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Contains fulltext : 282324.pdf (Publisher’s version ) (Open Access) BACKGROUND: Vitamin D deficiency is frequently found in patients with chronic obstructive pulmonary disease (COPD). Vitamin D has antimicrobial, anti-inflammatory, and immunomodulatory effects. Therefore, supplementation may prevent COPD exacerbations, particularly in deficient patients. OBJECTIVES: We aimed to assess the effect of vitamin D supplementation on exacerbation rate in vitamin D-deficient patients with COPD. METHODS: We performed a multicenter, double-blind, randomized controlled trial. COPD patients with ≥1 exacerbations in the preceding year and a vitamin D deficiency (15-50 nmol/L) were randomly allocated in a 1:1 ratio to receive either 16,800 International Units (IU) vitamin D3 or placebo once a week during 1 y. Primary outcome of the study was exacerbation rate. Secondary outcomes included time to first and second exacerbations, time to first and second hospitalizations, use of antibiotics and corticosteroids, pulmonary function, maximal respiratory mouth pressure, physical performance, skeletal muscle strength, systemic inflammatory markers, nasal microbiota composition, and quality of life. RESULTS: The intention-to-treat population consisted of 155 participants. Mean ± SD serum 25-hydroxyvitamin D [25(OH)D] concentration after 1 y was 112 ± 34 nmol/L in the vitamin D group, compared with 42 ± 17 nmol/L in the placebo group. Vitamin D supplementation did not affect exacerbation rate [incidence rate ratio (IRR): 0.90; 95% CI: 0.67, 1.21]. In a prespecified subgroup analysis in participants with 25(OH)D concentrations of 15-25 nmol/L (n = 31), no effect of vitamin D supplementation was found (IRR: 0.91; 95% CI: 0.43, 1.93). No relevant differences were found between the intervention and placebo groups in terms of secondary outcomes. CONCLUSIONS: Vitamin D supplementation did not reduce exacerbation rate in COPD patients with a vitamin D deficiency.This trial was registered at clinicaltrials.gov as NCT02122627.

Testosterone therapy is the cornerstone in the care of men with hypogonadism and transgender males. Gel and intramuscular injections are most frequently used and are registered and included in the international guidelines. The specific preparation should be selected according to the patient’s preference, cost, availability, and formulation-specific properties. As the majority of men with hypogonadism and transgender males require lifelong treatment with testosterone, it is important to utilize a regimen that is effective, safe, inexpensive, and convenient to use with optimal mimicking of the physiological situation. This systematic review reviews current literature on differences between the three most used testosterone preparations in adult men with hypogonadism and transgender males. Although it appeared hardly any comparative studies have been carried out, there are indications of differences between the preparations, for example, on the stability of testosterone levels, hematocrit, bone mineral density, and patient satisfaction. However, there are no studies on the effects of testosterone replacement on endpoints such as cardiovascular disease in relation to hematocrit or osteoporotic fractures in relation to bone mineral density. The effect of testosterone therapy on health-related quality of life is strongly underexposed in the reviewed studies, while this is a highly relevant outcome measure from a patient perspective. In conclusion, current recommendations on testosterone treatment appear to be based on data primarily from non-randomized clinical studies and observational studies. The availability of reliable comparative data between the different preparations will assist in the process of individual decision-making to choose the most suitable formula.

Contains fulltext : 247486.pdf (Publisher’s version ) (Open Access) 10 p.

Additional file 2: A. Methods for patient involvement. B. Search strategy in PubMed. C. Data collection forms.

Additional file 1:. Checklist for the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) 2015 statement.

