One in eight older adults use cannabis products, suggesting need to screen for risks

 More older Americans use cannabis now than before the pandemic, with 12% saying they've consumed a THC-containing substance in the past year and 4% saying they do so multiple times a week, according to a new study of people aged 50 to 80. Those who drink alcohol at risky levels have a much higher rate of cannabis use.

The new findings, published in the journal Cannabis and Cannabinoids Research by a team from the University of Michigan's Institute for Healthcare Policy and Innovation, suggest a need for more education and screening of older adults for cannabis-related risks.

"As the stress of the pandemic and the increased legalization of cannabis by states converged, our findings suggest cannabis use increased among older adults nationally. Older adults represent a vulnerable age group for cannabis use due to interactions with medications, risky driving, cannabis-related mental health impacts and increased possibility of falls and memory issues," said Anne Fernandez, Ph.D., an addiction psychologist in the U-M Addiction Center and Department of Psychiatry who led the study.

The data in the study come from the National Poll on Healthy Aging, which IHPI runs with funding from AARP and Michigan Medicine, U-M's academic medical center. The national poll of 2,023 older adults was taken in January 2021, nine months into the official pandemic declaration and just as the first COVID-19 vaccines were being made available to the groups at the highest risk.

The 12% overall past-year use of cannabis seen in the new study is higher than the 9.5% seen in 2019 by other researchers pre-pandemic, and far higher than the 3% seen in another study in 2006, when only 12 states had passed medical cannabis laws. The NPHA in 2017 found that 6% of older adults had used cannabis for medical purposes.

In the new study, in addition to the 4% who said they use cannabis products four or more times a week, another 5% said they use cannabis once a month or less. The poll question asked about use of any product containing THC, the main psychoactive component of cannabis—including edibles—and used multiple common names for cannabis. It did not differentiate between medical and recreational use of cannabis.

Older adults who said they were unemployed, those who said they were unmarried and had no partner, and those who said they drank alcohol were more likely to say they used cannabis.

Fernandez notes an especially concerning finding: those whose alcohol use was high enough to cause physical and psychological harms were nearly eight times as likely to say they had used cannabis in the past year. But even those with low-risk alcohol drinking patterns were more than twice as likely to say they had used cannabis in the past year.

This group of dual-substance users is one that doctors and public health officials should pay special attention to, she said.

"Other research has shown that using both alcohol and cannabis increases the chance that a person will drive while impaired," she explained. "They are also more likely to have physical and mental health issues, including substance use disorders. Screening for alcohol use, cannabis use, and other drug use could help more people get counseling and reduce their risk and risk to others."

While there were no statistical differences among older adults by age, health or mental health status, income or education, those who said they had Hispanic backgrounds were less likely than non-Hispanic older adults to say they used cannabis. Fernandez says this is consistent with other research showing lower cannabis use in the Latino community.

She advises any older adult who chooses to use cannabis products for any reason to be open with their health care provider about it, especially if they also drink alcohol or take certain medications. Physicians, nurse practitioners and pharmacists can advise if any medications a person is taking might interact with cannabis, including ones for insomnia, depression and anxiety, opioid-containing pain medications, seizure medications, and blood thinners.

In addition to Fernandez, the study's authors are U-M addiction psychologist Lara Coughlin, Ph.D., poll deputy director Erica S. Solway, Ph.D., poll manager Dianne C. Singer, poll director Jeffrey T. Kullgren, M.D., M.S., M.P.H., poll data lead Matthias Kirch, M.S. and Preeti N. Malani, M.D., former poll director and current poll senior advisor.

More information: Anne C. Fernandez et al, Prevalence and Frequency of Cannabis Use Among Adults Ages 50–80 in the United States, Cannabis and Cannabinoid Research (2023). DOI: 10.1089/can.2023.0056

https://medicalxpress.com/news/2023-12-older-adults-cannabis-products-screen.html

Human behavior guided by fast changes in dopamine levels

 What happens in the human brain when we learn from positive and negative experiences? To help answer that question and better understand decision-making and human behavior, scientists are studying dopamine.

Dopamine is a neurotransmitter produced in the brain that serves as a chemical messenger, facilitating communication between nerve cells in the brain and the body. It is involved in functions such as movement, cognition and learning. While dopamine is most known for its association with positive emotions, scientists are also exploring its role in negative experiences.

