Search

Abstract Background Paracetamol is the most consumed medicine globally. Its accessibility contributes to common overdose. Paracetamol overdose is responsible for > 50% of acute liver failure cases, making it the second most common reason for a liver transplant. Rapid quantitation of paracetamol is crucial to guide treatment of paracetamol overdose. Current tests require invasive sampling and relatively long turnaround times. Paper arrow-mass spectrometry (PA-MS) combines sample collection, extraction, separation, enrichment and ionisation onto a single paper strip, achieving rapid, accurate, cost-effective and eco-friendly analysis direct from raw human saliva. Methods To validate PA-MS against an established test, 17 healthy adults were recruited. Samples were collected before and at 15, 30, 60, 120 and 240 min after ingesting 1 g of paracetamol. Plasma measured with an established clinical test served as the reference standard to validate PA-MS with three biofluids—plasma, resting saliva (RS) and stimulated saliva (SS). Participants’ views of blood, RS and SS sampling procedures were assessed qualitatively. Cross-validation was assessed using Lin’s concordance correlation coefficients (CCC), Bland–Altman difference plots, and ratios of PA-MS to the reference standard test. Results PA-MS using stimulated saliva offers a reliable alternative to intravenous blood sampling. The CCC is 0.93, the mean difference with the reference test is − 0.14 mg/L, and the ratios compared to the reference test are 0.84–1.27 from correlated samples collected at 5 intervals over 4 h for each participant. Conclusions Paracetamol detection from SS with PA-MS provides a reliable result that can aid timely treatment decisions. Differences between paracetamol concentration in resting and stimulated saliva were also identified for the first time, highlighting the importance of standardising saliva collection methods in general. This study marks a major milestone towards rapid and convenient saliva analysis.

Abstract The trail making test (TMT) is a commonly used tool for evaluating executive functions, and the activation of cerebral oxygenation in the prefrontal cortex (PFC) during the test can reflect the participation of executive function. This study aimed to compare the differences in cerebral oxygenation in the PFC between the computer- and paper-based versions of the TMT and provide a theoretical basis for the optimization and clinical application of the computer-based version. A total of 32 healthy adult participants completed the computer- and paper-based TMT Types A and B. Cerebral oxygenation changes in the PFC were monitored during the experiment using near-infrared spectroscopy. Moreover, average changes in oxyhemoglobin (Δoxy-Hb) levels at the baseline and during activation periods in different types of testing were compared and analyzed. The number of correct connections in the computer-based version Type B was less than that in the paper-based version Type B (p

Abstract Background Education was affected during the COVID-19 pandemic, and there was a need to adapt the learning approaches to the situation. At the University of Gadjah Mada, many essential soft skills of healthcare professionals are taught using the interprofessional education (IPE) approach on-site. Our university responded to this crisis by offering online classes and similar types of training. Post-administration of the course, a peer-assessment was conducted, and it was used to provide feedback on the work or performance of peers among students. Peer assessment was done using paper-based and a mobile application during COVID-19. This study aimed to share a best practice for the implementation of a rank-based peer-assessment application for longitudinal interprofessional education in the community setting and to compare the score distribution of a rank-based peer-assessment before and after using mobile application. Methods Quantitative research design was used by processing secondary data on student peer assessment scores from 3 bachelor programs (medicine, nursing, nutritionist) Community and Family Health Care with Interprofessional Education (CFHC-IPE) in Faculty of Medicine, Nursing, and Public Health, Universitas Gadjah Mada. 4,790 students from 2018 to 2022 (5 years) were tracked before, during, and after the COVID-19 pandemic. The assessments carried out were offline, online, and blended learning, respectively. The assessment was carried out using a paper-based method before and during the pandemic, online-based with a mobile application was used. Thus, the peer-assessment was conducted manually or using paper-based method using a 5-rank scoring system. In 2019, the peer assessment was carried out using a mobile application and applied a 10-rank scoring system. Results The rank-based peer assessment can be well implemented to make students assess their friends more objectively, with an average score 82.02 ± 8.68. The rightward shift in the distribution of scores indicates that the average score has improved after using the mobile application compared to before its use. (82.02 ± 8.68 vs. 62.39 ± 11.13, p

Abstract Background Rib fractures are one of the most common traumatic injuries and may result in significant morbidity and mortality. Despite growing evidence, technological advances and increasing acceptance, surgical stabilization of rib fractures (SSRF) remains not uniformly considered in trauma centers. Indications, contraindications, appropriate timing, surgical approaches and utilized implants are part of an ongoing debate. The present position paper, which is endorsed by the World Society of Emergency Surgery (WSES), and supported by the Chest Wall Injury Society, aims to provide a review of the literature investigating the use of SSRF in rib fracture management to develop graded position statements, providing an updated guide and reference for SSRF. Methods This position paper was developed according to the WSES methodology. A steering committee performed the literature review and drafted the position paper. An international panel of experts then critically revised the manuscript and discussed it in detail, to develop a consensus on the position statements. Results A total of 287 studies (systematic reviews, randomized clinical trial, prospective and retrospective comparative studies, case series, original articles) have been selected from an initial pool of 9928 studies. Thirty-nine graded position statements were put forward to address eight crucial aspects of SSRF: surgical indications, contraindications, optimal timing of surgery, preoperative imaging evaluation, rib fracture sites for surgical fixation, management of concurrent thoracic injuries, surgical approach, stabilization methods and material selection. Conclusion This consensus document addresses the key focus questions on surgical treatment of rib fractures. The expert recommendations clarify current evidences on SSRF indications, timing, operative planning, approaches and techniques, with the aim to guide clinicians in optimizing the management of rib fractures, to improve patient outcomes and direct future research.

Abstract Background In healthcare research and practice, intervention and implementation fidelity represent the steadfast adherence to core components of research-supported interventions and the strategies employed for their implementation. Evaluating fidelity involves determining whether these core components were delivered as intended. Without fidelity data, the results of complex interventions cannot be meaningfully interpreted. Increasingly, the necessity for firmness and strict adherence by implementers and their organizations has been questioned, with calls for flexibility to accommodate contextual conditions. This shift makes contemporary fidelity a balancing act, requiring researchers to navigate various tensions. This debate paper explores these tensions, drawing on experiences from developing fidelity assessments in two ongoing effectiveness-implementation hybrid trials. Main body First, given often scarce knowledge about the core components of complex interventions and implementation strategies, decisions about fidelity requirements involve a degree of subjective reasoning. Researchers should make these decisions transparent using theory or logic models. Second, because fidelity is context-dependent and applies to both interventions and implementation strategies, researchers must rethink fidelity concepts with every study while balancing firmness and flexibility. This is particularly crucial for hybrid studies, with their differing emphasis on intervention and implementation fidelity. Third, fidelity concepts typically focus on individual behaviors. However, since organizational and system factors also influence fidelity, there is a growing need to define fidelity criteria at these levels. Finally, as contemporary fidelity concepts prioritize flexible over firm adherence, building, evaluating, and maintaining fidelity in healthcare research has become more complex. This complexity calls for intensified efforts to expand the knowledge base for pragmatic and adaptive fidelity measurement in trial and routine healthcare settings. Conclusion Contemporary conceptualizations of fidelity place greater demands on how fidelity is examined, necessitating the expansion of fidelity frameworks to include organizational and system levels, the service- and study-specific conceptualizations of intervention and implementation fidelity, and the development of pragmatic approaches for assessing fidelity in research and practice. Continuing to build knowledge on how to balance requirements for firmness and flexibility remains a crucial task within the field of implementation science.

