Does serous tubal intraepithelial carcinoma (STIC) metastasize? The clonal relationship between STIC and subsequent high-grade serous carcinoma in BRCA1/2 mutation carriers several years after risk-reducing salpingo-oophorectomy.

OBJECTIVE: The majority of high-grade serous carcinomas (HGSC) of the ovary, fallopian tube, and peritoneum arise from the precursor lesion called serous tubal intraepithelial carcinoma (STIC). It has been postulated that cells from STICs exfoliate into the peritoneal cavity and give rise to peritoneal HGSC several years later. While co-existent STICs and HGSCs have been reported to share similarities in their mutational profiles, clonal relationship between temporally distant STICs and HGSCs have been infrequently studied and the natural history of STICs remains poorly understood. METHODS: We performed focused searches in two national databases from the Netherlands and identified a series of BRCA1/2 germline pathogenic variant (GPV) carriers (n = 7) who had STIC, and no detectable invasive carcinoma, at the time of their risk-reducing salpingo-oophorectomy (RRSO), and later developed peritoneal HGSC. The clonal relationship between these STICs and HGSCs was investigated by comparing their genetic mutational profile by performing next-generation targeted sequencing. RESULTS: Identical pathogenic mutations and loss of heterozygosity of TP53 were identified in the STICs and HGSCs of five of the seven patients (71%), confirming the clonal relationship of the lesions. Median interval for developing HGSC after RRSO was 59 months (range: 24-118 months). CONCLUSION: Our results indicate that cells from STIC can shed into the peritoneal cavity and give rise to HGSC after long lag periods in BRCA1/2 GPV carriers, and argues in favor of the hypothesis that STIC lesions may metastasize.

Mindfulness-based stress reduction for menopausal symptoms after risk-reducing salpingo-oophorectomy (PURSUE study): a randomised controlled trial.

OBJECTIVE: To assess the short- and long-term effects of mindfulness-based stress reduction (MBSR) on the resulting quality of life, sexual functioning, and sexual distress after risk-reducing salpingo-oophorectomy (RRSO). DESIGN: Randomised controlled trial. SETTING: A specialised family cancer clinic of the university medical center Groningen. POPULATION: Sixty-six women carriers of the BRCA1/2 mutation who developed at least two moderate-to-severe menopausal symptoms after RRSO. METHODS: Women were randomised to an 8-week MBSR training programme or to care as usual (CAU). MAIN OUTCOME MEASURES: Change in the Menopause-Specific Quality of Life Questionnaire (MENQOL), the Female Sexual Function Index, and the Female Sexual Distress Scale, administered from baseline at 3, 6, and 12 months. Linear mixed modelling was applied to compare the effect of MBSR with CAU over time. RESULTS: At 3 and 12 months, there were statistically significant improvements in the MENQOL for the MBSR group compared with the CAU group (both P = 0.04). At 3 months, the mean MENQOL scores were 3.5 (95% confidence interval, 95% CI 3.0-3.9) and 3.8 (95% CI 3.3-4.2) for the MBSR and CAU groups, respectively; at 12 months, the corresponding values were 3.6 (95% CI 3.1-4.0) and 3.9 (95% CI 3.5-4.4). No significant differences were found between the MBSR and CAU groups in the other scores. CONCLUSION: Mindfulness-based stress reduction was effective at improving quality of life in the short- and long-term for patients with menopausal symptoms after RRSO; however, it was not associated with an improvement in sexual functioning or distress. TWEETABLE ABSTRACT: Mindfulness improves menopause-related quality of life in women after risk-reducing salpingo-oophorectomy.

Mindfulness, cognitive behavioural and behaviour-based therapy for natural and treatment-induced menopausal symptoms: a systematic review and meta-analysis.

