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
Aims The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal... Show moreAims The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin-kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (>= 1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI.Methods and results Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77-0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77-0.99; P = 0.032) and Type 2 (0.77, 0.61-0.97; P = 0.025), but not Type 4 MI.Conclusion After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types. Show less
The diversity in medicine and the scope of both non-invasive and invasive diagnostic instruments and treatments for ischemic heart disease have grown exponentially the last few decades. The... Show moreThe diversity in medicine and the scope of both non-invasive and invasive diagnostic instruments and treatments for ischemic heart disease have grown exponentially the last few decades. The objective of this thesis was to establish the value of different imaging techniques and treatments targeting different stages of ischemic heart disease. The results reported have demonstrated that multimodality imaging is of high relevance in patients with ischemic heart disease, facilitating the decision-making process in different groups of patients and allowing medical and (non-)invasive treatments to be better tailored to individual cases from prevention to treatment while potentially improving prognoses. Show less
Cardiovascular disease (CVD) is the leading cause of death in women in the Western world. In this thesis, several studies are presented examining the association between recurrent miscarriage and... Show moreCardiovascular disease (CVD) is the leading cause of death in women in the Western world. In this thesis, several studies are presented examining the association between recurrent miscarriage and cardiovascular disease. Main aim of this thesis was to assess whether miscarriages are independently associated with an increased risk of cardiovascular disease later in life. And, if this was true, to identify cardiovascular risk factors and predict long term cardiovascular disease risk in women with a history of recurrent miscarriage. We found an increased risk of ischemic heart disease in women with a history of two (multivariate analysis HR 1.82) and three or more miscarriages (HR 3.18), irrespective whether consecutive or not (chapter 2). Women with a history of recurrent miscarriage have significantly higher 10- and 30-year cardiovascular risk scores compared to women with a history of no miscarriage. These results indicate an opportunity for the early identification of women prone to cardiovascular disease later in life. Women with a history of two or more miscarriages must be made aware of their increased cardiovascular risk and appropriate risk factor modifications will have to be offered, for example life style advises; weight management and smoking control. Show less
This thesis shows that an attempt to deprescribe preventive cardiovascular medication in 40 to 70 year old low-risk patients under surveillance of the GP is safe in the short term. The... Show moreThis thesis shows that an attempt to deprescribe preventive cardiovascular medication in 40 to 70 year old low-risk patients under surveillance of the GP is safe in the short term. The deprescribing consultation should be patient-centered in order to optimally judge overtreatment.Decision-making could be improved if more personalised risk scores were available, that assess an individual’s CVD risk and benefit of treatment. Opportunities for future development of these personalised risk scores lie in the use of routinely registered patient data.Overall, this thesis’ findings provide both practical tools for GPs to judge overtreatment in low-risk patients, as well as valuable information for policy makers revising the cardiovascular risk management guideline. Show less
The main objective of this thesis was to improve cardiovascular risk assessment in primary care. Chapter 2 provides evidence that coded diagnosis from general practice electronic health... Show moreThe main objective of this thesis was to improve cardiovascular risk assessment in primary care. Chapter 2 provides evidence that coded diagnosis from general practice electronic health records are a feasible and valid alternative to self-report to define diabetes cases in epidemiological studies. Based on the results of focus group discussions with research participants confronted with an incidental finding, as described in Chapter 3, we concluded that a detailed study protocol is needed on the disclosure of incidental findings before recruitment of participants. We gave several recommendations to improve the disclosure of incidental findings. Our findings in Chapter 4 suggest that it is important to inform the general practitioner and the research participants about the individual cardiovascular test results. Only participants with an estimated intermediate of high cardiovascular risk should receive a recommendation to consult their general practitioner. In Chapter 5, we concluded that inviting patients with overweight or obesity for cardiovascular risk assessment can help to identify a substantial additional group of patients at increased cardiovascular risk. In Chapter 6, we did not find evidence that cardiovascular risk assessment can be improved when non-invasive markers of hepatic steatosis are added to an established risk estimation system. Show less
Without a proper treatment, critical congenital heart defects (CCHD) lead to death in the first month of life. Timely diagnosis is pivotal for reducing morbidity and mortality. Pulse oximetry is... Show moreWithout a proper treatment, critical congenital heart defects (CCHD) lead to death in the first month of life. Timely diagnosis is pivotal for reducing morbidity and mortality. Pulse oximetry is used in many countries to screen newborns for CCHD. However, this screening has not been implemented in the Netherlands, because of the unique perinatal care system, with a high home birth rate and early discharge after hospital deliveries. This thesis describes research performed to assess the feasibility, accuracy, acceptability and costs of neonatal screening for CCHD with pulse oximetry in the Dutch perinatal care system. To do this, the protocol that is used in the United States and Scandinavia was adapted to fit the working scheme of community midwives. Show less
