Sex Differences in the Quality of Diabetes Care in the Netherlands (ZODIAC-45)

OBJECTIVE:Our aim was to investigate whether trends in quality of diabetes care differ between sexes in the Netherlands from 1998 till 2013. RESEARCH DESIGN AND METHODS:In this prospective observational cohort study quality of care was measured using process and outcome measures in patients with type 2 diabetes in primary care. Trend and absolute differences between sexes were investigated for patients 53 mmol/mol; this decreased to approximately 29% in both sexes in 2013. Patients having a systolic blood pressure >140 mmHg decreased from 70% to 42%, and from 80% to 40% in men and women 20% over 10 years decreased from 15% to 3% in men and from 18% to 3% in women. CONCLUSIONS:Quality of diabetes care has improved considerably in the period 1998-2013 in both sexes. Possibly relevant trend differences between sexes were observed for HbA1c, systolic blood pressure, BMI and smoking. The predicted mortality risk decreased over time in both sexes. Except for BMI in both age groups and systolic blood pressure in patients ≥75 years, no evident poorer risk factor control in women compared to men was found at the end of the study period

Patient Activation in Type 2 Diabetes:Does It Differ between Men and Women?

Background. Aim was to investigate whether the degree of patient activation of patients with type 2 diabetes (T2D) is different between men and women. Furthermore, we investigated which factors are associated with patient activation in men and women. Methods. This cross-sectional study included 1615 patients with T2D from general practices. Patient activation was measured with the Patient Activation Measure (PAM) questionnaire. Multivariate linear regression analyses were used to investigate the association between gender and patient activation. Stratified analyses according to gender were performed to investigate which factors are associated with patient activation. Results. No association between gender and PAM score was found after adjustment for all selected confounders (p=0.094). In men, lower age (p=0.001), a higher WHO-5 score (p<0.001), and a lower BMI (p=0.013) were associated with a higher PAM score. In women, a higher WHO-5 score (p<0.017) and the absence of macrovascular complications (p<0.031) were associated with a higher PAM score. Conclusion. There is no difference in the degree of patient activation of men and women with T2D. Age, well-being, and BMI were found to be associated with patient activation in men, whereas well-being and macrovascular complications were found to be associated with patient activation in women

Heart failure after treatment for breast cancer

Background: We aimed to develop dose–response relationships for heart failure (HF) following radiation and anthracyclines in breast cancer treatment, and to assess HF associations with trastuzumab and endocrine therapies. Methods and results: A case–control study was performed within a cohort of breast cancer survivors treated during 1980–2009. Cases (n = 102) had HF as first cardiovascular diagnosis and were matched 1:3 on age and date of diagnosis. Individual cardiac radiation doses were estimated, and anthracycline doses and use of trastuzumab and endocrine therapy were abstracted from oncology notes. For HF cases who received radiotherapy, the estimated median mean heart dose (MHD) was 6.8 Gy [interquartile range (IQR) 0.9–13.7]. MHD was not associated with HF risk overall [excess rate ratio (ERR) = 1%/Gy, 95% confidence interval (CI) −2 to 10]. In patients treated with anthracyclines, exposure of ≥20% of the heart to ≥20 Gy was associated with a rate ratio of 5.7 (95% CI 1.7–21.7) compared to <10% exposed to ≥20 Gy. For cases who received radiotherapy, median cumulative anthracycline dose was 247 mg/m2 (IQR 240–319). A dose-dependent increase was observed after anthracycline without trastuzumab (ERR = 1.5% per mg/m2, 95% CI 0.5–4.1). After anthracycline and trastuzumab, the rate ratio was 34.9 (95% CI 11.1–110.1) compared to no chemotherapy. Conclusions: In absence of anthracyclines, breast cancer radiotherapy was not associated with increased HF risk. Strongly elevated HF risks were observed after treatment with anthracyclines and also after treatment with trastuzumab. The benefits of these systemic treatments usually exceed the risks of HF, but our results emphasize the need to support ongoing efforts to evaluate preventative strategies

Diagnostic tools for early detection of cardiac dysfunction in childhood cancer survivors:Methodological aspects of the Dutch late effects after childhood cancer (LATER) cardiology study

Background: Cancer therapy-related cardiac dysfunction and heart failure are major problems in long-term childhood cancer survivors (CCS). We hypothesize that assessment of more sensitive echo- and electrocardiographic measurements, and/or biomarkers will allow for improved recognition of patients with cardiac dysfunction before heart failure develops, and may also identify patients at lower risk for heart failure. Objective: To describe the methodology of the Dutch LATER cardiology study (LATER CARD). Methods: The LATER CARD study is a cross-sectional study in long-term CCS treated with (potentially) cardiotoxic cancer therapies and sibling controls. We will evaluate 1) the prevalence and associated (treatment related) risk factors of subclinical cardiac dysfunction in CCS compared to sibling controls and 2) the diagnostic value of echocardiography including myocardial strain and diastolic function parameters, blood biomarkers for cardiomyocyte apoptosis, oxidative stress, cardiac remodeling and inflammation and ECG or combinations of them in the surveillance for cancer therapy-related cardiac dysfunction. From 2017 to 2020 we expect to include 1900 CCS and 500 siblings. Conclusions: The LATER CARD study will provide knowledge on different surveillance modalities for detection of cardiac dysfunction in long-term CCS at risk for heart failure. The results of the study will enable us to improve long-term follow-up surveillance guidelines for CCS at risk for heart failure

