Impact of high-risk Human Papillomavirus genotyping in cervical disease in the Northern region of Portugal: Real-world data from regional cervical cancer screening program.

Cervical cancer prevention is based on primary prevention with vaccines against Human Papillomavirus (HPV) and secondary prevention by screening with High-Risk-HPV (Hr-HPV) detection. Since 2017, cervical cancer screening in women aged 25-60 years has been performed in Portugal using Hr-HPV detection, followed by cytology in Hr-HPV-positive cases. Herein we report the prevalence of Hr-HPV genotypes and cytological abnormalities among 462 401 women (mean age: 43.73 ± 10.79; median age: 45; range: 24-66 years) that participated in the Regional Cervical Cancer Screening Program of the Northern Region of Portugal, performed between August 2016 and December 2021. Overall, we describe a prevalence rate of 12.50% for Hr-HPV varying from 20.76% at age 25% to 8.32% at age 64. The five most common Hr-HPV genotypes identified were HPV-68 (16.09%), HPV-31 (15.30%), HPV-51 (12.96%), HPV-16 (11.06%), and HPV-39 (11.01%). The prevalence of Hr-HPV included in the nonavalent vaccine (HPV-9valent) was 55.00% ranging from 47.78% to 59.18% across different age groups. Considering positive Hr-HPV cases, 65.68% had a Negative for Intraepithelial Lesion or Malignancy (NILM) cytology, 20.83% atypical squamous cells of undetermined significance (ASC-US), 8.85% Low-Grade Squamous Intraepithelial Lesion (LSIL), 1.65% High-Grade Squamous Intraepithelial Lesion (HSIL), 2.85% ASC-H, 0.09% Atypical Glandular Cells, 0.02% Adenocarcinomas, and 0.02% Squamous Cell Carcinoma (SCC). Our analysis revealed that HPV-9val genotypes were responsible for 52.13% NILM, 59.21% ASC-US, 55.06% LSIL, 90.14% HSIL, 83.50% ASC-H, and 100.00% SCC. Furthermore, multiple Hr-HPV infections (risk ratio [RR] = 1.46; 95% confidence interval [CI] 1.34-1.58), HPV-16/18 (RR = 5.16; 95% CI 4.75-5.93), or HPV-9val genotypes (RR = 5.23; 95% CI 4.68-5.85) were associated with a significant risk of developing > HSIL (p < 0.001). To date, this is the largest study on Hr-HPV genotyping in cervical cancer screening that includes data from a complete cycle of the screening program. Our findings suggest a high prevalence of HPV-9valent genotypes and a significant association with an increased risk of developing > HSIL. This constitutes important data for health authorities, which may help define the future of vaccination and cervical cancer screening strategies.

Evaluation of the Implementation and Diagnostic Accuracy of the Paris Classification for Reporting Urinary Cytology in Voided Urine Specimens: A Cyto-Histological Correlation Study in a Cancer Center.

INTRODUCTION: The Paris classification highlights the need to focus on accurately identifying high-grade urothelial carcinoma (HGUC). Herein, we aimed to assess the overall implementation and diagnostic performance of the Paris classification for reporting urinary cytology in a cancer center. METHODS: All urinary cytology reports from July 2018 to December 2019 were collected (n = 1,240). Only voided urine samples were included (n = 1,180). Risk of high-grade malignancy (ROHM) was calculated for each Paris category. The diagnostic performance of urinary cytology was assessed, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. RESULTS: The distribution of categories was: 0.3% unsatisfactory, 90.5% negative for HGUC, 5.6% atypical urothelial cells (AUC), 1.6% suspicious for HGUC, 1.9% HGUC, and 0.1% other malignancies. No diagnosis of low-grade urothelial neoplasia was given. The ROHM was 21.4% for negative for HGUC, 66.7% for AUC, 91.7% for suspicious for HGUC, and 100% for HGUC. When using suspicious for HGUC as a cutoff, the diagnostic performance of urinary cytology in identifying HGUC histology was 46% sensitivity, 98% specificity, 96% PPV, 68% NPV, and 74% accuracy. CONCLUSION: Specificity of urinary cytology was very high (with only 1 false-positive result), which is important since this will trigger a clinical intervention. The ROHM for each category was in accordance with literature, except for AUC where ROHM was slightly higher (66.7%). This may be explained by the study population characteristics (cancer center; many patients treated with intravesical therapies; lack of clinical annotation for patients referred from outside institutions).

