Recent Submissions

  • Kwaliteitsindicatoren voor de verloskunde: vóór ons, dóór ons!

    Kooistra, M; Franx, A; Schuitemaker, N; Wolf, H; Graafmans, W (Reed Elsevier, 2007-11)
  • Lifestyle Interventions Are Cost-Effective in People With Different Levels of Diabetes Risk: Results from a modeling study.

    Jacobs-van der Bruggen, Monique A M; Bos, Griët; Bemelmans, Wanda J; Hoogenveen, Rudolf T; Vijgen, Sylvia M; Baan, Caroline A (2007-01-01)
    OBJECTIVE: In the current study we explore the long-term health benefits and cost-effectiveness of both a community-based lifestyle program for the general population (community intervention) and an intensive lifestyle intervention for obese adults, implemented in a health care setting (health care intervention). RESEARCH DESIGN AND METHODS: Short-term intervention effects on BMI and physical activity were estimated from the international literature. The National Institute for Public Health and the Environment Chronic Diseases Model was used to project lifetime health effects and effects on health care costs for minimum and maximum estimates of short-term intervention effects. Cost-effectiveness was evaluated from a health care perspective and included intervention costs and related and unrelated medical costs. Effects and costs were discounted at 1.5 and 4.0% annually. RESULTS: One new case of diabetes per 20 years was prevented for every 7-30 participants in the health care intervention and for every 300-1,500 adults in the community intervention. Intervention costs needed to prevent one new case of diabetes (per 20 years) were lower for the community intervention (euro2,000-9,000) than for the health care intervention (euro5,000-21,000). The cost-effectiveness ratios were euro3,100-3,900 per quality-adjusted life-year (QALY) for the community intervention and euro3,900-5,500 per QALY for the health care intervention. CONCLUSIONS: Health care interventions for high-risk groups and community-based lifestyle interventions targeted to the general population (low risk) are both cost-effective ways of curbing the growing burden of diabetes.
  • Disparities in stroke preventive care in general practice did not explain socioeconomic disparities in stroke.

    Avendano, Mauricio; Boshuizen, Hendriek C; Schellevis, F G; Mackenbach, Johan P; Lenthe, Frank J van; Bos, G A M van den (2006-12-01)
    OBJECTIVE: To assess socioeconomic disparities in stroke incidence and in the quality of preventive care for stroke in the Netherlands. STUDY DESIGN AND SETTINGS: A total of 190,664 patients who registered in 96 general practices were followed up for 12 months. Data were collected on diagnoses, referrals, prescriptions, and diagnostic procedures. Hazard ratios (HR) were calculated to assess the association between educational level and stroke incidence. Multilevel logistic regression was used to assess socioeconomic disparities in the quality of preventive care for stroke precursors. RESULTS: Lower educational level was associated with higher incidence of stroke in men (HR=1.36, 95% CI=1.06-1.74) but not in women. Among both men and women, there were socioeconomic disparities in the prevalence of hypertension, hypercholesterolemia, diabetes, angina pectoris, heart failure, and peripheral artery disease. Lower educated hypercholesterolemia patients under medication were less likely to be prescribed statins (odds ratio=0.62, 95% CI=0.42-0.91). However, for other precursors of stroke, there were no major disparities in the quality of preventive care. CONCLUSION: There are socioeconomic disparities in stroke incidence among men but not among women. Socioeconomic differences in factors such as hypertension and diabetes are likely to contribute to stroke disparities. However, general practitioners (GPs) provide care of a similar quality to patients from different socioeconomic groups.
  • Public health implications of using various case definitions in The Netherlands during the worldwide SARS outbreak.

