[Vulnerable groups for COVID-19 control measures]. / COVID-19: over welke mensen maken we ons extra zorgen?

The COVID-19 outbreak and its control measures affect the life, livelihood and way of life of many. Vulnerable groups may require different information, practical, emotional and financial support, depending on their specific vulnerabilities. Early reports for the Dutch government on the impacts of COVID-19 control measures were used for drafting a preliminary overview of vulnerable groups and their vulnerabilities. The overview may serve as first step towards a scoping review and be of use in the professional discussion for targeting and finetuning the support to the groups most in need.

Electronic characterization of redox (non)-innocent Fe2S2 reference systems: a multi K-edge X-ray spectroscopic study.

Di-iron dithiolate hydrogenase model complexes are promising systems for electrocatalytic production of dihydrogen and have therefore been spectroscopically and theoretically investigated in this study. The direct effect of ligand substitution on the redox activity of the complex is examined. In order to understand and eventually optimize such systems, we characterised both metal and ligand in detail, using element specific X-ray absorption Fe- and S-K edge XAS. The (electronic) structure of three different [Fe2S2] hydrogenase systems in their non-reduced state was investigated. The effect of one- and two-electron reduction on the (electronic) structure was subsequently investigated. The S K-edge XAS spectra proved to be sensitive to delocalization of the electron density into the aromatic ring. The earlier postulated charge and spin localization in these complexes could now be measured directly using XANES. Moreover, the electron density (from S K-edge XANES) could be directly correlated to the Fe-CO bond length (from Fe K-edge EXAFS), which are in turn both related to the reported catalytic activity of these complexes. The delocalization of the electron density into the conjugated π-system of the aromatic moieties lowers the basicity of the diiron core and since protonation occurs at the diiron (as a rate determining step), lowering the basicity decreases the extent of protonation and consequently the catalytic activity.

Spectroscopic and theoretical investigation of the [Fe2(bdt)(CO)6] hydrogenase mimic and some catalyst intermediates.

In [Fe-Fe] hydrogenase mimic systems the ene-1,2-dithiolene ligands play an important role in the stabilisation of the redox-active metal center. This is demonstrated by the benzenedithiolene (bdt) analogue, featuring six terminal carbonyl ligands connected to a di-iron metal center, i.e. [Fe2(bdt)(CO)6]. Here we present a combined experimental and theoretical study that elucidates key intermediates [Fe2(bdt)(CO)6]1- and [Fe2(bdt)(µ-CO)(CO)5]2- in the electrocatalytic production of dihydrogen. A DFT study shows that [Fe2(bdt)(CO)6]1- is the kinetic product after the first one electron reduction, while the previously proposed bridging intermediate species [Fe2(bdt)(µ-CO)(CO)5]1- is kinetically inaccessible. The doubly reduced species [Fe2(bdt)(µ-CO)(CO)5]2- was for the first time structurally characterized using EXAFS. XANES analysis confirms the existence of reduced iron zero species and confirms the distorted geometry that was suggested by the DFT calculations. Combining IR, UV-vis and XAS spectroscopic results with TD-DFT and FEFF calculations enabled us to assign the key-intermediate [Fe2(bdt)(CO)6]2-. This study emphasizes the strengths of combining computational chemistry with advanced spectroscopy techniques.

Medieval women's early involvement in manuscript production suggested by lapis lazuli identification in dental calculus.

During the European Middle Ages, the opening of long-distance Asian trade routes introduced exotic goods, including ultramarine, a brilliant blue pigment produced from lapis lazuli stone mined only in Afghanistan. Rare and as expensive as gold, this pigment transformed the European color palette, but little is known about its early trade or use. Here, we report the discovery of lapis lazuli pigment preserved in the dental calculus of a religious woman in Germany radiocarbon-dated to the 11th or early 12th century. The early use of this pigment by a religious woman challenges widespread assumptions about its limited availability in medieval Europe and the gendered production of illuminated texts.

Intraoperative and postoperative risk factors for anastomotic leakage and pneumonia after esophagectomy for cancer.

