Background: In order to improve medical care for uveal melanoma (UM) patients, we need to monitor disease and survival to guide our research efforts. We analyzed the data of UM patients who... Show moreBackground: In order to improve medical care for uveal melanoma (UM) patients, we need to monitor disease and survival to guide our research efforts. We analyzed the data of UM patients who underwent an enucleation at the Leiden University Medical Center over the last five decades and investigated trends in patient and tumor characteristics and survival. Methods: Data were collected from charts and pathology reports from all patients who underwent an enucleation for UM between 1973 and 2019 (n = 1,212), of which 1,066 were primary enucleations; data were analyzed according to five time periods: 1973-1979 (n = 209), 1980-1989 (n = 148), 1990-1999 (n = 174), 2000-2009 (n = 280), and 2010-2019 (n = 401). Results: Over time, mean patient age at the time of enucleation for UM increased from 54.9 to 64.7 years (p < 0.001), more tumors showed histopathological involvement of the ciliary body (p < 0.001), and were classified in a high TNM/AJCC class (p < 0.001). Overall, the 5- and 10-year UM-related survival rates were 0.68 and 0.59, respectively. Over time, survival showed no change in patients with tumors in AJCC stages I or III, with recently a slightly worse survival in stage II UM (p = 0.02). Conclusion: Between 1973 and 2019, we found similar rates of UM-related survival following enucleation, although we noticed a strong increase in more unfavorable patient and tumor characteristics over time, such as an older age and larger tumor size. The lack of improvement indicates that more research should take place to develop adjuvant treatments to prevent metastases and efficient treatments once metastases develop. Show less
Introduction: No studies have reported mental health symptom comparisons prior to and during COVID-19 in vulnerable medical populations.Objective: To compare anxiety and depression symptoms among... Show moreIntroduction: No studies have reported mental health symptom comparisons prior to and during COVID-19 in vulnerable medical populations.Objective: To compare anxiety and depression symptoms among people with a pre-existing medical condition and factors associated with changes.Methods: Pre-COVID-19 Scleroderma Patient-centered Intervention Network Cohort data were linked to COVID-19 data from April 2020. Multiple linear and logistic regression were used to assess factors associated with continuous change and >= 1 minimal clinically important difference (MCID) change for anxiety (PROMIS Anxiety 4a v1.0; MCID = 4.0) and depression (Patient Health Questionnaire-8; MCID = 3.0) symptoms, controlling for pre-COVID-19 levels.Results: Mean anxiety symptoms increased 4.9 points (95% confidence interval [CI] 4.0 to 5.7). Depression symptom change was negligible (0.3 points; 95% CI-0.7 to 0.2). Compared to France (N = 159), adjusted anxiety symptom change scores were significantly higher in the United Kingdom (N = 50; 3.3 points, 95% CI 0.9 to 5.6), United States (N = 128; 2.5 points, 95% CI 0.7 to 4.2), and Canada (N = 98; 1.9 points, 95% CI 0.1 to 3.8). Odds of >= 1 MCID increase were 2.6 for the United Kingdom (95% CI 1.2 to 5.7) but not significant for the United States (1.6, 95% CI 0.9 to 2.9) or Canada (1.4, 95% CI 0.7 to 2.5). Older age and adequate financial resources were associated with less continuous anxiety increase. Employment and shorter time since diagnosis were associated with lower odds of a >= 1 MCID increase.Conclusions: Anxiety symptoms, but not depression symptoms, increased dramatically during COVID-19 among people with a pre-existing medical condition. Show less
Maarse, B.C.E.; Loh, N.Y.; Karpe, F.; Rosendaal, F.R.; Heemst, D. van; Mook-Kanamori, D.O.; ... ; Noordam, R. 2020
Background and aims: Outdoor temperature and bright sunlight may directly and/or indirectly modulate systemic metabolism. We assessed the associations between outdoor temperature and bright... Show moreBackground and aims: Outdoor temperature and bright sunlight may directly and/or indirectly modulate systemic metabolism. We assessed the associations between outdoor temperature and bright sunlight duration with metabolomics.Methods and results: Cross-sectional analyses were undertaken in non-diabetic individuals from the Oxford BioBank (OBB; N = 6368; mean age 47.0 years, males 44%) and the Netherlands Epidemiology of Obesity (NEO; N = 5916; mean age 55.6 years, males 43%) study. Data on mean outdoor bright sunlight and temperature were collected from local weather stations in the week prior to blood sampling. Fasting serum levels of 148 metabolites, including 14 lipoprotein subclasses, were measured using NMR spectroscopy. Linear regression analyses were performed to assess the associations between mean outdoor temperature and bright sunlight duration with metabolomics adjusted for age, sex, body mass index, season and either outdoor temperature or bright sunlight. A higher mean outdoor