Institut für Klinische Epidemiologie und Biometrie
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- asthma (2)
- cohort studies (2)
- heart failure (2)
- ischemic stroke (2)
- mental health (2)
- stroke (2)
- tinnitus (2)
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Institute
- Institut für Klinische Epidemiologie und Biometrie (27)
- Deutsches Zentrum für Herzinsuffizienz (DZHI) (8)
- Graduate School of Life Sciences (5)
- Medizinische Klinik und Poliklinik I (4)
- Klinik und Poliklinik für Anästhesiologie (ab 2004) (3)
- Neurologische Klinik und Poliklinik (3)
- Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie (2)
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (2)
- Institut für Informatik (1)
- Kinderklinik und Poliklinik (1)
Sonstige beteiligte Institutionen
Prediction of tinnitus perception based on daily life mHealth data using country origin and season
(2022)
Tinnitus is an auditory phantom perception without external sound stimuli. This chronic perception can severely affect quality of life. Because tinnitus symptoms are highly heterogeneous, multimodal data analyses are increasingly used to gain new insights. MHealth data sources, with their particular focus on country- and season-specific differences, can provide a promising avenue for new insights. Therefore, we examined data from the TrackYourTinnitus (TYT) mHealth platform to create symptom profiles of TYT users. We used gradient boosting engines to classify momentary tinnitus and regress tinnitus loudness, using country of origin and season as features. At the daily assessment level, tinnitus loudness can be regressed with a mean absolute error rate of 7.9% points. In turn, momentary tinnitus can be classified with an F1 score of 93.79%. Both results indicate differences in the tinnitus of TYT users with respect to season and country of origin. The significance of the features was evaluated using statistical and explainable machine learning methods. It was further shown that tinnitus varies with temperature in certain countries. The results presented show that season and country of origin appear to be valuable features when combined with longitudinal mHealth data at the level of daily assessment.
Background
The Dermatophagoides pteronyssinus molecule Der p 23 is a major allergen whose clinical relevance has been shown in cross‐sectional studies. We longitudinally analysed the trajectory of Der p 23‐specific IgE antibody (sIgE) levels throughout childhood and youth, their early‐life determinants and their clinical relevance for allergic rhinitis and asthma.
Methods
We obtained sera and clinical data of 191 participants of the German Multicentre Allergy Study, a prospective birth cohort. Serum samples from birth to 20 years of age with sIgE reactivity to Der p 23 in a customised semiquantitative microarray were newly analysed with a singleplex quantitative assay. Early mite exposure was assessed by measuring the average content of Der p 1 in house dust at 6 and 18 months.
Results
Der p 23‐sIgE levels were detected at least once in 97/191 participants (51%). Prevalence of Der p 23 sensitisation and mean sIgE levels increased until age 10 years, plateaued until age 13 years and were lowest at age 20 years. Asthma, allergic rhinitis (AR) and atopic dermatitis (AD) were more prevalent in Der p 23‐sensitised children, including those with monomolecular but persistent sensitisation (11/97, 11%). A higher exposure to mites in infancy and occurrence of AD before 5 years of age preceded the onset of Der p 23 sensitisation, which in turn preceded a higher incidence of asthma.
Conclusions
Der p 23 sensitisation peaks in late childhood and then decreases. It is preceded by early mite exposure and AD. Asthma and AR can occur in patients persistently sensitised to Der p 23 as the only mite allergen, suggesting the inclusion of molecular testing of Der p 23‐sIgE for subjects with clinical suspicion of HDM allergy but without sIgE to other major D.pt. allergens.
Tinnitus is an auditory phantom perception in the ears or head in the absence of a corresponding external stimulus. There is currently no effective treatment available that reliably reduces tinnitus. Educational counseling is a treatment approach that aims to educate patients and inform them about possible coping strategies. For this feasibility study, we implemented educational material and self-help advice in a smartphone app. Participants used the educational smartphone app unsupervised during their daily routine over a period of four months. Comparing the tinnitus outcome measures before and after smartphone-guided treatment, we measured changes in tinnitus-related distress, but not in tinnitus loudness. Improvements on the Tinnitus Severity numeric rating scale reached an effect size of 0.408, while the improvements on the Tinnitus Handicap Inventory (THI) were much smaller with an effect size of 0.168. An analysis of user behavior showed that frequent and intensive use of the app is a crucial factor for treatment success: participants that used the app more often and interacted with the app intensively reported a stronger improvement in the tinnitus. Between study allocation and final assessment, 26 of 52 participants dropped out of the study. Reasons for the dropouts and lessons for future studies are discussed in this paper.
