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Background: Current vancomycin monitoring guidelines recommend monitoring 24-hour area under the concentration-time curve (AUC) to minimum inhibitory concentration ratios for patients with serious methicillin-resistant Staphylococcus aureus infections. However, there are sparse data on the safety, feasibility, and efficacy of vancomycin AUC monitoring for outpatients. Traditional AUC pharmacokinetic calculations require 2 concentrations, while bayesian software allows for single-concentration AUC estimations., Methods: We conducted a single-center, quasi-experimental, interrupted time series study of patients enrolled in the outpatient parenteral antimicrobial therapy program at our institution for vancomycin management. Our institution implemented a pharmacist-driven vancomycin AUC monitoring program from September 2019 to February 2020, and again from September 2022 to March 2023. Patients enrolled underwent vancomycin monitoring using an AUC goal of 400-600 mg⋅h/L, estimated through bayesian modeling. Patients enrolled in the outpatient parenteral antimicrobial therapy program from July 2021 through August 2022 for trough-based monitoring were used for comparison. The primary outcome was nephrotoxicity incidence, defined as a serum creatinine increase by ≥0.5 mg/dL or ≥50% during outpatient vancomycin therapy., Results: We enrolled 63 patients in the AUC group and 60 patients in the trough-based group. Nephrotoxicity was significantly lower in the AUC cohort (6.3% vs 23.3%; P = .01). The number of unusable vancomycin concentrations was also significantly lower in the AUC cohort (0% vs 6%; P < .01). There was no difference in composite 90-day all-cause mortality or readmission (33.3% vs 38.3%; P = .56)., Conclusions: Following implementation of a pharmacist-driven AUC monitoring program, patients were less likely to develop nephrotoxicity during outpatient vancomycin therapy., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The high frequency of antibiotic use in US nursing homes is a public health concern. Facility-level prescribing patterns may provide a measure for antibiotic stewardship targeting., Methods: An analysis of 2018-2019 data from linked files from the Centers for Medicaid and Medicare was conducted. Multilevel generalized linear models were used to calculate odds ratios for antibiotic receipt for calendar year 2019 using the 2018 facility prescribing rate., Results: In 2019, 186,274 (19%) residents were prescribed an antibiotic. The most frequently prescribed class of antibiotics was cephalosporins (26%), and the average duration of antibiotic use was 9 days. Residents who were dually eligible for Medicare and Medicaid had 37% increased odds of antibiotic receipt (all adjusted odds ratio (aOR): 1.37, 95% confidence interval [CI]: 1.35, 1.39). The 2018 facility prescribing rate was associated with 14% increased odds of antibiotic receipt in 2019 in NHs in the medium (11.9%-20.2%) prescribing category (all aOR: 1.14, 95% CI: 1.11, 1.17) and 36% increased odds of antibiotic receipt in NHs in the high (> 20.3%) prescribing category (all aOR: 1.36, 95% CI: 1.32, 1.40) when compared with the lowest (0%-11.8%) prescribing category., Conclusions: Antibiotic stewardship strategies should target nursing homes with high antibiotic prescribing rates and high populations of dually eligible patients to improve care in this population., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Dalbavancin has been used off-label to treat invasive bacterial infections in vulnerable populations like people who use drugs (PWUD) because of its broad gram-positive coverage and unique pharmacological properties. This retrospective, multisite study examined clinical outcomes at 90 days in PWUD versus non-PWUD after secondary treatment with dalbavancin for bacteremia, endocarditis, osteomyelitis, septic arthritis, and epidural abscesses., Methods: Patients at 3 teaching hospitals who received dalbavancin for an invasive infection between March 2016 and May 2022 were included. Characteristics of PWUD and non-PWUD, infection highlights, hospital stay and treatment, and outcomes were compared using χ 2 for categorical variables, t test for continuous variables, and nonparametric tests where appropriate., Results: There were a total of 176 patients; 78 were PWUD and 98 were non-PWUD. PWUD were more likely to have a patient-directed discharge (26.9% vs 3.1%; P < .001) and be lost to follow-up (20.5% vs 7.14%; P < .01). Assuming loss to follow-up did not achieve clinical cure, 73.1% of PWUD and 74.5% of non-PWUD achieved clinical cure at 90 days ( P = .08)., Conclusions: Dalbavancin was an effective treatment option for invasive gram-positive infections in our patient population. Despite higher rates of patient-directed discharge and loss to follow-up, PWUD had similar rates of clinical cure at 90 days compared to non-PWUD., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Long-acting lipoglycopeptides such as dalbavancin may have utility in patients with Gram-positive bloodstream infections (BSI), particularly in those with barriers to discharge or who require prolonged parenteral antibiotic courses. A retrospective cohort study was performed to provide further multicenter real-world evidence on dalbavancin use as a sequential therapy for Gram-positive BSI., Methods: One hundred fifteen patients received dalbavancin with Gram-positive BSI, defined as any positive blood culture or diagnosed with infective endocarditis, from 13 centers geographically spread across the United States between July 2015 and July 2021., Results: Patients had a mean (SD) age of 48.5 (17.5) years, the majority were male (54%), with many who injected drugs (40%). The most common infection sources (non-exclusive) were primary BSI (89%), skin and soft tissue infection (SSTI) (25%), infective endocarditis (19%), and bone and joint infection (17%). Staphylococcus aureus accounted for 72% of index cultures, coagulase-negative Staphylococcus accounted for 18%, and Streptococcus species in 16%. Dalbavancin started a median (Q 1 -Q 3 ) of 10 (6-19) days after index culture collection. The most common regimen administered was dalbavancin 1500 mg as one dose for 50% of cases. The primary outcome of composite clinical failure occurred at 12.2%, with 90-day mortality at 7.0% and 90-day BSI recurrence at 3.5%., Conclusions: Dalbavancin may serve as a useful tool in facilitating hospital discharge in patients with Gram-positive BSI. Randomized controlled trials are anticipated to validate dalbavancin as a surrogate to current treatment standards., (© 2024. The Author(s).)