    Timen, A; Doornum, G J J van; Schutten, M; Conyn-van Spaendonck, M A E; Meer, J W M van der; Osterhaus, A D M E; Steenbergen, J E van (2006-12-01)
    This study analysed the consequences of deviation from the WHO case definition for the assessment of patients with suspected severe acute respiratory syndrome (SARS) in The Netherlands during 2003. Between 17 March and 7 July 2003, as a result of dilemmas in balancing sensitivity and specificity, five different case definitions were used. The patients referred for SARS assessment were analysed from a public health perspective. None of the patients referred had SARS, based on serological and virological criteria. Nevertheless, all 72 patients required thorough assessment and, depending on the results of the assessment, institution of appropriate prevention and control measures. Changing case definitions caused confusion in classifying cases. A centralised assessment of the reported cases by a team with clinical and public health expertise (epidemiological and geographical risk assessment) is a practical solution for addressing differences in applying case definitions. The burden of managing non-cases is an important issue when allocating public health resources, and should be taken into account during the preparation phase, rather than during an outbreak. This applies not only to SARS, but also to other public health threats, such as pandemic influenza or a bioterrorist episode.
  • Health-related quality of life and mental health problems after a disaster: Are chronically ill survivors more vulnerable to health problems?

    Berg, Bellis van den; Velden, Peter G van der; Yzermans, C Joris; Stellato, Rebecca K; Grievink, Linda (2006-12-01)
    Studies have shown that the chronically ill are at higher risk for reduced health-related quality of life (HRQL) and for mental health problems. A combination with traumatic events might increase this risk. This longitudinal study among 1216 survivors of a disaster examines whether chronically ill survivors had a different course of HRQL and mental health problems compared to survivors without chronic diseases. HRQL and mental health problems were measured 3 weeks, 18 months and 4 years post-disaster. Data on pre-disaster chronic diseases was obtained from the electronic medical records of general practitioners. Random coefficient analyses showed significant interaction effects for social functioning, bodily pain and emotional role limitations at T2 only. Chronically ill survivors did not consistently have a different course of general health, physical role limitations, and mental health problems. In conclusion, chronic diseases were not an important risk factor for impaired HRQL and mental health problems among survivors.
  • Ethanol Intake and Risk of Lung Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).

    Rohrmann, Sabine; Linseisen, Jakob; Boshuizen, Hendriek C; Whittaker, John; Agudo, Antonio; Vineis, Paolo; Boffetta, Paolo; Jensen, Majken K; Olsen, Anja; Overvad, Kim; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise; Bergmann, Manuela M; Boeing, Heiner; Allen, Naomi E; Key, Timothy J; Bingham, Sheila A; Khaw, Kay-Tee; Kyriazi, Georgia; Soukara, Stavroula; Trichopoulou, Antonia; Panico, Salvatore; Palli, Domenico; Sieri, Sabina; Tumino, Rosario; Peeters, Petra H M; Bueno-de-Mesquita, H Bas; Büchner, Frederike L; Gram, Inger Torhild; Lund, Eiliv; Ardanaz, Eva; Chirlaque, María-Dolores; Dorronsoro Iraeta, Miren; Pérez, Maria-José Sánchez; Quirós, José Ramón; Berglund, Göran; Janzon, Lars; Rasmuson, Torgny; Weinehall, Lars; Ferrari, Pietro; Jenab, Mazda; Norat, Teresa; Riboli, Elio (2006-12-01)
    Within the European Prospective Investigation into Cancer and Nutrition (EPIC), the authors examined the association of ethanol intake at recruitment (1,119 cases) and mean lifelong ethanol intake (887 cases) with lung cancer. Information on baseline and past alcohol consumption, lifetime tobacco smoking, diet, and the anthropometric characteristics of 478,590 participants was collected between 1992 and 2000. Cox proportional hazards regression was used to calculate multivariate-adjusted hazard ratios and 95% confidence intervals. Overall, neither ethanol intake at recruitment nor mean lifelong ethanol intake was significantly associated with lung cancer. However, moderate intake (5-14.9 g/day) at recruitment (hazard ratio (HR) = 0.76, 95% confidence interval (CI): 0.63, 0.90) and moderate mean lifelong intake (HR = 0.80, 95% CI: 0.66, 0.97) were associated with a lower lung cancer risk in comparison with low consumption (0.1-4.9 g/day). Compared with low intake, a high (>/=60 g/day) mean lifelong ethanol intake tended to be related to a higher risk of lung cancer (HR = 1.29, 95% CI: 0.93, 1.74), but high intake at recruitment was not. Although there was no overall association between ethanol intake and risk of lung cancer, the authors cannot rule out a lower risk for moderate consumption and a possibly increased risk for high lifelong consumption.
  • Body mass index, waist circumference and waist-hip ratio and serum levels of IGF-I and IGFBP-3 in European women.

