Martin Wolkewitz

• PhD
• Senior Researcher at University of Freiburg

Background The advancement of Artificial Intelligence, particularly Large Language Models (LLMs), is rapidly progressing. LLMs, such as OpenAI’s GPT, are becoming vital in scientific and medical processes, including text production, knowledge synthesis, translation, patient communication and data analysis. However, the outcome quality needs to be e...

Background There are no contemporary data on the burden of healthcare-associated infections (HAIs) in New Zealand. Objectives To estimate the economic burden of HAIs in adults in New Zealand public hospitals by number and monetary value of bed days lost; number of deaths, number of life years lost, and the monetary value (in NZ dollars); Accident...

Background The spread of several severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) variants of concern (VOCs) has repeatedly led to increasing numbers of coronavirus disease 2019 (COVID-19) patients in German intensive care units (ICUs), resulting in capacity shortages and even transfers of COVID-19 intensive care patients between f...

This study aims to develop and apply multistate models to estimate, forecast, and manage hospital length of stay during the COVID-19 epidemic without using any external packages. Data from Bellvitge University Hospital in Barcelona, Spain, were analyzed, involving 2285 hospitalized COVID-19 patients with moderate to severe conditions. The implement...

Background The independent effects of extranasal only carriage, carriage at multiple bodily sites, or the bacterial load of colonizing Staphylococcus aureus (SA) on the risk of developing SA surgical site infections and postoperative bloodstream infections (SA SSI/BSIs) are unclear. We aimed to quantify these effects in this large prospective cohor...

Objectives Many studies have attempted to determine the disease severity and patterns of COVID-19. However, at the beginning of the pandemic, the complex patients’ trajectories were only descriptively reported, and many analyses were worryingly prone to time-dependent-, selection-, and competing risk biases. Multi-state models avoid these biases by...

Introduction The fight against SARS-CoV-2 has been a major task worldwide since it was first identified in December 2019. An imperative preventive measure is the availability of efficacious vaccines while there is also a significant interest in the protective effect of a previous SARS-CoV-2 infection on a subsequent infection (natural protection ra...

Background Extended illness-death models (a specific class of multistate models) are a useful tool to analyse situations like hospital-acquired infections, ventilation-associated pneumonia, and transfers between hospitals. The main components of these models are hazard rates and transition probabilities. Calculation of different measures and their...

Background In late 2021, the German statutory health insurance (SHI) funds reported average expenditures for the treatment of coronavirus disease 2019 (COVID-19) intensive care patients without mechanical ventilation at €8,000 and even more than €30,000 for those with mechanical ventilation. In this context, there is currently no further informatio...

Introduction This study aims to discuss and assess the impact of three prevalent methodological biases: competing risks, immortal-time bias, and confounding bias in real-world observational studies evaluating treatment effectiveness. We use a demonstrative observational data example of COVID-19 patients to assess the impact of these biases and prop...

Background The spread of several severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) variants of concern (VOC) repeatedly led to increasing numbers of coronavirus disease 2019 (COVID-19) patients in German intensive care units (ICUs), resulting in capacity shortages and even transfers of COVID-19 intensive care patients between federa...

Importance Staphylococcus aureus surgical site infections (SSIs) and bloodstream infections (BSIs) are important complications of surgical procedures for which prevention remains suboptimal. Contemporary data on the incidence of and etiologic factors for these infections are needed to support the development of improved preventive strategies. Obje...

Background Real-world observational data are an important source of evidence on the treatment effectiveness for patients hospitalized with coronavirus disease 2019 (COVID-19). However, observational studies evaluating treatment effectiveness based on longitudinal data are often prone to methodological biases such as immortal time bias, confounding...

Background: Immune suppression has been implicated in the occurrence of pneumonia in critically ill patients. We tested the hypothesis that Intensive Care Unit (ICU)-acquired pneumonia is associated with broad host immune aberrations in the trajectory to pneumonia, encompassing inflammatory, endothelial and coagulation responses. We compared plasm...

Multistate methodology proves effective in analyzing hospitalized coronavirus disease 2019 (COVID-19) patients with emerging variants in real time. An analysis of 2,548 admissions in Freiburg, Germany, showed reduced severity over time in terms of shorter hospital stays and higher discharge rates when comparing more recent phases with earlier phase...