temperature was associated with increased serum concentrations of lipoprotein (sub)particles (beta (SE) = 0.064 (0.018) SD per 5 degrees C, p = 5.03e(-4)) and certain amino acids such as phenylalanine (0.066 (0.016) SD, p = 6.44e(-05)) and leucine (0.111 (0.018) SD, p = 1.25e(-09)). In contrast, longer duration of bright sunlight was specifically associated with lower concentrations of very low-density lipoprotein (sub)particles (e.g., VLDL cholesterol (-0.024 (0.005) SD per 1-h bright sunlight, p = 8.06e(-6))). The direction of effects was generally consistent between the OBB and NEO, although effect sizes were generally larger in the OBB.Conclusions: Increased bright sunlight duration is associated with an improved metabolic profile whilst higher outdoor temperature may adversely impact cardiometabolic health. (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. Show less
The fact that most healthcare resources are spend on a small subgroup of patients with an unfavourable prognosis has long been recognized. Therefore change is needed in terms of an improved... Show moreThe fact that most healthcare resources are spend on a small subgroup of patients with an unfavourable prognosis has long been recognized. Therefore change is needed in terms of an improved identification of patients with an unfavourable prognosis, early in their treatment course, which may facilitate proactive approaches to improve outcomes. We discussed two conceptually distinct constructs of predictors of prognosis in order to improve the identification of patients with an unfavourable prognosis. First, the level of control of the chronic condition as a predictor could reflect to some extent the presence of a multitude of other risk factors. Second, information on early treatment response had better predictive ability for long-term outcomes and so acts as a proxy for treatment effectiveness. Treatment effectiveness depends on different aspects e.g. adequateness of initial treatment and/or drugs, the mutual trust between clinician and patient and behavioral aspects such as treatment adherence. Treatment response adds an insight that can be acted upon; guiding personalized decisions in the treatment plan. In conclusion, this thesis leads to improvement of personalized medicine and thereby could increase the efficient use of healthcare resources, with the early identification of patients at risk of an unfavourable prognosis. 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
The aim of this thesis was to unravel a selection of a multitude of potential causal pathways that may underlie the association between excess body fat and cardiovascular disease, such as... Show moreThe aim of this thesis was to unravel a selection of a multitude of potential causal pathways that may underlie the association between excess body fat and cardiovascular disease, such as adipokines, inflammation, HDL-cholesterol and postprandial triglyceride response, and cholesteryl ester transfer protein (CETP). We showed that hs-CRP and GlycA as measures of inflammation, adiponectin, and leptin are not associated with clinical and subclinical cardiovascular disease in the general population. However, all may be relevant markers of disease risk. Also, postprandial triglyceride excursions, genetically-determined CETP and HDL-cholesterol, while not related with subclinical atherosclerosis in the general population, may be interesting targets to pursue in women and men separately, and in subgroups of individuals at high-cardiovascular risk. Show less
BackgroundTo evaluate the association between crowding and transmission of viral respiratory infectious diseases, we investigated the change in transmission patterns of influenza and COVID-19... Show moreBackgroundTo evaluate the association between crowding and transmission of viral respiratory infectious diseases, we investigated the change in transmission patterns of influenza and COVID-19 before and after a mass gathering event (i.e., carnival) in the Netherlands.MethodsInformation on individual hospitalizations related to the 2017/2018 influenza epidemic were accessed from Statistics Netherlands. The influenza cases were stratified between non-carnival and carnival regions. Distributions of influenza cases were plotted with time and compared between regions. A similar investigation in the early outbreak of COVID-19 was also conducted using open data from the Dutch National Institute for Public Health and the Environment.ResultsBaseline characteristics between non-carnival and carnival regions were broadly similar. There were 13,836 influenza-related hospitalizations in the 2017/2018 influenza epidemic, and carnival fell about 1week before the peak of these hospitalizations. The distributions of new influenza-related hospitalizations per 100,000 inhabitants with time between regions followed the same pattern with a surge of new cases in the carnival region about 1week after carnival, which did not occur in the non-carnival region. The increase of new cases for COVID-19 in the carnival region exceeded that in the non-carnival region about 1week after the first case was reported, but these results warrant caution as for COVID-19 there were no cases reported before the carnival and social measures were introduced shortly after carnival.ConclusionIn this study, a mass gathering event (carnival) was associated with aggravating the spread of viral respiratory infectious diseases. Show less
