• Do Physical Activity, Social Cohesion, and Loneliness Mediate the Association Between Time Spent Visiting Green Space and Mental Health?

      van den Berg, Magdalena M; van Poppel, Mireille; van Kamp, Irene; Ruijsbroek, Annemarie; Triguero-Mas, Margarita; Gidlow, Christoffer; Nieuwenhuijsen, Mark J; Gražulevičiene, Regina; van Mechelen, Willem; Kruize, Hanneke; Maas, Jolanda (2019-02-01)
      This cross-sectional study investigated whether physical activity, social cohesion, and loneliness mediate the association between time spent visiting green spaces and perceived mental health and vitality. Questionnaire data were collected from 3,948 residents from 124 neighborhoods across four European cities. Multilevel linear regression analysis revealed positive, but weak, associations between time spent visiting green space and Medical Outcome Study Short Form (SF-36) mental health and vitality score, which suggest small mental health benefits. Single mediation analyses showed that different indicators of physical activity (total, during leisure time, and walking during leisure time), social cohesion, and loneliness were mediators. Multiple mediation analyses showed that physical activity during leisure time and loneliness may explain about 25% of the relationship. The unmediated part of the association suggests that other mediators may explain the association.
    • Developmental dysplasia of the hip in children with Down syndrome: comparison of clinical and radiological examinations in a local cohort.

      van Gijzen, Anouk F M; Rouers, Elsbeth D M; van Douveren, Florens Q M P; Dieleman, Jeanne; Hendriks, Johannes G E; Halbertsma, Feico J J; Bok, Levinus A (2019-02-01)
      Guidelines for children with Down syndrome (DS) suggest to perform an annual hip screening to enable early detection of developmental dysplasia of the hip (DDH). How to perform this screening is not described. Delayed detection can result in disabling osteoarthritis of the hip. Therefore, we determined the association between clinical history, physical, and radiological examination in diagnosing DDH in children with DS. Referral centers for children with DS were interviewed to explore variety of hip examination throughout the Netherlands. Clinical features of 96 outclinic children were retrospectively collected. Clinical history was taken, physical examination was performed, and X-ray of the hip was analyzed. All the referral centers performed physical examination and clinical history; however, 20% performed X-ray. Following physical examination according to Galeazzi test 26.9% and to limited abduction 10.8% of the outclinic-studied children were at risk for DDH. Radiological examination showed moderate or severe abnormal deviating migration rate of 14.6% resp. 11.5% in the right and left hip. However, no association between clinical history, physical examination, and radiological examination was found.Conclusion: Clinical history and physical examination are insufficient to timely detect DDH in children with Down syndrome. Thereby regular radiological examination of the hip is advised. What is Known: • Developmental dysplasia of the hip (DDH) in people with Down syndrome (DS) develops during childhood. • Guidelines for medical support of children with DS suggest an annual hip screening to enable early detection of hip damaging. How to perform this annual screening is not described. What is New: • This study shows no association between clinical history, physical and radiological examination of the hip. • We recommend regular radiological examination of the hip in children with DS in order to identify DDH early up to 16 years of age.
    • Comparison of two schedules of two-dose priming with the ten-valent pneumococcal conjugate vaccine in Nepalese children: an open-label, randomised non-inferiority controlled trial.

