Cholesterol-lowering medications aim to prevent cardiovascular events, caused by arteriosclerosis. Older adults (75 years and older) have a high cardiovascular risk based on age alone, and it is... Show moreCholesterol-lowering medications aim to prevent cardiovascular events, caused by arteriosclerosis. Older adults (75 years and older) have a high cardiovascular risk based on age alone, and it is estimated that 1 in 3 older adults use cholesterol-lowering medication. The vast majority (96% in the Netherlands) use a statin.The appropriateness of cholesterol-lowering medication for older adults is under debate. While there is strong evidence for the benefits of statins in relatively healthy older adults with a history of cardiovascular disease, for other groups the evidence is less convincing. Also, statins are associated with hindering side effects. In this thesis, various aspects of the appropriateness of cholesterol-lowering medication for older adults were studied, using different research designs. Five recurrent themes were of the utmost importance in the assessment of the appropriateness of cholesterol-lowering medication in older adults; 1) the individual context of a patient, 2) life expectancy, 3) hindering side effects, 4) cardiovascular history, and 5) the complexity of health problems. Based in these five themes, five key questions were distilled that can be used in a systematic evaluation of the appropriateness of cholesterol- lowering treatment for an individual patient. Show less
Introduction: Major depressive disorder (MDD) is common, and recurrence rates are high. Preventive Cognitive Therapy (PCT), has been shown to prolong time to recurrence and reduce risk of... Show moreIntroduction: Major depressive disorder (MDD) is common, and recurrence rates are high. Preventive Cognitive Therapy (PCT), has been shown to prolong time to recurrence and reduce risk of recurrence(s) over 2-10 years in patients with recurrent depression. Objective: The aim of the study was to examine the effectiveness of PCT over 20 years on time to first recurrence, cumulative proportion of first recurrences, percentage of depression-free time, mean severity of recurrences, and the number of recurrences within a patient. Methods: Adults remitted from recurrent MDD were randomized to PCT or Treatment As Usual (TAU). Clinical outcomes were assessed using the SCID over 20 years. We used Cox regression analyses, Kaplan-Meier analyses, ANOVA, and negative binomial regression and tested for interaction with the number of previous episodes. Results: There was a significant interaction effect for number of previous episodes with treatment condition on time to first recurrence (Wald[1, n = 172] = 8.840, p = 0.003). For participants with more than 3 previous episodes, the mean time to recurrence was 4.8 years for PCT versus 1.6 years for TAU; the cumulative proportion of first recurrences was 87.5% for PCT and 100% for TAU. For participants with more than 3 previous episodes, exploratory analyses suggest that PCT had 53% less recurrences and percentage of depression-free time was significantly higher compared to TAU. There were no significant effects on mean severity. Conclusions: Up to 20 years, for MDD patients with more than 3 previous episodes, those who received PCT had significantly longer time to a first recurrence and lower recurrence risk and may have less recurrences and more depression-free time compared to TAU. This suggests long term protective effects of PCT up to 20-years. Show less
Sacco, S.; Amin, F.M.; Ashina, M.; Bendtsen, L.; Deligianni, C.I.; Gil-Gouveia, R.; ... ; Lampl, C. 2022
Background A previous European Headache Federation (EHF) guideline addressed the use of monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway to prevent migraine. Since... Show moreBackground A previous European Headache Federation (EHF) guideline addressed the use of monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway to prevent migraine. Since then, randomized controlled trials (RCTs) and real-world evidence have expanded the evidence and knowledge for those treatments. Therefore, the EHF panel decided to provide an updated guideline on the use of those treatments. Methods The guideline was developed following the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. The working group identified relevant questions, performed a systematic review and an analysis of the literature, assessed the quality of the available evidence, and wrote recommendations. Where the GRADE approach was not applicable, expert opinion was provided. Results We found moderate to high quality of evidence to recommend eptinezumab, erenumab, fremanezumab, and galcanezumab in individuals with episodic and chronic migraine. For several important clinical questions, we found not enough evidence to provide evidence-based recommendations and guidance relied on experts' opinion. Nevertheless, we provided updated suggestions regarding the long-term management of those treatments and their place with respect to the other migraine preventatives. Conclusion Monoclonal antibodies targeting the CGRP pathway are recommended for migraine prevention as they are effective and safe also in the long-term. Show less