Ovarian cancer ascites proteomic profile reflects metabolic changes during disease progression.

Ovarian cancer (OC) patients develop ascites, an accumulation of ascitic fluid in the peritoneal cavity anda sign of tumour dissemination within the peritoneal cavity. This body fluid is under-researched, mainly regarding the ascites formed during tumour progression that have no diagnostic value and, therefore, are discarded. We performed a discovery proteomics study to identify new biomarkers in the ascites supernatant of OC patients. In this preliminary study, we analyzed a small amount of OC ascites to highlight the importance of not discarding such biological material during treatment, which could be valuable for OC management. Our findings reveal that OC malignant ascitic fluid (MAF) displays a proliferative environment that promotes the growth of OC cells that shift the metabolic pathway using alternative sources of nutrients, such as the cholesterol pathway. Also, OC ascites drained from patients during treatment showed an immunosuppressive environment, with up-regulation of proteins from the signaling pathways of IL-4 and IL-13 and down-regulation from the MHC-II. This preliminary study pinpointed a new protein (Transmembrane Protein 132A) in the OC context that deserves to be better explored in a more extensive cohort of patients' samples. The proteomic profile of MAF from OC patients provides a unique insight into the metabolic kinetics of cancer cells during disease progression, and this information can be used to develop more effective treatment strategies.

Follicular thyroid carcinoma.

Follicular thyroid carcinoma is being diagnosed less and less frequently despite the increasing incidence of well-differentiated thyroid carcinomas everywhere. This review will discuss the reasons underlying such an observation focusing on the evolution of the morphological and immunohistochemical diagnostic criteria of follicular thyroid tumors. It will address the differential diagnosis between follicular carcinoma and three tumor types--follicular adenoma, follicular variant of papillary carcinoma and poorly differentiated carcinoma--as well as the problems raised by the newly described categories of follicular tumors: follicular tumor of uncertain malignant potential, well-differentiated tumor of uncertain malignant potential and well-differentiated carcinoma, not otherwise specified. Finally, the prognostic and therapeutic significance of some promising molecular biomarkers will be discussed within the frame of the aforementioned histopathological classification.

The UK Royal College of Pathologists thyroid fine-needle aspiration diagnostic classification is a robust tool for the clinical management of abnormal thyroid nodules.

OBJECTIVE: To compare the outcomes and evaluate the relative risk of thyroid cancer by using the UK thyroid fine-needle aspiration (FNA) cytological diagnostic categories, with the main objective being the clarity of patient management. STUDY DESIGN: Results of thyroid FNA reported as Thy3a, Thy3f, Thy4, and Thy5 were correlated with histological outcomes. The specificity and positive predictive value (PPV; risk of malignancy) for each reporting category was assessed. RESULTS: Of a total of 873 thyroid FNAs, 237 (27%) were reported as 'abnormal': 40 (4.6%) as Thy3a, 119 (13.6%) as Thy3f, 20 (2.2%) as Thy4, and 58 (6.6%) as Thy 5. The final outcomes were available in 136 (57%) cases which underwent surgical resection (25, 60, 55, and 74% of Thy3a, Thy3f, Thy4, and Thy5, respectively). The known outcomes of the Thy3a category were too low to be statistically significant. The specificity and PPV of the Thy3f, Thy4, and Thy5 (equivalent to the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) IV, V, and VI) categories were 50, 50, and 100% and 28, 64, and 100%, respectively. The PPV of Thy3f for diagnosis of 'neoplasms' (benign and malignant) was 63%. CONCLUSION: The current thyroid FNA classification system used in the UK, which is comparable to TBSRTC, offers a sound basis for clear communication on which the management of patients with abnormal thyroid FNA findings can be based. Categories Thy3f, Thy4, and Thy5 carry a progressively rising risk of malignancy, justifying their continuing use. Diagnostic category Thy5 'malignant' is robust and can be used as a sure indication of a definitive surgical management.

Hedonic thresholds and ideal sodium content reduction of bread loaves.

