Eliminating Hepatitis C, now that there's a cure (even though it's expensive)

 There's growing discussion about eliminating Hep C in the U.S., doing appropriate deals with the two drug companies whose patents still run for another six years.

Fleurence RL, Collins FS. A National Hepatitis C Elimination Program in the United States: A Historic Opportunity. JAMA. 2023;329(15):1251–1252. doi:10.1001/jama.2023.3692

"One of the most dramatic scientific achievements of the last few decades has been the development of direct-acting antivirals (DAAs) that can cure hepatitis C in more than 95% of people infected. But 9 years after the first such treatment was approved in the United States, the simple 8- to 12-week oral cure is not reaching a significant fraction of the more than 2.4 million US residents chronically infected with hepatitis C.1 More than 15 000 US residents die of hepatitis C every year unnecessarily. In its fiscal year 2024 budget proposal, the Biden-Harris administration has put forward a bold 5-year program to put the nation on course to eliminate hepatitis C in the United States.

"The consequences of untreated hepatitis C can be severe: cirrhosis, liver failure, hepatocellular cancer, and death. Curative treatment stops transmission, prevents liver cancer and liver failure, and saves lives. It is even likely to be cost-saving, by avoiding expensive medical treatments for liver failure and liver cancer. So why is this not a public health success story? One major reason is that many people with hepatitis C have poor access to health care and experience other chronic health and social inequities. Hepatitis C disproportionately affects individuals without insurance, American Indian and Alaska Native persons, non-Hispanic Black persons, justice-involved populations, and people who use illicit drugs.2

...

"Among those diagnosed, hepatitis C treatment coverage is far below what is needed to achieve elimination goals. Only about one-third of people diagnosed with hepatitis C who have private insurance, Medicare, or Medicaid get treated, and the proportion is probably even lower for those without insurance.4 This is in part due to current restrictions, such as requirements for patient sobriety, requirements to document evidence of liver fibrosis, and the restriction of access to treatment only to those seen by specialists, that have been put in place by public and private insurers in reaction to the high cost of DAAs ($90 000 per patient initially, still around $20 000). Low rates of treatment may also reflect the complexity of traversing the full cascade of care in our health care delivery system.

"Addressing this missed opportunity can save both lives and money. A national effort can build on lessons from programs launched by jurisdictions such as the states of Louisiana and Washington, the Cherokee Nation, the Veterans Health Administration, and the Federal Bureau of Prisons. For example, the Veterans Health Administration has treated more than 92 000 veterans with hepatitis C virus since 2014, with cure rates exceeding 90%.5 A key lesson from these initiatives is that success requires both managing the cost of the medications and developing a comprehensive public health effort to identify persons with hepatitis C and link them to care.

...

"the program aims to provide broad access to curative hepatitis C medications. A key element will be a national subscription model to purchase DAAs for those who are particularly underserved today: Medicaid beneficiaries, justice-involved populations, people without insurance, and American Indian and Alaska Native individuals who are treated through the Indian Health Service. With this approach to drug purchasing pioneered in Louisiana,7 the federal government will negotiate with manufacturers to purchase as much treatment as needed for all individuals in the designated groups. The pharmaceutical industry can expect more revenue for DAAs for these populations than it is receiving today, but at a much lower per-patient cost. That’s a win-win. Beyond the subscription model, the program will seek to provide additional co-pay assistance to Medicare beneficiaries. Private insurers will also be strongly encouraged to increase coverage for hepatitis C testing and treatment and limit out-of-pocket costs where possible."

Telehealth restrictions and medical aid in dying/death with dignity

 Medical aid in dying (MAID) is now available to some extent in eleven U.S. jurisdictions (10 States and the District of Columbia), mostly with the requirement that eligible patients are within six months of dying naturally.  So these patients are pretty ill, which makes it difficult for some of them--particularly rural patients--to schedule in-person final appointments with their physicians, to receive the drugs that they will take.  Telehealth appointments and prescriptions have been important for these patients, and those may be going away.