BACKGROUND: During menopause women experience vasomotor and psychosexual symptoms that cannot entirely be alleviated with hormone replacement therapy (HRT). Besides, HRT is contraindicated after breast cancer. OBJECTIVES: To review the evidence on the effectiveness of psychological interventions in reducing symptoms associated with menopause in natural or treatment-induced menopausal women. SEARCH STRATEGY: Medline/Pubmed, PsycINFO, EMBASE and AMED were searched until June 2017. SELECTION CRITERIA: Randomised controlled trials (RCTs) concerning natural or treatment-induced menopause, investigating mindfulness or (cognitive-)behaviour-based therapy were selected. Main outcomes were frequency of hot flushes, hot flush bother experienced, other menopausal symptoms and sexual functioning. DATA COLLECTION AND ANALYSIS: Study selection and data extraction were performed by two independent researchers. A meta-analysis was performed to calculate the standardised mean difference (SMD). MAIN RESULTS: Twelve RCTs were included. Short-term (<20 weeks) effects of psychological interventions in comparison to no treatment or control were observed for hot flush bother (SMD -0.54, 95% CI -0.74 to -0.35, P < 0.001, I2  = 18%) and menopausal symptoms (SMD -0.34, 95% CI -0.52 to -0.15, P < 0.001, I2  = 0%). Medium-term (≥20 weeks) effects were observed for hot flush bother (SMD -0.38, 95% CI -0.58 to -0.18, P < 0.001, I2  = 16%). [Correction added on 9 July 2018, after first online publication: there were miscalculations of the mean end point scores for hot flush bother and these have been corrected in the preceding two sentences.] In the subgroup treatment-induced menopause, consisting of exclusively breast cancer populations, as well as in the subgroup natural menopause, hot flush bother was reduced by psychological interventions. Too few studies reported on sexual functioning to perform a meta-analysis. CONCLUSIONS: Psychological interventions reduced hot flush bother in the short and medium-term and menopausal symptoms in the short-term. These results are especially relevant for breast cancer survivors in whom HRT is contraindicated. There was a lack of studies reporting on the influence on sexual functioning. TWEETABLE ABSTRACT: Systematic review: psychological interventions reduce bother by hot flushes in the short- and medium-term.

Characteristics of Lynch syndrome associated ovarian cancer.

OBJECTIVE: To describe clinical characteristics of Lynch syndrome associated ovarian cancer and the efficacy of surveillance in the early detection of these ovarian cancers. METHODS: All Lynch syndrome associated ovarian cancer cases identified in either the Dutch Lynch syndrome registry (DLSR) between 1987 and 2016, and/or the cohort at the University Medical Center Groningen (UMCG) between 1993 and 2016 were included. Clinical data on age at diagnosis, mutation type, histological type, FIGO stage, treatment, follow-up and gynecological surveillance were collected. RESULTS: A total of 46/798 (6%) women in the DLSR and 7/80 (9%) in the UMCG cohort were identified as LS associated ovarian cancer patients. The median age at ovarian cancer diagnosis was 46.0 years (range 20-75 years). The most frequently reported histological type was endometrioid adenocarcinoma (40%; n = 21) and serous carcinoma (36%; n = 19). Most tumors (87%; n = 46) were detected at an early stage (FIGO I/II). Forty-one of 53 (77%) patients were diagnosed with ovarian cancer before LS was diagnosed. In the other 12/53 (23%) women, ovarian cancer developed after starting annual gynecological surveillance for LS; three ovarian cancers were screen-detected in asymptomatic women. Overall survival was 83%. CONCLUSION: Ovarian cancer in women with LS has a wide age-range of onset, is usually diagnosed at an early stage with predominantly endometrioid type histology and a good overall survival. The early stage at diagnosis could not be attributed to annual gynecological surveillance.

Does early response to intravenous glucocorticoids predict the final outcome in patients with moderate-to-severe and active Graves' orbitopathy?

