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Hepatopancreaticobiliary Resection Arginine Immunomodulation (PRIMe) trial: protocol for a randomised phase II trial of the impact of perioperative immunomodulation on immune function following resection for hepatopancreaticobiliary malignancy

Por: Behman · R. · Auer · R. C. · Bubis · L. · Xu · G. · Coburn · N. G. · Martel · G. · Hallet · J. · Balaa · F. · Law · C. · Bertens · K. A. · Abou Khalil · J. · Karanicolas · P. J.
Introduction

Surgical stress results in immune dysfunction, predisposing patients to infections in the postoperative period and potentially increasing the risk of cancer recurrence. Perioperative immunonutrition with arginine-enhanced diets has been found to potentially improve short-term and cancer outcomes. This study seeks to measure the impact of perioperative immunomodulation on biomarkers of the immune response and perioperative outcomes following hepatopancreaticobiliary surgery.

Methods and analysis

This is a 1:1:1 randomised, controlled and blinded superiority trial of 45 patients. Baseline and perioperative variables were collected to evaluate immune function, clinical outcomes and feasibility outcomes. The primary outcome is a reduction in natural killer cell killing as measured on postoperative day 1 compared with baseline between the control and experimental cohorts.

Ethics and dissemination

This trial has been approved by the research ethics boards at participating sites and Health Canada (parent control number: 223646). Results will be distributed widely through local and international meetings, presentation, publication and ClinicalTrials.gov (identifier: NCT04549662). Any modifications to the protocol will be communicated via publications and ClinicalTrials.gov.

Trial registration number

ClinicalTrials.gov identifier: NCT04549662.

Epigenetic repression of antiviral genes by SARS-CoV-2 NSP1

by Dimitrios G. Anastasakis, Daniel Benhalevy, Nicolas Çuburu, Nihal Altan-Bonnet, Markus Hafner

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades the innate immune machinery through multiple viral proteins, including nonstructural protein 1 (NSP1). While NSP1 is known to suppress translation of host mRNAs, the mechanisms underlying its immune evasion properties remain elusive. By integrating RNA-seq, ribosome footprinting, and ChIP-seq in A549 cells we found that NSP1 predominantly represses transcription of immune-related genes by favoring Histone 3 Lysine 9 dimethylation (H3K9me2). G9a/GLP H3K9 methyltransferase inhibitor UNC0638 restored expression of antiviral genes and restricted SARS-CoV-2 replication. Our multi-omics study unravels an epigenetic mechanism underlying host immune evasion by SARS-CoV-2 NSP1. Elucidating the factors involved in this phenomenon, may have implications for understanding and treating viral infections and other immunomodulatory diseases.

Regional variation and temporal trends in transcatheter and surgical aortic valve replacement in Switzerland: A population-based small area analysis

by Carla Schenker, Maria M. Wertli, Lorenz Räber, Alan G. Haynes, Arnaud Chiolero, Nicolas Rodondi, Radoslaw Panczak, Drahomir Aujesky

Background

Aortic valve stenosis (AS) is the most common valvular heart disease and if severe, is treated with either transcatheter (TAVR) or surgical aortic valve replacement (SAVR). We assessed temporal trends and regional variation of these interventions in Switzerland and examined potential determinants of geographic variation.

Methods

We conducted a population-based analysis using patient discharge data from all Swiss public and private acute care hospitals from 2013 to 2018. We generated hospital service areas (HSAs) based on patient flows for TAVR. We calculated age-standardized mean procedure rates and variation indices (extremal quotient [EQ] and systematic component of variation [SCV]). Using multilevel regression, we calculated the influence of calendar year and regional demographics, socioeconomic factors (language, insurance status), burden of disease, and number of cardiologists/cardiovascular surgeons on geographic variation.

Results

Overall, 8074 TAVR and 11,825 SAVR procedures were performed in 8 HSAs from 2013 to 2018. Whereas the age-/sex-standardized rate of TAVR increased from 12 to 22 procedures/100,000 persons, the SAVR rate decreased from 33 to 24 procedures during this period. After full adjustment, the predicted TAVR and SAVR rates varied from 12 to 22 and 20 to 35 per 100,000 persons across HSAs, respectively. The regional procedure variation was low to moderate over time, with a low overall variation in TAVR (EQ 1.9, SCV 3.9) and SAVR (EQ 1.6, SCV 2.2). In multilevel regression, TAVR rates increased annually by 10% and SAVR rates decreased by 5%. Determinants of higher TAVR rates were older age, male sex, living in a German speaking area, and higher burden of disease. A higher proportion of (semi)private insurance was also associated with higher TAVR and lower SAVR rates. After full adjustment, 10.6% of the variance in TAVR and 18.4% of the variance in SAVR remained unexplained. Most variance in TAVR and SAVR rates was explained by language region and insurance status.