Now, a new study from researchers at Wake Forest University School of Medicine published Dec. 1 in Science Advances shows that dopamine release in the human brain plays a crucial role in encoding both reward and punishment prediction errors. This means that dopamine is involved in the process of learning from both positive and negative experiences, allowing the brain to adjust and adapt its behavior based on the outcomes of these experiences.

"Previously, research has shown that dopamine plays an important role in how animals learn from 'rewarding' (and possibly 'punishing') experiences. But, little work has been done to directly assess what dopamine does on fast timescales in the human brain," said Kenneth T. Kishida, Ph.D., associate professor of physiology and pharmacology and neurosurgery at Wake Forest University School of Medicine.

"This is the first study in humans to examine how dopamine encodes rewards and punishments and whether dopamine reflects an 'optimal' teaching signal that is used in today's most advanced artificial intelligence research."

For the study, researchers on Kishida's team utilized fast-scan cyclic voltammetry, an electrochemical technique, paired with machine learning, to detect and measure dopamine levels in real-time (i.e., 10 measurements per second). However, this method is challenging and can only be performed during invasive procedures such as deep-brain stimulation (DBS) brain surgery. DBS is commonly employed to treat conditions such as Parkinson's disease, essential tremor, obsessive-compulsive disorder and epilepsy.

Kishida's team collaborated with Atrium Health Wake Forest Baptist neurosurgeons Stephen B. Tatter, M.D., and Adrian W. Laxton, M.D., who are also both faculty members in the Department of Neurosurgery at Wake Forest University School of Medicine, to insert a carbon fiber microelectrode deep into the brain of three participants at Atrium Health Wake Forest Baptist Medical Center who were scheduled to receive DBS to treat essential tremor.

While the participants were awake in the operating room, they played a simple computer game. As they played the game, dopamine measurements were taken in the striatum, a part of the brain that is important for cognition, decision-making, and coordinated movements.

During the game, participants' choices were either rewarded or punished with real monetary gains or losses. The game was divided into three stages in which participants learned from positive or negative feedback to make choices that maximized rewards and minimized penalties. Dopamine levels were measured continuously, once every 100 milliseconds, throughout each of the three stages of the game.

"We found that dopamine not only plays a role in signaling both positive and negative experiences in the brain, but it seems to do so in a way that is optimal when trying to learn from those outcomes. What was also interesting, is that it seems like there may be independent pathways in the brain that separately engage the dopamine system for rewarding versus punishing experiences. Our results reveal a surprising result that these two pathways may encode rewarding and punishing experiences on slightly shifted timescales separated by only 200 to 400 milliseconds in time," Kishida said.

Kishida believes that this level of understanding may lead to a better understanding of how the dopamine system is affected in humans with psychiatric and neurological disorders. Kishida said additional research is needed to understand how dopamine signaling is altered in psychiatric and neurological disorders.

"Traditionally, dopamine is often referred to as 'the pleasure neurotransmitter,"' Kishida said. "However, our work provides evidence that this is not the way to think about dopamine. Instead, dopamine is a crucial part of a sophisticated system that teaches our brain and guides our behavior. That dopamine is also involved in teaching our brain about punishing experiences is an important discovery and may provide new directions in research to help us better understand the mechanisms underlying depression, addiction, and related psychiatric and neurological disorders."

More information: Paul Sands et al, Sub-second fluctuations in extracellular dopamine encode reward and punishment prediction errors in humans, Science Advances (2023). DOI: 10.1126/sciadv.adi4927. www.science.org/doi/10.1126/sciadv.adi4927

https://medicalxpress.com/news/2023-12-human-behavior-fast-dopamine.html

Ukraine conducts new attack on Russian railway deep in Siberia - source

 Ukraine's domestic spy agency has detonated explosives on a Russian railway line deep in Siberia, the second attack this week on military supply routes in the area, a Ukrainian source told Reuters on Friday.

The incidents appear to show Kyiv's readiness and ability to conduct sabotage attacks deep inside Russia and disrupt Russian logistics far from the front lines of Moscow's 21-month-old war in Ukraine.

The source, who declined to be identified, said the explosives were detonated as a freight train crossed the Chertov Bridge in Siberia's Buryatia region, which borders Mongolia and is thousands of kilometres from Ukraine.