Background The spread of several SARS-CoV-2 variants of concern (VOC) led to increasing numbers of patients with coronavirus disease 2019 (COVID-19) in German intensive care units (ICU), resulting in capacity shortages and even transfers of COVID-19 ICU patients between federal states in late 2021. Comprehensive evidence on the impact of predominan...

Methodological biases are common in observational studies evaluating treatment effectiveness. The objective of this study is to emulate a target trial in a competing risks setting using hospital-based observational data. We extend established methodology accounting for immortal time bias and time-fixed confounding biases to a setting where no survi...

Purpose Early identification of high-risk patients is an important component in improving infection prevention. The SAPS2, APACHE2, Core-10-TISS, and SOFA scores are already widely used to estimate mortality, morbidity and nursing workload, but this study evaluated their usefulness in assessing a patient’s risk of ICU-acquired infection. Methods W...

Purpose When studying nosocomial infections, resource-efficient sampling designs such as nested case-control, case-cohort, and point prevalence studies are preferred. However, standard analyses of these study designs can introduce selection bias, especially when interested in absolute rates and risks. Moreover, nosocomial infection studies are ofte...

Background Randomized controlled trials (RCTs) and cohort studies are the most common study design types used to assess treatment effects of medical interventions. We aimed to hypothetically pool bodies of evidence (BoE) from RCTs with matched BoE from cohort studies included in the same systematic review. Methods BoE derived from systematic revie...

Objectives Population-based estimates of excess length of stay following hospital-acquired bacteraemia are few and prone to time-dependent bias. We investigated excess length of stay and readmission following hospital-acquired bacteraemia. Methods This population-based cohort study included the North Denmark Region adult population hospitalised fo...

Background Randomized controlled trials (RCTs) and cohort studies are the most common study design types used to assess the treatment effects of medical interventions. To evaluate the agreement of effect estimates between bodies of evidence (BoE) from randomized controlled trials (RCTs) and cohort studies and to identify factors associated with dis...

The COVID-19 pandemic has led to a high interest in mathematical models describing and predicting the diverse aspects and implications of the virus outbreak. Model results represent an important part of the information base for the decision process on different administrative levels. The Robert-Koch-Institute (RKI) initiated a project whose main go...

Zusammenfassung Hintergrund Zeitdynamische Prognosemodelle spielen eine zentrale Rolle zur Steuerung von intensivmedizinischen COVID-19-Kapazitäten im Pandemiegeschehen. Ein wichtiger Vorhersagewert (Prädiktor) für die zukünftige intensivmedizinische (ITS-)COVID-19-Bettenbelegungen ist die Anzahl der SARS-CoV-2-Neuinfektionen in der Bevölkerung, d...

The quality and persistence of children’s humoral immune response following SARS-CoV-2 infection remains largely unknown but will be crucial to guide pediatric SARS-CoV-2 vaccination programs. Here, we examine 548 children and 717 adults within 328 households with at least one member with a previous laboratory-confirmed SARS-CoV-2 infection. We ass...

We commented on the publication by Tleyjeh et al regarding the overlooked shortcomings of observational studies of interventions in Coronavirus Disease 2019. Although we agree with Tleyjeh and colleagues on the issue of the competing risk bias in observational studies, the recommendations on the application of the Fine-Gray model provided by the au...

Coronavirus disease-2019, also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was a disaster in 2020. Accurate and early diagnosis of coronavirus disease-2019 (COVID-19) is still essential for health policymaking. Reverse transcriptase-polymerase chain reaction (RT-PCR) has been performed as the operational gold standard for...

Background: Our retrospective study evaluates the impact on short - and long-term outcome according to the graft selection during emergency coronary revascularization surgery. Methods: 339 Patients with acute coronary syndrome undergoing emergency coronary bypass surgery at our institution from 2008 until 2018 were analyzed using propensity scor...

Objectives In 2017, a point-prevalence survey was conducted with 12,931 patients in 96 hospitals across Switzerland as part of the national strategy to prevent healthcare-associated infections (HAIs). We present novel statistical methods to assess incidence proportions of HAI and attributable length-of-stay (LOS) in point-prevalence surveys. Metho...

Background: Long-term persistence of antibodies against SARS-CoV-2, particularly the SARS-CoV-2 Spike Trimer, determines individual protection against infection and potentially viral spread. The quality of children's natural humoral immune response following SARS-CoV-2 infection is yet incompletely understood but crucial to guide pediatric SARS-CoV...

