A septate uterus is a uterine anomaly that may affect reproductive outcome, and is associated with an increased risk for miscarriage, subfertility and preterm birth. Resection of the septum is ...subject of debate. There is no convincing evidence concerning its effectiveness and safety. This study aims to assess whether hysteroscopic septum resection improves reproductive outcome in women with a septate uterus.
A multi-centre randomised controlled trial comparing hysteroscopic septum resection and expectant management in women with recurrent miscarriage or subfertility and diagnosed with a septate uterus. The primary outcome is live birth, defined as the birth of a living foetus beyond 24 weeks of gestational age. Secondary outcomes are ongoing pregnancy, clinical pregnancy, miscarriage and complications following hysteroscopic septum resection. The analysis will be performed according to the intention to treat principle. Kaplan-Meier curves will be constructed, estimating the cumulative probability of conception leading to live birth rate over time. Based on retrospective studies, we anticipate an improvement of the live birth rate from 35% without surgery to 70% with surgery. To demonstrate this difference, 68 women need to be randomised.
Hysteroscopic septum resection is worldwide considered as a standard procedure in women with a septate uterus. Solid evidence for this recommendation is lacking and data from randomised trials is urgently needed.
Dutch trial registry ( NTR1676 , 18th of February 2009).
The purpose of this study was to examine the variation in surgical treatment rates of patients with distal radius fractures across Dutch hospitals. We obtained all reimbursement data for the ...treatment of distal radius fractures for 2012 and 2013 categorized by hospital. The surgical rate across hospitals was corrected for possible explanatory variables using linear regression analyses. We analysed a total of 95,754 reimbursements. The operative rate ranged from 0% to 23%, with a mean of 9.6%. Hospital type, the percentage of females, the percentage of patients over 65, the mean age, average socioeconomic status and the total number of patients treated explained only 2.6% of the observed differences in the operative rate among hospitals in 2012 and 11.6% in 2013. Our results suggest that subjective factors, such as surgeon’s opinions and preferences, significantly influence therapeutic decisions in patients with distal radius fractures.
Level of evidence: III
Mevalonate kinase deficiency (MKD) is characterized by recurrent fevers and flares of systemic inflammation, caused by biallelic loss-of-function mutations in MVK. The underlying disease mechanisms ...and triggers of inflammatory flares are poorly understood because of the lack of in vivo models. We describe genetically modified mice bearing the hypomorphic mutation p.Val377Ile (the commonest variant in patients with MKD) and amorphic, frameshift mutations in Mvk. Compound heterozygous mice recapitulated the characteristic biochemical phenotype of MKD, with increased plasma mevalonic acid and clear buildup of unprenylated GTPases in PBMCs, splenocytes, and bone marrow. The inflammatory response to LPS was enhanced in compound heterozygous mice and treatment with the NLRP3 inflammasome inhibitor MCC950 prevented the elevation of circulating IL-1beta, thus identifying a potential inflammasome target for future therapeutic approaches. Furthermore, lines of mice with a range of deficiencies in mevalonate kinase and abnormal prenylation mirrored the genotype-phenotype relationship in human MKD. Importantly, these mice allowed the determination of a threshold level of residual enzyme activity, below which protein prenylation is impaired. Elevated temperature dramatically but reversibly exacerbated the deficit in the mevalonate pathway and the defective prenylation in vitro and in vivo, highlighting increased body temperature as a likely trigger of inflammatory flares.
Optimal development of fertilized eggs into preimplantation embryos is essential for reproduction. Although mammalian oocytes ovulated after luteinizing hormone (LH) stimulation can be fertilized and ...promoted into early embryos in vitro, little is known about ovarian factors important for the conditioning of eggs for early embryo development. Because LH interacts only with ovarian somatic cells, its potential regulation of oocyte functions is presumably mediated by local paracrine factors. We performed DNA microarray analyses of ovarian transcripts and identified brain-derived neurotrophic factor (BDNF) secreted by granulosa and cumulus cells as an ovarian factor stimulated by the preovulatory LH surge. Ovarian BDNF acts on TrkB receptors expressed exclusively in oocytes to enhance first polar body extrusion of oocytes and to promote the in vitro development of zygotes into preimplantation embryos. Furthermore, in vivo treatment with a Trk receptor inhibitor suppressed first polar body extrusion and the progression of zygotes into blastocysts. Thus, ovarian BDNF is important to nuclear and cytoplasmic maturation of the oocyte, which is essential for successful oocyte development into preimplantation embryos. Treatment with BDNF could condition the cultured oocytes for optimal progression into the totipotent blastocysts.
Abstract
Background
In recent years it has become clear that fetal anomalies can already be detected at the end of the first trimester of pregnancy by two-dimensional (2D) ultrasound. This is why ...increasingly in developed countries the first trimester anomaly scan is being offered as part of standard care. We have developed a Virtual Reality (VR) approach to improve the diagnostic abilities of 2D ultrasound. Three-dimensional (3D) ultrasound datasets are used in VR assessment, enabling real depth perception and unique interaction. The aim of this study is to investigate whether first trimester 3D VR ultrasound is of additional value in terms of diagnostic accuracy for the detection of fetal anomalies. Health-related quality of life, cost-effectiveness and also the perspective of both patient and ultrasonographer on the 3D VR modality will be studied.
Methods
Women in the first trimester of a high risk pregnancy for a fetus with a congenital anomaly are eligible for inclusion. This is a randomized controlled trial with two intervention arms. The control group receives ‘care as usual’: a second trimester 2D advanced ultrasound examination. The intervention group will undergo an additional first trimester 2D and 3D VR ultrasound examination. Following each examination participants will fill in validated questionnaires evaluating their quality of life and healthcare related expenses. Participants’ and ultrasonographers’ perspectives on the 3D VR ultrasound will be surveyed. The primary outcome will be the detection of fetal anomalies. The additional first trimester 3D VR ultrasound examination will be compared to ‘care as usual’. Neonatal or histopathological examinations are considered the gold standard for the detection of congenital anomalies. To reach statistical significance and 80% power with a detection rate of 65% for second trimester ultrasound examination and 70% for the combined detection of first trimester 3D VR and second trimester ultrasound examination, a sample size of 2800 participants is needed.