PURPOSE: Intravenous glucocorticoids (ivGCs) given as 12-weekly infusions are the first-line treatment for moderate-to-severe and active Graves' orbitopathy (GO), but they are not always effective. In this study, we evaluated whether response at 6 weeks correlated with outcomes at 12 (end of intervention) and 24 (follow-up) weeks, particularly in patients initially unresponsive. METHODS: Our database (Bartalena et al. J Clin Endocrinol Metab 97:4454-4463, 10), comprising 159 patients given three different cumulative doses of methylprednisolone (2.25, 4.98, 7.47 g) was analyzed, pooling data for analyses. Responses at 6 weeks were compared with those at 12 and 24 weeks using three outcomes: overall ophthalmic involvement [composite index (CI)]; quality of life (QoL); Clinical Activity Score (CAS). Responses were classified as "Improved", "Unchanged", "Deteriorated", compared to baseline. RESULTS: Deteriorated patients at 6 weeks for CI (n = 8) remained in the same category at 12 weeks and 7/8 at 24 weeks. Improved patients at 6 weeks for CI (n = 51) remained in the same category in 63% and 53% of cases at 12 and 24 weeks, respectively. Unchanged patients at 6 weeks (n = 100) eventually improved in 28% of cases (CI), 58% (CAS), 32% (QoL). There was no glucocorticoid dose-dependent difference in the influence of early response on later outcomes. CONCLUSIONS: Patients who deteriorate at 6 weeks after ivGCs are unlikely to benefit from continuing ivGCs. Patients unresponsive at 6 weeks still have a significant possibility of improvement later. Accordingly, they may continue ivGC treatment, or, alternatively, possibly stop ivGCs and be switched to a second-line treatment.

Seven-year follow-up of unilateral multifocal pseudophakia in a child.

The purpose of the study was to report the long-term outcome of unilateral implantation of a multifocal intraocular lens (IOL) in a pediatric cataract. This study was carried out at Tertiary Academic Ophthalmology Department, AMC, Amsterdam. This is a case report study of a 7-year-old child with a unilateral irradiation cataract, in whom an apodized diffractive multifocal IOL (SN6D3, Alcon) was implanted at the time of cataract surgery. During the follow-up period, visual acuity was preserved at logMAR -0.1; the child did not develop amblyopia. Binocular single vision was established. Few glistenings were seen on the IOL. The non-operated eye developed more myopia during the follow-up period than the multifocally implanted eye. Straylight was increased to log(s) 1.83. Patient and parents satisfaction were high. In selected cases, unilateral implantation of apodized diffractive multifocal IOLs leads to good long-term results in terms of visual acuity and patient satisfaction. No untoward effects were seen, including few glistenings on the IOL. Straylight is increased, but subjectively not disturbing.

[The impact of fireworks: the context of facial trauma]. / De impact van vuurwerk: achtergronden van het aangezichtsletsel.

In the Netherlands the general public can legally use fireworks on New Year's Eve. Despite the fact that the public is well aware of the dangers of fireworks, fireworks accidents occur in which the victims suffer a variety of injuries. In addition to burns, injuries to fingers and/or hands are most common. However, injuries to the eye, which can also involve facial trauma, frequently occur as well. Trauma mainly occurs as a result of the destructive effects of the wave of pressure released by the explosion. The best preventive measure would be to prohibit the use of fireworks by amateurs. Until such time, people should be advised to wear protective fireworks glasses when outside so that damage to the eyes from legal fireworks at least can be prevented.

Reducing contrast medium volume and tube voltage in CT angiography of the pulmonary artery.