Abstract Background This case study examines the application of Integrated Enhanced Cognitive Behavioural Therapy (I-CBTE) for a patient with severe, longstanding anorexia nervosa and multiple comorbidities, including organic hallucinosis, complex post-traumatic stress disorder (CPTSD), and severe self-harm. Such complex presentations often result in patients falling between services, which can lead to high chronicity and increased mortality risk. Commentaries from two additional patients who have recovered from severe and longstanding anorexia nervosa are included. Case study The patient developed severe anorexia nervosa and hallucinosis after a traumatic brain injury in 2000. Despite numerous hospitalisations and various psychotropic medications in the UK and France, standard treatments were ineffective for 17 years. However, Integrated Enhanced Cognitive Behaviour Therapy (I-CBTE) using a whole-team approach and intensive, personalised psychological treatment alongside nutritional rehabilitation proved effective. Methods In this paper, we describe the application of the I-CBTE model for individuals with severe, longstanding, and complex anorexia nervosa, using lived experience perspectives from three patients to inform clinicians. We also outline the methodology for adapting the model to different presentations of the disorder. Outcomes The patient achieved and maintained full remission from her eating disorder over the last 6 years, highlighting the benefit of the I-CBTE approach in patients with complex, longstanding eating disorder histories. Successful treatment also saved in excess of £360 k just by preventing further hospitalisations and not accounting for the improvement in her quality of life. This suggests that this method can improve outcomes and reduce healthcare costs. Conclusion This case study, with commentaries from two patients with histories of severe and longstanding anorexia nervosa, provides a detailed description of the practical application of I-CBTE for patients with severe and longstanding eating disorders with complex comorbidities, and extensive treatment histories. This offers hope for patients and a framework for clinicians to enhance existing treatment frameworks, potentially transforming the trajectory of those traditionally deemed treatment resistant. Recommendations We advocate the broader integration of CBT for EDs into specialist services across the care pathway to help improve outcomes for patients with complex eating disorders. Systematic training and supervision for multidisciplinary teams in this specialised therapeutic approach is recommended. Future research should investigate the long-term effectiveness of I-CBTE through longitudinal studies. Patient feedback on experiences of integrated models of care such as I-CBTE is also needed. In addition, systematic health economics studies should be conducted.

Abstract This viewpoint paper focuses on challenges for Swiss physiotherapy education institutes related to the transition towards evidence-based practice and the incorporation of advanced roles within the profession. To tackle such challenges, it is essential to establish structured pathways and competency frameworks and position physiotherapists as integral contributors to innovative healthcare.

Abstract Micro-credentials are an element of the European Skills Agenda 2020. This five-year plan aims to develop improved applied and broader work skills in response to system demands from employers, industry and communities. Within the labour market, employees increasingly want to obtain new skills-based qualifications in a relatively short period of time. Micro-credentials, as a form of lifelong learning, in the health care sector provide significant opportunities for upskilling the workforce in response to rapid changes in health care and service delivery. Moreover, micro-credentials have also been introduced in the context of undergraduate and postgraduate education within the process of accelerated digitalisation during the pandemic. However, despite its relevance, there is limited discussion about the implications and challenges of micro-credentials in the healthcare sciences. According to the findings that emerged from a review of policy documents and scientific papers, a reflective exercise has been conducted to debate the possibilities and challenges of emerging education based on micro-credentials within health care education and employment. Health care delivery is multidisciplinary and statutorily regulated to protect citizens. In such a complex sector, developing a micro-credential friendly ecosystem will require cooperation between various stakeholders if its potential is to be effectively realised.

Abstract Despite the implementation of preventive measures to counteract the obesity epidemics, the prevalence of childhood obesity is still alarming all over the world. Childhood obesity is the most common risk factor for both cardiovascular and metabolic diseases. In fact, an earlier onset of obesity can cause a greater risk of adiposity tracking across the lifespan and consequently a longer exposure to cardiometabolic risk factors. Accumulating evidence provided by prospective and intervention studies demonstrated the link between pediatric obesity and selected subclinical signs of cardiovascular damage (atherosclerosis and left ventricular hypertrophy), or fatal and not fatal cardiovascular events as early as 40 years of age. The numerous guidelines and scientific documents published in the last years demonstrate the relevance of assessing cardiometabolic risk factors in children and adolescents with OB. This Position paper, released by experts of the “Childhood Obesity study group” within the Italian Society for Pediatric Endocrinology and Diabetology, aims to review the assessment of cardiometabolic risk factors and comorbidities in children and adolescents with OW/OB on the light of the most recent scientific evidence. The main recommendations are: (a) early detection of comorbidities, including hypertension, dyslipidemia, prediabetes/type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, polycystic ovary syndrome, inactivity, obstructive sleep apnea and decline in kidney function; (b) weight loss treatment, which is associated with a reduction of all cardiometabolic risk factors; (c) specific treatment of comorbidities, through lifestyle modifications or pharmacological treatment added to lifestyle for suitable individuals; d). monitoring comorbidities for mitigating future morbidity and mortality.

Abstract Background As the opioid epidemic continues to have a major negative impact across the US, community pharmacies have come under scrutiny from legal systems attempting to hold them accountable for their role in over dispensing and lack of patient intervention. While the most available tool for monitoring patients’ opioid use is Prescription Drug Monitoring Programs (PDMP), these do not provide pharmacists with actionable information and decision support. Our study addresses this gap through three objectives: [1] incorporate validated opioid risk metric thresholds into a PDMP platform to create the Opioid Risk Reduction Clinical Decision Support (ORRCDS) tool; [2] assess ORRCDS’ ability to reduce patient opioid risk; [3] assess ORRCDS’ sustainability and viability for broader dissemination in community pharmacy. Methods For objective 1, our team is partnering with leadership from the largest US PDMP organization and a top-five pharmacy chain to implement ORRCDS into the pharmacy chain’s workflow following the Guideline Implementation with Decision Support (GUIDES) framework. For objective 2, our team will conduct a type-1 implementation mixed methods study using a 2-arm parallel group clustered randomized design. We anticipate enrolling ~ 6,600 patients with moderate and high opioid use risk during the 6-month enrollment phase across 80 pharmacies. This sample size will provide 96.3% power to detect a 5% or greater difference in responder rate between the intervention and control arm. Responders are patients with moderate-risk at baseline who reduce to low-risk or those with high-risk at baseline who reduce to moderate or low-risk at 180 days post last intervention. To accomplish objective 3, we will use the Consolidated Framework for Implementation Research (CFIR) to develop and execute cross-sectional qualitative interviews with pharmacists (n = 15), pharmacy leaders (n = 15), and PDMP leaders (n = 15) regarding long term adoption and sustainability of the ORRCDS tool. Conclusions A PDMP tool that addresses moderate- and high-risk opioid use is not available in community pharmacy. This study will implement ORRCDS in a large retail pharmacy chain that will include additional screening and guidance to pharmacy staff to address risky opioid medication use. Our results will make critical advancements for protecting patient health and addressing the opioid epidemic.

Abstract This autobiographical paper recounts the recovery journey of Lorna Collins, a survivor of severe and enduring anorexia nervosa (SE-AN). Her story begins with a traumatic brain injury at the age of 18, leading to a complex eating disorder that persisted for over two decades. Despite over 30 hospital admissions and various treatment modalities, her condition only worsened, compounded by other mental health challenges. The paper describes these multifaceted struggles, including mistreatment in healthcare, self-harm, further trauma and near-fatal illness. The author aims to culminate her story in an uplifting manner, by highlighting the pivotal role that integrated cognitive behaviour therapy, artistic expression, and a renewed connection with her family have made on her recovery. Collins’ account is not only a personal testimony but also offers critical insights into the shortcomings of traditional eating disorder treatments and the importance of personalised, holistic approaches in mental health care. Lorna’s story aims to bring hope, challenge the concept of SEED and form part of a growing evidence-base that recovery is possible irrespective of duration or eating disorder severity.

Abstract Mendelian randomization (MR) is a powerful epidemiological method for causal inference. However, its recent surge in popularity has brought two concerning trends. First, the public availability of summary results from genome-wide association studies has led to an explosion of low-quality two-sample mendelian randomization (2SMR) studies. These studies add minimal – if any – value and overwhelm reviewers and journals. Second, the availability of large datasets with individual-level genotype data, like UK Biobank, has spurred the development and use of novel MR methods. However, some methods are being applied without proper testing, leading to misleading results, as exemplified by recent spurious findings that are being retracted and/or corrected relating to vitamin D. What can editors and peer reviewers do to handle the deluge of 2SMR studies and the premature application of highly complex MR methods? We advise editors to simply reject papers that only report 2SMR findings, with no additional supporting evidence. For reviewers receiving such papers, we provide a template for rejection. In addition, reviewers should demand rigorous testing of novel methods, including through the use of positive and negative controls before they are applied. Rejecting non-contributory 2SMR papers and imposing intensive scrutiny to novel methods is crucial if the scientific community is to reclaim MR.