Hodgkin lymphoma and testicular cancer survivors have an increased risk of developing second primary gastrointestinal malignancies. Whether the pathogenesis of the gastrointestinal malignancies in... Show moreHodgkin lymphoma and testicular cancer survivors have an increased risk of developing second primary gastrointestinal malignancies. Whether the pathogenesis of the gastrointestinal malignancies in cancer survivors differs from cancer in the general population is unknown. This thesis investigated the pathogenesis of gastrointestinal malignancies in Hodgkin lymphoma and testicular cancer survivors. Furthermore, the effectiveness of colorectal cancer surveillance is investigated in these cancer survivors. Additionally, this thesis will focus on mismatch repair deficiency, as identification of Lynch syndrome could have implications for the patients and implications for treatment choice. Show less
Nemeth, B.; Kaaij, M. van der; Nelissen, R.; Wijnen, J.K. van; Drost, K.; Blauw, G.J. 2022
Background Hip and pelvic fractures do commonly occur among older adults. This pilot study aimed to evaluate the effect of introduction of the WOLK hip airbag on the incidence of hip fractures.... Show moreBackground Hip and pelvic fractures do commonly occur among older adults. This pilot study aimed to evaluate the effect of introduction of the WOLK hip airbag on the incidence of hip fractures. Methods A retrospective study was performed among 969 participants residing within 11 long-term care facilities for older patients, belonging to one large healthcare organization in The Netherlands. The intervention concerned application of 45 WOLK hip-airbags, distributed among selected residents of the long-term care facilities. Inclusion criteria; physically active participants with a pelvic circumference between 90-125 cm able to wear the hip airbag. Exclusion criteria; participants who continuously removed the hip airbag themselves or participants who depended on a wheelchair for mobility. Main outcome measures were the occurrence of falls and hip, pelvic and other fractures. Results The incidence of hip and pelvic fractures declined from 3.3/100 person years to 1.8/100 person years during the study for an Incidence Rate Ratio (IRR) of 0.55 (95% confidence interval (95%CI) 0.34-0.87) in the entire study population. The incidence of other fractures did not decline during the study period (IRR 0.72;95%CI 0.37-1.40). The incidence of falls declined to some extent during the study (IRR 0.88; 95%CI 0.83-0.93). Conclusions After introduction of the WOLK hip airbag a reduction of the incidence of hip and pelvic fractures by almost half was observed in older patients residing in long-term care facilities, even though only 45 hip airbags were distributed among the 969 residents. As selection bias cannot be ruled out in this study, the results of this pilot study warrant replication by a future clinical trial to determine true effectiveness of this intervention. Show less
Bleeding events are frequently encountered in hemato-oncology patients. To prevent this, in periods of thrombocytopenia patients receive prophylactic platelet transfusions, based on the platelet... Show moreBleeding events are frequently encountered in hemato-oncology patients. To prevent this, in periods of thrombocytopenia patients receive prophylactic platelet transfusions, based on the platelet counts. However, beside platelet counts many other patients factors likely contribute to the bleeding risk.In this thesis we focus on describing current clinical practice to prevent bleedings in a subpopulation of patients with persistent deep thrombocytopenia, risk factors for bleeding, and prediction of bleeding. We also describe a ongoing study which aims to identify and quantify risk factors in future.With this knowledge, in the ultimate goal is to predict bleeding more accurate based on patient characteristics and/or biomarkers. This could be a first step towards more personalized bleeding prevention strategies. Show less
