2023 White Paper on Recent Issues in Bioanalysis: ISR for ADA Assays, the Rise of dPCR vs qPCR, International Reference Standards for Vaccine Assays, Anti-AAV TAb Post-Dose Assessment, NanoString Validation, ELISpot as Gold Standard (Part 3 - Recommendations on Gene Therapy, Cell Therapy, Vaccines Immunogenicity & Technologies; Biotherapeutics Immunogenicity & Risk Assessment; ADA/NAb Assay/Reporting Harmonization).

The 17th Workshop on Recent Issues in Bioanalysis (17th WRIB) took place in Orlando, FL, USA on June 19-23, 2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 17th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on "EU IVDR 2017/746 Implementation and impact for the Global Biomarker Community: How to Comply with these NEW Regulations" and on "US FDA/OSIS Remote Regulatory Assessments (RRAs)" were the special features of the 17th edition. As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues. This 2023 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2023 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations on Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity. Part 1A (Mass Spectrometry Assays and Regulated Bioanalysis/BMV), P1B (Regulatory Inputs) and Part 2 (Biomarkers, IVD/CDx, LBA and Cell-Based Assays) are published in volume 16 of Bioanalysis, issues 8 and 9 (2024), respectively.

The Experience of Burnout in the SRNA Population and Association With Situational and Demographic Factors.

There is limited research regarding student registered nurse anesthetist (SRNA) burnout. To our knowledge there is no recently published work that has explored the associations between characteristics of SRNAs and burnout. Addressing this gap could establish the SRNA experience of burnout, identify demographic characteristics and situational factors that may correlate with burnout, and lay the foundation for future research. The purpose of this exploratory descriptive study was to assess the SRNA experience of burnout and any relationship between burnout to demographic or situational factors via the Oldenburg Burnout Inventory-S and demographic questions.The research questions were: 1) Do SRNAs experience different levels of burnout during the didactic curricula and/or clinical training element of nurse anesthesia school? 2) Is there an association between SRNA burnout and demographic or situational factors? Power analysis set the minimum n at 421. Five hundred thirty SRNAs responded to the randomized survey through the American Association of Nurse Anesthesiology. Data analysis was conducted using one-way ANOVA, Spearman's rho, 2-tailed t-test, and Chi square analysis. More hours in class per week correlated with lower exhaustion scores. Higher disengagement scores were reported by SRNAs further in their training, while more hours per week in clinical correlated with both higher disengagement scores and increased total burnout scores.

A study on the feasibility of delivering a psychologically informed ward-based intervention on an acute mental health ward.

Acute mental health inpatient wards have been criticized for being nontherapeutic. The study aimed to test the feasibility of delivering a psychologically informed intervention in these settings. This single-arm study evaluated the feasibility of clinical psychologists delivering a ward-based psychological service model over a 6-month period on two acute mental health wards. Data were gathered to assess trial design parameters and the feasibility of gathering patient/staff outcome data. Psychologists were able to deliver key elements of the intervention. Baseline staff and patient participant recruitment targets were met. However, there was significant patient attrition at follow-up, with incorrect contact details on discharge being the primary reason. Implementation of a ward-based psychological intervention appears feasible when implemented flexibly. It is feasible to recruit staff and patient participants and to collect staff outcome measures over a 6-month period. However, greater efforts need to be taken to trace patient movement following discharge.

Barriers to Home Hemodialysis Across Saskatchewan, Canada: A Cross-Sectional Survey of In-Center Dialysis Patients.

