Showing posts with label medicine. Show all posts
Showing posts with label medicine. Show all posts

Friday, March 1, 2024

Medical aid in dying--the ongoing debate in Britain

 The Guardian has this opinion piece, connected to the current debate in England about medically assisted dying, and the slippery slope:

I’m glad the debate on assisted dying is forging ahead. But few understand why it frightens so many  by Frances Ryan

"On Thursday, MPs published the findings of a 14-month inquiry into assisted dying. The inquiry – which attracted more than 68,000 responses from the public – made no conclusive statement but instead collected evidence as a “significant and useful resource” for future debates.

That debate is no longer abstract. Legislation is making its way through the parliaments of Scotland, Jersey and the Isle of Man that, if passed, would enable competent adults who are terminally ill to be provided at their request with assistance to end their life.

...

"And yet it also feels a disservice to pretend that any of this is simple or that giving autonomy to some would not potentially harm others. It is deeply telling that among the many voices calling for a new assisted dying law, I have heard no human rights groups, celebrity or politician mention concerns – as advocated by many disability activists – that a law change could lead to disabled people being coerced into euthanasia, or feeling they had no other option.

We only need look to the countries that have legalised assisted dying in recent years to see these fears realised. One study reported the euthanasia of a number of Dutch people who were said simply to have felt unable to live with having a learning disability or autism. Many included being lonely as a key cause of unbearable suffering.

...

"This is not to say that the UK shouldn’t go down the path of legalising assisted dying, but we must at least do so with eyes wide open. The right to die does not exist in a vacuum: it fundamentally alters the doctor-patient relationship, and risks making members of society who are already vulnerable that little bit more insecure. Perhaps that is a price worth paying to end some terminally ill people’s suffering. Perhaps it is too much to ask. There are no black and white boxes to tick labelled “right” and “wrong” – just the messy, painful grey of being human.

In the coming months, politicians will correctly dedicate hours to discussing the right to a good death. Imagine, though, if they were to give equal attention to the right to a good life: from building social housing, exploring a basic income, investing in mental and physical health services, to – as the inquiry recommends – funding universal coverage of palliative care and more specialists in end-of-life pain."

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Earlier:

Friday, January 12, 2024

Thursday, December 14, 2023

Managing blood supplies by using blood more judiciously

Medpage has the story:

Doing More With Less Blood — Blood management programs can save money and resources  by Steven Frank, MD 

"At Johns Hopkins, since our patient blood management efforts began in 2012, we launched two distinct programs running side by side synergistically. The first program aims to reduce avoidable transfusions for the roughly 99% of patients who accept blood, while the second program provides optimal care for the remaining 1% of patients who wish to avoid transfusion for personal or religious reasons, the vast majority of whom are Jehovah's Witnesses. 
...
"treating preoperative anemia with $4 worth of iron tablets to avoid using $400 worth of blood just makes sense. Wouldn't you rather come to surgery with your own red blood cells, rather than needing a transfusion with someone else's?

""Keeping the blood in the patient" is the other major concept behind patient blood management. Simple things can reduce bleeding, such as keeping patients warm during surgery; lowering the blood pressure (controlled hypotension); tranexamic acid (an inexpensive medication that reduces bleeding by about 30%opens in a new tab or window); Cell Savers to return surgical blood loss to the patient; and using smaller phlebotomy tubes to send lab tests. All of these strategies can be bundled together to achieve this goal.

"After a decade of experience, we crunched the numbers to assess our return on investment (ROI) with our comprehensive patient blood management program, while also looking at patient outcomes. The bottom line was a 7.5-fold ROI, meaning that for every dollar spent on patient blood management, over $7 were either saved or generated in return. This calculation is based on a $3 million annual reduction in blood acquisition cost, along with a $5 million annual net margin on revenue generated by caring for patients under the Center for Bloodless Medicine and Surgery.

"At the same time, clinical outcomes were either the same or better while giving less blood. Heart attack, stroke, thrombotic events, and respiratory and kidney problems were unchanged, while the incidence of hospital-acquired infection decreased. This latter finding is very believable based on high-level evidence (meta-analysis of 18 randomized trials) that transfusions predispose patients to infections. Furthermore, by avoiding transfusions for those who do not need them, we make more blood available for those who really do -- like trauma victims and cancer patients.