Discussion
First trimester 3D VR detection of fetal anomalies may improve patients’ quality of life through reassurance or earlier identification of malformations. Results of this study will provide policymakers and healthcare professionals with the highest level of evidence for cost-effectiveness of first trimester ultrasound using a 3D VR approach.
Trial registration
Dutch Trial Registration number
NTR6309
, date of registration 26 January 2017.
The WHO European Region (EUR) has adopted the goal of eliminating measles and rubella but individual countries perform differently in achieving this goal. Measles virus spread across the EUR by ...mobile groups has recently led to large outbreaks in the insufficiently vaccinated resident population. As an instrument for monitoring the elimination process and verifying the interruption of endemic virus transmission, molecular surveillance has to provide valid and representative data. Irrespective of the country's specific situation, it is required to ensure the functionality of the laboratory surveillance that is supported by the WHO Global Measles and Rubella Laboratory Network.
To investigate whether the molecular surveillance in the EUR is adequate for the challenges in the elimination phase, we addressed the quality assurance of molecular data, the continuity and intensity of molecular monitoring, and the analysis of transmission chains.
Published articles, the molecular External Quality Assessment Programme of the WHO, the Centralized Information System for Infectious Diseases of the WHO EUR and the WHO Measles and Rubella Nucleotide Surveillance databases served as information sources.
Molecular proficiency testing conducted by the WHO in 2016 has shown that the expertise for measles and rubella virus genotyping exists in all parts of the EUR. The analysis of surveillance data reported nationally to the WHO in 2013–2016 has revealed some countries with outbreaks but not sufficiently representative molecular data. Long-lasting supranational MV transmission chains were identified.
A more systematic molecular monitoring and recording of the transmission pattern for the whole EUR could help to create a meaningful picture of the elimination process.
This study describes a minimally invasive procedure for stabilization of the distal radioulnar joint, using a suture-button construct placed percutaneously in the direction of the distal oblique ...bundle in the distal interosseous membrane. In five cadaveric specimens, placement of the suture-button suspension system reduced dorsal displacement of the radius in an unstable distal radioulnar joint to baseline values, both in neutral position and in pronation and supination. These results indicate the possibility of minimally invasive treatment for distal radioulnar joint instability.
Purpose To allow physicians to be more selective in their request for a radiograph of the wrist and to potentially reduce costs, the Amsterdam Wrist Rules (AWR) have been developed, externally ...validated, and recently also implemented. The aim of this study was to conduct an incremental cost analysis and budget impact analysis of the implementation of the AWR at the emergency department (ED) in the Netherlands. Methods A cost-minimisation analysis to determine the expected cost savings for implementation of the Amsterdam Wrist Rules. The incremental difference in costs before and after implementation of the AWR was based on the reduction in costs for radiographs, the cost savings due to reduction of ED consultation times and the costs of a re-evaluation appointment by a physician. Results In the Netherlands, implementation of the AWR could potentially result in 6% cost savings per patient with a wrist injury. In addition, implementation of the AWR resulted in €203,510 cost savings annually nationwide. In the sensitivity analysis, an increase in physician compliance to 100% substantially increased the potential total amount of annual cost savings to €610,248, which is 6% of total costs before implementation. Variation in time spent at the ED, a decrease and increase in costs and patients presenting annually at the ED did not change the cost savings substantially. Conclusion Implementation of the AWR has been shown to reduce direct and indirect costs and can, therefore, result in considerable savings of healthcare consumption and expenditure.
In patients undergoing solid organ transplantation, the presence of an interleukin-1 (IL-1) driven disease may require the addition of IL-1 inhibiting drugs to the standard immunosuppressive regimen ...to protect against inflammation and negative graft outcome. Three patients undergoing renal transplantation were treated perioperatively with the interleukin-1 receptor antagonist anakinra. Kidney function increased rapidly in all three and the only complications seen were minor infections.
studies report associations between serum and urinary levels of IL-1β and IL-1 receptor antagonist and negative graft outcome, and studies in animals and two small human trials illustrate a possible protective effect of anti-IL-1 therapy after solid organ transplantation. Peri- and postoperative use of anakinra is safe and effective in patients undergoing renal transplantation.
To determine methicillin-resistant Staphylococcus aureus (MRSA) carriage in poultry and slaughterhouse personnel, 40 Dutch broiler flocks, in six slaughterhouses and 466 personnel were sampled. Of ...the employees, 26 were positive (5·6%), indicating a higher risk of exposure when compared to the general Dutch population (0·1%). This risk was significantly higher for personnel having contact with live animals (5·2%) – especially hanging broilers on the slaughterline (20·0%) – than for all other personnel (1·9%). Conventional electric stunning conferred a significantly higher risk of MRSA carriage for employees than CO2 stunning (9·7% vs. 2·0%). A total of 405 broilers were sampled upon their arrival at the slaughterhouse, of which 6·9% were positive. These broilers originated from 40 Dutch slaughter flocks of which 35·0% were positive. MRSA contamination in the different compartments of slaughterhouses increased during the production day, from 8% to 35%. Of the 119 MRSA isolates, predominantly livestock-associated MRSA ST398 was found, although 27·7% belonged to ST9 (spa type t1430). There is an increased risk of MRSA carriage in personnel working at broiler slaughterhouses, particularly those having contact with live animals.
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