Purpose To explore the experiences and preferences of population‐based research participants to whom an incidental finding was communicated. Materials and Methods Of the 2580 participants of the Netherlands Epidemiology of Obesity (NEO) study who underwent magnetic resonance imaging (MRI) scanning of the abdomen, heart, and/or brain, an incidental finding with presumed health importance was disclosed to 56 (2%) participants. These participants were invited to discuss their experiences regarding the communication of the finding by the NEO research team in a focus group discussion. Transcripts of the discussions were analyzed using thematic content analysis with an open coding system. Results Twenty‐three persons participated in four discussions: 57% male; mean age 58 years; 74% findings were suspect for a malignancy. Overall, the participants were grateful for the disclosure of the incidental finding. They had assumed that any finding would be disclosed, and this was an important reason to participate in research. None regretted their informed consent to be notified about incidental findings. Disclosure of the finding had great impact on the lives of most participants. Difficulties with the transition from research participant to patient were frequently mentioned. Conclusion This study provides information to improve the communication of incidental findings by 1) giving clear information about which findings will be disclosed, and 2) demarcating the transition from research participant to patient, by making clear arrangements with medical specialists to guarantee careful follow‐up of the finding.

Item does not contain fulltext OBJECTIVE: To study the relative contribution of surrogates for mechanical stress and systemic processes with osteoarthritis (OA) in weight-bearing and non-weight-bearing joints. METHODS: The Netherlands Epidemiology of Obesity study is a population-based cohort including 6673 participants (range 45-65 years, 56% women, median body mass index 26 kg/m(2)). Weight (kg) and fat mass (kg) were measured, fat-free mass (kg) was calculated. The metabolic syndrome was defined following the Adult Treatment Panel III criteria. Knee and hand OA were defined according to the American College of Rheumatology clinical criteria.Logistic regression analyses were performed to associate surrogates for mechanical stress (such as weight, fat-free mass) and systemic processes (such as metabolic syndrome) with OA in knees alone, knees and hands or hands alone, adjusted for age, sex, height, smoking, education and ethnicity, and when appropriate for metabolic factors and weight. RESULTS: Knee, knee and hand, and hand OA were present in 10%, 4% and 8% of the participants, respectively. Knee OA was associated with weight and fat-free mass, adjusted for metabolic factors (OR 1.49 (95% CI 1.32 to 1.68) and 2.05 (1.60 to 2.62), respectively). Similar results were found for OA in knees and hands (OR 1.51 (95% CI 1.29 to 1.78) and 2.17 (95% CI 1.52 to 3.10) respectively). Hand OA was associated with the metabolic syndrome, adjusted for weight (OR 1.46 (95% CI 1.06 to 2.02)). CONCLUSIONS: In knee OA, whether or not in co-occurrence with hand OA, surrogates for mechanical stress are suggested to be the most important risk factors, whereas in hand OA alone, surrogates for systemic processes are the most important risk factors.

Item does not contain fulltext Purpose To test the hypothesis that hepatic triglyceride content is associated with subclinical vascular impairment and is not confounded by various cardiometabolic risk factors. Materials and Methods This study was approved by the institutional review board, and all participants gave written informed consent. In this cross-sectional analysis of baseline measurements of the Netherlands Epidemiology of Obesity study, a population-based cohort study, 1899 participants (52% men; mean age, 55 years +/- 6 [standard deviation]) underwent magnetic resonance (MR) spectroscopy and MR imaging to assess hepatic triglyceride content, aortic pulse wave velocity (PWV), and visceral fat. Carotid intima-media thickness (IMT) was acquired and measured by trained research nurses according to standard procedures. Multivariate regression analyses were used to study associations of hepatic triglyceride content with total and regional aortic PWV and carotid IMT while adjusting for several possible confounding factors, including the metabolic syndrome. Results Total aortic PWV (mean difference, 0.5 m/sec; 95% confidence interval [CI]: 0.3, 0.7) and carotid IMT (mean difference, 37 mum; 95% CI: 25, 49) were higher in participants with hepatic steatosis. After adjusting for various covariates, a 10-fold increase in hepatic triglyceride content was associated with an increased mean aortic PWV of 0.19 m/sec (95% CI: 0.03, 0.36) in total and an increased mean aortic PWV of 0.42 m/sec (95% CI: 0.03, 0.81) in the abdominal segment. A 10-fold increase in hepatic triglyceride content was also associated with an increased mean carotid IMT of 15 mum (95% CI: 0, 29) but not after additional adjustments for visceral and total body fat. Conclusion In this relatively large population-based cohort study, hepatic triglyceride content was associated with aortic pulse wave velocity and carotid IMT. These associations were only partly explained by the metabolic syndrome and visceral adiposity, suggesting a possible specific contribution of hepatic steatosis to subclinical vascular impairment. (c) RSNA, 2017 Online supplemental material is available for this article.

