Diagnosestrategien in der Allgemeinmedizin: Der Beitrag von deduktivem Hypothesentesten und getriggerten Routinefragen

Hintergrund: Die Diagnosestellung ist eine der anspruchsvollsten kognitiven Aufgaben eines Arztes. In kurzer Zeit muss eine große Anzahl an diagnostischen Möglichkeiten evaluiert werden. Insbesondere in der Allgemeinmedizin kommt der Anamneseerhebung, die ohne technische Mittel auskommt, eine zentrale Bedeutung zu. Bisherige Untersuchungen zum diagnostischen Vorgehen fanden unter unrealistischen Bedingungen statt und postulierten vor allem ein hypothetiko-deduktives Vorgehen (Elstein et al. 1978). Demnach werden früh Hypothesen gebildet, die dann eine aktive hypothesen-geleitete Informationssuche strukturieren. Dieses Vorgehen ist als kognitiv hoch anspruchsvoll anzusehen. Es ist zu vermuten, dass es nicht in jedem Fall sinnvoll eingesetzt werden kann. Im Sinne einer „adaptiven Toolbox“ (Gigerenzer und Todd 1999) werden vermutlich weitere heuristische Fragestrategien durch Allgemeinmediziner genutzt. Die Rolle von Routinefragen als kognitive Strategie wurde in der bisherigen Forschung kaum beachtet und meist negativ formuliert. In der vorliegenden Arbeit werden getriggerte Routinefragen erstmals als ein positives diagnostisches Instrument formuliert und untersucht. Diese Routinefragen werden durch ein Symptom getriggert und evaluieren ein Organsystem ohne durch eine Hypothese geleitetet zu werden. Ziel der vorliegenden Arbeit war es die Rolle der kognitiven Strategien deduktives Hypothesentesten und getriggerte Routinefragen erstmals an realen empirischen Daten im allgemeinmedizinischen Setting zu untersuchen. Methoden: Es wurde eine Querschnittsstudie mit 12 Allgemeinmedizinern durchgeführt. Unabhängig vom Beratungsanliegen wurden 282 Konsultationen auf Video aufgezeichnet. 134 dieser Konsultationen enthielten mindestens eine diagnostische Episode. Insgesamt wurden 163 diagnostische Episoden ausgewertet. Nach jeder Konsultation reflektierten die Ärzte in einem halb-standardisierten Interview den vorangegangenen diagnostischen Prozess. Die Konsultationen und Interviews wurden transkribiert und anschließend mittels qualitativer und quantitativer Methoden analysiert. Der hierbei verwendete Kodierbaum basierte auf bereits publizierten Theorien, sowie Erfahrungswissen aus der Primärversorgung. Ergebnisse: Deduktives Hypothesentesten konnte nur in 39 % der diagnostischen Episoden identifiziert werden. Die entwickelten diagnostischen Hypothesen variieren je nach Situation zwischen sehr spezifisch und abstrakt. Bei der Hypothesenentwicklung und der Informationssuche spiegelten sich die Besonderheiten des allgemeinmedizinischen Settings stark wieder. Insbesondere konnte eine frühe Hypothesenentwicklung auf Basis von komplexem und vielschichtigem Kontextwissen identifiziert werden. Jeder teilnehmende Allgemeinmediziner nutzte getriggerte Routinefragen als diagnostische Strategie. Getriggerte Routinefragen konnten in 38% der diagnostischen Episoden identifiziert werden. Es fanden sich respiratorische, gastrointestinale, urogenitale und globale getriggerte Routinefragen. Die Fragen sind inhaltlich mit dem Präsentiersymptom des Patienten assoziiert. Sie werden genutzt um eine systematische Übersicht über die Symptome des Patienten zu gewinnen, bei der Reorientierung im diagnostischen Raum und bei der Reduktion der diagnostischen Unsicherheit. Diskussion: Im Ergebnis der vorliegenden Studie wird das hypothetiko-deduktive Modell deutlich relativiert. Deduktives Hypothesentesten bildet nur einen Teil der verwendeten kognitiven Fragestrategien ab. Ein mindestens ebenso relevanter Baustein der „adpativen Toolbox“ des diagnostischen Prozesses sind getriggerte Routinefragen. Getriggerte Routinefragen sind als Bindeglied zwischen offenen Strategien, wie dem Induktiven Streifen und dem sehr spezifischen deduktiven Hypothesentesten zu lokalisieren. Sie helfen interessante Areale des diagnostischen Raumes zu explorieren, wenn eine Informationssuche mittels spezifischer Hypothesen diesen unangemessen einschränken würde und kognitiv zu aufwendig wäre. Deduktives Hypothesentesten und getriggerte Routinefragen als diversifizierte kognitive Fragestrategien sind Bestandteil eines hoch adaptiven Prozesses der Informationssuche in der unsicheren Entscheidungsumgebung der Allgemeinmedizin. Sie können in ein umfassenderes Modell von „bounded rationality“ für komplexe Entscheidungssituationen integriert werden

