9 research outputs found
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Patterns of Antibacterial Use and Impact of Age, Race/Ethnicity, and Geographic Region on Antibacterial Use in an Outpatient Medicaid Cohort
Study objectivesTo describe patterns of outpatient antibacterial use among California Medicaid (Medi-Cal) fee-for-service system beneficiaries, and to investigate the influence of demographic factors-age, race/ethnicity, state county, and population density-on those patterns.DesignRetrospective analysis of administrative claims data.Data sourceMedi-Cal fee-for-service system claims database.PatientsAll outpatient Medi-Cal fee-for-service system beneficiaries enrolled between 2006 and 2011 who had at least one systemic antibacterial claim.Measurements and main resultsRates of antibacterial prescribing and the proportion of broad-spectrum antibacterial use were measured over the study period and among age, racial/ethnic, and geographic (county) groups. Of the 10,018,066 systemic antibacterial claims selected for analysis, antibacterial prescribing rates decreased from 542 claims/1000 beneficiaries in 2006 to 461 claims/1000 beneficiaries in 2011 (r = -0.971, p=0.0012; τ-b = -1.00, p=0.009). Among age groups, children had the highest rate of use (605 claims/1000 beneficiaries, χ(2) (2) = 320,000, p<0.001); among racial/ethnic groups, Alaskan Natives and Native Americans had the highest rate of use (1086/1000 beneficiaries, χ(2) (5) = 197,000, p<0.001). Broad-spectrum antibacterial prescribing increased from 28.1% (95% confidence interval [CI] 28.1-28.2%) to 32.7% (95% CI 32.6-32.8%) over the study period. Senior age groups and whites received the highest proportions of broad-spectrum agents (53.4% [95% CI 52.5-54.3%] and 36.6% [95% CI 36.6-36.7%], respectively). Population density was inversely related to both overall antibacterial use (ρ = -0.432, p=0.0018) and broad-spectrum antibacterial prescribing (ρ = -0.359, p<0.001). The rate of prescribing decreased over the study period for all antibacterial classes with the exception of macrolides and sulfonamides. Amoxicillin was the most frequently prescribed agent.ConclusionOverall and broad-spectrum antibacterial use in the Medi-Cal fee-for-service program are less than that observed nationally. Significant variations in prescribing exist between age and racial/ethnic groups, and heavily populated areas are associated with both less antibacterial use and less broad-spectrum antibacterial prescribing. Studies are needed to determine the reasons for the observed differences in antibacterial use among demographic groups
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Trauma to the ankylotic spine: imaging spectrum of vertebral and soft tissue injuries
The objectives of the study were to review the clinical entities that can cause ankylosis of the spine and to illustrate the spectrum of traumatic injury patterns. Ankylosing spondylitis, diffuse idiopathic systemic hyperostosis, degenerative spondyloarthropathy, and spinal canal stenosis can render the spine susceptible to trivial trauma. Multidetector computed tomography and magnetic resonance imaging can accurately diagnose vertebral and soft tissue traumatic injury patterns in this patient population
Vancomycin MIC Does Not Predict 90-Day Mortality, Readmission, or Recurrence in a Prospective Cohort of Adults with Staphylococcus aureus Bacteremia
Staphylococcus aureus bacteremia (SAB) is a tremendous health burden. Previous studies examining the association of vancomycin MIC and outcomes in patients with SAB have been inconclusive. This study evaluated the association between vancomycin MICs and 30- or 90-day mortality in individuals with SAB. This was a prospective cohort study of adults presenting from 2008 to 2013 with a first episode of SAB. Subjects were identified by an infection surveillance system. The main predictor was vancomycin MIC by MicroScan. The primary outcomes were death at 30 and 90 days, and secondary outcomes included recurrence, readmission, or a composite of death, recurrence, and readmission at 30 and 90 days. Covariates included methicillin susceptibility, demographics, illness severity, comorbidities, infectious source, and antibiotic use. Cox proportional-hazards models with propensity score adjustment were used to estimate 30- and 90-day outcomes. Of 429 unique first episodes of SAB, 11 were excluded, leaving 418 individuals for analysis. Eighty-three (19.9%) participants had a vancomycin MIC of 2 μg/ml. In the propensity-adjusted Cox model, a vancomycin MIC of 2 μg/ml compared to <2 μg/ml was not associated with a greater hazard of mortality or composite outcome of mortality, readmission, and recurrence at either 30 days (hazard ratios [HRs] of 0.86 [95% confidence interval {CI}, 0.41, 1.80] [P = 0.70] and 0.94 [95% CI, 0.55, 1.58] [P = 0.80], respectively) or 90 days (HRs of 0.91 [95% CI, 0.49, 1.69] [P = 0.77] and 0.69 [95% CI, 0.46, 1.04] [P = 0.08], respectively) after SAB diagnosis. In a prospective cohort of patients with SAB, vancomycin MIC was not associated with 30- or 90-day mortality or a composite of mortality, disease recurrence, or hospital readmission
