• Bloodstream infections, antibiotic resistance and the practice of blood culture sampling in Germany: study design of a Thuringia-wide prospective population-based study (AlertsNet).

      Karch, André; Schmitz, Roland P; Rißner, Florian; Castell, Stefanie; Töpel, Sandra; Jakob, Matthias; Brunkhorst, Frank M; Mikolajczyk, Rafael T; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2015)
      Bloodstream infections are a major cause of death worldwide; blood culture (BC) sampling remains the most important tool for their diagnosis. Current data suggest that BC rates in German hospitals are considerably lower than recommended; this points to shortfalls in the application of microbiological analyses. Since early and appropriate BC diagnostics are associated with reduced case fatality rates and a shorter duration of antimicrobial therapy, a multicomponent study for the improvement of BC diagnostics was developed.
    • Care for MRSA carriers in the outpatient sector: a survey among MRSA carriers and physicians in two regions in Germany.

      Raupach-Rosin, Heike; Rübsamen, Nicole; Szkopek, Sebastian; Schmalz, Oliver; Karch, André; Mikolajczyk, Rafael; Castell, Stefanie; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2016)
      Little is known about the management of methicillin-resistant Staphylococcus aureus (MRSA) carriers in the German outpatient sector and about the impact of MRSA on their daily life. Reimbursement for MRSA related costs in the German outpatient sector is available since 2012, but its impact has not been studied yet. The aim of the study was to analyze the outpatient management of MRSA carriers from both, physicians' and MRSA carriers' perspective.
    • Cerebrospinal fluid tau levels are a marker for molecular subtype in sporadic Creutzfeldt-Jakob disease.

      Karch, André; Hermann, Peter; Ponto, Claudia; Schmitz, Matthias; Arora, Amandeep; Zafar, Saima; Llorens, Franc; Müller-Heine, Annika; Zerr, Inga; Helmholtz Centre for infection research, Inhoffenstr. 7, D-38124 Braunschweig, Germany. (2015-05)
      The molecular subtype of sporadic Creutzfeldt-Jakob disease (sCJD) is an important prognostic marker for patient survival. However, subtype determination is not possible during lifetime. Because the rate of disease progression is associated with the molecular subtype, this study aimed at investigating if total tau, a marker of neuronal death, allows premortem diagnosis of molecular subtype when codon 129 genotype is known. Two hundred ninety-six sCJD patients were tested for their cerebrospinal fluid total tau level at the time of diagnosis and were investigated for their sCJD subtype postmortem. There was a significant association between tau levels and the prion protein type in patients with codon 129 MM (p < 0.001), MV (p = 0.004), and VV (p = 0.001) genotype. Receiver operating characteristic analyses showed values of area under the curve of 0.76-0.80 for the different genotypes indicating a good diagnostic validity of the test. Total tau can be used as a diagnostic test for the assessment of prion protein type when codon 129 genotype is known. It provides valuable information for physicians and next of kin about the further course of disease.
    • Changes in incidence of anogenital warts diagnoses after the introduction of human papillomavirus vaccination in Germany-an ecologic study.

      Mikolajczyk, Rafael T; Kraut, Angela A; Horn, Johannes; Schulze-Rath, Renate; Garbe, Edeltraut; BIPS-Institute for Epidemiology and Prevention Research, Bremen, Germany. miko@bips.uni-bremen.de (2013-01)
      In a large health insurance database in Germany, incidence of anogenital warts among 15- to 19-year-old females decreased from 316/100,000 person-years in 2007 to 242 in 2008 (23% reduction, P = 0.0001). The decrease started between the first and second quarter of 2007 (human papillomavirus vaccination was introduced in March 2007).
    • Changes in risk perceptions during the 2014 Ebola virus disease epidemic: results of two consecutive surveys among the general population in Lower Saxony, Germany.