Die Erhebung der alltäglichen Funktionsfähigkeit mithilfe von Skalen zu instrumentellen
Aktivitäten des täglichen Lebens (IADL) ist essenziell zur Erfassung der individuellen und
gesellschaftlichen Konsequenzen von klinischen und subklinischen Erkrankungen. Im
deutschsprachigen Raum existieren jedoch nur wenige validierte Instrumente zur Erfassung von
IADL. Da all diese Skalen für ein geriatrisches Patientenkollektiv entwickelt wurden, haben sie
wichtige Schwächen in der Anwendung bei jüngeren Patientengruppen (insbesondere die
fehlende Erfassung beruflicher Funktionsfähigkeit). Aus diesem Grund wurde im Rahmen der
vorliegenden Arbeit mit dem Functioning Assessment Short Test (FAST) ein bereits in
mehreren Sprachen validiertes, für erwachsene Patienten jedweden Alters konzipiertes
Instrument mit sehr guten psychometrischen Kennwerten ins Deutsche übertragen und
hinsichtlich Validität und Reliabilität untersucht. Die deutschsprachige Variante des FAST
wurde durch standardisierte vorwärts-rückwärts-Übersetzung aus dem Englischen erstellt und
ist als Selbstausfüllerfragebogen konzipiert. Die Skala enthält 23 ordinal skalierte Einzelitems,
aus denen sich ein Summenscore berechnen lässt, wobei höhere Werte für eine schlechtere
alltägliche Funktionsfähigkeit stehen. Der Fragebogen wurde zwischen 2017 und 2018 an
insgesamt 120 Teilnehmern in Würzburg und Münster getestet, von denen 60 aus
bevölkerungsbasierten Kohortenstudien stammten und je 30 Patienten aufgrund eines
ischämischen Schlaganfalls oder einer akuten Depression stationär behandelt wurden. Als Maß
für die Reliabilität des Instrumentes wurde die Übereinstimmung zwischen Selbst- und
Fremdeinschätzung der alltäglichen Funktionsfähigkeit (Fremdeinschätzung durch Angehörige
der Teilnehmer bzw. behandelnde Ärzte / Psychologen) mithilfe des FAST gewählt. Die
Validität der Skala wurde durch die Messung von Korrelationen des FAST Summenscores mit
gängigen Skalen zu Depressivität (PHQ-D-9, CES-D), Angstsymptomatik (PHQ-GAD-7),
gesundheitsbezogener Lebensqualität (SF-12, EQ-5D) und kognitiver Leistungsfähigkeit
(MOCA) erhoben. Daneben erfolgte eine uni- und multivariate Regression zur Erhebung des
Einflusses der o.g. Skalen und relevanter Vorerkrankungen auf den Summenscore des FAST.
Die Reliabilitätsanalyse zeigte für die Probanden aus der Allgemeinbevölkerung ein moderates
(ICC 0.50 (95%-CI 0.64 – 0.54), für die Patienten mit akutem ischämischem Schlaganfall ein
gutes (ICC 0.65 (95%-CI 0.55 – 0.75) und für die stationär behandelten Patienten mit
Depression ein schlechtes Ergebnis (ICC 0.11 (95%-CI 0.02 – 0.20). Hinsichtlich der
Konstruktvalidität zeigte sich in der bevölkerungsbasierten Stichprobe eine signifikante
Korrelation des FAST Summenscores mit PHQ-D-9, CES-D, PHQ-GAD-7 und psychischer
Summenskala der SF-12. In der univariablen Regression waren PHQ-D9, PHQ-GAD-7,
psychische Summenskala des SF-12 und das Vorliegen von chronischem Rückenschmerz
signifikante Prädiktoren für den FAST Summenscore. In der multivariablen Analyse verblieben
SF-12 und chronischer Rückenschmerz als signifikante Einflussfaktoren. In der Stichprobe von
Patienten mit akutem ischämischem Schlaganfall zeigte sich eine signifikante, negative
Korrelation des FAST Summenscores mit dem MOCA.
Zusammenfassend zeigte die deutschsprachige Variante des FAST moderate bis gute
psychometrische Kennwerte in der Allgemeinbevölkerung und bei Patienten mit akutem
ischämischem Schlaganfall, während die Ergebnisse bei stationär behandelten Patienten mit
Depression schlecht waren. Aufgrund der kleinen Fallzahl der untersuchten Stichproben und
des fehlenden Assessment von Test-Retest-Reliabilität sollten vor der breiten Anwendung des
FAST im deutschsprachigen Raum weitere psychometrische Prüfungen des Instruments
erfolgen.