Conclusion

The geographic variation in TAVR and SAVR rates was low to moderate across Swiss regions and largely explained by differences in regional demographics and socioeconomic factors. The use of TAVR increased at the expense of SAVR over time.

Effects of service dogs on children with ASD’s symptoms and parents’ well-being: On the importance of considering those effects with a more systemic perspective

by Nicolas Dollion, Margot Poirier, Florian Auffret, Nathe François, Pierrich Plusquellec, Marine Grandgeorge, Handi’Chiens , Fondation Mira

The integration of a service dog can have numerous benefits for children with Autism Spectrum Disorder (ASD). However, although integration takes place within a family, little is known about the dynamics of these benefits on the family microsystem. Thus, the aim of our study was to propose a more systemic perspective, not only by investigating the benefits of SD integration, but also by exploring the relationships between improvements in children with ASD, parents’ well-being, parenting strategies and the quality of the child-dog relationship. Twenty parent-child with ASD dyads were followed before, as well as 3 and 6 months after service dog integration. At each stage, parents completed an online survey which included: the Autism Behavior Inventory (ABI-S), the State-Trait Anxiety Inventory (STAI-Y), the Parenting Stress Index Short Version (PSI-SF), the Monash Dog Owner Relationship Scale (MDORS) and the Parenting Styles and Dimensions Questionnaire (PSDQ). First, repeated measure one-way ANOVAs revealed that both children’s ASD symptoms and parents’ anxiety decreased significantly after service dog integration. Additionally, Spearman correlations revealed that the more ASD symptoms decreased, the more parent’s anxiety and parenting stress also decreased. Second, the quality of the child-dog relationship appeared to contribute to those benefits on both children’s ASD symptoms and parents’ well-being. Interestingly, parenting strategies seemed to adapt according to these benefits and to the quality of the child-dog relationship. Through a more systemic perspective, this study highlighted that the integration of a service dog involved reciprocal and dynamic effects for children with ASD and their parents, and shed new light on the processes that may underlie the effects of a service dog for children with ASD.

A longitudinal investigation of structural empowerment profiles among healthcare employees

Abstract

Purpose

Research on structural empowerment has typically adopted a variable-centered perspective, which is not ideal to study the combined effects of structural empowerment components. This person-centered investigation aims to enhance our knowledge about the configurations, or profiles, of healthcare employees' perceptions of the structural empowerment dimensions present in their workplace (opportunity, information, support, and resources). Furthermore, this study considers the replicability and stability of these profiles over a period of 2 years, and their outcomes (perceived quality of care, and positive and negative affect).

Design

Participants completed the same self-reported questionnaires twice, 2 years apart.

Methods

A sample of 633 healthcare employees (including a majority of nurses and nursing assistants) participated. Latent transition analyses were performed.

Results

Five profiles were identified: Low Empowerment, High Information, Normative, Moderately High Empowerment, and High Empowerment. Membership into the Normative and Moderately High Empowerment profiles demonstrated a high level of stability over time (79.1% to 83.2%). Membership in the other profiles was either moderately stable (43.5% for the High Empowerment profile) or relatively unstable (19.7% to 20.4% for the Low Empowerment and High Information profiles) over time. More desirable outcomes (i.e., higher positive affect and quality of care, and lower negative affect) were observed in the High Empowerment profile.

Conclusions

These results highlight the benefits of high structural empowerment, in line with prior studies suggesting that structural empowerment can act as a strong organizational resource capable of enhancing the functioning of healthcare professionals. These findings additionally demonstrate that profiles characterized by the highest or lowest levels of structural empowerment were less stable over time than those characterized by more moderate levels.

Clinical Relevance

From an intervention perspective, organizations and managers should pay special attention to employees perceiving low levels of structural empowerment, as they experience the worst outcomes. In addition, they should try to maintain high levels of structural empowerment within the High Empowerment profile, as this profile is associated with the most desirable consequences. Such attention should be fruitful, considering the instability of the High Empowerment and Low Empowerment profiles over time.

Registration

NCT04010773 on ClinicalTrials.gov (4 July, 2019).

COVID-19’s impact on worker stress in human service organizations: The mediating role of inclusion

by Magdalena Calderón-Orellana, Andrés Aparicio, Nicolás López–Huenante

Human service organizations faced extraordinary challenges due to COVID-19. Despite the increasing interest and research in this new scenario, there has been limited discussion about the impact of COVID-19 on workers, the challenges they faced, and the resulting stress. This study aimed to analyze the impact of COVID-19 on work-related stress and the mediating role of inclusion among workers in human service organizations in Chile during the pandemic. The research design was quantitative and involved a sample of 173 workers from civil society organizations who were contacted during the pandemic. The study confirmed that individuals most affected by the pandemic experienced higher levels of work-related stress, and that inclusion played a negative mediating role in this relationship. This article highlights the importance of relationships, decision-making processes, and access to information in reducing stress in post-COVID scenarios for organizations that traditionally handle crises.

