Patients’ experience of recurrent/metastatic head and neck squamous cell carcinoma and their perspective on the EORTC QLQC30 and QLQ-H&N35 questionnaires: a qualitative study

Abstract Background Head and neck squamous cell carcinoma (HNSCC) and its associated treatments may affect all aspects of patients’ health-related quality of life (HRQoL). Although the EORTC QLQ-H&N35 is regularly administered to patients with HNSCC, there is a paucity of studies re-assessing the conceptual relevance of this patient-reported outcome (PRO) measure from a patient perspective. Furthermore, the content validity of the EORTC QLQ-C30 has not been widely documented in patients with recurrent and/or metastatic HNSCC. The objectives of this study were to understand patients’ experiences of recurrent/metastatic HNSCC and its treatments, and to evaluate the conceptual relevance and acceptability of the EORTC QLQ-C30 and QLQ-H&N35 from a patient perspective for use in clinical trials. Methods A literature review and clinician interviews were conducted to inform in-depth semi-structured telephone interviews with US patients who had received treatment for recurrent and/or metastatic HNSCC in the preceding 12 months. Interview transcripts were analysed thematically using ATLAS.ti v7; patient quotes were coded to identify concepts and themes to develop a conceptual model of HNSCC experience. Results Fourteen patients were interviewed (71% male, aged 35–84 years). Patients reported few symptoms pre-diagnosis including neck lump/swelling (n = 7/14, 50%) and/or difficulty swallowing (n = 3/14, 21%). Treatments generally comprised surgery and chemotherapy and/or radiotherapy. A number of side effects from all treatments were reported. Numbness, difficulty speaking and pain were the most reported side effects of surgery (n = 4/8, 50%); weight loss and fatigue were the most reported side effects of chemotherapy and/or radiotherapy (n = 8/13, 61%). All side effects negatively impacted patients’ HRQoL. Patients generally found the QLQ-C30 and QLQ H&N35 content to be understandable and conceptually relevant; excessive mucous production and neuropathic symptoms were among the suggested additions. Conclusions HNSCC and its diverse symptoms and treatments have a negative impact on many aspects of patients’ lives. A number of reported symptoms including difficulty speaking and swallowing, localised pain and fatigue may be important for treatment benefit evaluation in clinical trials from a patient perspective. The QLQ-C30 and QLQ-H&N35 are generally relevant and suitable for use in clinical trials. However, some items could be amended/added to ensure conceptual comprehensiveness of these measures

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

A stand-alone multi-scent olfactory display with a sliding scent switching Mechanism

Here we report on the design, construction, and testing of a multi-scent olfactory display that is intended as promotional tool for smell-related events. Our system used off-the-shelf spray bottles for scent generation, with a control and actuation system constructed around it. The spray bottle is actuated using a solenoid valve, combined with a fan to help deliver the aroma to the user. Scent switching is achieved by sliding the spray bottles on a fixed rail. A step motor is then used to select scents accurately. The final unit can release up to four different scents and testing results show that the unit can be controlled for scent delivery at a range of firing rates

Integrated probe system for measuring soil carbon dioxide concentrations

This article outlines the design and implementation of an internet-of-things (IoT) platform for the monitoring of soil carbon dioxide (CO2) concentrations. As atmospheric CO2 continues to rise, accurate accounting of major carbon sources, such as soil, is essential to inform land management and government policy. Thus, a batch of IoT-connected CO2 sensor probes were developed for soil measurement. These sensors were designed to capture spatial distribution of CO2 concentrations across a site and communicate to a central gateway using LoRa. CO2 concentration and other environmental parameters, including temperature, humidity and volatile organic compound concentration, were logged locally and communicated to the user through a mobile (GSM) connection to a hosted website. Following three field deployments in summer and autumn, we observed clear depth and diurnal variation of soil CO2 concentration within woodland systems. We determined that the unit had the capacity to log data continuously for a maximum of 14 days. These low-cost systems have great potential for better accounting of soil CO2 sources over temporal and spatial gradients and possibly flux estimations. Future testing will focus on divergent landscapes and soil conditions

Temporal Trends of Enrollment by Sex and Race in Major Cardiovascular Randomized Clinical Trials