The train had been using a backup railway line after an attack on a nearby tunnel a day earlier caused trains to be diverted, the source said.

Baza, a Russian media outlet with security sources, said diesel fuel tanks had ignited on a train using the backup route and that six goods wagons had caught fire. It reported no casualties and said the cause of the explosions was unknown.

The Ukrainian source, who said both operations were conducted by the Security Service of Ukraine (SBU), gave a similar assessment of the damage, citing Russian Telegram channels.

Reuters could not independently verify the accounts or assess whether the route is used for military supplies. Russian Railways declined to comment on the latest incident. The regional branch of Russia's Investigative Committee did not immediately respond to a written request for comment.

The Ukrainian source said on Thursday the SBU had detonated explosives in the earlier attack as a cargo train moved through the Severomuysky tunnel in Buryatia.

Russian investigators have concluded that train was blown up in a "terrorist act" by unidentified individuals, the Moscow-based Kommersant newspaper cited unnamed sources as saying.

Russian Railways, the state company that operates the vast rail network, said traffic had been diverted along a new route after the first attack, slightly increasing journey times but not interrupting transport.

The Ukrainian source said the second attack had anticipated the diversion of rail traffic and targeted the backup route at Chertov Bridge, which is on Russia's Baikal-Amur Mainline traversing Eastern Siberia and the Russian Far East.

Russia's Trans-Siberian Railway is widely seen as more important for Russian freight transport than the Baikal-Amur Mainline.

A Russian industry source who declined to be identified said the backup route was functioning and being used by trains carrying freight on Friday afternoon.

https://news.yahoo.com/ukraine-conducts-attack-russian-railway-153117067.html

Hospital Prices in Medicaid Managed Care

 Jeffrey Marr, BA¹; Yang Wang, PhD¹; Jianhui Xu, PhD¹; et al

 doi:10.1001/jamanetworkopen.2023.44841

Introduction

As of 2020, 70% of Medicaid beneficiaries (57 million) were insured through Medicaid managed care (MMC), in which a private insurer covers a beneficiary’s medical care in exchange for fixed payments from state Medicaid agencies.¹ A key role of MMC insurers is to negotiate prices with hospitals. MMC prices have important implications for government health expenditures and access to care for Medicaid beneficiaries. However, little is known about MMC prices.² We used hospitals’ self-disclosed pricing information to characterize MMC hospital prices.

Methods

This cross-sectional study obtained data on MMC outpatient hospital prices from Turquoise Health (as of July 3, 2023), which compiles prices reported by hospitals complying with the Hospital Price Transparency rule.^3,4 We included 30 shoppable services, as defined by the Centers for Medicare & Medicaid Services, and emergency department (ED) visits that were paid by Medicare through the Outpatient Prospective Payment System. We calculated the traditional Medicare rate for each hospital and each service in 37 states and the District of Columbia with a significant presence of MMC, expressing median MMC prices among insurers at that hospital as a percentage of the Medicare rate. We summarized prices as a percentage of the Medicare rate following prior research on health care prices.⁵ We analyzed median prices as a percentage of the Medicare rate across 3 procedure categories (surgery and medicine, imaging, and ED) both nationally and at the state level. Details on sample selection, including the set of procedures and states, are included in the eMethods and eTable in Supplement 1. This study followed the STROBE reporting guidelines. No institutional review board approval was sought because no human participants were involved in the study. Analysis was conducted using Stata, version 17 (StataCorp) and R, version 4.3.0 (R Project for Statistical Computing).

Results

Our sample included prices reported by 1487 general acute care hospitals. Across outpatient service types, the median MMC prices varied from 69.8% of the Medicare rate (IQR, 40.5%-107.6%) for outpatient surgery and medicine services to 83.6% of the Medicare rate (IQR, 45.5%-143.7%) for ED services to 120.3% of the Medicare rate (IQR, 82.8%-210.9%) for imaging services (Figure 1).

Median MMC prices relative to the Medicare rate varied across states (Figure 2). Median MMC prices for surgery and medicine were highest in North Dakota (133.0% of Medicare) and lowest in West Virginia (18.6%). Median MMC prices for imaging were highest in Utah (371.7% of Medicare) and lowest in Wisconsin (52.0%). Median MMC prices for ED visits were highest in Washington, DC (176.9% of Medicare), and lowest in Wisconsin (26.0%). Prices by service category were correlated across states. State-level correlation coefficients were 0.49 for surgery and medicine and imaging, 0.70 for surgery and medicine and ED, and 0.56 for imaging and ED.

