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.

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.

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.

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.

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.

The high prevalence of playing-related musculoskeletal disorders (PRMDs) and its associated factors in amateur musicians playing in student orchestras: A cross-sectional study.

OBJECTIVE: Despite the high number of amateur musicians in the general population, little is known about the musculoskeletal health of amateur musicians. Playing a musical instrument is supposed to be a risk factor for the development of musculoskeletal complaints. This study aimed to evaluate playing-related musculoskeletal disorders (PRMDs) among amateur musicians playing in student orchestras. DESIGN: A cross-sectional study. PARTICIPANTS: 357 members of eleven Dutch student orchestras across the Netherlands were included in this study. INTERVENTION: A paper-based questionnaire on PRMDs was used. OUTCOME MEASURES: Sociodemographic characteristics and PRMDs were evaluated using an adaptation of the Nordic Musculoskeletal Questionnaire (NMQ) and the music module of the Disabilities of Shoulder and Hand (DASH) questionnaire. RESULTS: The year prevalence of PRMDs among amateur musicians was 67.8%. Female gender, younger age, higher BMI and playing a string instrument were independently associated with a higher prevalence of PRMDs. The left shoulder was affected more frequently in violinists and violists, whereas the right hand and wrist were more frequently affected in woodwind instrumentalists. Of the subjects with PRMDs during the last week, the score of the music module of the DASH was 18.8 (6.3-31.2). DISCUSSION: This study is the first to report on PRMDs and its associated factors in a large group of amateur musicians. The prevalence of PRMDs in amateur musicians is high, however the DASH scores reflect a confined impact of these PRMDs on their functioning as a musician. Preventive measures are needed aiming at reducing PRMDs among amateur musicians.

Assessment of occupational and dietary exposure to pesticide residues.

Plant protection products (PPPs) are pesticides containing at least one active substance that drives specific actions against pests (diseases). PPPs are regulated in the EU and cannot be placed on the market or used without prior authorisation. EFSA assesses the possible risks of the use of active substances to humans and environment. Member States decide whether or not to approve their use at EU level. Furthermore, Member States decide at national level on the authorisation of PPPs containing approved substances. In agriculture, exposure to PPPs and their residues during occupational tasks is estimated prior to product authorisation, using models fed with study-specific (e.g. absorption, dissipation) and default values. Exposure of workers to pesticide residues reduces with the pesticide's dissipation time during crop-related tasks. However, the current risk assessment gap is that no methodology is available to calculate the re-entry interval (REI) for workers, which specifies how long they should wear personal protective clothing during their first entry into pesticide-sprayed crops. Protective clothing (such as gloves) can reduce pesticide residue exposure to an acceptable level of worker safety. Within the European Food Risk Assessment Fellowship Programme (EU-FORA) assignment, a methodology was developed to calculate agricultural-use-specific and pesticide-specific REIs for which period workers should wear gloves. This was an assignment of the Dutch Ministry of Social Affairs and Employment. Another important aspect of risk assessment to ensure consumer safety is dietary risk assessment. A critical evaluation of residue studies and metabolism of the pesticide in question in crops results in a residue definition for dietary risk assessment and for enforcement and monitoring to define maximum residue limits allowed legally on or in raw agricultural commodities when applying pesticides according to good agricultural practices. This work was assigned by the Dutch Ministry of Health, Welfare and Sport and contributes to the work of the Joint FAO/WHO Meeting on Pesticide Residues.

Effect of interpregnancy interval on the success rate of trial of labor after cesarean.

OBJECTIVE: The objective of this study is to investigate the association between interpregnancy interval and success of vaginal birth after cesarean. STUDY DESIGN: Retrospective 10-year cohort study of pregnant women with one prior cesarean, who opted for trial of labor (n=36 653). Interpregnancy interval is the time between cesarean and next conception. Vaginal birth success rates were compared between six interval groups. Analysis was performed pooled as well as stratified for induction of labor. Adjusted odds ratios were calculated. RESULTS: Success rate in the reference group (12 to 24 months) was 72%. Success rates were similar among those with an interval of less than 24 months. Intervals of 24 months or more showed a decrease in success rate; 70% in 24- to 35-month intervals (adjusted odds ratio 0.92 (0.87 to 0.98)), 67% in 36- to 59-month intervals (adjusted odds ratio 0.87 (0.81 to 0.94)) and 62% in intervals of more than 60 months (adjusted odds ratio 0.77 (0.67 to 0.88)). CONCLUSION: An interpregnancy interval of <24 months is not associated with a decreased success of vaginal birth after cesarean. Success rates decrease when interval increases.