(1) Background: The aim of this study is to assess perioperative therapy in stage IA-III pancreatic cancer cross-validating the German Cancer Registry Group of the Society of German Tumor Centers — Network for Care, Quality, and Research in Oncology, Berlin (GCRG/ADT) and the National Cancer Database (NCDB). (2) Methods: Patients with clinical stage IA-III PDAC undergoing surgery alone (OP), neoadjuvant therapy (TX) + surgery (neo + OP), surgery+adjuvantTX (OP + adj) and neoadjuvantTX + surgery + adjuvantTX (neo + OP + adj) were identified. Baseline characteristics, histopathological parameters, and overall survival (OS) were evaluated. (3) Results: 1392 patients from the GCRG/ADT and 29,081 patients from the NCDB were included. Patient selection and strategies of perioperative therapy remained consistent across the registries for stage IA-III pancreatic cancer. Combined neo + OP + adj was associated with prolonged OS as compared to neo + OP alone (17.8 m vs. 21.3 m, p = 0.012) across all stages in the GCRG/ADT registry. Similarly, OS with neo + OP + adj was improved as compared to neo + OP in the NCDB registry (26.4 m vs. 35.4 m, p < 0.001). (4) Conclusion: The cross-validation study demonstrated similar concepts and patient selection criteria of perioperative therapy across clinical stages of PDAC. Neoadjuvant therapy combined with adjuvant therapy is associated with improved overall survival as compared to either therapy alone.
1 Summary
Left ventricular (LV) ejection fraction (EF) and global longitudinal strain (GLS) are the most commonly used measures of LV function. Yet, they are highly dependent on loading conditions since higher afterload yields lower systolic deformation and thereby a lower LVEF and GLS – despite presumably unchanged LV myocardial contractile strength. Invasive pressure-volume loop measurements represent the reference standard to assess LV function, also considering loading conditions. However, this procedure cannot be used in serial investigations or large sample populations due to its invasive nature. The novel concept of echocardiography-derived assessment of myocardial work (MyW) is based on LV pressure-strain loops, may be a valuable alternative to overcome these challenges, and may also be used with relative ease in large populations. As MyW also accounts for afterload, it is considered less load-dependent than LVEF and GLS.
The current PhD work addresses the application and clinical characterization of MyW, an innovative echocardiographic tool. As the method is new, we focused on four main topics:
(a) To establish reference values for MyW indices, i.e., Global Work Index (GWI), Global Constructive Work (GCW), Global Wasted Work (GWW), and Global Work Efficiency (GWE); we addressed a wide age range and evaluated the association of MyW indices with age, sex and other clinical and echocardiography parameters in apparently cardiovascular healthy individuals.
(b) To investigate the impact of cardiovascular (CV) risk factors on MyW indices and characterize the severity of subclinical LV deterioration in the general population.
(c) To assess the association of the LV geometry, i.e., LV mass and dimensions, with MyW indices.
(d) To evaluate in-hospital dynamics of MyW indices in patients hospitalized for acute heart failure (AHF).
For the PhD thesis, we could make use of two larger cohorts:
The STAAB population-based cohort study prospectively recruited and phenotyped a representative sample (5,000 individuals) of the general population of the City of Würzburg, aged 30-79 years and free from symptomatic heart failure at the time of inclusion. We focused on the first half of the study sample (n=2473 individuals), which fulfilled the anticipated strata regarding age and sex.
The Acute Heart Failure (AHF) Registry is a prospective clinical registry recruiting and phenotyping consecutive patients admitted for decompensated AHF to the Department of Medicine I, University Hospital Würzburg, and observing the natural course of the disease. The AHF Registry focuses on the pathophysiological understanding, particularly in relation to the early phase after cardiac decompensation, with the aim to improve diagnosis and better-tailored treatment of patients with AHF. For the current study, we concentrated on patients who provided pairs of echocardiograms acquired early after index hospital admission and prior to discharge.
