Koning, H.J. de

Optimisation of volume-doubling time cutoff for fast-growing lung nodules in CT lung cancer screening reduces false-positive referrals (Article)

2013-03-19T00:00:00Z

Objective: To retrospectively investigate whether optimisation of volume-doubling time (VDT) cutoff for fast-growing nodules in lung cancer screening can reduce false-positive referrals. Methods: Screening participants of the NELSON study underwent low-dose CT. For indeterminate nodules (volume 50-500 mm3), follow-up CT was performed 3 months after baseline. A negative baseline screen resulted in a regular second-round examination 1 year later. Subjects referred to a pulmonologist because of a fast-growing (VDT <400 days) solid nodule in the baseline or regular second round were included in this study. Histology was the reference for diagnosis, or stability on subsequent CTs, confirming benignity. Mean follow-up of non-resected nodules was 4.4 years. Optimisation of the false-positive rate was evaluated at maintained sensitivity for lung cancer diagnosis with VDT <400 days as reference. Results: Sixty-eight fast-growing nodules were included; 40 % were malignant. The optimal VDT cutoff for the 3-month follow-up CT after baseline was 232 days. This cutoff reduced false-positive referrals by 33 % (20 versus 30). For the regular second round, VDTs varied more among malignant nodules, precluding lowering of the VDT cutoff of 400 days. Conclusion: All malignant fast-growing lung nodules referred after the 3-month follow-up CT in the baseline lung cancer screening round had VDT ≤232 days. Lowering the VDT cutoff may reduce false-positive referrals. Key Points: • Lung nodules are common in CT lung cancer screening, most being benign • Short-term follow-up CT can identify fast-growing intermediate-size lung nodules • Most fast-growing nodules on short-term follow-up CT still prove to be benign • A new volume-doubling time (VDT) cut-off is proposed for lung screening • The optimised VDT cutoff may decrease false-positive case referrals for lung cancer

An educational cartoon accelerates amblyopia therapy and improves compliance, especially among children of immigrants (Article)

2012-11-01T00:00:00Z

Purpose: We showed previously that an educational cartoon that explains without words why amblyopic children should wear their eye patch improves compliance, especially in children of immigrant parents who speak Dutch poorly. We now implemented this cartoon in clinics in low socioeconomic status (SES) areas with a large proportion of immigrants and clinics elsewhere in the Netherlands. Design: Clinical, prospective, nonrandomized, preimplementation, and postimplementation study. Participants: Amblyopic children aged 3 to 6 years who started occlusion therapy. Methods: Preimplementation, children received standard orthoptic care. Postimplementation, children starting occlusion therapy received the cartoon in addition. At implementation, treating orthoptists followed a course on compliance. In low SES areas, compliance was measured electronically during 1 week. Main Outcome Measures: The clinical effects of the cartoon - electronically measured compliance, outpatient attendance rate, and speed of reduction in interocular-acuity difference (SRIAD) - averaged over 15 months of observation. Results: In low SES areas, 114 children were included preimplementation versus 65 children postimplementation; elsewhere in the Netherlands, 335 versus 249 children were included. In low SES areas, mean electronically measured compliance was 52.0% preimplementation versus 62.3% postimplementation (P=0.146); 41.8% versus 21.6% (P=0.043) of children occluded less than 30% of prescribed occlusion time. Attendance rates in low SES areas were 60.3% preimplementation versus 76.0% postimplementation (P=0.141), and 82.7% versus 84.5%, respectively, elsewhere in the Netherlands. In low SES areas, the SRIAD was 0.215 log/year preimplementation versus 0.316 log/year postimplementation (P=0.025), whereas elsewhere in the Netherlands, these were 0.244 versus 0.292 log/year, respectively (P=0.005; the SRIAD's improvement was significantly better in low SES areas than elsewhere, P=0.0203). This advantage remained after adjustment for confounding factors. Overall, 25.1% versus 30.1% (P=0.038) had completed occlusion therapy after 15 months. Conclusions: After implementation of the cartoon, electronically measured compliance improved, attendance improved, acuity increased more rapidly, and treatment was shorter. This may be due, in part, to additional measures such as the course on compliance. However, that these advantages were especially pronounced in children in low SES areas with a large proportion of immigrants who spoke Dutch poorly supports its use in such areas. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Do women make an informed choice about participating in breast cancer screening? A survey among women invited for a first mammography screening examination (Article)

2012-11-01T00:00:00Z

Objective: To determine the level of informed choice in women invited for breast cancer screening for the first time. Methods: To determine the content of decision-relevant knowledge, 16 experts were asked to judge whether each of 51 topics represented essential information to enable informed choices. To assess the level of informed choices, a questionnaire was then sent to all 460 invited women in the south-western part of the Netherlands who turned 50 in August 2008. Results: Of all 229 respondents, 95% were deemed to have sufficient knowledge as they answered at least 8 out of 13 items correctly. In 90% there was consistency between intention (not) to participate and attitude. As a result, 88% made an informed choice. Sixty-eight percent of women responded correctly on the item of over-diagnosis. Even if all non-respondents were assumed to have no knowledge, 50% of the total group invited to participate still had sufficient knowledge. Conclusions: Women were deemed to have sufficient relevant knowledge of the benefits and harms if they answered at least half of the items correctly. Practice implications: To further increase informed choices in breast cancer screening, information on some of the possible harms merits further attention.

Quality-of-life effects of prostate-specific antigen screening (Article)

2012-08-16T00:00:00Z

Background: After 11 years of follow-up, the European Randomized Study of Screening for Prostate Cancer (ERSPC) reported a 29% reduction in prostate-cancer mortality among men who underwent screening for prostate-specific antigen (PSA) levels. However, the extent to which harms to quality of life resulting from overdiagnosis and treatment counterbalance this benefit is uncertain. Methods: On the basis of ERSPC follow-up data, we used Microsimulation Screening Analysis (MISCAN) to predict the number of prostate cancers, treatments, deaths, and quality-adjusted life-years (QALYs) gained after the introduction of PSA screening. Various screening strategies, efficacies, and quality-of-life assumptions were modeled. Results: Per 1000 men of all ages who were followed for their entire life span, we predicted that annual screening of men between the ages of 55 and 69 years would result in nine fewer deaths from prostate cancer (28% reduction), 14 fewer men receiving palliative therapy (35% reduction), and a total of 73 life-years gained (average, 8.4 years per prostate-cancer death avoided). The number of QALYs that were gained was 56 (range, -21 to 97), a reduction of 23% from unadjusted life-years gained. To prevent one prostate-cancer death, 98 men would need to be screened and 5 cancers would need to be detected. Screening of all men between the ages of 55 and 74 would result in more life-years gained (82) but the same number of QALYs (56). Conclusions: The benefit of PSA screening was diminished by loss of QALYs owing to postdiagnosis long-term effects. Longer follow-up data from both the ERSPC and quality-of-life analyses are essential before universal recommendations regarding screening can be made. (Funded by the Netherlands Organization for Health Research and Development and others.) Copyright

Informing on prenatal screening for Down syndrome prior to conception. An empirical and ethical perspective (Article)

2012-03-01T00:00:00Z

In most Western countries, information on prenatal screening for Down syndrome is provided in the first-trimester of pregnancy. The purpose of this study was to examine whether this information should additionally be provided before pregnancy to improve the informed decision-making process. In an empirical study, we obtained data from pregnant women with respect to their preferences regarding information on prenatal screening preconceptionally. Questionnaire data (n=510) showed that 55.7% of responding women considered participating in prenatal screening for Down syndrome before pregnancy. 28.0% of women possessed information on prenatal screening preconceptionally. 84.6% preferred not to receive information preconceptionally in retrospect. In an ethical analysis, we elaborated on these preferences by weighing pros and cons. We considered two arguments against the provision of information on prenatal screening preconceptionally: women's preference to receive information in a step-by-step manner, and the risk of providing a directive message. We identified three reasons supporting its provision preconceptionally: the likelihood of making an informed decision could, firstly, be increased by "unchaining" the initial information from possible subsequent decisions, and, secondly, by providing women sufficient time to deliberate. Thirdly, the probability of equal access to prenatal screening may increase. To conclude with, we propose to incorporate an information offer on prenatal screening for Down syndrome in preconception care consultations. By offering information, instead of providing information, prospective parents are enabled to either accept or decline the information, which respects both their right to know and their right not-to-know.

Sexual function with localized prostate cancer: Active surveillance vs radical therapy (Article)

2012-01-20T00:00:00Z

Objective: To compare sexual function of men with localized prostate cancer (PCa) on active surveillance (AS) with similar patients who received radical therapy. Patients And Methods: Two groups of men with screening-detected localized PCa were compared. The first were men on AS within the prospective protocol-based Prostate Cancer Research International: Active Surveillance study. The second were men participating in the European Randomized Study of Screening for Prostate Cancer study who had received radical prostatectomy (RP) or radiation therapy (RT). Questionnaires were completed at two different timepoints after diagnosis or treatment (6 and 12-18 months). These contained 10 items on sexual function, the mental and physical component summary from the Short-Form 12-item health survey, the Center for Epidemiologic Studies Depression scale depression measure and the State Trait Anxiety Inventory general anxiety measure. Sexual function was compared between groups, and determinants were analysed in multivariable analysis, adjusting for baseline differences. Results: A total of 65-68% of men on AS, 35-36% of those who underwent RP, 36-37% of those who underwent RT and 36% of men in the RP and RT groups combined (combined Tx) were sexually active. A total of 20-30% of men in the AS group, 86-91% of men in the RP group, 56-60% of men in the RT group and 71-76% of men in the combined Tx group were sexually inactive as a result of erectile dysfunction. A total of 44-51% of men in the AS group, 96% of men in the RP group, 73-76% of men in the RT group and 84-85% of men in the combined Tx group who were sexually active had problems getting or keeping an erection. In multivariable analysis these differences were significant, except for AS vs RT. Conclusions: Men with localized PCa on AS were more often sexually active than similar men who received radical therapy, especially RP. If not sexually active, this was less often attributable to erectile dysfunction for those on AS. If sexually active, this was less often associated with problems getting or keeping an erection for those on AS. The study was non-randomized; the latest advances in RP and RT might impact results. © 2012 THE AUTHORS. BJU INTERNATIONAL

Mammography screening and risk of breast cancer death: A population-based case - Control study (Article)

2012-01-01T00:00:00Z

Background: Because the efficacy of mammography screening had been shown in randomized controlled trials, the focus has turned on its effectiveness within the daily practice. Using individual data of women invited to screening, we conducted a case-control study to assess the effectiveness of the Dutch population-based program of mammography screening. Methods: Cases were women who died from breast cancer between 1995 and 2003 and were closely matched to five controls on year of birth, year of first invitation, and number of invitations before case's diagnosis. ORs and 95% confidence intervals (CI) for the association between attending either of three screening examinations prior to diagnosis and the risk of breast cancer death were calculated using conditional logistic regression and corrected for self-selection bias. Results: We included 755 cases and 3,739 matched controls. Among the cases, 29.8% was screen-detected, 34.3% interval-detected, and 35.9% never-screened. About 29.5% of the never-screened cases had stage IV tumor compared with 5.3% of the screen-detected and 15.1% of the interval-detected cases. The OR (95% CIs), all ages (49-75 years), was 0.51 (0.40-0.66) and for the age groups 50-69, 50-75, and 70-75 years were 0.61 (0.47-0.79), 0.52 (CI 0.41-0.67), and 0.16 (0.09-0.29), respectively. Conclusion: The study provides evidence for a beneficial effect of early detection by mammography screening in reducing the risk of breast cancer death among women invited to and who attended the screening. Impact: This is the first case-control study that accurately accounts for equal screening opportunity for both cases and matched controls by number of invitations before case's diagnosis.

Reactie op het artikel van G.A. Bonneux en Philippe Autier, 'Bevolkingsonderzoek naar borstkanker loont niet. Screening heeft nauwelijks invloed op sterfte' (Ned Tijdschr Geneeskd. 2011;155:A3774) (Miscellaneous)

2011-11-28T00:00:00Z

Inleiding. Daling sterfte Gerandomiseerde trials onder bijna 350.000 vrouwen hebben aangetoond dat onder gerandomiseerde en daarna voor borstkankerscreening uitgenodigde vrouwen van 50 jaar en ouder de sterfte aan borstkanker met 25% was gedaald ten opzichte van gerandomiseerde en niet-uitgenodigde groepen vrouwen (1). De Cochrane-groep schreef in 2000 dat de gerandomiseerde trials niet goed waren, maar in de recentere Cochrane reviews kwam men hier op terug (2, 3). Essentiële trial-publicaties waren niet meegenomen (4); er was geen rekening gehouden met geprotocolleerde screening in de controle-groep van de Canadese studie en zelfselectie (5), en de aanvankelijke mate van trial-kwaliteit verdeling (let wel: er werd niet screeningskwaliteit bedoeld) moest afgezwakt worden. Naast gerandomiseerd onderzoek is er klinisch en pathologisch bewijs (6) dat met toenemende groei van de tumor als gevolg van groeifactoren het aantal bloedvaten rondom de tumor toeneemt. De kans op positieve lymfklieren en uitzaaiingen wordt daarmee vergroot, proportioneel naar tumorgrootte (en feitelijk dus proportioneel naar omringende vaatgroei). Het wegnemen van de tumor derhalve indien deze nog klein is, verkleint de kans op uitzaaiingen en daarmee borstkankersterfte. Na deze trials is bevolkingsonderzoek vaak regionaal-gewijs geïmplementeerd; in Finland zijn zelfs geboortecohorten gerandomiseerd tussen vroege en late uitnodiging. Evaluaties van deze implementaties tonen ook in de niet-trial setting borstkanker sterfte-reducties van 37-70% aan voor gescreende vrouwen (7).

Re: Disease-specific survival of men with prostate cancer detected during the screening interval: Results of the european randomized study of screening for prostate cancerrotterdam after 11 years of follow-up (Article)

2011-11-01T00:00:00Z

Identification of chronic obstructive pulmonary disease in lung cancer screening computed tomographic scans (Article)

2011-10-26T00:00:00Z

Context: Smoking is a major risk factor for both cancer and chronic obstructive pulmonary disease (COPD). Computed tomography (CT)-based lung cancer screening may provide an opportunity to detect additional individuals with COPD at an early stage. Objective: To determine whether low-dose lung cancer screening CT scans can be used to identify participants with COPD. Design, Setting, and Patients: Single-center prospective cross-sectional study within an ongoing lung cancer screening trial. Prebronchodilator pulmonary function testing with inspiratory and expiratory CT on the same day was obtained from 1140 male participants between July 2007 and September 2008. Computed tomographic emphysema was defined as percentage of voxels less than -950 Hounsfield units (HU), and CT air trapping was defined as the expiratory:inspiratory ratio of mean lung density. Chronic obstructive pulmonary disease was defined as the ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) of less than 70%. Logistic regression was used to develop a diagnostic prediction model for airflow limitation. Main Outcome Measures: Diagnostic accuracy of COPD diagnosis using pulmonary function tests as the reference standard. Results: Four hundred thirty-seven participants (38%) had COPD according to lung function testing. A diagnostic model with CT emphysema, CT air trapping, body mass index, pack-years, and smoking status corrected for overoptimism (internal validation) yielded an area under the receiver operating characteristic curve of 0.83 (95% CI, 0.81-0.86). Using the point of optimal accuracy, the model identified 274 participants with COPD with 85 false-positives, a sensitivity of 63% (95% CI, 58%-67%), specificity of 88% (95% CI, 85%-90%), positive predictive value of 76% (95% CI, 72%-81%); and negative predictive value of 79% (95% CI, 76%-82%). The diagnostic model showed an area under the receiver operating characteristic curve of 0.87 (95% CI, 0.86-0.88) for participants with symptoms and 0.78 (95% CI, 0.76-0.80) for those without symptoms. Conclusion: Among men who are current and former heavy smokers, low-dose inspiratory and expiratory CT scans obtained for lung cancer screening can identify participants with COPD, with a sensitivity of 63% and a specificity of 88%.

Modeling the impact of population screening on breast cancer mortality in the United States (Article)

2011-10-01T00:00:00Z

Objective: Optimal US screening strategies remain controversial. We use six simulation models to evaluate screening outcomes under varying strategies. Methods: The models incorporate common data on incidence, mammography characteristics, and treatment effects. We evaluate varying initiation and cessation ages applied annually or biennially and calculate mammograms, mortality reduction (vs. no screening), false-positives, unnecessary biopsies and over-diagnosis. Results: The lifetime risk of breast cancer death starting at age 40 is 3% and is reduced by screening. Screening biennially maintains 81% (range 67% to 99%) of annual screening benefits with fewer false-positives. Biennial screening from 50-74 reduces the probability of breast cancer death from 3% to 2.3%. Screening annually from 40 to 84 only lowers mortality an additional one-half of one percent to 1.8% but requires substantially more mammograms and yields more false-positives and over-diagnosed cases. Conclusion: Decisions about screening strategy depend on preferences for benefits vs. potential harms and resource considerations.

