Pharmacological pain relief and fear of childbirth in low risk women; secondary analysis of the RAVEL study

Acknowledgements We would like to thank all of the participants in our study and the midwives and gynaecologists of the participating practices and hospitals respectively. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on request.Peer reviewedPublisher PD

Імунологічні аспекти діагностики та лікування постгістеректомічного синдрому

В статье представлены данные клинико-иммунологического, вегетологического, психологического статуса 80 женщин, страдающих постгистерэктомическими расстройствами с целью поиска оптимальных подходов к терапии. Установлено, что постгистерэктомический синдром сопровождается различными изменениями нейровегетативной регуляции, коррелирующими с гормонально-иммунологическими нарушениями. Стабильные положительные клинико-иммунологические сдвиги у пациенток с постгистерэктомическим синдромом показали высокую эффективность включения иммунокорригирующих препаратов для оптимизации терапевтических мероприятий в борьбе с указанной патологией.Basing on clinical, immunological, vegetologycal investigations in 80 women with posthysterectomy disorders with the purpose of search of optimum pathogenetic approaches to therapy. It has been found that a posthysterectomy syndrome is accompanied by the different changes neyrovegetatic regulationand also psychoemotional disorders. New important hormonal and immunological aspects of pathogenesis were determinated. Stable positive clinical and immunological changes at patients with a postgysterektomy syndrome showed high effect of including of immunological correction for the complex of treatment of patients with this pathology

Potential improvement of pregnancy outcome through prenatal small for gestational age detection

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA. OBJECTIVE: To assess differences in mode of delivery and pregnancy outcome between prenatally detected and nonprenatally detected small for gestational age (SGA) neonates born at term.STUDY DESIGN: We performed a retrospective multicenter cohort study. All singleton infants, born SGA in cephalic position between 36(0/7) and 41(0/7) weeks gestation, were classified as either prenatally detected SGA or nonprenatally detected SGA. With propensity score matching we created groups with comparable baseline characteristics. We compared these groups for composite adverse perinatal outcome, labor induction, and cesarean section rates.RESULTS: We included 718 SGA infants, of whom 555 (77%) were not prenatally detected. Composite adverse neonatal outcome did not differ statistically significant between the matched prenatally detected and the nonprenatally detected group (5.5 vs. 7.4%, odds ratio [OR] 0.74, 95% confidence interval [CI]: 0.30-1.8). However, perinatal mortality only occurred in the nonprenatally detected group (1.8% [3/163] in the matched cohort, 1.3% [7/555] in the complete cohort). In the propensity matched prenatally detected SGA group both induction of labor (57 vs. 9%, OR 14.0, 95% CI: 7.4-26.2) and cesarean sections (20 vs. 8%, OR 2.9, 95% CI: 1.5-5.8) were more often performed compared with the nonprenatally detected SGA group.CONCLUSION: Prenatal SGA detection at term allows timely induction of labor and cesarean sections thus potentially preventing stillbirth

Natural variability of TRAIL, IP-10, and CRP in healthy adults - The "HERACLES" study

A novel host-protein score (called MMBV) helps to distinguish bacterial from viral infection by combining the blood concentrations of three biomarkers: tumour necrosis factor related apoptosis inducing ligand (TRAIL), interferon gamma induced protein 10 (IP-10), and C-reactive protein (CRP). These host biomarkers are differentially expressed in response to bacterial versus viral acute infection. We conducted a prospective study, with a time series design, in healthy adult volunteers in the Netherlands. The aim was to determine the variability of TRAIL, IP-10, and CRP and the MMBV score in healthy adults across time. Up to six blood samples were taken from each healthy volunteer over a period of up to four weeks. In 77 healthy participants without recent or current symptoms, MMBV scores (maximal) were bacterial in 1.3 % and viral (or other non-infectious etiology) in 93.5 % of participants. There was little variation in the mean concentrations of TRAIL (74.5 pg/ml), IP-10 (113.6 pg/ml), and CRP (1.90 mg/L) as well as the MMBV score. The variability of biomarker measurement was comparable to the precision of the measurement platform for TRAIL, IP-10, and CRP. Our findings establish the mean values of these biomarkers and MMBV in healthy individuals and indicate little variability between and within individuals over time, supporting the potential utility of this novel diagnostic to detect infection-induced changes

Do efficacy results obtained from randomized controlled trials translate to effectiveness data from observational studies for relapsing–remitting multiple sclerosis?

Background: Randomized controlled trials are considered the gold standard in regulatory decision making, as observational studies are known to have important methodological limitations. However, real-world evidence may be helpful in specific situations. This review investigates how the effect estimates obtained from randomized controlled trials compare to those obtained from observational studies, using drug therapy for relapsing–remitting multiple sclerosis as an example. Study Design and Setting: A systematic review of randomized controlled trials and observational studies was conducted. The primary outcome was the annualized relapse rate. Using (network) meta-analysis together with posterior predictive distributions, the drug-specific rate ratios from the network of randomized controlled trials were compared with those from the network of observational studies. Results: Effect estimates from 26 observational studies showed greater magnitudes and were less precise compared to estimates obtained from 21 randomized controlled trials. Twenty of the 28 treatment comparisons between designs had similar rate ratios. Seven inconsistencies in observed rate ratios could be attributed to two specific disease-modifying therapies. Conclusion: In this case study, estimates from observational studies predominantly agreed with estimates from randomized controlled trials given their posterior predictive distributions. Multiple observational studies together may therefore supplement additional pivotal randomized controlled trials in relapsing–remitting multiple sclerosis, for instance facilitating the extrapolation of trial results to the broader patient population