    Gram, Inger Torhild; Norat, Teresa; Rinaldi, Sabina; Dossus, Laure; Lukanova, Annekatrin; Téhard, B; Clavel-Chapelon, Françoise; Gils, C H van; Noord, P A H van; Peeters, Petra H M; Bueno-de-Mesquita, H Bas; Nagel, Gabriele; Linseisen, Jakob; Lahmann, Petra H; Boeing, Heiner; Palli, Domenico; Sacerdote, Carlotta; Panico, Salvatore; Tumino, Rosario; Sieri, Sabina; Dorronsoro Iraeta, Miren; Quirós, José Ramón; Navarro, Carmen A; Barricarte, Aurelio; Tormo, M-J; González, Carlos Alberto; Overvad, Kim; Paaske Johnsen, S; Olsen, Anja; Tjønneland, Anne; Travis, R; Allen, Naomi E; Bingham, Sheila A; Khaw, Kay-Tee; Stattin, P; Trichopoulou, Antonia; Kalapothaki, V; Psaltopoulou, Theodora; Casagrande, Corinne; Riboli, Elio; Kaaks, Rudolf (2006-11-01)
    OBJECTIVE: To examine the relationship between body mass index (BMI) and waist-hip ratio (WHR) with serum levels of insulin-like growth factor-I (IGF-I), and its binding protein (IGFBP)-3. DESIGN: Cross-sectional study on 2139 women participating in a case-control study on breast cancer and endogenous hormones. Data on lifestyle and reproductive factors were collected by means of questionnaires. Body height, weight, waist and hip circumferences were measured. Serum levels of IGF-I and insulin-like binding protein (IGFBP)-3 were measured by enzyme-linked immunosorbent assays. Adjusted mean levels of IGF-I and IGFBP-3 across quintiles of BMI, waist circumference, and WHR were calculated by linear regression. Results were adjusted for potential confounders associated with IGF-I and IGFBP-3. RESULTS: Adjusted mean serum IGF-I values were lower in women with BMI<22.5 kg/m(2) or BMI>29.2 kg/m(2) compared to women with BMI within this range (P(heterogeneity)<0.0001, P(trend)=0.35). Insulin-like growth factor-I was not related to WHR after adjustment for BMI. IGF-binding protein-3 was linearly positively related to waist and WHR after mutual adjustment. The molar ratio IGF-I/IGFBP-3 had a non-linear relation with BMI and a linear inverse relationship with WHR (P (trend)=0.005). CONCLUSIONS: Our data confirm the nonlinear relationship of circulating IGF-I to total adiposity in women. Serum IGFBP-3 was positively related to central adiposity. These suggest that bioavailable IGF-I levels could be lower in obese compared to non-obese women and inversely related to central adiposity.
  • Review of global regulations concerning biowaivers for immediate release solid oral dosage forms.

    Gupta, E; Barends, D M; Yamashita, E; Lentz, K A; Harmsze, A M; Shah, V P; Dressman, J B; Lipper, R A (2006-11-01)
    The regulations with respect to biowaivers for immediate release (IR) solid oral dosage forms in the USA, the EU, Japan and from the World Health Organization (WHO) are summarized and compared. Two case studies are presented, one from our own files and one from the open literature, showing the similarities and the differences among the qualification requirements of the four systems. The regulatory experience gained up to now is reviewed and expected future trends are discussed.
  • Polymorphisms in the NPY and AGRP genes and body fatness in Dutch adults.

