Risk of preterm birth after prior term cesarean.

OBJECTIVE: To determine the risk of overall preterm birth (PTB) and spontaneous PTB in a pregnancy after a caesarean section (CS) at term. DESIGN: Longitudinal linked national cohort study. SETTING: The Dutch Perinatal Registry (1999-2009). POPULATION: 268 495 women with two subsequent singleton pregnancies were identified. METHODS: A cohort study based on linked registered data from two subsequent pregnancies in the Netherlands. MAIN OUTCOME MEASURES: The incidence of overall PTB and spontaneous PTB with subgroup analysis on gestational age at first delivery and type of CS (planned or unplanned). RESULTS: Of 268 495 women with a singleton first pregnancy who delivered at term, 15.76% (n = 42 328) had a CS. The incidence of PTB in the second pregnancy was 2.79% (n = 1182) in women with a previous CS versus 2.46% (n = 5570) in women with a previous vaginal delivery (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.07-1.21). This increased risk is mainly driven by an increased risk of spontaneous PTB after previous CS at term (aOR 1.50, 95% CI 1.38-1.70). Analysis for type of CS compared with vaginal delivery showed an aOR on spontaneous PTB of 1.86 (95% CI 1.58-2.18) for planned CS and an aOR of 1.40 (95% CI 1.24-1.58) for unplanned CS. CONCLUSIONS: CS at term is associated with a marginally increased risk of spontaneous PTB in a subsequent pregnancy. TWEETABLE ABSTRACT: Caesarean section at term is associated with a marginally increased risk of spontaneous PTB in a subsequent pregnancy.

Cytosolic 5'-nucleotidase 1A autoantibody profile and clinical characteristics in inclusion body myositis.

OBJECTIVES: Autoantibodies directed against cytosolic 5'-nucleotidase 1A have been identified in many patients with inclusion body myositis. This retrospective study investigated the association between anticytosolic 5'-nucleotidase 1A antibody status and clinical, serological and histopathological features to explore the utility of this antibody to identify inclusion body myositis subgroups and to predict prognosis. MATERIALS AND METHODS: Data from various European inclusion body myositis registries were pooled. Anticytosolic 5'-nucleotidase 1A status was determined by an established ELISA technique. Cases were stratified according to antibody status and comparisons made. Survival and mobility aid requirement analyses were performed using Kaplan-Meier curves and Cox proportional hazards regression. RESULTS: Data from 311 patients were available for analysis; 102 (33%) had anticytosolic 5'-nucleotidase 1A antibodies. Antibody-positive patients had a higher adjusted mortality risk (HR 1.89, 95% CI 1.11 to 3.21, p=0.019), lower frequency of proximal upper limb weakness at disease onset (8% vs 23%, adjusted OR 0.29, 95% CI 0.12 to 0.68, p=0.005) and an increased prevalence of excess of cytochrome oxidase deficient fibres on muscle biopsy analysis (87% vs 72%, adjusted OR 2.80, 95% CI 1.17 to 6.66, p=0.020), compared with antibody-negative patients. INTERPRETATION: Differences were observed in clinical and histopathological features between anticytosolic 5'-nucleotidase 1A antibody positive and negative patients with inclusion body myositis, and antibody-positive patients had a higher adjusted mortality risk. Stratification of inclusion body myositis by anticytosolic 5'-nucleotidase 1A antibody status may be useful, potentially highlighting a distinct inclusion body myositis subtype with a more severe phenotype.

A cross-sectional study to assess the long-term health status of patients with lower respiratory tract infections, including Q fever.

Patients with a lower respiratory tract infection (LRTI) might be at risk for long-term impaired health status. We assessed whether LRTI patients without Q fever are equally at risk for developing long-term symptoms compared to LRTI patients with Q fever. The study was a cross-sectional cohort design. Long-term health status information of 50 Q fever-positive and 32 Q fever-negative LRTI patients was obtained. Health status was measured by the Nijmegen Clinical Screening Instrument. The most severely affected subdomains of the Q fever-positive group were 'general quality of life' (40%) and 'fatigue' (40%). The most severely affected subdomains of the Q fever-negative group were 'fatigue' (64%) and 'subjective pulmonary symptoms' (35%). Health status did not differ significantly between Q fever-positive LRTI patients and Q fever-negative LRTI patients for all subdomains, except for 'subjective pulmonary symptoms' (P = 0·048).