The role of the (18)F-fluorodeoxyglucose-positron emission tomography scan in the Nederlands Leuvens Longkanker Screenings Onderzoek lung cancer screening trial (Article)

2011-10-01T00:00:00Z

Background: In computed tomography lung cancer screening programs, up to 30% of all resections are futile. OBJECTIVE: To investigate whether a preoperative positron emission tomography (PET) after a conclusive or inconclusive nonsurgical workup will reduce the resection rate for benign disease in test-positive participants of a lung cancer screening program. Methods: (18)F-Fluorodeoxyglucose-PET scans were made in 220 test positives. Nodules were classified as positive, indeterminate, or negative based on visual comparison with background activity. Gold standard for a positive PET was the presence of cancer in the resection specimen or the detection of cancer during more than 2 years follow-up. Sensitivity, specificity, positive predictive value, and negative predictive value (NPV) were calculated at participant level and 95% confidence intervals (CIs) constructed. Results: The sensitivity of PET to detect cancer was 84.2% (95% CI: 77.6-90.7%), the specificity 75.2% (95% CI: 67.1-83.3), the positive predictive value 78.9% (95% CI: 71.8-86.0), and the NPV 81.2% (95% CI: 73.6-88.8). The resection rate for benign disease was 23%, but 26% of them had a diagnosis with clinical consequences. A preoperative PET after an inconclusive nonsurgical workup reduced the resection rate for benign lesions by 11 to 15%, at the expense of missing 12 to 18% lung cancer cases. A preoperative PET after a conclusive nonsurgical workup reduced the resection rate by 78% at the expense of missing 3% lung cancer cases. Conclusion: A preoperative PET scan in participants with an inconclusive nonsurgical workup is not recommended because of the very low NPV, but after a conclusive nonsurgical workup, the resection rate for benign disease can be decreased by 72%.

Prediction of higher mortality reduction for the UK Breast Screening Frequency Trial: A model-based approach on screening intervals (Article)

2011-09-27T00:00:00Z

Background: The optimal interval between two consecutive mammograms is uncertain. The UK Frequency Trial did not show a significant difference in breast cancer mortality between screening every year (study group) and screening every 3 years (control group). In this study, the trial is simulated in order to gain insight into the results of the trial and to predict the effect of different screening intervals on breast cancer mortality. Methods: UK incidence, life tables and information from the trial were used in the microsimulation model MISCAN-Fadia to simulate the trial and predict the number of breast cancer deaths in each group. To be able to replicate the trial, a relatively low sensitivity had to be assumed. Results: The model simulated a larger difference in tumour size distribution between the two groups than observed and a relative risk (RR) of 0.83 of dying from breast cancer in the study group compared with the control group. The predicted RR is lower than that reported from the trial (RR 0.93), but within its 95% confidence interval (0.63-1.37). Conclusion: The present study suggests that there is benefit of shortening the screening interval, although the benefit is probably not large enough to start annual screening.

Digital mammography screening: Weighing reduced mortality against increased overdiagnosis (Article)

2011-09-01T00:00:00Z

Objective: Digital mammography has been shown to increase the detection of ductal carcinoma. in situ (DCIS) compared to screen-film mammography. The benefits and risks of such an increase were assessed. Methods: Breast cancer detection rates were compared between 502,574 screen-film and 83,976 digital mammograms performed between 2004 and 2006 among Dutch screening participants. The detection rates were then modeled using a baseline model and two extreme models that respectively assumed a high rate of progression and no progression of preclinical DCIS to invasive cancer. With these models, breast cancer mortality and overdiagnosis were predicted. Results: The DCIS detection rate was significantly higher at digital mammography (1.2 per 1000 mammograms (95% C.I. 1.0-1.5)) than at screen-film mammography (0.7 per 1000 mammograms (95% C.I. 0.6-0.7)). Consequently, 287 (range progressive- non progressive model: 1-598) extra breast cancer deaths per 1,000,000 women (a 4.4% increase) were predicted to be prevented. An extra 401 (range: 165-2271) cancers would be overdiagnosed (a 21% increase). Conclusion: Modeling predicted that digital mammography screening would further reduce breast cancer mortality by 4.4%, at a 21% increased overdiagnosis rate. The consequences of digital screening, however, are sensitive to underlying assumptions on the natural history of DCIS.

Informed decision-making in prenatal screening for Down's syndrome: What knowledge is relevant? (Article)

2011-08-01T00:00:00Z

Objective: To determine the content of decision-relevant knowledge needed for informed decision-making about (non-) participation in prenatal screening for Down's syndrome (DS), in order to develop a knowledge questionnaire for routine application in large-scale programme evaluations. Methods: A generic list of content domains for knowledge about screening was extracted from the literature. Items reflecting specific knowledge domains were constructed. An expert group of professionals and pregnant women expressed whether domains and items represented decision-relevant information. Results: All presented domains were scored as (very) important. Options when receiving an 'increased probability for DS' test result, the meaning of this result, the aim of the screening, and voluntary nature of the test were scored as most important. The condition being screened for, prevalence, and the screening procedure were scored as relatively less important, with a high amount of expert consensus. Conclusion: A knowledge measure for prenatal screening for DS was developed, based on domains and items acquired by expert consensus. Practice implications: This measure of decision-relevant knowledge can be used in routine, large-scale evaluations of the procedure for offering information about prenatal screening for DS.

Disease-specific survival of men with prostate cancer detected during the screening interval: Results of the European Randomized Study of Screening for Prostate Cancer-Rotterdam after 11 years of follow-up (Article)

2011-08-01T00:00:00Z

Background: In a screening program, interval cancers are cancers diagnosed between two screening visits. Objective: To assess the disease-specific survival (DSS) of men with prostate cancer (PCa) detected during the screening interval. Design, setting, and participants: Within the European Randomized Study of Screening for Prostate Cancer section Rotterdam, 42 376 men identified from population registries (55-74 yr of age) were randomized to a screening or control arm. The median follow-up was 11 yr. Intervention: Men with prostate-specific antigen ≥3.0 ng/ml were recommended to undergo lateralized sextant biopsy. The screening interval was 4 yr. Measurements: The disease-specific mortality of men with interval cancers was compared with that of men with PCa in the control arm; the secondary end point was overall mortality. An independent committee determined the causes of death. Results and limitations: In the screening arm, 139 men were diagnosed with interval cancer of whom 8 died of the disease. In the control arm, the corresponding numbers were 1149 and 128, respectively. When comparing men with interval cancer to men with PCa in the control arm, no statistically significant difference in disease-specific mortality (hazard ratio [HR]:1.12; 95% confidence interval [CI], 0.53-2.36; p = 0.77) and overall mortality (HR: 0.98; 95% CI, 0.68-1.38; p = 0.90) was found, adjusted for age, prognostic factors, and treatment modality. The follow-up is too limited to address the difference in DSS stratified for screening interval. Conclusions: In the setting of population-based PCa screening at 4-yr intervals, the DSS of men with interval cancer seems to be similar to that of men with PCa in the control arm. Given that interval cancers contribute significantly to PCa mortality, further benefit in DSS in the screening arm may be achieved by decreasing the occurrence of interval cancer. However, the balance between mortality reduction and overdiagnosis should be preserved. Trial registration: ISRCTN49127736.

Disease-specific survival of men with prostate cancer detected during the screening interval: Results of the European Randomized Study of Screening for Prostate Cancer-Rotterdam after 11 years of follow-up (Article)

2011-08-01T00:00:00Z

Asthma-like symptoms in the first year of life and health-related quality of life at age 12 months: the Generation R study (Article)

2011-07-27T00:00:00Z

Purpose: This study compares HRQOL among subgroups of infants with asthma-like symptoms to a subgroup without such symptoms and examines independent associations between asthma-like symptoms during the first year of life and HRQOL at age 12 months. Methods: Our study sample included 5,000 infants participating in the Generation R study. Their parents completed structured questionnaires to obtain information on asthma-like symptoms, HRQOL, infants', and maternal characteristics. Asthma-like symptoms were defined according to the number of positive answers to 12 items on lower respiratory symptoms. HRQOL was measured using the ITQOL. Higher scores indicated better HRQOL. Results: Infants with asthma-like symptoms had significantly lower HRQOL scores for all ITQOL scales. Among the subgroup with severe symptoms (4% of the infants), relevant deficits in HRQOL were observed for most ITQOL scales, particularly for General Health, Bodily Pain, and Family Activities (effect sizes ≥ 0.8). In multivariate linear models, asthma-like symptoms were independently associated with 6 ITQOL scales. The population attributable risks were especially high for Family Activities, General Health, Parental Emotional, and Parental Time. Conclusions: Asthma-like symptoms during the first year of life are associated with impaired quality of life at age 12 months. At population level, asthma-like symptoms were associated with lower HRQOL, regardless of symptom severity.

Long-term effects of lung cancer computed tomography screening on health-related quality of life: The NELSON trial (Article)

2011-07-01T00:00:00Z

The long-term effects of lung cancer computed tomography (CT) screening on health-related quality of life (HRQoL) have not yet been investigated. In the Dutch-Belgian Randomised Lung Cancer Screening Trial (NELSON trial), 1,466 participants received questionnaires before randomisation (T0), 2 months after baseline screening (screen group only; T1) and at 2-yr follow-up (T2). HRQoL was measured as generic HRQoL (12-item short-form questionnaire and EuroQoL questionnaire), anxiety (Spielberger State-Trait Anxiety Inventory) and lung cancer-specific distress (impact of event scale (IES)). Repeated measures of ANOVA were used to analyse differences between the screen and control groups, and between indeterminate (requiring a follow-up CT) and negative screening result groups. At T0 and T2 there were no significant differences in HRQoL scores over time between the screen and control groups, or between the indeterminate or negative second-round screening result group. There was a temporary increase in IES scores after an indeterminate baseline result (T0: mean 4.0 (95% CI 2.8-5.3); T1: mean 7.8 (95% CI 6.5-9.0); T2: mean 4.5 (95% CI 3.3-5.8)). At 2-yr follow-up, the HRQoL of screened subjects was similar to that of control subjects, the unfavourable short-term effects of an indeterminate baseline screening result had resolved and an indeterminate result at the second screening round had no impact on HRQoL. Copyright

Interpreting overdiagnosis estimates in population-based mammography screening (Article)

2011-07-01T00:00:00Z

Estimates of overdiagnosis in mammography screening range from 1% to 54%. This review explains such variations using gradual implementation of mammography screening in the Netherlands as an example. Breast cancer incidence without screening was predicted with a micro-simulation model. Observed breast cancer incidence (including ductal carcinoma in situ and invasive breast cancer) was modeled and compared with predicted incidence without screening during various phases of screening program implementation. Overdiagnosis was calculated as the difference between the modeled number of breast cancers with and the predicted number of breast cancers without screening. Estimating overdiagnosis annually between 1990 and 2006 illustrated the importance of the time at which overdiagnosis is measured. Overdiagnosis was also calculated using several estimators identified from the literature. The estimated overdiagnosis rate peaked during the implementation phase of screening, at 11.4% of all predicted cancers in women aged 0-100 years in the absence of screening. At steady-state screening, in 2006, this estimate had decreased to 2.8%. When different estimators were used, the overdiagnosis rate in 2006 ranged from 3.6% (screening age or older) to 9.7% (screening age only). The authors concluded that the estimated overdiagnosis rate in 2006 could vary by a factor of 3.5 when different denominators were used. Calculations based on earlier screening program phases may overestimate overdiagnosis by a factor 4. Sufficient follow-up and agreement regarding the chosen estimator are needed to obtain reliable estimates.

How does early detection by screening affect disease progression?: Modeling estimated benefits in prostate cancer screening (Article)

2011-07-01T00:00:00Z

Background. Simulation models are essential tools for estimating benefits of cancer screening programs. Such models include a screening-effect model that represents how early detection by screening followed by treatment affects disease-specific survival. Two commonly used screening-effect models are the stage-shift model, where mortality benefits are explained by the shift to more favorable stages, and the cure model, where early detection enhances the chances of cure from disease. Objective. This article describes commonly used screening-effect models and analyses their predicted mortality benefit in a model for prostate cancer screening. Method. The MISCAN simulation model was used to predict the reduction of prostate cancer mortality in the European Randomized Study of Screening for Prostate Cancer (ERSPC) Rotterdam. The screening-effect models were included in the model. For each model the predictions of prostate cancer mortality reduction were calculated. The study compared 4 screening-effect models, which are versions of the stage-shift model or the cure model. Results. The stage-shift models predicted, after a follow-up of 9 years, reductions in prostate cancer mortality varying from 38% to 63% for ERSPC-Rotterdam compared with a 27% reduction observed in the ERSPC. The cure models predicted reductions in prostate cancer mortality varying from 21% to 27%. Conclusions. The differences in predicted mortality reductions show the importance of validating models to observed trial mortality data. The stage-shift models considerably overestimated the mortality reduction. Therefore, the stage-shift models should be used with care, especially when modeling the effect of screening for cancers with long lead times, such as prostate cancer.

The impact of a lung cancer computed tomography screening result on smoking abstinence (Article)

2011-06-01T00:00:00Z

Receiving a lung cancer computed tomography screening result might be a teachable moment for smoking cessation, but it might also unintentionally reassure smokers to continue smoking. The objective of the present study was to investigate whether test results were associated with smoking abstinence in the Dutch-Belgian Randomised Controlled Lung Cancer Screening Trial (NELSON trial). Two random samples of male smokers who had received either only negative test results (n=550) or one or more indeterminate test result (n=440) were sent a questionnaire 2 yrs after randomisation. Smokers with an indeterminate result reported more quit attempts (p=0.02), but the prolonged abstinence rate in smokers receiving a negative test (46 (8.9%) out of 519 subjects) was comparable with the abstinence rate in smokers with one or more indeterminate results (48 (11.5%) out of 419 subjects) (p=0.19). A statistically insignificant increase was found after one or more indeterminate test result (10.9 and 15.0%, respectively) compared with receiving only negative test results (8.9%) (p=0.26). In conclusion, the outcome of the screening test had no impact on future smoking abstinence in male smokers, although all results suggest more favourable implications after one or more follow-up recommendations. Screening test outcomes could be used as a teachable moment for smoking cessation. Copyright

Informed decision-making about the fetal anomaly scan: What knowledge is relevant? (Article)

2011-06-01T00:00:00Z

Objectives This study had two objectives. The first was to determine the contents of relevant knowledge needed for informed decision-making (IDM) in second-trimester ultrasound screening for fetal anomalies, with the goal of developing a knowledge measure for use in large-scale program evaluations. The second was to compare the contents of decision-relevant knowledge for second-trimester ultrasound screening with those for first-trimester screening for Down syndrome using the combined test. Methods A generic list of content domains for knowledge about screening was extracted from the literature. Items reflecting specific knowledge domains for second-trimester ultrasound screening were constructed. An expert group of professionals and pregnant women expressed whether domains and items represented decision-relevant knowledge. Results Regarding second-trimester ultrasound screening, the experts scored all knowledge domains as (very) important. The meaning of an abnormal test result, the disorders being screened for, and the purpose of the screening were rated as very important for IDM, along with the voluntary nature of the test. All knowledge domains were included in the final measure. Importance ratings of knowledge domains for first-trimester Down syndrome screening and for second-trimester ultrasound screening were highly correlated (Pearson's r = 0.71). The domain 'consequences of a positive test result' was considered more important in first-trimester Down syndrome screening than in second-trimester ultrasound screening. Conclusions We have developed a knowledge measure for second-trimester ultrasound screening for fetal anomalies for use in routine, large-scale program evaluations.

Determinants and outcome of unsuccessful referral after positive screening in a large birth-cohort study of population-based vision screening (Article)

2011-06-01T00:00:00Z

Purpose: The efficacy of population-based vision screening is hampered by unsuccessful referral after a positive screening test. We studied the nature and causes of unsuccessful referral in a 7-year birth cohort study of vision screening in Rotterdam, the Netherlands. Methods: All parents of children who had been unsuccessfully referred were asked whether they recalled the referral. Reasons for noncompliance, if any, were identified using semi-structured interviews. Screening records were checked for written evidence of the referral. The parents' fluency in Dutch and their socioeconomic status were also assessed. Results: Of the 561 screen-positive children, 129 (23%) had not been referred successfully. For the current study, 97 parents were successfully contacted. Of these, 14 parents had been willingly noncompliant and 83 said they were unaware of the referral, with 47% having poor to moderate fluency in Dutch. In 53 cases, the screening charts contained no written evidence of any referral. Amblyopia was identified in 3 of the unsuccessful referrals. Conclusions: In this population-based screening program, 1 of 4 positively screened children was not successfully referred. Apart from parental noncompliance, the unsuccessful referrals can be explained by miscommunication, deficient documentation, and physician noncompliance with screening guidelines. An effective monitoring feedback system may improve the efficacy of child vision screening.

What if I don't treat my PSA-detected prostate cancer? Answers from three natural history models (Article)

2011-05-01T00:00:00Z

Background: Making an informed decision about treating a prostate cancer detected after a routine prostate-specific antigen (PSA) test requires knowledge about disease natural history, such as the chances that it would have been clinically diagnosed in the absence of screening and that it would metastasize or lead to death in the absence of treatment. Methods: We use three independently developed models of prostate cancer natural history to project risks of clinical progression events and disease-specific deaths for PSA-detected cases assuming they receive no primary treatment. Results: The three models project that 20%-33% of men have preclinical onset; of these 38%-50% would be clinically diagnosed and 12%-25% would die of the disease in the absence of screening and primary treatment. The risk that men age less than 60 at PSA detection with Gleason score 2-7 would be clinically diagnosed in the absence of screening is 67%-93% and would die of the disease in the absence of primary treatment is 23%-34%. For Gleason score 8 to 10 these risks are 90%-96% and 63%-83%. Conclusions: Risks of disease progression among untreated PSA-detected cases can be nontrivial, particularly for younger men and men with high Gleason scores. Model projections can be useful for informing decisions about treatment. Impact: This is the first study to project population-based natural history summaries in the absence of screening or primary treatment and risks of clinical progression events following PSA detection in the absence of primary treatment.

