Medical Aid in Dying Laws in the U.S.

 JAMA has a review of the current state of medical aid in dying in the 12 U.S. jurisdictions (if Delaware proceeds) that now allow it.

Medical Aid in Dying Laws: More Accessible in More States by Thaddeus Mason Pope, JD, PhD, JAMA. 2024;332(14):1139-1140. doi:10.1001/jama.2024.15925

"Delaware may soon become the 12th US jurisdiction to authorize medical aid in dying. The Ron Silverio/Heather Block End-of-Life Options Law1 becomes a statute as soon as the governor acts and takes effect once the Delaware Department of Health and Social Services promulgates regulations to implement the statute. Delaware could follow 11 other US jurisdictions that have authorized medical aid in dying; more than 15 000 patients have received prescriptions for medical aid in dying since 1998 in California, Colorado, Hawaiʻi, Maine, Montana, New Jersey, New Mexico, Oregon, Vermont, Washington, and Washington, DC.

...

"Medical aid in dying has become an increasingly prominent end-of-life option. More than 20 states considered new medical aid in dying legislation in 2024, and most of the 11 jurisdictions that previously authorized medical aid in dying have amended their original statutes during the past 5 years (eTable in the Supplement).2-6 When enacting or amending medical aid in dying statutes, state policymakers have been carefully recalibrating the balance between safety and access

...

"Medical aid in dying is only available to terminally ill adults with decision-making capacity. They must have an “incurable and irreversible illness” with a prognosis of 6 months or less. If patients can navigate the other eligibility requirements and safeguards, they can get a prescription for lethal medications that they might later self-ingest to hasten their death.6

"Hospice and palliative care are often sufficient to address the suffering of patients, and one-third of those who receive medical aid in dying prescriptions never obtain them from the pharmacy or ingest them.3,4 Most of the remaining patients administer the prescriptions by mixing the powdered drugs with 2 oz to 3 oz of apple juice or push a plunger on a feeding or rectal tube. The patients fall asleep within minutes and usually die within an hour. There is never intravenous administration of the prescriptions or clinician- or third-party administration of the prescriptions.

...

"The Delaware end-of-life options law would require the patient to make 3 requests, 2 of which must be separated by at least 15 days.1 A waiting period has been a requirement in all jurisdictions that have authorized medical aid in dying. However, significant evidence showed that many patients either died or lost decision-making capacity before expiration of the waiting period.4 Many states (California, Colorado, Hawaiʻi, New Mexico, Oregon, and Washington) have either shortened their waiting periods or permit the waiting period to be waived when the patient is likely to die or lose decision-making capacity.

"The Delaware end-of-life options law would be limited to residents of Delaware1; however, for nonresidents, Delaware residency can be established by renting an apartment in Delaware.4 Residency requirements remain an additional hurdle in a long list of obstacles that terminally ill patients must navigate to become eligible. Within the past 2 years, both Oregon and Vermont removed their residency requirements.2,4,6 And the constitutionality of New Jersey’s residency requirement is being challenged in federal court.6 Nationwide, many bills proposed in 2024 omitted residency preconditions.

...

"Commentators regularly express concerns about the use of medical aid in dying in Canada7 and in Europe. It is important to protect vulnerable populations from coercion, duress, and inadequately considered choices; patients should not be steered toward choosing to request medical aid in dying. In addition, the adverse effects of orally ingested medications must be mitigated.4 In California, SB 1196 would have probably solved that problem by permitting (self-administered) intravenous administration of the end-of-life prescriptions. However, any change that would allow intravenous administration and other new and imminent expansions for medical aid in dying raise their own set of novel challenges for US clinicians.

"Given the number of bills and other indicators of interest, medical aid in dying is likely to be authorized in more states over the next few years, and the use medical aid in dying is likely to increase with more accessible terms and conditions. Although medical aid in dying continues to be used by less than 1% of dying patients,2 it is becoming a more integral part of end-of-life care."

