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1. CDC Yellow Book 2020

Author: (CDC), Centers for Disease Control and..., primary
Published: 2019
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2. Biomarker A plus T-: is this Alzheimer's disease or not? A combined CSF and pathology study

Author: Alzheimer’s Disease Neuroimaging Initiative, Vromen, Eleonora M, de Boer, Sterre C M, Teunissen, Charlotte E, Rozemuller, Annemieke, Sieben, Anne, Bjerke, Maria, Visser, Pieter Jelle, Bouwman, Femke H, Engelborghs, Sebastiaan, Tijms, Betty M, Clinical Biology, Clinical sciences, Neuroprotection & Neuromodulation, and Neurology
Subjects: autopsy, Neuroscience(all), neurology, biomarker, CSF, Alzheimer’s disease, AT(N)
Abstract: The biological definition of Alzheimer's disease using CSF biomarkers requires abnormal levels of both amyloid (A) and tau (T). However, biomarkers and corresponding cutoffs may not always reflect the presence or absence of pathology. Previous studies suggest that up to 32% of individuals with autopsy-confirmed Alzheimer's disease show normal CSF p-tau levels in vivo, but these studies are sparse and had small sample sizes. Therefore, in three independent autopsy cohorts, we studied whether or not CSF A+T- excluded Alzheimer's disease based on autopsy. We included 215 individuals, for whom ante-mortem CSF collection and autopsy had been performed, from three cohorts: (i) the Amsterdam Dementia Cohort (ADC) [n = 80, 37 (46%) Alzheimer's disease at autopsy, time between CSF collection and death 4.5 ± 2.9 years]; (ii) the Antwerp Dementia Cohort (DEM) [n = 92, 84 (91%) Alzheimer's disease at autopsy, time CSF collection to death 1.7 ± 2.3 years]; and (iii) the Alzheimer's Disease Neuroimaging Initiative (ADNI) [n = 43, 31 (72%) Alzheimer's disease at autopsy, time CSF collection to death 5.1 ± 2.5 years]. Biomarker profiles were based on dichotomized CSF Aβ1-42 and p-tau levels. The accuracy of CSF AT profiles to detect autopsy-confirmed Alzheimer's disease was assessed. Lastly, we investigated whether the concordance of AT profiles with autopsy diagnosis improved when CSF was collected closer to death in 9 (10%) DEM and 30 (70%) ADNI individuals with repeated CSF measurements available. In total, 50-73% of A+T- individuals and 100% of A+T+ individuals had Alzheimer's disease at autopsy. Amyloid status showed the highest accuracy to detect autopsy-confirmed Alzheimer's disease (accuracy, sensitivity and specificity in the ADC: 88%, 92% and 84%; in the DEM: 87%, 94% and 12%; and in the ADNI cohort: 86%, 90% and 75%, respectively). The addition of CSF p-tau did not further improve these estimates. We observed no differences in demographics or degree of Alzheimer's disease neuropathology between A+T- and A+T+ individuals with autopsy-confirmed Alzheimer's disease. All individuals with repeated CSF measurements remained stable in Aβ1-42 status during follow-up. None of the Alzheimer's disease individuals with a normal p-tau status changed to abnormal; however, four (44%) DEM individuals and two (7%) ADNI individuals changed from abnormal to normal p-tau status over time, and all had Alzheimer's disease at autopsy. In summary, we found that up to 73% of A+T- individuals had Alzheimer's disease at autopsy. This should be taken into account in both research and clinical settings.
Published: 2023

3. Time course of phosphorylated-tau181 in blood across the Alzheimer’s disease spectrum

Author: Marc Suárez-Calvet, Alexis Moscoso, Alzheimer’s Disease Neuroimaging Initiative, Anniina Snellman, Nicholas J. Ashton, Juan Lantero Rodriguez, Michael Schöll, Kaj Blennow, Henrik Zetterberg, Thomas K. Karikari, Michel J. Grothe, Instituto de Salud Carlos III, European Commission, BrightFocus Foundation, Swedish Alzheimer Foundation, Swedish Brain Foundation, Stiftelsen Dementia, Agneta Prytz-Folkes & Gösta Folkes Foundation, Aina Wallströms and Mary-Ann Sjöbloms Foundation, Anna Lisa and Brother Björnsson’s Foundation, Ministerio de Ciencia, Innovación y Universidades (España), Swedish Research Council, European Research Council, Alzheimer Drug Discovery Foundation, Dementia Research Institute (UK), Knut and Alice Wallenberg Foundation, Alzheimer's Disease Neuroimaging Initiative, National Institutes of Health (US), Department of Defense (US), National Institute on Aging (US), National Institute of Biomedical Imaging and Bioengineering (US), and Canadian Institutes of Health Research
Subjects: 0301 basic medicine, Threonine, Oncology, positron emission tomography, Meso scale, 0302 clinical medicine, Cerebrospinal fluid, Health care, Blood plasma, Medicine, Longitudinal Studies, Prospective Studies, tau, Phosphorylation, Prospective cohort study, media_common, AcademicSubjects/SCI01870, Disease spectrum, Brain, blood biomarkers, 3. Good health, Disease Progression, Biomarker (medicine), Christian ministry, Alzheimer’s disease, Swedish government, medicine.medical_specialty, Library science, tau Proteins, cerebrospinal fluid, 03 medical and health sciences, Neuroimaging, Alzheimer Disease, Political science, Internal medicine, media_common.cataloged_instance, Humans, Dementia, European union, Beta (finance), business.industry, Neurofibrillary tangle, Original Articles, medicine.disease, Editor's Choice, 030104 developmental biology, Positron-Emission Tomography, Time course, AcademicSubjects/MED00310, Neurology (clinical), sense organs, business, 030217 neurology & neurosurgery, Biomarkers, Dementia research
Abstract: Alzheimer’s Disease Neuroimaging Initiative., Tau phosphorylated at threonine 181 (p-tau181) measured in blood plasma has recently been proposed as an accessible, scalable, and highly specific biomarker for Alzheimer’s disease. Longitudinal studies, however, investigating the temporal dynamics of this novel biomarker are lacking. It is therefore unclear when in the disease process plasma p-tau181 increases above physiological levels and how it relates to the spatiotemporal progression of Alzheimer’s disease characteristic pathologies. We aimed to establish the natural time course of plasma p-tau181 across the sporadic Alzheimer’s disease spectrum in comparison to those of established imaging and fluid-derived biomarkers of Alzheimer’s disease. We examined longitudinal data from a large prospective cohort of elderly individuals enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (n = 1067) covering a wide clinical spectrum from normal cognition to dementia, and with measures of plasma p-tau181 and an 18F-florbetapir amyloid-β PET scan at baseline. A subset of participants (n = 864) also had measures of amyloid-β1–42 and p-tau181 levels in CSF, and another subset (n = 298) had undergone an 18F-flortaucipir tau PET scan 6 years later. We performed brain-wide analyses to investigate the associations of plasma p-tau181 baseline levels and longitudinal change with progression of regional amyloid-β pathology and tau burden 6 years later, and estimated the time course of changes in plasma p-tau181 and other Alzheimer’s disease biomarkers using a previously developed method for the construction of long-term biomarker temporal trajectories using shorter-term longitudinal data. Smoothing splines demonstrated that earliest plasma p-tau181 changes occurred even before amyloid-β markers reached abnormal levels, with greater rates of change correlating with increased amyloid-β pathology. Voxel-wise PET analyses yielded relatively weak, yet significant, associations of plasma p-tau181 with amyloid-β pathology in early accumulating brain regions in cognitively healthy individuals, while the strongest associations with amyloid-β were observed in late accumulating regions in patients with mild cognitive impairment. Cross-sectional and particularly longitudinal measures of plasma p-tau181 were associated with widespread cortical tau aggregation 6 years later, covering temporoparietal regions typical for neurofibrillary tangle distribution in Alzheimer’s disease. Finally, we estimated that plasma p-tau181 reaches abnormal levels ∼6.5 and 5.7 years after CSF and PET measures of amyloid-β, respectively, following similar dynamics as CSF p-tau181. Our findings suggest that plasma p-tau181 increases are associated with the presence of widespread cortical amyloid-β pathology and with prospective Alzheimer’s disease typical tau aggregation, providing clear implications for the use of this novel blood biomarker as a diagnostic and screening tool for Alzheimer’s disease., M.J.G. is supported by the “Miguel Servet” program [CP19/00031] of the Spanish Instituto de Salud Carlos III (ISCIII-FEDER). T.K.K. holds a research fellowship from the Brightfocus Foundation (#A2020812F), and is further supported by the Swedish Alzheimer Foundation (Alzheimerfonden; #AF-930627), the Swedish Brain Foundation (Hjärnfonden; #FO2020-0240), the Swedish Dementia Foundation (Demensförbundet), the Agneta Prytz-Folkes & Gösta Folkes Foundation (#2020-00124), the Aina (Ann) Wallströms and Mary-Ann Sjöbloms Foundation, the Anna Lisa and Brother Björnsson’s Foundation, Gamla Tjänarinnor, and the Gun and Bertil Stohnes Foundation. A.S. is supported by the Paulo Foundation and the Orion Research Foundation. M.S.C. received funding from the European Union’s Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie action grant agreement No 752310, and currently receives funding from Instituto de Salud Carlos III (PI19/00155) and from the Spanish Ministry of Science, Innovation and Universities (Juan de la Cierva Programme grant IJC2018-037478-I). H.Z. is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), and the UK Dementia Research Institute at UCL. K.B. is supported by the Swedish Research Council (#2017-00915), the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB-201809-2016615), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986), and European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236). M.S. is supported by the Knut and Alice Wallenberg Foundation (Wallenberg Centre for Molecular and Translational Medicine; KAW 2014.0363), the Swedish Research Council (#2017-02869), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-813971), and the Swedish Alzheimer Foundation (#AF-740191). Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada.
Published: 2020

4. Atlas55+: Brain Functional Atlas of Resting-State Networks for Late Adulthood

Author: Loic Labache, Sophia Frangou, Gaelle E. Doucet, Marc Joliot, Paul M. Thompson, and Alzheimer’s Disease Neuroimaging Initiative
Subjects: Male, Cognitive Neuroscience, Rest, Biology, late adulthood, Older population, Cellular and Molecular Neuroscience, Atlas (anatomy), medicine, Connectome, Humans, Young adult, AcademicSubjects/MED00385, Aged, Aged, 80 and over, Resting state fMRI, medicine.diagnostic_test, AcademicSubjects/SCI01870, Brain atlas, aging, resting-state networks, brain functional atlas, Brain, Human brain, Middle Aged, Magnetic Resonance Imaging, medicine.anatomical_structure, Cohort, Original Article, AcademicSubjects/MED00310, Female, Functional magnetic resonance imaging, Cartography
Abstract: Currently, several human brain functional atlases are used to define the spatial constituents of the resting-state networks (RSNs). However, the only brain atlases available are derived from samples of young adults. As brain networks are continuously reconfigured throughout life, the lack of brain atlases derived from older populations may influence RSN results in late adulthood. To address this gap, the aim of the study was to construct a reliable brain atlas derived only from older participants. We leveraged resting-state functional magnetic resonance imaging data from three cohorts of healthy older adults (total N = 563; age = 55–95 years) and a younger-adult cohort (N = 128; age = 18–35 years). We identified the major RSNs and their subdivisions across all older-adult cohorts. We demonstrated high spatial reproducibility of these RSNs with an average spatial overlap of 67%. Importantly, the RSNs derived from the older-adult cohorts were spatially different from those derived from the younger-adult cohort (P = 2.3 × 10−3). Lastly, we constructed a novel brain atlas, called Atlas55+, which includes the consensus of the major RSNs and their subdivisions across the older-adult cohorts. Thus, Atlas55+ provides a reliable age-appropriate template for RSNs in late adulthood and is publicly available. Our results confirm the need for age-appropriate functional atlases for studies investigating aging-related brain mechanisms.
Published: 2020

5. Smooth-threshold multivariate genetic prediction incorporating gene–environment interactions

Author: Masao Ueki, Gen Tamiya, and for Alzheimer’s Disease Neuroimaging Initiative
Subjects: AcademicSubjects/SCI01140, Multivariate statistics, AcademicSubjects/SCI00010, Genome-wide association study, smooth thresholding, QH426-470, Biology, Machine learning, computer.software_genre, AcademicSubjects/SCI01180, genetic prediction, Linear regression, Genetics, Feature (machine learning), Computer Simulation, Gene–environment interaction, gene–environment interaction, Molecular Biology, Genetics (clinical), Statistical hypothesis testing, Investigation, Models, Genetic, business.industry, fungi, Univariate, food and beverages, Regression, AcademicSubjects/SCI00960, Regression Analysis, Gene-Environment Interaction, Artificial intelligence, business, computer, Genome-Wide Association Study
Abstract: We propose a genetic prediction modeling approach for genome-wide association study (GWAS) data that can include not only marginal gene effects but also gene–environment (GxE) interaction effects—i.e., multiplicative effects of environmental factors with genes rather than merely additive effects of each. The proposed approach is a straightforward extension of our previous multiple regression-based method, STMGP (smooth-threshold multivariate genetic prediction), with the new feature being that genome-wide test statistics from a GxE interaction analysis are used to weight the corresponding variants. We develop a simple univariate regression approximation to the GxE interaction effect that allows a direct fit of the STMGP framework without modification. The sparse nature of our model automatically removes irrelevant predictors (including variants and GxE combinations), and the model is able to simultaneously incorporate multiple environmental variables. Simulation studies to evaluate the proposed method in comparison with other modeling approaches demonstrate its superior performance under the presence of GxE interaction effects. We illustrate the usefulness of our prediction model through application to real GWAS data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI)., G3: Genes, Genomes, Genetics, 11(12), art. no. jkab278; 2021
Published: 2021

6. Deep Sequencing to Detect Diversity of Trypanosoma cruzi Infection in Patients Coinfected With Human Immunodeficiency Virus and Chagas Disease

Author: Bowman, Natalie M, Balasubramanian, Sujata, Gilman, Robert H, Parobek, Christian, Calderon, Maritza, Waltmann, Andreea, Messenger, Louisa A, Sanchez, Leny, Bern, Caryn, Juliano, Jonathan J, and Working Group on Chagas Disease in Bolivia and Peru
Subjects: fungi, parasitic diseases, food and beverages
Abstract: Chagas disease, caused by Trypanosoma cruzi, can reactivate and cause severe acute disease in immunocompromised patients such as those infected with human immunodeficiency virus (HIV). We conducted amplicon deep sequencing of a 327-bp fragment of the tcscd5 gene using an Ion Torrent PGM directly from clinical samples from HIV patients with high parasitemia. We describe the within-host diversity, both characterizing the discrete typing unit of the infections and confirming the presence of multistrain infections, directly from clinical samples. This method can rapidly provide information on the genetic diversity of T. cruzi infection, which can have direct impacts on clinical disease.
Published: 2021

7. Body Mass Index and Polygenic Risk for Alzheimer’s Disease Predict Conversion to Alzheimer’s Disease

Author: Kate E Valerio, Jasmeet P. Hayes, Scott M. Hayes, Sarah Prieto, M S Alexander N Hasselbach, Jena N Moody, Mark W. Logue, and Alzheimer’s Disease Neuroimaging Initiative
Subjects: Oncology, Male, Aging, medicine.medical_specialty, THE JOURNAL OF GERONTOLOGY: Biological Sciences, Context (language use), Neuroimaging, Disease, Risk Assessment, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Sex Factors, Alzheimer Disease, Risk Factors, Internal medicine, medicine, Humans, Cognitive Dysfunction, Genetic risk, Risk factor, 030304 developmental biology, Aged, 2. Zero hunger, 0303 health sciences, business.industry, medicine.disease, Prognosis, Obesity, United States, Cohort, Disease Progression, Polygenic risk score, Female, Geriatrics and Gerontology, business, Body mass index, 030217 neurology & neurosurgery, Biomarkers, Genome-Wide Association Study
Abstract: Body mass index (BMI) is a risk factor for Alzheimer’s disease (AD) although the relationship is complex. Obesity in midlife is associated with increased risk for AD, whereas evidence supports both higher and lower BMI increasing risk for AD in late life. This study examined the influence of individual differences in genetic risk for AD to further clarify the relationship between late-life BMI and conversion to AD. Participants included 52 individuals diagnosed as having mild cognitive impairment (MCI) at baseline who converted to AD within 24 months and 52 matched MCI participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. BMI was measured at baseline. Genetic risk for AD was assessed via genome-wide polygenic risk scores. Conditional logistic regression models were run to determine if BMI and polygenic risk predicted conversion to AD. Results showed an interaction between BMI and genetic risk, such that individuals with lower BMI and higher polygenic risk were more likely to convert to AD relative to individuals with higher BMI. These results remained significant after adjusting for cerebrospinal fluid biomarkers of AD. Exploratory sex-stratified analyses revealed this relationship only remained significant in males. These results show that higher genetic risk in the context of lower BMI predicts conversion to AD in the next 24 months, particularly among males. These findings suggest that genetic risk for AD in the context of lower BMI may serve as a prodromal risk factor for future conversion to AD.
Published: 2021

8. Plasma levels of phosphorylated tau 181 are associated with cerebral metabolic dysfunction in cognitively impaired and amyloid-positive individuals

Author: Serge Gauthier, Sulantha Mathotaarachchi, Min Su Kang, Nicholas J. Ashton, Gleb Bezgin, Cecile Tissot, Tharick A. Pascoal, Alzheimer’s Disease Neuroimaging Initiative, Kaj Blennow, Firoza Z. Lussier, Melissa Savard, Thomas K. Karikari, Henrik Zetterberg, Mira Chamoun, Andrea Lessa Benedet, Pedro Rosa-Neto, Jaime Fernandez Arias, Yi-Ting Wang, Anniina Snellman, Joseph Therriault, and Juan Lantero Rodriguez
Subjects: 0301 basic medicine, Apolipoprotein E, Oncology, medicine.medical_specialty, Amyloid, Disease, phosphorylated tau, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, Internal medicine, brain glucose metabolism, medicine, Effects of sleep deprivation on cognitive performance, plasma, Fluorodeoxyglucose, metabolic dysfunction, business.industry, AcademicSubjects/SCI01870, General Engineering, Editor's Choice, 030104 developmental biology, Cohort, Original Article, AcademicSubjects/MED00310, Cognitively impaired, business, Alzheimer’s disease, 030217 neurology & neurosurgery, medicine.drug
Abstract: Alzheimer’s disease biomarkers are primarily evaluated through MRI, PET and CSF methods in order to diagnose and monitor disease. Recently, advances in the assessment of blood-based biomarkers have shown promise for simple, inexpensive, accessible and minimally invasive tools with diagnostic and prognostic value for Alzheimer’s disease. Most recently, plasma phosphorylated tau181 has shown excellent performance. The relationship between plasma phosphorylated tau181 and cerebral metabolic dysfunction assessed by [18F]fluorodeoxyglucose PET in Alzheimer’s disease is still unknown. This study was performed on 892 older individuals (297 cognitively unimpaired; 595 cognitively impaired) from the Alzheimer’s Disease Neuroimaging Initiative cohort. Plasma phosphorylated tau181 was assessed using single molecular array technology and metabolic dysfunction was indexed by [18F]fluorodeoxyglucose PET. Cross-sectional associations between plasma and CSF phosphorylated tau181 and [18F]fluorodeoxyglucose were assessed using voxelwise linear regression models, with individuals stratified by diagnostic group and by β-amyloid status. Associations between baseline plasma phosphorylated tau181 and longitudinal (24 months) rate of brain metabolic decline were also assessed in 389 individuals with available data using correlations and voxelwise regression models. Plasma phosphorylated tau181 was elevated in β-amyloid positive and cognitively impaired individuals as well as in apolipoprotein E ε4 carriers and was significantly associated with age, worse cognitive performance and CSF phosphorylated tau181. Cross-sectional analyses showed strong associations between plasma phosphorylated tau181 and [18F]fluorodeoxyglucose PET in cognitively impaired and β-amyloid positive individuals. Voxelwise longitudinal analyses showed that baseline plasma phosphorylated tau181 concentrations were significantly associated with annual rates of metabolic decline in cognitively impaired individuals, bilaterally in the medial and lateral temporal lobes. The associations between plasma phosphorylated tau181 and reduced brain metabolism, primarily in cognitively impaired and in β-amyloid positive individuals, supports the use of plasma phosphorylated tau181 as a simple, low-cost, minimally invasive and accessible tool to both assess current and predict future metabolic dysfunction associated with Alzheimer’s disease, comparatively to PET, MRI and CSF methods., Graphical Abstract Graphical Abstract, Lussier et al. report that plasma phosphorylated tau181 is associated cross-sectionally with CSF phosphorylated tau181 and [18F]fluorodeoxyglucose PET in 823 individuals from the Alzheimer’s Disease Neuroimaging Initiative cohort. The authors also report a significant association between baseline plasma p-tau181 and longitudinal change in brain glucose metabolism indexed by [18F]fluorodeoxyglucose PET.
Published: 2021

9. CDC Yellow Book 2024 : Health Information for International Travel

Author: Centers for Disease Control and Prevention (CDC) and Centers for Disease Control and Prevention (CDC)
Subjects: Vaccination, Travel--Health aspects, Medical geography
Abstract: For over half a century, the CDC Yellow Book has been a trusted resource, providing international travelers and clinicians with expert guidance for safe and healthy travel abroad. Along with disease-specific prevention and treatment recommendations, this comprehensive reference text provides readers with the background and context needed to understand and address health threats associated with all types of international travel. FEATURED IN THIS EDITION: · Precautions for international travelers during the coronavirus disease 2019 (COVID-19) pandemic, including links to updated information on related CDC and US government websites · Updates on practicing travel medicine in a virtual environment · New standalone vaccine tables for bacterial and viral diseases with links to the relevant Advisory Committee on Immunization Practices and US FDA websites · Safe international travel with pets and service animals · Advice for obtaining healthcare abroad including guidance on different types of travel insurance · Guidelines for self-treating common travel conditions including altitude illness, jet lag, motion sickness, and travelers'diarrhea · Detailed maps showing the distribution of travel-associated infections and diseases, including dengue and meningococcal meningitis · Country-specific mosquito avoidance, yellow fever vaccine, and malaria prevention recommendations · Food and drink precautions, plus updated water-disinfection techniques · Expanded content on safe international travel for specific groups including: LGBTQ+ individuals, highly allergic travelers, travelers with substance use issues, and medical tourists · Specialized recommendations for non-leisure travelers, study abroad, work-related travel, and travel to mass gatherings · Health insights for 14 popular destinations and itineraries in Africa and the Middle East, the Americas and the Caribbean, and Asia · Considerations for newly arrived adoptees, immigrants, and refugees
Published: 2023

10. Cerebrovascular disease promotes tau pathology in Alzheimer’s disease

Author: A. Iván Hernández, Herman Moreno, Alzheimer’s Disease Neuroimaging Initiative, Sabrina Simoes, Anthony G. Chesebro, Lina Pedraza, Frank C. Barone, Gloria Patricia Baena-Caldas, Milankumar Kothiya, Krystal K. Laing, José A. Luchsinger, Kay C. Igwe, Molly E. Zimmerman, Adam M. Brickman, Jie Li, Alexander L. Houck, and Patrick J. Lao
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, Ischemia, White matter, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, mental disorders, medicine, tau, medicine.diagnostic_test, business.industry, AcademicSubjects/SCI01870, General Engineering, Magnetic resonance imaging, white matter hyperintensities, medicine.disease, Hyperintensity, cerebrovascular disease, 030104 developmental biology, medicine.anatomical_structure, plasma biomarkers, Cerebral hemisphere, Biomarker (medicine), Original Article, AcademicSubjects/MED00310, business, Alzheimer’s disease, 030217 neurology & neurosurgery, Braak staging
Abstract: Small vessel cerebrovascular disease, visualized as white matter hyperintensities on T2-weighted magnetic resonance imaging, contributes to the clinical presentation of Alzheimer’s disease. However, the extent to which cerebrovascular disease represents an independent pathognomonic feature of Alzheimer's disease or directly promotes Alzheimer’s pathology is unclear. The purpose of this study was to examine the association between white matter hyperintensities and plasma levels of tau and to determine if white matter hyperintensities and tau levels interact to predict Alzheimer’s disease diagnosis. To confirm that cerebrovascular disease promotes tau pathology, we examined tau fluid biomarker concentrations and pathology in a mouse model of ischaemic injury. Three hundred ninety-one participants from the Alzheimer’s Disease Neuroimaging Initiative (74.5 ± 7.1 years of age) were included in this cross-sectional analysis. Participants had measurements of plasma total-tau, cerebrospinal fluid beta-amyloid, and white matter hyperintensities, and were diagnosed clinically as Alzheimer’s disease (n = 97), mild cognitive impairment (n = 186) or cognitively normal control (n = 108). We tested the relationship between plasma tau concentration and white matter hyperintensity volume across diagnostic groups. We also examined the extent to which white matter hyperintensity volume, plasma tau, amyloid positivity status and the interaction between white matter hyperintensities and plasma tau correctly classifies diagnostic category. Increased white matter hyperintensity volume was associated with higher plasma tau concentration, particularly among those diagnosed clinically with Alzheimer’s disease. Presence of brain amyloid and the interaction between plasma tau and white matter hyperintensity volume distinguished Alzheimer’s disease and mild cognitive impairment participants from controls with 77.6% and 63.3% accuracy, respectively. In 63 Alzheimer’s Disease Neuroimaging Initiative participants who came to autopsy (82.33 ± 7.18 age at death), we found that higher degrees of arteriosclerosis were associated with higher Braak staging, indicating a positive relationship between cerebrovascular disease and neurofibrillary pathology. In a transient middle cerebral artery occlusion mouse model, aged mice that received transient middle cerebral artery occlusion, but not sham surgery, had increased plasma and cerebrospinal fluid tau concentrations, induced myelin loss, and hyperphosphorylated tau pathology in the ipsilateral hippocampus and cerebral hemisphere. These findings demonstrate a relationship between cerebrovascular disease, operationalized as white matter hyperintensities, and tau levels, indexed in the plasma, suggesting that hypoperfusive injury promotes tau pathology. This potential causal association is supported by the demonstration that transient cerebral artery occlusion induces white matter damage, increases biofluidic markers of tau, and promotes cerebral tau hyperphosphorylation in older-adult mice., Plasma-derived total-tau concentration is highly correlated with WMH volume, an MRI marker of small vessel ischaemic damage, particularly among individuals with clinical Alzheimer’s disease. A parallel mouse model confirmed white matter damage, hyperphosphorylated tau pathology and elevated tau concentration in plasma and CSF due to surgically induced ischaemic injury., Graphical Abstract Graphical Abstract
Published: 2020