Statnews has the story:

Dying patients protest looming telehealth crackdown By JoNel Aleccia 

"Online prescribing rules for controlled drugs were relaxed three years ago under emergency waivers to ensure critical medications remained available during the COVID-19 pandemic. Now, the U.S. Drug Enforcement Agency has proposed a rule that would reinstate most previously longstanding requirements that doctors see patients in person before prescribing narcotic drugs such as Oxycontin, amphetamines such as Adderall, and a host of other potentially dangerous drugs.

"The aim is to reduce improper prescribing of these drugs by telehealth companies that boomed during the pandemic. Given the ongoing opioid epidemic, allowing continued broad use of telemedicine prescribing “would pose too great a risk to the public health and safety,” the proposed rule said. It also cracks down on how doctors can prescribe other less-addictive drugs, like Xanax, used to treat anxiety, and buprenorphine, a narcotic used to treat opioid addiction.

...

"The proposal has sparked a massive backlash, including more than 35,000 comments to a federal portal and calls from advocates, members of Congress and medical groups to reconsider certain patients or provisions.

“They completely forgot that there was a population of people who are dying,” said Dr. Lonny Shavelson, a California physician who chairs the American Clinicians Academy on Medical Aid in Dying, a coalition of doctors who help patients access care under so-called right-to-die laws.

"Among the biggest complaints: The rule would delay or block access for patients who seek medically assisted suicide and hospice care, critics said. Many of the comments — including nearly 10,000 delivered in person to DEA offices — came from doctors and patients protesting the effect of the rule on seriously ill and dying patients."

Medical aid in dying: access for children, and for mental illness

Two recent articles discuss whether there should be categorical limits on medical aid in dying (MAID).  In the Netherlands, the law now permits euthanasia for children in certain horrific situations, and in Canada, a debate continues about the status of patients with mental illness.

 From The Conversation:

Dutch government to expand euthanasia law to include children aged one to 12 – an ethicist’s view  by Dominic Wilkinson

"Ernst Kuipers, the Dutch health minister, recently announced that regulations were being modified to allow doctors to actively end the lives of children aged one to 12 years who were terminally ill and suffering unbearably.

"Previously, assisted dying was an option in the Netherlands in rare cases in younger children (under one year) and in some older teenagers who requested voluntary euthanasia. Until now, Belgium was the only country in the world to allow assisted dying in children under 12.

...

"Dutch paediatricians and parents had reported that in a small number of cases, children and families were experiencing distressing suffering at the end of life despite being provided with palliative care.

"That included, for example, children with untreatable brain tumours who developed relentless vomiting, screaming, and seizures in their dying phase. Or children with epilepsy resistant to all treatment with tens to hundreds of seizures a day.

"The study recommended improvements in access to palliative care for children, as well as altering regulation to provide the option of assisted dying in these extreme cases.

"It has been suggested that five to ten children a year might be eligible for this option in the Netherlands.

*********

From the NYT, an opinion piece:

Medical Assistance in Dying Should Not Exclude Mental Illness By Clancy Martin

"I am a Canadian, where eligible adults have had the legal right to request medical assistance in dying (MAID) since June 2016. Acceptance of MAID has been spreading, and it is now legal in almost a dozen countries and 10 U.S. states and Washington, D.C. To my mind, this is moral progress: When a person is in unbearable physical agony, suffering from a terminal disease, and death is near, surely it is compassionate to help end the pain, if the person so chooses.

"But a debate has arisen in Canada because the law was written to include those living with severe, incurable mental illness. This part of the law was meant to take effect this year but was recently postponed until 2024."

Transplantation: progress and continued shortcomings

 Here's a guest essay from the NYT that focuses on a different set of shortcomings of organ transplantation than organ availability. The author writes about how her long history of immunosuppression, to keep her transplanted organ(s) alive, has left her vulnerable to cancer.

My Transplanted Heart and I Will Die Soon.  By Marine Buffard

"My 35 years living with two different donor hearts (I was 25 at the time of the first transplant) — finishing law school, getting married, becoming a mother and writing two books — has felt like a quest to outlast a limited life expectancy. 