      Kandasamy, Rama; Gurung, Meeru; Thorson, Stephen; Yu, Ly-Mee; Galal, Ushma; Voysey, Merryn; Kelly, Sarah; Wahl, Brian; Berbers, Guy; Finnegan, Kier; Ansari, Imran; Paudel, Krishna; Murdoch, David R; O'Brien, Katherine L; Kelly, Dominic F; Goldblatt, David; Shrestha, Shrijana; Pollard, Andrew J (2019-02-01)
      Nepalese infants receive ten-valent pneumococcal conjugate vaccine (PCV10) with a 1 month interval between priming doses for programmatic reasons. We aimed to investigate whether immune responses to PCV10 serotypes were non-inferior if the second priming dose of PCV10 was delivered at a 1 month interval as opposed to a 2 month interval. We did an open-label, randomised, parallel group trial in healthy Nepalese infants aged 40-60 days at Patan Hospital, Kathmandu, Nepal. Children were eligible for inclusion if they were healthy, were born at more than or equal to 37 weeks' gestation, were residing in Kathmandu, and had not had any previous vaccinations other than BCG, and oral polio vaccine. Participants were randomly assigned (1:1) by means of a computer-generated list with randomly varying permuted block sizes accessed through a validated web-based interface, to receive PCV10 either at 6 weeks and 10 weeks of age (6 + 10 group) or at 6 weeks and 14 weeks of age (6 + 14 group), with both groups receiving a booster at 9 months of age. Laboratory staff, masked to study intervention, analysed serum samples for antibodies against PCV10 serotypes by ELISA. The primary outcome was to determine whether the 6 + 10 schedule was non-inferior to the 6 + 14 schedule at 9 months of age, on the basis of the proportion of infants with serotype-specific IgG greater than or equal to 0·35 μg/mL. Non-inferiority was established with a 10% margin, and the primary endpoint was measured in a modified intention-to-treat population, which included only participants who successfully had a blood sample collected. This trial is registered at ClinicalTrials.gov, number NCT02385513. Between Aug 21, 2015, and April 4, 2016, 304 Nepalese children were randomly assigned to either the 6 + 10 group (n=152) or the 6 + 14 group (n=152). At 9 months of age, the 6 + 10 schedule was non-inferior for serotype 5 (79 [55·2%] of 143 vs 78 [53·4%] of 146, difference 1·82% [95% CI -9·6 to 13·25], p=0·021), serotype 9V (66 [46·1%] of 143 vs 55 [37·6%] of 146, difference 8·48% [-2·84 to 19·8], p=0·001), serotype 14 (110 [77·4%] of 142 vs 110 [74·8%] of 147, difference 2·63% [-7·27 to 12·54], p=0·006), and serotype 19F (135 [95%] of 142 vs 146 [100%] of 146, difference -4·92% [-9·86 to 0], p=0·022). At the same timepoint, non-inferiority was not shown for serotype 1 (36 [25·1%] of 143 vs 42 [28·5%] of 147, difference -3·39% [95% CI -13·56 to 6·77], p=0·102), serotype 4 (70 [48·9%] of 143 vs 87 [59·1%] of 147, difference -10·23% [-21·64 to 1·18], p=0·516), serotype 6B (96 [67·1%] of 143 vs 114 [77·5%] of 147, difference -10·41% [-20·65 to -0·18], p=0·532), serotype 7F (99 [69·2%] of 143 vs 109 [74·1%] of 147, difference -4·91% [-15·26 to 5·42], p=0·168), serotype 18C (89 [62·2%] of 143 vs 114 [77·5%] of 147, difference -15·31% [-25·78 to -4·83], p=0·840), and serotype 23F (37 [25·8%] of 143 vs 41 [27·8%] of 147, difference -2·01% [-12·19 to 8·16], p=0·062). After the booster dose, at 10 months of age, there were no significant differences in immunogenicity (proportion of children with antibody greater than or equal to 0.35 μg/mL) for any of the ten serotypes, when comparing the two schedules. Serious adverse events occurred in 32 participants, 11 (7%) of 152 in the 6 + 10 group and 21 (14%) of 152 in the 6  +  14 group. The 6 week, 14 week, and 9 month schedule should be implemented where possible. However, post-booster responses, which are thought to drive herd immunity, were similar in the two schedules. Therefore, the 6 week, 10 week, and 9 month schedule is an alternative that can be used when logistically necessary, and is expected to provide herd protection.
    • Predicting soil N supply and yield parameters in peat grasslands.

      Deru JGC; Bloem J; Goede R de; Hoekstra N; Keidel H; Kloen H; Nierop A; Rutgers M; Schouten T (2019-02)
    • SPECIES SENSITIVITY DISTRIBUTIONS FOR USE IN ENVIRONMENTAL PROTECTION, ASSESSMENT AND MANAGEMENT OF AQUATIC ECOSYSTEMS FOR 12,386 CHEMICALS.

