Convalescent plasma: the picture is getting clearer

 Slowly, there is evidence accumulating that convalescent plasma is helpful in treating patients with severe Covid, if it is administered early.  There is also evidence that it doesn't help much once the disease has become well established, particularly when the primary symptoms become due to the body's own immune reaction.  These caveats help explain why early reports did not find an effect of convalescent plasma--i.e. it helped only a subset of the patients to whom it was administered. But for those it was sometimes life saving. Here is a recent paper from the New England Journal of Medicine.

Convalescent Plasma for Covid-19–Induced ARDS in Mechanically Ventilated Patients by Benoît Misset, M.D., Michael Piagnerelli, M.D., Ph.D., Eric Hoste, M.D., Ph.D., Nadia Dardenne, M.Sc., David Grimaldi, M.D., Ph.D., Isabelle Michaux, M.D., Ph.D., Elisabeth De Waele, M.D., Ph.D., Alexander Dumoulin, M.D., Philippe G. Jorens, M.D., Ph.D., Emmanuel van der Hauwaert, M.D., Frédéric Vallot, M.D., Stoffel Lamote, M.D., et al., October 26, 2023, N Engl J Med 2023; 389:1590-1600 DOI: 10.1056/NEJMoa2209502

"Abstract

BACKGROUND

Passive immunization with plasma collected from convalescent patients has been regularly used to treat coronavirus disease 2019 (Covid-19). Minimal data are available regarding the use of convalescent plasma in patients with Covid-19–induced acute respiratory distress syndrome (ARDS).

METHODS

In this open-label trial, we randomly assigned adult patients with Covid-19–induced ARDS who had been receiving invasive mechanical ventilation for less than 5 days in a 1:1 ratio to receive either convalescent plasma with a neutralizing antibody titer of at least 1:320 or standard care alone. Randomization was stratified according to the time from tracheal intubation to inclusion. The primary outcome was death by day 28.

RESULTS

A total of 475 patients underwent randomization from September 2020 through March 2022. Overall, 237 patients were assigned to receive convalescent plasma and 238 to receive standard care. Owing to a shortage of convalescent plasma, a neutralizing antibody titer of 1:160 was administered to 17.7% of the patients in the convalescent-plasma group. Glucocorticoids were administered to 466 patients (98.1%). At day 28, mortality was 35.4% in the convalescent-plasma group and 45.0% in the standard-care group (P=0.03). In a prespecified analysis, this effect was observed mainly in patients who underwent randomization 48 hours or less after the initiation of invasive mechanical ventilation. Serious adverse events did not differ substantially between the two groups.

CONCLUSIONS

The administration of plasma collected from convalescent donors with a neutralizing antibody titer of at least 1:160 to patients with Covid-19–induced ARDS within 5 days after the initiation of invasive mechanical ventilation significantly reduced mortality at day 28. This effect was mainly observed in patients who underwent randomization 48 hours or less after ventilation initiation."

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Here are my posts on convalescent plasma, and the confusing initial reports about its effects.

Photos from the daily market design activity at Stanford

Two photos remind me of the day to day market design activity at Stanford. 

Tinglong Dai joined our Wednesday market design coffee and sent along this picture. (You can see who came by plane and who came by bike...)  He wrote about his visit here.

And Matias Cersosimo successfully defended his dissertation on Friday, which  included market design experiments like this one.

 Welcome to the club, Matias.

Design of (international) kidney exchange: ex-post rejection versus ex-ante withholding

 Here's a paper by several Dutch computer scientists, which seems to be motivated by the problem of international kidney exchange within the EU, in which there are lots of concerns about fairness between countries.  But (as the paper notes) these could also apply to individual transplant centers, in the U.S. context.  The thrust of the paper is that looking for exchanges that won't be rejected ex post in a full information environment may be more productive than looking for ways to incentivize countries or transplant centers to reveal their full sets of patient donor pairs in an incomplete information environment.

