A Role for Antimicrobial Stewardship in Clinical Sepsis Pathways: A Prospective Interventional Study

© 2017 by The Society for Healthcare Epidemiology of America. All rights reserved. OBJECTIVE To evaluate the impact of early infectious diseases (ID) antimicrobial stewardship (AMS) intervention on inpatient sepsis antibiotic management. DESIGN Interventional, nonrandomized, controlled study. SETTING Tertiary-care referral hospital, Sydney, Australia. PATIENTS Consecutive, adult, non-intensive care unit (non-ICU) inpatients triggering an institutional clinical sepsis pathway from May to August 2015. INTERVENTION All patients reviewed by an ID Fellow within 24 hours of sepsis pathway trigger underwent case review and clinic file documentation of recommendations. Those not reviewed by an ID Fellow were considered controls and received standard sepsis pathway care. The primary outcome was antibiotic appropriateness 48 hours after sepsis trigger. RESULTS In total, 164 patients triggered the sepsis pathway: 6 patients were excluded (previous sepsis trigger); 158 patients were eligible; 106 had ID intervention; and 52 were control cases. Of these 158 patients, 91 (58%) had sepsis, and 15 of these 158 (9.5%) had severe sepsis. Initial antibiotic appropriateness, assessable in 152 of 158 patients, was appropriate in 80 (53%) of these 152 patients and inappropriate in 72 (47%) of these patients. In the intervention arm, 93% of ID Fellow recommendations were followed or partially followed, including 53% of cases in which antibiotics were de-escalated. ID Fellow intervention improved antibiotic appropriateness at 48 hours by 24% (adjusted risk ratio, 1.24; 95% confidence interval, 1.04-1.47; P=.035). The appropriateness agreement among 3 blinded ID staff opinions was 95%. Differences in intervention and control group mortality (13% vs 17%) and median length of stay (13 vs 17.5 days) were not statistically significant. CONCLUSION Sepsis overdiagnosis and delayed antibiotic optimization may reduce sepsis pathway effectiveness. Early ID AMS improved antibiotic management of non-ICU inpatients with suspected sepsis, predominantly by de-escalation. Further studies are needed to evaluate clinical outcomes. Infect Control Hosp Epidemiol 2017;38:1032-1038

Recent Trends on the Future of Graduate Education in the Pharmaceutical Sciences and Research

Harmonization of pharmacy education has to be made a global agenda that will encompass the developments that have taken place in basic, medical, pharmaceutical sciences in serving the needs and expectations of the society. The professional pharmacy curriculum is designed to produce pharmacists who have the abilities and skills to provide drug information, education, and pharmaceutical care to patients; manage the pharmacy and its medication distribution and control systems; and promote public health. Required coursework for all pharmacy students includes pharmaceutical chemistry; pharmaceutics (drug dosage forms, delivery, and disposition in the human body) pharmacology; therapeutics (the clinical use of drugs and dietary supplements in patients); drug information and analysis; pharmacy administration (including pharmacy law, bioethics, health systems, pharmacoeconomics, medical informatics); clinical skills (physical assessment, patient counseling, drug therapy monitoring for appropriate selection, dose, effect, interactions, use); and clinical pharmacy practice in pharmacies, industry, health maintenance organizations, hospital wards, and ambulatory care clinics

Severe acute hepatitis and acute liver failure of unknown origin in children:a questionnaire-based study within 34 paediatric liver centres in 22 European countries and Israel, April 2022

To detect potential concern about severe acute hepatitis in children, we conducted a survey among 50 ERN RARE-LIVER centres. By 26 April 2022, 34 centres, including 25 transplant centres, reported an estimated median of 3-5, 0-2 and 3-5 cases in 2021, 2020 and 2019 and a mean of 2 (range: 0-8) cases between January and April 2022 (mean in 10 large liver transplant centres: 3). Twelve centres reported suspicion of an increase, but no rise. Following a report by the United Kingdom (UK) on 5 April 2022 on the occurrence of cases of severe acute hepatitis in children aged 16 years or under, the World Health Organization (WHO) raised concerns about the possibility of an epidemic [1,2]. By 21 April, 169 possible or confirmed cases were reported fulfilling the WHO case definition [3]. The cause of the hepatitis is unknown but a link to a virus infection has been suggested due to the epidemiological pattern of cases [4,5]. The hepatitis can progress to paediatric acute liver failure (pALF) necessitating urgent liver transplantation to avoid multi-organ failure [6]. We intended to assess whether a rise in incidence of severe acute hepatitis or pALF could be observed between 1 January and 26 April 2022 in comparison to previous years, within the European Reference Network on Hepatological Diseases (ERN RARE-LIVER) [7]

