Thromboembolic complications remain a major public health burden, making antithrombotic agents one of the most widely prescribed groups of medication, but the treatment is often challenging as it... Show moreThromboembolic complications remain a major public health burden, making antithrombotic agents one of the most widely prescribed groups of medication, but the treatment is often challenging as it at the same time increases risk of bleeding. With nationwide data from Statistics Netherlands, antithrombotic therapy and relevant clinical outcomes were comprehensively examined in the patient population of atrial fibrillation, overall or among those with comorbid cancer. The results suggest the patient population was increasingly receiving anticoagulants, driven by the newly introduced medication- direct oral anticoagulant and guided by the CHA2DS2-VASc score, and meanwhile the patient population experienced fewer ischemic stroke and major bleeding. In spite of these promising changes, suboptimal medication adherence and potential underuse of anticoagulants remain directions for further improvement. Antithrombotic agent use during pregnancy was also examined in the general Dutch pregnant population, which featured a surge in antiplatelet prescriptions, and risk of preeclampsia/eclampsia decreased and several newborn outcomes improved simultaneously. Together, the studies presented in this thesis provide an overview of antithrombotic therapy in the Netherlands in recent years, providing insights for further improving this treatment and relevant patient outcomes. Show less
Rosendal, C.; Arlien-Soborg, M.C.; Nielsen, E.H.; Andersen, M.S.; Feltoft, C.L.; Kistorp, C.; ... ; J. dal 2024
Acromegaly is a rare disease and thus challenging to accurately quantify epidemiologically. In this comprehensive literature review, we compare different approaches to studying acromegaly from an... Show moreAcromegaly is a rare disease and thus challenging to accurately quantify epidemiologically. In this comprehensive literature review, we compare different approaches to studying acromegaly from an epidemiological perspective and describe the temporal evolution of the disease pertaining to epidemiological variables, clinical presentation and mortality. We present updated epidemiological data from the population-based Danish cohort of patients with acromegaly (AcroDEN), along with meta-analyses of existing estimates from around the world.Based on this, we conclude that the incidence, prevalence and age at acromegaly diagnosis are all steadily increasing, but with considerable variation between studies. An increased number of incidental cases may contribute to the increase in incidence and age at diagnosis, respectively. The clinical features at presentation are trending toward a milder disease phenotype at diagnosis, and advances in therapeutic options have reduced the mortality of patients with acromegaly to a level similar to that of the general population. Moreover, the underlying cause of death has shifted from cardiovascular to malignant neoplastic diseases. Show less
This thesis addresses potential threats to the validity of observational epidemiological studies. Examples of these potential sources of bias are confounding, missing data, selection bias, and... Show moreThis thesis addresses potential threats to the validity of observational epidemiological studies. Examples of these potential sources of bias are confounding, missing data, selection bias, and measurement error. Although various methods have been developed to mitigate these biases, it is often unclear which methods can be used in which empirical settings. It is also common that issues discussed in methodological studies are overlooked in clinical research. Thus, we investigated problems ofmissing data, selection bias, and measurement error occurring in several specific observational settings and discuss how to optimally handle them. Show less