Detection of child abuse in emergency departments: A multi-centre study (Article)

2011-05-01T00:00:00Z

Objective: This study examines the detection rates of suspected child abuse in the emergency departments of seven Dutch hospitals complying and not complying with screening guidelines for child abuse. Design: Data on demographics, diagnosis and suspected child abuse were collected for all children aged ≤18 years who visited the emergency departments over a 6-month period. The completion of a checklist of warning signs of child abuse in at least 10% of the emergency department visits was considered to be compliance with screening guidelines. Results: A total of 24 472 visits were analysed, 54% of which took place in an emergency department complying with screening guidelines. Child abuse was suspected in 52 children (0.2%). In 40 (77%) of these 52 cases, a checklist of warning signs had been completed compared with a completion rate of 19% in the total sample. In hospitals complying with screening guidelines for child abuse, the detection rate was higher (0.3%) than in those not complying (0.1%, p<0.001). Conclusion: During a 6-month period, emergency department staff suspected child abuse in 0.2% of all children visiting the emergency department of seven Dutch hospitals. The numbers of suspected abuse cases detected were low, but an increase is likely if uniform screening guidelines are widely implemented.

Racial disparities in breast cancer mortality - Response (Article)

2011-05-01T00:00:00Z

Population-based mammography screening below age 50: Balancing radiation-induced vs prevented breast cancer deaths (Article)

2011-03-29T00:00:00Z

Introduction:Exposure to ionizing radiation at mammography screening may cause breast cancer. Because the radiation risk increases with lower exposure age, advancing the lower age limit may affect the balance between screening benefits and risks. The present study explores the benefit-risk ratio of screening before age 50.Methods:The benefits of biennial mammography screening, starting at various ages between 40 and 50, and continuing up to age 74 were examined using micro-simulation. In contrast with previous studies that commonly used excess relative risk models, we assessed the radiation risks using the latest BEIR-VII excess absolute rate exposure-risk model.Results:The estimated radiation risk is lower than previously assessed. At a mean glandular dose of 1.3 mGy per view that was recently measured in the Netherlands, biennial mammography screening between age 50 and 74 was predicted to induce 1.6 breast cancer deaths per 100 000 women aged 0-100 (range 1.3-6.3 extra deaths at a glandular dose of 1-5 mGy per view), against 1121 avoided deaths in this population. Advancing the lower age limit for screening to include women aged 40-74 was predicted to induce 3.7 breast cancer deaths per 100 000 women aged 0-100 (range 2.9-14.4) at biennial screening, but would also prevent 1302 deaths.Conclusion:The benefits of mammography screening between age 40 and 74 were predicted to outweigh the radiation risks.

Randomized controlled trial of screening for type 2 diabetes mellitus in obese subjects (Internal Report)

2011-03-25T00:00:00Z

The impact on socio-emotional development and quality of life of language impairment in 8-year-old children (Article)

2011-01-01T00:00:00Z

Aim: To estimate the impact of different types of language disorders on socio-emotional development and health-related quality of life (HRQOL) in 8-year-old children. Method: In a prospective cohort including 13 427 newborns, of 10 911 eligible children (66 excluded because of intellectual disability or foreign language, 2448 lost to follow-up due to house moves, refusal, death or other reasons) written consent was obtained from the parents of 6051 then 8-year-old children (55%). Questionnaires, completed by the parents of 4745 children (2323 males, 2412 females) and the teachers of 4771 children (2360 males, 2411 females), included validated measures to define type of language disorder and to assess socio-emotional development and HRQOL. Results: In 377 (8.2%) children, speech/language disorders were identified. Children with receptive language disorders had more unfavourable scores for extraversion (9.7, 99% CI 9.3-10.1, p=0.006), school attitude (7.8, 99% CI 7.4-8.2; p<0.001), agreeableness (9.1, 99% CI 8.6-9.6, p<0.001; normal ranges 7-13), and quality of life (49.6, 99% CI 48.8-51.0, p<0.001; normal range 40-60), as compared to children without these disorders. Pragmatic disorders and suspected autism were associated with the most unfavourable scores, for school attitude 8.1 (99% CI 6.9-9.3, p<0.001) and 7.5 (99% CI 6.1-8.9, p=0.002), and for quality of life 42.9 (99% CI 40.3-45.5, p<0.001) and 36.2 (99% CI 30.0-42.4, p<0.001). Interpretation: Language impairment at school age has a large impact on children's behaviour and daily life. © The Authors. Journal compilation

Race-specific impact of natural history, mammography screening, and adjuvant treatment on breast cancer mortality rates in the United States (Article)

2011-01-01T00:00:00Z

Background: U.S. Black women have higher breast cancer mortality rates than White women despite lower incidence. The aim of this study is to investigate how much of the mortality disparity can be attributed to racial differences in natural history, uptake of mammography screening, and use of adjuvant therapy. Methods: Two simulation models use common national race, and age-specific data for incidence, screening and treatment dissemination, stage distributions, survival, and competing mortality from 1975 to 2010. Treatment effectiveness and mammography sensitivity are assumed to be the same for both races. We sequentially substituted Black parameters into the White model to identify parameters that drive the higher mortality for Black women in the current time period. Results: Both models accurately reproduced observed breast cancer incidence, stage and tumor size distributions, and breast cancer mortality for White women. The higher mortality for Black women could be attributed to differences in natural history parameters (26-44%), use of adjuvant therapy (11-19%), and uptake of mammography screening (7-8%), leaving 38% to 46% unexplained. Conclusion: Black women appear to have benefited less from cancer control advances than White women, with a greater race-related gap in the use of adjuvant therapy than screening. However, a greater portion of the disparity in mortality appears to be due to differences in natural history and undetermined factors.

Informed decision making does not affect health-related quality of life in lung cancer screening (NELSON trial) (Article)

2010-12-01T00:00:00Z

Background: It is believed that making an informed decision about (screening) participation is associated with better health-related quality of life (HRQoL) outcomes. This is the first study in cancer screening to explore this association in subjects participating in a lung cancer computed tomography (CT) screening trial. Methods: Participants that made either an informed decision to participate (n = 155) or not (n = 133) were selected for this study. Differences in HRQoL, measured as generic HRQoL (Short Form 12 [SF-12] and EuroQol questionnaire [EQ-5D]), anxiety/distress (State-Trait Anxiety Inventory [STAI-6], Impact of Event Scale [IES] and Consequences of Screening-Lung Cancer [COS-LC]), were tested with Mann-Whitney U tests and ANOVA at three assessment points (when deciding about participation, before trial randomisation and 2 months after receiving the CT result). Results: Subjects who made an informed decision to participate had no better scores than those who did not make an informed decision for 23 out of 24 HRQoL comparisons, except for a better mean score for mental health (Mental Component Summary (MCS) = 53.9 ± 9.2 versus 51.0 ± 10.1, p = 0.003) before randomisation. For subjects with an indeterminate CT result (n = 64), no significant differences were found between subjects with (n = 35) or without (n = 29) an informed decision. Conclusion: Subjects who did not make an informed decision to participate in lung cancer CT screening trial did not experience worse HRQoL during screening than subjects who did make an informed decision, either in general or after receiving an indeterminate result.

Disease-specific mortality may underestimate the total effect of prostate cancer screening (Article)

2010-12-01T00:00:00Z

Objectives To study the difference between the disease-specific and excess mortality rate in the European Randomized Study of Screening for Prostate Cancer section Rotterdam. Methods A total of 42,376 men were randomized to systematic screening or usual care. The excess number of deaths was defined as the difference between the observed number of deaths in the prostate cancer (PC) patients and the expected number of deaths up to 31 December 2006. The expected number was derived from mortality of all study participants before a possible diagnosis with PC. The disease-specific mortality rate was based on the number of men who died from PC. The excess mortality rate based on the arm-specific excess number of deaths and the disease-specific mortality rate were compared between the two study arms. Results The overall mortality rate was not significantly different between the intervention and the control arms of the study: RR 1.02 (95% CI 0.98-1.07). The disease-specific mortality rate was 0.42 men per 1000 person-years in the intervention and 0.48 men per 1000 person-years in the control arm: RR 0.86 (95% CI 0.64-1.17). The excess mortality rate was 0.40 per 1000 personyears in the intervention arm and 0.61 men per 1000 person-years in the control arm, and the RR for excess mortality was 0.66 (95% CI 0.39-1.13). Conclusions In contrast to the disease-specific mortality rates an increased difference in the excess mortality rates was observed between the two arms. This observation may be due to a systematic underestimation of the disease-specific deaths, and/or an additional disease-related mortality that is measured by an excess mortality analysis but not by a disease-specific mortality.

Foreword: Meeting the challenge of prostate cancer (Article)

2010-11-01T00:00:00Z

Prostate cancer is a key medical and public health challenge. Though it is currently the most common cancer among men in Europe, its natural history, prognosis and treatment are poorly understood in comparison to breast cancer. Prostate cancers diagnosed are very small and prediction of their progression at the individual level is difficult and hence need for aggressive management is unclear. The number of randomised treatment trials remains shamefully small and hence the relative effectiveness of the new treatment modalities introduced is unclear.

Lead-time in the european randomised study of screening for prostate cancer (Article)

2010-11-01T00:00:00Z

Background: Lead-time is defined as the time by which screening advances the diagnosis compared with absence of screening. A sufficiently long lead-time needs to be achieved so that cancer can be detected while still curable. A very short lead-time may indicate poor sensitivity of the screening test, while a very long lead-time suggests overdiagnosis. Material and methods: In the first screening round, a total of 56,294 men aged 55-74 years were screened with serum prostate specific antigen (PSA) in five countries of the European Randomised Study of Screening for Prostate Cancer (ERSPC) with an overall detection rate (prevalence) of 2.8% (1972 prostate cancers). Prostate cancer incidence among 92,142 men randomly allocated to the control arm of the trial was also assessed. Lead-time was estimated as the time required to accumulate a similar cumulative risk of prostate cancer in the control arm to the detection rate in the intervention arm, i.e. from the ratio of detection rate (prevalence of screen-detected cases) and expected incidence (cumulative risk). Results: Using a serum PSA cut-off of 4 ng/ml, the mean lead-time in the whole study population was estimated as 6.8 years (95% confidence interval (95% CI) 7.9-8.4). It was 8 years in The Netherlands, 6 in Sweden and Finland, 5 in Italy and 4 in Belgium. The mean lead-time was similar, 6-7 years, at ages 50-64 years, but close to 8 years among men aged 65-74 years. A lower PSA cut-off level of 3 ng/ml used in Sweden and The Netherlands prolonged the mean lead-time by approximately 1 year. Lead-time based on advanced prostate cancer only was slightly shorter, mean 5.3 years (95% CI 4.6-6.0). The lead-time for the second screening round was slightly shorter than that for the first (5.9, 95% CI 5.4-6.4), reflecting a similar relation between detection rate and control group incidence. Conclusion: The lead-time for prostate cancer found in ERSPC substantially exceeded that found for breast, cervical and colorectal cancer screening. One round of prostate cancer screening can advance clinical diagnosis by 4-8 years. Overdiagnosis or detection of non-progressive tumours may contribute substantially to the lead-time.

PSA levels and cancer detection rate by centre in the European Randomized Study of Screening for Prostate Cancer (Article)

2010-11-01T00:00:00Z

Background: To describe the variation in PSA level by age group and screening round in the ERSPC centres and the variation in cancer detection rates in relation to the underlying prostate cancer incidence. Methods: Individual data on men invited for the first and second screening rounds according to protocol (excluding early recalls and interval cancers) were obtained from the central database of the ERSPC (cut-off date 31st December 2006). Data were compared between and within centres for the core age group (55-69 at entry). The cancer detection rate (CDR) was compared with the expected background prostate cancer incidence rate in the absence of screening adjusted for the incidence rate in non-attenders and the control arm (IRS). Results: Mean PSA values in the age groups 55-59 years and 65-69 years showed little variation by centre, except for the Dutch centre, where an increase from 1.6 to 1.8 ng/ml and a decline from 2.9 to 2.5 ng/ml was observed, respectively. Most tumours were detected at the PSA range 4.0-9.9 ng/ml, with a shift to more cancer detection at 3.0-3.9 ng/ml in the second screening round. There was high variability in the CDR between the centres in both the first (16-46 per 1000) and the second screening rounds (14-50 per 1000). Although the ratio CDR/IRS was less variable, it is somewhat lower in Italy and Switzerland (12 and 14,respectively) and higher in the Netherlands (28), than in most other centres and in Belgium the ratio increased markedly, from 20 to 44 between the first and second rounds. Conclusion: There was no clear evidence of a relationship between the underlying incidence and mean PSA levels at screening or the cancer detection rate.

Blinded and uniform causes of death verification in cancer screening: A major influence on the outcome of a prostate cancer screening trial? (Article)

2010-11-01T00:00:00Z

Background: To assess the agreement between the causes of death assigned by a blinded and uniform review panel of the Rotterdam section of the European Randomised Study of Screening for Prostate Cancer and the official vital statistics and to explore the possible effect of the use of either of these two sources on the outcome of the screening trial. Methods: A total of 670 deaths amongst men with prostate cancer, reviewed by the causes of death committee (CODC) up to 31st December 2006 were included in this study. The kappa statistics with confidence intervals (CI), sensitivity and specificity of the official statistics were determined, with the CODC considered the gold standard. The rate ratio (RR) and 95% confidence intervals (95% CI) for prostate cancer mortality, official statistics relative to CODC, were calculated following the Mantel-Haenszel procedure. Results: The overall concordance and the kappa between official statistics and the CODC were 90.6% and 0.76 (0.71-0.82), remaining comparable when only the CODC category definitely prostate cancer was applied, with the sensitivity of official statistics increasing from 88.3% to 91.3% and specificity hardly changing (91.3% and 90.5%). High specificity and lower sensitivity is observed in the screening arm, whilst the opposite was seen in the control arm in men aged 55-69 and 70-74 years at entry. Considerable lower false positive rate was seen for both age groups in the screening arm (3.9% and 4.7%) compared to the control arm (8.4% and 14.3%). A statistically significant excess of prostate cancer death was observed for the official statistics in the age group 70-74 years, 1.53 (1.07-2.19), whilst it was not significant for men aged 55-69 at entry, 1.06 (0.83-1.36). Conclusion: In the Rotterdam ERSPC section, official statistics tended to overreport prostate cancer as an underlying cause of death, particularly in the age group 70-plus in the control arm, which would overestimate the true effect in favour of screening.

Ethnic differences in participation in prenatal screening for Down syndrome: A register-based study (Article)

2010-10-01T00:00:00Z

Objective: To assess ethnic differences in participation in prenatal screening for Down syndrome in the Netherlands. Methods: Participation in prenatal screening was assessed for the period 1 January 2009 to 1 July 2009 in a defined postal code area in the southwest of the Netherlands. Data on ethnic origin, socio-economic background and age of participants in prenatal screening were obtained from the Medical Diagnostic Centre and the Department of Clinical Genetics. Population data were obtained from Statistics Netherlands. Logistic regression models were used to assess ethnic differences in participation, adjusted for socio-economic and age differences. Results: The overall participation in prenatal screening was 3865 out of 15 093 (26%). Participation was 28% among Dutch women, 15% among those from Turkish ethnic origin, 8% among those from North-African origin, 15% among those from Aruban/Antillean origin and 26% among women from Surinamese origin. Conclusions: Compared to Dutch women, those from Turkish, North-African, Aruban/Antillean and other non-Western ethnic origin were less likely to participate in screening. It was unexpected that women from Surinamese origin equally participated. It should be further investigated to what extent participation and non-participation in these various ethnic groups was based on informed decision-making.

Early detection and counselling intervention of asthma symptoms in preschool children: Study design of a cluster randomised controlled trial (Article)

2010-09-17T00:00:00Z

Background. Prevention of childhood asthma is an important public health objective. This study evaluates the effectiveness of early detection of preschool children with asthma symptoms, followed by a counselling intervention at preventive child health centres. Early detection and counselling is expected to reduce the prevalence of asthma symptoms and improve health-related quality of life at age 6 years. Methods/design. This cluster randomised controlled trial was embedded within the Rotterdam population-based prospective cohort study Generation R in which 7893 children (born between April 2002 and January 2006) participated in the postnatal phase. Sixteen child health centres are involved, randomised into 8 intervention and 8 control centres. Since June 2005, an early detection tool has been applied at age 14, 24, 36 and 45 months at the intervention centres. Children who met the intervention criteria received counselling intervention (personal advice to parents to prevent smoke exposure of the child, and/or referral to the general practitioner or asthma nurse). The primary outcome was asthma diagnosis at age 6 years. Secondary outcomes included frequency and severity of asthma symptoms, health-related quality of life, fractional exhaled nitric oxide and airway resistance at age 6 years. Analysis was according to the intention-to-treat principle. Data collection will be completed end 2011. Discussion. This study among preschool children provides insight into the effectiveness of early detection of asthma symptoms followed by a counselling intervention at preventive child health centres. Trial registration. Current Controlled Trials ISRCTN15790308.

Does participation to screening unintentionally influence lifestyle behaviour and thus lifestyle-related morbidity? (Article)

2010-08-01T00:00:00Z

Cancer is a leading cause of death worldwide and the burden could be reduced by evidence-based strategies for the primary prevention of cancer, the early detection of malignancies and more adequate treatment of cancer patients. Previous research has shown that lifestyle factors are associated with common cancers and that several cancer screening programmes are cost-effective in reducing cancer-specific mortality. But, some recent studies reported that participants of screening programs might unintentionally change their lifestyle. Cancer screening might be a teachable moment or, on the other hand, have a false health certificate effect. Despite that the evidence is scarce, cancer screening might have opportunities for lifestyle improvements, although a possible health certificate effect still remains. Integrated approaches to combine primary and secondary prevention have the potential to optimise the efforts to improve cancer prevention and survival. More research is warranted to investigate evidence-based approaches.

