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Specific nanoprobe design for MRI: Targeting laminin in the blood-brain barrier to follow alteration due to neuroinflammation

by Juan F. Zapata-Acevedo, Mónica Losada-Barragán, Johann F. Osma, Juan C. Cruz, Andreas Reiber, Klaus G. Petry, Amael Caillard, Audrey Sauldubois, Daniel Llamosa Pérez, Aníbal José Morillo Zárate, Sonia Bermúdez Muñoz, Agustín Daza Moreno, Rafaela V. Silva, Carmen Infante-Duarte, William Chamorro-Coral, Rodrigo E. González-Reyes, Karina Vargas-Sánchez

Chronic neuroinflammation is characterized by increased blood-brain barrier (BBB) permeability, leading to molecular changes in the central nervous system that can be explored with biomarkers of active neuroinflammatory processes. Magnetic resonance imaging (MRI) has contributed to detecting lesions and permeability of the BBB. Ultra-small superparamagnetic particles of iron oxide (USPIO) are used as contrast agents to improve MRI observations. Therefore, we validate the interaction of peptide-88 with laminin, vectorized on USPIO, to explore BBB molecular alterations occurring during neuroinflammation as a potential tool for use in MRI. The specific labeling of NPS-P88 was verified in endothelial cells (hCMEC/D3) and astrocytes (T98G) under inflammation induced by interleukin 1β (IL-1β) for 3 and 24 hours. IL-1β for 3 hours in hCMEC/D3 cells increased their co-localization with NPS-P88, compared with controls. At 24 hours, no significant differences were observed between groups. In T98G cells, NPS-P88 showed similar nonspecific labeling among treatments. These results indicate that NPS-P88 has a higher affinity towards brain endothelial cells than astrocytes under inflammation. This affinity decreases over time with reduced laminin expression. In vivo results suggest that following a 30-minute post-injection, there is an increased presence of NPS-P88 in the blood and brain, diminishing over time. Lastly, EAE animals displayed a significant accumulation of NPS-P88 in MRI, primarily in the cortex, attributed to inflammation and disruption of the BBB. Altogether, these results revealed NPS-P88 as a biomarker to evaluate changes in the BBB due to neuroinflammation by MRI in biological models targeting laminin.

Raman difference spectroscopy and U-Net convolutional neural network for molecular analysis of cutaneous neurofibroma

by Levi Matthies, Hendrik Amir-Kabirian, Medhanie T. Gebrekidan, Andreas S. Braeuer, Ulrike S. Speth, Ralf Smeets, Christian Hagel, Martin Gosau, Christian Knipfer, Reinhard E. Friedrich

In Neurofibromatosis type 1 (NF1), peripheral nerve sheaths tumors are common, with cutaneous neurofibromas resulting in significant aesthetic, painful and functional problems requiring surgical removal. To date, determination of adequate surgical resection margins–complete tumor removal while attempting to preserve viable tissue–remains largely subjective. Thus, residual tumor extension beyond surgical margins or recurrence of the disease may frequently be observed. Here, we introduce Shifted-Excitation Raman Spectroscopy in combination with deep neural networks for the future perspective of objective, real-time diagnosis, and guided surgical ablation. The obtained results are validated through established histological methods. In this study, we evaluated the discrimination between cutaneous neurofibroma (n = 9) and adjacent physiological tissues (n = 25) in 34 surgical pathological specimens ex vivo at a total of 82 distinct measurement loci. Based on a convolutional neural network (U-Net), the mean raw Raman spectra (n = 8,200) were processed and refined, and afterwards the spectral peaks were assigned to their respective molecular origin. Principal component and linear discriminant analysis was used to discriminate cutaneous neurofibromas from physiological tissues with a sensitivity of 100%, specificity of 97.3%, and overall classification accuracy of 97.6%. The results enable the presented optical, non-invasive technique in combination with artificial intelligence as a promising candidate to ameliorate both, diagnosis and treatment of patients affected by cutaneous neurofibroma and NF1.