"Given the ongoing blood shortages that we are facing, which has been called a "crisis" in the blood industry, patient blood management looks like a giant step towards the triple aim in medicine: improving the patient experience, clinical outcomes, and cost."
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See, earlier in the NEJM:

by Harvey G. Klein, M.D., J. Chris Hrouda, B.H.S., and Jay S. Epstein, M.D., October 12, 2017
N Engl J Med 2017; 377:1485-1488
DOI: 10.1056/NEJMsb1706496

Wednesday, December 13, 2023

Black market monkeys for medical research

 Monkeys used in medical research are supposed to come from carefully bred laboratory colonies, but the rising price has led to black markets, which is bad for both monkeys and for medical researchers. (And monkeys are useful for medical research because of their relatively close relation to humans, which makes for difficult conversations regardless of their source...)

The Guardian has the story:

$20,000 monkeys: inside the booming illicit trade for lab animals  by Phoebe Weston

"An international shortage of lab monkeys has driven up prices, incentivising a booming illicit trade. The problem risks undermining research, creating new pandemics, and fuelling wildlife trafficking. As the trade expands, a once-thriving species is now on the edge: in 2022, it was added to the IUCN list of endangered species. Some animal rights activists are calling to end the trade altogether.

"Long-tailed macaques are the most heavily traded primate species in the world, according to a paper published in September, and much of this is for laboratory research. The US National Association for Biological Research says non-human primates remain a critical resource for research, with about 70,000 monkeys imported a year to study infectious diseases, the brain and the creation of new drugs. Difficulty getting monkeys is compromising important research, Sacha says. Before the pandemic he was paying between $2,000 (£1,600) and $5,000 for an animal. Now, it’s about $20,000. “For a couple of years during lockdown it was near impossible to get them,” he says.

"He is not alone. Almost two-thirds of researchers struggled to find monkeys in 2021, according to a report from the US National Academies of Sciences, Engineering, and Medicine, which found that the supply of monkeys for research is at crisis point. According to an article in Science, the report is the “strongest government statement yet on the precarious state of monkey research”. A similar picture is coming from Europe, where a shortage of monkeys has resulted in some research being abandoned.

"Long-tailed macaques (the monkey most commonly used in medical research) are protected under international trade law and special permits are required to import the animals into the US.

"Laboratories need pathogen-free primates that are in good condition and so do not want monkeys that have been wild-caught. With prices so high, however, traffickers are incentivised to catch them in the wild and launder them in via established breeding colonies.

"For decades, China was the largest supplier, but it banned the wild animal trade in 2020 in light of the Covid pandemic. Demand for monkeys increased significantly in the following years, but supply did not. Cambodia has since significantly increased exports to plug the gap and tap into this increasingly lucrative market.

...

"Animal rights campaigners want the US government to end the “cruel trade”, saying it poses a significant threat to public health. The National Academies report says investing in non-animal “organ on a chip” technology could reduce overall demand.

"It also recommended that the US expand its domestic breeding facilities – which it can then regulate. Sacha says: “We shouldn’t be reliant on external countries for these animals that are really critical to our ability to test new therapeutics and vaccines and medicines.”

Monday, December 4, 2023

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.

Thursday, October 19, 2023

Blood use in the U.S., in JAMA

 Here are a collection of articles, some of which suggest that we may in the not so distant future face a shortage of whole blood in the U.S., the need for which is so far filled by uncompensated donors (unlike the need for plasma, which is presently filled by compensated donors...).  One issue is that apparently ambulance companies aren't easily compensated for beginning transfusion on the way to the hospital, which could save lives.


Original Investigation

Caring for the Critically Ill Patient

Red Blood Cell Transfusion in the Intensive Care Unit

Senta Jorinde Raasveld, MD; Sanne de Bruin, MD, PhD; Merijn C. Reuland, MD; et al.

"RBC transfusion was common in patients admitted to ICUs worldwide between 2019 and 2022, with high variability across centers in transfusion practices."

Editorial: Precision in Transfusion Medicine ; Matthew D. Neal, MD; Beverley J. Hunt, MD

"blood transfusion practice has come a long way, but further efforts toward precision medicine are required to ensure that patients receive the most effective components. These products should be matched to patients as individuals who have unique antigens and a variable host response, and how to use the appropriate blood components in different clinical settings must be understood."