11. The Impact of 6 and 12 Months in Space on Human Brain Structure and Intracranial Fluid Shifts

Author: Ajitkumar P. Mulavara, Nichole E. Beltran, Kathleen E. Hupfeld, Heather R. McGregor, Patti A Reuter-Lorenz, Rachael D. Seidler, Alzheimer’s Disease Neuroimaging Initiative, Yiri E. De Dios, Ofer Pasternak, Igor S. Kofman, Scott J. Wood, Jessica K. Lee, Roy Riascos, and Jacob J. Bloomberg
Subjects: 0301 basic medicine, medicine.medical_specialty, Muskel- und Knochenstoffwechsel, Spaceflight, Exploration of Mars, Fluid shift, law.invention, spaceflight, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, free water, medicine, ventricular volume, gray matter volume, General Environmental Science, business.industry, Human brain, cortical thickness, 030104 developmental biology, medicine.anatomical_structure, 13. Climate action, Flight experience, Cardiology, Free water, General Earth and Planetary Sciences, Ventricular volume, Original Article, sense organs, business, 030217 neurology & neurosurgery, Reference dataset
Abstract: As plans develop for Mars missions, it is important to understand how long-duration spaceflight impacts brain health. Here we report how 12-month (n = 2 astronauts) versus 6-month (n = 10 astronauts) missions impact brain structure and fluid shifts. We collected MRI scans once before flight and four times after flight. Astronauts served as their own controls; we evaluated pre- to postflight changes and return toward preflight levels across the 4 postflight points. We also provide data to illustrate typical brain changes over 7 years in a reference dataset. Twelve months in space generally resulted in larger changes across multiple brain areas compared with 6-month missions and aging, particularly for fluid shifts. The majority of changes returned to preflight levels by 6 months after flight. Ventricular volume substantially increased for 1 of the 12-month astronauts (left: +25%, right: +23%) and the 6-month astronauts (left: 17 ± 12%, right: 24 ± 6%) and exhibited little recovery at 6 months. Several changes correlated with past flight experience; those with less time between subsequent missions had larger preflight ventricles and smaller ventricular volume increases with flight. This suggests that spaceflight-induced ventricular changes may endure for long periods after flight. These results provide insight into brain changes that occur with long-duration spaceflight and demonstrate the need for closer study of fluid shifts.
Published: 2020

12. Women can bear a bigger burden: ante- and post-mortem evidence for reserve in the face of tau

Author: Leonardino A. Digma, Alzheimer’s Disease Neuroimaging Initiative, Sarah J. Banks, Diane M. Jacobs, James B. Brewer, Robert A. Rissman, and John Madsen
Subjects: sex differences, medicine.medical_specialty, Aging, Clinical Trials and Supportive Activities, Audiology, Neurodegenerative, verbal memory, Standard Uptake Value Ratio, Logical address, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, Clinical Research, medicine, Acquired Cognitive Impairment, Rey Auditory Verbal Learning Test, Memory impairment, tau, 030304 developmental biology, 0303 health sciences, General Engineering, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer’s Disease Neuroimaging Initiative, Alzheimer's disease, Brain Disorders, Dementia, Original Article, Verbal memory, Psychology, Alzheimer’s disease, 030217 neurology & neurosurgery, Sex characteristics
Abstract: In this study, we aimed to assess whether women are able to withstand more tau before exhibiting verbal memory impairment. Using data from 121 amyloid-β-positive Alzheimer’s Disease Neuroimaging Initiative participants, we fit a linear model with Rey Auditory Verbal Learning Test score as the response variable and tau-PET standard uptake value ratio as the predictor and took the residuals as an estimate of verbal memory reserve for each subject. Women demonstrated higher reserve (i.e. residuals), whether the Learning (t = 2.78, P = 0.006) or Delay (t = 2.14, P = 0.03) score from the Rey Auditory Verbal Learning Test was used as a measure of verbal memory ability. To validate these findings, we examined 662 National Alzheimer’s Coordinating Center participants with a C2/C3 score (Consortium to Establish a Registry for Alzheimer’s Disease) at autopsy. We stratified our National Alzheimer’s Coordinating Center sample into Braak 1/2, Braak 3/4 and Braak 5/6 subgroups. Within each subgroup, we compared Logical Memory scores between men and women. Men had worse verbal memory scores within the Braak 1/2 (Logical Memory Immediate: β = −5.960 ± 1.517, P, In this study, we demonstrated in two independent cohorts that, for a given level of tau pathology, women perform better than men on verbal memory tests. Our findings suggest that women exhibit cognitive reserve, such that they are able to tolerate more tau before showing verbal memory impairment., Graphical Abstract Graphical Abstract
Published: 2020

13. Presumed small vessel disease, imaging and cognition markers in the Alzheimer's Disease Neuroimaging Initiative

Author: Neurologen, Brain, Circulatory Health, Alzheimer's Disease Neuroimaging Initiative, Neurologen, Brain, Circulatory Health, and Alzheimer's Disease Neuroimaging Initiative
Published: 2021

14. Complement C7 is a novel risk gene for Alzheimer's disease in Han Chinese

Author: Deng-Feng Zhang, Xiong-Jian Luo, Yu Fan, Dong Wang, Chen Zhang, Min Xu, Ming Li, Guihong Wang, Yiru Fang, Tianzi Jiang, Li-Li Kong, Rongcan Luo, Guo-Dong Li, Jin Li, Hong-Yan Jiang, Rui Bi, Chunjiu Zhong, Hejiang Zhou, Yong-Gang Yao, Alzheimer's Disease Neuroimaging Initiative, Liwen Tan, Yong Wu, and Nengyin Sheng
Subjects: Multidisciplinary, neuroimaging, Mutant, Wild type, 02 engineering and technology, Disease, Odds ratio, Biology, Alzheimer's disease, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, 3. Good health, 0104 chemical sciences, Complement system, Immunology, Biology & Biochemistry, Missense mutation, C7, whole-exome sequencing, 0210 nano-technology, Gene, Exome sequencing, complement system, Research Article
Abstract: Alzheimer's disease is the most common neurodegenerative disease, and has a high level of genetic heritability and population heterogeneity. In this study, we performed the whole-exome sequencing of Han Chinese patients with familial and/or early-onset Alzheimer's disease, followed by independent validation, imaging analysis and function characterization. We identified an exome-wide significant rare missense variant rs3792646 (p.K420Q) in the C7 gene in the discovery stage (P = 1.09 × 10−6, odds ratio = 7.853) and confirmed the association in different cohorts and a combined sample (1615 cases and 2832 controls, Pcombined = 2.99 × 10−7, odds ratio = 1.930). The risk allele was associated with decreased hippocampal volume and poorer working memory performance in early adulthood, thus resulting in an earlier age of disease onset. Overexpression of the mutant p.K420Q disturbed cell viability, immune activation and β-amyloid processing. Electrophysiological analyses showed that the mutant p.K420Q impairs the inhibitory effect of wild type C7 on the excitatory synaptic transmission in pyramidal neurons. These findings suggested that C7 is a novel risk gene for Alzheimer's disease in Han Chinese.
Published: 2018

15. Identification of seven novel loci associated with amino acid levels using single-variant and gene-based tests in 8545 Finnish men from the METSIM study

Author: Teslovich, T. M. (Tanya M), Kim, D. S. (Daniel Seung), Yin, X. (Xianyong), Stančáková, A. (Alena), Jackson, A. U. (Anne U.), Wielscher, M. (Matthias), Naj, A. (Adam), Perry, J. R. (John R.B.), Huyghe, J. R. (Jeroen R.), Stringham, H. M. (Heather M.), Davis, J. P. (James P.), Raulerson, C. K. (Chelsea K.), Welch, R. P. (Ryan P.), Fuchsberger, C. (Christian), Locke, A. E. (Adam E.), Sim, X. (Xueling), Chines, P. S. (Peter S.), Narisu, N. (Narisu), Kangas, A. J. (Antti J.), Soininen, P. (Pasi), G. o. (Genetics of Obesity-Related Liver Disease Consortium (GOLD)), T. A. (The Alzheimer’s Disease Genetics Consortium (ADGC)), T. D. (The DIAbetes Genetics Replication And Meta-analysis (DIAGRAM)), Ala-Korpela, M. (Mika), Gudnason, V. (Vilmundur), Musani, S. K. (Solomon K.), Järvelin, M.-R. (Marjo-Riitta), Schellenberg, G. D. (Gerard D.), Speliotes, E. K. (Elizabeth K.), Kuusisto, J. (Johanna), Collins, F. S. (Francis S.), Boehnke, M. (Michael), Laakso, M. (Markku), Mohlke, K. L. (Karen L.), Teslovich, T. M. (Tanya M), Kim, D. S. (Daniel Seung), Yin, X. (Xianyong), Stančáková, A. (Alena), Jackson, A. U. (Anne U.), Wielscher, M. (Matthias), Naj, A. (Adam), Perry, J. R. (John R.B.), Huyghe, J. R. (Jeroen R.), Stringham, H. M. (Heather M.), Davis, J. P. (James P.), Raulerson, C. K. (Chelsea K.), Welch, R. P. (Ryan P.), Fuchsberger, C. (Christian), Locke, A. E. (Adam E.), Sim, X. (Xueling), Chines, P. S. (Peter S.), Narisu, N. (Narisu), Kangas, A. J. (Antti J.), Soininen, P. (Pasi), G. o. (Genetics of Obesity-Related Liver Disease Consortium (GOLD)), T. A. (The Alzheimer’s Disease Genetics Consortium (ADGC)), T. D. (The DIAbetes Genetics Replication And Meta-analysis (DIAGRAM)), Ala-Korpela, M. (Mika), Gudnason, V. (Vilmundur), Musani, S. K. (Solomon K.), Järvelin, M.-R. (Marjo-Riitta), Schellenberg, G. D. (Gerard D.), Speliotes, E. K. (Elizabeth K.), Kuusisto, J. (Johanna), Collins, F. S. (Francis S.), Boehnke, M. (Michael), Laakso, M. (Markku), and Mohlke, K. L. (Karen L.)
Abstract: Comprehensive metabolite profiling captures many highly heritable traits, including amino acid levels, which are potentially sensitive biomarkers for disease pathogenesis. To better understand the contribution of genetic variation to amino acid levels, we performed single variant and gene-based tests of association between nine serum amino acids (alanine, glutamine, glycine, histidine, isoleucine, leucine, phenylalanine, tyrosine, and valine) and 16.6 million genotyped and imputed variants in 8545 non-diabetic Finnish men from the METabolic Syndrome In Men (METSIM) study with replication in Northern Finland Birth Cohort (NFBC1966). We identified five novel loci associated with amino acid levels (P = < 5×10−8): LOC157273/PPP1R3B with glycine (rs9987289, P = 2.3×10−26); ZFHX3 (chr16:73326579, minor allele frequency (MAF) = 0.42%, P = 3.6×10−9), LIPC (rs10468017, P = 1.5×10−8), and WWOX (rs9937914, P = 3.8×10−8) with alanine; and TRIB1 with tyrosine (rs28601761, P = 8×10−9). Gene-based tests identified two novel genes harboring missense variants of MAF < 1% that show aggregate association with amino acid levels: PYCR1 with glycine (Pgene = 1.5×10−6) and BCAT2 with valine (Pgene = 7.4×10−7); neither gene was implicated by single variant association tests. These findings are among the first applications of gene-based tests to identify new loci for amino acid levels. In addition to the seven novel gene associations, we identified five independent signals at established amino acid loci, including two rare variant signals at GLDC (rs138640017, MAF=0.95%, Pconditional = 5.8×10−40) with glycine levels and HAL (rs141635447, MAF = 0.46%, Pconditional = 9.4×10−11) with histidine levels. Examination of all single variant association results in our data revealed a strong inverse relationship between effect size and MAF (Ptrend<0.001). These novel signals provide further insight into the molecular mechanisms of amino acid metabolism and potentially, their perturba
Published: 2018

16. Morphometric network differences in ageing versus Alzheimer’s disease dementia

Author: Renaud La Joie, Julie Gonneaud, Jacob W. Vogel, Alexa Pichet Binette, Alzheimer’s Disease Neuroimaging Initiative, Judes Poirier, John C.S. Breitner, Sylvia Villeneuve, D. Louis Collins, Pedro Rosa-Neto, and Etienne Vachon-Presseau
Subjects: Gerontology, Adult, Male, Aging, Adolescent, Disease, Grey matter, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Atrophy, Alzheimer Disease, medicine, Dementia, Humans, Cognitive Dysfunction, Risk factor, 030304 developmental biology, Aged, Aged, 80 and over, 0303 health sciences, business.industry, Brain, Cognition, Original Articles, Middle Aged, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Frontal lobe, Ageing, Disease Progression, Female, Neurology (clinical), business, Cognition Disorders, 030217 neurology & neurosurgery
Abstract: Age being the main risk factor for Alzheimer’s disease, it is particularly challenging to disentangle structural changes related to normal brain ageing from those specific to Alzheimer’s disease. Most studies aiming to make this distinction focused on older adults only and on a priori anatomical regions. Drawing on a large, multi-cohort dataset ranging from young adults (n = 468; age range 18–35 years), to older adults with intact cognition (n = 431; age range 55–90 years) and with Alzheimer’s disease (n = 50 with late mild cognitive impairment and 71 with Alzheimer’s dementia, age range 56–88 years), we investigated grey matter organization and volume differences in ageing and Alzheimer’s disease. Using independent component analysis on all participants’ structural MRI, we first derived morphometric networks and extracted grey matter volume in each network. We also derived a measure of whole-brain grey matter pattern organization by correlating grey matter volume in all networks across all participants from the same cohort. We used logistic regressions and receiver operating characteristic analyses to evaluate how well grey matter volume in each network and whole-brain pattern could discriminate between ageing and Alzheimer’s disease. Because increased heterogeneity is often reported as one of the main features characterizing brain ageing, we also evaluated interindividual heterogeneity within morphometric networks and across the whole-brain organization in ageing and Alzheimer’s disease. Finally, to investigate the clinical validity of the different grey matter features, we evaluated whether grey matter volume or whole-brain pattern was related to clinical progression in cognitively normal older adults. Ageing and Alzheimer’s disease contributed additive effects on grey matter volume in nearly all networks, except frontal lobe networks, where differences in grey matter were more specific to ageing. While no networks specifically discriminated Alzheimer’s disease from ageing, heterogeneity in grey matter volumes across morphometric networks and in the whole-brain grey matter pattern characterized individuals with cognitive impairments. Preservation of the whole-brain grey matter pattern was also related to lower risk of developing cognitive impairment, more so than grey matter volume. These results suggest both ageing and Alzheimer’s disease involve widespread atrophy, but that the clinical expression of Alzheimer’s disease is uniquely associated with disruption of morphometric organization.
Published: 2020

17. Regional imaging genetic enrichment analysis

Author: Li Shen, Andrew J. Saykin, Alzheimer’s Disease Neuroimaging Initiative, Shannon L. Risacher, Shan Cong, Xiaohui Yao, Jingwen Yan, and Jason H. Moore
Subjects: Statistics and Probability, Computer science, Neuroimaging, Machine learning, computer.software_genre, Biochemistry, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Voxel, Alzheimer Disease, medicine, Humans, Molecular Biology, 030304 developmental biology, 0303 health sciences, medicine.diagnostic_test, business.industry, Brain, Original Papers, Computer Science Applications, Computational Mathematics, Computational Theory and Mathematics, Positron emission tomography, Positron-Emission Tomography, Tomography, Artificial intelligence, business, computer, 030217 neurology & neurosurgery, Alzheimer's Disease Neuroimaging Initiative
Abstract: Motivation Brain imaging genetics aims to reveal genetic effects on brain phenotypes, where most studies examine phenotypes defined on anatomical or functional regions of interest (ROIs) given their biologically meaningful interpretation and modest dimensionality compared with voxelwise approaches. Typical ROI-level measures used in these studies are summary statistics from voxelwise measures in the region, without making full use of individual voxel signals. Results In this article, we propose a flexible and powerful framework for mining regional imaging genetic associations via voxelwise enrichment analysis, which embraces the collective effect of weak voxel-level signals and integrates brain anatomical annotation information. Our proposed method achieves three goals at the same time: (i) increase the statistical power by substantially reducing the burden of multiple comparison correction; (ii) employ brain annotation information to enable biologically meaningful interpretation and (iii) make full use of fine-grained voxelwise signals. We demonstrate our method on an imaging genetic analysis using data from the Alzheimer’s Disease Neuroimaging Initiative, where we assess the collective regional genetic effects of voxelwise FDG-positron emission tomography measures between 116 ROIs and 565 373 single-nucleotide polymorphisms. Compared with traditional ROI-wise and voxelwise approaches, our method identified 2946 novel imaging genetic associations in addition to 33 ones overlapping with the two benchmark methods. In particular, two newly reported variants were further supported by transcriptome evidences from region-specific expression analysis. This demonstrates the promise of the proposed method as a flexible and powerful framework for exploring imaging genetic effects on the brain. Availability and implementation The R code and sample data are freely available at https://github.com/lshen/RIGEA. Supplementary information Supplementary data are available at Bioinformatics online.
Published: 2019

18. CDC Yellow Book 2020

Author: Centers for Disease Control and... (CDC)
Subjects: human activities
Abstract: The CDC Yellow Book offers everything travelers and healthcare providers need to know for safe and healthy travel abroad. This 2020 edition includes: country-specific risk guidelines for yellow fever and malaria, including expert recommendations and 26 detailed, country-level maps; detailed maps showing distribution of travel-related illnesses, including dengue, Japanese encephalitis, meningococcal meningitis, and schistosomiasis; guidelines for self-treating common travel conditions, including altitude illness, jet lag, motion sickness, and travelers’ diarrhea; expert guidance on food and drink precautions to avoid illness, plus water-disinfection techniques for travel to remote destinations; specialized guidelines for non-leisure travelers, study abroad, work-related travel, and travel to mass gatherings; advice on medical tourism, complementary and integrative health approaches, and counterfeit drugs; health insights around 15 popular tourist destinations and itineraries; advising travelers with specific needs, including those with chronic medical conditions or weakened immune systems, health care workers, humanitarian aid workers, long-term travelers and expatriates, and last-minute travellers; considerations for newly arrived adoptees, immigrants, and refugees.
Published: 2019
Full Text: View/download PDF

19. CDC Yellow Book 2020 : Health Information for International Travel

Author: Centers for Disease Control and Prevention (CDC) and Centers for Disease Control and Prevention (CDC)
Subjects: Epidemics--Periodicals, Vaccination--Periodicals, Travel--Health aspects--Periodicals, Communicable diseases--Prevention--Periodicals, Americans--Health aspects--Foreign countries--Periodicals
Abstract: The definitive reference for travel medicine, updated for 2020!'A beloved travel must-have for the intrepid wanderer.'-Publishers Weekly'A truly excellent and comprehensive resource.'-Journal of Hospital Infection The CDC Yellow Book offers everything travelers and healthcare providers need to know for safe and healthy travel abroad. This 2020 edition includes: · Country-specific risk guidelines for yellow fever and malaria, including expert recommendations and 26 detailed, country-level maps · Detailed maps showing distribution of travel-related illnesses, including dengue, Japanese encephalitis, meningococcal meningitis, and schistosomiasis · Guidelines for self-treating common travel conditions, including altitude illness, jet lag, motion sickness, and travelers'diarrhea · Expert guidance on food and drink precautions to avoid illness, plus water-disinfection techniques for travel to remote destinations · Specialized guidelines for non-leisure travelers, study abroad, work-related travel, and travel to mass gatherings · Advice on medical tourism, complementary and integrative health approaches, and counterfeit drugs · Updated guidance for pre-travel consultations · Advice for obtaining healthcare abroad, including guidance on different types of travel insurance · Health insights around 15 popular tourist destinations and itineraries · Recommendations for traveling with infants and children · Advising travelers with specific needs, including those with chronic medical conditions or weakened immune systems, health care workers, humanitarian aid workers, long-term travelers and expatriates, and last-minute travelers · Considerations for newly arrived adoptees, immigrants, and refugees Long the most trusted book of its kind, the CDC Yellow Book is an essential resource in an ever-changing field -- and an ever-changing world.
Published: 2020

20. Prediction of conversion to Alzheimer’s disease using deep survival analysis of MRI images

Author: Nakagawa, Tomonori, Ishida, Manabu, Naito, Junpei, NAGAI, Atsushi, Yamaguchi, Shuhei, Onoda, Keiichi, Alzheimer’s Disease Neuroimaging Initiative, Nakagawa, Tomonori, Ishida, Manabu, Naito, Junpei, NAGAI, Atsushi, Yamaguchi, Shuhei, Onoda, Keiichi, and Alzheimer’s Disease Neuroimaging Initiative
Published: 2020

21. CDC Health Information for International Travel 2016

Author: Centers for Disease Control and Prevention Centers for Disease Control and Prevention and Centers for Disease Control and Prevention Centers for Disease Control and Prevention
Subjects: Travel, Vaccination, Travel--Health aspects
Abstract: Amid recent changes in global health, the public interest in travelers'safety has never been greater. For both international travelers and the health professionals who care for them, CDC Health Information for International Travel (more commonly known as The Yellow Book) is the definitive resource for preventing illness and injury in a globalized world. This 2016 edition offers the US government's most current health recommendations for travelers to international destinations, including disease risk maps, country-specific guidelines, and vaccine requirements and recommendations. The book also offers updated guidance for specific types of travel and travelers, including: · Precautions for immunocompromised travelers and disabled travelers · Guidance for the pregnant, last-minute, or resource-limited traveler · Health considerations for newly arrived adoptees, immigrants, and refugees · Advice for air crews, humanitarian aid workers, and health care workers traveling to provide care overseas Written by a team of experts at CDC on the forefront of travel medicine, The Yellow Book provides a user-friendly, vital resource for those in the business of keeping travelers healthy abroad.
Published: 2015

22. Identification of seven novel loci associated with amino acid levels using single-variant and gene-based tests in 8545 Finnish men from the METSIM study

Author: The DIAbetes Genetics Replication And Meta-analysis (DIAGRAM), Teslovich, T.M., Naj, A., Genetics of Obesity-Related Liver Disease Consortium (GOLD), Ala-Korpela, M., Speliotes, E.K., Jarvelin, M.-R., Schellenberg, G.D., Boehnke, M., Musani, S.K., Jackson, A.U., Locke, A.E., Huyghe, J.R., Welch, R.P., Chines, P.S., Gudnason, V., Kuusisto, J., Narisu, N., Davis, J.P., The Alzheimer's Disease Genetics Consortium (ADGC), Stringham, H.M., Stan��kov��, A., Laakso, M., Soininen, P., Fuchsberger, C., Mohlke, K.L., Sim, X., Raulerson, C.K., Yin, X., Kim, D.S., Kangas, A.J., Wielscher, M., and Perry, J.R.B.
Abstract: Comprehensivemetabolite profiling capturesmany highly heritable traits, including amino acid levels, which are potentially sensitive biomarkers for disease pathogenesis. To better understand the contribution of genetic variation to amino acid levels, we performed single variant and gene-based tests of association between nine serumamino acids (alanine, glutamine, glycine, histidine, isoleucine, leucine, phenylalanine, tyrosine, and valine) and 16.6million genotyped and imputed variants in 8545 nondiabetic Finnishmen fromtheMETabolic Syndrome In Men (METSIM) study with replication in Northern Finland Birth Cohort (NFBC1966).We identified five novel loci associated with amino acid levels (P = < 5��10-8): LOC157273/PPP1R3B with glycine (rs9987289, P = 2.3��10-26); ZFHX3 (chr16:73326579,minor allele frequency (MAF) = 0.42%, P = 3.6��10-9), LIPC (rs10468017, P = 1.5��10-8), and WWOX (rs9937914, P = 3.8��10-8) with alanine; and TRIB1 with tyrosine (rs28601761, P = 8��10-9). Gene-based tests identified two novel genes harboringmissense variants ofMAF < 1% that show aggregate association with amino acid levels: PYCR1 with glycine (Pgene = 1.5��10-6) and BCAT2 with valine (Pgene = 7.4��10-7); neither gene was implicated by single variant association tests. These findings are among the first applications of gene-based tests to identify new loci for amino acid levels. In addition to the seven novel gene associations, we identified five independent signals at established amino acid loci, including two rare variant signals at GLDC (rs138640017,MAF=0.95%, Pconditional = 5.8��10-40) with glycine levels and HAL (rs141635447,MAF = 0.46%, Pconditional = 9.4��10-11) with histidine levels. Examination of all single variant association results in our data revealed a strong inverse relationship between effect size and MAF (Ptrend < 0.001). These novel signals provide further insight into the molecularmechanisms of amino acidmetabolismand potentially, their perturbations in disease.
Published: 2018
Full Text: View/download PDF