Global public policies have advocated strategies for reducing sodium consumption due to the high incidence of non-communicable chronic diseases (NCDs) worldwide. The objectives of this study were to identify the bread loaves sodium content considered as ideal by the consumers and determine hedonic thresholds. In this descriptive cross-sectional study, 114 consumers evaluated the ideal sodium content in bread loaves by the Just About Right (JAR) test, (first sensorial stage) studying four decreased levels of sodium (10%, 20%, 30%, 40%) from the mean values observed from bread in 11 food composition tables from various regions of the world, and Brazil. This ideal sodium content was used as the control in pairwise acceptance tests with five other reduced-sodium samples of bread loaves (10%, 30%, 50%, 70%, 100% of reduction from the control), and hedonic threshold tests were performed with 156 consumers (a second stage sensorial test of five sessions). The data from the JAR were analyzed by a regression analysis graph and correlated with the consumption of salt and family income range by a Principal Component Analysis with a 5% significance level. In the Hedonic Threshold tests, each paired session was analyzed by Student's t-test (test t), and an adjusted regression graph was built. The Compromised Acceptance Threshold (CAT) was performed, where the calculated t corresponded to the tabulated t. In the Hedonic Rejection Threshold (HRT), the hedonic scale five ("indifferent" term) was considered. The average sodium content of bread marketed in different regions of the world was 457 mg Na/100 g of bread, and the ideal sodium content observed was 395 mg Na/100 g of bread. The gender, age and income family rates as well as attitudes and knowledge regarding the salt consumption of the trial consumers were not directly related to the evaluations of the bread loaves in the JAR test, according to the Principal Components Analysis at p ≤ 0.05. From this ideal content, a 42% reduction was possible according to the CAT test (267 mg Na/100 g of bread), and more reductions were acceptable until an 85% (to 58 mg Na/100 g of bread) reduction, as the samples began to be rejected according to HRT test. These findings demonstrated that this methodology can be applied to sodium reduction product formulations and bread as a food matrix. With this kind of methodology, it is possible to provide to the bakery industry a methodology to know a safe region to work on food reformulations and subsidize the formulation of new products without compromising consumer acceptability, in addition to meeting the demand for safer food.

Cytohistological correlation in serous effusions using the newly proposed International System for Reporting Serous Fluid Cytopathology: Experience of an oncological center.

BACKGROUND: Cytological analysis is part of the initial etiological evaluation of serous effusions. The newly proposed International System for Reporting Serous Fluid Cytopathology (ISRSFC) aims to standardize reporting. METHODS: All pleural and peritoneal effusion samples admitted for cytological analysis at our institution between 2012 and 2016, and pericardial effusion samples admitted between 2008 and 2018, were reviewed and reclassified according to the ISRSFC. Risk of malignancy (ROM) and performance parameters were calculated. RESULTS: 1496 pleural effusion samples were reclassified: 12(0.8%) non-diagnostic (ND), 944(63.1%) negative for malignancy (NFM), 9(0.6%) atypia of undetermined significance (AUS), 54(3.6%) suspicious of malignancy (SFM) and 477(31.9%) malignant (M). 64 pericardial effusion samples were reclassified: 23(35.9%) NFM, 1(1.6%) AUS, 4(6.3%) SFM and 36(56.2%) M. 763 peritoneal effusion samples were reclassified: 5(0.7%) ND, 457(59.9%) NFM, 12(1.6%) AUS, 37(4.8%) SFM and 252(33%) M. The ROM was, respectively, for each of the aforementioned categories, 57.1%, 23.9%, 50%, 76.2%, 100% in pleural effusions, 100%, 26.3%, 62.5%, 91.7%, 100% in peritoneal effusions and 0% for NFM, 0% for AUS and 100% for M in pericardial effusions. Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were, respectively, 61.6%, 100%, 100%, 73.3%, 81.3% for pleural, 100%, 100%, 100%, 100%, 100% for pericardial and 61.2%, 100%, 100%, 70%, 79.7% for peritoneal effusion samples. CONCLUSION: Serous effusion cytology has a high specificity and positive predictive value and a modest sensitivity and negative predictive value, supporting its role in confirming the diagnosis of malignancy. The ISRSFC will increase standardization and reproducibility in reporting, leading to improved clinical decision-making.