      Posthuma, Leo; van Gils, Jos; Zijp, Michiel C; van de Meent, Dik; de Zwart, Dick (2019-01-24)
      The present paper considers the collection and use of ecotoxicity data for risk assessment with Species Sensitivity Distributions (SSDs) of chemical pollution in surface water. SSDs are used to quantify the likelihood that critical effect levels are exceeded. This fits to the European Water Framework Directive, which suggest using models to assess the likelihood that chemicals affect water quality for management prioritization. We derived SSDs based on chronic and acute ecotoxicity test data for 12,386 compounds. The log-normal SSDs are characterized by the median and the standard deviation of log-transformed ecotoxicity data and by a quality score. A case study illustrates the utility of SSDs for water quality assessment and management prioritization. We quantified the chronic and acute mixture toxic pressure of mixture exposures for >22,000 water bodies in Europe for 1,760 chemicals for which we had both exposure and hazard data. Results show the likelihood of mixture exposures exceeding a negligible effect level and increasing species loss, respectively. The SSDs presented in this paper represent a versatile and comprehensive approach to prevent, assess and manage chemical pollution problems. This article is protected by copyright. All rights reserved.
    • The role of analytical chemistry in exposure science: Focus on the aquatic environment.

      Hernández, F; Bakker, J; Bijlsma, L; de Boer, J; Botero-Coy, A M; Bruinen de Bruin, Y; Fischer, S; Hollender, J; Kasprzyk-Hordern, B; Lamoree, M; López, F J; Laak, T L Ter; van Leerdam, J A; Sancho, J V; Schymanski, E L; de Voogt, P; Hogendoorn, E A (2019-01-23)
      Exposure science, in its broadest sense, studies the interactions between stressors (chemical, biological, and physical agents) and receptors (e.g. humans and other living organisms, and non-living items like buildings), together with the associated pathways and processes potentially leading to negative effects on human health and the environment. The aquatic environment may contain thousands of compounds, many of them still unknown, that can pose a risk to ecosystems and human health. Due to the unquestionable importance of the aquatic environment, one of the main challenges in the field of exposure science is the comprehensive characterization and evaluation of complex environmental mixtures beyond the classical/priority contaminants to new emerging contaminants. The role of advanced analytical chemistry to identify and quantify potential chemical risks, that might cause adverse effects to the aquatic environment, is essential. In this paper, we present the strategies and tools that analytical chemistry has nowadays, focused on chromatography hyphenated to (high-resolution) mass spectrometry because of its relevance in this field. Key issues, such as the application of effect direct analysis to reduce the complexity of the sample, the investigation of the huge number of transformation/degradation products that may be present in the aquatic environment, the analysis of urban wastewater as a source of valuable information on our lifestyle and substances we consumed and/or are exposed to, or the monitoring of drinking water, are discussed in this article. The trends and perspectives for the next few years are also highlighted, when it is expected that new developments and tools will allow a better knowledge of chemical composition in the aquatic environment. This will help regulatory authorities to protect water bodies and to advance towards improved regulations that enable practical and efficient abatements for environmental and public health protection.
    • Combined effects of dissolved organic matter, pH, ionic strength and halides on photodegradation of oxytetracycline in simulated estuarine waters.

      Zhang, Ya-Nan; Zhao, Jianchen; Zhou, Yangjian; Qu, Jiao; Chen, Jingwen; Li, Chao; Qin, Weichao; Zhao, Yahui; Peijnenburg, Willie J G M (2019-01-23)
      Estuarine waters of variable compositions are sinks for many micropollutants. The varying water properties can impact the photodegradation of organic pollutants. In this study, the combined effects of dissolved organic matter (DOM), pH, ionic strength, and halides on the photodegradation of the model organic pollutant oxytetracycline (OTC) were investigated. Suwannee River natural organic matter (SRNOM) was used as a representative DOM. The results showed that the observed photolysis rate constant (kobs) of OTC increased rapidly upon increase of pH. SRNOM induced a 11.0-17.9% decrease of the kobs for OTC. In the presence of SRNOM, the ionic strength and specific halide effects promote OTC photodegradation with a 39.2-84.2% and 7.1-28.8% increase of the kobs, respectively. The effects of SRNOM, ionic strength and halides on OTC photodegradation are pH-dependent. Direct photolysis half-lives (t1/2) of OTC were estimated in view of the more important role of direct photolysis compared to indirect photolysis. The estimated t1/2 values decreased from 187.4-206.6 d to 34.4-36.6 d as the pH increases in the Yellow River estuarine region. The results of this research demonstrate that the photodegradation rate of OTC increases rapidly in the gradient from river water to marine water in estuarine regions.
    • Evaluation and enumeration of online test providers for sexually transmitted infections, specifically chlamydia, in the Netherlands.