OBJECTIVES: Persistent air leak (PAL; >5days after surgery) is the most common complication after pulmonary resection and associated with prolonged hospital stay and increased morbidity.... Show moreOBJECTIVES: Persistent air leak (PAL; >5days after surgery) is the most common complication after pulmonary resection and associated with prolonged hospital stay and increased morbidity. Literature is contradictory about the prevention and treatment of PAL. Variation is therefore hypothesized. The aim of this study is to understand the variation in the incidence, preventive management and treatment of PAL.METHODS: Data from the Dutch Lung Cancer Audit for Surgery were combined with results of an online survey among Dutch thoracic surgeons. The national incidence of PAL and case-mix corrected between-hospital variation were calculated in patients who underwent an oncological (bi)lobectomy or segmentectomy between January 2012 and December 2018. By multivariable logistic regression, factors associated with PAL were assessed. A survey was designed to assess variation in (preventive) management and analysed using descriptive statistics. Hospital-level associations between management strategies and PAL were assessed by univariable linear regression.RESULTS: Of 12382 included patients, 9.0% had PAL, with a between-hospital range of 2.6-19.3%. Factors associated with PAL were male sex, poor lung function, low body mass index, high American Society of Anesthesiologists (ASA) score, pulmonary comorbidity, upper lobe resection, (bi)lobectomy (vs segmentectomy), right-sided tumour and robotic-assisted thoracic surgery. Perioperative (preventive) management of PAL differed widely between hospitals. When using water seal compared to suction drainage, the average incidence of PAL decreased 2.9%.CONCLUSIONS: In the Netherlands, incidence and perioperative (preventive) management of PAL vary widely. Using water seal instead of suction drainage and increasing awareness are potential measures to reduce this variation. Show less
This thesis aims to improve the early identification of mental healthproblems (MHPs) in children by developing a prediction model for MHPs inchildren based on readily available information from... Show moreThis thesis aims to improve the early identification of mental healthproblems (MHPs) in children by developing a prediction model for MHPs inchildren based on readily available information from electronic patient recordsfrom general practice.The prediction models for child MHPs, based on the data from the electronichealth records of general practitioners (GPs), have not yet performed wellenough to be used safely in daily practice. A number of relevant predictivecharacteristics have been identified: characteristics such as physicalcomplaints (e.g. abdominal pain or headache) and characteristics related tohigher health care use (e.g. more than two GP visits or a laboratoryexamination in the previous year) were age-independent predictors of MHPs.Awareness of (a combination of) these characteristics can help GPs to identifyMHPs at an early stage.To investigate whether merging information from preventive youth healthcare(PYH) and GPs in one algorithm can improve the identification of MHPs, wecombined information from the electronic files of PYH and GPs. However, themodels based on these combined data did not outperform the models based on GPdata alone. Several individual characteristics measured in PYH turned out to bepredictors for MHPs in general practice. Show less
Reigadas, E.; Prehn, J. van; Falcone, M.; Fitzpatrick, F.; Vehreschild, M.J.G.T.; Kuijper, E.J.; ... ; Study Grp Host Microbiota Interact 2021
Background: Clostridioides difficile infection (CDI) remains the leading cause of healthcare-associated diarrhoea, despite existing guidelines for infection control measures and antimicrobial... Show moreBackground: Clostridioides difficile infection (CDI) remains the leading cause of healthcare-associated diarrhoea, despite existing guidelines for infection control measures and antimicrobial stewardship. The high associated health and economic burden of CDI calls for novel strategies to prevent the development and spread of CDI in susceptible patients. Objectives: We aim to review CDI prophylactic treatment strategies and their implementation in clinical practice. Sources: We searched PubMed, Embase, Emcare, Web of Science, and the COCHRANE Library databases to identify prophylactic interventions aimed at prevention of CDI. The search was restricted to articles published in English since 2012. Content: A toxin-based vaccine candidate is currently being investigated in a phase III clinical trial. However, a recent attempt to develop a toxin-based vaccine has failed. Conventional probiotics have not yet proved to be an effective strategy for prevention of CDI. New promising microbiota-based interventions that bind and inactivate concomitantly administered antibiotics, such as ribaxamase and DAV-132, have been developed. Prophylaxis of CDI with C. difficile antibiotics should not be performed routinely and should be considered only for secondary prophylaxis in very selected patients who are at the highest imminent risk for recurrent CDI (R-CDI) after a thorough evaluation. Faecal microbiota transplantation (FMT) has proved to be a very effective treatment for patients with multiple recurrences. Bezlotoxumab provides protection against R-CDI, mainly in patients with primary episodes and a high risk of relapse. Implications: There are no proven effective, evidenced-based prophylaxis options for primary CDI. As for secondary prevention, FMT is considered the option of choice in patients with multiple recurrences. Bezlotoxumab can be added to standard treatment for patients at high risk for R-CDI. The most promising strategies are those aimed at reducing changes in intestinal microbiota and development of a new effective non-toxin-based vaccine. Elena Reigadas, Clin Microbiol Infect 2021;27:1777 (c) 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved. Show less