Caring for the Critically Ill Patient

Small-Volume Blood Collection Tubes to Reduce Transfusions in Intensive Care: The STRATUS Randomized Clinical Trial

Deborah M. Siegal, MD; Emilie P. Belley-Côté, MD, PhD; Shun Fu Lee, PhD; et al.

Caring for the Critically Ill Patient

Emergency Department Resuscitative Endovascular Balloon Occlusion of the Aorta in Trauma Patients With Exsanguinating Hemorrhage: The UK-REBOA Randomized Clinical Trial

Jan O. Jansen, PhD; Jemma Hudson, PhD; Claire Cochran, MSc; et al.

Editorial: Contemporary Adjuncts to Hemorrhage Control ; Samuel A. Tisherman, MD; Megan L. Brenner, MD

Caring for the Critically Ill Patient

Early and Empirical High-Dose Cryoprecipitate for Hemorrhage After Traumatic Injury: The CRYOSTAT-2 Randomized Clinical Trial

Ross Davenport, PhD; Nicola Curry, MD; Erin E. Fox, PhD; et al.

Editorial: Contemporary Adjuncts to Hemorrhage Control; Samuel A. Tisherman, MD; Megan L. Brenner, MD


Special Communication

Red Blood Cell Transfusion: 2023 AABB International Guidelines

Jeffrey L. Carson, MD; Simon J. Stanworth, MD, DPhil; Gordon Guyatt, MD; et al.

Earn CME credit

Viewpoint

From Product to Patient—Transfusion and Patient Blood Management

Matthew A. Warner, MD; Linda Shore-Lesserson, MD; Carolyn Burns, MD

"Recent years have also exposed vulnerabilities in blood inventories. As the most prominent example, the COVID-19 pandemic led to cancellations of many community-based and mobile blood collections, culminating in the declaration of a national blood crisis by the American Red Cross for the first time in history. In response, the American Medical Association, in partnership with the American Hospital Association and American Nurses Association, issued a joint statement in January 2022 describing the worst blood shortage in more than a decade and urging blood donation from all eligible persons. Not long after, the AABB, in collaboration with 17 leading US health care and blood collection organizations, launched the Alliance for a Strong Blood Supply to track and coordinate information and public communications about blood inventories and explore mechanisms to improve blood supply resilience."

The Bloody Transfusion Problem

John B. Holcomb, MD; William K. Hoots, MD; Travis M. Polk, MD

"Preventable death after injury is a national crisis. Worldwide, injury accounts for more deaths than malaria, tuberculosis, and HIV combined and is increasing.1 Trauma is largely a condition of young people and is the leading cause of life-years lost between 1 and 75 years of age, and costs to the US are estimated at $4.2 trillion a year.2 As is always the case, lessons learned on recent battlefields have improved civilian care, and the most impactful intervention has been the increased use of blood products as a primary resuscitation fluid.

"During the past decade several large, prospective, multicenter, randomized, federally funded studies have improved outcomes and changed practice.3,4 Transfusing blood as early as possible to patients with hemorrhagic shock saves lives, and fewer patients die from exsanguination when receiving a balanced transfusion of platelets, red blood cells, and plasma or whole blood. This is true in the hospital but is especially so in the prehospital setting, where blood products decrease mortality from 33% to 23%.4 When all indicated blood products are available and given early, deaths due to hemorrhage decrease and care is cost-effective. However, of the 2045 hospitals to which the American Red Cross supplied blood components in 2019, 33% did not routinely have platelets ready to transfuse to bleeding patients, and more than 78% of those hospitals are in a rural setting.4 Emergency medical services (EMS) agencies and hospitals that do not have all blood products immediately available cannot provide optimal care. Unfortunately, the blood products required to save lives are not uniformly available to all persons, and implementation of these proven lifesaving interventions is uneven, largely because of supply and policy reasons.

"To remedy this disparity, we believe there are 3 significant hurdles to overcome: (1) enabling a reliable strategy for insuring an adequate blood product supply by developing new shelf-stable blood products and by providing greater financial support for donor blood collection and processing; (2) insuring adequate reimbursement for current and new blood products in the hospital setting and removing the limitation of prehospital provider scope of practice and ability to bill for all blood products; and (3) sustaining consistent and appropriate research funding for trauma studies of hemorrhagic shock in both pediatric and adult populations. 

...

"Blood collection and processing centers are operating at a loss because remuneration has not kept pace with ever-increasing costs of regulatory required infectious disease testing.

