Lancet
-
Randomized Controlled Trial Multicenter Study
Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial.
Why is this a landmark trial?
Three reasons:
- Clinical significance of the findings: reducing maternal mortality.
- Relevance to much of world's population, in particular to low resource settings where post-partum haemorrhage (PPH) is disproportionately burdensome.
- Quality – a massive, double-blinded randomised controlled trial.
So, what did they do?
They randomised 20,060 women with PPH to receive either 1g of tranexamic acid (100mg/min slow IV) or placebo, across 21 countries and 193 hospitals. Although only 569 (2.8%) patients were from a high resource country (UK).
What did they find?
Mortality due to haemorrhage was reduced by almost 20% (RR 0.81, NNT 267) after receiving tranexamic acid (TXA), and by 30% (RR 0.69) when given within 3 hours of birth.
Hysterectomies were not reduced by TXA use. There was no increased risk of thromboembolic events.
Be smart
While on the surface this suggests we should move to routine use of TXA in managing all PPH, the risk of PPH-death in most high resource countries is relatively low. 99% of all PPH deaths are in low resource countries.
In the WOMAN trial the risk of death in the placebo group was 1.9%. In contrast the latest maternal mortality data from MBRACE-UK (2014-16) reports 0.78 haemorrhage-deaths per 100,000 maternities, which using a conservative 5% PPH incidence (depending on definition), yields a PPH-mortality risk of 0.016% – 100x less than the study population.
Thus in a high resource setting the TXA NNT to avoiding one maternal death is generously at least 20,000 PPH cases.
In high resource settings, TXA use should be considered second-line therapy in managing severe PPH when other measures are inadequate. In low resource settings where maternal PPH mortality Is high, TXA reduces maternal mortality and should be routinely used.
Context is everything.
summary -
Randomized Controlled Trial
Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial.
IgA nephropathy is thought to be associated with mucosal immune system dysfunction, which manifests as renal IgA deposition that leads to impairment and end-stage renal disease in 20-40% of patients within 10-20 years. In this trial (NEFIGAN) we aimed to assess safety and efficacy of a novel targeted-release formulation of budesonide (TRF-budesonide), designed to deliver the drug to the distal ileum in patients with IgA nephropathy. ⋯ Pharmalink AB.
-
Kidney transplantation has become a routine procedure in the treatment of patients with kidney failure, and requires collaboration of experts from different disciplines, such as nephrology, surgery, immunology, pathology, infectious disease medicine, cardiology, and oncology. Grafts can be obtained from deceased or living donors, with different logistical requirements and implications for long-term graft patency. 1-year graft survival rates are greater than 95% in many centres but improvement of long-term function remains a challenge. ⋯ Tolerance induction by mixed chimerism without toxic conditioning and with a low risk of graft versus host disease is a visionary but realistic goal. Some of these innovations are already used in modern transplant centres and will allow advancement in long-term allograft preservation.
-
Acute kidney injury (AKI) is a multifaceted syndrome that occurs in different settings. The course of AKI can be variable, from single hit and complete recovery, to multiple hits resulting in end-stage renal disease. No interventions to improve outcomes of established AKI have yet been developed, so prevention and early diagnosis are key. ⋯ Use of balanced crystalloid solutions versus normal saline remains controversial. Renal replacement therapy should only be started on the basis of hard criteria, but should not be delayed when criteria are met. On the basis of recent evidence, the risk of contrast-induced AKI might be overestimated for many conditions.
-
We explored the variation in country mortality rates in the paediatric population receiving renal replacement therapy across Europe, and estimated how much of this variation could be explained by patient-level and country-level factors. ⋯ ERA-EDTA and ESPN.