High-Risk human papillomavirus genotype distribution in the Northern region of Portugal: Data from regional cervical cancer screening program.

High-Risk Human papillomavirus (HR-HPV) full genotyping methods have been described as of great potential use in epidemiology and preventive strategies, including cervical cancer screening and HPV vaccination. We characterized the prevalence and distribution of HR-HPV genotypes in cervico-vaginal samples obtained from the Regional Cervical Cancer Screening Program from the Northern Region of Portugal. HR-HPV genotyping was performed using Anyplex™ II HPV-HR Detection kit in 105,458 women enrolled between August 2016 and December 2017. HR-HPVs were detected in 10,665 women (10.2%) with a prevalence ranging from 6.2 to 17.1% depending on age, and from 8.7 to 10.7% depending on geographical location. Multiple infections with two or more HR-HPVs were detected in 2736 (25.7%) of HR-HPV women ranging from 16.5 to 31.0% depending on age. Amongst HR-HPV positive women, HPV-16 (17.5%), HPV-39 (16.7%), HPV-31 (15.0%), HPV-68 (13.2%), HPV-52 (10.7%) and HPV-51 (10.6%) were the most common genotypes in our population, being HPV-16 more frequent in women aged from 30 to 45 years and HPV-39 in 50-65 years. Results also show that HPV16/18 are present in 22.1% and HPV16/18/31/33/45/52/58 in 47.6% of HR-HPV positive women. This is the largest study on HR-HPV genotyping for Cervical Cancer Screening in European populations and provides critical data for program management and vaccine policy.

ALK-negative anaplastic large cell lymphoma with urinary bladder involvement diagnosed in urine cytology: A case report and literature review.

Anaplastic large cell lymphoma is an aggressive T-cell neoplasm. It rarely involves the urinary bladder, with just twelve cases reported thus far and only one being ALK-negative. Immunophenotyping (particularly for ALK) is mandatory, both for prognostic and therapeutic reasons. Herein, we report the case of a patient with an ALK-negative anaplastic large cell lymphoma involving the bladder which was diagnosed and fully characterized by immunocytochemistry in urine cytology. The patient underwent a cystoscopy and the urine sample disclosed tumor diathesis background and aggregates of atypical cells, with evidence of multinucleation and mitotic figures. Immunocytochemistry revealed strong membrane/Golgi positivity for CD30 and negativity for ALK. The patient was submitted to transurethral resection for therapeutic purposes, which confirmed the diagnosis. To the best of our knowledge, this represents only the third case of anaplastic large cell lymphoma with bladder involvement diagnosed in urine cytology and the very first with diagnostic findings allowing for immunophenotyping of the disease in a bladder wash. The present report reinforces the role of urine cytology as a suitable method for establishing an earlier diagnosis and characterization of the disease, avoiding submitting patients to invasive procedures like transurethral resections. Diagn. Cytopathol. 2017;45:354-358. © 2016 Wiley Periodicals, Inc.

TERT, BRAF, and NRAS in Primary Thyroid Cancer and Metastatic Disease.

Context: Little is known about the frequency of key mutations in thyroid cancer metastases and its relationship with the primary tumor genotype. Objectives: To evaluate the frequency of TERT promoter (TERTp), BRAF, and NRAS mutations in metastatic thyroid carcinomas, analyzing primary thyroid tumors, lymph node metastases (LNMs), and distant metastases. Design and Patients: Mutation analysis was performed in 437 tissue samples from 204 patients, mainly with papillary thyroid carcinomas (PTCs; n = 180), including 196 LNMs and 56 distant metastases. All the distant metastases included corresponded to radioiodine-refractory metastatic tissue. Results: We found the following mutation frequency in primary PTCs, LNMs, and distant metastases, respectively: TERTp: 12.9%, 10.5%, and 52.4%; BRAF: 44.6%, 41.7%, and 23.8%; and NRAS: 1.2%, 1.3%, and 14.3%. There was a significant concordance between the primary tumor genotype and the corresponding LNM for all the genes, in particular BRAF-mutated PTC. The overall concordance between primary tumors and respective distant metastases was low. In the group of patients with PTCs, we found a high frequency of TERTp mutations and a low frequency of BRAF mutations in distant metastases, in comparison with the paired primary tumors. When present in distant metastases, BRAF mutations frequently coexisted with TERTp mutations. Conclusions: When the genotype of primary tumors is compared with the genotype of LNMs, the concordance is high for all the genes studied. On the other hand, distant metastases show an enrichment in TERTp mutations and a decrease in BRAF mutations. TERTp mutations may play a role in distant metastases.