      den Daas, Chantal; Sukel, Bob; Bos, Hanna; van den Broek, Ingrid (2019-01-22)
      Online testing for STIs might complement regular care provided by general practitioners or STI clinics. Two types of online testing can be distinguished, self-testing and self-sampling (sending sample to a laboratory for diagnosis). Online testing can occur without consultation with a healthcare professional, therefore information given by providers is essential for informed decision-making. We aimed to enumerate online test providers in the Netherlands focusing on chlamydia tests, to evaluate information using quality indicators and to gain insight on the proportion of online testing in the STI testing arena. We performed a systematic internet search to identify online STI test providers. Twenty quality indicators were evaluated on their websites; indicator scores were weighted by level of importance (expert opinion). High scoring providers were recommended, on the condition that the sensitivity and specificity of the test were above 95% and providers included a follow-up procedure in case of a positive result. Finally, providers were contacted to inquire about the number of sold tests, positivity rates and demographic characteristics of testers. Five out of 12 identified self-sample test providers could be recommended, versus zero out of eight self-test providers. Self-sample test providers gave complete and correct information on more indicators (67%) compared with self-test providers (38%). In 2015, an estimated 30 000-40 000 self-sample tests were purchased, and 12 000-25 000 self-tests, which is roughly 10%-15% of the total number of STI tests. This evaluation shows that some online self-sample test providers could be put forward as way of STI testing complementing regular testing options. None of the self-test providers were recommended. Regularly evaluating online test providers is advised to improve quality of the information on the websites. Finally, self-testing might not be suited for all populations as most information is provided in written format only.
    • Changes in dietary intake, plasma carotenoids and erythrocyte membrane fatty acids in breast cancer survivors after a lifestyle intervention: results from a single-arm trial.

      Buckland, G; Travier, N; Arribas, L; Del Barco, S; Pernas, S; Zamora, E; Bellet, M; Cirauqui, B; Margelí, M; Muñoz, M; Tusquets, I; Arcusa, A; Javierre, C; Moreno, F; Valverde, Y; Jansen, E; Chajès, V; Castro, C; Agudo, A (2019-01-21)
      The influence of nutrition on breast cancer prognosis is still inconclusive and therefore dietary interventions incorporating dietary biomarkers are needed to confirm compliance with dietary goals and clarify biological mechanisms. The present study assessed whether a lifestyle intervention in breast cancer survivors could affect dietary biomarkers of fruit and vegetables and fatty acids. In this phase II single-arm trial, 37 overweight/obese early stage breast cancer patients completed a 12-week diet and exercise intervention. The intervention involved 1-h weekly diet sessions delivered by a dietician and 75-min bi-weekly physical activity sessions of moderate-to-high intensity led by trained monitors. Before and after the intervention, three 24-h dietary recalls were carried out to calculate nutrient intakes and, in addition, blood samples were taken to measure plasma carotenoids, vitamin E and retinol concentrations and erythrocyte membrane fatty acid (EFA) composition. Wilcoxon signed rank tests were used to assess changes in dietary and biomarkers measurements over the intervention period. After the intervention, there was a significant increase in the intake of dietary carotenoids (+15.1% compared to baseline) but not plasma carotenoids levels (+6.3%). Regarding the EFA levels, we observed a significant decrease in percentage of saturated fatty acids (-1.4%) and n-6 polyunsaturated fatty acids (-2.9%) and an increase in monounsaturated fatty acids (1.7%) and total and long-chain n-3 polyunsaturated fatty acids (by 13.1% and 13.7%, respectively). A favourable decrease in the ratio of long-chain n-6 to n-3 polyunsaturated fatty acids (-9.1%) was also observed. After a short-term diet and exercise intervention in overweight/obese breast cancer survivors, we observed significant changes in dietary nutrients and fatty acid biomarkers, suggesting positive dietary changes that could be relevant for breast cancer prognosis.
    • Regional differences in chlamydia and gonorrhoeae positivity rate among heterosexual STI clinic visitors in the Netherlands: contribution of client and regional characteristics as assessed by cross-sectional surveillance data.

