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Gavin: Hello, and welcome to the Lancet Voice. It's August 2021, and I'm Gavin Cleaver. Her Life Matters is the striking name of a new documentary which examines the frustrations of a small team of scientists who, having proven that tranexamic acid has a significant effect in stopping women bleeding to death after giving birth, have come up against roadblocks in trying to get the treatment introduced to maternity wards around the world.
Tranexamic acid has been around since the 1950s, and is regularly used in dentistry, for example. The woman trial, conducted in 2017, showed that when women receive tranexamic acid within three hours of giving birth, risk of death is cut by 30%. So why isn't it routinely used to treat postpartum hemorrhage?
Jessamy and I spoke to two of the authors of the study about their attempts to have tranexamic acid introduced into maternity wards worldwide. Both of the authors were involved in the new documentary, Her Life Matters, and they're both from the London School of Hygiene and Tropical Medicine. Professor Halima Shakur Still is a professor of global health clinical trials at LSHTM, and she's also the co director of LSHTM's clinical trials unit, and Professor Ian Roberts is a professor of epidemiology, also at LSHTM.
We're here today to talk about tranexamic acid and postpartum hemorrhage and kind of the progress that's been made, or lack of, since the woman trial in 2017, which was published in The Lancet. Probably we should start off by talking a little bit about postpartum hemorrhage. How prevalent is it globally?
How much of a problem is it generally? And how is it currently treated?
Haleema: If I were to say to you, a woman will die from postpartum hemorrhage every six minutes, worldwide. But even with that, it doesn't actually give us an indication about how big this problem is because Most women survive, but they end up losing their womb and their ability to have children.
So about 14 million women every year suffer a postpartum hemorrhage.
Gavin: That's quite staggering really, isn't it? What are the kind of current treatments? So obviously we're here today talking about tranexamic acid, but we're going to talk as well a little about how It's not being as, as used as often as it could be given the results of the woman trial.
What are the current treatments?
Ian: There are a whole range of treatments. The main focus seems to be on drugs that contract the uterus. It's believed that something called uterine atony is an important cause of postpartum hemorrhage. The uterus sort of clamps down on itself after delivery of the placenta and that clamping down squeezes all the blood vessels so they don't bleed.
And so a class of drugs called uterotonics seem to be very much the focus of attention. Although having said that, the evidence that they reduce Postpartum hemorrhage death is not there. They reduce bleeding, but tranexamic acid is the only drug that's ever been shown to reduce death from postpartum hemorrhage, ever.
Reducing maternal deaths is a United Nations Sustainable Development Goal. So it's a goal of the world and then we've got this treatment that can help them meet that goal. All they have to do is make sure that every woman who has a postpartum hemorrhage gets this treatment, but it's been almost completely ignored so far.
Gavin: So how successful was tranexamic acid in, in, in treating postpartum hemorrhage?
Ian: Tranexamic acid reduced death. due to bleeding by about a third. It has to be given quickly because the treatment's more effective when it's given quickly, and women die quickly, so you have to give it to them, before their moribund.
So if tranexamic acid's given within three hours of injury, it reduces the risk. of death from postpartum hemorrhage by about a third, which is exactly the same as in trauma patients. So the basic pathophysiology is very similar. You've got acute onset of kind of traumatic bleeding to some extent.
And so the results of the woman trial are entirely consistent with what's gone before. And that makes the results even more compelling.
Haleema: So we we combined the data from CRASH 2 and the woman trial, and what we showed was that with every 15 minute you delay giving the treatment, you lose 10 percent of the benefit.
So by three hours, there's actually no benefit after that. in the women trial we also observed that most women who die from bleeding die within the first three hours anyway. So unless we intervene really early we're not going to get the best benefit from this treatment.
Jessamy: So it's incredible to have this very cheap and very effective drug for such an awful condition and you clearly have struggle trying to get this sort of implemented and you've made this documentary, Her Life Matters.
How did that come about? Can you tell us what's the backstory?
Haleema: It started with Crash 2, really. You suddenly work, you work for many years on a trial and then there's this one day where you have results. So Five years of recruitment, six months of developing protocol, data cleaning, all those kinds of things, years of work, and then suddenly you have this result.