Bongers-Karmaoui, M.N.; Jaddoe, V.W.V.; Roest, A.A.W.; Gaillard, R. 2020
Stress inducement by physical exercise requires major cardiovascular adaptations in both adults and children to maintain an adequate perfusion of the body. As physical exercise causes a stress... Show moreStress inducement by physical exercise requires major cardiovascular adaptations in both adults and children to maintain an adequate perfusion of the body. As physical exercise causes a stress situation for the cardiovascular system, cardiovascular exercise stress tests are widely used in clinical practice to reveal subtle cardiovascular pathology in adult and childhood populations with cardiac and cardiovascular diseases. Recently, evidence from small studies suggests that the cardiovascular stress response can also be used within research settings to provide novel insights on subtle differences in cardiovascular health in non-diseased adults and children, as even among healthy populations an abnormal response to physical exercise is associated with an increased risk of cardiovascular diseases. This narrative review is specifically focused on the possibilities of using the cardiovascular stress response to exercise combined with advanced imaging techniques in pediatric population-based studies focused on the early origins of cardiovascular diseases. We discuss the physiology of the cardiovascular stress response to exercise, the type of physical exercise used to induce the cardiovascular stress response in combination with advanced imaging techniques, the obtained measurements with advanced imaging techniques during the cardiovascular exercise stress test and their associations with cardiovascular health outcomes. Finally, we discuss the potential for cardiovascular exercise stress tests to use in pediatric population-based studies focused on the early origins of cardiovascular diseases. 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.
Najm, A.; Kostine, M.; Pauling, J.D.; Ferreira, A.C.; Stevens, K.; Smith, E.; ... ; Sepriano, A. 2020
Background Multidisciplinary collaboration is defined as a collective work involving multiple disciplines and is common in clinical care and research. Our aim was to describe current clinical and... Show moreBackground Multidisciplinary collaboration is defined as a collective work involving multiple disciplines and is common in clinical care and research. Our aim was to describe current clinical and research collaboration among young specialists and to identify unmet needs in this area. Methods An online survey was disseminated by email and social media to members of the EMerging EUlar NETwork, the Young Nephrologists' Platform, the Paediatric Rheumatology European Society Emerging Rheumatologists and Researchers and the European Academy of Allergy and Clinical Immunology Junior Members. Results Of 303 respondents from 36 countries, 61% were female, 21% were aged below 30 years and 67% were aged 31-40 years. Young rheumatologists were the most represented (39%), followed by young nephrologists (24%), young paediatricians (20%), young allergologists (11%) then young internists (3%) and 3% other specialities. Collaborations were reported frequently by phone and email, also by various combined clinics while common local multidisciplinary meetings were uncommon. 96% would like to develop clinical research collaborations and 69% basic research collaborations. The majority of young specialists would be interested in online (84%) and/or 1-2 days (85%) common courses including case discussion (81%) and training workshops (85%), as well as webinars recorded with several specialists on a specific disease (96%). Conclusions This collaborative initiative highlighted wishes from young specialists for developing (1) regular local multidisciplinary meetings to discuss complex patients, (2) clinical research collaboration with combined grants and (3) multidisciplinary online projects such as common courses, webinars and apps. Show less
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
Spek, L. van der; Sanglier, S.; Mabeya, H.M.; Akker, T. van den; Mertens, P.L.J.M.; Houweling, T.A.J. 2020