23. Statistical Model of Dynamic Markers of the Alzheimer’s Pathological Cascade

Author: Deborah A. Lowe, Lisa Geraci, Jared F. Benge, Alzheimer’s Disease Neuroimaging Initiative, Steve Balsis, Rachelle S. Doody, Tabina K. Choudhury, and Robert Tirso
Subjects: Male, Social Psychology, Neuroimaging, Neuropsychological Tests, The Journal of Gerontology: Psychological Sciences, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Item response theory, Activities of Daily Living, medicine, Dementia, Humans, 0501 psychology and cognitive sciences, Effects of sleep deprivation on cognitive performance, Aged, Models, Statistical, medicine.diagnostic_test, business.industry, 05 social sciences, Brain, Cognition, medicine.disease, Magnetic Resonance Imaging, Cognitive test, Clinical Psychology, Positron emission tomography, Case-Control Studies, Positron-Emission Tomography, Disease Progression, Female, Geriatrics and Gerontology, business, Gerontology, Neuroscience, 030217 neurology & neurosurgery, Biomarkers, Alzheimer's Disease Neuroimaging Initiative
Abstract: Objectives Alzheimer's disease (AD) is a progressive disease reflected in markers across assessment modalities, including neuroimaging, cognitive testing, and evaluation of adaptive function. Identifying a single continuum of decline across assessment modalities in a single sample is statistically challenging because of the multivariate nature of the data. To address this challenge, we implemented advanced statistical analyses designed specifically to model complex data across a single continuum. Method We analyzed data from the Alzheimer's Disease Neuroimaging Initiative (ADNI; N = 1,056), focusing on indicators from the assessments of magnetic resonance imaging (MRI) volume, fluorodeoxyglucose positron emission tomography (FDG-PET) metabolic activity, cognitive performance, and adaptive function. Item response theory was used to identify the continuum of decline. Then, through a process of statistical scaling, indicators across all modalities were linked to that continuum and analyzed. Results Findings revealed that measures of MRI volume, FDG-PET metabolic activity, and adaptive function added measurement precision beyond that provided by cognitive measures, particularly in the relatively mild range of disease severity. More specifically, MRI volume, and FDG-PET metabolic activity become compromised in the very mild range of severity, followed by cognitive performance and finally adaptive function. Conclusion Our statistically derived models of the AD pathological cascade are consistent with existing theoretical models.
Published: 2018

24. MFN2 mutations in Charcot–Marie–Tooth disease alter mitochondria-associated ER membrane function but do not impair bioenergetics

Author: Department of Defense (US), National Institutes of Health (US), J. Willard Marriott Foundation, American Parkinson Disease Association, Fondazione Cariparo, European Research Council, Wellcome Trust, Newton Fund, European Commission, Larrea, Delfina, Pera, Marta, Gonnelli, Adriano, Quintana-Cabrera, Ruben, Akman, H. Orhan, Guardia-Laguarta, Cristina, Velasco, Kevin R., Area-Gomez, Estela, Dal Bello, Federica, De Stefani, Diego, Horvath, Rita, Shy, Michael E., Schon, Eric A., Giacomello, Marta, Department of Defense (US), National Institutes of Health (US), J. Willard Marriott Foundation, American Parkinson Disease Association, Fondazione Cariparo, European Research Council, Wellcome Trust, Newton Fund, European Commission, Larrea, Delfina, Pera, Marta, Gonnelli, Adriano, Quintana-Cabrera, Ruben, Akman, H. Orhan, Guardia-Laguarta, Cristina, Velasco, Kevin R., Area-Gomez, Estela, Dal Bello, Federica, De Stefani, Diego, Horvath, Rita, Shy, Michael E., Schon, Eric A., and Giacomello, Marta
Abstract: Charcot–Marie–Tooth disease (CMT) type 2A is a form of peripheral neuropathy, due almost exclusively to dominant mutations in the nuclear gene encoding the mitochondrial protein mitofusin-2 (MFN2). However, there is no understanding of the relationship of clinical phenotype to genotype. MFN2 has two functions: it promotes inter-mitochondrial fusion and mediates endoplasmic reticulum (ER)–mitochondrial tethering at mitochondria-associated ER membranes (MAM). MAM regulates a number of key cellular functions, including lipid and calcium homeostasis, and mitochondrial behavior. To date, no studies have been performed to address whether mutations in MFN2 in CMT2A patient cells affect MAM function, which might provide insight into pathogenesis. Using fibroblasts from three CMT2AMFN2 patients with different mutations in MFN2, we found that some, but not all, examined aspects of ER–mitochondrial connectivity and of MAM function were indeed altered, and correlated with disease severity. Notably, however, respiratory chain function in those cells was unimpaired. Our results suggest that CMT2AMFN2 is a MAM-related disorder but is not a respiratory chain-deficiency disease. The alterations in MAM function described here could also provide insight into the pathogenesis of other forms of CMT.
Published: 2019

25. CDC Yellow Book 2018: Health Information for International Travel

Author: Centers for Disease Control and Prevention CDC and Centers for Disease Control and Prevention CDC
Subjects: Vaccination, Travel, Communicable diseases, Travel--Health aspects, International travel
Abstract: THE ESSENTIAL WORK IN TRAVEL MEDICINE -- NOW COMPLETELY UPDATED FOR 2018 As unprecedented numbers of travelers cross international borders each day, the need for up-to-date, practical information about the health challenges posed by travel has never been greater. For both international travelers and the health professionals who care for them, the CDC Yellow Book 2018: Health Information for International Travel is the definitive guide to staying safe and healthy anywhere in the world. The fully revised and updated 2018 edition codifies the U.S. government's most current health guidelines and information for international travelers, including pretravel vaccine recommendations, destination-specific health advice, and easy-to-reference maps, tables, and charts. The 2018 Yellow Book also addresses the needs of specific types of travelers, with dedicated sections on: · Precautions for pregnant travelers, immunocompromised travelers, and travelers with disabilities · Special considerations for newly arrived adoptees, immigrants, and refugees · Practical tips for last-minute or resource-limited travelers · Advice for air crews, humanitarian workers, missionaries, and others who provide care and support overseas Authored by a team of the world's most esteemed travel medicine experts, the Yellow Book is an essential resource for travelers -- and the clinicians overseeing their care -- at home and abroad.
Published: 2017

26. Harmonising data collection from osteoarthritis studies to enable stratification: recommendations on core data collection from an Arthritis Research UK clinical studies group

Author: Kingsbury, SR, Corp, N, Watt, F, Felson, DT, O'Neill, TW, Holt, CA, Jones, RK, Conaghan, PG, Arthritis Research UK Osteoarthritis and Crystal Disease Clinical Studies Group working group, and Arden, N
Subjects: osteoarthritis, clinical trials, stratification, prognosis, personalized medicine
Abstract: OBJECTIVE: Treatment of OA by stratifying for commonly used and novel therapies will likely improve the range of effective therapy options and their rational deployment in this undertreated, chronic disease. In order to develop appropriate datasets for conducting post hoc analyses to inform approaches to stratification for OA, our aim was to develop recommendations on the minimum data that should be recorded at baseline in all future OA interventional and observational studies. METHODS: An Arthritis Research UK study group comprised of 32 experts used a Delphi-style approach supported by a literature review of systematic reviews to come to a consensus on core data collection for OA studies. RESULTS: Thirty-five systematic reviews were used as the basis for the consensus group discussion. For studies with a primary structural endpoint, core domains for collection were defined as BMI, age, gender, racial origin, comorbidities, baseline OA pain, pain in other joints and occupation. In addition to the items generalizable to all anatomical sites, joint-specific domains included radiographic measures, surgical history and anatomical factors, including alignment. To demonstrate clinical relevance for symptom studies, the collection of mental health score, self-efficacy and depression scales were advised in addition to the above. CONCLUSIONS: Currently it is not possible to stratify patients with OA into therapeutic groups. A list of core and optional data to be collected in all OA interventional and observational studies was developed, providing a basis for future analyses to identify predictors of progression or response to treatment.
Published: 2017
Full Text: View/download PDF

27. Art in Science : Selections From EMERGING INFECTIOUS DISEASES

Author: Polyxeni Potter, Centers for Disease Control and Prevention, Polyxeni Potter, and Centers for Disease Control and Prevention
Subjects: Communicable diseases--Epidemiology, Arts, Medicine in art, Art
Abstract: Since 1995, the Centers for Disease Control and Prevention has published Emerging Infectious Diseases, a public health journal that endeavors to improve scientific understanding of disease emergence, prevention, and elimination. Widely known for its leading research in infectious disease, EID is also recognized for its unique aesthetic, which brings together visual art from across periods and, through prose, makes it relatable to the journal's science-minded readership. In Art in Science: Selections from Emerging Infectious Diseases, the journal's highly popular fine-art covers are contextualized with essays that address how the featured art relates to science, and to us all. Through the combined covers and essays, the journal's contents -- topics such as infections, contagions, disease emergence, antimicrobial resistance -- find larger context amid topics such as poverty and war, the hazards of global travel, natural disasters, and human-animal interactions. This collection of 92 excerpts and covers from Emerging Infectious Diseases will be of interest to readers of the journal or to anyone who wishes to reach across the aisle between art and science.
Published: 2014

28. CDC Health Information for International Travel 2014 : The Yellow Book

Author: Centers for Disease Control and Prevention and Centers for Disease Control and Prevention
Subjects: Travel, Vaccination, Travel--Health aspects
Abstract: Health risks are real and ever-changing, especially while traveling abroad. To stay abreast of the most up-to-date health recommendations, experienced travelers and health care professionals have always relied on CDC's user-friendly Health Information for International Travel (commonly known as the The Yellow Book) as their one indispensable guide. Updated biennially by a team of almost two hundred experts-including both CDC staff and travel medicine experts--this book is the only publication that contains all of the official government recommendations for international travel. Clearly written and featuring full-color illustrations, the book provides easy-to-read disease risk maps, information on where to find health care during travel, advice for those traveling with infants and children, a comprehensive catalog of diseases, and detailed country-specific health warnings. For example, the section on the Caribbean lays out the recommended immunizations and examines specific health risks for travelers to the region, ranging from malaria to dengue, yellow fever, and traveler's diarrhea. But the book goes beyond the risk of disease to discuss dangers such as violent crime-fortunately, not a great danger to tourists in the area-and also to remind travelers that the single greatest cause of injury death among visitors are traffic accidents. The section on the Caribbean also notes hurricane season and outlines the risks involved in snorkeling, diving, and other water activities common to the area. Every facet of the previous edition has been revisited and revised where necessary, including country-by-country immunization suggestions and new drug information. For the primary care clinician, the specialized travel medicine clinician, or the avid or first-time international traveler, this book is an indispensable safety net, providing readers with everything they need to know to prevent or to seek treatment for illness abroad.
Published: 2014

29. Copy-number variation of the neuronal glucose transporter gene SLC2A3 and age of onset in Huntington's disease

Author: Vittori, Angelica, Breda, Carlo, Repici, Mariaelena, Orth, Michael, Roos, Raymund A. C., Outeiro, Tiago F., Giorgini, Flaviano, Hollox, Edward J, REGISTRY investigators of the European Huntington's Disease Network, and Romano, Silvia.
Subjects: Male, diploidy, DNA Copy Number Variations, Glucose Transporter Type 3, B lymphocyte, animal experiment, cag repeat, Gene Dosage, copy number variation, Articles, drosophila, cohort analysis, drosophila melanogaster, Cell Line, Up-Regulation, Cohort Studies, Disease Models, Animal, Huntington Disease, Animals, Drosophila Proteins, Humans, Female, Age of Onset, Phylogeny
Abstract: Huntington's disease (HD) is a devastating neurodegenerative disorder which is inherited in an autosomal dominant manner. HD is caused by a trinucleotide CAG repeat expansion that encodes a polyglutamine stretch in the huntingtin (HTT) protein. Mutant HTT expression leads to a myriad of cellular dysfunctions culminating in neuronal loss and consequent motor, cognitive and psychiatric disturbances in HD patients. The length of the CAG repeat is inversely correlated with age of onset (AO) in HD patients, while environmental and genetic factors can further modulate this parameter. Here, we explored whether the recently described copy-number variation (CNV) of the gene SLC2A3—which encodes the neuronal glucose transporter GLUT3—could modulate AO in HD. Strikingly, we found that increased dosage of SLC2A3 delayed AO in an HD cohort of 987 individuals, and that this correlated with increased levels of GLUT3 in HD patient cells. To our knowledge this is the first time that CNV of a candidate gene has been found to modulate HD pathogenesis. Furthermore, we found that increasing dosage of Glut1—the Drosophila melanogaster homologue of this glucose transporter—ameliorated HD-relevant phenotypes in fruit flies, including neurodegeneration and life expectancy. As alterations in glucose metabolism have been implicated in HD pathogenesis, this study may have important therapeutic relevance for HD.
Published: 2014

30. Do new biologics meet the unmet medical need in rheumatoid arthritis? Safety and efficacy of abatacept following B-cell depletion

Author: Walker, Ulrich A, Courvoisier, Delphine S, Dudler, Jean, Aeberli, Daniel, von Kempis, Johannes, Scherer, Almut, Finckh, Axel, and on behalf of the, Swiss Clinical Quality Management Programme in Rheumatic Disease
Subjects: Male, Oncology, medicine.medical_specialty, Immunoconjugates, Population, 610 Medicine & health, Antirheumatic Agents/adverse effects, Abatacept, Arthritis, Rheumatoid, Biological Agents/adverse effects, Rheumatology, Internal medicine, medicine, Humans, Pharmacology (medical), Immunoconjugates/adverse effects, education, Aged, ddc:616, B-Lymphocytes, Biological Products, education.field_of_study, business.industry, Middle Aged, medicine.disease, Antirheumatic Agents, Drug class, Arthritis, Rheumatoid/drug therapy, B-Lymphocytes/drug effects, Rheumatoid arthritis, Immunology, Cohort, Female, Rituximab, business, Switzerland, medicine.drug
Abstract: Sir, anti TNF-α agents (aTNFs) are the most commonly prescribed biological agents in RA. More recently abatacept (ABA), a T-cell costimulation modulator, and rituximab (RTX), a monoclonal antibody directed against CD20, have become available. Observational studies suggest that switching to a new drug class may be more effective in uncontrolled RA than switching to a class of biologics to which the patient had unsuccessfully been exposed [1]. Information about the efficacy and safety of cycling strategies through third-line biologics is lacking. This study aimed to analyse the effectiveness and safety of switching patients to ABA as the third biological class after failure of aTNF plus RTX. The Swiss Clinical Quality Management (SCQM) programme for RA is a longitudinal population-based cohort, which has been approved by the local ethics committees of all participating centres [2]. For this analysis, we collected all the …
Published: 2011
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31. Structure and activities of adult congenital heart disease programmes in Europe

Author: Moons, P, Meijboom, F J, Baumgartner, H, Trindade, P T, Huyghe, E, Kaemmerer, H, ESC Working Group on Grown-up Congenital Heart Disease, Moons, P, Meijboom, F J, Baumgartner, H, Trindade, P T, Huyghe, E, Kaemmerer, H, and ESC Working Group on Grown-up Congenital Heart Disease
Published: 2010

32. Automated MRI Measures Identify Individuals with Mild Cognitive Impairment and Alzheimer's Disease

Author: Desikan, Rahul S., Cabral, Howard J., Hess, Christopher P., Dillon, William P., Glastonbury, Christine M., Weiner, Michael W., Schmansky, Nicholas J., Salat, David, Greve, Douglas, Buckner, Randy, Fischl, Bruce, and Alzheimer’s Disease Neuroimaging Initiative
Subjects: MRI, mild cognitive impairment, Alzheimer’s disease, diagnostic marker
Abstract: Mild cognitive impairment can represent a transitional state between normal ageing and Alzheimer's disease. Non-invasive diagnostic methods are needed to identify mild cognitive impairment individuals for early therapeutic interventions. Our objective was to determine whether automated magnetic resonance imaging-based measures could identify mild cognitive impairment individuals with a high degree of accuracy. Baseline volumetric T1-weighted magnetic resonance imaging scans of 313 individuals from two independent cohorts were examined using automated software tools to identify the volume and mean thickness of 34 neuroanatomic regions. The first cohort included 49 older controls and 48 individuals with mild cognitive impairment, while the second cohort included 94 older controls and 57 mild cognitive impairment individuals. Sixty-five patients with probable Alzheimer's disease were also included for comparison. For the discrimination of mild cognitive impairment, entorhinal cortex thickness, hippocampal volume and supramarginal gyrus thickness demonstrated an area under the curve of 0.91 (specificity 94%, sensitivity 74%, positive likelihood ratio 12.12, negative likelihood ratio 0.29) for the first cohort and an area under the curve of 0.95 (specificity 91%, sensitivity 90%, positive likelihood ratio 10.0, negative likelihood ratio 0.11) for the second cohort. For the discrimination of Alzheimer's disease, these three measures demonstrated an area under the curve of 1.0. The three magnetic resonance imaging measures demonstrated significant correlations with clinical and neuropsychological assessments as well as with cerebrospinal fluid levels of tau, hyperphosphorylated tau and abeta 42 proteins. These results demonstrate that automated magnetic resonance imaging measures can serve as an in vivo surrogate for disease severity, underlying neuropathology and as a non-invasive diagnostic method for mild cognitive impairment and Alzheimer's disease., Psychology, Version of Record
Published: 2009
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33. Managing Advanced HIV Disease in a Public Health Approach

Author: Ford, Nathan, Meintjes, Graeme, Calmy, Alexandra, Bygrave, Helen, Migone, Chantal, Vitoria, Marco, Penazzato, Martina, Vojnov, Lara, Doherty, Meg, Guideline Development Group for Managing Advanced HIV Disease and Rapid Initiation of Antiretroviral Therapy, and Letang, Emilio
Subjects: Public health, HIV (Viruses), VIH (Virus), Salut pública
Abstract: In 2017, the World Health Organization (WHO) published guidelines for the management of advanced human immunodeficiency virus (HIV) disease within a public health approach. Recent data suggest that more than a third of people starting antiretroviral therapy (ART) do so with advanced HIV disease, and an increasing number of patients re-present to care at an advanced stage of HIV disease following a period of disengagement from care. These guidelines recommend a standardized package of care for adults, adolescents, and children, based on the leading causes of morbidity and mortality: tuberculosis, severe bacterial infections, cryptococcal meningitis, toxoplasmosis, and Pneumocystis jirovecii pneumonia. A package of targeted interventions to reduce mortality and morbidity was recommended, based on results of 2 recent randomized trials that both showed a mortality reduction associated with delivery of a simplified intervention package. Taking these results and existing recommendations into consideration, WHO recommends that a package of care be offered to those presenting with advanced HIV disease; depending on age and CD4 cell count, the package may include opportunistic infection screening and prophylaxis, including fluconazole preemptive therapy for those who are cryptococcal antigen positive and without evidence of meningitis. Rapid ART initiation and intensified adherence interventions should also be proposed to everyone presenting with advanced HIV disease.

34. Activation-induced deaminase is critical for the establishment of DNA methylation patterns prior to the germinal center reaction

Author: Dieter Weichenhan, Tianlu Li, Felipe Prosper, Sven Kracker, Pere Soler-Palacín, Lennart Hammarström, Andrea Martín-Nalda, Javier Rodríguez-Ubreva, Anne Durandy, Mónica Martínez-Gallo, Romina Dieli-Crimi, Anna G. Ferreté-Bonastre, Pavlo Lutsik, Ángel F. Álvarez-Prado, Laura Ciudad, Bodo Grimbacher, Jacques G. Rivière, Carsten Speckmann, Christoph Plass, Esteban Ballestar, Christian Klemann, Amaya Vilas-Zornoza, Hassan Abolhassani, Francesc Català-Moll, Roger Colobran, Institut Català de la Salut, [Català-Moll F, Ferreté-Bonastre AG, Li T, Ciudad L] Epigenetics and Immune Disease Group, Josep Carreras Research Institute (IJC), 08916 Badalona, Barcelona, Spain. Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L’Hospitalet de Llobregat, Barcelona, Spain. [Weichenhan D, Lutsik P] Division of Cancer Epigenomics, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. [Martínez-Gallo M, Dieli-Crimi R] Divisió d’Immunologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca en Immunologia Diagnòstica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Rivière JG, Martín-Nalda A, Soler-Palacín P] Unitat de Patologia Infecciosa i Immunodeficiències de Pediatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Grup de Recerca d’Infecció en els Pacients Pediàtrics Immunodeprimits, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Spain. [Colobran R] Divisió d’Immunologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca en Immunologia Diagnòstica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Spain. Departament de Biologia Cel·lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: AcademicSubjects/SCI00010, Bisulfite sequencing, ADN, Autoimmunity, Cèl·lules B - Immunologia, Hyper-IgM Immunodeficiency Syndrome, 0302 clinical medicine, AID, Activation-induced (cytidine) deaminase, Otros calificadores::Otros calificadores::/inmunología [Otros calificadores], 0303 health sciences, B-Lymphocytes, ADN - Metilació, medicine.anatomical_structure, células::células::células sanguíneas::leucocitos::leucocitos mononucleares::linfocitos::linfocitos B [ANATOMÍA], DNA methylation, Metilació, Rearrangements, Sequencing reveals, Cèl·lules B, Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, DNA::Whole Genome Sequencing [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Naive B cell, Somatic hypermutation, Receptors, Antigen, B-Cell, Biology, Methylation, Cells::Antibody-Producing Cells::B-Lymphocytes [ANATOMY], 03 medical and health sciences, técnicas de investigación::técnicas genéticas::análisis de secuencias::análisis de secuencias de ADN::secuenciación del genoma completo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Other subheadings::Other subheadings::/immunology [Other subheadings], B-Cell receptor, Cytidine Deaminase, Genetics, medicine, Immune Tolerance, Humans, B cell, Seqüència de nucleòtids, 030304 developmental biology, B cells, Genetic Phenomena::DNA Methylation [PHENOMENA AND PROCESSES], Whole Genome Sequencing, Hypermutation, Gene regulation, Chromatin and Epigenetics, Germinal center, fenómenos genéticos::metilación del ADN [FENÓMENOS Y PROCESOS], DNA, DNA Methylation, Germinal Center, Molecular biology, Induced cytidine deaminase, Demethylation, Super-enhancers, DNA demethylation, biology.protein, Transcription factor, Class-switch recombination, Transcriptome, Immunologic Memory, 030217 neurology & neurosurgery
Abstract: Limfòcits b; Metilació de l'ADN; Genoma Linfocitos b; Metilación de ADN; Genoma B-lymphocytes; DNA methylation; Genome Activation-induced deaminase (AID) initiates antibody diversification in germinal center B cells by deaminating cytosines, leading to somatic hypermutation and class-switch recombination. Loss-of-function mutations in AID lead to hyper-IgM syndrome type 2 (HIGM2), a rare human primary antibody deficiency. AID-mediated deamination has been proposed as leading to active demethylation of 5-methycytosines in the DNA, although evidence both supports and casts doubt on such a role. In this study, using whole-genome bisulfite sequencing of HIGM2 B cells, we investigated direct AID involvement in active DNA demethylation. HIGM2 naïve and memory B cells both display widespread DNA methylation alterations, of which ∼25% are attributable to active DNA demethylation. For genes that undergo active demethylation that is impaired in HIGM2 individuals, our analysis indicates that AID is not directly involved. We demonstrate that the widespread alterations in the DNA methylation and expression profiles of HIGM2 naïve B cells result from premature overstimulation of the B-cell receptor prior to the germinal center reaction. Our data support a role for AID in B cell central tolerance in preventing the expansion of autoreactive cell clones, affecting the correct establishment of DNA methylation patterns. Spanish Ministry of Science, Innovation and Universities [SAF2017-88086-R to E.B.]; cofunded by FEDER funds/European Regional Development Fund (ERDF)—a way to build Europe. E.B is supported by Instituto de Salud Carlos III (ISCIII), Ref. AC18/00057, associated with i-PAD project (ERARE European Union program); P.L. and C.P. are supported by the German Cancer Aid project CO-CLL [70113869]; B.G. is funded by the Deutsche Forschungsgemeinschaft [GR1617/14-1/iPAD, SFB1160/2_B5, RESIST–EXC 2155–Project ID 390874280, CIBSS–EXC-2189–Project ID 390939984]; BMBF [GAIN 01GM1910A]. Funding for open access charge: Spanish Ministry of Science, Innovation and Universities [SAF2017-88086-R].
Published: 2021

35. Lymphopenia Is Associated With Poor Outcomes of Patients With Community-Acquired Pneumonia and Sepsis

Author: Catia Cilloniz, Hector Peroni, Antoni Torres, Carolina Garcia-Vidal, Jesus F. Bermejo-Martin, Albert Gabarrus, Juan M. Pericàs, Institut Català de la Salut, [Cilloniz C, Gabarrús A] Department of Pneumology, Hospital Clinic of Barcelona, Barcelona, Spain. August Pi i Sunyer Biomedical Research Institute–IDIBAPS, University of Barcelona, Barcelona, Spain. Biomedical Research Networking Centres in Respiratory Diseases (Ciberes) Barcelona, Spain. [Peroni HJ] Respiratory Medicine Unit, Internal Medicine Department, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina. Emergency Department, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina. [García-Vidal C] Infectious Disease Department, Hospital Clinic of Barcelona, Barcelona, Spain. [Pericàs JM] Infectious Disease Department, Hospital Clinic of Barcelona, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Bermejo-Martin J] Group for Biomedical Research in Sepsis (BioSepsis), Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo de San Vicente, Salamanca, Spain. Hospital Universitario Río Hortega de Valladolid, Valladolid, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: medicine.medical_specialty, Pneumònia adquirida a la comunitat - Mortalitat, Pleural effusion, enfermedades respiratorias::enfermedades pulmonares::neumonía [ENFERMEDADES], Nursing home resident, outcomes, Respiratory Tract Diseases::Lung Diseases::Pneumonia [DISEASES], law.invention, Major Articles, Sepsis, sepsis, 03 medical and health sciences, 0302 clinical medicine, Community-acquired pneumonia, law, Other subheadings::Other subheadings::Other subheadings::/mortality [Other subheadings], enfermedades hematológicas y linfáticas::enfermedades hematológicas::trastornos leucocitarios::leucopenia::linfopenia [ENFERMEDADES], Diabetes mellitus, Internal medicine, Medicine, pneumonia, 030212 general & internal medicine, Limfopènia - Diagnòstic, Otros calificadores::Otros calificadores::Otros calificadores::/mortalidad [Otros calificadores], business.industry, infecciones bacterianas y micosis::infección::infecciones adquiridas en la comunidad [ENFERMEDADES], 030208 emergency & critical care medicine, lymphopenia, medicine.disease, Intensive care unit, infection, Hemic and Lymphatic Diseases::Hematologic Diseases::Leukocyte Disorders::Leukopenia::Lymphopenia [DISEASES], Pneumonia, Infectious Diseases, AcademicSubjects/MED00290, Oncology, Observational study, Bacterial Infections and Mycoses::Infection::Community-Acquired Infections [DISEASES], business
Abstract: Background Lymphopenia is a marker of poor prognosis in patients with community-acquired pneumonia (CAP), yet its impact on outcomes in patients with CAP and sepsis remains unknown. We aim to investigate the impact of lymphopenia on outcomes, risk of intensive care unit (ICU) admission, and mortality in CAP patients with sepsis. Methods This was a retrospective, observational study of prospectively collected data from an 800-bed tertiary teaching hospital (2005–2019). Results Of the 2203 patients with CAP and sepsis, 1347 (61%) did not have lymphopenia, while 856 (39%) did. When compared with the nonlymphopenic group, patients with sepsis and lymphopenia more frequently required ICU admission (P = .001), had a longer hospital length of stay (P ˂ .001), and presented with a higher rate of in-hospital (P ˂ .001) and 30-day mortality (P = .001). Multivariable analysis showed that C-reactive protein ≥15 mg/dL, lymphopenia, pleural effusion, and acute respiratory distress syndrome within 24 hours of admission were risk factors for ICU admission; age ≥80 years was independently associated with decreased ICU admission. In addition, age ≥80 years, chronic renal disease, chronic neurologic disease, being a nursing home resident, lymphopenia, and pleural effusion were independently associated with increased 30-day mortality, whereas pneumococcal vaccination, diabetes mellitus, and fever were independently associated with reduced 30-day mortality. Conclusions Lymphopenia was independently associated with risk of ICU admission and higher in-hospital and 30-day mortality in patients with CAP and sepsis. Early identification of lymphopenia could help identify septic patients with CAP who require or will shortly require critical care.
Published: 2021

36. Human Immunodeficiency Virus Continuum of Care in 11 European Union Countries at the End of 2016 Overall and by Key Population: Have We Made Progress?