AIM: To evaluate image quality after contrast medium (CM) and tube voltage reduction in computed tomography angiography (CTA) of the pulmonary artery. MATERIALS AND METHODS: Thirty-three patients referred for CTA of the pulmonary artery for suspected pulmonary embolism were included. Patients were randomly assigned to Protocol I (100 ml of 350 mg iodine/ml iodinated CM; n=16) or Protocol II (50 ml of 350 mg iodine/ml iodinated CM; n=17). Dual-energy CT (80 kV and 140 kV) was performed in all patients. An averaged weighted series equivalent to a 120 kV image acquisition was reconstructed. The mean attenuation value of CM was measured at eight positions in the pulmonary trunk and pulmonary arteries. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Qualitative assessment of the vascular enhancement was performed independently by two experienced radiologists using a three-point scale. Mean attenuation values, image noise, CNR, and SNR of images with 50 ml CM and images with 100 ml CM were compared and mean attenuation values, image noise, CNR, and SNR in 80 kV images and 120 kV images were compared. For qualitative analysis, interobserver variability was analysed using Cohen's kappa statistics. RESULTS: The mean attenuation values in Protocol I and Protocol II were not significantly different at 80 kV (634.6±168.3 versus 537.9±146.7 HU; p=0.088) and 120 kV (482.8±127.7 versus 410.4±106.0 HU; p=0.085). The mean attenuation value at 80 kV was significantly higher than the mean attenuation value at 120 kV in Protocols I and II (p<0.001). The CNR and SNR were higher at 120 kV than at 80 kV in both protocols (p=0.000-0.019); however, there were no significant differences in the CNR and SNR between both protocols (p=0.600-0.952). Qualitative (subjective) analysis showed no statistical significant difference between Protocols I and II (p=0.524-1.000). CONCLUSION: Low tube voltage (80 kV) CTA using 50 ml CM is not inferior to CTA at 120 kV using 100 ml CM.

The optimal number of heifer calves to be reared as dairy replacements.

Dairy farmers often keep almost all their newborn heifer calves despite the high cost of rearing. By rearing all heifer calves, farmers have more security and retain flexibility to cope with the uncertainty in the availability of replacement heifers in time. This uncertainty is due to mortality or infertility during the rearing period and the variation in culling rate of lactating cows. The objective of this study is to provide insight in the economically optimal number of heifer calves to be reared as replacements. A herd-level stochastic simulation model was developed specific for this purpose with a herd of 100 dairy cows; the biological part of the model consisted of a dairy herd unit and rearing unit for replacement heifers. The dairy herd unit included variation in the number of culled dairy cows. The rearing unit incorporated variation in the number of heifers present in the herd by including uncertainty in mortality and variation in fertility. The dairy herd unit and rearing unit were linked by the number of replacement heifers and culled dairy cows. When not enough replacement heifers were available to replace culled dairy cows, the herd size was temporarily reduced, resulting in an additional cost for the empty slots. When the herd size reached 100 dairy cows, the available replacement heifers that were not needed were sold. It was assumed that no purchase of cows and calves occurred. The optimal percentage of 2-wk-old heifer calves to be retained was defined as the percentage of heifer calves that minimized the average net costs of rearing replacement heifers. In the default scenario, the optimal retention was 73% and the total net cost of rearing was estimated at €40,939 per herd per year. This total net cost was 6.5% lower than when all heifer calves were kept. An earlier first-calving age resulted in an optimal retention of 75%, and the net costs of rearing were €581 per herd per year lower than in the default scenario. For herds with a lower or higher culling rate of dairy cows (10 or 40% instead of 25% in the default scenario), it was optimal to retain 35 or 100% of the heifer calves per year. Herds that had a lower or higher cost of empty slots (€50 or €120 per month instead of €82 in the default scenario) had an optimal retention of 49 or 83% per year; the optimal retention percentage was dependent on farm and herd characteristics. For Dutch dairy farming conditions, it was not optimal to keep all heifer calves.

Ectopic brain tissue in the orbit: 5-year follow-up.

A neonate presented with a dilated pupil of the left eye. Magnetic Resonance Imaging (MRI) showed a mass in the left inferior part of the orbit. Incisional biopsy was performed. Histopathological examination revealed ectopic brain tissue. The patient had a 5-year follow-up without any growth on MRI. Ectopic brain tissue in the orbit is a rare finding in the literature, almost all involved infants or neonates. Pathogenesis is still unknown.

Outcome of BRCA1- compared with BRCA2-associated ovarian cancer: a nationwide study in the Netherlands.