Objective To investigate the effect of daily whole-body bathing (WBB) using disposable washcloth wipes/caps impregnated with an antiseptic solution containing the quaternary ammonium base compound didecyl dimethyl ammonium chloride (DDAC) Methods A prospective double-blind randomized-crossover trial was conducted to compare WBB of adult ICU patien...

Background: The COVID-19 pandemic has led to a high interest in mathematical models describing and predicting the diverse aspects and implications of the virus outbreak. Model results represent an important part of the information base for the decision process on different administrative levels. The Robert-Koch-Institute (RKI) initiated a project w...

Background and objective Observational studies may provide valuable evidence on real-world causal effects of drug effectiveness in patients with Coronavirus Disease 2019 (COVID-19). Since patients are usually observed from hospital admission to discharge and drug initiation starts during hospitalization, advanced statistical methods are needed to a...

Objectives Hospital-acquired infections (HAIs) place a substantial burden on health systems. Tools are required to quantify the change in this burden as a result of a preventive intervention. We aim to estimate how much a reduction in the rate of hospital-acquired infections translates into a change in hospital mortality and length of stay. Method...

Background: Already at the time of hospital admission, clinicians require simple tools to identify hospitalized COVID-19 patients at high risk of mortality. Such tools can significantly improve resource allocation and patient management within hospitals. From the statistical point of view, extended time-to-event models are required to account for c...

Background Bloodstream infections (BSI) caused by Enterobacteriaceae show increasing frequency of resistance to third-generation cephalosporin (3GC) antibiotics on the African continent but the mortality impact has not been quantified. Methods We used historic data from six African hospitals to assess the impact of 3GC resistance on clinical outco...

[This corrects the article DOI: 10.1093/jacamr/dlaa130.].

Objectives To systematically summarize the evidence on how to collect, analyse and report antimicrobial resistance (AMR) surveillance data to inform antimicrobial stewardship (AMS) teams providing guidance on empirical antibiotic treatment in healthcare settings. Methods The research group identified 10 key questions about the link between AMR sur...

Background Reported mortality of hospitalised Coronavirus Disease-2019 (COVID-19) patients varies substantially, particularly in critically ill patients. So far COVID-19 in-hospital mortality and modes of death under state of the art care have not been systematically studied. Methods This retrospective observational monocenter cohort study was per...

Objectives: Many trials investigate potential effects of treatments for coronavirus disease 2019. To provide sufficient information for all involveddecision-makers (clinicians, public health authorities, and drug regulatory agencies), a multiplicity of endpoints must be considered. The objectives are to provide hands-on statistical guidelines for...

Importance: Carriage of Staphylococcus aureus is associated with S aureus infection. However, associations between S aureus carriage and the development of S aureus intensive care unit (ICU) pneumonia (SAIP) have not been quantified accurately, and interpretation of available data is hampered because of variations in definitions. Objective: To q...

Introduction: Transmissions of opportunistic bacterial pathogens between neonates increase the risk of infections with negative repercussions, including higher mortality, morbidity and permanent disabilities. The probability of transmissions between patients is contingent on a set of intrinsic (patient-related) and extrinsic (ward-related) risk fa...

Background: The pressures exerted by the pandemic of COVID-19 pose an unprecedented demand on health care services. Hospitals become rapidly overwhelmed when patients requiring life-saving support outpace available capacities. We here describe methods used by a university hospital to forecast caseloads and time to peak incidence. Methods: We dev...

Background The posterior wall of the proximal internal carotid artery (ICA) is the predilection site for the development of stenosis. To optimally prevent stroke, identification of new risk factors for plaque progression is of high interest. Therefore, we studied the impact of carotid geometry and wall shear stress on cardiovascular magnetic resona...

By definition, in-hospital patient data are restricted to the time between hospital admission and discharge (alive or dead). For hospitalised cases of COVID-19, a number of events during hospitalization are of interest regarding the influence of risk factors on the likelihood of experiencing these events. The same is true for predicting times from...

Background The clinical progress of patients hospitalized due to COVID-19 is often associated with severe pneumonia which may require intensive care, invasive ventilation, or extracorporeal membrane oxygenation (ECMO). The length of intensive care and the duration of these supportive therapies are clinically relevant outcomes. From the statistical...

Background Reported mortality of hospitalised COVID-19 patients varies substantially, particularly in critically ill patients. So far COVID-19 in-hospital mortality and modes of death under optimised care conditions have not been systematically studied.Methods This retrospective observational monocenter cohort study was performed after implementati...

