bluuebunny/crossref_metadata_2025 huggingface dataset:
School health promotion and the consumption of water and sugar-sweetened beverages in secondary schools: a cross-sectional multilevel study
Authors: Vonk Lisanne , Eekhout Iris , Huijts Tim , Levels Mark , Jansen Maria W. J.
Published: July 2023

Background

Overweight among adolescents remains a serious concern worldwide and can have major health consequences in later life, such as cardiovascular diseases and cancer. Still, 33% of secondary school adolescents in the Netherlands consume sugar-sweetened beverages daily and over 26% do not consume water every day. The Dutch Healthy School program was developed to support schools in stimulating healthier lifestyles by focusing on health education, school environments, identifying students’ health problems, and school policy. We examined the variation between secondary schools regarding the daily consumption of water and sugar-sweetened beverages and whether this variation can be explained by differences between schools regarding Healthy School certification, general school characteristics, and the school population.

Methods

We performed a cross-sectional multilevel study. We used data from the national Youth Health Monitor of 2019 on secondary schools (grades 8 and 10, age range about 12 to 18 years) of seven Public Health Services and combined these with information regarding Healthy School certification and general school- and school population characteristics. Our outcomes were daily consumption of water and sugar-sweetened beverages. In total, data from 51,901 adolescents from 191 schools were analysed. We calculated the intraclass correlation to examine the variation between schools regarding our outcomes. Thereafter, we examined whether we could explain this variation by the included characteristics.

Results

The school-level explained 4.53% of the variation in the consumption of water and 2.33% of the variation in the consumption of sugar-sweetened beverages. This small variation in water and sugar-sweetened consumption could not be explained by Healthy School certification, yet some general school- and school population characteristics did: the proportion of the school population with at least one parent with high educational attainment, the educational track of the adolescents, urbanicity (only for water consumption) and school type (only for sugar-sweetened beverages consumption).

Conclusions

The low percentages of explained variation indicate that school-level characteristics in general (including Healthy School certification) do not matter substantially for the daily consumption of water and sugar-sweetened beverages. Future research should examine whether school health promotion can contribute to healthier lifestyles, and if so, under which level of implementation and school conditions.
Risk factors for newly-developed cardiovascular disease and quality of life during the COVID − 19 pandemic: an analysis of the English longitudinal study of ageing
Authors: Patel Mubarak , Uthman Olalekan
Published: July 2023

Introduction

The COVID-19 pandemic had a wide range of effects on the English population, including on health and quality of life due to the subsequent lockdown restrictions set.

Aims

To investigate longitudinal changes in developing cardiovascular disease (CVD) and how that affects quality of life from pre-pandemic and during two lockdowns in England, in adults aged 50 years and above, and what factors are associated with this.

Methods

Wave 9 of the core English Longitudinal Study of Ageing (ELSA) and Waves 1 and 2 of the ELSA COVID-19 sub-study were used to investigate the factors associated with developing CVD between timepoints, and what factors alongside CVD are associated with quality of life.

Results

Higher age and depression were associated with newly-developed CVD from pre-COVID to both COVID sub-study waves. Additionally, body mass index (BMI) increased odds of CVD and physical activity decreased odds. Non-White ethnicity, depression, females, and developing CVD were lower associated with quality of life. Decreased age and increased physical activity were associated with higher quality of life.

Discussion

Ethnicity was not associated with newly-developed CVD but was associated with quality of life. Other factors of importance include age, depression, gender, and physical activity. Findings are informative for future risk stratification and treatment strategies, especially while the COVID-19 pandemic is ongoing.
Effects of adverse childhood health experiences on cognitive function in Chinese middle-aged and older adults: mediating role of depression
Authors: Wang Gaoling , Zhou Yuqin , Duan Jing , Kan Qianqian , Cheng Zhaopeng , Tang Shaoliang
Published: July 2023

Background

Adverse childhood experiences are critical factors in depression and cognitive decrease, but the effect of adverse childhood health experiences (ACHEs) on cognitive function and the role of depression have not been fully studied.

Methods

Data were taken from the China Health and Retirement Longitudinal Study (CHARLS) of 2014 and 2018. This study used indicators of situational memory ability and mental status to measure cognitive capacity. Besides analyzing the different types of ACHEs, scores for ACHEs were calculated to represent the severity of ACHEs. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess depression. The analysis of this study employed two different analytical strategies in order to examine the mediated effects of depression. We used Sobel’s test and Baron and Kenny’s causal step approach, which utilized a generalized least squares regression model. Furthermore, a logistic regression model was used to evaluate the robustness of the Karlson-Holm-Breen (KHB) approach.