Preparing an E-learning-based Speech Therapy (EST) efficacy study: Identifying suitable outcome measures to detect within-subject changes of speech intelligibility in dysarthric speakers.

We explored the suitability of perceptual and acoustic outcome measures to prepare E-learning based Speech Therapy (EST) efficacy tests regarding speech intelligibility in dysarthric speakers. Eight speakers with stroke (n=3), Parkinson's disease (n=4) and traumatic brain injury (n=1) participated in a 4 weeks EST trial. A repeated measures design was employed. Perceptual measures were (a) scale ratings for "ease of intelligibility" and "pleasantness" in continuous speech and (b) orthographic transcription scores of semantically unpredictable sentences. Acoustic measures were (c) "intensity during closure" (ΔIDC) in the occlusion phase of voiceless plosives, (d) changes in the vowel space of /a/, /e/ and /o/ and (e) the F0 variability in semantically unpredictable sentences. The only consistent finding concerned an increased (instead of the expected decreased) ΔIDC after EST, possibly caused by increased speech intensity without articulatory adjustments. The importance of suitable perceptual and acoustic measures for efficacy research is discussed.

Does EU legislation allow the use of the Benchmark Dose (BMD) approach for risk assessment?

Hazard characterisation is largely based on an approach of (statistically) comparing dose groups with the controls in order to derive points of departure such as no-observed-adverse-effect levels (NOAELs) or lowest-observed-adverse-effect levels (LOAELs). This approach suggests the absence of any relevant effect at the NOAEL. The NOAEL approach has been debated for decades. A recent Scientific Opinion by the European Food Safety Authority (EFSA) concluded that the Benchmark Dose (BMD) approach should be preferred over the NOAEL approach for deriving human (health-based) limit or guidance values. Nonetheless, the BMD approach is used infrequently within European regulatory frameworks. The reason for this may lie in legislation or guidelines requiring the use of the NOAEL approach. In this context, various EU regulatory frameworks were examined on such demands. Interestingly, no single legislation was identified containing statutory requirements in conflict with the use of the BMD approach.

Routine screening for Coxiella burnetii infection during pregnancy: a clustered randomised controlled trial during an outbreak, the Netherlands, 2010.

Between 2007 and 2010, the Netherlands experienced one of the largest outbreaks of Q fever. Since asymptomatic Coxiella burnetii infection has been associated with maternal and obstetric complications, evidence about the effectiveness of routine screening during pregnancy in outbreak areas is needed. We performed a clustered randomised controlled trial during the Dutch outbreak, in which 55 midwife centres were randomised to recruit pregnant women for an intervention or control strategy. In both groups a serum sample was taken between 20 and 32 weeks of gestation. In the intervention group (n=536), the samples were analysed immediately by indirect immunofluorescence assay for the presence of IgM and IgG (phase I/II) and treatment was given during pregnancy in case of an acute or chronic infection. In the control group (n=693), sera were frozen for analysis after delivery. In both groups 15% were seropositive. In the intervention group 2.2% of the women were seropositive and had an obstetric complication, compared with 1.4% in the control group (Odds ratio: 1.54 (95% confidence interval 0.60-3.96)). During a large Q fever outbreak, routine C. burnetii screening starting at 20 weeks of gestation was not associated with a relevant reduction in obstetric complications and should therefore not be recommended.

End-to-end learning with interpretation on electrohysterography data to predict preterm birth.