Kidney exchange in Brazil, continued (with pictures)

 In August I posted about a trip to Brazil with Mike Rees where we traveled with Dr. Gustavo Ferreira, the director of transplantation at the hospital Santa Casa de Misericórdia de Juiz de Fora

Part of our trip was spent in the capital, Brasilia, talking to the government about extending Brazilian transplant law to allow kidney exchange, after which we went to Juiz de Fora.  Here's my blog post about that trip:  Kidney exchange in Brazil: prelude. 

That post concluded by saying "On Saturday we had an exciting finish to the trip, but it's not my story to tell yet, so I'll blog again after there is an official announcement."

Now Brazil's first three-way kidney exchange has been announced, as part of a clinical trial that I hope will help change Brazilian law to allow kidney exchange as a regular medical procedure.  The three donors and three recipients all did well, and left the hospital very shortly after the actual surgeries, but came back to tell their stories to the Brazilian news show Profissão Repórter (Professional Reporter). You can see the video here  https://globoplay.globo.com/v/12997336/

It's in Portuguese but you will quickly get the idea, presented even more briefly on Instagram by the transplant nephrologist Dr. Juliana Bastos here: https://www.instagram.com/reel/DA4JBVIsFta/?igsh=d2hnb3hoNjJxN2I4     where you can see the three incompatible patient-donor pairs rearrange themselves for the camera into the three-way exchange in which each patient received an organ from a compatible donor. (Dr. Bastos recently added a PhD to her MD, with a dissertation on kidney exchange.)

Here's another Instagram link to the video.

I had the privilege of observing parts of five of the six surgeries (three nephrectomies and three transplants), and some pictures are below.  

If someone directs a movie about this kind of transplant surgery, there will be two dramatic scenes, one in which the donated kidney is carried across the hall to the transplant operating room, and the second showing the moment the clamps are removed from the blood vessels of the transplanted kidney, so that it turns from grey to pink as blood returns to it. 

But here's a photo I took at  the start of what I think is the most dramatic moment of the surgery, as the artery from the kidney is just about to be connected to the artery of the recipient.

The artery from the donated kidney is the small white tube being pointed to by the instrument held in the fingers at the top right of the picture. Immediately in front of it--the long red tube--is the artery of the recipient, to which it must be connected so that blood can again flow to the kidney.  Notice that a small incision has already been made in the recipient's artery--this is where the two will be attached. The connection has to be perfect, so that the blood can flow without obstruction that could cause a clot.

The surgeon who first figured out how to do this kind of vascular surgery, Dr. Alexis Carrel, won the 1912 The Nobel Prize in Physiology or Medicine

I was able to follow the proceedings thanks to the running commentary offered to me by the Brazilian surgeons and by Mike Rees (who wasn't busy doing surgery). That wasn't the only kind of support Mike offered me in the OR (as I balanced on a pair of stools to better appreciate the commentary):

And here's a post-op picture of most of the big team that made it happen:

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Parabéns ao Gustavo e à Juliana! Congratulations. Your work and leadership can make a big difference not just to your patients, but to people all over Brazil.

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Earlier:

Monday, August 12, 2024

Kidney exchange in Brazil: prelude

IV fluid shortages in the U.S.--perhaps we should allow international imports?

There's a hurricane-induced shortage of intravenous (IV) fluid.  Maybe we should import some? (But...international borders...)

An obstacle is that FDA approval of the factories is usually needed, but can be (and in the past has been) suspended, to allow imports from places that do their own high quality inspection (like Australia and Ireland in 2017--I guess it's good that the labels are in English) .  

More generally, after the Covid pandemic we learned of the fragility of supply chains that have concentrated overseas sources (like surgical masks from Wuhan).  The reaction has been to onshore more production. But concentrated domestic production also makes for fragile supply chains, and being able to diversify to overseas producers could strengthen them.