Results

In this study, 6301 individuals who met the requirements of the study were included. We found that being confined to bed (ACHE3) (β=-0.3846, p = 0.022) in childhood had a negative impact on cognitive function. Similarly, ACHEs had a negative effect on cognitive function (β=-0.0819, p = 0.090). And after the depression had been introduced into the model, the regression coefficient of ACHEs on cognitive function was no longer significant (β=-0.0170, p = 0.727). The Sobel test showed that for ACHE3, the mediated proportion of the total effect of depression was 36.92%. While for ACHEs, the proportion of the mediated effect of depression was 70.11%. Finally, a robustness test of the mediating effect using the KHB method revealed that the mediating effect still existed. Further, based on different gender, age, and educational levels, the heterogeneity test indicated that the relationship between ACHEs and cognitive function and mediating effects of the depression were different as well as passing the robustness test of the interaction.

Conclusion

The decline in cognition had been shown to be correlated with ACHEs and depression mediated this relationship. Positive interventions might help to improve cognitive performance in individuals suffering from ACHEs and depression.
Socioeconomic and environmental factors associated with waterpipe tobacco smoking among Iranian adults: a PERSIAN cohort-based cross-sectional study
Authors: Moghadam Telma Zahirian , Zandian Hamed , Fazlzadeh Mehdi , Kalan Mohammad Ebrahimi , Pourfarzi Farhad
Published: July 2023

Background

Waterpipe tobacco smoking (WTS) is associated with several deleterious health outcomes. We sought to estimate the prevalence of WTS and explore socioeconomic inequalities associated with this culturally-rooted tobacco smoking practice among Iranian adults.

Methods

A cross-sectional analysis was conducted among 20,460 adults (ages 18 and older) enrolled in the PERSIAN cohort study during 2020. Data were collected on socioeconomic status (SES), lifestyle, alcohol consumption, cigarette smoking, and several risk factors related to non-communicable diseases. The concentration curve and relative concentration index (RCI) were administered to assess and quantify the SES-based inequality in WTS.

Results

Overall age-adjusted prevalence of past-month WTS was 5.1% (95%CI:4.6–5.8), with about 1% for women and 10.6 for men. Age-adjusted prevalence of WTS was higher among younger adults, men, cigarette smokers, obese adults, and those with higher SES. The RCI estimation showed that WTS is more popular among adults with high income and education. WTS was higher among younger adults, cigarette smokers, obese adults, and those with higher SES.

Conclusion

There is a clear socioeconomic inequality in WTS, with a higher prevalence among adults with higher income and education. The findings suggest the need for targeted interventions to address this inequality and reduce the prevalence of WTS among high-income communities.
High accuracy epidermal growth factor receptor mutation prediction via histopathological deep learning
Authors: Zhao Dan , Zhao Yanli , He Sen , Liu Zichen , Li Kun , Zhang Lili , Zhang Xiaojun , Wang Shuhao , Che Nanying , Jin Mulan
Published: July 2023

Background

The detection of epidermal growth factor receptor (EGFR) mutations in patients with non-small cell lung cancer is critical for tyrosine kinase inhibitor therapy. EGFR detection requires tissue samples, which are difficult to obtain in some patients, costing them the opportunity for further treatment. To realize EGFR mutation prediction without molecular detection, we aimed to build a high-accuracy deep learning model with only haematoxylin and eosin (H&E)-stained slides.

Methods

We collected 326 H&E-stained non-small cell lung cancer slides from Beijing Chest Hospital, China, and used 226 slides (88 with EGFR mutations) for model training. The remaining 100 images (50 with EGFR mutations) were used for testing. We trained a convolutional neural network based on ResNet-50 to classify EGFR mutation status on the slide level.

Results

The sensitivity and specificity of the model were 76% and 74%, respectively, with an area under the curve of 0.82. When applying the double-threshold approach, 33% of the patients could be predicted by the deep learning model as EGFR positive or negative with a sensitivity and specificity of 100.0% and 87.5%. The remaining 67% of the patients got an uncertain result and will be recommenced to perform further examination. By incorporating adenocarcinoma subtype information, we achieved 100% sensitivity in predicting EGFR mutations in 37.3% of adenocarcinoma patients.

Conclusions

Our study demonstrates the potential of a deep learning-based EGFR mutation prediction model for rapid and cost-effective pre-screening. It could serve as a high-accuracy complement to current molecular detection methods and provide treatment opportunities for non-small cell lung cancer patients from whom limited samples are available.
Investigation of frailty markers including a novel biomarker panel in emergency laparotomy: protocol of a prospective cohort study
Authors: Ng Hwei Jene , Quasim Tara , Rattray Nicholas J. W. , Moug Susan
Published: July 2023

Background

Emergency laparotomy (EmLAP) is one of the commonest emergency operations performed in the United Kingdom (approximately 30, 000 laparotomies annually). These potentially high-risk procedures can be life changing with frail patients and/ or older adults (≥ 65 years) having the poorest outcomes, including mortality. There is no gold standard of frailty assessment and no clinical chemical biomarkers existing in practice. Early detection of subclinical changes or deficits at the molecular level are essential in improving our understanding of the biology of frailty and ultimately improving patient outcomes. This study aims primarily to compare preoperative frailty markers, including a blood-based biomarker panel, in their ability to predict 30 and 90-day mortality post-EmLAP. The secondary aim is to analyse the influence of perioperative frailty on morbidity and quality of life post-EmLAP.