And then What do you do with it? In Crash 2, we weren't prepared for what else we needed to do beyond publication because the standard thing we do in academia is we publish and it's how, the institution measure our performance as long as we publish, that's okay. But When we had the result for crash two, we realized we had this moral obligation, that we had this knowledge.
And unless we made people aware of this knowledge, patients aren't going to benefit because we spoke to colleagues who've done other trial. For example, the eclampsia. trial where they looked at magnesium sulfate for preeclampsia. And 20 years later, women still weren't benefiting. And we felt this was too long.
So for a woman, we started planning even before we had the trial results. We wanted to make sure it got into guidelines. We wanted to make sure it was an essential medicine, but. Most doctors don't read scientific papers, so we also had to think of other ways of making them aware of the results. We had things like mass media campaign, we did art sculptures, all kinds of different ways to engage doctors in the results.
But, It's very difficult to change behavior and establish medical knowledge because I remember us sitting on, we had results but we hadn't published yet and we were at a meeting and the discussion was around, we already have all information needed to save women but all we have to do is disseminate. I think we need new information as well as the dissemination.
And now we have this new information that's it's no longer new, it's well over three years. But getting it to where it's needed most, we're coming up against barriers we hadn't anticipated because we thought cheap generic drug, over a hundred manufacturers globally, available in most countries, but it's still not getting to where into the hospital where women are.
Ian: So I think to change behavior you need information, but the information's got to be packaged in a way that's received by humans, and the only thing that humans remember are emotionally compelling stories. I'm going back to the previous issue, really, that, we learned that in the CRASH 2 trial, that actually getting good results and publishing them in a medical journal is necessary, but not sufficient.
And so with a woman trial we were much more on. on the ball, the need to collect, emotionally compelling stories and to use the whole sort of range of creative tools like cartoons, poems, songs whatever there is. Part of the motivation to make The woman trial documentary when we went up to the documentary filmmakers to start with they say You know if you had to say what in a few lines what this film is about And basically what we said is well women are just getting shafted Everybody's bangs the drum and says how important this issue is But they don't do The obvious, there were not randomized trials of better treatments for postpartum hemorrhage.
There were a lot of people, wringing their hands and saying how difficult it is to do this and that and the other. Then we got a great result. And then they don't want to implement it, or the, the political response is weak. The response from the British government was very weak.
We were writing to the Secretary of State for Health, Secretary of State for International Development, now there isn't one. We were writing to these people, the political response has been very lukewarm. It was a trial funded by the British government and Gates and Wellcome, but the British government was the funder.
Now, if you fund something, you've got an obligation to do something with the results. It's not parlor game.
Haleema: But even in countries where you have a high maternal mortality rate, some countries did well. Some countries a lot of countries did nothing, Pakistan, for example, the hospitals at least the government hospitals, the tranexamic acid was made freely available.
And in fact, they implemented all of that even before tranexamic acid was put into the WHO treatment guidelines. And before it became an essential medicine, you also saw in the film, the response from Nigeria. So even though you had political engagement, it didn't go beyond that, the drugs available in country, but it's not getting beyond that point because this drug is so cheap and it can save lives and it should be made available like it was in Pakistan, freely available for when women need it.
need it because at the moment, if a doctor wants to give it in Nigeria, in Zambia, in many countries, a husband or a family member is sent outside of the hospital to buy it and bring it back. So firstly, you can't assure the quality of the drug that they're buying. And secondly, as we said, this is a.
critical time to treatment intervention. So if they take an hour to get the drug, by the time they come back, it can be too late. So I think we can call on our own governments, but we also need to call on the governments for countries where women are dying from postpartum hemorrhage to do something about it.
Jessamy: I mean you've obviously been on this extraordinary journey and I just wondered whether we might finish up by having you guys reflect on this journey of, as an academic, this process of how we converge on a consensus, on the agreed treatment for something and how that is then translated into clinical practice or into public health and those things that you've learned or that have become clear and difficult.
about that process, about those interactions that you have to have with politicians and, the multilateral system or
Haleema: Yeah, I remember us having the results and speaking to the WHO about the results. There was a quite positive response from the WHO, but they said that don't just accept results from a single clinical trial and that we needed to get a systematic review of the evidence done, which we did.