Estimation of Influenza Vaccine Effectiveness from Routine Surveillance Data

BACKGROUND: Influenza vaccines are reviewed each year, and often changed, in an effort to maintain their effectiveness against drifted influenza viruses. There is however no regular review of influenza vaccine effectiveness during, or at the end of, Australian influenza seasons. It is possible to use a case control method to estimate vaccine effectiveness from surveillance data when all patients in a surveillance system are tested for influenza and their vaccination status is known. METHODOLOGY/PRINCIPAL FINDINGS: Influenza-like illness (ILI) surveillance is conducted during the influenza season in sentinel general practices scattered throughout Victoria, Australia. Over five seasons 2003-7, data on age, sex and vaccination status were collected and nose and throat swabs were offered to patients presenting within three days of the onset of their symptoms. Swabs were tested using a reverse transcriptase polymerase chain reaction (RT-PCR) test. Those positive for influenza were sent to the World Health Organization (WHO) Collaborating Centre for Reference and Research on Influenza where influenza virus culture and strain identification was attempted. We used a retrospective case control design in five consecutive influenza seasons, and estimated influenza vaccine effectiveness (VE) for patients of all ages to be 53% (95% CI 38-64), but 41% (95% CI 19-57) adjusted for age group and year. The adjusted VE for all adults aged at least 20 years, the age groups for whom a benefit of vaccination could be shown, was 51% (95% CI 34-63). Comparison of VE estimates with vaccine and circulating strain matches across the years did not reveal any significant differences. CONCLUSIONS/SIGNIFICANCE: These estimates support other field studies of influenza vaccine effectiveness, given that theoretical considerations suggest that these values may underestimate true effectiveness, depending on test specificity and the ratio of the influenza ILI attack rate to the non-influenza ILI attack rate. Incomplete recording of vaccination status and under-representation of children in patients from whom a swab was collected limit the data. Improvements have been implemented for prospective studies

Proliferation and estrogen signaling can distinguish patients at risk for early versus late relapse among estrogen receptor positive breast cancers

Introduction: We examined if a combination of proliferation markers and estrogen receptor (ER) activity could predict early versus late relapses in ER-positive breast cancer and inform the choice and length of adjuvant endocrine therapy. Methods: Baseline affymetrix gene-expression profiles from ER-positive patients who received no systemic therapy (n = 559), adjuvant tamoxifen for 5 years (cohort-1: n = 683, cohort-2: n = 282) and from 58 patients treated with neoadjuvant letrozole for 3 months (gene-expression available at baseline, 14 and 90 days) were analyzed. A proliferation score based on the expression of mitotic kinases (MKS) and an ER-related score (ERS) adopted from Oncotype DX® were calculated. The same analysis was performed using the Genomic Grade Index as proliferation marker and the luminal gene score from the PAM50 classifier as measure of estrogen-related genes. Median values were used to define low and high marker groups and four combinations were created. Relapses were grouped into time cohorts of 0-2.5, 0-5, 5-10 years. Results: In the overall 10 years period, the proportional hazards assumption was violated for several biomarker groups indicating time-dependent effects. In tamoxifen-treated patients Low-MKS/Low-ERS cancers had continuously increasing risk of relapse that was higher after 5 years than Low-MKS/High-ERS cancers [0 to 10 year, HR 3.36; p = 0.013]. High-MKS/High-ERS cancers had low risk of early relapse [0-2.5 years HR 0.13; p = 0.0006], but high risk of late relapse which was higher than in the High-MKS/Low-ERS group [after 5 years HR 3.86; p = 0.007]. The High-MKS/Low-ERS subset had most of the early relapses [0 to 2.5 years, HR 6.53; p < 0.0001] especially in node negative tumors and showed minimal response to neoadjuvant letrozole. These findings were qualitatively confirmed in a smaller independent cohort of tamoxifen-treated patients. Using different biomarkers provided similar results. Conclusions: Early relapses are highest in highly proliferative/low-ERS cancers, in particular in node negative tumors. Relapses occurring after 5 years of adjuvant tamoxifen are highest among the highly-proliferative/high-ERS tumors although their risk of recurrence is modest in the first 5 years on tamoxifen. These tumors could be the best candidates for extended endocrine therapy