Methods

A prospective single centred observational study will be conducted on 150 patients ≥ 40 years of age that undergo EmLAP. Patients will be included according to the established NELA (National Emergency Laparotomy Audit) criteria. The variables collected include demographics, co-morbidities, polypharmacy, place of residence, indication and type of surgery (as per NELA criteria) and prognostic NELA score. Frailty will be assessed using: a blood sample for ultra-high performance liquid chromatography mass spectrometry analysis; preoperative CT abdomen pelvis (sarcopenia) and Rockwood Clinical Frailty Scale (CFS). Patients will be followed up for 90 days. Variables collected include blood samples (at post operative day 1, 7, 30 and 90), place of residence on discharge, morbidity, mortality and quality of life (EQ-5D-5 L). The frailty markers will be compared between groups of frail (CFS ≥ 4) and non-frail using statistical methods such as regression model and adjusted for appropriate confounding factors.

Discussion

This study hypothesises that frailty level changes following EmLAP in frail and non- frail patients, irrespective of age. We propose that non- frail patients will have better survival rates and report better quality of life compared to the frail. By studying the changes in metabolites/ biomarkers in these patients and correlate them to frailty status pre-surgery, this highly novel approach will develop new knowledge of frailty and define a new area of clinical biomolecular research.

Trial registration

ClinicalTrials.gov: NCT05416047. Registered on 13/06/2022 (retrospectively registered).
Expert consensus on relevant topics for undergraduate paediatric dental curriculum using the fuzzy Delphi method: a new direction for Malaysian dental education
Authors: Lin Galvin Sim Siang , Chin Yu Jie , Chong Rob Son , Baharin Fadzlinda , Syed Saadun Tarek Wafa Sharifah Wade’ah Wafa , Dziaruddin Nabihah
Published: July 2023

Background

Paediatric dentistry is a branch of dental specialty that focuses on dental care for children from infancy through adolescence. However, there is no standardised national undergraduate paediatric dental curriculum in Malaysia. The present study aimed to identify relevant topics for undergraduate paediatric dental curricula and to determine the appropriate cognitive and psychomotor levels for each topic based on the consensus among paediatric dental experts.

Methods

Potential relevant undergraduate paediatric dentistry topics were initially drafted and revised according to the revised national competency statement. The final draft included 65 topics clustered under 18 domains. A fuzzy Delphi method was used and experts who fulfilled the inclusion criteria were invited to anonymously ranked the importance of relevant topics using a five-point Likert scale and proposed suitable cognitive and psychomotor levels for each topic. Fuzzy evaluation was then performed, and experts were considered to have reached a consensus if the following three conditions were achieved: (a). the difference between the average and expert rating data was ≤ 0.2; (b). the average expert consensus was ˃70%; and (c). the average fuzzy number was ≥ 0.5. Subsequently, the mean ratings were used to determine the cognitive and psychomotor levels.

Results

20 experts participated in the survey. 64 out of 65 paediatric dentistry topics were deemed acceptable. The average fuzzy number ranged from 0.36 to 0.85, while the average Likert score ranged from 3.05 to 5.00. The topic “Dental amalgam” was rejected based on expert consensus since the average fuzzy number was 0.36. The most significant topic was “Pit and fissure sealant”, followed by “Preventive advice”, “Early childhood caries”, “Dental caries in children & adolescent”, “Management of dental caries in paediatric patients”, and “Consent” which were equally ranked as the second most important topics. According to Bloom’s and Simpson’s taxonomies, most of the paediatric dentistry topics were rated adequate for undergraduate students at the cognitive level of “Apply” (C3) and a psychomotor level of “Guided response” (P3).

Conclusion

The current study successfully identified relevant undergraduate paediatric dentistry topics using the fuzzy Delphi method, which can facilitate future educators to improve existing Malaysian undergraduate paediatric dental curricula.
Awareness of physicians and dentists in Serbia about the association between periodontitis and systemic diseases: a cross-sectional study
Authors: Stojilković Marija , Gušić Ivana , Prodanović Dušan , Ilić Miloš , Pecikozić Nevena , Veljović Tanja , Mirnić Jelena , Đurić Milanko
Published: July 2023

Background

Strong evidence supports the association between periodontitis and certain systemic diseases. The aim of the present study was to evaluate the knowledge of a group of physicians and dentists in Serbia regarding this topic and assess their professional actions to prevent and control both periodontal and systemic diseases.

Methods

An anonymous self-administered structured questionnaire was sent to the available e-mail addresses of randomly selected healthcare providers working in Serbia. According to the inclusion criteria, general practitioners, specialists, general dentists, and specialists working in government hospitals and private practices in various cities in Serbia were recruited in the study. The questionnaire consisted of 17 questions divided into three parts. The first part recorded the sociodemographic characteristics of participants, the second part included questions about the clinical manifestation and etiology of periodontitis, as well as knowledge of the association between periodontitis and systemic diseases, and the third part included questions about professional procedures for the prevention and control of periodontitis and systemic diseases.

