This thesis aims to improve the treatment of patients with stage III melanoma. The first part describes different aspects of treatment with Talimogene Laherparepvec (T-VEC), a genetically modified... Show moreThis thesis aims to improve the treatment of patients with stage III melanoma. The first part describes different aspects of treatment with Talimogene Laherparepvec (T-VEC), a genetically modified herpes virus, which is used as oncolytic immunotherapy for skin and lymph node metastases in melanoma patients. We show that patients with a low tumor burden have the best outcomes, suggesting T-VEC should be used earlier on in the course of the disease. We present a prediction model, allowing a more accurate selection of patients for T-VEC monotherapy. Two studies focused on the use of T-VEC in clinical practice and the results allowed us to make recommendations on the use of PET/CT and dermoscopy during T-VEC treatment. Part two focuses on the value of surveillance and screening imaging in high-risk melanoma patients. We show that FDG-PET/CT is a valuable imaging tool to detect recurrence after complete resection of stage III disease, even shortly after surgery (before starting adjuvant therapy). Finally, we conclude that nodal staging with US as adjunct to SLNB is useful in the work- up of stage IIB/C melanoma, as it can lead to alterations in treatment and prevent unnecessary surgery. Show less
For people with chronic kidney disease (CKD), adhering to a range of self-management tasks—such as healthy eating, frequent physical activity, and non-smoking—is crucial. However, changing health... Show moreFor people with chronic kidney disease (CKD), adhering to a range of self-management tasks—such as healthy eating, frequent physical activity, and non-smoking—is crucial. However, changing health behaviors is difficult. To support patients in doing so, an eHealth care pathway was developed and evaluated. The results provide different insights into patients' priorities and care needs. Many individuals with CKD experience problems in self-management, which can be hindered by many different barriers of which a common one is psychological distress. Therefore, personalized interventions are needed with screening and treatment of both psychological distress and suboptimal self-management, tailored to the specific barriers and needs of the individual patient. The E-GOAL eHealth care pathway is an example of such a personalized intervention, combining cognitive behavioral therapy with self-management support. Patients were enthusiastic about the eHealth care pathway. However, in a randomized study, the intervention was not effective in reducing psychological distress compared with regular care only. Patients did experience improvements in areas of functioning and self-management that they prioritized themselves. These mixed results show that interventions could be implemented that are person-tailored, with personalized outcomes that reflect individually meaningful treatment goals and improvements for every patient. Show less
In individuals with tuberculosis-infection – until recently referred to as latent tuberculosis infection – the risk of progression to active tuberculosis (reactivation) varies strongly. Among those... Show moreIn individuals with tuberculosis-infection – until recently referred to as latent tuberculosis infection – the risk of progression to active tuberculosis (reactivation) varies strongly. Among those at increased risk of reactivation are patients with an impaired immune system, e.g. due to immunosuppressive therapy. Therefore, prior to planned immunosuppression, patients are screened for tuberculosis-infection and subsequently treated in case of infection. Current screening methods include the Mantoux test, Interferon-γ release assays (i.e., the QuantiFERON-TB Gold Plus and T-SPOT.TB) and chest X-ray. However, despite screening, cases of reactivation continue to occur – in part due to the lack of a gold standard test for tuberculosis-infection. Therefore, the aims of this thesis were to increase the diagnostic sensitivity for tuberculosis-infection prior to immunosuppression. Using various (novel) methods we showed that approximately two-thirds of all QuantiFERON-TB Gold Plus results just below the manufacturer’s cut-off (in the borderline range) are caused by Mycobacterium tuberculosis-infection, which now warrants preventive treatment in patients with such a result. Furthermore, we quantified the diagnostic accuracy of chest X-ray for tuberculosis-infection and showed that using a novel ultra-low dose CT scanning technique, sensitivity for tuberculosis-infection could be significantly increased by three-fold compared to chest X-ray. Show less
