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  • Side effects and efficacy of renal sparing immunosuppression in pediatric liver transplantation-A single center matched cohort study.

    Leiskau, Christoph; Rajanayagam, Jeremy; Pfister, Eva-Doreen; Goldschmidt, Imeke; Junge, Norman; Karch, André; Lerch, Christian; Richter, Nicolas; Lehner, Frank; Schrem, Harald; Baumann, Ulrich; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Blackwell Publishing Inc., 2018-01-01)
    Immunosuppressive combination therapy with MMF can reduce CNI associated nephrotoxicity. We investigated effectiveness and safety of de novo MMF-tacrolimus based immunosuppression after pLTx. Patients after pLTx receiving immunosuppression with MMF/tacrolimus (MMF/TAC) were compared to retrospectively selected age- and diagnosis-matched patients with tacrolimus monotherapy (TAC) and cyclosporine/prednisolone therapy (CSA) (19 patients each, n = 57). Effectiveness, renal function and side effects were analyzed for 1 year after pLTx. Tacrolimus reduction in combination therapy (0.7 μg/L over the year) was lower than aspired (2 μg/L). Acute BPAR occurred equally in MMF/TAC and TAC groups (31.6% each), being slightly higher in CSA group (42.1%; OR = 1.5; 95% CI = 0.42-5.44; P = .5). GFR deteriorated comparably in all 3 groups (P < .01 each) without significant differences between the groups. Septicemia was detected significantly more often in MMF/TAC (73.6%) than in TAC (31.6%) (OR 4.17; 1.07-16.27; P = .04). EBV reactivation occurred more often in CSA patients (84.2%) than in MMF/TAC (47.4%; OR 5.16; 0.98-27.19; P = .05) and TAC patients (52.6%; OR 8.16; 1.48-44.89; P = .02) the same was true for other viral infections (47.4% (CSA) vs 15.8% (TAC); OR 4.21; 0.95-18.55; P = .05). Our study does not provide additional evidence for a benefit of initial use of MMF/TAC over TAC regarding renal function, but raises concerns regarding a potentially increased risk of serious infections under MMF/TAC compared to TAC monotherapy at equivalent renal outcome; our study is, however, limited by the minor CNI reduction in combination therapy.
  • Assessing the Concepts and Designs of 58 Mobile Apps for the Management of the 2014-2015 West Africa Ebola Outbreak: Systematic Review.

    Tom-Aba, Daniel; Nguku, Patrick Mboya; Arinze, Chinedu Chukwujekwu; Krause, Gerard; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (2018-10-29)
    The use of mobile phone information technology (IT) in the health sector has received much attention especially during the 2014-2015 Ebola virus disease (EVD) outbreak. mHealth can be attributed to a major improvement in EVD control, but there lacks an overview of what kinds of tools were available and used based on the functionalities they offer. We aimed to conduct a systematic review of mHealth tools in the context of the recent EVD outbreak to identify the most promising approaches and guide further mHealth developments for infectious disease control. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched for all reports on mHealth tools developed in the context of the 2014-2015 EVD outbreak published between January 1, 2014 and December 31, 2015 on Google Scholar, MEDLINE, CAB Abstracts (Global Health), POPLINE, and Web of Science in any language using the search strategy: ("outbreak" OR "epidemic") AND ("mobile phone" OR "smartphone" OR "smart phone" OR "mobile phone" OR "tablet" OR "mHealth") AND ("Ebola" OR "EVD" OR "VHF" OR "Ebola virus disease" OR "viral hemorrhagic fever") AND ("2014" OR "2015"). The relevant publications were selected by 2 independent reviewers who applied a standardized data extraction form on the tools' functionalities. We identified 1220 publications through the search strategy, of which 6.31% (77/1220) were original publications reporting on 58 specific mHealth tools in the context of the EVD outbreak. Of these, 62% (34/55) offered functionalities for surveillance, 22% (10/45) for case management, 18% (7/38) for contact tracing, and 6% (3/51) for laboratory data management. Only 3 tools, namely Community Care, Sense Ebola Followup, and Surveillance and Outbreak Response Management and Analysis System supported all four of these functionalities.
  • The Global Hepatitis B Virus Genotype Distribution Approximated from Available Genotyping Data.