We did it in record time because I've. I personally believe that getting it into WHO guidelines will be something really substantial and would impact care worldwide. So we did everything possible to get it into guidelines and the WHO worked with us as well. So within six months of the results, we got it into guidelines.
And I thought, fantastic, but very quickly realized. that like the publication, this was yet another publication. It had almost no impact. Then starting working with ministers of health and in country working with our national coordinators to try and influence politicians and realizing that they will tell you what They think you want to hear, but then there's no action afterwards and realizing that you cannot stop this lobbying because unless we can get keep the message alive, it will just die and it will be 20 years down the line.
We're still. saying exactly the same thing and I don't think I, knowing that this treatment can reduce the risk of a mother bleeding to death by a third, we can wait another 10, 20 years for women to start benefiting.
Ian: In terms of Halima and I we both have clinical backgrounds, so we do research, but we think it's a sort of better way, a more efficient way of being clinically active in a way.
So if it doesn't really have an impact, then we're not really doing our job. But when it comes to this treatment, I think there's a big element of market failure. And the big advantage of tranexamic acid is that it's a cheap generic drug, but that's also its big disadvantage because If this was a patented drug, there would be a huge army of lobbyists everywhere, making sure that this drug was accessible, paid for, everything.
And because this is a cheap generic drug, that huge workforce is not there. And So we've got a small workforce, so we've got a small workforce trying to do what we, what this huge workforce normally does. What we've got is absolutely outstanding evidence, and that's how I That's our ace, really. The evidence is really strong and so we hope with this documentary that the wider medical community and even the public can get behind this and become the workforce that a patented drug would normally have.
Gavin: Thank you so much to Halima and to Ian for sharing their experiences. If you're interested in the struggle to introduce tranexamic acid into maternity wards You can watch their documentary online now for free at herlifematters. lshtm. ac. uk Brazil has been hard hit by COVID since the start of the pandemic.
We wanted to find out what the difficulties have been, where Brazil is now, and what the future looks like for Brazil's COVID efforts. For this, Dr. Thaiso Vila, editor in chief of our new journal, The Lancet Regional Health Americas, based in Rio, Brazil, spoke with Professor Wilson Savino, former president of the Brazilian Society of Immunology and currently coordinator of strategies for regional and national integration at the Oswaldo Cruz Foundation, or Fiocruz, which functions as a national institute for health in Brazil.
Taissa: I'm Dr. Thais Avila, the Editor in Chief of the Lancet Regional Health Americas and I'm based here in Rio de Janeiro, Brazil. I'm joined today by Dr. Savino who is an immunologist at the Oswaldo Cruz Institute, to talk to about Brazil's struggle with COVID over the last 16 months.
I want to take a couple of steps back and start from the beginning.
As a coordinator of the National Strategic Integration of Fiocruz, what are your thoughts on the early response of Brazil to the pandemics, let's say back in March 2020?
Wilson: First of all, thanks for the question. The problem of becoming political issues in many countries, including in Brazil, is necessarily not good for coping with the pandemic.
And this happened in many countries and It also happened in Brazil by March. There was a situation room for COVID also that began to be mounted at the level of the ministry of health by the previous minister of health. So what happened is after that left the Ministry of Health, we do not have continuity of this emergency room for coping with COVID 19.
This was really something very important because if you take Brazil with the geographical dimensions and heterogeneity and the fact that we have 220 million people in the country distribute in a federative way. So Brazil is a federative republic and the system, the unified health system in Brazil is subdivided in federal state layers and municipality layers.
It was absolutely necessary to have something working at the federal layer, which unfortunately Did not happen. So as the time went by, the states began to take actions, municipality began to take actions, but it was still we're lacking of a federal coordination. And for example, there were Cities in which quarantine was made more seriously than others and the economic pressure against total lockdown was very important in different parts of the country.
So it was very difficult to cope with by the fact that we did not have a strong federal coordination of all actions. that were taking place in Brazil at the same time. And I think this is was actually harmful for a better way to cope with these pandemics.