Breast cancer is a heterogeneous disease with substantial variability in outcome, risk factors and response to treatment. Therefore, a better understanding of the factors influencing breast cancer... Show moreBreast cancer is a heterogeneous disease with substantial variability in outcome, risk factors and response to treatment. Therefore, a better understanding of the factors influencing breast cancer outcome could lead to improved prognostication and better stratification of patients into treatment subgroups. To this end, we investigated the association of hereditary genetic variants and non-genetic breast cancer risk factors with breast cancer outcome, and assessed the evidence of potential differential associations across specific tumor subtypes and patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment. We focused on two breast cancer outcomes, namely survival and risk of developing a second breast cancer in the contralateral breast (contralateral breast cancer).Based on data from a large international cohort of breast cancer patients, we found clear associations of several known lifestyle breast cancer risk factors with survival in breast cancer patients, independently from specific tumor subtype, and of coding hereditary genetic variants in five known breast cancer susceptibility genes with contralateral breast cancer risk. There was also evidence of association of coding hereditary genetic variants in three known breast cancer genes with breast cancer-specific survival (time to death due to breast cancer), although weaker than for contralateral breast cancer risk. These factors could be incorporated into prediction models for breast cancer outcome thereby potentially improving prognostic estimates and breast cancer counseling. In particular, the findings related to contralateral breast cancer risk are relevant to treatment decisions, follow-up and screening of breast cancer patients. Show less
Stroke is one of the leading causes of disability and death worldwide. Prevention of stroke is therefore essential. Effective prevention should be tailored to the clinical characteristics,... Show moreStroke is one of the leading causes of disability and death worldwide. Prevention of stroke is therefore essential. Effective prevention should be tailored to the clinical characteristics, lifestyle, and environment of the individual, among others. This is also known as precision prevention. An important example illustrating the need for precision prevention is the existence of sex differences in stroke occurrence. In practice, for predicting stroke risk, only traditional risk factors (such as smoking and hypertension) are included, and women-specific risk factors are not yet routinely included. As a result, women with an increased risk of stroke may be missed, which also prevents timely initiation of preventive treatments. In this thesis, I tried to lay the foundation for precision prevention of stroke in women.Part I discussed the pathophysiology underlying women-specific risk factors for stroke, and gender differences in the clinical presentation of stroke. I found that the mechanisms underlying the relationship between women-specific risk factors and stroke, in particular the relationship between migraine and cerebral infarctions, seem to be particularly significant in the childbearing phase of life.In Part II, I described how health data from the EHR can be used to develop prediction models for the risk of myocardial infarction or stroke specifically for women under 50 years of age, and found that women-specific risk factors can add value in the predictions. However, there is still a long way to go to actually implement these models in practice, such as testing them on new datasets, and complying with current laws and regulations for safe application. Show less
Purpose Recent data have shown a decreasing overall mortality in acromegaly over the last decades. However, cancer incidence and cancer-related mortality still appear to be increased. Our aim was... Show morePurpose Recent data have shown a decreasing overall mortality in acromegaly over the last decades. However, cancer incidence and cancer-related mortality still appear to be increased. Our aim was to obtain updated epidemiological data from Norway in a clinically well-defined cohort with complete register-based follow-up.Methods Patients diagnosed with acromegaly from South-Eastern Norway between 1999-2019 (n = 262) and age and sex matched population controls (1:100) were included (n = 26,200). Mortality and cancer data were obtained from the Norwegian Cause of Death and Cancer Registry. Mortality and cancer incidence were compared by Kaplan-Meier analyses and Cox regression; we report hazard ratios (HRs) with 95% confidence intervals (95% CI).Results Median age at diagnosis was 48.0 years (interquartile range (IQR): 37.6-58.0). Mean annual acromegaly incidence rate was 4.7 (95% CI 4.2-5.3) cases/10(6) person-years, and the point prevalence (2019) was 83 (95% CI 72.6-93.5) cases/10(6) persons. Overall mortality was not increased in acromegaly, HR 0.8 (95% CI 0.5-1.4), cancer-specific and cardiovascular-specific mortality was also not increased (HR: 0.7 (95% CI 0.3-1.8) and 0.8 (95% CI: 0.3-2.5) respectively). The HR for all cancers was 1.45 (1.0-2.1; p = 0.052).Conclusion In this large cohort study, covering the period 1999-2019, patients were treated with individualized multimodal management. Mortality was not increased compared to the general population and comparable with recent registry studies from the Nordic countries and Europe. Overall cancer risk was slightly, but not significantly increased in the patients. Show less