    Velkov, Stoyan; Ott, Jördis J; Protzer, Ulrike; Michler, Thomas; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (2018-10-15)
    Hepatitis B virus (HBV) is divided into nine genotypes, A to I. Currently, it remains unclear how the individual genotypes contribute to the estimated 250 million chronic HBV infections. We performed a literature search on HBV genotyping data throughout the world. Over 900 publications were assessed and data were extracted from 213 records covering 125 countries. Using previously published HBV prevalence, and population data, we approximated the number of infections with each HBV genotype per country and the genotype distribution among global chronic HBV infections. We estimated that 96% of chronic HBV infections worldwide are caused by five of the nine genotypes: genotype C is most common (26%), followed by genotype D (22%), E (18%), A (17%) and B (14%). Genotypes F to I together cause less than 2% of global chronic HBV infections. Our work provides an up-to-date analysis of global HBV genotyping data and an initial approach to estimate how genotypes contribute to the global burden of chronic HBV infection. Results highlight the need to provide HBV cell culture and animal models that cover at least genotypes A to E and represent the vast majority of global HBV infections to test novel treatment strategies.
  • Optimized Management of Endovascular Treatment for Acute Ischemic Stroke.

    Schregel, Katharina; Behme, Daniel; Tsogkas, Ioannis; Knauth, Michael; Maier, Ilko; Karch, André; Mikolajczyk, Rafael; Bähr, Mathias; Schäper, Jörn; Hinz, José; Liman, Jan; Psychogios, Marios-Nikos; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (2018-01-18)
    This manuscript describes a streamlined protocol for the management of patients with acute ischemic stroke, which aims at the minimization of time from hospital admission to reperfusion. Rapid restoration of cerebral blood flow is essential for the outcomes of patients with acute ischemic stroke. Endovascular treatment (EVT) has become the standard of care to accomplish this in patients with acute stroke due to large vessel occlusion (LVO). To achieve reperfusion of ischemic brain regions as fast as possible, all in-hospital time delays have to be carefully avoided. Therefore, management of patients with acute ischemic stroke was optimized with an interdisciplinary standard operating procedure (SOP). Stroke neurologists, diagnostic as well as interventional neuroradiologists, and anesthesiologists streamlined all necessary processes from patient admission and diagnosis to EVT of eligible patients. Target times for every step were established. Actually achieved times were prospectively recorded along with clinical data and imaging scores for all endovascularly treated stroke patients. These data were regularly analyzed and discussed in interdisciplinary team meetings. Potential issues were evaluated and all staff involved was trained to adhere to the SOP. This streamlined patient management approach and enhanced interdisciplinary collaboration reduced time from patient admission to reperfusion significantly and was accompanied by a beneficial effect on clinical outcomes.
  • Interactive Feedback of Data Quality in Clinical Research. A Case Study from an Infectious Diseases Cohort.

    Glöckner, Stephan; Schindler, Daniela; Karch, André; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (2018-01-01)
    To improve data quality, clinical cohort studies require ongoing centralized data monitoring. Results of data quality monitoring are often reported in a general format, without individual feedback for different types of users within the research consortium. Several R packages provide the possibility for an easy to use approach to analyze and communicate information in interactive web-based forms. This article describes a pilot, which is applied in a German infectious disease cohort using interactive feedback and gamification to report data quality, to ultimately increase the quality of research outcomes.
  • Pathogenic functions of host microbiota.