      Obenauer, Julie; Rübsamen, Nicole; Garsevanidze, Ekaterine; Karch, André; Mikolajczyk, Rafael T; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-05-15)
      The Ebola virus disease (EVD) outbreak 2014 received extensive news media coverage, which faded out before the outbreak ended. News media coverage impacts risk perception; it is, however, unclear if the components of risk perception (affective and cognitive responses) change differently over time. In an online panel, we asked participants (n = 1376) about EVD risk perceptions at the epidemic's peak (November 2014) and after news media coverage faded out (August 2015). We investigated worry (affective response), perceived likelihood of infection, perceived personal impact, and coping efficacy (dimensions of cognitive response), and knowledge about transmission. Differences between the surveys with respect to manifestations of affective and cognitive dimensions were tested using the Wilcoxon signed-rank test. The association between individual change in knowledge and worries about EVD in the first survey was investigated using linear regression. In November 2014, the survey was filled in by 974 participants. Ten months later, 662 of them were still members of the online panel and were invited to the follow-up survey. Among the 620 respondents, affective response decreased between the surveys. Knowledge about EVD also decreased; however, participants worried about EVD in 2014 had increased knowledge in 2015. Perceived likelihood of infection decreased over time, while perceived personal impact and coping efficacy did not. Risk communication appealing to cognitive reactions by informing clearly on the risk of infection in unaffected countries may decrease inappropriate behaviors.
    • Clustering of developmental delays in Bavarian preschool children - a repeated cross-sectional survey over a period of 12 years.

      Stich, Heribert L; Krämer, Alexander; Mikolajczyk, Rafael T (2014)
      While most children display a normal development, some children experience developmental delays compared to age specific development milestones assessed during school entry examination. Data exist on prevalence of delays in single areas, but there is lack of knowledge regarding the clustering patterns of developmental delays and their determinants.
    • Comorbidities in ADHD children treated with methylphenidate: a database study.

      Kraut, Angela A; Langner, Ingo; Lindemann, Christina; Banaschewski, Tobias; Petermann, Ulrike; Petermann, Franz; Mikolajczyk, Rafael T; Garbe, Edeltraut; Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany. (2013)
      Methylphenidate (MPH) is the most common drug treatment of attention deficit / hyperactivity disorder (ADHD) in children. Treatment with MPH is contraindicated in the presence of certain psychiatric, cerebro- and cardiovascular conditions. We assessed MPH treatment prevalence and incidence and the frequency of comorbid conditions related to these contraindications in new MPH users compared to a control group without ADHD and ADHD medication.
    • Comparison of response patterns in different survey designs: a longitudinal panel with mixed-mode and online-only design.

      Rübsamen, Nicole; Akmatov, Manas K; Castell, Stefanie; Karch, André; Mikolajczyk, Rafael; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017)
      Increasing availability of the Internet allows using only online data collection for more epidemiological studies. We compare response patterns in a population-based health survey using two survey designs: mixed-mode (choice between paper-and-pencil and online questionnaires) and online-only design (without choice).
    • Cost-effectiveness of human papillomavirus vaccination in Germany.

      Damm, Oliver; Horn, Johannes; Mikolajczyk, Rafael T; Kretzschmar, Mirjam E E; Kaufmann, Andreas M; Deleré, Yvonne; Ultsch, Bernhard; Wichmann, Ole; Krämer, Alexander; Greiner, Wolfgang; Hemholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017)
      The aim of this study was to assess the cost-effectiveness of human papillomavirus (HPV) vaccination in addition to the current cervical cancer screening programme in Germany using a dynamic transmission model.
    • Current and future effects of varicella and herpes zoster vaccination in Germany - Insights from a mathematical model in a country with universal varicella vaccination.