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.

Surgical Treatment of the Accessory Navicular (Os Tibiale Externum) in Dancers: A Retrospective Case Series.

This study is to draw attention to a relatively common anatomical anomaly and its possible operative treatment in dancers. The accessory navicular, or os tibiale externum, is an accessory bone on the medial side of the navicular of the foot at the insertion of the posterior tibial tendon (PTT). It can cause obvious hyperpronation, medial foot pain, and a limited and painful relevé in dancers. To the best of our knowledge, this is the first report on the operative treatment of the accessory navicular exclusively in dancers. Six dancers (10 feet) were treated in our clinic for a symptomatic accessory navicular Type II. Five of them (eight feet) underwent surgery, two unilaterally and three bilaterally (at the same time). All five had an excellent result at mean follow-up of 4.7 years, given that they fully resumed their professional dance activities without restriction, discomfort, or residual symptoms. One patient stopped dancing for unrelated reasons and became symptom free without further (surgical) treatment. Although no conclusions can be drawn from a retrospective case series and other treatment modalities were not considered, simple excision of a symptomatic accessory navicular Type II seems to be a good choice in dancers.

The Influence of a Sudden Increase in Playing Time on Playing-Related Musculoskeletal Complaints in High-Level Amateur Musicians in a Longitudinal Cohort Study.

BACKGROUND: Several studies in the domain of professional musicians describe the relation between playing time and the occurrence of musculoskeletal complaints in professional musicians. To date, no longitudinal cohort study into this relationship has been performed and no amateur musicians were studied. Therefore, the aim of this study is to examine the causal relationship between a sudden increase in playing time among amateur musicians on the occurrence of musculoskeletal complaints in a prospective cohort study. METHODS: All members of two national Dutch Students Orchestras were asked to participate in the study. These project-based orchestras, consisting of high-level amateurs, followed a nine-hour rehearsing schedule for ten consecutive days. On the first day (t0) and after one week (t1) the subjects were asked to complete a paper-based questionnaire including sociodemographic characteristics, music-related questions, questions regarding playing-related musculoskeletal complaints and the music module of the disabilities of arm, shoulder and hand questionnaire. RESULTS: The NSO consisted of 85 and the NESKO of 41 members during the study period. 59 subjects completed the questionnaire at both timepoints (response rate 47%). 9 subjects were excluded for being a music academy student, leaving 50 subjects (mean age 22.1, 72% female) suitable for analysis. During the rehearsal week, the prevalence of at least one playing-related musculoskeletal complaint increased from 28% to 80%. The most frequently affected areas were the neck, upper and lower back, hand/and or wrists and shoulders. The DASH music module score increased from 14 at t0 to 23 at t1. CONCLUSION: A point prevalence of 28% at the start of the study that increased remarkably to 80% within a one-week period. Future research should evaluate other risk factors for musculoskeletal complaints in amateur musicians. These risk factors should be the base for the development of preventive measures.

Trial of labor after cesarean: attempted operative vaginal delivery versus emergency repeat cesarean, a prospective national cohort study.

OBJECTIVE: To compare neonatal and maternal outcomes of attempted operative vaginal delivery with emergency repeat cesarean in trial of labor after cesarean. STUDY DESIGN: Prospective 8-year cohort analysis using the Netherlands Perinatal Registry, including women with one prior cesarean giving birth through operative vaginal delivery or emergency repeat cesarean (n=12860). A multivariate analysis was performed. Odds ratios (OR) and adjusted odds ratios (aOR) were calculated. RESULTS: Attempted operative vaginal delivery increases the risk on neonatal birth trauma (aOR 15.0 (5.94 to 38.0)) and postpartum hemorrhage (aOR 2.59 (2.17 to 3.09)), and lowers the risk of wet lung syndrome (aOR 0.53 (0.35 to 0.80)) and neonatal convulsions (aOR 0.47 (0.24 to 0.91)). CONCLUSION: We found a highly increased risk of neonatal birth trauma and a moderately increased risk of postpartum hemorrhage but slightly lower risks of wet lung syndrome and neonatal convulsions after attempted operative vaginal delivery compared with emergency repeat cesarean.

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.