Results

A total of 1301 health participants, 739 (57.8%) physicians and 562 (43.2%) dentists, were included in this cross-sectional study. Most respondents (94.7%) were aware of the association between periodontitis and general health. The highest percentage of respondents associated diabetes mellitus and periodontitis. Factors significantly associated with higher knowledge were female sex (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.37–2.52; p < 0.001) and dental profession (OR, 5.86; 95% CI], 4.03–8.53; p < 0.001). Participants who had higher knowledge score were more likely to ask their patients about gum/systematic health (p < 0.001) and refer them to dentists/physicians (p < 0.001).

Conclusions

It was concluded that compared to the group of dentists, the group of physicians had less knowledge of the relationship between periodontitis and systemic diseases. The female gender was significantly associated with better knowledge. A better understanding of this topic is associated with better clinical practice.
Russian nurses’ readiness for transcultural care of palliative patients
Authors: Kasimovskaya Nataliya , Geraskina Natalia , Fomina Elena , Ivleva Svetlana , Krivetskaya Maria , Ulianova Nina , Zhosan Marina
Published: July 2023

Palliative care involves an approach aimed at improving the quality of life of patients and their families, who are forced to cope with the problems associated with life-threatening diseases. This definition includes a growing group of patients around the world. It requires an extension of the definition of patients in need of palliative care in countries such as Russia and a significant improvement in the work of nursing personnel with these patients. This study aims to determine the level of preparedness of nursing personnel for specialized care (transcultural care) and the quality of care provided to palliative patients. The presented findings of the study demonstrate the relevance of developing transcultural competence, which enables significant improvement in the quality of life of palliative patients. The analysis of medical workers’ assessment of the level of specific training and their intercultural preparedness was conducted based on hospices (Moscow). A survey was conducted among 113 medical workers of the middle level of education aged between 28 and 56 (average of 44.2 years) and experience in palliative care ranged from 3 to 18 years (average of 9.5 years). The Intercultural Readiness Check (IRC) test, widely used to assess nursing staff worldwide, was used for the survey to determine the level of readiness for transcultural care. A strong correlation was found between a number of the test scales and measures of participants’ age and experience. The presented material demonstrates the realization of an interdisciplinary approach to the issues of specific training of nursing personnel in the field of “transcultural care” in providing palliative care to incurable patients.
Attitudes pregnant women in Türkiye towards holistic complementary and alternative medicine and influencing factors: a web-based cross-sectional study
Authors: Küçükkaya Burcu , Işık Hafsa Kübra
Published: July 2023

Background

Pregnant women turn to holistic complementary and alternative medicine to cope with problems associated with the changes they experience during pregnancy. This study aimed to determine the attitudes of pregnant women in Türkiye toward holistic complementary and alternative medicine and influencing factors.

Methods

This cross-sectional exploratory study was carried out between June and November 2022 with a web-based questionnaire distributed via social media and communication platforms. Two hundred and twenty-one pregnant women participated in the study. A "Participant Identification Form" and the "Attitudes towards Holistic Complementary and Alternative Medicine Questionnaire" were used to collect the data. Logistic regression analysis was used to determine correlations between variables and scale scores.

Results

It was determined that 84.2% of the participants had knowledge about traditional and complementary therapies, and 77.8% used traditional and complementary therapies. The participants reported that they preferred faith (77.4%), energy healing (76.9%), massage (75.6%), diet (74.2%), meditation/yoga (62.0%), and herbal (59.7%) traditional and complementary therapies the most, and most of them used these methods to reduce nausea, vomiting, edema, and fatigue during pregnancy. The mean Attitudes towards Holistic Complementary and Alternative Medicine Questionnaire score of the participants was 35.0 (5.04). It was seen that having high school or higher education (p < 0.05), having an income more than expenses (p < 0.001), having received advice from nurses when having a complaint (p < 0.001), having knowledge about traditional and complementary therapies (p < 0.001), and being a practitioner who received services of traditional and complementary therapies (p < 0.001) were positively associated with the utilization of traditional and complementary therapies.

Conclusion

In this study, it was determined that the attitudes of pregnant women towards holistic complementary and alternative medicine were high. Their personal characteristics, as well as their knowledge and practice of holistic complementary and alternative medicine affected their attitudes towards holistic complementary and alternative medicine. Obstetrics nurses/midwives should actively participate in training programs on traditional and complementary therapies focused on pregnant women.
Clinical learning environments across two different healthcare settings using the undergraduate clinical education environment measure
Authors: Benamer Hani TS , Alsuwaidi Laila , Khan Nusrat , Jackson Lisa , Lakshmanan Jeyaseelan , Ho Samuel B. , Kellett Catherine , Alsheikh-Ali Alawi , Stanley Adrian G
Published: July 2023

Background

The clinical placements of our medical students are almost equally distributed across private and public sectors. This study aims to assess medical students’ perceptions of their Clinical learning Environment (CLE) across these two different healthcare settings, using the Undergraduate Clinical Education Environment Measure (UCEEM).