Author: Vourli, G., Noori, T., Pharris, A., Porter, K., Axelsson, M., Begovac, J., Cazein, F., Costagliola, D., Cowan, S., Croxford, S., Monforte, A. D., Delpech, V., Diaz, A., Girardi, E., Gunsenheimer-Bartmeyer, B., Hernando, V., Leierer, G., Lot, F., Nunez, O., Obel, N., Op de Coul, E., Paraskeva, D., Patrinos, S., Reiss, P., Schmid, D., Sonnerborg, A., Suligoi, B., Supervie, V., van Sighem, A., Zangerle, R., Touloumi, G., Egle, A., Kanatschnig, M., Ollinger, A., Rieger, A., Schmied, B., Wallner, E., Dewasurendra, D., Gisinger, M., Kitchen, M., Plattner, A., Rieser, E., Sarcletti, M., Greil, R., Schachner, M., Skocic, M., Muller, M., Aichwalder, R., Chromy, D., Grabmeier-Pfstershammer, K., Skoll, M., Touzeau, V., Cichon, P., Wolf-Nussmuller, S., Laferl, H., Zoufaly, A., Genger-Hackl, C., Kapper, A., Schneeberger, T., Trattner, E., Schober, G., Atzl, M., Hartmann, B., Puchhammer-Stockl, E., Berg, J., Appoyer, H., Rappold, M., Strickner, S., Schindelwig, K., Ledergerber, B., Fatkenheuer, G., Gerstof, J., Kronborg, G., Pedersen, C., Larsen, C. S., Pedersen, G., Mohey, R., Nielsen, L., Weise, L., Kvinesdal, B., Jensen, J., Abgrall, S., Bernard, L., Billaud, E., Boue, F., Boyer, L., Cabie, A., Caby, F., Canestri, A., Cotte, L., de Truchis, P., Duval, X., Duvivier, C., Enel, P., Fischer, H., Gasnault, J., Gaud, C., Grabar, S., Khuong-Josses, M. A., Launay, O., Marchand, L., Mary-Krause, M., Matheron, S., Melica-Gregoire, G., Melliez, H., Meynard, J. L., Nacher, M., Pavie, J., Piroth, L., Poizot-Martin, I., Pradier, C., Reynes, J., Rouveix, E., Simon, A., Slama, L., Tattevin, P., Tissot-Dupont, H., Biga, J., Kurth, T., Jacquemet, N., Guiguet, M., Leclercq, S., Lievre, L., Marshall, E., Roul, H., Selinger-Leneman, H., Potard, V., Benveniste, O., Breton, G., Lupin, C., Bourzam, E., Girard, P. M., Fonquernie, L., Valin, N., Lefebvre, B., Sebire, M., Pialoux, G., Lebrette, M. G., Tibaut, P., Adda, A., Hamidi, M., Cadranel, J., Lavole, A., Parrot, A., Bouchaud, O., Vignier, N., Mechai, F., Makhlouf, S., Honore, P., Bergmann, J. F., Delcey, V., Lopes, A., Sellier, P., Parrinello, M., Oksenhendler, E., Gerard, L., Molina, J. M., Rozenbaum, W., Denis, B., De Castro, N., Lascoux, C., Yazdanpanah, Y., Lariven, S., Joly, V., Rioux, C., Poupard, M., Taverne, B., Sutton, L., Masse, V., Genet, P., Wifaq, B., Gerbe, J., Grefe, S., Dupont, C., Freire Maresca, A., Reimann, E., Bloch, M., Meier, F., Mortier, E., Zeng, F., Montoya, B., Perronne, C., Mathez, D., Marigot-Outtandy, D., Berthe, H., Greder Belan, A., Terby, A., Godin Collet, C., Marque Juillet, S., Ruquet, M., Roussin-Bretagne, S., Colardelle, P., Granier, F., Laurichesse, J. J., Perronne, V., Akpan, T., Marcou, M., Daneluzzi, V., Veyssier-Belot, C., Masson, H., Welker, Y., Brazille, P., Kahn, J. E., Zucman, D., Majerholc, C., Fourn, E., Bornarel, D., Chambrin, V., Kansau, I., Raho-Moussa, M., Lelievre, J. D., Saidani, M., Chesnel, C., Dumont, C., Vittecoq, D., Derradji, O., Bolliot, C., Goujard, C., Teicher, E., Mole, M., Bourdic, K., Salmon, D., Le Jeunne, C., Guet, P., Pietri, M. P., Pannier Metzger, E., Marcou, V., Loulergue, P., Dupin, N., Morini, J. P., Deleuze, J., Gerhardt, P., Chanal, J., Weiss, L., Lucas, M. L., Jung, C., Ptak, M., Viard, J. P., Ghosn, J., Gazalet, P., Cros, A., Maignan, A., Lortholary, O., Rouzaud, C., Touam, F., Benhadj, K., Consigny, P. H., Bossi, P., Gergely, A., Cessot, G., Durand, F., Beck-Wirth, G., Michel, C., Benomar, M., Rey, D., Partisani, M., Cheneau, C., Batard, M. L., Fischer, P., Leclercq, P., Blanc, M., Morand, P., Epaulard, O., Signori-Schmuck, A., Laurichesse, H., Jacomet, C., Vidal, M., Coban, D., Casanova, S., Fresard, A., Guglielminotti, C., Botelho-Nevers, E., Brunon-Gagneux, A., Ronat, V., Verdon, R., Dargere, S., Haustraete, E., Feret, P., Goubin, P., Chavanet, P., Fillion, A., Croisier, D., Gohier, S., Arvieux, C., Souala, F., Chapplain, J. M., Ratajczak, M., Rohan, J., Faller, J. P., Ruyer, O., Gendrin, V., Toko, L., Chirouze, C., Hustache-Mathieu, L., Faucher, J. F., Proust, A., Magy-Bertrand, N., Gil, H., Meaux-Ruault, N., Sotto, A., Rouanet, I., Mauboussin, J. M., Doncesco, R., Jacques, G., May, T., Rabaud, C., Andre, M., Delestan, M., Bouillon, M. P., Bani-Sadr, F., Rouger, C., Berger, J. L., Nguyen, Y., Marchou, B., Delobel, P., Martin Blondel, G., Cuzin, L., Biezunski, N., Alric, L., Bonnet, D., Guivarch, M., Palacin, A., Payssan, V., Ajana, F., Meybeck, A., Viget, N., Pugliese, P., Roger, P. M., Rosenthal, E., Durant, J., Cua, E., Naqvi, A., Perbost, I., Risso, K., Quinsat, D., Raphael, St., Del Giudice, P., Dides, P. Y., Sambuc, R., Antolini-Bouvenot, M. S., Druart, P., Meddeb, L., Ravaux, I., Menard, A., Tomei, C., Dhiver, C., Moreau, J., Mokhtari, S., Soavi, M. J., Tomas, V., Bregigeon, S., Faucher, O., Obry-Roguet, V., Ritleng, A. S., Petit, N., Bartoli, C., Ruiz, J. M., Blanc, D., Allegre, T., Sordage, M., Riou, J. M., Faudon, C., Slama, B., Zerazhi, H., Boulat, O., Chebrek, S., Beyrne, M., Granet Brunello, P., Pellissier, L., Bonnabel, D., Cohen Valensi, R., Mouchet, B., Mboungou, G., Lafeuillade, A., Hope-Rapp, E., Hittinger, G., Philip, G., Lambry, V., Raf, F., Allavena, C., Hall, N., Reliquet, V., Chidiac, C., Ferry, T., Perpoint, T., Miailhes, P., Boibieux, A., Livrozet, J. M., Makhlouf, D., Brunel, F., Chiarello, P., Hoen, B., Lamaury, I., Fabre, I., Samar, K., Duvallon, E., Clavel, C., Stegmann, S., Walter, V., Adriouch, L., Huber, F., Vanticlke, V., Couppie, P., Abel, S., Pierre-Francois, S., Ricaud, C., Rodet, R., Wartel, G., Sautron, C., Poubeau, P., Borgherini, G., Camuset, G., Arasteh, K., Kowohl Vivantes, S., Schurmann, D., Warncke Charite, M., Rockstroh, J., Wasmuth, J., Hass, S., Jensen, B. O., Feind, C., Esser, S., Schenk-Westkamp, P., Haberl, A., Stephan, C., Plettenberg, A., Kuhlendahl, F., Adam, A., Weitner, L., Schewe, K., Goey, H., Fenske, S., Buhk, T., Stellbrink, H. J., Hofmann, C., Hansen, S., Degen, O., Heuer, M., Stoll, M., Gerschmann, S., Horst, H., Trautmann, S., Gillor, D., Bogner, J., Sonntag, B., Salzberger, B., Fritzsche, C., Adamis, G., Antoniadou, A., Chini, M., Chrysos, G., Gikas, A., Gogos, H. A., Katsarou, O., Lazanas, M., Metallidis, S., Panagopoulos, P., Paparizos, V., Papastamopoulos, V., Paraskevis, D., Psychogiou, M., Sambatakou, H., Sipsas, N. V., Pantazis, N., Papadopoulos, A., Nitsotolis, T., Xylomenos, G., Marangos, M. N., Kouramba, A., Kontos, A., Lioni, A., Tsachouridou, O., Kourkounti, S., Ganitis, A., Barbounakis, E., d'Arminio Monforte, A., Antinori, A., Andreoni, M., Castagna, A., Castelli, F., Cauda, R., Di Perri, G., Galli, M., Iardino, R., Ippolito, G., Lazzarin, A., Marchetti, G. C., Rezza, G., von Schloesser, F., Viale, P., Ceccherini-Silberstein, F., Cozzi-Lepri, A., Lo Caputo, S., Mussini, C., Puoti, M., Perno, C. F., Bai, F., Balotta, C., Bandera, A., Bonora, S., Borderi, M., Calcagno, A., Capetti, A., Capobianchi, M. 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Sotto A., Rouanet I., Mauboussin J.M., Doncesco R., Jacques G., May T., Rabaud C., Andre M., Delestan M., Bouillon M.P., Bani-Sadr F., Rouger C., Berger J.L., Nguyen Y., Marchou B., Delobel P., Martin Blondel G., Cuzin L., Biezunski N., Alric L., Bonnet D., Guivarch M., Palacin A., Payssan V., Ajana F., Meybeck A., Viget N., Pugliese P., Roger P.M., Rosenthal E., Durant J., Cua E., Naqvi A., Perbost I., Risso K., Quinsat D., Raphael St., Del Giudice P., Dides P.Y., Sambuc R., Antolini-Bouvenot M.S., Druart P., Meddeb L., Ravaux I., Menard A., Tomei C., Dhiver C., Moreau J., Mokhtari S., Soavi M.J., Tomas V., Bregigeon S., Faucher O., Obry-Roguet V., Ritleng A.S., Petit N., Bartoli C., Ruiz J.M., Blanc D., Allegre T., Sordage M., Riou J.M., Faudon C., Slama B., Zerazhi H., Boulat O., Chebrek S., Beyrne M., Granet Brunello P., Pellissier L., Bonnabel D., Cohen Valensi R., Mouchet B., Mboungou G., Lafeuillade A., Hope-Rapp E., Hittinger G., Philip G., Lambry V., Raf F., Allavena C., Hall N., Reliquet V., Chidiac C., Ferry T., Perpoint T., Miailhes P., Boibieux A., Livrozet J.M., Makhlouf D., Brunel F., Chiarello P., Hoen B., Lamaury I., Fabre I., Samar K., Duvallon E., Clavel C., Stegmann S., Walter V., Adriouch L., Huber F., Vanticlke V., Couppie P., Abel S., Pierre-Francois S., Ricaud C., Rodet R., Wartel G., Sautron C., Poubeau P., Borgherini G., Camuset G., Arasteh K., Kowohl Vivantes S., Schurmann D., Warncke Charite M., Rockstroh J., Wasmuth J., Hass S., Jensen B.O., Feind C., Esser S., Schenk-Westkamp P., Haberl A., Stephan C., Plettenberg A., Kuhlendahl F., Adam A., Weitner L., Schewe K., Goey H., Fenske S., Buhk T., Stellbrink H.J., Hofmann C., Hansen S., Degen O., Heuer M., Stoll M., Gerschmann S., Horst H., Trautmann S., Gillor D., Bogner J., Sonntag B., Salzberger B., Fritzsche C., Adamis G., Antoniadou A., Chini M., Chrysos G., Gikas A., Gogos H.A., Katsarou O., Lazanas M., Metallidis S., Panagopoulos P., Paparizos V., Papastamopoulos V., Paraskevis D., Psychogiou M., Sambatakou H., Sipsas N.V., Pantazis N., Papadopoulos A., Nitsotolis T., Xylomenos G., Marangos M.N., Kouramba A., Kontos A., Lioni A., Tsachouridou O., Kourkounti S., Ganitis A., Barbounakis E., d'Arminio Monforte A., Antinori A., Andreoni M., Castagna A., Castelli F., Cauda R., Di Perri G., Galli M., Iardino R., Ippolito G., Lazzarin A., Marchetti G.C., Rezza G., von Schloesser F., Viale P., Ceccherini-Silberstein F., Cozzi-Lepri A., Lo Caputo S., Mussini C., Puoti M., Perno C.F., Bai F., Balotta C., Bandera A., Bonora S., Borderi M., Calcagno A., Capetti A., Capobianchi M.R., Cicalini S., Cingolani A., Cinque P., Di Biagio A., Gianotti N., Gori A., Guaraldi G., Lapadula G., Lichtner M., Madeddu G., Maggiolo F., Marchetti G., Monno L., Nozza S., Pinnetti C., Quiros Roldan E., Rossotti R., Rusconi S., Santoro M.M., Saracino A., Sarmati L., Fanti I., Galli L., Lorenzini P., Rodano A., Macchia M., Tavelli A., Carletti F., Carrara S., Di Caro A., Graziano S., Petroni F., Prota G., Trufa S., Giacometti A., Costantini A., Barocci V., Angarano G., Milano E., Suardi C., Donati V., Verucchi G., Castelnuovo F., Minardi C., Menzaghi B., Abeli C., Cacopardo B., Celesia B., Vecchiet J., Falasca K., Pan A., Lorenzotti S., Sighinolf L., Segala D., Blanc P., Vichi F., Cassola G., Viscoli C., Alessandrini A., Bobbio N., Mazzarello G., Fondaco L., Bonfanti P., Molteni C., Chiodera A., Milini P., Nunnari G., Pellicano G., Rizzardini G., Cannizzo E.S., Moioli M.C., Piolini R., Bernacchia D., Salpietro S., Tincati C., Puzzolante C., Migliorino C., Sangiovanni V., Borgia G., Esposito V., Di Flumeri G., Gentile I., Rizzo V., Cattelan A.M., Marinello S., Cascio A., Trizzino M., Francisci D., Schiaroli E., Parruti G., Sozio F., Magnani G., Ursitti M.A., Cristaudo A., Vullo V., Acinapura R., Moschese D., Capozzi M., Mondi A., Rivano Capparuccia M., Iaiani G., Latini A., Gagliardini R., Plazzi M.M., De Girolamo G., Vergori A., Cecchetto M., Viviani F., De Vito A., Rossetti B., Montagnani F., Franco A., Fontana Del Vecchio R., Di Giuli C., Caramello P., Orofno G.C., Sciandra M., Bassetti M., Londero A., Manfrin V., Battagin G., Starnini G., Ialungo A., van der Valk M., Geerlings S.E., Goorhuis A., Hovius J.W., Lempkes B., Nellen F.J.B., van der Poll T., Prins J.M., van Vugt M., Wiersinga W.J., Wit F.W.M.N., van Duinen M., van Eden J., Hazenberg A., van Hes A.M.H., Pijnappel F.J.J., Smalhout S.Y., Weijsenfeld A.M., Jurriaans S., Back N.K.T., Zaaijer H.L., Berkhout B., Cornelissen M.T.E., Schinkel C.J., Wolthers K.C., Peters E.J.G., van Agtmael M.A., Bomers M., Sigalof K.C.E., Heitmuller M., Laan L.M., Ang C.W., van Houdt R., Jonges M., van Prehn J., Kuijpers T.W., Pajkrt D., Scherpbier H.J., de Boer C., van der Plas A., van den Berge M., Stegeman A., Baas S., Hage de Loof L., Wintermans B., Veenemans J., Pronk M.J.H., Ammerlaan H.S.M., de Munnik E.S., Jansz A.R., Tjhie J., Wegdam M.C.A., Deiman B., Scharnhorst V., van Eeden A., Brokking W., Elsenburg L.J.M., Nobel H., Damen M., van Kasteren M.E.E., Berrevoets M.A.H., Brouwer A.E., Adams A., de Kruijf-Van de Wiel B.A.F.M., Keelan-Pfaf S., van der Ven B., Buiting A.G.M., Murck J.L., Versteeg D., de Vries-Sluijs T.E.M.S., Bax H.I., van Gorp E.C.M., Nouwen J.L., Rijnders B.J.A., Schurink C.A.M., Verbon A., de Jong-Peltenburg N.C., Bassant N., van Beek J.E.A., Vriesde M., van Zonneveld L.M., van den Berg-Cameron H.J., de Groot J., Boucher C.A.B., Koopmans M.P.G., van Kampen J.J.A., Fraaij P.L.A., van Rossum A.M.C., Vermont C.L., van der Knaap L.C., Visser E., Branger J., Douma R.A., Duijf-Van de Ven C.J.H.M., Schippers E.F., van Nieuwkoop C., van IJperen J.M., Geilings J., van der Hut G., van Burgel N.D., Leyten E.M.S., Gelinck L.B.S., Mollema F., Davids-Veldhuis S., Wildenbeest G.S., Heikens E., Groeneveld P.H.P., Bouwhuis J.W., Lammers A.J.J., Kraan S., van Hulzen A.G.W., Kruiper M.S.M., van der Bliek G.L., Bor P.C.J., Bloembergen P., Wolfagen M.J.H.M., Ruijs G.J.H.M., Kroon F.P., de 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Pedreira J.D., Galera C., Albendin H., Iborra A., Campillo M.A., Vidal A., Amador C., Pasquau F., Ena J., Benito C., Fenoll V., Mohamed-Balghata M.O., Gomez M.A., Alberto de Zarraga M., Rivas M.E., Gorgolas M., Svedhem-Johansson V., Flamholc L., Gisslen M., Hejdeman B., Norgren H., Wendahl S., Global Health, Infectious diseases, AII - Infectious diseases, APH - Aging & Later Life, ANS - Neuroinfection & -inflammation, Internal medicine, Medical Microbiology and Infection Prevention, AMS - Rehabilitation & Development, VU University medical center, Amsterdam Gastroenterology Endocrinology Metabolism, Pediatric surgery, Neurology, Amsterdam Neuroscience - Neurodegeneration, Pulmonary medicine, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Ethics, Law & Medical humanities, APH - Quality of Care, ACS - Pulmonary hypertension & thrombosis, Amsterdam Neuroscience - Neuroinfection & -inflammation, Amsterdam Reproduction & Development (AR&D), APH - Societal Participation & Health, Pediatrics, HAL-SU, Gestionnaire, National and Kapodistrian University of Athens (NKUA), University College of London [London] (UCL), Public Health Agency of Sweden, University of Zagreb, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Statens Serum Institut [Copenhagen], Public Health England [London], Università degli Studi di Milano = University of Milan (UNIMI), Instituto de Salud Carlos III [Madrid] (ISC), Istituto Nazionale di Malattie Infettive 'Lazzaro Spallanzani' (INMI), Robert Koch Institute [Berlin] (RKI), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), University of Copenhagen = Københavns Universitet (UCPH), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Hellenic Center for Disease Control and Prevention, Amsterdam UMC - Amsterdam University Medical Center, Austrian Agency for Health and Food Safety (AGES), Department of Infectious Diseases, Institution of Medicine, Karolinska University Hospital and Karolinska Institutet, Istituto Superiore di Sanita [Rome], Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), University of Athens Medical School [Athens], Vourli, G, Noori, T, Pharris, A, Porter, K, Axelsson, M, Begovac, J, Cazein, F, Costagliola, D, Cowan, S, Croxford, S, Monforte, A, Delpech, V, Diaz, A, Girardi, E, Gunsenheimer-Bartmeyer, B, Hernando, V, Leierer, G, Lot, F, Nunez, O, Obel, N, Op de Coul, E, Paraskeva, D, Patrinos, S, Reiss, P, Schmid, D, Sonnerborg, A, Suligoi, B, Supervie, V, van Sighem, A, Zangerle, R, Touloumi, G, Egle, A, Kanatschnig, M, Ollinger, A, Rieger, A, Schmied, B, Wallner, E, Dewasurendra, D, Gisinger, M, Kitchen, M, Plattner, A, Rieser, E, Sarcletti, 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Leclercq, S, Lievre, L, Marshall, E, Roul, H, Selinger-Leneman, H, Potard, V, Benveniste, O, Breton, G, Lupin, C, Bourzam, E, Girard, P, Fonquernie, L, Valin, N, Lefebvre, B, Sebire, M, Pialoux, G, Lebrette, M, Tibaut, P, Adda, A, Hamidi, M, Cadranel, J, Lavole, A, Parrot, A, Bouchaud, O, Vignier, N, Mechai, F, Makhlouf, S, Honore, P, Bergmann, J, Delcey, V, Lopes, A, Sellier, P, Parrinello, M, Oksenhendler, E, Gerard, L, Molina, J, Rozenbaum, W, Denis, B, De Castro, N, Lascoux, C, Yazdanpanah, Y, Lariven, S, Joly, V, Rioux, C, Poupard, M, Taverne, B, Sutton, L, Masse, V, Genet, P, Wifaq, B, Gerbe, J, Grefe, S, Dupont, C, Freire Maresca, A, Reimann, E, Bloch, M, Meier, F, Mortier, E, Zeng, F, Montoya, B, Perronne, C, Mathez, D, Marigot-Outtandy, D, Berthe, H, Greder Belan, A, Terby, A, Godin Collet, C, Marque Juillet, S, Ruquet, M, Roussin-Bretagne, S, Colardelle, P, Granier, F, Laurichesse, J, Perronne, V, Akpan, T, Marcou, M, Daneluzzi, V, Veyssier-Belot, C, Masson, H, Welker, Y, Brazille, P, Kahn, J, Zucman, D, Majerholc, C, Fourn, E, Bornarel, D, Chambrin, V, Kansau, I, Raho-Moussa, M, Lelievre, J, Saidani, M, Chesnel, C, Dumont, C, Vittecoq, D, Derradji, O, Bolliot, C, Goujard, C, Teicher, E, Mole, M, Bourdic, K, Salmon, D, Le Jeunne, C, Guet, P, Pietri, M, Pannier Metzger, E, Marcou, V, Loulergue, P, Dupin, N, Morini, J, Deleuze, J, Gerhardt, P, Chanal, J, Weiss, L, Lucas, M, Jung, C, Ptak, M, Viard, J, Ghosn, J, Gazalet, P, Cros, A, Maignan, A, Lortholary, O, Rouzaud, C, Touam, F, Benhadj, K, Consigny, P, Bossi, P, Gergely, A, Cessot, G, Durand, F, Beck-Wirth, G, Michel, C, Benomar, M, Rey, D, Partisani, M, Cheneau, C, Batard, M, Fischer, P, Leclercq, P, Blanc, M, Morand, P, Epaulard, O, Signori-Schmuck, A, Laurichesse, H, Jacomet, C, Vidal, M, Coban, D, Casanova, S, Fresard, A, Guglielminotti, C, Botelho-Nevers, E, Brunon-Gagneux, A, Ronat, V, Verdon, R, Dargere, S, Haustraete, E, Feret, P, Goubin, P, Chavanet, P, Fillion, A, Croisier, D, Gohier, S, Arvieux, C, Souala, F, Chapplain, J, Ratajczak, M, Rohan, J, Faller, J, Ruyer, O, Gendrin, V, Toko, L, Chirouze, C, Hustache-Mathieu, L, Faucher, J, Proust, A, Magy-Bertrand, N, Gil, H, Meaux-Ruault, N, Sotto, A, Rouanet, I, Mauboussin, J, Doncesco, R, Jacques, G, May, T, Rabaud, C, Andre, M, Delestan, M, Bouillon, M, Bani-Sadr, F, Rouger, C, Berger, J, Nguyen, Y, Marchou, B, Delobel, P, Martin Blondel, G, Cuzin, L, Biezunski, N, Alric, L, Bonnet, D, Guivarch, M, Palacin, A, Payssan, V, Ajana, F, Meybeck, A, Viget, N, Pugliese, P, Roger, P, Rosenthal, E, Durant, J, Cua, E, Naqvi, A, Perbost, I, Risso, K, Quinsat, D, Raphael, S, Del Giudice, P, Dides, P, Sambuc, R, Antolini-Bouvenot, M, Druart, P, Meddeb, L, Ravaux, I, Menard, A, Tomei, C, Dhiver, C, Moreau, J, Mokhtari, S, Soavi, M, Tomas, V, Bregigeon, S, Faucher, O, Obry-Roguet, V, Ritleng, A, Petit, N, Bartoli, C, Ruiz, J, Blanc, D, Allegre, T, Sordage, M, Riou, J, Faudon, C, Slama, B, Zerazhi, H, Boulat, O, Chebrek, S, Beyrne, M, Granet Brunello, P, Pellissier, L, Bonnabel, D, Cohen Valensi, R, Mouchet, B, Mboungou, G, Lafeuillade, A, Hope-Rapp, E, Hittinger, G, Philip, G, Lambry, V, Raf, F, Allavena, C, Hall, N, Reliquet, V, Chidiac, C, Ferry, T, Perpoint, T, Miailhes, P, Boibieux, A, Livrozet, J, Makhlouf, D, Brunel, F, Chiarello, P, Hoen, B, Lamaury, I, Fabre, I, Samar, K, Duvallon, E, Clavel, C, Stegmann, S, Walter, V, Adriouch, L, Huber, F, Vanticlke, V, Couppie, P, Abel, S, Pierre-Francois, S, Ricaud, C, Rodet, R, Wartel, G, Sautron, C, Poubeau, P, Borgherini, G, Camuset, G, Arasteh, K, Kowohl Vivantes, S, Schurmann, D, Warncke Charite, M, Rockstroh, J, Wasmuth, J, Hass, S, Jensen, B, Feind, C, Esser, S, Schenk-Westkamp, P, Haberl, A, Stephan, C, Plettenberg, A, Kuhlendahl, F, Adam, A, Weitner, L, Schewe, K, Goey, H, Fenske, S, Buhk, T, Stellbrink, H, Hofmann, C, Hansen, S, Degen, O, Heuer, M, Stoll, M, Gerschmann, S, Horst, H, Trautmann, S, Gillor, D, Bogner, J, Sonntag, B, Salzberger, B, Fritzsche, C, Adamis, G, Antoniadou, A, Chini, M, Chrysos, G, Gikas, A, Gogos, H, Katsarou, O, Lazanas, M, Metallidis, S, Panagopoulos, P, Paparizos, V, Papastamopoulos, V, Paraskevis, D, Psychogiou, M, Sambatakou, H, Sipsas, N, Pantazis, N, Papadopoulos, A, Nitsotolis, T, Xylomenos, G, Marangos, M, Kouramba, A, Kontos, A, Lioni, A, Tsachouridou, O, Kourkounti, S, Ganitis, A, Barbounakis, E, d'Arminio Monforte, A, Antinori, A, Andreoni, M, Castagna, A, Castelli, F, Cauda, R, Di Perri, G, Galli, M, Iardino, R, Ippolito, G, Lazzarin, A, Marchetti, G, Rezza, G, von Schloesser, F, Viale, P, Ceccherini-Silberstein, F, Cozzi-Lepri, A, Lo Caputo, S, Mussini, C, Puoti, M, Perno, C, Bai, F, Balotta, C, Bandera, A, Bonora, S, Borderi, M, Calcagno, A, Capetti, A, Capobianchi, M, Cicalini, S, Cingolani, A, Cinque, P, Di Biagio, A, Gianotti, N, Gori, A, Guaraldi, G, Lapadula, G, Lichtner, M, Madeddu, G, Maggiolo, F, Monno, L, Nozza, S, Pinnetti, C, Quiros Roldan, E, Rossotti, R, Rusconi, S, Santoro, M, Saracino, A, Sarmati, L, Fanti, I, Galli, L, Lorenzini, P, Rodano, A, Macchia, M, Tavelli, A, Carletti, F, Carrara, S, Di Caro, A, Graziano, S, Petroni, F, Prota, G, Trufa, S, Giacometti, A, Costantini, A, Barocci, V, Angarano, G, Milano, E, Suardi, C, Donati, V, Verucchi, G, Castelnuovo, F, Minardi, C, Menzaghi, B, Abeli, C, Cacopardo, B, Celesia, B, Vecchiet, J, Falasca, K, Pan, A, Lorenzotti, S, Sighinolf, L, Segala, D, Blanc, P, Vichi, F, Cassola, G, Viscoli, C, Alessandrini, A, Bobbio, N, Mazzarello, G, Fondaco, L, Bonfanti, P, Molteni, C, Chiodera, A, Milini, P, Nunnari, G, Pellicano, G, Rizzardini, G, Cannizzo, E, Moioli, M, Piolini, R, Bernacchia, D, Salpietro, S, Tincati, C, Puzzolante, C, Migliorino, C, Sangiovanni, V, Borgia, G, Esposito, V, Di Flumeri, G, Gentile, I, Rizzo, V, Cattelan, A, Marinello, S, Cascio, A, Trizzino, M, Francisci, D, Schiaroli, E, Parruti, G, Sozio, F, Magnani, G, Ursitti, M, Cristaudo, A, Vullo, V, Acinapura, R, Moschese, D, Capozzi, M, Mondi, A, Rivano Capparuccia, M, Iaiani, G, Latini, A, Gagliardini, R, Plazzi, M, De Girolamo, G, Vergori, A, Cecchetto, M, Viviani, F, De Vito, A, Rossetti, B, Montagnani, F, Franco, A, Fontana Del Vecchio, R, Di Giuli, C, Caramello, P, Orofno, G, Sciandra, M, Bassetti, M, Londero, A, Manfrin, V, Battagin, G, Starnini, G, Ialungo, A, van der Valk, M, Geerlings, S, Goorhuis, A, Hovius, J, Lempkes, B, Nellen, F, van der Poll, T, Prins, J, van Vugt, M, Wiersinga, W, Wit, F, van Duinen, M, van Eden, J, Hazenberg, A, van Hes, A, Pijnappel, F, Smalhout, S, Weijsenfeld, A, Jurriaans, S, Back, N, Zaaijer, H, Berkhout, B, Cornelissen, M, Schinkel, C, Wolthers, K, Peters, E, van Agtmael, M, Bomers, M, Sigalof, K, Heitmuller, M, Laan, L, Ang, C, van Houdt, R, Jonges, M, van Prehn, J, Kuijpers, T, Pajkrt, D, Scherpbier, H, de Boer, C, van der Plas, A, van den Berge, M, Stegeman, A, Baas, S, Hage de Loof, L, Wintermans, B, Veenemans, J, Pronk, M, Ammerlaan, H, de Munnik, E, Jansz, A, Tjhie, J, Wegdam, M, Deiman, B, Scharnhorst, V, van Eeden, A, Brokking, W, Elsenburg, L, Nobel, H, Damen, M, van Kasteren, M, Berrevoets, M, Brouwer, A, Adams, A, de Kruijf-Van de Wiel, B, Keelan-Pfaf, S, van der Ven, B, Buiting, A, Murck, J, Versteeg, D, de Vries-Sluijs, T, Bax, H, van Gorp, E, Nouwen, J, Rijnders, B, Schurink, C, Verbon, A, de Jong-Peltenburg, N, Bassant, N, van Beek, J, Vriesde, M, van Zonneveld, L, van den Berg-Cameron, H, de Groot, J, Boucher, C, Koopmans, M, van Kampen, J, Fraaij, P, van Rossum, A, Vermont, C, van der Knaap, L, Visser, E, Branger, J, Douma, R, Duijf-Van de Ven, C, Schippers, E, van Nieuwkoop, C, van IJperen, J, Geilings, J, van der Hut, G, van Burgel, N, Leyten, E, Gelinck, L, Mollema, F, Davids-Veldhuis, S, Wildenbeest, G, Heikens, E, Groeneveld, P, Bouwhuis, J, Lammers, A, Kraan, S, van Hulzen, A, Kruiper, M, van der Bliek, G, Bor, P, Bloembergen, P, Wolfagen, M, Ruijs, G, Kroon, F, de Boer, M, Scheper, H, Jolink, H, Dorama, W, van Holten, N, Claas, E, Wessels, E, den Hollander, J, El Moussaoui, R, Pogany, K, Kastelijns, M, Smit, J, Smit, E, Struik-Kalkman, D, Tearno, C, van Niekerk, T, Pontesilli, O, Lowe, S, Oude Lashof, A, Posthouwer, D, Ackens, R, Burgers, K, Schippers, J, Weijenberg-Maes, B, van Loo, I, Havenith, T, Weijer, S, van Vonderen, M, Kampschreur, L, Faber, S, Steeman-Bouma, R, Weel, J, Kootstra, G, Delsing, C, van der Burg-Van de Plas, M, Heins, H, Kortmann, W, van Twillert, G, Renckens, R, Ruiter-Pronk, D, van Truijen-Oud, F, Cohen Stuart, J, Jansen, E, Hoogewerf, M, Rozemeijer, W, van der Reijden, W, Sinnige, J, Brinkman, K, van den Berk, G, Blok, W, Frissen, P, Lettinga, K, Schouten, W, Veenstra, J, Vrouenraets, S, Brouwer, C, Geerders, G, Hoeksema, K, Kleene, M, Knapen, M, van der Meche, I, Mulder-Seeleman, E, Toonen, A, Wijnands, S, Kwa, D, van Crevel, R, van Aerde, K, Doferhof, A, Henriet, S, ter Hofstede, H, Hoogerwerf, J, Keuter, M, Richel, O, Albers, M, Grintjes-Huisman, K, de Haan, M, Marneef, M, Strik-Albers, R, Rahamat-Langendoen, J, Stelma, F, Burger, D, Gisolf, E, Hassing, R, Claassen, M, ter Beest, G, van Bentum, P, Langebeek, N, Tiemessen, R, Swanink, C, van Lelyveld, S, Soetekouw, R, van der Prijt, L, van der Swaluw, J, Bermon, N, Jansen, R, Herpers, B, Veenendaal, D, Verhagen, D, Lauw, F, van Broekhuizen, M, van Wijk, M, Bierman, W, Bakker, M, Kleinnijenhuis, J, Kloeze, E, Middel, A, Scholvinck, E, Stienstra, Y, Verhage, A, Wouthuyzen-Bakker, K, Boonstra, A, de Groot-De Jonge, H, van der Meulen, P, de Weerd, D, Niesters, H, van Leer-Buter, C, Knoester, M, Hoepelman, A, Arends, J, Barth, R, Bruns, A, Ellerbroek, P, Mudrikova, T, Oosterheert, J, de Regt, M, Schadd, E, van Zoelen, M, Aarsman, K, Grifoen-Van Santen, B, de Kroon, I, van Rooijen, C, van Berkel, M, Schuurman, R, Verduyn-Lunel, F, Wensing, A, Bont, L, Geelen, S, Loefen, Y, Wolfs, T, Nauta, N, Zaheri, S, Boyd, A, Bezemer, D, Smit, C, Hillebregt, M, de Jong, A, Woudstra, T, Bergsma, D, Meijering, R, van de Sande, L, Rutkens, T, van der Vliet, S, de Groot, L, van den Akker, M, Bakker, Y, El Berkaoui, A, Bezemer, M, Bretin, N, Djoechro, E, Geerlinks, J, Kruijne, E, Lodewijk, C, Lucas, E, van der Meer, R, Munjishvili, L, Paling, F, Peeck, B, Ree, C, Regtop, R, Ruijs, Y, Schoorl, M, Schnorr, P, Tuijn, E, Veenenberg, L, Witte, E, Tuk, B, Moreno, S, del Amo, J, Dalmau, D, Navarro, M, Gonzalez, M, Blanco, J, Garcia, F, Rubio, R, Iribarren, J, Gutierrez, F, Vidal, F, Berenguer, J, Gonzalez, J, Sobrino, P, Alejos, B, Alvarez, D, Jarrin, I, Moreno, C, Munoz-Fernandez, M, Garcia-Merino, I, Rico, C, de la Fuente, J, Torre, A, Portilla, J, Merino, E, Reus, S, Boix, V, Giner, L, Gadea, C, Portilla, I, Pampliega, M, Diez, M, Rodriguez, J, Sanchez-Paya, J, Podzamczer, D, Imaz, E, Van Den Eyncle, E, Di Yacovo, S, Sumoy, M, Gomez, J, Hernandez, J, Aleman, M, Alonso, M, Hernandez, M, Diaz-Flores, F, Garcia, D, Pelazas, R, Asensi, V, Valle, E, Carton, J, Perez, V, Molina, M, Garcia, J, Carrera, E, Pulido, F, Bisbal, O, Matarranz, M, Lagarde, M, Rubio-Martin, R, Hernando, A, Bermejo, L, Dominguez, L, Arrizabalaga, J, Aramburu, M, Camino, X, Rodriguez-Arrondo, F, von Wichmann, M, Tome, L, Goenaga, M, Bustinduy, M, Galparsoro, H, Ibarguren, M, Aguado, M, Umerez, M, Masia, M, Lopez, C, Padilla, S, Navarro, A, Montolio, F, Robledano, C, Colome, J, Adsuar, A, Pascual, R, Carlos, F, Martinez, M, Fernandez, M, Garcia, E, Muga, R, Tor, J, Sanvisens, A, Bernaldo de Quiros Lopez, J, Miralles, P, Gutierrez, I, Ramirez, M, Padilla, B, Gijon, P, Carrero, A, Aldamiz-Echevarria, T, Tejerina, F, Parras, F, Balsalobre, P, Diez, C, Peraire, J, Vilades, C, Veloso, S, Vargas, M, Lopez-Dupla, M, Olona, M, Aguilar, A, Sirvent, J, Alba, V, Calavia, O, Montero, M, Lacruz, J, Blanes, M, Calabuig, E, Cuellar, S, Lopez, J, Salavert, M, de la Serna, I, Arribas, J, Montes, M, Pena, J, Arribas, B, Castro, J, Zamora, J, Perez, I, Estebanez, M, Garcia, S, Diaz, M, Alcariz, N, Mingorance, J, Montero, D, Gonzalez, A, Isabel de Jose, M, de los Santos, I, Sanz, J, Salas, A, Sarria, C, Berrocal, A, Garcia-Fraile, L, Oteo, J, Ibarra, V, Metola, L, Sanz, M, Perez-Martinez, L, Pascual, A, Ramos, C, Arazo, P, Gil, D, Jaen, A, Cairo, M, Irigoyen, D, Jordano, Q, Xercavins, M, Martinez-Lacasa, J, Velli, P, Font, R, Sanmarti, M, Ibanez, L, Rivero, M, Casado, M, Diaz, J, Uriz, J, Reparaz, J, Irigoyen, C, Arraiza, M, Segura, F, Amengual, M, Navarro, G, Sala, M, Cervantes, M, Pineda, V, Segura, V, Anton, E, Nogueras, M, Casado, J, Dronda, F, Moreno, A, Elias, M, Lopez, D, Gutierrez, C, Madrid, N, Lamas, A, Marti, P, de Diaz, A, Serrrano, S, Donat, L, Cano, A, Bernal, E, Munoz, A, Pena, A, Munoz, L, Parra, J, Alvarez, M, Chueca, N, Guillot, V, Vinuesa, D, Fernandez, J, Del Romero, J, Rodriguez, C, Puerta, T, Carrio, J, Vera, M, Ballesteros, J, Domingo, P, Sambeat, M, Lamarca, K, Mateo, G, Gutierrez, M, Fernandez, I, Antela, A, Losada, E, Riera, M, Penaranda, M, Leyes, M, Ribas, M, Campins, A, Vidal, C, Gil, L, Fanjul, F, Marinescu, C, Ribera, E, Santos, J, Marquez, M, Viciana, I, Palacios, R, Gonzalez, C, Viciana, P, Leal, M, Lopez-Cortes, L, Espinosa, N, Munoz, J, Zubero, M, Baraia-Etxaburu, J, Ibarra, S, Ferrero, O, Lopez de Munain, J, Camara, M, Lopez, I, de la Pena, M, Suarez-Garcia, I, Malmierca, E, Olalla, J, del Arco, A, de la Torre, J, Prada, J, Caracuel, Z, Lopez-Lirola, A, Lozano, A, Fernandez, E, Martinez, O, Vera, F, Martinez, L, Alcaraz, B, Jimeno, A, Poveda, E, Pernas, B, Mena, A, Grandal, M, Castro, A, Pedreira, J, Galera, C, Albendin, H, Iborra, A, Campillo, M, Vidal, A, Amador, C, Pasquau, F, Ena, J, Benito, C, Fenoll, V, Mohamed-Balghata, M, Gomez, M, Alberto de Zarraga, M, Rivas, M, Gorgolas, M, Svedhem-Johansson, V, Flamholc, L, Gisslen, M, Hejdeman, B, Norgren, H, and Wendahl, S
Subjects: Male, 0301 basic medicine, Psychological intervention, Human immunodeficiency virus (HIV), Medizin, Continuum of care, Europe, HIV infection, Key population, Sex, Anti-Retroviral Agents, Continuity of Patient Care, European Union, HIV, Humans, HIV Infections, medicine.disease_cause, key population, 0302 clinical medicine, HIV Infection, 030212 general & internal medicine, Men having sex with men, media_common, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Transmission (medicine), Infectious Diseases, AcademicSubjects/MED00290, HIV infection, continuum of care, sex, key population, Europe, Microbiology (medical), Population, Socio-culturale, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), SDG 3 - Good Health and Well-being, medicine, media_common.cataloged_instance, European union, education, Pandemics, continuum of care, sex, business.industry, SARS-CoV-2, COVID-19, medicine.disease, 030112 virology, Major Articles and Commentaries, Anti-Retroviral Agent, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Demography
Abstract: Background High uptake of antiretroviral treatment (ART) is essential to reduce human immunodeficiency virus (HIV) transmission and related mortality; however, gaps in care exist. We aimed to construct the continuum of HIV care (CoC) in 2016 in 11 European Union (EU) countries, overall and by key population and sex. To estimate progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, we compared 2016 to 2013 estimates for the same countries, representing 73% of the population in the region. Methods A CoC with the following 4 stages was constructed: number of people living with HIV (PLHIV); proportion of PLHIV diagnosed; proportion of those diagnosed who ever initiated ART; and proportion of those ever treated who achieved viral suppression at their last visit. Results We estimated that 87% of PLHIV were diagnosed; 92% of those diagnosed had ever initiated ART; and 91% of those ever on ART, or 73% of all PLHIV, were virally suppressed. Corresponding figures for men having sex with men were: 86%, 93%, 93%, 74%; for people who inject drugs: 94%, 88%, 85%, 70%; and for heterosexuals: 86%, 92%, 91%, 72%. The proportion suppressed of all PLHIV ranged from 59% to 86% across countries. Conclusions The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control., Standardized definitions were used to estimate a 4-stage continuum of human immunodeficiency virus (HIV) care in 11 European Union (EU) countries in 2016. The EU is close to the 90-90-90 target, with the main challenge being the percentage of undiagnosed infections.
Published: 2020
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37. Seeding and Establishment of Legionella pneumophila in Hospitals: Implications for Genomic Investigations of Nosocomial Legionnaires’ Disease

