皇家自由医院

BACKGROUND:Whether anticoagulation alone is an adequate treatment for acute, intermediate-risk pulmonary embolism is uncertain. METHODS:We conducted a multinational, adaptive-design trial with blinded outcome adjudication. Patients with intermediate-risk pulmonary embolism (with a ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter of ≥1.0 and an elevated troponin level) were eligible if they had at least two indicators of cardiorespiratory distress (systolic blood pressure of ≤110 mm Hg, a heart rate of ≥100 beats per minute, or a respiratory rate of >20 breaths per minute). Patients were randomly assigned to undergo ultrasound-facilitated, catheter-directed fibrinolysis with alteplase plus anticoagulation (the intervention group) or anticoagulation alone (the control group) according to prespecified treatment protocols. The primary outcome was a composite of pulmonary embolism-related death, cardiorespiratory decompensation or collapse, or symptomatic recurrence of pulmonary embolism within 7 days. RESULTS:The intention-to-treat population comprised 544 patients: 273 in the intervention group and 271 in the control group. The mean (±SD) age was 58.2±13.5 years, and 42.6% of the patients were women. A primary-outcome event occurred in 11 patients (4.0%; 95% confidence interval [CI], 2.3 to 7.1) in the intervention group and 28 (10.3%; 95% CI, 7.2 to 14.5) in the control group (relative risk, 0.39; 95% CI, 0.20 to 0.77; P = 0.005). The effect was driven primarily by a lower risk of cardiorespiratory decompensation or collapse in the intervention group. Major bleeding occurred within 7 days after randomization in 11 patients (4.1%) in the intervention group and 6 (2.2%) in the control group (P = 0.32); major bleeding occurred within 30 days in 11 patients (4.1%) and 8 patients (3.0%), respectively (P = 0.64). No substantial between-group differences in the incidence of other serious adverse events were observed up to 30 days after randomization; no intracranial hemorrhage occurred. CONCLUSIONS:In patients with acute, intermediate-risk pulmonary embolism, ultrasound-facilitated, catheter-directed fibrinolysis plus anticoagulation led to a lower risk of the composite of pulmonary embolism-related death, cardiopulmonary decompensation or collapse, or symptomatic recurrence of pulmonary embolism within 7 days than anticoagulation alone. (Funded by Boston Scientific; HI-PEITHO ClinicalTrials.gov number, NCT04790370.).

This ENETS guidance paper, developed by a multidisciplinary working group, provides up-to-date and practical advice on the diagnosis and management of lung and thymic carcinoids, based on recent developments and study results. These recommendations aim to provide practical recommendations for the diagnosis, treatment and follow-up of these tumours, and pave the road for more standardised care for our patients expecting improved outcomes. This paper is structured on a question-answer format in order to address common dilemmas encountered in clinical practice, including controversial issues and areas of uncertainty, based on the best available evidence and expert opinion when good quality evidence is not available. Each recommendation will provide a level of evidence and grade of recommendation as per the GRADE system (adapted from the Infectious Disease Society of United States Public Health Service grading system).

Postpartum haemorrhage (PPH) is a leading cause of maternal death. Preventing PPH can spare women from experiencing the trauma and risks of PPH, reduce the strain on overstretched health systems, and probably produce better outcomes than a strategy solely focused on PPH treatment. Prevention of PPH is often interpreted as provision of uterotonic drugs to contract the uterus at the time of childbirth. Although uterotonics are a central strategy for PPH prevention, several other approaches can prevent PPH or ameliorate its severity. These approaches include addressing the unmet need for contraception, remedying anaemia and other modifiable risk factors for PPH, optimising medical conditions that predispose to PPH, and tackling the rise in caesarean births in many countries. Effective delivery of preventive care requires early and regular antenatal care and planned birth at appropriately resourced health facilities. Social and behavioural change interventions for improving contraceptive provision and uptake, targeting adolescents, postpartum women, geographically remote communities, and families on low income, are a priority. Effective interventions to tackle anaemia include the management of heavy menstrual bleeding, pre-pregnancy or antenatal haemoglobin testing and oral or intravenous iron treatment, dietary improvements, and-on rare occasions-blood transfusion. Risk factors for PPH that need attention include high BMI, multiple pregnancy, gestational diabetes, pre-eclampsia, macrosomia, and several medical conditions. Caesarean births are associated with a substantial increase in PPH risk and should therefore only be done when medically indicated. A Cochrane network meta-analysis of 122 trials, with 121 931 women, found that the combinations of oxytocin plus misoprostol, or oxytocin plus ergometrine, were the most effective prophylaxis for PPH when given at the time of childbirth; however, these combinations had a higher risk of side-effects compared with single-drug prophylaxis. Oxytocin and carbetocin were the most effective single drugs for PPH prophylaxis, with minimal side-effects. Single uterotonic prophylaxis with either oxytocin or carbetocin is, therefore, recommended for routine prophylaxis. However, if oxytocin or carbetocin is not accessible, misoprostol is an alternative. Combination prophylaxis with oxytocin plus misoprostol can be considered for women at high risk of PPH. Ergometrine alone and oxytocin plus ergometrine combination are no longer recommended due to hypertension-related safety concerns. A robust implementation approach that engages various stakeholders to promote change, ensures the supply of quality-assured medicines and devices, provides training and support, and secures ongoing political and financial commitment is necessary to translate evidence into global impact.

Postpartum haemorrhage (PPH) is common, affecting an estimated 13% of women having vaginal birth and 31% of women having caesarean birth. Successful management of PPH requires early and accurate diagnosis and effective treatment. A systematic review found that subjective visual estimation of blood loss misses 52% of PPH diagnoses at vaginal birth (pooled sensitivity 48%, 95% CI 44-53), and probably more at caesarean birth. The WHO-International Federation of Gynecology and Obstetrics-International Confederation of Midwives consolidated guidelines on PPH therefore recommend objective quantification of blood loss with products such as a calibrated blood collection drape. When supported by a robust implementation strategy and a first-response treatment bundle, objective measurement of blood loss and monitoring of vital signs has been shown to diagnose PPH accurately and early, and improve clinical outcomes. Refractory PPH can progress to life-threatening PPH, which should be managed by a multidisciplinary team providing aggressive resuscitation and targeted treatment. Saving the life of a woman with excessive postpartum bleeding is a race against time. The six delays to avoid are: (1) in the diagnosis (by use of objective cumulative blood loss measurement and early trigger criteria), (2) in the first-response treatment (by authorising midwives to administer all components of a standardised bundle of interventions), (3) in the escalation (by use of explicit escalation criteria and red flags), (4) in the use of temporising measures (eg, non-pneumatic anti-shock garment), (5) in the identification and targeted management of any specific causes of bleeding, and (6) in the provision of blood and blood products. Quick actions to avoid these delays can mean the difference between life and death for a woman with PPH.