Lung cancer screening and smoking abstinence: 2 Year follow-up data from the Dutch - Belgian randomised controlled lung cancer screening trial (Article)

2010-07-01T00:00:00Z

Background: Lung cancer screening may provide a new opportunity for attempts to quit among smokers or might delay smoking cessation, but studies to date failed to provide evidence for this. This study investigated the effect of lung cancer screening on smoking abstinence in male smokers participating in the Dutch - Belgian randomised controlled lung cancer screening trial (NELSON trial). Methods: In the NELSON trial, 50- to 75-year-old participants at high risk for developing lung cancer were randomised to either lung cancer screening or no screening. Smoking behaviour was evaluated in two random samples of male smokers in the screen (n=641) and control arm (n=643) before (T0) and 2 years after randomisation (T1). In addition, the data were also analysed by intention-to-treat (ITT) analysis, as recommended in smoking cessation intervention trials, although non-response in screening trials can also be due to reasons other than continued smoking. Results: Almost 17% (16.6%) of the trial participants quit smoking, which is higher than the 3-7% found in the general adult population. However, screening was associated with a lower prolonged abstinence rate (14.5%) compared with no screening (19.1%) (OR 1.40, 95% CI 1.01 to 1.92; p<0.05). No stastistically significant difference was found after performing an ITT analysis. Conclusions: This study showed that all trial participants were inclined to stop smoking more than average, which suggests that screening is a teachable moment to improve smoking behaviour. In those who underwent screening the smoking abstinence rate was significantly lower than for the control group, although the difference was modest. After ITT analysis this difference was no longer observed. Clinical trial number: ISRCTN63545820.

Rotterdam AMBlyopia screening effectiveness study: Detection and causes of amblyopia in a large birth cohort (Article)

2010-07-01T00:00:00Z

Purpose. The Dutch population-based child health monitoring program includes regular preverbal (age range, 1-24 months) and preschool (age range, 36-72 months) vision screening. This study is on the contribution of an organized vision screening program to the detection of amblyopia. Methods. A 7-year birth cohort study of 4624 children was started in 1996/1997 in Rotterdam. Vision screening data were obtained from the child screening centers. Treating orthoptists working at the regional ophthalmology departments provided information about diagnosis and treatment. The diagnosis was reviewed by two experts. The parents provided additional information on their child's eye history through written questionnaires and telephone interviews. At age 7 years, the children underwent a final examination by the study orthoptists. Results. Of the 3897 children still living in Rotterdam by 2004, 2964 (76.1%) underwent the final examination. Amblyopia was diagnosed in 100 (3.4%) of these (95% CI, 2.7-4.0). At age 7, 23% had visual acuity >0.3 logMAR. Amblyopia was caused by refractive error (n = 42), strabismus (n = 19), combined-mechanism (n = 30), deprivation (n = 7), or unknown (n = 2). Eighty-three amblyopia cases had been detected before age 7. Amblyopia detection followed positive results in vision screening in 56 children, either preverbal (n = 15) or preschool (n = 41). Twenty-six other amblyopes were self-referred (n = 12, before a first positive screening test), especially strabismic or combined-mechanism amblyopia; data were uncertain for one other positively screened amblyopic child. Amblyopia remained undetected until age 7 due to unsuccessful referral (n = 4, three with visual acuity >0.3 logMAR at age 7) or false-negative screening (n = 13).Conclusions. Most cases of amblyopia were detected by vision screening with visual acuity measurement. Preverbal screening contributed little to the detection of refractive amblyopia.

A comparison of parent-reported wheezing or shortness of breath among infants as assessed by questionnaire and physician-interview: The Generation R study (Article)

2010-05-01T00:00:00Z

Purpose The prevalence of asthma symptoms among preschool children is difficult to determine with accuracy because no gold standard is available for diagnosis. The aim of this study was to compare parent-reported wheezing or shortness of breath among infants as assessed by questionnaire and physician-interview. Methods We studied 1,202 children participating in the Generation R study. Their parents completed a written questionnaire at home when the infant was 12 months old, including items on wheezing or shortness of breath. During the regular free-of-charge youth healthcare visit at age 14 months, the physician interviewed the parents to assess the presence of wheezing or shortness of breath. Results The prevalence of wheezing or shortness of breath estimated from questionnaire was significantly higher than from physician-interview (36% vs. 20%; P < 0.001): observed agreement 73% (kappa 0.36). Only 41% of questionnaire-reported symptoms were assessed through the physician-interview, while 73% of physician-interviewed symptoms were reported in the questionnaire. Compared with infants in the subgroup with agreement on the presence of wheezing or shortness of breath, the infants in the subgroups without agreement significantly less often received anti-asthma medication and significantly less often had abnormal respiratory sounds or bronchiolitis or croup, and their mothers were significantly less often working. The proportion of infants receiving anti-asthma medication was higher in interview-data compared with questionnaire-data (22.7% vs. 3.9%; P < 0.001). Conclusions Questionnaire yielded higher prevalence rates for wheezing or shortness of breath than physician-interview. Physician-reported symptoms are associated with a higher proportion of infants receiving anti-asthma medication. Parent-reported asthma symptoms should be confirmed by pediatricians whenever possible. Pediatr Pulmonol. 2010; 45:500-507.

A randomised controlled trial on the effectiveness of bracing patients with idiopathic scoliosis: Failure to include patients and lessons to be learnt (Article)

2010-05-01T00:00:00Z

Trials often do not succeed in including as many patients as anticipated beforehand. The aim of this paper was to describe why we were not able to include more than a few patients in our randomized controlled treatment trial on the effectiveness of bracing patients with idiopathic scoliosis, and to describe which lessons can be learnt. A pilot study on the willingness to participate in such a trial was conducted amongst 21 patients and their parents. A description of how we prepared and designed this trial, the problems we faced and how we tried to improve the inclusion are given. A total of four patients were included, and 14 refused to participate in an 18-month period. There were a lot less eligible patients than anticipated (40 instead of 100 per year), and the patients' participation rate was much lower than we had found in our pilot study (21% instead of 70%). The trial failed to include more than a few patients because of an overestimation of the number of eligible patients and because a lot less eligible patients were willing to participate compared to our pilot study. One reason for a low participation rate could be that this trial evaluated a frequently used existing treatment instead of a new treatment, and patients and parents might be afraid of not being treated (despite an intensive secure system for the control arm).

Are low- and middle-income countries becoming the victim of Western debates about breast screening? (Letter To Editor)

2010-04-29T00:00:00Z

Comparing coronary artery calcium and thoracic aorta calcium for prediction of all-cause mortality and cardiovascular events on low-dose non-gated computed tomography in a high-risk population of heavy smokers (Article)

2010-04-01T00:00:00Z

Background: Coronary artery calcium (CAC) and thoracic aorta calcium (TAC) can be detected simultaneously on low-dose, non-gated computed tomography (CT) scans. CAC has been shown to predict cardiovascular (CVD) and coronary (CHD) events. A comparable association between TAC and CVD events has yet to be established, but TAC could be a more reproducible alternative to CAC in low-dose, non-gated CT. This study compared CAC and TAC as independent predictors of all-cause mortality and cardiovascular events in a population of heavy smokers using low-dose, non-gated CT. Methods: Within the NELSON study, a population-based lung cancer screening trial, the CT screen group consisted of 7557 heavy smokers aged 50-75 years. Using a case-cohort study design, CAC and TAC scores were calculated in a total of 958 asymptomatic subjects who were followed up for all-cause death, and CVD, CHD and non-cardiac events (stroke, aortic aneurysm, peripheral arterial occlusive disease). We used Cox proportional-hazard regression to compute hazard ratios (HRs) with adjustment for traditional cardiovascular risk factors. Results: A close association between the prevalence of TAC and increasing levels of CAC was established (p<0.001). Increasing CAC and TAC risk categories were associated with all-cause mortality (p for trend=0.01 and 0.001, respectively) and CVD events (p for trend <0.001 and 0.03, respectively). Compared with the lowest quartile (reference category), multivariate-adjusted HRs across categories of CAC were higher (all-cause mortality, HR: 9.13 for highest quartile; CVD events, HR: 4.46 for highest quartile) than of TAC scores (HR: 5.45 and HR: 2.25, respectively). However, TAC is associated with non-coronary events (HR: 4.69 for highest quartile, p for trend=0.01) and CAC was not (HR: 3.06 for highest quartile, p for trend=0.40). Conclusions: CAC was found to be a stronger predictor than TAC of all-cause mortality and CVD events in a high-risk population of heavy smokers scored on low-dose, non-gated CT. TAC, however, is stronger associated with non-cardiac events than CAC and could prove to be a preferred marker for these events.

Prostate-specific antigen screening in the United States vs in the European randomized study of screening for prostate cancer-Rotterdam (Article)

2010-03-01T00:00:00Z

Dissemination of prostate-specific antigen (PSA) testing in the United States coincided with an increasing incidence of prostate cancer, a shift to earlier stage disease at diagnosis, and decreasing prostate cancer mortality. We compared PSA screening performance with respect to prostate cancer detection in the US population vs in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC-Rotterdam). We developed a simulation model for prostate cancer and PSA screening for ERSPC-Rotterdam. This model was then adapted to the US population by replacing demography parameters with US-specific ones and the screening protocol with the frequency of PSA tests in the US population. We assumed that the natural progression of prostate cancer and the sensitivity of a PSA test followed by a biopsy were the same in the United States as in ERSPC-Rotterdam. The predicted prostate cancer incidence peak in the United States was then substantially higher than the observed prostate cancer incidence peak (13.3 vs 8.1 cases per 1000 man-years). However, the actual observed incidence was reproduced by assuming a substantially lower PSA test sensitivity in the United States than in ERSPC-Rotterdam. For example, for nonpalpable local-or regional-stage cancers (ie, stage T1M0), the estimates of PSA test sensitivity were 0.26 in the United States vs 0.94 in ERSPC-Rotterdam. We conclude that the efficacy of PSA screening in detecting prostate cancer was lower in the United States than in ERSPC-Rotterdam.

Life expectancy of screen-detected invasive breast cancer patients compared with women invited to the Nijmegen Screening Program (Article)

2010-02-01T00:00:00Z

BACKGROUND: Screening can lead to earlier detection of breast cancer and thus to an improvement in survival. The authors studied the life expectancy of women with screen-detected invasive breast cancer (patients) compared with women invited to the breast cancer screening program in Nijmegen, the Netherlands (comparison group). METHODS: Each patient diagnosed between 1975 and 2006 was randomly age-matched with a woman invited in the same calendar year and free from breast cancer at the time of diagnosis of the patient. Survival analyses were performed to study differences in life expectancy. RESULTS: The life expectancy for 858 patients was 6 years shorter than for the comparison group. However, for 360 patients with small (<15 mm) invasive breast cancer, life expectancy was similar to that of the comparison group. In contrast, for patients detected with larger tumors (≥15 mm) the life expectancy was 6 to 12 years shorter, depending on tumor size. Furthermore, life expectancy was modified by screening history. For patients who had a negative screening examination 2 years before the detection of their breast cancer, the difference in life expectancy from the comparison group became smaller for the larger tumor sizes (≥15 mm). CONCLUSIONS: In conclusion, about 40% (360 of 858) of all women with invasive screen-detected breast cancer have the same life expectancy as women from the comparison group (reflecting the general population). For women diagnosed with larger tumors at diagnosis, life expectancy diminishes with increasing tumor size and is modified by screening history.

The authors reply (Article)

2010-01-01T00:00:00Z

Patients' preferences for scoliosis brace treatment: a discrete choice experiment (Article)

2010-01-01T00:00:00Z

Abstract STUDY DESIGN: Discrete choice experiment. OBJECTIVE: To investigate the reduction in the risk of surgery that scoliosis patients would require in order to consider brace treatment as acceptable, and to elicit the trade-offs individuals make between characteristics of brace treatment. SUMMARY OF BACKGROUND DATA: The effectiveness of brace treatment in idiopathic scoliosis patients has not been established in randomized controlled trials (RCTs). Treatment with a brace can be quite bothersome. Patients' preferences for brace treatment are unknown. Insight into patients' preferences for (characteristics of) brace treatment will be useful for future trials and for the development of braces that may optimize compliance with brace treatment. METHODS: A total of 197 patients who had completed treatment (brace and/or surgery) for scoliosis were approached for the study, of which 135 gave informed consent. A discrete choice experiment was designed in which patients had to choose between hypothetical brace treatment profiles that differed in following 4 treatment attributes: effectiveness, visibility, discomfort, and treatment duration. A multinomial logit model was used to analyze the relative importance of these attributes. Subgroup analyses were conducted for brace-only, brace-surgery, and surgery-only patients. RESULTS: The response rate was 86% (116/135). All treatment attributes proved to be important for patients' choices. All subgroups were prepared to initiate treatment with a Boston brace if the brace would reduce the need for surgery by 53%. Risk reductions in a range of 32% to 74% were required for acceptance of a treatment duration of 3 years. CONCLUSION: Scoliosis patients stated to be prepared to undergo brace treatment only if it provides sizeable reduction of the risk of surgery. Effectiveness and discomfort in wearing a brace were the most important determinants of the choices. These results are important if RCTs would conclusively establish that bracing is effective, and show directions for the further technical development of braces to increase the compliance with brace treatment.

Short-term health-related quality of life consequences in a lung cancer CT screening trial (NELSON) (Article)

2010-01-01T00:00:00Z

Background: In lung cancer CT screening, participants often have an indeterminate screening result at baseline requiring a follow-up CT. In subjects with either an indeterminate or a negative result after screening, we investigated whether health-related quality of life (HRQoL) changed over time and differed between groups in the short term.Methods: A total of 733 participants in the NELSON trial received four questionnaires: T0, before randomisation; T1, 1 week before the baseline screening; T2, 1 day after the screening; and T3, 2 months after the screening results but before the 3-month follow-up CT. HRQoL was measured as generic HRQoL (the 12-item Short Form, SF-12; the EuroQol questionnaire, EQ-5D), anxiety (the Spielberger State-Trait Anxiety Inventory, STAI-6), and lung-cancer-specific distress (the Impact of Event Scale, IES). For analyses, repeated-measures analysis of variance was used, adjusted for covariates.Results: Response to each questionnaire was 88% or higher. Scores on SF-12, EQ-5D, and STAI-6 showed no clinically relevant changes over time. At T3, IES scores that were clinically relevant increased after an indeterminate result, whereas these scores showed a significant decrease after a negative result. At T3, differences in IES scores between the two baseline result groups were both significant and clinically relevant (P<0.01).Conclusion: This longitudinal study among participants of a lung cancer screening programme showed that in the short term recipients of an indeterminate result experienced increased lung-cancer-specific distress, whereas the HRQoL changes after a negative baseline screening result may be interpreted as a relief.

Management of lung nodules detected by volume CT scanning (Article)

2009-12-03T00:00:00Z

BACKGROUND: The use of multidetector computed tomography (CT) in lung-cancer screening trials involving subjects with an increased risk of lung cancer has highlighted the problem for the clinician of deciding on the best course of action when noncalcified pulmonary nodules are detected by CT. METHODS: A total of 7557 participants underwent CT screening in years 1, 2, and 4 of a randomized trial of lung-cancer screening. We used software to evaluate a noncalcified nodule according to its volume or volume-doubling time. Growth was defined as an increase in volume of at least 25% between two scans. The first-round screening test was considered to be negative if the volume of a nodule was less than 50 mm3, if it was 50 to 500 mm3 but had not grown by the time of the 3-month follow-up CT, or if, in the case of those that had grown, the volume-doubling time was 400 days or more. RESULTS: In the first and second rounds of screening, 2.6% and 1.8% of the participants, respectively, had a positive test result. In round one, the sensitivity of the screen was 94.6% (95% confidence interval [CI], 86.5 to 98.0) and the negative predictive value 99.9% (95% CI, 99.9 to 100.0). In the 7361 subjects with a negative screening result in round one, 20 lung cancers were detected after 2 years of follow-up. CONCLUSIONS: Among subjects at high risk for lung cancer who were screened in three rounds of CT scanning and in whom noncalcified pulmonary nodules were evaluated according to volume and volume-doubling time, the chances of finding lung cancer 1 and 2 years after a negative first-round test were 1 in 1000 and 3 in 1000, respectively. (Current Controlled Trials number, ISRCTN63545820.). Copyright

Overdetection, overtreatment and costs in prostate-specific antigen screening for prostate cancer (Article)

2009-12-01T00:00:00Z

Background:Prostate cancer screening with prostate-specific antigen (PSA) has shown to reduce prostate cancer mortality in the European Randomised study of Screening for Prostate Cancer (ERSPC) trial. Overdetection and overtreatment are substantial unfavourable side effects with consequent healthcare costs. In this study the effects of introducing widespread PSA screening is evaluated.Methods:The MISCAN model was used to simulate prostate cancer growth and detection in a simulated cohort of 100 000 men (European standard population) over 25 years. PSA screening from age 55 to 70 or 75, with 1, 2 and 4-year-intervals is simulated. Number of diagnoses, PSA tests, biopsies, treatments, deaths and corresponding costs for 100 000 men and for United Kingdom and United States are compared.Results:Without screening 2378 men per 100 000 were predicted to be diagnosed with prostate cancer compared with 4956 men after screening at 4-year intervals. By introducing screening, the costs would increase with 100% to \[euro]60 695 000. Overdetection is related to 39% of total costs (\[euro]23 669 000). Screening until age 75 is relatively most expensive because of the costs of overtreatment.Conclusion:Introduction of PSA screening will increase total healthcare costs for prostate cancer substantially, of which the actual screening costs will be a small part.