Methods

76 undergraduate medical students (Year 5 and 6), were invited to participate. Data were collected using an online UCEEM with additional questions related to demographics and case load exposure. The UCEEM consists of two overarching domains of experiential learning and social participation, with four subdomains of learning opportunities, preparedness, workplace interaction, and inclusion.

Results

38 questionnaires were received. Of 225 responses to the individual UCEEM items, 51 (22.6%) scored a mean of ≥ 4 (range 4-4.5, representing strong areas), 31 (13.7%) scored a mean of ≤ 3 (range 2.1-3, needing attention) and 143 (63.6%) scored a mean of 3.1–3.9 (areas that could be improved). The majority (63%) of the case load exposure responses scored a mean of ≥ 4 (range 4-4.5). Compared to the private sittings, there is a significant reduction in total UCEEM (p = 0.008), preparedness for student entry (p = 0.003), and overarching dimension of social participation (p = 0.000) scores for the public sector. Similarly, both workplace interaction patterns and student inclusion and equal treatment scored significantly lower for the public sector (p = 0.000 and p = 0.011 respectively). Two out of three case load exposure items scored significantly higher for the public sector (p = 0.000).

Discussion

The students’ CLE perceptions were generally positive. The lower UCEEM ratings in the public sector items were related to student entry preparedness, workplace interactions, student inclusiveness and workforce equity of treatment. In contrast the students were exposed to more variety and larger number of patients in the public sector. These differences indicated some significantly different learning environments between the two sectors.
A six-year teaching life supportive first aid program to eventually generate peer trainer pupils: a prospective case control study
Authors: von Amelunxen Berndt , Kirk Samantha , Hind Julian , Illibauer Jennifer , Krall Christoph , Lessing Sebastian , Noyelle Aurelien , Murphy Peter M J , Sterz Fritz
Published: July 2023

Background

Out of hospital cardiac arrest is a life-threatening condition. To improve the chances of survival, lay-person cardio-pulmonary-resuscitation (CPR) is a crucial factor. Many bystanders fail to react appropriately, even if life supporting first aid (LSFA) programs and campaigns including CPR tried to increase the handling of basic cardiac life support. To achieve an enhanced learning of CPR a pupil’s grade after grade teaching program was established in a school with medical students.

Methods

The learning of CPR was investigated in a prospective, case-controlled study at an international school. Pupils (12 ± 3 years old) joining our LSFA courses (n = 538, female: 243, attendance for evaluation: 476) were compared to a control group (n = 129, female: 52, attendance for evaluation: 102). Surveys and quality of CPR (QCPR%) through a computer linked “Resusci Anne” dummy were compared with Chi-squared tests, t-tests pair wisely, and by one-way ANOVA.

Results

Knowledge and skills on the “Resusci Anne” were significantly better in trained grade 9 pupils compared to the control group (QCPR, 59 vs. 25%). The number of LSFA courses each grade 9 student had, correlated with improved practical performance (r2 = 0.21, p < 0.001). The willingness to deliver CPR to strangers increased with improved practical performance. Attitudes towards performing CPR were high in all participating grades.

Conclusion

Repetitive teaching LSFA to grade 5–9 pupil’s grade after grade by medical students has been successfully established. Pupils who finish the program will eventually be able to teach LSFA to younger students. This is furthermore a good way of sharing a “learning by teaching” role and it enables to have more pupils as trainers who can provide instruction to a larger number of pupils with the purpose of having a better-trained population in LSFA.
An analysis of the learning styles and attitudes of foreign students in a post-baccalaureate medical education program
Authors: Hsu Hsiang-Chin , Sung Tzu-Ching
Published: July 2023

In a scenario of ongoing changes in the theory and methodology of teaching, student-centered practices are crucial in improving teaching and learning outcomes. This study aimed to evaluate whether the learning styles and attitudes (connected and separate knowing) associated with the curriculum differ among medical students. The research subjects consisted of 43 first- and second-year medical students attending a post-baccalaureate medical education program exclusively for foreign students at a comprehensive university in Kaohsiung City, Taiwan. A self-administered Attitudes Toward Thinking and Learning Survey (ATTLS) was used to assess the differences in learning styles and attitudes among grades, gender, and nationality of these post-baccalaureate medical students. The reliability value of Cronbach Alpha coefficients for all items of ATTLS was 0.93. These medical students reported significantly higher connected knowing styles than separate knowing. The average score of the connected knowing for first-year students taking the "International Health" course is significantly higher than that of second-year students taking the "Population Health and Sustainable Development" course. There is no difference in the separate knowing between these two curricula. The learning styles and attitudes of students participating in the teaching process showed no difference in grade, gender, and nationality. The evidence that there is a significant interaction effect of grade, gender, and nationality examined with the separate knowing, rather than the connected knowing, suggests that this heterogenicity of learning methodology needs to be considered and integrated into future teaching methods.
Design and implementation of a web-based, respondent-driven sampling solution
Authors: McGowan Catherine R. , Ekoriko Promise , Alhaffar Mervat , Cassidy-Seyoum Sarah , Whitbread Steven , Rogers Phil , Bell Lucy , Checchi Francesco
Published: July 2023

Background

Respondent-driven sampling (RDS) refers both to a chain-referral sampling method and an analytical model for analysing sampled data. Web-based respondent-driven sampling (webRDS) uses internet-based recruitment coupled with an electronic survey to carry out RDS studies; there is currently no commercially available webRDS solution. We designed and developed a webRDS solution to support a research study aimed at estimating conflict-attributable mortality in Yemen. Our webRDS solution is composed of an existing survey platform (i.e. ODK) and a bespoke RDS system. The RDS system is designed to administer and manage an RDS survey cascade and includes: (1) an application programming interface, (2) a study participant client, and (3) an administrator interface. We report here on the design of the webRDS solution and its implementation.