Prediction of preterm birth is a difficult task for clinicians. By examining an electrohysterogram, electrical activity of the uterus that can lead to preterm birth can be detected. Since signals associated with uterine activity are difficult to interpret for clinicians without a background in signal processing, machine learning may be a viable solution. We are the first to employ Deep Learning models, a long-short term memory and temporal convolutional network model, on electrohysterography data using the Term-Preterm Electrohysterogram database. We show that end-to-end learning achieves an AUC score of 0.58, which is comparable to machine learning models that use handcrafted features. Moreover, we evaluate the effect of adding clinical data to the model and conclude that adding the available clinical data to electrohysterography data does not result in a gain in performance. Also, we propose an interpretability framework for time series classification that is well-suited to use in case of limited data, as opposed to existing methods that require large amounts of data. Clinicians with extensive work experience as gynaecologist used our framework to provide insights on how to link our results to clinical practice and stress that in order to decrease the number of false positives, a dataset with patients at high risk of preterm birth should be collected. All code is made publicly available.

Relation between Q fever notifications and Coxiella burnetii infections during the 2009 outbreak in The Netherlands.

Large outbreaks of Q fever in the Netherlands from 2007 to 2009 were monitored using notification data of acute clinical Q fever. However, the notification system provides no information on infections that remain subclinical or for which no medical attention is sought. The present study was carried out immediately after the peak of the 2009 outbreak to estimate the ratio between Coxiella burnetii infections and Q fever notifications. In 23 postcode areas in the high-incidence area, notification rates were compared with seroconversion rates in blood donors from whom serial samples were available. This resulted in a ratio of one Q fever notification to 12.6 incident infections of C. burnetii. This ratio is time and place specific and is based on a small number of seroconversions, but is the best available factor for estimating the total number of infections. In addition, as subclinical C. burnetii infection may lead to chronic Q fever, the ratio can be used to estimate the expected number of chronic Q fever patients in the coming years and as input for cost­benefit analyses of screening options.

Shifting priorities in the aftermath of a Q fever epidemic in 2007 to 2009 in The Netherlands: from acute to chronic infection.

From 2007 to 2009, the Netherlands faced large seasonal outbreaks of Q fever, in which infected dairy goat farms were identified as the primary sources. Veterinary measures including vaccination of goats and sheep and culling of pregnant animals on infected farms seem to have brought the Q fever problem under control. However, the epidemic is expected to result in more cases of chronic Q fever among risk groups in the coming years. In the most affected area, in the south of the country, more than 12% of the population now have antibodies against Coxiella burnetii. Questions remain about the follow-up of acute Q fever patients, screening of groups at risk for chronic Q fever, screening of donors of blood and tissue, and human vaccination. There is a considerable ongoing research effort as well as enhanced veterinary and human surveillance.

SARS-CoV-2 transmitters have more than three times higher viral loads than non-transmitters - Practical use of viral load for disease control.

BACKGROUND: Quantitative results of SARS-CoV-2 testing reported as viral load copies/mL can provide valuable information, but are rarely used in practice. We analyze whether viral load in the upper respiratory tract is correlated with transmission and disease course and how this information can be used in practice. STUDY DESIGN: Municipal Health Service (MHS) and clinical patients ≥18 years tested positive for SARS-CoV-2 with RT-PCR between June 1 and September 25, 2020 were included. Transmission was defined as an index having at least one contact tested positive. Test delay was defined as the time between symptom onset and SARS-CoV-2 testing. RESULTS: 683 patients were included (656 MHS and 27 clinical patients). The viral load was considerably lower among clinical patients compared to MHS patients: median log10 copies/mL 2.51 (IQR -1.52 - 6.46) vs 4.92 (IQR -0.54 - 8.26), p < 0.0001. However, the test delay was higher for clinical patients (median 7 [IQR 2 - 19] vs 3 [IQR 0 - 26] days, p < 0.0001). SARS-CoV-2 transmitters showed much higher viral loads than non-transmitters (log10 copies/mL 5.23 [IQR -0.52 - 8.26] vs 4.65 [IQR -0.72 - 8.00], p < 0.0001), but not for those with a test delay > 7 days. Higher viral loads were significantly correlated with older age and with more (severe) COVID-19 related symptoms. CONCLUSION: Indexes that transmitted SARS-CoV-2 had more than three times higher viral loads than non-transmitters. Viral load information can be useful during source and contact tracing to prioritize indexes with highest risk of transmission, taking into account the test delay.