Landelijke evaluatie van bevolkingsonderzoek naar borstkanker in Nederland. 1990-2007 (XII). Het twaalfde evaluatierapport (Research Report)

2009-12-01T00:00:00Z

Introduction: The last detailed report from the National Evaluation Team for Breast cancer screening (NETB) on the Dutch breast cancer screening programme appeared in 2005. It presented the screening results up until the end of 2003 which, however, were incomplete for some regions. The same applies to the two brief interim reports that were released in 2006 and 2007. The new evaluation report adds four reporting years to the entire evaluation period, i.e. those from 2004- 2007. The fact that this 12th report by the NETB is based on complete nationwide data on the screening activities of all nine screening regions is particularly good news. This is thanks to the additional efforts made by the two regions that had had a backlog of screened women’s follow-up data for years, enabling the backlog to be eliminated by spring 2009. It also enabled the optimum analysis of 18 years of national population research, and the presentation of the results without qualification. Unfortunately, this does not apply to the data on interval cancers which, subsequent to 1999, are far from being fully available at national level....

Screening for child abuse at emergency departments: a systematic review (Article)

2009-11-11T00:00:00Z

Introduction: Child abuse is a serious problem worldwide and can be difficult to detect. Although children who experience the consequences of abuse will probably be treated at an emergency department, detection rates of child abuse at emergency departments remain low. OBJECTIVE: To identify effective interventions applied at emergency departments that significantly increase the detection rate of confirmed cases of child abuse. DESIGN: This review was carried out according to the Cochrane Handbook. Two reviewers individually searched Pubmed, The Cochrane Library, EMBASE, Web of Science, and CINAHL for papers that met the inclusion criteria. RESULTS: Fifteen papers describing interventions were selected and reviewed; four of these were finally included and assessed for quality. In these studies the intervention consisted of a checklist of indicators of risk for child abuse. After implementation, the rate of detected cases of suspected child abuse increased by 180% (weighted mean in 3 studies). The number of confirmed cases of child abuse, reported in two out of four studies, showed no significant increase. CONCLUSIONS: Interventions at emergency departments to increase the detection rate of cases of confirmed child abuse are scarce in the literature. Past study numbers and methodology have been inadequate to show conclusive evidence on effectiveness.

Prostate Cancer Mortality Reduction by Prostate-Specific Antigen-Based Screening Adjusted for Nonattendance and Contamination in the European Randomised Study of Screening for Prostate Cancer (ERSPC) (Article)

2009-10-01T00:00:00Z

Background: Prostate-specific antigen (PSA) based screening for prostate cancer (PCa) has been shown to reduce prostate specific mortality by 20% in an intention to screen (ITS) analysis in a randomised trial (European Randomised Study of Screening for Prostate Cancer [ERSPC]). This effect may be diluted by nonattendance in men randomised to the screening arm and contamination in men randomised to the control arm. Objective: To assess the magnitude of the PCa-specific mortality reduction after adjustment for nonattendance and contamination. Design, setting, and participants: We analysed the occurrence of PCa deaths during an average follow-up of 9 yr in 162 243 men 55-69 yr of age randomised in seven participating centres of the ERSPC. Centres were also grouped according to the type of randomisation (ie, before or after informed written consent). Intervention: Nonattendance was defined as nonattending the initial screening round in ERSPC. The estimate of contamination was based on PSA use in controls in ERSPC Rotterdam. Measurements: Relative risks (RRs) with 95% confidence intervals (CIs) were compared between an ITS analysis and analyses adjusting for nonattendance and contamination using a statistical method developed for this purpose. Results and limitations: In the ITS analysis, the RR of PCa death in men allocated to the intervention arm relative to the control arm was 0.80 (95% CI, 0.68-0.96). Adjustment for nonattendance resulted in a RR of 0.73 (95% CI, 0.58-0.93), and additional adjustment for contamination using two different estimates led to estimated reductions of 0.69 (95% CI, 0.51-0.92) to 0.71 (95% CI, 0.55-0.93), respectively. Contamination data were obtained through extrapolation of single-centre data. No heterogeneity was found between the groups of centres. Conclusions: PSA screening reduces the risk of dying of PCa by up to 31% in men actually screened. This benefit should be weighed against a degree of overdiagnosis and overtreatment inherent in PCa screening.

Informed participation in a randomised controlled trial of computed tomography screening for lung cancer (Article)

2009-09-01T00:00:00Z

The actual lung cancer (screening) knowledge, attitudes, risk perceptions, reasons to participate in or decline participation, and informed decisions of subjects who decided to or decided not to participate in the Dutch-Belgian randomised controlled trial for lung cancer screening in high-risk subjects (the NELSON trial) were evaluated. A total of 2,500 high-risk subjects were asked to complete a questionnaire 3 weeks after they had received a brochure with information about the trial. Differences in knowledge, attitude and risk perception between participants and nonparticipants were analysed with logistic regression analyses adjusted for sex and smoking status. The questionnaire response of trial participants was 80% (n=889) whereas the response of nonparticipants was low (7%, n=97) and selective. Participants' responses to knowledge items on lung cancer as a disease were on average more often correct (mean±SD 68±17%) than items on lung cancer screening (49±29%). Participants had adequate knowledge on lung cancer screening (51%) more often than the nonparticipants (38%; p=0.009). Of the decisions regarding participation, 49% were uninformed, mainly due to insufficient knowledge. Most of the participants (99%) and 64% of the nonparticipants had a positive attitude towards lung cancer screening. Additional efforts are required to improve the knowledge and understanding of subjects who are in the process of decision-making regarding participation in a lung cancer screening trial. Copyright

Cost-effectiveness of opportunistic versus organised mammography screening in Switzerland (Article)

2009-07-31T00:00:00Z

Test sensitivity in the European prostate cancer screening trial: Results from Finland, Sweden, and the Netherlands (Article)

2009-07-01T00:00:00Z

Test sensitivity pertains to the ability of a test to identify subjects with the target disorder. In cancer screening, test sensitivity can be estimated using interval cancer incidence as an indicator of false-negative result. A randomized trial provides the optimal approach for estimating test sensitivity, as the control arm provides the expected rates. We estimated the sensitivity of the prostate-specific antigen test using incidence method, i.e., based on incidence of interval cancer among subjects with negative screening results, compared with that in the control arm. Data from three centers in the European randomized screening trial were used to estimate interval cancer incidence (II) among 39,389 men with negative screening tests. This was compared with incidence among the 79,525 men in the control arm of the trial (Ic) to estimate test sensitivity (S = 1 - II/ IC). Confidence intervals were calculated using simulations, assuming that the number of cases follows a Poisson distribution. The estimated test sensitivity following the first screen was 0.87 (0.83-0.92) in Finland, 0.87 (0.62-1.00) in Sweden, and 0.93 (95% confidence interval, 0.90-0.96) in the Netherlands. There was some indication of a higher test sensitivity for aggressive cancers (0.85-0.98 for non-organ-confined cases or Gleason 8-10) and for the second screening round (approximately 0.85-0.95). Test sensitivity varied to some extent between the three centers in the European trial, probably reflecting variation in screening protocols, but was acceptable in the first screening round, and may be better for aggressive cancers and in the second screening round. Copyright

De mysterieuze massa. Inaugurele rede bij het aanvaarden van de Bijzondere leerstoel 'Evaluatie van vroegopsporing van ziekten' (Inaugural Lecture)

2009-06-29T00:00:00Z

... Het leven is een mysterie. En geldt dit niet des te meer voor zijn tegenhanger, de dood? Er zijn talrijke theorieën omtrent de oorsprong van het leven, dan wel het einde van het leven. In dit Darwinjaar is de evolutietheorie, en daarmee de eindigheid van ons bestaan, populairder dan ooit. Er is het scheppingsverhaal met een indicatie van het oneindige van ons bestaan; er is de theorie van een oneindig bewustzijn, geformuleerd op basis van bijna-dood ervaringen van patiënten. Er bestaan Japanse verhalen over shinigami’s, engelen des doods, die met het schrijven van je naam in een zogenaamde ‘death note’ je tijdstip van overlijden bepalen. Deze shinigami’s zouden tegenwoordig, uit verveling of om niet als streber te worden aangemerkt, steeds minder vaak namen noteren. ...

Role of baseline nodule density and changes in density and nodule features in the discrimination between benign and malignant solid indeterminate pulmonary nodules (Article)

2009-06-01T00:00:00Z

Purpose: To retrospectively evaluate whether baseline nodule density or changes in density or nodule features could be used to discriminate between benign and malignant solid indeterminate nodules. Materials and methods: Solid indeterminate nodules between 50 and 500 mm3(4.6-9.8 mm) were assessed at 3 and 12 months after baseline lung cancer screening (NELSON study). Nodules were classified based on morphology (spherical or non-spherical), shape (round, polygonal or irregular) and margin (smooth, lobulated, spiculated or irregular). The mean CT density of the nodule was automatically generated in Hounsfield units (HU) by the Lungcare©software. Results: From April 2004 to July 2006, 7310 participants underwent baseline screening. In 312 participants 372 solid purely intra-parenchymal nodules were found. Of them, 16 (4%) were malignant. Benign nodules were 82.8 mm3(5.4 mm) and malignant nodules 274.5 mm3(8.1 mm) (p = 0.000). Baseline CT density for benign nodules was 42.7 HU and for malignant nodules -2.2 HU (p = ns). The median change in density for benign nodules was -0.1 HU and for malignant nodules 12.8 HU (p < 0.05). Compared to benign nodules, malignant nodules were more often non-spherical, irregular, lobulated or spiculated at baseline, 3-month and 1-year follow-up (p < 0.0001). In the majority of the benign and malignant nodules there was no change in morphology, shape and margin during 1 year of follow-up (p = ns). Conclusion: Baseline nodule density and changes in nodule features cannot be used to discriminate between benign and malignant solid indeterminate pulmonary nodules, but an increase in density is suggestive for malignancy and requires a shorter follow-up or a biopsy.

Screening and prostate-cancer mortality in a randomized european study (Article)

2009-03-26T00:00:00Z

Background The European Randomized Study of Screening for Prostate Cancer was initiated in the early 1990s to evaluate the effect of screening with prostate-specific-antigen(PSA) testing on death rates from prostate cancer. Methods We identified 182,000 men between the ages of 50 and 74 years through registries in seven European countries for inclusion in our study. The men were randomly assigned to a group that was offered PSA screening at an average of once every 4 years or to a control group that did not receive such screening. The predefined core age group for this study included 162,243 men between the ages of 55 and 69 years. The primary outcome was the rate of death from prostate cancer. Mortality follow-up was identical for the two study groups and ended on December 31, 2006. Results In the screening group, 82% of men accepted at least one offer of screening. During a median follow-up of 9 years, the cumulative incidence of prostate cancer was 8.2% in the screening group and 4.8% in the control group. The rate ratio for death from prostate cancer in the screening group, as compared with the control group, was 0.80(95% confidence interval [CI], 0.65 to 0.98; adjusted P = 0.04). The absolute risk difference was 0.71 death per 1000 men. This means that 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer. The analysis of men who were actually screened during the first round(excluding subjects with noncompliance) provided a rate ratio for death from prostate cancer of 0.73(95% CI, 0.56 to 0.90). Conclusions PSA-based screening reduced the rate of death from prostate cancer by 20% but was associated with a high risk of overdiagnosis.(Current Controlled Trials number, ISRCTN49127736.) Copyright

Lead time and overdiagnosis in prostate-specific antigen screening: Importance of methods and context (Article)

2009-03-01T00:00:00Z

Background The time by which prostate-specific antigen (PSA) screening advances prostate cancer diagnosis, called the lead time, has been reported by several studies, but results have varied widely, with mean lead times ranging from 3 to 12 years. A quantity that is closely linked with the lead time is the overdiagnosis frequency, which is the fraction of screen-detected cancers that would not have been diagnosed in the absence of screening. Reported overdiagnosis estimates have also been variable, ranging from 25% to greater than 80% of screen-detected cancers.Methods We used three independently developed mathematical models of prostate cancer progression and detection that were calibrated to incidence data from the Surveillance, Epidemiology, and End Results program to estimate lead times and the fraction of overdiagnosed cancers due to PSA screening among US men aged 54-80 years in 1985-2000. Lead times were estimated by use of three definitions. We also compared US and earlier estimates from the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC) that were calculated by use of a microsimulation screening analysis (MISCAN) model.ResultsThe models yielded similar estimates for each definition of lead time, but estimates differed across definitions. Among screen-detected cancers that would have been diagnosed in the patients' lifetimes, the estimated mean lead time ranged from 5.4 to 6.9 years across models, and overdiagnosis ranged from 23% to 42% of all screen-detected cancers. The original MISCAN model fitted to ERSPC Rotterdam data predicted a mean lead time of 7.9 years and an overdiagnosis estimate of 66%; in the model that was calibrated to the US data, these were 6.9 years and 42%, respectively.ConclusionThe precise definition and the population used to estimate lead time and overdiagnosis can be important drivers of study results and should be clearly specified.

Delayed diagnosis of breast cancer in women recalled for suspicious screening mammography (Article)

2009-03-01T00:00:00Z

Purpose: To determine the frequency, pathology and causes of a delay in cancer diagnosis in women recalled for suspicious screening mammography. Methods: We included all 290,943 screening mammograms of women aged 50-75 years, who underwent biennial screening mammography between 1st January 1995 and 1st January 2006. During a follow-up period of at least 2 years, clinical data, breast imaging reports, biopsy results and breast surgery reports were collected of all 3513 women with a positive screening result. Tumour stages of breast cancers with a diagnostic delay (defined as breast cancer confirmation more than 3 months following a positive mammography screen) were compared with those of cancers diagnosed within 3 months following referral and with interval cancers. Results: A diagnostic delay occurred in 97 (6.5%) of 1503 screen-detected cancers. These 97 false-negative assessments comprised significantly more ductal cancers in situ (26.8%) than did cancers with an adequate assessment after recall (15.5%, p = 0.004) or interval cancers (3.7%, p < 0.001). Compared with interval cancers, cancers with a false-negative assessment had a more favourable tumour size (T1a-c, 87.3% versus T1a-c, 46.4%; p < 0.001) and showed significantly fewer cases with axillary lymph node metastases (22.5% versus 48.2%; p < 0.001). Between hospitals having performed the workup of at least 500 referred women each, the percentage of women with a false-negative assessment varied from 5.0% to 9.1% (p = 0.03). In these hospitals, improper classification of lesions at diagnostic mammography comprised 64.4% of false-negative assessments. Conclusion: We found that 6.5% of recalled women experienced a delay in breast cancer diagnosis, with significant performance variations between hospitals.

Limited contamination in the Dutch-Belgian randomized lung cancer screening trial (NELSON) (Article)

2009-01-01T00:00:00Z

Purpose of this study was to determine the rate of contamination, defined as lung cancer screening in the control arm, of the Dutch-Belgian randomized lung cancer screening trial (NELSON) as contamination adversely affects the power of a trial. The NELSON cohort includes 15,822 high-risk current and former smokers, aged 50-75 years, equally randomized to the screen and control arm. Questionnaires were sent to a sample of 1460 male subjects of the control arm, stratified on smoking determinants. The response rate was 73.0%. The participants were asked whether they received a chest X-ray or CT scan in the last 4 years and, if so, when and for what reason it had been performed. Examinations performed after randomization because of "Precaution" or "No examination was offered by NELSON" were regarded as contamination. In the first 24 months after randomization 3.1% (2.3-3.8%) of the respondents received a lung cancer screening examination. Contamination reached a non-significant peak within the first 3 months after randomization, with a lower limit of 2.5 and an upper limit of 3.1 per 1000 person-months. This screening rate did not differ from the background rates in the last 18 months before randomization. No significant differences were observed between current and former smokers. In conclusion, the rate of contamination among male subjects of the control arm of the NELSON trial is low and is not likely to jeopardize the power of the trial.

Smooth or attached solid indeterminate nodules Detected at baseline CT screening in the NELSON study: Cancer risk during 1 year of follow-up (Article)

2009-01-01T00:00:00Z

Purpose: To retrospectively determine whether baseline nodule characteristics at 3-month and 1-year volume doubling time (VDT) are predictive for lung cancer in solid indeterminate noncalcified nodules (NCNs) detected at baseline computed tomographic (CT) screening. Materials and Methods: The study, conducted between April 2004 and May 2006, was institutional review board approved. Patient consent was waived for this retrospective evaluation. NCNs between 5 and 10 mm in diameter (n = 891) were evaluated at 3 months and 1 year to assess growth (VDT < 400 days). Baseline assessments were related to growth at 3 months and 1 year by using x2and Mann-Whitney U tests. Baseline assessments and growth were related to the presence of malignancy by using univariate and multivariate logistic regression analyses. Results: At 3 months and at 1 year, 8% and 1% of NCNs had grown, of which 15% and 50% were malignant, respectively. One-year growth was related to morphology (P < .01), margin (P < .0001), location (P < .001), and size (P < .01). All cancers were nonspherical and purely intra-parenchymal, without attachment to vessels, the pleura, or fissures. In nonsmooth unattached nodules, a volume of 130 mm3or larger was the only predictor for malignancy (odds ratio, 6.3; 95% confidence interval [CI]: 1.7, 23.0). After the addition of information on the 3-month VDT, large volume (odds ratio, 4.9; 95% CI: 1.2, 20.1) and 3-month VDT (odds ratio, 15.6; 95% CI: 4.5, 53.5) helped predict malignancy. At 1 year, only the 1-year growth remained (odds ratio, 213.3; 95% CI: 18.7, 2430.9) as predictor for malignancy. Conclusion: In smooth or attached solid indeterminate NCNs, no malignancies were found at 1-year follow-up. In nonsmooth purely intraparenchymal NCNs, size is the main baseline predictor for malignancy. When follow-up data are available, growth is a strong predictor for malignancy, especially at 1-year follow-up.