Tommel, J.; Evers, A.W.M.; Hamersvelt, H.W. van; Dijk, S. van; Chavannes, N.H.; Wirken, L.; ... ; Middendorp, H. van 2022
Background: Kidney failure and dialysis treatment have a large impact on a patient's life. Patients experience numerous, complex symptoms and usually have multiple comorbid conditions. Despite the... Show moreBackground: Kidney failure and dialysis treatment have a large impact on a patient's life. Patients experience numerous, complex symptoms and usually have multiple comorbid conditions. Despite the multitude of problems, patients often have priorities for improvement of specific aspects of their functioning, which would be helpful for clinicians to become informed of. This highlights a clear need for patient-centered care in this particular patient group, with routine screening as a vital element to timely recognize symptoms and tailored treatment to match individual patients' needs and priorities. By also providing feedback on patient's screening results to the patient itself, the patient is empowered to actively take control in one's mostly uncontrollable disease process. The current paper describes the study design of a multicenter randomized controlled trial evaluating the effectiveness of the "E-HEealth treatment in Long-term Dialysis" (E-HELD) intervention. This therapist-guided Internet-based cognitive-behavioral therapy (ICBT) intervention is focused on and personalized to the myriad of problems that dialysis patients experience and prioritize. Methods: After a screening procedure on adjustment problems, 130 eligible dialysis patients will be randomized to care as usual or the E-HELD intervention. Patients will complete questionnaires on distress (primary outcome measure), several domains of functioning (e.g., physical, psychological, social), potential predictors and mediators of treatment success, and the cost-effectiveness of the intervention, at baseline, 6-month follow-up, and 12-month follow-up. In addition, to take account of the personalized character of the intervention, the Personalized Priority and Progress Questionnaire (PPPQ) will be administered which is a personalized instrument to identify, prioritize, and monitor individual problems over time. Discussion: The present study design will provide insight in the effectiveness of tailored ICBT in patients with kidney failure who are treated with dialysis. When proven effective, the screening procedure and the subsequent ICBT intervention could be implemented in routine care to detect, support, and treat patients struggling with adjustment problems. Show less
This thesis highlights, firstly, the importance of early CRC detection by presenting results of a CRC diagnostic proteomic biomarker signature with high discriminative power. Secondly, a strong... Show moreThis thesis highlights, firstly, the importance of early CRC detection by presenting results of a CRC diagnostic proteomic biomarker signature with high discriminative power. Secondly, a strong robust, independent prognostic tumor stroma ratio (TSR) biomarker, which confirms to be of important clinical value. The TSR has the ability to stratify colon cancer patients according to their prognostic outcome in a highly reproducible and low-cost manner. It has shown to link patients with a high intra tumor stromal content and a worse prognosis. Literature shows a wealth of evidence that supports this prognostic value in CRC as well as in other cancers. This PhD research therefore concludes that it should be implemented in the official guidelines of the TNM classification to improve stratification for CRC patients in daily routine pathological evaluation. The prospective, international, multicentre UNITED study will hopefully overcome the last hurdle for this clinical implementation. Lastly, this thesis offers more insight in the elusiveness of the tumor microenvironment and stromatogenesis that contributes to the aggressiveness of some CRC tumors. The biological differences, interconnections and changes in the microenvironment presented give multiple leads for further research and new personalized treatment possibilities. Show less