Background Reported mortality of hospitalised COVID-19 patients varies substantially, particularly in critically ill patients. So far COVID-19 in-hospital mortality and modes of death under optimised care conditions have not been systematically studied. Methods This retrospective observational monocenter cohort study was performed after implementat...

Background: There is a continuing need for in-depth and updated knowledge about the epidemiology of surgical site infections (SSIs) caused by Staphylococcus aureus to support the development of effective preventive interventions. The ASPIRE-SSI study aims primarily to determine the incidence of S. aureus SSIs and postoperative bloodstream infection...

Background The pressures exerted by the pandemic of COVID-19 pose an unprecedented demand on health care services. Hospitals become rapidly overwhelmed when patients requiring life-saving support outpace available capacities. We here describe methods used by a university hospital to forecast caseloads and time to peak incidence. Methods We develope...

Background The clinical progress of patients hospitalized due to COVID-19 is often associated with severe pneumonia which may require intensive care, invasive ventilation, or extracorporeal membrane oxygenation (ECMO). The length of intensive care and the duration of these supportive therapies are clinically relevant outcomes. From the statistical...

Background: Many trials are now underway to inform decision-makers on potential effects of treatments for COVID-19. To provide sufficient information for all involved decision-makers (clinicians, public health authorities, drug regulatory agencies) a multiplicity of endpoints must be considered. It is a challenge to generate detailed high quality e...

Background: Intensive care units represent one of the largest clinical cost centers in hospitals. Mechanical ventilation accounts for a significant share of this cost. There is a relative dearth of information quantifying the impact of ventilation on daily ICU cost. We thus determine daily costs of ICU care, incremental cost of mechanical ventilat...

Hospital-acquired infections (HAIs) are a common complication in inpatient care. We investigate the incentives to prevent HAIs under the German DRG-based reimbursement system. We analyze the relationship between resource use and reimbursements for HAI in 188,731 patient records from the University Medical Center Freiburg (2011-2014), comparing case...

Background Reported mortality of hospitalised Coronavirus Disease-2019 (COVID-19) patients varies substantially, particularly in critically ill patients. So far COVID-19 in-hospital mortality and modes of death under state of the art care have not been systematically studied. Methods This retrospective observational monocenter cohort study was pe...

Importance Carriage of Staphylococcus aureus is associated with S aureus infection. However, associations between S aureus carriage and the development of S aureus intensive care unit (ICU) pneumonia (SAIP) have not been quantified accurately, and interpretation of available data is hampered because of variations in definitions. Objective To quant...

The impact of mechanical ventilation on the daily costs of intensive care unit (ICU) care is largely unknown. We thus conducted a systematic search for studies measuring the daily costs of ICU stays for general populations of adults (age ≥18 years) and the added costs of mechanical ventilation. The relative increase in the daily costs was estimated...

Background: Although catheter-associated urinary tract infection (CA-UTI) is a major healthcare-related problem worldwide, there is a scarcity of current data from countries with high antimicrobial resistance rates. We aimed to determine the clinical outcomes of patients with CA-UTI compared to those of patients with other sources of complicated u...

Background: Pseudomonas aeruginosa-related pneumonia is an ongoing healthcare challenge. Estimating its financial burden is complicated by the time-dependent nature of the disease. Methods: Two hundred thirty-six cases of Pseudomonas aeruginosa-related pneumonia were recorded at a 2000 bed German teaching hospital between 2011 and 2014. Thirty-f...

In hospital epidemiology, logistic regression is a popular model to study risk factors of hospital‐acquired infections. One key issue in this analysis is how to incorporate the time dependency of acquiring an infection during the hospital stay. In the applied literature, researchers often simply adjust for the entire length of hospital stay, which...

Background: Antimicrobial stewardship interventions and programmes aim to ensure effective treatment while minimizing antimicrobial-associated harms including resistance. Practice in this vital area is undermined by the poor quality of research addressing both what specific antimicrobial use interventions are effective and how antimicrobial use im...

Background: Hospital-acquired infections have not only gained increasing attention clinically, but also methodologically, as a time-varying exposure. While methods to appropriately estimate extra length of stay (LOS) have been established and are increasingly used in the literature, proper estimation of cost figures has lagged behind. Methods: A...