Abstract Background Unhealthy diet is a key risk factor for Non-Communicable Diseases (NCDs) that contribute to increased morbidity and premature mortality. With increased computer literacy and mobile phone penetration, there is a high opportunity for mobile application-based interventions. The current study was conducted to develop a mobile application to monitor dietary intake and to assess its acceptability and effectiveness in diet control compared to a similar paper-based intervention. A mobile application was developed based on research evidence and opinions of local experts. The mobile application was introduced to a selected group of office workers who were in preparation, action, and maintenance stages of the Trans Theoretical Model (TTM) and a paper-based intervention was used as the comparator. Socio-demographic data were collected through a self-administered questionnaire. Participants were followed up for three months for adherence. The effectiveness of interventions was assessed at the end of three months by comparing the progressive change in the stage of change and the change from unhealthy to healthy dietary intake between two groups as primary and secondary outcomes respectively. Results Among 123 office workers who participated in the study, 19.5% preferred the mobile intervention over the paper-based intervention. Younger, unmarried office workers and those who do not have children, had a higher acceptance for the mobile intervention (p

Abstract Software that employs screening prioritization through active learning (AL) has accelerated the screening process significantly by ranking an unordered set of records by their predicted relevance. However, failing to find a relevant paper might alter the findings of a systematic review, highlighting the importance of identifying elusive papers. The time to discovery (TD) measures how many records are needed to be screened to find a relevant paper, making it a helpful tool for detecting such papers. The main aim of this project was to investigate how the choice of the model and prior knowledge influence the TD values of the hard-to-find relevant papers and their rank orders. A simulation study was conducted, mimicking the screening process on a dataset containing titles, abstracts, and labels used for an already published systematic review. The results demonstrated that AL model choice, and mostly the choice of the feature extractor but not the choice of prior knowledge, significantly influenced the TD values and the rank order of the elusive relevant papers. Future research should examine the characteristics of elusive relevant papers to discover why they might take a long time to be found.

Abstract Background Academic paper writing holds significant importance in the education of medical students, and poses a clear challenge for those whose first language is not English. This study aims to investigate the effectiveness of employing large language models, particularly ChatGPT, in improving the English academic writing skills of these students. Methods A cohort of 25 third-year medical students from China was recruited. The study consisted of two stages. Firstly, the students were asked to write a mini paper. Secondly, the students were asked to revise the mini paper using ChatGPT within two weeks. The evaluation of the mini papers focused on three key dimensions, including structure, logic, and language. The evaluation method incorporated both manual scoring and AI scoring utilizing the ChatGPT-3.5 and ChatGPT-4 models. Additionally, we employed a questionnaire to gather feedback on students’ experience in using ChatGPT. Results After implementing ChatGPT for writing assistance, there was a notable increase in manual scoring by 4.23 points. Similarly, AI scoring based on the ChatGPT-3.5 model showed an increase of 4.82 points, while the ChatGPT-4 model showed an increase of 3.84 points. These results highlight the potential of large language models in supporting academic writing. Statistical analysis revealed no significant difference between manual scoring and ChatGPT-4 scoring, indicating the potential of ChatGPT-4 to assist teachers in the grading process. Feedback from the questionnaire indicated a generally positive response from students, with 92% acknowledging an improvement in the quality of their writing, 84% noting advancements in their language skills, and 76% recognizing the contribution of ChatGPT in supporting academic research. Conclusion The study highlighted the efficacy of large language models like ChatGPT in augmenting the English academic writing proficiency of non-native speakers in medical education. Furthermore, it illustrated the potential of these models to make a contribution to the educational evaluation process, particularly in environments where English is not the primary language.

Abstract Background In the healthcare domain today, despite the substantial adoption of electronic health information systems, a significant proportion of medical reports still exist in paper-based formats. As a result, there is a significant demand for the digitization of information from these paper-based reports. However, the digitization of paper-based laboratory reports into a structured data format can be challenging due to their non-standard layouts, which includes various data types such as text, numeric values, reference ranges, and units. Therefore, it is crucial to develop a highly scalable and lightweight technique that can effectively identify and extract information from laboratory test reports and convert them into a structured data format for downstream tasks. Methods We developed an end-to-end Natural Language Processing (NLP)-based pipeline for extracting information from paper-based laboratory test reports. Our pipeline consists of two main modules: an optical character recognition (OCR) module and an information extraction (IE) module. The OCR module is applied to locate and identify text from scanned laboratory test reports using state-of-the-art OCR algorithms. The IE module is then used to extract meaningful information from the OCR results to form digitalized tables of the test reports. The IE module consists of five sub-modules, which are time detection, headline position, line normalization, Named Entity Recognition (NER) with a Conditional Random Fields (CRF)-based method, and step detection for multi-column. Finally, we evaluated the performance of the proposed pipeline on 153 laboratory test reports collected from Peking University First Hospital (PKU1). Results In the OCR module, we evaluate the accuracy of text detection and recognition results at three different levels and achieved an averaged accuracy of 0.93. In the IE module, we extracted four laboratory test entities, including test item name, test result, test unit, and reference value range. The overall F1 score is 0.86 on the 153 laboratory test reports collected from PKU1. With a single CPU, the average inference time of each report is only 0.78 s. Conclusion In this study, we developed a practical lightweight pipeline to digitalize and extract information from paper-based laboratory test reports in diverse types and with different layouts that can be adopted in real clinical environments with the lowest possible computing resources requirements. The high evaluation performance on the real-world hospital dataset validated the feasibility of the proposed pipeline.

Abstract Background Monitoring hand hygiene compliance (HHC) of healthcare providers (HCPs) in healthcare facilities is critical for hand hygiene (HH) promotion. However, less is known about the cost and effectiveness of different HHC monitoring tools. In this study, we aimed to compare various health economic indicators corresponding to electronic system-based monitoring (ESM) and manual paper-based monitoring (MPM) for HHC to provide evidence-based advice for HHC monitoring measures targeted selecting. Methods A before and after study in 40 clinical departments with 4,524 healthcare providers was conducted from December 2022 to January 2023 (MPM implementation phase) and March 2023 to May 2023 (ESM implementation phase). The cost-effectiveness, cost-efficiency, the extent of the Hawthorne effect, and indirect cost-benefit of the two monitoring methods were compared. Results The total cost spent on ESM for the 40 departments (17,702.92 CNY) was 4,123.76 CNY lower than that of MPM (21,826.68 CNY). The HHC of MPM (80.16%) was higher than that of ESM (69.82%) (p

Abstract Emergency general surgeons often provide care to severely ill patients requiring surgical interventions and intensive support. One of the primary drivers of morbidity and mortality is perioperative bleeding. In general, when addressing life threatening haemorrhage, blood transfusion can become an essential part of overall resuscitation. However, under all circumstances, indications for blood transfusion must be accurately evaluated. When patients decline blood transfusions, regardless of the reason, surgeons should aim to provide optimal care and respect and accommodate each patient’s values and target the best outcome possible given the patient’s desires and his/her clinical condition. The aim of this position paper was to perform a review of the existing literature and to provide comprehensive recommendations on organizational, surgical, anaesthetic, and haemostatic strategies that can be used to provide optimal peri-operative blood management, reduce, or avoid blood transfusions and ultimately improve patient outcomes.

Abstract We propose that while examining homologies and convergences in auditory-motor synchronization between humans and non-human animals is informative, examining differences in behaviour and brain mechanisms can help to better define the boundaries of the phenomena.