    Rossum, Caroline T M van; Pijl, H; Adan, R A H; Hoebee, Barbara; Seidell, J C (2006-10-01)
    OBJECTIVE: To investigate the association between DNA polymorphisms in the NPY and AGRP genes and body fatness. DESIGN AND METHODS: The association between the AGRP Ala67Thr or the NPY Leu7Pro polymorphisms and indicators of body fatness (baseline leptin levels, body mass index (BMI) values and prevalence of overweight) are investigated in 582 participants of two large cohorts in The Netherlands (total 18 500 adult men and women), aged 20-40 years whose weight remained relatively constant or whose weight increased substantially (range 5.5-47 kg) during a mean follow-up of 7 years. RESULTS: No consistent associations were found for the indicators of body fatness for men and women. Among women, BMI values, leptin levels and prevalence of overweight were not statistically different for carriers of the mutant alleles compared to that of the non-carriers. Among men, carriers of the Thr67-allele of the AGRP gene had similar leptin levels, but higher BMI values compared to those with the genotyping Ala67/Ala67: mean adjusted BMI 25.6 kg/m2 (95% CI 24.3-27.0) vs 23.9 kg/m2 (23.6-24.3). Also, the risk of being overweight at baseline tended to be higher for male carriers of the Thr67-allele of the AGRP gene (OR 2.52; 95% CI 0.86-7.4). Furthermore, male carriers of the Pro7-allele of the NPY gene had on average higher leptin levels and BMI values vs non-carriers of this allele: 4.7 microg/l (95% CI 3.7-6.0) and 25.7 kg/m2 (95% CI 24.4-27.0) vs 3.1 microg/l (95% CI 2.9-3.4) and 23.9 kg/m2 (95% CI 23.5-24.3), respectively. These male carriers had also a higher risk on being overweight at baseline (OR 3.3 (95% CI 1.2-8.9)) compared to non-carriers of the Pro7-allele. CONCLUSION: The consistent findings among men suggest that the NPY Leu7Pro polymorphism (or another linked marker) might be involved in the development of obesity at younger ages. The findings for the AGRP Ala67Thr were less consistent and need further investigation. Among women, these polymorphisms do not play an important role.
  • Health care costs in the last year of life--the Dutch experience.

    Polder, Johan J; Barendregt, Jan J; Oers, Hans van (2006-10-01)
    Health expenditure depends heavily on age. Common wisdom is that the age pattern is dominated by costs in the last year of life. Knowledge about these costs is important for the debate on the future development of health expenditure. According to the 'red herring' argument traditional projection methods overestimate the influence of ageing because improvements in life expectancy will postpone rather than raise health expenditure. This paper has four objectives: (1) to estimate health care costs in the last year of life in the Netherlands; (2) to describe age patterns and differences between causes of death for men and women; (3) to compare cost profiles of decedents and survivors; and (4) to use these figures in projections of future health expenditure. We used health insurance data of 2.1 million persons (13% of the Dutch population), linked at the individual level with data on the use of home care and nursing homes and causes of death in 1999. On average, health care costs amounted to 1100 Euro per person. Costs per decedent were 13.5 times higher and approximated 14,906 Euro in the last year of life. Most costs related to hospital care (54%) and nursing home care (19%). Among the major causes of death, costs were highest for cancer (19,000 Euro) and lowest for myocardial infarctions (8068 Euro). Between the other causes of death, however, cost differences were rather limited. On average costs for the younger decedents were higher than for people who died at higher ages. Ten per cent of total health expenditure was associated with the health care use of people in their last year of life. Increasing longevity will result in higher costs because people live longer. The decline of costs in the last year of life with increasing age will have a moderate lowering effect. Our projection demonstrated a 10% decline in the growth rate of future health expenditure compared to conventional projection methods.
  • Using registries in general practice to estimate countrywide morbidity in The Netherlands.

