Serotype 3 Experimental Human Pneumococcal Challenge (EHPC) study protocol: dose ranging and reproducibility in a healthy volunteer population (challenge 3)

Introduction

Since the introduction of pneumococcal conjugate vaccines, pneumococcal disease rates have declined for many vaccine-type serotypes. However, serotype 3 (SPN3) continues to cause significant disease and is identified in colonisation epidemiological studies as one of the top circulating serotypes in adults in the UK. Consequently, new vaccines that provide greater protection against SPN3 colonisation/carriage are urgently needed. The Experimental Human Pneumococcal Challenge (EHPC) model is a unique method of determining pneumococcal colonisation rates, understanding acquired immunity, and testing vaccines in a cost-effective manner. To enhance the development of effective pneumococcal vaccines against SPN3, we aim to develop a new relevant and safe SPN3 EHPC model with high attack rates which could be used to test vaccines using small sample size.

Methods and analysis

This is a human challenge study to establish a new SPN3 EHPC model, consisting of two parts. In the dose-ranging/safety study, cohorts of 10 healthy participants will be challenged with escalating doses of SPN3. If first challenge does not lead into colonisation, participants will receive a second challenge 2 weeks after. Experimental nasopharyngeal (NP) colonisation will be determined using nasal wash sampling. Using the dose that results in ≥50% of participants being colonised, with a high safety profile, we will complete the cohort with another 33 participants to check for reproducibility of the colonisation rate. The primary outcome of this study is to determine the optimal SPN3 dose and inoculation regime to establish the highest rates of NP colonisation in healthy adults. Secondary outcomes include determining density and duration of experimental SPN3 NP colonisation and characterising mucosal and systemic immune responses to SPN3 challenge.

Ethics and dissemination

This study is approved by the NHS Research and Ethics Committee (reference 22/NW/0051). Findings will be published in peer-reviewed journals and reports will be made available to participants.

Efficient assessment of brain fog and fatigue: Development of the Fatigue and Altered Cognition Scale (FACs)

by Timothy R. Elliott, Yu-Yu Hsiao, Kathleen Randolph, Randall J. Urban, Melinda Sheffield-Moore, Richard B. Pyles, Brent E. Masel, Tamara Wexler, Traver J. Wright

Debilitating symptoms of fatigue and accompanying “brain fog” are observed among patients with various chronic health conditions. Unfortunately, an efficient and psychometrically sound instrument to assess these co-occurring symptoms is unavailable. Here, we report the development and initial psychometric properties of the Fatigue and Altered Cognition Scale (the FACs), a measure of self-reported central fatigue and brain fog. Traumatic brain injury (TBI) was chosen to model and develop the FACs due to research team expertise and established links between TBI and the symptom complex. Potential items were generated by researchers and clinicians with experience treating these symptoms, drawing from relevant literature and review of patient responses to measures from past and current TBI studies. The 20 candidate items for the FACs—ten each to assess altered cognition (i.e., brain fog) and central fatigue–were formatted on an electronic visual analogue response scale (eVAS) via an online survey. Demographic information and history of TBI were obtained. A total of 519 participants consented and provided usable data (average age = 40.23 years; 73% female), 204 of whom self-reported a history of TBI (75% reported mild TBI). Internal consistency and reliability values were calculated. Confirmatory factor analysis (CFA) examined the presumed two-factor structure of the FACs and a one-factor solution for comparison. A measurement invariance test of the two latent constructs (altered cognition, fatigue) among participants with and without TBI was conducted. All items demonstrated normal distribution. Cronbach’s alpha coefficients indicated good internal consistency for both factors (α’s = .95). Omega reliability values were favorable (α’s = .95). CFA supported the presumed two-factor model and item loadings which outperformed the one-factor model. Measurement invariance found the two-factor structure was consistent between the two groups. Implications of these findings, study limitations, and potential use of the FACs in clinical research and practice are discussed.

Cardiac response to water activities in children with Long QT syndrome type 1

by Anna Lundström, Urban Wiklund, Annika Winbo, Håkan Eliasson, Marcus Karlsson, Annika Rydberg

Background

Swimming is a genotype-specific trigger in long QT syndrome type 1 (LQT1).