...

"More than 55 000 additional donors will be required for just the prehospital blood program implementation.6 Increasing the blood supply will require novel solutions combining remuneration for donors, increased reimbursement for blood collection centers, modern efforts to recruit younger donors, and streamlined regulatory and financial reimbursement pathways for new blood products that are shelf stable at room temperature for years.

...

"scope of practice, reimbursement barriers, and the inability to bill for transfusions provided in air or ground ambulances are significant obstacles to the widespread availability of prehospital blood programs."

Redefining Blood Donation—Path to Inclusivity and Safety

Pampee P. Young, MD, PhD; Paula Saa, PhD

Video: Gay and Bisexual Men Can Now Donate Blood—Why This Matters

"The journey to establish equitable blood donation policies can be likened to the myth of Theseus navigating the Labyrinth. Just as Theseus ventured into the complex maze to save Athenians from the Minotaur, the blood industry has been navigating the intricacies of research, regulation, and public sentiments to secure a safe blood supply and equitable policies. With the advancements in testing and the changing policies as our guiding thread, we are dedicated to ensuring fairness, equality, and safety, led by evidence and a deep commitment to humanity."

Editorial

Precision in Transfusion Medicine

Matthew D. Neal, MD; Beverley J. Hunt, MD

Contemporary Adjuncts to Hemorrhage Control

Samuel A. Tisherman, MD; Megan L. Brenner, MD

Medical News & Perspectives

Could Universal Donor Blood Be Made in the Laboratory?

Bridget M. Kuehn

"In the face of chronic national and international blood supply shortages, scientists are renewing efforts to achieve the holy grail of transfusion—laboratory-made universal donor blood."

JAMA Revisited

The Status of Blood Transfusion

"Originally Published September 29, 1923 | JAMA. 1923;81(13):1114- 1115."

JAMA Patient Page

Blood Donation

Kristin Walter, MD, MS

Video: Gay and Bisexual Men Can Now Donate Blood—Why This Matters

Video

Gay and Bisexual Men Can Now Donate Blood—Why This Matters


Monday, September 25, 2023

Smart toilets and data privacy

 Something to sit and think about:

Smart toilets could leak your medical data, warn security experts. by Matthew Sparkes New Scientist, Volume 259, Issue 3456, 2023, Page 14, ISSN 0262-4079, https://doi.org/10.1016/S0262-4079(23)01720-7. 

"A range of start-ups and research projects have developed smart toilets to monitor everything from heart rate to the consistency of stools and the presence of certain proteins in urine that indicate disease. One device even features an “anus camera” that takes a photo from below for identification, something that has been described as the “polar opposite of facial recognition”.*

...

"One concern was the privacy of people other than the owner: are visitors consenting to have photographs or measurements taken? There were also worries about the risk of losing sensitive data to hackers, as well as the possibility of companies selling the data on. And if smart toilets were installed in public areas or workplaces, there would be questions about who has access to that data, it was argued.The group of experts concluded that smart toilets shouldn't be sold as consumer devices, but instead as medical devices that have to meet high regulatory standards for privacy and safety (arXiv, doi.org/ksx5).

"Chase Moyle at smart toilet start-up Coprata says he set out to build a consumer device because creating a medical device under US Food and Drug Administration regulations would raise the price by a factor of 10. It would also mean that, in the US, insurance companies would only offer it to people with diagnosed conditions.

...

"Alan Woodward at the University of Surrey, UK, says so-called internet of things (IoT) devices, such as heart rate monitors and CCTV cameras, have often been found to have security flaws, including a smart toilet with a computer-controlled bidet. He fears the same could be true for medical-focused smart toilets. “With a lot of IoT devices, security has never been uppermost in the mind and yet something like a smart toilet is collecting some very personal data,” he says. “They're making these weird devices because they can, but nobody's thought through ‘should we?’”

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See also (for the first instance of that quote I can find):

‘Smart toilet’ monitors for signs of disease. A disease-detecting “precision health” toilet can sense multiple signs of illness through automated urine and stool analysis, a new Stanford study reports.  April 6, 2020 - By Hanae Armitage, Stanford Medicine News

"One of the most important aspects of the smart toilet may well be one of the most surprising — and perhaps unnerving: It has a built-in identification system. “The whole point is to provide precise, individualized health feedback, so we needed to make sure the toilet could discern between users,” Gambhir said. “To do so, we made a flush lever that reads fingerprints.” The team realized, however, that fingerprints aren’t quite foolproof. What if one person uses the toilet, but someone else flushes it? Or what if the toilet is of the auto-flush variety?