Genees & kunst 10: tenth symposium on medical problems of dancers & musicians, universitair medisch centrum, Utrecht, March 27, 2010.

On Saturday, March 27th, 2010, the Dutch Performing Arts Medicine Association (NVDMG) organized a scientific and artistic Jubilee symposium "Genees & Kunst 10" for its 5th anniversary and 10th member assembly, at the University Medical Centre Utrecht, The Netherlands. During his opening speech, dr. Rietveld, president of NVDMG, mentioned the successful first 5 years and the vitality of the NVDMG, and he emphasized the importance of performing arts medicine, given the large proportion of performing artists (at least 14% of all patients) in an average Dutch family physician's practice. Scientific presentations, interspersed with dance and music performances, were given by several medical specialists. Abstracts of these presentations are published here as the symposium proceedings.

Advantage of bimodal fitting in prosody perception for children using a cochlear implant and a hearing aid.

Cochlear implants are largely unable to encode voice pitch information, which hampers the perception of some prosodic cues, such as intonation. This study investigated whether children with a cochlear implant in one ear were better able to detect differences in intonation when a hearing aid was added in the other ear ("bimodal fitting"). Fourteen children with normal hearing and 19 children with bimodal fitting participated in two experiments. The first experiment assessed the just noticeable difference in F0, by presenting listeners with a naturally produced bisyllabic utterance with an artificially manipulated pitch accent. The second experiment assessed the ability to distinguish between questions and affirmations in Dutch words, again by using artificial manipulation of F0. For the implanted group, performance significantly improved in each experiment when the hearing aid was added. However, even with a hearing aid, the implanted group required exaggerated F0 excursions to perceive a pitch accent and to identify a question. These exaggerated excursions are close to the maximum excursions typically used by Dutch speakers. Nevertheless, the results of this study showed that compared to the implant only condition, bimodal fitting improved the perception of intonation.

N-Glycans mediate the apical sorting of a GPI-anchored, raft-associated protein in Madin-Darby canine kidney cells.

Glycosyl-phosphatidylinositol (GPI)- anchored proteins are preferentially transported to the apical cell surface of polarized Madin-Darby canine kidney (MDCK) cells. It has been assumed that the GPI anchor itself acts as an apical determinant by its interaction with sphingolipid-cholesterol rafts. We modified the rat growth hormone (rGH), an unglycosylated, unpolarized secreted protein, into a GPI-anchored protein and analyzed its surface delivery in polarized MDCK cells. The addition of a GPI anchor to rGH did not lead to an increase in apical delivery of the protein. However, addition of N-glycans to GPI-anchored rGH resulted in predominant apical delivery, suggesting that N-glycans act as apical sorting signals on GPI-anchored proteins as they do on transmembrane and secretory proteins. In contrast to the GPI-anchored rGH, a transmembrane form of rGH which was not raft-associated accumulated intracellularly. Addition of N-glycans to this chimeric protein prevented intracellular accumulation and led to apical delivery.

Novel aspects of postprandial lipemia in relation to atherosclerosis.

Postprandial hyperlipidemia is considered to be a substantial risk factor for atherosclerosis. Interestingly, this concept has never been supported by randomized clinical trials. The difficulty lies in the fact that most interventions aimed to reduce postprandial lipemia, will also affect LDL-C levels. The atherogenic mechanisms of postprandial lipids and lipoproteins can be divided into direct lipoprotein-mediated and indirect effects; the latter, in part, by inducing an inflammatory state. Elevations in postprandial triglycerides (TG) have been related to the increased expression of postprandial leukocyte activation markers, up-regulation of pro-inflammatory genes in endothelial cells and involvement of the complement system. This set of events is part of the postprandial inflammatory response, which is one of the recently identified potential pro-atherogenic mechanisms of postprandial lipemia. Especially, complement component 3 levels show a close correlation with postprandial lipemia and are also important determinants of the metabolic syndrome. In clinical practice, fasting TG are frequently used as reflections of postprandial lipemia due to the close correlation between the two. The use of serial capillary measurements in an out-of-hospital situation is an alternative for oral fat loading tests. Daylong TG profiles reflect postprandial lipemia and are increased in conditions like the metabolic syndrome, type 2 diabetes and atherosclerosis. Studies are needed to elucidate the role of postprandial inflammation in atherogenesis and to find new methods in order to reduce selectively the postprandial inflammatory response. Future studies are needed to find new methods in order to reduce selectively the postprandial inflammatory response.

