Moritz Berger

University of Bonn | Uni Bonn · Institute of Biomedical Statistics, Computer Science and Epidemiology

Random survival forests (RSF) can be applied to many time‐to‐event research questions and are particularly useful in situations where the relationship between the independent variables and the event of interest is rather complex. However, in many clinical settings, the occurrence of the event of interest is affected by competing events, which means...

Background Conditional logistic regression trees have been proposed as a flexible alternative to the standard method of conditional logistic regression for the analysis of matched case–control studies. While they allow to avoid the strict assumption of linearity and automatically incorporate interactions, conditional logistic regression trees may s...

Macular Telangiectasia Type 2 (MacTel) is a chronic, progressive disease of the central retina characterized by vascular and neurodegenerative changes. As there is currently no treatment for non-neovascular MacTel, there is a dearth for biomarkers identifying eyes with an increased risk for disease progression for patient counseling and clinical tr...

The tree-structured varying coefficient model (TSVC) is a flexible regression approach that allows the effects of covariates to vary with the values of the effect modifiers. Relevant effect modifiers are identified inherently using recursive partitioning techniques. To quantify uncertainty in TSVC models, we propose a procedure to construct confide...

Purpose The Treatment exit Options For non-infectious Uveitis (TOFU) registry documents disease courses for non-anterior non-infectious uveitis entities with and without treatment to generate more evidence for clinical management recommendations including treatment exit strategies. In this article, we present the participants’ baseline characterist...

Objectives Impaired perivascular clearance has been suggested as a contributing factor to the pathogenesis of Alzheimer disease (AD). However, it remains unresolved when the anatomy of the perivascular space (PVS) is altered during AD progression. Therefore, this study investigates the association between PVS volume and AD progression in cognitivel...

This paper presents a semi-parametric modeling technique for estimating the survival function from a set of right-censored time-to-event data. Our method, named pseudo-value regression trees (PRT), is based on the pseudo-value regression framework, modeling individual-specific survival probabilities by computing pseudo-values and relating them to a...

As most rare diseases, intermediate uveitis lacks reliable endpoints necessary for randomized clinical trials. Therefore, we investigated longitudinal changes of retinal and choriocapillaris perfusion on optical coherence tomography angiography (OCT-A) in intermediate uveitis and their prognostic value for future best corrected visual acuity (BCVA)...

Neuroinflammation is a hallmark of Alzheimer’s disease (AD) and both positive and negative associations of individual inflammation-related markers with brain structure and cognitive function have been described. We aimed to identify inflammatory signatures of CSF immune-related markers that relate to changes of brain structure and cognition across...

Risk assessment before interventions in elderly patients becomes more and more vital due to an increasing number of elderly patients requiring surgery. Existing risk scores are often not tailored to marginalized groups such as patients aged 80 years or older. We aimed to develop an easy-to-use and readily applicable risk assessment tool that implem...

Purpose Prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been observed in immunocompromised hosts. Early monotherapy with direct-acting antivirals or monoclonal antibodies, as recommended by the international guidelines, does not prevent this with certainty. Dual therapies may therefore have a synergistic effec...

Spinocerebellar ataxia type 3/Machado–Joseph disease (SCA3) is the most common autosomal dominant ataxia. In view of the development of targeted therapies, knowledge of early biomarker changes is needed. We analyzed cross‐sectional data of 292 SCA3 mutation carriers. Blood concentrations of mutant ATXN3 were high before and after ataxia onset, whil...

This study aimed to determine the retest variability of quantitative fundus autofluorescence (QAF) in patients with and without age-related macular degeneration (AMD) and evaluate the predictive value of patient reliability indices on retest reliability. A total of 132 eyes from 68 patients were examined, including healthy individuals and those wit...

Background Cognitive decline is a key outcome of clinical studies in Alzheimer’s disease (AD). Objective To determine effects of global amyloid load as well as hippocampus and basal forebrain volumes on longitudinal rates and practice effects from repeated testing of domain specific cognitive change in the AD spectrum, considering non-linear effec...

Purpose Prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been observed in immunocompromised hosts. Early monotherapy with direct-acting antivirals or monoclonal antibodies, as recommended in the international guidelines, does not prevent this with certainty. Dual therapies might therefore act synergistically. M...

Background: SARS-CoV-2 immunogenicity in patients with gastrointestinal cancer (GI cancer) following second and third vaccination was analyzed. Methods: A total of 125 patients under active anticancer therapy or in follow-up care were included in this prospective study. Seroprevalence of SARS-CoV-2 anti-spike and surrogate neutralization antibod...