To investigate the association between hepatic triglyceride content and left ventricular (LV) diastolic function while taking potential confounding factors into account, including the components of the metabolic syndrome.The study was approved by the institutional review board, and all participants gave informed consent. In this cross-sectional analysis of baseline data from the Netherlands Epidemiology of Obesity study, a population-based, prospective cohort study, participants (45% men; mean age ± standard deviation, 55.3 years ± 6.2) underwent magnetic resonance (MR) spectroscopy and MR imaging to assess hepatic triglyceride content and LV diastolic heart function (ratio of peak filling rates of the early filling phase and atrial contraction [E/A ratio]). Multivariate linear regression analysis was performed while adjusting for confounding factors, and results were additionally stratified according to body mass index.Adjustment for age, sex, heart rate, alcohol consumption, pack-years of smoking, all components of the metabolic syndrome, and visceral adiposity attenuated crude observed associations. A 10-fold increase in hepatic triglyceride content was associated with a change in mean E/A ratio of -0.004 (95% confidence interval [CI]: -0.134, 0.125) in the total study population, -0.194 (95% CI: -0.430, 0.042) in the normal-weight subgroup, 0.079 (95% CI: -0.090, 0.248) in the overweight subgroup, and -0.109 (95% CI: -0.186, -0.032) in the obese subgroup.Fatty liver itself could, at least in obesity, pose a risk of myocardial dysfunction above and beyond known cardiovascular risk factors that are clustered within the metabolic syndrome. The association in the obese subgroup was small, and future studies with larger samples sizes are required to investigate to what extent the association exists and differs in normal-weight, overweight, and obese persons to unravel its clinical relevance.

Contains fulltext : 96794.pdf (Publisher’s version ) (Closed access) OBJECTIVES: To examine the relationship between obesity and depressive symptoms taking into account different measures for obesity (body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR)) and different depressive symptom clusters. DESIGN: Cross-sectional population-based survey. SETTING: Baseline data of the Nijmegen Biomedical Study. PARTICIPANTS: One thousand two hundred eighty-four persons aged 50 to 70. MEASUREMENTS: Obesity (BMI, WC, and WHR) and depressive symptoms were measured, the latter using the Beck Depression Inventory (BDI). Principal components analysis of the BDI items yielded two factors, one representing a cognitive-affective symptom cluster and the other a somatic-affective symptom cluster. Multiple regression analyses corrected for confounders were conducted for each measure of obesity, with separate models testing the BDI sum score and the depression symptom clusters. RESULTS: BMI was significantly associated with BDI sum score (beta=0.12, P