Results

We consulted members of the Yemeni diaspora throughout the development of the solution. Technical obstacles were largely the result of: WhatsApp’s policies on bulk messaging and automated messaging behaviour, the inherent constraints of SMS messaging, and SMS filtering behaviour. Language support was straight-forward yet time consuming. Survey uptake was lower than expected. Factors which may have impacted uptake include: our use of consumable survey links, low interest amongst the diaspora population, lack of material incentives, and the length and subject matter of the survey itself. The SMS/WhatsApp messaging integration was relatively complex and limited the information we could send potential participants.

Conclusion

Despite lower-than expected survey uptake we believe our webRDS solution provides efficient and flexible means to survey a globally diverse population.
Staff perspectives on the influence of patient characteristics on alarm management in the intensive care unit: a cross-sectional survey study
Authors: Balzer Felix , Agha-Mir-Salim Louis , Ziemert Nicole , Schmieding Malte , Mosch Lina , Prendke Mona , Wunderlich Maximilian Markus , Memmert Belinda , Spies Claudia , Poncette Akira-Sebastian
Published: July 2023

Background

High rates of clinical alarms in the intensive care unit can result in alarm fatigue among staff. Individualization of alarm thresholds is regarded as one measure to reduce non-actionable alarms. The aim of this study was to investigate staff’s perceptions of alarm threshold individualization according to patient characteristics and disease status.

Methods

This is a cross-sectional survey study (February-July 2020). Intensive care nurses and physicians were sampled by convenience. Data was collected using an online questionnaire.

Results

Staff view the individualization of alarm thresholds in the monitoring of vital signs as important. The extent to which alarm thresholds are adapted from the normal range varies depending on the vital sign monitored, the reason for clinical deterioration, and the professional group asked. Vital signs used for hemodynamic monitoring (heart rate and blood pressure) were most subject to alarm individualizations. Staff are ambivalent regarding the integration of novel technological features into alarm management.

Conclusions

All relevant stakeholders, including clinicians, hospital management, and industry, must collaborate to establish a “standard for individualization,” moving away from ad hoc alarm management to an intelligent, data-driven alarm management. Making alarms meaningful and trustworthy again has the potential to mitigate alarm fatigue – a major cause of stress in clinical staff and considerable hazard to patient safety.

Trial registration

The study was registered at ClinicalTrials.gov (NCT03514173) on 02/05/2018.
Development of consensus-driven SPIRIT and CONSORT extensions for early phase dose-finding trials: the DEFINE study
Authors: Solovyeva Olga , Dimairo Munyaradzi , Weir Christopher J. , Hee Siew Wan , Espinasse Aude , Ursino Moreno , Patel Dhrusti , Kightley Andrew , Hughes Sarah , Jaki Thomas , Mander Adrian , Evans Thomas R. Jeffry , Lee Shing , Hopewell Sally , Rantell Khadija Rerhou , Chan An-Wen , Bedding Alun , Stephens Richard , Richards Dawn , Roberts Lesley , Kirkpatrick John , de Bono Johann , Yap Christina
Published: July 2023

Background

Early phase dose-finding (EPDF) trials are crucial for the development of a new intervention and influence whether it should be investigated in further trials. Guidance exists for clinical trial protocols and completed trial reports in the SPIRIT and CONSORT guidelines, respectively. However, both guidelines and their extensions do not adequately address the characteristics of EPDF trials. Building on the SPIRIT and CONSORT checklists, the DEFINE study aims to develop international consensus-driven guidelines for EPDF trial protocols (SPIRIT-DEFINE) and reports (CONSORT-DEFINE).

Methods

The initial generation of candidate items was informed by reviewing published EPDF trial reports. The early draft items were refined further through a review of the published and grey literature, analysis of real-world examples, citation and reference searches, and expert recommendations, followed by a two-round modified Delphi process. Patient and public involvement and engagement (PPIE) was pursued concurrently with the quantitative and thematic analysis of Delphi participants’ feedback.

