• Ensuring Food Integrity by Metrology and FAIR Data Principles.

      Rychlik, Michael; Zappa, Giovanna; Añorga, Larraitz; Belc, Nastasia; Castanheira, Isabel; Donard, Olivier F X; Kouřimská, Lenka; Ogrinc, Nives; Ocké, Marga C; Presser, Karl; Zoani, Claudia (2018)
      Food integrity is a general term for sound, nutritive, healthy, tasty, safe, authentic, traceable, as well as ethically, safely, environment-friendly, and sustainably produced foods. In order to verify these properties, analytical methods with a higher degree of accuracy, sensitivity, standardization and harmonization and a harmonized system for their application in analytical laboratories are required. In this view, metrology offers the opportunity to achieve these goals. In this perspective article the current global challenges in food analysis and the principles of metrology to fill these gaps are presented. Therefore, the pan-European project METROFOOD-RI within the framework of the European Strategy Forum on Research Infrastructures (ESFRI) was developed to establish a strategy to allow reliable and comparable analytical measurements in foods along the whole process line starting from primary producers until consumers and to make all data findable, accessible, interoperable, and re-usable according to the FAIR data principles. The initiative currently consists of 48 partners from 18 European Countries and concluded its "Early Phase" as research infrastructure by organizing its future structure and presenting a proof of concept by preparing, distributing and comprehensively analyzing three candidate Reference Materials (rice grain, rice flour, and oyster tissue) and establishing a system how to compile, process, and store the generated data and how to exchange, compare them and make them accessible in data bases.
    • Enterovirus type D68 en acute slappe verlamming: een nieuw duo?

      van Dissel, J T; Meijer, A (2017)
      Following a case of acute flaccid paralysis after infection with enterovirus type D68, we highlight current understanding of the causal role of enterovirus infection in this neurological syndrome. Acute flaccid paralysis is a rare complication of enterovirus infections. Such viruses have become a more common cause of severe respiratory-tract infections, especially in children with underlying lung disease such as asthma.
    • [Environment and the "Health in All Policies" approach-an overview].

      Zeeb, Hajo; Hilderink, Henk; Forberger, Sarah (2018-04-24)
      One quarter of the global disease burden could be avoided with management strategies for environmental risk factors such as air and water pollution, food contamination, injuries and poor road safety. Many decisions influencing health are made outside the health sector; thus, the joint consideration and implementation of health and environmental factors in the relevant policies are becoming increasingly important.
    • Environmental and nutritional impact of diets with less meat and dairy – Modeling studies in Dutch children

      Temme, E. H. M.; Bakker, H. M. E.; Brosens, M. C. C.; Verkaik-Kloosterman, J.; van Raaij, J. M. A.; Ocké, M. C. (2013-10-14)
    • Environmental assessment of bio-based chemicals in early-stage development: a review of methods and indicators

      Broeren, Martijn L.M.; Zijp, Michiel C.; Waaijers-van der Loop, Susanne L.; Heugens, Evelyn H.W.; Posthuma, Leo; Worrell, Ernst; Shen, Li; Copernicus Institute of Sustainable Development, Group Energy and Resources; Utrecht University; Utrecht the Netherlands; National Institute for Public Health and the Environment; Bilthoven the Netherlands; National Institute for Public Health and the Environment; Bilthoven the Netherlands; National Institute for Public Health and the Environment; Bilthoven the Netherlands; National Institute for Public Health and the Environment; Bilthoven the Netherlands; Copernicus Institute of Sustainable Development, Group Energy and Resources; Utrecht University; Utrecht the Netherlands; Copernicus Institute of Sustainable Development, Group Energy and Resources; Utrecht University; Utrecht the Netherlands (2017-07)
    • Environmental contamination with Toxocara spp. eggs in public parks and playground sandpits of Greater Lisbon, Portugal.