"They added a small scanner that images a rather camera-shy part of the body. You might call it the polar opposite of facial recognition. In other words, to fully reap the benefits of the smart toilet, users must make their peace with a camera that scans their anus.

“We know it seems weird, but as it turns out, your anal print is unique,” Gambhir said. The scans — both finger and nonfinger — are used purely as a recognition system to match users to their specific data. No one, not you or your doctor, will see the scans."

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Also, Meet the winners of the 2023 Ig Nobel Prizes 

"Public Health Prize

Citation: "Seung-min Park, for inventing the Stanford Toilet, a device that uses a variety of technologies—including a urinalysis dipstick test strip, a computer vision system for defecation analysis, an anal-print sensor paired with an identification camera, and a telecommunications link—to monitor and quickly analyze the substances that humans excrete."

Friday, September 22, 2023

Support for hepatitis C human challenge studies, in The Lancet Gastroenterology & Hepatology

 Here's a call for action, in The Lancet Gastroenterology & Hepatology:

Joint statement in support of hepatitis C human challenge studies by Harvey J Alter, Eleanor Barnes, Mia J Biondi, Andrea L Cox, Jake D Eberts, Jordan J Feld, T Jake Liang, Josh Morrison, Charles M Rice, Naglaa H Shoukry, David L Thomas, Jennifer Van Gennip, Charles Weijer, on behalf of other signatories †, Published:September 20, 2023 DOI:https://doi.org/10.1016/S2468-1253(23)00314-X

"We, the 121 undersigned, believe that human challenge studies among adult volunteers will be critical in the development of hepatitis C vaccines.

...

"Despite the advent of safe and highly effective direct-acting antiviral (DAA) treatments, the ongoing toll of hepatitis C remains high among low-income and middle-income countries and vulnerable populations such as people who inject drugs. Millions of new infections occur annually, outpacing cures in some regions,1 with progress further disrupted by the COVID-19 pandemic. Without a change in strategy and the development of new tools, we will not reach the ambitious goal set out by WHO of elimination of viral hepatitis as a public health threat by 2030. This will require an effective hepatitis C vaccine—“the best insurance for the future”, as highlighted by a recent announcement of the White House national hepatitis C elimination programme.2

...

"Human challenge studies for a hepatitis C vaccine could accelerate vaccine development dramatically. The effort to establish the model and test an initial vaccine candidate could take as little as 3 years. If that candidate fails, subsequent studies to test others could provide evidence of efficacy as quickly as 1 year.

"It is only because of the remarkably effective treatments that we can now consider human challenge studies for hepatitis C. With DAAs, cure rates of people without cirrhosis are reliably over 98%, with highly effective salvage regimens for the few who do not respond to a first course of therapy.5,  6 We are confident that in the era of DAAs, human challenge studies can be done in accordance with the highest ethical and safety standards. Healthy volunteers providing fully informed consent would be infected for at most 6 months before treatment and would be free to go about their lives with the right to request treatment and withdrawal from a study at any time. Acute infection causes no or few symptoms in most, and unlike in most challenge studies, where the risk of transmission necessitates quarantine of participants, the risk of passing hepatitis C to others is very low in day-to-day life.

"The impact of a vaccine would be enormous: reducing transmission, preventing cirrhosis, and most importantly, markedly reducing the rate of liver cancer, the world's second-most deadly cancer in terms of total fatalities.7 The global success of hepatitis B vaccine in achieving these goals exemplifies the importance of an effective hepatitis C vaccine. With the prospect of such a significant advance, we have confidence that people will volunteer to participate in hepatitis C challenge studies, and with such a strong team of experts worldwide, we are confident this approach will lead to the development of a successful hepatitis C vaccine."

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Here's the full list of 121 signers of the letter

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1Day Sooner has a related web page with some background: https://www.1daysooner.org/hepatitis-c-open-letter

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Earlier related posts:

Monday, May 15, 2023

Tuesday, September 12, 2023

New technologies and new controversies: using CRISPR to edit human genes

 New technologies are often accompanied by new repugnancies, i.e. by controversies about their moral appropriateness. The future of using CRISPR to edit human genes is still before us, and its history (even to date) has yet to be written. But I'm struck by how it both interacts with and recapitulates older controversies and repugnancies, including those involving HIV, and adoption and assisted reproduction.

