Introducing a machine learning algorithm for delirium prediction-the Supporting SURgery with GEriatric Co-Management and AI project (SURGE-Ahead).

INTRODUCTION: Post-operative delirium (POD) is a common complication in older patients, with an incidence of 14-56%. To implement preventative procedures, it is necessary to identify patients at risk for POD. In the present study, we aimed to develop a machine learning (ML) model for POD prediction in older patients, in close cooperation with the PAWEL (patient safety, cost-effectiveness and quality of life in elective surgery) project. METHODS: The model was trained on the PAWEL study's dataset of 878 patients (no intervention, age ≥ 70, 209 with POD). Presence of POD was determined by the Confusion Assessment Method and a chart review. We selected 15 features based on domain knowledge, ethical considerations and a recursive feature elimination. A logistic regression and a linear support vector machine (SVM) were trained, and evaluated using receiver operator characteristics (ROC). RESULTS: The selected features were American Society of Anesthesiologists score, multimorbidity, cut-to-suture time, estimated glomerular filtration rate, polypharmacy, use of cardio-pulmonary bypass, the Montreal cognitive assessment subscores 'memory', 'orientation' and 'verbal fluency', pre-existing dementia, clinical frailty scale, age, recent falls, post-operative isolation and pre-operative benzodiazepines. The linear SVM performed best, with an ROC area under the curve of 0.82 [95% CI 0.78-0.85] in the training set, 0.81 [95% CI 0.71-0.88] in the test set and 0.76 [95% CI 0.71-0.79] in a cross-centre validation. CONCLUSION: We present a clinically useful and explainable ML model for POD prediction. The model will be deployed in the Supporting SURgery with GEriatric Co-Management and AI project.

Supporting SURgery with GEriatric Co-Management and AI (SURGE-Ahead): A study protocol for the development of a digital geriatrician.

INTRODUCTION: Geriatric co-management is known to improve treatment of older adults in various clinical settings, however, widespread application of the concept is limited due to restricted resources. Digitalization may offer options to overcome these shortages by providing structured, relevant information and decision support tools for medical professionals. We present the SURGE-Ahead project (Supporting SURgery with GEriatric co-management and Artificial Intelligence) addressing this challenge. METHODS: A digital application with a dashboard-style user interface will be developed, displaying 1) evidence-based recommendations for geriatric co-management and 2) artificial intelligence-enhanced suggestions for continuity of care (COC) decisions. The development and implementation of the SURGE-Ahead application (SAA) will follow the Medical research council framework for complex medical interventions. In the development phase a minimum geriatric data set (MGDS) will be defined that combines parametrized information from the hospital information system with a concise assessment battery and sensor data. Two literature reviews will be conducted to create an evidence base for co-management and COC suggestions that will be used to display guideline-compliant recommendations. Principles of machine learning will be used for further data processing and COC proposals for the postoperative course. In an observational and AI-development study, data will be collected in three surgical departments of a University Hospital (trauma surgery, general and visceral surgery, urology) for AI-training, feasibility testing of the MGDS and identification of co-management needs. Usability will be tested in a workshop with potential users. During a subsequent project phase, the SAA will be tested and evaluated in clinical routine, allowing its further improvement through an iterative process. DISCUSSION: The outline offers insights into a novel and comprehensive project that combines geriatric co-management with digital support tools to improve inpatient surgical care and continuity of care of older adults. TRIAL REGISTRATION: German clinical trials registry (Deutsches Register für klinische Studien, DRKS00030684), registered on 21st November 2022.

Digitalization of adverse event management in oncology to improve treatment outcome-A prospective study protocol.

