Implementing personalized medicine in diabetic kidney disease: Stakeholders' perspectives.

The promise of personalized medicine to deliver "the right treatments at the right time to the right person" is the next frontier in healthcare. However, to implement personalized medicine in chronic diseases such as diabetes mellitus and diabetic kidney disease (DKD), a number of different aspects need to be taken into account. Better risk stratification and more precise options for treatment need to be developed and included in clinical practice guidelines. A patient's unique psychological, social and environmental situation also drive disease progression and outcomes. Appraising the cost effectiveness of precision medicines is necessary, not just as the cost of new therapies, but also the cost of diagnosis with novel methodologies and averted complications. As the prevalence of DKD grows worldwide to epidemic proportions, challenges such as global disparities in resources, access to healthcare and prevalence need to be addressed. This review considers these issues to achieve the short and longer-term goals of implementing personalized medicine in clinical practice.

High protein S activity due to C4b-binding protein deficiency in a 34-year-old Surinamese female with ischemic retinopathy.

In this study, we present the first case of a 34-year-old Surinamese female with ischemic retinopathy and increased free protein S due to C4BP deficiency. Possibly, the low PS/C4BP complex level has increased the risk of arterial thrombosis in our patient.

Non-LDL dyslipidemia is prevalent in the young and determined by lifestyle factors and age: The LifeLines cohort.

BACKGROUND AND AIMS: Non-LDL dyslipidemia (NLD) confers cardiovascular risk, and prevalence rates appear to be high in elderly populations. Small cohorts have identified several lifestyle, anthropometric, and medical factors associated with NLD. We aimed to assess sex- and age-specific prevalence of NLD in a contemporary population cohort (n = 167 729), and to identify independent determinants of NLD, focusing on lifestyle, anthropometric, and medical factors. METHODS: The prevalence of NLD was assessed per 10-year age intervals in adults without cardiovascular disease not using lipid-modifying drugs from the Dutch LifeLines cohort. NLD was defined as low HDL-cholesterol or high triglycerides or high remnant cholesterol as per guideline cut-off values. Multivariable regression was used to identify factors independently associated with NLD. Determinants included age, smoking, alcohol use, physical activity, diet, BMI, diabetes mellitus (DM), chronic kidney disease, and in women, menopausal state and oral contraceptive use. RESULTS: NLD occurred in 15-19% of women and 13-30% of men in this cohort, with the highest prevalence of 30% in 35-55 year old men. In most age groups, the prevalence in women was lower than in men. Obesity (both sexes: Odds ratio (OR) 5.3, 95% confidence interval (95%CI) 5.0-5.7), current smoking (men: OR 1.8, 95%CI 1.7-1.9; women OR 2.2, 95%CI 2.1-2.3), and DM (men: OR 2.2, 95%CI 1.8-2.6; women: OR 2.7, 95%CI 2.3-3.1) were strongly associated with NLD. CONCLUSIONS: NLD already occurs frequently at an early age. Modifiable lifestyle choices, obesity, and DM were strong determinants of NLD. Public health efforts could substantially contribute to decrease NLD.

Time to improve statin prescription guidelines in low-risk patients?

Background The challenge of the primary prevention of cardiovascular disease (CVD) is to identify patients who would benefit from treatment with statins. Statins are currently prescribed to many patients, even those at a low 10-year risk of CVD. These latter patients may not be eligible for statins according to current guidelines. Design This study investigated the prescription of guideline-consistent (according to guidelines) and guideline-inconsistent (not according to guidelines) lipid-lowering treatment in primary prevention in a large contemporary Dutch cohort study (Lifelines). Methods Lifelines is a large cohort study from the Netherlands. Participants were recruited between 2006 and 2013. They completed questionnaires and underwent a physical examination. Participants with previous CVD were excluded. Statins and ezetimibe were grouped as statin treatment. The Dutch guideline on cardiovascular management was used to assess eligibility for statins. Results Of 147,785 participants, 7092 (4.8%) reported statin treatment. In 4667 (66%) participants, statin treatment was inconsistent with the Dutch guideline. A total of 78% of these participants had a low 10-year predicted CVD risk. Multivariable logistic regression analysis showed that female sex and smoking were strongly associated with guideline-inconsistent treatment. Interestingly, 65% of the these participants had low-density lipoprotein cholesterol levels above the 95th percentile, adjusted for age and sex, two or more major risk factors of CVD or a positive family history of premature CVD. Therefore treatment might be reasonable. Conclusions There is a large inconsistency between guideline recommendations and the prescription of statins in clinical practice in the Netherlands. This is especially true for patients with low CVD risk. Many of these patients probably had risk-increasing circumstances justifying treatment.

Lipid and lipoprotein reference values from 133,450 Dutch Lifelines participants: Age- and gender-specific baseline lipid values and percentiles.

BACKGROUND: Lipids and lipoproteins are recognized as the most important modifiable risk factors for cardiovascular disease. Although reference values for the major lipoproteins, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides, have been collected in numerous studies and cohorts, complete contemporary percentile-based reference values are underreported. OBJECTIVE: We set out to provide such reference lipid data using a large contemporary population-based cohort study. STUDY DESIGN AND SETTING: Lifelines is a cross-sectional population-based Dutch cohort study. We analyzed 133,540 adult fasting participants without cardiovascular disease and without lipid-lowering drug use. Lipid levels were directly measured and selected percentiles of all lipid parameters were calculated. Friedewald LDL-C estimation was calculated as well. RESULTS: From 20 till 49 years of age, men were found to exhibit a steep 64% increase of LDL-C (median +54 mg/dL), while triglyceride levels increased almost two-fold. In women, LDL-C levels did not change from 18 till 35 years, followed by a steep 42% increase till 59 years (median +42 mg/dL). In contrast to men, triglycerides were stable in ageing women. Overall, Friedewald LDL-C levels are lower compared with the direct measurement, especially with increasing triglyceride levels. CONCLUSIONS: This observational study highlights striking gender- and age-related differences in plasma lipid profiles. The given reference ranges of plasma lipids can assist in early identification of individuals with hypocholesterolemia and hypercholesterolemia, especially familial hypercholesterolemia. These reference ranges are available for physicians and patients at www.my-cholesterol.care/.

[Diagnostics and treatment of calf vein thrombosis]. / Diagnostiek en behandeling van kuitvenetrombose.

Calf vein thrombosis is a much-debated entity. The literature shows that progression to deep venous thrombosis or pulmonary embolism occurs infrequently and is usually detected using serial two-point ultrasonography. Additionally, undetected and untreated calf vein thrombosis is not associated with serious adverse events in large management trials studying diagnostic strategies for suspected deep venous thrombosis. Recurrent venous thromboembolism can occur after calf vein thrombosis, but anticoagulant treatment does not reduce the incidence. In this article, three case histories describe the anatomical considerations for proper diagnosis of calf vein thrombosis, some aspects of the natural course, and the treatment that these patients received. A case is made for restrictive use of prolonged anticoagulation therapy as a means to reduce thromboembolic complications. Because symptomatic treatment has not been studied, expert opinion suggests a short (3-week) course of therapeutically-dosed low-molecular-weight heparin.