Clinical Questions Research Articles

Update on Cytomegalovirus Infection Management in Allogeneic Hematopoietic Stem Cell Transplant Recipients. A Consensus Document of the Spanish Group for Hematopoietic Transplantation and Cell Therapy (GETH-TC).

Cytomegalovirus (CMV) infection is a common complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and in patients receiving novel hematological therapies. Its impact on morbidity and mortality necessitates effective management strategies. Despite recent advances in diagnostics and treatment, unresolved questions persist regarding monitoring and treatment, prompting the need for updated recommendations. A consensus was reached among a panel of experts selected for their expertise in CMV research and clinical practice. Key clinical areas and questions were identified based on previous surveys and literature reviews. Recommendations were formulated through consensus and graded using established guidelines. Recommendations were provided for virological monitoring, including the timing and frequency of CMV DNAemia surveillance, especially during letermovir (LMV) prophylaxis. We evaluated the role of CMV DNA load quantification in diagnosing CMV disease, particularly pneumonia and gastrointestinal involvement, along with the utility of specific CMV immune monitoring in identifying at-risk patients. Strategies for tailoring LMV prophylaxis, managing breakthrough DNAemia, and implementing secondary prophylaxis in refractory cases were outlined. Additionally, criteria for initiating early antiviral treatment based on viral load dynamics were discussed. The consensus provides updated recommendations for managing CMV infection in hematological patients, focusing on unresolved issues in monitoring, prophylaxis, treatment, and resistance. These recommendations aim to guide clinical practice and improve outcomes in this high-risk population. Further research is warranted to validate these recommendations and address ongoing challenges in CMV management with emerging antiviral combinations, particularly in pediatric populations.

The Predictive Value of Gamma-Glutamyl Transferase on Jaundice Clearance in Biliary Atresia: An Evidence-Based Case Report and Meta-Analysis

Background: Biliary atresia (BA) is a neonatal condition characterized by the obstruction of extrahepatic bile ducts. Case: A 2-year-old female with BA underwent a Kasai procedure at 3 months of age. Despite the surgery, she developed persistent jaundice and abdominal enlargement. Preoperative laboratory findings revealed elevated liver enzymes, GGT, and bilirubin levels. This case raises the clinical question of whether preoperative GGT levels can predict JC after the Kasai procedure, in addition to its role in diagnosis. Methods: A systematic literature search was performed on 4 databases (PubMed, Scopus, Cochrane, and Proquest) by using relevant keywords and identified seven high quality studies. Results: Five studies found higher GGT levels in patients who achieved JC following Kasai surgery, compared to those with unsuccessful jaundice clearance (JUC). However, two studies reported conflicting findings. A pooled analysis indicated a non-significant trend toward higher GGT levels in the JC group compared to the JUC group (WMD: 65.6, 95% CI: -58.6; 189.8). Conclusion: Elevated preoperative GGT levels may be associated with improved JC in BA patients. However, further investigation to validate these findings, determine the optimal role of GGT in assessing prognosis, and later, guiding treatment decisions in BA patients.

Estimand Framework and Statistical Considerations for Integrated Analysis of Clinical Trial Safety Data.

Safety analyses play a pivotal role in drug development, ensuring the protection of patients while advancing innovative pharmaceuticals to market. A single study generally does not have sufficient sample size to evaluate all important safety events with reasonable precision and may not cover the full target population for the investigational treatment. Integrated analyses (pooled or meta-analysis) over several studies may be helpful in that regard. But without a structured conscious workflow accompanied with appropriate statistical methods for the integrated analysis, this can easily take a route compromising the interpretation. In this article we apply the ICH estimand framework to clinical trial integration and summarize respective critical statistical assumptions to ensure the integrated analyses are interpretable. The estimand framework is valuable for developing principles for a deeper understanding of the critical statistical aspects of planning an integrated safety analysis. Our principles address the clinical question of interest, estimand and estimation. Special focus was given to the criteria for inclusion and exclusion of the component studies in the integrated analysis, and to integration of estimates pertaining to signal detection. Performing an integrated analysis and its preparatory steps calls for a good understanding of the clinical question of interest and its estimand, care and sound practice, to enable interpretation and avoid introducing unnecessary bias. It is valuable to use the estimand framework not only for efficacy evaluations, but also for safety evaluations in clinical trials and for integrated safety analyses.