The New Yorker has the story:

The Transformative, Alarming Power of Gene Editing. A rogue scientist showed that crispr gives humans the ability to transform ourselves. But should we?  By Dana Goodyear  September 2, 2023

"The Chinese researcher He Jiankui was jailed for creating customized babies. Some observers argue that the real problem wasn’t him—it was the lure of the technology.

...

"To start, he would focus on what he believed was an achievable task: eradicating a disease governed by a single gene. He selected aids, an illness regarded in China as both pernicious and shameful but one for which there might be an elegant fix. H.I.V. enters human cells by way of a receptor created by a gene called CCR5. JK planned to use the gene-editing tool crispr to disrupt CCR5 in human embryos, which would, in theory, render the babies impervious to infection.

"The experiment required volunteers, and, through a chat group associated with an H.I.V./aids charity, he began recruiting couples: H.I.V.-positive men married to uninfected women. Chinese law denies in-vitro fertilization and adoption to H.I.V.-positive people, and natural conception carries a risk of transmission. For couples with an infected partner, JK’s program was a chance at parenthood. It promised confidentiality, which was critical for a marginalized community; an H.I.V. diagnosis in China can cost a person his job. The treatments would take place discreetly, at facilities where only key employees were aware of the experiment.

...

"as scientists from around the world prepared for a gene-editing conference in Hong Kong, JK released a series of YouTube videos, announcing the birth of a set of twins, edited as embryos with crispr. A slim, nervous-seeming man in a pale-blue shirt, he looked earnestly into the camera and said, “Two beautiful little Chinese girls named Lulu and Nana came crying into the world, as healthy as any other babies.” He went on to explain how, when each was only a single cell, he had used crispr to delete CCR5. “I understand my work will be controversial,” he said. “But I believe families need this technology, and I’m willing to take the criticism for them.”

"China’s state-run media celebrated the news, but the scientific community reacted with dismay. A group of Chinese researchers condemned the study as madness. David Baltimore, a Nobel Prize-winning biologist who chaired the Hong Kong event, called it “irresponsible,” saying, “I think there has been a failure of self-regulation by the scientific community.

...

"There were three edited babies, he acknowledged: along with Lulu and Nana, another was on the way.

...

"The Chinese government swiftly withdrew its enthusiasm for JK’s research, and, soon after he returned to the mainland, his lab was locked and he was placed under house arrest. In 2019, he was sentenced to three years in prison for “illegal medical practices,” and fined nearly half a million dollars. Two of his collaborators were given lesser sentences and fined. Among scientists, there was a pervasive sense of embarrassment. JK had misused a powerful technology and gambled with the health of children—experimental subjects he himself had created—without, in the scientists’ view, a compelling medical reason to compensate for the risk. Urnov told me, “He has taken a jar of tar, poured it over the field of crispr, and left an indelible stain. We will never wash that stain off. I am prepared to say that he’s not a fellow-scientist. He’s persona non grata.”

"JK was released from prison in the spring of 2022, and quickly resumed his efforts at gene editing. 

...

"He said that his new lab would be a nonprofit providing affordable gene therapy for rare conditions, and that he would focus first on Duchenne muscular dystrophy, a fatal disease that causes irreversible muscle damage, primarily in boys. This time, his patients would be not embryos but young children desperate for a cure. I asked if it was an attempt to redeem himself in the scientific community. “I don’t know if I’d use the word ‘redeem,’ ” he said. “I want to do it to help people today.”

...

"As for the debacle that his experiment had caused, JK would admit to no greater error than bad timing. “I do acknowledge that I have done it too quickly,” he said. In one of his YouTube videos, he predicted that in twenty or thirty years gene-edited babies will no longer be controversial, or even remarkable. He likened himself to the pioneering founder of the field of I.V.F., Robert Edwards, whose career had followed a heroic arc. In 1978, when the first I.V.F. baby was born, Edwards was a figure of scandal and opprobrium. In 2010, he was awarded the Nobel Prize."

Monday, September 4, 2023

Covid medication: allocation, information, hesitancy, and uptake: what are some things we have learned?