Background: Sepsis guidelines recommend daily review to de-escalate or stop antibiotics in appropriate patients. This randomized, controlled trial evaluated an opt-out protocol to decrease unnecessary antibiotics in patients with suspected sepsis., Methods: We evaluated non-intensive care adults on broad-spectrum antibiotics despite negative blood cultures at 10 US hospitals from September 2018 through May 2020. A 23-item safety check excluded patients with ongoing signs of systemic infection, concerning or inadequate microbiologic data, or high-risk conditions. Eligible patients were randomized to the opt-out protocol vs usual care. Primary outcome was post-enrollment antibacterial days of therapy (DOT). Clinicians caring for intervention patients were contacted to encourage antibiotic discontinuation using opt-out language. If continued, clinicians discussed the rationale for continuing antibiotics and de-escalation plans. To evaluate those with zero post-enrollment DOT, hurdle models provided 2 measures: odds ratio of antibiotic continuation and ratio of mean DOT among those who continued antibiotics., Results: Among 9606 patients screened, 767 (8%) were enrolled. Intervention patients had 32% lower odds of antibiotic continuation (79% vs 84%; odds ratio, 0.68; 95% confidence interval [CI], .47-.98). DOT among those who continued antibiotics were similar (ratio of means, 1.06; 95% CI, .88-1.26). Fewer intervention patients were exposed to extended-spectrum antibiotics (36% vs 44%). Common reasons for continuing antibiotics were treatment of localized infection (76%) and belief that stopping antibiotics was unsafe (31%). Thirty-day safety events were similar., Conclusions: An antibiotic opt-out protocol that targeted patients with suspected sepsis resulted in more antibiotic discontinuations, similar DOT when antibiotics were continued, and no evidence of harm., Clinical Trials Registration: NCT03517007., Competing Interests: Potential conflicts of interest. E. D. A. reports grants or contracts from the University of Maryland (paid to author), University of Chicago (paid to author), CDC Prevention Epicenter Program (paid to institution), Oxford University Clinical Research Unit (paid to author), CDC (paid to institution), and DASON Member Hospital Contracts (paid to institution); royalties or licenses from UpToDate (paid to author); consulting fees from the American College of Clinical Pharmacy (paid to author), Hospital Association of New York State (paid to author), Sarah Moreland Russel Consulting (paid to author), and HealthTrackRX (paid to author); and support for attending meetings and/or travel from the American Society of Microbiology (paid to author), Pew Charitable Trusts (paid to author), and Oxford University Clinical Research Unit (paid to institution). A. E. D. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Merck & Co (paid to author). M. Z. D. reports grants or contracts from the National Institutes of Health, GSK, Johnson & Johnson, and Contrafect (paid to institution); support for attending meetings and/or travel from GSK; and participation on a data and safety monitoring board or advisory board for GSK (paid to author). D. J. A. reports grants or contracts from Agency for Healthcare Research and Quality (to institution), royalties or licenses from UpToDate Online (paid to author), and other financial or nonfinancial interests from Infection Control Education for Major Sports, LLC (owner). M. K. reports grants or contracts from Agency for Healthcare Research and Quality (paid to institution) and the Massachusetts Department of Public Health (paid to institution) and royalties or licenses from UpToDate (paid to author). R. W. M. reports grants or contracts from the CDC (paid to institution) and the Agency for Healthcare Research and Quality (paid to institution), royalties or licenses from UpToDate, Inc. (paid to author), speaker honoraria for the North Carolina Statewide Program for Infection Control and Epidemiology (paid to author), support for attending meetings and/or travel from the Society for Healthcare Epidemiology of America, and is on the Society for Healthcare Epidemiology of America Board of Trustees. A. P. reports grants from Clinical and Translational Science Award (to Biostatistics, Epidemiology, and Research Design Core, within the Biostatistics and Bioinformatics Department at Duke University). J. C. P. reports serving on the advisory boards for Shionogi, Inc, and Gilead Sciences, Inc. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. 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Aim: To evaluate the efficiency of Bayesian modeling software and first-order pharmacokinetic (PK) equations to calculate vancomycin area under the concentration-time curve (AUC) estimations., Methods: Unblinded, crossover, quasi-experimental study at a tertiary care hospital for patients receiving intravenous vancomycin. Vancomycin AUC monitoring was compared using Bayesian modeling software or first-order PK equations. The primary endpoint was the time taken to estimate the AUC and determine regimen adjustments. Secondary endpoints included the percentage of vancomycin concentrations usable for AUC calculations and acute kidney injury (AKI)., Results: Of the 124 patients screened, 34 patients had usable vancomycin concentrations that led to 44 AUC estimations. Without electronic health record (EHR) integration, the time from assessment to intervention in the Bayesian modeling platform was a median of 9.3 min (quartiles Q 1 -Q 3 7.8-12.4) compared to 6.8 min (Q 1 -Q 3 4.8-8.0) in the PK equations group ( p = 0.004). With simulated Bayesian software integration into the EHR, however, the median time was 3.8 min (Q 1 -Q 3 2.3-6.9, p = 0.019). Vancomycin concentrations were usable in 88.2% in the Bayesian group compared to 48.3% in the PK equation group and there were no cases of AKI., Conclusion: Without EHR integration, Bayesian software was more time-consuming to assess vancomycin dosing than PK equations. With simulated integration, however, Bayesian software was more time efficient. In addition, vancomycin concentrations were more likely to be usable for calculations in the Bayesian group.