Background: A decade ago, it was demonstrated that the difference in survival between older patients and younger patients with colorectal cancer (CRC) was mainly due to mortality in the first... Show moreBackground: A decade ago, it was demonstrated that the difference in survival between older patients and younger patients with colorectal cancer (CRC) was mainly due to mortality in the first postoperative year. Over the last few years, improvements -especially in perioperative care-have increased survival. The current research investigates whether a survival gap between younger and older patients with CRC still exists on a national level in four European countries. Methods: Population-based data from Belgium, the Netherlands, Norway, and Sweden were collected from patients that underwent surgical resection for primary stage I-III CRC between 2007 and 2016. Relative survival and conditional relative survival (CS), with the condition of surviving the first postoperative year, were calculated for colon and rectal cancer separately, stratified for country and age category (< 65, 65-75, >= 75 years). In addition, relative excess risk of death (RER) was estimated, and one-year excess mortality was calculated. Results: Data of 206,024 patients were analyzed. In general, compared to patients < 65 years, patients >= 75 years had a worse survival during the first year after surgery, which was most pronounced in Belgium (RER colon cancer 2.5 [95% confidence interval (CI) 2.3-2.8] and RER rectal cancer 2.6 [95% CI 2.3-2.9]). After surviving the first year, CS was mostly not statistically different between patients < 65 years and patients >= 75 years with stage I-II, with the exception of stage II colon cancer in Belgium. However, CS remained worse in the largest part of the patients & GE;75 years with stage III colon or rectal cancer (except for rectal cancer in Norway). Conclusions: Although differences exist between the countries, the survival gap between young and older patients is based mainly on early mortality and remains only for stage III disease after surviving the first year. Show less
Objective We aimed to investigate whether serum anti-N-methyl-D-aspartate-receptor GluN1 (previously NR1) antibody (NMDAR1-abs) seropositivity impacts cognitive function (CF) in the long term... Show moreObjective We aimed to investigate whether serum anti-N-methyl-D-aspartate-receptor GluN1 (previously NR1) antibody (NMDAR1-abs) seropositivity impacts cognitive function (CF) in the long term following ischemic stroke. Methods Data were used from the PROSpective Cohort with Incident Stroke-Berlin. NMDAR1-abs (IgM/IgA/IgG) were measured with cell-based assays from serum obtained within 7 days after the first-ever stroke. Seropositivity was defined as titers >= 1:10, low titers as <= 1:100 and high titers as > 1:100. We assessed CF at 1, 2 and 3 years after stroke with the Telephone Interview for Cognitive Status-modified (TICS-m) and used crude and propensity score adjusted inverse probability weighted generalized linear models to estimate the impact of NMDAR1-abs serostatus on TICS-m. Results Data on NMDAR1-abs (median day of sampling = 4[IQR = 2-5]) were available in 583/621 PROSCIS-B patients (39% female; median NIHSS = 2[IQR = 1-4]; median MMSE = 28[IQR:26-30]), of whom 76(13%) were seropositive (IgM: n = 48/IgA: n = 43/IgG: n = 2). Any NMDAR1-abs seropositivity had no impact on TICS-m compared to seronegative patients (beta crude = 0.69[95%CI = - 0.84 to 2.23]; beta adjusted = 0.65[95%CI = - 1.00 to 2.30]). Patients with low titers scored better on TICS-m compared to seronegative patients (beta crude = 2.33[95%CI = 0.76 to 3.91]; beta adjusted = 2.47[95%CI = 0.75 to 4.19]); in contrast, patients with high titers scored lower on TICS-m (beta crude = -2.82[95%CI = - 4.90 to - 0.74], beta adjusted = - 2.96[95%CI = - 5.13 to - 0.80]), compared to seronegative patients. Conclusion In our study, NMDAR1-abs seropositivity did not affect CF over 3 years after a first mild to moderate ischemic stroke. CF differed according to NMDAR1-abs serum titer, with patients with high NMDAR1-abs titers having a less favorable cognitive outcome compared to seronegative patients. Show less