Discussion

Medicaid prices have been believed to be lower than Medicare prices.⁶ Existing research has found this to be the case for Medicaid fee-for-service hospital prices.² However, the results of this study suggest that MMC outpatient hospital prices vary widely and are sometimes above Medicare rates, especially for imaging services. This study was limited by hospitals’ potential reporting errors, incomplete reporting by hospitals, and the lack of data to weight prices by use. Additionally, the pricing information does not include Medicaid supplemental lump-sum payments, a sizable share of Medicaid payments to hospitals.²

This study suggests that MMC hospital prices may affect government health expenditures and access to care for Medicaid beneficiaries. Further research should examine the causes of the variation in MMC hospital prices, including potential market and policy factors.

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2812254

'AMA: Some AI Use in Medicine Should Require Docs' Consent'

 The American Medical Association (AMA) this week called for requiring physician consent for some uses of artificial intelligence as it released its recommended principles for the use of AI in medicine.

"The AMA recognizes the immense potential of health care AI in enhancing diagnostic accuracy, treatment outcomes, and patient care," said AMA President Jesse M. Ehrenfeld, MD, MPH, in a statement. "However, this transformative power comes with ethical considerations and potential risks that demand a proactive and principled approach to the oversight and governance of health care AI."

The AMA said health plans should seek to use AI to simplify administrative tasks and reduce workflow burdens. There's potential for AI-enabled technologies to
cut down on paperwork, but they may "not be designed or supervised effectively, creating access barriers for patients and limiting essential benefits."

The AMA principles also noted that physicians could face increased risks for liability when they rely on AI-enabled tools and systems sold with little transparency about data and algorithms underpinning these products.

AMA said it will advocate to ensure that physician liability for the use of AI-enabled technologies is limited and adheres to current approaches to medical malpractice, even as legal theory about liability and accountability in this field evolves.

And the AMA's principles called for greater transparency about insurers' use of AI in automated decision-making systems that can "deny care more rapidly, often with little or no human review." Recent lawsuits against insurers have highlighted new concerns over insurers' use of AI in prior authorization to deny care.

Health plans using automated decision-making systems should be required to engage in regular audits to ensure use of these systems do not increase claims denials or coverage limitations, or otherwise decrease access to care, AMA said.

"In some instances, payors instantly reject claims on medical grounds without opening or reviewing the patient's medical record," the AMA said. "Rather than payors making determinations based on individualized patient care needs, reports show that decisions are based on algorithms developed using average or 'similar patients' pulled from a database."

Patient privacy remains a concern as "data hungry" AI tools gain greater access to patient records via interoperable systems, AMA said. In many cases, companies developing AI-enabled products create legal arrangements that bring them under the Health Insurance Portability and Accountability Act (HIPAA) rules.

"Yet even HIPAA cannot protect patients from the 'black box' nature of AI, which makes the use of data opaque," AMA said. "AI system outputs may also include inferences that reveal personal data or previously confidential details about individuals. This can result in a lack of accountability and trust and exacerbate data privacy concerns."

"Lagging" Oversight

In the principles, the AMA also highlighted the current gaps in US government oversight and regulation of AI in medicine. There's currently no national standard to guide the development and adoption of many applications of AI to medicine, AMA said.

Instead there's a patchwork.

For example, the Food and Drug Administration (FDA) regulates AI-enabled medical devices, but many other AI-enabled technologies fall outside the scope of the agency's oversight. The Federal Trade Commission and the Health and Human Services Office for Civil Rights have oversight over some aspects of AI, but their authorities "are limited and [are] not adequate to ensure appropriate development and deployment of AI," AMA said.

"With a lagging effort toward adoption of national governance policies or oversight of AI, it is critical that the physician community engage in development of policies to help inform physician and patient education, and guide engagement with these new technologies," the AMA said.

https://www.medscape.com/viewarticle/998961

Dark Side of GLP-1 Receptor Agonists

 The approval of the GLP-1 receptor agonist semaglutide for weight regulation in January 2023 ushered in a new era of obesity therapy. In recent months, however, drug regulatory authorities have also documented rare, occasionally severe side effects associated with the use of these agents in diabetes therapy that doctors may not necessarily have been aware of.