      Götz, Hannelore M; van Oeffelen, Louise Aam; Hoebe, Christian J P A; van Benthem, Birgit Hb (2019-01-21)
      To assess to what extent triage criteria, client and regional characteristics explain regional differences in Retrospective cross-sectional study on the Dutch STI surveillance database of all 24 STI clinics. STI clinic visits of heterosexual persons in 2015 with a Ct (n=101 495) and/or Ng test (n=101 081). Ct and Ng positivity and 95% CI was assessed for each STI clinic. Two-level logistic regression analyses were performed to calculate the percentage change in regional variance (PCV) after adding triage criteria (model 1), other client characteristics (model 2) and regional characteristics (model 3) to the empty model. The contribution of single characteristics was determined after removing them from model 3.
    • Is quality of life impairment associated with chronic diseases dependent on educational level?

      Galenkamp, Henrike; van Oers, Hans A M; Kunst, Anton E; Stronks, Karien (2019-01-18)
      Previous research indicates that quality of life impairment as a result of chronic diseases differs between socioeconomic groups, but the pattern seems to vary between health-related quality of life (HRQOL) outcomes. We tested for a one-item and a multi-item outcome whether associations between diseases and HRQOL varied between educational levels. Data come from Dutch participants of HELIUS (N =4615, aged 18-70). Education was defined as low, middle or high. Myocardial infarction, angina pectoris, hypertension, diabetes, obesity and depressed mood were measured using physical examination and/or self-report. Outcomes were fair/poor self-rated health (SRH) and physical (PCS) and mental (MCS) SF-12 scores. Interaction terms and relative excess risk due to interaction (RERI) were used as measures of additive interaction. SRH and PCS were worst in lower educated participants, whereas MCS was worst in middle educated participants. Out of thirty-six interactions tested, four were statistically significant, with risks of poor HRQOL being both larger and smaller in low vs. high education groups. Obesity was associated with smaller risk of fair/poor SRH in low vs. high educated [RERI=-2.49 (-4.66; -0.33)]. Depressed mood was associated with more [b=-3.34 (-6.14; -0.54)] and hypertension with less reduction in PCS [b=1.23 (0.18; 2.27)] in middle vs. high educated. Depressed mood was highly associated with MCS, but less so in middle vs. high educated [b=4.09 (0.72; 7.47)]. Despite a higher prevalence of diseases in low education groups, if measured in absolute terms, most diseases were not associated with larger impairment of HRQOL in lower vs. higher educated groups, regardless of the outcome measure used.
    • Potential gains in health expectancy by improving lifestyle: an application for European regions.

      Füssenich, Koen; Nusselder, Wilma J; Lhachimi, Stefan K; Boshuizen, Hendriek C; Feenstra, Talitha F (2019-01-17)
      Prevention aiming at smoking, alcohol consumption, and BMI could potentially bring large gains in life expectancy (LE) and health expectancy measures such as Healthy Life Years (HLY) and Life Expectancy in Good Perceived Health (LEGPH) in the European Union. However, the potential gains might differ by region. A Sullivan life table model was applied for 27 European countries to calculate the impact of alternative scenarios of lifestyle behavior on life and health expectancy. Results were then pooled over countries to present the potential gains in HLY and LEGPH for four European regions. Simulations show that up to 4 years of extra health expectancy can be gained by getting all countries to the healthiest levels of lifestyle observed in EU countries. This is more than the 2 years to be gained in life expectancy. Generally, Eastern Europe has the lowest LE, HLY, and LEGPH. Even though the largest gains in LEPGH and HLY can also be made in Eastern Europe, the gap in LE, HLY, and LEGPH can only in a small part be closed by changing smoking, alcohol consumption, and BMI. Based on the current data, up to 4 years of good health could be gained by adopting lifestyle as seen in the best-performing countries. Only a part of the lagging health expectancy of Eastern Europe can potentially be solved by improvements in lifestyle involving smoking and BMI. Before it is definitely concluded that lifestyle policy for alcohol use is of relatively little importance compared to smoking or BMI, as our findings suggest, better data should be gathered in all European countries concerning alcohol use and the odds ratios of overconsumption of alcohol.
    • Fast approximate computation of cervical cancer screening outcomes by a deterministic multiple-type HPV progression model.