Heus, E. de; Duijts, S.F.A.; Zwan, J.M. van der; Kapiteijn, E.; Dijkum, E.J.M.N. van; Herpen, C.M.L. van; Merkx, M.A.W. 2022
Introduction: Epidemiological discrepancies exist between rare and common can-cers. The aim of this population-based study was to compare rare versus common adult solid cancers in the Netherlands,... Show moreIntroduction: Epidemiological discrepancies exist between rare and common can-cers. The aim of this population-based study was to compare rare versus common adult solid cancers in the Netherlands, by providing incidence, prevalence and survival rates, evaluating trends in survival and comparing individual entities within domains and families.Methods: All adult patients with malignant solid cancers in the Netherlands between 1995 and 2019 were identified from the Netherlands Cancer Registry. Data on patient, tumour and treatment characteristics were collected, and relative survival and survival trends were ana-lysed.Results: A total of 170,628 patients with rare adult solid cancers and 806,023 patients with common adult solid cancers were included. Rare cancers accounted for 18% of all cancer di-agnoses (mean incidence), and 15% of the total ten-year cancer prevalence during 2010-2019. Overall 5-year survival was worse for rare cancers than for common cancers (52.0% versus 68.7%). Between 1995-1999 and 2015-2019, 5-year survival rates for rare cancers increased to a lesser extent (from 46.2% to 52.6%, i.e. 6.4%) than for common cancers (56.9% Show less
Coeliac disease is an immune-mediated condition characterized by chronic inflammation of the small bowel with villous atrophy driven by gluten ingestion in genetically predisposed individuals. It... Show moreCoeliac disease is an immune-mediated condition characterized by chronic inflammation of the small bowel with villous atrophy driven by gluten ingestion in genetically predisposed individuals. It occurs frequently in both children and adults, affecting 1-4% of the population. The disease is associated with both gastrointestinal and extra-intestinal symptoms related to malabsorption and/or immune activation, and autoantibodies to tissue transglutaminase. Removal of gluten from the diet results in resolution of symptoms and enteropathy in the majority of patients. A good diagnostic work-up is important to avoid unnecessary restrictive diets in children. In this review on pediatric coeliac disease, we address epidemiology including predisposing environmental factors and possible preventive strategies, as well as the clinical presentation, diagnosis and follow-up. Show less
Background: Splanchnic vein thrombosis (SVT) is an uncommon manifestation of venous thromboembolism. Epidemiological data on SVT-related mortality rate is not available to date.& nbsp;Methods:... Show moreBackground: Splanchnic vein thrombosis (SVT) is an uncommon manifestation of venous thromboembolism. Epidemiological data on SVT-related mortality rate is not available to date.& nbsp;Methods: We investigated time trends in SVT-related mortality rate, 2008-2019, in Veneto, an Italian high income region of approximatively 5,000,000 inhabitants. SVT-related deaths were identified by the following ICD-10 codes: I81 (portal vein thrombosis), K75.1 (phlebitis of portal vein), K76.3 (liver infarction), K76.5 (hepatic veno-occlusive disease) or I82.0 (Budd-Chiari syndrome).& nbsp;Results: During the study period, a total of 557,932 deaths were recorded. SVT was reported in 823 cases; 776 (94%) consisted of portal vein thrombosis. The age-standardized SVT-related mortality rate varied from 1.47 (year 2008) to 1.52 (year 2019) per 100,000 person-years. An increase in the cause-specific annual mortality rate was observed in women (0.56 in 2008 to 1.04 per 100,000 person-years in 2019; average annual percent change +5.7%, 95%CI +3.1; +8.3%). In men, the cause-specific mortality rate moved from 2.53 in 2008 to 2.03 per 100,000 person-years in 2019 (average annual percent change-1.2%, 95%CI-4.0; +1.6%). After conditioning for age and sex, the odds of having a concomitant liver disease were higher for SVT-related deaths (OR 31.6; 95% CI 17.1-37.0) compared with non-SVT-related deaths. This also applies to gastrointestinal cancers (OR 1.28; 95% CI 1.07-1.55), although to a lesser extent.& nbsp;Conclusions: We report first epidemiological estimates of SVT-related mortality in a Western country. These values will serve as a reference to weight novel potential factors associated with SVT-related death and interpret them from an epidemiological perspective. Show less