A recent study reported increased mortality of heads in government. To avoid the time-dependent bias (also known as immortal-time bias), survival from last election was compared between election winners and runners-up. We claim that this data manipulation results in bias due to conditioning on future events; survival should be compared from first e...

The population attributable fraction (PAF) is a popular epidemiological measure for the burden of a harmful exposure within a population. It is often interpreted causally as the proportion of preventable cases after an elimination of exposure. Originally, the PAF was defined for cohort studies of fixed length with a baseline exposure or cross‐secti...

The population‐attributable fraction (PAF) quantifies the public health impact of a harmful exposure. Despite being a measure of significant importance, an estimand accommodating complicated time‐to‐event data is not clearly defined. We discuss current estimands of the PAF used to quantify the public health impact of an internal time‐dependent expo...

The public health impact of a harmful exposure can be quantified by the population‐attributable fraction (PAF). The PAF describes the attributable risk due to an exposure and is often interpreted as the proportion of preventable cases if the exposure was extinct. Difficulties in the definition and interpretation of the PAF arise when the exposure o...

Background: Length of stay evaluations are very common to determine the burden of nosocomial infections. However, there exist fundamentally different methods to quantify the prolonged length of stay associated with nosocomial infections. Previous methodological studies emphasized the need to account for the timing of infection in order to differen...

The population-attributable fraction (PAF) quantifies the public health impact of a harmful exposure. Despite being a measure of significant importance an estimand accommodating complicated time-to-event data is not clearly defined. We discuss current estimands of the PAF used to quantify the public health impact of an internal time-dependent expos...

The public health impact of a harmful exposure can be quantified by the population-attributable fraction (PAF). The PAF describes the attributable risk due to an exposure and is often interpreted as the proportion of preventable cases if the exposure could be extinct. Difficulties in the definition and interpretation of the PAF arise when the expos...

The population-attributable fraction (PAF) is a popular epidemiological measure for the burden of a harmful exposure within a population. It is often interpreted causally as proportion of preventable cases after an elimination of exposure. Originally, the PAF has been defined for cohort studies of fixed length with a baseline exposure or cross-sect...

Objective: To study the impact of duration of mechanical ventilation, hospitalization and multiple ventilation episodes on the development of pneumonia while accounting for extubation as a competing event. Design: A multicenter data base from a Spanish surveillance network was used to conduct a retrospective analysis of prospectively collected inte...

Background: The impact of valve surgery on outcomes of Staphylococcus aureus infective endocarditis (SAIE) remains controversial. We tested the hypothesis that early valve surgery (EVS) improves survival by using a novel approach that allows for inclusion of major confounders in a time-dependent way. Methods: EVS was defined as valve surgery wit...

The expected excess length‐of‐stay is an established concept to assess the health and economic impact of nosocomial, that is, hospital‐acquired infections such as ventilation‐acquired pneumonia in intensive care. Estimation must account for the timing of infection as in a multistate perspective, because common retrospective comparisons yield inflat...

Objective Competing risks are a necessary consideration when analyzing risk factors for nosocomial infections (NIs). In this article, we identify additional information that a competing risks analysis provides in a hospital setting. Furthermore, we improve on established methods for nested case-control designs to acquire this information. Methods...

Innovations are urgently required for clinical development of antibacterials against multidrug-resistant organisms. Therefore, a European, public-private working group (STAT-Net; part of Combatting Bacterial Resistance in Europe [COMBACTE]), has reviewed and tested several innovative trials designs and analytical methods for randomized clinical tri...

Objectives: We aim to examine the effect of early adequate treatment in comparison with inadequate or delayed treatment on being extubated or discharged alive over time, in patients with Pseudomonas aeruginosa-related ventilator-associated pneumonia. Design: Retrospective analyses of a prospective observational multicenter cohort study. Setting...

Objectives: To evaluate whether a hospital-wide infection control programme (ICP) is effective at reducing the burden of healthcare-associated infections (HAIs) and associated severe sepsis/septic shock or death (severe HAIs). Methods: Prospective, quasi-experimental study with two surveillance periods (09/2011-08/2012; 05/2013-08/2014). Startin...

Background In many studies the information of patients who are dying in the hospital is censored when examining the change in length of hospital stay (cLOS) due to hospital-acquired infections (HIs). While appropriate estimators of cLOS are available in literature, the existence of the bias due to censoring of deaths was neither mentioned nor discu...