Freiheitsentziehende Maßnahmen in Alten- und Pflegeheimen – Analyse ihrer rechtlichen Voraussetzungen und der Möglichkeiten ihrer praktischen Anwendung

Ausführliche Betrachtung der Voraussetzungen für die Genehmigungsbedürftigkeit und die Genehmigungsfähigkeit freiheitsentziehender Maßnahmen. Kurze Erläuterung der gerichtlichen Genehmigungsverfahrens und Darstellung der haftungsrechtlichen Folgen bei Rechtswidrigkeit oder Unterlassen einer freiheitsentziehenden Maßnahme. Hinweis auf mögliche Alternativen

Preoperative CYFRA 21-1 and CEA as Prognostic Factors in Patients with Stage I Non-Small Cell Lung Cancer

Objective: To validate the prognostic value of preoperative levels of CYFRA 21-1, CEA and the corresponding tumor marker index (TMI) in patients with stage I non-small cell lung cancer (NSCLC). Methods: Two hundred forty stage I NSCLC patients (80 in pT1 and 160 in pT2; 100 squamous cell carcinomas, 91 adenocarcinomas, 32 large-cell carcinomas, 17 with other histologies; 171 males and 69 females) who had complete resection (R0) between 1986 and 2004 were included in the analysis. CYFRA 21-1 and CEA were measured using the Elecsys system (Roche) and AxSym-System (Abbott), respectively. Univariate analysis was performed using the Kaplan-Meier method to identify potential associations between survival and age, gender, CYFRA 21-1, CEA and TMI. Results: Overall 3- and 5-year survival rates were 74 and 64%, respectively. Male gender (p = 0.0009) and age 1 70 years (p = 0.0041) were associated with a worse prognosis; there were no differences between pT1 and pT2 nor between histological subtypes. Three- year survival was 72% for CYFRA 21-1 levels > 3.3 ng/ml versus 75% for levels 6.7 ng/ ml versus 75% for CEA 70 years were associated with a worse outcome, but elevated levels of CEA and CYFRA 21-1, and TMI risk were not. Copyright (C) 2008 S. Karger AG, Basel

Expression Profiling the Temperature-Dependent Amphibian Response to Infection by Batrachochytrium dendrobatidis

Amphibians are experiencing a panzootic of unprecedented proportions caused by the emergence of Batrachochytrium dendrobatidis (Bd). However, all species are not equally at risk of infection, and risk is further modified by environmental variables, specifically temperature. In order to understand how, and when, hosts mount a response to Bd we analysed infection dynamics and patterns of gene expression in the model amphibian species Silurana (Xenopus) tropicalis. Mathematical modelling of infection dynamics demonstrate the existence of a temperature-dependent protective response that is largely independent of the intrinsic growth-rate of Bd. Using temporal expression-profiling by microarrays and qRT-PCR, we characterise this response in the main amphibian lymphoid tissue, the spleen. We demonstrate that clearance of Bd at the host-optimal temperature is not clearly associated with an adaptive immune response, but rather is correlated with the induction of components of host innate immunity including the expression of genes that are associated with the production of the antimicrobial skin peptide preprocareulein (PPCP) as well as inflammatory responses. We find that adaptive immunity appears to be lacking at host-optimal temperatures. This suggests that either Bd does not stimulate, or suppresses, adaptive immunity, or that trade-offs exist between innate and adaptive limbs of the amphibian immune system. At cold temperatures, S. tropicalis loses the ability to mount a PPCP-based innate response, and instead manifests a more pronounced inflammatory reaction that is characterised by the production of proteases and higher pathogen burdens. This study demonstrates the temperature-dependency of the amphibian response to infection by Bd and indicates the influence that changing climates may exert on the ectothermic host response to pathogens

