• Association between Embolic Stroke Patterns, ESUS Etiology, and New Diagnosis of Atrial Fibrillation: A Secondary Data Analysis of the Find-AF Trial.

      Maier, Ilko L; Schregel, Katharina; Karch, André; Weber-Krueger, Mark; Mikolajczyk, Rafael T; Stahrenberg, Raoul; Gröschel, Klaus; Bähr, Mathias; Knauth, Michael; Psychogios, Marios-Nikos; et al. (2017)
      Background. Atrial fibrillation (AF) is an important cause of embolic stroke of undetermined source (ESUS). Imaging-patterns like multiple infarcts, simultaneous involvement of different circulations, infarcts of different ages, and isolated cortical infarcts are likely to indicate cardioembolic stroke. The aim of our study was to evaluate the association between embolic stroke patterns, ESUS, and the new diagnosis of AF. Methods. Stroke etiology and imaging characteristics from patients included in the Find-AF study were obtained. Embolic stroke patterns in CT- or MR-imaging were correlated with the diagnosis of ESUS as well as the short- (on baseline ECG and during 7-day Holter) and long-term (12-month follow-up) diagnosis of AF. Results. From 281 patients included in the Find-AF study, 127 (45.2%) patients with ischemic lesions detected in CT or MRI were included. 26 (20.5%) of these patients had ESUS. At least one embolic stroke pattern was detected in 67 (52.7%) patients. Embolic stroke patterns were not associated with ESUS (OR 1.57, 0.65-3.79, p = 0.317), the short-term (OR 0.64, 0.26-1.58, p = 0.327) or long-term diagnosis of AF (OR 0.72, 0.31-1.68, p = 0.448). Conclusions. This secondary data analysis of the Find-AF study could not provide evidence for an association between embolic stroke patterns, ESUS, and the new diagnosis of AF.
    • 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.
    • The Risk of Hospitalizations with Injury Diagnoses in a Matched Cohort of Children and Adolescents with and without Attention Deficit/Hyperactivity Disorder in Germany: A Database Study.

      Lindemann, Christina; Langner, Ingo; Banaschewski, Tobias; Garbe, Edeltraut; Mikolajczyk, Rafael T; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr.7, 38124 Braunschweig, Germany. (2017)
      Attention deficit/hyperactivity disorder (ADHD) is a common neuropsychiatric disorder in children and adolescents worldwide, and children with ADHD have elevated risk of injuries. Our aim was to assess the risk of hospitalizations with injury diagnoses and their various subtypes in children and adolescents with newly diagnosed ADHD compared to those without ADHD, as well as to study sex effects on this risk in the setting of the German health care system.
    • ["I cannot kiss my wife"- An Analysis of Daily Experiences of MRSA-carriers].

      Raupach-Rosin, H; Klett-Tammen, C J; Schmalz, O; Karch, A; Castell, S; Mikolajczyk, Rafael T; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2016-12)
      Objectives: There are no data available on the quality of care after discharge from hospital and only limited data are available on the psychosocial effects of being an MRSA carrier within the German health system.Methods:Patients who tested positive for MRSA in the previous year were invited to take part in focus groups.Results:2 focus groups with a total of 9 MRSA-carriers were conducted. The level of knowledge about MRSA differed between participants. In some cases, lack of information led to uncertainty and inappropriate measures to counteract MRSA. Some participants restricted their social contacts, especially to children, in order to prevent transmission. Patients experienced stigmatization in the health care system more often in inpatient care than in the outpatient sector. Only in a few cases both eradication therapy and swabs for control purposes were carried out.Conclusions:Information about the appropriate treatment and management of MRSA should be made available to patients more easily; in particular, patients need to be informed that MRSA is no threat to healthy individuals. Despite the desire of MRSA-carriers to become MRSA negative, treatment and control of MRSA seem to have low priority in the ambulant health care sector in Germany.
    • Population-level impact, herd immunity, and elimination after human papillomavirus vaccination: a systematic review and meta-analysis of predictions from transmission-dynamic models.