Giustozzi, M.; Valerio, L.; Agnelli, G.; Becattini, C.; Fronk, E.M.; Klok, F.A.; ... ; Barco, S. 2021
Introduction: Sex and the presence of specific provoking risk factors, along with age, influence the presentation and prognosis of venous thromboembolism (VTE). We investigated the presentation,... Show moreIntroduction: Sex and the presence of specific provoking risk factors, along with age, influence the presentation and prognosis of venous thromboembolism (VTE). We investigated the presentation, course and quality of life in women and men with acute VTE classified according to their VTE provoking factors.Methods: PREFER in VTE is an international, non-interventional registry of patients with a first episode of acute symptomatic VTE. Baseline provoking factors were classified as follows: major transient, minor transient, active cancer, and none identifiable. The primary outcome was recurrent VTE. Quality of life and treatment satisfaction were secondary outcomes.Results: Of 3,455 patients with acute VTE, 1,623 (47%) were women. The mean age at the time of VTE was 61 (SD 18) in women, 60 (SD 15) in men. The distribution of provoking risk factors was similar between sexes, despite a tendency for higher frequency of minor and major transient risk factors in women, and cancer or unprovoked VTE in men. At 12-month follow-up, VTE recurrence was reported in 74 (6.5%) women and 80 (6.4%) men (absolute risk difference-0.1%, 95% CI-1.9%; +2.1%). In patients with unprovoked VTE, the VTE recurrence rate was 38/612 (6.2%) in women and 53/798 (6.6%) in men (absolute risk difference-0.4, 95% CI-3.0; +2.1%). Multivariable Cox regressions confirmed the absence of sex differences. Quality of life and treatment satisfaction scores one year after VTE were lower in women than in men irrespective of the provoking risk factors (p<0.001 for both scores).Conclusions: Despite differences in the provoking risk factors for VTE, women and men had a similar rate VTE recurrence at one year. After acute VTE, women had lower quality of life and treatment satisfaction scores. Show less
Bos, M.M.; Goulding, N.J.; Lee, M.A.; Hofman, A.; Bot, M.; Pool, R.; ... ; Lawlor, D.A. 2021
Background Sleep traits are associated with cardiometabolic disease risk, with evidence from Mendelian randomization (MR) suggesting that insomnia symptoms and shorter sleep duration increase... Show moreBackground Sleep traits are associated with cardiometabolic disease risk, with evidence from Mendelian randomization (MR) suggesting that insomnia symptoms and shorter sleep duration increase coronary artery disease risk. We combined adjusted multivariable regression (AMV) and MR analyses of phenotypes of unfavourable sleep on 113 metabolomic traits to investigate possible biochemical mechanisms linking sleep to cardiovascular disease. Methods We used AMV (N = 17,368) combined with two-sample MR (N = 38,618) to examine effects of self-reported insomnia symptoms, total habitual sleep duration, and chronotype on 113 metabolomic traits. The AMV analyses were conducted on data from 10 cohorts of mostly Europeans, adjusted for age, sex, and body mass index. For the MR analyses, we used summary results from published European-ancestry genome-wide association studies of self-reported sleep traits and of nuclear magnetic resonance (NMR) serum metabolites. We used the inverse-variance weighted (IVW) method and complemented this with sensitivity analyses to assess MR assumptions. Results We found consistent evidence from AMV and MR analyses for associations of usual vs. sometimes/rare/never insomnia symptoms with lower citrate (- 0.08 standard deviation (SD)[95% confidence interval (CI) - 0.12, - 0.03] in AMV and - 0.03SD [- 0.07, - 0.003] in MR), higher glycoprotein acetyls (0.08SD [95% CI 0.03, 0.12] in AMV and 0.06SD [0.03, 0.10) in MR]), lower total very large HDL particles (- 0.04SD [- 0.08, 0.00] in AMV and - 0.05SD [- 0.09, - 0.02] in MR), and lower phospholipids in very large HDL particles (- 0.04SD [- 0.08, 0.002] in AMV and - 0.05SD [- 0.08, - 0.02] in MR). Longer total sleep duration associated with higher creatinine concentrations using both methods (0.02SD per 1 h [0.01, 0.03] in AMV and 0.15SD [0.02, 0.29] in MR) and with isoleucine in MR analyses (0.22SD [0.08, 0.35]). No consistent evidence was observed for effects of chronotype on metabolomic measures. Conclusions Whilst our results suggested that unfavourable sleep traits may not cause widespread metabolic disruption, some notable effects were observed. The evidence for possible effects of insomnia symptoms on glycoprotein acetyls and citrate and longer total sleep duration on creatinine and isoleucine might explain some of the effects, found in MR analyses of these sleep traits on coronary heart disease, which warrant further investigation. Show less
