinical success is useful when considering different therapeutic approaches. Conclusions: In a national cohort of VA patients with MRSA pneumonia, treatment was the only modifiable variable predicting clinical success

A Lower Bound for Quantum Phase Estimation

We obtain a query lower bound for quantum algorithms solving the phase estimation problem. Our analysis generalizes existing lower bound approaches to the case where the oracle Q is given by controlled powers Q^p of Q, as it is for example in Shor's order finding algorithm. In this setting we will prove a log (1/epsilon) lower bound for the number of applications of Q^p1, Q^p2, ... This bound is tight due to a matching upper bound. We obtain the lower bound using a new technique based on frequency analysis.Comment: 7 pages, 1 figur

Universal Scaling of Wave Propagation Failure in Arrays of Coupled Nonlinear Cells

We study the onset of the propagation failure of wave fronts in systems of coupled cells. We introduce a new method to analyze the scaling of the critical external field at which fronts cease to propagate, as a function of intercellular coupling. We find the universal scaling of the field throughout the range of couplings, and show that the field becomes exponentially small for large couplings. Our method is generic and applicable to a wide class of cellular dynamics in chemical, biological, and engineering systems. We confirm our results by direct numerical simulations.Comment: 4 pages, 3 figures, RevTe

Comparative Effectiveness of Exclusive Exposure to Nafcillin or Oxacillin, Cefazolin, Piperacillin/Tazobactam, and Fluoroquinolones Among a National Cohort of Veterans With Methicillin-Susceptible \u3cem\u3eStaphylococcus aureus\u3c/em\u3e Bloodstream Infection

Objective: Beta-lactam antibiotics are recommended as first-line for treatment of methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia. The objective of this study was to compare effectiveness of anti-MSSA therapies among bacteremia patients exclusively exposed to 1 antimicrobial. Method: This was a national retrospective cohort study of patients hospitalized in Veterans Affairs medical centers with MSSA bacteremia from January 1, 2002, to October 1, 2015. Patients were included if they were treated exclusively with nafcillin, oxacillin, cefazolin, piperacillin/tazobactam, or fluoroquinolones (moxifloxacin and levofloxacin). We assessed 30-day mortality, time to discharge, inpatient mortality, 30-day readmission, and 30-day S. aureus reinfection. Hazard ratios (HRs) and 95% confidence intervals (CI) were calculated using propensity-score (PS) matched Cox proportional hazards regression model. Results: When comparing nafcillin/oxacillin (n = 105) with cefazolin (n = 107), 30-day mortality was similar between groups (PS matched n = 44; HR, 0.67; 95% CI, 0.11–4.00), as were rates of the other outcomes assessed. As clinical outcomes did not vary between nafcillin/oxacillin and cefazolin, they were combined for comparison with piperacillin/tazobactam (n = 113) and fluoroquinolones (n = 103). Mortality in the 30 days after culture was significantly lower in the nafcillin/oxacillin/cefazolin group compared with piperacillin/tazobactam (PS matched n = 48; HR, 0.10; 95% CI, 0.01–0.78), and similar when compared with fluoroquinolones (PS matched n = 32; HR, 1.33; 95% CI, 0.30–5.96). Conclusions: In hospitalized patients with MSSA bacteremia, no difference in mortality was observed between nafcillin/oxacillin and cefazolin or fluoroquinolones. However, higher mortality was observed with piperacillin/tazobactam as compared with nafcillin/oxacillin/cefazolin, suggesting it may not be as effective as a monotherapy in MSSA bacteremia

New Developments in Quantum Algorithms

In this survey, we describe two recent developments in quantum algorithms. The first new development is a quantum algorithm for evaluating a Boolean formula consisting of AND and OR gates of size N in time O(\sqrt{N}). This provides quantum speedups for any problem that can be expressed via Boolean formulas. This result can be also extended to span problems, a generalization of Boolean formulas. This provides an optimal quantum algorithm for any Boolean function in the black-box query model. The second new development is a quantum algorithm for solving systems of linear equations. In contrast with traditional algorithms that run in time O(N^{2.37...}) where N is the size of the system, the quantum algorithm runs in time O(\log^c N). It outputs a quantum state describing the solution of the system.Comment: 11 pages, 1 figure, to appear as an invited survey talk at MFCS'201

Antibiotic Resistance Rates for Pseudomonas aeruginosa Clinical Respiratory and Bloodstream Isolates Among the Veterans Affairs Healthcare System from 2009 to 2013