At the moment, over 350.000 chemicals are registered worldwide for production and use. Their application, however, may harm human health and the environment. To manage the safety of chemicals,... Show moreAt the moment, over 350.000 chemicals are registered worldwide for production and use. Their application, however, may harm human health and the environment. To manage the safety of chemicals, particular chemical legislations are in place, which make use of risk and hazard assessments. However, there are several challenges for current risk and hazard assessments, including i) a lack of (reliable) data, and ii) a relative slow and inefficient evaluation and regulation process. In this thesis, I investigate specifically whether more extensive and targeted use of chemical similarity within risk and hazard assessment has the potential to improve these aspects. Chemical similarity could be a valuable factor as similarities between two chemicals could be a sign of similar physicochemical and/or toxic properties. The separate sections within this thesis specifically focus on chemical similarity in relation to screening, data generation and evaluation of substances. The results of this thesis indicate that chemical similarity could be used to identify and evaluate hazardous properties of single and groups of chemicals. Accordingly, I promote more extensive use of chemical similarity within risk and hazard assessment as it has the ability to circumvent several issues related to a lack of data and evaluation efficiency. Show less
Overbeek, K.A.; Goggins, M.G.; Dbouk, M.; Levink, I.J.M.; Koopmann, B.D.M.; Chuidian, M.; ... ; Int Canc Pancreas Screening Consor 2022
BACKGROUND & AIMS: To successfully implement imaging-based pancreatic cancer (PC) surveillance, understanding the timeline and morphologic features of neoplastic progression is key. We aimed to... Show moreBACKGROUND & AIMS: To successfully implement imaging-based pancreatic cancer (PC) surveillance, understanding the timeline and morphologic features of neoplastic progression is key. We aimed to investigate the progression to neoplasia from serial prediagnostic pancreatic imaging tests in high-risk individuals and identify factors associated with successful early detection. METHODS: We retrospectively examined the development of pancreatic abnormalities in high-risk individuals who were diagnosed with PC or underwent pancreatic surgery, or both, in 16 international surveillance programs. RESULTS: Of 2552 high-risk individuals under surveillance, 28 (1%) developed neoplastic progression to PC or high-grade dysplasia during a median follow-up of 29 months after baseline (interquartile range [IQR], 40 months). Of these, 13 of 28 (46%) presented with a new lesion (median size, 15 mm; range 7-57 mm), a median of 11 months (IQR, 8; range 317 months) after a prior examination, by which time 10 of 13 (77%) had progressed beyond the pancreas. The remaining 15 of 28 (54%) had neoplastic progression in a previously detected lesion (12 originally cystic, 2 indeterminate, 1 solid), and 11 (73%) had PC progressed beyond the pancreas. The 12 patients with cysts had been monitored for 21 months (IQR, 15 months) and had a median growth of 5 mm/y (IQR, 8 mm/y). Successful early detection (as high-grade dysplasia or PC confined to the pancreas) was associated with resection of cystic lesions (vs solid or indeterminate lesions (odds ratio, 5.388; 95% confidence interval, 1.525-19.029) and small lesions (odds ratio, 0.890/mm; 95% confidence interval 0.812-0.976/mm). CONCLUSIONS: In nearly half of high-risk individuals developing high-grade dysplasia or PC, no prior lesions are detected by imaging, yet they present at an advanced stage. Progression can occur before the next scheduled annual examination. More sensitive diagnostic tools or a different management strategy for rapidly growing cysts are needed. Show less
Seekles, S.J.; Dam, J. van; Arentshorst, M.; Ram, A.F.J. 2022
Weak acids, such as sorbic acid, are used as chemical food preservatives by the industry. Fungiovercome this weak-acid stress by inducing cellular responses mediated by transcription factors. In... Show moreWeak acids, such as sorbic acid, are used as chemical food preservatives by the industry. Fungiovercome this weak-acid stress by inducing cellular responses mediated by transcription factors. In ourresearch, a large-scale sorbic acid resistance screening was performed on 100 A. niger sensu stricto strains isolated fromvarious sources to study strain variability in sorbic acid resistance. Theminimal inhibitory concentration of undissociated (MICu) sorbic acid at pH = 4 in the MEB of the A. niger strains varies between 4.0 mMand 7.0 mM, with the average out of 100 strains being 4.8 0.8 mM, when scored after 28 days. MICu valueswere roughly 1mMlowerwhen tested in commercial ice tea. Genome sequencingof the most sorbic-acid-sensitive strain among the isolates revealed a premature stop codon inside thesorbic acid response regulator encoding gene sdrA. Repairing this missense mutation increased thesorbic acid resistance, showing that the sorbic-acid-sensitive phenotype of this strain is caused by theloss of SdrA function. To identify additional transcription factors involved in weak-acid resistance,a transcription factor knock-out library consisting of 240 A. niger deletion strains was screened. Thescreen identified a novel transcription factor,WarB, which contributes to the resistance against a broadrange of weak acids, including sorbic acid. The roles of SdrA,WarA andWarB in weak-acid resistance,including sorbic acid, were compared by creating single, double and the triple knock-out strains. Allthree transcription factors were found to have an additive effect on the sorbic acid stress response. Show less