The ageing of the world’s population requires new methods to prevent adverse outcomes such as delirium in older patients after surgery. Delirium is an expression of depleted reserves, which in turn... Show moreThe ageing of the world’s population requires new methods to prevent adverse outcomes such as delirium in older patients after surgery. Delirium is an expression of depleted reserves, which in turn decreases a patient’s resilience and makes a patient more frail. It may be triggered due to precipitating risk factors that shift the balance and overflow a patient’s resilience. A systematic review and meta-analysis demonstrated that delirium can be prevented by implementing multicomponent interventions. Therefore, a new multicomponent prehabilitation intervention was designed. The incidence of delirium was successfully reduced by implementing this prehabilitation program, however no effects were seen on all other short-term outcomes. On the long term, postoperative delirium increases the risk of 1-year mortality over 4 times and is associated with decreased functional outcomes after 6 and 12 months. Moreover, surgery and subsequent delirium affect the quality of life of patients and caregivers and may lead to depressive symptoms. Faster return to preoperative functioning may therefore be key to a faster return to preoperative quality of life. Future perioperative care pathways focusing on delirium prevention, optimisation and fast return to baseline functioning after surgery, should begin prior to hospital admission and end long after discharge. Show less
Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. For many years guidelines have listed optimal preventive therapy. More recently, novel therapeutic options have... Show moreCardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. For many years guidelines have listed optimal preventive therapy. More recently, novel therapeutic options have broadened the options for state-of-the-art CV risk management (CVRM). In the majority of patients with CVD, risk lowering can be achieved by utilising standard preventive medication combined with lifestyle modifications. In a minority of patients, add-on therapies should be considered to further reduce the large residual CV risk. However, the choice of which drug combination to prescribe and in which patients has become increasingly complicated, and is dependent on both the absolute CV risk and the reason for the high risk. In this review, we discuss therapeutic decisions in CVRM, focusing on (1) the absolute CV risk of the patient and (2) the pros and cons of novel treatment options. Show less
Shaw, L.J.; Blankstein, R.; Bax, J.J.; Ferencik, M.; Bittencourt, M.S.; Min, J.K.; ... ; Narula, J. 2021
Coronary computed tomographic angiography (CCTA) provides a wealth of clinically meaningful information beyond anatomic stenosis alone, including the presence or absence of nonobstructive... Show moreCoronary computed tomographic angiography (CCTA) provides a wealth of clinically meaningful information beyond anatomic stenosis alone, including the presence or absence of nonobstructive atherosclerosis and high-risk plaque features as precursors for incident coronary events. There is, however, no uniform agreement on how to identify and quantify these features or their use in evidence-based clinical decision-making. This statement from the Society of Cardiovascular Computed Tomography and North American Society of Cardiovascular Imaging addresses this gap and provides a comprehensive review of the available evidence on imaging of coronary atherosclerosis. In this statement, we provide standardized definitions for high-risk plaque (HRP) features and distill the evidence on the effectiveness of risk stratification into usable practice points. This statement outlines how this information should be communicated to referring physicians and patients by identifying critical elements to include in a structured CCTA report - the presence and severity of atherosclerotic plaque (descriptive statements, CAD-RADS (TM) categories), the segment involvement score, HRP features (e.g., low attenuation plaque, positive remodeling), and the coronary artery calcium score (when performed). Rigorous documentation of atherosclerosis on CCTA provides a vital opportunity to make recommendations for preventive care and to initiate and guide an effective care strategy for at-risk patients. (C) 2020 Published by Elsevier Inc. on behalf of Society of Cardiovascular Computed Tomography. Show less
Niemantsverdriet, E.; Dakkak, Y.J.; Burgers, L.E.; Bonte-Mineur, F.; Steup-Beekman, G.M.; Kooij, S.M. van der; ... ; Helm-van Mil, A.H.M. van der 2020