Objectives: To determine how pharmacists with formal antimicrobial stewardship program (ASP) responsibilities prioritize their time and pharmacists without formal antimicrobial stewardship program responsibilities contribute to ASP activities., Design: A nationwide survey., Respondents: Members of the American College of Clinical Pharmacy who subscribe to the following practice and research network e-mail listservs: infectious diseases, adult medicine, cardiology, critical care, hematology-oncology, immunology and transplantation, and pediatrics., Methods: A survey was distributed via listservs. Respondents were asked about their personal and institutional demographics and ASP activities., Results: In total, 245 pharmacists responded: 135 pharmacists with formal antimicrobial stewardship program responsibilities; 110 pharmacists without formal antimicrobial stewardship program responsibilities. Although most respondents had completed a general pharmacy residency (85%), only 20% had completed an infectious diseases (ID) specialty residency. Among pharmacists with formal antimicrobial stewardship program responsibilities, one-third had no formal training or certification in ID or ASP. Pharmacists without formal antimicrobial stewardship program responsibilities spent ∼12.5% of their time per week on ASP activities, whereas pharmacists with formal antimicrobial stewardship program responsibilities spent 28% of their time performing non-ASP activities. Pharmacists with formal antimicrobial stewardship program responsibilities were more likely than pharmacists without formal antimicrobial stewardship program responsibilities to perform antibiotic guideline development ( P < .001), antibiotic-related education ( P = .002), and direct notification of rapid diagnostic results ( P = .018). Pharmacists with formal antimicrobial stewardship program responsibilities without formal ID training or certification spent less time on ASP activities and were more likely to perform lower-level interventions., Conclusions: Many ASP activities are being performed by pharmacists without formal ID training. To ensure the future success of ASPs, pharmacists with formal antimicrobial stewardship program responsibilities should have adequate training to meet more advanced metrics, and more pharmacists without formal antimicrobial stewardship program responsibilities should be included in basic interventions., (© The Author(s) 2022.)