Statnews has the story:

White House should declare national emergency over IV fluid shortages caused by Helene, says hospital group. Hurricane Helene shuttered a Baxter plant that manufactures 60% of IV solutions for the U.S.  By Brittany Trang 

"Amid Hurricane Helene shuttering a major IV solution manufacturing plant and Hurricane Milton now barreling toward other IV manufacturing facilities in central Florida, the American Hospital Association on Monday asked the Biden administration to declare a shortage of IV solutions and invoke national emergency powers to ease the crisis. 

'In late September, Hurricane Helene shut down a Baxter plant in Marion, N. C., which manufactures approximately 60% of the IV solutions for the U.S. Both Baxter and “all other suppliers” of IV solutions have restricted how much their customers can order and have stopped taking new customers, AHA president Rick Pollack wrote in the organization’s letter to Biden. As a result, hospitals have declared internal shortages and restricted IV use. 

...

"In addition, the letter asked for the government to declare a national emergency and public health emergency so that Medicare and Medicaid rules around IV infusions can become more flexible, and to invoke the Defense Production Act to expand the production of IV solutions and bags. The AHA also suggested the government put the Federal Trade Commission and Department of Justice on alert for price gouging during the shortage.

Another step the FDA could take is to allow the importation of IV bags from other countries,* as it did when Hurricane Maria shut down Baxter’s Puerto Rico-based IV saline plants in 2017. That shortage mostly affected small IV bags. According to Vizient, a health care performance improvement company, the North Carolina Baxter plant is largely a producer of large IV bags, including saline, dextrose, and Ringer’s lactate solutions.

#####

*In 2017: "To address a shortage of intravenous solution bags exacerbated by Hurricane Maria, the Food and Drug Administration has granted permission for a health supply company to import certain products to the United States from Australia and Ireland."

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Related:

Wednesday, August 28, 2024

WHO Says Countries Should Be Self-Sufficient In (Unremunerated) Organs And Blood, by Krawiec and Roth

The NAS proposes that bans on studying marijuana and its effects should be relaxed

 The National Academy of Sciences has just issued a new report on marijuana and public health.  Among their recommendations is that bans on research should be rescinded. (Because marijuana is currently a Schedule I drug in the Controlled Substances Act, it's hard to get permission to study it and its effects...)

Cannabis Policy Impacts Public Health and Health Equity (2024)

The first four patients who received transplants of organs from genetically modified pigs

 NBC reports on the four patients who have so far received organ transplants from genetically modified pigs.

Their loved ones died after receiving pig organ transplants. The families have no regrets. Four people have received hearts or kidneys from pigs. Some of their relatives recount a roller coaster of hope and uncertainty. By Aria Bendix

"David Bennett Sr., had severe congestive heart failure and wasn’t a candidate for a human transplant. He knew he would likely die soon. There was nothing more to do — other than take a chance on a novel, cutting-edge surgery. Bennett Sr. and his son agreed it was worth the risk.  

"The achievement made headlines around the world after the transplant surgery in January 2022.

...

"But two months later, Bennett Sr.’s body rejected the heart and he died at age 57. In a paper, his doctors at the University of Maryland Medical Center explained that his body had likely produced too many antibodies that fought off the new organ.

...

Three other patients have followed in Bennett Sr.’s footsteps and received pig organs, most recently a pig kidney transplant in April. Together, they represent the pioneer patients of the burgeoning field of xenotransplantation. For their families, three of which spoke to NBC News about the experience, the journey came with a roller coaster of emotions, from uncertainty to blind hope — and, ultimately, admiration for their loved one’s decision. 

...

"None of the patients survived more than three months. To the public, that might seem like failure. But to the families, the transplants accomplished their goals: to buy their loved ones more time and advance research that could potentially save lives one day."

