2023 White Paper on Recent Issues in Bioanalysis: Deuterated Drugs; LNP; Tumor/FFPE Biopsy; Targeted Proteomics; Small Molecule Covalent Inhibitors; Chiral Bioanalysis; Remote Regulatory Assessments; Sample Reconciliation/Chain of Custody (PART 1A - Recommendations on Mass Spectrometry, Chromatography, Sample Preparation Latest Developments, Challenges, and Solutions and BMV/Regulated Bioanalysis PART 1B - Regulatory Agencies' Inputs on Regulated Bioanalysis/BMV, Biomarkers/IVD/CDx/BAV, Immunogenicity, Gene & Cell Therapy and Vaccine).

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 this NEW Regulation" 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 covers the recommendations on Mass Spectrometry Assays, Regulated Bioanalysis/BMV (Part 1A) and Regulatory Inputs (Part 1B). Part 2 (Biomarkers, IVD/CDx, LBA and Cell-Based Assays) and Part 3 (Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity) are published in volume 16 of Bioanalysis, issues 7 and 8 (2024), respectively.

Knowledge and awareness of infection control practices among nursing professionals: A cross-sectional survey from South Asia and the Middle East.

BACKGROUND: The proficiency of nursing professionals in the infection prevention and control (IPC) practices is a core component of the strategy to mitigate the challenge of healthcare associated infections. AIM: To test knowledge of nurses working in intensive care units (ICU) in South Asia and Middle East countries on IPC practices. METHODS: An online self-assessment questionnaire based on various aspects of IPC practices was conducted among nurses over three weeks. RESULTS: A total of 1333 nurses from 13 countries completed the survey. The average score was 72.8% and 36% of nurses were proficient (mean score > 80%). 43% and 68.3% of respondents were from government and teaching hospitals, respectively. 79.2% of respondents worked in < 25 bedded ICUs and 46.5% in closed ICUs. Statistically, a significant association was found between the knowledge and expertise of nurses, the country's per-capita income, type of hospitals, accreditation and teaching status of hospitals and type of ICUs. Working in high- and upper-middle-income countries (ß = 4.89, 95%CI: 3.55 to 6.22) was positively associated, and the teaching status of the hospital (ß = -4.58, 95%CI: -6.81 to -2.36) was negatively associated with the knowledge score among respondents. CONCLUSION: There is considerable variation in knowledge among nurses working in ICU. Factors like income status of countries, public vs private and teaching status of hospitals and experience are independently associated with nurses' knowledge of IPC practices.

Comparison of ROX index (SpO2/FIO2 ratio/respiratory rate) with a modified dynamic index incorporating PaO2/FIO2 ratio and heart rate to predict high flow nasal cannula outcomes among patients with acute respiratory failure: a single centre retrospective study.

BACKGROUND: High flow nasal cannula (HFNC) is increasingly being used to support patients with acute respiratory failure (ARF) and to avoid need for intubation. However, almost one third of the patients do not respond and require escalation of respiratory support. Previously, ROX index (SpO2/FIO2 [SF] ratio/respiratory rate) has been validated among pneumonia patients to facilitate early recognition of patients likely to fail HFNC and therefore, benefit from timely interventions. However, it has been postulated that incorporation of PaO2/FIO2 (PF) ratio from arterial blood gas (ABG) analysis may better predict the outcome of HFNC compared to indices that utilizes SF ratio. Similarly, heart rate increase after HFNC therapy initiation has been found to be associated with HFNC failure. Therefore, we aimed to compare ROX index with a new modified index to predict HFNC outcomes among ARF patients. MATERIALS AND METHODS: This single centre 2-year retrospective study included ARF patients of varying etiologies treated with HFNC. The modified index incorporated heart rate and substituted PF ratio for SF ratio in addition to respiratory rate. We named the index POX-HR and calculated Delta POX-HR index as the difference pre- and post-HFNC initiation POX-HR. We also recorded ROX index at the time when post-HFNC initiation ABG was done ('post-HFNC initiation ROX') and calculated Delta ROX. HFNC success was defined as no need of escalation of respiratory support or discharged to ward within 48 h of HFNC initiation, or successful wean off HFNC for at least 12 h. Evaluation was performed using area under the receiver operating characteristic curve (AUROC) and cut-offs assessed for prediction of HFNC outcomes. RESULTS: One hundred eleven patients were initiated on HFNC for ARF, of whom 72 patients (64.9%) had HFNC success. Patients with HFNC failure had significantly lower values for all the indices. At median of 3.33 h (IQR 1.48-7.24 h), Delta POX-HR demonstrated the best prediction accuracy (AUROC 0.813, 95% CI 0.726-0.900). A Delta POX-HR > 0.1 was significantly associated with a lower risk of HFNC failure. CONCLUSIONS: Our proposed modified dynamic index (Delta POX-HR) may facilitate early and accurate prediction of HFNC outcomes compared to ROX index among ARF patients of varied etiologies.