Aims Various drugs increase the risk of out-of-hospital cardiac arrest (OHCA) in the general population by impacting cardiac ion channels, thereby causing ventricular tachycardia/fibrillation (VTNF... Show moreAims Various drugs increase the risk of out-of-hospital cardiac arrest (OHCA) in the general population by impacting cardiac ion channels, thereby causing ventricular tachycardia/fibrillation (VTNF). Dihydropyridines block L-type calcium channels, but their association with OHCA risk is unknown. We aimed to study whether nifedipine and/or amlodipine, often-used dihydropyridines, are associated with increased OHCA risk, and how these drugs impact on cardiac electrophysiology.Methods and results We conducted a case-control study with VT/VF-documented OHCA cases with presumed cardiac cause from ongoing population-based OHCA registries in the Netherlands and Denmark, and age/sex/index date-matched nonOHCA controls (Netherlands: PHARMO Database Network, Denmark: Danish Civil Registration System). We included 2503 OHCA cases, 10 543 non-OHCA controls in Netherlands, and 8101 OHCA cases, 40 505 nonOHCA controls in Denmark. To examine drug effects on cardiac electrophysiology, we performed single-cell patch-clamp studies in human-induced pluripotent stem cell-derived cardiomyocytes. Use of high-dose nifedipine (>= 60 mg/day), but not low-dose nifedipine (<60 mg/day) or amlodipine (any-dose), was associated with higher OHCA risk than non-use of dihydropyridines [Netherlands: adjusted odds ratios (ORadj) 1.45 (95% confidence interval 1.02-2.07), Denmark: 1.96 (1.18-3.25)] or use of amlodipine [Netherlands: 2.31 (1.54-3.47), Denmark: 2.20 (1.32-3.67)]. Out-of-hospital cardiac arrest risk of (high-dose) nifedipine use was not further increased in patients using nitrates, or with a history of ischaemic heart disease. Nifedipine and amlodipine blocked L-type calcium channels at similar concentrations, but, at clinically used concentrations, nifedipine caused more L-type calcium current block, resulting in more action potential shortening.Conclusion High-dose nifedipine, but not low-dose nifedipine or any-dose amlodipine, is associated with increased OHCA risk in the general population. Careful titration of nifedipine dose should be considered. 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.
Hondel, K. van den; Runtuwene, N.; Bergen, A. van; Gilissen, R.; Punt, P.; Reijnders, U.; Buster, M. 2020
Background: Research has shown a higher prevalence of individuals lying dead unnoticed in their homes (domestic-setting corpses) in Amsterdam, compared to adjacent less urbanized cities and... Show moreBackground: Research has shown a higher prevalence of individuals lying dead unnoticed in their homes (domestic-setting corpses) in Amsterdam, compared to adjacent less urbanized cities and villages.Objective: To determine if there is a difference in incidence of domestic-setting corpses in the four major cities in the Netherlands and identifying demographic patterns accounting for possible differences.Methods: Data of domestic-setting corpses with a post mortem interval of at least 14 days were extracted from forensic registrations of the four largest cities in the Netherlands. These data were analysed using Poisson-regression and compared to numbers of Statistics Netherlands to calculate the incidence rate of domestic- setting corpses. Only single households were included.Results: The incidence of DSC14 is not significantly different between Amsterdam, The Hague and Rotterdam. The incidence rate of DSC in these cities is almost twice as high compared to Utrecht (corrected for age and sex 1,9; 95% CI:1,1-3,0).Conclusion: The incidence rate of DSC14 is comparable in the three largest cities of the Netherlands, and significantly higher compared to the smallest of the four (Utrecht). Possibly the lower number in Utrecht is related to less loneliness, a higher social participation and a difference in architecture. Show less