Abstract Background White matter hyperintensities (WMH) in subjects across the Alzheimer’s disease (AD) spectrum with minimal vascular pathology suggests that amyloid pathology—not just arterial hypertension—impacts WMH, which in turn adversely influences cognition. Here we seek to determine the effect of both hypertension and Aβ positivity on WMH,...

Introduction: Data on immune response rates following vaccination for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in patients with hepatobiliary carcinoma (HBC) are rare. However, impaired immunogenicity must be expected due to the combination of chronic liver diseases (CLDs) with malignancy and anticancer treatment. Methods: In...

Elderly patients are at a high risk of suffering from postoperative death. Personalized strategies to improve their recovery after intervention are therefore urgently needed. A popular way to analyze postoperative mortality is to develop a prognostic model that incorporates risk factors measured at hospital admission, e.g. comorbidities. When build...

Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3) is the most common autosomal dominant ataxia. In view of the development of targeted therapies for SCA3, precise knowledge of stage-dependent fluid and MRI biomarker changes is needed. We analyzed cross-sectional data of 292 SCA3 mutation carriers including 57 pre-ataxic individuals, and 1...

Background The NIA-AA proposed amyloid-tau-neurodegeneration (ATN) as a classification system for AD biomarkers. The amyloid cascade hypothesis (ACH) implies a sequence across ATN groups that patients might undergo during transition from healthy towards AD: A−T−N−➔A+T−N−➔A+T+N−➔A+T+N+. Here we assess the evidence for monotonic brain volume decline...

Background In preclinical Alzheimer’s disease, it is unclear why some individuals with amyloid pathologic change are asymptomatic (stage 1), whereas others experience subjective cognitive decline (SCD, stage 2). Here, we examined the association of stage 1 vs. stage 2 with structural brain reserve in memory-related brain regions. Methods We tested...

Background: Skin and soft tissue infections (SSTIs) are common conditions with severe and potentially life-threatening outcomes. However, the use of antibiotics to treat these infections is controversial. Purpose: This study was to identify the microorganisms responsible for facial SSTIs, their antibiotic sensitivities, and the therapeutic outco...

Conditional logistic regression (CLR) is the indisputable standard method for the analysis of matched case‐control studies. However, CLR is strongly restricted with respect to the inclusion of non‐linear effects and interactions of confounding variables. A novel tree‐based modeling method is proposed which accounts for this issue and provides a fle...

Discrete hazard models are widely applied for the analysis of time-to-event outcomes that are intrinsically discrete or grouped versions of continuous event times. Commonly, one assumes that the effect of explanatory variables on the hazard can be described by a linear predictor function. This, however, may be not appropriate when non-linear effect...

Drusen are hallmarks of early and intermediate age-related macular degeneration (AMD) but their quantification remains a challenge. We compared automated drusen volume measurements between different OCT devices. We included 380 eyes from 200 individuals with bilateral intermediate (iAMD, n = 126), early (eAMD, n = 25) or no AMD (n = 49) from the MA...

Purpose: To report the prevalence and topographic distribution of structural characteristics in study participants with age-related macular degeneration (AMD) and controls in the cross-sectional study part of the MACUSTAR study (ClinicalTrials.gov Identifier: NCT03349801). Design: European, multicenter cohort study. Subjects: 301 eyes of 301 s...

Background Posterior white matter hyperintensities (WMH) in subjects across the Alzheimer's disease (AD) spectrum with minimal vascular pathology suggests that amyloid pathology—not just arterial hypertension—impacts WMH, adversely influencing cognition. Here we seek to determine the effect of both hypertension and Aβ positivity on WMH, and their i...

The aim of this study was the development of a statistical model for reliable prediction of Posterior Airway Space (PAS) changes in lateral cephalograms (LCR) of patients after bimaxillary orthognathic surgery. The LCRs of patients who underwent bimaxillary orthognathic surgery were retrospectively analyzed. The anteroposterior dimension of the PAS...

Endocannabinoid (eCB) signaling is markedly decreased in the hippocampus (Hip) of aged mice, and the genetic deletion of the cannabinoid receptor type 1 (CB1) leads to an early onset of cognitive decline and age-related histological changes in the brain. Thus, it is hypothesized that cognitive aging is modulated by eCB signaling through CB1. In the...