Mapping the cultural characteristics of subcontinent students and the challenges to their academic success.

This study explores the cultural characteristics of subcontinent students and maps the characteristics to the challenges to their academic success. Interviews of fifty staff from an Australian university indicated that both teaching and professional staff held similar views on the characteristics of subcontinent students. Significant characteristics included respect for teachers, the need for continual guidance, a tendency to group, and a propensity to negotiate. The identified challenges to the academic success of subcontinent students were a lack of engagement with staff, inadequate critical thinking, poor communication skills, academic integrity issues and unrealistic expectations. Armed with a better understanding of the subcontinent student cohort, this study encourages teaching and professional staff to find ways to develop a more inclusive educational environment that builds students up for success.

In-hospital cardiac arrest incidence and outcomes in the era of COVID-19: an observational study in a Singapore hospital.

BACKGROUND: COVID-19 pandemic has resulted in significant strain on healthcare resources and this requires diligent resource re-allocation. We aim to describe the incidence and outcomes of in-hospital cardiac arrest (IHCA) during this period as compared to non-pandemic period. METHODS: We conducted a retrospective study in a tertiary care hospital in Singapore. The study compared the incidence and outcomes of code blue activations over a 3-month period from March to May 2020 (COVID-19 period) with the same months in 2019 (pre-COVID-19 period). The primary outcome of the study was the rate of survival to hospital discharge for IHCA. The secondary outcomes included incidence of all code blue activation per 1000 hospital admissions, incidence of IHCA per 1000 hospital admissions. OUTCOMES: The rate of survival to hospital discharge for IHCA was 5.88% in the COVID-19 period as compared to 10.0% in the pre-COVID-19 period [odds ratio (OR), 0.72; 95% confidence interval (CI), 0.26-1.95]. Compared to pre-COVID-19 period, there were more IHCA incidences per 1000 hospital admissions in the COVID-19 period (1.86 vs 1.03; OR, 1.81; 95% CI, 0.78-4.41). CONCLUSIONS: The study observed a trend towards higher incidence of IHCA and lower rate of survival to hospital discharge during COVID-19 pandemic compared to pre-COVID-19 period.

Impact of implementing novel automated code blue activation system on in-hospital cardiac arrest: A single center study.

BACKGROUND: Prompt identification and management of patients having clinical deterioration on wards is one of the key steps to reduce in-hospital cardiac arrests (IHCA). Our organization implemented a novel Automated Code Blue Alert and Activation (ACBAA) system since 1st March 2018. METHODS: We conducted a retrospective before-and-after ACBAA system implementation study in JurongHealth Campus (JHC) of National University Health system (NUHS), Singapore. In JHC, code blue can be activated by both manual activation and ACBAA system activation from 1st March 2018. The ACBAA system will be activated when any of the pre-defined peri-arrest criteria is met. The primary outcome of the study was the incidence of IHCA. The secondary outcome included return of spontaneous circulation (ROSC) of IHCA and in-hospital survival to home discharge of code blue activation. OUTCOMES: The incidence of IHCA per 1000 hospital admissions after-ACBAA system implementation was 14.6% lower than before-ACBAA system though not statistically significant [relative risk (RR): 0.86, 95% confidence interval (CI) 0.55-1.34, P > 0.05]. Compared to the before-ACBAA system period, the after-ACBAA system period had a trend for higher rate of survival to home discharge after IHCA (RR: 2.13, 95% CI 0.65-6.93, P > 0.05) with good neurological outcome. CONCLUSIONS: Implementation of a novel ACBAA system has shown a trend in reducing IHCA incidence. In the era of digitalised healthcare system, the ACBAA system is practical and advisable to implement in order to reduce IHCA. Further studies are required to validate the criteria for peri-arrest code blue activation.

Bowel ulceration following tocilizumab administration in a COVID-19 patient.

Tocilizumab, a monoclonal antibody against interleukin-6, has been used to treat cytokine release syndrome (CRS) in a subset of patients with severe COVID-19 disease. Acute ulcerative bowel disease has been only rarely documented in patients treated for rheumatological conditions. The gastrointestinal side effects seen when used in the context of COVID-19 are unknown. We present a case of COVID-19 CRS in which acute terminal ileum and perforated caecal ulceration evolved after tocilizumab exposure. We raise awareness of a possible causal relationship between even a single dose of tocilizumab and gut ulceration in patients with COVID-19. Any such drug enteropathy relationship requires watchful monitoring during upcoming trials of tocilizumab in patients with COVID-19.