Cronicidad: Significado construido por los cuidadores y las personas cuidadas

Introducción: Las enfermedades crónicas no transmisibles van en aumento, ocasionando discapacidad y dependencia en quien la padece, así como la necesidad de un cuidador. La cronicidad es un concepto que se ha analizado desde la mirada de la persona que la padece, dejando un vacío en la comprensión del significado para el cuidador.

Objetivo: comprender el significado de la cronicidad para las personas con Enfermedades crónicas no transmisibles y sus cuidadores informales.

Materiales y métodos: investigación cualitativa fenomenológica-hermenéutica según la propuesta de Van Manen, muestreo casual orientado por criterio, participaron 10 personas enfermas y 9 cuidadores. Los criterios de rigor de credibilidad y confirmabilidad, confiabilidad y la transferibilidad, garantizaron la calidad del estudio.

Resultados: emergieron los siguientes temas: Brindar y recibir cuidado como un acto de amor; unión de la familia; enfrentarse a la dureza; Recibir, brindar y buscar apoyo; Estar pendiente; Cambio de vida; Proceso de aprendizaje; una compañía para toda la vida; Imponer restricciones, limitaciones y pérdidas.

Conclusiones: el significado de la cronicidad para los cuidadores y las personas enfermas es complejo, dinámico y multidimensional; por lo tanto, es necesario realizar intervenciones que ayuden a mitigar el impacto que esta produce en la vida de este binomio.

Investigating low rates of compliance to graduated compression therapy for chronic venous insufficiency: A systematic review

Abstract

Chronic venous insufficiency (CVI) is a chronic lower limb progressive disorder with significant burden. Graduated compression therapy is the gold-standard treatment, but its underutilisation, as indicated in recent literature, may be contributing to the growing burden of CVI. The aim of this systematic review is to determine the reasons for poor compliance in patients who are prescribed graduated compression therapy in the management of chronic venous insufficiency. A systematic review of the literature was conducted to identify the reasons for non-compliance in wearing graduated compression therapy in the management of chronic venous insufficiency. The keyword search was conducted through Medline, PubMed, CINAHL, Cochrane library, AMED, and Embase databases from 2000 to April 2023. Qualitative and quantitative studies were included with no study design or language limits imposed on the search. The study populations were restricted to adults aged over 18 years, diagnosed with chronic venous insufficiency. Of the 856 studies found, 80 full-text articles were reviewed, with 14 being eligible for the review. Due to the variability in study designs, the results were summarised rather than subjected to meta-analysis. There are five main overarching themes for non-compliance, which are physical limitations, health literacy, discomfort, financial issues, and psychosocial issues with emerging sub-themes. Graduated compression therapy has the potential to reduce the burden of chronic venous insufficiency if patients are more compliant with their prescription.

Depression and anxiety among nurses during the COVID‐19 pandemic: Longitudinal results over 2 years from the multicentre VOICE–EgePan study

Abstract

Aims

To examine symptoms of depression and generalised anxiety among nurses over 2 years during the pandemic and compare them to the general population.

Background

The COVID-19 pandemic has led to a significant increase in mental stress among the population worldwide. Nursing staff have been identified as being under remarkable strain.

Design

A multicentre prospective longitudinal study.

Methods

Symptoms of depression and generalised anxiety in 507 nurses were examined at four different time points (T1: April–July 2020, T2: November 2020–January 2021, T3: May–July 2021, T4: February–May 2022). Results were compared with values of the German general population, presence of gender-specific differences was analysed and frequencies of clinically relevant levels of depression and anxiety were determined.

Results

Throughout the study (T1–T4), a significant increase in depressive and anxiety symptoms was observed. At all four measurement time points, nurses showed significantly higher prevalence for depression and anxiety compared to the German general population. No significant gender differences were found. Frequencies for probable depression and generalised anxiety disorder among nurses were: 21.6% and 18.5% (T1), 31.4% and 29.2% (T2), 29.5% and 26.2% (T3), 33.7% and 26.4% (T4).