Diagnostic and Therapeutic Indications of Different Types of Mandibular Advancement Design for Patients with Obstructive Sleep Apnea Syndrome: Indications from Literature Review and Case Descriptions.

Mandibular advancement devices (MADs) are considered a primary alternative treatment for adults with moderate to severe obstructive sleep apnea (OSA) who are unable to tolerate or do not respond to continuous positive airway pressure (CPAP) therapy, supported by substantial scientific evidence. While a range of designs and materials for MADs are commercially available, there is a lack of clear diagnostic guidelines to assist clinicians in selecting the most appropriate device based on a multidisciplinary evaluation of OSA patients. This narrative review seeks to outline the key characteristics of MADs that clinicians should evaluate during both the diagnostic and treatment phases for patients with OSA. An extensive search of academic databases was conducted to gather relevant studies that address therapeutic and diagnostic recommendations for the design and titration of MADs. The search was carried out across EMBASE, Scopus, PubMed, and Web of Science up to May 2024. From a total of 1445 identified citations, 1103 remained after duplicate removal. Based on the inclusion criteria, the full text of 202 articles was retrieved, and 70 studies were ultimately included in this review. The extracted data were organized to generate clinical insights, aimed at guiding orthodontists in optimizing diagnostic and decision-making processes for treating OSA patients with MADs. The analysis led to the identification of key clinical questions that can assist orthodontists in enhancing their approach and choosing the appropriate appliance basing on the diagnosis and clinical dento-orofacial characteristics. Bibloc appliances could be preferred over mono-bloc devices due to the possibility of arranging the mandibular advancement according to the patient's clinical condition and orofacial symptoms. Provisional devices could be used as screening tools to verify the patient's adherence to the therapy. Regardless of the MAD design, type and programmed advancement, it must be under-lined that the rule of the orthodontist/dental specialist is secondary to the other sleep-medicine specialists (ORL, pulmonologist) and must be related to (1) a preliminary assessment of MAD usage (dental anatomical conditions), (2) testing a diagnostic MAD usable during a sleep examination (PSG or DISE), (3) final treatment with a definitive MAD.

The GETAID: 40 years of a family story in IBD.

The Groupe d'Etude sur les Affections Inflammatoires Digestives (GETAID) was founded in Paris in 1983 by Professor R Modigliani and colleagues. From the beginning, the aim of this international (France, Belgium and Switzerland), multicentre, French-speaking group was to address clinical questions raised by patients or physicians in their daily practice or the inflammatory bowel diseases community, by focusing on clinical research on treatments through randomised controlled trials, prospective cohorts and cross-sectional studies, quantifying the severity of various facets of the disease when necessary for these studies. This approach very innovative has contributed to the advancement of knowledge in inflammatory bowel diseases by publishing more than 120 original articles in peer-reviewed journals throughout the GETAID 40-year history, most of them in top publications in gastroenterology and hepatology journals. In this paper, we will see what GETAID's contribution has been over the last four decades, review reasons for success and forthcoming challenges.

Evaluation of accuracies of large language models in answering clinical questions related to mediterranean diet on cardiodiabesity

Abstract Objectives: To explore a method to answer clinical questions (CQs) pertaining to the MedDiet on cardiodiabesity. Methods: We assessed the accuracies of responses provided by large language models (LLMs) to CQs pertaining to the MedDiet on cardiodiabesity. Additionally, a comparative analysis of CQs was conducted among various LLMs, including Claude, Gemini, GPT-4, DoctorGLM, Bencao and HuatuoGPT with one-way analysis of variance, accuracies, and Shannon entropies. Results: The results of ANOVA show that there are significant discrepancies between the CQ and LLM groups, thereby warranting further analysis. The results of accuracies and Shannon entropies show that GPT-4 and Bencao have the highest accuracy (0.978) in responses to CQs among the all six LLMs according to cardiovascular experts. Conclusions: We endorse GPT-4 as the preferred model for responding to CQs related to MedDiet on cardiodiabesity. Concurrently, other LLMs also exhibit the potential to response to these CQs.

Development of the International Federation for Surgery of Obesity and Metabolic Disorders-European Chapter (IFSO-EC) Grade-Based Guidelines on the Surgical Treatment of Obesity Using Multimodal Strategies: Design and Methodological Aspects.