Testing at home - The screening of the future? (Article)

2009-01-01T00:00:00Z

High affective risk perception is associated with more lung cancer-specific distress in CT screening for lung cancer (Article)

2008-12-01T00:00:00Z

Screening for cancer can cause distress. People who perceive their risk of cancer as high may be more vulnerable to distress. This study evaluated whether participants of a lung cancer Computed Tomography (CT) screening trial with a high affective risk perception of developing lung cancer had a higher level of lung cancer-specific distress during CT screening. Furthermore, we evaluated whether participants perceived their risk of developing lung cancer differently 6 months after screening compared with 1 day before screening. A total of 351 subsequent participants of the NELSON-trial (Dutch-Belgian randomized controlled trial for lung cancer screening in high-risk subjects), who were randomized to the screen arm, were asked to fill in questionnaires 1 day before and 6 months after screening. Lung cancer-specific distress (Impact of Event Scale (IES)), generic health-related quality of life (SF-12) and affective risk perception were assessed. One day before screening, the participants with a high affective risk perception (n = 47/321, 14.6%) had significantly higher (i.e., worse) median IES scores than participants with a low affective risk perception (11.5 vs. 2.0, p < 0.01). Although median IES scores were significantly lower 6 months after screening than 1 day before screening, participants with a high affective risk perception still showed significantly higher IES scores than participants with a low affective risk perception (6.5 vs. 1.0, p < 0.01). Six months after screening, significantly less participants (10.5%) felt that their risk of developing lung cancer was high than 1 day before screening (14.5%) (p < 0.01). Levels of distress were not severe, but were elevated compared to participants with a low affective risk perception, and therefore, attention for this group is recommended.

Breast cancer screening: evidence for false reassurance? (Article)

2008-11-08T00:00:00Z

Tumour stage distribution at repeated mammography screening is, unexpectedly, often not more favourable than stage distribution at first screenings. False reassurance, i.e., delayed symptom presentation due to having participated in earlier screening rounds, might be associated with this, and unfavourably affect prognosis. To assess the role of false reassurance in mammography screening, a consecutive group of 155 breast cancer patients visiting a breast clinic in Rotterdam (The Netherlands) completed a questionnaire on screening history and self-observed breast abnormalities. The length of time between the initial discovery of breast abnormalities and first consultation of a general practitioner ("symptom-GP period") was compared between patients with ("screening group") and without a previous screening history ("control group"), using Kaplan-Meier survival curves and log-rank testing. Of the 155 patients, 84 (54%) had participated in the Dutch screening programme at least once before tumour detection; 32 (38%) of whom had noticed symptoms. They did not significantly differ from control patients (n = 42) in symptom-GP period (symptom-GP period > or = 30 days: 31.2% in the symptomatic screened group, 31.0% in the control group; p = 0.9). Only 2 out of 53 patients (3.8%) with screen-detected cancer had noticed symptoms prior to screening, reporting symptom-GP periods of 2.5 and 4 years. The median period between the first GP- and breast clinic visit was 7.0 days (95% C.I. 5.9-8.1) in symptomatic screened patients and 6.0 days (95% C.I. 4.0-8.0) in control patients. Our results show that false reassurance played, at most, only a minor role in breast cancer screening.

Limited value of shape, margin and CT density in the discrimination between benign and malignant screen detected solid pulmonary nodules of the NELSON trial (Article)

2008-11-01T00:00:00Z

Purpose: To evaluate prospectively the value of size, shape, margin and density in discriminating between benign and malignant CT screen detected solid non-calcified pulmonary nodules. Material and methods: This study was institutional review board approved. For this study 405 participants of the NELSON lung cancer screening trial with 469 indeterminate or potentially malignant solid pulmonary nodules (>50 mm3) were selected. The nodules were classified based on size, shape (round, polygonal, irregular) and margin (smooth, lobulated, spiculated). Mean nodule density and nodule volume were automatically generated by software. Analyses were performed by univariate and multivariate logistic regression. Results were presented as likelihood ratios (LR) with 95% confidence intervals (CI). Receiver operating characteristic analysis was performed for mean density as predictor for lung cancer. Results: Of the 469 nodules, 387 (83%) were between 50 and 500 mm3, 82 (17%) >500 mm3, 59 (13%) malignant, 410 (87%) benign. The median size of the nodules was 103 mm3(range 50-5486 mm3). In multivariate analysis lobulated nodules had LR of 11 compared to smooth; spiculated nodules a LR of 7 compared to smooth; irregular nodules a LR of 6 compared to round and polygonal; volume a LR of 3. The mean nodule CT density did not predict the presence of lung cancer (AUC 0.37, 95% CI 0.32-0.43). Conclusion: In solid non-calcified nodules larger than 50 mm3, size and to a lesser extent a lobulated or spiculated margin and irregular shape increased the likelihood that a nodule was malignant. Nodule density had no discriminative power.

Does “Normal” Aging Imply Urinary, Bowel, and Erectile Dysfunction? A General Population Survey (Article)

2008-10-25T00:00:00Z

We assessed if urinary, bowel, and sexual dysfunction and associated bother were part of the “normal” aging process in the general male Dutch population. Methods Randomly selected participants of a screening trial were mailed a questionnaire on dysfunction and bother in the urinary, bowel, and sexual domains. A Dutch version of the Expanded Prostate Cancer Index Composite (EPIC) was used. Results Three thousand eight hundred ten (3810) men responded (81%), mean age 67 years, range 58 to 78. The prevalence of urinary dysfunction was low, and although the difference between younger versus older men was significant (P <0.001), it did not exceed the minimal important difference. Bowel dysfunction and bother were not related to age. Erectile dysfunction was reported by 19%, ranging from 12% in the youngest to 26% in the oldest group (P <0.001). The overall use of erectile aids was negatively associated with the satisfaction with sex life and positively with the importance attached to it (P <0.001), but not with age or sexual activity. Conclusions Urinary and bowel dysfunction were not part of the “normal” aging process. Erectile dysfunction was significantly more prevalent in older men. In men treated for localized prostate cancer, decreasing urinary or bowel function is thus not attributable to age, but may well be related to prior treatment. Decreasing erectile function, however, may be attributable to other causes as wellt. These data provide a benchmark for urologic functioning in men after treatment relative to age-related patterns, and will enable better interpretation of treatment outcomes.

Impressive time-related influence of the Dutch screening programme on breast cancer incidence and mortality, 1975-2006 (Article)

2008-10-15T00:00:00Z

The aim of this study was to assess changes in the trends in breast cancer mortality and incidence from 1975 to 2006 among Dutch women, in relation to the implementation of the national breast cancer screening programme. Screening started in 1989 for women aged 50-69 and was extended to women aged 70-75 years in 1998 (attendance rate approximately >80%). A joinpoint Poisson regression analysis was used to identify significant changes in rates over time. Breast cancer mortality rates increased until 1994 (age group 35-84), but thereafter showed a marked decline of 2.3-2.8% per annum for the age groups 55-64 and 65-74 years, respectively. For the age group of 75-84 years, a decrease started in the year 2001. In women aged 45-54, an early decline in breast cancer mortality rates was noted (1971-1980), which is ongoing from 1992. For all ages, breast cancer incidence rates showed an increase between 1989 and 1993, mainly caused by the age group 50-69, and thereafter, a moderate increase caused by age group 70-74 years. This increase can partly be explained by the introduction of screening. The results indicate an impressive decrease in breast cancer mortality in the age group invited for breast cancer screening, starting to show quite soon after implementation.

Effect of nodule characteristics on variability of semiautomated volume measurements in pulmonary nodules detected in a lung cancer screening program (Article)

2008-08-01T00:00:00Z

Purpose: To retrospectively assess volume measurement variability in solid pulmonary nodules (volume, 15-500 mm3) detected at lung cancer screening and to quantify the independent effects of nodule morphology, size, and location. Materials and Methods: This retrospective study was a substudy of the screening program that was approved by the Dutch Ministry of Health, and all participants provided written informed consent. Two independent readers used semiautomated software to measure the volume of pulmonary nodules detected in 6774 participants aged 50-75 years (5917 men). Nodules were classified according to their location (purely intraparenchymal, pleural based, juxtavascular, or fissure attached), morphology (smooth, polylobulated, spiculated, or irregular), and size (<50 mm3or >50 mm3). The level of agreement was expressed by using the absolute values of the relative volume differences (RVDs). Multivariate logistic regression analysis was performed, and odds ratios (ORs) were computed to quantify the independent effects of morphology, location, and size on RVD categories. Results: Altogether, 4225 nodules in 2239 participants were included. Complete agreement in volume was obtained for 3646 (86%) of the nodules. Disagreement was small (absolute value of RVD < 5%) for 173 (4%) nodules, moderate (absolute value of RVD ≥ 5% but < 15%) for 232 (6%), and large (absolute value of RVD ≥ 15%) for 174 (4%). Multivariate analysis showed that the ORs of volume disagreement were 15.7, 3.1, and 1.9 for irregular, spiculated, and polylobulated nodules, respectively; 3.5, 2.6, and 2.1 for juxtavascular, pleural-based, and fissure-attached nodules, respectively; and 1.3 for large nodules compared with smooth, purely intraparenchymal, and small reference nodules. Conclusion: Nodule morphology, location, and size influence volume measurement variability, particularly for juxtavascular and irregular nodules.

Impact of computed tomography screening for lung cancer on participants in a randomized controlled trial (NELSON trial) (Article)

2008-07-15T00:00:00Z

BACKGROUND. Computed tomography (CT) screening is an important new tool for the early detection of lung cancer. In the current study, the authors assessed the discomfort associated with CT scanning and the subsequent wait for results and health-related quality of life (HRQoL) over time. METHODS. A total of 351 participants in the Dutch-Belgian randomized controlled trial for lung cancer screening in high-risk subjects (the NELSON trial) who had an appointment for a baseline CT scan were asked to complete questionnaires regarding their experienced discomfort and HRQoL before, 1 day after, and approximately 6 months after the CT scan. HRQoL was measured as generic HRQoL (12-item Short Form [SF-12] and EuroQol questionnaire [EQ-5D]), generic anxiety (State-Trait Anxiety Inventory [STAI-6]), and lung cancer-specific distress (Impact of Event Scale [IES]). Approximately 76.9% of the participants completed all 3 questionnaires. RESULTS. Approximately 87% to 99% of participants reported experiencing no discomfort related to the CT scan. The median SF-12, EQ-5D, STAI-6, and IES scores did not appear to change relevantly over time. Approximately 46.0% and 51.3%, respectively, of the participants reported discomfort in connection with having to wait for the results of the CT scan and dreading those results. These patients had relevantly higher STAI-6 and IES scores (P < .01) (unfavorable) at all 3 assessments. CONCLUSIONS. The current evaluation of the potential adverse effects of CT screening for lung cancer on HRQoL demonstrated no negative effects. However, waiting for the CT scan results was reported to be discomforting by approximately half of the participants. Minimizing the waiting time for the test results is merefore recommended.

Improving cancer control in the European Union: Conclusions from the Lisbon round-table under the Portuguese EU Presidency, 2007 (Article)

2008-07-01T00:00:00Z

Cancer is a major cause of morbidity and mortality in the European Union (EU), and a public health burden. Improving cancer control in the EU will require implementation of efficient strategies within Member States and better policy coordination between them. In cooperation between the rotating EU Presidencies of Germany (2007), Portugal (2007) and Slovenia (2008), special attention was devoted to an integrated approach to cancer control in EU policies and programmes. A round-table focussed on national cancer plans, population-based cancer registries and cancer screening programmes was held during the Health Strategies in Europe meeting in Lisbon in July 2007, under the Portuguese Presidency. These three topics were selected as critical for improving cancer control at both national and European levels. The round-table was designed to produce a set of recommendations to inform EU cancer policy. This paper provides a résumé of the conclusions and recommendations, to stimulate wider discussion and policy development. The conclusions of the meeting were presented at the Employment, Social Policy, Health and Consumer Affairs Council in December 2007 and cancer was included in the Council Conclusions for the new European Health Strategy. Success in cancer control will require consistent attention from future EU Presidencies, such as the initiative of the Slovenian EU Presidency in early 2008.

In reply (Article)

2008-06-01T00:00:00Z

In Reply (Article)

2008-06-01T00:00:00Z

Introduction of additional double reading of mammograms by radiographers: Effects on a biennial screening programme outcome (Article)

2008-06-01T00:00:00Z

Purpose: To determine the effect of introducing radiographer double reading, in addition to standard radiologist double reading, on screening mammography outcome. Methods: In period A, 66,225 mammograms were read by two screening radiologists. In period B, 78,325 mammograms were read by two radiographers in addition and radiologists were blinded to the referral opinion of the radiographers. Mammograms, for which only radiographers had suggested referral, (i.e. cases that would only be referred by technologists) were re-evaluated by the screening radiologists. Women were referred if at least one radiologist considered this necessary, and diagnostic costs of these additional referrals were estimated. Results: In period A, 322 cancers were diagnosed after referral of 678 women. During period B, radiologists initially referred 1122 patients and 411 cancers were detected. Radiologists' referral rate was higher in period B than in period A (1.43% versus 1.02%, p < 0.001), as well as the cancer detection rate per 1000 women screened (CDR) (5.25 versus 4.86, p = 0.3). The positive predictive value of referral (PPV) was 36.6% versus 47.5% (p < 0.001). In period B, radiologist review of 544 additional positive radiographer readings led to 102 extra referrals, with 29 additional cancers detected, resulting in an overall referral rate of 1.56% (compared to period A, p < 0.001), an overall CDR of 5.62 (p = 0.048) and an overall PPV of 35.9% (p < 0.001). Workup expenses of the 102 additional referrals were €60,274. Conclusion: Additional radiographer double reading detected cancers that would have been missed by radiologists. Mean expenses for diagnostic confirmation of these extra cancers was €2078 per cancer.

Bracing patients with idiopathic scoliosis: Design of the Dutch randomized controlled treatment trial (Article)

2008-05-26T00:00:00Z

Background. The effectiveness of bracing patients with IS has not yet been convincingly established due to a lack of RCTs. Some authors suggest that their results confirm that bracing is effective; others conclude that the effectiveness of bracing is doubtful or recommend a RCT. The aim of this study was to establish whether bracing patients with idiopathic scoliosis (IS) in an early stage will result in at least 5 degrees less mean progression of the curvature compared to the control group after two years of follow-up. Methods. A randomized controlled trial was designed. Eligible patients are girls and boys in the age group 8-15 years whose diagnosis of IS has been established by an orthopedic surgeon, who have not yet been treated by bracing or surgery, and for whom further growth of physical height is still expected based on medical examination and maturation characteristics (Risser ? 2). The Cobb angle of the eligible patient should either be minimally 22 and maximally 29 degrees with established progression of more than 5 degrees, or should be minimally 30 and maximally 35 degrees; established progression for the latter is not necessary. A total of 100 patients will be included in this trial. The intervention group will be treated with full-time Boston brace wear; the control group will not be braced. Every four months, each patient will have a physical and an X-ray examination. The main outcomes will be the Cobb angle two years after inclusion and health-related quality of life. Discussion. The results of this trial will be of great importance for the discussion on early treatment for scoliosis. Furthermore, the result will also be important for screening for scoliosis policies. Trial registration. Nederlands Trialregister ISRCTN36964733.

Utilization and cost of diagnostic imaging and biopsies following positive screening mammography in the southern breast cancer screening region of the Netherlands, 2000-2005 (Article)

2008-05-20T00:00:00Z

We prospectively assessed trends in utilization and costs of diagnostic services of screen-positive women in a biennial breast cancer screening program for women aged 50-75 years. All 2,062 women with suspicious findings at screening mammography in the southern region of the Netherlands between 1 January 2000 and 1 July 2005 (158,997 screens) were included. Data were collected on any diagnostic examinations, interventional procedures, and surgical consultations with two-year follow-up. We used national reimbursement rates to estimate imaging costs and percutaneous biopsy costs. Cost prices, charged by hospitals, were used to estimate open surgical biopsy costs and surgical consultation costs. The largest increase in utilization of diagnostic procedures per 100 referrals was observed for axillary ultrasound (from 3.9 in 2000 to 33.5 in 2005) and for stereotactic core biopsy (from 2.1 in 2000 to 26.8 in 2005). Per 100 referrals, the open surgical biopsy rate decreased from 34.7 (2000) to 4.6 (2005) and the number of outpatient surgical consultations fluctuated between 269.8 (2000) and 309.7 (2004). Mean costs for the diagnosis of one cancer were €1,501 and ranged from €1,223 (2002) to €1,647 (2003). Surgical biopsies comprised 54.1% of total diagnostic costs for women screened in 2000, but decreased to 9.9% for women screened in 2005. Imaging costs increased from 23.7 to 43.8%, percutaneous biopsy costs from 9.9 to 27.2%, and consultation costs from 12.3 to 19.1%. We conclude that diagnostic costs per screen-detected cancer remained fairly stable through the years, although huge changes in the use of different diagnostic procedures were observed.