BACKGROUND: Recent studies suggested an improved overall survival (OS) for BRCA2- versus BRCA1-associated epithelial ovarian cancer (EOC), whereas the impact of chemotherapy is not yet clear. In a nationwide cohort, we examined the results of primary treatment, progression-free survival (PFS), treatment-free interval (TFI), and OS of BRCA1 versus BRCA2 EOC patients. METHODS: Two hundred and forty-five BRCA1- and 99 BRCA2-associated EOC patients were identified through all Dutch university hospitals. Analyses were carried out with the Pearson's Chi-square test, Kaplan-Meier, and Cox regression methods. RESULTS: BRCA1 patients were younger at EOC diagnosis than BRCA2 patients (51 versus 55 years; P < 0.001), without differences regarding histology, tumor grade, and International Federation of Gynecology and Obstetrics (FIGO) stage. Complete response rates after primary treatment, including chemotherapy, did not differ between BRCA1 (86%) and BRCA2 patients (90%). BRCA1 versus BRCA2 patients had a shorter PFS (median 2.2 versus 3.9 years, respectively; P = 0.006), TFI (median 1.7 versus 2.8 years; P = 0.009), and OS (median 6.0 versus 9.7 years; P = 0.04). Differences could not be explained by age at diagnosis, FIGO stage or type of treatment. CONCLUSIONS: PFS and OS were substantially longer in BRCA2- than in BRCA1-associated EOC patients. While response rates after primary treatment were similarly high in both groups, TFI, as surrogate for chemosensitivity, was significantly longer in BRCA2 patients.

The additional value of endometrial sampling in the early detection of endometrial cancer in women with Lynch syndrome.

OBJECTIVE: Based on previous studies, standard gynecological screening consisting of annual transvaginal ultrasonography (TVU) was added with endometrial sampling in women with Lynch syndrome (LS). The aim of this study was to evaluate the additional value of endometrial sampling in detecting (pre)malignancies of the endometrial tissue in women with LS or first-degree relatives. METHODS: All women above 30 years of age with LS or first-degree relatives at 50% risk of LS are offered annual gynecological screening in our family cancer clinic. Endometrial screening results from January 2003-December 2007 (period I: standard screening by transvaginal sonography and serum CA125) were compared with screening results from January 2008-June 2012 (period II: standard screening added with endometrial sampling). RESULTS: Seventy five women (300 patient years) were screened annually. There were 266 screening visits, 117 in period I and 149 in period II. In period I, four premalignant endometrial lesions were detected and one endometrial carcinoma (FIGO stage IB). In period II, two premalignancies were found. None of the lesions would have been missed without standard endometrial sampling. No interval endometrial cancers were detected in this study. CONCLUSION: In this study, annual endometrial screening seems an effective screening tool in the detection of premalignancies and early endometrial cancer in women with LS. Adding standard endometrial sampling to annual TVU has no additional value in the early detection of (pre)malignant endometrial lesions in women with LS in this study.

First-calving age and first-lactation milk production on Dutch dairy farms.