Prevalence and clinical features of adverse food reactions in Portuguese adults.

BACKGROUND: Only one previous study, via telephone call, on the prevalence of self-reported food allergies has been performed in Portugal, in a small sample of adults. The objective of this study was to determine the prevalence of self-reported and probable food allergy, analyze the clinical features and involved foods in Portuguese adults. METHODS: Population-based, cross-sectional study performed in various healthcare centres from central Portugal. All 1436 randomly selected individuals (median age: 45 years, 50.6 % female) replied to a validated food allergy questionnaire by phone. Those who reported an adverse food reaction were invited to come to the hospital, where clinical history was taken, skin prick (SPT) and prick-prick skin (SPPT) tests were performed and food allergen-specific IgE levels (sIgE) were determined. An open oral challenge was performed in selected cases. Cases of positive clinical history of immediate (up to 2 h after ingestion) reaction in association with positive food sIgE levels and/or skin prick tests were classified as IgE-associated probable food allergy. Cases of positive clinical history of delayed (more than 2 h after ingestion) and negative food sIgE levels independently of positive SPT or SPPT results were classified as non-IgE associated probable food allergy. RESULTS: The prevalence of probable food allergy in our sample was 1 %, with shellfish and fish as the most frequently implicated foods. IgE-mediated probable food allergy occurred in 0.71 % of cases, with shellfish, peanut and nuts mainly involved. Cutaneous symptoms were most frequently reported. Prevalence values and food types were discrepant between self-reported and probable food allergies. CONCLUSIONS: The prevalence of probable food allergies in Portuguese adults is low, is mostly related to shellfish, peanut and nuts and most frequently involves cutaneous symptoms.

[Choosing wisely when prescribing statins]. / Verstandig kiezen bij het voorschrijven van statinen.

The Dutch campaign 'Verstandig kiezen', based on the American programme 'Choosing wisely', aims to improve quality in healthcare, with attention to cost control. The 'Choosing wisely'-based programme can be applied in the choice of a statin. Atorvastatin and rosuvastatin are regarded as equal choices in various guidelines regarding cardiovascular risk management. Generic atorvastatin is available, and is approximately 25 times cheaper than rosuvastatin in almost equipotent doses. Rosuvastatin provides a greater LDL reduction than atorvastatin. Patient LDL targets can usually be achieved with atorvastatin, and rosuvastatin is not needed. At group level, there are no relevant differences in adverse-events profile between both statins. Atorvastatin and rosuvastatin do have different pharmacokinetic interactions. When changing medication, good provision of information is a prerequisite for patient satisfaction and compliance. We advise use of atorvastatin instead of rosuvastatin as drug of choice when the LDL target is not reached using simvastatin. However, under specific conditions, rosuvastatin should be the treatment of choice. Efficacy and adverse effects should then be evaluated at individual patient level.

Perceptions of cardiovascular risk among patients with hypertension or diabetes.

We aimed to examine risk perceptions among patients at moderate to high cardiovascular risk. A questionnaire about perceived absolute risk of myocardial infarction and stroke was sent to 2424 patients with hypertension or diabetes. Response rate was 86.3% and 1557 patients without atherosclerotic disease were included. Actual cardiovascular risk was calculated by using Framingham risk functions. A total of 363 (23.3%) of the 1557 patients did not provide any risk estimates and these were particularly older patients, patients with a lower educational level, and patients reporting no alcohol consumption. The remaining 1194 patients tended to overestimate their risk. In 42.3% (497/1174) and 46.8% (541/1155) of the cases, patients overestimated their actual 10-year risk for myocardial infarction and stroke, respectively, by more than 20%. Older age, smoking, familial history of cardiovascular disease (CVD), and actual absolute risk predicted higher levels of perceived absolute risk. Male sex, higher scores for an internal health locus of control, lower scores for a physician locus of control, and self-rated excellent or (very) good health were positively related to higher accuracy. In conclusion, patients showed inadequate perceptions of their absolute risk of cardiovascular events and physicians should thus provide greater information about absolute risk when offering preventive therapy.