Abstract Inquiry-based learning (IBL) is a type of problem-based learning. While IBL aims at reflecting the work of practicing researchers, only some students will pursue an academic career. We therefore designed a course that provides opportunities for IBL by applying participant observation to internship work experience inside and outside academia. Using this internship course as an example, we investigated, how master’s students in health science executed an IBL assignment regarding the application of participant observation and presentation of findings. In addition, the understanding of occupational fields provided through the IBL assignment was examined. To determine whether learning objectives were met, a document analysis of IBL assignments comprising presentation slides and field protocols was performed. Within content analysis, a category grid was used examining (a) suitability of chosen research objectives, (b) execution of field protocols, (c) sufficiency of reporting and (d) extent of reflection. 49 IBL assignments from the years 2020–2022 were included. Sides of IBL observations were: (a) organizations providing health care (n = 28); (b) administrations of health care (n = 8); and (c) research institutes (n = 13). Within students’ field protocols, the level of detail of descriptions differed. 30 assignments included reflection on the methods used and research experience. In about a third of IBL assignments, indication of observation type, theoretical background and data analysis was missing. Using participant observation of internship work-experience for IBL can serve as a teaching tool for students to develop methodological skills. For future courses, we developed a checklist to strengthen reporting, reflection and use of theory. As internships are often integrated in degree programs in health sciences similar courses could be implemented in different programs, given qualified methodological guidance.

Abstract Background Undocumented immigrants face many obstacles in accessing emergency healthcare. Legal uncertainties, economic constraints, language differences, and cultural disparities lead to delayed medical care and thereby exacerbate health inequities. Addressing the healthcare needs of this vulnerable group is crucial for both humanitarian and public health reasons. Comprehensive strategies are needed to ensure equitable health outcomes. Objective This study aimed to identify and analyze the barriers undocumented immigrants face in accessing emergency healthcare services and the consequences on health outcomes. Methods We used a scoping review methodology that adhered to established frameworks. Utilizing MEDLINE/PubMed, Embase, Web of Science, PsychoInfo, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), we identified 153 studies of which 12 focused on the specific challenges that undocumented immigrants encounter when accessing emergency healthcare services based on the inclusion and exclusion criteria. Results The results show that undocumented immigrants encounter significant barriers to emergency healthcare, including legal, financial, linguistic, and cultural challenges. Key findings were the extensive use of emergency departments as primary care due to lack of insurance and knowledge of alternatives, challenges faced by health professionals in providing care to undocumented migrants, increased hospitalizations due to severe symptoms and lack of healthcare access among undocumented patients, and differences in emergency department utilization between irregular migrants and citizens. The findings also serve as a call for enhanced healthcare accessibility and the dismantling of existing barriers to mitigate the adverse effects on undocumented immigrants' health outcomes. Conclusions Undocumented immigrants' barriers to emergency healthcare services are complex and multifaceted and therefore require multifaceted solutions. Policy reforms, increased healthcare provider awareness, and community-based interventions are crucial for improving access and outcomes for this vulnerable population. Further research should focus on evaluating the effectiveness of these interventions and exploring the broader implications of healthcare access disparities.

Abstract Background Cardiovascular toxicity represents a significant adverse consequence of cancer therapies, yet there remains a paucity of effective biomarkers for its timely monitoring and diagnosis. To give a first evidence able to elucidate the role of Growth Differentiation Factor 15 (GDF15) in the context of cancer diagnosis and its specific association with cardiac indicators in cancer patients, thereby testing its potential in predicting the risk of CTRCD (cancer therapy related cardiac dysfunction). Methods Analysis of differentially expressed genes (DEGs), including GDF15, was performed by utilizing data from the public repositories of the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Cardiomyopathy is the most common heart disease and its main clinical manifestations, such as heart failure and arrhythmia, are similar to those of CTRCD. Examination of GDF15 expression was conducted in various normal and cancerous tissues or sera, using available database and serum samples. The study further explored the correlation between GDF15 expression and the combined detection of cardiac troponin-T (c-TnT) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP), assessing the combined diagnostic utility of these markers in predicting risk of CTRCD through longitudinal electrocardiograms (ECG). Results GDF15 emerged as a significant DEG in both cancer and cardiomyopathy disease models, demonstrating good diagnostic efficacy across multiple cancer types compared to healthy controls. GDF15 levels in cancer patients correlated with the established cardiac biomarkers c-TnT and NT-proBNP. Moreover, higher GDF15 levels correlated with an increased risk of ECG changes in the cancer cohort. Conclusion GDF15 demonstrated promising diagnostic potential in cancer identification; higher GDF15, combined with elevated cardiac markers, may play a role in the monitoring and prediction of CTRCD risk.

Abstract Obesity is the one of the most important components of metabolic syndrome. Because obesity related hypertension accounts for two thirds of essential hypertension, managing obesity and metabolic syndrome is a crucial task in the management of hypertension. However, the current non-pharmacological therapies have limitations for achieving or maintaining ideal body weight. Recently, glucagon-like peptide-1 receptor agonists (GLP1-RAs) have demonstrated excellent weight control effects, accompanied by corresponding reductions in blood pressure. GLP1-RAs have shown cardiovascular and renal protective effects in cardiovascular outcome trials both in primary and secondary prevention. In this document, the Korean Society of Hypertension intends to remark the current clinical results of GLP1-RAs and recommend the government and health-policy makers to define obesity as a disease and to establish forward-looking policies for GLP1-RA treatment for obesity treatment, including active reimbursement policies.

Abstract Gray mold of roses, caused by the necrotrophic fungal pathogen Botrytis cinerea, is an economically notorious disease and a well-known economic menace, leading to substantial annual losses estimated at no less than 30% of production. This disease takes a toll not only on the marketability of cut rose flowers but also on consumer and importer confidence due to the unsightly symptoms it induces. This fungus influences the rose foliage throughout cultivation, transportation, storage, and marketing. The interplay of conducive environmental conditions and genetic factors plays significant roles in developing the rose gray mold on rose flowers during the pre- and post-harvest phases. Nevertheless, the molecular mechanisms underlying B. cinerea-rose interactions are poorly understood, and the knowledge of how rose plants defend themselves against B. cinerea infection is not comprehensively investigated. It is worth noting that breeding for resistance to discover genetically resistant roses toward gray mold was unsuccessful despite research conducted over the past century. Consequently, synthetic fungicides remain the primary approach to controlling Botrytis blight in roses during the pre- and post-harvest stages. However, this measure has several drawbacks, including the emergence of fungicide-resistant B. cinerea and endangering human and animal health due to chemical residues in the food chain. This review aims to offer a comprehensive update on recent research findings on the biology and management of B. cinerea infection in roses and to propose novel strategies for managing gray mold disease.

Abstract Numerous researchers and institutions have been developing in ovo sexing technologies to improve animal welfare by identifying male embryos in an early embryonic stage and disposing of them before pain perception. This review gives a complete overview of the technological approaches reported in papers and patents by performing a thorough search using Web of Science and Patstat/Espacenet databases for papers and patents, respectively. Based on a total of 49 papers and 115 patent families reported until May 2023 worldwide, 11 technology categories were defined: 6 non-optical and 5 optical techniques. Every category was described for its characteristics while assessing its potential for application. Next, the dynamics of the publications of in ovo sexing techniques in both paper and patent fields were described through growth curves, and the interest or actual status was visualized using the number of paper citations and the actual legal status of the patents. When comparing the reported technologies in papers to those in patents, scientific gaps were observed, as some of the patented technologies were not reported in the scientific literature, e.g., ion mobility and mass spectrometry approaches. Generally, more diverse approaches in all categories were found in patents, although they do require more scientific evidence through papers or industrial adoption to prove their robustness. Moreover, although there is a recent trend for non-invasive techniques, invasive methods like analyzing DNA through PCR or hormones through immunosensing are still being reported (and might continue to be) in papers and patents. It was also observed that none of the technologies complies with all the industry requirements, although 5 companies already entered the market. On the one hand, more research and harmony between consumers, industry, and governments is necessary. On the other hand, close monitoring of the market performance of the currently available techniques will offer valuable insights into the potential and expectations of in ovo sexing techniques in the poultry industry.