Farmers attempting to reduce first-calving age (FCA) need to understand which rearing management factors influence FCA and first-lactation milk production (FLP). Reduced FCA might be associated with lower FLP. This study describes the association between herd FCA, FLP, and several herd-level health and rearing management variables and describes the association between FCA and FLP at the cow level. It uses data from a 2010 survey of 100 Dutch dairy farms about general management, colostrum and milk feeding, housing, cleanliness, healthcare, disease, and breeding. It also used available data on FCA and 305-d FLP at both cow and herd level. The associations between median FCA and median FLP of the herd and herd-level health and rearing management variables were determined using multivariate regression analysis. The median FCA was associated with minimum age of first insemination, feeding of waste milk, and the amount of milk given preweaning. The median FLP was associated with median FCA and vaccination status for bovine respiratory syncytial virus. The association between FCA and FLP (based on 8,454 heifers) was analyzed with a single-effect linear mixed model, where the dependent variable was either FCA or relative FCA (defined as the difference between FCA of the heifer and median FCA of the herd to which they belonged). Heifers having an FCA of 24 mo produced, on average, 7,164 kg of milk per 305 d, and calving 1 mo earlier gave 143 kg less milk per 305 d. When FCA did not deviate from the median herd FCA, heifers produced, on average, 7,272 kg of milk per 305 d. From the median FCA of the herd, heifers calving 1 mo earlier produced 90 kg of milk per 305 d less, and heifers calving 1 mo later produced 86 kg per 305 d more. This is the first study that explained FLP using relative FCA. It assumes that heifers raised within the same farm have similar development because they are similarly managed. Similar management is reflected by the median FCA of the herd, with a deviation of the heifer's FCA from median FCA reflecting the heifer's development relative to the herd's average. The advantage of using relative FCA was that it accounts for between-farm differences in rearing management. It showed that earlier insemination without adjusting management to ensure sufficient development lowers FLP. An economic optimum exists between rearing costs, FCA, and FLP and, as a consequence, decisions with regard to young stock management should be made with care.

Dutch dairy farmers' perspectives on culling reasons and strategies.

Since the abolishment of the milk quota system in Europe in 2014 and the introduction of environmental policies such as the phosphate rights system in the Netherlands, the reasons for culling dairy cows might have changed. The aim of this study was to determine the culling reasons for dairy cattle and to identify farmers' culling strategies and their intentions regarding the alteration of indicated culling strategies. To this end, an online questionnaire was distributed among dairy farmers nationally that resulted in 207 responses. Results showed that the most frequent culling reasons were related to problems with reproduction, udder, and hoof health. Primiparous cows were primarily culled for miscellaneous reasons such as injury, reproduction failure, and low milk yield. Multiparous cows were culled predominantly for reproduction failure, udder health and hoof health reasons. Most respondents indicated that they consider formulating a culling strategy, based on certain rules of thumb regarding the most common reasons for culling. Most farmers also reported that culling decisions on their farms were perceived to be unavoidable, though reproductive culling decisions are primarily voluntary. Most respondents stated that they intended to reduce the culling rate for better economic gain did not intend to alter the amount of replacement stock reared. The applied rules of thumb regarding culling strategies do not seem to have changed since the policy changes in dairy farming. The question remains whether farmers' rules of thumb might have made them unaware of the actual economic consequences of their culling strategies under the altered situation.

Factors underlying Dutch farmers' intentions to adapt their agronomic management to reduce Fusarium species infection in wheat.

Infection of wheat by Fusarium species can lead to Fusarium Head Blight (FHB) and mycotoxin contamination, thereby reducing food quality and food safety, and leading to economic losses. Agronomic management through the implementation of various pre-harvest measures can reduce the probability of Fusarium spp. infection in the wheat field. To design interventions that could stimulate wheat farmers to (further) improve their agronomic management to reduce FHB, it is key to understand farmers' behaviour towards adapting their management. The aim of this paper was to understand the intention, underlying behavioural constructs, and beliefs of Dutch wheat farmers to adapt their agronomic management to reduce FHB and mycotoxin contamination in wheat, applying the Theory of Planned Behaviour (TPB). Data were collected from 100 Dutch wheat farmers via a questionnaire. The standard TPB analysis was extended with an assessment of the robustness of the belief results to account for the statistical validity of the analysis on TPB beliefs (i.e. to address the so-called expectancy-value muddle). Forty-six percent of the farmers had a positive intention to change their management in the next 5 years. The two behavioural constructs significantly related to this intention were attitude and social norm, whereas association with the perceived behavioural control construct was insignificant indicating that farmers did not perceive any barriers to change their behaviour. Relevant attitudinal beliefs indicated specific attributes of wheat, namely yield, quality and safety (lower mycotoxin contamination). This indicates that strengthening these beliefs-by demonstrating that a change in management will result in a higher yield and quality and lower mycotoxin levels-will result in a stronger attitude and, subsequently, a higher intention to change management. Interventions to strengthen these beliefs should preferably go by the most important referents for social norms, which were the buyers and the farmer cooperatives in this study.