    Gijsen, Ronald; Poos, Marinus J J C (2006-10-01)
    OBJECTIVE: Examining the possibility of using data from registries in general practice in order to present morbidity figures concerning a broad range of major diseases for the Dutch population. STUDY DESIGN: Qualitative and quantitative analysis of registered diagnoses. METHODS: Quantitative data from six registries were obtained. In addition, information about the registration process was obtained and discussed with representatives of the registries. Subjects for discussion were the general characteristics of the registries and disease-specific rules. RESULTS: Some important differences exist in the characteristics of the registries and the disease-specific coding rules for computing incidence and prevalence. However, for most diseases the rules of two or more registries corresponded with each other, so that a selection of registries that measured the occurrence of a particular disease in a similar way could be made. Nevertheless, for some age categories rather large differences between registries were observed. The best estimates for the whole country were calculated as the average incidence and prevalence of the selected registries. CONCLUSIONS: Data that were originally obtained during patient care can be made usable for public health policy purposes. To further improve the quality of data and to increase the usefulness of these data for public health policy purposes, more efforts are required.
  • Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a public-health threat.

    Grundmann, Hajo; Aires-de-Sousa, Marta; Boyce, John; Tiemersma, Edine (2006-09-02)
    Staphylococcus aureus is a gram-positive bacterium that colonises the skin and is present in the anterior nares in about 25-30% of healthy people. Dependent on its intrinsic virulence or the ability of the host to contain its opportunistic behaviour, S aureus can cause a range of diseases in man. The bacterium readily acquires resistance against all classes of antibiotics by one of two distinct mechanisms: mutation of an existing bacterial gene or horizontal transfer of a resistance gene from another bacterium. Several mobile genetic elements carrying exogenous antibiotic resistance genes might mediate resistance acquisition. Of all the resistance traits S aureus has acquired since the introduction of antimicrobial chemotherapy in the 1930s, meticillin resistance is clinically the most important, since a single genetic element confers resistance to the most commonly prescribed class of antimicrobials--the beta-lactam antibiotics, which include penicillins, cephalosporins, and carbapenems.
  • Explaining sex differences in chronic musculoskeletal pain in a general population.

    Wijnhoven, Hanneke A H; Vet, Henrica C W de; Picavet, H Susan J (2006-09-01)
    Many studies report a female predominance in the prevalence of chronic musculoskeletal pain (CMP) but the mechanisms explaining these sex differences are poorly understood. Data from a random postal questionnaire survey in the Dutch general population were used to examine whether sex differences in the prevalences of CMP are due to sex differences in the distribution of known potential risk factors for CMP (exposure model) and/or to the different importance of risk factors for CMP (i.e. show different strength of association) in men and women (vulnerability model). In the present analyses, 909 men and 1178 women aged 25-65 were included. CMP was defined as pain lasting longer than 3 months and was assessed for 10 anatomical locations (neck, shoulder, higher back, elbow, wrist/hand, lower back, hip, knee, ankle, foot). Sex differences in CMP could not be explained by a different distribution of age, educational level, smoking status, overweight, physical activity, and pain catastrophizing. Having no paid job was associated with CMP, explaining part of the sex differences, but its role seems complex. Risk factors with a sex-specific association were: overweight (all pain locations) and older age (lower extremities)--both having only an effect among women--and pain catastrophizing (upper extremities), which was stronger associated with CMP among men than among women. In conclusion, sex differences in prevalence of CMP may partly be explained by sex differences in vulnerability to risk factors for CMP. Future research towards sex-specific identification of risk factors for CMP is warranted. Eventually this may lead to sex-specific prevention and management of CMP.
  • Modeling predicted that tobacco control policies targeted at lower educated will reduce the differences in life expectancy.