How to deal with incidentally detected pulmonary nodules less than 10 mm in size on CT in a healthy person (Article)

2008-05-01T00:00:00Z

The high frequency of non-calcified pulmonary nodules (NCN) <10 mm incidentally detected on a multi-detector CT (MDCT) of the chest raises the question of how clinicians and radiologists should deal with these nodules. Management algorithms for solitary pulmonary nodules >10 mm do not carry across to sub-centimeter lesions. Purpose of this review is to provide a 10-step approach for routinely detected sub-centimeter NCN on a MDCT in healthy persons in order to be able to make an optimal discrimination between benign and malignant NCNs. Recommendations are primarily based on individual cancer risk, the presence or absence of calcifications and nodule size. In nodules >4-5 mm nodule consistency, margin and shape should be taken into account. Next steps in the nodule evaluation are the assessment of localization, nodule number, presence or absence of growth and volume doubling time. Growth is defined as a volume doubling time of 400 days or less, based on volumetry. For nodules <4 mm, a follow-up CT at 12 months is recommended in high risk persons, whilst for low-risk persons no follow-up is needed. If no growth is observed at 12 months, no further follow-up is required. For solid, smooth or attached indeterminate NCN between 5 and 10 mm we recommend an annual repeat scan, whilst for purely intra-parenchymal nodules a 3-month repeat scan should be made to assess growth. Growing lesions with a volume doubling time <400 days require further work-up and diagnosis, otherwise an annual repeat scan to assess growth is recommended.

A Cluster-Randomized Trial of Screening for Language Delay in Toddlers: Effects on School Performance and Language Development at Age 8 (Article)

2008-03-14T00:00:00Z

OBJECTIVE. The goal of this study was to assess the effects of screening and early treatment of preschool children for language delay on language development and school performance at age 8. METHODS. A cluster-randomized, controlled trial and follow-up study of 55 child health centers in 6 geographic regions were conducted from January 2002 to September 2005. A total of 9419 children who were from the general population and aged 15 months at entry were studied. School type end school progress was known for 5406 (57.4%) children. In the intervention group, a structured screening instrument was conducted twice (at ages 15/18 and 24 months), and usual care was applied in the control group. The screening instrument consisted of a uniform set of questions for the parents and test elements for the child. A positive screen result was followed by multidisciplinary assessments at speech and hearing centers and subsequent early treatment if needed. Percentages of children who attended a special school, repeated a class because of language problems, and scored low on standardized language tests, in intention-to-screen analyses, were measured. RESULTS. At age 8, 2.7% in the intervention group and 3.7% in the control group attended a special school, 6.1% vs 4.9% had repeated a grade, 8.8% vs 9.7% had deficient oral language performance, 4.7% vs 4.7% had deficient reading, and 2.8% vs 4.2% had deficient spelling. CONCLUSIONS. Screening toddlers for language delays reduces the number of children who require special education and leads to improved language performance at age 8. Nationwide implementation of the screening might be recommended.

Estimating the effectiveness of screening for scoliosis: a case-control study (Article)

2008-01-01T00:00:00Z

OBJECTIVE: The aim of this study was to test the hypothesis that screening for scoliosis is effective in reducing the need for surgical treatment. METHODS: The study was a case-control study. A total of 125 consecutive patients who were treated surgically for idiopathic scoliosis between January 2001 and October 2004 and who were born on or after January 1, 1984, were invited; 108 agreed to participate. A total of 216 control subjects were selected randomly and anonymously, matched with respect to age and gender. For 279 adolescents, exact screening exposure and outcomes could be analyzed. Case subjects were recruited from 4 university and 6 nonuniversity Dutch hospitals; control subjects were recruited from all 37 municipal health services in The Netherlands. RESULTS: Screen-detected patients received diagnoses at a significantly younger age than did otherwise-detected patients (10.8 +/- 2.6 vs 13.4 +/- 1.7 years). In total, 32.8% of the surgically treated patients had been screened between 11 and 14 years of age, compared with 43.4% of the control subjects. The odds ratio for being exposed to screening was 0.64. In total, 28% of the patients were diagnosed as having scoliosis before 11 years of age. CONCLUSIONS: Our results showed no evidence that screening for scoliosis reduced the need for surgery. Abolishing screening seems justified, especially because the effectiveness of early treatment with bracing is still strongly debated. A randomized, controlled trial on the effectiveness of treating patients with idiopathic scoliosis with bracing is urgently needed.

Response shift due to diagnosis and primary treatment of localized prostate cancer: a then-test and a vignette study (Article)

2007-12-01T00:00:00Z

Aim Whether a prostate cancer diagnosis induces response shift has not been established so far. Therefore, we assessed response shift in men who were diagnosed with localized prostate cancer. Patients and methods Out of 3,892 men who completed a questionnaire before screening, 82 were subsequently diagnosed with prostate cancer. Response shift was assessed in 52 (response 63%) by the then-test (EuroQol self-rating of health, Short-Form 36 mental health and vitality) and a novel method: rating of vignettes relating to side effects of prostate cancer treatment (urinary, bowel and erectile dysfunction). Three then-tests were conducted: two referencing pre-diagnosis (measured pre- and post-treatment), and one referencing pre-treatment (measured post-treatment). Results Then-test scores of pre-diagnosis health were significantly higher than original scores, indicating a more positive judgement in retrospect. Then-test scores of pre-treatment health were lower than original scores. Especially the vignette on erectile dysfunction was rated less bad after diagnosis versus before (P < 0.001, moderate effect size). Conclusions We found evidence for response shift in men who were diagnosed with prostate cancer. Men evaluated urinary, bowel, and erectile dysfunction as less bad after they had become patients who can expect to experience these side effects. The rating of vignettes is a promising additional technique to assess response shift.

Answer to the Letter to the Editor of I. Aprile et al. concerning “Health-related quality of life in patients with adolescent idiopathic scoliosis after treatment: short-term effects after brace or surgical treatment” (by Bunge EM et al. Eur Spine J 16: 83–89, 2007) (Letter To Editor)

2007-11-01T00:00:00Z

This author’s reply refers to the article http://dx.doi.org/10.1007/s00586-007-0461-4

A decade of breast cancer screening in the Netherlands: Trends in the preoperative diagnosis of breast cancer (Article)

2007-11-01T00:00:00Z

Purpose: In a prospective, multi-institutional follow-up study we describe the trends in the preoperative pathologic confirmation of breast cancer of women who underwent breast cancer screening between 1995 and 2005. Methods: We included all women aged 50-75 years who underwent biennial screening mammography in the southern breast cancer screening region of the Netherlands between February 13, 1995 and December 22, 2004. Clinical data, breast imaging reports, biopsy results and breast surgery reports were collected of all women with a positive screening result. Follow-up lasted through the next biennial screening examination and was approximately two years for all referred women. Results: Of 258,900 mammographic screening examinations, 3,064 (1.2%) were positive screens. The majority of women (92%) were analyzed in four regional hospitals and workup yielded breast cancer in 1,332 women. From 1995 to 2005, the percentage of breast cancer cases that underwent percutaneous biopsy prior to surgery, increased from 42.4 to 100%. The proportion of cancers with a preoperative diagnosis of malignancy by percutaneous biopsy, increased from 27.1% in 1995 to 92.7% in 2004. Preoperative breast cancer confirmation by fine needle aspiration cytology (FNAC) gradually decreased from 91.3% to 14.5%, whereas preoperative confirmation by ultrasound guided core biopsy (USCB) or stereotactic core needle biopsy (SCNB) increased from 8.7% to 69.1% and from 0 to 17.4% respectively. Conclusions: A preoperative diagnosis of breast cancer is currently obtained in more than 90% of breast cancer patients. The increase in preoperative breast cancer diagnosis through 1995-2004 is correlated with the introduction of SNCB and increased use of USCB at the expense of FNAC.

Health-Related Quality of Life in Adolescents with Wheezing Attacks (Article)

2007-11-01T00:00:00Z

Purpose: The purpose of this study was to evaluate health-related quality of life in adolescents with wheezing attacks using self-reported data, and to determine independent associations between wheezing attacks and quality of life using multivariate linear regression models. Methods: Our study sample included 933 of 1071 eligible adolescents who participated in a study in two Municipal Health Services in the Netherlands. Wheezing was defined based on selected questions from the International Study of Asthma and Allergies in Childhood. Quality of life was measured using the Child Health Questionnaire-Child Form (CHQ-CF). Higher scores indicated better quality of life. Results: According to the adolescents, 72 (7.7%) and 24 (2.6%) had less than four and, at least four wheezing attacks during the past year, respectively. Compared with adolescents who never wheezed, adolescents with wheezing attacks had significantly lower quality of life scores for nine out of 10 CHQ-CF scales. Except for the Role Physical and Family Activities scales, relevant differences in quality of life were observed for all scales among adolescents who reported at least four wheezing attacks during the past year; most affected were the Bodily Pain, General Health, Self Esteem, and Mental Health scales. In multivariate linear regression models, wheezing attacks remained significantly associated with quality of life for nine out of 10 CHQ-CF scales. Conclusions: Wheezing attacks are independently associated with several dimensions of health-related quality of life in adolescents. Specifically, the presence of at least four wheezing attacks during the past year was associated with relevant deficits in quality of life.

Passive coping and psychological distress in women adhering to regular breast cancer surveillance (Article)

2007-09-01T00:00:00Z

Since 2000 the MRISC study evaluates the psychological consequences of regular breast cancer surveillance for women at increased risk for hereditary breast cancer. Coping style way influence these psychological consequences. In a cohort of 357 women at increased risk for hereditary breast cancer, the impact of coping styles on the course, divided into level and trend of psychological distress (general and breast cancer specific) was examined, around two consecutive surveillance appointments. With structural equation modelling we found passive coping to be associated with higher levels of both general and breast cancer specific distress. Seeking social support, expression of emotions and thinking comforting thoughts were associated with lower levels of psychological distress. Coping style was not associated with the trend of psychological distress around the two surveillance appointments. it is recommendable to take coping styles into account when counselling these high-risk women. Copyright

Additional double reading of screening mammograms by radiologic technologists: Impact on screening performance parameters (Article)

2007-08-01T00:00:00Z

Background: Studies have shown that having mammography technologists review screening mammograms in addition to radiologist review may increase the number of breast cancers that are detected at screening mammography. We prospectively examined the effects on screening performance of adding independent double reading of screening mammograms by technologists to standard double reading by radiologists. Methods: Twenty-one screening mammography technologists and eight certified screening radiologists participated in this study. From January 1, 2003, to January 1, 2005, all 61251 screening mammograms obtained at two mammography screening units in The Netherlands were independently read (although the second reader was not blinded to the first reader's interpretation) by two technologists and, in turn, by two radiologists. Radiologists were blinded to the referral opinion of the technologists. During a 2-year follow-up period, we collected clinical data, breast imaging reports, biopsy results, and breast surgery reports of all women with a positive screening result (i.e., those that required additional imaging) from any reader. The distributions of categorical variables between subgroups were compared using chi-square or Fisher's exact tests. Differences in referral and detection by radiologists and technologists were assessed using McNemar's test. All statistical tests were two-sided. Results: The radiologists referred 905 women (referral rate = 1.48%, 95% confidence interval [CI] = 1.38% to 1.57%), of whom 323 had breast cancer, corresponding to a positive predictive value of referral (PPV) of 35.7% (95% CI = 32.6% to 38.8%). Review of 446 additional technologist-positive readings led to another 80 referrals, resulting in the detection of 22 additional cancers. These extra referrals increased the initial referral rate from 1.48% to 1.61% (difference = 0.13%; 95% CI = 0.10% to 0.16%) and the cancer detection rate (CDR) from 5.27 to 5.63 cancers per 1000 women screened (difference = 0.36 cancers per 1000 women screened; 95% CI = 0.24 to 0.55). With technologist double reading only, 829 women would have been referred (referral rate = 1.35%, 95% CI = 1.26% to 1.45%); among these women, 286 cancers were diagnosed (PPV = 34.5%, 95% CI = 31.3% to 37.7%; CDR = 4.67 cancers per 1000 women screened, 95% CI = 4.13 to 5.21). Referral of all 1351 radiologist- and/ or technologist-positive readings would have led to 362 cancers found at screening. The cancer detection rate for radiologist double reading would have increased from 5.27 to 5.91 cancers per 1000 women screened (relative increase = 12.1%, 95% CI = 8.8% to 16.5%; difference = 0.64 cancers per 1000 women screened, 95% CI = 0.47 to 0.87). Conclusion: A referral strategy that includes all technologist-positive readings, which would have increased the cancer detection rate while maintaining a low referral rate, should be considered.

Tumor characteristics and detection method in the MRISC screening program for the early detection of hereditary breast cancer (Article)

2007-05-01T00:00:00Z

In the MRISC study, women with an inherited risk for breast cancer were screened by a 6-month clinical breast examination (CBE) and yearly MRI and mammography. We found that the MRISC screening scheme could facilitate early breast cancer diagnosis and that MRI was a more sensitive screening method than mammography, but less specific. In the current study we investigated the contribution of MRI in the early detection of breast cancer in relation to tumor characteristics. From November 1999 to October 2003, 1909 women were included and 50 breast cancers were detected, of which 45 were evaluable and included in the current study. We compared the characteristics of tumors detected by MRI-only with those of all other (non-palpable) screen-detected tumors. Further, we compared the sensitivity of mammography and MRI within subgroups according to different tumor characteristics. Twenty-two (49%) of the 45 breast cancers were detected by MRI and not visible at mammography, of which 20 (44%) were also not palpable (MRI-only detected tumors). MRI-only detected tumors were more often node-negative than other screen-detected cancers (94 vs. 59%; P = 0.02) and tended to be more often ≤1 cm (58 vs. 31%; P = 0.11). MRI was more sensitive than mammography for a wide spectrum of invasive tumor characteristics i.e., size, nodal status, histology, grade and ER status. Half of the breast cancers detected in this study were visible by MRI only and these tumors were smaller and significantly more often node-negative than other screen-detected tumors, suggesting that MRI makes an important contribution to the early detection of hereditary breast cancer.

Cost-effectiveness of different reading and referral strategies in mammography screening in the Netherlands (Article)

2007-04-01T00:00:00Z

In mammography screening with double reading, different strategies can be used when the readers give discordant recommendations for referral. We investigated whether the results of the Dutch breast cancer screening programme can be optimised by replacing the standard referral strategy by consensus. Twenty-six screening radiologists independently and blinded to outcome read a test set consisting of previous screening mammograms of 250 cases (screen-detected and interval cancers) and 250 controls. Their referral recommendations were paired and, in case of discrepancy, re-read according to three referral strategies: (1) decision by one of the readers; (2) arbitration by a third reader; (3) referral if both readers agree (consensus). Data allowed studying other referral strategies, including referral if any reader suggests, as well. Double reading with referral if any reader suggests resulted in a 1.03 times higher sensitivity (76.6%) and a 1.31 times higher referral rate (1.26%) than double reading with consensus. To estimate the cost-effectiveness, the outcomes were used in a microsimulation model. Even if double reading with referral if any reader suggests results in four times as high referral rates and an accompanying increase of biopsies or other invasive procedures, the cost-effectiveness of €4,190 per life-year gained may well be in the range of acceptable cost-effectiveness for Dutch health care programmes.

Side-effects of treatment for localized prostate cancer: Are they valued differently by patients and healthy controls? (Article)

2007-04-01T00:00:00Z

OBJECTIVES: To determine how men treated for localized prostate cancer and who had permanent side-effects, and healthy controls, would value five descriptions of health states associated with side-effects of treatment for localized prostate cancer, hypothesising that patients would value the health states as less detrimental than men with no prostate cancer. PATIENTS, SUBJECTS AND METHODS: In previous research, patients with prostate cancer reported high generic quality-of-life scores after primary treatment, despite side-effects; it was suggested that these patients accepted the side-effects, i.e. urinary, bowel and sexual dysfunction, as 'part of the bargain' because they felt they were saved from a life-threatening disease. Thus, we asked 54 men who had been treated for localized prostate cancer and had permanent side-effects, and 53 healthy controls, to value five descriptions of health states. All respondents valued all descriptions using two valuation methods, a visual analogue scale (VAS, range 0-100) and time trade-off (TTO, range 0-1). The respondent functioning was assessed using the EuroQol-5D, completed with items on urinary, bowel and sexual function. RESULTS: Patients and healthy controls had similar valuations for nine of the 10 comparisons (five health states by two methods). Valuations in both groups resulted in the same ranking order of states on the TTO and one exchange in rank order on the VAS. CONCLUSIONS: When asked to value five health states associated with side-effects of treatment for localized prostate cancer, there was no difference in the valuation of erectile, urinary and bowel dysfunction between patients with permanent side-effects after treatment and healthy controls. More likely explanations for the high generic quality-of-life scores after primary treatment for prostate cancer are a response shift and insensitivity of generic health-related quality-of-life measures.

Risk-based selection from the general population in a screening trial: Selection criteria, recruitment and power for the Dutch-Belgian randomised lung cancer multi-slice CT screening trial (NELSON) (Article)

2007-02-15T00:00:00Z

A method to obtain the optimal selection criteria, taking into account available resources and capacity and the impact on power, is presented for the Dutch-Belgian randomised lung cancer screening trial (NELSON). NELSON investigates whether 16-detector multi-slice computed tomography screening will decrease lung cancer mortality compared to no screening. A questionnaire was sent to 335,441 (mainly) men, aged 50-75. Smoking exposure (years smoked, cigarettes/day, years quit) was determined, and expected lung cancer mortality was estimated for different selection scenarios for the 106,931 respondents, using lung cancer mortality data by level of smoking exposure (US Cancer Prevention Study I and II). Selection criteria were chosen so that the required response among eligible subjects to reach sufficient sample size was minimised and the required sample size was within our capacity. Inviting current and former smokers (quit ≤ 10 years ago) who smoked >15 cigarettes/day during >25 years or >10 cigarettes/day during >30 years was most optimal. With a power of 80%, 17,300-27,900 participants are needed to show a 20-25% lung cancer mortality reduction 10 years after randomisation. Until October 18, 2005 11,103 (first recruitment round) and 4,325 (second recruitment round) (total = 15,428) participants have been randomised. Selecting participants for lung cancer screening trials based on risk estimates is feasible and helpful to minimize sample size and costs. When pooling with Danish trial data (n = ±4,000) NELSON is the only trial without screening in controls that is expected to have 80% power to show a lung cancer mortality reduction of at least 25% 10 years after randomisation.