    Rath, Silke; Rud, Tatjana; Karch, André; Pieper, Dietmar Helmut; Vital, Marius; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (2018-09-28)
    It is becoming evident that certain features of human microbiota, encoded by distinct autochthonous taxa, promote disease. As a result, borders between the so-called opportunistic pathogens, pathobionts, and commensals are increasingly blurred, and specific targets for manipulating microbiota to improve host health are becoming elusive. In this study, we focus on the functions of host bacterial communities that have the potential to cause disease, proposing the term "pathogenic function (pathofunction)". The concept is presented via three distinct examples, namely, the formation of (i) trimethylamine, (ii) secondary bile acids, and (iii) hydrogen sulfide, which represent metabolites of the gut microbiota linked to the development of non-communicable diseases. Using publicly available metagenomic and metatranscriptomic data (n = 2975), we quantified those pathofunctions in health and disease and exposed the key players. Pathofunctions were ubiquitously present with increased abundances in patient groups. Overall, the three pathofunctions were detected at low mean concentrations (< 1% of total bacteria carried respective genes) and encompassed various taxa, including uncultured members. We outline how this function-centric approach, where all members of a community exhibiting a particular pathofunction are redundant, can contribute to risk assessment and the development of precision treatment directing gut microbiota to increase host health.
  • Immune monitoring after pediatric liver transplantation - the prospective ChilSFree cohort study.

    Goldschmidt, Imeke; Karch, André; Mikolajczyk, Rafael; Mutschler, Frauke; Junge, Norman; Pfister, Eva Doreen; Möhring, Tamara; d'Antiga, Lorenzo; McKiernan, Patrick; Kelly, Deirdre; Debray, Dominique; McLin, Valérie; Pawlowska, Joanna; Hierro, Loreto; Daemen, Kerstin; Keil, Jana; Falk, Christine; Baumann, Ulrich; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-05-16)
    Although trough levels of immunosuppressive drugs are largely used to monitor immunosuppressive therapy after solid organ transplantation, there is still no established tool that allows for a validated assessment of functional degree of immunosuppression or the identification of clinically relevant over- or under-immunosuppression, depending on graft homeostasis. Reliable non-invasive markers to predict biopsy proven acute rejection (BPAR) do not exist. Literature data suggest that longitudinal measurements of immune markers might be predictive of BPAR, but data in children are scarce. We therefore propose an observational prospective cohort study focusing on immune monitoring in children after liver transplantation. We aim to describe immune function in a cohort of children before and during the first year after liver transplantation and plan to investigate how the immune function profile is associated with clinical and laboratory findings. In an international multicenter prospective approach, children with end-stage liver disease who undergo liver transplantation are enrolled to the study and receive extensive immune monitoring before and at 1, 2, 3, 4 weeks and 3, 6, 12 months after transplantation, and whenever a clinically indicated liver biopsy is scheduled. Blood samples are analyzed for immune cell numbers and circulating levels of cytokines, chemokines and factors of angiogenesis reflecting immune cell activation. Statistical analysis will focus on the identification of trajectorial patterns of immune reactivity predictive for systemic non-inflammatory states, infectious complications or BPAR using joint modelling approaches. The ChilSFree study will help to understand the immune response after pLTx in different states of infection or rejection. It may provide insight into response mechanisms eventually facilitating immune tolerance towards the graft. Our analysis may yield an applicable immune panel for non-invasive early detection of acute cellular rejection, with the prospect of individually tailoring immunosuppressive therapy. The international collaborative set-up of this study allows for an appropriate sample size which is otherwise difficult to achieve in the field of pediatric liver transplantation.
  • Survival of children after liver transplantation for hepatocellular carcinoma.