Background Caesarean section (C-section) rates are often low among the poor and very high among the better-off in low- and middle-income countries. We examined to what extent these differences are... Show moreBackground Caesarean section (C-section) rates are often low among the poor and very high among the better-off in low- and middle-income countries. We examined to what extent these differences are explained by medical need in an African context. Methods We analyzed electronic records of 12,209 women who gave birth in a teaching hospital in Kenya in 2014. C-section rates were calculated by socioeconomic position (SEP), using maternal occupation (professional, small business, housewife, student) as indicator. We assessed if women had documented clinical indications according to hospital guidelines and if socioeconomic differences in C-section rates were explained by indication. Results Indication for C-section according to hospital guidelines was more prevalent among professionals than housewives (16% vs. 9% of all births). The C-section rate was also higher among professionals than housewives (21.1% vs. 15.8% [OR 1.43; 95%CI 1.23-1.65]). This C-section rate difference was largely explained by indication (4.7 of the 5.3 percentage point difference between professionals and housewives concerned indicated C-sections, often with previous C-section as indication). Repeat C-sections were near-universal (99%). 43% of primary C-sections had no documented indication. Over-use was somewhat higher among professionals than housewives (C-section rate among women without indication: 6.6 and 5.5% respectively), which partly explained socioeconomic differences in primary C-section rate. Conclusions Socioeconomic differences in C-section rates can be largely explained by unnecessary primary C-sections and higher supposed need due to previous C-section. Prevention of unnecessary primary C-sections and promoting safe trial of labor should be priorities in addressing C-section over-use and reducing inequalities. Tweetable abstract Unnecessary primary C-sections and ubiquitous repeat C-sections drive overall C-section rates and C-section inequalities. Show less
Objectives Further knowledge about typical hand osteoarthritis (OA) characteristics is needed for the development of new classification criteria for hand OA.Methods In a cross-sectional multi... Show moreObjectives Further knowledge about typical hand osteoarthritis (OA) characteristics is needed for the development of new classification criteria for hand OA.Methods In a cross-sectional multi-centre international study, a convenience sample of patients from primary and secondary/tertiary care with a physician-based hand OA diagnosis (n = 128) were compared with controls with hand complaints due to inflammatory or non-inflammatory conditions (n = 70). We examined whether self-reported, clinical, radiographic and laboratory findings were associated with hand OA using logistic regression analyses. Discrimination between groups was assessed by calculating the area under receiver operating curves (AUC).Results Strong associations with hand OA were observed for radiographic osteophytes (OR = 1.62, 95% CI 1.40 to 1.88) and joint space narrowing (JSN) (OR = 1.57, 95% CI 1.36 to 1.82) in the distal interphalangeal (DIP) joints with excellent discrimination (AUC = 0.82 for both). For osteophytes and JSN, we found acceptable discrimination between groups in the proximal interphalangeal joints (AUC = 0.77 and 0.78, respectively), but poorer discrimination in the first carpometacarpal joints (AUC = 0.67 and 0.63, respectively). Painful DIP joints were associated with hand OA, but were less able to discriminate between groups (AUC = 0.67). Age and family history of OA were positively associated with hand OA, whereas negative associations were found for pain, stiffness and soft tissue swelling in metacarpophalangeal joints, pain and marginal erosions in wrists, longer morning stiffness, inflammatory biomarkers and autoantibodies.Conclusions Differences in symptoms, clinical findings, radiographic changes and laboratory tests were found in patients with hand OA versus controls. Radiographic OA features, especially in DIP joints, were best suited to discriminate between groups. Show less
Najm, A.; Alunno, A.; Sivera, F.; Ramiro, S.; Haines, C.; Working Grp Training Rheumatology 2020
Objectives To gain insight into current methods and practices for the assessment of competences during rheumatology training, and to explore the underlying priorities and rationales for competence... Show moreObjectives To gain insight into current methods and practices for the assessment of competences during rheumatology training, and to explore the underlying priorities and rationales for competence assessment.Methods We used a qualitative approach through online focus groups (FGs) of rheumatology trainers and trainees, separately. The study included five countries-Denmark, the Netherlands, Slovenia, Spain and the United Kingdom. A summary of current practices of assessment of competences was developed, modified and validated by the FGs based on an independent response to a questionnaire. A prioritising method (9 Diamond technique) was then used to identify and justify key assessment priorities.Results Overall, 26 participants (12 trainers, 14 trainees) participated in nine online FGs (2 per country, Slovenia 1 joint), totalling 12 hours of online discussion. Strong nationally (the Netherlands, UK) or institutionally (Spain, Slovenia, Denmark) standardised approaches were