Endotracheal intubation skill acquisition by medical students

During the course of their training, medical students may receive introductory experience with advanced resuscitation skills. Endotracheal intubation (ETI – the insertion of a breathing tube into the trachea) is an example of an important advanced resuscitation intervention. Only limited data characterize clinical ETI skill acquisition by medical students. We sought to characterize medical student acquisition of ETI procedural skill.11Presented as a poster discussion on 17 October 2007 at the annual meeting of the American Society of Anesthesiologists in San Francisco, CA.The study included third-year medical students participating in a required anesthesiology clerkship. Students performed ETI on operating room patients under the supervision of attending anesthesiologists. Students reported clinical details of each ETI effort, including patient age, sex, Mallampati score, number of direct laryngoscopies and ETI success. Using mixed-effects regression, we characterized the adjusted association between ETI success and cumulative ETI experience.ETI was attempted by 178 students on 1,646 patients (range 1–23 patients per student; median 9 patients per student, IQR 6–12). Overall ETI success was 75.0% (95% CI 72.9–77.1%). Adjusted for patient age, sex, Mallampati score and number of laryngoscopies, the odds of ETI success improved with cumulative ETI encounters (odds ratio 1.09 per additional ETI encounter; 95% CI 1.04–1.14). Students required at least 17 ETI encounters to achieve 90% predicted ETI success.In this series medical student ETI proficiency was associated with cumulative clinical procedural experience. Clinical experience may provide a viable strategy for fostering medical student procedural skills

Toxin-Specific Antibodies for the Treatment of Clostridium difficile: Current Status and Future Perspectives †

Therapeutic agents targeting bacterial virulence factors are gaining interest as non-antibiotic alternatives for the treatment of infectious diseases. Clostridium difficile is a Gram-positive pathogen that produces two primary virulence factors, enterotoxins A and B (TcdA and TcdB), which are responsible for Clostridium difficile-associated disease (CDAD) and are targets for CDAD therapy. Antibodies specific for TcdA and TcdB have been shown to effectively treat CDAD and prevent disease relapse in animal models and in humans. This review summarizes the various toxin-specific antibody formats and strategies under development, and discusses future directions for CDAD immunotherapy, including the use of engineered antibody fragments with robust biophysical properties for systemic and oral delivery

Aluminum oxide barrier coatings on polymer films for food packaging applications

In the field of packaging, barrier layers are functional films, which can be applied to polymeric substrates with the objective of enhancing their end-use properties. For food packaging applications, the packaging material is required to preserve packaged food stuffs and protect them from a variety of environmental influences, particularly moisture and oxygen ingress and UV radiation. Aluminum metallized films are widely used for this purpose. More recently, transparent barrier coatings based on aluminum oxide or silicon oxide have been introduced in order to fulfill requirements such as product visibility, microwaveability or retortability. With the demand for transparent barrier films for low-cost packaging applications growing, the use of high-speed vacuum deposition techniques, such as roll-to-roll metallizers, has become a favorable and powerful tool. In this study, aluminum oxide barrier coatings have been deposited onto biaxially oriented polypropylene and polyethylene terephthalate film substrates via reactive evaporation using an industrial 'boat-type' roll-to-roll metallizer. The coated films have been investigated and compared to uncoated films in terms of barrier properties, surface topography, roughness and surface energy using scanning electron microscopy, atomic force microscopy and contact angle measurement. Coating to substrate adhesion and coating thickness have been examined via peel tests and transmission electron microscopy, respectively. © 2013 Elsevier B.V