      Horn, Johannes; Karch, André; Damm, Oliver; Kretzschmar, Mirjam E; Siedler, Anette; Ultsch, Bernhard; Weidemann, Felix; Wichmann, Ole; Hengel, Hartmut; Greiner, Wolfgang; Mikolajczyk, Rafael T; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2016-07-02)
      Varicella zoster virus (VZV) is primarily known for causing varicella in childhood, but can reactivate again as herpes zoster (HZ) after a period of latency, mainly in persons older than 50 years. Universal varicella vaccination was introduced in Germany in 2004, while HZ vaccination has not been recommended yet. We aimed to quantify the potential long-term effects of universal childhood varicella vaccination and HZ vaccination of the elderly on varicella and HZ incidence in Germany over a time horizon of 100 years, using a transmission model calibrated to pre-vaccination data and validated against early post-vaccination data. Using current vaccination coverage rates of 87% (64%) with one (two) varicella vaccine dose(s), the model predicts a decrease in varicella cases by 89% for the year 2015. In the long run, the incidence reduction will stabilize at about 70%. Under the assumption of the boosting hypothesis of improved HZ protection caused by exposure to VZV, the model predicts a temporary increase in HZ incidence of up to 20% for around 50 years. HZ vaccination of the elderly with an assumed coverage of 20% has only limited effects in counteracting this temporary increase in HZ incidence. However, HZ incidence is shown to decrease in the long-term by 58% as vaccinated individuals get older and finally reach age-classes with originally high HZ incidence. Despite substantial uncertainties around several key variables, the model's results provide valuable insights that support decision-making regarding national VZV vaccination strategies.
    • Deciding on the mode of birth after a previous caesarean section - An online survey investigating women's preferences in Western Switzerland.

      Bonzon, Magali; Gross, Mechthild M; Karch, André; Grylka-Baeschlin, Susanne; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-04-21)
      promoting vaginal births after caesarean section (VBAC) for eligible women and increasing rates of successful VBACs are the best strategies to reduce the number of repeat caesarean sections (CS). Knowledge of factors that are associated with women's decision-making around mode of birth after CS is important when developing strategies to promote VBAC. This study assessed which factors are associated with women's preferences for VBAC versus elective repeat caesarean section (ERCS) in a new pregnancy after one previous caesarean in Switzerland.
    • Deficits in knowledge, attitude, and practice towards blood culture sampling: results of a nationwide mixed-methods study among inpatient care physicians in Germany.

      Raupach-Rosin, Heike; Duddeck, Arne; Gehrlich, Maike; Helmke, Charlotte; Huebner, Johannes; Pletz, Mathias W; Mikolajczyk, Rafael; Karch, André; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-02-15)
      Blood culture (BC) sampling rates in Germany are considerably lower than recommended. Aim of our study was to assess knowledge, attitudes, and practice of physicians in Germany regarding BC diagnostics.
    • Development and validation of a diagnostic model for early differentiation of sepsis and non-infectious SIRS in critically ill children - a data-driven approach using machine-learning algorithms.

      Lamping, Florian; Jack, Thomas; Rübsamen, Nicole; Sasse, Michael; Beerbaum, Philipp; Mikolajczyk, Rafael T; Boehne, Martin; Karch, André; HZI, Helmholtz Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig Germany. (BioMedCentral, 2018-03-15)
      BACKGROUND: Since early antimicrobial therapy is mandatory in septic patients, immediate diagnosis and distinction from non-infectious SIRS is essential but hampered by the similarity of symptoms between both entities. We aimed to develop a diagnostic model for differentiation of sepsis and non-infectious SIRS in critically ill children based on routinely available parameters (baseline characteristics, clinical/laboratory parameters, technical/medical support). METHODS: This is a secondary analysis of a randomized controlled trial conducted at a German tertiary-care pediatric intensive care unit (PICU). Two hundred thirty-eight cases of non-infectious SIRS and 58 cases of sepsis (as defined by IPSCC criteria) were included. We applied a Random Forest approach to identify the best set of predictors out of 44 variables measured at the day of onset of the disease. The developed diagnostic model was validated in a temporal split-sample approach. RESULTS: A model including four clinical (length of PICU stay until onset of non-infectious SIRS/sepsis, central line, core temperature, number of non-infectious SIRS/sepsis episodes prior to diagnosis) and four laboratory parameters (interleukin-6, platelet count, procalcitonin, CRP) was identified in the training dataset. Validation in the test dataset revealed an AUC of 0.78 (95% CI: 0.70-0.87). Our model was superior to previously proposed biomarkers such as CRP, interleukin-6, procalcitonin or a combination of CRP and procalcitonin (maximum AUC = 0.63; 95% CI: 0.52-0.74). When aiming at a complete identification of sepsis cases (100%; 95% CI: 87-100%), 28% (95% CI: 20-38%) of non-infectious SIRS cases were assorted correctly. CONCLUSIONS: Our approach allows early recognition of sepsis with an accuracy superior to previously described biomarkers, and could potentially reduce antibiotic use by 30% in non-infectious SIRS cases. External validation studies are necessary to confirm the generalizability of our approach across populations and treatment practices.
    • Diagnostic profiles of patients with late-onset Creutzfeldt-Jakob disease differ from those of younger Creutzfeldt-Jakob patients: a historical cohort study using data from the German National Reference Center.