Pseudomonas aeruginosa is a major cause of healthcare-associated infections and resistance among isolates is an increasing burden. The study purpose was to describe national resistance rates for clinical P. aeruginosa respiratory and bloodstream cultures and the prevalence of multidrug-resistant (MDR) P. aeruginosa within the Veterans Affairs (VA). MDR was defined as non-susceptibility to at least one drug in at least 3 of the following 5 categories: carbapenems, extended-spectrum cephalosporins, aminoglycosides, and piperacillin/tazobactam. We reviewed 24,562 P. aeruginosa respiratory and bloodstream isolates across 126 VA facilities between 2009 to 2013. Most isolates were collected from inpatient settings (82%). Resistance was highest in fluoroquinolones (33%) and exceeded 20% for all classes assessed (carbapenems, extended-spectrum cephalosporins, aminoglycosides, and piperacillin/tazobactam). Resistance was higher in inpatient settings and in respiratory isolates. Prevalence of MDR was 20% overall (22% for inpatient isolates, 11% outpatient, 21% respiratory, 17% bloodstream). Our findings are consistent with previous surveillance report

Weak biofilm formation among carbapenem-resistant Klebsiella pneumoniae

Biofilm formation of multidrug and extensively drug resistant Klebsiella pneumoniaeisolates is poorly understood. We investigated 139 diverse clinical K. pneumoniaeisolates that possess various resistance patterns to evaluate the relationship between biofilm formation and resistance. Antimicrobial resistance was compared among a diverse collection of weak versus strong biofilm-forming K. pneumoniae, and predictors of strong biofilm formation were identified. Multi-drug resistant isolates were more common among weak (97.9%) versus strong biofilm formers (76%; P = 0.002). Carbapenem-resistant K. pneumoniae were 91% less likely to form strong biofilm (odds ratio 0.09; 95% confidence interval 0.02–0.33). The statistically significant inverse relationship between biofilm formation and antibiotic resistance suggests that virulence may be a trade-off for survival

Enhancing innovation between scientific and indigenous knowledge: pioneer NGOs in India

Abstract Background Until recently, little attention has been paid to local innovation capacity as well as management practices and institutions developed by communities and other local actors based on their traditional knowledge. This paper doesn't focus on the results of scientific research into innovation systems, but rather on how local communities, in a network of supportive partnerships, draw knowledge for others, combine it with their own knowledge and then innovate in their local practices. Innovation, as discussed in this article, is the capacity of local stakeholders to play an active role in innovative knowledge creation in order to enhance local health practices and further environmental conservation. In this article, the innovative processes through which this capacity is created and reinforced will be defined as a process of "ethnomedicine capacity". Methods The field study undertaken by the first author took place in India, in the State of Tamil Nadu, over a period of four months in 2007. The data was collected through individual interviews and focus groups and was complemented by participant observations. Results The research highlights the innovation capacity related to ethnomedical knowledge. As seen, the integration of local and scientific knowledge is crucial to ensure the practices anchor themselves in daily practices. The networks created are clearly instrumental to enhancing the innovation capacity that allows the creation, dissemination and utilization of 'traditional' knowledge. However, these networks have evolved in very different forms and have become entities that can fit into global networks. The ways in which the social capital is enhanced at the village and network levels are thus important to understand how traditional knowledge can be used as an instrument for development and innovation. Conclusion The case study analyzed highlights examples of innovation systems in a developmental context. They demonstrate that networks comprised of several actors from different levels can synergistically forge linkages between local knowledge and formal sciences and generate positive and negative impacts. The positive impact is the revitalization of perceived traditions while the negative impacts pertain to the transformation of these traditions into health commodities controlled by new elites, due to unequal power relations

DEPTOR Is an mTOR Inhibitor Frequently Overexpressed in Multiple Myeloma Cells and Required for Their Survival

The mTORC1 and mTORC2 pathways regulate cell growth, proliferation, and survival. We identify DEPTOR as an mTOR-interacting protein whose expression is negatively regulated by mTORC1 and mTORC2. Loss of DEPTOR activates S6K1, Akt, and SGK1, promotes cell growth and survival, and activates mTORC1 and mTORC2 kinase activities. DEPTOR overexpression suppresses S6K1 but, by relieving feedback inhibition from mTORC1 to PI3K signaling, activates Akt. Consistent with many human cancers having activated mTORC1 and mTORC2 pathways, DEPTOR expression is low in most cancers. Surprisingly, DEPTOR is highly overexpressed in a subset of multiple myelomas harboring cyclin D1/D3 or c-MAF/MAFB translocations. In these cells, high DEPTOR expression is necessary to maintain PI3K and Akt activation and a reduction in DEPTOR levels leads to apoptosis. Thus, we identify a novel mTOR-interacting protein whose deregulated overexpression in multiple myeloma cells represents a mechanism for activating PI3K/Akt signaling and promoting cell survival.Howard Hughes Medical Institute (Investigator)Dana-Farber Cancer Institute (High-Tech Research Fund)National Cancer Institute (U.S.)National Institutes of Health (U.S.) (Intramural Research Program)American Cancer SocietyCanadian Institutes of Health Research (Fellowship)American Diabetes Association (Fellowship)W. M. Keck FoundationNational Institutes of Health (U.S.) (R01 CA103866)National Institutes of Health (U.S.) (NIH; R01 AI47389