Background: The prevalence of obesity is already a worldwide health concern. The development of straightforward guidelines regarding the whole available armamentarium (i.e., medical, endoscopic, and surgical interventions in conjunction with a guidance program) is paramount to offering the best multimodal approach to patients with obesity. Methods: The International Federation for Surgery of Obesity and Metabolic Disorders-European Chapter (IFSO-EC) identified a panel of experts to develop the present guidelines. The panel formulated a series of clinical questions (based on the patient, intervention, comparison, and outcome conceptual framework), which have been voted on and approved. A GRADE methodology will be applied to assess the quality of evidence and formulate recommendations employed to minimize selection and information biases. This approach aims to enhance the reliability and validity of recommendations, promoting greater adherence to the best available evidence. Results: These guidelines are intended for adult patients with a body mass index (BMI) ≥ 30 kg/m2 who are candidates for metabolic bariatric surgery (MBS). The expert panel responsible for developing these guidelines comprised 25 panelists (92% were bariatric surgeons) and 3 evidence reviewers, with an average age of 50.1 ± 10.2 years. The panel focused on 3 key questions regarding the combined use of structured lifestyle interventions, approved obesity management medications, and endoscopic weight loss procedures with MBS. Conclusions: The complexity of obesity as a chronic disease requires a comprehensive knowledge of all the available and feasible therapeutic options. The IFSO-EC society felt the urgent need to develop methodologically valid guidelines to give a full picture and awareness of the possible surgical and non-surgical therapeutic strategies employed with a multimodal approach.

Methodological components, structure and quality assessment tools for evidence summaries: a scoping review.

The objective of this review was to identify and map the available information related to the definition, structure, and core methodological components of evidence summaries, as well as to identify any indicators of quality. Evidence summaries offer a practical solution to overcoming some of the barriers present in evidence-based health care, such as lack of access to evidence at the point of care, and the knowledge and expertise to evaluate the quality and translate the evidence into clinical decision-making. However, lack of transparency in reporting and inconsistencies in the methodology of evidence summary development have previously been cited and pose problems for end-users (eg, clinicians, policymakers). Any English-language resource that described the methodological development or appraisal of an evidence summary was included. PubMed, Embase, and CINAHL (EBSCOhost) were systematically searched in November 2019, with no limits on the search. The search was updated in June 2021 and January 2023. Gray literature searches and pearling of references of included sources were also conducted at the same time as the database searches. All resources (ie, articles, papers, books, dissertations, reports, and websites) were eligible for inclusion in the review if they evaluated or described the development or appraisal of an evidence summary methodology within a point-of-care context and were published in English. Literature reviews (eg, systematic reviews, rapid reviews), including summaries of evidence on interventions or health care activities that either measure effects, a phenomena of interest, or where the objective was the development, description or evaluation of methods without a clear point-of-care target, were excluded from the review. A total of 76 resources (n=56 articles from databases and n=20 reports from gray literature sources) were included in the review. The most common type/name included critically appraised topic (n=18) and evidence summary (n=17). A total of 25 resources provided a definition of an evidence summary: commonalities included a clinical question; a structured, systematic literature search; a description of literature selection; and appraisal of evidence. Of these 25, 16 included descriptors such as brief, concise, rapid, short, succinct and snapshot. The reported methodological components closely reflected the definition results, with the most reported methodological components being a systematic, multi-database search, and critical appraisal. Evidence summary examples were mostly presented as narrative summaries and usually included a reference list, background or clinical context, and recommendations or implications for practice or policy. Four quality assessment tools and a systematic review of tools were included. The findings of this study highlight the wide variability in the definition, language, methodological components and structure used for point-of-care resources that met our definition of an evidence summary. This scoping review is one of the first steps aimed at improving the credibility and transparency of evidence summaries in evidence-based health care, with further research required to standardize the definitions and methodologies associated with point-of-care resources and accepted tools for quality assessment. A Chinese-language version of the abstract of this review is available at http://links.lww.com/SRX/A59, studies ineligible following full-text review http://links.lww.com/SRX/A60.