Kortlever, T.L.; Jonge, L. de; Wisse, P.H.A.; Seriese, I.; Otto-Terlouw, P.; Leerdam, M.E. van; ... ; Lansdorp-Vogelaar, I. 2021
The COVID-19 pandemic has affected many healthcare services worldwide. Like many other nations, the Netherlands experienced large numbers of individuals affected by COVID-19 in 2020, leading to... Show moreThe COVID-19 pandemic has affected many healthcare services worldwide. Like many other nations, the Netherlands experienced large numbers of individuals affected by COVID-19 in 2020, leading to increased demands on hospitals and intensive care units. The Dutch Ministry of Health decided to suspend the Dutch biennial fecal immunochemical test (FIT) based colorectal cancer (CRC) screening program from March 16, 2020. FIT invitations were resumed on June 3. In this study, we describe the short-term effects of this suspension on a myriad of relevant screening outcomes. As a result of the suspension, a quarter of the individuals due for screening between March and November 2020 had not received their invitation for FIT screening by November 30, 2020. Furthermore, 57.8% of those who received a consecutive FIT between the restart and November 30, 2020, received it outside the upper limit of the standard screening interval (26 months). Median time between positive FIT and colonoscopy did not change as a result of the pandemic. Participation rates of FIT screening and follow-up colonoscopy in the months just before and during the suspension were significantly lower than expected, but returned to normal levels after the suspension. Based on the anticipated 2020 cohort size, we estimate that the number of individuals with advanced neoplasia currently detected up until November 2020 was 31.2% lower compared to what would have been expected without a pandemic. Future studies should monitor the impact on long-term screening outcomes as a result of the pandemic. Show less
Background The onset of the COVID-19 pandemic forced the Dutch national screening program to a halt and increased the burden on health care services, necessitating the introduction of specific... Show moreBackground The onset of the COVID-19 pandemic forced the Dutch national screening program to a halt and increased the burden on health care services, necessitating the introduction of specific breast cancer treatment recommendations from week 12 of 2020. We aimed to investigate the impact of COVID-19 on the diagnosis, stage and initial treatment of breast cancer. Methods Women included in the Netherlands Cancer Registry and diagnosed during four periods in weeks 2-17 of 2020 were compared with reference data from 2018/2019 (averaged). Weekly incidence was calculated by age group and tumor stage. The number of women receiving initial treatment within 3 months of diagnosis was calculated by period, initial treatment, age, and stage. Initial treatment, stratified by tumor behavior (ductal carcinoma in situ [DCIS] or invasive), was analyzed by logistic regression and adjusted for age, socioeconomic status, stage, subtype, and region. Factors influencing time to treatment were analyzed by Cox regression. Results Incidence declined across all age groups and tumor stages (except stage IV) from 2018/2019 to 2020, particularly for DCIS and stage I disease (p < 0.05). DCIS was less likely to be treated within 3 months (odds ratio [OR](wks2-8): 2.04, ORwks9-11: 2.18). Invasive tumors were less likely to be treated initially by mastectomy with immediate reconstruction (ORwks12-13: 0.52) or by breast conserving surgery (ORwks14-17: 0.75). Chemotherapy was less likely for tumors diagnosed in the beginning of the study period (ORwks9-11: 0.59, ORwks12-13: 0.66), but more likely for those diagnosed at the end (ORwks14-17: 1.31). Primary hormonal treatment was more common (ORwks2-8: 1.23, ORwks9-11: 1.92, ORwks12-13: 3.01). Only women diagnosed in weeks 2-8 of 2020 experienced treatment delays. Conclusion The incidence of breast cancer fell in early 2020, and treatment approaches adapted rapidly. Clarification is needed on how this has affected stage migration and outcomes. Show less
