Search

Abstract Previously established World Health Organization (WHO) International Standards (IS) for anti-HPV16 and HPV18 antibodies are used to harmonize results across human papillomavirus (HPV) serology assays. Here, we present an international collaborative study to establish ISs for antibodies against HPV6 (NIBSC code 19/298), HPV11 (20/174), HPV31 (20/176), HPV33 (19/290), HPV45 (20/178), HPV52 (19/296) and HPV58 (19/300). The candidate standards were prepared using sera from naturally infected individuals. Each candidate was shown to be monospecific for reactivity against its indicated HPV type except for the HPV11 candidate, which was also reactive against other types. Expression of antibody levels relative to the relevant candidate IS reduced inter-laboratory variation allowing greater comparability between laboratories. Based on these results, the WHO Expert Committee on Biological Standardization established each of the 7 candidates as the 1st IS for antiserum to its indicated HPV type for use in the standardization of HPV pseudovirion-based neutralization and antibody-binding assays.

Parents, particularly mothers, of autistic children may be especially vulnerable to the negative effects of COVID-19. The current longitudinal study examined changes in psychological distress (anxiety, depression, stress) and marital functioning of mothers and fathers of autistic children across three time points between April and October 2020, and the extent to which pre-COVID factors predicted changes in these outcomes. Participants were 94 mothers and 58 fathers of autistic children drawn from a larger longitudinal study about family relationships and autistic children's mental health that began prior to the pandemic. Results indicated that mothers reported higher levels of psychological distress compared to fathers in July and October 2020. Although, on average, levels of psychological distress and marital functioning did not significantly change for mothers and fathers, pre-pandemic child functioning and marital satisfaction predicted individual differences in change in marital satisfaction during the pandemic for mothers. Implications of the findings are discussed.

ABSTRACT: Background: This study aimed to validate respiratory-resolved five-dimensional (5D) flow cardiovascular magnetic resonance (CMR) against real-time two-dimensional (2D) phase-contrast MRI, assess the impact of number of respiratory states, and measure the impact of respiration on hemodynamics in congenital heart disease (CHD) patients. Methods: Respiratory-resolved 5D flow MRI-derived net and peak flow measurements were compared to real-time 2D phase-contrast MRI-derived measurements in 10 healthy volunteers. Pulmonary-to-systemic flow ratios (Qp:Qs) were measured in 19 CHD patients and aortopulmonary collateral burden was measured in 5 Fontan patients. Additionally, the impact of number of respiratory states on measured respiratory-driven net flow changes was investigated in 10 healthy volunteers and 19 CHD patients (shunt physiology, n = 11, single ventricle disease [SVD], n = 8). Results: There was good agreement between 5D flow MRI and real-time 2D phase-contrast–derived net and peak flow. Respiratory-driven changes had a good correlation (rho = 0.64, p

To determine safety and effectiveness of percutaneous interventions performed by interventional radiologists at a single institution over 2 decades in patients with dialysis access steal syndrome (DASS). A retrospective review of fistulograms from 2001 to 2021 (N = 11,658) was performed. In total, 286 fistulograms in 212 patients with surgically created dialysis accesses met inclusion criterion of fistulography for suspected DASS. Chart review collected data regarding patient demographics, comorbidities, access characteristics, fistulography findings, intervention(s) performed, and outcomes. Procedures with and without DASS intervention were compared. Odds ratios (ORs), adjusted for age, sex, comorbidities, access characteristics, and multiple within-patient events, were calculated using logistic regression to determine associations between steal intervention status and outcome variables: (a) major adverse events, (b) access preservation, and (c) follow-up surgery. A percutaneously treatable cause of DASS was present in 128 cases (45%). Treatment of DASS lesions was performed in 118 cases. Fifteen embolizations were also performed in patients without DASS lesions. Technical success of DASS interventions, defined by the Society of Interventional Radiology (SIR) reporting standards, was 94%; 54% of interventions resulted in DASS symptom improvement at a median follow-up of 15 days. Patients with steal intervention had 60% lower odds of follow-up surgery (OR, 0.4; P =.007). There was no difference in major adverse events (P =.98) or access preservation (P =.13) between groups. In this retrospective cohort study, approximately half of DASS fistulograms revealed a percutaneously treatable cause of steal. Over half of DASS interventions resulted in symptomatic relief. Percutaneous intervention was associated with lower odds of follow-up surgery without compromising access preservation. [Display omitted] [ABSTRACT FROM AUTHOR]

Previously established World Health Organization (WHO) International Standards (IS) for anti-HPV16 and HPV18 antibodies are used to harmonize results across human papillomavirus (HPV) serology assays. Here, we present an international collaborative study to establish ISs for antibodies against HPV6 (NIBSC code 19/298), HPV11 (20/174), HPV31 (20/176), HPV33 (19/290), HPV45 (20/178), HPV52 (19/296) and HPV58 (19/300). The candidate standards were prepared using sera from naturally infected individuals. Each candidate was shown to be monospecific for reactivity against its indicated HPV type except for the HPV11 candidate, which was also reactive against other types. Expression of antibody levels relative to the relevant candidate IS reduced inter-laboratory variation allowing greater comparability between laboratories. Based on these results, the WHO Expert Committee on Biological Standardization established each of the 7 candidates as the 1st IS for antiserum to its indicated HPV type for use in the standardization of HPV pseudovirion-based neutralization and antibody-binding assays., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Two candidate International Standards for meningococcal capsular group W and Y (MenW and MenY, respectively) polysaccharides were assessed for their suitability as quantitative standards in various physicochemical assays. The study was designed to evaluate the intended purpose of these standards, namely, to standardize the quantification of the respective polysaccharide content in meningococcal polysaccharide and conjugate vaccines and their intermediate components. Twelve laboratories from eleven different countries participated in the collaborative study of candidate preparations for International Standards for MenW and MenY polysaccharide (coded 16/152 and 16/206, respectively). Unitage was assigned using the Resorcinol assay. Our proposals, on the basis of data from the Resorcinol assay were: 1) candidate standard for MenW polysaccharide (16/152) to be assigned a content of 1.015 ± 0.071 mg MenW polysaccharide per ampoule (expanded uncertainty with coverage factor k = 2.13, corresponding to a 95 % level of confidence) and 2) candidate standard for MenY polysaccharide (16/206) be assigned a content of 0.958 ± 0.076 mg MenY polysaccharide per ampoule (expanded uncertainty with coverage factor k = 2.26, corresponding to a 95 % level of confidence). The amount of polysaccharide per ampoule remained consistent under all stability conditions over a 36-month period., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