Author: Isabelle Podglajen, S. Jarraud, M. Mentasti, Simon R. Harris, Timothy G. Harrison, Julian Parkhill, Baharak Afshar, Victoria J. Chalker, Sophia David, Christophe Ginevra, The Wellcome Trust Sanger Institute [Cambridge], Public Health England [London], European Programme for Public Health Microbiology Training (EUPHEM), European Centre for Disease Prevention and Control (ECDC), Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Legionella, Service de Microbiologie [CHU GeorgesPompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Parkhill, Julian [0000-0002-7069-5958], Apollo - University of Cambridge Repository, European Centre for Disease Prevention and Control [Stockholm, Sweden] (ECDC), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, bacterial genomics, Diving, Disease, Bioinformatics, Legionella pneumophila, Genotype, Phylogeny, education.field_of_study, Molecular Epidemiology, Cross Infection, biology, Genomics, Hospitals, 3. Good health, Infectious Diseases, whole-genome sequencing, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, nosocomial infections, [SDV.IMM]Life Sciences [q-bio]/Immunology, Legionnaires' disease, Legionnaires\textquoteright disease, Legionnaires' Disease, Water Microbiology, Pneumonia (non-human), Sequence Analysis, Legionnaires’ disease, Microbiology (medical), Legionella, 030106 microbiology, Population, Microbiology, 03 medical and health sciences, medicine, Major Article, Humans, education, Molecular epidemiology, business.industry, Computational Biology, Sequence Analysis, DNA, DNA, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, respiratory tract diseases, Molecular Typing, Editor's Choice, business
Abstract: Summary Whole-genome sequencing can be used to support or refute suspected links between hospital water systems and Legionnaires’ disease cases. However, caveats regarding the interpretation of genomic data from Legionella pneumophila are described that should be considered in future investigations., Background. Legionnaires’ disease is an important cause of hospital-acquired pneumonia and is caused by infection with the bacterium Legionella. Because current typing methods often fail to resolve the infection source in possible nosocomial cases, we aimed to determine whether whole-genome sequencing (WGS) could be used to support or refute suspected links between cases and hospitals. We focused on cases involving a major nosocomial-associated strain, L. pneumophila sequence type (ST) 1. Methods. WGS data from 229 L. pneumophila ST1 isolates were analyzed, including 99 isolates from the water systems of 17 hospitals and 42 clinical isolates from patients with confirmed or suspected hospital-acquired infections, as well as isolates obtained from or associated with community-acquired sources of Legionnaires’ disease. Results. Phylogenetic analysis demonstrated that all hospitals from which multiple isolates were obtained have been colonized by 1 or more distinct ST1 populations. However, deep sampling of 1 hospital also revealed the existence of substantial diversity and ward-specific microevolution within the population. Across all hospitals, suspected links with cases were supported with WGS, although the degree of support was dependent on the depth of environmental sampling and available contextual information. Finally, phylogeographic analysis revealed that hospitals have been seeded with L. pneumophila via both local and international spread of ST1. Conclusions. WGS can be used to support or refute suspected links between hospitals and Legionnaires’ disease cases. However, deep hospital sampling is frequently required due to the potential coexistence of multiple populations, existence of substantial diversity, and similarity of hospital isolates to local populations.
Published: 2017
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38. Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