Taissa: Brazil is among the most unequal nations in the world.
And we know from research in other countries and also in Brazil, that the socioeconomic disparities are an important part. of how COVID 19 affects the country. How much of what's happening in Brazil and what happened in the beginning, would you say, is linked to not taking into account these disparities in the handling of the pandemic?
Wilson: I think that not taking into account was really, in a general way, was really something that enlarged the spread of the disease. And I can say that because, for example, around the headquarters of the Zoldo Cruz Foundation in Rio, there are some communities which live in very poor conditions. What Fiocruz has done Locally was to work with people there because we had actually before a sort of a direct communications between us with communities leaders in this poor neighborhoods and actually this did have a very positive effect in the way these poor communities could deal with the pandemic and the spread of the pandemic.
Dealing with inequalities is very difficult because the inequalities exist because we have, a disproportionate distribution of incomes and with this disproportionate pressures, economic pressures. So for example, it has been defined. In the city of Sao Paulo that rich people in the rich neighborhoods could be more rapidly more hospitalized, but died much less.
than people from poor neighborhoods. So inequalities are really something horrible, actually. And we could be, we should be ashamed from that. Together with the inequalities is the fact of fake news every day. Generated throughout the country disparities between positions, political, not political, but position from politicians on the use of masks on, closing schools, closing shopping centers, et cetera.
It could be less. Less worse than it was, than it still is. People don't deserve to suffer just because they are poor.
Taissa: Brazil still managed to secure local production of two vaccines, very, we'd say, early on. Both Bhutan Institute and the few crews you've mentioned before and you've worked for so many years and they are both internationally recognized institutions in vaccine development and they managed to locally produce two different vaccines and distribute in the country, but with less than 15 percent of the population fully immunized at this point.
So we're July 2021st and we still can't pass 20 percent of vaccinated people in a country that was once a world model for mass vaccinations. Why do you think we're struggling this time?
Wilson: There are different reasons that can explain together what's happening in terms of low rate of vaccination so far, and I should say different things.
First of all, as I said, Brazil has a very long experience of producing locally vaccines and a very high level organized program vaccination. So this is very important. We had and we are still dealing with a something that did not happen for 100 years, which is this pandemics. And the world tried to secure vaccines for countries, for different countries.
Let us say that in Brazil, there were two different and independent initiatives, one by Butantan Institute that decide at the level of state of Sao Paulo, to buy and to have a technology transfer to produce the CoronaVac vaccine, with a technology that was already established. at Butantan Institute and it worked well.
The option that the Osvaldo Cruz Foundation, together with the Department of Science and Technology of the Ministry of Health, of choosing Oxford AstraZeneca vaccine, if you think about pandemics, this pandemics and the future, I think it was a good choice. Because at the time we chose the Oxford AstraZeneca product is that we can now be able in Brazil to produce in large scale a vaccine with the technology that was used for the production of the Oxford AstraZeneca vaccine.
And this is very important because the future of vaccines, and this is I'm not saying this by myself, but, many experts in vaccines say that the future of vaccines will be dealing with the genomics of the pathogens. So this model of a genovirus is something that is within the future scenario.
And the fact that Phil Cruz decided to do that, I think it's very important. Having said that, there is something else I'd like to point out. First, there was a rush for buying vaccines throughout the world. And one of the things that all of us know is that some rich countries decided to buy different vaccines.
And paid a lot to do that as a sort of batting in different products so that to be sure that one or two would be effective, but at that time, almost one year ago, actually, nobody knew exactly the effectiveness of each of these vaccines. that were being developed were in phase two or phase three phases of clinical trials.
So Brazil did not have this attitude. There was one thing that was very good. There were studies comparing different vaccines and the option for Oxford AstraZeneca was a science based and also, code 10 for transportation. Again, Brazil is not a small country, so this could, should also be taken into account.