    Baumann, Ulrich; Adam, René; Duvoux, Christophe; Mikolajczyk, Rafael; Karam, Vincent; D'Antiga, Lorenzo; Chardot, Christophe; Coker, Ahmet; Colledan, Michele; Ericzon, Bo-Goran; Line, Pål Dag; Hadzic, Nedim; Isoniemi, Helena; Klempnauer, Jürgen L; Reding, Raymond; McKiernan, Patrick J; McLin, Valérie; Paul, Andreas; Salizzoni, Mauro; Furtado, Emanuel San Bento; Schneeberger, Stefan; Karch, André; the European Liver and Intestine Transplant Association; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-01-01)
    Hepatocellular carcinoma (HCC) in childhood differs from adult HCC because it is often associated with inherited liver disease. It is, however, unclear whether liver transplantation (LT) for HCC in childhood with or without associated inherited disease has a comparable outcome to adult HCC. On the basis of data from the European Liver Transplant Registry (ELTR), we aimed to investigate if there are differences in patient and graft survival after LT for HCC between children and adults and between patients with underlying inherited versus noninherited liver disease, respectively. We included all 175 children who underwent LT for HCC and were enrolled in ELTR between 1985 and 2012. Of these, 38 had an associated inherited liver disease. Adult HCC patients with (n = 79) and without (n = 316, matched by age, sex, and LT date) inherited liver disease served as an adult comparison population. We used multivariable piecewise Cox regression models with shared frailty terms (for LT center) to compare patient and graft survival between the different HCC groups. Survival analyses demonstrated a superior longterm survival of children with inherited liver disease when compared with children with HCC without inherited liver disease (hazard ratio [HR], 0.29; 95% CI, 0.10-0.90; P = 0.03) and adults with HCC with inherited liver disease (HR, 0.27; 95% CI, 0.06-1.25; P = 0.09). There was no survival difference between adults with and without inherited disease (HR, 1.05; 95% CI, 0.66-1.66; P = 0.84). In conclusion, the potential survival advantage of children with an HCC based on inherited disease should be acknowledged when considering transplantation and prioritization for these patients. Further prospective studies accounting for tumor size and extension at LT are necessary to fully interpret our findings. Liver Transplantation 24 246-255 2018 AASLD.
  • Development of a Bead-Based Multiplex Assay for the Analysis of the Serological Response against the Six Pathogens HAV, HBV, HCV, CMV, T. gondii, and H. pylori.

    Filomena, Angela; Pessler, Frank; Akmatov, Manas K; Krause, Gérard; Duffy, Darragh; Gärtner, Barbara; Gerhard, Markus; Albert, Matthew L; Joos, Thomas O; Schneiderhan-Marra, Nicole; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-10-30)
    The spread of infectious diseases and vaccination history are common subjects of epidemiological and immunological research studies. Multiplexed serological assays are useful tools for assessing both current and previous infections as well as vaccination efficacy. We developed a serological multi-pathogen assay for hepatitis A, B and C virus, cytomegalovirus (CMV),
  • Global, regional, and national levels and causes of maternal mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