Results

The Delphi survey included 79 new or modified SPIRIT-DEFINE (n = 36) and CONSORT-DEFINE (n = 43) extension candidate items. In Round One, 206 interdisciplinary stakeholders from 24 countries voted and 151 stakeholders voted in Round Two. Following Round One feedback, one item for CONSORT-DEFINE was added in Round Two. Of the 80 items, 60 met the threshold for inclusion (≥ 70% of respondents voted critical: 26 SPIRIT-DEFINE, 34 CONSORT-DEFINE), with the remaining 20 items to be further discussed at the consensus meeting. The parallel PPIE work resulted in the development of an EPDF lay summary toolkit consisting of a template with guidance notes and an exemplar.

Conclusions

By detailing the development journey of the DEFINE study and the decisions undertaken, we envision that this will enhance understanding and help researchers in the development of future guidelines. The SPIRIT-DEFINE and CONSORT-DEFINE guidelines will allow investigators to effectively address essential items that should be present in EPDF trial protocols and reports, thereby promoting transparency, comprehensiveness, and reproducibility.

Trial registration

SPIRIT-DEFINE and CONSORT-DEFINE are registered with the EQUATOR Network (https://www.equator-network.org/).
CMA mediates resistance in breast cancer models
Authors: Lo Dico Alessia , Martelli C. , Corsi F. , Porro D. , Ottobrini L. , Bertoli G.
Published: July 2023

Background

Breast cancer (BC) is the most common malignancy in women and the second leading cause of cancer-related death; chemoresistance is still a clinical challenge mainly because of the different molecular features of this kind of tumour. Doxorubicin (Doxo) is widely used despite its adverse effects and the common onset of resistance. Chaperone-Mediated Autophagy (CMA) has been identified as an important mechanism through which chemotherapeutics can exert their cytotoxic effects and, in this context, LAMP-2A, the key player of CMA, can be a useful biomarker.

Methods

A cohort of patients and breast cancer cells have been screened for Doxo effect and CMA activation by analysing the LAMP-2A level. Molecular silencing has been used to clarify CMA role in BC responsiveness to treatments. Low Doxo doses were combined with other drugs (TMZ or PX-478, a HIF-1α inhibitor) to evaluate their cytotoxic ability and their role in modulating CMA.

Results

In this paper, we showed that CMA is an important mechanism mediating the responsiveness of breast cancer cell to different treatments (Doxo and TMZ, as suggested by triple negative cells that are TMZ-resistant and fails to activate CMA). The LAMP-2A expression level was specific for different cell lines and patient-derived tumour subtypes, and was also useful in discriminating patients for their survival rates. Moreover, molecular silencing or pharmacological blockage of HIF-1α activity reverted BC resistance to TMZ. The combination of low-dose Doxo with TMZ or PX-478 showed that the drug associations have synergistic behaviours.

Conclusion

Here, we demonstrated that CMA activity exerts a fundamental role in the responsiveness to different treatments, and LAMP-2A can be proposed as a reliable prognostic biomarker in breast cancer. In this context, HIF-1α, a potential target of CMA, can also be assessed as a valuable therapeutic target in BC in view of identifying new, more efficient and less toxic therapeutic drug combinations. Moreover, the possibility to combine Doxo with other drugs acting on different but coherent molecular targets could help overcome resistance and open the way to a decrease in the dose of the single drugs.
Novel inflammatory mediator profile observed during pediatric heart surgery with cardiopulmonary bypass and continuous ultrafiltration
Authors: Bierer Joel , Stanzel Roger , Henderson Mark , Sett Suvro , Sapp John , Andreou Pantelis , Marshall Jean S. , Horne David
Published: July 2023

Background

Cardiopulmonary bypass (CPB) is associated with systemic inflammation, featuring increased levels of circulating pro-inflammatory cytokines. Intra-operative ultrafiltration extracts fluid and inflammatory factors potentially dampening inflammation-related organ dysfunction and enhancing post-operative recovery. This study aimed to define the impact of continuous subzero-balance ultrafiltration (SBUF) on circulating levels of major inflammatory mediators.

Methods

Twenty pediatric patients undergoing cardiac surgery, CPB and SBUF were prospectively enrolled. Blood samples were collected prior to CPB initiation (Pre-CPB Plasma) and immediately before weaning off CPB (End-CPB Plasma). Ultrafiltrate effluent samples were also collected at the End-CPB time-point (End-CPB Effluent). The concentrations of thirty-nine inflammatory factors were assessed and sieving coefficients were calculated.

Results

A profound increase in inflammatory cytokines and activated complement products were noted in plasma following CBP. Twenty-two inflammatory mediators were detected in the ultrafiltrate effluent. Novel mediators removed by ultrafiltration included cytokines IL1-Ra, IL-2, IL-12, IL-17A, IL-33, TRAIL, GM-CSF, ET-1, and the chemokines CCL2, CCL3, CCL4, CXCL1, CXCL2 and CXCL10. Mediator extraction by SBUF was significantly associated with molecular mass < 66 kDa (Chi2 statistic = 18.8, Chi2 with Yates’ correction = 16.0, p < 0.0001). There was a moderate negative linear correlation between molecular mass and sieving coefficient (Spearman R = − 0.45 and p = 0.02). Notably, the anti-inflammatory cytokine IL-10 was not efficiently extracted by SBUF.