    Bemelmans, W J E; Lenthe, Frank J van; Hoogenveen, R; Kunst, A; Deeg, D J H; Brandt, P A van den; Goldbohm, R A; Verschuren, W M Monique (2006-09-01)
    BACKGROUND AND OBJECTIVE: To estimate the effects of reducing the prevalence of smoking in lower educated groups on educational differences in life expectancy. METHODS: A dynamic Markov-type multistate transition model estimated the effects on life expectancy of two scenarios. A "maximum scenario" where educational differences in prevalence of smoking disappear immediately, and a "policy target-scenario" where difference in prevalence of smoking is halved over a 20-year period. The two scenarios were compared to a reference scenario, where smoking prevalences do not change. Five Dutch cohort studies, involving over 67,000 participants aged 20 to 90 years, provided relative mortality risks by educational level, and smoking habits were assessed using national data of more than 120,000 persons. RESULTS: In the reference scenario, the difference in life expectancy at age 40 between highest and lowest educated groups was 5.1 years for men and 2.7 years for women. In the "maximum scenario" these differences were reduced to 3.6 years for men and 1.7 years for women (reduction approximately 30%), and in the "policy target-scenario" differences were 4.7 years for men and 2.4 years for women (reduction approximately 10%). CONCLUSION: Theoretically, educational differences in life expectancy would be reduced by 30% at maximum, if variations in smoking prevalence were eliminated completely. In practice, tobacco control policies that are targeted at the lower educated may reduce the differences in life expectancy by approximately 10%.
  • Hand rub consumption and hand hygiene compliance are not indicators of pathogen transmission in intensive care units.

    Eckmanns, T; Schwab, F; Bessert, J; Wettstein, R; Behnke, M; Grundmann, Hajo; Rüden, H; Gastmeier, P (2006-08-01)
    The objective of this study was to investigate whether nosocomial infection (NI) rates, hand hygiene compliance rates and the amount of alcohol-based hand rub used for hand disinfection are useful indicators of pathogen transmission in intensive care units (ICUs), and whether they could be helpful in identifying infection control problems. All isolates of 10 of the most frequent pathogens from patients who were hospitalized in an ICU for >48 h were genotyped to identify transmission episodes in five ICUs. The incidence of transmission was correlated with hand hygiene compliance, hand rub consumption and NI rates. The incidence of transmission episodes varied between 2.8 and 6.8 in the five ICUs. The NI rate was 8.6-22.5 per 1000 patient-days, hand hygiene compliance was 30-47% and hand rub consumption was 57-102 L per 1000 patient-days. There was no correlation between the incidence of transmission episodes and hand rub consumption or hand hygiene compliance. The correlation between transmission rates and NI rates was 0.4 (P = 0.5), and with the exclusion of one ICU, it was 1 (P < 0.01). The incidence of NI is a relatively good indicator for the identification of pathogen transmissions, but hand rub consumption and hand hygiene compliance, at least with the relatively low level of compliance found in this study, are not indicators of pathogen transmission.
  • Ambient particulate matter affects cardiac recovery in a Langendorff ischemia model.