Abstract Purpose Formal coercion in psychiatry is widely studied yet much less is known about pressures patients may experience, partly because of the very few measures available. The goal of this study was to validate the P-PSY35 (Pressures in Psychiatry Scale) and provide a paper-and-pencil and a computerised adaptive test (CAT) to measure pressures experienced by patients in psychiatry. Methods The P-PSY35 items were developed with users. Patients were evaluated during psychiatric hospitalisation or through an online survey. Mokken scale analysis and Item response theory (IRT) were used to select and estimate the items parameters. A Monte-Carlo simulation was performed to evaluate the number of items needed to transform the paper-and-pencil test into a reliable psychometric CAT. Results A total of 274 patients were assessed. The P-PSY35 demonstrated good internal validity, internal consistency, convergent and divergent validity. The P-PSY35 could be substantially shortened while maintaining excellent reliability using the CAT procedure. Conclusion The P-PSY35 was developed in collaboration with users. It is a psychometrically rigorous tool designed to measure experienced pressures in French-language. The development and successful validation of the P-PSY35 represent a welcome step towards implementing and evaluating programs aimed at reducing negative consequences of coercion.

Abstract Background In low-middle income countries, healthcare providers primarily use paper health records for capturing data. Paper health records are utilized predominately due to the prohibitive cost of acquisition and maintenance of automated data capture devices and electronic medical records. Data recorded on paper health records is not easily accessible in a digital format to healthcare providers. The lack of real time accessible digital data limits healthcare providers, researchers, and quality improvement champions to leverage data to improve patient outcomes. In this project, we demonstrate the novel use of computer vision software to digitize handwritten intraoperative data elements from smartphone photographs of paper anesthesia charts from the University Teaching Hospital of Kigali. We specifically report our approach to digitize checkbox data, symbol-denoted systolic and diastolic blood pressure, and physiological data. Methods We implemented approaches for removing perspective distortions from smartphone photographs, removing shadows, and improving image readability through morphological operations. YOLOv8 models were used to deconstruct the anesthesia paper chart into specific data sections. Handwritten blood pressure symbols and physiological data were identified, and values were assigned using deep neural networks. Our work builds upon the contributions of previous research by improving upon their methods, updating the deep learning models to newer architectures, as well as consolidating them into a single piece of software. Results The model for extracting the sections of the anesthesia paper chart achieved an average box precision of 0.99, an average box recall of 0.99, and an mAP0.5-95 of 0.97. Our software digitizes checkbox data with greater than 99% accuracy and digitizes blood pressure data with a mean average error of 1.0 and 1.36 mmHg for systolic and diastolic blood pressure respectively. Overall accuracy for physiological data which includes oxygen saturation, inspired oxygen concentration and end tidal carbon dioxide concentration was 85.2%. Conclusions We demonstrate that under normal photography conditions we can digitize checkbox, blood pressure and physiological data to within human accuracy when provided legible handwriting. Our contributions provide improved access to digital data to healthcare practitioners in low-middle income countries.

Abstract Background In response to the imperative need for standardized support for adolescent Gender Dysphoria (GD), the Italian Academy of Pediatrics, in collaboration with the Italian Society of Pediatrics, the Italian Society for Pediatric Endocrinology and Diabetes, Italian Society of Adolescent Medicine and Italian Society of Child and Adolescent Neuropsychiatry is drafting a position paper. The purpose of this paper is to convey the author's opinion on the topic, offering foundational information on potential aspects of gender-affirming care and emphasizing the care and protection of children and adolescents with GD. Main body Recognizing that adolescents may choose interventions based on their unique needs and goals and understanding that every individual within this group has a distinct trajectory, it is crucial to ensure that each one is welcomed and supported. The approach to managing individuals with GD is a multi-stage process involving a multidisciplinary team throughout all phases. Decisions regarding treatment should be reached collaboratively by healthcare professionals and the family, while considering the unique needs and circumstances of the individual and be guided by scientific evidence rather than biases or ideologies. Politicians and high court judges should address discrimination based on gender identity in legislation and support service development that aligns with the needs of young people. It is essential to establish accredited multidisciplinary centers equipped with the requisite skills and experience to effectively manage adolescents with GD, thereby ensuring the delivery of high-quality care. Conclusion Maintaining an evidence-based approach is essential to safeguard the well-being of transgender and gender diverse adolescents.

Abstract Background Workers in pulp and paper factories are continuously exposed to paper dust. Excessive exposure to paper dust can cause respiratory disease. Information about the prevalence of chronic respiratory symptoms and dust exposure levels among workers in pulp and paper factories is not available in Ethiopia. The aim of this study was, therefore, to assess personal total dust exposure levels, the prevalence of chronic respiratory symptoms and their associated risk factors among workers in Ethiopian pulp and paper factories. Methods A comparative cross-sectional study was conducted. A total of 40 dust measurements were carried out on 20 randomly selected workers. To assess chronic respiratory symptoms and associated factors, 434 workers from two paper factories and controls were interviewed using a standard questionnaire adapted from the American Thoracic Society (ATS). Gravimetric analyses of the filters were undertaken using a standard microbalance. Poisson regression was performed for comparing the prevalence of symptoms and risk factors for the two groups. Multivariable analyses were conducted to identify factors associated with chronic respiratory symptoms. Result The arithmetic mean (AM) and geometric mean (GM) of dust exposure levels among the paper factories workers were 11.3 (± 7.7) and 10.2 (± 1.4) mg/m3 respectively. This exposure level exceeded the threshold limit value recommended for total dust (10 mg/m3). The prevalence of having at least one chronic respiratory symptom was about 51% among the workers in paper factories. The prevalence ratio of having chronic respiratory symptoms among paper factory workers was 5.6 times higher (PR = 6, 95% CI 3.5–10.3) than in the controls. Chronic respiratory symptoms were significantly associated with factors such as an educational status of less than grade 9, being employed in the work sections of the factories, having work experience of 5 years and above, working more than 8 h per day and having a past history of occupation and respiratory illnesses. Conclusion The dust concentration in the paper factories exceeded the acceptable recommended limit value of 10 mg/m3. The prevalence of chronic respiratory symptoms among paper factory workers was higher than among controls. The main determining factors for chronic respiratory symptoms among the workers were the specific work section such as production section, low income, having past history of respiratory illnesses, the number of years of working and low educational status. This finding indicated the need for improving the working conditions in paper factories in Ethiopia.

Abstract Background In line with the impetus traceable among the nursing staff, studies regarding the perception of Unfinished Care among students have increased in recent years as also recommended by some policy documents in the consideration that, as future members of the staff, they are expected to raise concerns about failures in the standards of care. However, no discussion of their methodological requirements has been provided to date. The aim of this study is to debate Unfinished Care explorations among nursing students and developing recommendations. Methods A Rapid Review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, followed by a scientific discussion based on empirical evidence that emerged from the review combined with expert knowledge. Medline, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus databases were searched up to May 2022. Results In the last five years, seven studies have been conducted by researchers affiliated at the university level, involving from 18 to 737 undergraduate students across Europe. By critically analysing their key aspects, there are derived some recommendations in conducting investigations in this field as, (a) the hidden meaning of Unfinished Care investigations among students by also deciding which concept is mostly appropriate to investigate; (b) the need of establishing alliances with the clinical settings in order to involve them in such explorations; (c) more complex research methods capable of exploring this issue among students by promoting learning outcomes and not only a simple data collection; and (e) the influences of these explorations on students’ wellbeing, as well as on ethical implications and that regarding the relationship between the healthcare services and the universities. Conclusion Policymakers consider students to be key informants of the quality of nursing care issues witnessed during their clinical placements. The related emerging line of research is intriguing because of the underlying methodological, ethical and system complexities that need to be addressed according to some considerations.