described. Most groups identified providing frequent formative feedback to trainees for developmental purposes as the highest priority. Most discussions identified a need for improvement, particularly in developing streamlined approaches to portfolios that remain close to clinical practice, protecting time for quality observation and feedback, and adopting systematic approaches to incorporating teamwork and professionalism into assessment systems.Conclusion This paper presents a clearer picture of the current practice on the assessment of competences in rheumatology in five European countries and the underlying rationale of trainers' and trainees' priorities. This work will inform EULAR Points-to-Consider for the assessment of competences in rheumatology training across Europe. Show less
Aims Data on the early course and use of systemic thrombolysis in pregnant women with pulmonary embolism associated or not with haemodynamic failure are scarce. We investigated these aspects using... Show moreAims Data on the early course and use of systemic thrombolysis in pregnant women with pulmonary embolism associated or not with haemodynamic failure are scarce. We investigated these aspects using the information from the German Nationwide Inpatient Registry (years 2005-2016). Methods and results In Germany, all diagnoses referring to hospitalized patients are coded according to the International Classification of Diseases and Related Health Problems, 10th Revision with German Modification. We analysed data of pregnant women aged 18-50 years for whom the following diagnoses were recorded during hospitalization: (i) pulmonary embolism (I26) during pregnancy or peripartum (O09) or (ii) obstetric thromboembolism (O88.2). Haemodynamic failure at any time during the in-hospital stay was defined as need for cardiopulmonary resuscitation (OPS code 8-77) or the presence of shock (International Classification of Diseases and Related Health Problems, 10th Revision with German Modification code R57). The primary study outcome was in-hospital death. A total of 8 271 327 births were registered in Germany from 2005 to 2016. During this 12 year time period, there were 1846 hospitalizations for pregnancy-associated pulmonary embolism in patients aged 18-50, corresponding to 2.2 [95% confidence interval (CI): 2.1-2.3] cases every 10 000 births and 0.2% of all hospitalizations for pulmonary embolism in Germany. The median age was 31 years, and the median length of hospitalization was 8 days. A total of 63 deaths were reported, corresponding to an overall in-hospital fatality rate of 3.4% (95% CI: 2.7-4.4) and a pulmonary embolism-related mortality rate of 0.8 (95% CI: 0.6-1.0) per 100 000 (live) births per year. Pulmonary embolism-related deaths in hospitalized pregnant women represented 14% of all maternal deaths recorded in Germany between 2005 and 2016. A total of 135 (7.3%) women had haemodynamic failure, of whom 51 (37.8%) received systemic thrombolysis and 50 (37.0%) died. Conclusions Pulmonary embolism-related fatality remains substantial in pregnant women with pulmonary embolism and represents a frequent cause of maternal mortality. The use of systemic thrombolysis was reported in one third of pregnant women with pulmonary embolism and haemodynamic failure. Better preventive and management strategies should be urgently implemented in this vulnerable patient group. Show less
Purpose Rib fractures following thoracic trauma are frequently encountered injuries and associated with a significant morbidity and mortality. The aim of this study was to provide current data on... Show morePurpose Rib fractures following thoracic trauma are frequently encountered injuries and associated with a significant morbidity and mortality. The aim of this study was to provide current data on the epidemiology, in-hospital outcomes and 30-day mortality of rib fractures, and to evaluate these results for different subgroups. Methods A nationwide retrospective cohort study was performed with the use of the Dutch Trauma Registry which covers 99% of the acutely admitted Dutch trauma population. All patients aged 18 years and older admitted to the hospital between January 2015 and December 2017 with one or more rib fractures were included. Incidence rates were calculated using demographic data from the Dutch Population Register. Subgroup analyses were performed for flail chest, polytrauma, primary thoracic trauma, and elderly patients. Results A total of 14,850 patients were admitted between 2015 and 2017 with one or more rib fractures, which was 6.0% of all trauma patients. Of these, 573 (3.9%) patients had a flail chest, 4438 (29.9%) were polytrauma patients, 9273 (63.4%) were patients with primary thoracic trauma, and 6663 (44.9%) were elderly patients. The incidence rate of patients with rib fractures for the entire cohort was 29 per 100.000 person-years. The overall 30-day mortality was 6.9% (n = 1208) with higher rates observed in flail chest (11.9%), polytrauma (14.8%), and elderly patients (11.7%). The median hospital length of stay was 6 days (IQR, 3-11) and 37.3% were admitted to the intensive care unit (ICU). Conclusions Rib fractures are a relevant and frequently occurring problem among the trauma population. Subgroup analyses showed that there is a substantial heterogeneity among patients with rib fractures with considerable differences regarding the epidemiology, in-hospital outcomes, and 30-day mortality. Show less