      Karch, André; Raddatz, Lena Maria; Ponto, Claudia; Hermann, Peter; Summers, David; Zerr, Inga; Department of Neurology, National Reference Center for TSE, Clinical Dementia Center, University Medical School Göttingen, Göttingen, Germany, andre.karch@helmholtz-hzi.de. (2014-05)
      In contrast to other neurodegenerative diseases, sporadic Creutzfeldt-Jakob disease (sCJD) is rarely diagnosed in patients older than 75 years. Data describing the characteristics of sCJD in the very old are rare and inconclusive. Therefore, a historical cohort study was designed to evaluate clinical, cerebrospinal fluid (CSF), electroencephalography (EEG), and magnetic resonance imaging (MRI) features of this group. Patients older than 75 years identified via the German surveillance program from 2001 to 2012 (n = 73) were compared to a random subsample of sCJD patients younger than 75 (n = 73) from the same time period using an historical cohort design. Older patients showed a faster disease progression represented by an earlier point of diagnosis and a shorter survival time (p < 0.001). In the early stages of disease, older patients presented slightly more often with dementia (p = 0.127) or dysarthria (p = 0.238), whereas disorders of the extrapyramidal (p = 0.056) and visual system (p = 0.015) were more common in the younger group. Atypical MRI profiles such as MRI lesions restricted to one hemisphere (p < 0.001) or cortical lesions only (p = 0.258) were found more frequently in patients older than 75 years, whereas typical cortical and basal ganglia hyperintensities were more common in the younger group (p = 0.001). We demonstrated for the first time that patients with late-onset sCJD differ from younger sCJD patients with respect to MRI profiles and initial clinical presentation, but not among CSF markers. Misclassification of Creutzfeldt-Jakob disease cases in patients older than 75 years seems likely due to atypical clinical and radiological presentation. This might contribute to lower sCJD incidence rates in this age group.
    • Early versus Late Admission to Labor Affects Labor Progression and Risk of Cesarean Section in Nulliparous Women.

      Mikolajczyk, Rafael T; Zhang, Jun; Grewal, Jagteshwar; Chan, Linda C; Petersen, Antje; Gross, Mechthild M; Helmholtz Centre of infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2016)
      Rates of cesarean section increase worldwide, and the components of this increase are partially unknown. A strong role is prescribed to dystocia, and at the same time, the diagnosis of dystocia is highly subjective. Previous studies indicated that risk of cesarean is higher when women are admitted to the hospital early in the labor.
    • Ebola risk perception in Germany, 2014.

      Rübsamen, Nicole; Castell, Stefanie; Horn, Johannes; Karch, André; Ott, Jördis J; Raupach-Rosin, Heike; Zoch, Beate; Krause, Gérard; Mikolajczyk, Rafael; Helmholtz Centre for infection research, Inhoffenstr. 7, D-38124 Braunschweig, Germany. (2015-06)
      Ebola virus disease (EVD) outbreaks have occurred during the past 5 decades, but none has affected European countries like the 2014 epidemic in West Africa. We used an online questionnaire to investigate risk perceptions in Germany during this epidemic peak. Our questionnaire covered risk perceptions, knowledge about transmission routes, media use, reactions to the outbreak, attitudes toward measures to prevent the spread of EVD and vaccination against EVD, and willingness to volunteer for aid missions. Of 974 participants, 29% indicated that they worried about EVD, 4% correctly stated virus transmission routes, and 75% incorrectly rated airborne transmission and transmission by asymptomatic patients as possible. Many indicated that if a patient were flown to Germany for treatment in a nearby hospital, they would adapt preventive behavior. Although most participants were not worried about EVD at the current stage of the epidemic, misperceptions regarding transmission were common and could trigger inappropriate behavior changes.
    • Effect of beta-blocker therapy on the risk of infections and death after acute stroke--a historical cohort study.