An international hybrid meeting held 21-22 June 2023 in Ottawa, Canada brought together regulators, scientists, and industry experts to discuss a set of principles and best practices in the development and implementation of standards. Although the use of international standards (ISs) and international units (IUs) has been an essential part of ensuring human and animal vaccine quality in the past decades, the types and uses of standards have expanded with technological advances in manufacture and testing of vaccines. The needs of stakeholders are evolving in response to the ever-increasing complexity, diversity, and number of vaccine products as well as increasing efforts to replace animal-based potency tests with in vitro assays that measure relevant quality attributes. As such, there must be a concomitant evolution in the design and implementation of both international and in-house standards. Concomitantly, greater harmonization of regulatory expectations must be achieved through collaboration with standard-setting organizations, national control laboratories and manufacturers. Stakeholders provided perspectives on challenges and several recommendations emerged as essential to advancing agreed upon objectives., (Copyright © 2024. Published by Elsevier Ltd.)

At present, quality control of diphtheria vaccines by both manufacturers and national control laboratories relies heavily on in vivo assays to confirm potency. As part of the VAC2VAC project we have developed a monoclonal antibody (mAb) enzyme-linked immunosorbent assay (ELISA) to measure the relative amount and quality of diphtheria toxoid (DTxd) in diphtheria-tetanus based vaccines and believe this test has the potential to play a key role in a control strategy no longer including an in vivo potency test. The mAb ELISA is highly specific, has good dilutional linearity, and is suitable for detecting DTxd in a range of different human vaccine products. We demonstrate the ability of the assay to discriminate between batches of different content and quality using vaccine batches that were prepared to contain differing amounts of DTxd or were altered by exposure to heat or oxidative stress. We also demonstrate successful transfer of the method to other laboratories and show that different diphtheria antigen materials may be able to serve as a reference antigen for local standardization of the method. The assay is ideally suited for incorporation into a consistency approach for routine diphtheria vaccine quality control testing and may be suitable to serve as the stability indicating test in replacement of the current in vivo potency test.

Antigen identity, quantity and integrity are key factors to be evaluated as part of consistency testing of tetanus vaccines. Here we have developed a monoclonal antibody sandwich ELISA to measure the relative amount and quality of tetanus toxoid (TTxd) in human and animal tetanus vaccines. The ELISA is highly specific, has good dilutional linearity, and is suitable for detecting TTxd in a range of different products. We have demonstrated the ability of the assay to discriminate between batches of different content, using vaccine batches that had been prepared to contain differing amounts of TTxd, and of different quality, using samples of non-adjuvanted TTxd that had been exposed to sonication and final lot vaccines that had been exposed to heat or oxidative stress. We have also demonstrated successful transfer of the method to other laboratories and have shown that different tetanus antigen materials may be able to serve as a reference antigen for standardization of the method. The results show this test has the potential to play a key role in a control strategy no longer including an in vivo potency test.

An international collaborative study was jointly organised by the World Health Organization (WHO) and the European Directorate for the Quality of Medicines & HealthCare (EDQM) to establish the WHO 3 rd International Standard (IS) for Prekallikrein activator (PKA) and European Pharmacopoeia (Ph. Eur.) PKA in albumin Biological Reference Preparation (BRP) batch 7. Twenty-six laboratories took part in the study to calibrate these replacement batches, as well as an additional reserve batch for the WHO IS, against the current WHO 2 nd IS for PKA (02/168). Ph. Eur. PKA in albumin BRP batch 6 was also included to evaluate the continuity of the consecutive batches of BRP. The centrally calculated overall Huber's means based on the results from laboratories with at least two valid assays were 29.6 and 29.6 IU/ampoule for the candidate WHO 3 rd IS (Sample A) and reserve batch (Sample B), and were 38.4 and 37.0 IU/vial for the current BRP batch 6 (Sample C) and the candidate BRP batch 7 (Sample D). The intra-laboratory variation expressed as coefficient of variation (CV) ranged between 1.4 and 16.6 %. The inter-laboratory variation expressed as CV based on Huber's means ranged between 4.4 and 5.4 %. The Huber's mean activity of Sample D against Sample C was 36.6 IU/vial with a CV of 1.7 %. These results confirm the good continuity of the consecutive batches of BRP. Based on the results of this study, it is recommended to establish Sample A as the WHO 3 rd IS for PKA with an assigned potency of 30 IU/ampoule and Sample D as the Ph. Eur. PKA in albumin BRP batch 7 with an assigned potency of 37 IU/vial. Sample B is intended to be kept as a future reserve replacement WHO IS., (© Council of Europe 2024.)