    Kassebaum, Nicholas J; Bertozzi-Villa, Amelia; Coggeshall, Megan S; Shackelford, Katya A; Steiner, Caitlyn; Heuton, Kyle R; Gonzalez-Medina, Diego; Barber, Ryan; Huynh, Chantal; Dicker, Daniel; Templin, Tara; Wolock, Timothy M; Ozgoren, Ayse Abbasoglu; Abd-Allah, Foad; Abera, Semaw Ferede; Abubakar, Ibrahim; Achoki, Tom; Adelekan, Ademola; Ademi, Zanfina; Adou, Arsène Kouablan; Adsuar, José C; Agardh, Emilie E; Akena, Dickens; Alasfoor, Deena; Alemu, Zewdie Aderaw; Alfonso-Cristancho, Rafael; Alhabib, Samia; Ali, Raghib; Al Kahbouri, Mazin J; Alla, François; Allen, Peter J; AlMazroa, Mohammad A; Alsharif, Ubai; Alvarez, Elena; Alvis-Guzmán, Nelson; Amankwaa, Adansi A; Amare, Azmeraw T; Amini, Hassan; Ammar, Walid; Antonio, Carl A T; Anwari, Palwasha; Arnlöv, Johan; Arsenijevic, Valentina S Arsic; Artaman, Ali; Asad, Majed Masoud; Asghar, Rana J; Assadi, Reza; Atkins, Lydia S; Badawi, Alaa; Balakrishnan, Kalpana; Basu, Arindam; Basu, Sanjay; Beardsley, Justin; Bedi, Neeraj; Bekele, Tolesa; Bell, Michelle L; Bernabe, Eduardo; Beyene, Tariku J; Bhutta, Zulfiqar; Bin Abdulhak, Aref; Blore, Jed D; Basara, Berrak Bora; Bose, Dipan; Breitborde, Nicholas; Cárdenas, Rosario; Castañeda-Orjuela, Carlos A; Castro, Ruben Estanislao; Catalá-López, Ferrán; Cavlin, Alanur; Chang, Jung-Chen; Che, Xuan; Christophi, Costas A; Chugh, Sumeet S; Cirillo, Massimo; Colquhoun, Samantha M; Cooper, Leslie Trumbull; Cooper, Cyrus; da Costa Leite, Iuri; Dandona, Lalit; Dandona, Rakhi; Davis, Adrian; Dayama, Anand; Degenhardt, Louisa; De Leo, Diego; del Pozo-Cruz, Borja; Deribe, Kebede; Dessalegn, Muluken; deVeber, Gabrielle A; Dharmaratne, Samath D; Dilmen, Uğur; Ding, Eric L; Dorrington, Rob E; Driscoll, Tim R; Ermakov, Sergei Petrovich; Esteghamati, Alireza; Faraon, Emerito Jose A; Farzadfar, Farshad; Felicio, Manuela Mendonca; Fereshtehnejad, Seyed-Mohammad; de Lima, Graça Maria Ferreira; Forouzanfar, Mohammad H; França, Elisabeth B; Gaffikin, Lynne; Gambashidze, Ketevan; Gankpé, Fortuné Gbètoho; Garcia, Ana C; Geleijnse, Johanna M; Gibney, Katherine B; Giroud, Maurice; Glaser, Elizabeth L; Goginashvili, Ketevan; Gona, Philimon; González-Castell, Dinorah; Goto, Atsushi; Gouda, Hebe N; Gugnani, Harish Chander; Gupta, Rahul; Gupta, Rajeev; Hafezi-Nejad, Nima; Hamadeh, Randah Ribhi; Hammami, Mouhanad; Hankey, Graeme J; Harb, Hilda L; Havmoeller, Rasmus; Hay, Simon I; Pi, Ileana B Heredia; Hoek, Hans W; Hosgood, H Dean; Hoy, Damian G; Husseini, Abdullatif; Idrisov, Bulat T; Innos, Kaire; Inoue, Manami; Jacobsen, Kathryn H; Jahangir, Eiman; Jee, Sun Ha; Jensen, Paul N; Jha, Vivekanand; Jiang, Guohong; Jonas, Jost B; Juel, Knud; Kabagambe, Edmond Kato; Kan, Haidong; Karam, Nadim E; Karch, André; Karema, Corine Kakizi; Kaul, Anil; Kawakami, Norito; Kazanjan, Konstantin; Kazi, Dhruv S; Kemp, Andrew H; Kengne, Andre Pascal; Kereselidze, Maia; Khader, Yousef Saleh; Khalifa, Shams Eldin Ali Hassan; Khan, Ejaz Ahmed; Khang, Young-Ho; Knibbs, Luke; Kokubo, Yoshihiro; Kosen, Soewarta; Defo, Barthelemy Kuate; Kulkarni, Chanda; Kulkarni, Veena S; Kumar, G Anil; Kumar, Kaushalendra; Kumar, Ravi B; Kwan, Gene; Lai, Taavi; Lalloo, Ratilal; Lam, Hilton; Lansingh, Van C; Larsson, Anders; Lee, Jong-Tae; Leigh, James; Leinsalu, Mall; Leung, Ricky; Li, Xiaohong; Li, Yichong; Li, Yongmei; Liang, Juan; Liang, Xiaofeng; Lim, Stephen S; Lin, Hsien-Ho; Lipshultz, Steven E; Liu, Shiwei; Liu, Yang; Lloyd, Belinda K; London, Stephanie J; Lotufo, Paulo A; Ma, Jixiang; Ma, Stefan; Machado, Vasco Manuel Pedro; Mainoo, Nana Kwaku; Majdan, Marek; Mapoma, Christopher Chabila; Marcenes, Wagner; Marzan, Melvin Barrientos; Mason-Jones, Amanda J; Mehndiratta, Man Mohan; Mejia-Rodriguez, Fabiola; Memish, Ziad A; Mendoza, Walter; Miller, Ted R; Mills, Edward J; Mokdad, Ali H; Mola, Glen Liddell; Monasta, Lorenzo; de la Cruz Monis, Jonathan; Hernandez, Julio Cesar Montañez; Moore, Ami R; Moradi-Lakeh, Maziar; Mori, Rintaro; Mueller, Ulrich O; Mukaigawara, Mitsuru; Naheed, Aliya; Naidoo, Kovin S; Nand, Devina; Nangia, Vinay; Nash, Denis; Nejjari, Chakib; Nelson, Robert G; Neupane, Sudan Prasad; Newton, Charles R; Ng, Marie; Nieuwenhuijsen, Mark J; Nisar, Muhammad Imran; Nolte, Sandra; Norheim, Ole F; Nyakarahuka, Luke; Oh, In-Hwan; Ohkubo, Takayoshi; Olusanya, Bolajoko O; Omer, Saad B; Opio, John Nelson; Orisakwe, Orish Ebere; Pandian, Jeyaraj D; Papachristou, Christina; Park, Jae-Hyun; Caicedo, Angel J Paternina; Patten, Scott B; Paul, Vinod K; Pavlin, Boris Igor; Pearce, Neil; Pereira, David M; Pesudovs, Konrad; Petzold, Max; Poenaru, Dan; Polanczyk, Guilherme V; Polinder, Suzanne; Pope, Dan; Pourmalek, Farshad; Qato, Dima; Quistberg, D Alex; Rafay, Anwar; Rahimi, Kazem; Rahimi-Movaghar, Vafa; ur Rahman, Sajjad; Raju, Murugesan; Rana, Saleem M; Refaat, Amany; Ronfani, Luca; Roy, Nobhojit; Pimienta, Tania Georgina Sánchez; Sahraian, Mohammad Ali; Salomon, Joshua A; Sampson, Uchechukwu; Santos, Itamar S; Sawhney, Monika; Sayinzoga, Felix; Schneider, Ione J C; Schumacher, Austin; Schwebel, David C; Seedat, Soraya; Sepanlou, Sadaf G; Servan-Mori, Edson E; Shakh-Nazarova, Marina; Sheikhbahaei, Sara; Shibuya, Kenji; Shin, Hwashin Hyun; Shiue, Ivy; Sigfusdottir, Inga Dora; Silberberg, Donald H; Silva, Andrea P; Singh, Jasvinder A; Skirbekk, Vegard; Sliwa, Karen; Soshnikov, Sergey S; Sposato, Luciano A; Sreeramareddy, Chandrashekhar T; Stroumpoulis, Konstantinos; Sturua, Lela; Sykes, Bryan L; Tabb, Karen M; Talongwa, Roberto Tchio; Tan, Feng; Teixeira, Carolina Maria; Tenkorang, Eric Yeboah; Terkawi, Abdullah Sulieman; Thorne-Lyman, Andrew L; Tirschwell, David L; Towbin, Jeffrey A; Tran, Bach X; Tsilimbaris, Miltiadis; Uchendu, Uche S; Ukwaja, Kingsley N; Undurraga, Eduardo A; Uzun, Selen Begüm; Vallely, Andrew J; van Gool, Coen H; Vasankari, Tommi J; Vavilala, Monica S; Venketasubramanian, N; Villalpando, Salvador; Violante, Francesco S; Vlassov, Vasiliy Victorovich; Vos, Theo; Waller, Stephen; Wang, Haidong; Wang, Linhong; Wang, XiaoRong; Wang, Yanping; Weichenthal, Scott; Weiderpass, Elisabete; Weintraub, Robert G; Westerman, Ronny; Wilkinson, James D; Woldeyohannes, Solomon Meseret; Wong, John Q; Wordofa, Muluemebet Abera; Xu, Gelin; Yang, Yang C; Yano, Yuichiro; Yentur, Gokalp Kadri; Yip, Paul; Yonemoto, Naohiro; Yoon, Seok-Jun; Younis, Mustafa Z; Yu, Chuanhua; Jin, Kim Yun; El Sayed Zaki, Maysaa; Zhao, Yong; Zheng, Yingfeng; Zhou, Maigeng; Zhu, Jun; Zou, Xiao Nong; Lopez, Alan D; Naghavi, Mohsen; Murray, Christopher J L; Lozano, Rafael (2014-09-13)
    The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100,000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery. We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values. 292,982 (95% UI 261,017-327,792) maternal deaths occurred in 2013, compared with 376,034 (343,483-407,574) in 1990. The global annual rate of change in the MMR was -0·3% (-1·1 to 0·6) from 1990 to 2003, and -2·7% (-3·9 to -1·5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0·4% (0·2-0·6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956·8 (685·1-1262·8) in South Sudan to 2·4 (1·6-3·6) in Iceland. Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa.
  • Cerebrospinal Fluid Total Prion Protein in the Spectrum of Prion Diseases.