      Brisson, Marc; Bénard, Élodie; Drolet, Mélanie; Bogaards, Johannes A; Baussano, Iacopo; Vänskä, Simopekka; Jit, Mark; Boily, Marie-Claude; Smith, Megan A; Berkhof, Johannes; et al. (2016-11)
      Modelling studies have been widely used to inform human papillomavirus (HPV) vaccination policy decisions; however, many models exist and it is not known whether they produce consistent predictions of population-level effectiveness and herd effects. We did a systematic review and meta-analysis of model predictions of the long-term population-level effectiveness of vaccination against HPV 16, 18, 6, and 11 infection in women and men, to examine the variability in predicted herd effects, incremental benefit of vaccinating boys, and potential for HPV-vaccine-type elimination.
    • Top 25 Global Causes of Disability-Adjusted Life-Years (DALYs) in Children Younger Than 5 Years, Both Sexes, 1990 and 2013

      The Global Burden of Disease Pediatrics Collaboration; Karch, André; et al.; Institute for Health Metrics and Evaluation, University of Washington, 2301 Fifth Ave, Ste 600, Seattle, WA 98121 (JAMA Network, 2016-10-25)
      mportance The literature focuses on mortality among children younger than 5 years. Comparable information on nonfatal health outcomes among these children and the fatal and nonfatal burden of diseases and injuries among older children and adolescents is scarce. Objective To determine levels and trends in the fatal and nonfatal burden of diseases and injuries among younger children (aged <5 years), older children (aged 5-9 years), and adolescents (aged 10-19 years) between 1990 and 2013 in 188 countries from the Global Burden of Disease (GBD) 2013 study. Evidence Review Data from vital registration, verbal autopsy studies, maternal and child death surveillance, and other sources covering 14 244 site-years (ie, years of cause of death data by geography) from 1980 through 2013 were used to estimate cause-specific mortality. Data from 35 620 epidemiological sources were used to estimate the prevalence of the diseases and sequelae in the GBD 2013 study. Cause-specific mortality for most causes was estimated using the Cause of Death Ensemble Model strategy. For some infectious diseases (eg, HIV infection/AIDS, measles, hepatitis B) where the disease process is complex or the cause of death data were insufficient or unavailable, we used natural history models. For most nonfatal health outcomes, DisMod-MR 2.0, a Bayesian metaregression tool, was used to meta-analyze the epidemiological data to generate prevalence estimates. Findings Of the 7.7 (95% uncertainty interval [UI], 7.4-8.1) million deaths among children and adolescents globally in 2013, 6.28 million occurred among younger children, 0.48 million among older children, and 0.97 million among adolescents. In 2013, the leading causes of death were lower respiratory tract infections among younger children (905 059 deaths; 95% UI, 810 304-998 125), diarrheal diseases among older children (38 325 deaths; 95% UI, 30 365-47 678), and road injuries among adolescents (115 186 deaths; 95% UI, 105 185-124 870). Iron deficiency anemia was the leading cause of years lived with disability among children and adolescents, affecting 619 (95% UI, 618-621) million in 2013. Large between-country variations exist in mortality from leading causes among children and adolescents. Countries with rapid declines in all-cause mortality between 1990 and 2013 also experienced large declines in most leading causes of death, whereas countries with the slowest declines had stagnant or increasing trends in the leading causes of death. In 2013, Nigeria had a 12% global share of deaths from lower respiratory tract infections and a 38% global share of deaths from malaria. India had 33% of the world’s deaths from neonatal encephalopathy. Half of the world’s diarrheal deaths among children and adolescents occurred in just 5 countries: India, Democratic Republic of the Congo, Pakistan, Nigeria, and Ethiopia. Conclusions and Relevance Understanding the levels and trends of the leading causes of death and disability among children and adolescents is critical to guide investment and inform policies. Monitoring these trends over time is also key to understanding where interventions are having an impact. Proven interventions exist to prevent or treat the leading causes of unnecessary death and disability among children and adolescents. The findings presented here show that these are underused and give guidance to policy makers in countries where more attention is needed.
    • Global, regional, national, and selected subnational levels of stillbirths, neonatal, infant, and under-5 mortality, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015.