Optimism and pessimism on psychedelic drugs as medicine

 "Psychedelics" may prove to be a broad church, with psilocybin and LSD quite different from MDMA, etc., but here are two articles that express very different views about the progress towards making them part of standard medical practice.

Here's some optimism in Columbia Magazine:

The Magic and Mystery of Psychedelic Therapies.  As new trials show that psilocybin and LSD may help treat depression and anxiety, mental-health providers get ready for a revolution.  By Paul Hond |

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And here's some pessimism, in the NYT:

How Psychedelic Research Got High on Its Own Supply, By Caty Enders

"The drug company Lykos Therapeutics had spent much of this year expecting to vault to meteoric heights. It had sent an application to the Food and Drug Administration seeking approval to use MDMA to treat post-traumatic stress disorder. Lykos expected F.D.A. approval; it was banking on it.

"And then on Aug. 9, the F.D.A.’s decision came through: rejection. It was the capstone to months of increasingly loud concerns being voiced over the quality of Lykos’s clinical trials. And in the wake of the F.D.A. decision, the journal Psychopharmacology retracted three papers related to research on MDMA, citing “unethical conduct,” an apparent reference to allegations of sexual abuse on the part of an unlicensed therapist at one of the trial sites. Several of the authors of the retracted papers were affiliated with Lykos.

"It is a shocking decrescendo for a drug that had been promoted for years as best positioned to lead a psychedelic mental health revolution. The F.D.A.’s rejection signals greater uncertainty for the future of psychedelic medicine."

Travel for medical aid in dying

 CBS has the story:

Why Americans are traveling to Vermont and Oregon to die

""Dying with medical assistance wasn't an option when Milano learned in early 2023 that her disease was incurable. At that point, she would have had to travel to Switzerland — or live in the District of Columbia or one of the 10 states where medical aid in dying was legal.

"But Vermont lifted its residency requirement in May 2023, followed by Oregon two months later. (Montana effectively allows aid in dying through a 2009 court decision, but that ruling doesn't spell out rules around residency. And though New York and California recently considered legislation that would allow out-of-staters to secure aid in dying, neither provision passed.)

...

"At least 26 people have traveled to Vermont to die, representing nearly 25% of the reported assisted deaths in the state from May 2023 through this June, according to the Vermont Department of Health. In Oregon, 23 out-of-state residents died using medical assistance in 2023, just over 6% of the state total, according to the Oregon Health Authority."

Medical aid in dying debated in NY, extended in the Netherlands

 Here are two related stories, one from the NYT about a debate on whether to allow medical aid in dying in New York State. The other is from Fox News, about the medically assisted death of a physically healthy young woman afflicted with a frightful psychiatric disorder.

In New York, there's a debate about whether to become the 11th state to legalize medical aid in dying.  Some of the opponents worry about a slippery slope, leading to the Netherlands, where mental illnesses can qualify candidates for such aid.

Here's the NYT on the debate in NY:

Doctor-Assisted Death Is Legal in 10 States. Could New York Be No. 11? Activists have renewed attention on legislation related to the emotional issue of so-called medical aid in dying that has long languished in Albany.

"New York is one of 19 states where lawmakers are considering bills that would legalize medical aid in dying, a practice that is legal in 10 states and Washington, D.C.

"The bill in New York would allow mentally competent, terminally ill adults with no more than six months to live to request prescriptions from their doctors for life-ending medication. The patients would have to be able to ingest the medication on their own, and only the person seeking to die could request the prescription.

...

"Opponents worry that some patients might choose to end their lives based on an inaccurate prognosis or after being pressured to do so. And while the current bill is restricted to terminally ill people, they worry that lawmakers could expand eligibility for medical aid in dying after any initial legislation is passed."

*************

Here's Fox News on the Netherlands:

Physically healthy Dutch woman dies by assisted suicide at age 29. Zoraya ter Beek died by assisted suicide in the Netherlands last week.  By Kendall Tietz Fox News,  June 1, 2024

"29-year-old Zoraya ter Beek's life was terminated last week after waiting three years for final approval for her euthanasia, which is legal in the Netherlands if the patient is deemed to be experiencing "unbearable suffering with no prospect of improvement."