"When millions of people are treated with medications like semaglutide, even relatively rare side effects occur in a large number of individuals," said Susan Yanovski, MD, codirector of the Office of Obesity Research at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, in a JAMA news report.

Despite the low incidence of these adverse events and the likelihood that the benefits outweigh these risks in individuals with severe obesity, doctors and patients should be aware of these serious side effects, she added.

GLP-1 receptor agonists like semaglutide or liraglutide mimic certain intestinal hormones. Almost all their characteristic side effects involve the gastrointestinal tract: nausea, vomiting, constipation, and diarrhea. However, these are not the rare, severe side effects that are gaining increasing attention.

Severe Gastric Problems

A recent analysis published in JAMA shows that GLP-1 receptor agonists are associated with a ninefold higher risk of pancreatitis, compared with bupropion, an older weight-loss medication. Patients receiving GLP-1 receptor agonists also had four times more frequent intestinal obstruction and more than three times more frequent gastroparesis. The absolute risks for these complications, however, were less than 1% per year of use.

There were no indications of an increased risk for gallbladder diseases. Acute pancreatitis and acute gallbladder diseases are known complications of GLP-1 receptor agonists.

These results "reinforce that these are effective medications, and all medications have side effects," said Yanovski. She emphasized that despite a significant increase in relative risk, however, the absolute risk remains very low.

Anesthetic Complications

In the spring of 2023, reports of patients taking GLP-1 receptor agonists and vomiting or aspirating food during anesthesia surfaced in some scientific journals. It was particularly noticeable that some of these patients vomited unusually large amounts of stomach contents, even though they had not eaten anything, as directed by the doctor before the operation.

Experts believe that the slowed gastric emptying intentionally caused by GLP-1 receptor agonists could be responsible for these problems.

The American Society of Anesthesiologists now recommends that patients do not take GLP-1 receptor agonists on the day of surgery and discontinue weekly administered agents like Wegovy 7 days before the procedure.

Increased Suicidality Risk?

In July, case reports of depression and suicidal ideation led the European Medicines Agency to investigate about 150 cases of potential self-harm and suicidal thoughts in patients who had received liraglutide or semaglutide. The review now also includes other GLP-1 receptor agonists. Results of the review process are expected this month.

Yanovski noted that it is unclear whether these incidents are caused by the drugs, but suicidal thoughts and suicidal behavior have also been observed with other medications for obesity treatment (eg, rimonabant). "It is certainly a good idea to use these medications cautiously in patients with a history of suicidality and monitor the patients accordingly," she said.

Long-Term Safety

GLP-1 receptor agonists likely need to be used long term, potentially for life, for the effects on body weight to persist. Whether there are side effects and complications that only become apparent over time is currently unknown — especially when these medications are used for weight reduction.

Studies in rodents have suggested an increased risk of medullary thyroid carcinomas. Whether a similar signal exists in humans may only become apparent in many years. In patients who have had medullary thyroid carcinoma themselves or in the family, dulaglutide, liraglutide, semaglutide, and tirzepatide, a dual GLP-1/GIP receptor agonist, are contraindicated.

With dual agonists like tirzepatide or even triple agonists like retatrutide (GLP-1/GIP/glucagon), patients can lose significantly more weight than with the monoagonist semaglutide. Gastrointestinal events were also frequent in studies of dual agonists.

Awaiting Guideline Updates

Guidelines for using these new medications are still scarce. "There are clinical guidelines for obesity therapy, but they were all written before the GLP-1 receptor agonists came on the market," said Yanovski. "Medical societies are currently working intensively to develop new guidelines to help doctors use these medications safely and effectively in clinical practice."

https://www.medscape.com/viewarticle/998986

Rude Awakening on Trying to Keep Donor Hearts Usable With Common Hormone Infusions

 Giving unstable brain-dead heart donors intravenous levothyroxine did not lead to more hearts being transplanted, a randomized trial showed.

In hemodynamically unstable potential donors, administering the thyroid hormone supplement after brain death did not significantly improve donor heart utilization compared with saline placebo, with transplantation rates of 54.9% and 53.2%, respectively (adjusted risk ratio 1.01, 95% CI 0.97-1.07), reported Rajat Dhar, MD, of Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, and colleagues.