Dijk, W.B. van; Fiolet, A.T.L.; Schuit, E.; Sammani, A.; Groenhof, T.K.J.; Graaf, R. van der; ... ; Mosterd, A. 2021
Objective: This study aimed to validate trial patient eligibility screening and baseline data collection using text-mining in electronic healthcare records (EHRs), comparing the results to those of... Show moreObjective: This study aimed to validate trial patient eligibility screening and baseline data collection using text-mining in electronic healthcare records (EHRs), comparing the results to those of an international trial.Study Design and Setting: In three medical centers with different EHR vendors, EHR-based text-mining was used to automatically screen patients for trial eligibility and extract baseline data on nineteen characteristics. First, the yield of screening with automated EHR text-mining search was compared with manual screening by research personnel. Second, the accuracy of extracted baseline data by EHR text mining was compared to manual data entry by research personnel.Results: Of the 92,466 patients visiting the out-patient cardiology departments, 568 (0.6%) were enrolled in the trial during its recruitment period using manual screening methods. Automated EHR data screening of all patients showed that the number of patients needed to screen could be reduced by 73,863 (79.9%). The remaining 18,603 (20.1%) contained 458 of the actual participants (82.4% of participants). In trial participants, automated EHR text-mining missed a median of 2.8% (Interquartile range [IQR] across all variables 0.4-8.5%) of all data points compared to manually collected data. The overall accuracy of automatically extracted data was 88.0% (IQR 84.7-92.8%).Conclusion: Automatically extracting data from EHRs using text-mining can be used to identify trial participants and to collect baseline information. (C) 2020 The Authors. Published by Elsevier Inc. Show less
Mismatch repair (MMR) testing is recommended in the Netherlands for all patients under 70 years of age with newly diagnosed colorectal cancer (CRC) in order to identify Lynch syndrome. T1 CRC can... Show moreMismatch repair (MMR) testing is recommended in the Netherlands for all patients under 70 years of age with newly diagnosed colorectal cancer (CRC) in order to identify Lynch syndrome. T1 CRC can be removed by local excision or oncological surgical resection. We evaluated the frequency of MMR testing in pT1 lesions within the Dutch CRC screening cohort. pT1 CRC diagnosed within the Dutch population-based screening program from 2016-2018 were identified by the Dutch pathology registry (PALGA). Pathology reports were evaluated, including registration of MMR testing (by immunohistochemistry and/or microsatellite instability PCR). Frequency of MMR testing was compared between pT1 tumors that were treated by local (endoscopic or transanal) excision and oncological surgical resections. A total of 3.692 pT1 CRCs were diagnosed (median age 63 years, 61.4% males). MMR testing was performed in 83% and uptake increased over time (71% in 2016 to 92% in 2018, p<0.01). MMR testing was significantly more often performed in younger patients and in academic hospitals. When pT1 CRC was treated by oncological surgical resection (n=1.132), MMR testing was performed in 89% of cases and was known prior to oncological resection in 51% of cases. MMR testing occurred significantly less often in case of local excision (80% of n=2.560) compared to oncological surgical resection (p<0.01). MMR testing was performed in 83% of T1 CRCs and uptake increased over time. MMR testing was more frequently performed in pT1 CRC resected by oncological surgical resection compared with local excision. Show less
The objectives of this thesis, aimed to reduce overtreatment of ductal carcinoma in situ (DCIS) of the breast, were : 1) to evaluate the risk of underestimation after a diagnosis of DCIS and the... Show moreThe objectives of this thesis, aimed to reduce overtreatment of ductal carcinoma in situ (DCIS) of the breast, were : 1) to evaluate the risk of underestimation after a diagnosis of DCIS and the interrater reliability in the histopathological classification of DCIS, important conditions in order to safely adopt an active surveillance strategy for low-risk DCIS, 2) to investigate associations of clinicopathological factors with the risk of developing ipsilateral invasive breast cancer after treatment of DCIS and 3) to analyze the extent of response of DCIS, adjacent to HER2-positive breast cancer, to neoadjuvant systemic therapy and to investigate associations of clinicopathological factors with DCIS response.We have taken significant steps on the road towards conquering overtreatment of DCIS: by having identified several clinicopathological prognostic factors in pure DCIS, by providing reassuring evidence regarding underestimation in the context of active surveillance, by stressing the need for improvement of interrater reliability in histopathological classification, and by showing that the presence of DCIS adjacent to HER2-positive breast cancer should not preclude the option of breast conserving surgery. Show less