...

"Organ transplantation is mired in stagnant science and antiquated, imprecise medicine that fails patients and organ donors. And I understand the irony of an incredibly successful and fortunate two-time heart transplant recipient making this case, but my longevity also provides me with a unique vantage point. Standing on the edge of death now, I feel compelled to use my experience in the transplant trenches to illuminate and challenge the status quo.

"Over the last almost four decades a toxic triad of immunosuppressive medicines — calcineurin inhibitors, antimetabolites, steroids — has remained essentially the same with limited exceptions. These transplant drugs (which must be taken once or twice daily for life, since rejection is an ongoing risk and the immune system will always regard a donor organ as a foreign invader) cause secondary diseases and dangerous conditions, including diabetes, uncontrollable high blood pressure, kidney damage and failure, serious infections and cancers. The negative impact on recipients is not offset by effectiveness: the current transplant medicine regimen does not work well over time to protect donor organs from immune attack and destruction.

"My first donor heart died of transplant medicines’ inadequate protection of the donor heart from rejection; my second will die most likely from their stymied immune effects that give free rein to cancer.

...

"Without vigorous pushback, hospitals and physicians have been allowed to set an embarrassingly low bar for achievement. Indeed, the prevailing metric for success as codified by the Health Resources and Services Administration is only one year of post-transplant survival, which relieves pressure for improvement."

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

That one year of measured graft survival is both too short, as the author points out, and too long.  By penalizing transplant centers for transplants that fail to survive a year, the current regulations make transplant centers too risk averse, so that kidney transplants that would have only, say, an 85% chance of working well are often not conducted, leaving patients to remain on dialysis, often til death,  for that 85% chance of life.

Transplantation is, still, a modern miracle. But until we can do without it, we'll have to keep trying to do it better.

Comstockery and abortifacients, on the way to the Supreme Court

 The Comstock Act of 1873 made it a Federal crime to distribute information or medicines for contraception or abortion, and more generally on material judged to be for "any indecent or immoral purpose."  The 1965 ruling in Griswold vs. Connecticut found the bans on contraception to be unconstitutional, and the bans on pornography were strictly limited the year before in the case Jacobellis v. Ohio.  But the Act reared its head again when it was cited by a Federal judge in Texas, Matthew J. Kacsmaryk, in his ruling that the abortion inducing drug mifepristone was illegal to distribute anywhere in the U.S., including in states where abortion is legal.

Michelle Goldberg in the NYT writes about "The Hideous Resurrection of the Comstock Act"

"suddenly, the prurient sanctimony that George Bernard Shaw called “Comstockery” is running rampant in America. As if inspired by Comstock’s horror of “literary poison” and “evil reading,” states are outdoing one another in draconian censorship. In March, Oklahoma’s Senate passed a bill that, among other things, bans from public libraries all content with a “predominant tendency to appeal to a prurient interest in sex.” Amy Werbel, the author of “Lust on Trial: Censorship and the Rise of American Obscenity in the Age of Anthony Comstock,” described how Comstock tried to suppress photographs of cross-dressing women. More than a century later, Tennessee has banned drag performances on public property, with more states likely to follow.

"And now, thanks to a rogue judge in Texas, the Comstock Act itself could be partly reimposed on America. Though the act had been dormant for decades and Congress did away with its prohibitions on birth control in 1971, it was never fully repealed. And with Roe v. Wade gone, the Christian right has sought to make use of it. The Comstock Act was central to the case brought by a coalition of anti-abortion groups in Texas seeking to have Food and Drug Administration approval of mifepristone, part of the regimen used in medication abortion, invalidated. And it is central to the anti-abortion screed of an opinion by Matthew J. Kacsmaryk, the judge, appointed by Donald Trump, who on Friday ruled in their favor.

...

"On Friday a Washington State judge issued an opinion directly contradicting Kacsmaryk’s and ordering the F.D.A. to continue to make mifepristone available. The dispute now is likely headed to the Supreme Court."