The main findings of the PhD thesis were:
From the STAAB cohort study, we determined the feasibility of large-scale MyW derivation and the accuracy of the method. We established reference values for MyW indices based on 779 analyzable, apparently healthy participants (mean age 49 ± 10 years, 59% women), who were in sinus rhythm, free from CV risk factors or CV disease, and had no significant LV valve disease. Apart from GWI, there were no associations of other MyW indices with sex. Further, we found a disparate association with age, where MyW showed stable values until the age of 45 years, with an upward shift occurring beyond the age of 45. A higher age decade was associated with higher GWW and lower GWE, respectively. MyW indices only correlated weakly with common echocardiographic parameters, suggesting that MyW may add incremental information to clinically established parameters.
Further analyses from the STAAB cohort study contributed to a better understanding of the impact of CV risk factors on MyW indices and the association of LV geometry with LV performance. We demonstrated that CV risk factors impacted selectively on GCW and GWW. Hypertension appears to profoundly compromise the work of the myocardium, in particular, by increasing both GCW and GWW. The LV in hypertension seems to operate at a higher energy level yet lower efficiency. Other classical CV risk factors (Diabetes mellitus, Obesity, Dyslipidemia, Smoking) – independent of blood pressure – impacted consistently and adversely on GCW but did not affect GWW. Further, all CV risk factors affected GWE adversely.
We observed that any deviation from a normal LV geometric profile was associated with alterations on MyW. Of note, MyW was sensitive to early changes in LV mass and dimensions. Individuals with normal LV geometry yet established arterial hypertension exhibited a MyW pattern that is typically found in LV hypertrophy. Therefore, such a pattern might serve as an early sign of myocardial damage in hypertensive heart disease and might aid in risk stratification and primary prevention.
From the AHF Registry, we selected individuals with serial in-hospital echocardiograms and described in-hospital changes in myocardial performance during recompensation. In patients presenting with a reduced ejection fraction (HFrEF), decreasing N-terminal pro-natriuretic peptide (NT-proBNP) levels as a surrogate of successful recompensation were associated with an improvement in GCW and GWI and consecutively in GWE. In contrast, in patients presenting with a preserved ejection fraction (HFpEF), there was no significant change in GCW and GWI. However, unsuccessful recompensation, i.e., no change or an increase in NT-proBNP levels, was associated with an increase in GWW. This suggests a differential myocardial response to de- and recompensation depending on the HF phenotype.
Further, GWW as a surrogate of inappropriate LV energy consumption was elevated in all patients with AHF (compared to reference values) and was not associated with conventional markers as LVEF or NT-proBNP. In an exploratory analysis, GWW predicted the risk of death or rehospitalization within six months after discharge. Hence, GWW might carry incremental information beyond conventional markers of HF severity.
Für die Diagnose und Therapie von Brustkrebs existiert die nationale evidenz- und konsensbasierte S3-Leitlinie. Die klinischen Krebsregister stellen sektor- und facharztübergreifende Diagnose- und Therapiedaten zur Qualitätssicherung bereit. Bislang fehlen jedoch Daten bezüglich patient-reported outcome measures (PROMs). Aufgrund des demographischen Wandels werden Brustkrebserkrankungen vor allem in ländlichen Regionen weiter zunehmen, weshalb Versorgungsstrukturen für alle Patientinnen erreichbar sein sollten. Es wurde ein patientenorientiertes Registerkonzept (Breast Cancer Care for patients with metastatic disease (BRE-4-MED)) für den metastasierten Brustkrebs entwickelt und hinsichtlich vordefinierter Machbarkeitskriterien pilotiert. An der BRE-4-MED-Pilotstudie nahmen 31 Patientinnen (96.8% weiblich) teil. Die bayernweite Erreichbarkeit zu brustkrebsspezifischen Versorgungsstrukturen wurde mithilfe einer Geographic Information System (GIS)-Analyse untersucht. Anhand von Leitlinienempfehlungen und Ergebnissen der BRE-4-MED-Pilotstudie wurden relevante Versorgungsstrukturen identifiziert. Die Ergebnisse der Pilotstudie zeigen, dass die Integration von Primär- und Sekundärdaten aus verschiedenen Quellen in ein zentrales Studienregister machbar ist und die erforderlichen organisatorischen Prozesse (z. B. data linkage mit Krebsregister) funktionieren. Die Ergebnisse der Erreichbarkeitsanalyse verdeutlichen, dass es keine bayernweite Erreichbarkeit zu brustkrebsspezifischen Versorgungsstrukturen gibt. Am stärksten war dieser Zusammenhang in grenznahen Regionen ausgeprägt. Die vorliegende Arbeit zeigt Chancen für eine patientenorientierte, qualitätsgesicherte Brustkrebsversorgung unabhängig vom Wohnort auf.