Background: Omadacycline is an aminomethylcycline antimicrobial approved by the US Food and Drug Administration in 2018 for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. It has in vitro activity against nontuberculous mycobacteria, including Mycobacterium abscessus complex, but clinical data for this indication are lacking., Methods: Omadacycline use was reviewed at an 804-bed academic medical center. Patients were included if they received omadacycline for culture-proven M abscessus disease in 2019., Results: Four patients received omadacycline for the treatment of culture-positive M abscessus disease in 2019. Two patients had cutaneous disease, 1 had pulmonary disease, and 1 had osteomyelitis and bacteremia. The patients received omadacycline for a median duration of 166 days (range, 104-227) along with a combination of other antimicrobial agents. Omadacycline-containing regimens were associated with a clinical cure in 3 of 4 patients, with 1 patient improving on ongoing treatment. Omadacycline's tolerability was acceptable for patients with M abscessus disease, with 1 patient discontinuing therapy in month 6 due to nausea., Conclusions: Omadacycline is a novel oral option for the treatment of M abscessus disease, for which safe and effective options are needed. Although this case series is promising, further data are required to determine omadacycline's definitive role in the treatment of M abscessus disease., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Antiretroviral therapy has advanced significantly since zidovudine was first approved. Although 31 antiretrovirals have been approved by the FDA, only about half of those are commonly used. Newer, more tolerable agents have made human immunodeficiency virus into a chronic condition, which can be managed with medication. The most common antiretroviral regimens consist of 2 nucleoside reverse transcriptase inhibitors plus a third agent, often an integrase inhibitor because of better tolerability and fewer drug interactions than other regimens. Understanding the dosage forms, adverse effects, and drug interactions of antiretrovirals allow clinicians to choose the most appropriate regimen for their patient. New developments, such as branded generic regimens and long-acting intramuscular injections, may play a larger role in the future., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Antimicrobial stewardship programs (ASPs) aim to provide optimal antimicrobial therapy to patients quickly to improve the likelihood of overcoming infection while reducing the risk of adverse effects. Rapid diagnostic tests (RDTs) for infectious diseases have become an integral tool for ASPs to achieve these aims., Content: This review explored the demonstrated clinical value of longer-standing technologies and implications of newer RDTs from an antimicrobial stewardship perspective. Based on available literature, the focus was on the use of RDTs in bloodstream infections (BSIs), particularly those that perform organism identification and genotypic resistance detection, phenotypic susceptibility testing, and direct specimen testing. Clinical implications of rapid testing among respiratory, central nervous system, and gastrointestinal infections are also reviewed., Summary: Coupling RDTs with ASPs facilitates the appropriate and timely use of test results, translating into improved patient outcomes through optimization of antimicrobial use. These benefits are best demonstrated in the use of RDT in BSIs. Rapid phenotypic susceptibility testing offers the potential for early pharmacokinetic/pharmacodynamic optimization, and direct specimen testing on blood may allow ASPs to initiate appropriate therapy and/or tailor empiric therapy even sooner than other RDTs. RDTs for respiratory, central nervous system, and gastrointestinal illnesses have also shown significant promise, although more outcome studies are needed to evaluate their full impact., (© 2018 American Association for Clinical Chemistry.)