    Villar-Piqué, Anna; Schmitz, Matthias; Lachmann, Ingolf; Karch, André; Calero, Olga; Stehmann, Christiane; Sarros, Shannon; Ladogana, Anna; Poleggi, Anna; Santana, Isabel; Ferrer, Isidre; Mitrova, Eva; Žáková, Dana; Pocchiari, Maurizio; Baldeiras, Inês; Calero, Miguel; Collins, Steven J; Geschwind, Michael D; Sánchez-Valle, Raquel; Zerr, Inga; Llorens, Franc; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-07-30)
    Cerebrospinal fluid (CSF) total prion protein (t-PrP) is decreased in sporadic Creutzfeldt-Jakob disease (sCJD). However, data on the comparative signatures of t-PrP across the spectrum of prion diseases, longitudinal changes during disease progression, and levels in pre-clinical cases are scarce. T-PrP was quantified in neurological diseases (ND, n = 147) and in prion diseases from different aetiologies including sporadic (sCJD, n = 193), iatrogenic (iCJD, n = 12) and genetic (n = 209) forms. T-PrP was also measured in serial lumbar punctures obtained from sCJD cases at different symptomatic disease stages, and in asymptomatic prion protein gene (PRNP) mutation carriers. Compared to ND, t-PrP concentrations were significantly decreased in sCJD, iCJD and in genetic prion diseases associated with the three most common mutations E200K, V210I (associated with genetic CJD) and D178N-129M (associated with fatal familial insomnia). In contrast, t-PrP concentrations in P102L mutants (associated with the Gerstmann-Sträussler-Scheinker syndrome) remained unaltered. In serial lumbar punctures obtained at different disease stages of sCJD patients, t-PrP concentrations inversely correlated with disease progression. Decreased mean t-PrP values were detected in asymptomatic D178-129M mutant carriers, but not in E200K and P102L carriers. The presence of low CSF t-PrP is common to all types of prion diseases regardless of their aetiology albeit with mutation-specific exceptions in a minority of genetic cases. In some genetic prion disease, decreased levels are already detected at pre-clinical stages and diminish in parallel with disease progression. Our data indicate that CSF t-PrP concentrations may have a role as a pre-clinical or early symptomatic diagnostic biomarker in prion diseases as well as in the evaluation of therapeutic interventions.
  • 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.
  • Antibiotic use on paediatric inpatients in a teaching hospital in the Gambia, a retrospective study.