Pituitary tumors are not rare if prevalence rates from autopsy or radiological series are considered; approximately 0.5% of all pituitary adenomas will come to medical attention. Less than 0.1% of... Show morePituitary tumors are not rare if prevalence rates from autopsy or radiological series are considered; approximately 0.5% of all pituitary adenomas will come to medical attention. Less than 0.1% of these pituitary adenomas will become malignant, and probably around 0.5% of all detected adenomas will display an aggressive course. However, the exact incidence of both aggressive pituitary adenomas and pituitary carcinomas is unknown, as most data come from series with selected patients, such as surgically treated patients, which is likely not a reflection of all patients with a pituitary adenoma. An aggressive pituitary adenoma is not well-defined; even though an overarching definition, capturing both immunohistochemical and clinical characteristics is probably not waterproof, adoption of a widely accepted definition will be very helpful to harmonize research and establish more reliable epidemiological data. Show less
The prevalence of obesity is increasing worldwide. In particular abdominal obesity is a well-established risk factor for cardiometabolic diseases. The excess risk of abdominal obesity is due to fat... Show moreThe prevalence of obesity is increasing worldwide. In particular abdominal obesity is a well-established risk factor for cardiometabolic diseases. The excess risk of abdominal obesity is due to fat in the visceral area and in and around the organs (ectopic fat), such as in the liver. The main aim of this thesis was therefore to study whether lifestyle can reduce the amount of visceral fat and liver fat.Firstly, in a systematic review and meta-analysis of randomized controlled trials, we concluded that a diet high in proteins decreases liver fat compared with a diet high in carbohydrates. A diet high in fat did not lead to changes in liver fat compared with a diet high in carbohydrates. Within fat types, saturated fat leads to more liver fat accumulation than unsaturated fat. Secondly, we studied diet at multiple levels in the Netherlands Epidemiology of Obesity study, which is a population based cohort study of middle-aged men and women with directly assessed measured of adiposity. When studying food groups rather than nutrients, we observed that consumption of sweet snacks are positively associated with liver fat content, also after taking into account total body fat. Likewise, consumption of fruit and vegetables and plant-based fats and oils was associated with less visceral fat. A better adherence to the current Dutch dietary guidelines, as indicated by a higher score on the 15-component Dutch Healthy Diet Index, was associated with less total body fat, less visceral fat and liver fat. The associations with visceral fat and liver fat remained present after taking into account total body fat, indicating that the associations are indeed specific for visceral and liver fat rather than merely representing associations with overall adiposity. Associations were not driven by one component in particular, indicating the importance of an overall healthy diet. When we studied alcohol intake separately, each additional serving of alcoholic beverages per day was also associated with more liver fat. Moreover, replacing one alcoholic serving with one non-alcoholic serving was associated with less liver fat. Replacing the same amount of calories of alcoholic beverages with sugar sweetened beverages was equally associated with liver fat, whereas replacement with milk was associated with less liver fat. Lastly, we observed that objectively measured sedentary time was associated with more total body fat, visceral fat and liver fat. Replacing 30 minutes of sedentary time per day with moderate to vigorous physical activity, but not light physical activity was associated with less total body fat, visceral fat and liver fat. These associations with visceral fat and liver fat disappeared after additional adjustment for total body fat, indicating that there is no extra effect on visceral fat and liver fat beyond effects via total body fat.Results described in this thesis hint towards the importance of considering diet as a whole, instead of separate components, which is in line with the current dietary guidelines. Sedentary behaviour should be replaced with moderate to vigorous physical activity rather than light physical activity. Alcohol should not be replaced with sugar sweetened beverages, but rather with milk, coffee or tea. 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