Background: We present a study protocol for a randomized, double-blind, placebo-controlled trial that investigates the hypothesis if intervention in the symptomatic phase preceding clinical... Show moreBackground: We present a study protocol for a randomized, double-blind, placebo-controlled trial that investigates the hypothesis if intervention in the symptomatic phase preceding clinical arthritis (clinically suspect arthralgia (CSA)) is effective in preventing progression from subclinical inflammation to clinically apparent persistent arthritis. Currently, rheumatoid arthritis (RA) can be recognized and diagnosed when arthritis (joint swelling) has become detectable at physical examination. Importantly, at this time, the immune processes have already matured, chronicity is established, and patients require long-standing treatment with disease-modifying anti-rheumatic drugs. The TREAT EARLIER trial studies the hypothesis that intervention in the symptomatic phase preceding clinical arthritis is more often successful in permanent disease modification because of less matured underlying disease processes.Methods: A two-level definition to identify patients that are prone to develop RA is used. First, patients should have CSA and recent-onset arthralgia (< 1 year) that is suspect to progress to RA according to the expertise of the treating rheumatologist. Second, patients need to have subclinical inflammation of the hand or foot joints at 1.5 T MRI. The trial aims to recruit 230 participants from secondary care hospital settings across the south-west region of The Netherlands. Intervention will be randomly assigned and includes a single-dose of intramuscular 120 mg methylprednisolon followed by methotrexate (increasing dose to 25 mg/week orally) or placebo (both; injection and tablets) over the course of 1 year. Thereafter, participants are followed for another year. The primary endpoint is the development of clinically detectable arthritis, either fulfilling the 2010 criteria for RA or unclassified clinical arthritis of >= 2 joints, which persists for at least 2 weeks. DMARD-free status is a co-primary endpoint. The patient-reported outcomes functioning, along with workability and symptoms, are key secondary endpoints. Participants, caregivers (including those assessing the endpoints), and scientific staff are all blinded to the group assignment.Discussion: This proof-of-concept study is the logical consequence of pre-work on the identification of patients with CSA with MRI-detected subclinical joint inflammation. It will test the hypothesis whether intervention in patients in this early phase with the cornerstone treatment of classified RA (methotrexate) hampers the development of persistent RA and reduce the disease burden of RA. Show less
Advances in cancer treatments have improved clinical outcomes, leading to an increasing population of cancer survivors. However, this success is associated with high rates of short- and long-term... Show moreAdvances in cancer treatments have improved clinical outcomes, leading to an increasing population of cancer survivors. However, this success is associated with high rates of short- and long-term cardiovascular (CV) toxicities. The number and variety of cancer drugs and CV toxicity types make long-term care a complex undertaking. This requires a multidisciplinary approach that includes expertise in oncology, cardiology and other related specialties, and has led to the development of the cardio-oncology subspecialty. This paper aims to provide an overview of the main adverse events, risk assessment and risk mitigation strategies, early diagnosis, medical and complementary strategies for prevention and management, and long-term follow-up strategies for patients at risk of cancer therapy-related cardiotoxicities. Research to better define strategies for early identification, follow-up and management is highly necessary. Although the academic cardio-oncology community may be the best vehicle to foster awareness and research in this field, additional stakeholders (industry, government agencies and patient organizations) must be involved to facilitate cross-discipline interactions and help in the design and funding of cardio-oncology trials. The overarching goals of cardio-oncology are to assist clinicians in providing optimal care for patients with cancer and cancer survivors, to provide insight into future areas of research and to search for collaborations with industry, funding bodies and patient advocates. However, many unmet needs remain. This document is the product of brainstorming presentations and active discussions held at the Cardiovascular Round Table workshop organized in January 2020 by the European Society of Cardiology. Show less
In this thesis, the transition from a population-based approach to individualized therapy for the prevention of VT following lower-leg cast immobilization and knee arthroscopy is discussed.