BACKGROUND: Despite clinical and lifestyle advantages of home hemodialysis (HHD) compared with in-center hemodialysis (ICHD), it remains underutilized in our province. The aim of the study was to explore the patients' perception and to identify the barriers to use of HHD in Saskatchewan, Canada. OBJECTIVES: The primary objective of the study was to evaluate and explore patient perceptions of HHD and to identify the obstacles for adoption of HHD in Saskatchewan. The secondary objective was to examine variations in the patients' perceptions and barriers to HHD by center (main dialysis units vs satellite dialysis units). DESIGN: This is a cross-sectional observational survey study. SETTING: Two major centers (Regina and Saskatoon) and 5 associated satellite units attached to each center across the province of Saskatchewan. PATIENTS: We approached all prevalent ICHD patients across Saskatchewan, 398 agreed to participate in the study. MEASUREMENTS: Self-reported barriers to HHD were assessed using a questionnaire. METHODS: A questionnaire was designed to determine the patients' perceived barriers to HHD. Descriptive statistics was used to present the data. Chi-square and Mann-Whitney U test were used to compare the patients' responses between main and satellite units. RESULTS: Satisfaction with current dialysis care (91%), increase in utility bills (65%), fear of catastrophic events at home (59%), medicalization of one's home (54%), and knowledge deficits toward treatment modalities (54%) were the main barriers to HHD uptake. Compared with patients dialyzing in our main units, satellite patients chose not to pursue HHD more frequently because they had greater satisfaction with their current dialysis unit care (97% vs 87%, P < .001), felt more comfortable dialyzing under the supervision of medical staff (95% vs 86%, P < .007), could not afford additional utility costs (92% vs 45%, P < .001), were unaware of the risks and benefits of HHD (83% vs 33%, P < .001), had concerns over time commitments for training to HHD (69% vs 32%, P < .001), and had concern for family burnout (60.8% vs 40.6%, P < .001). LIMITATIONS: We used questionnaires to quantify known barriers, and this prevents inclusion of additional barriers that individual patients may consider important. Cross-sectional data can only be used as a snapshot. Only 398 patients agreed to participate, and the results cannot be generalized to 740 prevalent HD patients. We did not capture data on demographics (age, income, and literacy level), comorbidities, and dialysis vintage, which would have been helpful in interpretation of the results. CONCLUSIONS: Satisfaction with in-center care, lack of awareness and education, specifically in the satellite population, concerns with family burnout, expenses associated with utilities, and training time will need to be addressed to increase the uptake of HHD. TRIAL REGISTRATION: The study was not registered on a publicly accessible registry as it did not involve any health care intervention on human participants.

CONTEXTE: Malgré les avantages sur le plan clinique et sur le mode de vie du patient, l'hémodialyse à domicile (HDD) demeure sous-utilisée en Saskatchewan comparativement à l'hémodialyse en centre hospitalier (HDCH). Nous souhaitions explorer les perceptions des patients à l'égard de l'HDD et déterminer les obstacles qui en limitent l'utilisation dans cette province. OBJECTIFS: Dans un premier lieu, l'étude visait à connaître les perceptions des patients à l'égard de l'HDD et à cerner les facteurs limitant son adoption comme modalité en Saskatchewan (Canada). On souhaitait ensuite