Author: Ezzati, M. and Zhou, B. and Bentham, J. and Di Cesare, M. and Bixby, H. and Danaei, G. and Hajifathalian, K. and Taddei, C. and Carrillo-Larco, R.M. and Djalalinia, S. and Khatibzadeh, S. and Lugero, C. and Peykari, N. and Zhang, W.Z. and Bennett, J. and Bilano, V. and Stevens, G.A. and Cowan, M.J. and Riley, L.M. and Chen, Z. and Hambleton, I.R. and Jackson, R.T. and Kengne, A.P. and Khang, Y.-H. and Laxmaiah, A. and Liu, J. and Malekzadeh, R. and Neuhauser, H.K. and Sorić, M. and Starc, G. and Sundström, J. and Woodward, M. and Abarca-Gómez, L. and Abdeen, Z.A. and Abu-Rmeileh, N.M. and Acosta-Cazares, B. and Adams, R.J. and Aekplakorn, W. and Afsana, K. and Aguilar-Salinas, C.A. and Agyemang, C. and Ahmad, N.A. and Ahmadvand, A. and Ahrens, W. and Ajlouni, K. and Akhtaeva, N. and Al-Raddadi, R. and Ali, M.M. and Ali, O. and Alkerwi, A. and Aly, E. and Amarapurkar, D.N. and Amouyel, P. and Amuzu, A. and Andersen, L.B. and Anderssen, S.A. and Ängquist, L.H. and Anjana, R.M. and Ansong, D. and Aounallah-Skhiri, H. and Araújo, J. and Ariansen, I. and Aris, T. and Arlappa, N. and Arveiler, D. and Aryal, K.K. and Aspelund, T. and Assah, F.K. and Assunção, M.C.F. and Avdicová, M. and Azevedo, A. and Azizi, F. and Babu, B.V. and Bahijri, S. and Balakrishna, N. and Bamoshmoosh, M. and Banach, M. and Bandosz, P. and Banegas, J.R. and Barbagallo, C.M. and Barceló, A. and Barkat, A. and Barros, A.J.D. and Barros, M.V. and Bata, I. and Batieha, A.M. and Batyrbek, A. and Baur, L.A. and Beaglehole, R. and Romdhane, H.B. and Benet, M. and Benson, L.S. and Bernabe-Ortiz, A. and Bernotiene, G. and Bettiol, H. and Bhagyalaxmi, A. and Bharadwaj, S. and Bhargava, S.K. and Bi, Y. and Bikbov, M. and Bista, B. and Bjerregaard, P. and Bjertness, E. and Bjertness, M.B. and Björkelund, C. and Blokstra, A. and Bo, S. and Bobak, M. and Boeing, H. and Boggia, J.G. and Boissonnet, C.P. and Bongard, V. and Borchini, R. and Bovet, P. and Braeckman, L. and Brajkovich, I. and Branca, F. and Breckenkamp, J. and Brenner, H. and Brewster, L.M. and Bruno, G. and Bueno-de-Mesquita, H.B. and Bugge, A. and Burns, C. and Bursztyn, M. and de León, A.C. and Cacciottolo, J. and Cai, H. and Cameron, C. and Can, G. and Cândido, A.P.C. and Capuano, V. and Cardoso, V.C. and Carlsson, A.C. and Carvalho, M.J. and Casanueva, F.F. and Casas, J.-P. and Caserta, C.A. and Chamukuttan, S. and Chan, A.W. and Chan, Q. and Chaturvedi, H.K. and Chaturvedi, N. and Chen, C.-J. and Chen, F. and Chen, H. and Chen, S. and Cheng, C.-Y. and Dekkaki, I.C. and Chetrit, A. and Chiolero, A. and Chiou, S.-T. and Chirita-Emandi, A. and Chirlaque, M.-D. and Cho, B. and Cho, Y. and Christofaro, D.G. and Chudek, J. and Cifkova, R. and Cinteza, E. and Claessens, F. and Clays, E. and Concin, H. and Cooper, C. and Cooper, R. and Coppinger, T.C. and Costanzo, S. and Cottel, D. and Cowell, C. and Craig, C.L. and Crujeiras, A.B. and Cruz, J.J. and D'Arrigo, G. and d'Orsi, E. and Dallongeville, J. and Damasceno, A. and Dankner, R. and Dantoft, T.M. and Dauchet, L. and Davletov, K. and De Backer, G. and De Bacquer, D. and de Gaetano, G. and De Henauw, S. and de Oliveira, P.D. and De Smedt, D. and Deepa, M. and Dehghan, A. and Delisle, H. and Deschamps, V. and Dhana, K. and Di Castelnuovo, A.F. and Dias-da-Costa, J.S. and Diaz, A. and Dickerson, T.T. and Do, H.T.P. and Dobson, A.J. and Donfrancesco, C. and Donoso, S.P. and Döring, A. and Dorobantu, M. and Doua, K. and Drygas, W. and Dulskiene, V. and Džakula, A. and Dzerve, V. and Dziankowska-Zaborszczyk, E. and Eggertsen, R. and Ekelund, U. and El Ati, J. and Elliott, P. and Elosua, R. and Erasmus, R.T. and Erem, C. and Eriksen, L. and Eriksson, J.G. and Escobedo-de la Peña, J. and Evans, A. and Faeh, D. and Fall, C.H. and Farzadfar, F. and Felix-Redondo, F.J. and Ferguson, T.S. and Fernandes, R.A. and Fernández-Bergés, D. and Ferrante, D. and Ferrari, M. and Ferreccio, C. and Ferrieres, J. and Finn, J.D. and Fischer, K. and Föger, B. and Foo, L.H. and Forslund, A.-S. and Forsner, M. and Fouad, H.M. and Francis, D.K. and Franco, M.C. and Franco, O.H. and Frontera, G. and Fuchs, F.D. and Fuchs, S.C. and Fujita, Y. and Furusawa, T. and Gaciong, Z. and Galvano, F. and Garcia-de-la-Hera, M. and Gareta, D. and Garnett, S.P. and Gaspoz, J.-M. and Gasull, M. and Gates, L. and Geleijnse, J.M. and Ghasemian, A. and Ghimire, A. and Giampaoli, S. and Gianfagna, F. and Gill, T.K. and Giovannelli, J. and Goldsmith, R.A. and Gonçalves, H. and Gonzalez-Gross, M. and González-Rivas, J.P. and Gorbea, M.B. and Gottrand, F. and Graff-Iversen, S. and Grafnetter, D. and Grajda, A. and Grammatikopoulou, M.G. and Gregor, R.D. and Grodzicki, T. and Grøntved, A. and Grosso, G. and Gruden, G. and Grujic, V. and Gu, D. and Guan, O.P. and Gudmundsson, E.F. and Gudnason, V. and Guerrero, R. and Guessous, I. and Guimaraes, A.L. and Gulliford, M.C. and Gunnlaugsdottir, J. and Gunter, M. and Gupta, P.C. and Gupta, R. and Gureje, O. and Gurzkowska, B. and 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S.T. and McLachlan, S. and McLean, R.M. and McLean, S.B. and McNulty, B.A. and Mediene-Benchekor, S. and Medzioniene, J. and Meirhaeghe, A. and Meisinger, C. and Menezes, A.B. and Menon, G.R. and Meshram, I.I. and Metspalu, A. and Meyer, H.E. and Mi, J. and Mikkel, K. and Miller, J.C. and Minderico, C.S. and Miquel, J.F. and Miranda, J.J. and Mirrakhimov, E. and Mišigoj-Durakovic, M. and Modesti, P.A. and Mohamed, M.K. and Mohammad, K. and Mohammadifard, N. and Mohan, V. and Mohanna, S. and Yusoff, M.F.M.D. and Møllehave, L.T. and Møller, N.C. and Molnár, D. and Momenan, A. and Mondo, C.K. and Monyeki, K.D.K. and Moon, J.S. and Moreira, L.B. and Morejon, A. and Moreno, L.A. and Morgan, K. and Moschonis, G. and Mossakowska, M. and Mostafa, A. and Mota, J. and Motlagh, M.E. and Motta, J. and Msyamboza, K.P. and ThetMu, T. and Muiesan, M.L. and Müller-Nurasyid, M. and Murphy, N. and Mursu, J. and Musil, V. and Nabipour, I. and Nagel, G. and Naidu, B.M. and Nakamura, H. and Námešná, J. and 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and Peixoto, S.V. and Peltonen, M. and Pereira, A.C. and Peters, A. and Petersmann, A. and Petkeviciene, J. and Pham, S.T. and Pigeot, I. and Pikhart, H. and Pilav, A. and Pilotto, L. and Pitakaka, F. and Piwonska, A. and Plans-Rubió, P. and Polašek, O. and Porta, M. and Portegies, M.L.P. and Pourshams, A. and Poustchi, H. and Pradeepa, R. and Prashant, M. and Price, J.F. and Puder, J.J. and Puiu, M. and Punab, M. and Qasrawi, R.F. and Qorbani, M. and Bao, T.Q. and Radic, I. and Radisauskas, R. and Rahman, M. and Raitakari, O. and Raj, M. and Rao, S.R. and Ramachandran, A. and Ramos, E. and Rampal, L. and Rampal, S. and Rangel Reina, D.A. and Redon, J. and Reganit, P.M. and Ribeiro, R. and Riboli, E. and Rigo, F. and Rinke de Wit, T.F. and Ritti-Dias, R.M. and Robinson, S.M. and Robitaille, C. and Rodríguez-Artalejo, F. and Rodriguez-Perez, M.C. and Rodríguez-Villamizar, L.A. and Rojas-Martinez, R. and Romaguera, D. and Ronkainen, K. and Rosengren, A. and Roy, J.G.R. and Rubinstein, A. 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M.L. and Tynelius, P. and Tzourio, C. and Ueda, P. and Ugel, E.E. and Ulmer, H. and Uusitalo, H.M.T. and Valdivia, G. and Valvi, D. and van der Schouw, Y.T. and Van Herck, K. and Van Minh, H. and van Rossem, L. and Van Schoor, N.M. and van Valkengoed, I.G.M. and Vanderschueren, D. and Vanuzzo, D. and Vatten, L. and Vega, T. and Velasquez-Melendez, G. and Veronesi, G. and Verschuren, W.M.M. and Verstraeten, R. and Victora, C.G. and Viet, L. and Viikari-Juntura, E. and Vineis, P. and Vioque, J. and Virtanen, J.K. and Visvikis-Siest, S. and Viswanathan, B. and Vlasoff, T. and Vollenweider, P. and Voutilainen, S. and Wade, A.N. and Wagner, A. and Walton, J. and Wan Bebakar, W.M. and Wan Mohamud, W.N. and Wanderley, R.S., Jr. and Wang, M.-D. and Wang, Q. and Wang, Y.X. and Wang, Y.-W. and Wannamethee, S.G. and Wareham, N. and Wedderkopp, N. and Weerasekera, D. and Whincup, P.H. and Widhalm, K. and Widyahening, I.S. and Wiecek, A. and Wijga, A.H. and Wilks, R.J. and Willeit, J. and Willeit, P. and Williams, E.A. and Wilsgaard, T. and Wojtyniak, B. and Wong-McClure, R.A. and Wong, J.Y.Y. and Wong, T.Y. and Woo, J. and Wu, A.G. and Wu, F.C. and Wu, S. and Xu, H. and Yan, W. and Yang, X. and Ye, X. and Yiallouros, P.K. and Yoshihara, A. and Younger-Coleman, N.O. and Yusoff, A.F. and Zainuddin, A.A. and Zambon, S. and Zampelas, A. and Zdrojewski, T. and Zeng, Y. and Zhao, D. and Zhao, W. and Zheng, W. and Zheng, Y. and Zhu, D. and Zhussupov, B. and Zimmermann, E. and Cisneros, J.Z. and NCD Risk Factor Collaboration (NCD-RisC), Imperial College London, London, W2 1PG, United Kingdom, Imperial College London, United Kingdom, University of Kent, United Kingdom, Middlesex University, United Kingdom, Harvard TH Chan School of Public Health, United States, Cleveland Clinic, United States, Universidad Peruana Cayetano Heredia, Peru, Tehran University of Medical Sciences, Iran, Ministry of Health and Medical Education, Iran, Brandeis University, United States, Mulago Hospital, Uganda, Uganda Heart Institute, Uganda, World Health Organization, Switzerland, University of Oxford, United Kingdom, The University of the West Indies, Barbados, University of Auckland, New Zealand, South African Medical Research Council, South Africa, Seoul National University, South Korea, National Institute of Nutrition, India, Capital Medical University Beijing An Zhen Hospital, China, Robert Koch Institute, Germany, German Center for Cardiovascular Research, Germany, University of Zagreb, Croatia, University of Ljubljana, Slovenia, Uppsala University, Sweden, University of New South Wales, Australia, Caja Costarricense de Seguro Social, Costa Rica, Al-Quds University, Palestine, Birzeit University, Palestine, Instituto Mexicano del Seguro Social, Mexico, The University of Adelaide, Australia, Mahidol University, Thailand, BRAC, Bangladesh, Instituto Nacional de Ciencias Médicas y Nutricion, Mexico, University of Amsterdam, Netherlands, Ministry of Health Malaysia, Malaysia, Non- Communicable Diseases Research Center, Iran, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Germany, National Center for Diabetes and Endocrinology, Jordan, Kazakh National Medical University, Kazakhstan, King Abdulaziz University, Saudi Arabia, Universiti Malaysia Sabah, Malaysia, Luxembourg Institute of Health, Luxembourg, World Health Organization Regional Office for the Eastern Mediterranean, Egypt, Bombay Hospital and Medical Research Centre, India, Lille University and Hospital, France, London School of Hygiene and Tropical Medicine, United Kingdom, Western Norway University of Applied Sciences, Norway, Norwegian School of Sport Sciences, Norway, Bispebjerg and Frederiksberg Hospitals, Denmark, Madras Diabetes Research Foundation, India, Komfo Anokye Teaching Hospital, Ghana, National Institute of Public Health, Tunisia, Universidade do Porto, Portugal, Norwegian Institute of Public Health, Norway, Strasbourg University and Hospital, France, Nepal Health Research Council, Nepal, University of Iceland, Iceland, University of Yaoundé 1, Cameroon, Federal University of Pelotas, Brazil, Regional Authority of Public Health, Banska Bystrica, Slovakia, University of Porto Medical School, Portugal, Shahid Beheshti University of Medical Sciences, Iran, Indian Council of Medical Research, India, University of Science and Technology, Yemen, Medical University of Lodz, Poland, Medical University of Gdansk, Poland, Universidad Autónoma de Madrid, Spain, University of Palermo, Italy, Pan American Health Organization, United States, Université Mohammed V de Rabat, Morocco, University of Pernambuco, Brazil, Dalhousie University, Canada, Jordan University of Science and Technology, Jordan, University of Sydney, Australia, University Tunis El Manar, Tunisia, CAFAM University Foundation, Colombia, University of Utah School of Medicine, United States, Lithuanian University of Health Sciences, Lithuania, University of São Paulo, Brazil, BJ Medical College, India, Chirayu Medical College, India, SL Jain Hospital, India, Shanghai Jiao-Tong University School of Medicine, China, Ufa Eye Research Institute, Russian Federation, University of Southern Denmark, Denmark, University of Greenland, Greenland, University of Oslo, Norway, University of Gothenburg, Sweden, National Institute for Public Health and the Environment, Netherlands, University of Turin, Italy, University College London, United Kingdom, German Institute of Human Nutrition, Germany, Universidad de la República, Uruguay, CEMIC, Argentina, Toulouse University School of Medicine, France, University Hospital of Varese, Italy, Ministry of Health, Seychelles, University of Lausanne, Switzerland, Ghent University, Belgium, Universidad Central de Venezuela, Venezuela, Bielefeld University, Germany, German Cancer Research Center, Germany, Cork Institute of Technology, Ireland, Hadassah-Hebrew University Medical Center, Israel, Universidad de La Laguna, Spain, University of Malta, Malta, Vanderbilt University, United States, Canadian Fitness and Lifestyle Research Institute, Canada, Istanbul University, Turkey, Universidade Federal de Juiz de Fora, Brazil, Cardiologia di Mercato S. Severino, Italy, Karolinska Institutet, Sweden, University of Porto, Portugal, Santiago de Compostela University, Spain, Associazione Calabrese di Epatologia, Italy, India Diabetes Research Foundation, India, Duke-NUS Medical School, Singapore, National Institute of Medical Statistics, India, Academia Sinica, Taiwan, Capital Institute of Pediatrics, China, Duke University, United States, Kailuan General Hospital, China, The Gertner Institute for Epidemiology and Health Policy Research, Israel, University of Bern, Switzerland, Ministry of Health and Welfare, Taiwan, Victor Babes University of Medicine and Pharmacy Timisoara, Romania, Murcia Regional Health Council, Spain, Seoul National University College of Medicine, South Korea, Korea Centers for Disease Control and Prevention, South Korea, Universidade Estadual Paulista, Brazil, Medical University of Silesia, Poland, Charles University in Prague, Czech Republic, Carol Davila University of Medicine and Pharmacy, Romania, Katholieke Universiteit Leuven, Belgium, Agency for Preventive and Social Medicine, Austria, University of Southampton, United Kingdom, IRCCS Istituto Neurologico Mediterraneo Neuromed, Italy, Institut Pasteur de Lille, France, CIBEROBN, Spain, National Council of Research, Italy, Universidade Federal de Santa Catarina, Brazil, Eduardo Mondlane University, Mozambique, Bispebjerg and Frederiksberg Hospital, Denmark, Lille University Hospital, France, Erasmus Medical Center Rotterdam, Netherlands, University of Montreal, Canada, French Public Health Agency, France, Universidade do Vale do Rio dos Sinos, Brazil, National Council of Scientific and Technical Research, Argentina, National Institute of Nutrition, Viet Nam, University of Queensland, Australia, Istituto Superiore di Sanità, Italy, Universidad de Cuenca, Ecuador, Helmholtz Zentrum München, Germany, Ministère de la Santé et de la Lutte Contre le Sida, Cote d'Ivoire, The Cardinal Wyszynski Institute of Cardiology, Poland, University of Latvia, Latvia, National Institute of Nutrition and Food Technology, Tunisia, Institut Hospital del Mar d'Investigacions Mèdiques, Spain, University of Stellenbosch, South Africa, Karadeniz Technical University, Turkey, National Institute for Health and Welfare, Finland, Queen's University of Belfast, United Kingdom, University of Zurich, Switzerland, Centro de Salud Villanueva Norte, Spain, The University of the West Indies, Jamaica, Hospital Don Benito-Villanueva de la Serena, Spain, Ministry of Health, Argentina, Council for Agricultural Research and Economics, Italy, Pontificia Universidad Católica de Chile, Chile, University of Manchester, United Kingdom, University of Tartu, Estonia, Universiti Sains Malaysia, Malaysia, Umeå University, Sweden, Dalarna University, Sweden, Federal University of São Paulo, Brazil, Hospital Universitario Son Espases, Spain, Hospital de Clinicas de Porto Alegre, Brazil, Universidade Federal do Rio Grande do Sul, Brazil, Kindai University, Japan, Kyoto University, Japan, Medical University of Warsaw, Poland, University of Catania, Italy, CIBER en Epidemiología y Salud Pública, Spain, University of KwaZulu-Natal, South Africa, Geneva University Hospitals, Switzerland, Australian Bureau of Statistics, Australia, Wageningen University, Netherlands, B P Koirala Institute of Health Sciences, Nepal, University of Insubria, Italy, Ministry of Health, Israel, The Andes Clinic of Cardio-Metabolic Studies, Venezuela, National Institute of Hygiene, Epidemiology and Microbiology, Cuba, Université de Lille 2, France, Institute for Clinical and Experimental Medicine, Czech Republic, Children'sMemorial Health Institute, Poland, Alexander Technological Educational Institute, Greece, Jagiellonian University Medical College, Poland, Azienda Ospedaliera Universitaria Policlinico Vittorio Emanuele, Italy, University of Novi Sad, Serbia, National Center of Cardiovascular Diseases, China, Singapore Eye Research Institute, Singapore, Icelandic Heart Association, Iceland, Universidad Icesi, Colombia, King's College London, United Kingdom, International Agency for Research on Cancer, France, Healis-Sekhsaria Institute for Public Health, India, Eternal Heart Care Centre and Research Institute, India, University of Ibadan, Nigeria, Children's Memorial Health Institute, Poland, Institute for Clinical Effectiveness and Health Policy, Argentina, Danish Cancer Society Research Centre, Denmark, Kyushu University, Japan, Tulane University, United States, Chinese Center for Disease Control and Prevention, China, Academic Medical Center of University of Amsterdam, Netherlands, National Institute of Public Health, Mexico, Oulu University Hospital, Finland, Chronic Diseases Research Center, Iran, University of Hong Kong, Hong Kong, The Chinese University of Hong Kong, Hong Kong, University of Western Australia, Australia, Celal Bayar University, Turkey, Heart Institute, Brazil, Fundación Oftalmológica de Santander, Colombia, University of Oran 1, Algeria, Independent Public Health Specialist, Myanmar, Ministry of Health, Myanmar, Peking University, China, VU University Medical Center and VU University, Netherlands, American University of Beirut, Lebanon, Cairo University, Egypt, National Institute of Health and Nutrition, Japan, Aga Khan University, Pakistan, UHC Zagreb, Croatia, Niigata University, Japan, Hadassah University Medical Center, Israel, Duke- NUS Medical School, Singapore, Norwegian University of Science and Technology, Norway, University of Zagreb School of Medicine, Croatia, Heart Foundation, Australia, National Health Insurance Service, South Korea, Guangzhou 12th Hospital, China, Simon Fraser University, Canada, Ruprecht-Karls- University of Heidelberg, Germany, Research Centre for Prevention and Health, Denmark, World Health Organization Country Office, India, Czestochowa University of Technology, Poland, University of Crete, Greece, Universiti Kebangsaan Malaysia, Malaysia, Johns Hopkins Bloomberg School of Public Health, United States, University of Eastern Finland, Finland, National Institute of Epidemiology, India, University of Münster, Germany, Israel Center for Disease Control, Israel, Research Institute for Primordial Prevention of Noncommunicable Disease, Iran, VU University Medical Center, Netherlands, Kyrgyz State Medical Academy, Kyrgyzstan, Research Institute of Child Nutrition, Germany, University of Cambridge, United Kingdom, Medical University of Innsbruck, Austria, Muhimbili University of Health and Allied Sciences, Tanzania, National Cancer Center, South Korea, Institute of Tropical Medicine, Belgium, Tartu University Clinics, Estonia, Ministry of Health and Quality of Life, Mauritius, Polish Academy of Sciences Anthropology Unit in Wroclaw, Poland, University of Zürich, Switzerland, University of Groningen, Netherlands, North-West University, South Africa, National Institute of Public Health, Czech Republic, University of Jyväskylä, Finland, Amrita Institute of Medical Sciences, India, All India Institute of Medical Sciences, India, African Population and Health Research Center, Kenya, Ministerio de Salud Pública, Cuba, Sahlgrenska Academy, Sweden, Endocrinology and Metabolism Research Center, Iran, Food and Agriculture Organization of the United Nations, Italy, National University of Singapore, Singapore, Tampere University Hospital, Finland, University of Cape Town, South Africa, West Virginia University, United States, Oswaldo Cruz Foundation Rene Rachou Research Institute, Brazil, National Taiwan University, Taiwan, University of Chinese Academy of Sciences, China, University Medicine Greifswald, Germany, Consejería de Sanidad Junta de Castilla y León, Spain, University of Uppsala, Sweden, Universidade Federal de Ouro Preto, Brazil, The Jikei University School of Medicine, Japan, National Research Council, Italy, Baker Heart and Diabetes Institute, Australia, Agricultural University of Athens, Greece, Hospital Israelita Albert Einstein, Brazil, Shiraz University of Medical Sciences, Iran, Institute of Internal and Preventive Medicine, Russian Federation, Harokopio University, Greece, University of Otago, New Zealand, University of Padova, Italy, Lausanne University Hospital, Switzerland, CIBERCV, Spain, Emory University, United States, UiT The Arctic University of Norway, Norway, Cape Peninsula University of Technology, South Africa, Gorgas Memorial Institute of Health Studies, Panama, Brown University, United States, University of Edinburgh, United Kingdom, Statistics Canada, Canada, University College Dublin, Ireland, Institut National de la Santé et de la Recherche Médicale, France, Lusófona University, Portugal, Universita' degli Studi di Firenze, Italy, Ain Shams University, Egypt, Hypertension Research Center, Iran, University of Pécs, Hungary, Seoul National University Children's Hospital, South Korea, University Medical Science, Cuba, Universidad de Zaragoza, Spain, RCSI Dublin, Ireland, La Trobe University, Australia, International Institute of Molecular and Cell Biology, Poland, Ahvaz Jundishapur University of Medical Sciences, Iran, Gorgas Memorial Institute of Public Health, Panama, World Health Organization Country Office, Malawi, Department of Public Health, Myanmar, University of Brescia, Italy, Bushehr University of Medical Sciences, Iran, Ulm University, Germany, Kobe University, Japan, Suraj Eye Institute, India, University Medicine of Greifswald, Germany, INSERM, France, National Institute of Hygiene and Epidemiology, Viet Nam, The University of Pharmacy and Medicine of Ho Chi Minh City, Viet Nam, Hanoi Medical University, Viet Nam, National Hospital of Endocrinology, Viet Nam, Miami Veterans Affairs Healthcare System, United States, University of Turku Tyks, Finland, Heartfile, Pakistan, Eastern Mediterranean Public Health Network, Jordan, Tachikawa General Hospital, Japan, Academic Hospital of Paramaribo, Suriname, Ministry of Health, Brunei Darussalam, University of Madeira, Portugal, MRC Lifecourse Epidemiology Unit, United Kingdom, Aarhus University, Denmark, Kwame Nkrumah University of Science and Technology, Ghana, Institute for Social and Preventive Medicine, Switzerland, University of Coimbra, Portugal, Cancer Prevention and Research Institute, Italy, Ruprecht-Karls-University of Heidelberg, Germany, IRCCS Casa Sollievo della Sofferenza, Italy, Zayed University, United Arab Emirates, Catholic University of Daegu, South Korea, Jivandeep Hospital, India, University Hospital Centre Zagreb, Croatia, University Medical Center Utrecht, Netherlands, Vietnam National Heart Institute, Viet Nam, University of Sarajevo, Bosnia and Herzegovina, Cardiovascular Prevention Centre Udine, Italy, Ministry of Health and Medical Services, Solomon Islands, Public Health Agency of Catalonia, Spain, University of Split, Croatia, Digestive Oncology Research Center, Iran, Digestive Disease Research Institute, Iran, Alborz University of Medical Sciences, Iran, Ministry of Health, Viet Nam, University of Turku, Finland, Universiti Putra Malaysia, Malaysia, University of Malaya, Malaysia, University of Valencia, Spain, University of the Philippines, Philippines, Minas Gerais State Secretariat for Health, Brazil, Health Center San Agustín, Spain, PharmAccess Foundation, Netherlands, Universidade Nove de Julho, Brazil, Public Health Agency of Canada, Canada, Canarian Health Service, Spain, Universidad Industrial de Santander, Colombia, Instituto Nacional de Salud Pública, Mexico, Sitaram Bhartia Institute of Science and Research, India, Marmara University, Turkey, CIBER de Epidemiología y Salud Pública, Spain, University of Helsinki, Finland, National Institute of Health, Peru, Catalan Department of Health, Spain, Universidade de Lisboa, Portugal, University of Sao Paulo Clinics Hospital, Brazil, South Karelia Social and Health Care District, Finland, Isfahan Cardiovascular Research Center, Iran, Research and Education Institute of Child Health, Cyprus, Hospital Italiano de Buenos Aires, Argentina, Lagos State University College of Medicine, Nigeria, The University of Tokyo, Japan, Samsung Medical Center, South Korea, Federal University of Santa Catarina, Brazil, St Vincent's Hospital, Australia, Academic Medical Center Amsterdam, Netherlands, University of Bari, Italy, Lund University, Sweden, University of Copenhagen, Denmark, Institut Régional de Santé Publique, Benin, University of Bordeaux, France, University of Leuven, Belgium, Bonn University, Germany, Sotiria Hospital, Greece, National Institute of Public Health- National Institute of Hygiene, Poland, Fu Jen Catholic University, Taiwan, Ministry of Health, Jordan, Health Service of Murcia, Spain, IB-SALUT Area de Salut de Menorca, Spain, Institut de Recherche pour le Développement, France, Hellenic Health Foundation, Greece, GovernmentMedical College, India, Sefako Makgatho Health Science University, South Africa, Addis Ababa University, Ethiopia, Dasman Diabetes Institute, Kuwait, Ministry of Health, New Zealand, Universidad Centro-Occidental Lisandro Alvarado, Venezuela, University of Tampere Tays Eye Center, Finland, Utrecht University, Netherlands, Hanoi University of Public Health, Viet Nam, Amsterdam Public Health Research Institute, Netherlands, Universidade Federal de Minas Gerais, Brazil, Finnish Institute of Occupational Health, Finland, Universidad Miguel Hernandez, Spain, North Karelian Center for Public Health, Finland, University of the Witwatersrand, South Africa, University of Strasbourg, France, Institute for Medical Research, Malaysia, Xinjiang Medical University, China, Capital Medical University, China, St George's, University of London, United Kingdom, Medical University of Vienna, Austria, Universitas Indonesia, Indonesia, National Institute of Public Health-National Institute of Hygiene, Poland, Institute of Food and Nutrition Development of Ministry of Agriculture, China, Children's Hospital of Fudan University, China, University of Cyprus, Cyprus, Universiti Teknologi MARA, Malaysia, Inner Mongolia Medical University, China, Universidad Politécnica de Madrid, Spain, State University of Montes Claros, Brazil, and University of Limpopo, South Africa
Subjects: sense organs
Abstract: Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups. © The Author(s) 2018.
Published: 2018