Conclusion

During the pandemic, symptoms of depression and generalised anxiety among nurses increased significantly and remained elevated. Their symptom levels were permanently higher than in the general population. These findings strongly suggest that the circumstances of the pandemic severely affected nurses´ mental health.

Relevance to Clinical Practice

The COVID-19 pandemic caused a great mental strain on caregivers. This study was able to demonstrate the significant increase in depression and anxiety among nurses during the pandemic. It highlights the urgent need for prevention, screening and support systems in hospitals.

Implications for the Profession

Supportive programmes and preventive services should be developed, not least to prevent the growing shortage of nurses in the health care systems.

Reporting Method

The study adhered to relevant EQUATOR guidelines. The STROBE checklist for cohort study was used as the reporting method.

Patient Contribution

Five hundred and seven nurses completed the questionnaire and provided data for analysis.

Trial and Protocol Registration

The study was registered with the German Clinical Trials Register (https://drks.de/search/en) under the following ID: DRKS00021268.

Nurses' use of an advisory decision support system in ambulance services: A qualitative study

Abstract

Aim

To illuminate from the perspective of nurses in ambulance services the experiences of using a web-based advisory decision support system to assess care needs and refer patients.

Design

Inductive and descriptive approaches.

Method

Thirteen semi-structured interviews were conducted in the spring of 2020. The data were analysed through the reflexive thematic analysis.

Results

The Swedish web-based advisory decision support system (ADSS) was found to strengthen nurses' feelings of security when they assess patients' care needs, promote their competence and professional pride, and help them manage stress. However, the system also generated difficulties for nurses to adjust to the dynamic ambulance team and revealed a discrepancy between their professional roles and responsibilities to refer patients and provide self-care advice. The nurses thought that the support system facilitated their increased participation and helped them understand patients and significant others by offering transparency in assessment and decision making. Thus, the support system provides nurses with an opportunity to strengthen patients' independence through information and education. However, in the care relationship, nurses worked to overcome patients' expectations.

Conclusion

Nurses using the ADSS increased their security while performing assessments and referrals and found new opportunities to provide information and promote understanding of their decisions. However, nursing care values can be threatened when new support systems are introduced, especially as ambulance services become increasingly protocol-driven.

Implications for Profession and/or Patient Care

These findings have implications for nurses' work environments and help them maintain consistency in making medical assessments and in providing equivalent self-care advice when referring patients to the different levels of care. The findings will also impact researchers and policymakers who formulate decision support systems.

Reporting Method

Consolidated criteria for reporting qualitative research (COREQ).

Patient or Public Contribution

None.

Integrating genomics into Canadian oncology nursing policy: Insights from a comparative policy analysis

Abstract

Aim

To learn from two jurisdictions with mature genomics-informed nursing policy infrastructure—the United States (US) and the United Kingdom (UK)—to inform policy development for genomics-informed oncology nursing practice and education in Canada.

Design

Comparative document and policy analysis drawing on the 3i + E framework.

Methods

We drew on the principles of a rapid review and identified academic literature, grey literature and nursing policy documents through a systematic search of two databases, a website search of national genomics nursing and oncology nursing organizations in the US and UK, and recommendations from subject matter experts on an international advisory committee. A total of 94 documents informed our analysis.

Results

We found several types of policy documents guiding genomics-informed nursing practice and education in the US and UK. These included position statements, policy advocacy briefs, competencies, scope and standards of practice and education and curriculum frameworks. Examples of drivers that influenced policy development included nurses' values in aligning with evidence and meeting public expectations, strong nurse leaders, policy networks and shifting healthcare and policy landscapes.

Conclusion

Our analysis of nursing policy infrastructure in the US and UK provides a framework to guide policy recommendations to accelerate the integration of genomics into Canadian oncology nursing practice and education.

Implications for the profession

Findings can assist Canadian oncology nurses in developing nursing policy infrastructure that supports full participation in safe and equitable genomics-informed oncology nursing practice and education within an interprofessional context.