Contains fulltext : 88255.pdf (Publisher’s version ) (Closed access) BACKGROUND: To compare apolipoprotein B (apoB), non-high-density lipoprotein-cholesterol (non-HDL-c) and low-density lipoprotein-cholesterol (LDL-c) for identifying individuals with a deteriorated cardiovascular (CV) risk profile, including a panel of subclinical atherosclerosis measurements and prevalent cardiovascular disease (CVD) in a Dutch population-based cohort. METHODS: Clinical and biochemical measurements and a panel of noninvasive parameters of subclinical atherosclerosis were determined in 1517 individuals, aged 50-70 years. RESULTS: Both men and women with increasing levels of apoB and non-HDL-c were more obese, had higher blood pressure and fasting glucose levels, and a more atherogenic lipid profile. Furthermore, compared to the reference group (composed of those with apoB, non-HDL-c and LDL-c levels in the bottom quartiles), participants with high apoB and high non-HDL-c levels had a lower ankle-brachial index at rest (-3.5% and -3.1%, respectively) and after exercise (-6.3% and -4.7%, respectively), a thicker near wall (+4.8% and +4.2%, respectively), far wall (both +6.2%), and mean intima-media thickness (+5.7% and +5.3%, respectively) and more plaques (+54.2% and +54.3%, respectively). In addition, they also showed increased stiffness parameters (e.g. pulse wave velocity both +3.6%). Less clear differences in CV risk profile and subclinical atherosclerosis parameters were observed when participants were stratified by LDL-c level. Furthermore, apoB but not LDL-c detected prevalent CVD, and non-HDL-c only detected prevalent CVD in men. The discriminatory power for prevalent CVD expressed as area under the receiver operating characteristic curve was 0.60 (P < 0.001) for apoB, 0.57 (P = 0.001) for non-HDL-c and 0.54 (P = 0.108) for LDL-c. CONCLUSION: Our data support the use of first apoB and secondly non-HDL-c above LDL-c for identifying individuals from the general population with a compromised CV phenotype. 01 december 2010

Contains fulltext : 79889.pdf (Publisher’s version ) (Open Access) Phenylketonuria (PKU) is a classical example of an inherited metabolic disease, in which mental retardation can be prevented successfully by using a diet. However, in adult PKU new problems occur, such as vitamin deficiencies, osteoporosis and the maternal PKU syndrome. The aim of this review article is to provide guidelines for the clinician to understand and manage PKU in adults.

Contains fulltext : 53566.pdf (Publisher’s version ) (Closed access) We analysed the diversity of tenascin-X (TNX) species in serum and studied parameters that could affect determination of TNX levels in serum. Using western blot analysis we identified at least seven distinct TNX species, ranging from 75 kDa to the presumably full-length 450 kDa form. Purification of serum TNX followed by sequence analysis positively identified two major TNX species of 75 and 140 kDa. We found that serum TNX binds to tropoelastin but not to fibrillar collagens. We conclude that serum TNX is composed of distinct molecular species that retain functional activity.

In contrast to structured, integrated risk assessment in primary care, unstructured risk factor screening outside primary care and corresponding recommendations to consult a general practitioner (GP) are often based on one abnormal value of a single risk factor. This study investigates the advantages and disadvantages of unstructured screening of blood pressure and cholesterol outside primary care.After the baseline visit of the Netherlands Epidemiology of Obesity study (population-based prospective cohort study in persons aged 45-65 years, recruited 2008-2012) all participants received a letter with results of blood pressure and cholesterol, and a recommendation to consult a GP if results were abnormal. Four years after the start of the study, participants received a questionnaire about the follow-up of their results.The study population consisted of 6343 participants, 48% men, mean age 56 years, mean body mass index 30 kg/m(2). Of all participants 66% had an abnormal result and, of these, 49% had a treatment indication based on the risk estimation system SCORE-NL 2006. Of the 25% of the participants who did not consult a GP, 40% had a treatment indication. Of the participants with an abnormal result 19% were worried, of whom 60% had no treatment indication.In this population 51% of the participants with an abnormal result had unnecessarily received a recommendation to consult a GP, and 10% were unnecessarily worried. GPs should be informed about the complete risk assessment, and only participants at intermediate or high risk should receive a recommendation to consult a GP.