Effect evaluation of outpatient long-term video EEGs for people with seizure disorders – study protocol of the ALVEEG project: a randomized controlled trial in Germany

BackgroundEpilepsy and other seizure disorders account for a high disease burden in Germany. As a timely diagnosis and accurate treatment are crucial, improving the management of these disorders is important. Outside of Germany, outpatient long-term video EEGs (ALVEEGs) have demonstrated the potential to support the diagnosis and management of epilepsy and other seizure disorders. This study aims to evaluate the implementation of ALVEEGs as a new diagnostic pathway in eastern parts of Germany to diagnose epilepsy and other seizure disorders and to assess if ALVEEGs are equally effective as the current inpatient-monitoring gold standard, which is currently only available at a limited number of specialized centers in Germany.MethodsALVEEG is a prospective, multicenter, randomized controlled equivalence trial, involving five epilepsy centers in the eastern states of Germany. Patients will be randomized into either intervention (IG) or control group (CG), using a permuted block randomization. The sample size targeted is 688 patients, continuously recruited over the trial. The IG will complete an ALVEEG in a home setting, including getting access to a smartphone app to document seizure activity. The CG will receive care as usual, i.e., inpatient long-term video-EEG monitoring. The primary outcome is the proportion of clinical questions being solved in the IG compared to the CG. Secondary outcomes include hospital stays, time until video EEG, time until diagnosis and result discussion, patients’ health status, quality of life and health competence, and number and form of epilepsy-related events and epileptiform activity. Alongside the trial, a process implementation and health economic evaluation will be conducted.DiscussionThe extensive evaluation of this study, including an implementation and health economic evaluation, will provide valuable information for health policy decision-makers to optimize future delivery of neurological care to patients affected by epilepsy and other seizure disorders and on the uptake of ALVEEG into standard care in Germany.Trial registrationGerman Clinical Trials Register (DRKS00032220), date registered: December 11, 2023.

Chinese expert consensus on the application of electrolytes in parenteral nutrition (2024 edition)

As essential nutrients for human beings, electrolytes play a central role in nutritional and metabolic support treatment. To further standardize the use of electrolyte preparations in parenteral nutrition, the China International Exchange and Promotive Association for Medical and Health Care Clinical Nutrition Health Branch, Chinese Medical Doctor Association Nutritionist Professional Committee, Chinese Society of Parenteral and Enteral Nutrition, and Chinese Nutrition Society Branch of Clinical Nutrition, invited authoritative experts in the fields of critical medicine, emergency medicine, internal medicine, surgery, and pharmacology in China to create this expert consensus. This consensus was based on the latest guidelines and evidence-based medicine at home and abroad, and combined with the actual clinical medical environment in China. This consensus covered the following topics: electrolytes monitoring during parenteral nutrition, risk assessment and nutritional treatment of refeeding syndrome, electrolytes supplementation during parenteral nutrition for various diseases (including severe diseases, heart failure, post-surgical short bowel syndrome, perioperative period, trauma, diabetic foot, chronic kidney disease, liver disease, neonates), and the compatibility principles of electrolyte preparations in parenteral nutrition. Finally, 13 clinical questions and 26 recommendations were proposed aiming at providing scientific, standardized, and practical guidance for the rational application of electrolytes in parenteral nutrition.

The spectrum of indications for ultralong-term EEG monitoring

PurposeWe assessed clinical cases to investigate the spectrum of indications for ultra-longterm EEG monitoring using a subcutaneous implantable device in adult patients with focal epilepsy. MethodsElectronic charts were reviewed from patients undergoing ultra-longterm recordings at the European Epilepsy centers Barcelona, Freiburg and Vienna. Specific patient settings approached in the three centers were analyzed, and the main clinical question was extracted. Results from recordings were analyzed based on the specific results and information obtained. Results24 patients in whom ultra-longterm recordings were available were analyzed. A total of 11 main indications for subcutaneous long-term EEG recordings were identified, including the identification of active epilepsy in patients with low seizure frequency, under- and overreporting of patients, differentiation of non-epileptic from epileptic events, assessment of seizure severity, circadian and multidian rhythms of seizure occurrence, validation of treatment efficacy, improvement of patient-based reporting and medicolegal evidence for seizure freedom. This is reported with patient-specific case vignettes. ConclusionUltra-longterm monitoring using subcutaneous implantable EEG devices can provide relevant diagnostic and treatment information in a large spectrum of clinical situations. This is discussed considering the intrinsic limitations of the method related to spatial coverage, sensitivity and validity as a biomarker of ongoing seizures.

PICO to PICOS: Weak Supervision to Extend Datasets with New Labels.