Markets in human milk, placenta, and feces

I've blogged earlier about markets for breast milk, but here is an article that considers them also in connection with placenta and feces: 

The Law of Self-Eating—Milk, Placenta, and Feces Consumption by Mathilde Cohen, Law, Technology and Humans, 3(1), pp.109-122.

"Milk, Placenta, and Feces 

"Since antiquity at least, there have been markets in human milk. Until the twentieth century, they relied primarily on wet nurses hired (or forced) to nurse infants directly on the breast.14Ancient Egyptian, Greek, and Roman pharmacopeias called for human milk as a therapeutic substance to treat burns as well as ailments affecting the ears, eyes, and genitals.15Traditional Chinese medicine  employed  human  milk  in  a  variety  of  preparations  to  cure  diseases,  such  as  debilitation,  arthritis,  rheumatism, voicelessness, amenorrhea, eye infections, and poisoning.16

"Today, markets in human milk continue to thrive.17Such markets assume two main forms: 1) informal markets through which people give or sell their milk peer-to-peer via their social circles or online; and 2) formal markets whereby profit or non-profit organizations, such as milk banks and commercial human milk companies, collect, process, and distribute milk to hospitals and a few outpatients for a fee. Human milk is sought after by three main categories of consumers: infants, adults, and researchers.

...

"Placenta

"Human placentas are used for spiritual, nutritional, medical, pharmaceutical, and cosmetic purposes. Placentophagy, or the act of eating one’s placenta after childbirth, has been practiced in the Global North since the beginningof the home-and natural-birth movement in the 1970s.22It is not an unprecedented phenomenon. Indeed, historian Jacques Gélis reported that:

    "Placentophagy, the custom of eating the newly expelled placenta,     has existed at various times amongst people of very different         cultures. From the sixteenth century onwards, European travellers to     the new world were much struck by this custom, which they         unfailingly reported.23

"According to Gélis, placentophagy was also practiced in Europe; however, “doctors and churchmen  were  more  and  more repelled, from the end of the seventeenth century onwards, by this custom . . . so ‘repugnant to humanity."  In the past decade, placentophagy has reemerged as a mainstream practice in the U.S., where it has been described as “anew  American  birth ritual.25

"Few randomized controlled trials have corroborated the benefits of placentophagy. However, placenta eaters are motivated by the hope of obtaining nourishment, hastening post-birth recovery, warding off postpartum depression, facilitating lactation, as well as spiritual motives, such as connecting with the baby and the environment. Placentas can be eaten raw or cooked."

...

"Minimally processed placental membranes have significant commercial and medical potential to treat, among other indications, eye diseases and acute and chronic wounds. The for-profit American company MiMedx also “grinds up amniotic tissue from placenta into an injectable product to treat tendinitis, strains, and other ailments.”29Much  like  human  milk,placentas  are increasingly seen as reservoirs of stem cells and thus are attractive to the field of regenerative and tissue engineering, and, more recently, as potential sources for treating coronavirus patients."

...

"Feces

"Excrement is typically regarded as disgusting; however, the medical use of human and animal feces has a long record. Heinrichvon Staden notes that:

"Most prominent among the ingredients in the Hippocratic pharmacological ‘dirt’ arsenal is the excrement of various animals. ..  .  the  belief  in  the  therapeutic  usefulness  of  excrement  was  shared  by  ancient  Mesopotamian,  Egyptian,  Greek,  Chinese, Talmudic, and Indian healers. . . . There is, therefore, abundant evidence that . . . ‘excrement therapy’—was a cross-cultural phenomenon extant already in the ancient world.32

"In Chinese medicine, human feces were used 1,700 years ago as a “suspension by mouth for patients who had food poisoning or severe diarrhea.”33

"Fast forward to the twentieth century, the community of microorganisms that dwell in the human gut has been shown to play a crucial role in human health. Fecal microbiota transplantation (“FMT”) was first identified in the modern scientific literature in 195834and has rapidly grown in popularity since the early 2010s. FMT consists in the delivery of processed stool from a healthy donor into the intestinal tract of a sick person via an enema, colonoscopy, naso-duodenal tube, capsules, or other means. As microbiologist Mark Smith and his colleagues noted, “the goal is to displace pathogenic microbes from the intestine by re-establishing a healthy microbial community.”35FMT  has  proven  strikingly  effective  in  treating Clostridium  difficile, a potentially lethal infection that most commonly affects older adults in hospitals or in long-term care facilities, typically after the  use  of  antibiotics."

