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相似文献
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 (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.
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. 相似文献
To characterize the frequency and pattern of hypokalemia (serum potassium level less than 3.5 mmol/L) after theophylline poisoning, we prospectively evaluated 88 consecutive patients with theophylline intoxication (serum theophylline concentration greater than or equal to 0.165 mmol/L). This mean admission serum theophylline concentration of this cohort was 0.331 mmol/L, with a range of 0.165 to 0.982 mmol/L. The simultaneous mean serum potassium concentration was 3.36 mmol/L (range, 2.20 to 5.80 mmol/L). Fifty-three patients (60%) were hypokalemic on hospital arrival. When, on the basis of recent ingestion, patients were separated into acute, chronic, or acute-on-chronic categories of theophylline intoxication, significant differences in serum potassium were found: Patients with acute theophylline intoxication had a mean serum potassium concentration of 2.94 mmol/L; 85% were hypokalemic. In contrast, patients with chronic theophylline intoxication had a mean serum potassium concentration of 3.83 mmol/L, with a 32% frequently of hypokalemia. These data demonstrate that hypokalemia is common after theophylline intoxication and has a significantly higher incidence after acute overdose. The difference in the frequency of hypokalemia between patients with acute vs chronic intoxication has unclear origins but may be related to the disparities in clinical course (particularly the appearance of seizures and cardiac arrhythmias) that have been observed after acute vs chronic theophylline intoxication. 相似文献
Identifying methods to improve assay sensitivity in randomized clinical trials (RCTs) may facilitate the discovery of efficacious pain treatments. RCTs evaluating pain treatments typically use average pain intensity (API) or worst pain intensity (WPI) as the primary efficacy outcome. However, little evidence is available comparing the assay sensitivity of these 2 measures. In this systematic review and meta-analysis, we comprehensively reviewed all low back pain, osteoarthritis pain, fibromyalgia, diabetic peripheral neuropathy pain, and postherpetic neuralgia RCTs that used a parallel group design. Eligibility required: 1) primary RCT report published between 1980 and 2016, 2) comparing 1 or more active, efficacious pharmacologic pain treatment(s) with placebo, and 3) providing data on the standardized effect size (SES) for API as well as WPI for all treatment arms. Twenty-seven active versus placebo comparisons were identified in 23 eligible articles. Using a random-effects meta-analysis, API SES and WPI SES did not differ significantly (difference?=??.021, 95% confidence interval = ?.047 to .004, P?=?.12). The findings indicate that, depending on the objectives of the study, either API or WPI could be used as a primary outcome measure in clinical trials for the chronic pain conditions included in this analysis.
Perspective
Understanding the comparative assay sensitivity of API and WPI may advance pain treatment research. A meta-analysis of trials of efficacious pharmacologic treatments in 5 pain conditions did not show a statistically significant difference between the assay sensitivity of API and WPI. 相似文献
Patients triggering rapid response team (RRT) intervention are at high risk for adverse outcomes. Data on symptom burden of these patients do not currently exist, and current symptom management and communication practices of RRT clinicians are unknown.
Objectives
We sought to identify the symptom experience of RRT patients and observe how RRT clinicians communicate with patients and their families.
Methods
We conducted a prospective observational study from August to December 2015. Investigators attending RRT events measured frequencies of symptom assessment, communication, and supportive behaviors by RRT clinicians. As the rapid response event concluded, investigators measured patient-reported pain, dyspnea, and anxiety using a numeric rating scale of 0 (none) to 10 (most severe), with uncontrolled symptoms defined as numeric rating scale score of ≥4.
Results
We observed a total of 52 RRT events. RRT clinicians assessed for pain during the event in 62% of alert patients, dyspnea in 38%, and anxiety in 21%. Goals of care were discussed during 3% of events and within 24 hours in 13%. For the primary outcome measure, at the RRT event conclusion, 44% of alert patients had uncontrolled pain, 39% had uncontrolled dyspnea, and 35% had uncontrolled anxiety.
Conclusion
Hospitalized patients triggering RRT events have a high degree of uncontrolled symptoms that are infrequently assessed and treated. Although these patients experience an acute change in medical status and are at high risk for adverse outcomes, goals-of-care discussions with RRT patients or families are rarely documented in the period after the events. 相似文献