Background: Women and racialized minorities continue to be underrepresented in cardiovascular (CV) trial outcomes data, despite comprising a significant global burden of CV disease. This study evaluated the impact of trial characteristics on the temporal enrollment of women and racialized minorities in prominent CV trials published in the period 1986-2023. Methods: MEDLINE was searched for CV trials published in The Lancet, the Journal of the American Medical Association, and the New England Journal of Medicine. Participant and investigator demographics, types of interventions, clinical indications, and funding sources were compared according to the enrollment of women or racialized minorities. Results: From 799 studies, including 4,071,921 patients, the enrollment of women and racialized minorities significantly increased from 1986 to 2023 (both P ≤ 0.001). Although the enrollment of women varied by trial indication, comprising 25.0% of coronary artery disease, 35.2% of noncoronary and/or vascular disease, 13.8% of heart failure, 17.0% of arrhythmia, and 28.7% of other CV trials (P ≤ 0.001), it did not differ by peer-reviewed vs industry funding. First authors who were women were more likely than first authors who were men to enroll significantly more women (P = 0.01). Conclusions: Active efforts to increase diverse enrollment, along with improved reporting, including of sex and race, in future CV trials may increase the generalizability of their findings and applicability to global populations. RÉsumÉ: Contexte: Les femmes et les groupes racisés demeurent sous-représentés dans les données de résultats d’essais cliniques sur les maladies cardiovasculaires (CV) malgré l’important fardeau global associé à ces maladies. Cette étude visait à évaluer l’effet des caractéristiques des essais sur la sélection temporelle des femmes et des membres de groupes racisés dans les essais portant principalement sur les maladies CV durant la période de 1986 à 2023. Méthodologie: La base de données MEDLINE a été consultée à la recherche d’essais sur les maladies CV publiés dans The Lancet, Journal of the American Medical Association et New England Journal of Medicine. Les données démographiques des participants et des chercheurs, les types d’interventions, les indications cliniques et les sources de financement ont été comparés en fonction de la sélection des femmes ou des membres de groupes racisés. Résultats: Dans 799 études cumulant 4 071 921 patients, la sélection des femmes et des membres de groupes racisés a augmenté significativement entre 1986 et 2023 (p ≤ 0,001 dans les deux cas). Bien que la sélection des femmes variait en fonction des indications des essais, soit 25,0 % dans les essais portant sur les coronaropathies, 35,2 % pour les maladies non coronariennes et/ou vasculaires, 13,8 % pour l’insuffisance cardiaque, 17,0 % pour l’arythmie et 28,7 % pour d’autres maladies CV (p ≤ 0,001), elle ne différait pas selon que les études étaient révisées par des pairs ou qu’elles étaient financées par l’industrie. Lorsqu’une femme était l’autrice principale, le nombre de femmes sélectionnées était susceptible d’être plus élevé que lorsque l’auteur principal était un homme (p = 0,01). Conclusions: Des efforts actifs pour diversifier davantage la sélection des participants et mieux rendre compte des différences, notamment en ce qui concerne le sexe et la race, pourraient élargir la portée des conclusions des futurs essais sur les maladies CV et leur application à l’ensemble de la population

Practice guidelines for endoscopic ultrasound-guided celiac plexus neurolysis

Objectives: The objective of guideline was to provide clear and relevant consensus statements to form a practical guideline for clinicians on the indications, optimal technique, safety and efficacy of endoscopic ultrasound guided celiac plexus neurolysis (EUS-CPN). Methods: Six important clinical questions were determined regarding EUS-CPN. Following a detailed literature review, 6 statements were proposed attempting to answer those questions. A group of expert endosonographers convened in Chicago, United States (May 2016), where the statements were presented and feedback provided. Subsequently a consensus group of 35 expert endosonographers voted based on their individual level of agreement. A strong recommendation required 80% voter agreement. The modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria were used to rate the strength of recommendations and the quality of evidence. Results: Eighty percent agreement was reached on 5 of 6 consensus statements, 79.4% agreement was reached on the remaining one. Conclusions: EUS-CPN is efficacious, should be integrated into the management of pancreas cancer pain, and can be considered early at the time of diagnosis of inoperable disease. Techniques may still vary based on operator experience. Serious complications exist, but are rare

Practice guidelines for endoscopic ultrasound-guided celiac plexus neurolysis

Objectives: The objective of guideline was to provide clear and relevant consensus statements to form a practical guideline for clinicians on the indications, optimal technique, safety and efficacy of endoscopic ultrasound guided celiac plexus neurolysis (EUS-CPN). Methods: Six important clinical questions were determined regarding EUS-CPN. Following a detailed literature review, 6 statements were proposed attempting to answer those questions. A group of expert endosonographers convened in Chicago, United States (May 2016), where the statements were presented and feedback provided. Subsequently a consensus group of 35 expert endosonographers voted based on their individual level of agreement. A strong recommendation required 80% voter agreement. The modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria were used to rate the strength of recommendations and the quality of evidence. Results: Eighty percent agreement was reached on 5 of 6 consensus statements, 79.4% agreement was reached on the remaining one. Conclusions: EUS-CPN is efficacious, should be integrated into the management of pancreas cancer pain, and can be considered early at the time of diagnosis of inoperable disease. Techniques may still vary based on operator experience. Serious complications exist, but are rare