Morbidity and mortality after esophagectomy are often related to anastomotic leakage or pneumonia. This study aimed to assess the relationship of intraoperative and postoperative vital parameters with anastomotic leakage and pneumonia after esophagectomy. Consecutive patients who underwent transthoracic esophagectomy with cervical anastomosis for esophageal cancer from January 2012 to December 2013 were analyzed. Univariable and multivariable logistic regression analyses were used to determine potential associations of hemodynamic and respiratory parameters with anastomotic leakage or pneumonia. From a total of 82 included patients, 19 (23%) developed anastomotic leakage and 31 (38%) experienced pneumonia. The single independent factor associated with an increased risk of anastomotic leakage in multivariable analysis included a lower minimum intraoperative pH (OR 0.85, 95% CI 0.77-0.94). An increased risk of pneumonia was associated with a lower mean arterial pressure (MAP) in the first 12 hours after surgery (OR 0.93, 95% CI 0.86-0.99) and a higher maximum intraoperative pH (OR 1.14, 95% CI 1.02-1.27). Interestingly, no differences were noted for the MAP and inotrope requirement between patients with and without anastomotic leakage. A lower minimum intraoperative pH (below 7.25) is associated with an increased risk of anastomotic leakage after esophagectomy, whereas a lower postoperative average MAP (below 83 mmHg) and a higher intraoperative pH (above 7.34) increase the risk of postoperative pneumonia. These parameters indicate the importance of setting strict perioperative goals to be protected intensively.

Estimating the risk of dengue transmission from Dutch blood donors travelling to Suriname and the Dutch Caribbean.

BACKGROUND: The risk of dengue transmitted by travellers is known. Methods to estimate the transmission by transfusion (TT) risk from blood donors travelling to risk areas are available, for instance, the European Up-Front Risk Assessment Tool (EUFRAT). This study aimed to validate the estimated risk from travelling donors obtained from EUFRAT. METHODS: Surveillance data on notified dengue cases in Suriname and the Dutch Caribbean islands (Aruba, Curaçao, St. Maarten, Bonaire, St. Eustatius and Saba) in 2001-2011 was used to calculate local incidence rates. Information on travel and donation behaviour of Dutch donors was collected. With the EUFRAT model, the TT risks from Dutch travelling donors were calculated. Model estimates were compared with the number of infections in Dutch travellers found by laboratory tests in the Netherlands. RESULTS: The expected cumulative number of donors becoming infected during travels to Suriname and the Dutch Caribbean from 2001 to 2011 was estimated at 5 (95% CI, 2-11) and 86 (45-179), respectively. The infection risk inferred from the laboratory-based study was 19 (9-61) and 28 (14-92). Given the independence of the data sources, these estimates are remarkably close. The model estimated that 0·02 (0·001-0·06) and 0·40 (0·01-1·4) recipients would have been infected by these travelling donors. CONCLUSIONS: The EUFRAT model provided an estimate close to actual observed number of dengue infections. The dengue TT risk among Dutch travelling donors can be estimated using basic transmission, travel and donation information. The TT risk from Dutch donors travelling to Suriname and the Dutch Caribbean is small.

Serial and panel analyses of biomarkers do not improve the prediction of bacteremia compared to one procalcitonin measurement.

OBJECTIVES: We evaluated the value of a single biomarker, biomarker panels, biomarkers combined with clinical signs of sepsis, and serial determinations of biomarkers in the prediction of bacteremia in patients with sepsis. METHODS: Adult patients visiting the emergency department because of a suspected infection with at least two of the following symptoms: temperature >38.3°C or <36°C, heart rate >90/min, respiratory rate >20/min, chills, altered mental status, systolic blood pressure <90 mmHg, MAP <65 mmHg, and hyperglycemia in the absence of diabetes mellitus were included. Procalcitonin (PCT), interleukin-6 (IL-6), lipopolysaccharide-binding protein (LBP), C-reactive protein (CRP) were measured, and two blood cultures were taken. The analyses included: (1) determination of the biomarker with the highest predictive value for bacteremia and to examine the predictive value of this biomarker in combination with other biomarkers; (2) analysis of the best biomarker data in combination with clinical signs of sepsis; and (3) analysis of serial determinations of the best biomarker. RESULTS: Of 342 included patients, PCT had the best predictive value for bacteremia with an area under the curve of 0.80, sensitivity 89%, specificity 58%. The predictive value of a combination of PCT plus a panel of other biomarkers, clinical signs, or analysis of serial PCT levels did not lead to a significant improvement of the predictive value of PCT alone. CONCLUSIONS: The ability of PCT to predict bacteremia in patients with sepsis does not further improve when combined with IL-6, LBP, CRP, clinical signs, or serial measurements. Naturally, this does not exclude that a panel of other biomarkers may lead to different results.

Non-adherence to antimicrobial treatment guidelines results in more broad-spectrum but not more appropriate therapy.

Mortality in patients admitted with sepsis is high and the increasing incidence of infections with multiresistant bacteria is a worldwide problem. Many hospitals have local antimicrobial guidelines to assure effective treatment and limit the use of broad-spectrum antibiotics, thereby reducing the selection of resistant bacteria. We evaluated adherence to the antimicrobial treatment guidelines of our hospital in patients presenting to the emergency department (ED) with sepsis and assessed the in vitro susceptibility of isolated pathogens to the guideline-recommended treatment and the prescribed treatment. We included all adult patients with a known or suspected infection and two or more extended systemic inflammatory response syndrome (SIRS) criteria. Patients who did not receive antimicrobial treatment, presented with infections not included in the guidelines, or had more than one possible focus of infection were excluded. A total of 276 ED visits (262 patients) were included. Guideline-concordant treatment was prescribed in 168 visits (61%). In the case of guideline-disconcordant treatment, 87% was more broad-spectrum than guideline-recommended treatment. A microbiological diagnosis was established in 96 visits (35%). The susceptibility of the pathogens isolated from patients treated with guideline-concordant treatment (n=68) and guideline-disconcordant treatment (n=28) to guideline-recommended treatment (91% versus 89%) and to prescribed treatment (91% versus 93%) was similar (p=0.77 and p=0.79, respectively). In conclusion, non-adherence to the guidelines occurred frequently and resulted in more broad-spectrum empirical therapy. This did not result in a higher rate of susceptibility of the isolated pathogens to the prescribed empirical therapy.

The effects of implementation of the Surviving Sepsis Campaign in the Netherlands.

To reduce unintentional and avoidable adverse events in patients in hospitals in the Netherlands, a patient safety agency (VMS) programme was launched in 2008. Among the VMS topics, the programme 'optimal therapy in severe sepsis', according to the international Surviving Sepsis Campaign (SSC), aims to improve early diagnosis and treatment of sepsis to reduce sepsis mortality by 15% before the end of 2012. We analysed compliance data submitted to the international SSC database from the Netherlands and compared these data with published international SS C results. Data of 863 patients, representing 6% of the international data (n=14,209), were used for analysis. In the Netherlands, the resuscitation bundle compliance improved significantly from 7% at baseline to 27% after two years (p=0.002). Internationally, the resuscitation bundle compliance increased significantly from 11 to 31% (p.

Epidemiology, surveillance and control of infectious diseases in the European overseas countries and territories, 2011.

The 25 European overseas countries and territories (OCTs) are closely associated with the European Union (EU) through the four related UE Member States: Denmark, France, the Netherlands and the United Kingdom. In 2008 and 2009, these four EU Member States, in association with the European Centre for Disease Prevention and Control (ECDC), reviewed the OCTs' needs, with the objectives of documenting their capacity to prevent and respond to infectious diseases outbreaks, and identifying deficiencies. This Euroroundup is based on the review's main findings, and presents an overview of the OCTs' geography and epidemiology, briefly introduces the legal basis on which they are linked to the EU and describes the surveillance and infectious disease response systems. As a result of their diversity the OCTs have heterogeneous epidemiological profiles. A common factor, however, is that the main burden of disease is non-communicable. Nevertheless, OCTs remain vulnerable to infectious diseases outbreaks. Their capacity for surveillance, early detection and response to such outbreaks is generally limited, with laboratory capacity issues and lack of human resources. Avenues for capacity strengthening should be explored by the OCTs and the related EU Member States, in collaboration with ECDC and regional public health networks where these exist.

Increasing maternal age at first pregnancy planning: health outcomes and associated costs.

OBJECTIVES: To describe the consequences in terms of health outcomes, care and associated healthcare costs for three hypothetical cohorts of women planning their first pregnancy at a fixed, different age. DESIGN: Decision model based on data from perinatal registries and the literature. SETTING: The Netherlands. POPULATION: 3 hypothetical cohorts of 100, 000 women aged 23, 29 and 36 years, planning a first pregnancy. MAIN OUTCOME MEASURES: Live birth, pregnancy complications for mother and child and associated healthcare costs. Results For the three cohorts of 23-, 29- and 36-year-old women, 1.6%, 4.6% and 14% of women would not succeed in an ongoing pregnancy (spontaneous or after assisted reproductive technology). The cohort aged 36 gave 9% more miscarriages, 8% more fertility treatment and 1.4% more multiple births than the cohort aged 29. The proportion of caesarean sections among low risk women was 4.9% and 11% higher respectively for the cohorts aged 29 and 36, compared with the cohort aged 23 at start. Eventually, 98%, 95% and 85% of the women in each of the three cohorts gave live birth. The costs for the two older cohorts were €415 and €1662 higher per ongoing pregnancy than the cohort aged 23 years. CONCLUSIONS: Spontaneous conception and mode of delivery are most susceptible to increasing maternal age leading to involuntary childlessness and non-spontaneous labour. The increase in assisted reproduction technology, twin pregnancies and delivery complications results in higher costs along with fewer ongoing pregnancies at higher age.

Ethnic differences in stillbirth and early neonatal mortality in The Netherlands.

BACKGROUND: Ethnic disparities in perinatal mortality are well known. This study aimed to explore the contribution of demographic, socioeconomic, health behavioural and pre-existent medical risk factors among different ethnic groups on fetal and early neonatal mortality. METHODS: We assessed perinatal mortality from 24.0 weeks' gestation onwards in 554 234 singleton pregnancies of nulliparous women in the linked Netherlands Perinatal Registry over the period 2000-2006. Logistic regression modelling was used. RESULTS: Considerable ethnic differences in perinatal mortality exist especially in fetal mortality. Maternal age, socioeconomic status and pre-existent diseases could not explain these ethnic differences. Late booking visit could explain some differences. Compared with the Dutch, African women had an increased fetal mortality risk of OR 1.7 (95% CI 1.4 to 2.1); South Asian women, 1.8 (1.4 to 2.3); other non-Western women, 1.3 (1.1 to 1.6) and Turkish/Moroccan women, 1.3 (1.1 to 1.4). The risk on early neonatal mortality was only increased in other non-Western women, OR 1.3 (1.0 to 1.8). Ethnic differences were even present in the women without risk factors including preterm births. Mortality risk for East Asian and other Western women was lower or comparable with the Dutch. CONCLUSION: Important ethnic differences in fetal mortality exist, especially among women of African and South Asian origin. Ethnic minorities should be more acquainted with the significance of early start of prenatal care. Tailored prenatal care for women with African and South Asian origin seems necessary. More research on underlying cause of deaths is needed by ethnic group.

Travel time from home to hospital and adverse perinatal outcomes in women at term in the Netherlands.

OBJECTIVE: To study the effect of travel time, at the start or during labour, from home to hospital on mortality and adverse outcomes in pregnant women at term in primary and secondary care. DESIGN: Population-based cohort study from 2000 up to and including 2006. SETTING: The Netherlands Perinatal Registry. POPULATION: A total of 751,926 singleton term hospital births. METHODS: We assessed the impact of travel time by car, calculated from the postal code of the woman's residence to the 99 maternity units, on neonatal outcome. Logistic regression modelling with adjustments for gestational age, maternal age, parity, ethnicity, socio-economic status, urbanisation, tertiary care centres and volume of the hospital was used. MAIN OUTCOME MEASURES: Mortality (intrapartum, and early and late neonatal mortality) and adverse neonatal outcomes (mortality, Apgar <4 and/or admission to a neonatal intensive care unit). RESULTS: The mortality was 1.5 per 1000 births, and adverse outcomes occurred in 6.0 per 1000 births. There was a positive relationship between longer travel time (≥20 minutes) and total mortality (OR 1.17, 95% CI 1.002-1.36), neonatal mortality within 24 hours (OR 1.51, 95% CI 1.13-2.02) and with adverse outcomes (OR 1.27, 95% CI 1.17-1.38). In addition to travel time, both delivery at 37 weeks of gestation (OR 2.23, 95% CI 1.81-2.73) or 41 weeks of gestation (OR 1.52, 95% CI 1.29-1.80) increased the risk of mortality. CONCLUSIONS: A travel time from home to hospital of 20 minutes or more by car is associated with an increased risk of mortality and adverse outcomes in women at term in the Netherlands. These findings should be considered in plans for the centralisation of obstetric care.

Peripheral site ligand-oxime conjugates: A novel concept towards reactivation of nerve agent-inhibited human acetylcholinesterase.

A conceptually novel approach to the design of reactivators of nerve agent-inhibited acetylcholinesterase (AChE) is presented. The concept comprises the linkage of a peripheral site ligand via a spacer to a reactivating moiety with the eventual goal to develop non-ionic reactivators with sufficient affinity for AChE to induce reactivation and potentially improved blood-brain barrier penetration. Herein, the first step towards that goal-the synthesis and biological evaluation of a peripheral site ligand conjugated to a charged pyridinium oxime is discussed. It was found, that the introduction of the peripheral site ligand not only increased affinity of the construct for AChE but also enhanced reactivation of nerve agent-inhibited AChE.

Indicators for intervention during the expulsive second-stage arrest of labour.

OBJECTIVE: To identify antepartum and intrapartum indicators of obstetric interventions during the expulsive second-stage arrest of labour. DESIGN: Retrospective cohort study. SETTING: The Netherlands. POPULATION: A cohort of 389,086 women with singleton, cephalic, term, live-birth deliveries from 2002 to 2004 who had entered the expulsive second stage of labour. Of all these deliveries, 37,899 (9.7%) were complicated by expulsive second-stage arrest of labour. Women with a prior Caesarean section or women undergoing an elective Caesarean section were excluded. METHODS: All deliveries in the Netherlands from 2002 to 2004 were registered in the Netherlands Perinatal Registry, which contains the linked and validated data of three databases. Uni- and multivariable logistic regression analyses were performed. MAIN OUTCOME MEASURES: Ante- and intrapartum indicators for interventions during expulsive second-stage arrest of labour. RESULTS: Primiparous delivery was the most important antepartum indicator for intervention during expulsive second-stage arrest. Using multivariable analysis the following antepartum indicators were associated with intervention for expulsive second-stage arrest of primiparous labour: maternal age, gestational age, diabetes, hypertension and labour induction. Prominent intrapartum indicators for primiparous deliveries were fetal head position and oxytocin augmentation. CONCLUSION: Multiple significant antepartum and intrapartum indicators associated with intervention for expulsive second-stage arrest of labour were identified in this large retrospective study. Prominent were the associations of parity, maternal age and fetal head position with expulsive second-stage arrest. The identified factors should be further evaluated in prospective studies that aim to develop prediction models.

Internal medicine residents' knowledge about sepsis: effects of a teaching intervention.

The short- and long-term effects of a single teaching intervention for internal medicine residents are not known. Since sepsis is a prevalent and important disease and both therapeutic and diagnostic interventions have been protocolized, we investigated the effects of a sepsis-based single teaching intervention. A prospective before-and-after education study was performed among residents who attended a regional professional training for internal medicine. All residents who participated were invited to complete a questionnaire about the assessment of symptoms and the diagnosis and treatment of sepsis. The questionnaire was filled out before, directly after, and four to six months after the teaching intervention. The overall questionnaire score was expressed on a 0 to 10 scale. A total of 253 questionnaires from 109 training-grade doctors were collected. At baseline, the 'assessment of symptoms of sepsis' score was significantly lower than the 'diagnosis and treatment' score. Following the education session, training-grade doctors' knowledge about sepsis definitions and diagnosis and treatment of sepsis increased from (mean +/- SD ) 6.1 +/- 1.6 to 8.2 +/- 1.2 (p<0.0001. Moreover, four to six months after the teaching intervention, this effect was sustained (p<0.0001 compared with test 1), resulting in a mean score of 7.6 +/- 1.1. Our single teaching intervention resulted in improved and sustained knowledge on the assessment of symptoms, diagnosis and treatment of sepsis.

Anonymous non-response analysis in the ABCD cohort study enabled by probabilistic record linkage.

Selective non-response is an important threat to study validity as it can lead to selection bias. The Amsterdam Born Children and their Development study (ABCD-study) is a large cohort study addressing the relationship between life style, psychological conditions, nutrition and sociodemographic background of pregnant women and their children's health. Possible selective non-response and selection bias in the ABCD-study were analysed using national perinatal registry data. ABCD-study data were linked with national perinatal registry data by probabilistic medical record linkage techniques. Differences in the prevalence of relevant risk factors (sociodemographic and care-related factors) and birth outcomes between respondents and non-respondents were tested using Pearson chi-squared tests. Selection bias (i.e. bias in the association between risk factors and specific outcomes) was analysed by regression analysis with and without adjustment for participation status. The ABCD non-respondents were significantly younger, more often non-western, and more often multiparae. Non-respondents entered antenatal care later, were more often under supervision of an obstetrician and had a spontaneous delivery more often. Non-response however, was not significantly associated with preterm birth (odds ratio 1.10; 95% CI 0.93, 1.29) or low birthweight (odds ratio 1.16; 95% CI 0.98, 1.37) after adjustment for sociodemographic risk factors. The associations found between risk factors and adverse pregnancy outcomes were similar for respondents and non-respondents. Anonymised record linkage of cohort study data with national registry data indicated that selective non-response was present in the ABCD-study, but selection bias was acceptably low and did not influence the main study questions.

Local structure of reaction intermediates probed by time-resolved x-ray absorption near edge structure spectroscopy.

A method for the analysis of time-resolved x-ray absorption near edge structure (XANES) spectra is proposed. It combines principal component analysis of the series of experimental spectra, multidimensional interpolation of theoretical XANES as a function of structural parameters, and ab initio XANES calculations. It allows to determine the values of structural parameters for intermediates of chemical reactions and the concentrations of different states as a function of time. This approach is tested using numerically generated data and its possibilities and limitations are discussed. The application of this method to a reaction with methylrhenium trioxide catalyst in solution, for which experimental data were measured using stopped-flow energy-dispersive x-ray absorption spectroscopy technique, is demonstrated. Possibilities and limitations of this experimental technique are also discussed.

Decreasing perinatal mortality in The Netherlands, 2000-2006: a record linkage study.

BACKGROUND: The European PERISTAT-1 study showed that, in 1999, perinatal mortality, especially fetal mortality, was substantially higher in The Netherlands than in other European countries. The aim of this study was to analyse the recent trend in Dutch perinatal mortality and the influence of risk factors. METHODS: A nationwide retrospective cohort study of 1,246,440 singleton births in 2000-2006 in The Netherlands. The source data were available from three linked registries: the midwifery registry, the obstetrics registry and the neonatology/paediatrics registry. The outcome measure was perinatal mortality (fetal and early neonatal mortality). The trend was studied with and without risk adjustment. Five clinical distinct groups with different perinatal mortality risks were used to gain further insight. RESULTS: Perinatal mortality among singletons declined from 10.5 to 9.1 per 1000 total births in the period 2000-2006. This trend remained significant after full adjustment (odds ratio 0.97; 95% CI 0.96 to 0.98) and was present in both fetal and neonatal mortality. The decline was most prominent among births complicated by congenital anomalies, among premature births (32.0-36.6 weeks) and among term births. Home births showed the lowest mortality risk. CONCLUSIONS: Dutch perinatal mortality declined steadily over this period, which could not be explained by changes in known risk factors including high maternal age and non-western ethnicity. The decline was present in all risk groups except in very premature births. The mortality level is still high compared with European standards.

The role of inflammation on atherosclerosis, intermediate and clinical cardiovascular endpoints in type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with increased cardiovascular morbidity and mortality. Sub-clinical systemic inflammation is often present in T2DM patients. Systemic inflammation has also been implicated in the pathophysiology of atherosclerosis. This review investigates the direct evidence present in literature for the effect of inflammation on atherosclerosis, specifically in the setting of T2DM. Special emphasis is given to the pathogenesis of atherosclerosis as well as intermediate and clinical cardiovascular endpoints. The important role of deteriorated endothelial function in T2DM was excluded from the analysis. METHODS: Extensive literature searches were performed using the PubMed and Web of Science databases. Articles were identified, retrieved and accepted or excluded based on predefined criteria. RESULTS: Substantial evidence was found for an important inflammatory component in the pathogenesis of atherosclerosis in T2DM, demonstrated by inflammatory changes in plaque characteristics and macrophage infiltration. Most epidemiologic studies found a correlation between inflammation markers and intermediate cardiovascular endpoints, especially intima-media thickness. Several, but not all clinical trials in T2DM found that reducing sub-clinical inflammation had a beneficial effect on intermediate endpoints. When regarding cardiovascular events however, current literature consistently indicates a strong relationship between inflammation and clinical endpoints in subjects with T2DM. CONCLUSION: Current literature provides direct evidence for a contribution of inflammatory responses to the pathogenesis of atherosclerosis in T2DM. The most consistent relation was observed between inflammation and clinical endpoints.