    Chaw, Pa Saidou; Schlinkmann, Kristin Maria; Raupach-Rosin, Heike; Karch, André; Pletz, Mathias W; Huebner, Johannes; Nyan, Ousman; Mikolajczyk, Rafael; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-01-01)
    Antibiotics are useful but increasing resistance is a major problem. Our objectives were to assess antibiotic use and microbiology testing in hospitalized children in the Gambia. We conducted a retrospective analysis of paediatric inpatient data at The Edward Francis Small Teaching Hospital in Banjul, The Gambia. We extracted relevant data from the admission folders of all patients (aged > 28 days to 15 years) admitted in 2015 (January-December), who received at least one antibiotic for 24 h. We also reviewed the microbiology laboratory record book to obtain separate data for the bacterial isolates and resistance test results of all the paediatric inpatients during the study period. Over half of the admitted patients received at least one antibiotic during admission (496/917) with a total consumption of 670.7 Days of Antibiotic Therapy/1000 Patient-Days. The clinical diagnoses included an infectious disease for 398/496, 80.2% of the patients on antibiotics, pneumonia being the most common (184/496, 37.1%). There were 51 clinically relevant bacterial isolates, More than half of the admitted patients received antibiotics. The reported antibiotic resistance was highest to the most commonly used antibiotics such as ampicillin. Efforts to maximize definitive antibiotic indication such as microbiological testing prior to start of antibiotics should be encouraged where possible for a more rational antibiotic use.
  • 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.
  • Adolescent health in the Eastern Mediterranean Region: findings from the global burden of disease 2015 study.