    Bagate, Karim; Meiring, James J; Gerlofs-Nijland, Miriam E; Cassee, Flemming R; Wiegand, Herbert; Osornio-Vargas, Alvaro; Borm, Paul J A (2006-08-01)
    Exposure to ambient particulate matter (PM) is associated with increased mortality and morbidity among subjects with cardiovascular impairment. We hypothesized that exposure of spontaneously hypertensive (SH) rats to PM impairs the recovery of cardiovascular performance after coronary occlusion and reperfusion-ischemia. SH rats were exposed by intratracheal instillation to saline, standard urban PM (Ottawa dust EHC-93, 10 mg/kg body weight) or endotoxin (lipopolysaccharides LPS, 350 EU/animal) to induce a similar pulmonary inflammation. At 4 h postexposure, hearts were isolated and retrograde perfused in a Langendorff model. The experimental protocol included 35 min of coronary occlusion followed by 120 min of reperfusion, during which left ventricular developing pressure (LDVP), coronary flow (CF), and heart rate (HR) were measured. Baseline LVDP in particle-instilled SH rats was significantly decreased compared to saline-instilled animals. In addition, after ischemia the recovery of LDVP was much slower in rats pretreated with PM or LPS compared to saline instilled rats. The direct effects of the soluble PM fraction and the role of Zn2+ were also tested cardiomyocytes (H9C2 cells). Both particle-free filtrate and Zn2+ inhibited ATP or ionophore-stimulated calcium influx in cardiomyocytes. This inhibitory effect was related to an effect on calcium channels, as shown with Nifedipine. This study provides evidence that exposure to instillation of PM has reversible acute effects on the recovery of cardiac physiological parameters after ischemia. The effect may be caused by a direct action of soluble metals on calcium homeostasis in heart, but pulmonary inflammation may also play a significant role.
  • Multi-centre first-trimester screening for Down syndrome in the Netherlands in routine clinical practice.

    Schielen, P C J I; Leeuwen-Spruijt, M van; Belmouden, I; Elvers, L H; Jonker, M; Loeber, J G (2006-08-01)
    OBJECTIVES: This is the first report on the results of a first-trimester combined-test screening programme in the Netherlands in a multi-centre routine clinical setting. METHODS: Between July 2002 and May 2004, blood samples were taken from subjects in 44 centres in the Netherlands and sent to our laboratory to assay for maternal serum concentrations of fbeta-hCG and PAPP-A. Fetal nuchal translucency (NT) was measured in the participating centres at a gestational age (GA) of 10-14 weeks. Results of those pregnancies for which a combined biochemical and NT risk was calculated were included in the epidemiological analysis of this study. RESULTS: A total of 4033 singleton pregnancies were included in the analysis. The median maternal age of the analysed group was 36.5 years. The distribution of GA was biphasic, with median GA of 10.3 and 12.1 weeks, respectively. The detection rate using the combined ultrasound and serum screening at a cut-off level of 1 in 250 was 71% (15/21), with a screen-positive rate of 4.7%. CONCLUSION: The results of this study show that the first-trimester combined test is suitable as a prenatal screening test in a multi-centre routine clinical setting in the Netherlands. Strict performance evaluation should identify weaknesses in the organisation that impair the performance of the test. Here, the performance of NT was especially identified as a candidate for improvement.
  • Intakes of 4 dietary lignans and cause-specific and all-cause mortality in the Zutphen Elderly Study.

    Milder, Ivon E J; Feskens, Edith J M; Arts, Ilja C W; Bueno-de-Mesquita, H Bas; Hollman, Peter C H; Kromhout, Daan (2006-08-01)
    BACKGROUND: Plant lignans are converted to enterolignans that have antioxidant and weak estrogen-like activities, and therefore they may lower cardiovascular disease and cancer risks. OBJECTIVE: We investigated whether the intakes of 4 plant lignans (lariciresinol, pinoresinol, secoisolariciresinol, and matairesinol) were inversely associated with coronary heart disease (CHD), cardiovascular diseases (CVD), cancer, and all-cause mortality. DESIGN: The Zutphen Elderly Study is a prospective cohort study in which 570 men aged 64-84 y were followed for 15 y. We recently developed a database and used it to estimate the dietary intakes of 4 plant lignans. Lignan intake was related to mortality with the use of Cox proportional hazards analysis. RESULTS: The median total lignan intake in 1985 was 977 microg/d. Tea, vegetables, bread, coffee, fruit, and wine were the major sources of lignan. The total lignan intake was not related to mortality. However, the intake of matairesinol was inversely associated with CHD, CVD, and all-cause mortality (P
  • Analysis of epidemiological cohort data on smoking effects and lung cancer with a multi-stage cancer model.