 I've posted before about how informational advertising about vaccine availability and safety seems to have had a positive effect on vaccination rates among disadvantaged populations. There was particular concern in the U.S. at one point that Black people were less likely to receive vaccines and other medications than other Americans.

Today's post collects several papers about the effect of randomly allocating invitations for temporarily scarce Covid medications, while giving members of disadvantaged groups a higher probability of receiving an invitation.  Included will be an editorial warning us that we shouldn't be satisfied to judge the outcome of a market design by its intended outcome ("Moving Beyond Intent and Realizing Health Equity").

There are market design lessons in these last few years of Covid experience that I hope will help make the responses to future pandemics more effective. Not least of these is that the allocation of public health  and medical resources turns out to be quite different from  the allocation of other kinds of resources, in many important ways that reflect the broader economic and social environments in which different kinds of allocation takes place.

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Here's a paper in the most recent issue of JAMA Health Forum, by a team that includes both medical professionals and market designers.

Weighted Lottery to Equitably Allocate Scarce Supply of COVID-19 Monoclonal Antibody , by Erin K. McCreary, PharmD1; Utibe R. Essien, MD, MPH2,3; Chung-Chou H. Chang, PhD4,5; Rachel A. Butler, MHA, MPH6; Parag Pathak, PhD7; Tayfun Sönmez, PhD8; M. Utku Ünver, PhD8; Ashley Steiner, BS9; Maddie Chrisman, PT, DPT10; Derek C. Angus, MD, MPH11; Douglas B. White, MD, MAS11, JAMA Health Forum. 2023;4(9):e232774. Sept. 1, doi:10.1001/jamahealthforum.2023.2774 

"Objective  To describe the development and use of a weighted lottery to allocate a scarce supply of tixagevimab with cilgavimab as preexposure prophylaxis to COVID-19 for immunocompromised individuals and examine whether this promoted equitable allocation to disadvantaged populations.

"Design, Setting, and Participants  This quality improvement study analyzed a weighted lottery process from December 8, 2021, to February 23, 2022, that assigned twice the odds of drug allocation of 450 tixagevimab with cilgavimab doses to individuals residing in highly disadvantaged neighborhoods according to the US Area Deprivation Index (ADI) in a 35-hospital system in Pennsylvania, New York, and Maryland. In all, 10 834 individuals were eligible for the lottery. Weighted lottery results were compared with 10 000 simulated unweighted lotteries in the same cohort performed after drug allocation occurred.

"Main Outcomes:  Proportion of individuals from disadvantaged neighborhoods and Black individuals who were allocated and received tixagevimab with cilgavimab.

"Results:  Of the 10 834 eligible individuals, 1800 (16.6%) were from disadvantaged neighborhoods and 767 (7.1%) were Black. Mean (SD) age was 62.9 (18.8) years, and 5471 (50.5%) were women. A higher proportion of individuals from disadvantaged neighborhoods was allocated the drug in the ADI-weighted lottery compared with the unweighted lottery (29.1% vs 16.6%; P < .001). The proportion of Black individuals allocated the drug was greater in the weighted lottery (9.1% vs 7.1%; P < .001). Among the 450 individuals allocated tixagevimab with cilgavimab in the ADI-weighted lottery, similar proportions of individuals from disadvantaged neighborhoods accepted the allocation and received the drug compared with those from other neighborhoods (27.5% vs 27.9%; P = .93). However, Black individuals allocated the drug were less likely to receive it compared with White individuals (3 of 41 [7.3%] vs 118 of 402 [29.4%]; P = .003).

...

"Conclusions and Relevance:  The findings of this quality improvement study suggest an ADI-weighted lottery process to allocate scarce resources is feasible in a large health system and resulted in more drug allocation to and receipt of drug by individuals who reside in disadvantaged neighborhoods. Although the ADI-weighted lottery also resulted in more drug allocation to Black individuals compared with an unweighted process, they were less likely to accept allocation and receive it compared with White individuals. Further strategies are needed to ensure that Black individuals receive scarce medications allocated."

...

"The lottery was repeated over several weeks, but we chose to examine only the first assignment. The interpretation of later rounds is problematic because eventually all individuals were offered tixagevimab with cilgavimab. By focusing on the first draw, we can specifically evaluate whether the intent of the lottery was met."