Vancomycin MIC Does Not Predict 90-Day Mortality, Readmission, or Recurrence in a Prospective Cohort of Adults with Staphylococcus aureus Bacteremia
Staphylococcus aureus bacteremia (SAB) is a tremendous health burden. Previous studies examining the association of vancomycin MIC and outcomes in patients with SAB have been inconclusive. This study evaluated the association between vancomycin MICs and 30- or 90-day mortality in individuals with SAB. This was a prospective cohort study of adults presenting from 2008 to 2013 with a first episode of SAB. Subjects were identified by an infection surveillance system. The main predictor was vancomycin MIC by MicroScan. The primary outcomes were death at 30 and 90 days, and secondary outcomes included recurrence, readmission, or a composite of death, recurrence, and readmission at 30 and 90 days. Covariates included methicillin susceptibility, demographics, illness severity, comorbidities, infectious source, and antibiotic use. Cox proportional-hazards models with propensity score adjustment were used to estimate 30- and 90-day outcomes. Of 429 unique first episodes of SAB, 11 were excluded, leaving 418 individuals for analysis. Eighty-three (19.9%) participants had a vancomycin MIC of 2 μg/ml. In the propensity-adjusted Cox model, a vancomycin MIC of 2 μg/ml compared to <2 μg/ml was not associated with a greater hazard of mortality or composite outcome of mortality, readmission, and recurrence at either 30 days (hazard ratios [HRs] of 0.86 [95% confidence interval {CI}, 0.41, 1.80] [P = 0.70] and 0.94 [95% CI, 0.55, 1.58] [P = 0.80], respectively) or 90 days (HRs of 0.91 [95% CI, 0.49, 1.69] [P = 0.77] and 0.69 [95% CI, 0.46, 1.04] [P = 0.08], respectively) after SAB diagnosis. In a prospective cohort of patients with SAB, vancomycin MIC was not associated with 30- or 90-day mortality or a composite of mortality, disease recurrence, or hospital readmission
Interprofessional peer teaching: The value of a pharmacy student-led pharmacology course for physical therapy students
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Fragment Binding to the Nsp3 Macrodomain of SARS-CoV-2 Identified Through Crystallographic Screening and Computational Docking
ABSTRACT The SARS-CoV-2 macrodomain (Mac1) within the non-structural protein 3 (Nsp3) counteracts host-mediated antiviral ADP-ribosylation signalling. This enzyme is a promising antiviral target because catalytic mutations render viruses non-pathogenic. Here, we report a massive crystallographic screening and computational docking effort, identifying new chemical matter primarily targeting the active site of the macrodomain. Crystallographic screening of diverse fragment libraries resulted in 214 unique macrodomain-binding fragments, out of 2,683 screened. An additional 60 molecules were selected from docking over 20 million fragments, of which 20 were crystallographically confirmed. X-ray data collection to ultra-high resolution and at physiological temperature enabled assessment of the conformational heterogeneity around the active site. Several crystallographic and docking fragment hits were validated for solution binding using three biophysical techniques (DSF, HTRF, ITC). Overall, the 234 fragment structures presented explore a wide range of chemotypes and provide starting points for development of potent SARS-CoV-2 macrodomain inhibitors
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Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) macrodomain within the nonstructural protein 3 counteracts host-mediated antiviral adenosine diphosphate-ribosylation signaling. This enzyme is a promising antiviral target because catalytic mutations render viruses nonpathogenic. Here, we report a massive crystallographic screening and computational docking effort, identifying new chemical matter primarily targeting the active site of the macrodomain. Crystallographic screening of 2533 diverse fragments resulted in 214 unique macrodomain-binders. An additional 60 molecules were selected from docking more than 20 million fragments, of which 20 were crystallographically confirmed. X-ray data collection to ultra-high resolution and at physiological temperature enabled assessment of the conformational heterogeneity around the active site. Several fragment hits were confirmed by solution binding using three biophysical techniques (differential scanning fluorimetry, homogeneous time-resolved fluorescence, and isothermal titration calorimetry). The 234 fragment structures explore a wide range of chemotypes and provide starting points for development of potent SARS-CoV-2 macrodomain inhibitors