      Otero, David; Alho, Ana M; Nijsse, Rolf; Roelfsema, Jeroen; Overgaauw, Paul; Madeira de Carvalho, Luís (2018-02-06)
      Toxocarosis is a zoonotic parasitic disease transmitted from companion animals to humans. Environmental contamination with Toxocara eggs is considered to be the main source of human infections. In Portugal, knowledge regarding the current situation, including density, distribution and environmental contamination by Toxocara spp., is largely unknown. The present study investigated environmental contamination with Toxocara spp. eggs, in soil and faecal samples collected from public parks and playground sandpits in Greater Lisbon, Portugal. A total of 151 soil samples and 135 canine faecal samples were collected from 7 public sandpits and 12 public parks, over a 4 month-period. Soil samples were tested by a modified centrifugation and sedimentation/flotation technique and faecal samples were tested by an adaptation of the Cornell-Wisconsin method. Molecular analysis and sequencing were performed to discriminate Toxocara species in the soil. Overall, 85.7% of the sandpits (6/7) and 50.0% of the parks (6/12) were contaminated with Toxocara spp. eggs. The molecular analysis of soil samples showed that, 85.5% of the sandpits and 34.4% of the parks were contaminated with Toxocara cati eggs. Faecal analysis showed that 12.5% of the sandpits and 3.9% of the parks contained Toxocara canis eggs. In total, 53.0% of soil and 5.9% of faecal samples were positive for Toxocara spp. Additionally, 56.0% of the eggs recovered from the samples were embryonated after 60 days of incubation, therefore considered viable and infective. The average density was 4.2 eggs per hundred grams of soil. Public parks and playground sandpits in the Lisbon area were found to be heavily contaminated with T. cati eggs, representing a serious menace to public health as the studied areas represent common places where people of all ages, particularly children, recreate. This study sounds an alarm bell regarding the necessity to undertake effective measures such as reduction of stray animals, active faecal collection by pet owners, awareness campaigns and control strategies to decrease the high risk to both animal and human health.
    • Environmental determinants of fruit and vegetable consumption among adults: a systematic review.

      Kamphuis, Carlijn B M; Giskes, Katrina; Bruijn, Gert-Jan de; Wendel-Vos, Wanda; Brug, Johannes; Lenthe, Frank J van (2006-10-01)
      The current ecological approach in health behaviour research recognises that health behaviour needs to be understood in a broad environmental context. This has led to an exponential increase in the number of studies on this topic. It is the aim of this systematic review to summarise the existing empirical evidence pertaining to environmental influences on fruit and vegetable (FV) consumption. The environment was defined as 'all factors external to the individual'. Scientific databases and reference lists of selected papers were systematically searched for observational studies among adults (18-60 years old), published in English between 1 January 1980 and 31 December 2004, with environmental factor(s) as independent factor(s), and fruit intake, vegetable intake or FV intake combined as one outcome measure as dependent factor(s). Findings showed there was a great diversity in the environmental factors studied, but that the number of replicated studies for each determinant was limited. Most evidence was found for household income, as people with lower household incomes consistently had a lower FV consumption. Married people had higher intakes than those who were single, whereas having children showed mixed results. Good local availability (e.g. access to one's own vegetable garden, having low food insecurity) seemed to exert a positive influence on intake. Regarding the development of interventions, improved opportunities for sufficient FV consumption among low-income households are likely to lead to improved intakes. For all other environmental factors, more replicated studies are required to examine their influence on FV intake.
    • Environmental Risk Assessment Strategy for Nanomaterials.

      Scott-Fordsmand, Janeck J; Peijnenburg, Willie J G M; Semenzin, Elena; Nowack, Bernd; Hunt, Neil; Hristozov, Danail; Marcomini, Antonio; Irfan, Muhammad-Adeel; Jiménez, Araceli Sánchez; Landsiedel, Robert; Tran, Lang; Oomen, Agnes G; Bos, Peter M J; Hund-Rinke, Kerstin (2017-10-19)
      An Environmental Risk Assessment (ERA) for nanomaterials (NMs) is outlined in this paper. Contrary to other recent papers on the subject, the main data requirements, models and advancement within each of the four risk assessment domains are described, i.e., in the: (i) materials, (ii) release, fate and exposure, (iii) hazard and (iv) risk characterisation domains. The material, which is obviously the foundation for any risk assessment, should be described according to the legislatively required characterisation data. Characterisation data will also be used at various levels within the ERA, e.g., exposure modelling. The release, fate and exposure data and models cover the input for environmental distribution models in order to identify the potential (PES) and relevant exposure scenarios (RES) and, subsequently, the possible release routes, both with regard to which compartment(s) NMs are distributed in line with the factors determining the fate within environmental compartment. The initial outcome in the risk characterisation will be a generic Predicted Environmental Concentration (PEC), but a refined PEC can be obtained by applying specific exposure models for relevant media. The hazard information covers a variety of representative, relevant and reliable organisms and/or functions, relevant for the RES and enabling a hazard characterisation. The initial outcome will be hazard characterisation in test systems allowing estimating a Predicted No-Effect concentration (PNEC), either based on uncertainty factors or on a NM adapted version of the Species Sensitivity Distributions approach. The risk characterisation will either be based on a deterministic risk ratio approach (i.e., PEC/PNEC) or an overlay of probability distributions, i.e., exposure and hazard distributions, using the nano relevant models.
    • Environmental surveillance during an outbreak of tularaemia in hares, the Netherlands, 2015.