    Karch, Andre; GBD 2015 Eastern Mediterranean Region Adolescent Health Collaborators.; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-05-01)
    The 22 countries of the East Mediterranean Region (EMR) have large populations of adolescents aged 10-24 years. These adolescents are central to assuring the health, development, and peace of this region. We described their health needs. Using data from the Global Burden of Disease Study 2015 (GBD 2015), we report the leading causes of mortality and morbidity for adolescents in the EMR from 1990 to 2015. We also report the prevalence of key health risk behaviors and determinants. Communicable diseases and the health consequences of natural disasters reduced substantially between 1990 and 2015. However, these gains have largely been offset by the health impacts of war and the emergence of non-communicable diseases (including mental health disorders), unintentional injury, and self-harm. Tobacco smoking and high body mass were common health risks amongst adolescents. Additionally, many EMR countries had high rates of adolescent pregnancy and unmet need for contraception. Even with the return of peace and security, adolescents will have a persisting poor health profile that will pose a barrier to socioeconomic growth and development of the EMR.
  • Global, regional, and national burden of neurological disorders during 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.

    GBD 2015 Neurological Disorders Collaborator Group.; Karch, André; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-11-01)
    BACKGROUND: Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level. METHODS: We estimated global and country-specific prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for various neurological disorders that in the GBD classification have been previously spread across multiple disease groupings. The more inclusive grouping of neurological disorders included stroke, meningitis, encephalitis, tetanus, Alzheimer's disease and other dementias, Parkinson's disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, medication overuse headache, brain and nervous system cancers, and a residual category of other neurological disorders. We also analysed results based on the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility, to identify patterns associated with development and how countries fare against expected outcomes relative to their level of development. FINDINGS: Neurological disorders ranked as the leading cause group of DALYs in 2015 (250·7 [95% uncertainty interval (UI) 229·1 to 274·7] million, comprising 10·2% of global DALYs) and the second-leading cause group of deaths (9·4 [9·1 to 9·7] million], comprising 16·8% of global deaths). The most prevalent neurological disorders were tension-type headache (1505·9 [UI 1337·3 to 1681·6 million cases]), migraine (958·8 [872·1 to 1055·6] million), medication overuse headache (58·5 [50·8 to 67·4 million]), and Alzheimer's disease and other dementias (46·0 [40·2 to 52·7 million]). Between 1990 and 2015, the number of deaths from neurological disorders increased by 36·7%, and the number of DALYs by 7·4%. These increases occurred despite decreases in age-standardised rates of death and DALYs of 26·1% and 29·7%, respectively; stroke and communicable neurological disorders were responsible for most of these decreases. Communicable neurological disorders were the largest cause of DALYs in countries with low SDI. Stroke rates were highest at middle levels of SDI and lowest at the highest SDI. Most of the changes in DALY rates of neurological disorders with development were driven by changes in YLLs. INTERPRETATION: Neurological disorders are an important cause of disability and death worldwide. Globally, the burden of neurological disorders has increased substantially over the past 25 years because of expanding population numbers and ageing, despite substantial decreases in mortality rates from stroke and communicable neurological disorders. The number of patients who will need care by clinicians with expertise in neurological conditions will continue to grow in coming decades. Policy makers and health-care providers should be aware of these trends to provide adequate services.
  • Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970-2016: a systematic analysis for the Global Burden of Disease Study 2016.

    GBD 2016 Mortality Collaborators.; Karch, André; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-09-16)
  • Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.

    GBD 2016 Disease and Injury Incidence and Prevalence Collaborators.; Karch, André; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-09-16)

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