Thrombin generation in obstetric haemorrhage

The haemostatic system undergoes significant changes during pregnancy, particularly at term, leading to alterations in coagulation factors and anticoagulants. These changes result in an increase in procoagulant factors, such as, fibrinogen, factor VIII, and von Willebrand factor, along with reduced levels of anticoagulants like protein S. Consequently, a procoagulable state is established. Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide and may be caused or exacerbated by haemostatic impairment. Current research efforts have primarily focussed on examining coagulation factors and traditional laboratory investigations to monitor PPH and guide replacement of coagulation factors with fresh frozen plasma (FFP). Thrombin generation can be used to measure the integrated effects of procoagulant factors and so give an overview of haemostatic competence. There has been limited research into changes in thrombin generation during PPH and its potential to identify women who might benefit from FFP infusion. This thesis investigated thrombin generation in obstetric patients experiencing PPH and compared the results with non-bleeding pregnant women and non-pregnant participants. The main findings are that thrombin generation confirmed the prothrombotic state at term and remained raised or normal during almost all cases of PPH. This suggests that FFP would not improve haemostasis in most cases of PPH. By examining thrombin generation, a more comprehensive understanding of the haemostatic alterations in PPH can be obtained with the aim to improve individualised treatment

Die Facharztweiterbildung in Deutschland: Ein narrativer Überblick

The structure and content of the training phase following completion of medical school, referred to in most countries as postgraduate medical training, varies between countries. The purpose of this article is to give national and international readers an overview of the organisation and structure of postgraduate medical training in Germany. The content and duration of postgraduate training in Germany are stipulated by state medical boards, officially termed associations (Landesärztekammer). In a periodically updated decree, the federal German medical association (Bundesärztekammer) provides a template for postgraduate medical training structure (Musterweiterbildungsordnung), which is adapted by the state medical associations. Admission to postgraduate medical training in Germany takes place by way of open, free-market selection. Based on the traditional assumption that junior doctors acquire all necessary clinical skills “on the job”, formal education in the form of seminars, lectures, or preorganised, detailed rotation plans through various specialties or wards is largely absent. Requirements for postgraduate medical training focus on the fulfilment of broad categories of rotations rather than specific content or gaining competencies. With few exceptions, no structured educational programs with curricular learning objectives exist. Limited funding impedes program development and expansion. Junior doctors bear the primary organisational responsibility in their training, which often results in extended training times and dissatisfaction. Structured training programs which prioritise skill-building and formal education are needed to support junior doctors and ensure their competence in primary and specialty care.Die strukturellen und inhaltlichen Aspekte der Facharztweiterbildung (Englisch: postgraduate medical training) sind in vielen Ländern verschieden. Dieser Artikel soll nationalen und internationalen Leser*innen einen Überblick über die Organisation und Struktur der Facharztweiterbildung in Deutschland geben. Der Inhalt und die Dauer der Facharztweiterbildung werden durch die Landesärztekammern festgelegt. Die Weiterbildungsordnungen der Landesärztekammern orientieren sich an der von der Bundesärztekammer veröffentlichten Musterweiterbildungsordnung. Ärzt*innen in Weiterbildung in Deutschland bewerben sich auf offene Stellen im offenen, kompetitiven Arbeitsmarkt. Es wird weitgehend erwartet, dass die notwendigen Kompetenzen und Kenntnisse über die tägliche Arbeit im jeweiligen Fachgebiet erworben werden. Formale Weiterbildungsangebote im Sinne von Seminaren oder Vorlesungen sowie organisierte Rotationen durch verschiedene Weiterbildungsabschnitte werden selten oder nicht angeboten. Es gibt nur wenige strukturierte Weiterbildungsprogramme und wenig Förderung hierfür, sodass die Ärztin/der Arzt in Weiterbildung selbst für die Erfüllung der Anforderungen der Weiterbildungsordnung verantwortlich ist. Dies führt häufig zu verlängerten Weiterbildungszeiten und Unzufriedenheit mit der Weiterbildung. Strukturierte Weiterbildungsprogramme und eine Professionalisierung der Weiterbildung müssen in Deutschland erst noch etabliert werden, um Ärzt*innen in Weiterbildung beim gesicherten Kompetenzerwerb zu unterstützen