      Janse, Ingmar; Maas, Miriam; Rijks, Jolianne M; Koene, Miriam; van der Plaats, Rozemarijn Qj; Engelsma, Marc; van der Tas, Peter; Braks, Marieta; Stroo, Arjan; Notermans, Daan W; de Vries, Maaike C; Reubsaet, Frans; Fanoy, Ewout; Swaan, Corien; Kik, Marja Jl; IJzer, Jooske; Jaarsma, Ryanne I; van Wieren, Sip; de Roda-Husman, Ana Maria; van Passel, Mark; Roest, Hendrik-Jan; van der Giessen, Joke (2017-08-31)
      Tularaemia, a disease caused by the bacterium Francisella tularensis, is a re-emerging zoonosis in the Netherlands. After sporadic human and hare cases occurred in the period 2011 to 2014, a cluster of F. tularensis-infected hares was recognised in a region in the north of the Netherlands from February to May 2015. No human cases were identified, including after active case finding. Presence of F. tularensis was investigated in potential reservoirs and transmission routes, including common voles, arthropod vectors and surface waters. F. tularensis was not detected in common voles, mosquito larvae or adults, tabanids or ticks. However, the bacterium was detected in water and sediment samples collected in a limited geographical area where infected hares had also been found. These results demonstrate that water monitoring could provide valuable information regarding F. tularensis spread and persistence, and should be used in addition to disease surveillance in wildlife.
    • Environmental Surveillance of Zoonotic Francisella tularensis in the Netherlands

      Janse, Ingmar; van der Plaats, Rozemarijn Q. J.; de Roda Husman, Ana Maria; van Passel, Mark W. J. (2018-05-08)
    • An Enzyme-Linked Immunosorbent Spot Assay Measuring Borrelia burgdorferi B31-Specific Interferon Gamma-Secreting T Cells Cannot Discriminate Active Lyme Neuroborreliosis from Past Lyme Borreliosis: a Prospective Study in the Netherlands.

      van Gorkom, T; Sankatsing, S U C; Voet, W; Ismail, D M; Muilwijk, R H; Salomons, M; Vlaminckx, B J M; Bossink, A W J; Notermans, D W; Bouwman, J J M; Kremer, K; Thijsen, S F T (2018-04)
      Two-tier serology testing is most frequently used for the diagnosis of Lyme borreliosis (LB); however, a positive result is no proof of active disease. To establish a diagnosis of active LB, better diagnostics are needed. Tests investigating the cellular immune system are available, but studies evaluating the utility of these tests on well-defined patient populations are lacking. Therefore, we investigated the utility of an enzyme-linked immunosorbent spot (ELISpot) assay to diagnose active Lyme neuroborreliosis. Peripheral blood mononuclear cells (PBMCs) of various study groups were stimulated by using Borrelia burgdorferi strain B31 and various recombinant antigens, and subsequently, the number of Borrelia-specific interferon gamma (IFN-γ)-secreting T cells was measured. We included 33 active and 37 treated Lyme neuroborreliosis patients, 28 healthy individuals treated for an early manifestation of LB in the past, and 145 untreated healthy individuals. The median numbers of B. burgdorferi B31-specific IFN-γ-secreting T cells/2.5 × 105 PBMCs did not differ between active Lyme neuroborreliosis patients (6.0; interquartile range [IQR], 0.5 to 14.0), treated Lyme neuroborreliosis patients (4.5; IQR, 2.0 to 18.6), and treated healthy individuals (7.4; IQR, 2.3 to 14.9) (P = 1.000); however, the median number of B. burgdorferi B31-specific IFN-γ-secreting T cells/2.5 × 105 PBMCs among untreated healthy individuals was lower (2.0; IQR, 0.5 to 3.9) (P ≤ 0.016). We conclude that the Borrelia ELISpot assay, measuring the number of B. burgdorferi B31-specific IFN-γ-secreting T cells/2.5 × 105 PBMCs, correlates with exposure to the Borrelia bacterium but cannot be used for the diagnosis of active Lyme neuroborreliosis.
    • Epidemic spread of recombinant noroviruses with four capsid types in Hungary.