As with all cancer screening programmes, the expected reduction in cancer cases and deaths must be weighed against the burden of screening and possible side effects. The aim of this thesis is to... Show moreAs with all cancer screening programmes, the expected reduction in cancer cases and deaths must be weighed against the burden of screening and possible side effects. The aim of this thesis is to provide insights in consequences of colorectal cancer screening participation from a surgical perspective. We investigated potential harm in terms of serious morbidity from colonoscopy, additional findings on imaging, and psychological impacts following a positive faecal immunochemical test (FIT) result. Second, studies were performed to gain more in-depth insight into surgical referral patterns for benign colorectal lesions and CRC lesions with only submucosal invasion (pT1), thereby contributing to the understanding of whether early diagnosis following CRC screening results in better surgical outcomes. Third, surgical outcomes of screen-detected patients were compared with symptomatic patients. Show less
van't Hof, M.; Nieuwenhuyzen, A.D.Y. van; Berckelaer-Onnes, I. van; Deen, M.; Hoek, H.W.; Ester, W.A. 2021
We investigated the effect of a live online educational program in 93 Dutch Youth and Family Center (YFC) physicians who were screening for Autism Spectrum Disorder (ASD) in the general child... Show moreWe investigated the effect of a live online educational program in 93 Dutch Youth and Family Center (YFC) physicians who were screening for Autism Spectrum Disorder (ASD) in the general child population. The educational program raised the physicians' level of specific ASD knowledge and it remained higher at six months follow-up (p < .01). Their self-confidence in detecting ASD was also higher and maintained at follow-up (p < .01). The educational program had no effect on the physicians' stigmatizing attitudes toward mental illness nor on the number of potential ASD referrals in children of 4-6 years of age. In conclusion, the online educational program on early detection of ASD has a six month long effect on YFC physicians' level of ASD knowledge and self-confidence. Show less
Zand, E.G. van ’t; Schuyt, P.M.; Crijns, J.H. 2021
In de financiële sector vinden steeds meer integriteitstoetsingen en -screenings plaats. Het beoordelen van integriteit draait niet alleen om strafrechtelijke antecedenten, maar ook om... Show moreIn de financiële sector vinden steeds meer integriteitstoetsingen en -screenings plaats. Het beoordelen van integriteit draait niet alleen om strafrechtelijke antecedenten, maar ook om toezichtantecedenten, (fiscaal) bestuursrechtelijke antecedenten, financiële antecedenten en tuchtrechtelijke antecedenten. Juridisch-empirisch onderzoek laat zien dat de financiële sector zich kenmerkt door een bont geschakeerd palet aan instanties die integriteitseisen stellen, het gedrag van professionals en ondernemingen toetsen en daarvoor onderling gegevens over antecedenten delen. Aangezien het totale integriteitsinstrumentarium veel overlap kent, is meer duidelijkheid over hoe lang, op welke wijze en in welke contexten antecedenten kunnen doorwerken onontbeerlijk. Daarbij lijkt het aangewezen meer oog te hebben voor de consistentie en systematiek in het totale systeem van integriteitstoetsingen en -screenings. Show less
BACKGROUND & AIMS: We evaluated the incidence of interval cancers between the first and second rounds of colorectal cancer (CRC) screening with the FOB-Gold fecal immunochemical test (FIT), and... Show moreBACKGROUND & AIMS: We evaluated the incidence of interval cancers between the first and second rounds of colorectal cancer (CRC) screening with the FOB-Gold fecal immunochemical test (FIT), and the effects of different cutoff values and patient sex and age.METHODS: We collected data from participants in a population-based CRC screening program in the Netherlands who had a negative result from a first-round of FIT screening. We calculated the cumulative incidence of interval cancer after a negative result from a FIT and the sensitivity of the FIT for detection of CRC at a low (15 mu g Hb/g feces) and high (47 mu g Hb/g feces) cutoff