Contains fulltext : 51073.pdf (Publisher’s version ) (Closed access) Toll-like receptor (TLR)-4 is an important pattern recognition receptor for Candida albicans, playing a role in innate host defense. We investigated whether there is an association between the TLR4 Asp299Gly or TLR4 Thr399Ile polymorphism, and the occurrence of Candida bloodstream infection. We performed a case-control study, involving 43 patients with a Candida bloodstream infection and 166 healthy individuals. TLR4 Asp299Gly and Thr399Ile polymorphisms were assessed, as well as cytokine production after stimulation of peripheral blood mononuclear cells (PBMC) with Candida albicans. We observed that the prevalence of TLR4 Asp299Gly polymorphism was found to be higher in patients with Candida bloodstream infection than in controls (26% versus 10%; OR 3.0; 95%CI 1.3-6.9). All patients bearing the Asp299Gly polymorphism were also positive for the Thr399Ile allele, a linkage well described in literature. IL-10 production was higher in C. albicans-stimulated PBMC from volunteers bearing the TLR4 Asp299Gly polymorphism, and a similar tendency was observed in TLR4 Asp299Gly heterozygous patients who had recovered from candidemia. These findings show that the TLR4 Asp299Gly/Thr399Ile polymorphisms are associated with an increased susceptibility to Candida bloodstream infections, and an increased production of IL-10 is probably involved in this effect.

Item does not contain fulltext Classical homocystinuria is associated with arterial vascular diseases and venous thrombosis. In the last decade, many studies, including some prospective studies, have been published indicating that moderate hyperhomocysteinaemia is also a risk factor for venous thrombosis. The 677C>T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is an important cause of mild hyperhomocysteinaemia. Recent metaanalyses show an elevated risk of venous thrombosis for subjects with the TT-genotype. Based on the concept of 'Mendelian randomisation', this observation supports the hypothesis that hyperhomocysteinaemia is a causal risk factor for venous thrombosis. The results of one homocysteine-lowering trial regarding venous thrombosis are awaited at the end of 2003. In this paper the current evidence for hyperhomocysteinaemia as a risk factor for venous thrombosis is being discussed.

Objectives The purpose was to determine prevalence of enchondromas and atypical cartilaginous tumour/chondrosarcoma grade 1 (ACT/CS1) of the knee on MRI in a large cohort study, namely the Netherlands Epidemiology of Obesity (NEO) study. Methods Participants aged 45 to 65 years were prospectively included, oversampling overweight and obese persons. Within a subgroup of participants, MRI of the right knee was performed and screened for incidental cartilaginous tumours, as defined by their characteristic location and appearance. Results Forty-nine cartilaginous tumours were observed in 44 out of 1285 participants (estimated population prevalence 2.8 %, 95 % CI 2.0–4.0 %). Mean largest tumour diameter was 12 mm (range 2–31 mm). Eight participants with a tumour larger than 20 mm or a tumour with aggressive features were referred to rule out low-grade chondrosarcoma. One was lost to follow-up, three had histologically proven ACT/CS1 and four had dynamic contrast MRI findings consistent with benign enchondroma. Conclusions Incidental cartilaginous tumours were relatively common on knee MRI and may be regarded as a normal concurrent finding. However, more tumours than expected were ACT/CS1. Because further examination was performed only when suspicion of chondrosarcoma was high, the actual prevalence might be even higher. Key Points • Incidental cartilaginous tumours are relatively common on knee MRI. • Most incidental cartilaginous tumours are small and lack suspicious features. • Small cartilaginous tumours without suspicious findings may be a normal concurrent finding. • Large tumours and/or those with suspicious findings should be further investigated. • Atypical cartilaginous tumour/chondrosarcoma grade 1 was found more often than expected.