Abstract Background Paediatric orthopaedics is a significant and difficult for undergraduate students to master. During the COVID-19 pandemic, we used the WeChat platform to combine the advantages offered by problem-based learning (PBL), case-based learning (CBL) and paper review teaching methods to establish a new blended online teaching model and demonstrated its feasibility and effectiveness. Objective This study aims to demonstrate the feasibility and effectiveness of a new blended pedagogical method that uses the WeChat platform and combines PBL, CBL and paper review. Methods We enrolled 22 students participating in the Department of Paediatric Orthopaedics. They participated in the WeChat blended pedagogy mode. Their departmental rotation examination scores were compared with those of 23 students who participated in the traditional teaching method. Moreover, an anonymous questionnaire was used to evaluate students’ perceptions and experiences. Results The total average scores of students who participated in the WeChat blended pedagogy mode and the traditional teaching method were 47.27 and 44.52, respectively. There were no statistically significant differences between the online teaching mode and the traditional teaching method in terms of possessing professional accomplishment, gaining knowledge and promoting interpersonal skills (P = 0.07, P = 0.12 and P = 0.65, respectively). In terms of independent clinical thinking, self-improving capability and improving clinical skills, the scores associated with the WeChat blended pedagogy mode were 8.00, 8.00 and 6.00, whereas those associated with the traditional teaching method were 6.70, 6.87 and 7.48. The overall satisfaction with the WeChat blended pedagogy mode reached 100%. A total of 64%, 86%, 68%, 64% and 59% of students chose very large or large in response to the items concerning professional accomplishment, knowledge absorption, independent clinical thinking skills, English reading and literature exploring capacity, as well as interpersonal skills, respectively. Fifteen participants claimed that the WeChat blended pedagogy mode was less helpful to them with regard to promoting the improvement of their clinical skills. Nine students claimed that the WeChat blended pedagogy mode was time-consuming. Conclusions Our study verified the feasibility and effectiveness of the WeChat blended pedagogy mode for undergraduate paediatric orthopaedics internships. Trial Registration Retrospectively registered.

Abstract Background Efficient monitoring of glucose concentration in the human body necessitates the utilization of electrochemically active sensing materials in nonenzymatic glucose sensors. However, prevailing limitations such as intricate fabrication processes, lower sensitivity, and instability impede their practical application. Herein, ternary Cu-Co-Ni-S sulfides nanoporous network structure was synthesized on carbon fiber paper (CP) by an ultrafast, facile, and controllable technique through on-step cyclic voltammetry, serving as a superior self-supporting catalytic electrode for the high-performance glucose sensor. Results The direct growth of free-standing Cu-Co-Ni-S on the interconnected three-dimensional (3D) network of CP boosted the active site of the composites, improved ion diffusion kinetics, and significantly promoted the electron transfer rate. The multiple oxidation states and synergistic effects among Co, Ni, Cu, and S further promoted glucose electrooxidation. The well-architected Cu-Co-Ni-S/CP presented exceptional electrocatalytic properties for glucose with satisfied linearity of a broad range from 0.3 to 16,000 μM and high sensitivity of 6829 μA mM− 1 cm− 2. Furthermore, the novel sensor demonstrated excellent selectivity and storage stability, which could successfully evaluate the glucose levels in human serum. Notably, the novel Cu-Co-Ni-S/CP showed favorable biocompatibility, proving its potential for in vivo glucose monitoring. Conclusion The proposed 3D hierarchical morphology self-supported electrode sensor, which demonstrates appealing analysis behavior for glucose electrooxidation, holds great promise for the next generation of high-performance glucose sensors.

Abstract Small extracellular vesicle–derived microRNAs (sEV-miRNAs) have emerged as promising noninvasive biomarkers for early cancer diagnosis. Herein, we developed a molecular probe based on three-dimensional (3D) multiarmed DNA tetrahedral jumpers (mDNA-Js)-assisted DNAzyme activated by Na+, combined with a disposable paper-based electrode modified with a Zr-MOF–rGO–Au NP nanocomplex (ZrGA) to fabricate a novel biosensor for sEV-miRNAs Assay. Zr-MOF tightly wrapped by rGO was prepared via a one-step method, and it effectively aids electron transfer and maximizes the effective reaction area. In addition, the mechanically rigid, and nanoscale-addressable mDNA-Js assembled from the bottom up ensure the distance and orientation between fixed biological probes as well as avoid probe entanglement, considerably improving the efficiency of molecular hybridization. The fabricated bioplatform achieved the sensitive detection of sEV-miR-21 with a detection limit of 34.6 aM and a dynamic range from100 aM to 0.2 µM. In clinical blood sample tests, the proposed bioplatform showed results highly consistent with those of qRT-PCRs and the signal increased proportionally with the NSCLC staging. The proposed biosensor with a portable wireless USB-type analyzer is promising for the fast, easy, low-cost, and highly sensitive detection of various nucleic acids and their mutation derivatives, making it ideal for POC biosensing.

Abstract The ARASENS trial recruited 1306 men with metastatic hormone sensitive prostate cancer. It investigated the effect of androgen deprivation therapy (ADT) and systemic therapy docetaxel in combination with a third novel drug – daralutamide, compared with placebo on overall survival. Triple therapy with ADT, docetaxel and darolutamide resulted in improved overall survival rates as compared with ADT, docetaxel and placebo (HR 0.68; 95% CI, 0.57–0.80; p

Abstract Background As the older population increases, the need for early detection of cognitive decline is also increasing. In this study, we examined whether our paper–pencil type group examination for cognitive assessment (PAPLICA) could detect the effects of years of education and aging. Methods PAPLICA was conducted on 829 older people. The inclusion criteria were age 60 years or older and the ability to come to the event site alone. The exclusion criteria were participants with a medical or psychiatric disorder or dementia.One examiner conducted the test on a group of approximately 10–20 people in approximately 25 min. Participants were instructed on tackling the issues projected on the projector, and their answers were recorded in a response booklet. Results An independent sample t-test was performed for years of education, and ANCOVA was performed for aging. Among the test items included in PAPLICA, the Speed I and Letter fluency tests were unable to detect the effects of aging. Furthermore, the age at which the effect of aging manifests varies depending on the test item. For instance, a decline in scores in the Speed I and Picture ECR Free recall tests was observed in the 70–74 age group; for that of Word DRT, Picture ECR cued recall, and Similarity, in the 75–79 age group; for CFT, in the 80–84 age group, and for CLOX, the decline was observed in the 85 ≤ age group. Conclusions PAPLICA, similar to other neuropsychological tests, was able to detect the effects of years of education and aging. Future testing should be conducted on different demographics to identify the differences in patterns of cognitive decline.

Abstract Adverse Outcome Pathways (AOPs) have been proposed to facilitate mechanistic understanding of interactions of chemicals/materials with biological systems. Each AOP starts with a molecular initiating event (MIE) and possibly ends with adverse outcome(s) (AOs) via a series of key events (KEs). So far, the interaction of engineered nanomaterials (ENMs) with biomolecules, biomembranes, cells, and biological structures, in general, is not yet fully elucidated. There is also a huge lack of information on which AOPs are ENMs-relevant or -specific, despite numerous published data on toxicological endpoints they trigger, such as oxidative stress and inflammation. We propose to integrate related data and knowledge recently collected. Our approach combines the annotation of nanomaterials and their MIEs with ontology annotation to demonstrate how we can then query AOPs and biological pathway information for these materials. We conclude that a FAIR (Findable, Accessible, Interoperable, Reusable) representation of the ENM-MIE knowledge simplifies integration with other knowledge. Scientific contribution This study introduces a new database linking nanomaterial stressors to the first known MIE or KE. Second, it presents a reproducible workflow to analyze and summarize this knowledge. Third, this work extends the use of semantic web technologies to the field of nanoinformatics and nanosafety.

Abstract Kidney stones, a persistent urological condition, continue to affect people globally. In this critical review, we examine the work of Borghi et al. who evaluated patients with idiopathic stone formation and randomised 99 patients to increased water intake (≥ 2 L/day) and 100 patients to usual care in a 5-year randomized controlled trial. The study examined baseline urine volume in individuals with idiopathic calcium stones, recurrence rates, and relevant biochemical factors. The study found reduced recurrence rate (12.1% vs. 27% (p = 0.008)), and time to recurrence with increased water intake (38.7 ± 13.2 months) vs. (25 ± 16.4 months) (p = 0.016). These findings inform clinical practice, contributing to the guideline recommendations that kidney stone patients should aim for fluid intake of at least 2.5 L per day to prevent stone recurrence.