Hand-labelling clinical corpora can be costly and inflexible, requiring re-annotation every time new classes need to be extracted. PICO (Participant, Intervention, Comparator, Outcome) information extraction can expedite conducting systematic reviews to answer clinical questions. However, PICO frequently extends to other entities such as Study type and design, trial context, and timeframe, requiring manual re-annotation of existing corpora. In this paper, we adapt Snorkel's weak supervision methodology to extend clinical corpora to new entities without extensive hand labelling. Specifically, we enrich the EBM-PICO corpus with new entities through an example of "Study type and design" extraction. Using weak supervision, we obtain programmatic labels on 4,081 EBM-PICO documents, achieving an F1-score of 85.02% on the test set.

Improving accuracy of GPT-3/4 results on biomedical data using a retrieval-augmented language model.

Large language models (LLMs) have made a significant impact on the fields of general artificial intelligence. General purpose LLMs exhibit strong logic and reasoning skills and general world knowledge but can sometimes generate misleading results when prompted on specific subject areas. LLMs trained with domain-specific knowledge can reduce the generation of misleading information (i.e. hallucinations) and enhance the precision of LLMs in specialized contexts. Training new LLMs on specific corpora however can be resource intensive. Here we explored the use of a retrieval-augmented generation (RAG) model which we tested on literature specific to a biomedical research area. OpenAI's GPT-3.5, GPT-4, Microsoft's Prometheus, and a custom RAG model were used to answer 19 questions pertaining to diffuse large B-cell lymphoma (DLBCL) disease biology and treatment. Eight independent reviewers assessed LLM responses based on accuracy, relevance, and readability, rating responses on a 3-point scale for each category. These scores were then used to compare LLM performance. The performance of the LLMs varied across scoring categories. On accuracy and relevance, the RAG model outperformed other models with higher scores on average and the most top scores across questions. GPT-4 was more comparable to the RAG model on relevance versus accuracy. By the same measures, GPT-4 and GPT-3.5 had the highest scores for readability of answers when compared to the other LLMs. GPT-4 and 3.5 also had more answers with hallucinations than the other LLMs, due to non-existent references and inaccurate responses to clinical questions. Our findings suggest that an oncology research-focused RAG model may outperform general-purpose LLMs in accuracy and relevance when answering subject-related questions. This framework can be tailored to Q&A in other subject areas. Further research will help understand the impact of LLM architectures, RAG methodologies, and prompting techniques in answering questions across different subject areas.

ESPEN practical guideline on clinical nutrition in hospitalized patients with acute or chronic kidney disease

Hospitalized patients often have acute kidney disease (AKD) or chronic kidney disease (CKD), with important metabolic and nutritional consequences. Moreover, in case kidney replacement therapy (KRT) is started, the possible impact on nutritional requirements cannot be neglected. On this regard, the present guideline aims to provide evidence-based recommendations for clinical nutrition in hospitalized patients with KD. The standard operating procedure for ESPEN guidelines was used. Clinical questions were defined in both the PICO format, and organized in subtopics when needed, and in non-PICO questions for the more general topics. The literature search was from January 1st, 1999 until January 1st, 2020. Each question led to one or more recommendation/statement and related commentaries. Existing evidence was graded, as well as recommendations and statements were developed and agreed upon in a multistage consensus process. The present guideline provides 32 evidence-based recommendations and 8 statements, defining how to assess nutritional status, how to define patients at risk, how to choose the route of feeding, and how to integrate nutrition with KRT. In the final online voting, a strong consensus was reached in 84% at least of recommendations and 100% of statements. The presence of KD in hospitalized patients identifies a highly heterogeneous group of subjects with widely varying nutrient needs and intakes. Considering the high nutritional risk related with this clinical condition, an individualized approach consisting of nutritional status evaluation and monitoring, frequent evaluation of nutritional requirements, and careful integration with KRT should be planned to avoid both underfeeding and overfeeding. Practical recommendations and statements were developed, aiming at defining suggestions for everyday clinical practice in the individualization of nutritional support in this patient setting. Literature areas with scarce or without evidence were also identified, thus requiring further basic or clinical research.