Impact

This study informs Canadian policy development for genomics-informed oncology nursing education and practice. The experiences of other countries demonstrate that change is incremental, and investment from strong advocates and collaborators can accelerate the integration of genomics into nursing. Though this research focuses on oncology nursing, it may also inform other nursing practice contexts influenced by genomics.

Youth, caregiver and healthcare professional perspectives on planning the implementation of a trauma‐informed care programme: A qualitative study

Abstract

Aims

To explore youth, caregiver and staff perspectives on their vision of trauma-informed care, and to identify and understand potential considerations for the implementation of a trauma-informed care programme in an inpatient mental health unit within a paediatric hospital.

Design and Methods

We applied the Interpretive Description approach, guided by complexity theory and the Implementation Roadmap, and used Applied Thematic Analysis methods.

Findings

Twenty-five individuals participated in individual or group interviews between March and June 2022, including 21 healthcare professionals, 3 youth and 1 caregiver. We identified two overarching themes. The first theme, ‘Understanding and addressing the underlying reasons for distress’, related to participants’ understanding and vision of TIC in the current setting comprising: (a) ‘Participants’ understanding of TIC’; (b) ‘Trauma screening and trauma processing within TIC’; (c) ‘Taking “a more individualized approach”’; (d) ‘Unit programming’; and (e) “Connecting to the community”. The second theme, ‘Factors that support or limit successful TIC implementation’ comprises: (a) ‘The need for a broad “cultural shift”’; (b) ‘The physical environment on the unit’; and (c) ‘Factors that may limit successful implementation’.

Conclusion

We identified five key domains to consider within trauma-informed care implementation: (a) the centrality of engagement with youth, caregivers and staff in trauma-informed care delivery and implementation, (b) trauma-informed care core programme components, (c) factors that may support or limit success in implementing trauma-informed care within the mental health unit and (d) hospital-wide and (e) the importance of intersectoral collaboration (partnering with external organizations and sectors).

Impact

When implementing TIC, there is an ongoing need to increase clarity regarding TIC interventions and implementation initiatives. Youth, caregiver and healthcare professional participants shared considerations important for planning the delivery and implementation of trauma-informed care in their setting. We identified five key domains to consider within trauma-informed care implementation: (a) the centrality of relational engagement, (b) trauma-informed care programme components, (c) factors that may support or limit successful implementation of trauma-informed care within the mental health unit and (d) hospital-wide and (e) the importance of intersectoral collaboration. Organizations wishing to implement trauma-informed care should consider ongoing engagement with all relevant knowledge user groups throughout the process.

Reporting Method

Standards for Reporting Qualitative Research (SRQR).

Patient or Public Contribution

The local hospital research institute's Patient and Family Advisory Committee reviewed the draft study methods and provided feedback.

Biomechanical and neuromuscular characteristics in patients with traumatic anterior shoulder instability undergoing arthroscopic Bankart repair: a clinical prospective cohort study protocol

Por: Malmberg · C. · Andreasen · K. R. · Bencke · J. · Kjaer · B. H. · Holmich · P. · Barfod · K. W.
Introduction

Traumatic shoulder dislocation is a common shoulder injury, especially among the young and active population. More than 95% of dislocations are anterior, in which the humeral head is forced beyond the anterior glenoid rim. The injury leads to increased joint laxity and recurrence rates are high. There is evidence that the shoulder biomechanics and neuromuscular control change following dislocation, but the existing literature is scarce, and it remains to be established if and how these parameters are useful in the clinical setting. The aim of this exploratory prospective cohort study is to investigate biomechanical and neuromuscular outcomes in patients with traumatic anterior shoulder instability undergoing arthroscopic Bankart repair, to test the hypothesis that examinations of these characteristics are applicable in the clinical setting to assess shoulder instability.

Methods and analysis

This is a prospective multicentre cohort study with repeated measures of 30 patients undergoing arthroscopic Bankart repair. With carefully selected and completely non-invasive examination methods, we will investigate biomechanical and neuromuscular outcomes in the affected shoulders once presurgically and twice post surgically at 6 and 12 months. Patients’ contralateral shoulders are investigated once to establish a preinjury level.