Blom, Danny, Bart Smeulders, and Frits Spieksma. "Rejection-Proof Mechanisms for Multi-Agent Kidney Exchange." Games and Economic Behavior (2023).

Abstract: Kidney exchange programs (KEPs) increase kidney transplantation by facilitating the exchange of incompatible donors. Increasing the scale of KEPs leads to more opportunities for transplants. Collaboration between transplant organizations (agents) is thus desirable. As agents are primarily interested in providing transplants for their own patients, collaboration requires balancing individual and common objectives. In this paper, we consider ex-post strategic behavior, where agents can modify a proposed set of kidney exchanges. We introduce the class of rejection-proof mechanisms, which propose a set of exchanges such that agents have no incentive to reject them. We provide an exact mechanism and establish that the underlying optimization problem is 

we also describe computationally less demanding heuristic mechanisms. We show rejection-proofness can be achieved at a limited cost for typical instances. Furthermore, our experiments show that the proposed rejection-proof mechanisms also remove incentives for strategic behavior in the ex-ante setting, where agents withhold information.

Fairness in algorithms: Hans Sigrist Prize to Aaron Roth

 The University of Bern's Hans Sigrist Prize has been awarded to Penn computer scientist Aaron Roth, and will be celebrated today.

Here are today's symposium details and schedule:

The Hans Sigrist Symposium

Data Science: The Power of the Human Mind for the Sake of Humankind

Here's an interview:

Aaron Roth: Pioneer of fair algorithms  In December 2023, the most highly endowed prize of the University of Bern will go to the US computer scientist Aaron Roth. His research aims to incorporate social norms into algorithms and to better protect privacy.  by Ivo Schmucki 

"There are researchers who sit down and take on long-standing problems and just solve them, but I am not smart enough to do that," says Aaron Roth. "So, I have to be the other kind of researcher. I try to define a new problem that no one has worked on yet but that might be interesting."

"Aaron Roth's own modesty may stand in the way of understanding the depth of his contributions. In fact, when he authored his doctoral thesis on differential privacy about 15 years ago and then wrote on the fairness of algorithms a few years later, terms like “Artificial Intelligence” and “Machine Learning” were far from being as firmly anchored in our everyday lives as they are today. Aaron Roth was thus a pioneer, laying the foundation for a new branch of research.

"I am interested in real problems. Issues like data protection are becoming increasingly important as more and more data is generated and collected about all of us," says Aaron Roth about his research during the Hans Sigrist Foundation’s traditional interview with the prize winner. He focuses on algorithmic fairness, differential privacy, and their applications in machine learning and data analysis.

...

"It is important that more attention is paid to these topics," says Mathematics Professor Christiane Tretter, chair of this year's Hans Sigrist Prize Committee. Tretter says that many people perceive fairness and algorithms as two completely different poles, situated in different disciplines and incompatible with each other. "It is fascinating that Aaron Roth’s work shows that this is not a contradiction."

...

"The first step to improving the analysis of large data sets is to be aware of the problem: "We need to realize that data analysis can be problematic. Once we agree on this, we can consider how we can solve the problems," says Aaron Roth."

UNOS ends its liver exchange pilot program

UNOS has shuttered it's liver exchange pilot program, after less than a year, without having performed any liver exchange transplants. (My understanding is that this wasn't part of UNOS's OPTN contract, but part of its activities as a private company.)

A colleague forwarded me this announcement:

"After careful consideration and evaluation, we regret to announce the discontinuation of the UNOS Liver Paired Donation Pilot Program (LPDPP).

The UNOS LPDPP was launched with the noble goal of matching candidates in need of a liver transplant with living donors from across the United States. Top-tier transplant programs from around the country participated in the program, entering pairs to be matched for transplantation.

 Despite the enthusiasm and dedication of the UNOS LPDPP Steering Committee, participating hospitals, a visionary funder and UNOS Labs staff, we must acknowledge that the program faced significant challenges. Regrettably, no matches were made, and no transplants occurred during the course of the pilot.