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Closely related reports:

White, D.B., McCreary, E.K., Chang, C.C.H., Schmidhofer, M., Bariola, J.R., Jonassaint, N.N., Persad, G., Truog, R.D., Pathak, P., Sonmez, T. and Unver, M.U., 2022. A multicenter weighted lottery to equitably allocate scarce COVID-19 therapeutics. American Journal of Respiratory and Critical Care Medicine, 206(4), pp.503-506.

Rubin, E., Dryden-Peterson, S.L., Hammond, S.P., Lennes, I., Letourneau, A.R., Pathak, P., Sonmez, T. and Ünver, M.U., 2021. A novel approach to equitable distribution of scarce therapeutics: institutional experience implementing a reserve system for allocation of COVID-19 monoclonal antibodies. Chest, 160(6), pp.2324-2331.*

White, D.B. and Angus, D.C., 2020. A proposed lottery system to allocate scarce COVID-19 medications: promoting fairness and generating knowledge. Jama, 324(4), pp.329-330.

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And here's an editorial in the same issue of JAMA Health Forum as the most recent article, pointing out that less-disadvantaged patients among those living in census blocks identified as disadvantaged (in particular  commercially insured and White patients) were much more likely to receive the treatment:

Moving Beyond Intent and Realizing Health Equity, by Atheendar S. Venkataramani, MD, PhD, Invited Commentary, September 1, 2023, JAMA Health Forum. 2023;4(9):e232525. doi:10.1001/jamahealthforum.2023.2525

"In a study published in this issue of JAMA Health Forum, McCreary and colleagues3 report on a landmark effort at the University of Pittsburgh Medical Center (UPMC) to distribute equitably a scarce monoclonal antibody resource, tixagevimab with cilgavimab, for COVID-19 preexposure prophylaxis in immunocompromised individuals. In December 2021, UPMC received an allotment of 450 doses of tixagevimab with cilgavimab from the Pennsylvania Department of Health to cover a large health system with 35 hospitals and 800 outpatient facilities through February 2022. In an ex ante effort to mitigate health disparities and respond to guidance from the Commonwealth of Pennsylvania to allocate scarce resources in a manner that accounts for multiple ethical objectives, UPMC convened an advisory group of clinicians, community stakeholders, and experts in community outreach.

...

"The lottery was constructed using the Area Deprivation Index (ADI) to ensure that patients in highly disadvantaged neighborhoods had an equal opportunity to access tixagevimab with cilgavimab. Patients living in neighborhoods with ADIs above a specific cutoff that has been shown to best target less affluent, rural, and Black patients received 2 entries in the lottery, compared with 1 entry for patients in more advantaged neighborhoods. In their study, McCreary and colleagues3 found that this process resulted in equitable access: similar proportions of individuals in more advantaged and more disadvantaged neighborhoods (about 28% in each group) received tixagevimab with cilgavimab during the study period, although Black patients who were allocated the drug in the lottery were significantly less likely to receive it compared with White patients (7.3% vs 29.4%).

...

"Having identified its patient population, UPMC required only patient addresses as well as publicly available data on ADIs to implement the lottery intervention. The ADIs are defined at the census block group level, which include about 1000 residents on average. Thus, UPMC was able to achieve equitable opportunity to access tixagevimab with cilgavimab across small localities with very different socioeconomic profiles.

...

On the other hand, higher-resolution data that specifically measure the types of intersecting, reinforcing, and cumulative disadvantages faced by historically marginalized groups5 may be needed to achieve equitable outcomes across other dimensions, such as race and ethnicity. Within census blocks, patients assigned the same ADI levels but who may have faced relatively fewer structural barriers compared with Black patients or patients receiving Medicaid—namely, commercially insured and White patients—were more likely to access tixagevimab with cilgavimab conditional on being allocated to receive it in the lottery

...

"The lower rates of drug receipt among Black patients also underscores the importance of complementary investments and operational decisions to address additional structural barriers to accessing medical technology.

...

"The study by McCreary and colleagues3 represents the type of courageous and rigorous work that is needed to chart a path forward in determining how best to bridge the access gap for leading-edge medical technology. Future work would benefit from the same type of clarity demonstrated in this study by including clear definitions for how equity should be operationalized, attempting to address fragmentation between clinical services and services that address social drivers of health, aligning incentives, and addressing historical barriers that have made it difficult to achieve health equity."

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*Earlier:

Saturday, August 14, 2021