Quantification of the relative ellipsoid zone reflectivity (rEZR) might be a structural surrogate parameter for an early disease progression in the context of age-related macular degeneration (AMD). Within the European multicenter, cross-sectional MACUSTAR study, we have devised an automatic approach to determine the mean rEZR [arbitrary units, AU]...

Clinical discrimination of posterior uveitis entities remains a challenge. This exploratory, cross-sectional study investigated the green (GEFC) and red emission fluorescent components (REFC) of retinal and choroidal lesions in posterior uveitis to facilitate discrimination of the different entities. Eyes were imaged by color fundus photography, sp...

Importance Posterior white matter hyperintensities (WMH) in subjects across the Alzheimer’s disease (AD) spectrum with minimal vascular pathology suggests that amyloid pathology —not just arterial hypertension— impacts WMH, adversely influencing cognition. Objective To characterise the effects of AD pathology, namely β-amyloid (Aβ) and hypertensio...

With ever-improving driver assistance systems and large touchscreens becoming the main in-vehicle interface, drivers are more tempted than ever to engage in distracting non-driving-related tasks. However, little research exists on how driving automation affects drivers' self-regulation when interacting with center stack touchscreens. To investigate...

Importance: There is a need for validated clinical end points that are reliably able to quantify potential therapeutic effects of future treatments targeting age-related macular degeneration (AMD) before the onset of serious visual impairment. Objective: To assess the reliability and discriminatory power of 5 simple chart-based visual function (...

Introduction: One of the most important geriatric syndromes is dizziness in conjunction with gait disorder and consequent falls. There are various differential diagnoses for dizziness, one of them is benign paroxysmal positional vertigo (BPPV). Objectives: A targeted diagnostic work-up and treatment of BPPV can prevent subsequent falls and a dec...

Background The NIA-AA proposed Amyloid-Tau-Neurodegeneration (ATN) as a classification system for AD biomarkers. The Amyloid Cascade Hypothesis (ACH) implies a sequence across ATN groups that patients might undergo during transition from healthy towards AD: A-T-N-→A+T-N-→A+T+N-→A+T+N+. Here we assess the evidence for monotonic brain volume decline...

Introduction: It is uncertain whether subjective cognitive decline (SCD) in individuals who seek medical help serves the identification of the initial symptomatic stage 2 of the Alzheimer's disease (AD) continuum. Methods: Cross-sectional and longitudinal data from the multicenter, memory clinic-based DELCODE study. Results: The SCD group show...

Purpose: To quantify the impact of the mode of administration (MOA) on scores of the Vision Impairment in Low Luminance (VILL) questionnaire. Methods: The VILL questionnaire was implemented using different MOAs (paper, interview, electronic), in addition to a demographical survey of adult participants recruited at an outpatient eye clinic, with...

Background/aims To further validate the Vision Impairment in Low Luminance (VILL) questionnaire, which captures visual functioning and vision-related quality of life (VRQoL) under low luminance, low-contrast conditions relevant to age-related macular degeneration (AMD). Methods The VILL was translated from German into English (UK), Danish, Dutch,...

Background: Recent guidelines suggest that benzodiazepine premedication should be avoided in elderly patients, though with limited supporting evidence. Objective: We conducted a secondary analysis of the POSE data to explore the association of premedication in patients aged 80 years or older with 30-day mortality. Design: We used propensity sc...

BACKGROUND: Recent guidelines suggest that benzodiazepine premedication should be avoided in elderly patients, though with limited supporting evidence. OBJECTIVE: We conducted a secondary analysis of the POSE data to explore the association of premedication in patients aged 80 years or older with 30-day mortality. DESIGN: We used propensity score m...

The potential of location‐shift models to find adequate models between the proportional odds model and the non‐proportional odds model is investigated. It is demonstrated that these models are very useful in ordinal modelling. While proportional odds models are often too simple, non‐proportional odds models are typically unnecessary complicated and...

Background Recruiting asymptomatic participants with early disease stages into studies is challenging and only little is known about facilitators and barriers to screening and recruitment of study participants. Thus we assessed factors associated with screening rates in the MACUSTAR study, a multi-centre, low-interventional cohort study of early st...

Background Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated gastrointestinal food allergy mainly affecting infants and young children. Allergic FPIES reactions differ from IgE-mediated food allergies, e.g. regarding elicitors and clinical course. Objective The aim of our study was to describe causative agents and developme...