      2016-10-08
      Established in 2000, Millennium Development Goal 4 (MDG4) catalysed extraordinary political, financial, and social commitments to reduce under-5 mortality by two-thirds between 1990 and 2015. At the country level, the pace of progress in improving child survival has varied markedly, highlighting a crucial need to further examine potential drivers of accelerated or slowed decreases in child mortality. The Global Burden of Disease 2015 Study (GBD 2015) provides an analytical framework to comprehensively assess these trends for under-5 mortality, age-specific and cause-specific mortality among children under 5 years, and stillbirths by geography over time.
    • Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015.

      GBD 2015 Mortality and Causes of Death Collaborators; Karch, André; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2016-10-08)
      Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.
    • Partial verification bias and incorporation bias affected accuracy estimates of diagnostic studies for biomarkers that were part of an existing composite gold standard.

      Karch, Annika; Koch, Armin; Zapf, Antonia; Zerr, Inga; Karch, André; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2016-10)
      To investigate how choice of gold standard biases estimates of sensitivity and specificity in studies reassessing the diagnostic accuracy of biomarkers that are already part of a lifetime composite gold standard (CGS).
    • 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.
    • 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.
    • Infection prevention at preschool age - What is reasonable? [Infektionsprävention im Kindergartenalter -Was ist sinnvoll?]

      Schlinkmann, K.M.; Raupach-Rosin, H.; Hübner, J., (2016-01)
      Akute respiratorische und gastrointestinale Infektionen stellen die am weitesten verbreiteten Infektionserkrankungen im Kindesalter dar und generieren hohe Kosten. Bezüglich des Immunsystems ist neben der Infektionsabwehr auch die Immuntoleranz zu beachten. Daraus ergibt sich die Frage nach einer Ausgestaltung der Infektionsprävention, bei der negative Effekte auf die Immuntoleranz vermieden werden. Eine Handreichung dazu bieten die Hygienehypothese und die „old friends“ Theorie, die die Unterschiede in der Rolle der Pathogene für die Entwicklung des Immunsystems mit der gemeinsamen Evolution erklärt. Daraus lassen sich Implikationen für die Infektionsprävention ableiten: Bezüglich der Mikroorganismen, die für die Ausbildung der Toleranz verantwortlich sind (sog. old friends, z.B. Mikroorganismen, die das Mikrobiom bilden), können sich übertriebene Hygienemaßnahmen negativ auswirken. Pathogene, die eine dauerhafte Immunität auslösen oder tödlich verlaufen können (sog. crowd infections, z.B. Masern) haben diese Rolle nicht – angesichts der Risiken sollte hier eine spezifische Prävention mittels Impfung erfolgen. Die meisten akuten respiratorischen und gastrointestinalen Infektionen fallen in eine weitere Gruppe ohne bleibende Immunantwort (z.B. Rhinovirusinfektionen), deren Rolle für die Immuntoleranz bisher unklar ist. Für diese Infektionen können unspezifische Präventionsmaßnahmen eingesetzt werden. Gesicherte Evidenz liegt für die Effektivität von Handhygiene sowie von Barriere- und Isolationsmaßnahmen zur Verhinderung der Infektionsübertragung vor. Hingegen gibt es für Maßnahmen zur Stärkung der Immunität keine oder bestenfalls kontroverse Evidenz. Der traditionelle Zusammenhang zwischen Kälte und Erkältung erscheint fraglich und daher auch die Bedeutsamkeit der entsprechenden Präventionsmaßnahmen. Unklar ist, in welchem Umfang einzelne Maßnahmen von Eltern eingesetzt werden, und ob die Exposition gegenüber den leichten akuten Infektionen doch immunologisch eine Rolle spielt. 2
    • Predictors of the patient-centered outcomes of surgical carpal tunnel release - a prospective cohort study.