Provision of information and advice in cardiovascular care: clinical performance of general practitioners.

The aim of this study was to assess the provision of information and advice by general practitioners (GPs) with respect to patients with hypertension, hypercholesterolaemia, or cardiovascular disease. The study relied on the prospective recording of patient encounters by GPs. Performance indicators were selected from the Dutch national guidelines for general practice. The GPs (n=195) completed 5330 encounter forms. High levels of performance were found with regard to advice on smoking cessation and the provision of information (e.g. information about alarm symptoms or the aim of treatment). Low levels of performance were found with regard to advice on salt consumption, alcohol consumption, weight reduction and physical exercise for patients with hypertension. Discussion of compliance with the therapy in case of hypercholesterolaemia, advice on physical exercise in case of angina pectoris and advice on foot care in case of peripheral arterial disease also showed a substantial gap between recommended and actual care. Performance rates varied considerably across GPs. The patient and GP characteristics examined in this study contributed very little to the clinical performance.

Process evaluation of a multifaceted intervention to improve cardiovascular disease prevention in general practice.

OBJECTIVES: To perform a process evaluation of a multifaceted intervention to improve cardiovascular and diabetes care in general practice. METHODS: The feasibility of the intervention, carried out by outreach visitors in 62 practices, was addressed by evaluating whether the intervention programme was performed as planned and the extent to which it was accepted by the practice team. In addition, the costs of the programme were determined. RESULTS: The intervention was largely carried out as planned, although the intervention period had to be extended by three months. Of the 18 topics that could be addressed during the intervention period, 12 (mean) were addressed. The number of outreach visits per practice was 15.2 (mean), each visit lasted about one hour. Most practice members endorsed both the key recommendations for clinical decision-making and cardiovascular risk profiling. The majority of GPs (range 63-98%) agreed with the guidelines for clinical decision-making, and 29-97% had a positive opinion about the guidelines for practice organisation. According to practice staff members, the outreach visitor had sufficient knowledge and skills to support them in changing the practice organisation. GPs were less positive about the outreach visitor's knowledge and skills in optimising clinical decision-making; however 78% believed that the outreach visitor contributed to effecting change in their clinical decision-making. The total costs of the intervention per practice were Euro 4317. CONCLUSIONS: This process evaluation demonstrated that the intervention was usually carried out as planned and achieved a high satisfaction rating from the participating practice members.

TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas.

CONTEXT: Telomerase promoter mutations (TERT) were recently described in follicular cell-derived thyroid carcinomas (FCDTC) and seem to be more prevalent in aggressive cancers. OBJECTIVES: We aimed to evaluate the frequency of TERT promoter mutations in thyroid lesions and to investigate the prognostic significance of such mutations in a large cohort of patients with differentiated thyroid carcinomas (DTCs). DESIGN: This was a retrospective observational study. SETTING AND PATIENTS: We studied 647 tumors and tumor-like lesions. A total of 469 patients with FCDTC treated and followed in five university hospitals were included. Mean follow-up (±SD) was 7.8 ± 5.8 years. MAIN OUTCOME MEASURES: Predictive value of TERT promoter mutations for distant metastasization, disease persistence at the end of follow-up, and disease-specific mortality. RESULTS: TERT promoter mutations were found in 7.5% of papillary carcinomas (PTCs), 17.1% of follicular carcinomas, 29.0% of poorly differentiated carcinomas, and 33.3% of anaplastic thyroid carcinomas. Patients with TERT-mutated tumors were older (P < .001) and had larger tumors (P = .002). In DTCs, TERT promoter mutations were significantly associated with distant metastases (P < .001) and higher stage (P < .001). Patients with DTC harboring TERT promoter mutations were submitted to more radioiodine treatments (P = .009) with higher cumulative dose (P = .004) and to more treatment modalities (P = .001). At the end of follow-up, patients with TERT-mutated DTCs were more prone to have persistent disease (P = .001). TERT promoter mutations were significantly associated with disease-specific mortality [in the whole FCDTC (P < .001)] in DTCs (P < .001), PTCs (P = .001), and follicular carcinomas (P < .001). After adjusting for age at diagnosis and gender, the hazard ratio was 10.35 (95% confidence interval 2.01-53.24; P = .005) in DTC and 23.81 (95% confidence interval 1.36-415.76; P = .03) in PTCs. CONCLUSIONS: TERT promoter mutations are an indicator of clinically aggressive tumors, being correlated with worse outcome and disease-specific mortality in DTC. TERT promoter mutations have an independent prognostic value in DTC and, notably, in PTC.