      Maier, Ilko L; Karch, André; Mikolajczyk, Rafael; Bähr, Mathias; Liman, Jan; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2015)
      Infections are a frequent cause for prolonged hospitalization and increased mortality after stroke. Recent studies revealed a stroke-induced depression of the peripheral immune system associated with an increased susceptibility for infections. In a mice model for stroke, this immunosuppressive effect was reversible after beta-blocker administration. The aim of our study was to investigate the effect of beta-blocker therapy on the risk of infections and death after stroke in humans.
    • Effect of Disease Definition on Perceived Burden of Acute Respiratory Infections in Children: A Prospective Cohort Study Based on Symptom Diaries.

      Zoch, Beate; Günther, Annette; Karch, André; Mikolajczyk, Rafael; Helmholtz-Zentrum für Infektionsfrschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-10)
      Acute respiratory infections (ARIs) are among the most frequent childhood diseases in Western countries. Assessment of ARI episodes for research purposes is usually based on parent-administered retrospective questionnaires or prospective symptom diaries. The aim of our analysis was to compare the effect of ARI definitions on the corresponding disease burden in a prospective cohort study using symptom diaries.
    • Effects of pathogen dependency in a multi-pathogen infectious disease system including population level heterogeneity - a simulation study.

      Bakuli, Abhishek; Klawonn, Frank; Karch, André; Mikolajczyk, Rafael T; Helmholtz-Zentrum für Infektionsforschung, GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-12-13)
      Increased computational resources have made individual based models popular for modelling epidemics. They have the advantage of incorporating heterogeneous features, including realistic population structures (like e.g. households). Existing stochastic simulation studies of epidemics, however, have been developed mainly for incorporating single pathogen scenarios although the effect of different pathogens might directly or indirectly (e.g. via contact reductions) effect the spread of each pathogen. The goal of this work was to simulate a stochastic agent based system incorporating the effect of multiple pathogens, accounting for the household based transmission process and the dependency among pathogens.
    • Effects of Workflow Optimization in Endovascularly Treated Stroke Patients - A Pre-Post Effectiveness Study.

      Schregel, Katharina; Behme, Daniel; Tsogkas, Ioannis; Knauth, Michael; Maier, Ilko; Karch, André; Mikolajczyk, Rafael; Hinz, José; Liman, Jan; Psychogios, Marios-Nikos; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2016-01-01)
      Endovascular treatment of acute ischemic stroke has become standard of care for patients with large artery occlusion. Early restoration of blood flow is crucial for a good clinical outcome. We introduced an interdisciplinary standard operating procedure (SOP) between neuroradiologists, neurologists and anesthesiologists in order to streamline patient management. This study analyzes the effect of optimized workflow on periprocedural timings and its potential influence on clinical outcome. Data were extracted from a prospectively maintained university hospital stroke database. The standard operating procedure was established in February 2014. Of the 368 acute stroke patients undergoing endovascular treatment between 2008 and 2015, 278 patients were treated prior to and 90 after process optimization. Outcome measures were periprocedural time intervals and residual functional impairment. After implementation of the SOP, time from symptom onset to reperfusion was significantly reduced (median 264 min prior and 211 min after SOP-introduction (IQR 228-32 min and 161-278 min, respectively); P<0.001). Especially faster supply of imaging and prompt transfer of patients to the angiography suite contributed to this effect. Time between hospital admission and groin puncture was reduced by half after process optimization (median 64 min after versus 121 min prior to SOP-introduction (IQR 54-77 min and 96-161 min, respectively); P<0.001). Clinical outcome was significantly better after workflow optimization as measured with the modified Rankin Scale (common odds ratio (OR) 0.56; 95% CI 0.32-0.98; P = 0.038). Optimization of workflow and interdisciplinary teamwork significantly improved the outcome of patients with acute ischemic stroke due to a significant reduction of in-hospital examination, transportation, imaging and treatment times.