Conclusions

CPB is associated with a burden of circulating inflammatory mediators, and SBUF selectively extracts twenty of these pro-inflammatory factors while preserving the key anti-inflammatory regulator IL-10. Ultrafiltration could potentially function as an immunomodulatory therapy during pediatric cardiac surgery.

Trial registration ClinicalTrials.gov, NCT05154864. Registered retrospectively on December 13, 2021. https://clinicaltrials.gov/ct2/show/record/NCT05154864.
A systematic review and meta-analysis of urinary biomarkers in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)
Authors: Taccori Asher , Maksoud Rebekah , Eaton-Fitch Natalie , Patel Maharshi , Marshall-Gradisnik Sonya
Published: July 2023

Background

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multifactorial illness that affects many body systems including the immune, nervous, endocrine, cardiovascular, and urinary systems. There is currently no universal diagnostic marker or targeted treatment for ME/CFS. Urine is a non-invasive sample that provides biomarkers that may have the potential to be used in a diagnostic capacity for ME/CFS. While there are several studies investigating urine-based biomarkers for ME/CFS, there are no published systematic reviews to summarise existing evidence of these markers. The aim of this systematic review was to compile and appraise literature on urinary-based biomarkers in ME/CFS patients compared with healthy controls.

Methods

Three databases: Embase, PubMed, and Scopus were searched for articles pertaining to urinary biomarkers for ME/CFS compared with healthy controls published between December 1994 to December 2022. The final articles included in this review were determined through application of specific inclusion and exclusion criteria. Quality and bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Case Control Studies. A meta-analysis according to Cochrane guidelines was conducted on select studies, in particular, those that investigate urinary free cortisol levels in ME/CFS patients compared to healthy controls using the program STATA 17.

Results

Twenty-one studies were included in this review. All of the studies investigated urinary-based markers in ME/CFS patients compared with healthy controls. The reported changes in urinary outputs include urinary free cortisol (38.10%), carnitine (28.6%), iodine (4.76%), and the metabolome (42.86%). In most cases, there was minimal overlap in the main outcomes measured across the studies, however, differences in urinary free cortisol between ME/CFS patients and healthy controls were commonly reported. Seven studies investigating urinary free cortisol were included in the meta-analysis. While there were significant differences found in urinary free cortisol levels in ME/CFS patients, there was also substantial heterogeneity across the included studies that makes drawing conclusions difficult.

Conclusions

There is limited evidence suggesting a consistent and specific potential urinary-based biomarker for ME/CFS. Further investigations using more standardised methodologies and more stringent case criteria may be able to identify pathophysiological differences with diagnostic potential in ME/CFS patients compared with healthy controls.
The use of alpha 1 thymosin as an immunomodulator of the response against SARS-Cov2
Authors: Espinar-Buitrago M. S. , Tarancon-Diez L. , Vazquez-Alejo E. , Magro-Lopez E. , Genebat M. , Romero-Candau F. , Leal M. , Muñoz-Fernandez M. A.
Published: July 2023

Background

Since the beginning of SARS-CoV2 pandemic, the mortality rate among elderly patients (60–90 years) has been around 50%, so age has been a determining factor of a worse COVID-19 prognosis. Associated with age, the thymic function involution and depletion plays an important role, that could be related to a dysregulated and ineffective innate and adaptive immune response against SARS-CoV2. Our study aims to further in vitro effect of human Thymosin-alpha-1 (α1Thy) treatment on the immune system in population groups with different thymic function levels in the scenario of SARS-CoV2 infection.

Results

Activation markers such as CD40, CD80 and TIM-3 were upregulated in α1Thy presence, especially in plasmacytoid dendritic cells (pDCs) and, with increased TNFα production was observed compared to untreated condition. Co-cultures of CD4 + and CD8 + T cells with DCs treated with α1Thy in response to SARS-CoV2 peptides showed a decrease in the cytokine production compared to the condition without α1Thy pre-treated. A decrease in CD40L activation co-receptor expression in CD8 + LTs was also observed, as well as an increase in PD1 in CD4 + TLs expression in both age groups. In fact, there are no age-related differences in the immunomodulatory effect of the hormone, and it seems that effector memory and terminally differentiated memory T lymphocyte subsets were the most actively influenced by the immunomodulatory α1Thy effect. Finally, the polyfunctionality measured in SARS-CoV2 Specific-T cells response was maintained in α1Thy presence in total and memory subpopulations CD4 + and CD8 + T-cells, despite decreased proinflammatory cytokines production.

Conclusion

The hormone α1Thy could reduce, through the modulation of DCs, the amount of proinflammatory cytokines produced by T cells. Moreover, α1Thy improve lymphocyte functionality and could become a beneficial therapeutic alternative as an adjuvant in SARS-CoV2 treatment either in the acute phase after infection or reinfection. In addition, the effect on the T immune response means that α1Thy can be incorporated into the vaccination regimen, especially in the most immunologically vulnerable individuals such as the elderly.

Subjects

Thymosin alpha 1, Dendritic cells, SARS-CoV2-specific T cells response, Immunomodulation