Sex differences among children, adolescents and young adults for mental health service use within inpatient and outpatient settings, before and during the COVID-19 pandemic: a population-based study in Ontario, Canada

Por: Moin · J. S. · Vigod · S. N. · Plumptre · L. · Troke · N. · Asaria · M. · Papanicolas · I. · Wodchis · W. P. · Brail · S. · Anderson · G.
Objectives

The pandemic and public health response to contain the virus had impacts on many aspects of young people’s lives including disruptions to daily routines, opportunities for social, academic, recreational engagement and early employment. Consequently, children, adolescents and young adults may have experienced mental health challenges that required use of mental health services. This study compared rates of use for inpatient and outpatient mental health services during the pandemic to pre-pandemic rates.

Design

Population-based repeated cross-sectional study.

Setting

Publicly delivered mental healthcare in primary and secondary settings within the province of Ontario, Canada.

Participants

All children 6–12 years of age (n=2 043 977), adolescents 13–17 years (n=1 708 754) and young adults 18–24 years (n=2 286 544), living in Ontario and eligible for provincial health insurance between March 2016 and November 2021.

Primary outcome measures

Outpatient mental health visits to family physicians and psychiatrists for: mood and anxiety disorders, alcohol and substance abuse disorders, other non-psychotic mental health disorders and social problems. Inpatient mental health visits to emergency departments and hospitalisations for: substance-related and addictive disorders, anxiety disorders, assault-related injuries, deliberate self-harm and eating disorders. All outcomes were analysed by cohort and sex.

Results

During the pandemic, observed outpatient visit rates were higher among young adults by 19.01% (95% CI: 15.56% to 22.37%; 209 vs 175 per 1000) and adolescent women 24.17% (95% CI: 18.93% to 29.15%; 131 vs 105 per 1000) for mood and anxiety disorders and remained higher than expected. Female adolescents had higher than expected usage of inpatient care for deliberate self-harm, eating disorders and assault-related injuries.

Conclusions

Study results raise concerns over prolonged high rates of mental health use during the pandemic, particularly in female adolescents and young women, and highlights the need to better monitor and identify mental health outcomes associated with COVID-19 containment measures and to develop policies to address these concerns.

Tiempo de respuesta al timbre; una oportunidad para mejorar el flujo de trabajo

Introducción. Actualmente el timbre conecta a los pacientes con la expectativa de una asistencia inmediata cuando perciben una necesidad, ya sea para asistencia de rutina o tengan un cambio agudo en su condición. El tiempo de atención al timbre impacta en la calidad de atención, satisfacción del paciente, y el flujo de trabajo. El objetivo fue describir el tiempo promedio de la respuesta al timbre en la Unidad Coronaria. Metodología. Estudio transversal del tiempo de respuesta al timbre estratificado por turno. Se recogieron datos sociodemográficos de los pacientes, los motivos de la llamada al timbre, y la satisfacción de los pacientes de forma anónima y digital. Resultados. Se analizaron 200 timbres, con un tiempo promedio de 5’42”. El promedio de edad de los pacientes que accionaron el timbre fue de 56 años, de los cuales 51% eran mujeres. Los principales motivos de llamada fueron la movilización (24.9%) e higiene/eliminación (19.2%), y los pacientes se mostraron satisfechos siempre o casi siempre (81%) con el tiempo de atención al timbre. No se halló una asociación entre los días de internación y la cantidad de llamadas al timbre. Discusión. A pesar de que el tiempo es superior a los “minutos dorados”, los pacientes presentan un elevado grado de satisfacción. La variabilidad de los tiempos en los distintos turnos y los principales motivos de llamada por turno muestran un enorme desafío en la gestión de enfermería para anticipar y priorizar las necesidades que el paciente transmite a través del timbre.

Abstract

Introduction. Currently, the call light connects patients with the expectation of immediate assistance when they perceive a need, whether it is for routine assistance or a sudden change in their condition. The response time to the call bell impacts the quality of care, patient satisfaction, and workflow. The objective of this study was to describe the average response time to the call bell in the Coronary Unit. Methodology. A cross-sectional study of response time to the call bell stratified by shift, over 3 days, with a minimum of 7 days between each day. Sociodemographic data of patients, reasons for the call bell, and patient satisfaction were collected anonymously and digitally. Results. 200 call bells were analyzed, with an average response time of 5'42". The average age was 56 years, with 51% being female. The main reasons for calling were mobilization (24.9%) and hygiene/elimination (19.2%). Most patients were satisfied with the response time to the call bell (81% always or almost always). There was no association found between length of stay and the number of call bells. Discussion. Despite the response time being longer than the "golden minutes," patients show a high degree of satisfaction. The variability of response times in different shifts and the main reasons for calling by shift show a huge challenge in nursing management to anticipate and prioritize the needs that the patient expresses through the call bell.

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