...

"Despite these differences, milk, placenta, and feces share two sets of core similarities that justify their grouping in this analysis. First, milk, placenta, and feces are tissues that can be severed from the body without harm or risk of harm. Notably, milk and feces  are  replenishable  bodily  substances,  while  the  placenta  is  a  transient  organ  expelled  from  the  body  during  childbirth. Thus, far from constituting “corpse medicine”42(i.e., medicine that uses human materials obtained from dead bodies), the use of such substances can be characterized as living food or medicine. There are also no adverse health effects associated with the act of donation. Quite the opposite, good health requires that people eject the milk, placenta, and feces they produce from their bodies.  

...

"Second, these three products have similar channels of circulation, including via private, domestic consumption, peer-to-peer markets, medical and research institutions, and global markets in foods, drugs, and cosmetics. This wide scope for circulation is possible due to the potential for DIY treatments alongside higher tech uses involving special processing and expertise. Milk, placenta, and feces are collected, processed, and distributed by banks similar to other tissue banks; however, aspiring consumers can  also  obtain  milk,  placenta,  and  feces  and  use  them  on  their  own.  Unlike  blood  transfusion  or  organ  transplantation,  no professional expertise or complicated equipment is necessary to achieve basic forms of consumption. Milk, placenta, and fecescan be obtained directly from their producersafter some screening (or not) and consumed as is or minimally processed at home. Conversely, bio-banks systematically screen donors, subjecting them and their samples to a battery of tests, before processing their  products  in  various  ways;  for  example,  by freezing,  thawing,  pooling,  enriching,  freeze-drying  (in  the  case  of  milk), irradiating (in the  case of placenta), encapsulating (in the  case of stool). This is a fast-evolving field.

...

"No uniform perspective  has emerged on the  legal  classification of the  various body materials consumed by humans. In this respect, milk, placenta, and feces provide a case in point, as they do not fit neatly within the standard legal classifications for comparable products, such as foods, drugs, tissues, cosmetic ingredients, or waste products. Different countries have adopted contrasting legal regimes—or no regimes at all—to regulate these substances.

...

"In  the  so-called  post-colonial  era,  the  law  of  self-consumption  illustrates  the broader phenomenon of a “jurisprudence of disgust,” to use an expression that Alison Young developed to describe the legal censorship of provocative or “obscene” artwork.71A  significant  dimension  of  contemporary  law  making  can  be  characterized  as  a  response  to  what  is  considered disgusting around or among us, which reflects an endeavor to confine and tame what repulses us. This is particularly obvious in the context of what legal scholar Kim Krawiec calls “taboo trades” (and economist Alvin Roth dubs “repugnant markets”); that is, the exchanges and transactions of products that are considered culturally immoral and uncaring, such as those involving organs, babies, sex, drugs, and corruption."

Opioids and Appalachia by Sally Satel

 Sally Satel, who has treated patients in Appalachia, writes movingly of the drug addiction problem there. Here's a paragraph that sets the stage.

"The history of opioid pain relievers in Appalachia is a prime illustration of the fact that drug epidemics rarely burst onto the scene out of nowhere. Instead, they find their place in regions that are already home to an established base of individuals who abuse similar drugs. Thus illicit OxyContin, a more potent opioid, efficiently gained popularity over Percocet and Vicodin in the same way heroin would substitute for prescription opioids as the latter grew scarce after 2010."

That's from Opioids and Appalachia by Sally Satel, in the current issue of National Affairs.

The whole thing is well worth reading; here are a few more paragraphs that caught my eye.