39. Long-term outcomes of switching to gonadotrophins versus continuing with clomiphene citrate, with or without intrauterine insemination, in women with normogonadotropic anovulation and clomiphene failure

Author: E M, Bordewijk, T I, Jannink, N S, Weiss, T, de Vries, M, Nahuis, A, Hoek, M, Goddijn, B W, Mol, M, van Wely, Reproductive Origins of Adult Health and Disease (ROAHD), Obstetrics and gynaecology, Amsterdam Reproduction & Development (AR&D), Internal medicine, Gastroenterology and hepatology, Center for Reproductive Medicine, APH - Methodology, and APH - Personalized Medicine
Subjects: cumulative live birth, Reproductive Medicine, clomiphene citrate, Rehabilitation, PCOS, Obstetrics and Gynecology, ovulation induction, gonadotrophins
Abstract: STUDY QUESTIONWhat are the long-term outcomes after allocation to use of gonadotrophins versus clomiphene citrate (CC) with or without IUI in women with normogonadotropic anovulation and clomiphene failure?SUMMARY ANSWERAbout four in five women with normogonadotropic anovulation and CC failure had a live birth, with no evidence of a difference in pregnancy outcomes between the allocated groups.WHAT IS KNOWN ALREADYCC has long been used as first line treatment for ovulation induction in women with normogonadotropic anovulation. Between 2009 and 2015, a two-by-two factorial multicentre randomized clinical trial in 666 women with normogonadotropic anovulation and six cycles of CC failure was performed (M-ovin trial). This study compared a switch to gonadotrophins with continued treatment with CC for another six cycles, with or without IUI within 8 months. Switching to gonadotrophins increased the chance of conception leading to live birth by 11% over continued treatment with CC after six failed ovulatory cycles, at a cost of €15 258 per additional live birth. The addition of IUI did not significantly increase live birth rates.STUDY DESIGN, SIZE, DURATIONIn order to investigate the long-term outcomes of switching to gonadotrophins versus continuing treatment with CC, and undergoing IUI versus continuing with intercourse, we conducted a follow-up study. The study population comprised all women who participated in the M-ovin trial.PARTICIPANTS/MATERIALS, SETTING, METHODSThe participating women were asked to complete a web-based questionnaire. The primary outcome of this study was cumulative live birth. Secondary outcomes included clinical pregnancies, multiple pregnancies, miscarriage, stillbirth, ectopic pregnancy, fertility treatments, neonatal outcomes and pregnancy complications.MAIN RESULTS AND THE ROLE OF CHANCEWe approached 564 women (85%), of whom 374 (66%) responded (184 allocated to gonadotrophins; 190 to CC). After a median follow-up time of 8 years, 154 women in the gonadotrophin group had a live birth (83.7%) versus 150 women in the CC group (78.9%) (relative risk (RR) 1.06, 95% CI 0.96–1.17). A second live birth occurred in 85 of 184 women (49.0%) in the gonadotrophin group and in 85 of 190 women (44.7%) in the CC group (RR 1.03, 95% CI 0.83–1.29). Women allocated to gonadotrophins had a third live birth in 6 of 184 women (3.3%) and women allocated to CC had a third live birth in 14 of 190 women (7.4%). There were respectively 12 and 11 twins in the gonadotrophin and CC groups. The use of fertility treatments in the follow-up period was comparable between both groups. In the IUI group, a first live birth occurred in 158 of 192 women (82.3%) and while in the intercourse group, 146 of 182 women (80.2%) reached at least one live birth (RR: 1.03 95% CI 0.93–1.13; 2.13%, 95% CI −5.95, 10.21).LIMITATIONS, REASONS FOR CAUTIONWe have complete follow-up results for 57% of the women.There were 185 women who did not respond to the questionnaire, while 102 women had not been approached due to missing contact details. Five women had not started the original trial.WIDER IMPLICATIONS OF THE FINDINGSWomen with normogonadotropic anovulation and CC failure have a high chance of reaching at least one live birth. In terms of pregnancy rates, the long-term differences between initially switching to gonadotrophins are small compared to continuing treatment with CC.STUDY FUNDING/COMPETING INTEREST(S)The original study received funding from the Dutch Organization for Health Research and Development (ZonMw number: 80-82310-97-12067). A.H. reports consultancy for development and implementation of a lifestyle App, MyFertiCoach, developed by Ferring Pharmaceutical Company. M.G. receives unrestricted grants for scientific research and education from Ferring, Merck and Guerbet. B.W.M. is supported by an NHMRC Investigatorgrant (GNT1176437). B.W.M. reports consultancy for ObsEva and Merck and travel support from Merck. All other authors have nothing to declare.TRIAL REGISTRATION NUMBERThis follow-up study was registered in the OSF Register, https://osf.io/pf24m. The original M-ovin trial was registered in the Netherlands Trial Register, number NTR1449.
Published: 2023
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40. Access flow volume (Qa) and survival in a haemodialysis population

Author: Maarten G. J. Snoeijs, Reshabh Yadav, Michael W.M. Gerrickens, Roel H.D. Vaes, Marc R. Scheltinga, Sander M. J. van Kuijk, MUMC+: KIO Kemta (9), RS: CAPHRI - R2 - Creating Value-Based Health Care, Vascular Surgery, MUMC+: MA Med Staf Spec Vaatchirurgie (9), and RS: Carim - V03 Regenerative and reconstructive medicine vascular disease
Subjects: Male, Dilution technique, medicine.medical_treatment, Population, survival, STENOSIS, DISEASE, End stage renal disease, Arteriovenous Shunt, Surgical, Renal Dialysis, VASCULAR ACCESS, Medicine, Humans, In patient, CARDIAC-OUTPUT, education, Cardiovascular mortality, Aged, Proportional Hazards Models, Aged, 80 and over, RISK, Transplantation, education.field_of_study, PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY, end-stage renal disease, Receiver operating characteristic, business.industry, ARTERIOVENOUS-FISTULA, MORTALITY, Middle Aged, access flow, haemodialysis, CREATION, ROC Curve, Nephrology, Regional Blood Flow, HEART, Hemodialysis, business, Nuclear medicine
Abstract: Background The aim of this study was to determine associations between characteristics of arteriovenous access (AVA) flow volume (Qa; mL/min) and 4-year freedom from cardiovascular mortality (CVM) in haemodialysis (HD) patients. Methods HD patients who received a primary AVA between January 2010 and December 2017 in one centre were analysed. Initial Qa was defined as the first Qa value obtained in a well-functioning AVA by a two-needle dilution technique. Actual Qa was defined as access flow at a random point in time. Changes in actual Qa were expressed per 3-month period. CVM was assessed according to the European Renal Association–European Dialysis and Transplant Association classification. The optimal cut-off point for initial Qa was identified by a receiver operating characteristics curve. A joint modelling statistical technique determined longitudinal associations between Qa characteristics and 4-year CVM. Results A total of 5208 Qa measurements (165 patients; 103 male, age 70 ± 12 years, autologous AVA n = 146, graft n = 19) were analysed. During follow-up (December 2010–January 2018, median 36 months), 79 patients (48%) died. An initial Qa Conclusions Studying novel AVA Qa characteristics may contribute to understanding excess CVM in HD patients.
Published: 2022

41. Exploratory Analysis of the Economically Justifiable Price of a Hypothetical RSV Vaccine for Older Adults in the Netherlands and the United Kingdom

Author: Zeevat, F, Luttjeboer, J, Paulissen, J H J, van der Schans, J, Beutels, P, Boersma, C, Postma, M J, Nair, Harish, Campbell, Harry, Openshaw, Peter, Beutels, Philippe, Bont, Louis, Pollard, Andrew, Molero, Eva, Martinon-Torres, Federico, Heikkinen, Terho, Meijer, Adam, Kølsen Fischer, Thea, van den Berge, Maarten, Giaquinto, Carlo, Kieffer, Alexia, Demont, Clarisse, Gallichan, Scott, Dormitzer, Philip, Leach, Amanda, Dillon, Laura, Aerssens, Jeroen, Rosen, Brian, RESCEU Investigators, Value, Affordability and Sustainability (VALUE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Microbes in Health and Disease (MHD)
Subjects: Rsv vaccine, business.industry, Cost effectiveness, Incidence (epidemiology), MEDLINE, The Netherlands, Exploratory analysis, United Kingdom, Vaccination, Infectious Diseases, Elderly, Older adults, Preventive intervention, Immunology and Allergy, Medicine, Cost-effectiveness, Human medicine, Respiratory Syncytial Virus, business, Biology, health care economics and organizations, RSV Vaccines, Demography
Abstract: Background In older adults, the burden of respiratory syncytial virus (RSV) resembles that of influenza and may even be considered worse due to the lack of preventive interventions. This study was performed to identify the available literature on RSV infection in older adults, and to provide updated exploratory results of the cost-effectiveness of a hypothetical RSV vaccine in the Netherlands and the United Kingdom. Methods A literature search was performed in Medline and EMBASE on 11 November 2019, which served as input for a static decision-tree model that was used to estimate the EJP, for an RSV vaccine applying different willingness-to-pay (WTP) thresholds. WTP thresholds applied were €20 000 and €50 000 per quality-adjusted life-year for the Netherlands, and £20 000 and £30 000 per quality-adjusted life-year for the United Kingdom. Analyses were—in line with country-specific guidelines—conducted from a societal perspective for the Netherlands and a third-party payer perspective for the United Kingdom. The robustness of the cost-effectiveness results was tested in sensitivity analysis. Results After screening the literature, 3 studies for the Netherlands and 6 for the United Kingdom remained to populate the country-specific models. In the base case analysis for the Netherlands (mean RSV incidence, 3.32%), justifiable vaccine prices of €16.38 and €50.03 were found, based on applying the lower and higher WTP thresholds, respectively. Similarly, for the United Kingdom (mean incidence, 7.13%), vaccine prices of £72.29 and £109.74 were found, respectively. Conclusion RSV vaccination may well be cost-effective in both the Netherlands and the United Kingdom, depending on the exact RSV incidence, vaccine effectiveness and price. However, sensitivity analysis showed that the results were robust based on varying the different parameter estimates and assumptions. With RSV vaccines reaching the final stages of development, a strong need exists for cost-effectiveness studies to understand economically justifiable pricing of the vaccine.
Published: 2022

42. Hypomyelination with atrophy of the basal ganglia and cerebellum: further delineation of the phenotype and genotype–phenotype correlation

Author: Hamilton, Em, Polder, E, Vanderver, A, Naidu, S, Schiffmann, R, Fisher, K, Raguz, Ab, Blumkin, L, H-ABC Research Group, Battini, R, Van Berkel CG, Waisfisz, Q, Simons, C, Taft, Rj, Abbink, Te, Wolf, Ni, Van Der Knaap MS, Functional Genomics, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Pediatric surgery, Human genetics, and NCA - Brain mechanisms in health and disease
Subjects: Cerebral atrophy, Dystonia, Pathology, medicine.medical_specialty, Ataxia, medicine.diagnostic_test, Putamen, Magnetic resonance imaging, Original Articles, Biology, medicine.disease, Leukoencephalopathy, Atrophy, SDG 3 - Good Health and Well-being, medicine, Cerebellar atrophy, Neurology (clinical), medicine.symptom
Abstract: Hypomyelination with atrophy of the basal ganglia and cerebellum is a rare leukoencephalopathy that was identified using magnetic resonance imaging in 2002. In 2013, whole exome sequencing of 11 patients with the disease revealed that they all had the same de novo mutation in TUBB4A, which encodes tubulin β-4A. We investigated the mutation spectrum in a cohort of 42 patients and the relationship between genotype and phenotype. Patients were selected on the basis of clinical and magnetic resonance imaging abnormalities that are indicative of hypomyelination with atrophy of the basal ganglia and cerebellum. Genetic testing and a clinical inventory were performed, and sequential magnetic resonance images were evaluated using a standard protocol. The heterozygous TUBB4A mutation observed in the first 11 patients was the most common (25 patients). Additionally, 13 other heterozygous mutations were identified, located in different structural domains of tubulin β-4A. We confirmed that the mutations were de novo in all but three patients. In two of these three cases we lacked parental DNA and in one the mutation was also found in the mother, most likely due to mosaicism. Patients showed a phenotypic continuum ranging from neonatal to childhood disease onset, normal to delayed early development and slow to more rapid neurological deterioration. Neurological symptomatology consisted of extrapyramidal movement abnormalities, spasticity, ataxia, cognitive deficit and sometimes epilepsy. Three patients died and the oldest living patient was 29 years of age. The patients' magnetic resonance images showed an absent or disappearing putamen, variable cerebellar atrophy and highly variable cerebral atrophy. Apart from hypomyelination, myelin loss was evident in several cases. Three severely affected patients had similar, somewhat atypical magnetic resonance image abnormalities. The study results were strongly suggestive of a genotype-phenotype correlation. The 25 patients with the common c.745G>A mutation generally had a less rapidly progressive disease course than the 17 cases with other TUBB4A mutations. Overall, this work demonstrates that the distinctive magnetic resonance imaging pattern for hypomyelination with atrophy of the basal ganglia and cerebellum defines a homogeneous clinical phenotype of variable severity. Patients almost invariably have prominent extrapyramidal movement abnormalities, which are rarely seen in patients with hypomyelination of different origin. A dominant TUBB4A mutation is also associated with dystonia type 4, in which magnetic resonance images of the brain seem normal. It is highly likely that there is a disease continuum associated with TUBB4A mutations, of which hypomyelination with atrophy of the basal ganglia and cerebellum and dystonia type 4 are the extremes. This would indicate that extrapyramidal movement abnormalities constitute the core feature of the disease spectrum related to dominant TUBB4A mutations and that all other features are variable. © 2014 The Author.
Published: 2014
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43. Deficiency of myeloid PHD proteins aggravates atherogenesis via macrophage apoptosis and paracrine fibrotic signalling

Author: Marion J.J. Gijbels, Judith C. Sluimer, Ulf Hedin, Christoph Kuppe, J. De Bruijn, Thomas L. Theelen, Javier Perales-Patón, Rafael Kramann, Peter Carmeliet, Barend Mees, Leon J. Schurgers, Chris P. M. Reutelingsperger, E. Biessen, Elke Marsch, Andrew H. Baker, Jasper A. F. Demandt, Han Jin, Julio Saez-Rodriguez, K. van Kuijk, Ljubica Perisic Matic, Internal Medicine, RS: Carim - B07 The vulnerable plaque: makers and markers, Pathologie, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Moleculaire Genetica, Vascular Surgery, MUMC+: MA Med Staf Spec Vaatchirurgie (9), RS: Carim - V03 Regenerative and reconstructive medicine vascular disease, Biochemie, and RS: Carim - B02 Vascular aspects thrombosis and Haemostasis
Subjects: 0301 basic medicine, EXPRESSION, Myeloid, Physiology, INHIBITION, Apoptosis, Inflammation, HYPOXIA, HIF-1-ALPHA, 030204 cardiovascular system & hematology, Mice, 03 medical and health sciences, Paracrine signalling, 0302 clinical medicine, In vivo, VASCULAR CALCIFICATION, fibroblasts, Physiology (medical), medicine, OSTEOPONTIN, Animals, Macrophage, RNA, Messenger, Osteopontin, Hypoxia, Fibroblast, Mice, Knockout, Gene knockdown, biology, Chemistry, Macrophages, Fibroblasts, Fibrosis, Plaque, Atherosclerotic, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, ATHEROSCLEROSIS, inflammation, CELLS, Cancer research, biology.protein, RNA, Collagen, atherosclerosis, medicine.symptom, Cardiology and Cardiovascular Medicine
Abstract: AIMS: Atherosclerotic plaque hypoxia is detrimental for macrophage function. Prolyl hydroxylases (PHDs) initiate cellular hypoxic responses, possibly influencing macrophage function in plaque hypoxia. Thus, we aimed to elucidate the role of myeloid PHDs in atherosclerosis.METHODS & RESULTS: Myeloid specific PHD knockout (PHDko) mice were obtained via bone marrow transplantation (PHD1ko, PHD3ko) or conditional knockdown through lysozyme M-driven Cre recombinase (PHD2cko). Mice were fed high cholesterol diet for 6-12 weeks to induce atherosclerosis. Aortic root plaque size was significantly augmented 2.6-fold in PHD2cko, and 1.4-fold in PHD3ko compared to controls, but was unchanged in PHD1ko mice. Macrophage apoptosis was promoted in PHD2cko and PHD3ko mice in vitro and in vivo, via the HIF1α/BNIP3 axis. Bulk and single cell RNA data of PHD2cko bone-marrow-derived macrophages (BMDM) and plaque macrophages, respectively, showed enhanced HIF1α/BNIP3 signaling, which was validated in vitro by siRNA silencing. Human plaque BNIP3 mRNA was positively associated with plaque necrotic core size, suggesting similar pro-apoptotic effects in human. Further, PHD2cko plaques displayed enhanced fibrosis, while macrophage collagen breakdown by matrix metalloproteinases, collagen production and proliferation were unaltered. Instead, PHD2cko BMDMs enhanced fibroblast collagen secretion in a paracrine manner. In silico analysis of macrophage-fibroblast communication predicted SPP1 (osteopontin) signaling as regulator, which was corroborated by enhanced plaque SPP1 protein in vivo. Increased SPP1 mRNA expression upon PHD2cko was preferentially observed in foamy plaque macrophages expressing "triggering receptor expressed on myeloid cells-2" (TREM2hi) evidenced by single-cell RNA, but not in neutrophils. This confirmed enhanced fibrotic signaling by PHD2cko macrophages to fibroblasts, in vitro as well as in vivo.CONCLUSION: Myeloid PHD2cko and PHD3ko enhanced atherosclerotic plaque growth and macrophage apoptosis, while PHD2cko macrophages further activated collagen secretion by fibroblasts in vitro, likely via paracrine SPP1 signaling through TREM2hi macrophages.TRANSLATIONAL OUTLOOK: This study shows that myeloid PHD isoforms PHD2 and PHD3 worsen plaque characteristics and phenotype, such as plaque size, macrophage accumulation, apoptosis, and collagen accumulation in mice. We show both direct effects on macrophages and paracrine effects of macrophage PHD2 loss on vessel wall fibroblast populations. Broad spectrum-PHD inhibitors, e.g. Roxadustat, are currently being prescribed to chronic kidney disease patients, who are already at risk for cardiovascular disease. When considering this study and the pro-fibrotic and pro-apoptotic effects we report, broad PHD inhibition may therefore be sub-optimal and more targeted PHD inhibition of PHD1 should be considered.
Published: 2022
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44. Standard ganciclovir dosing results in slow decline of cytomegalovirus viral loads

Author: Märtson, Anne-Grete, Sturkenboom, Marieke G. G., Knoester, Marjolein, van der Werf, Tjip S., Alffenaar, Jan-Willem C., Hope, William, Edwina, Angela E., Burgerhof, Johannes G. M., Berger, Stefan P., de Joode, Anoek, Damman, Kevin, Verschuuren, Erik A. M., Blokzijl, Hans, Bakker, Martijn, Touw, Daan J., rtson, Anne-Grete Mä, and Microbes in Health and Disease (MHD)
Subjects: Pharmacology, Microbiology (medical), Antiviral Agents/therapeutic use, viruses, virus diseases, Cytomegalovirus, Viral Load, Antiviral Agents, Editor's Choice, AcademicSubjects/MED00290, Infectious Diseases, Ganciclovir/therapeutic use, AcademicSubjects/MED00740, Humans, Valganciclovir, Pharmacology (medical), AcademicSubjects/MED00230, Ganciclovir, Original Research
Abstract: Background Cytomegalovirus (CMV) can cause severe disease, including rejection in transplant recipients. Ganciclovir and its oral prodrug valganciclovir have been used as first-line therapy for CMV disease in transplant recipients. The exposure targets of ganciclovir are not exactly known, and toxicity and resistance have interfered with ganciclovir therapy. Objectives To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of ganciclovir in transplant recipients. Methods We used patient data from a previous observational study on ganciclovir therapeutic drug monitoring (TDM) in prophylaxis and therapy. The ganciclovir concentrations and CMV viral loads were determined during routine clinical care. The PK/PD population modelling and simulations were done with non-parametric methodology using the Pmetrics program. Results Eighty-five patients were included in the PK modelling. The final PK model was a two-compartment model with first-order absorption and elimination. A subset of 17 patients on CMV therapy were included in the PD modelling. A median of 4 (range 2–8) viral loads were obtained per patient. A simulation of 10 000 patients showed that an approximately 1 log10 reduction of CMV viral load will be observed after 12.5 days at the current recommended dose. Conclusions The developed linked PK/PD population model and subsequent PD simulations showed slow decline of CMV viral load and it appears that dosing of (val)ganciclovir in this study might have been inadequate to achieve fast reduction of viral load. It is clear that further studies are needed to specify the PD effects of ganciclovir by performing systematic measurements of both ganciclovir concentrations and CMV viral loads.
Published: 2022

45. Viral coinfections in hospitalized Coronavirus disease 2019 patients recruited to the international severe acute respiratory and emerging infections consortium WHO clinical characterisation protocol UK study