Overall and Disease-Specific Survival of Patients with Screen-Detected Prostate Cancer in the European Randomized Study of Screening for Prostate Cancer, Section Rotterdam (Article)

2007-02-01T00:00:00Z

Introduction: This report describes survival data of participants of the European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam, diagnosed with prostate cancer (pCA) during the first round of screening, the prevalence screen. Patients and methods: pCA characteristics from cases diagnosed during the first screening round from December 1993 to March 2000 are shown. During follow-up, data were collected by semiannual patient chart review for the first 5 yr and annually thereafter. The causes of death are scored according to the diagnosis of the treating physician and are not based on the review of the independent causes-of-death committee. Overall and disease-specific survival graphs are shown in Kaplan-Maier projections and compared with expected survival outcomes for males in the same age categories from the Dutch provinces of North Holland and Flevoland. Statistical evaluation was based on Cox regression analysis. Results: During the prevalence screening, 1014 patients were diagnosed with pCA. Median follow up was 55 mo, 126 (12.4%) patients died, 20 (2.0%) of pCA. Overall 5-yr observed and expected disease-specific survival was 97.7% and 82%, respectively. In the multivariate analysis, a Gleason sum of 4+4 or higher (p = 0.025) was predictive of pCA death. Conclusions: The observed survival data are in line with the literature and the expected favorable outcome for a screened population. The proportion of men dying from pCA is still small, and a 10-yr follow-up period for the final evaluation of the ERSPC may be too short.

Detecting language problems: Accuracy of five language screening instruments in preschool children (Article)

2007-02-01T00:00:00Z

To identify a simple and effective screening instrument for language delays in 3-year-old children the reliability, validity, and accuracy of five screening instruments were examined. A postal questionnaire sent to parents of 11423 children included the Dutch version of the General Language Screen (GLS), the Van Wiechen (VW) items, the Language Screening Instrument for 3- to 4-year-olds, consisting of a parent form (LSI-PF) and a child test (LSI-CT), and parents' own judgement of their child's language development on a visual analogue scale (VAS). The response rate was 78% or 8877 children. Reliability (internal consistency) was found to be acceptable (α=0.67-0.72) for all instruments. Significant correlations between the screening instruments (r=0.29-0.55, p<0.01) indicated good concurrent validity. Accuracy was estimated by the sensitivity, specificity, and receiver operating characteristic (ROC) curves against two reference tests based on parent report and specialists' judgement. If the test would classify approximately 5% of the population as screen-positive, the mean sensitivity was 50% assigning between 20% and 30% of the population as screen-positive, the mean sensitivity was 77%. The sensitivity was lowest for the LSI-CT (range 43-62%), whereas short instruments like the LSI-PF, VW, and the one-item VAS exhibited high levels of sensitivity (range 50-86%). The area under the ROC curves, ranged from 0.75 to 0.87. Apparently, short and simple parent report instruments like the LSI-PF and the one-item VAS perform remarkably well in detecting language delays in preschool children.

Feasibility, acceptability, and quality of Internet-administered adolescent health promotion in a preventive-care setting (Article)

2007-02-01T00:00:00Z

An Internet tool for monitoring, personalized feedback and referral was developed to support routine adolescent preventive care and was compared with usual practice using paper and pencil (P&P). A total of 1071 students (average age 15 years) from seven secondary schools were randomly assigned to the Internet or P&P group. The Internet group received a health and health-behavior assessment, tailored feedback on health and health behavior (specifically fruit consumption), and an online referral to see a physician/nurse if necessary. The P&P group received the same assessment, preprinted generic advice on fruit consumption and a mailed referral (where applicable). Students and physicians/nurses completed evaluation forms to assess indicators of feasibility, acceptability (i.e. satisfaction) and quality of each administration mode. Student participation rate was 87%. The electronic health feedback was positively evaluated. Students perceived the Internet-tailored fruit advice as more pleasant, more personally targeted and more enjoyable, but less credible than the generic preprinted advice (P < 0.01). No differences in indicators of acceptability and quality of consultation were found (P ≥ 0.05). Thus, the Internet can be a valuable tool to support physicians/nurses in the field of preventive care. It is recommended to further optimize and evaluate the Internet as a tool.

Prediction of Indolent Prostate Cancer: Validation and Updating of a Prognostic Nomogram (Article)

2007-01-01T00:00:00Z

Purpose: Screening with serum prostate specific antigen testing leads to the detection of many prostate cancers early in their natural history. Statistical models have been proposed to predict indolent cancer. We validated and updated model predictions for a screening setting. Materials and Methods: We selected 247 patients with clinical stage T1C or T2A from the European Randomized Study on Screening for Prostate Cancer who were treated with radical prostatectomy. We validated a nomogram that had previously been developed in a clinical setting. Predictive characteristics were serum prostate specific antigen, ultrasound prostate volume, clinical stage, prostate biopsy Gleason grade, and total length of cancer and noncancer tissue in biopsy cores. Indolent cancer was defined as pathologically organ confined cancer 0.5 cc or less in volume without poorly differentiated elements. Logistic regression was used to update the previous model and examine the contribution of other potential predictors. Results: Overall 121 of 247 patients (49%) had indolent cancer, while the average predicted probability was around 20% (p <0.001). Effects of individual variables were similar to those found before and discriminative ability was adequate (AUC 0.76). An updated model was constructed, which merely recalibrated the nomogram and did not apply additional predictors. Conclusions: Prostate cancers identified in a screening setting have a substantially higher likelihood of being indolent than those predicted by a previously proposed nomogram. However, an updated model can support patients and clinicians when the various treatment options for prostate cancer are considered.

Health-related quality of life in patients with adolescent idiopathic scoliosis after treatment: Short-term effects after brace or surgical treatment (Article)

2007-01-01T00:00:00Z

For treatment of teenagers with progressive adolescent idiopathic scoliosis in an early stage, two options are generally considered: treatment with a brace or observation followed by surgery if necessary. Many doctors and patients prefer conservative treatment (i.e. brace treatment) to surgical treatment, because surgery of the spine is generally considered a drastic intervention. Because potential differences in health-related quality of life (HRQoL) after treatment between braced and surgically treated patients are not well explored, this study aimed to determine whether short-term differences exist in HRQoL between adolescents treated with a brace or treated surgically. A cross-sectional analysis of HRQoL was made of 109 patients with adolescent idiopathic scoliosis who, after completing treatment, filled out the Dutch SRS-22 Patient Questionnaire. All patients had been treated either with a brace or surgery, or with a brace followed by surgery. Patients treated surgically had significantly higher mean scores in the satisfaction with management domain than those treated with a brace. No other consistent differences in HRQoL were found between patients treated with a brace and patients treated surgically. Gender, curve type and curve size had no relevant effect on HRQoL. We conclude that short-term differences in HRQoL after treatment in adolescent patients with idiopathic scoliosis are negligible and cannot support preference of one treatment above the other.

Health-related quality of life in preschool children with wheezing and dyspnea: Preliminary results from a random general population sample (Article)

2005-10-01T00:00:00Z

Respiratory symptoms have a high prevalence among preschool children (5-20%). This study evaluated the impact of parent-reported respiratory symptoms on health-related quality of life (HRQOL) using the TNO-AZL Preschool Children Quality of Life (TAPQOL) questionnaire. A random general population sample of 500 parents of 3-46-month old children was mailed a questionnaire containing the TAPQOL and questions on the prevalence of respiratory symptoms. The impact of respiratory symptoms on HRQOL was analysed using the Mann-Whitney test and linear regression analysis. Response rate was 83%. The prevalence of combined 'wheezing and dyspnea' during the past 4 weeks was 10%. For the sleeping, appetite, lung problems, skin problems, communication, and positive mood TAPQOL scales, HRQOL was significantly lower in the subgroup with 'wheezing and dyspnea' (n = 41) than in the subgroup without symptoms (n = 321); large effect sizes were observed for lung problems (2.06) and sleeping (0.80). In multivariate analysis, adjusted for age and gender of the child, 'wheezing and dyspnea' were associated with the scales sleeping, appetite, lung problems, communication, and positive mood (p < 0.05). In conclusion, decreases in HRQOL among preschoolers with parent-reported respiratory symptoms are measurable with the TAPQOL. We recommend studying the impact of doctor-diagnosed respiratory symptoms on HRQOL in future studies.

Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition (Article)

2004-01-01T00:00:00Z

BACKGROUND: The value of regular surveillance for breast cancer in women with a genetic or familial predisposition to breast cancer is currently unproven. We compared the efficacy of magnetic resonance imaging (MRI) with that of mammography for screening in this group of high-risk women. METHODS: Women who had a cumulative lifetime risk of breast cancer of 15 percent or more were screened every six months with a clinical breast examination and once a year by mammography and MRI, with independent readings. The characteristics of the cancers that were detected were compared with the characteristics of those in two different age-matched control groups. RESULTS: We screened 1909 eligible women, including 358 carriers of germ-line mutations. Within a median follow-up period of 2.9 years, 51 tumors (44 invasive cancers, 6 ductal carcinomas in situ, and 1 lymphoma) and 1 lobular carcinoma in situ were detected. The sensitivity of clinical breast examination, mammography, and MRI for detecting invasive breast cancer was 17.9 percent, 33.3 percent, and 79.5 percent, respectively, and the specificity was 98.1 percent, 95.0 percent, and 89.8 percent, respectively. The overall discriminating capacity of MRI was significantly better than that of mammography (P<0.05). The proportion of invasive tumors that were 10 mm or less in diameter was significantly greater in our surveillance group (43.2 percent) than in either control group (14.0 percent [P<0.001] and 12.5 percent [P=0.04], respectively). The combined incidence of positive axillary nodes and micrometastases in invasive cancers in our study was 21.4 percent, as compared with 52.4 percent (P<0.001) and 56.4 percent (P=0.001) in the two control groups. CONCLUSIONS: MRI appears to be more sensitive than mammography in detecting tumors in women with an inherited susceptibility to breast cancer.

Measuring disease specific quality of life in localized prostate cancer: The Dutch experience (Article)

2003-06-01T00:00:00Z

Objective: We aimed at developing and testing a Dutch health-related quality of life measure for localized prostate cancer patients. Methods: Scales on urinary and bowel function and bother from the UCLA Prostate Cancer Index (PCI) underwent formal linguistic and cultural translation. PCI sexual scales were replaced by an existing Dutch sexual activities module (SAc). After qualitative pilot testing 389 patients with localized prostate cancer (mean age 67 ± 7 years) completed the measure before and at 2 time points after primary treatment. Psychometric properties (feasibility, score distribution, reliability, construct validity and responsiveness to change) of the new instrument were analyzed. Results: Response rates ranged from 93% at baseline to 87% after treatment. Urinary and bowel function scales showed Cronbach's αs >0.7. Urinary function and bother, and bowel function and bother were significantly correlated. Pre- vs. post-prostatectomy effect sizes were >0.9 only for urinary scales; while pre- vs. post-radiotherapy effect sizes were >0.75 only for bowel scales. Six months after baseline erectile dysfunction was reported by 64% of respondents, either as a problem in sexual activity or as a reason for not being sexually active. Conclusion: The Dutch PCI and SAc performed well in men treated for early stage prostate cancer.

Lead times and overdetection due to prostate-specific antigen screening: estimates from the European Randomized Study of Screening for Prostate Cancer (Article)

2003-01-01T00:00:00Z

BACKGROUND: Screening for prostate cancer advances the time of diagnosis (lead time) and detects cancers that would not have been diagnosed in the absence of screening (overdetection). Both consequences have considerable impact on the net benefits of screening. METHODS: We developed simulation models based on results of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC), which enrolled 42,376 men and in which 1498 cases of prostate cancer were identified, and on baseline prostate cancer incidence and stage distribution data. The models were used to predict mean lead times, overdetection rates, and ranges (corresponding to approximate 95% confidence intervals) associated with different screening programs. RESULTS: Mean lead times and rates of overdetection depended on a man's age at screening. For a single screening test at age 55, the estimated mean lead time was 12.3 years (range = 11.6-14.1 years) and the overdetection rate was 27% (range = 24%-37%); at age 75, the estimates were 6.0 years (range = 5.8-6.3 years) and 56% (range = 53%-61%), respectively. For a screening program with a 4-year screening interval from age 55 to 67, the estimated mean lead time was 11.2 years (range = 10.8-12.1 years), and the overdetection rate was 48% (range = 44%-55%). This screening program raised the lifetime risk of a prostate cancer diagnosis from 6.4% to 10.6%, a relative increase of 65% (range = 56%-87%). In annual screening from age 55 to 67, the estimated overdetection rate was 50% (range = 46%-57%) and the lifetime prostate cancer risk was increased by 80% (range = 69%-116%). Extending annual or quadrennial screening to the age of 75 would result in at least two cases of overdetection for every clinically relevant cancer detected. CONCLUSIONS: These model-based lead-time estimates support a prostate cancer screening interval of more than 1 year.

Mammographic screening: evidence from randomised controlled trials (Article)

2003-01-01T00:00:00Z

BACKGROUND: All randomised breast cancer screening trials have shown a reduction in breast cancer mortality in the 'invited for mammography' screening arm compared with the 'control arm' for women aged 50 years and older at randomisation (overall 25%). However, individually published point estimates differ and concern has been raised about methodological quality and outcome measures. Materials and Methods Review of the evidence on breast cancer mortality reduction and discussion of the causes of difference in point estimates in the five Swedish and Canadian trials. A summary of the prerequisites for methodological quality and its available evidence from the trials is given. Data to support breast cancer mortality as a correct outcome measure are presented. RESULTS: There is no reason not to use breast cancer mortality as an outcome measure for trials intended to reduce breast cancer mortality, both from a clinical and a methodological point of view. Everything possible was performed in these trials in order to determine this outcome measure as accurately as possible. The fact that a few of the trials showed a relatively large breast cancer mortality reduction and others far lower reduction rates is irrelevant, if one does not consider the background situation in the region before the trial started, the design of the trial or quality of screening. CONCLUSIONS: There seems no reason to change or halt the current nation-wide population-based screening programmes. Nor is there any justifiable reason for negative reports towards women or professionals.

Pathologic features of prostate cancer found at population-based screening with a four-year interval (Article)

2001-01-01T00:00:00Z

BACKGROUND: The currently recommended frequency for prostate-specific antigen (PSA) screening tests for prostate cancer is 1 year, but the optimal screening interval is not known. Our goal was to determine if a longer interval would compromise the detection of curable prostate cancer. METHODS: A cohort of 4491 men aged 55-75 years, all participants in the Rotterdam section of the European Randomized Study of (population-based) Screening for Prostate Cancer, were invited to participate in an initial PSA screening. Men who received that screening were invited for a second screen 4 years later. Pathology findings from needle biopsy cores were compared for men in both rounds. Statistical tests were two-sided. RESULTS: A total of 4133 men were screened in the first round (the prevalence screen), and 2385 were screened in the second round. The median amount of cancer in needle biopsy sets was 7.0 mm (95% confidence interval [CI] = 5.4 mm to 8.6 mm) in the first round and 4.1 mm (95% CI = 2.6 mm to 5.6 mm) in the second round (P =.001). Thirty-six percent of the adenocarcinomas detected in the first round but only 16% of those detected in the second round had a Gleason score of 7 or higher (mean difference = 20% [95% CI = 10% to 30%]; P<.001). Whereas 25% of the adenocarcinomas detected in the first round had adverse prognostic features, only 6% of those detected in the second round did (mean difference = 19% [95% CI = 11% to 26%]; P<.001). Baseline PSA values were predictive for the amount of tumor in biopsies in men with cancer in the first round but not for that in the second round. CONCLUSION: Most large prostate cancers with high serum PSA levels were effectively detected in a prevalence screen. In this population, a screening interval of 4 years appears to be short enough to constrain the development of large tumors, although it is inconclusive whether this will result in a survival benefit.

Cost effectiveness of shortening screening interval or extending age range of NHS breast screening programme: computer simulation study (Article)

1998-01-01T00:00:00Z

OBJECTIVE: To compare the cost effectiveness of two possible modifications to the current UK screening programme: shortening the screening interval from three to two years and extending the age of invitation to a final screen from 64 to 69. DESIGN: Computer simulation model which first simulates life histories for women in the absence of a screening programme for breast cancer and then assesses how these life histories would be changed by introducing different screening policies. The model was informed by screening and cost data from the NHS breast screening programme. SETTING: North West region of England. MAIN OUTCOME MEASURES: Numbers of deaths prevented, life years gained, and costs. RESULTS: Compared with the current breast screening programme both modifications would increase the number of deaths prevented and the number of life years saved. The current screening policy costs 2522 pounds per life year gained; extending the age range of the programme would cost 2612 pounds and shortening the interval 2709 pounds per life year gained. The marginal cost per life year gained of extending the age range of the screening programme is 2990 pounds and of shortening the screening interval is 3545 pounds. CONCLUSIONS: If the budget for the NHS breast screening programme were to allow for two more invitations per woman, substantial mortality reductions would follow from extending the age range screened or reducing the screening interval. The difference between the two policies is so small that either could be chosen.

The effects and costs of breast cancer screening (Doctoral Thesis)

1993-06-09T00:00:00Z

With the research described in this thesis, both the concept of screening and the underlying model earlier described have been extended to include the impact on almost all aspects after or beyond the screening examination itself: impact on advanced disease late in life, on assessment and primary treatment for women and for health care, on quality of life, impact on financial cost and impact on the situation of the disease in a population outside the invited or screened group