"The churn of pills — diverting, using, and selling them — soon had eastern Kentucky, southeastern Ohio, and West Virginia pulsing with crime. Realtors routinely told home sellers not to leave pills in their medicine chests during open houses. Funeral directors and hospice nurses cautioned the bereaved not to mention in obituaries that their loved ones had succumbed to cancer — a red flag signaling that huge bottles of pills were likely on the premises. In eastern Kentucky, local law enforcement was often stymied by close ties between people within communities. Loyalty within large families and fear of retaliation by neighbors made it hard to cultivate informants and to impanel neutral juries that would convict when prosecutors proved their case.

...

"Appalachians seemed to take the corruption in grudging stride. In one survey, 90% of over 100 Kentuckians working in law enforcement, health, and community governance said the rural OxyContin problem in the early 2000s was "fueled by a cultural acceptance of drug misuse." Indeed, many residents tolerated unlawful activity, since it generated revenue for the community from sales of pills to outsiders. This happened in places like Williamson, West Virginia — dubbed "Pilliamson" — where the local Wellness Center was a hub of reckless prescribing. Cash-laden out-of-staters flocked there to buy painkillers and, in a small area near the center, trade and sell those pills.

"Pablo Escobar and El Chapo couldn't have set things up any better," wrote Eyre. "The coal barons no longer ruled Appalachia. Now it was the painkiller profiteers."

...

"Today, opioid pills are no longer pouring into Appalachia as they once did; highly lethal products like fentanyl-laced heroin, methamphetamine, and counterfeit fentanyl pills are what people are selling."

Reconsideration of covid convalescent plasma

Recently Statnews reported that Covid convalescent plasma (CCP) may in fact be useful in preventing severe illness, despite the fact that earlier clinical trials did not show success in reversing severe illness:

Covid convalescent plasma: the ‘little engine that could’  By Michael J. Joyner, Nigel Paneth and Arturo Casadevall

"Unlike monoclonal antibodies, which can be defeated by new SARS-CoV-2 variants, CCP collected from vaccinated donors after recent breakthrough infections (VaxCCP) evolves with the variants and retains the ability to neutralize them. What makes CCP an even more promising therapy is that there are now many potential donors available in the U.S. who have been vaccinated and had recent breakthrough infections.

...

"An array of data, including randomized controlled trials and careful retrospective studies, show a clear survival benefit when CCP is given to immunocompromised individuals who test positive for SARS-CoV-2. There are also impressive case reports and case series showing that Covid convalescent plasma, especially VaxCCP, is effective in patients with smoldering Covid-19.

...

"the early “major” RCTs that tested the efficacy of CCP on survival in hospitalized patients tested the wrong use case. These studies treated patients who were too sick for too long to benefit from antibody therapy. But the major “negative” trials all showed evidence of effectiveness among people who received CCP earlier, who were not already desperately ill, who were immunocompromised, or who received the most antibodies. Unfortunately, these positive signals, which were consistent with impressive real-world data on Covid-19 and CCP, were buried under the top-line results."

*********

Earlier posts on convalescent plasma

Australia legalizes medical use of psychedelics

 Scott Cunningham points out that Australia has become the first country to legalize the medical use of certain psychedelics. 

Here's the announcement from the Australian Government's Therapeutic Goods Administration (TGA)

Change to classification of psilocybin and MDMA to enable prescribing by authorised psychiatrists

"From 1 July this year, medicines containing the psychedelic substances psilocybin and MDMA (3,4-methylenedioxy-methamphetamine) can be prescribed by specifically authorised psychiatrists for the treatment of certain mental health conditions.

The Therapeutic Goods Administration (TGA) will permit the prescribing of MDMA for the treatment of post-traumatic stress disorder and psilocybin for treatment-resistant depression. These are the only conditions where there is currently sufficient evidence for potential benefits in certain patients.