      Reuter, Gábor; Vennema, Harry; Koopmans, Marion P G; Szücs, György (2006-01-01)
      BACKGROUND: Noroviruses are common pathogens in gastro-enteritis outbreaks in humans worldwide. Noroviruses are genetically diverse group of viruses with multiple genogroups (GG) and genotypes. More recently, naturally occurring recombinant noroviruses were described. These viruses had a distinct polymerase gene sequence (designated GGIIb/Hilversum) and were disseminated through waterborne and food-borne transmission in Europe. OBJECTIVES: Our aim was to characterize these emerging recombinant noroviruses causing outbreaks of gastro-enteritis in Hungary. STUDY DESIGN: From January 2001 to May 2004, samples containing "GGIIb/Hilversum polymerase" (GGIIb-pol) were selected for analysis of the viral capsid region (ORF2) by reverse transcription-polymerase chain reaction (RT-PCR) and sequencing. RESULTS: Thirty-four (14.4%) of 236 confirmed norovirus outbreaks were caused by the variant lineage with the GGIIb-pol. Four different recombinants were detected with capsids of Hu/NLV/GGII/Mexico/1989 (n=9, 43%), Hu/NLV/GGII/Snow Mountain/1976 (n=6, 28%), Hu/NLV/GGII/Hawaii/1971 (n=4, 19%) and Hu/NLV/GGII/Lordsdale/1993 (n=1, 5%). CONCLUSIONS: In Hungary, emerging recombinant noroviruses became the second most common norovirus variants-next to GGII-4/Lordsdale virus-causing epidemics of gastroenteritis in the last 4 years.
    • Epidemiological links between tuberculosis cases identified twice as efficiently by whole genome sequencing than conventional molecular typing: A population-based study.

      Jajou, Rana; Neeling, Albert de; Hunen, Rianne van; Vries, Gerard de; Schimmel, Henrieke; Mulder, Arnout; Anthony, Richard; Hoek, Wim van der; Soolingen, Dick van (2018)
      Patients with Mycobacterium tuberculosis isolates sharing identical DNA fingerprint patterns can be epidemiologically linked. However, municipal health services in the Netherlands are able to confirm an epidemiological link in only around 23% of the patients with isolates clustered by the conventional variable number of tandem repeat (VNTR) genotyping. This research aims to investigate whether whole genome sequencing (WGS) is a more reliable predictor of epidemiological links between tuberculosis patients than VNTR genotyping.
    • Epidemiological Risk Factors for Animal Influenza A Viruses Overcoming Species Barriers.

      Harris, Kate A; Freidl, Gudrun S; Munoz, Olga S; von Dobschuetz, Sophie; De Nardi, Marco; Wieland, Barbara; Koopmans, Marion P G; Stärk, Katharina D C; van Reeth, Kristien; Dauphin, Gwen; Meijer, Adam; de Bruin, Erwin; Capua, Ilaria; Hill, Andy A; Kosmider, Rowena; Banks, Jill; Stevens, Kim; van der Werf, Sylvie; Enouf, Vincent; van der Meulen, Karen; Brown, Ian H; Alexander, Dennis J; Breed, Andrew C (2017-05-18)
      Drivers and risk factors for Influenza A virus transmission across species barriers are poorly understood, despite the ever present threat to human and animal health potentially on a pandemic scale. Here we review the published evidence for epidemiological risk factors associated with influenza viruses transmitting between animal species and from animals to humans. A total of 39 papers were found with evidence of epidemiological risk factors for influenza virus transmission from animals to humans; 18 of which had some statistical measure associated with the transmission of a virus. Circumstantial or observational evidence of risk factors for transmission between animal species was found in 21 papers, including proximity to infected animals, ingestion of infected material and potential association with a species known to carry influenza virus. Only three publications were found which presented a statistical measure of an epidemiological risk factor for the transmission of influenza between animal species. This review has identified a significant gap in knowledge regarding epidemiological risk factors for the transmission of influenza viruses between animal species.
    • Epidemiologie van gastro-enteritis bij jonge kinderen op kinderdagverblijven.