      Vänskä, Simopekka; Bogaards, Johannes A; Auranen, Kari; Lehtinen, Matti; Berkhof, Johannes (2019-01-16)
      Cervical cancer arises differentially from infections with up to 14 high-risk human papillomavirus (HPV) types, making model-based evaluations of cervical cancer screening strategies computationally heavy and structurally complex. Thus, with the high number of HPV types, microsimulation is typically used to investigate cervical cancer screening strategies. We developed a feasible deterministic model that integrates varying natural history of cervical cancer by the different high-risk HPV types with compressed mixture representations of the screened population, allowing for fast computation of screening interventions. To evaluate the method, we built a corresponding microsimulation model. The outcomes of the deterministic model were stable over different levels of compression and agreed with the microsimulation model for all disease states, screening outcomes, and levels of cancer incidence. The compression reduced the computation time more than 1000 fold when compared to microsimulation in a cohort of 1 million women. The compressed mixture representations enable the assessment of uncertainties surrounding the natural history of cervical cancer and screening decisions in a computationally undemanding way.
    • Cardiovascular Risk Factors Associated With Venous Thromboembolism.

      Gregson, John; Kaptoge, Stephen; Bolton, Thomas; Pennells, Lisa; Willeit, Peter; Burgess, Stephen; Bell, Steven; Sweeting, Michael; Rimm, Eric B; Kabrhel, Christopher; Zöller, Bengt; Assmann, Gerd; Gudnason, Vilmundur; Folsom, Aaron R; Arndt, Volker; Fletcher, Astrid; Norman, Paul E; Nordestgaard, Børge G; Kitamura, Akihiko; Mahmoodi, Bakhtawar K; Whincup, Peter H; Knuiman, Matthew; Salomaa, Veikko; Meisinger, Christa; Koenig, Wolfgang; Kavousi, Maryam; Völzke, Henry; Cooper, Jackie A; Ninomiya, Toshiharu; Casiglia, Edoardo; Rodriguez, Beatriz; Ben-Shlomo, Yoav; Després, Jean-Pierre; Simons, Leon; Barrett-Connor, Elizabeth; Björkelund, Cecilia; Notdurfter, Marlene; Kromhout, Daan; Price, Jackie; Sutherland, Susan E; Sundström, Johan; Kauhanen, Jussi; Gallacher, John; Beulens, Joline W J; Dankner, Rachel; Cooper, Cyrus; Giampaoli, Simona; Deen, Jason F; Gómez de la Cámara, Agustín; Kuller, Lewis H; Rosengren, Annika; Svensson, Peter J; Nagel, Dorothea; Crespo, Carlos J; Brenner, Hermann; Albertorio-Diaz, Juan R; Atkins, Robert; Brunner, Eric J; Shipley, Martin; Njølstad, Inger; Lawlor, Deborah A; van der Schouw, Yvonne T; Selmer, Randi Marie; Trevisan, Maurizio; Verschuren, W M Monique; Greenland, Philip; Wassertheil-Smoller, Sylvia; Lowe, Gordon D O; Wood, Angela M; Butterworth, Adam S; Thompson, Simon G; Danesh, John; Di Angelantonio, Emanuele; Meade, Tom (2019-01-16)
      It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. A panel of several established cardiovascular risk factors.
    • Endpoint sensitivity in Amphibian Metamorphosis Assay.

      Dang, ZhiChao (2019-01-15)
      The Amphibian Metamorphosis Assay (AMA) is a screening test for detecting chemicals with thyroid activity. There is little experience in data interpretation and in using AMA data for screening, testing and identifying endocrine disruptors. To investigate the sensitivity of different endpoints of the AMA, the publically available data for 57 thyroid active and inactive chemicals were compiled and analyzed. Endpoints body weight and length appeared as sensitive as apical thyroid responsive endpoints hind limb length (HLL) and developmental stage (DS) for 12 thyroid active chemicals. The sensitivity of body weight, length and HLL was comparable, which is higher than that of DS for 45 thyroid inactive chemicals. The decision logic of the AMA suggests that an advanced development alone indicates thyroid activity. The analysis here showed that advanced development at day 7 could indicate thyroid activity of a chemical. However, advanced development at day 21 may be influenced by thyroid inactive chemicals. Among 39 thyroid inactive chemicals, which affected one or more endpoints, 33% and 77% induced changes in HLL and/or DS at day 7 and 21, respectively; only 10% influenced thyroid histology. These results showed that apical thyroid responsive endpoints HLL and DS are influenced by thyroid active chemicals as well as thyroid inactive chemical. Both endpoints should be combined with thyroid histology for the identification of thyroid active chemicals. The use of the AMA in a testing strategy to identify chemicals with thyroid activity is discussed.
    • Trends in antimicrobial management of gonorrhoea by general practitioners in Amsterdam, the Netherlands, between 2010 and 2016: a cross-sectional study.