Author: Vink, Elen, Davis, Chris, Maclean, Alasdair, Pascall, David, Mcdonald, Sarah, Gunson, Rory, Hardwick, Hayley, Oosthuyzen, Wilna, Openshaw, Peter, Baillie, J Kenneth, Semple, Malcolm, Ho, Antonia, Barclay, Wendy, Bogaert, Debby, Chand, Meera, Chechi, Kanta, Cooke, Graham, Filipe, Ana da Silva, Silva, Thushan De, Docherty, Annemarie, Correia, Gonçalo dos Santos, Dumas, Marc-Emmanuel, Dunning, Jake, Fletcher, Tom, Green, Christoper, Greenhalf, William, Griffin, Julian, Gupta, Rishi, Harrison, Ewen, Hiscox, Julian, Ho, Antonia Ying Wai, Holden, Karl, Horby, Peter, Ijaz, Samreen, Khoo, Saye, Klenerman, Paul, Law, Andrew, Lewis, Matthew, Liggi, Sonia, Lim, Wei Shen, Maslen, Lynn, Mentzer, Alexander, Merson, Laura, Meynert, Alison, Moore, Shona, Noursadeghi, Mahdad, Olanipekun, Michael, Osagie, Anthonia, Palmarini, Massimo, Palmieri, Carlo, Paxton, William, Pollakis, Georgios, Price, Nicholas, Rambaut, Andrew, Robertson, David, Russell, Clark, Sancho-Shimizu, Vanessa, Sands, Caroline, Scott, Janet, Sigfrid, Louise, Solomon, Tom, Sriskandan, Shiranee, Stuart, David, Summers, Charlotte, Swann, Olivia, Takats, Zoltan, Takis, Panteleimon, Tedder, Richard, Thompson, A, Thomson, Emma, Thwaites, Ryan, Turtle, Lance Cw, Zambon, Maria, Drake, Thomas, Fairfield, Cameron, Knight, Stephen, Mclean, Kenneth, Murphy, Derek, Norman, Lisa, Pius, Riinu, Shaw, Catherine, Connor, Marie, Dalton, Jo, Gamble, Carrol, Girvan, Michelle, Halpin, Sophie, Harrison, Janet, Jackson, Clare, Lee, James, Marsh, Laura, Plotkin, Daniel, Roberts, Stephanie, Saviciute, Egle, Clohisey, Sara, Hendry, Ross, Knight, Susan, Lahnsteiner, Eva, Leeming, Gary, Norris, Lucy, Scott-Brown, James, Tait, Sarah, Wham, Murray, Clark, Richard, Coutts, Audrey, Donnelly, Lorna, Fawkes, Angie, Gilchrist, Tammy, Hafezi, Katarzyna, Macgillivray, Louise, Maclean, Alan, Mccafferty, Sarah, Morrice, Kirstie, Murphy, Lee, Wrobel, Nicola, Adeniji, Kayode, Agranoff, Daniel, Agwuh, Ken, Ail, Dhiraj, Aldera, Erin, Alegria, Ana, Allen, Sam, Angus, Brian, Ashish, Abdul, Atkinson, Dougal, Bari, Shahedal, Barlow, Gavin, Barnass, Stella, Barrett, Nicholas, Bassford, Christopher, Basude, Sneha, Baxter, David, Beadsworth, Michael, Bernatoniene, Jolanta, Berridge, John, Berry, Colin, Best, Nicola, Bothma, Pieter, Brittain-Long, Robin, Bulteel, Naomi, Burden, Tom, Burtenshaw, Andrew, Caruth, Vikki, Chadwick, David, Chambler, Duncan, Chee, Nigel, Child, Jenny, Chukkambotla, Srikanth, Clark, Tom, Collini, Paul, Cosgrove, Catherine, Cupitt, Jason, Cutino-Moguel, Maria-Teresa, Dark, Paul, Dawson, Chris, Dervisevic, Samir, Donnison, Phil, Douthwaite, Sam, Drummond, Andrew, Durand, Ingrid, Dushianthan, Ahilanadan, Dyer, Tristan, Evans, Cariad, Eziefula, Chi, Fegan, Chrisopher, Finn, Adam, Fullerton, Duncan, Garg, Sanjeev, Garg, Atul, Gkrania-Klotsas, Effrossyni, Godden, Jo, Goldsmith, Arthur, Graham, Clive, Grammatikopoulos, Tassos, Hardy, Elaine, Hartshorn, Stuart, Harvey, Daniel, Havalda, Peter, Hawcutt, Daniel, Hobrok, Maria, Hodgson, Luke, Hormis, Anil, Howard, Joanne, Jacobs, Michael, Jain, Susan, Jennings, Paul, Kaliappan, Agilan, Kasipandian, Vidya, Kegg, Stephen, Kelsey, Michael, Kendall, Jason, Kerrison, Caroline, Kerslake, Ian, Koch, Oliver, Koduri, Gouri, Koshy, George, Laha, Shondipon, Laird, Steven, Larkin, Susan, Leiner, Tamas, Lillie, Patrick, Limb, James, Linnett, Vanessa, Little, Jeff, Lyttle, Mark, Macmahon, Michael, Macnaughton, Emily, Mankregod, Ravish, Masson, Huw, Matovu, Elijah, Mccullough, Katherine, Mcewen, Ruth, Meda, Manjula, Mills, Gary, Minton, Jane, Mirfenderesky, Mariyam, Mohandas, Kavya, Mok, Quen, Moon, James, Moore, Elinoor, Morgan, Patrick, Morris, Craig, Mortimore, Katherine, Moses, Samuel, Mpenge, Mbiye, Mulla, Rohinton, Murphy, Michael, Nagarajan, Thapas, Nagel, Megan, Nelson, Mark, Norris, Lillian, O'Shea, Matthew, Ostermann, Marlies, Otahal, Igor, Pais, Mark, Panchatsharam, Selva, Papakonstantinou, Danai, Papineni, Padmasayee, Paraiso, Hassan, Patel, Brij, Pattison, Natalie, Pepperell, Justin, Peters, Mark, Phull, Mandeep, Pintus, Stefania, Planche, Tim, Post, Frank, Price, David, Prout, Rachel, Rae, Nikolas, Reschreiter, Henrik, Reynolds, Tim, Richardson, Neil, Roberts, Mark, Roberts, Devender, Rose, Alistair, Rousseau, Guy, Ruge, Bobby, Ryan, Brendan, Saluja, Taranprit, Cole, Sarah, Schmid, Matthias, Shah, Aarti, Shankar-Hari, Manu, Shanmuga, Prad, Sharma, Anil, Shawcross, Anna, Pooni, Jagtur Singh, Sizer, Jeremy, Smith, Richard, Snelson, Catherine, Spittle, Nick, Staines, Nikki, Stambach, Tom, Stewart, Richard, Subudhi, Pradeep, Szakmany, Tamas, Tatham, Kate, Thomas, Jo, Thompson, Chris, Thompson, Robert, Tridente, Ascanio, Tupper-Carey, Darell, Twagira, Mary, Vallotton, Nick, Vancheeswaran, Rama, Vincent-Smith, Lisa, Visuvanathan, Shico, Vuylsteke, Alan, Waddy, Sam, Wake, Rachel, Walden, Andrew, Welters, Ingeborg, Whitehouse, Tony, Whittaker, Paul, Whittington, Ashley, Wijesinghe, Meme, Williams, Martin, Wilson, Lawrence, Winchester, Stephen, Wiselka, Martin, Wolverson, Adam, Wootton, Daniel, Workman, Andrew, Yates, Bryan, Young, Peter, Shaw, Victoria, Ahmed, Katie, Armstrong, Jane, Ashworth, Milton, Asiimwe, Innocent, Bakshi, Siddharth, Barlow, Samantha, Booth, Laura, Brennan, Benjamin, Bullock, Katie, Carlucci, Nicola, Cass, Emily, Catterall, Benjamin, Clark, Jordan, Clarke, Emily, Cooper, Louise, Cox, Helen, Davis, Christopher, Dincarslan, Oslem, Carracedo, Alejandra Doce, Dunn, Chris, Dyer, Philip, Elliott, Angela, Evans, Anthony, Finch, Lorna, Fisher, Lewis, Flaherty, Lisa, Foster, Terry, Garcia-Dorival, Isabel, Gunning, Philip, Hartley, Catherine, Holmes, Anthony, Jensen, Rebecca, Jones, Christopher, Jones, Trevor, Khandaker, Shadia, King, Katharine, Kiy, Robyn, Koukorava, Chrysa, Lake, Annette, Lant, Suzannah, Latawiec, Diane, Lavelle-Langham, Lara, Lefteri, Daniella, Lett, Lauren, Livoti, Lucia, Mancini, Maria, Massey, Hannah, Maziere, Nicole, Mcevoy, Laurence, Mclauchlan, John, Metelmann, Soeren, Miah, Nahida, Middleton, Joanna, Mitchell, Joyce, Murphy, Ellen, Penrice-Randal, Rebekah, Pilgrim, Jack, Prince, Tessa, Reynolds, Will, Ridley, P Matthew, Sales, Debby, Shears, Rebecca, Small, Benjamin, Subramaniam, Krishanthi, Szemiel, Agnieska, Taggart, Aislynn, Tanianis-Hughes, Jolanta, Thomas, Jordan, Trochu, Erwan, Tonder, Libby Van, Wilcock, Eve, Zhang, J Eunice, Keating, Seán, Donegan, Cara, Spencer, Rebecca, Donohue, Chloe, Griffiths, Fiona, Investigators, ISARIC4C, Monterey Bay Aquarium Research Institute (MBARI), Monterey Bay Aquarium Research Institute, West of Scotland Specialist Virology Centre, Gartnavel General Hospital, Glasgow, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, University of Liverpool, Alder Hey Children's Hospital, Department of Infectious Disease Epidemiology [London] (DIDE), Imperial College London, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Imperial College London - National Heart and Lung Institute, and Division of Computational and Systems Medicine, Imperial College London, London, SW7 2AZ, UK
Subjects: Infectious Diseases, PCR, rhinovirus, Oncology, SARS-CoV-2, [SDV]Life Sciences [q-bio], surveillance, disease severity, respiratory virus
Abstract: Background We conducted this study to assess the prevalence of viral coinfection in a well characterized cohort of hospitalized coronavirus disease 2019 (COVID-19) patients and to investigate the impact of coinfection on disease severity. Methods Multiplex real-time polymerase chain reaction testing for endemic respiratory viruses was performed on upper respiratory tract samples from 1002 patients with COVID-19, aged Results A coinfecting virus was detected in 20 (2.0%) participants. Multivariable analysis revealed no significant risk factors for coinfection, although this may be due to rarity of coinfection. Likewise, ordinal logistic regression analysis did not demonstrate a significant association between coinfection and increased disease severity. Conclusions Viral coinfection was rare among hospitalized COVID-19 patients in the United Kingdom during the first 18 months of the pandemic. With unbiased prospective sampling, we found no evidence of an association between viral coinfection and disease severity. Public health interventions disrupted normal seasonal transmission of respiratory viruses; relaxation of these measures mean it will be important to monitor the prevalence and impact of respiratory viral coinfections going forward.
Published: 2022
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46. Use of sponge-assisted endoluminal vacuum therapy for the treatment of colorectal anastomotic leaks: expert panel consensus

Author: Willem A Bemelman, Alberto Arezzo, Tomasz Banasiewicz, Richard Brady, Eloy Espín-Basany, Omar Faiz, Rosa M Jimenez-Rodriguez, Institut Català de la Salut, [Bemelman WA] Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. [Arezzo A] Department of Surgical Sciences, University of Torino, Turin, Italy. [Banasiewicz T] Poznan University of Medical Sciences, Department of General, Endocrinological Surgery and Gastroenterological Oncology, Poznań, Poland. [Brady R] Newcastle Centre for Bowel Disease Research Group, Department of Colorectal Surgery, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK. [Espín-Basany E] Unitat de Cirurgia de Còlon i Recte, Servei de Cirurgia General i Digestiva, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Faiz O] St Mark’s Hospital, London, UK. [Jimenez-Rodriguez RM] Unidad de Coloproctología, Department of Surgery, Hospital Universitario Virgen del Rocío, Sevilla, Spain, Vall d'Hebron Barcelona Hospital Campus, Surgery, CCA - Cancer Treatment and Quality of Life, and Amsterdam Gastroenterology Endocrinology Metabolism
Subjects: Consensus, Còlon - Càncer - Cirurgia - Complicacions, Vacuum, Presa de decisions, Anastomotic Leak, Otros calificadores::Otros calificadores::/cirugía [Otros calificadores], General Medicine, Recte - Càncer - Cirurgia - Complicacions, neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales [ENFERMEDADES], Psychological Phenomena::Mental Processes::Thinking::Decision Making::Consensus [PSYCHIATRY AND PSYCHOLOGY], Other subheadings::Other subheadings::/surgery [Other subheadings], Pathological Conditions, Signs and Symptoms::Pathologic Processes::Postoperative Complications::Anastomotic Leak [DISEASES], Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [DISEASES], afecciones patológicas, signos y síntomas::procesos patológicos::complicaciones posoperatorias::fuga anastomótica [ENFERMEDADES], Humans, fenómenos psicológicos::procesos mentales::pensamiento::toma de decisión::consenso [PSIQUIATRÍA Y PSICOLOGÍA], Colorectal Neoplasms, Negative-Pressure Wound Therapy
Abstract: Background Anastomotic leaks represent one of the most significant complications of colorectal surgery and are the primary cause of postoperative mortality and morbidity. Sponge-assisted endoluminal vacuum therapy (EVT) has emerged as a minimally invasive technique for the management of anastomotic leaks; however, there are questions regarding patient selection due to the heterogeneous nature of anastomotic leaks and the application of sponge-assisted EVT by surgeons. Method Seven colorectal surgical experts participated in a modified nominal group technique to establish consensus regarding key questions that arose from existing gaps in scientific evidence and the variability in clinical practice. After a bibliographic search to identify the available evidence and sequential meetings with participants, a series of recommendations and statements were formulated and agreed upon. Results Thirty-seven recommendations and statements on the optimal use of sponge-assisted EVT were elaborated on and unanimously agreed upon by the group of experts. The statements and recommendations answer 10 key questions about the indications, benefits, and definition of the success rate of sponge-assisted EVT for the management of anastomotic leaks. Conclusion Although further research is needed to resolve clinical and technical issues associated with sponge-assisted EVT, the recommendations and statements produced from this project summarize critical aspects to consider when using sponge-assisted EVT and to assist those involved in the management of patients with colorectal anastomotic leaks.
Published: 2022

47. National point prevalence study on carriage of multidrug-resistant microorganisms in Dutch long-term care facilities in 2018

Author: Esther, van Kleef, Cornelia C H, Wielders, Leo M, Schouls, Sabiena G, Feenstra, Cees M P M, Hertogh, Marc J M, Bonten, Yolanda, van Weert, Alma, Tostmann, Mariken, van der Lubben, Sabine C, de Greeff, Elma, Smeets, and Microbes in Health and Disease (MHD)
Subjects: 0301 basic medicine, Microbiology (medical), Klebsiella pneumoniae, 030106 microbiology, Population, Prevalence, beta-Lactamases/genetics, beta-Lactamases, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, 0302 clinical medicine, Antibiotic resistance, Environmental health, Escherichia coli, Medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, education, Escherichia coli Infections, Pharmacology, education.field_of_study, Molecular epidemiology, biology, business.industry, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, bacterial infections and mycoses, Long-Term Care, Long-term care, Escherichia coli/genetics, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Infectious Diseases, Carriage, Multilocus sequence typing, business, Multilocus Sequence Typing
Abstract: Objectives Long-term care facilities (LTCFs) may act as a reservoir of ESBL-producing Enterobacterales (ESBL-E) and carbapenemase-producing Enterobacterales (CPE) for hospitals and the general population. In this study, we estimated the prevalence and molecular epidemiology of rectal carriage with ESBL-E and CPE in residents of Dutch LTCFs between March 2018 and December 2018. Methods LTCFs were geographically selected across the country. For each LTCF, a random sample of residents were tested for ESBL-E and CPE in 2018. To identify risk factors for high carriage prevalence and/or individual carriage, characteristics of LTCFs and of a subset of the tested residents were collected. WGS was conducted on isolates from LTCFs with an ESBL-E prevalence of >10% and all CPE isolates to identify institutional clonal transmission. Results A total of 4420 residents of 159 LTCFs were included. The weighted mean ESBL-E prevalence was 8.3% (95% CI: 6.8–10.0) and no CPE were found. In 53 LTCFs (33%), where ESBL-E prevalence was >10%, MLST using WGS (wgMLST) was performed. This included 264 isolates, the majority being Escherichia coli (n = 224) followed by Klebsiella pneumoniae (n = 30). Genetic clusters were identified in more than half (30/53; 57%) of high ESBL-positive LTCFs. Among the E. coli isolates, blaCTX-M-15 (92/224; 41%) and blaCTX-M-27 (40/224; 18%) were the most prevalent ESBL-encoding genes. For K. pneumoniae isolates, the most common was blaCTX-M-15 (23/30; 80%). Conclusions The estimated prevalence of ESBL-E rectal carriage in Dutch LTCFs is 8.3% and resistance is observed mainly in E. coli with predominance of blaCTX-M-15 and blaCTX-M-27. ESBL-E prevalence in LTCFs seems comparable to previously reported prevalence in hospitals and the general population.
Published: 2021

48. Birthweight and other perinatal outcomes of singletons conceived after assisted reproduction compared to natural conceived singletons in couples with unexplained subfertility

Author: INeS, Monique H. Mochtar, R I Tjon-Kon Fat, Annemieke Hoek, M. van Wely, A.J. Bensdorp, N A Danhof, Ben W.J. Mol, J Wessel, Frank J.M. Broekmans, Femke Mol, Reproductive Origins of Adult Health and Disease (ROAHD), Center for Reproductive Medicine, ARD - Amsterdam Reproduction and Development, APH - Methodology, and APH - Personalized Medicine
Subjects: Male, Percentile, medicine.medical_specialty, Pregnancy Rate, Birth weight, Population, Controlled ovarian hyperstimulation, Fertilization in Vitro, 03 medical and health sciences, 0302 clinical medicine, Belgium, Ovulation Induction, Pregnancy, medicine, unexplained subfertility, Birth Weight, Humans, Prospective Studies, education, Child, laboratory procedures, reproductive and urinary physiology, 030304 developmental biology, Netherlands, Randomized Controlled Trials as Topic, 0303 health sciences, education.field_of_study, 030219 obstetrics & reproductive medicine, Obstetrics, business.industry, Reproductive Epidemiology, Rehabilitation, Obstetrics and Gynecology, Gestational age, Original Articles, medicine.disease, AcademicSubjects/MED00905, female genital diseases and pregnancy complications, ovarian stimulation, Pregnancy rate, Reproductive Medicine, birthweight, Premature birth, Infertility, perinatal outcomes, Female, business, Live birth, Follow-Up Studies
Abstract: STUDY QUESTION Does assisted reproduction, such as ovarian stimulation and/or laboratory procedures, have impact on perinatal outcomes of singleton live births compared to natural conception in couples with unexplained subfertility? SUMMARY ANSWER Compared to natural conception, singletons born after intrauterine insemination with ovarian stimulation (IUI-OS) had a lower birthweight, while singletons born after IVF had comparable birthweights, in couples with unexplained subfertility. WHAT IS KNOWN ALREADY Singletons conceived by assisted reproduction have different perinatal outcomes such as low birthweight and a higher risk of premature birth than naturally conceived singletons. This might be due to the assisted reproduction, such as laboratory procedures or the ovarian stimulation, or to an intrinsic factor in couples with subfertility. STUDY DESIGN, SIZE, DURATION We performed a prospective cohort study using the follow-up data of two randomized clinical trials performed in couples with unexplained subfertility. We evaluated perinatal outcomes of 472 live birth singletons conceived after assisted reproduction or after natural conception within the time horizon of the studies. PARTICIPANTS/MATERIALS, SETTING, METHODS To assess the possible impact of ovarian stimulation we compared the singletons conceived after IUI with FSH or clomiphene citrate (CC) and IVF in a modified natural cycle (IVF-MNC) or standard IVF with single embryo transfer (IVF-SET) to naturally conceived singletons in the same cohorts. To further look into the possible effect of the laboratory procedures, we put both IUI and IVF groups together into IUI-OS and IVF and compared both to singletons born after natural conception. We only included singletons conceived after fresh embryo transfers. The main outcome was birthweight presented as absolute weight in grams and gestational age- and gender-adjusted percentiles. We calculated differences in birthweight using regression analyses adjusted for maternal age, BMI, smoking, parity, duration of subfertility and child gender. MAIN RESULTS AND THE ROLE OF CHANCE In total, there were 472 live birth singletons. Of the 472 singleton pregnancies, 209 were conceived after IUI-OS (136 with FSH and 73 with CC as ovarian stimulation), 138 after IVF (50 after IVF-MNC and 88 after IVF-SET) and 125 were conceived naturally. Singletons conceived following IUI-FSH and IUI-CC both had lower birthweights compared to naturally conceived singletons (adjusted difference IUI-FSH −156.3 g, 95% CI −287.9 to −24.7; IUI-CC −160.3 g, 95% CI −316.7 to −3.8). When we compared IVF-MNC and IVF-SET to naturally conceived singletons, no significant difference was found (adjusted difference IVF-MNC 75.8 g, 95% CI −102.0 to 253.7; IVF-SET −10.6 g, 95% CI −159.2 to 138.1). The mean birthweight percentile was only significantly lower in the IUI-FSH group (−7.0 percentile, 95% CI −13.9 to −0.2). The IUI-CC and IVF-SET group had a lower mean percentile and the IVF-MNC group a higher mean percentile, but these groups were not significant different compared to the naturally conceived group (IUI-CC −5.1 percentile, 95% CI −13.3 to 3.0; IVF-MNC 4.4 percentile, 95% CI −4.9 to 13.6; IVF-SET −1.3 percentile, 95% CI −9.1 to 6.4). Looking at the laboratory process that took place, singletons conceived following IUI-OS had lower birthweights than naturally conceived singletons (adjusted difference −157.7 g, 95% CI −277.4 to −38.0). The IVF group had comparable birthweights with the naturally conceived group (adjusted difference 20.9 g, 95% CI −110.8 to 152.6). The mean birthweight percentile was significantly lower in the IUI-OS group compared to the natural group (−6.4 percentile, 95% CI −12.6 to −0.1). The IVF group was comparable (0.7 percentile, 95% CI −6.1 to 7.6). LIMITATIONS, REASONS FOR CAUTION The results are limited by the number of cases. The data were collected prospectively alongside the randomized controlled trials, but analyzed as treated. WIDER IMPLICATIONS OF THE FINDINGS Our data suggest IUI in a stimulated cycle may have a negative impact on the birthweight of the child and possibly on pre-eclampsia. Further research should look into the effect of different methods of ovarian stimulation on placenta pathology and pre-eclampsia in couples with unexplained subfertility using naturally conceived singletons in the unexplained population as a reference. STUDY FUNDING/COMPETING INTEREST(S) Both initial trials were supported by a grant from ZonMW, the Dutch Organization for Health Research and Development (INeS 120620027, SUPER 80-83600-98-10192). The INeS study also had a grant from Zorgverzekeraars Nederland, the Dutch association of healthcare insurers (09-003). B.W.J.M. is supported by an NHMRC investigator Grant (GNT1176437) and reports consultancy for ObsEva, Merck Merck KGaA, Guerbet and iGenomix, outside the submitted work. A.H. reports grants from Ferring Pharmaceutical company (the Netherlands), outside the submitted work. F.J.M.B. receives monetary compensation as a member of the external advisory board for Merck Serono (the Netherlands), Ferring Pharmaceutics BV (the Netherlands) and Gedeon Richter (Belgium), he receives personal fees from educational activities for Ferring BV (the Netherlands) and for advisory and consultancy work for Roche and he receives research support grants from Merck Serono and Ferring Pharmaceutics BV, outside the submitted work. The remaining authors have nothing to disclose. TRIAL REGISTRATION NUMBER INeS study Trial NL915 (NTR939); SUPER Trial NL3895 (NTR4057)
Published: 2021

49. Predominance of CTX-M-15-producing ST131 strains among ESBL-producing Escherichia coli isolated from asylum seekers in the Netherlands

Author: Xuewei Zhou, Erik Bathoorn, John W. A. Rossen, Ymkje Stienstra, Alewijn Ott, Alexander W. Friedrich, Spyros Pournaras, Sofanne J Ravensbergen, Sigrid Rosema, Silvia García-Cobos, Christina Louka, and Microbes in Health and Disease (MHD)
Subjects: Microbiology (medical), Veterinary medicine, Refugee, Population, Esbl production, Phylogenetic relatedness, Biology, medicine.disease_cause, beta-Lactamases, Escherichia coli, medicine, Humans, AcademicSubjects/MED00740, Pharmacology (medical), education, Escherichia coli Infections, Phylogeny, Netherlands, Original Research, Pharmacology, Refugees, education.field_of_study, Anti-Bacterial Agents, AcademicSubjects/MED00290, Infectious Diseases, Dutch Population, Multilocus sequence typing, AcademicSubjects/MED00230, Asylum seeker, Multilocus Sequence Typing
Abstract: ObjectivesNumerous studies show increased prevalence of MDR bacteria amongst asylum seekers, but data on the molecular profiles of such strains are limited. We aimed to evaluate the molecular profiles of ESBL-producing Escherichia coli (ESBL-E. coli) strains isolated from asylum seekers and investigate their phylogenetic relatedness.MethodsWGS data of ESBL-E. coli isolates from asylum seekers, retrieved from 1 January to 31 December 2016, were analysed to assess MLST STs, fim types, phylogroups and resistance genes. Fifty-two ESBL-E. coli isolates from the Dutch–German border region were used for genome comparison purposes as a control group.ResultsAmong 112 ESBL-E. coli isolates from asylum seekers, originating mostly from Syria (n = 40) and Iraq (n = 15), the majority belonged to ST131 (21.4%) and ST10 (17.0%). The predominant gene for β-lactam resistance was blaCTX-M-15 (67.9%), followed by the often co-detected blaTEM-1B (39.3%). No mcr or carbapenemase genes were detected. The majority of the strains belonged to phylogroups B2 (38.4%) and A (32.1%), carrying fimH27 (25%) and fimH30 (19.6%). A core genome MLST minimum spanning tree did not reveal clusters containing strains from the asylum seekers and the control group. Five clusters were formed within the asylum seeker group, by strains isolated from people originating from different countries.ConclusionsThe most frequently isolated clones in this study were isolated on a regular basis within the Dutch population before the increase in the asylum seeker population. No mcr- or carbapenemase-producing clones were detected among the asylum seeker population. Minor clustering was observed amongst the asylum seeker strains.
Published: 2021
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50. Cross-trait analyses with migraine reveal widespread pleiotropy and suggest a vascular component to migraine headache

Author: The International Headache Genetics Consortium, Siewert, Katherine M., Klarin, Derek, Damrauer, Scott M., Chang, Kyong Mi, Tsao, Philip S., Assimes, Themistocles L., Smith, George Davey, Voight, Benjamin F., Anttila, Verneri, Palta, Priit, Muona, Mikko, Kallela, Kaarlo Mikko, Koiranen, Markku, Lehtimäki, Terho, Sarin, Antti-Pekka, Wedenoja, Juho, Färkkilä, Markus, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Kurki, Mitja Ilari, Hämäläinen, Eija Inkeri, Eriksson, Johan G., Salomaa, Veikko, Heikkilä, Kauko, Männikkö, Minna, Hiekkala, Marjo, Kajanne, Risto, Kaprio, Jaakko, Aromaa, Arpo J., Raitakari, Olli, Järvelin, Marjo-Riitta, Wessman, Maija, Palotie, Aarno, Radiology & Nuclear Medicine, Epidemiology, Internal Medicine, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, Medicum, HUS Neurocenter, Clinicum, Department of Neurosciences, Department of Public Health, Neurologian yksikkö, HUS Helsinki and Uusimaa Hospital District, Research Programs Unit, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Centre of Excellence in Complex Disease Genetics, Biosciences, and Aarno Palotie / Principal Investigator
Subjects: 0301 basic medicine, Linkage disequilibrium, Genetic correlation, Epidemiology, Migraine Disorders, Population, Genome-wide association study, Bioinformatics, Corrections, 3124 Neurology and psychiatry, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Pleiotropy, Pleiotropism, Mendelian randomization, Humans, Medicine, AcademicSubjects/MED00860, migraine, education, Migraine, education.field_of_study, business.industry, Headache, 3112 Neurosciences, Genetic Pleiotropy, Mendelian Randomization Analysis, General Medicine, medicine.disease, Miscellaneous, Phenotype, 030104 developmental biology, Migranya, Cefalàlgia, business, headache, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Background Nearly a fifth of the world’s population suffer from migraine headache, yet risk factors for this disease are poorly characterized. Methods To further elucidate these factors, we conducted a genetic correlation analysis using cross-trait linkage disequilibrium (LD) score regression between migraine headache and 47 traits from the UK Biobank. We then tested for possible causality between these phenotypes and migraine, using Mendelian randomization. In addition, we attempted replication of our findings in an independent genome-wide association study (GWAS) when available. Results We report multiple phenotypes with genetic correlation (P < 1.06 × 10−3) with migraine, including heart disease, type 2 diabetes, lipid levels, blood pressure, autoimmune and psychiatric phenotypes. In particular, we find evidence that blood pressure directly contributes to migraine and explains a previously suggested causal relationship between calcium and migraine. Conclusions This is the largest genetic correlation analysis of migraine headache to date, both in terms of migraine GWAS sample size and the number of phenotypes tested. We find that migraine has a shared genetic basis with a large number of traits, indicating pervasive pleiotropy at migraine-associated loci.
Published: 2020

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