value.RESULTS: Among the 485,112 participants with a negative result from a FIT, 544 interval cancers were detected; 126 were in the 111,800 participants with negative results from a FIT with the lowcutoff value and 418 were in the 373,312 FIT participants with negative results from a FIT with the high cutoff value. The mean age of participants tested with the low cutoff value was 72.0 years and the mean age of participants tested the high cutoff value was 66.7 years. The age-adjusted 2-year cumulative incidence of interval cancer after a negative result from a FIT were 9.5 per 10,000 persons at the low cutoff value vs 13.8 per 10,000 persons at the high cutoff value (P < .005). The age-adjusted sensitivity of the FIT for CRC were 90.5% for the low cutoff value vs 82.9% for the high cutoff (P < .0001). The FIT identified men with CRC with 87.4% sensitivity and women with CRC with 82.6% sensitivity (P < .001).CONCLUSIONS: In an analysis of data from a FIT population-based screening program in the Netherlands, we found that incidence of interval CRC after a negative result from a FIT to be low. Although the sensitivity of detection of CRC decreased with a higher FIT cutoff value, it remained above 80%. Show less
Obdeijn, I.M.; Mann, R.M.; Loo, C.C.E.; Lobbes, M.; Voormolen, E.M.C.; Deurzen, C.H.M. van; ... ; Hereditary Breast Ovarian Canc Res 2020
Purpose BRCA2 mutation carriers are offered annual breast screening with MRI and mammography. The aim of this study was to investigate the supplemental value of mammographic screening over MRI... Show morePurpose BRCA2 mutation carriers are offered annual breast screening with MRI and mammography. The aim of this study was to investigate the supplemental value of mammographic screening over MRI screening alone. Methods In this multicenter study, proven BRCA2 mutation carriers, who developed breast cancer during screening using both digital mammography and state-of-art breast MRI, were identified. Clinical data were reviewed to classify cases in screen-detected and interval cancers. Imaging was reviewed to assess the diagnostic value of mammography and MRI, using the Breast Imaging and Data System (BI-RADS) classification allocated at the time of diagnosis. Results From January 2003 till March 2019, 62 invasive breast cancers and 23 ductal carcinomas in situ were diagnosed in 83 BRCA2 mutation carriers under surveillance. Overall screening sensitivity was 95.2% (81/85). Four interval cancers occurred (4.7% (4/85)). MRI detected 73 of 85 breast cancers (sensitivity 85.8%) and 42 mammography (sensitivity 49.9%) (p < 0.001). Eight mammography-only lesions occurred. In 1 of 17 women younger than 40 years, a 6-mm grade 3 DCIS, retrospectively visible on MRI, was detected with mammography only in a 38-year-old woman. The other 7 mammography-only breast cancers were diagnosed in women aged 50 years and older, increasing sensitivity in this subgroup from 79.5% (35/44) to 95.5% (42/44) (p <= 0.001). Conclusions In BRCA2 mutation carriers younger than 40 years, the benefit of mammographic screening over MRI was very small. In carriers of 50 years and older, mammographic screening contributed significantly. Hence, we propose to postpone mammographic screening in BRCA2 mutation carriers to at least age 40. Show less
van't Hof, M.; Berckelaer-Onnes, I. van; Deen, M.; Neukerk, M.C.; Bannink, R.; Daniels, A.M.; ... ; Ester, W.A. 2020
Professionals' limited knowledge on mental health and their stigmatizing attitudes toward mental illness can delay the diagnosis of autism. We evaluated the knowledge on Autism Spectrum Disorder ... Show moreProfessionals' limited knowledge on mental health and their stigmatizing attitudes toward mental illness can delay the diagnosis of autism. We evaluated the knowledge on Autism Spectrum Disorder (ASD) and stigmatizing attitudes in 93 physicians at Dutch Youth and Family Centers (YFC). These physicians screen for psychiatric symptoms in children. We show that their general ASD knowledge scored 7.1 (SD 1.2), but their specific ASD knowledge was only 5.7 (SD 1.7) (weighted means on 1-10 scale, 1 = least knowledge, 10 = most knowledge). Our physicians had positive attitudes toward mental illness (CAMI scores 2.18 (SD 0.33) to 2.22 (SD 0.40) on a 5-point Likert scale) but they had higher levels of stigmatizing attitudes than other Western healthcare professionals. Their levels were considerably lower than in non-Western professionals. We found no relations between ASD knowledge, stigmatizing attitudes and demographic variables. In conclusion, ASD knowledge and stigmatizing attitudes toward mental illness in Dutch YFC physicians require attention. Show less
