A Retrospective Database Analysis of Neonatal Morbidities to Evaluate a Composite Endpoint for Use in Preterm Labor Clinical Trials

Objective To propose and assess a composite endpoint (CE) of neonatal benefit based on neonatal mortality and morbidities by gestational age (GA) for use in preterm labor clinical trials. Study Design A descriptive, retrospective analysis of the Medical University of South Carolina Perinatal Information System database was conducted. Neonatal morbidities were assessed for inclusion in the CE based on clinical significance/risk of childhood neurodevelopmental impairment, frequency, and association with GA in a mother– neonate linked cohort, comprising women with uncomplicated singleton pregnancies delivered at !24 weeks’ GA. Results Among 17,912 mother–neonate pairs, neonates were at a risk of numerous severe but infrequent morbidities. Clinically important, predominantly rare events were combined into a CE comprising neonatal mortality and morbidities, which decreased in frequency with increasing GA. The highest CE frequency occurred at \u3c31 weeks. High frequency of respiratory distress syndrome, bronchopulmonary dysplasia, and sepsis drove the CE. Median length of hospital stay was longer at all GAs in those with the CE compared with those without. Conclusions Descriptive epidemiological assessment and clinical input were used to develop a CE to measure neonatal benefit, comprising clinically meaningful outcomes. These empirical data and CE allowed trials investigating tocolytics to be sized appropriately

Patientâ level Factors and the Quality of Care Delivered in Pediatric Emergency Departments

ObjectiveQuality of care delivered to adult patients in the emergency department (ED) is often associated with demographic and clinical factors such as a patient’s race/ethnicity and insurance status. We sought to determine whether the quality of care delivered to children in the ED was associated with a variety of patientâ level factors.MethodsThis was a retrospective, observational cohort study. Pediatric patients (<18 years) who received care between January 2011 and December 2011 at one of 12 EDs participating in the Pediatric Emergency Care Applied Research Network (PECARN) were included. We analyzed demographic factors (including age, sex, and payment source) and clinical factors (including triage, chief complaint, and severity of illness). We measured quality of care using a previously validated implicit review instrument using chart review with a summary score that ranged from 5 to 35. We examined associations between demographic and clinical factors and quality of care using a hierarchical multivariable linear regression model with hospital site as a random effect.ResultsIn the multivariable model, among the 620 ED encounters reviewed, we did not find any association between patient age, sex, race/ethnicity, and payment source and the quality of care delivered. However, we did find that some chief complaint categories were significantly associated with lower than average quality of care, including fever (â 0.65 points in quality, 95% confidence interval [CI] = â 1.24 to â 0.06) and upper respiratory symptoms (â 0.68 points in quality, 95% CI = â 1.30 to â 0.07).ConclusionWe found that quality of ED care delivered to children among a cohort of 12 EDs participating in the PECARN was high and did not differ by patient age, sex, race/ethnicity, and payment source, but did vary by the presenting chief complaint.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142981/1/acem13347_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142981/2/acem13347-sup-0001-DataSupplementS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142981/3/acem13347.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142981/4/acem13347-sup-0002-DataSupplementS2.pd

Point prevalence of penicillin allergy in hospital inpatients

Ten percent of the general population believe themselves to be allergic to beta-lactams, many erroneously. Alternative, broader-spectrum antibiotics are associated with increased drug costs and colonization with resistant organisms. A point prevalence study of hospital inpatients determined the local reported rate of penicillin allergy, the nature of allergy described, evidence of antimicrobial resistance and antimicrobial regimens used as a result. Of the 583 patients assessed, the overall rate of penicillin allergy was 13.7% [95% confidence interval (CI) 11-17%]. Rash was the most commonly reported reaction (27.5%, 95% CI 18-39%). Details of the nature of the penicillin allergy were poorly recorded on drug charts. Significantly higher rates of meticillin-resistant Staphylococcus aureus were seen in the allergic cohort (P=0.0065) compared with those without a label of penicillin allergy; this was also seen for vancomycin-resistant enterococci, but this did not reach significance. This study demonstrates an increase in detection of resistant organisms in penicillin-allergic patients which may result from use of broader-spectrum antibiotics in this group.Supports Open AccessPublished version, accepted version (12 month embargo

Is there a role of penicillin allergy in developing Clostridioides difficile infection?