Both cryotherapy and thermal ablation are treatment methods for cervical precancerous lesions in screening programs in resource constrained settings. However, for thermal ablation the World Health... Show moreBoth cryotherapy and thermal ablation are treatment methods for cervical precancerous lesions in screening programs in resource constrained settings. However, for thermal ablation the World Health Organization stated that there is insufficient data to define a standard treatment protocol. This study used an ex-vivo model to compare the tissue interaction of both cryotherapy and thermal ablation to contribute to a treatment protocol. We used porcine tissue to measure the temperature profile over time at 0, 2, 4 and 6 mm depth. For cryotherapy the standard double freeze method was used, thermal ablation was applied for one cycle of 60 s with 100 degrees C. Based on literature search we used 4 mm depth as landmark for the depth of precancerous lesions, and -10 degrees C for cryotherapy and 46 degrees C for thermal ablation as critical temperature to induce cell necrosis. Cryotherapy achieved the critical temperature for tissue necrosis (-10 degrees C) in 3 out of 6 experiments at 4 mm depth, median minimum temperature was -9.6 degrees C (IQR 25-75 -15.8 degrees C to -4.9 degrees C). Thermal ablation achieved the critical temperature for tissue necrosis (46 degrees C) in 3 out of 7 experiments at 4 mm depth, median maximum temperature was 43.1 degrees C (IQR 25-75 42.3 degrees C to 49.9 degrees C). Both treatment modalities achieved tissue necrosis at 4 mm depth in our ex-vivo model. For cryotherapy the double freeze technique should be used. For thermal ablation a single application less than 60 s might not be sufficient and multiple applications should be considered. Show less
Background: Different countries have adopted different containment and testing strategies for SARS-CoV-2. The difference in testing makes it difficult to compare the effect of different containment... Show moreBackground: Different countries have adopted different containment and testing strategies for SARS-CoV-2. The difference in testing makes it difficult to compare the effect of different containment strategies. This study proposes methods to allow a direct comparison and presents the results.Design: Publicly available data on the numbers of reported COVID-19-related deaths between 01 January and 17 April 2020 were compared between countries.Results: The numbers of cases or deaths per 100,000 inhabitants gave severely biased comparisons between countries. Only the number of deaths expressed as a percentage of the number of deaths on day 25 after the first reported COVID-19-related death allowed a direct comparison between countries. From this comparison clear differences were observed between countries, associated with the timing of the implementation of containment measures.Conclusions: Comparisons between countries are only possible when simultaneously taking into account that the virus does not arrive in all countries simultaneously, absolute numbers are incomparable due to different population sizes, rates per 100,000 of the population are incomparable because not all countries are affected homogeneously, susceptibility to death by COVID-19 can differ between populations, and a death is only reported as a COVID-19-related death if the patient was diagnosed with SARS-CoV-2 infection. With the current methods, all these factors were accounted for and an unbiased direct comparison between countries was established. This comparison confirmed that early adoption of containment strategies is key in flattening the curve of the epidemic. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. Show less
The continuous flow of new research articles on MDR-TB diagnosis, treatment, prevention and rehabilitation requires frequent update of existing guidelines. This review is aimed at providing... Show moreThe continuous flow of new research articles on MDR-TB diagnosis, treatment, prevention and rehabilitation requires frequent update of existing guidelines. This review is aimed at providing clinicians and public health staff with an updated and easy-to-consult document arising from consensus of Global Tuberculosis Network (GTN) experts.The core published documents and guidelines have been reviewed, including the recently published MDR-TB WHO rapid advice and ATS/CDC/ERS/IDSA guidelines.After a rapid review of epidemiology and risk factors, the clinical priorities on MDR-TB diagnosis (including whole genome sequencing and drug-susceptibility testing interpretations) and treatment (treatment design and management, TB in children) are discussed. Furthermore, the review comprehensively describes the latest information on contact tracing and LTBI management in MDR-TB contacts, while providing guidance on post-treatment functional evaluation and rehabilitation of TB sequelae, infection control and other public health priorities. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. Show less