[Diagnostic image (394). A man with a tissue fragment in the urine. Papillary necrosis]. / Diagnose in beeld (394). Een man met een weefselbrok in de urine. Necrose van een nierpapil.

A 54-year-old man with chronic renal failure due to diabetic nephropathy presented with macroscopic haematuria and excretion of necrotic tissue in the urine as a sign of papillary necrosis.

Posterior Ankle Impingement Syndrome and M. Flexor Hallucis Longus Tendinopathy in Dancers Results of Open Surgery.

Posterior ankle impingement syndrome (PAIS), the result of posterolateral soft tissue or bony impingement of the ankle, and tendinopathy of the flexor hallucis longus (FHL tendinopathy) in the ankle are common in dancers. If conservative treatment of these conditions fails to produce adequate results, surgical intervention might be necessary. However, outcomes of treatment by open surgery for these diagnoses have been described only in small series of dancers. For this study, data were extracted from clinical files and operative reports of an orthopaedic surgery clinic specialized in dance medicine. Prior to October 2016, 148 patients (82.1% female, median age 19 years) underwent 190 open procedures, 57 (30%) for FHL, 83 (43.7%) for PAIS, and 50 (26.3%) for a combination thereof. In 90.8% of cases, patients reported a "better" or "much better" postoperative outcome. There were only minor, transient complications that neither required re-intervention nor influenced outcome. Patients were followed up for a median of 157 days (interquartile range: 91-245 days). Those operated on by a lateral approach were discharged from follow-up earlier (lateral 113 days vs. 190 for medial approach, p = 0.005), but there was no difference in outcome at discharge. It is concluded that the open surgical treatment of PAIS and FHL tendinopathy in dancers has a high success rate and can be considered a successful standard operative procedure. More detailed information is needed about dance-specific outcomes and the early postoperative course of rehabilitation.

Operative Treatment of Posterior Ankle Impingement Syndrome and Flexor Hallucis Longus Tendinopathy in Dancers Open Versus Endoscopic Approach.

Posterior ankle impingement syndrome (PAIS) is a painful, usually limited plantar flexion of the ankle joint due to soft tissue impingement or a bony impediment often coinciding with tendinopathy of the flexor hallucis longus (FHL) behind the medial malleolus. In persistent complaints, the bony impediment is removed, the tunnel of the FHL tendon is released, or a combination of both procedures has traditionally been performed by open surgery. In 2000, an endoscopic surgical technique for PAIS and FHL tendinopathy was introduced. To date there is no evidence of the superiority of one surgical technique over the other in dancers; both the open and the endoscopic approach provide up to 90% good and excellent long-term results. We compared the first 20 consecutive open procedures with the first 19 consecutive endoscopic procedures in dancers, all operated by the same orthopaedic surgeon. The postoperative outcomes were reviewed by studying the patient files, clinical evaluation, American Orthopaedic Foot and Ankle Society (AOFAS) scoring, and we administered a dance-specific questionnaire. The results in the open group were: nine excellent, nine good, one moderate, and one poor (90% excellent and good). In the endoscopic group: nine excellent, six good, three moderate, one poor (79% excellent and good). Both groups returned to dance (barre) at a median of 8 weeks (IQR: 2). The direct postoperative morbidity in the endoscopic group was less favorable and was mainly related to hematomas and an inflammatory response or deep scar tissue formation. There were no major complications requiring re-intervention. Although the two small groups of patients and the retrospective character of our descriptive study do not allow firm conclusions or statistical analysis of subgroups, the results of this study indicate that the open approach seems to be better than the endoscopic approach in the surgical treatment of PAIS and FHL tendinopathy in dancers.