Abstract Background The advent of Personalized Medicine (PM) holds significant promise in revolutionizing healthcare by tailoring treatments to individual patients based on their data. However, its successful implementation requires the seamless integration of innovative technologies and presents formidable challenges in terms of sustainability. To tackle these challenges head-on, the International Consortium for Personalized Medicine (ICPerMed) was established, and the IC2PerMed project, as part of this consortium, seeks to foster collaboration between the European Union (EU) and China in the field of Personalized Medicine. Based on the results collected by the project, the objective of this study is to discern the key priorities for the implementation of Personalised Medicine concerning Information and Communication Technologies (ICT) and Big Data and digital solutions, with a particular emphasis on data management and protection. Methods A Delphi survey was conducted to gather expert’s consensus on the main priorities for actions on Information and Communication Technologies (ICT) and Big Data and digital solutions in the field of Personalized Medicine. Results The survey identified seven priorities in the area of Big Data and digital solutions, including data interoperability, standards, security measures, and international partnerships. Additionally, twelve priorities were identified for the innovation-to-market process, emphasizing cost-effectiveness, need assessment, and value definition in resource allocation. Conclusions The effective implementation of new technologies in Personalized Medicine research and practice is essential for the advancement of healthcare systems in both the European and Chinese contexts. The identified priorities play a pivotal role in promoting the sustainability of health systems and driving innovation in the implementation of Personalized Medicine. Addressing challenges related to data interoperability, standards, security, international collaboration, cost-effectiveness, and value assessment is of utmost importance in order to propel the progress of Personalized Medicine in healthcare systems.

Abstract In this critical review, we explore the study design, strengths and limitations of the paper: “Two-Year Outcomes of Sacral Neuromodulation Versus OnabotulinumtoxinA for Refractory Urgency Urinary Incontinence: A Randomized Trial.” The paper reports 24 month follow-up data of the landmark ROSETTA trial. This multi-centre, open-labelled parallel randomised trial allocated females 1:1 to receive Sacral Neuromodulation (SNM) or OnabotulinumtoxinA(BTX) 200 units (U). The primary outcome was change in mean daily urinary urgency incontinence episodes (UUIE) over 24 months. The study did not demonstrate a difference between treatments (-3.88 vs. -3.50 episodes per day), however women treated with BTX were more satisfied; but reported higher rates of UTI. The two treatments provide comparable third-line treatment options for patients with refractory urgency urinary incontinence.

Abstract Background Laccase-based biosensors are efficient for detecting phenolic compounds. However, the instability and high cost of laccases have hindered their practical utilization. Results In this study, we developed hierarchical manganese dioxide–copper phosphate hybrid nanoflowers (H–Mn–Cu NFs) as excellent laccase-mimicking nanozymes. To synthesize the H–Mn–Cu NFs, manganese dioxide nanoflowers (MnO2 NFs) were first synthesized by rapidly reducing potassium permanganate using citric acid. The MnO2 NFs were then functionalized with amine groups, followed by incubation with copper sulfate for three days at room temperature to drive the coordination interaction between the amine moieties and copper ions and to induce anisotropic growth of the petals composed of copper phosphate crystals, consequently yielding H–Mn–Cu NFs. Compared with those of free laccase, at the same mass concentration, H–Mn–Cu NFs exhibited lower K m (~ 85%) and considerably higher V max (~ 400%), as well as significantly enhanced stability in the ranges of pH, temperature, ionic strength, and incubation periods evaluated. H–Mn–Cu NFs also catalyzed the decolorization of diverse dyes considerably faster than the free laccase. Based on these advantageous features, a paper microfluidic device incorporating H–Mn–Cu NFs was constructed for the convenient visual detection of phenolic neurotransmitters, including dopamine and epinephrine. The device enabled rapid and sensitive quantification of target neurotransmitters using an image acquired using a smartphone. Conclusions These results clearly show that H–Mn–Cu NFs could be potential candidates to replace natural laccases for a wide range of applications in biosensing, environmental protection, and biotechnology. Graphical Abstract

Abstract Background The prevalence and death rate arising from malaria infection, and emergence of other diseases showing similar symptoms to malaria require the development of malaria-specific and sensitive devices for its diagnosis. To address this, the design and fabrication of low-cost, rapid, paper-based analytical devices (µPAD) using surface-immobilized aptamers to detect the presence of a recombinant malarial biomarker—Plasmodium falciparum lactate dehydrogenase (rPfLDH)—is reported in this study. Methods Test zones on paper surfaces were created by covalently immobilizing streptavidin to the paper, subsequently attaching biotinylated aptamers to streptavidin. Aptamers selectively bound rPfLDH. The measurement of captured rPfLDH enzyme activity served as the means of detecting this biomarker. Enzyme activity across three replicate sensors was digitally quantified using the colorimetric Malstat assay. Results Screening of several different aptamers reported in the literature showed that aptamers rLDH7 and 2008s immobilized in this manner specifically recognised and captured PfLDH. Using rLDH7, the sensitivity of the µPAD sensor was evaluated and the µPAD sensor was applied for preferential detection of rPfLDH, both in buffered solutions of the protein and in spiked serum and red blood cell lysate samples. In buffered solutions, the test zone of the µPAD sensor exhibited a K D of 24 ± 11 nM and an empirical limit of detection of 17 nM, respectively, a limit similar to commercial antibody-based sensors exposed to rPfLDH. The specific recognition of 133 nM rPfLDH in undiluted serum and blood samples was demonstrated by the µPAD. Conclusion The reported µPAD demonstrates the potential of integrating aptamers into paper-based malarial rapid diagnostic tests. Graphical Abstract The assembly of µPAD sensors using APTEC assay principles for the detection the malarial biomarker, lactate dehydrogenase enzymes from Plasmodium falciparum (PfLDH). The aptamers immobilized at the test zones capture the PfLDH in samples. After washing the unbound sample components from the zones, Malstat assay reagents are added for colour development, proportional to the amount of captured PfLDH.

Abstract Enhanced perioperative care protocols become the standard of care in elective surgery with a significant improvement in patients’ outcome. The key element of the enhanced perioperative care protocol is the multimodal and interdisciplinary approach targeted to the patient, focused on a holistic approach to reduce surgical stress and improve perioperative recovery. Enhanced perioperative care in emergency general surgery is still a debated topic with little evidence available. The present position paper illustrates the existing evidence about perioperative care in emergency surgery patients with a focus on each perioperative intervention in the preoperative, intraoperative and postoperative phase. For each item was proposed and approved a statement by the WSES collaborative group.

Abstract Introduction The Ministry of Public Health in Lebanon is in the process of converting the surveillance reporting from a cumbersome paper-based system to a web-based electronic platform (DHIS-2) to have real-time information for early detection of alerts and outbreaks and for initiating a prompt response. Objectives This paper aimed to document the Lebanese experience in implementing DHIS-2 for the disease surveillance system. It also targets to assess the improvement of reporting rates and timeliness of the reported data and to disclose the encountered challenges and opportunities. Methodology This is a retrospective description of processes involved in the implementation of the DHIS-2 tool in Lebanon. Initially, it was piloted for the school-based surveillance in 2014; then its use was extended in May 2017 to cover other specific surveillance systems. This included all surveillance programs collecting aggregate data from hospitals, medical centers, dispensaries, or laboratories at the first stage. As part of the national roll-out process, the online application was developed. The customized aggregated-based datasets, organization units, user accounts, specific and generic dashboards were generated. More than 80 training sessions were conducted throughout the country targeting 1290 end-users including health officers at the national and provincial levels, focal persons who were working in all public and private hospitals, laboratories, and medical centers as well. Completeness and timeliness of reported data were compared before and after the implementation of DHIS-2. The unveiled challenges and the main lessons learned during the roll-out process were discussed. Results For laboratory-based surveillance, completeness of reporting increased from 70.8% in May to 89.6% in October. Timeliness has improved from 25 to 74%. For medical centers, an improvement of 8.1% for completeness and 9.4% in timeliness was recorded before and after training sessions. For zero reporting, completeness remains the same (88%) and timeliness has improved from 74 to 87%. The main challenges faced during the implementation of DHIS-2 were mainly infrastructural and system-related in addition to poor internet connectivity, limited workforce, and frequent changes to DHIS-2 versions. Conclusion Implementation of DHIS-2 improved timeliness and completeness for aggregated data reporting. Continued on-site support, monitoring, and system enhancement are needed to improve the performance of DHIS-2.