Background: Splenic injury can occur through multiple mechanisms and may result in various degrees of residual immunocompetence. Functionally or anatomically asplenic patients are at higher risk for infection, particularly with encapsulated bacteria. Vaccination is recommended to prevent infection with these organisms; however, the recommendations are routinely updated, and vaccine selection and timing are complex., Methods: Review of the pertinent English-language literature, including the recommendations of the U.S. Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices., Results: Overwhelming post-splenectomy infection is associated with high morbidity and mortality rates. Patients requiring splenectomy for trauma-related injury appear to be at lower risk for infection than those undergoing splenectomy for a hematologic or oncologic indication. Initial vaccination is dependent on immunization history but generally should consist of the 13-valent pneumococcal conjugate, quadrivalent meningococcal conjugate, meningococcal serogroup B, and Haemophilus influenzae serotype b (Hib) vaccines. Antimicrobial prophylaxis for certain asplenic patients, such as children under the age of five y, may be indicated., Conclusion: Immunization remains a key measure to prevent overwhelming post-splenectomy infection. Consideration of new recommendations and indications, possible interactions, and timing remains important to including optimal response to the vaccines.

Glycosylation and intracellular assembly of monoclonal antibodies (MAbs) is important for glycan profile consistency. To better understand how these factors may be influenced by a lower redox potential, an IgG1-producing NS0 cell line was grown in the presence of varying concentrations of dithiothreitol (DTT). Cultures were monitored for growth and culture redox potential (CRP) with glycan heterogeneity determined using a HILIC-HPLC method. Macroheterogeneity was unchanged in all conditions whereas the Galactosylation Index (GI) decreased by as much as 50% in cultures with lower CRP or higher dithiothreitol levels. This shift in GI is reflected in more agalactosylated and asialylated species being produced. The MAb assembly pathway was determined using radioactive isotope 35 S incorporated into nascent IgG1 molecules. The assembly pathway for this IgG1 was shown to progress via HC→HC 2 →HC 2 LC→HC 2 LC 2 in all conditions tested and autoradiographs highlighted that the ratio of heavy chain dimer to heavy chain monomer increased over time with increasing DTT concentrations. This increase and correspondingly lower GI values may be due to disruption of the disulfide bonds at higher levels of assembly. A change in the assembly pathway may alter the final IgG glycan pattern and lead to control mechanisms that influence glycan profiles of MAbs., (Copyright © 2017. Published by Elsevier B.V.)

Depopulation of birds has always been an effective method not only to control the transmission of avian influenza in bird populations but also to eliminate influenza viruses. We introduce a Filippov avian-only model with culling of susceptible and/or infected birds. For each susceptible threshold level [Formula: see text], we derive the phase portrait for the dynamical system as we vary the infected threshold level [Formula: see text], focusing on the existence of endemic states; the endemic states are represented by real equilibria, pseudoequilibria and pseudo-attractors. We show generically that all solutions of this model will approach one of the endemic states. Our results suggest that the spread of avian influenza in bird populations is tolerable if the trajectories converge to the equilibrium point that lies in the region below the threshold level [Formula: see text] or if they converge to one of the pseudoequilibria or a pseudo-attractor on the surface of discontinuity. However, we have to cull birds whenever the solution of this model converges to an equilibrium point that lies in the region above the threshold level [Formula: see text] in order to control the outbreak. Hence a good threshold policy is required to combat bird flu successfully and to prevent overkilling birds.