analyser les différences entre les perceptions des patients et les obstacles limitant l'utilisation de l'HDD selon le centre (service de dialyse principal ou cliniques satellites). TYPE D'ÉTUDE: Une étude transversale et observationnelle sous forme de sondage. CADRE: Deux importants centres hospitaliers (Régina et Saskatoon) et cinq cliniques satellites associées à chacun des centres et réparties dans toute la province. SUJETS: Nous avons approché tous les patients suivant des traitements d'HDCH en Saskatchewan et 398 personnes ont accepté de participer à l'étude. MESURES: Un questionnaire a permis de déterminer les obstacles des participants à l'utilisation de l'HDD. MÉTHODOLOGIE: Un questionnaire a été élaboré pour déterminer les barrières perçues par les patients en ce qui concerne le choix de l'HDD comme modalité. La statistique descriptive a été employée pour la présentation des données. Le test du Chi carré et le test U de Mann-Whitney ont été utilisés pour comparer les réponses des patients entre les centres de dialyse et les cliniques satellites. RÉSULTATS: Les principaux freins à l'adoption de l'HDD étaient la satisfaction avec la modalité actuelle (91 %), l'augmentation des factures des services publics (65 %), la peur qu'un incident catastrophique survienne à la maison (59 %), la médicalisation du domicile (54 %) et le manque de connaissances sur les différentes modalités de traitement (54 %). En comparaison des patients dialysés en centre, les patients des cliniques satellites décidaient plus souvent de ne pas adopter l'HDD parce qu'ils se disaient davantage satisfaits de leurs traitements actuels (97 % [cliniques satellites] c. 87 % [centre]; p<0,001). Ces patients se disaient également plus confortables de suivre leurs traitements sous supervision médicale (95 % c. 86 %; p<0,007), mentionnaient davantage leurs craintes face à une augmentation des coûts en services publics (92 c. 45 %; p<0,001), s'avéraient moins bien informés sur les risques et les bienfaits de l'HDD (83 % c.33 %; p<0,001), étaient plus préoccupés par l'investissement de temps requis pour se familiariser avec les procédures de l'HDD (69 % c. 32 %; p<0,001) et s'inquiétaient davantage des conséquences sur leur famille (60,8 % c. 40,6 %; p<0,001). LIMITES: Nous avons quantifié les facteurs limitant l'adoption de l'HDD à l'aide d'un questionnaire, ce qui a empêché l'inclusion d'obstacles supplémentaires considérés comme importants au plan individuel. Les données transversales ne peuvent être utilisées que comme un instantané. Seulement 398 patients ont accepté de participer à l'étude et ainsi, les résultats ne peuvent être généralisés aux 740 patients dialysés dans les établissements choisis. Nous n'avons pas colligé les données démographiques des patients (âge, niveau de revenus, littéracie), les maladies concomitantes, ni les antécédents de dialyse, ces données auraient été utiles pour l'interprétation des résultats. CONCLUSION: Les freins à l'adoption de l'HDD comme modalité de dialyse, soit la satisfaction envers les soins reçus en centre, le manque de connaissances et de formation pour cette modalité ­ particulièrement chez les patients des cliniques satellites ­ et les préoccupations en regard des conséquences sur la famille, des dépenses associées aux services publics et de l'investissement de temps requis pour se familiariser avec les procédures, devront être abordés si on souhaite que l'HDD soit adoptée par un plus grand nombre de patients. ENREGISTREMENT DE L'ESSAI: L'étude n'a pas été inscrite dans un registre accessible au public puisqu'elle n'implique aucune intervention sur les participants.