Abstract Background Bipolar disorder is one of the most burdensome severe mental disorders, characterized by high levels of personal and social disability. Patients often need an integrated pharmacological and non-pharmacological approach. Lithium is one of the most effective treatments available not only in psychiatry, but in the whole medicine, and its clinical efficacy is superior to that of other mood stabilizers. However, a declining trend on lithium prescriptions has been observed worldwide in the last 20 years, supporting the notion that lithium is a ‘forgotten drug’ and highlighting that the majority of patients with bipolar disorder are missing out the best available pharmacological option. Based on such premises, a narrative review has been carried out on the most common “misconceptions” and “stereotypes” associated with lithium treatment; we also provide a list of “good reasons” for using lithium in ordinary clinical practice to overcome those false myths. Main text A narrative search of the available literature has been performed entering the following keywords: “bipolar disorder”, “lithium”, “myth”, “mythology”, “pharmacological treatment”, and “misunderstanding”. The most common false myths have been critically revised and the following statements have been proposed: (1) Lithium should represent the first choice for the treatment of patients with bipolar disorder; (2) lithium treatment is effective in different patients’ groups suffering from bipolar disorder; (3) Drug–drug interaction risk can be easily managed during lithium treatment; (4) The optimal management of lithium treatment includes periodical laboratory tests; (5) Slow-release lithium formulation has advantages compared to immediate release formulation; (6) Lithium treatment has antisuicidal properties; (7) Lithium can be carefully managed during pregnancy. Conclusions In recent years, a discrepancy between evidence-based recommendations and clinical practice in using lithium treatment for patients with bipolar disorder has been highlighted. It is time to disseminate clear and unbiased information on the clinical efficacy, effectiveness, tolerability and easiness to use of lithium treatment in patients with bipolar disorder. It is necessary to reinvigorate the clinical and academic discussion about the efficacy of lithium, to counteract the decreasing prescription trend of one of the most effective drugs available in the whole medicine.

Abstract The South West Oncology Group’s 2000 randomised-control trial investigated the addition of maintenance intravesical bacillus Calmette-Guerin (BCG) to non-muscle invasive urothelial carcinoma (NMIUC) treatment. The results were published when the efficacy of BCG immunotherapy maintenance was unclear. Randomisation produced two arms, each containing 192 patients assessed to be at high risk of recurrence following induction BCG therapy for NMIUC. The treatment arm went on to receive three successive weekly intravesical and percutaneous BCG administrations at three months, six months and then six monthly for three years from the start of induction therapy. Recurrence free-survival (RFS), was higher in the maintenance arm with 41% (95%CI 35–49) RFS at five years in the control arm and 60% RFS (53–67 95% CI) in the maintenance arm (p

Abstract Impact Bronchopulmonary dysplasia has multiple definitions that are currently based on phenotypic characteristics. Using an unsupervised machine learning approach, we created BPD subclasses (e.g., endotypes) by clustering whole microarray data. T helper 17 cell differentiation was the most significant pathway differentiating the BPD endotypes. Introduction Bronchopulmonary dysplasia (BPD) is the most common complication of extreme prematurity. Discovery of BPD endotypes in an unbiased format, derived from the peripheral blood transcriptome, may uncover patterns underpinning this complex lung disease. Methods An unsupervised agglomerative hierarchical clustering approach applied to genome-wide expression of profiling from 62 children at day of life five was used to identify BPD endotypes. To identify which genes were differentially expressed across the BPD endotypes, we formulated a linear model based on least-squares minimization with empirical Bayes statistics. Results Four BPD endotypes (A, B,C,D) were identified using 7,319 differentially expressed genes. Across BPD endotypes, 5,850 genes had a p value

Abstract Background Broussonetia papyrifera (L.) L’Hér. ex Vent. has the characteristics of strong stress resistance, high crude protein content, and pruning tolerance. It is an ecological, economic, and medicinal plant. Polyploid plants usually perform better than their corresponding diploid plants in terms of nutrients, active substances, and stress resistance. Results In this study, the leaves, calli, and seeds of diploid B. papyrifera were used for tetraploid induction by colchicine. The induction effect of colchicine on B. papyrifera was summarized through the early morphology, chromosome count and flow cytometry. It was concluded that the best induction effect (18.6%) was obtained when the leaves of B. papyrifera were treated in liquid MS (Murashige and Skoog) medium containing 450 mg·L-1 colchicine for 3 d. The comparative analysis of the growth characteristics of diploid and tetraploid B. papyrifera showed that tetraploid B. papyrifera has larger ground diameter, larger stomata, thicker palisade tissue and thicker sponge tissue than diploid B. papyrifera. In addition, the measurement of photosynthetic features also showed that tetraploids had higher chlorophyll content and higher photosynthetic rates. Conclusion This study showed that tetraploid B. papyrifera could be obtained by treating leaves, callus and seeds with liquid and solid colchicine, but the induction efficiency was different. Moreover, there were differences in stomata, leaf cell structure and photosynthetic features between tetraploid B. papyrifera and its corresponding diploid. The induced tetraploid B. papyrifera can provide a technical basis and breeding material for the creation of B. papyrifera germplasm resources in the future.

Abstract Background An estimated 11 million individuals are released from U.S. jails and prisons each year. Individuals with a history of incarceration have higher rates of cardiovascular disease (CVD) events and mortality compared to the general population, especially in the weeks following release from carceral facilities. Healthy sleep, associated with cardiovascular health, is an underexplored factor in the epidemiology of CVD in this population. Incarcerated people may have unique individual, environmental, and institutional policy-level reasons for being sleep deficient. The social and physical environment within carceral facilities and post-release housing may synergistically affect sleep, creating disparities in sleep and cardiovascular health. Since carceral facilities disproportionately house poor and minoritized groups, population-specific risk factors that impact sleep may also contribute to inequities in cardiovascular outcomes. Methods This study is ancillary to an ongoing prospective cohort recruiting 500 individuals with known cardiovascular risk factors within three months of release from incarceration, the Justice-Involved Individuals Cardiovascular Disease Epidemiology (JUSTICE) study. The Sleep Justice study will measure sleep health among participants at baseline and six months using three validated surveys: the Pittsburgh Sleep Quality Index (PSQI), the STOP-Bang, and the Brief Index of Sleep Control. In a subsample of 100 individuals, we will assess sleep over the course of one week using wrist actigraphy, a validated objective measure of sleep that collects data on rest-activity patterns, sleep, and ambient light levels. Using this data, we will estimate and compare sleep health and its association with CVD risk factor control in individuals recently released from carceral facilities. Discussion The incarceration of millions of poor and minoritized groups presents an urgent need to understand how incarceration affects CVD epidemiology. This study will improve our understanding of sleep health among people released from carceral facilities and its potential relationship to CVD risk factor control. Using subjective and objective measures of sleep will allow us to identify unique targets to improve sleep health and mitigate cardiovascular risk in an otherwise understudied population.

Abstract Network meta-analysis compares multiple interventions and estimates the relative treatment effects between all interventions, combining both direct and indirect evidence. Recently, a framework was developed to assess the Risk Of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) which is part of the more comprehensive framework to evaluate the Confidence In the evidence for Network Meta-Analysis (CINeMA). To produce an overall risk of bias judgement for each network estimate, ROB-MEN: performs an assessment of the bias due to missing evidence in each possible pairwise comparison; combines the assessment with the contribution from the direct pairwise comparisons; considers the potential for small-study effects. To facilitate and semi-automate this process, ROB-MEN has been implemented in a user-friendly web-application ( https://cinema.ispm.unibe.ch/rob-men ). Here we provide a tutorial detailing the functionality and use of the application consisting of data upload, analysis configuration, output visualisation, and production of the tool’s output tables for recording the risk of bias assessment. We also illustrate an example application using the demo dataset available for download on the application’s homepage. The ROB-MEN web-application is open-source and freely available ( https://github.com/esm-ispm-unibe-ch/rob-men ).