    Schöllnberger, H; Manuguerra, M; Bijwaard, H; Boshuizen, Hendriek C; Altenburg, H P; Rispens, S M; Brugmans, M J P; Vineis, Paolo (2006-07-01)
    A stochastic two-stage cancer model is used to analyse the relation between lung cancer and cigarette smoking. The model contains the main rate-limiting stages of carcinogenesis, which include initiation, promotion (clonal expansion of initiated cells), malignant transformation and a lag time for tumour formation. Various data sets were used to test the model. These include the data of a large prospective collaborative project carried out in 10 different European countries, the European Prospective Investigation into Cancer and Nutrition (EPIC). This new data set has not been modelled before. The model is also tested on other published data from CPS-II (Cancer Prevention Study II) of the American Cancer Society and the British doctors' study. The analyses indicate that the EPIC data are best described with smoking dependence on the rates of malignant transformation and clonal expansion. With increasing smoking rates, saturation effects in the two exposure rate-dependent model parameters were observed. The results find confirmation in the biological literature, where both mutational effects and promotional effects of cigarette smoke are documented.
  • Anthropometric measures, endogenous sex steroids and breast cancer risk in postmenopausal women: a study within the EPIC cohort.

    Rinaldi, Sabina; Key, Timothy J; Peeters, Petra H M; Lahmann, Petra H; Lukanova, Annekatrin; Dossus, Laure; Biessy, Carine; Vineis, Paolo; Sacerdote, Carlotta; Berrino, Franco; Panico, Salvatore; Tumino, Rosario; Palli, Domenico; Nagel, Gabriele; Linseisen, Jakob; Boeing, Heiner; Roddam, Andrew; Bingham, Sheila A; Khaw, Kay-Tee; Chloptios, John; Trichopoulou, Antonia; Trichopoulos, Dimitrios; Tehard, Bertrand; Clavel-Chapelon, Françoise; González, Carlos Alberto; Larrañaga, Nerea; Barricarte, Aurelio; Quirós, José Ramón; Chirlaque, María-Dolores; Martinez, Carmen; Monninkhof, Evelyn; Grobbee, Diederick E; Bueno-de-Mesquita, H Bas; Ferrari, Pietro; Slimani, Nadia; Riboli, Elio; Kaaks, Rudolf (2006-06-01)
    In a large case-control study on breast cancer risk and serum hormone concentrations, nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we examined to what extent the relationship of excess body weight with breast cancer risk may be explained by changes in sex steroids. Height, weight, waist and hip circumferences, and serum measurements of testosterone [T], androstenedione [Delta4], dehydroepiandrosterone sulphate [DHEAS], estradiol [E2], estrone [E1] and sex-hormone binding globulin [SHBG] were available for 613 breast cancer cases, and 1,139 matched controls, who were all menopausal at the time of blood donation. Free T [fT] and free E2 [fE2] were calculated using mass action equations. Breast cancer risk was related to body mass index (BMI) (RR = 1.11 [0.99-1.25], per 5 kg/m2 increase in BMI), and waist (RR = 1.12 [1.02-1.24], per 10 cm increase) and hip circumferences (RR = 1.14 [1.02-1.27], per 10 cm increase). The increase in breast cancer risk associated with adiposity was substantially reduced after adjustment for any estrogens, especially for fE2 (from 1.11 [0.99-1.25] to 0.99 [0.87-1.12], from 1.12 [1.02-1.24] to 1.02 [0.92-1.14] and from 1.14 [1.02-1.27] to 1.05 [0.93-1.18] for BMI, waist and hip circumferences, respectively). A modest attenuation in excess risk was observed after adjustment for fT, but the remaining androgens had little effect on the association of body adiposity with breast cancer. Our data indicate that the relationship of adiposity with breast cancer in postmenopausal women could be partially explained by the increases in endogenous estrogens, and by a decrease in levels of SHBG.

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