And I think this, all this was very good. The point is that. We did not enter the rush to buy six vaccines at the same time. And so we are in shortage of vaccines when, we should have begin this vaccination. Yet, by now, I think we are producing considerable amounts of vaccines. And the very first experiments that have been already checked, some cities in Brazil and But to cut to city in the state of Sao Paulo is a very good example of that is that once there was a massive vaccination, the decay of spreading of infection was reduced to 90 percent of reduction of.
spread of the virus. So this is really something important. So we are dealing with many difficulties, but still we are, moving forward. And I should just finish this answer by saying that the role of the Oswaldo Cruz Foundation and the Butantan Institute is really crucial for the success. of what's happening in Brazil now, even though it's not enough yet, we are moving forward to, at least I hope, a good ratio of vaccination.
Although the subject of Vabrants of concern is still something that we should, be aware of.
Taissa: For the last two months, we saw an average of near 2, 000. Daily deaths in Brazil, which you just mentioned that it is dropping, but still we passed the unbelievable mark of 500, 000 cumulative deaths. In your opinion, is it time for another quarantine?
Wilson: There are different points concerning your last questions or this question. First of all, it is really a shame for the country to have much more than 500, 000 people that have already died in this pandemic. We cannot accept this. So this is the starting point for getting into your question. We cannot accept just like that and be, just looking without doing nothing.
Vaccination is for sure something. That will, that is already and will be very important to constrain somehow the spread of the virus. So the disease, so the hospitalizations, so the loss of people. Brazil do not, does not deserve to lose such amount of persons. I would not say another quarantine because what happened in Brazil in the beginning was spots.
Of local quarantine arrangements that again were heterogeneous in terms of how deep each city that actually did quarantine did, get into a severe lockdown, a intense lockdown. I prefer to talk about a well organized quarantine. And I think well organized quarantine, and when I say organized quarantine, I would say a federal coordination of what's happening in Brazil.
Again, with such a geographic inequality, heterogeneity from state to state, from city to city in the same state. This can be done actually because we have health councils at the level of municipalities in each state, health councils at the level of states. So if we work together in the three levels Of the national health system in Brazil, and we can then provide in a very coordinated way a general but precise scenario of what's going on so we can settle a another or a new quarantine in a very much organized way.
And I'm sure that this will really be effective as well. And together, With massive vaccination.
Taissa: Do you see that happening?
Wilson: I want that happens. As I think that for this to happen, a major attitude should be taken by all policymakers in health in Brazil, which is solidarity. with coordination. I think that solidarity in such a pandemic throughout the world, among the nations, within a country, among the states and municipalities, within the families, it's absolutely necessary.
So I think that one major message that should achieve the whole society is the need of solidarity is the fact that Each one and all of us together can do, much, much, much more than the sum of individual initiatives. And so I think that the most important message I could tell you now is that the solidarity, but true solidarity with organization at the different levels of the unified health system in Brazil, which by the way, is the only country that has a unified health system in a such huge population with more than 200 million people.
I think that if we do have, and we do settle, A organized solidarity initiative with different, lockdowns specifically in different cities, the areas if necessary, massive vaccination, massive distribution of masks. which, by the way, Phil Cruz is doing in the city of Rio de Janeiro. This is the most effective thing that we should learn and act concerning this pandemic.
And when I say learning for the present and learning for the future.
Taissa: And that goes really well with your piece that
Wilson: you
Taissa: recently wrote to us. And it's very touching.
Wilson: And it's true,
Taissa: I, I know it's just it's very touching when you say I have a quote here, cause I keep going back to it when you say it's unacceptable that developed countries establish export barriers, patent protections, mechanisms in the pandemic can't.
Text restricting technological transfer for producers in less developed country. The whole word must have equal access to vaccines and benefit from the transforming triad education, science and health. Putting people first and leaving no one behind is a very powerful sentence.
Gavin: Thank you to Savino and to Thaisa for those insights into public health and COVID in Brazil. Place's journal, The Lancet Regional Health Americas, is open access and has just published some of its first research. In the build up to its first issue coming out, they're open to submissions from around the Americas, and you can find out more about that on thelancet.
com. I'd like to thank you for listening to this episode of The Lancet Voice. If you're not subscribed yet, you can of course rectify that by searching for The Lancet Voice and picking the platform of your choice, and we hope to see you again next time for more stories from around the world of health and healthcare.