Purpose of review To explore the evidence for an association between penicillin allergy, antibiotic prescribing and Clostridioides difficile (CDI) infection. Recent findings Several studies have highlighted the differences in antibiotic prescribing in penicillin allergic patients and the impact on rates of C. difficile infection. Summary Penicillin allergy leads to higher incidences of prescriptions for antibiotics that are known to predispose to CDI. In turn CDI is more common in patients with penicillin allergy. Penicillin allergy is often erroneously ascribed to patients and should be challenged

Impact of penicillin allergy records on antibiotic costs and patient length of hospital stay: a single centre observational retrospective cohort.

Introduction Patients with penicillin allergy records are usually prescribed non-penicillin antibiotics and have worse health outcomes. This study explored the impact of penicillin allergy records on antibiotic treatment costs and on patient length of stay. Methods Patients prescribed a systemic antibacterial agent between April 2016 and March 2018 in a 750 bed English hospital were included. The following data were extracted for each patient hospital spell; age, sex, co-morbidity, infection treated, antibiotic usage (DDD), hospital length of stay, and penicillin allergy status. Multivariable log-linear modelling was used to determine the association between patients labelled as penicillin allergic and total antibiotic costs and length of stay. Using the above models, we estimated the potential reduction in total costs and hospital bed days of ‘de-labelling’ patients with penicillin allergy records. Results Penicillin allergy records were present in 14.3% of hospital admissions and were associated with an increase in non-penicillin antibiotic prescribing, a 28.4% increase in antibiotic costs and 5.5% longer length of hospital stay, relative to patients without a penicillin allergy record. Patients with penicillin allergy records accounted for an excess antibiotic spend of £10,637 (2.61% of annual antibiotic drug spend) and 3,522 excess bed days (3.87% of annual bed days). De-labelling 50% of patients with a self-reported allergy record would save an estimated £5,501 in antibiotic costs and £503,932 through reduced excess bed days Conclusion De-labelling patients with a self-reported allergy record has potential to reduce antibiotic costs but its biggest cost impact is via reduction in excess bed days

Clinical Confirmation of Pan-Amyloid Reactivity of Radioiodinated Peptide ¹²⁴I-p5+14 (AT-01) in Patients with Diverse Types of Systemic Amyloidosis Demonstrated by PET/CT Imaging

There are at least 20 distinct types of systemic amyloidosis, all of which result in the organ-compromising accumulation of extracellular amyloid deposits. Amyloidosis is challenging to diagnose due to the heterogeneity of the clinical presentation, yet early detection is critical for favorable patient outcomes. The ability to non-invasively and quantitatively detect amyloid throughout the body, even in at-risk populations, before clinical manifestation would be invaluable. To this end, a pan-amyloid-reactive peptide, p5+14, has been developed that is capable of binding all types of amyloid. Herein, we demonstrate the ex vivo pan-amyloid reactivity of p5+14 by using peptide histochemistry on animal and human tissue sections containing various types of amyloid. Furthermore, we present clinical evidence of pan-amyloid binding using iodine-124-labeled p5+14 in a cohort of patients with eight (n = 8) different types of systemic amyloidosis. These patients underwent PET/CT imaging as part of the first-in-human Phase 1/2 clinical trial evaluating this radiotracer (NCT03678259). The uptake of 124I-p5+14 was observed in abdominothoracic organs in patients with all types of amyloidosis evaluated and was consistent with the disease distribution described in the medical record and literature reports. On the other hand, the distribution in healthy subjects was consistent with radiotracer catabolism and clearance. The early and accurate diagnosis of amyloidosis remains challenging. These data support the utility of 124I-p5+14 for the diagnosis of varied types of systemic amyloidosis by PET/CT imaging