Objective

To examine the autonomic response to water activities in children and adolescents with LQT1.

Methods

In this cross-sectional study, LQT1 patients were age and sex matched to one healthy control subject. Electrocardiograms (ECGs) were recorded during face immersion (FI), swimming, diving, and whole-body submersion (WBS). Heart rate (HR) and heart rate variability (HRV) was measured. The high frequency (HF) component of HRV was interpreted to reflect parasympathetic activity, while the low frequency (LF) component was interpreted as reflecting the combined influence of sympathetic and parasympathetic activity on autonomic nervous modulation of the heart.

Results

Fifteen LQT1 patients (aged 7–19 years, all on beta-blocker therapy) and fifteen age and sex matched non-medicated controls were included. No significant ventricular arrhythmias were observed in the LQT1 population during the water activities. Out of these 15 matched pairs, 12 pairs managed to complete FI and WBS for more than 10 seconds and were subsequently included in HR and HRV analyses. In response to FI, the LQT1 group experienced a drop in HR of 48 bpm, compared to 67 bpm in the control group (p = 0.006). In response to WBS, HR decreased by 48 bpm in the LQT1 group and 70 bpm in the control group (p = 0.007). A significantly lower PTOT (p Conclusion

A significantly lower HR decrease in response to water activities was observed in LQT1 subjects on beta-blocker therapy, compared to matched non-medicated controls. The data suggests an impaired parasympathetic response in LQT1 children and adolescents. An aberrant autonomic nervous system (ANS) response may cause an autonomic imbalance in this patient group.

Acute care nurse managers' definitions of and barriers to well‐being: A thematic analysis of open‐ended survey questions

Abstract

Background

During the COVID-19 pandemic, acute care nurse managers functioned in a critical role by helping to advance the mission and goals of their organization while navigating a rapidly evolving healthcare landscape. This resulted in high levels of ongoing job-related stress which is linked to negative physical, psychological, and job-related outcomes. Little is known about the perceptions regarding their own professional well-being during this time.

Aim

The aim of this study was to qualitatively describe acute care nurse managers' perceptions of and barriers to their professional well-being.

Methods

Using a qualitative descriptive approach, nurse managers from a hospital system in the southwestern United States responded to two short-answer, survey-based questions in 2022: (1) “Describe the definition of nurse-manager well-being in your own words” and (2) “What do you feel is your biggest barrier to professional well-being?” Reflexive thematic analysis was utilized to analyze participant responses (N = 80).

Results

Professional well-being is a complex concept influenced by the nurse manager's ability to navigate work–life balance; care for their own physical, emotional, and spiritual selves; give and receive support from stakeholders; and manage feelings of thriving vs. struggling in the role. Barriers most cited as influencing well-being included having too little time to get things done coupled with increasing workloads, feeling stuck in the middle among stakeholders, and coping with ongoing staffing challenges.

Linking Evidence to Action

The definition of and barriers to well-being are influenced by the specific needs and experiences of the nurse manager. While not all barriers can be immediately removed, the identification of individual and organization-specific barriers needs to be taken seriously, reviewed by those who can promote change, and evidence-based solutions for improvement piloted or implemented when feasible.

¿Es más efectiva la fototerapia simple con cortinas reflectantes que la fototerapia doble para tratar la hiperbilirrubinemia en recién nacidos a término?

Objetivo principal: Conocer si el estudio realizado en el artículo original está elaborado con una calidad metodológica consistente como para constituir una evidencia fuerte. Metodología: Revisión crítica de un artículo original siguiendo unas pautas aconsejadas por la revista Evidentia. Resultados principales: Los resultados proponen que el uso de fototerapia simple con cortinas reflectantes es tan efectiva para el tratamiento de la hiperbilirrubinemia neonatal severa como el tratamiento con fototerapia doble. Varios estudios controlados aleatorizados han demostrado la mayor eficacia de la fototerapia al añadirle alrededor de la cuna unas cortinas que reflejaran la luz. Conclusión principal: Este artículo añade datos importantes al cuantificar hasta qué punto pueden ser efectivas las cortinas blancas añadidas a la fototerapia convencional ya que iguala la efectividad a la fototerapia doble. Nivel de evidencia: “alta”, según la escala GRADE.