 This decision to discontinue the program is a result of several factors, primarily the depletion of funding allocated to the pilot and other barriers to widespread adoption. While practical constraints have led us to this difficult decision, we are still committed to uncovering key insights that may help future efforts toward a national liver paired donation program and apply to other challenges facing the organ donation and transplant community.

 We would like to express our heartfelt gratitude to the Steering Committee, participating transplant programs’ staff, candidates and donors who agreed to be entered and the generous living liver recipient who funded this endeavor. Your dedication to saving lives through organ transplantation is truly commendable. These efforts have yielded valuable data and insights that will allow our community to continue to advance.

 While this chapter may be closing, our commitment to increasing the number of lives saved through organ donation and transplant remains unwavering. We will continue to explore innovative ways to improve access to organ transplants for those in need. We will be doing more investigation into the program’s barriers to success, unexpected challenges and opportunities for improvement, and we plan to share our discoveries with the community so we may all learn from the results.

 The program will officially end November 30, 2023, with the last match run on September 30, 2023."

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Earlier:

Friday, January 27, 2023

Liver exchange pilot program at UNOS

see also, from UNOS:

Liver paired donation — LPD

and this, from Medscape:

Can a Nationwide Liver Paired Donation Program Work?   by Lucy Hicks, January 30, 2023

"It is possible that the 1-year pilot program could run without performing any paired transplants, but that's unlikely if multiple pairs are enrolled in the system, the spokesperson said. At the time of this story's publication, the one enrolled pair are a mother and daughter who are registered at the UCHealth Transplant Center in Colorado.

...

"The pilot program requires that the donor bring one support person with them if they need to travel for the surgery, but undergoing major abdominal surgery from a transplant team they are not familiar with may be stressful, said Peter Abt, MD, a transplant " at the Hospital of the University of Pennsylvania and the Children's Hospital of Philadelphia. "That's a big ask," he said, "and I'm not sure many potential donors would be up to that."

"John Roberts, MD, a transplant surgeon at the University of California, San Francisco, agreed that the travel component may put additional stress on the donor, but "if it's the only way for the recipient to get a transplant, then the donor might be motivated," he added.

...

"Leishman agreed that the travel aspect appears to one of the greatest barriers to participants entering the program but noted that a goal of the pilot program is to understand better what works — and what doesn't — when considering a liver paired donation program on a national scale. "[Our] steering committee has put together a really nice framework that they think will work, but they know it's not perfect. We're going to have to tweak it along the way," she said."

Repugnant sales of art: deaccessioning, in Switzerland

 "Deaccessioning" is a repugnant transaction in the art world, in which it's often considered acceptable to sell art only to finance the purchase of other art, and not to keep a museum from going bankrupt.  I've written about this in the U.S. context, but it's an international phenomenon.

The NY Times has the story, from Switzerland:

Swiss Museum in Financial Straits Sells Three Cézannes for $53 Million. Museum Langmatt said the sales were necessary to keep its doors open. Critics had said they violated industry guidelines on when a museum should sell off parts of its collection.

"The Foundation Langmatt’s decision to sell the Cézannes earned wide criticism before the auction. The Swiss branch of the International Council of Museums, which said the sale was a clear breach of its guidelines for de-accessioning from museum collections, called for the paintings to be withdrawn.

"Professional blood donors" in India (where paying blood donors is illegal)

 India allows only unpaid blood donation, from altruistic donors or from "replacement donors" who are friends or relations of particular patients in need of blood (who must procure it before receiving it). There is a severe blood shortage, some of which is filled by black market "professional" blood donors, who are paid to pretend to be unpaid replacement donors.

Here's a story from the Indian news service Quint:

Out for Blood: Why Are Many Indians Forced To Seek 'Professional Blood Donors'? Although it is illegal, why is there a thriving market for paid blood donors in India?  by ANOUSHKA RAJESH and MAAZ HASAN

"Donating blood in exchange for money was banned in India in 1996. However, paying 'professional blood donors' to meet this requirement is still fairly common.

