Development of a Generic Anti-PEG Antibody Assay Using BioScale’s Acoustic Membrane MicroParticle Technology

Immunogenicity testing for PEGylated biotherapeutics should include methods to detect both anti-protein and anti-PEG antibodies (anti-PEG). Although some methods have been published for the detection of anti-PEG antibodies, the information is incomplete and, in some cases, reagents used (such as Tween-20) are known to interfere with detection. This rapid communication describes the use of BioScale’s Acoustic Membrane MicroParticle (AMMP®) technology using the ViBE® Workstation to measure anti-PEG antibodies in human serum samples. Briefly, a sample spiked with monoclonal human IgG anti-PEG antibody is diluted in buffer and incubated with paramagnetic beads coated with linear chain mPEG to capture anti-PEG antibodies. The complex is then captured on an acoustic membrane coated with Protein A. The change in mass on the membrane caused by the binding of the complex to the membrane results in a signal proportional to the mass of anti-PEG antibodies. The data indicate that an assay with a sensitivity of less than 1000 ng/mL for IgG is achievable. This level of sensitivity is better than current published reports on IgG anti-PEG antibody detection.KEY WORDS: acoustic membrane microparticle technology, anti-peg antibodies, emerging technology, immunogenicity assays, pegylated biotherapeutics     

Looking in the Mirror: Expanding Female Leadership in Academic Medicine

Digestive Diseases and Sciences -     

Impact of COVID-19 Pandemic on Training: Global Perceptions of Gastroenterology and Hepatology Fellows in the USA

Background

The COVID-19 pandemic has impacted numerous facets of healthcare workers’ lives. There have also been significant changes in Gastroenterology (GI) fellowship training as a result of the challenges presented by the pandemic.

Aims

We conducted a national survey of Gastroenterology fellows to evaluate fellows’ perceptions, changes in clinical duties, and education during the pandemic.

Methods

A survey was sent to Gastroenterology (GI) fellows in the USA. Information regarding redeployment, fellow restriction in endoscopy, outpatient clinics and inpatient consults, impact on educational activities, and available wellness resources was obtained. Fellows’ level of agreement with adjustments to clinical duties was also assessed.

Results

One hundred and seventy-seven Gastroenterology fellows responded, and 29.4% were redeployed to non-GI services during the pandemic. COVID-19 impacted all aspects of GI fellowship training in the USA (endoscopy, outpatient clinics, inpatient consults, educational activities). Fellows’ level of agreement in changes to various aspects of fellowship varied. 72.5% of respondents reported that their programs provided them with increased wellness resources to cope with the additional stress during the pandemic. For respondents with children, 17.6% reported no support with childcare.

Conclusions

Our results show that the COVID-19 pandemic has impacted GI fellowship training in the USA in multiple domains, including gastrointestinal endoscopy, inpatient consults, outpatient clinics, and educational conferences. Our study highlights the importance of considering and incorporating fellows’ viewpoints, as changes are made in response to the ongoing pandemic.

     

Pulmonary Function Testing in Patients with Tracheostomies: Feasibility and Technical Considerations

Purpose

Pulmonary function testing (PFT) in patients with tracheostomies has been perceived as difficult to perform and clinically unreliable. We studied the feasibility, quality, repeatability and clinical significance of PFT.

Methods

Patients with tracheostomies that underwent PFT from January 1, 2010 to February 29, 2012 were identified. Clinical history and PFT data were reviewed retrospectively.

Results

Fifty patients (88% men) were identified. Forty-seven (94%) patients were able to perform PFT. Acceptable repeatability was obtained for FVC in 39 (83%) and for FEV1 in 41 (87%). Patients with tracheostomies showed difficulty in meeting ATS end-of-test criteria; only 9 (19%) met plateau criteria and 25 (53%) had exhalation times of greater than 6 s. Obstructive pattern was observed in 30 (64%) and restrictive pattern in 9 (19%). DLCO measurements were attempted in 43 patients and satisfactorily obtained in 34 (79%).

Conclusions

PFT can be performed with reliability in patients with tracheostomies, and they are useful for detecting and classifying types of lung dysfunction.

     

Impact of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) on the speed of triage decision making for emergency department patients presenting with chest pain

Objective: Emergency department (ED) triage for acute cardiac ischemia in the primary teaching hospital in Geneva, Switzerland, is very accurate, but at the cost of very long ED stays. Thus, the authors sought: 1) to determine the impact of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI), incorporated into a computerized electrocardiograph, on length of stay and speed of triage decision making for ED patients presenting with symptoms suggesting acute cardiac ischemia, and 2) to study the ACI-TIPI’s impact on physicians of different training levels. Design: A seven-month prospective clinical trial with alternating-month experimental and control periods. Setting: An urban major teaching hospital in Geneva, Switzerland. Participants: Patients over the age of 18 years presenting to the ED with chest pain or other symptoms suggesting acute cardiac ischemia (acute myocardial infarction or unstable angina pectoris). Emergency department physicians, classified as novice (those in their first ED rotations) and experienced (those in their second or later ED rotations). Patients staying overnight in the ED (n=111) were excluded from the analysis. Intervention: During the experimental months, the computerized electrocardiograph printed the ACI-TIPI probability of acute cardiac ischemia at the top of each subject’s electrocardiogram. During control months, the probability was not provided. Measurements and main results: Among the 418 study subjects, for patients with acute ischemia seen by novice clinicians, the use of the ACI-TIPI decreased ED time from presentation to triage decision and ED release by 0.7 hour (19%) (p=0.007). Subgroup analyses for patients with acute myocardial infarction, patients with unstable angina pectoris, and patients given thrombolytic therapy also showed analogous decreases in ED time consistent with this finding. Other key determinants of ED length of stay included: age, whether the coronary care unit was full, whether patients received thrombolytic therapy, and whether admission was during the night shift. The experimental and control groups did not differ in triage disposition appropriateness or mortality. Conclusions: For ED patients with acute cardiac ischemia evaluated by novice clinicians, the ACI-TIPI substantially speeded ED decision making and triage. The suggestion of an impact on different cardiac ischemia subgroups and mortality deserves further larger clinical trials.     

Work and life stressors and psychological distress in the Canadian working population: a structural equation modelling approach to analysis of the 1994 National Population Health Survey

Work stressors are increasingly recognized as potentially important determinants of mental health status. We examined such relationships using a structural equation modelling approach with data on adult, working Canadians who participated in the first wave of the National Population Health Survey (NPHS). Work stressors formed a composite construct with paths from psychological demands, decision latitude, work social support and job insecurity, each measured through a reduced version of the Job Content Questionnaire. Life stressors also formed a composite construct composed of chronic stressors and recent life events. Psychological distress was the outcome, mediated by the latent effect constructs of mastery and self-esteem. Work stressors had consistently positive total effects on distress (sum of standardized path coefficients from 0.004 to 0.153 across gender-occupation strata), with all of these effects mediated through reduced self-esteem and mastery (work stressors to these mediators: -0.188 to -0.413). Life stressors had larger positive total effects on distress (0.462 to 0.536), with the majority of these effects direct.