Ethics and dissemination

The study was approved by the Capital Region Ethics Committee (journal-no: H-21027799) and the Capital Region Knowledge Center for Data Reviews (journal-no: P-2021-842) before patient recruitment began. The study results will be published in international peer-reviewed journals, online and in other relevant media, presented at medical conventions and disseminated to clinicians and patients as appropriate.

Trial registration number

NCT05250388.

Infiltration of CD3+ and CD8+ lymphocytes in association with inflammation and survival in pancreatic cancer

by Gerik W. Tushoski-Alemán, Kelly M. Herremans, Patrick W. Underwood, Ashwin Akki, Andrea N. Riner, Jose G. Trevino, Song Han, Steven J. Hughes

Background

Pancreatic ductal adenocarcinomas (PDAC) have heterogeneous tumor microenvironments relatively devoid of infiltrating immune cells. We aimed to quantitatively assess infiltrating CD3+ and CD8+ lymphocytes in a treatment-naïve patient cohort and assess associations with overall survival and microenvironment inflammatory proteins.

Methods

Tissue microarrays were immunohistochemically stained for CD3+ and CD8+ lymphocytes and quantitatively assessed using QuPath. Levels of inflammation-associated proteins were quantified by multiplexed, enzyme-linked immunosorbent assay panels on matching tumor and tissue samples.

Results

Our findings revealed a significant increase in both CD3+ and CD8+ lymphocytes populations in PDAC compared with non-PDAC tissue, except when comparing CD8+ percentages in PDAC versus intraductal papillary mucinous neoplasms (IPMN) (p = 0.5012). Patients with quantitatively assessed CD3+ low tumors (lower 50%) had shorter survival (median 273 days) compared to CD3+ high tumors (upper 50%) with a median overall survival of 642.5 days (p = 0.2184). Patients with quantitatively assessed CD8+ low tumors had significantly shorter survival (median 240 days) compared to CD8+ high tumors with a median overall survival of 1059 days (p = 0.0003). Of 41 proteins assessed in the inflammation assay, higher levels of IL-1B and IL-2 were significantly associated with decreased CD3+ infiltration (r = -0.3704, p = 0.0187, and r = -0.4275, p = 0.0074, respectively). Higher levels of IL-1B were also significantly associated with decreased CD8+ infiltration (r = -0.4299, p = 0.0045), but not IL-2 (r = -0.0078, p = 0.9616). Principal component analysis of the inflammatory analytes showed diverse inflammatory responses in PDAC.

Conclusion

In this work, we found a marked heterogeneity in infiltrating CD3+ and CD8+ lymphocytes and individual inflammatory responses in PDAC. Future mechanistic studies should explore personalized therapeutic strategies to target the immune and inflammatory components of the tumor microenvironment.

Struggling in the dehumanized world of COVID—An exploratory mixed‐methods study of frontline healthcare workers' experiences

Abstract

Aim

To explore healthcare workers' experiences of the changed caring reality during the COVID-19 pandemic in Sweden.

Design

An online fully mixed-methods design.

Methods

A web-based self-reported questionnaire with fixed and open-ended answers collected data from March to April 2021, analysed in three steps. First, free-text questions were analysed by qualitative content analysis. Then quantitative linear regression analyses using models covering stress and coping mechanisms were conducted. Finally, a meta-inference of qualitative and quantitative data emerged a new comprehensive understanding. The COREQ guidelines were used for reporting.

Results

Meta-inferenced results of quantitative and qualitative findings show the pandemic was a traumatic experience for healthcare workers. Main theme; When work became a frightening experience in a dehumanized reality, comprised four themes: Entering unprepared into a frightful, incomprehensible world; Sacrificing moral values and harbouring dilemmas in isolation; Lack of clear management; and Reorient in togetherness and find meaning in a changed reality. Qualitative results comprised four categories; Working in a dehumanized world; Living in betrayal of ones' own conscience; Lack of structure in a chaotic time and Regaining vitality together. Subdimensions comprehensibility and meaningfulness were associated significantly with post-traumatic stress disorder in multiple regression analysis. In multiple regression analysis, sense of coherence was the most prominent coping strategy.