...

"To see how easy it would be to 'arrange' a paid blood donor, FIT went to one of the busiest government hospitals in Delhi.

...

"All leads – from vendors to patient families and bootleg pharmacists – point us to Ashok (name changed). He sits, surrounded by 4-5 men, and is guarded when we make inquiries.

"He begins with the following line of questioning: 'Where is our patient admitted?  What surgery do they need?  Why couldn't we just get friends and relatives to donate?

"Posing as a patient's friend, the FIT reporter gives him preplanned answers. In the emergency ward.  He had an accident and needs surgery on his leg.  I donated blood a month ago. He has no family here, and everyone else we reached out to has refused.

"Only when he's satisfied with the answers, he says he would be able to 'arrange boys' by the next day, and that it would cost between Rs 3,500 to Rs 4,000.

...

"According to the Ministry of Health and Family Welfare, India's annual requirement for blood is around 1.5 crore units per year, while in reality, only around 1 crore units are available.

"This gap in supply and demand of blood poses a major public health crisis in the country. For example, around 70 percent of postpartum hemorrhage (PPH)-related deaths in India are due to lack of immediate availability of blood.

...

"The paid donors are generally young boys, between the ages of 20 and 25, from very poor backgrounds," says Dr Dubey. ""This will no doubt be detrimental to their health," he adds. Moreover, if caught, they face the risk of jail time.

"The protocol is to ask every donor a set of questions before we take their blood. "If they seem suspicious, we ask them questions like, 'how are you related to the patient?', 'what is the patient's name?', and 'what surgery are they having?', to sus them out. If we get enough proof, we either defer them, or hand them over to the cops," Dr Priyansha Gupta, PG resident, Public Health, who has worked in Delhi's AIIMS blood bank in the past.

"What, then, happens to the families who desperately need blood when their donors are deferred?

"Dr Dubey says they are referred to the social workers attached to the hospital to get them help.

...

"But you have to understand, blood is a scarce commodity, and there's only so much we have."

##########

Here's a story from the Hindustan Times (in 2022), which begins with some relevant background (before debunking myths that lead to a shortage of voluntary donors):

Common myths on blood shortage in India  "The article is authored by Dr Parth Sharma, researcher, Ranita De, researcher in Lancet Citizen's Commission on Reimagining India’s Health System and Dr Vaikunth Ramesh."

"The shortage of blood products has been a major public health problem in India. It is estimated that nearly 12,000 people lose their lives every single day due to the lack of blood products. Supporting a population of 1.4 billion, the present blood transfusion service is fragmented with a little over 3,700 blood centres of which about 70% are located in eight states only. As of 2020, 63 districts in India do not have a blood centre. Space crunch and a burgeoning population have led to the establishment of health care facilities without blood centres on their premises, which in turn depend on nearby blood or storage centres for access to safe blood.

"Unfortunately, India has one of the largest shortages of blood supplies globally, while several diseases requiring blood transfusions are on the rise.

"A recent study by Joy Mammen, et. al. estimated the shortage to be around 2.5 donations per 1,000 eligible donors which equals a shortage of 1 million units. Blood products are required not only for surgeries but also for patients suffering from various medical conditions causing severe anaemia. At present, the source of donated blood is a combination of voluntary donors and replacement donors. Although professional donors are forbidden by law, they still continue to persist in our system under the guise of replacement donors. Voluntary non-remunerated donors, who donate based on altruism and a sense of doing greater good for the community, unfortunately, account for only 80% of the donors in India.

#######

HT: I was directed to the above links from the Indian posting

India Policy Watch #2: Regulating SoHO  by Pranay Kotasthane, which was in part about the recent move in the EU to further restrict payment for Substances of Human Origin (SoHO), as discussed in

Saturday, November 4, 2023

The EU proposes strengthening bans on compensating donors of Substances of Human Origin (SoHOs)--op-ed in VoxEU by Ockenfels and Roth