OBJECTIVE To evaluate the effect of healthcare worker (HCW) influenza vaccination on the incidence of nosocomial influenza DESIGN Retrospective cross-sectional study SETTING A 550-bed tertiary-care academic medical center METHODS All admitted patients with a direct fluorescent antibody (DFA) or polymerase chain reaction (PCR) assay positive for influenza ordered between October 1 and May 31 from 2010 to 2015 were eligible for inclusion. Nosocomial influenza was defined as a positive influenza test collected ≥48 hours after admission in patients without influenza-like illness present within 24 hours of admission. Relative nosocomial influenza frequency was calculated by dividing the number of nosocomial cases by the total number of admitted patients with influenza for each season. A univariate logistic regression was used to determine the association between HCW influenza vaccination coverage and nosocomial influenza. RESULTS Over 5 seasons, 533 patients had positive influenza tests during their hospitalization; 29 of these patients (5.4%) acquired influenza during their hospitalization. HCW vaccination coverage increased over the 5 seasons from 47% to 90% (P<.001). Despite an initial decrease in relative nosocomial influenza frequency during the first year (9% to 4.9%), subsequent seasons failed to show an additional decrease in nosocomial infections (4.3%, 5.2%, and 4.8%, respectively); the overall decrease in nosocomial influenza from the first season to the final season was not significant (P=.282). No association was detected between HCW vaccination coverage and nosocomial influenza (odds ratio [OR], 0.990; 95% confidence interval [CI], 0.970-1.011). CONCLUSION HCW vaccination >50% may not have a significant effect on nosocomial influenza. Infect Control Hosp Epidemiol 2016;37:840-844.

Neoscytalidium dimidiatum is a mold known to cause onychomycosis and dermatomycosis; however, it is an extremely rare cause of systemic infection. We report a case of pulmonary infection with Neoscytalidium dimidiatum in an immunocompromised patient and discuss in vitro susceptibility data from this case and previous literature., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Highly pathogenic avian influenza H5N1 viruses can result in poultry and occasionally in human mortality. A safe and effective H5N1 vaccine is urgently needed to reduce the pandemic potential. Hemagglutinin (HA), a major envelope protein accounting for approximately 80% of spikes in influenza virus, is often used as a major antigen for subunit vaccine development. In this study, we conducted a systematic study of the immune response against influenza virus infection following immunization with recombinant HA proteins expressed in insect (Sf9) cells, insect cells that contain exogenous genes for elaborating N-linked glycans (Mimic) and mammalian cells (CHO). While the antibody titers are higher with the insect cell derived HA proteins, the neutralization and HA inhibition titers are much higher with the mammalian cell produced HA proteins. Recombinant HA proteins containing tri- or tetra-antennary complex, terminally sialylated and asialyated-galactose type N-glycans induced better protective immunity in mice to lethal challenge. The results are highly relevant to issues that should be considered in the production of fragment vaccines.

Industrial therapeutic protein production has been greatly improved through fed-batch development. In this study, improvement to the productivity of a tissue-plasminogen activator (t-PA) expressing Chinese hamster ovary (CHO) cell line was investigated in shake flask culture through the optimization of the fed-batch feed and the reduction of ammonia generation by glutamine replacement. The t-PA titer was increased from 33 mg/L under batch conditions to 250 mg/L with daily feeding starting after three days of culture. A commercially available fed-batch feed was supplemented with cotton seed hydrolysate and the four depleted amino acids, aspartic acid, asparagine, cysteine, and tyrosine. The fed-batch operation increased the generation of by-products such as lactate and ammonia that can adversely affect the fed-batch performance. To reduce the ammonia production, a glutamine-containing dipeptide, pyruvate, glutamate, and wheat gluten hydrolysate, were investigated as glutamine substitutes. To minimize the lag phase as the cells adjusted to the new energy source, a feed glutamine replacement process was developed where the cells were initially cultured with a glutamine containing basal medium to establish cell growth followed by feeding with a feed containing the glutamine substitutes. This two-step feed glutamine replacement process not only reduced the ammonia levels by over 45% but, in the case of using wheat gluten hydrolysate, almost doubled the t-PA titer to over 420 mg/L without compromising the t-PA product quality or glycosylation pattern. The feed glutamine replacement process combined with optimizing other feed medium components provided a simple, practical, and effective fed-batch strategy that could be applied to the production of other recombinant therapeutic proteins., (Copyright © 2012 American Institute of Chemical Engineers (AIChE).)