Genetic counseling of patients with ovarian carcinoma: acceptance, timing, and psychological wellbeing.

The new Dutch guidelines on hereditary and familial ovarian carcinoma recommend genetic testing of all patients with epithelial ovarian cancer (EOC). With this study, we aimed to obtain insight into (1) the acceptance and timing of the offer of genetic counseling in women with EOC, (2) reasons for accepting or declining genetic counseling, and (3) psychological differences between women who did and did not have genetic counseling. A multicenter questionnaire survey was performed in patients with EOC in four Dutch oncology centers. The questionnaire addressed whether, how, and when genetic counseling was offered, women's arguments to accept or decline genetic counseling, and included the Cancer Worry Scale (CWS) and the Hospital Anxiety and Depression Scale (HADS). A total of 67 women completed the questionnaire, of which 43 had genetic counseling. Despite a wide variability in the timing of the offer of genetic counseling, 89% of the women were satisfied with the timing. No significant differences were found between the CWS and HADS scores for the timing of the offer of genetic counseling and whether or not women had genetic counseling. Taking the small sample size into account, the results tentatively suggest that genetic counseling may have limited impact on the psychosocial wellbeing of women with EOC. Therefore, we assume that implementation of the new guidelines offering genetic counseling to all patients with EOC will not cause considerable additional burden to these patients.

Routine follow-up intervals in patients with high-grade squamous intraepithelial lesions (HSIL) and free excision margins can safely be increased in the first two years after Large Loop Excision of the Transformation Zone (LLETZ).

OBJECTIVE: To assess the compliance of HSIL patients to the national Dutch routine follow-up protocol in the first 2 years after LLETZ and to determine if based on the status of excision margins, follow-up intervals could be modified. METHODS: A prospective cohort study was performed in patients, referred because of an abnormal Pap smear between 1996 and 2004 and treated for HSIL with LLETZ. The Dutch national routine follow-up protocol orders a Pap smear after 6, 12 and 24 months, respectively. Follow-up results were completed by using PALGA, the nationwide network and registry of histo- and cytopathology in the Netherlands. To assess compliance to the follow-up protocol, adequate follow-up was defined as three cervical smears taken after 6 (+/-3), 12 (+/-3) and 24 (+/-3) months, respectively. RESULTS: Compliance to the first 2 years follow-up protocol declined from 86.2% to 64.8% to 51.2% for first, second and third follow-up cervical smears, respectively. Patients with involved excision margins had a three times higher overall risk of developing a subsequent HSIL after LLETZ as compared to patients with free excision margins (HR: 3.2, 95% CI=1.3-7.9, p=0.01). Risk for diagnosing HSIL during the first 12 months of follow-up for patients with free excision margins was only 1%. CONCLUSIONS: Compliance to the Dutch national routine follow-up protocol in HSIL patients after LLETZ is only moderate. For HSIL patients with free excision margins after LLETZ the first cytological follow-up interval can safely be increased to 12 months.

Farm-specific failure costs of production disorders in European organic dairy herds.

On-farm decision support in animal health management requires a tailor-made failure costs (FCs) assessment of production disorders for the individual farm. In our study we defined a generic framework to estimate the FC of production disorders in dairy cows. We converted the framework to a practical tool in which the farm-specific FC of mastitis, ketosis, lameness and metritis were estimated for 162 organic dairy farms in four European countries. Along with the structure of the framework, the FC estimation required three distinct types of model input: performance input (related to herd performance parameters), consequential input (related to the consequences of the disorders) and economic input (related to price levels). Input was derived from official herd recordings (e.g. test-day records and animal health recordings) and farmers' responses (e.g. questionnaire replies). The average FC of mastitis, ketosis, lameness and metritis amounted to € 96, € 21, € 43 and € 10 per cow per year, respectively. The variation in FC outcomes was high among farmers and countries. Overall ranking of the disorders based on absolute values was the same for all countries, with mastitis being the costliest disorder followed in order by lameness, ketosis, and metritis. Farm specific estimates can be used to rank production related disorders in terms of their associated failure costs and thus provide valuable insights for herd health management. The practical calculation tool developed in this study should be considered by farmers or herd health advisors to support their animal health practices or advice.