The prespecified recipient safety outcome -- graft survival at 30 days after transplantation -- occurred in 97.4% of transplanted hearts in the levothyroxine group and 95.5% in the saline group (P<0.001 for noninferiority). However, severe hypertension and tachycardia occurred in excess in the levothyroxine group, Dhar and colleagues noted in the New England Journal of Medicineopens in a new tab or window.

"Neither weaning from vasopressor therapy nor ejection fraction on echocardiography was better with levothyroxine than with normal saline, findings that suggest a lack of physiological benefit of levothyroxine on donor cardiovascular function," they wrote. "These results provide evidence that thyroid hormone administration does not improve donor stability or organ-transplantation rates."

In the trial, 12 of the 15 participating organ-procurement organizations (OPOs) had been using levothyroxine as part of their standard protocols for years. With the present results, several organizations have stopped using thyroid hormone in this setting, Dhar said in a statement.

Intravenous levothyroxine has been widely used in deceased donor care due to the theory that neurohormonal insufficiency after brain death leads to myocardial energy depletion and shock, and hormone supplementation should widen the net of usable organs. However, this was supported only by observational data.

"The few randomized trials that have evaluated administration of thyroid hormone to donors have focused on intermediate outcomes such as donor hemodynamics and were underpowered to evaluate organ utilization," Dhar and team wrote. "Despite little high-quality evidence, consensus guidelines continue to recommend thyroid hormone in hemodynamically unstable or heart-eligible donors."

"We found good evidence that this intervention we've been using for 40 years doesn't work," Dhar said in a press releaseopens in a new tab or window. "It's vital that we explore questions like this to ensure we are doing all we can for patients who need organs -- and to ensure that they receive the most benefit possible from the generous people who choose to donate organs."

Dhar and colleagues acknowledged that blinding was not feasible in their trial. Open-label use of levothyroxine was allowed after 12 hours and used in a minority of the control group. Moreover, they noted their trial did not test the more active thyroid hormone (T3 or triiodothyronine).

In an accompanying editorialopens in a new tab or window, Kiran Khush, MD, MAS, of Stanford University School of Medicine in California, noted that "even so, [this study] provides the most definitive data to date about donor thyroid hormone replacement therapy. The results have major clinical implications for OPOs around the country."

Khush cited data from the United Network for Organ Sharing suggesting that 48% of all potential organ donors and 55% of donors with left ventricular dysfunction were treated with levothyroxine from 2015 to 2022. Nearly half the OPOs nationwide routinely administer thyroid hormone during donor care, he added.

The present study included 852 hemodynamically unstable potential heart donors (mean age 36 years, over 30% women). Participants were randomly assigned to open-label infusion of IV levothyroxine (30 μg/hour for 12+ hours) or saline placebo within 24 hours of death according to neurologic criteria. The median time from declaration of brain death to levothyroxine or saline administration was 8 hours.

In addition to the main results of the trial, there were no differences between the levothyroxine and saline groups in terms of vasopressor requirements, donor ejection fraction, and number of organs transplanted (four per donor in both groups).

"It is very unusual to have a study of deceased organ donors of this size and with such sufficient rigor, but we believed the 4-year, multicenter research was critical to definitively answer this key question to enable better organ donor management," said study co-author Gary Marklin, MD, also of Washington University School of Medicine, in the press release.

The researchers said their patient sample was representative of the target population, and their findings may be generalizable to hemodynamically unstable heart donors.

Disclosures

The trial was supported by Mid-America Transplant with internal support from each organ procurement organization.

Dhar disclosed consulting to Marinus Pharmaceuticals and Mid-America Transplant.

Khush reported receiving research funding from the NIH and consulting to the Scientific Registry for Transplant Recipients.

Primary Source

New England Journal of Medicine

Source Reference: opens in a new tab or windowDhar R, et al "Intravenous levothyroxine for unstable brain-dead heart donors" N Engl J Med 2023; DOI: 10.1056/NEJMoa2305969.

Secondary Source

New England Journal of Medicine

Source Reference: opens in a new tab or windowKhush KK "The importance of randomized, controlled trials in the care of organ donors" N Engl J Med 2023; DOI: 10.1056/NEJMe2311964.

https://www.medpagetoday.com/transplantation/hearttransplantation/107620