The Oogenic Germline Starvation Response in C. elegans

Many animals alter their reproductive strategies in response to environmental stress. Here we have investigated how L4 hermaphrodites of Caenorhabditis elegans respond to starvation. To induce starvation, we removed food at 2 h intervals from very early- to very late-stage L4 animals. The starved L4s molted into adulthood, initiated oogenesis, and began producing embryos; however, all three processes were severely delayed, and embryo viability was reduced. Most animals died via ‘bagging,’ because egg-laying was inhibited, and embryos hatched in utero, consuming their parent hermaphrodites from within. Some animals, however, avoided bagging and survived long term. Long-term survival did not rely on embryonic arrest but instead upon the failure of some animals to produce viable progeny during starvation. Regardless of the bagging fate, starved animals showed two major changes in germline morphology: All oogenic germlines were dramatically reduced in size, and these germlines formed only a single oocyte at a time, separated from the remainder of the germline by a tight constriction. Both changes in germline morphology were reversible: Upon re-feeding, the shrunken germlines regenerated, and multiple oocytes formed concurrently. The capacity for germline regeneration upon re-feeding was not limited to the small subset of animals that normally survive starvation: When bagging was prevented ectopically by par-2 RNAi, virtually all germlines still regenerated. In addition, germline shrinkage strongly correlated with oogenesis, suggesting that during starvation, germline shrinkage may provide material for oocyte production. Finally, germline shrinkage and regeneration did not depend upon crowding. Our study confirms previous findings that starvation uncouples germ cell proliferation from germline stem cell maintenance. Our study also suggests that when nutrients are limited, hermaphrodites scavenge material from their germlines to reproduce. We discuss our findings in light of the recently proposed state of dormancy, termed Adult Reproductive Diapause

The Characterization of Varicella Zoster Virus–Specific T Cells in Skin and Blood during Aging

Reactivation of the varicella zoster virus (VZV) increases during aging. Although the effects of VZV reactivation are observed in the skin (shingles), the number and functional capacity of cutaneous VZV-specific T cells have not been investigated. The numbers of circulating IFN-γ-secreting VZV-specific CD4+ T cells are significantly decreased in old subjects. However, other measures of VZV-specific CD4+ T cells, including proliferative capacity to VZV antigen stimulation and identification of VZV-specific CD4+ T cells with an major histocompatibility complex class II tetramer (epitope of IE-63 protein), were similar in both age groups. The majority of T cells in the skin of both age groups expressed CD69, a characteristic of skin-resident T cells. VZV-specific CD4+ T cells were significantly increased in the skin compared with the blood in young and old subjects, and their function was similar in both age groups. In contrast, the number of Foxp3+ regulatory T cells and expression of the inhibitory receptor programmed cell death -1 PD-1 on CD4+ T cells were significantly increased in the skin of older humans. Therefore, VZV-specific CD4+ T cells in the skin of older individuals are functionally competent. However, their activity may be restricted by multiple inhibitory influences in situ

Genotype–phenotype associations within the Li-Fraumeni spectrum: a report from the German Registry

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by pathogenic TP53 variants. The condition represents one of the most relevant genetic causes of cancer in children and adults due to its frequency and high cancer risk. The term Li-Fraumeni spectrum reflects the evolving phenotypic variability of the condition. Within this spectrum, patients who meet specific LFS criteria are diagnosed with LFS, while patients who do not meet these criteria are diagnosed with attenuated LFS. To explore genotype–phenotype correlations we analyzed 141 individuals from 94 families with pathogenic TP53 variants registered in the German Cancer Predisposition Syndrome Registry. Twenty-one (22%) families had attenuated LFS and 73 (78%) families met the criteria of LFS. NULL variants occurred in 32 (44%) families with LFS and in two (9.5%) families with attenuated LFS (P value < 0.01). Kato partially functional variants were present in 10 out of 53 (19%) families without childhood cancer except adrenocortical carcinoma (ACC) versus 0 out of 41 families with childhood cancer other than ACC alone (P value < 0.01). Our study suggests genotype–phenotype correlations encouraging further analyses. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13045-022-01332-1

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements