Routinization of prenatal screening with the non-invasive prenatal test: pregnant women's perspectives.

Due to the favorable test characteristics of the non-invasive prenatal test (NIPT) in the screening of fetal aneuploidy, there has been a strong and growing demand for implementation. In the Netherlands, NIPT is offered within a governmentally supported screening program as a first-tier screening test for all pregnant women (TRIDENT-2 study). However, concerns have been raised that the test's favorable characteristics might lead to uncritical use, also referred to as routinization. This study addresses women's perspectives on prenatal screening with NIPT by evaluating three aspects related to routinization: informed choice, freedom to choose and (personal and societal) perspectives on Down syndrome. Nationwide, a questionnaire was completed by 751 pregnant women after receiving counseling for prenatal screening. Of the respondents, the majority (75.5%) made an informed choice for prenatal screening as measured by the multidimensional measure of informed choice (MMIC). Education level and religious affiliation were significant predictors of informed choice. The main reason to accept screening was "seeking reassurance" (25.5%), and the main reason to decline was "every child is welcome" (30.6%). The majority of respondents (87.7%) did not perceive societal pressure to test. Differences between test-acceptors and test-decliners in personal and societal perspectives on Down syndrome were found. Our study revealed high rates of informed decision-making and perceived freedom to choose regarding fetal aneuploidy screening, suggesting that there is little reason for concern about routinization of NIPT based on the perspectives of Dutch pregnant women. Our findings highlight the importance of responsible implementation of NIPT within a national screening program.

Aetiology of acute febrile illness in children in a high malaria transmission area in West Africa.

OBJECTIVES: Areas with declining malaria transmission in sub-Saharan Africa have recently witnessed important changes in the aetiology of childhood acute febrile illness (AFI). We describe the aetiology of AFI in a high malaria transmission area in rural Burkina Faso. METHODS: In a prospective hospital-based diagnostic study, children aged 3 months to 15 years with AFI were recruited and assessed using a systematic diagnostic protocol, including blood cultures, whole blood PCR on a selection of bacterial pathogens, malaria diagnostics and a multiplex PCR on nasopharyngeal swabs targeting 21 viral and 4 bacterial respiratory pathogens. RESULTS: A total of 589 children with AFI were enrolled from whom an infectious disease was considered in 575 cases. Acute respiratory tract infections, malaria and invasive bacterial infections (IBI) accounted for 179 (31.1%), 175 (30.4%) and 75 (13%) of AFI cases respectively; 16 (21.3%) of IBI cases also had malarial parasitaemia. A viral pathogen was demonstrated from the nasopharynx in 157 children (90.7%) with respiratory tract symptoms. Of all children with viral respiratory tract infections, 154 (92.4% received antibiotics, whereas no antibiotic was provided in 13 (17%) of IBI cases. CONCLUSIONS: Viral respiratory infections are a common cause of childhood AFI in high malaria transmission areas, next to malaria and IBI. These findings highlight the importance of interventions to improve targeted treatment with antimicrobials. Most patients with viral infections received antibiotics unnecessarily, while a considerable number with IBI did not receive antibiotics.

Perinatal exposure of rats to the HIV drug efavirenz affects medial prefrontal cortex cytoarchitecture.

Efavirenz (EFV) is used for antiretroviral treatment of HIV infection, and successfully inhibits viral replication and mother-to-child transmission of HIV during pregnancy and childbirth. Unfortunately, the drug induces neuropsychiatric symptoms such as anxiety and depressed mood and potentially affects cognitive performance. EFV acts on, among others, the serotonin transporter and serotonin receptors that are expressed in the developing brain. Yet, how perinatal EFV exposure affects brain cytoarchitecture remains unclear. Here, we exposed pregnant and lactating rats to EFV, and examined in the medial prefrontal cortex (mPFC) of their adult offspring the effects of the maternal EFV exposure on cortical architecture. We observed a significant decrease in the number of cells, mainly mature neurons, in the infra/prelimbic and cingulate cortices of adult offspring. Next, we found an altered cortical cytoarchitecture characterized by a significant reduction in deep- and superficial-layer cells. This was accompanied by a sharp increase in programmed cell death, as we identified a significantly higher number of cleaved Caspase-3-positive cells. Finally, the serotonergic and dopaminergic innervation of the mPFC subdomains was increased. Thus, the perinatal exposure to EFV provoked in the mPFC of adult offspring cell death, significant changes in cytoarchitecture, and disturbances in serotonergic and dopaminergic innervation. Our results are important in the light of EFV treatment of HIV-positive pregnant women, and its effect on brain development and cognitive behavior.

Is asymptomatic bacteriuria associated with short cervical length in women with a singleton pregnancy, a secondary analysis of two national cohort studies with small embedded randomized controlled trials.

OBJECTIVE: To assess the association between asymptomatic bacteriuria (ASB) and short cervical length (CL), since they are both associated with preterm delivery. STUDY DESIGN: In two prospective multicentre cohort studies, pregnant women were screened for the presence of ASB and short CL (≤25 mm). We compared CL in women with and without ASB. Both studies had a small randomised clinical trial embedded. RESULTS: Our study population comprised 1 610 women, of whom 114 were ASB positive. Median cervical length was similar in women with and without ASB (44.0 vs 44.0 mm, P = 0.60). More women in the ASB positive group had a short CL compared to the ASB negative group (1.8 % versus 0.4 %, P = 0.047)). The gestational age at delivery did not differ between the groups (ranging from 38 + 3 in women with ASB and short CL to 39 + 5 in women without ASB with a short CL P = 0.52). No preterm births occurred in women with a short cervical length (regardless of ASB status). In the women without ASB and no short CL 4.8 % had a preterm birth, in the women with ASB but not a short CL 4.1 % had a preterm birth. CONCLUSION: While ASB status did not influence median cervical length, we found a significant relationship between a short CL and ASB positive women. We found no statistical significant difference on the preterm birth rate and mean gestational age.

TRIDENT-2: National Implementation of Genome-wide Non-invasive Prenatal Testing as a First-Tier Screening Test in the Netherlands.

The Netherlands launched a nationwide implementation study on non-invasive prenatal testing (NIPT) as a first-tier test offered to all pregnant women. This started on April 1, 2017 as the TRIDENT-2 study, licensed by the Dutch Ministry of Health. In the first year, NIPT was performed in 73,239 pregnancies (42% of all pregnancies), 7,239 (4%) chose first-trimester combined testing, and 54% did not participate. The number of trisomies 21 (239, 0.33%), 18 (49, 0.07%), and 13 (55, 0.08%) found in this study is comparable to earlier studies, but the Positive Predictive Values (PPV)-96% for trisomy 21, 98% for trisomy 18, and 53% for trisomy 13-were higher than expected. Findings other than trisomy 21, 18, or 13 were reported on request of the pregnant women; 78% of women chose to have these reported. The number of additional findings was 207 (0.36%); these included other trisomies (101, 0.18%, PPV 6%, many of the remaining 94% of cases are likely confined placental mosaics and possibly clinically significant), structural chromosomal aberrations (95, 0.16%, PPV 32%,) and complex abnormal profiles indicative of maternal malignancies (11, 0.02%, PPV 64%). The implementation of genome-wide NIPT is under debate because the benefits of detecting other fetal chromosomal aberrations must be balanced against the risks of discordant positives, parental anxiety, and a potential increase in (invasive) diagnostic procedures. Our first-year data, including clinical data and laboratory follow-up data, will fuel this debate. Furthermore, we describe how NIPT can successfully be embedded into a national screening program with a single chain for prenatal care including counseling, testing, and follow-up.

Arrhythmogenicity of scuba diving: Holter monitoring in a hyperbaric environment.

INTRODUCTION: About 26% of diving-related fatalities are caused by cardiac disease, part of which might be associated with fatal arrhythmias. This raises the question as to whether fatal arrhythmias are being provoked by hyperbaric conditions themselves or if exercise or stress provokes the fatal arrhythmias in cases of underlying (ischemic) cardiac disease. OBJECTIVE: To measure the influence of hyperbaric conditions (50 msw) on cardiac conduction and arrhythmias in professional divers by means of ECG. METHODS: This is a prospective study on military divers in a hyperbaric chamber with continuous ECG monitoring using Holter registrations. Supraventricular and ventricular ectopy was registered during hyperbaric conditions. RR, PR, QRS, QT and QTc intervals were calculated at 50 msw and compared with ECGs at rest. RESULTS: Included were 17 male military divers who made 20 dives. A total of 10 PVCs, 45 PACs, four atrial runs and four atrial pairs were seen. Significant prolongation of the PR interval was seen and a decrease of in QRS duration at 50 msw. There was no significant change in the RR, QT and QTc intervals. CONCLUSION: In these divers, no clinically relevant arrhythmias were observed during wet dives in a recompression chamber at 50 msw. We observed a small prolongation of PR interval that is probably not clinically relevant in divers without any known conduction disorders.

Soluble TLR2 and 4 concentrations in cerebrospinal fluid in HIV/SIV-related neuropathological conditions.

HIV in the central nervous system (CNS) mainly infects microglial cells which are known to express toll-like receptors (TLRs). This paper aimed to study the role of soluble TLR2 (sTLR2), sTLR4, and other inflammatory markers in cerebrospinal fluid (CSF) in HIV/Simian immunodeficiency virus (SIV)-related neurological sequelae. We determined sTLR2 and sTLR4 levels in CSF and serum/plasma of SIV-infected rhesus macaques with and without neurological sequelae, as well as in HIV-infected patients with and without cognitive impairments and Alzheimer's disease (AD) patients and matched controls. CSF cytokines and chemokines levels were analyzed in macaques as markers of neuroinflammation, while neopterin and S100B CSF concentrations were measured in HIV-infected patients as microglial and astrocyte marker, respectively. We found detectable levels of sTLR2 and sTLR4 in CSF of macaques and humans. Furthermore, CSF sTLR2 and sTLR4 concentrations were higher in SIV-infected macaques with neurological sequelae compared to those without neurological complications (p = 0.0003 and p = 0.0006, respectively). CSF IL-8 and monocyte chemoattractant protein-1 (MCP-1) levels were elevated in macaques with neurological sequelae, and a positive correlation was found between CSF levels of sTLR2/4 and IL-8 and MCP-1. Also in humans, elevated CSF sTLR4 levels were found in HIV-infected patients with cognitive impairments compared to HIV-infected patients with normal cognition (p = 0.019). Unlike CSF S100B levels, neopterin correlated positively with sTLR2 and sTLR4. No difference was found in plasma and CSF sTLR2 and sTLR4 levels between AD patients and control subjects (p = 0.26). In conclusion, CSF sTLR2 and sTLR4 may play a role in HIV/SIV-related neuroinflammation and subsequent neuropathology.

Influence of cut-off value on prevalence of short cervical length.

OBJECTIVE: To assess the distribution of cervical length (CL) in a large cohort of asymptomatic low-risk women with singleton pregnancy and no previous preterm birth and to explain the low prevalence of short CL ≤ 30 mm in this cohort. METHODS: This was a secondary analysis of a multicenter cohort study with an embedded randomized controlled trial (Triple P trial; NTR-2078) on the prevention of preterm birth with progesterone. In the cohort study, CL was measured in asymptomatic low-risk women with singleton pregnancy to investigate its predictive capacity to identify those at increased risk for preterm birth. A short CL was defined by a cut-off value of ≤ 30 mm, based on existing literature. Women with a short CL were subsequently included in a randomized controlled trial evaluating the effect of progesterone, compared with placebo, on preterm birth. In total, 57 centers and 20 234 women participated in the study. Normal distributions for CL were simulated based on the mean and SD of the original data. The distribution of CL was assessed for each individual center and measurements were compared between levels of care: primary (29 ultrasound centers), secondary (21 general hospitals) and tertiary (seven university medical centers) care institutions. Comparison was also performed between centers with low, intermediate and high volume of CL measurements. CL distributions before (n = 12 284 women) and after (n = 7950 women) a national symposium, at which the prevalence of short CL measurements was addressed publicly, were analyzed. RESULTS: Between November 2009 and August 2013, 20 234 women had CL measurements, of whom 367 (1.8%) had a short CL. Mean ± SD CL was 44.2 ± 7.8 mm. A 'dip' in the distribution of CL measurements between 20 and 30 mm was observed, defined by a ratio of < 50% when comparing the number of measurements in observed and simulated normal distributions. The dip was present in 89% of participating centers. All centers showed a dip in the distribution of measurements ≤ 30 mm when analyzed according to the level of care and volume of measurements. A significant difference was found when comparing the distribution before and after publicly addressing the low prevalence of short CL (1.7% vs 2.0% of measurements were ≤ 30 mm, respectively; P < 0.001). CONCLUSIONS: A cut-off value of 30 mm for CL was used to include women in a randomized clinical trial that was embedded in a cohort study. We suggest that the use of a predefined cut-off value for a short cervix influences the distribution of the CL measurements. Since the measurement is not blinded, preference of assessors for the control or intervention arms may have introduced selection bias. This might have resulted in fewer measurements around the cut-off value. Other trials using similar designs could benefit from this observation and take precautions to avoid selection bias. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

[Splenomegaly in an Eritrean refugee: the hyper-reactive malaria splenomegaly syndrome.] / Splenomegalie bij een Eritrese vluchteling.

BACKGROUND: Hyper-reactive malaria splenomegaly (HMS) is a rare and potentially severe complication of malaria. It is likely that the incidence of patients with HMS will rise in the Netherlands due to the recent increase in asylum-seekers from Sub-Saharan Africa. It can be difficult to diagnose this disease, as this case shows. CASE DESCRIPTION: A 31-year-old male from Eritrea was admitted with fever and dyspnea, caused by an influenza A-infection. The patient also presented with cachexia, pronounced hepatosplenomegaly and pancytopenia. Microscopic diagnostic analysis for malaria was negative. HMS was eventually diagnosed through high-sensitivity qPCR for malaria, which showed the presence of a very low level of Plasmodium falciparum parasitemia; furthermore, IgM levels were high and malaria serology was strongly positive. CONCLUSION: HMS should be considered in patients from malaria-endemic areas presenting with splenomegaly and pancytopenia. Because standard diagnostics for malaria are often negative in this population, malaria serology and sensitive qPCR play an important diagnostic role.

Study of viremic profile in febrile specimens of chikungunya in Bandung, Indonesia.

BACKGROUND: Data regarding the viremia profile of chikungunya virus (CHIKV) infected patients especially during the pre-febrile period is limited. OBJECTIVE: To obtain virological kinetic data on CHIKV infections. STUDY DESIGN: A two-week community observation for dengue transmission was conducted in Bandung, Indonesia, from 2005 to 2009. Acute specimens from non-dengue febrile patients were screened by pan-alphavirus conventional RT-PCR. The positives were confirmed for CHIKV RNA by a specific RT-PCR followed by sequencing. Simultaneously these specimens were also cultured in Vero cells and tested for anti-CHIK IgM MAC-ELISA. All the available serial specimens,including the pre-febrile specimens, from confirmed CHIK cases, were tested by virus isolation, RT-PCR, qRT-PCR, and CHIK IgM ELISA. RESULTS: There were five laboratory confirmed CHIK cases identified and studied. Among these, viremia was determined to extend from as early as 6 days prior to until 13 days post fever onset. Quantitative RT-PCR showed viremia peaked at or near onset of illness. CONCLUSION: In this study, individuals were identified with viremia prior to fever onset and extending beyond the febrile phase. This extended viremic phase has the potential to impact transmission dynamics and thus the public health response to CHIK outbreaks.

Midpregnancy Cervical Length in Nulliparous Women and its Association with Postterm Delivery and Intrapartum Cesarean Delivery.

OBJECTIVE: To evaluate the association between midpregnancy cervical length and postterm delivery and cesarean delivery during labor. STUDY DESIGN: In a multicenter cohort study, cervical length was measured in low-risk singleton pregnancies between 16 and 22 weeks of gestation. From this cohort, we identified nulliparous women who delivered beyond 34 weeks and calculated cervical length quartiles. We performed logistic regression to compare the risk of postterm delivery and intrapartum cesarean delivery to cervical length quartiles, using the lowest quartile as a reference. We adjusted for induction of labor, maternal age, ethnicity, cephalic position, preexisting hypertension, and gestational age at delivery. RESULTS: We studied 5,321 nulliparous women. Women with cervical length in the 3rd and 4th quartile were more likely to deliver at 42(+0) to 42(+6) weeks (adjusted odds ratio [aOR] 2.02, 95% confidence interval [CI] 1.07-3.79 and aOR 1.97, 95% CI 1.06-3.67, respectively). The frequency of intrapartum cesarean delivery increased with cervical length quartile from 9.4% in the 1st to 14.9% in the 4th quartile (p = 0.01). This increase was only present in intrapartum cesarean delivery because of failure to progress and not because of fetal distress. CONCLUSION: The longer the cervix at midtrimester the higher the risk of both postterm delivery and intrapartum cesarean delivery.

New parameters available on Sysmex XE-5000 hematology analyzers contribute to differentiating dengue from leptospirosis and enteric fever.

INTRODUCTION: Distinguishing dengue virus infection from other febrile thrombocytopenic illnesses such as leptospirosis or enteric fever is important but difficult, due to the unavailability of reliable diagnostic tests. Sysmex XE-5000 hematology analyzers use fluorescence flow cytometry to quantitate new parameters including cells in the atypical lymphocyte area (AL), high-fluorescent lymphocyte counts (HFLC), immature granulocytes (IG), and immature platelets (IPF). This study aimed to investigate whether these parameters can help to discriminate between the diseases. MATERIAL AND METHODS: We compared hematocytometry performed by a Sysmex XE-5000 analyzer in Indonesian adults with dengue (n = 93), leptospirosis (n = 11), and enteric fever (n = 6) infection, and in healthy controls (n = 28). RESULTS: Receiver operating characteristic curves comparing dengue and leptospirosis showed that dengue was characterized by increased %AL (AUC 0.87; 95% CI 0.70-1.03), %HFLC (AUC 0.89; 95% CI 0.78-0.99), and %IPF (AUC 0.81; 95% CI 0.65-0.97), while patients with leptospirosis had increased %IG (AUC 0.86; 95% CI 0.71-1.02). Low %AL, %HFLC, and %IG supported a diagnosis of enteric fever. CONCLUSIONS: The detection of AL, HFLC, IG, and IPF by Sysmex XE-5000 hematology analyzers can help to differentiate between common causes of febrile illnesses with thrombocytopenia in dengue endemic areas. We recommend further investigating the discriminatory value of these parameters in clinical practice.

Multicentre randomized controlled trial comparing ferric(III)carboxymaltose infusion with oral iron supplementation in the treatment of preoperative anaemia in colorectal cancer patients.

BACKGROUND: At least a third of patients with a colorectal carcinoma who are candidate for surgery, are anaemic preoperatively. Preoperative anaemia is associated with increased morbidity and mortality. In general practice, little attention is paid to these anaemic patients. Some will have oral iron prescribed others not. The waiting period prior to elective colorectal surgery could be used to optimize a patients' physiological status. The aim of this study is to determine the efficacy of preoperative intravenous iron supplementation in comparison with the standard preoperative oral supplementation in anaemic patients with colorectal cancer. METHODS/DESIGN: In this multicentre randomized controlled trial, patients with an M0-staged colorectal carcinoma who are scheduled for curative resection and with a proven iron deficiency anaemia are eligible for inclusion. Main exclusion criteria are palliative surgery, metastatic disease, neoadjuvant chemoradiotherapy (5 × 5 Gy = no exclusion) and the use of Recombinant Human Erythropoietin within three months before inclusion or a blood transfusion within a month before inclusion. Primary endpoint is the percentage of patients that achieve normalisation of the haemoglobin level between the start of the treatment and the day of admission for surgery. This study is a superiority trial, hypothesizing a greater proportion of patients achieving the primary endpoint in favour of iron infusion compared to oral supplementation. A total of 198 patients will be randomized to either ferric(III)carboxymaltose infusion in the intervention arm or ferrofumarate in the control arm. This study will be performed in ten centres nationwide and one centre in Ireland. DISCUSSION: This is the first randomized controlled trial to determine the efficacy of preoperative iron supplementation in exclusively anaemic patients with a colorectal carcinoma. Our trial hypotheses a more profound haemoglobin increase with intravenous iron which may contribute to a superior optimisation of the patient's condition and possibly a decrease in postoperative morbidity. TRIAL REGISTRATION: ClincalTrials.gov: NCT02243735 .

Amyloid beta-42 (Aß-42), neprilysin and cytokine levels. A pilot study in patients with HIV related cognitive impairments.

HIV-associated dementia (HAD) is associated with amyloid-beta (Aß) deposition. This study measured CSF and plasma amyloid beta-42 (Aß-42), neprilysin (NEP) and cytokine levels in HIV-related cognitive impairments (HCI), HIV normal cognitive functioning (NF) and non-HIV controls. Our data showed a trend towards detectable plasma Aß-42 levels more frequently in HCI (67%), when compared to NF (29%) and controls (10%). We showed elevated IL-8 levels in CSF of HCI compared to NF, although not significant values. The data from this pilot study indicates that CSF IL-8 and plasma Aß-42 may be interesting biomarkers for the presence of HCI.

Preventing Preterm Birth with Progesterone in Women with a Short Cervical Length from a Low-Risk Population: A Multicenter Double-Blind Placebo-Controlled Randomized Trial.

OBJECTIVE: The objective of this study was to evaluate the effectiveness of vaginal progesterone in reducing adverse neonatal outcome due to preterm birth (PTB) in low-risk pregnant women with a short cervical length (CL). STUDY DESIGN: Women with a singleton pregnancy without a history of PTB underwent CL measurement at 18 to 22 weeks. Women with a CL ≤ 30 mm received vaginal progesterone or placebo. Primary outcome was adverse neonatal outcome, defined as a composite of respiratory distress syndrome, bronchopulmonary dysplasia, intracerebral hemorrhage > grade II, necrotizing enterocolitis > stage 1, proven sepsis, or death before discharge. Secondary outcomes included time to delivery, PTB before 32, 34, and 37 weeks of gestation. Analysis was by intention to treat. RESULTS: Between 2009 and 2013, 20,234 women were screened. A CL of 30 mm or less was seen in 375 women (1.8%). In 151 women, a CL ≤ 30 mm was confirmed with a second measurement and 80 of these women agreed to participate in the trial. We randomly allocated 41 women to progesterone and 39 to placebo. Adverse neonatal outcomes occurred in two (5.0%) women in the progesterone and in four (11%) women in the control group (relative risk [RR], 0.47; 95% confidence interval [CI], 0.09-2.4). The use of progesterone resulted in a nonsignificant reduction of PTB < 32 weeks (2.0 vs. 8.0%; RR, 0.33; 95% CI, 0.04-3.0) and < 34 weeks (7.0 vs. 10%; RR, 0.73; 95% CI, 0.18-3.1) but not on PTB < 37 weeks (15 vs. 13%; RR, 1.2; 95% CI, 0.39-3.5). CONCLUSION: In women with a short cervix, who are otherwise low risk, we could not show a significant benefit of progesterone in reducing adverse neonatal outcome and PTB.

Is cervical length associated with maternal characteristics?

OBJECTIVE: Women with a mid-trimester short cervical length (CL) are at increased risk for preterm delivery. Consequently, CL measurement is a potential screening tool to identify women at risk for preterm birth. Our objective was to assess possible associations between CL and maternal characteristics. STUDY DESIGN: A nationwide screening study was performed in which CL was measured during the standard anomaly scan among low risk women with a singleton pregnancy. Data on maternal height, pre-pregnancy weight, ethnicity, parity and gestational age at the time of the CL measurement were collected from January 2010 to December 2012. Univariable and multivariable linear regression analyses were performed to assess the relationship between CL and maternal characteristics. RESULTS: We included 5092 women. The mean CL was 44.3mm. No association was found between CL and maternal height or gestational age of the measurement. Maternal weight was associated with CL (p=0.007, adjusted R(2) 0.03). Separate analysis for BMI did not change these results. Ethnicity, known in 2702 out of 5092 women, was associated with CL (mean CL in Caucasian women 45.0mm, Asian 43.9mm, Mediterranean 43.1mm, and African 41.8mm, p=0.003), as well as parity (mean CL multiparous 45.3mm, nulliparous 43.5mm, p<0.0001). CONCLUSION: Shorter mid-trimester cervical length is associated with higher maternal weight, younger maternal age, nulliparity and non-Caucasian ethnicity, but not with maternal height.

Effect of e-learning on quality of cervical-length measurements.

OBJECTIVES: To assess the effect of implementation of a newly developed e-learning module on the quality of cervical-length measurements. METHODS: With the introduction of cervical-length (CL) measurement in a research setting, a CL measurement e-learning module (CLEM) was developed with the purpose to enhance the knowledge and skills of experienced ultrasonographers. CLEM was designed specifically for ultrasonographers who perform ultrasound in a general obstetrical practice but who do not regularly perform CL measurements. CLEM consists of five theoretical questions and three caliper-placement tests to learn the CL measurement technique. The quality of the CL measurements of CLEM participants was compared with images of non-participants using a CL measurement image score (CIS), defined as the sum of six items which assess the quality of the image. Each CLEM participant submitted five CL images and the images of non-CLEM participants were selected randomly from an ultrasound database. RESULTS: The CIS of the CLEM participants (n = 61) were significantly higher than those of non-CLEM participants (n = 23) (164.9 vs 155.6, respectively; P = 0.03). Visualization of the internal os and positioning of the calipers on the internal and external ora were found to have significantly higher CIS among the CLEM participants than among the non-CLEM participants (P = 0.001 and P < 0.001, respectively). CONCLUSIONS: Introducing CLEM may improve the quality of CL measurements obtained by trained and untrained sonographers.

Persisting arthralgia due to Mayaro virus infection in a traveler from Brazil: is there a risk for attendants to the 2014 FIFA World Cup?

The 2014 FIFA World Cup and the 2016 Olympic Games will attract large groups of visitors to Brazil. These visitors will be at risk for different arboviral infections, some of which not well known outside endemic areas. We report a case of a 52-year-old Dutch woman who presented with persistent arthralgia due to a Mayaro virus (MAYV) infection which she contracted in the Amazon basin in Brazil. MAYV is a mosquito-borne alphavirus which primarily circulates in humid tropical forests of South America. Infections are rarely reported in travelers and are characterized by an acute febrile illness which is often followed by a prolonged and sometimes incapacitating polyarthralgia. Both travelers and physicians should be aware of the risk of these arboviral infections and the importance of mosquito bite prevention should be stressed.

Platelet function alterations in dengue are associated with plasma leakage.

Severe dengue is characterised by thrombocytopenia, plasma leakage and bleeding. Platelets are important for preservation of endothelial integrity. We hypothesised that platelet activation with secondary platelet dysfunction contribute to plasma leakage. In adult Indonesian patients with acute dengue, we measured platelet activation status and the response to the platelet agonist TRAP using flow cytometer-based assays. Patients were monitored daily for plasma leakage by ultrasonography. Acute dengue was associated with platelet activation with an increased expression of the activated fibrinogen receptor (αIIbß3), the lysosomal marker CD63 and the alpha-granule marker CD62P (P-selectin). Upon maximal platelet activation by TRAP, platelet function defects were observed with a significantly reduced maximal activated αIIbß3 and CD63 expression and reduced platelet-monocyte and platelet-neutrophil complexes. Patients in the lowest tertile of activated αIIbß3 and CD63 expression had an odds ratio for plasma leakage of 5.2 (95% confidence interval [CI] 1.3-22.7) and 3.9 (95% CI 1.1-13.7), respectively, compared to the highest tertile. Platelet-derived serotonin has previously been related to plasma leakage and we found increased intra-platelet serotonin concentrations in our patients. In conclusion, platelet activation with platelet function alterations can be found in patients with acute dengue and this may contribute to dengue-associated plasma leakage.