Noordam, R.; Boersma, V.; Verkouter, I.; Cessie, S. le; Christen, T.; Lamb, H.J.; ... ; Mutsert, R. de 2020
Background and aims: In the present study, we assessed the extent of mediation by low-grade systemic inflammation and adipokines in the association between abdominal adiposity and insulin... Show moreBackground and aims: In the present study, we assessed the extent of mediation by low-grade systemic inflammation and adipokines in the association between abdominal adiposity and insulin resistance.Methods and results: In this cross-sectional analysis of baseline measurements of the Netherlands Epidemiology of Obesity study, total body fat (TBF) was measured in all (n = 5772) participants who did not have missing data and neither used glucose-lowering medication, and abdominal subcutaneous adipose tissue (aSAT) and visceral adipose tissue (VAT) were assessed by MRI in a random subgroup (n = 2448). C-reactive protein (CRP), adiponectin, and leptin were considered as potential mediators, and insulin resistance was assessed by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Mediation by CRP, adiponectin, and leptin was studied by including the mediators to the fully adjusted linear regression model. Participants had a mean (SD) age of 56 (6) years, TBF of 36 (9) %, VAT of 119 (61) cm2 and aSAT of 300 (111) cm2. Per SD of TBF, VAT and aSAT, HOMA-IR was 64% (95% confidence interval [CI]: 59-70), 33% (95% CI: 28-42) and 20% (95%CI: 14-26) higher, respectively. The association between aSAT and HOMA-IR fully disappeared after adjustment for leptin; the association between VAT and HOMA-IR attenuated after adjustment for leptin (22%) and adiponectin (15%). No mediation was observed by CRP, and mediation estimates were similar in men and women.Conclusion: Where leptin fully explained the aSAT-HOMA-IR association, the VAT-HOMA-IR association was only partly explained by leptin and adiponectin similarly in men and women. (C) 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved. Show less
Two hundred and fifty-three non-duplicate toxigenic Clostridium difficile isolates, collected from February 2012 to December 2014, were evaluated for phenotypic resistance to ten antimicrobial... Show moreTwo hundred and fifty-three non-duplicate toxigenic Clostridium difficile isolates, collected from February 2012 to December 2014, were evaluated for phenotypic resistance to ten antimicrobial drugs with the E-test gradient diffusion method. All strains of C. difficile were susceptible to metronidazole, vancomycin, and tigecycline. The metronidazole MIC values of the hyperepidemic PCR-ribotypes RT027 and RT176 were higher than those of non-epidemic PCR-ribotypes (p < 0.05, as evidenced by Mann-Whitney U test). In contrast, vancomycin susceptibility did not differ between hyperepidemic and non-epidemic strains, although the difference was almost significant (p = 0.065). Clostridium difficile RT027 and RT176 isolates could be assessed to five and four different susceptibility patterns, respectively, representing various combinations of resistance to different antimicrobial classes. A single point mutation (Thr82Ile) in the gyrA gene was detected in 11 (78.6%) of 14 isolates with high level of resistance to ciprofloxacin and moxifloxacin and four different types of single point mutations (Arg447Lys, Ser416Ala, Asp426Val, Asp426Asn) in the gyrB gene were detected in 4 strains, also with high level of resistance to ciprofloxacin and moxifloxacin. Four different point mutations were detected in the rpoB gene in 21 rifampicin-resistant strains of which one has not been reported previously, GIn489Leu. This study demonstrates the presence of multidrug-resistant C. difficile strains in Polish hospitals over the study period, irrespective of geographical location or reference level of the hospital. (C) 2020 Elsevier Ltd. All rights reserved. Show less