Results of Treatment of Posterior Ankle Impingement Syndrome and Flexor Hallucis Longus Tendinopathy in Dancers: A Systematic Review.

Dancing on pointe and relevé requires extreme plantar flexion of the talo-crural joint. Hence, these positions may lead to posterior ankle impingement syndrome (PAIS). PAIS often coincides with flexor hallucis longus tendinopathy (FHL tendinopathy, or "dancers' tendinitis"). Both injuries can appear in isolation as well. The goal of this review is to evaluate the results and the available levels of evidence of conservative and operative treatment (both open and endoscopic) of PAIS and FHL tendinopathy in dancers. It also offers an insight into the history of dance medical publications on this subject. In October 2016, a systematic search of PubMed, Embase, Cochrane, CINAHL, Web of Science, and (in French) ScienceDirect databases was undertaken. Five hundred and seventy-six publications were found, of which a total of 27 reported the results of operative treatment in 376 ankles (344 open, 32 endoscopic) in 324 dancers. The outcome was good to excellent in most cases (89%). The mean period of return to dance for all surgeries combined (PAIS and FHL tendinopathy, open and endo) was 11 weeks (range: 4 to 36 weeks), and for isolated FHL tendinopathy 16 weeks (range: 8 to 36 weeks). Only six publications reported the results of conservative treatment in 33 ankles (13 PAIS, 20 FHL tendinopathy) of 28 dancers, which does not allow for any evidence-based recommendations. Most studies failed to include dance-specific baseline characteristics, like dance style and level of participation. We concluded that only retrospective studies with levels of evidence four and five show that operative treatment for PAIS and FHL tendinopathy is successful with few complications. Since isolated PAIS, PAIS combined with FHL tendinopathy, and isolated FHL injuries appear to be different pathological entities, more research taking into account demography, dance type, and level of participation is needed to find out in which cases early operative management should be considered or avoided. The same applies to defining the place of endoscopic surgery in dancers and being able better to predict which pathology is likely to produce worse outcomes or delay the return to dance. Future research should have a prospective design, including dance-specific outcome scores both preand post-treatment. Furthermore, preferably a prospective randomized controlled design should be used to compare different conservative and operative treatment options.

Familiarity of general practitioners with Q fever decreases hospitalisation risk.

INTRODUCTION: Between 2007 and 2010, the Netherlands experienced large outbreaks of Q fever with over 4000 cases. There were unexplained geographical differences in hospitalisation rates of notified patients. We examined the extent of this geographic variation in Q fever hospitalisation and its potential association with general practitioner (GP) experience with Q fever. METHODS: We included Q fever cases notified by GPs in 2008 and 2009 in the affected public health region. We used linear regression to describe trends of hospitalisation over time and tested for statistical differences in hospitalisation between municipalities with the chi-square test. We used the number of previously diagnosed Q fever cases of an individual GP as a proxy for Q fever experience, grouped into four categories of GP experience (1; 2; 3-7 and 8 or more cases). We calculated adjusted odds ratios (OR) using logistic regression, taking into account clustering at the GP level. RESULTS: The proportion of hospitalised cases was highly variable between municipalities (range 0-56%, p-value < 0.001). The proportion of hospitalised cases decreased monthly by 0.7% (95% confidence interval (CI): 0.03-1.3%). The risk of hospitalisation was lower when GPs had seen eight or more Q fever cases compared with GPs who had seen only one case (OR 0.4 [95% CI: 0.2-0.8]). DISCUSSION: Our findings suggest that increased GP experience was associated with a reduction in hospitalisations. This supports the public health initiatives to disseminate epidemiological updates and information regarding diagnostic and therapeutic options for Q fever to GPs to reduce Q fever related hospitalisation.