      van Amerongen, Roos; Gazendam, Roel P; van Bergen, Jan E A M (2019-01-15)
      Sexually transmitted infections (STI) caused by multidrug resistant Neisseria gonorrhoea are an emerging threat to global health. In the Netherlands, the general practitioner (GP) provides the major part of STI care. In 2013 an update of the Dutch guideline was published, recommending a single dose of intramuscular ceftriaxone as treatment for gonorrhoea infections. Data from a Dutch General Practitioner research database was used to investigate the guideline implementation for the treatment of gonorrhoea. A survey was conducted to gain more insight in GPs experiences with the recommended intramuscular therapy. Data on STI-related episodes and STI-diagnoses for gonorrhoea, based on ICPC codes were obtained from the electronic medical records (EMRs) from 35 GPs in Amsterdam for the years 2010 to 2016. Questionnaires regarding the treatment preferences were sent to GPs participating in the research network database. The number of gonorrhoea cases treated with first choice therapy increased from 81% in 2010 (intramuscular cefotaxime or ceftriaxone) to 93% in 2015 (only cefttriaxone). The number of ceftriaxone prescriptions increased substantially from 30% in 2010 to 93% in 2015. GPs preferred a single intramuscular shot of a third-generation cephalosporin above multiple oral doses of other antibiotics. The results demonstrate a successful shift in the antimicrobial management of gonorrhoea infections to ceftriaxone monotherapy according to the national guideline. GPs in this higher prevalence area in Amsterdam reported limited barriers in the intramuscular administration of third-generation cephalosporins.
    • Collaborative emergency preparedness and response to cross-institutional outbreaks of multidrug-resistant organisms: a scenario-based approach in two regions of the Netherlands.

      de Vries, Marion; Kenis, Patrick; Kraaij-Dirkzwager, Marleen; Ruitenberg, Elis Joost; Raab, Jörg; Timen, Aura (2019-01-11)
      The likelihood of large-scale outbreaks of multidrug-resistant organisms (MDRO) is growing. MDRO outbreaks can affect a wide range of healthcare institutions. Control of such outbreaks requires structured collaboration between professionals from all involved healthcare institutions, but guidelines for cross-institutional procedures are, however, often missing. Literature indicates that such multi-actor collaboration is most promising when effective network brokers are present, and when the collaborative actors have clarity about the different roles and responsibilities in the outbreak response network, including collaborative structures and coordination roles. Studying these factors in an imaginary MDRO outbreak scenario, we gained insights into the expectations that health professionals in the Netherlands have in regard to the procedures required to best respond to any future cross-institutional MDRO outbreaks. For exploration purpose, a focus group discussion with ten healthcare professionals was held. Subsequently, an online-survey was conducted among 56 healthcare professionals in two Dutch regions. The survey data was analysed using social network analyses (clique analysis and centrality analysis), which provided insights into the collaborative structures and potential brokers in the outbreak response networks. Additionally, respondents were asked which healthcare institutions and which professions they would prefer as coordinating actors in the collaborative network. Our results show a relatively high level of perceived clarity about the roles and responsibilities that healthcare professionals have during a joint outbreak response. The regional outbreak response networks which were studied appeared inclusive and integrated, with many overlapping groups of fully-connected healthcare actors. Social network analyses resulted in the identification of several central actors from different healthcare institutions with the potential to take on a brokerage role in the collaboration. Actors in the outbreak response networks also showed to prefer several healthcare professionals to take on the coordination roles. Expected collaborative structures during an imaginary regional MDRO outbreak response are relatively dense and integrated. In regard to the coordination of an MDRO outbreak response, based on both the network analysis results and the preferred coordination roles, our findings support a governance structure with several healthcare institutions involved in responding to future cross-institutional MDRO outbreaks.
    • The human CD4 T cell response against mumps virus targets a broadly recognized nucleoprotein epitope.

      de Wit, Jelle; Emmelot, Maarten E; Poelen, Martien C M; Lanfermeijer, Josien; Han, Wanda G H; van Els, Cécile A C M; Kaaijk, Patricia (2019-01-09)
      Mumps outbreaks among vaccinated young adults stress the need for a better understanding of the mumps virus (MuV)-induced immunity. Antibody responses to MuV are well-characterized, but studies on T cell responses are limited. We recently isolated a MuV-specific CD4