...

"she tried various things to treat her mental illness, including 33 rounds of electroconvulsive therapy, in which electric currents jolt the brain. But, after her last treatment in August 2020, her psychiatrist told her, "There’s nothing more we can do for you. It’s never going to get any better."

...

"My whole friends and my support system, we really did it together," she had told The Free Press. Ter Beek reportedly saw herself as an ambassador for the Dutch euthanasia program and believed there is proper protocol in place to prevent abuse of the system. 

"We’ve had this law for more than 20 years," she had told the outlet. "There are really strict rules, and it’s really safe."

Organs, tissues, and medical devices are regulated very differently

 Here's an article in JAMA by a Michigan doctor and his Congresswoman, on the lack of regulation for some substances of human origin.

Urgent Need for Regulatory Oversight of Human Cells, Tissues, and Cellular and Tissue–Based Products, by Robert P. Dickson, MD; Deborah A. Dingell, MS, JAMA. 2024;331(20):1703-1704. doi:10.1001/jama.2024.6834

" In 2021, an outbreak of M tuberculosis occurred in the US when contaminated bone graft material was implanted into 113 patients, 77% of whom developed clinically apparent tuberculosis.

...

[Again in 2023] "the Centers for Disease Control and Prevention (CDC) had identified additional tuberculosis-infected patients who had received implants of the same product, harvested from the same donor. At final count, 36 patients in 7 states had undergone implantation of bone graft tissue contaminated with M tuberculosis.

...

"Given the rigorous safety testing required of most medical therapies, how could 2 lethal outbreaks of tuberculosis occur in as many years, arising from the same product, distributed by the same company?

"The answer lies in the FDA’s designation of this product as a human cells, tissues, and cellular and tissue–based product (HCT/P) (Table). This class of therapies, which includes bone grafts, skin grafts, and stem cells, is not subject to the same regulatory standards as pharmaceuticals, biological products (such as blood products and monoclonal antibodies), or organ transplants. This designation has profound regulatory and clinical consequences

Main causes of death around the world, 1990-2021

 Here's a recent article from the Lancet that traces leading causes of death around the world, in more than a thousand countries and subnational locations.  Kidney disease went from #18 in 1990 to #9 in 2019, to #11 in 2021 (when Covid entered the list at #2)  So it looks like the rest of the world is catching up to the developed world in chronic disease as compared to infectious disease.

Naghavi, Mohsen, Kanyin Liane Ong, Amirali Aali, Hazim S. Ababneh, Yohannes Habtegiorgis Abate, Cristiana Abbafati, Rouzbeh Abbasgholizadeh et al. "Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021." The Lancet (2024).

Most diseases are causing less premature death, but Diabetes and Chronic Kidney Disease (CKD) are among the few that are causing more premature death, along with Malaria, AIDS, Covid and Other Pandemic Related Mortality (OPRM). (War is not included in the study.)

Signaling in medical residency applications

 We're starting to see descriptive studies of how signals are being used in the labor market for new doctors.  Each medical specialty has chosen to adapt the kinds of signals used in Economics in its own way, with some specialties using only a handful of signals and others eliciting as many as 30.

Here are two papers from a recent issue of Academic Medicine.

Impact of Applicants’ Characteristics and Geographic Connections to Residency Programs on Preference Signaling Outcomes in the Match, by Benjamin, William J. MPH; Lenze, Nicholas R. MD, MPH; Bohm, Lauren A. MD; Thorne, Marc C. MD, MPH; Abraham, Reeni MD; Sepdham, Dan MD; Mihalic, Angela P. MD; Kupfer, Robbi A. MD,  Academic Medicine 99(4):p 437-444, April 2024. | DOI: 10.1097/ACM.0000000000005551

"Abstract

Purpose : To assess the impact of applicant and residency program characteristics on preference signaling outcomes in the Match during the first 2 years of implementation across 6 specialties.