The occurrence of adverse events frequently accompanies tumor treatments. Side effects should be detected and treated as soon as possible to maintain the best possible treatment outcome. Besides the standard reporting system Common Terminology Criteria for Adverse Events (CTCAE), physicians have recognized the potential of patient-reporting systems. These are based on a more subjective description of current patient reporting symptoms. Patient-reported symptoms are essential to define the impact of a given treatment on the quality of life and the patient's wellbeing. They also act against an underreporting of side effects which are paramount to define the actual value of a treatment for the individual patient. Here, we present a study protocol for a clinical trial that assesses the potential of a smartphone application for CTCAE conform symptom reporting and tracking that is adjusted to the standard clinical reporting system rather than symptom oriented descriptive trial tools. The presented study will be implemented in two parts, both lasting over six months. The first part will assess the feasibility of the application with 30 patients non-randomly divided into three equally-sized age groups (<55years, 55-75years, >75years). In the second part 36 other patients will be randomly assigned to two groups, one reporting using the smartphone and one not. This prospective second part will compare the impact of smartphone reported adverse events regarding applied therapy doses and quality of life to those of patients receiving standard care. We aim for early detection and treatment of adverse events in oncological treatment to improve patients' safety and outcomes. For this purpose, we will capture frequent adverse events of chemotherapies, immunotherapies, or other targeted therapies with our smartphone application. The presented trial is registered at the U.S. National Library of Medicine ClinicalTrials.gov (NCT04493450) on July 30, 2020.

Medication of Hydroxychloroquine, Remdesivir and Convalescent Plasma during the COVID-19 Pandemic in Germany-An Ethical Analysis.

This paper aims to analyze the ethical challenges in experimental drug use during the early stage of the COVID-19 pandemic, using Germany as a case study. In Germany uniform ethical guidelines were available early on nationwide, which was considered as desirable by other states to reduce uncertainties and convey a message of unity. The purpose of this ethical analysis is to assist the preparation of future guidelines on the use of medicines during public health emergencies. The use of hydroxychloroquine, remdesivir and COVID-19 convalescent plasma in clinical settings was analyzed from the perspective of the ethical principles of beneficence, non-maleficence, justice and autonomy. We observed that drug safety and drug distribution during the pandemic affects all four ethical principles. We therefore recommend to establish ethical guidelines (i) to discuss experimental treatment options with patients from all population groups who are in urgent need, (ii) to facilitate the recording of patient reactions to drugs in off-label use, (iii) to expand inclusion criteria for clinical studies to avoid missing potentially negative effects on excluded groups, and (iv) to maintain sufficient access to repurposed drugs for patients with prior conditions.

Content and Method of Information for Participants in Clinical Studies With Induced Pluripotent Stem Cells (iPSCs).

Research with induced pluripotent stem cells (iPSCs) involves specific ethical challenges, which should be addressed in the informed consent process. Up to now, little concern has been paid to the practice of information in iPSC-clinical studies. In order to fill this research gap, we have searched the documentation of the Research Ethics Committee at Ulm University from the years 2007 to 2019. In our previous research, we have identified 11 items for evaluation of the process of information in iPSC research. We used these items to analyze content and form of information provided for participants in the iPSC studies conducted at Ulm University and Ulm University Hospital in Germany. All analyzed studies provide general information regarding the study's aim, method, and collection of donor's personal data and specimen. The information for participants in these studies adheres to general guidelines for research involving human subjects; however, in several areas fails to take into account the specific nature of research with iPSCs. The majority of analyzed studies fail to provide information about possible individual consequences connected with genetic research, such as the possibility of re-identification of the donor or incidental findings acquired during research. Missing is also information about the possibility of future studies involving reproductive research or transplantation of cells and organs. The donor information process in all analyzed studies is conducted in form of the information sheet and oral information. The results of our research show that the process of informed consent in iPSC research should be updated as new developments emerge in this area. However, comprehension of information should not be jeopardized through information overload. Effective communication of essential information requires improved information methods tailored to the needs of participants, such as video animations, interactive consent modules or social media instruments.

Cancer, the Media and Dealing with Knowledge.