Минералогические исследования в пещерной системе Снежная-Меженного-Иллюзия (Западный Кавказ, Бзыбский хребет): предварительные результаты и направления дальнейших работ

В статье приводятся сведения о минеральном составе водных хемогенных и водных механических отложений в пещерной системе Снежная-Меженного-Иллюзия. В состав водных хемогенных отложений входят Mg- и Sr-содержащий кальцит, арагонит, гипс, гидромагнезит, целестин, стронцианит, доломит, гетит, рутил и циркон. Водные механические отложения сложены преимущественно доломитом, кварцем и кальцитом. В схожих по морфологии и микроклимату частях пещерной системы наблюдаются одинаковые вторичные минералы.У статті наводяться відомості про мінеральний склад водних хемогенних і водних механічних відкладень в печерній системі Сніжна-Меженого-Ілюзія. До складу водних хемогенних відкладень входять кальцит, який містить Mg і Sr, арагоніт, гіпс, гідромагнезіт, целестин, стронціаніт, доломіт, гетит, рутил і циркон. Водні механічні відкладення складені переважно доломітом, кварцом і кальцитом. У схожих за морфологєю та мікрокліматом частинах печерної системи спостерігаються однакові вторинні мінерали.The article presents the preliminary characteristic of the mineral composition of chemogenic formations and clastic deposits of Snezhnaya-Mezhennogo-Illusia cave system. Chemogenic formations are composed by Mg- and Sr-calcite, aragonite, gypsum and hydromagnesite, celestite, strontianite, dolomite, goethite, rutile and zircon. Clastic sediments are composed mainly by dolomite, quartz and calcite. Same secondary minerals are observed in those parts of the cave system that have similar morphology and microclimate

Applicability and added value of novel methods to improve drug development in rare diseases

The ASTERIX project developed a number of novel methods suited to study small populations. The objective of this exercise was to evaluate the applicability and added value of novel methods to improve drug development in small populations, using real world drug development programmes as reported in European Public Assessment Reports. The applicability and added value of thirteen novel methods developed within ASTERIX were evaluated using data from 26 European Public Assessment Reports (EPARs) for orphan medicinal products, representative of rare medical conditions as predefined through six clusters. The novel methods included were 'innovative trial designs' (six methods), 'level of evidence' (one method), 'study endpoints and statistical analysis' (four methods), and 'meta-analysis' (two methods) and they were selected from the methods developed within ASTERIX based on their novelty; methods that discussed already available and applied strategies were not included for the purpose of this validation exercise. Pre-requisites for application in a study were systematized for each method, and for each main study in the selected EPARs it was assessed if all pre-requisites were met. This direct applicability using the actual study design was firstly assessed. Secondary, applicability and added value were explored allowing changes to study objectives and design, but without deviating from the context of the drug development plan. We evaluated whether differences in applicability and added value could be observed between the six predefined condition clusters. Direct applicability of novel methods appeared to be limited to specific selected cases. The applicability and added value of novel methods increased substantially when changes to the study setting within the context of drug development were allowed. In this setting, novel methods for extrapolation, sample size re-assessment, multi-armed trials, optimal sequential design for small sample sizes, Bayesian sample size re-estimation, dynamic borrowing through power priors and fall-back tests for co-primary endpoints showed most promise - applicable in more than 40% of evaluated EPARs in all clusters. Most of the novel methods were applicable to conditions in the cluster of chronic and progressive conditions, involving multiple systems/organs. Relatively fewer methods were applicable to acute conditions with single episodes. For the chronic clusters, Goal Attainment Scaling was found to be particularly applicable as opposed to other (non-chronic) clusters. Novel methods as developed in ASTERIX can improve drug development programs. Achieving optimal added value of these novel methods often requires consideration of the entire drug development program, rather than reconsideration of methods for a specific trial. The novel methods tested were mostly applicable in chronic conditions, and acute conditions with recurrent episodes. The online version of this article (10.1186/s13023-018-0925-0) contains supplementary material, which is available to authorized users

How are "teaching the teachers" courses in evidence based medicine evaluated? A systematic review

Background Teaching of evidence-based medicine (EBM) has become widespread in medical education. Teaching the teachers (TTT) courses address the increased teaching demand and the need to improve effectiveness of EBM teaching. We conducted a systematic review of assessment tools for EBM TTT courses. To summarise and appraise existing assessment methods for teaching the teachers courses in EBM by a systematic review. Methods We searched PubMed, BioMed, EmBase, Cochrane and Eric databases without language restrictions and included articles that assessed its participants. Study selection and data extraction were conducted independently by two reviewers. Results Of 1230 potentially relevant studies, five papers met the selection criteria. There were no specific assessment tools for evaluating effectiveness of EBM TTT courses. Some of the material available might be useful in initiating the development of such an assessment tool. Conclusion There is a need for the development of educationally sound assessment tools for teaching the teachers courses in EBM, without which it would be impossible to ascertain if such courses have the desired effect