Organisational determinants of cardiovascular prevention in general practice.

OBJECTIVE: To assess organisational determinants in the prevention of cardiovascular disease. DESIGN: A cross-sectional study. SETTING AND SUBJECTS: 130 general practices in The Netherlands. Data were collected using questionnaires. A causal model was designed and analysed by path analysis. MAIN OUTCOME MEASURES: Relationships between preventive activities, practice management and practice characteristics. RESULTS: Important differences between adequacy of equipment and practice organisation were found. Record-keeping was significantly better when working experience of the GPs was less than 15 years, when the practice consisted only of female GPs, and when the practice had written protocols for cardiovascular disease management and the staff held regular scheduled meetings (teamwork). Teamwork also showed a significant relation with follow-up activities. The influence of non-measured variables in the model was considerable. CONCLUSION: In exploring the organisational setting as a barrier to prevention and disease management, the designed model showed no major effects. Despite the wide variety of practice organisational items investigated, a strong influence of non-measured variables was evident. Teamwork in the practices proved to be related to both follow-up and record-keeping. Younger and female GPs were further predictors of adequate record-keeping.

Improving quality of organizing cardiovascular preventive care in general practice by outreach visitors: a randomized controlled trial.

BACKGROUND: Adequate care for patients with cardiovascular risks requires an adequate practice organization. Educational outreach visits are a promising approach to modifying professional behavior. We aimed to assess whether the quality of cardiovascular preventive care in general practice can be improved through a comprehensive intervention implemented by an educational outreach visitor. METHODS: After baseline measurements, general practices (n = 124) in the southern half of The Netherlands were randomly allocated to either intervention or control group. The intervention, based on the educational outreach model, comprised 15 practice visits over a period of 21 months and addressed a large number of issues around task delegation, availability of instruments and patient leaflets, record-keeping, and follow-up routines. Twenty-one months after the start of the intervention, postintervention measurements were performed. The difference between ideal and actual practice in each aspect of organizing preventive care was defined as a deficiency score. Primary outcome measure was the difference in deficiency scores before and after the intervention. RESULTS: All practices completed both baseline and postintervention measurements. The difference in change between intervention and control group adjusted for baseline was statistically significant (P < 0.001) for each aspect of organizing preventive care. The largest absolute improvement was found for the number of preventive tasks performed by the practice assistant. CONCLUSIONS: This study showed that a comprehensive intervention implemented by outreach visitors was effective in improving organization of cardiovascular preventive care in general practice.

Organizing cardiovascular preventive care in general practice: determinants of a successful intervention.

BACKGROUND: Although outreach visitor interventions have proven to be effective, more detailed studies are needed to understand what elements of interventions work and why. In this study we investigate the determinants of success of an intervention for optimizing cardiovascular preventive care in general practice. METHODS: After baseline measurements and randomization, 62 general practices received a comprehensive intervention program, by means of outreach visitors, lasting 21 months. Data on practice management and preventive activities were gathered at baseline and at postintervention measurements. Key characteristics of the intervention considered possible determinants of success were gathered by questionnaire. The difference between ideal and actual practice in each aspect of organizing cardiovascular preventive care was calculated as a deficiency score. The difference between deficiency scores before and after the intervention were the main outcome measures. RESULTS: The key characteristic, duration of exposure to an aspect (in months), was positively related to the change in availability of separate clinics and in the amount of teamwork. The improvement in instruments and materials was positively related to the general practitioner's opinion about the given feedback. No relations were found between the key characteristics and changes in record-keeping or follow-up routines. CONCLUSIONS: Although implementation of a comprehensive prevention program is effective, we could not fully disentangle the "black box" of the intervention. The duration of exposure to an aspect of organizing cardiovascular care was the key determinant to success.