Conclusions

Forcing oneself to perform beyond one's limit, sacrificing moral values and lacking management was a traumatic experience to healthcare workers during the pandemic. Reorienting as a way of coping was possible in togetherness with colleagues. There is an urgency of interventions to meet the needs among healthcare workers who took on a frontline role during the COVID-19 pandemic and to prevent mental health illness in future crisis.

Patient or Public Contribution

No patient or public contribution.

Summary

The pandemic outbreak exposed frontline healthcare workers to unparallelled stress shown as negative for their mental health in several meta-analyses and systematic reviews. In-depth understanding on experiences and how symptoms of post-traumatic stress disorder relate to coping mechanisms have been scarcely explored. This study contributes to understanding on healthcare workers' experiences and the relation between lower sense of coherence and increased risk of developing symptoms of post-traumatic stress disorder.

Implications for Practice/Policy

This study might guide how to prepare for resilience in future emergencies.

Renegotiating identity. A Nordic study of adolescent's experiences of living with a parent having heart disease

Abstract

Aim

To explore adolescents' experiences of having a parent with heart disease.

Design

This qualitative study was performed with semi-structured individual interviews.

Methods

Interviews were conducted with 33 adolescents between 13 and 19 years old, who either had a mother or father with one of these diagnoses: ischemic heart disease, arrhythmia, heart failure, cardiac arrest or heart valve disease. The parent had been ill for at least 6 months and up to 5 years. The study was carried out in Denmark, Norway and Sweden between 2019 and 2022. The analysis was inspired by Reflexive Methodology.

Results

Three central themes emerged: Response to parental heart disease; Growing up ahead of time; and Strategies in a changed life situation. For the adolescents, heart disease was experienced as an acute and lethal disease that put their parents' lives in danger. New routines and roles not only changed everyday life within the family but they also enhanced maturity and appreciation of life. To maintain a balance in life, the adolescents pursued normality and sought a safe space to have a normal youthful life.

Conclusion

In a period known to be significant for development, life with parental heart disease appeared as a biographical disruption because adolescents renegotiated their identity to manage their new life situation.

Impact

It is important to help younger family members adapt to parental heart disease by informing them about possible reactions and supporting them in how to adapt to their new life by seeking breaks and normality.

Patient or Public Contribution

No patient or public involvement.

Factors associated with pressure ulcer and dehydration in long-term care settings in Ontario, Canada

by Mary Crea-Arsenio, Andrea Baumann, Valentina Antonipillai, Noori Akhtar-Danesh

Pressure ulcers and dehydration are common conditions among residents of long-term care facilities that result in negative health effects. They have been associated with signs of neglect and increased 30-day mortality among LTC residents. However, they are both preventable and with proper care can be effectively managed and treated. We conducted a retrospective cohort study to examine factors associated with pressure ulcers and dehydration among long-term care residents in the province of Ontario, Canada. Results indicated that close to one-fifth of residents were dehydrated (17.3%) or had a pressure ulcer (18.9%) during the study period. Advanced age was significantly associated with the presence of pressure ulcers and dehydration for both men and women. However, men were more likely to present with a pressure ulcer while women were more likely to exhibit symptoms of dehydration. Study findings also demonstrate the presence of both conditions being higher in municipal and not-for-profit homes compared to for-profit homes. The significant differences observed in relation to home ownership which require further investigation to identify the most relevant factors in explaining these differences. Overall, pressure ulcers and dehydration are preventable conditions that warrant attention from policymakers to ensure quality of care and resident safety are prioritized.