      Conzen, Catharina; Conzen, Michael; Rübsamen, Nicole; Mikolajczyk, Rafael; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2016)
      Carpal tunnel syndrome (CTS) causes a substantial burden of disease in society. While CTS can be resolved by surgical carpal tunnel release, it still remains unclear as to what degree outcomes depend on patients' characteristics. This study assesses patient-centered outcomes after surgical carpal tunnel release in a large outpatient clinic in Germany.
    • Measuring inter-rater reliability for nominal data - which coefficients and confidence intervals are appropriate?

      Zapf, Antonia; Castell, Stefanie; Morawietz, Lars; Karch, André; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2016)
      Reliability of measurements is a prerequisite of medical research. For nominal data, Fleiss' kappa (in the following labelled as Fleiss' K) and Krippendorff's alpha provide the highest flexibility of the available reliability measures with respect to number of raters and categories. Our aim was to investigate which measures and which confidence intervals provide the best statistical properties for the assessment of inter-rater reliability in different situations.
    • 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 T; 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.
    • 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.
    • Alcohol Drinking in University Students Matters for Their Self-Rated Health Status: A Cross-sectional Study in Three European Countries.

      Mikolajczyk, Rafael T; Sebena, Rene; Warich, Julia; Naydenova, Vihra; Dudziak, Urszula; Orosova, Olga; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2016)
      Alcohol drinking was linked to self-rated health in different populations, but the observed association was inconsistent. We studied the association among university students across three European countries with different patterns of drinking.
    • Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.

      GBD 2015 Child Mortality Collaborators; Karch, A. (2016)
      Non-fatal outcomes of disease and injury increasingly detract from the ability of the world's population to live in full health, a trend largely attributable to an epidemiological transition in many countries from causes affecting children, to non-communicable diseases (NCDs) more common in adults. For the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015), we estimated the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.
    • Analysis of Practical Identifiability of a Viral Infection Model.

      Nguyen, Van Kinh; Klawonn, Frank; Mikolajczyk, Rafael; Hernandez-Vargas, Esteban Abelardo; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2016)
      Mathematical modelling approaches have granted a significant contribution to life sciences and beyond to understand experimental results. However, incomplete and inadequate assessments in parameter estimation practices hamper the parameter reliability, and consequently the insights that ultimately could arise from a mathematical model. To keep the diligent works in modelling biological systems from being mistrusted, potential sources of error must be acknowledged. Employing a popular mathematical model in viral infection research, existing means and practices in parameter estimation are exemplified. Numerical results show that poor experimental data is a main source that can lead to erroneous parameter estimates despite the use of innovative parameter estimation algorithms. Arbitrary choices of initial conditions as well as data asynchrony distort the parameter estimates but are often overlooked in modelling studies. This work stresses the existence of several sources of error buried in reports of modelling biological systems, voicing the need for assessing the sources of error, consolidating efforts in solving the immediate difficulties, and possibly reconsidering the use of mathematical modelling to quantify experimental data.
    • Association between rates of caesarean section and maternal and neonatal mortality in the 21st century: a worldwide population-based ecological study with longitudinal data.

      Ye, J; Zhang, J; Mikolajczyk, Rafael; Torloni, M R; Gülmezoglu, A M; Betran, A P; Helmholtz Centre for Infectoion Research; Inhoffenstr.7 38124 Braunschweig; Germany. (2015-08-24)
      Caesarean section was initially performed to save the lives of the mother and/or her baby. Caesarean section rates have risen substantially worldwide over the past decades. In this study, we set out to compile all available caesarean section rates worldwide at the country level, and to identify the appropriate caesarean section rate at the population level associated with the minimal maternal and neonatal mortality.