Unlabelled: This study investigated the opinions of preceptors on select topics relevant to the benefits and rewards of precepting medical assisting (MA) students., Methods: A 35-item questionnaire was distributed to volunteer MA preceptors over the course of 1 year. Survey items prompted participants for information concerning background and previous experiences with MA students, as well as gathered opinions on the benefits, issues, and rewards of preceptorships., Results: Of the preceptors who gave evidence of their credentials, 98.43% were either practicing certified medical assistants (CMA-AAMA) or nurses. Respectively, 80.85% of CMAs and 80.00% of nurses felt that students provided the office with extra help and placed no financial burden on the practice. Approximately 44% ranked free continuing medical education (CME) credits as the most important reward. Written responses identified thank-you notes as an important demonstration of service, acknowledgment, and appreciation., Conclusion: MA preceptors consider students a beneficial aspect of their practice because they lighten strenuous workloads and stimulate preceptors to remain current in their professional fields. Noncompensated MA preceptors value both extrinsic (e.g., free CME credits) and intrinsic rewards (e.g., feedback and thank-you cards) and suggested that intrinsic rewards were of greater value.

Background: Pleural effusion is a common complication of cardiac surgery, but its characteristics and predisposing factors should be documented further. Our objective was to determine the prevalence, characteristics, and determinants of clinically significant pleural effusions, defined as those requiring therapeutic pleural drainage according to clinical assessment., Methods: The prevalence and characteristics of patients who had a pleural effusion within 30 days of undergoing coronary artery bypass graft, valve replacement, or both were analyzed retrospectively at our institution over a 2-year period., Results: Among the 2,892 patients included in the study (mean age, 66 years; men, 2,139), 192 patients (6.6%) had experienced a clinically significant pleural effusion in the 30 days postsurgery. These effusions occurred after a mean (+/- SD) duration of 6.6 +/- 5.9 days following interventions. Pleural fluid analysis was obtained in 114 patients (59.4%); all met the criteria for an exudate. Pleural fluid was hemorrhagic in 50% of cases. Age, body weight, baseline pulmonary function, and smoking status were similar between patients with and without effusion; however, the proportion of women; the number of patients with previous conditions of heart failure, atrial fibrillation, or peripheral vascular disease; and the number of patients receiving therapy with an anticoagulant or antiarrhythmic agent was higher in the pleural effusion group. Patients with pleural effusion had an increased prevalence of postoperative complications., Conclusions: Pleural effusion is a common complication of heart surgery, is associated with other postoperative complications, and is more frequent in women and in patients with associated cardiac or vascular comorbidities and medications used to treat those conditions., Trial Registration: ClinicalTrials.gov Identifier: NCT00665015.

Background: Over the last 12 years, the demographic and clinical characteristics of patients undergoing myocardial revascularization surgery have evolved rapidly. The goal of our study was to analyze the evolution of these trends and the results of these surgical interventions., Methods: We identified patients who underwent a first or second myocardial revascularization between 1993 and 2004, and we arbitrarily divided them into 2 groups: 1 cohort of patients who underwent surgery between 1993 and 1998 and 1 cohort of patients who underwent surgery between 1999 and 2004. We compared demographic and clinical characteristics between the 2 cohorts and determined which variables were significant predictors of morbidity and mortality., Results: From 1993 to 2004, 12 202 patients underwent a first (95.5%) or second (4.5%) myocardial revascularization. Patients in the later cohort presented with a high-risk profile. They were older and had metabolic syndrome or diabetes and peripheral vascular disease. On the other hand, there were fewer active smokers in this group. Whereas the rate of postoperative infarction and renal insufficiency was higher in the second cohort, this group had a lower incidence of stroke and prolonged mechanical ventilation and shorter hospital stays. Overall, observed mortality decreased in spite of a steady increase in predicted mortality. Identified predictors of mortality were age, stroke, female sex, nonelective surgery, renal insufficiency, peripheral vascular disease, chronic obstructive pulmonary disease, ventricular dysfunction and stenosis of the left main trunk., Conclusion: Our study confirmed current trends that show an increase in the at-risk population with dysmetabolic syndrome in cardiac surgery, as well as constant improvements in tertiary care in anesthesia and coronary surgery.