The evaluation of the performance of ChatGPT in the management of labor analgesia

ChatGPT4 is a leading large language model (LLM) chatbot released by OpenAI in 2023. ChatGPT4 can respond to free-text queries, answer questions and make suggestions regarding virtually any topic. ChatGPT4 has successfully answered anesthesia and even obstetric anesthesia knowledge-based questions with reasonable accuracy. However, ChatGPT4 has yet to be challenged in obstetric anesthesia clinical decision-making. Study Objective: In this study, we evaluated the performance of ChatGPT4 in the management of clinical labor analgesia scenarios compared to expert obstetric anesthesiologists. Intervention: Eight clinical questions with progressively increasing medical complexity were posed to ChatGPT4. Measurements: The ChatGPT4 responses were rated by seven expert obstetric anesthesiologists based on safety, accuracy and completeness of each response using a five-point Likert rating scale. Main Results:ChatGPT4 was deemed safe in 73% of responses to the presented obstetric anesthesia clinical scenarios (27% of responses were deemed unsafe). None of the ChatGPT4 responses were unanimously deemed to be safe by all seven expert obstetric anesthesiologists. Moreover, ChatGPT4 responses were overall partly accurate (score 4 out of 5) and somewhat incomplete (score 3.5 out of 5). Conclusions: In summary, approximately one quarter of all responses by ChatGPT4 were deemed unsafe by expert obstetric anesthesiologists. These findings may suggest the need for more fine-tuning and training of LLMs such as ChatGPT4 specifically for clinical decision making in obstetric anesthesia or other specialized medical fields. These LLMs may come to play an important future role in assisting obstetric anesthesiologists in clinical decision making and enhancing overall patient care.

Comparing suicide risk screening strategies in Spanish-speaking pediatric patients

BackgroundSuicide and suicidal behaviors pose significant global public health challenges, especially among young individuals. Effective screening strategies are crucial for addressing this crisis, with depression screening and suicide-specific tools being common approaches. This study compares their effectiveness by evaluating the Ask Suicide-Screening Questions (ASQ) against item 9 of the Patient Health Questionnaire-A (PHQ-A). MethodsThis study is a secondary analysis of the Argentinean-Spanish version of the ASQ validation study, an observational, cross-sectional, and multicenter study conducted in medical settings in Buenos Aires, Argentina. A convenience sample of pediatric outpatients/inpatients aged 10 to 18 years completed the ASQ, PHQ-A, and Suicide Ideation Questionnaire (SIQ) along with clinical and sociodemographic questions. ResultsA sample of 267 children and adolescents were included in this secondary analysis. Results show that the ASQ exhibited higher sensitivity (95.1%; 95% CI: 83% - 99%) compared to PHQ-A item 9 (73.1%; 95% CI: 57% - 85%), and superior performance in identifying suicide risk in youth. LimitationsThe study included a convenience sampling and was geographically restricted to Buenos Aires, Argentina. The study also lacked longitudinal follow-up to assess the predictive validity of these screening tools for suicide risk. ConclusionThe study highlights the ASQ's effectiveness in identifying suicide risk among youth, emphasizing the importance of specialized screening tools over depression screening tools alone for accurate risk assessment in this population.

Effects of Statistical Practices for Longitudinal Group Comparison of the Penetration-Aspiration Scale on Power and Effect Size Estimation: A Monte Carlo Simulation Study.

Multiple bolus trials are administered during clinical and research swallowing assessments to comprehensively capture an individual's swallowing function. Despite valuable information obtained from these boluses, it remains common practice to use a single bolus (e.g., the worst score) to describe the degree of dysfunction. Researchers also often collapse continuous or ordinal swallowing measures into categories, potentially exacerbating information loss. These practices may adversely affect statistical power to detect and estimate smaller, yet potentially meaningful, treatment effects. This study sought to examine the impact of aggregating and categorizing penetration-aspiration scale (PAS) scores on statistical power and effect size estimates. We used a Monte Carlo approach to simulate three hypothetical within-subject treatment studies in Parkinson's disease and head and neck cancer across a range of data characteristics (e.g., sample size, number of bolus trials, variability). Different statistical models (aggregated or multilevel) as well as various PAS reduction approaches (i.e., types of categorizations) were performed to examine their impact on power and the accuracy of effect size estimates. Across all scenarios, multilevel models demonstrated higher statistical power to detect group-level longitudinal change and more accurate estimates compared to aggregated (worst score) models. Categorizing PAS scores also reduced power and biased effect size estimates compared to an ordinal approach, though this depended on the type of categorization and baseline PAS distribution. Multilevel models should be considered as a more robust approach for the statistical analysis of multiple boluses administered in standardized swallowing protocols due to its high sensitivity and accuracy to compare group-level changes in swallowing function. Importantly, this finding appears to be consistent across patient populations with distinct pathophysiology (i.e., PD and HNC) and patterns of airway invasion. The decision to categorize a continuous or ordinal outcome should be grounded in the clinical or research question with recognition that scale reduction may negatively affect the quality of statistical inferences in certain scenarios.