Method : Data were obtained from the Texas Seeking Transparency in Application to Residency survey for applicants applying into otolaryngology during the 2020–2021 and 2021–2022 application cycles and into dermatology, internal medicine (categorical and preliminary year), general surgery, and urology during the 2021–2022 application cycle. The primary outcome was signal yield, defined as the number of interviews at signaled programs divided by the total number of signals sent. Associations with applicant-reported characteristics and geographic connections to residency programs were assessed using Wilcoxon rank sum testing, Spearman’s rank correlation testing, and ordinary least squares regression.

Results : 1,749 applicants with preference signaling data were included from internal medicine (n = 884), general surgery (n = 291), otolaryngology (n = 217), dermatology (n = 147), urology (n = 124), and internal medicine preliminary year (n = 86). On average 60.9% (standard deviation 32.3%) of signals resulted in an interview (signal yield). There was a stepwise increase in signal yield with the percentage of signals sent to programs with a geographic connection (57.3% for no signals vs. 68.9% for 5 signals, P < .01). Signal yield was positively associated with applicant characteristics, such as United States Medical Licensing Exam Step 1 and 2 scores, honors society membership, and number of publications (P < .01). Applicants reporting a lower class rank quartile were significantly more likely to have a higher percentage of their interviews come from signaled programs (P < .01).

Conclusions: Signal yield is significantly associated with geographic connections to residency programs and applicant competitiveness based on traditional metrics. These findings can inform applicants, programs, and specialties as preference signaling grows."

And here are the introductory paragraphs:

"The rising number of residency applications submitted per applicant has led to concerns that programs will not be able to adequately perform a holistic review of all applications and will instead rely on easily reviewed metrics, such as United States Medical Licensing Exam (USMLE) scores, class rank, and medical school reputation.1,2 In addition, COVID-19–related changes to the residency application process, such as the introduction of virtual interviewing and a cap on the number of away rotations medical students can complete, have limited applicants’ ability to informally express their interest in programs.3 Further, there is evidence that, while applying to the maximum number of programs is advantageous at the individual level, it leads to poorer overall results when all applicants follow this practice.2 To address this issue, new systems have been proposed, including personalized application paragraphs,4 program-specific messages,5 and preference signals.4,6,7

"Otolaryngology implemented a preference signaling system in 2021, which was based on theory developed by the American Economic Association (AEA) in 2006. The AEA used a preference signaling system for job market applicants, whereby applicants were allowed to express special interest in particular employers in their applications.8 Results from the AEA program highlighted that preference signals were beneficial to both candidates and employers in a labor market where employers are unable to provide full attention to every application they receive.9 Building off previous economic work, a computer simulation study run on 2014 otolaryngology Match data found that the number of interview invitations improved when applicants provided preferences on their Electronic Residency Application Service application; this result would have benefitted both programs and applicants.2

"Based on this research, the Otolaryngology Program Directors Association formally implemented a preference signaling system during the 2020–2021 application cycle in which applicants were granted 5 “signals” to send to residency programs prior to interviews indicating their strong interest in that program. Each program then received a list of the applicants who had sent them a signal.6,10,11 Data from the 2021 otolaryngology Match were notable for significantly increased interview rates at signaled programs across all levels of applicant competitiveness.10,12 Furthermore, the majority of program directors and applicants strongly supported the continuation of preference signaling.10,11 During the 2021–2022 application cycle, preference signaling pilot programs were implemented in 5 additional specialties: dermatology, internal medicine (categorical), internal medicine preliminary year, surgery (categorical), and urology, with each specialty using 5 signals per applicant, except dermatology, which used 3 signals"