Supporting regional pandemic management by enabling self-service reporting—A case report

by Richard Gebler, Martin Lehmann, Maik Löwe, Mirko Gruhl, Markus Wolfien, Miriam Goldammer, Franziska Bathelt, Jens Karschau, Andreas Hasselberg, Veronika Bierbaum, Toni Lange, Katja Polotzek, Hanns-Christoph Held, Michael Albrecht, Jochen Schmitt, Martin Sedlmayr

Background

The COVID-19 pandemic revealed a need for better collaboration among research, care, and management in Germany as well as globally. Initially, there was a high demand for broad data collection across Germany, but as the pandemic evolved, localized data became increasingly necessary. Customized dashboards and tools were rapidly developed to provide timely and accurate information. In Saxony, the DISPENSE project was created to predict short-term hospital bed capacity demands, and while it was successful, continuous adjustments and the initial monolithic system architecture of the application made it difficult to customize and scale.

Methods

To analyze the current state of the DISPENSE tool, we conducted an in-depth analysis of the data processing steps and identified data flows underlying users’ metrics and dashboards. We also conducted a workshop to understand the different views and constraints of specific user groups, and brought together and clustered the information according to content-related service areas to determine functionality-related service groups. Based on this analysis, we developed a concept for the system architecture, modularized the main services by assigning specialized applications and integrated them into the existing system, allowing for self-service reporting and evaluation of the expert groups’ needs.

Results

We analyzed the applications’ dataflow and identified specific user groups. The functionalities of the monolithic application were divided into specific service groups for data processing, data storage, predictions, content visualization, and user management. After composition and implementation, we evaluated the new system architecture against the initial requirements by enabling self-service reporting to the users.

Discussion

By modularizing the monolithic application and creating a more flexible system, the challenges of rapidly changing requirements, growing need for information, and high administrative efforts were addressed.

Conclusion

We demonstrated an improved adaptation towards the needs of various user groups, increased efficiency, and reduced burden on administrators, while also enabling self-service functionalities and specialization of single applications on individual service groups.

The impact of cineole treatment timing on common cold duration and symptoms: Non-randomized exploratory clinical trial

by Andreas Michalsen, Kim Goldenstein, Peter Kardos, Ludger Klimek, Jürgen Palm, Dajana Parganlija, Johannes Stöckl

Introduction

Common cold (CC) symptoms arise from an inflammatory response treatable with cineole and generally peak within two days, which complicates research implementation. We therefore explored the benefits of early cineole administration with enrolment of participants prior to CC onset.

Methods

Out of 522 adults enrolled in our phase IV, open-label, non-randomized, exploratory clinical trial (EudraCT No. 2020-000860-51), 329 developed a CC and used 200 mg cineole (Soledum®, CNL-1976) t.i.d. for max. 15 (± 2) days. Primary endpoint was burden of disease based on the Wisconsin Upper Respiratory Symptom Survey (WURSS-11).

Results

Comparing three strata based on time to treatment (≤ 12 h, > 12 to ≤ 24 h and > 24 h), earliest treatment resulted in lowest AUC-WURSS (Spearman correlation coefficient of 0.36) and reduced the overall burden of disease by 38% (p Conclusions

Early intervention shows clinical benefits relevant for the effective treatment of CC with cineole.

Genetic profiling of rat gliomas and cardiac schwannomas from life-time radiofrequency radiation exposure study using a targeted next-generation sequencing gene panel

by Ashley M. Brooks, Andrea Vornoli, Ramesh C. Kovi, Thai Vu T. Ton, Miaofei Xu, Ahmed Mashal, Eva Tibaldi, Federica Gnudi, Jian-Liang Li, Robert C. Sills, John R. Bucher, Daniele Mandrioli, Fiorella Belpoggi, Arun R. Pandiri