Nocturnal traffic noise has been associated with adverse health outcomes in exposed residents. Precise quantification of traffic noise effects on sleep is thus of great importance. Here we establish an exposure-response relationship for the awakening probability due to intermittent road traffic noise in suburban residents. We conducted a field stud...

Zusammenfassung Hintergrund und Ziel der Arbeit Für die klinische Sichtung in der Zentralen Notaufnahme (ZNA) existiert bisher für den Massenanfall von Verletzten kein standardisierter Sichtungsalgorithmus. Mit dem Erscheinen der vierten überarbeiteten und erweiterten Auflage des Manchester-Triage-Systems (MTS) wird dem Nutzer ein spezielles Präse...

enThe generalization performance of a risk prediction model can be evaluated by its calibration, which measures the agreement between predicted and observed outcomes on external validation data. Here, we propose methods for assessing the calibration of discrete time-to-event models in the presence of competing risks. Specifically, we consider the c...

Background The presentational flow chart “unwell adult” of the Manchester Triage System (MTS) occupies a special role in this triage system, defined as the nonspecific presentation of an emergency patient. Current scientific studies show that a considerable proportion of emergency room patients present with so-called "nonspecific complaints". The a...

In binary and ordinal regression one can distinguish between a location component and a scaling component. While the former determines the location within the range of the response categories, the scaling indicates variance heterogeneity. In particular since it has been demonstrated that misleading effects can occur if one ignores the presence of a...

A flexible semiparametric class of models is introduced that offers an alternative to classical regression models for count data as the Poisson and Negative Binomial model, as well as to more general models accounting for excess zeros that are also based on fixed distributional assumptions. The model allows that the data itself determine the distri...

Background and study aims We previously reported a case series of our first 182 colorectal endoscopic submucosal dissections (ESDs). In the initial series, 155 ESDs had been technically feasible, with 137 en bloc resections and 97 en bloc resections with free margins (R0). Here, we present long-term follow-up data, with particular emphasis on cases...

A SARS-CoV-2 super-spreading event occurred during carnival in a small town in Germany. Due to the rapidly imposed lockdown and its relatively closed community, this town was seen as an ideal model to investigate the infection fatality rate (IFR). Here, a 7-day ser-oepidemiological observational study was performed to collect information and biomat...

Backround and study aims Duodenal cancer is the cancer most often seen in patients with familial adenomatous polyposis (FAP) who have undergone risk-reducing colonic surgery. Almost all patients with FAP eventually develop duodenal adenomas and risk for duodenal cancer is up to 12 % with poor prognosis. In addition, there is a rising concern regard...

This article presents an overview of statistical methods for the analysis of discrete failure times with competing events. We describe the most commonly used modeling approaches for this type of data, including discrete versions of the cause‐specific hazards model and the subdistribution hazard model. In addition to discussing the characteristics o...

Hazard models are popular tools for the modeling of discrete time-to-event data. In particular two approaches for modeling time dependent effects are in common use. The more traditional one assumes a linear predictor with effects of explanatory variables being constant over time. The more flexible approach uses the class of semiparametric models th...

The potential of location-shift models to find adequate models between the proportional odds model and the non-proportional odds model is investigated. It is demonstrated that these models are very useful in ordinal modeling. While proportional odds models are often too simple, non proportional odds models are typically unnecessary complicated and...

The world faces an unprecedented SARS-CoV2 pandemic where many critical factors still remain unknown. The case fatality rates (CFR) reported in the context of the SARS-CoV-2 pandemic substantially differ between countries. For SARS-CoV-2 infection with its broad clinical spectrum from asymptomatic to severe disease courses, the infection fatality r...

Context: Quality requirements (QRs) are a topic of constant discussions both in industry and academia. Debates entwine around the definition of quality requirements, the way how to handle them, or their importance for project success. While many academic endeavors contribute to the body of knowledge about QRs, practitioners may have different views...

Random survival forests (RSF) are a powerful nonparametric method for building prediction models with a time-to-event outcome. RSF do not rely on the proportional hazards assumption and can be readily applied to both low- and higher-dimensional data. A remaining limitation of RSF, however, arises from the fact that the method is almost entirely foc...

Objective Early detection and treatment can prevent irreversible blindness from diabetic retinopathy (DR), which is the leading cause of visual impairment among working-aged adults worldwide. 80% of affected persons live in low- and middle-income countries, yet, lack of resources has largely prevented DR screening implementation in these world regi...