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The Relationship Between Program and Applicant Characteristics With Applicant Program Signals in the 2022 Residency Recruitment Cycle: Findings From 3 Specialties, by LaFemina, Jennifer MD; Rosman, Ilana S. MD; Wallach, Sara L. MD; Wise, Paul E. MD; Smink, Douglas S. MD, MPH; Fletcher, Laura PhD, Academic Medicine 99(4):p 430-436, April 2024. | DOI: 10.1097/ACM.0000000000005586

"Abstract

Purpose: Continuing increases in application volume have driven a national dialogue to reform the residency recruitment process. Program signaling allows applicants to express interest in a program at the preinterview stage with the goal of helping programs identify applicants with more genuine interest in their programs. This study explored the relationship between program signals and program and applicant characteristics.

Method: Participating dermatology, general surgery, and categorical internal medicine (IM) programs and applicants of the 2022 supplemental ERAS application (SuppApp) were included. Data from the SuppApp, the MyERAS Application for Residency Applicants (MyERAS), and the 2020 GME Track Survey were used. Cohen’s h was used to determine effect size, and chi-squared was used to determine statistical significance.

Results:There was an uneven distribution of signals to programs, with 25% of programs receiving about half of the signals across all 3 specialties. Programs with larger numbers of both residents and applicants received greater numbers of program signals relative to their program density, although this effect was small (h < 0.50, P < .001). No meaningful differences were seen across genders for any specialty. Only Hispanic applicants in IM sent a higher proportion of signals to programs with more underrepresented in medicine residents than White only applicants (40% vs 26%, h = 0.30, P < .001). Across all specialties, there was a small-to-moderate effect for international medical graduate (IMG) applicants sending a larger proportion of signals to programs with more IMG residents (h < 0.80, P < .001).

Conclusions: This first-year pilot study (i.e., SuppApp) provided initial evidence that supports the feasibility and fairness of program signals in residency selection. As program signals become more common across specialties, future research should continue to evaluate trends in where applicants send signals, and possible relationships between program and application characteristics."

"IMG applicants were more likely to signal programs with a greater proportion of IMG residents. The effect was small in dermatology and increased to moderate in GS and large in IM. In the NRMP’s 2022 Main Residency Match, 11 IMGs (U.S. and non-U.S.) matched into postgraduate year 2 dermatology, representing 2% of positions. This compares to the 10% and 38% IMG Match rate into GS and IM, respectively.21 While at this time, correlation of signal distribution and the likelihood of successfully matching is not available, these findings suggest that in general, IMG applicants sent more signals to programs they knew to be “IMG friendly” (i.e., more likely to accept IMGs), which they could easily identify with tools such as the Residency Explorer Tool22 and the Residency Programs List.23 However, if IMGs continue to send more signals to programs with already higher proportions of IMG residents, this may maintain the status quo or even further restrict the IMG applicant pool all programs are willing to consider during their resident selection process because programs with fewer IMGs will continue to receive a lower proportion of signals from IMG applicants. This could ultimately negatively affect diversity across programs"

Vatican statement on gender-affirming surgery and human dignity

 A new statement from the Vatican has been widely covered in the press.

Here's the story from the National Catholic Reporter:

Vatican condemns surrogacy, gender-affirming surgery, gender theory in new doctrinal note. Vatican doctrinal chief calls it 'painful' that some Catholics support gay criminalization  BY CHRISTOPHER WHITE, April 8, 2024

"Sex change operations, gender theory and surrogate motherhood pose grave threats to human dignity, according to a major new Vatican document released on April 8. 

While the highly anticipated treatise, "Dignitas Infinita: on Human Dignity," which has been the source of much speculation for months, offers a broadside against the creation of new rights motivated by sex and gender, it is largely a reiteration of long-held Catholic teaching on a number of social and moral concerns. 

The new document, however, seeks to elevate a number of social themes emphasized by Pope Francis during his decadelong papacy — such as poverty, migration and human trafficking — as being equally a part of the full panoply of potential threats to human dignity as bioethical concerns, such as abortion and euthanasia.   