The cancer hazard associated with lifetime exposure to radiofrequency radiation (RFR) was examined in Sprague Dawley (SD) rats at the Ramazzini Institute (RI), Italy. There were increased incidences of gliomas and cardiac schwannomas. The translational relevance of these rare rat tumors for human disease is poorly understood. We examined the genetic alterations in RFR-derived rat tumors through molecular characterization of important cancer genes relevant for human gliomagenesis. A targeted next-generation sequencing (NGS) panel was designed for rats based on the top 23 orthologous human glioma-related genes. Single-nucleotide variants (SNVs) and small insertion and deletions (indels) were characterized in the rat gliomas and cardiac schwannomas. Translational relevance of these genetic alterations in rat tumors to human disease was determined through comparison with the Catalogue of Somatic Mutations in Cancer (COSMIC) database. These data suggest that rat gliomas resulting from life-time exposure to RFR histologically resemble low grade human gliomas but surprisingly no mutations were detected in rat gliomas that had homology to the human IDH1 p.R132 or IDH2 p.R172 suggesting that rat gliomas are primarily wild-type for IDH hotspot mutations implicated in human gliomas. The rat gliomas appear to share some genetic alterations with IDH1 wildtype human gliomas and rat cardiac schwannomas also harbor mutations in some of the queried cancer genes. These data demonstrate that targeted NGS panels based on tumor specific orthologous human cancer driver genes are an important tool to examine the translational relevance of rodent tumors resulting from chronic/life-time rodent bioassays.

Further psychometric validation and test–retest reproducibility of the WOUND‐Q

Abstract

WOUND-Q is a condition-specific patient-reported outcome measure developed for all types of chronic wounds, located anywhere on the body. To establish reliability and validity of a patient-reported outcome measure, multiple pieces of evidence are required. The purpose of this study was to examine the measurement properties of 9 of the 13 WOUND-Q scales and perform a test–retest reproducibility study in an international sample. In August 2022, we invited members of an international online community (Prolific.com) with any type of chronic wound to complete a survey containing the WOUND-Q scales, the Wound-QoL and EQ-5D. A test–retest survey was performed 7 days after the first survey. It was possible to examine the reliability and validity of eight of the nine WOUND-Q scales by Rasch Measurement Theory (RMT). To examine test–retest reproducibility intraclass correlation coefficients (ICCs), the standard error of the measurement and the smallest detectable change were calculated. In total, 421 patients from 22 different countries with 11 different types of chronic wounds took part in this study. Our analyses provided further evidence of the reliability and validity of the scales measuring wound characteristics (assessment, drainage, smell), health-related quality of life (life impact, psychological, sleep, social) and wound treatment (dressing).

Predictors of professional burnout and fulfilment in a longitudinal analysis on nurses and healthcare workers in the COVID‐19 pandemic

Abstract

Aims and objectives

(1) To investigate the vulnerability of nurses to experiencing professional burnout and low fulfilment across 5 months of the COVID-19 pandemic. (2) To identify modifiable variables in hospital leadership and individual vulnerabilities that may mitigate these effects.

Background

Nurses were at increased risk for burnout and low fulfilment prior to the COVID-19 pandemic. Hospital leadership factors such as organisational structure and open communication and consideration of employee opinions are known to have positive impacts on work attitudes. Personal risk factors for burnout include symptoms of depression and anxiety.

Methods

Healthcare workers (n = 406 at baseline, n = 234 longitudinal), including doctors (n = 102), nurses (n = 94), technicians (n = 90) and non-clinical administrative staff (n = 120), completed 5 online questionnaires, once per month, for 5 months. Participants completed self-report questionnaires on professional fulfilment and burnout, perceptions of healthcare leadership, and symptoms of anxiety and depression. Participants were recruited from various healthcare settings in the southeastern United States. The STROBE checklist was used to report the present study.

Results

Both at baseline and across the 5 months, nurses working during the COVID-19 pandemic reported increased burnout and decreased fulfilment relative to doctors. For all participants, burnout remained largely steady and fulfilment decreased slightly. The strongest predictors of both burnout and fulfilment were organisational structure and depressive symptoms. Leadership consideration and anxiety symptoms had smaller, yet significant, relationships to burnout and fulfilment in longitudinal analyses.

Conclusions

Burnout and reduced fulfilment remain a problem for healthcare workers, especially nurses. Leadership styles and employee symptoms of depression and anxiety are appropriate targets for intervention.

Relevance to clinical practice

Leadership wishing to reduce burnout and increase fulfilment among employees should increase levels of organisational support and consideration and expand supports to employees seeking treatment for depression and anxiety.

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