Item does not contain fulltext Homocysteine may have an effect on risk of cardiovascular disease by stimulating procoagulant factors and/or impair anti-coagulant mechanisms or fibrinolysis. However, data in humans of such effects are sparse. In this intervention study, we examined the effect of homocysteine lowering by B-vitamin supplementation on prothrombin fragments 1 and 2 (F1 + 2), thrombin-antithrombin complex (TAT), and fibrin degradation products (D-dimer). The study comprised 118 healthy volunteers, 50 with homocysteine > 16 mumol/L and 68 with homocysteine < or = 16 mumol/L, who were randomized to placebo or high-dose B-vitamin supplements (5 mg folic acid, 0.4 mg hydroxycobalamin, and 50 mg pyridoxine) daily for 8 weeks. Although homocysteine concentrations were 27.7% (p < 0.0001) reduced in the B-vitamin group compared to the placebo group, no effect on F1 + 2 and TAT concentrations was observed. A 10.4% reduction was observed for D-dimer (p = 0.08). In conclusion, it appears that in healthy subjects homocysteine reduction by B-vitamin supplementation has a modest beneficial effect on clotting activation.

Item does not contain fulltext Venous thrombosis is a multicausal disease involving acquired and genetic factors. In this study we investigated a possible interaction between hyperhomocysteinemia (fasting or postload) and factor V Leiden or prothrombin G20210A on the risk of recurrent venous thrombosis. We also looked at the risk due to mutations in the MTHFR-gene (C677T and A1298C). We performed a case-control study in 171 patients with a history of recurrent venous thrombosis and 461 control subjects from the general population. Hyperhomocysteinemia (fasting or 6 h after an oral methionine load) was defined as a homocysteine concentration above the 90th percentile of the distributions in the control group. The odds ratio (adjusted for age and sex) for recurrent venous thrombosis was 1.8 (95% CI: 1.1 to 3.0) for fasting hyperhomocysteinemia, 5.1 (95% CI: 3.0 to 8.6) for factor V Leiden and 1.8 (95% CI: 0.7 to 4.2) for prothrombin G20210A. We found 14 patients and 3 controls with both hyperhomocysteinemia and factor V Leiden, which yielded an odds ratio of 11.6 (95% CI: 3.2 to 42.5). We found no interaction between hyperhomocysteinemia and prothrombin G20210A. The relative risk for MTHFR 677CT was 1.6 (95% CI: 1.1 to 2.4) and for MTHFR 677TT was 1.4 (95% CI: 0.7 to 2.8). The combined risk for MTHFR 677TT and factor V Leiden was 18.7 (95% CI: 3.3 to 108). We conclude that hyperhomocysteinemia and factor V Leiden are risk factors for recurrent venous thrombosis. The risk of thrombosis appeared high for individuals who had both risk factors.

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Contains fulltext : 137063.pdf (Publisher’s version ) (Open Access) OBJECTIVE: To investigate if the amount of fat mass (FM) or skeletal muscle mass (SMM) is more strongly associated with knee osteoarthritis (OA), in both men and women. METHODS: The Netherlands Epidemiology of Obesity (NEO) study is a population-based cohort aged 45-65 years, including 5313 participants (53% female, median body mass index (BMI) 29.9 kg/m(2)). FM (kg), fat percentage, SMM (kg) and skeletal muscle (SM) percentage were estimated using bioelectrical impedance analysis (BIA). Clinical OA was defined following the ACR criteria. Structural OA was defined based on magnetic resonance imaging (MRI) in 1142 participants. Logistic regression analyses were used to examine the associations of all body composition measures with clinical and structural knee OA per standard deviation (SD), stratified by sex and adjusted for age and height. RESULTS: Clinical or structural OA was present in 25% and 14% of women and 12% and 13% of men, respectively. FM and fat percentage were positively associated with clinical knee OA in men and women. SMM was positively associated, while the SM percentage was negatively associated with clinical OA in both men and women. The FM/SMM ratio was positively associated with clinical OA. All determinants showed even stronger ORs for structural knee OA. In men, SMM was more strongly associated with knee OA as compared to FM whereas in women, FM was most strongly associated. CONCLUSION: Especially a high FM/SMM ratio seems to be unfavorable in knee OA. In men, SMM is most strongly associated with knee OA whereas in women FM seems to be of most importance.