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A Cluster of Cefepime-induced Neutropenia during Outpatient Parenteral Antimicrobial Therapy
No full textA cluster of cefepime-induced neutropenia (CIN) was identified from June 2017 to May 2018 in a regional outpatient parenteral antimicrobial therapy population. Our data suggest prolonged courses of cefepime (≥2 weeks), administered by rapid intravenous push, were associated with a higher risk of CIN
Correction: Healthcare professionals\u27, students\u27, patients\u27 and donors\u27 perceptions of stem cell research and therapy: A systematic review protocol (BMJ Open (2019) 9 (e025801) DOI: 10.1136/bmjopen-2018-025801)
No full textThis article was previously published with incorrect affiliation of Dr Malissa Kay Shaw due to a software error. The correct affiliation of Dr Malissa Kay Shaw is: Graduate Institute of Humanities in Medicine, Taipei Medical University, Taipei, Taiwan
Duration of Exposure to Antipseudomonal β-Lactam Antibiotics in the Critically Ill and Development of New Resistance
No full textStudy Objective: Minimizing the duration of broad-spectrum antimicrobial exposure in the critically ill is a commonly used strategy aimed at preventing resistance. Our objective was to correlate the duration of exposure to antipseudomonal β-lactam antibiotics with the development of new resistance in critically ill patients. Design: Single-center, retrospective cohort study. Setting: A large, academic, tertiary care hospital. Patients: A total of 7118 adults with a discharge diagnosis of severe sepsis or septic shock who received at least one dose of cefepime, meropenem, or piperacillin-tazobactam during their hospitalization between 2010 and 2015. Measurements and Main Results: Cohort entry was defined as the first day of any antipseudomonal β-lactam initiation, and exposure was defined as the cumulative days of any antipseudomonal β-lactam exposure during the 60-day follow-up period. The primary outcome was development of new resistance to any antipseudomonal β-lactam \u3e 3 days after cohort entry. New resistance was defined as detection of resistance to any antipseudomonal β-lactam not identified within 180 days before cohort entry. Patients without an outcome (i.e., did not develop new resistance) or who died by day 60 were censored. Cox proportional hazards models were performed to assess the risk of development of new resistance to any antipseudomonal β-lactam with each additional day of exposure. Analyses of each individual antipseudomonal β-lactam were evaluated as secondary outcomes. Each additional day of exposure to any antipseudomonal β-lactam resulted in an adjusted hazard ratio (aHR) of 1.04 (95% confidence interval [CI] 1.04–1.05) for new resistance development. The risk of developing new resistance to cefepime, meropenem, and piperacillin-tazobactam for each additional day of exposure resulted in an aHR of 1.08 (95% CI 1.07–1.09), 1.02 (95% CI 1.01–1.03), and 1.08 (95% CI 1.06–1.09), respectively. Conclusion: Among critically ill patients who receive antipseudomonal β-lactam antibiotics, each additional day of exposure to cefepime, meropenem, and piperacillin-tazobactam is associated with an increased risk of new resistance development
Pharmacy student perceptions of the entrustable professional activities
No full textObjective. To determine pharmacy students’ perceptions and self-reported preparedness to perform the 15 core entrustable professional activities (EPA) established by the American Association of Colleges of Pharmacy for new pharmacy graduates. Methods. A random sample of Doctor of Pharmacy (PharmD) students from all four professional years at four universities were asked to indicate whether each of the 15 EPA statements was relevant to the practice of pharmacy and whether pharmacists were expected to perform the activity in multiple practice settings. Participants rated their self-perceived level of entrustability for each activity and indicated which three EPAs they felt most and least prepared to perform. Results. Four hundred twenty-three usable responses were received. The majority (67% indicated that pharmacists were expected to perform them in multiple practice settings with a high percentage of agreement. Students’ perceived need for supervision decreased from the P1 to P4 years. These data suggest that students’ confidence to perform some activities grew as they gained experience and knowledge. However, in some cases, the self-perceived need for supervision regressed as students better understood the complexity of the activity. The EPA statements students felt most and least prepared to perform varied by year in the program. Conclusion. The core EPA statements were consistently rated by pharmacy students as relevant to pharmacy practice and as an expectation in multiple settings. Students perceived that they require less supervision when performing EPA activities as they progressed through the curriculum
Correction: Deep language space neural network for classifying mild cognitive impairment and Alzheimer-type dementia (PLoS ONE (2018) 13:11 (e0205636) DOI: 10.1371/journal.pone.0205636)
No full textThere are errors in the Funding statement. The correct Funding statement is as follows: This study was funded in part by the Malaysian Ministry of Education via the Fundamental Research Grant Scheme (FRGS)-FRGS/2/2014/ICT07/MUSM/03/1. No additional external funding was received for this study
Sport and exercise in improving outcomes after solid organ transplantation: Overview from a UK meeting