Favorable long-term results of primary pterygium removal by bare sclera extirpation followed by a single 90Strontium application.

PURPOSE: To describe and compare long-term (> or = 36 months) effects of patients with 86 primary pterygia treated with bare sclera extirpation (BSE) followed by Beta-RT or by sham irradiation. METHODS: Prospective, multicenter, randomized, double-blind study. After BSE of their pterygium, patients were randomized to either Beta-RT or sham irradiation. In the case of Beta-RT, within 24 hours after the operation, a 90Sr eye applicator was used to deliver 2500 cGy to the sclera surface at a dose rate of between 200 and 250 cGy/min. Sham irradiation was given using the same type of applicator without the 90Sr layer. After treatment, both a masked ophthalmologist and a radiation oncologist performed follow-up examinations. These were continued until either a relapse occurred or at least 36 months had elapsed. RESULTS: Adequate follow-up was available of 86 pterygia in 81 patients, treated between February 1998 and September 2002. Fifty-two (60%) patients were male. The mean age of the patients was 50 years (range: 24-77). After a follow-up of at least 36 months (mean: 40 months, SD:13.9 months), 5 out of 44 eyes (11%) treated with Beta-RT showed a recurrence versus 32 out of 42 eyes (76%) treated with sham-RT (after a mean follow-up of 22 months) (p<0.001). In the Beta-RT group, 80% were satisfied with the cosmetic result, whereas in the sham group this percentage was 41% (p<0.001). In the Beta-RT group, no scar or a white scar could be detected in 86% of the treated eyes, versus in 24% of the sham irradiated eyes (p<0.001). A change of keratometry (Javal) was seen in 5 patients (12%) following Beta-RT compared to 16 (38%) after sham irradiation (p=0.002). Complications were few: a granuloma was seen in three patients after sham irradiation, mild limitation of abduction in two Beta-RT patients versus in five after sham irradiation, and mild scleromalacia in one Beta-RT patient. CONCLUSIONS: Bare sclera extirpation of a pterygium without adjuvant treatment has an unacceptably high recurrence rate and therefore should be considered obsolete. Bare sclera extirpation of a primary pterygium followed by a single-dose Beta-RT is a simple, effective, and safe treatment with lasting results and very few complications.

[Insufficient basis for the inclusion of Human papillomavirus vaccination in the National Immunisation Programme in The Netherlands]. / Onvoldoende gronden voor opname van vaccinatie tegen Humaan papillomavirus in het Rijksvaccinatieprogramma.

The Dutch Minister of Health, Welfare and Sportintends to implement Human papillomavirus (HPV) vaccination for 12-year-old girls and catch-up vaccination for 13- 16-year-old girls, as part of the National Immunisation Programme from September 2009 onwards. However, due to a well-organised screening programme, cervical cancer is not an important public health problem in the Netherlands any more, which limits the possible impact of HPV vaccination. Vaccine trials thus far have involved a relatively small number ofparticipants with limited follow-up, so the efficacy of the vaccine in preventing cervical cancer is not yet known. There are no data on frequency and severity of possible adverse events and the vaccine has not yet been tested in the intention-to-vaccinate group of 12-year-old girls. Even when we assume that HPV16/18-related cervical cancer is prevented on a lifelong basis, the cost-effectiveness ratio of HPV vaccination is estimated not to be favourable. In conclusion, HPV vaccination does not seem to be urgent in the Netherlands. Therefore we advise studying the safety in 12-year-old girls first while at the same time waiting for the longer follow-up results of ongoing trials.