The use of angiotensin II for the management of distributive shock: expert consensus statements

BackgroundDespite the growing body of evidence supporting the use of angiotensin II (ATII) in distributive shock, its integration into existing treatment algorithms requires careful consideration of factors related to patient comorbidities, hemodynamic parameters, cost-effectiveness, and risk–benefit balance. Moreover, several questions regarding its use in clinical practice warrant further investigations. To address these challenges, a group of Italian intensive care specialists (the panel) developed a consensus process using a modified Delphi technique.MethodsThe panel defined five clinical questions during an online scoping workshop and then provided a short list of statements related to each clinical question based on literature review and clinical experience. A total of 20 statements were collected. Two coordinators screened and selected the final list of statements to be included in the online survey, which consisted of 17 statements. The consensus was reached when ≥ 75% of respondents assigned a score within the 3-point range of 1–3 (disagreement) or 7–9 (agreement).ResultsOverall, a consensus on agreement was reached on 13 statements defining the existing gaps in scientific evidence, the possibility of evaluating the addition of drugs with different mechanisms of action for the treatment of refractory shock, the utility of ATII in reducing the catecholamine requirements in the treatment of vasopressor-resistant septic shock, and the effectiveness of ATII in treating patients in whom angiotensin-converting enzyme activity is reduced or pharmacologically blocked. It was widely shared that renin concentration can be used to identify patients who most likely benefit from ATII to restore vascular tone. Thus, the patients who might benefit most from using ATII were defined. Lastly, some potential barriers to the use of ATII were described.ConclusionsATII was recognized as a useful treatment to reduce catecholamine requirements in treating vasopressor-resistant septic shock. At the same time, the need for additional clinical trials to further elucidate the efficacy and safety of ATII, as well as investigations into potential mechanisms of action and optimization of treatment protocols in patients with refractory distributive shock, emerged.

A Comprehensive Examination of the Role of Epigenetic Factors in Multiple Sclerosis.

According to various research, the risk of multiple sclerosis (MS) is strongly influenced by genetic variations. Population, familial, and molecular studies provide strong empirical support for a polygenic pattern of inheritance, mainly due to relatively common allelic variants in the general population. The strongest MS susceptibility locus, which was unmistakably identified in tested populations, is the major histocompatibility complex on chromosome 6p21.3. However, the effect of a given predisposing variant remains modest, so there is the possibility that multiple gene-gene and/or gene-environment interactions could significantly increase the contribution of specific variants to the overall genetic risk. Furthermore, as is known, susceptibility genes can be subject to epigenetic modifications, which greatly increase the complexity of MS heritability. Investigating epigenetic and environmental factors can provide new opportunities for the molecular basis of the MS, which shows complicated pathogenesis. Although studies of epigenetic changes in MS only began in the last decade, a growing body of literature suggests that these may be involved in the development of MS. Here, we summarize recent studies regarding epigenetic changes related to MS initiation and progression. Furthermore, we discuss how current studies address important clinical questions and how future studies could be used in clinical practice.

Interpretation of the 2023 "Guidelines for parenteral nutrition in preterm infants: the American Society for Parenteral and Enteral Nutrition"

The "Guidelines for parenteral nutrition in preterm infants: the American Society for parenteral and enteral nutrition" were developed by the American Society for Parenteral and Enteral Nutrition and published in the Journal of Parenteral and Enteral Nutrition in September 2023. The guidelines provide recommendations on 12 key clinical questions regarding parenteral nutrition (PN) for preterm infants. In comparison to similar guidelines, this set offers more detailed perspectives on PN for preterm infants. It presents evidence-based recommendations for the commencement time, nutrient dosage, and composition of PN, considering primary outcomes such as growth and development, as well as secondary outcomes like sepsis, retinopathy of prematurity, parenteral nutrition-related liver disease, and jaundice. This article aims to interpret the guidelines to provide a reference for colleagues in the field.