No full textOutcomes after solid organ transplantation continue to improve, but premature loss of life remains a major concern, with death from cerebrovascular disease and cardiovascular disease accounting for around 20% late deaths. There are multiple contributory factors including preexisting, and the posttransplant development of, cardiometabolic conditions (such as hypertension, diabetes mellitus, hyperlipidemia, and obesity). There is accumulating evidence that the regular engagement in exercise is an important factor affecting outcomes before, during, and after transplantation; yet most waitlist candidates and recipients have reduced levels of physical activity. The mechanisms whereby physical activity is associated with better outcomes and a reduction in risk factors for cardiovascular disease are incompletely understood. Attempts to increase physical activity in the transplant population, as in the general population, have had limited success. Use of concepts from Nudge theory provides an evidence-based approach that may help increase physical activity and so reduce premature mortality. Both National and International Transplant Games provide a vehicle for increasing physical activity in this population and may also help to reduce premature death by providing a forum for mutual support for recipients and their families as well as an excellent forum for highlighting the success and impact of organ donation
Palbociclib and cetuximab in platinum-resistant and in cetuximab-resistant human papillomavirus-unrelated head and neck cancer: a multicentre, multigroup, phase 2 trial
No full textBackground: Most head and neck squamous-cell carcinomas (HNSCCs) are driven by p16INK4A inactivation and cyclin D1 overexpression that results in hyperactivation of cyclin-dependent kinase 4 and 6 (CDK4/6), rather than by the human papillomavirus (HPV). Deregulated cyclin D1 expression also causes resistance to EGFR inhibitors. We previously reported that palbociclib (a selective CDK4/6 inhibitor) given with cetuximab (an EGFR inhibitor) was safe. The aim of this study was to establish the proportion of patients achieving an objective response with palbociclib and cetuximab in recurrent or metastatic HNSCC. Methods: We did a multicentre, multigroup, phase 2 trial to evaluate the activity of palbociclib and cetuximab in platinum-resistant (group 1) and cetuximab-resistant (group 2) HPV-unrelated HNSCC. The study was done across eight university sites in the USA. Eligibility required measurable disease (according to Response Evaluation Criteria in Solid Tumors, version 1·1 [RECIST 1·1]), Eastern Cooperative Oncology Group (ECOG) performance status of 0–2, age of 18 years or older, and disease progression on platinum but cetuximab-naive (group 1) or disease progression on cetuximab (group 2). All patients received palbociclib orally (125 mg/day, on days 1–21) and intravenous cetuximab (400 mg/m2 on cycle one, day 1, then 250 mg/m2 once per week) in 28-day cycles. The primary endpoint was objective response (complete responses and partial responses per RECIST 1·1). Analyses were done per protocol. This trial was registered with ClinicalTrials.gov, NCT02101034, and is ongoing, but both groups are closed to accrual. Findings: Between Oct 19, 2015, and Nov 7, 2018, 62 patients were enrolled onto the trial: 30 patients were enrolled in group 1 and 32 in group 2. Median follow-up was 5·4 months (IQR 4·4–12·1) for group 1 and 5·5 months (4·3–8·3) for group 2. In group 1, of 28 evaluable patients, an objective response was achieved by 11 (39%; 95% CI 22–59). In group 2, of 27 evaluable patients, an objective response was achieved by five (19%; 6–38) in group 2. The most common grade 3–4 palbociclib-related adverse event was neutropenia (in 21 [34%] of 62 patients). No treatment-related deaths occurred. Interpretation: In patients with platinum-resistant or cetuximab-resistant HPV-unrelated HNSCC, palbociclib and cetuximab results in promising activity outcomes. Further studies of CDK4/6 inhibitors are warranted in HPV-unrelated HNSCC. Funding: Pfizer
Cluster analysis to define distinct clinical phenotypes among septic patients with bloodstream infections
No full textPrior attempts at identifying outcome determinants associated with bloodstream infection have employed a priori determined classification schemes based on readily identifiable microbiology, infection site, and patient characteristics. We hypothesized that even amongst this heterogeneous population, clinically relevant groupings can be described that transcend old a priori classifications. We applied cluster analysis to variables from three domains: patient characteristics, acuity of illness/clinical presentation and infection characteristics. We validated our clusters based on both content validity and predictive validity. Among 3715 patients with bloodstream infections from Barnes-Jewish Hospital (2008-2015), the most stable cluster arrangement occurred with the formation of 4 clusters. This clustering arrangement resulted in an approximately uniform distribution of the population: Cluster One Surgical Outside Hospital Transfers (21.5%), Cluster Two Functional Immunocompromised Patients (27.9%), Cluster Three Women with Skin and Urinary Tract Infection (28.7%) and Cluster Four Acutely Sick Pneumonia (21.8%). Staphylococcus aureus distributed primarily to Clusters Three (40%) and Four (25%), while nonfermenting Gram-negative bacteria grouped mainly in Clusters Two and Four (31% and 30%). More than half of the pneumonia cases occurred in Cluster Four. Clusters One and Two contained 33% and 31% respectively of the individuals receiving inappropriate antibiotic administration. Mortality was greatest for Cluster Four (33.8%, 27.4%, 19.2%, 44.6%; P\u3c.001), while Cluster One patients were most likely to be discharged to a nursing home. Our results support the potential for machine learning methods to identify homogenous groupings in infectious diseases that transcend old a priori classifications. These methods may allow new clinical phenotypes to be identified potentially improving the severity staging and development of new treatments for complex infectious diseases
Pathogen-Negative Sepsis-An Opportunity for Antimicrobial Stewardship
No full textSepsis is a common reason for empiric antibiotics among hospitalized patients. We found that the median duration of empiric antibiotics (interquartile range) was 6 (4-9) days among 1047 survivivors with pathogen-negative sepsis. These findings suggest that patients with pathogen-negative sepsis could represent an important opportunity for antimicrobial stewardship