Presented is a novel antibody production platform based on the fed-batch culture of recombinant, NS0-derived cell lines. A standardized fed-batch cell culture process was developed for five non-GS NS0 cell lines using enriched and optimized protein-free, cholesterol-free, and chemically defined basal and feed media. The process performed reproducibly and scaled faithfully from the 2-L to the 100-L bioreactor scale achieving a volumetric productivity of > 120 mg/L per day. Fed-batch cultures for all five cell lines exhibited significant lactate consumption when the cells entered the stationary or death phase. Peak and final lactate concentrations were low relative to a previously developed fed-batch process (FBP). Such low lactate production and high lactate consumption rates were unanticipated considering the fed-batch culture basal medium has an unconventionally high initial glucose concentration of 15 g/L, and an overall glucose consumption in excess of 17 g/L. The potential of this process platform was further demonstrated through additional media optimization, which has resulted in a final antibody concentration of 2.64 +/- 0.19 g/L and volumetric productivity of > 200 mg/L per day in a 13-day FBP for one of the five production cell lines. Use of this standardized protein-free, cholesterol-free NS0 FBP platform enables consistency in development time and cost effectiveness for manufacturing of therapeutic antibodies., ((c) 2006 Wiley Periodicals, Inc.)

Introduction: To evaluate the prevalence, risk factors and morbidity associated with gastrointestinal (GI) complications after cardiac surgery, with and without cardiopulmonary bypass, we carried out a retrospective cohort study at a university teaching hospital., Methods: We divided the 11,405 eligible adult patients into 2 groups: group A (operated on between January 1992 and June 1996) (4657 patients) and group B (operated on between July 1996 and December 2000) (6748 patients)., Results: We found 147 GI complications in 134 (1.2%) patients. The incidence of GI morbidity was similar for the 2 groups of patients (group A, n = 59/4657 [1.2%]; group B, n = 75/6748 [1.1%]. Patients from group B were older, obese, diabetic and presented with more peripheral and cerebrovascular disease. Bleeding, gastritis and ulcer with perforation, the most common of these GI events, were associated with the esophagus and stomach (67/147 [45.5%]). Other events that we documented included cholecystitis 10 (6.8%), pancreatitis 13 (8.8%), episodes of small and large bowel ischemia 17 (11.6%), pseudomembranous colitis 12 (8.3%) and diverticulitis 5 (3.4%). Mesenteric ischemia was responsible for 11 (37.9%) of the 29 deaths. Two hundred and ninety-three patients were revascularized without extracorporeal circulation during this study. In this group, we were able to pinpoint 5 (1.7%) GI complications with 3 cases of mesenteric ischemia. Multivariate analysis identified renal insufficiency, prolonged intubation and sepsis as significant, predictive variables of GI complications for the 2 groups of patients whereas the Parsonnet score and stroke were predictive for the second group., Conclusions: Although cardiac surgery is now being performed on older patients with significant comorbidity, we could not demonstrate a significant increase of GI complications after cardiac surgery. Off-pump coronary artery bypass does not seem to protect patients from these complications.

This study was designed in order to validate the respiratory mechanical variables measured by the Puritan-Bennett 7200a ventilator equipped with the 30/40 module. Two ventilators were connected to a lung model and submitted to several breathing patterns by modifying the respiratory rate, the tidal volume, the inspiratory flow-rate and the model resistance. The inspiratory flow-rate (V), tidal volume (VT), peak inspiratory pressure (Pmax), plateau pressure (Pplat) and PEEP measured by the ventilators were compared with the same variables measured at the connection between the breathing circuit and the lung model. The compliance (C30/40) and the resistance (R30/40) calculated by the 30/40 module were compared with those calculated by using the variables measured by the reference equipment. Both ventilators made a constant underestimation of V by 2.8 and 3.7 L.min-1, respectively. The VT was measured with a mean error of less than 10 ml but did not reflect the preselected values in the presence of an intrinsic PEEP. The Pplat was overestimated by 7 and 10%, respectively. The same calibration error was observed with Pmax which was also affected by a pressure gradient due to the resistance of the breathing circuit. Even in the absence of intrinsic PEEP, C30/40 presented an error due to the combination of the measurement errors on VT, Pplat and PEEP. Finally, R30/40 presented a high percentage of error due to the combination of the measurement errors on V, Pmax, and Pplat, and to a sporadic aberrant selection of V. Due to these numerous sources of error, the two ventilators studied did not give reliable estimates of resistance and compliance.(ABSTRACT TRUNCATED AT 250 WORDS)