Among the primary function of the media are conveying personal understanding and expanding the subjective knowledge of the recipient citizen. A particular challenge arising during this process is the mediation of medical knowledge. In addition to pure factual knowledge, it often involves subjective experiences, hopes and wishes. One example of this is media reports about cancer therapies. As a result of widespread media coverage since 2017, the public is under the impression that methadone is a promising treatment for cancer. This chapter analyzes the part played by the media and the ethical debate. The ethical issues that arise concern good scientific practice, patient autonomy and the media coverage of methadone. We conclude that, according to the current state of research, the promotion of methadone as a cure for cancer is ethically unacceptable. In this case the media are not fulfilling their task of imparting knowledge, because they are not communicating the current state of research or the associated ethical questions.

[The art of surgery in nuce : Introduction to Institutiones chirurgicae (1601) by Johannes Jessenius (1566-1621)]. / Chirurgische Kunst in nuce : Einführung zu Institutiones chirurgicae (1601) von Johannes Jessenius (1566­1621).

BACKGROUND: In 1601, Johannes Jessenius published the surgical work Institutiones chirurgicae, which is of particular importance for the history of surgery in Germany. So far, research has predominantly concentrated on the anatomical works of Jessenius; his surgical work including aspects of urology has not been the subject of investigation. OBJECTIVES: In the present article, we analyze the structure, reasoning, and linguistic means used by the author in this work. RESULTS: According to the introduction, surgery comprises three basic components: agens, actor or the surgeon, actio, the activity, that is, the operation, and per quae et quibus actio perficitur, which means instruments and medications. The operations are arranged in contrasts, solutio continuorum-junctio separatorum, the dissolution of the connected-connection of the separate, extirpatio superfluorum-recuperatio deficientium, to eliminate the superfluous-to restore the missing. The description of the instruments is also based on opposite pairs. DISCUSSION: The three elements of surgical work represent a reduction of what is stated in the Hippocratic text De officina. Thus, recognizable here is an ancient tradition, which was also known to the predecessors of Jessenius. CONCLUSIONS: At the beginning of the work, aspects of an introduction to the surgical work of the 16th century are briefly recapitulated. Jessenius adheres to this historical tradition including aspects of urology of this work. In the introduction, he refers to various medical writers, without directly adopting the texts. The surgical artistry that Jessenius stands for is of fundamental importance to this day.

Serum neprilysin and the risk of death in patients with out-of-hospital cardiac arrest of non-traumatic origin.

BACKGROUND: Early risk stratification remains an unmet clinical need in patients with in out-of-hospital cardiac arrest. We hypothesised that soluble neprilysin may represent a promising biomarker in patients with out-of-hospital cardiac arrest of non-traumatic origin and provide new pathobiological insight. METHODS: This pilot study was a biomarker analysis from the Heidelberg Resuscitation Registry. Serum soluble neprilysin levels on admission were measured in 144 patients with successful return of spontaneous circulation after out-of-hospital cardiac arrest of non-traumatic origin. The primary endpoint was time to all-cause mortality. KM Event Rates are reported. Cox models were adjusted for age, bystander resuscitation, initial ECG rhythm, baseline estimated glomerular filtration rate, baseline lactate, left ventricular function at baseline, and targeted temperature management. RESULTS: In total, 90 (62.5%) patients died over a follow-up of at least 30 days. Soluble neprilysin correlated weakly with high-sensitivity troponin T (r=0.18, P=0.032) but did not correlate significantly with estimated glomerular filtration rate (r=-0.12) or lactate (r=0.11). Patients with elevated soluble neprilysin levels on admission were at significantly higher risk of all-cause mortality (Q4 69.1% vs. Q1 48.4%). After multivariable adjustment, soluble neprilysin in the top quartile (Q4) was significantly associated with all-cause mortality (Q4 vs. Q1: adjusted hazard ratio 2.48 (1.20-5.12)). In an adjusted multimarker model including high-sensitivity troponin T and high-sensitivity C-reactive protein, soluble neprilysin and high-sensitivity troponin T remained independently associated with all-cause mortality (soluble neprilysin: adjusted hazard ratio 2.27 (1.08-4.78); high-sensitivity troponin T: adjusted hazard ratio 3.40 (1.63-7.09)). CONCLUSION: Soluble neprilysin, measured as early as on hospital admission, was independently associated with all-cause mortality in patients with out-of-hospital cardiac arrest of non-traumatic origin and may prove to be useful in the estimation of risk in these patients.