Maas, J.C. van der; Corbee, R.J.; Kroese, F.M.; Ridder, D.T.D. de; Vos, R.C.; Nielen, M.; Monninkhof, E. 2020
Background Overweight in children is a rising problem leading to serious consequences later in life. The Dutch guideline 'Obesity' for general practitioners recommends discussing obesity in... Show moreBackground Overweight in children is a rising problem leading to serious consequences later in life. The Dutch guideline 'Obesity' for general practitioners recommends discussing obesity in children regardless of the reason of consultation and provides diagnostic and therapeutic tools. However, limited literature indicates that general practitioners experience barriers to discuss this topic. The aim of this study was to determine current perceived barriers of general practitioners in discussing overweight during a regular consultation in children aged 4 to 12 years and to what extent they discuss the topic. Furthermore, we attempt to get more insight in the specific needs and ideas for improvement among GPs. Methods A semi-structured in-depth interview study was conducted. Dutch general practitioners with a broad range of demographic characteristics were invited to participate. The transcripts were analysed using a modified version of the constant comparative method. Using this method, we identified perceived barriers of general practitioners. Results Ten general practitioners were included in the study. Four major themes were identified in the interviews: absence of physical or mental complaints related to overweight, internal barriers of the general practitioners, the child's family background and logistics. Major barriers appeared to be a low consultation rate of these children, the sensitivity of the topic (e.g. fear for children's or parents' reactions and/or disturbance of the relation, influence on the self-esteem of the child, resistance in the parents), the absence of a long-standing relation between general practitioner and child or parent, the background of the child and lack of time or prioritizing. Conclusion Dutch general practitioners indicate to experience barriers and need tools for how to discuss children's overweight during regular consultations within the limited time available. The low consultation rate among children aged 4 to 12 years due to lack of physical complaints is mentioned as a new and important barrier. Therefore, the prior focus might be raising awareness among parents concerning overweight in children aged 4 to 12 years and, thereby, stressing the potential supporting role of primary care professionals in tackling the overweight of their child. Show less
Background In healthy BRCA1/2 mutation carriers, bilateral risk-reducing mastectomy (BRRM) strongly reduces the risk of developing breast cancer (BC); however, no clear survival benefit of BRRM... Show moreBackground In healthy BRCA1/2 mutation carriers, bilateral risk-reducing mastectomy (BRRM) strongly reduces the risk of developing breast cancer (BC); however, no clear survival benefit of BRRM over BC surveillance has been reported yet. Methods In this Dutch multicenter cohort study, we used multivariable Cox models with BRRM as a time-dependent covariable to estimate the associations between BRRM and the overall and BC-specific mortality rates, separately for BRCA1 and BRCA2 mutation carriers. Results During a mean follow-up of 10.3 years, 722 out of 1712 BRCA1 (42%) and 406 out of 1145 BRCA2 (35%) mutation carriers underwent BRRM. For BRCA1 mutation carriers, we observed 52 deaths (20 from BC) in the surveillance group, and 10 deaths (one from BC) after BRRM. The hazard ratios were 0.40 (95% CI 0.20-0.90) for overall mortality and 0.06 (95% CI 0.01-0.46) for BC-specific mortality. BC-specific survival at age 65 was 93% for surveillance and 99.7% for BRRM. For BRCA2 mutation carriers, we observed 29 deaths (7 from BC) in the surveillance group, and 4 deaths (no BC) after BRRM. The hazard ratio for overall mortality was 0.45 (95% CI 0.15-1.36). BC-specific survival at age 65 was 98% for surveillance and 100% for BRRM. Conclusion BRRM was associated with lower mortality than surveillance for BRCA1 mutation carriers, but for BRCA2 mutation carriers, BRRM may lead to similar BC-specific survival as surveillance. Our findings support a more individualized counseling based on BRCA mutation type. Show less