      Heusinkveld M; Mughini-Gras, L; Kortbeek T; Pelt W van (2016-06)
    • Epidemiologie van seksueel overdraagbare infecties

      van Bergen, Jan E A M; de Vries, Henry J C; van Benthem, Birgit H B (2018-05-18)
      Surveillance of sexually transmitted infections (STIs) in the Netherlands is based on data from the public health service (GGD) centres for sexual health and the Netherlands institute for health services research (NIVEL) data on primary care registrations. Epidemiological data show a strong increase in the number of bacterial STIs seen in recent decades, but the significance of this trend is unclear. Tests are, performed much more often and are more sensitive, and tests are carried out more often in people from selected high-risk groups; changes in the triage of testing behaviour can, therefore, influence interpretation of trends. Prevention, early detection and early treatment have led to a decrease in the number of new diagnoses of 'HIV infection'. Developments such as pre-exposure prophylaxis, mobile dating apps, sex under influence of drugs ('chemsex'), vaccinations, new technology for quick and simple diagnosis and self-testing mean that a tailored approach is required in combating infectious diseases and that additional surveillance methods are required alongside current methods.
    • Epidemiologische trends in cryptokokkose : De Cryptococcus gattii-uitbraak in Canada

      Hagen, F; Boekhout, T (RIVM, 2006-06-01)
      Cryptococcosis is, when untreated, a fatal disease, which in the Netherlands is mainly caused by the basidiomycetous yeast Cryptococcus neoformans, and in more rare cases by Cryptococcus gattii. Infections with C. gattii occur almost only in immunocompetent individuals, while C. neoformans has a predilection for immunodeficient humans. Another major epidemiological difference between both species is the restriction of C. gattii to tropical and sub-tropical regions, whereas C. neoformans can be found worldwide. However, the distribution pattern of C. gattii has dramatically changed by an ongoing outbreak in the temperate climate of Vancouver Island (British Columbia, Canada). Epidemiological research revealed that the outbreak is caused by the rare AFLP genotype 6 (= VGII) of C. gattii. Only a few strains of this genotype were known before this outbreak. Since the past decade, however, strains of this genotype are isolated more frequently, especially in South America. In the Netherlands, the number of infections with C. neoformans in HIV/AIDS patients shows a decreasing trend, due to the introduction of the HAART therapy. However, clinicians and microbiologists should also be alert for infections caused by C. gattii in (immunocompetent) individuals who travelled recently to Vancouver Island and the main land of British Columbia (Canada).
    • The epidemiology of varicella and herpes zoster in The Netherlands: implications for varicella zoster virus vaccination.

      Melker, Hester E de; Berbers, Guy A M; Hahné, Susan J M; Rümke, Hans; Hof, Susan van den; Wit, G Ardine de; Boot, Hein J (2006-05-01)
      We studied the epidemiology of varicella (chickenpox) and herpes zoster (shingles) in The Netherlands to assess the desirability to implement routine varicella zoster virus vaccination in The Netherlands. Data on seroprevalence of varicella zoster virus in the general population (1995-1996), consultations of general practitioners for varicella (2000-2002) and herpes zoster (1998-2001) and hospital admissions due to varicella (1994-2001) and herpes zoster (1994-2001) in The Netherlands were analysed. The seropositivity increased sharply with age from 18.4% for both 0- and 1-year-olds, to 48.9%, 59.0%, 75.7% and 93.0% for 2-, 3-, 4- and 5-year-olds, respectively, and varied between 97.5% and 100% for older age groups. The average annual incidence of GP-consultations amounted to 253.5 and 325.0 per 100,000 for varicella and herpes zoster, respectively. The incidence of hospital admission due to varicella and herpes zoster was 1.3 (2.3 including side diagnosis) and 2.7 (5.8) per 100,000, respectively. Whilst for varicella, the incidence of GP-consultations and hospital admissions were highest in childhood, for herpes zoster, these were highest in elderly. Insight into epidemiology of varicella zoster is needed for the assessment of the desirability of introduction of routine varicella zoster vaccination.
    • Epigenome-wide association study of adiposity and future risk of obesity-related diseases.