Accidental Insertion of a Peritoneal Dialysis Catheter in the Urinary Bladder.

Percutaneous insertion of a peritoneal dialysis (PD) catheter has inherent risks of complications, more so if done "blind" (without fluoroscopy and ultrasound guidance). Despite the perceived disadvantages, there are very few reported cases of mechanical complications after PD catheter insertion. We present an 81-year-old man who underwent percutaneous insertion of dual-cuffed coiled Tenckhoff PD catheter under local anesthesia by a trained nephrologist. The procedure was uneventful, and the patient was discharged 45 min later in a stable state. A day later, he noticed a decline in the urine output. A week later at a scheduled clinic visit, upon unclamping the PD catheter, there was a sudden gush of amber colored fluid. A diagnostic CT scan confirmed the presence of PD catheter entering the abdominal cavity inferior to the umbilicus and the distal end coiled in the urinary bladder. This case illustrates the need for prophylactic Foley catheterization in individuals at high risk for a distended bladder either as a consequence of a mechanical obstruction from an enlarged prostate or due to a neurogenic bladder while undergoing "blind" percutaneous placement.

Association of an Opioid Standard of Practice Intervention With Intravenous Opioid Exposure in Hospitalized Patients.

Importance: Opioids are commonly used to treat pain in hospitalized patients; however, intravenous administration carries an increased risk of adverse effects compared with oral administration. The subcutaneous route is an effective method of opioid delivery with favorable pharmacokinetics. Objective: To assess an intervention to reduce intravenous opioid use, total parenteral opioid exposure, and the rate of patients administered parenteral opioids. Design, Setting, and Participants: A pilot study was conducted in an adult general medical unit in an urban academic medical center. Attending physicians, nurse practitioners, and physician assistants who prescribed drugs were the participants. Use of opioids was compared between a 6-month control period and 3 months following education for the prescribers on opioid routes of administration. Interventions: Adoption of a local opioid standard of practice, preferring the oral and subcutaneous routes over intravenous administration, and education for prescribers and nursing staff on awareness of the subcutaneous route was implemented. Main Outcomes and Measures: The primary outcome was a reduction in intravenous doses administered per patient-day. Secondary measures included total parenteral and overall opioid doses per patient-day, parenteral and overall opioid exposure per patient-day, and daily rate of patients receiving parenteral opioids. Pain scores were measured on a standard 0- to 10-point Likert scale over the first 5 days of hospitalization. Results: The control period included 4500 patient-days, and the intervention period included 2459 patient-days. Of 127 patients in the intervention group, 59 (46.5%) were men; mean (SD) age was 57.6 (18.5) years. Intravenous opioid doses were reduced by 84% (0.06 vs 0.39 doses per patient-day, P < .001), and doses of all parenteral opioids were reduced by 55% (0.18 vs 0.39 doses per patient-day, P < .001). In addition, mean (SD) daily parenteral opioid exposure decreased by 49% (2.88 [0.72] vs 5.67 [1.14] morphine-milligram equivalents [MMEs] per patient-day). The daily rate of patients administered any parenteral opioid decreased by 57% (6% vs 14%; P < .001). Doses of opioids given by oral or parenteral route were reduced by 23% (0.73 vs 0.95 doses per patient-day, P = .02), and mean daily overall opioid exposure decreased by 31% (6.30 [4.12] vs 9.11 [7.34] MMEs per patient-day). For hospital days 1 through 3, there were no significant postintervention vs preintervention differences in mean reported pain score for patients receiving opioid therapy: day 1, -0.19 (95% CI, -0.94 to 0.56); day 2, -0.49 (95% CI, -1.01 to 0.03); and day 3, -0.54 (95% CI, -1.18 to 0.09). However, significant improvement was seen in the intervention group on days 4 (-1.07; 95% CI, -1.80 to -0.34) and 5 (-1.06; 95% CI, -1.84 to -0.27). Conclusions and Relevance: An intervention targeting the use of intravenous opioids may be associated with reduced opioid exposure while providing effective pain control to hospitalized adults.

Integrated motivational interviewing and cognitive-behavioural therapy for bipolar disorder with comorbid substance use.

Although comorbid substance use is a common problem in bipolar disorder, there has been little research into options for psychological therapy. Studies to date have concentrated on purely cognitive-behavioural approaches, which are not equipped to deal with the ambivalence to change exhibited by many towards therapy designed to change substance use. This paper provides the first report of an integrated psychological treatment approach for bipolar disorder with comorbid substance use. The intervention reported combines motivational interviewing and cognitive-behavioural therapy to address ambivalence and equips individuals with strategies to address substance use. Across five individual case studies, preliminary evidence is reported to support the acceptability and the feasibility of this approach. Despite most participants not highlighting their substance use as a primary therapy target, all but one exhibited reduced use of drugs or alcohol at the end of therapy, sustained at 6 months' follow-up. There was some evidence for improvements in mood symptoms and impulsiveness, but this was less clear-cut. The impact of social and relationship issues on therapy process and outcome is discussed. The implications of the current findings for future intervention research in this area are considered.

Rhodanine derivatives as inhibitors of JSP-1.

Dual-specificity phosphatases (DSPs) are a subclass within the protein tyrosine phosphatase family (PTPs). A series of rhodanine-based inhibitors was synthesized and shown to be novel, potent, and selective inhibitors against the DSP family member JNK-stimulating phosphatase-1 (JSP-1). Compounds of this class may be useful for the treatment of inflammatory and proliferative disorders.

Use of fluorescent sequence-specific polyamides to discriminate human chromosomes by microscopy and flow cytometry.

In this paper, we demonstrate the use of synthetic polyamide probes to fluorescently label heterochromatic regions on human chromosomes for discrimination in cytogenetic preparations and by flow cytometry. Polyamides bind to the minor groove of DNA in a sequence-specific manner. Unlike conventional sequence-specific DNA or RNA probes, polyamides can recognize their target sequence without the need to subject chromosomes to harsh denaturing conditions. For this study, we designed and synthesized a polyamide to target the TTCCA-motif repeated in the heterochromatic regions of chromosome 9, Y and 1. We demonstrate that the fluorescently labeled polyamide binds to its target sequence in both conventional cytogenetic preparations of metaphase chromosomes and suspended chromosomes without denaturation. Chromosomes 9 and Y can be discriminated and purified by flow sorting on the basis of polyamide binding and Hoechst 33258 staining. We generate chromosome 9- and Y-specific 'paints' from the sorted fractions. We demonstrate the utility of this technology by characterizing the sequence of an olfactory receptor gene that is duplicated on multiple chromosomes. By separating chromosome 9 from chromosomes 10-12 on the basis of polyamide fluorescence, we determine and differentiate the haplotypes of the highly similar copies of this gene on chromosomes 9 and 11.