Prednisolone Versus Colchicine for Acute Gout in Primary Care (COPAGO): protocol for a two-arm multicentre, pragmatic, prospective, randomized, double-blind, controlled clinical trial of prednisolone and colchicine for non-inferiority with a parallel group design

Background Gout is the most common form of rheumatic disease in which monosodium urate crystals are deposited in the joints followed by acute inflammatory reactions. There are various approved drugs that can be prescribed for pain relief during an acute gout attack. However, to date, no direct comparison of efficacy of colchicine and prednisolone for the treatment of acute gout attacks has been investigated. Furthermore, the majority of previous research studies were not only conducted in tertiary centres but also excluded patients with common comorbidities due to contraindications to naproxen. Methods This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial investigates whether prednisolone (intervention) is non-inferior to treatment with colchicine (active control) in patients with acute gout. Adult patients presenting with acute gout to their general practitioners in 60 practices across 3 university sites (Greifswald, Göttingen, and Würzburg) are eligible to participate in the study. Participants in the intervention group receive 30 mg prednisolone for 5 days. Those in the control group receive low-dose colchicine (day 1: 1.5 mg; days 2–5: 1 mg). The primary outcome is the absolute level of the most severe pain on day 3 (in the last 24 h) measured with an 11-item numerical rating scale. Day 0 is the day patients take their study medication for the first time. They are then asked to fill out a study diary the same time each day for pain quantification. Pain scores are used for comparison between the two medications. Secondary outcomes are average response to treatment, swelling, tenderness and physical function of the joint, patients’ global assessment of treatment success, use of additional pain medication and non-pharmacological pain therapies. For safety reasons, potential side effects and course of systolic blood pressure are assessed. Discussion This trial will provide evidence on the effectiveness of pain reduction and side effects of colchicine and prednisolone in acute gout in primary care. Trial registration ClinicalTrials.gov Identifier: NCT05698680 first posted on January 26, 2023 (retrospectively registered). URL of trial registry record: https://clinicaltrials.gov/study/NCT0569868

Acute obstetric coagulopathy during postpartum hemorrhage is caused by hyperfibrinolysis and dysfibrinogenemia: an observational cohort study

Background Postpartum hemorrhage (PPH) may be exacerbated by hemostatic impairment. Information about PPH-associated coagulopathy is limited, often resulting in treatment strategies based on data derived from trauma studies. Objectives To investigate hemostatic changes associated with PPH. Patients/Methods From a population of 11 279 maternities, 518 (4.6%) women were recruited with PPH ≥ 1000 mL or placental abruption, amniotic fluid embolism, or concealed bleeding. Routine coagulation and viscoelastometric results were collated. Stored plasma samples were used to investigate women with bleeds > 2000 mL or those at increased risk of coagulopathy defined as placenta abruption, amniotic fluid embolism, or need for blood components. Procoagulant factors were assayed and global hemostasis was assessed using thrombin generation. Fibrinolysis was investigated with D-dimer and plasmin/antiplasmin complexes. Dysfibrinogenemia was assessed using the Clauss/antigen ratio. Results At 1000 mL blood loss, Clauss fibrinogen was ≤2 g/L in 2.4% of women and 6/27 (22.2%) cases of abruption. Women with very large bleeds (>3000 mL) had evidence of a dilutional coagulopathy, although hemostatic impairment was uncommon. A subgroup of 12 women (1.06/1000 maternities) had a distinct coagulopathy characterized by massive fibrinolysis (plasmin/antiplasmin > 40 000 ng/mL), increased D-dimer, hypofibrinogenemia, dysfibrinogenemia, reduced factor V and factor VIII, and increased activated protein C, termed acute obstetric coagulopathy. It was associated with fetal or neonatal death in 50% of cases and increased maternal morbidity. Conclusions Clinically significant hemostatic impairment is uncommon during PPH, but a subgroup of women have a distinct and severe coagulopathy characterized by hyperfibrinolysis, low fibrinogen, and dysfibrinogenemia associated with poor fetal outcomes

Additional file 1 of Prednisolone Versus Colchicine for Acute Gout in Primary Care (COPAGO): protocol for a two-arm multicentre, pragmatic, prospective, randomized, double-blind, controlled clinical trial of prednisolone and colchicine for non-inferiority with a parallel group design

Additional file 1. Trial flow for patients