Echocardiography protocol for early detection of cardiac dysfunction in childhood cancer survivors in the multicenter DCCSS LATER 2 CARD study:Design, feasibility, and reproducibility

Background Cardiotoxicity is a well-known side effect after anthracyclines and chest radiotherapy in childhood cancer survivors (CCS). The DCCSS LATER 2 CARD (cardiology) study includes evaluation of echocardiographic measurements for early identification of CCS at highest risk of developing heart failure. This paper describes the design, feasibility, and reproducibility of the echocardiography protocol. Methods Echocardiograms from CCS and sibling controls were prospectively obtained at the participating centers and centrally analyzed. We describe the image acquisition, measurement protocol, and software-specific considerations for myocardial strain analyses. We report the feasibility of the primary outcomes of systolic and diastolic function, as well as reproducibility analyses in 30 subjects. Results We obtained 1,679 echocardiograms. Biplane ejection fraction (LVEF) measurement was feasible in 91% and 96% of CCS and siblings, respectively, global longitudinal strain (GLS) in 80% and 91%, global circumferential strain (GCS) in 86% and 89%, and >= 2 diastolic function parameters in 99% and 100%, right ventricle free wall strain (RVFWS) in 57% and 65%, and left atrial reservoir strain (LASr) in 72% and 79%. Intra-class correlation coefficients for inter-observer variability were 0.85 for LVEF, 0.76 for GLS, 0.70 for GCS, 0.89 for RVFWS and 0.89 for LASr. Intra-class correlation coefficients for intra-observer variability were 0.87 for LVEF, 0.82 for GLS, 0.82 for GCS, 0.85 for RVFWS and 0.79 for LASr. Conclusion The DCCSS LATER 2 CARD study includes a protocolized echocardiogram, with feasible and reproducible primary outcome measurements. This ensures high-quality outcome data for prevalence estimates and for reliable comparison of cardiac function parameters

Long-Term Morbidity and Health After Early Menopause Due to Oophorectomy in Women at Increased Risk of Ovarian Cancer:Protocol for a Nationwide Cross-Sectional Study With Prospective Follow-Up (HARMOny Study)

Background: BRCA1/2 mutation carriers are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) at 35 to 45 years of age. RRSO substantially decreases ovarian cancer risk, but at the cost of immediate menopause. Knowledge about the potential adverse effects of premenopausal RRSO, such as increased risk of cardiovascular disease, osteoporosis, cognitive dysfunction, and reduced health-related quality of life (HRQoL), is limited. Objective: The aim of this study is to assess the long-term health effects of premenopausal RRSO on cardiovascular disease, bone health, cognitive functioning, urological complaints, sexual functioning, and HRQoL in women with high familial risk of breast or ovarian cancer. Methods: We will conduct a multicenter cross-sectional study with prospective follow-up, nested in a nationwide cohort of women at high familial risk of breast or ovarian cancer. A total of 500 women who have undergone RRSO before 45 years of age, with a follow-up period of at least 10 years, will be compared with 250 women (frequency matched on current age) who have not undergone RRSO or who have undergone RRSO at over 55 years of age. Participants will complete an online questionnaire on lifestyle, medical history, cardiovascular risk factors, osteoporosis, cognitive function, urological complaints, and HRQoL. A full cardiovascular assessment and assessment of bone mineral density will be performed. Blood samples will be obtained for marker analysis. Cognitive functioning will be assessed objectively with an online neuropsychological test battery. Results: This study was approved by the institutional review board in July 2018. In February 2019, we included our first participant. As of November 2020, we had enrolled 364 participants in our study. Conclusions: Knowledge from this study will contribute to counseling women with a high familial risk of breast/ovarian cancer about the long-term health effects of premenopausal RRSO. The results can also be used to offer health recommendations after RRSO

Diagnostic tools for early detection of cardiac dysfunction in childhood cancer survivors: Methodological aspects of the Dutch late effects after childhood cancer (LATER) cardiology study

Background: Cancer therapy-related cardiac dysfunction and heart failure are major problems in long-term childhood cancer survivors (CCS). We hypothesize that assessment of more sensitive echo- and electrocardiographic measurements, and/or biomarkers will allow for improved recognition of patients with cardiac dysfunction before heart failure develops, and may also identify patients at lower risk for heart failure. Objective: To describe the methodology of the Dutch LATER cardiology study (LATER CARD). Methods: The LATER CARD study is a cross-sectional study in long-term CCS treated with (potentially) cardiotoxic cancer therapies and sibling controls. We will evaluate 1) the prevalence and associated (treatment related) risk factors of subclinical cardiac dysfunction in CCS compared to sibling controls and 2) the diagnostic value of echocardiography including myocardial strain and diastolic function parameters, blood biomarkers for cardiomyocyte apoptosis, oxidative stress, cardiac remodeling and inflammation and ECG or combinations of them in the surveillance for cancer therapy-related cardiac dysfunction. From 2017 to 2020 we expect to include 1900 CCS and 500 siblings. Conclusions: The LATER CARD study will provide knowledge on different surveillance modalities for detection of cardiac dysfunction in long-term CCS at risk for heart failure. The results of the study will enable us to improve long-term follow-up surveillance guidelines for CCS at risk for heart failure

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points