...

"Among the newly identified threats to human dignity are poverty; war; the travail of migrants; human trafficking; sexual abuse; violence against women; abortion; child surrogacy; euthanasia and assisted suicide; the marginalization of people with disabilities; gender theory; sex change; and digital violence.

Gender theory, according to the document, is a subject of considerable debate among scientific experts, and risks denying "the greatest possible difference that exists between living beings: sexual difference."  

The document repeats a frequent warning of Francis against "ideological colonization," where the pope has sharply criticized western governments for allegedly imposing their sexual values on the developing world. All efforts to eliminate sexual differences between men and women must be rejected, says the document. 

At the same time, the document also begins with a caveat that all persons, regardless of their sexual orientation, must be respected, and "every sign of unjust discrimination is to be carefully avoided, particularly any form of aggression and violence."

"For this reason," the document continues, "it should be denounced as contrary to human dignity the fact that, in some places, not a few people are imprisoned, tortured, and even deprived of the good of life solely because of their sexual orientation."  

Last year, Francis became the first pope to specifically condemn the criminalization of homosexuality and said that the Catholic Church must work towards an end to what he described as "unjust" laws that criminalize being gay. At present, at least 67 countries have laws criminalizing same-sex relations. 

In its brief section on gender-affirming surgeries, the document avoids using the term "transgender" and instead offers a muted prohibition against medical interventions for such purposes.

...

"Catholic LGBTQ groups criticized the new Vatican document within hours of its publication, saying it failed to acknowledge the concrete experience of transgender and nonbinary individuals.

New Ways Ministry, an advocacy group that had an historic meeting with Francis at the Vatican last October, said in a statement that the text "fails terribly" and shows the limits of the church's understand of human dignity.

...

"The new document also goes on to repeat the pope's recent call for an international ban on the rising practice of surrogate motherhood, declaring that the "legitimate desire to have a child cannot be transformed into a 'right to a child' that fails to respect the dignity of that child as the recipient of the gift of life."  

In January, Francis used his annual "State of the World" address to ambassadors accredited to the Holy See to push for a global ban on surrogacy. 

While the pope had previously condemned the practice, the pope's sweeping remarks on the topic — where he called it a "grave violation of the dignity of the woman and the child" — marked the first time he had made such a specific policy proposal. Last month, the Vatican's ambassador to the United Nations, Archbishop Gabriele Caccia, also pressed for an international prohibition against the practice. "

Interviews by lottery at Queens University School of Medicine

 Overwhelmed by large numbers of applications, and concerned about fairness, Queens University will set admissions thresholds (on grades and exam scores) and then determine by lottery which applicants move to the interview stage.

New admissions process improves equitable access to the Queen’s MD Program

"Queen’s Health Sciences (QHS) is adapting its MD Program admissions process to create a more inclusive entry point for all applicants, minimize systemic barriers to becoming a doctor, and increase student diversity.

"The renewed medical student admissions process will launch this fall, for 2025 admissions, and includes a pathway for lower socioeconomic status (SES) applicants and adjustments to the current Indigenous pathway. A new comprehensive approach to support the recruitment of Black students will launch in a second phase of this admissions change.  

...

"The MD Program will set admissions thresholds for grade point average (GPA), Medical College Admission Test (MCAT), and Casper (a situational judgment test) at levels that align with the potential for predicting success in medical school, without concern for the number of applicants who meet these thresholds. While the MD Program already posts GPA thresholds, as part of this change, MCAT thresholds will be posted as well. All applicants who meet these thresholds will be entered into a lottery to determine who will be invited to interviews. "

HT: Jonah Peranson (of National Matching Services)

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

Medical aid in dying, and slippery slopes--the debate in Britain

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:

Crisis in the Sustainability of the U.S. Blood System

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

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.”

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.

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