Saving whom? The ethical challenges of harvesting tissue from savior siblings.

PURPOSE OF THE STUDY: To discuss the ethical challenges for the therapeutic team when dealing with a young savior sibling as a potential tissue donor. BASIC PROCEDURES: Savior siblings are children that are created to serve a sibling as a donor of umbilical cord blood, bone marrow, or peripheral blood from which hematopoietic stem cells are derived. These cells are used for hematopoietic stem cell therapy, which is the only curative treatment for certain hemoglobinopathies. We used a case including a 19-year-old thalassemia patient and his two and a half year old sister from our practice as ethics consultants. Our methodological basis is the principlism approach by Beauchamp and Childress, consisting of four principles: autonomy, non-maleficence, beneficence, and justice. MAIN FINDINGS: We found that the main conflict arises between the autonomy of the savior sibling as well as the non-maleficence regarding her and the beneficence of the thalassemia patient. PRINCIPAL CONCLUSIONS: Decision-making is complex when decisions within the family are concerned, especially when non-competent young children are involved. The therapeutic team does not only have to recognize the principal vulnerability of children but also the different scales of vulnerability depending on their age.

The Archiv für Ohrenheilkunde (Archive of Otology): a structural analysis of the first 50 years (1864-1914).

In 1864, Anton von Tröltsch in Würzburg, Hermann Schwartze in Halle/Saale, and Adam Politzer in Vienna founded the Archiv für Ohrenheilkunde (Archive of Otology), the ancestor of the European Archives of Oto-Rhino-Laryngology and Head and Neck. It was the world's first journal solely devoted to otology, and thus to otorhinolaryngology. The aim of this study was to analyse the structure of this journal and its contents during the first 50 years of its publication, until it definitively became an otorhinolaryngological journal in 1915. A total of 2,271 articles were registered during this time. They were classified according to content topic, article type, and the number of figures and graphs that they contained. Almost three-quarters of the articles were related to purely otological topics, as implied by the journal's title. Until the turn of the twentieth century, the majority of the articles were original papers or case reports. The number of original papers declined over the decades in favour of case reports. One-third of each volume usually consisted of a vast variety of items, such as congress announcements, conference proceedings, and book reviews. The journal also maintained a wide variety of scientific and current social and political subjects. Otological reviews and conference proceedings were key landmarks of the journal. All of these various papers provided an overview of the historical organisation and development of otology between 1864 and 1914. At that time, the Archiv für Ohrenheilkunde was a leading national and international journal.

[Ancient dietetics - lifestyle and medicine]. / Antike diätetik-lebensweise und medizin.

The wide reaching meaning of eating and drinking is already recognized in antiquity. The declared aim of antique dietetics is the upbringing to a healthy lifestyle. Fundamental considerations of dietetic, theoretically organized ideas can be traced back to the Presocratics, who, for the first time in cultural history, let themselves be guided by direct observations from nature. Working from the meaning of dietetics as pure nutritional teaching, one can see in the Corpus Hippocraticum a significant, systematic attempt to put forth dietetics as a concept of lifestyle. Here a central aspect is that of equilibrium, as it is expressed in the rule of the four humours. Dietetics continually become a connecting link between Natural Philosophy and Anthropology and a lifestyle orientated to nature. Finally, Galen introduces a further systematization of the already existing and the increasingly modified. Nutrition and health are brought into association and the theoretical presupposed practically overturned. In late Antiquity dietetical outlooks continue to be discussed, which were transferred to the Middle Ages and still show practical relevance.