BACKGROUND: A clear understanding of the differences in the epidemiology of food allergy between rural and urban populations may provide insights into the causes of increasing prevalence of food... Show moreBACKGROUND: A clear understanding of the differences in the epidemiology of food allergy between rural and urban populations may provide insights into the causes of increasing prevalence of food allergy in the developed world.OBJECTIVE: We used a standardized methodology to determine the prevalence and types of food-specific allergic sensitization and food allergies in schoolchildren from urban and rural regions of China, Russia, and India.METHODS: The current study is a multicenter epidemiological survey of children recruited from 5 cities in China (Hong Kong and Guangzhou), Russia (Tomsk), and India (Bengaluru and Mysore) and 1 rural county in Southern China (Shaoguan). A total of 35,549 children aged 6 to 11 years from 3 countries participated in this survey. Random samples of children from 3 countries were first screened by the EuroPrevall screening questionnaire. Children with and without a history of adverse reactions to foods were then recruited for the subsequent case-control comparative studies. We determined the prevalence rates of food-specific IgE sensitization and food allergies using the predefined criteria.RESULTS: The prevalence rates of food-specific IgE sensitization (>= 0.7 kU/L) to at least 1 food were 16.6% in Hong Kong, 7.0% in Guangzhou, 16.8% in rural Shaoguan, 8.0% in Tomsk, and 19.1% in India. Using a definition of probable food allergy as reporting allergic symptoms within 2 hours of ingestion of a specific food plus the presence of allergic sensitization to the specific food (positive IgE and/or positive skin prick test result), the prevalence of food allergy was highest in Hong Kong (1.50%), intermediate in Russia (0.87%), and lowest in Guangzhou (0.21%), Shaoguan (0.69%), and India (0.14%). For children recruited from Hong Kong, both sensitization and food allergy were significantly higher in children who were born and raised in Hong Kong when compared with those who were born in mainland China and migrated to Hong Kong, highlighting the importance of early-life exposures in affecting the subsequent development of food sensitization and food allergy.CONCLUSIONS: There are wide variations in the prevalence of food-specific IgE sensitization and food allergy in the 3 participating countries. Food allergy appears to be less common when compared with developed countries. The variations in the prevalence of food allergen sensitization cannot be explained by the differences in the degree of urbanization. Despite the high prevalence of food-specific IgE sensitization in India and rural China, food allergy is still extremely uncommon. In addition to IgE sensitization, other factors must play important roles resulting in the clinical manifestations of food allergies. (C) 2019 American Academy of Allergy, Asthma & Immunology Show less
Inferring a person's smoking habit and history from blood is relevant for complementing or replacing self-reports in epidemiological and public health research, and for forensic applications.... Show moreInferring a person's smoking habit and history from blood is relevant for complementing or replacing self-reports in epidemiological and public health research, and for forensic applications. However, a finite DNA methylation marker set and a validated statistical model based on a large dataset are not yet available. Employing 14 epigenome-wide association studies for marker discovery, and using data from six population-based cohorts (N = 3764) for model building, we identified 13 CpGs most suitable for inferring smoking versus non-smoking status from blood with a cumulative Area Under the Curve (AUC) of 0.901. Internal fivefold cross-validation yielded an average AUC of 0.897 +/- 0.137, while external model validation in an independent population-based cohort (N = 1608) achieved an AUC of 0.911. These 13 CpGs also provided accurate inference of current (average AUC(crossvalidation) 0.925 +/- 0.021, AUC(externalvalidation)0.914), former (0.766 +/- 0.023, 0.699) and never smoking (0.830 +/- 0.019, 0.781) status, allowed inferring pack-years in current smokers (10 pack-years 0.800 +/- 0.068, 0.796; 15 pack-years 0.767 +/- 0.102, 0.752) and inferring smoking cessation time in former smokers (5 years 0.774 +/- 0.024, 0.760; 10 years 0.766 +/- 0.033, 0.764; 15 years 0.767 +/- 0.020, 0.754). Model application to children revealed highly accurate inference of the true non- smoking status (6 years of age: accuracy 0.994, N = 355; 10 years: 0.994, N = 309), suggesting prenatal and passive smoking exposure having no impact on model applications in adults. The finite set of DNA methylation markers allow accurate inference of smoking habit, with comparable accuracy as plasma cotinine use, and smoking history from blood, which we envision becoming useful in epidemiology and public health research, and in medical and forensic applications. Show less