      Campanella, Gianluca; Gunter, Marc J; Polidoro, Silvia; Krogh, Vittorio; Palli, Domenico; Panico, Salvatore; Sacerdote, Carlotta; Tumino, Rosario; Fiorito, Giovanni; Guarrera, Simonetta; Iacoviello, Licia; Bergdahl, Ingvar A; Melin, Beatrice; Lenner, Per; de Kok, Theo M C M; Georgiadis, Panagiotis; Kleinjans, Jos C S; Kyrtopoulos, Soterios A; Bueno-de-Mesquita, H Bas; Lillycrop, Karen A; May, Anne M; Onland-Moret, N Charlotte; Murray, Robert; Riboli, Elio; Verschuren, Monique; Lund, Eiliv; Mode, Nicolle; Sandanger, Torkjel M; Fiano, Valentina; Trevisan, Morena; Matullo, Giuseppe; Froguel, Philippe; Elliott, Paul; Vineis, Paolo; Chadeau-Hyam, Marc (2018-05-01)
      Obesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction.
    • Equalization of four cardiovascular risk algorithms after systematic recalibration: individual-participant meta-analysis of 86 prospective studies.

      Pennells, Lisa; Kaptoge, Stephen; Wood, Angela; Sweeting, Mike; Zhao, Xiaohui; White, Ian; Burgess, Stephen; Willeit, Peter; Bolton, Thomas; Moons, Karel G M; van der Schouw, Yvonne T; Selmer, Randi; Khaw, Kay-Tee; Gudnason, Vilmundur; Assmann, Gerd; Amouyel, Philippe; Salomaa, Veikko; Kivimaki, Mika; Nordestgaard, Børge G; Blaha, Michael J; Kuller, Lewis H; Brenner, Hermann; Gillum, Richard F; Meisinger, Christa; Ford, Ian; Knuiman, Matthew W; Rosengren, Annika; Lawlor, Debbie A; Völzke, Henry; Cooper, Cyrus; Marín Ibañez, Alejandro; Casiglia, Edoardo; Kauhanen, Jussi; Cooper, Jackie A; Rodriguez, Beatriz; Sundström, Johan; Barrett-Connor, Elizabeth; Dankner, Rachel; Nietert, Paul J; Davidson, Karina W; Wallace, Robert B; Blazer, Dan G; Björkelund, Cecilia; Donfrancesco, Chiara; Krumholz, Harlan M; Nissinen, Aulikki; Davis, Barry R; Coady, Sean; Whincup, Peter H; Jørgensen, Torben; Ducimetiere, Pierre; Trevisan, Maurizio; Engström, Gunnar; Crespo, Carlos J; Meade, Tom W; Visser, Marjolein; Kromhout, Daan; Kiechl, Stefan; Daimon, Makoto; Price, Jackie F; Gómez de la Cámara, Agustin; Wouter Jukema, J; Lamarche, Benoît; Onat, Altan; Simons, Leon A; Kavousi, Maryam; Ben-Shlomo, Yoav; Gallacher, John; Dekker, Jacqueline M; Arima, Hisatomi; Shara, Nawar; Tipping, Robert W; Roussel, Ronan; Brunner, Eric J; Koenig, Wolfgang; Sakurai, Masaru; Pavlovic, Jelena; Gansevoort, Ron T; Nagel, Dorothea; Goldbourt, Uri; Barr, Elizabeth L M; Palmieri, Luigi; Njølstad, Inger; Sato, Shinichi; Monique Verschuren, W M; Varghese, Cherian V; Graham, Ian; Onuma, Oyere; Greenland, Philip; Woodward, Mark; Ezzati, Majid; Psaty, Bruce M; Sattar, Naveed; Jackson, Rod; Ridker, Paul M; Cook, Nancy R; D'Agostino, Ralph B; Thompson, Simon G; Danesh, John; Di Angelantonio, Emanuele (2019-02-14)
      There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after 'recalibration', a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied. Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at 'high' 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29-39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22-24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44-51 such individuals using original algorithms, in contrast to 37-39 individuals with recalibrated algorithms. Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.