• 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 T; 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; et al. (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; et al. (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 T; 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, Gerard; Mikolajczyk, Rafael T; 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 T; 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 T; Hinz, José; Liman, Jan; Psychogios, Marios-Nikos; et al. (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.
    • Evaluating methods for intersectoral comparison of quality of care. A routine data analysis of elective percutaneous coronary interventions.

      Ohlmeier, C; Linder, R; Enders, D; Mikolajczyk, Rafael; Haverkamp, W; Horenkamp-Sonntag, D; Garbe, E; Leibniz Institute for Prevention Research and Epidemiology - BIPS, Achterstraße 30, 28359 Bremen, Germany. (2014)
      To compare the quality of care regarding the use of elective percutaneous coronary interventions (PCIs) in the inpatient and outpatient setting and to evaluate different methods of confounder control in this context.
    • Evaluation of pregnancy outcome records in the German Pharmacoepidemiological Research Database (GePaRD).

      Mikolajczyk, Rafael; Kraut, Aa; Garbe, E; Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany; Helmholtz Centre for Infection Research, Braunschweig, Germany; Medical School Hannover, Hannover, Germany. (2013-08)
      Routine health care data are a valuable source for the assessment of risks of drugs during pregnancy. Therefore, the aim of the current analysis was the evaluation of pregnancy outcome records in German health insurance data.
    • Evaluation of vaccination herd immunity effects for anogenital warts in a low coverage setting with human papillomavirus vaccine-an interrupted time series analysis from 2005 to 2010 using health insurance data.

      Thöne, Kathrin; Horn, Johannes; Mikolajczyk, Rafael T; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-08-14)
      Shortly after the human papillomavirus (HPV) vaccine recommendation and hence the reimbursement of vaccination costs for the respective age groups in Germany in 2007, changes in the incidence of anogenital warts (AGWs) were observed, but it was not clear at what level the incidence would stabilize and to what extent herd immunity would be present. Given the relatively low HPV vaccination coverage in Germany, we aimed to assess potential vaccination herd immunity effects in the German setting.
    • Factors associated with attrition in a longitudinal online study: results from the HaBIDS panel.

      Rübsamen, Nicole; Akmatov, Manas K; Castell, Stefanie; Karch, André; Mikolajczyk, Rafael T; Hemholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-08-31)
      Knowing about predictors of attrition in a panel is important to initiate early measures against loss of participants. We investigated attrition in both early and late phase of an online panel with special focus on preferences regarding mode of participation.
    • Feasibility of a birth cohort study dedicated to assessing acute infections using symptom diaries and parental collection of biomaterials.

      Zoch, Beate; Karch, André; Dreesman, Johannes; Monazahian, Masyar; Baillot, Armin; Mikolajczyk, Rafael; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2015)
      A birth cohort dedicated to studying infections in early childhood may be assisted by parental recording of symptoms on a daily basis and a collection of biomaterials. We aimed at testing the feasibility of this approach for use in a long-term study focusing on infections in children in Germany.
    • A feasibility trial to examine the social norms approach for the prevention and reduction of licit and illicit drug use in European University and college students

      Pischke, Claudia R; Zeeb, Hajo; van Hal, Guido; Vriesacker, Bart; McAlaney, John; Bewick, Bridgette M; Akvardar, Yildiz; Guillén-Grima, Francisco; Orosova, Olga; Salonna, Ferdinand; et al. (2012-10-18)
      Abstract Background Incorrect perceptions of high rates of peer alcohol and tobacco use are predictive of increased personal use in student populations. Correcting misperceptions by providing feedback has been shown to be an effective intervention for reducing licit drug use. It is currently unknown if social norms interventions are effective in preventing and reducing illicit drug use in European students. The purpose of this paper is to describe the design of a multi-site cluster controlled trial of a web-based social norms intervention aimed at reducing licit and preventing illicit drug use in European university students. Methods/Design An online questionnaire to assess rates of drug use will be developed and translated based on existing social norms surveys. Students from sixteen universities in seven participating European countries will be invited to complete the questionnaire. Both intervention and control sites will be chosen by convenience. In each country, the intervention site will be the university that the local principal investigator is affiliated with. We aim to recruit 1000 students per site (baseline assessment). All participants will complete the online questionnaire at baseline. Baseline data will be used to develop social norms messages that will be included in a web-based intervention. The intervention group will receive individualized social norms feedback. The website will remain online during the following 5 months. After five months, a second survey will be conducted and effects of the intervention on social norms and drug use will be measured in comparison to the control site. Discussion This project is the first cross-national European collaboration to investigate the feasibility of a social norms intervention to reduce licit and prevent illicit drug use among European university students. Final trial registration number DRKS00004375 on the ‘German Clinical Trials Register’.
    • A feasibility trial to examine the social norms approach for the prevention and reduction of licit and illicit drug use in European University and college students.

      Pischke, Claudia R; Zeeb, Hajo; van Hal, Guido; Vriesacker, Bart; McAlaney, John; Bewick, Bridgette M; Akvardar, Yildiz; Guillén-Grima, Francisco; Orosova, Olga; Salonna, Ferdinand; et al. (2012)
      Incorrect perceptions of high rates of peer alcohol and tobacco use are predictive of increased personal use in student populations. Correcting misperceptions by providing feedback has been shown to be an effective intervention for reducing licit drug use. It is currently unknown if social norms interventions are effective in preventing and reducing illicit drug use in European students. The purpose of this paper is to describe the design of a multi-site cluster controlled trial of a web-based social norms intervention aimed at reducing licit and preventing illicit drug use in European university students.