Prescribing will be limited to psychiatrists, given their specialised qualifications and expertise to diagnose and treat patients with serious mental health conditions, with therapies that are not yet well established. To prescribe, psychiatrists will need to be approved under the Authorised Prescriber Scheme by the TGA following approval by a human research ethics committee. The Authorised Prescriber Scheme allows prescribing permissions to be granted under strict controls that ensure the safety of patients.

The decision acknowledges the current lack of options for patients with specific treatment-resistant mental illnesses. It means that psilocybin and MDMA can be used therapeutically in a controlled medical setting. However, patients may be vulnerable during psychedelic-assisted psychotherapy, requiring controls to protect these patients.

For these specific uses, psilocybin and MDMA will be listed as Schedule 8 (Controlled Drugs) medicines in the Poisons Standard. For all other uses, they will remain in Schedule 9 (Prohibited Substances) which largely restricts their supply to clinical trials."

*********

Scott shares a post by Shane Pennington on drugs that contrasts the Australian (medical) decision with the U.S. Drug Enforcement Agency's (legal) decision to maintain the ban on these drugs, despite the growing medical evidence (from U.S. studies, on which the Australian government relied) that psychedelics have some important medical uses.

"To support its decision, the TGA relied heavily on studies conducted in the U.S. and recent U.S. Food and Drug Administration (FDA) decisions recognizing psilocybin and MDMA’s extraordinary therapeutic potential. Around the same time, DEA shot down a petition—based on those same arguments and evidence—that Matt and I submitted on behalf of a palliative-care doctor, requesting rescheduling of psilocybin under U.S. law. The DEA’s four-sentence analysis completely ignored the same studies and FDA decisions that persuaded the Australian regulator to reschedule.  

"The dramatically different fates of these similar petitions reveal a troubling reality about U.S. drug law: Under DEA’s watch, the scientific and medical determinations of the nation’s leading public health agency carry considerable weight around the world but are often ignored at home. That revelation should terrify anyone interested in rational, evidence-driven drug policy. "

******

But the States are the laboratory of democracy: here's an earlier related post.

Sunday, November 13, 2022

Colorado legalizes magic mushroom/psilocybin therapies

Evaluating kidney patients and donors without consideration of race

 Somewhere in the history of nephrology, a patient's race was included as a factor in estimating their kidney function.  This has at various times been important for various kinds of treatment, including of course preventive treatment, as well as starting dialysis, and entry and perhaps priority on kidney transplant waitlists. And it has also been important for evaluating the quality of deceased donor kidneys that can be offered for transplantation. There have been important recent changes in this, and more may be on the way. The current issue of JAMA devotes a number of articles to that, linked below.

Viewpoint Redressing the Harms of Race-Based Kidney Function Estimation Dinushika Mohottige, MD, MPH; Tanjala S. Purnell, PhD, MPH; L. Ebony Boulware, MD, MPH Audio: Race-Neutral Estimates of Kidney Function: Enhancing Equity Video: Race-Neutral Estimates of Kidney Function: Enhancing Equity Time to Abolish Metrics That Sustain Systemic Racism in Kidney Allocation John S. Gill, MD, MS; Burnett Kelly, MD, MBA; Marcello Tonelli, MD, SM Medical News & Perspectives Race-Based Equations Delayed Black Patients From Getting Onto Kidney Transplant Lists—An Unprecedented New Policy Seeks to Undo the Damage Jennifer Abbasi PREVIOUSLY PUBLISHED JAMA | Research Association of Estimated GFR Calculated Using Race-Free Equations With Kidney Failure and Mortality by Black vs Non-Black Race Orlando M. Gutiérrez, MD, MMSc; Yingying Sang, MS; Morgan E. Grams, MD, MHS, PhD; et al JAMA | Opinion Race-Free Estimation of Kidney Function: Clearing the Path Toward Kidney Health Equity L. Ebony Boulware, MD, MPH; Dinushika Mohottige, MD, MPH; Matthew L. Maciejewski, PhD JAMA Network Open | Research Association of the Estimated Glomerular Filtration Rate With vs Without a Coefficient for Race With Time to Eligibility for Kidney Transplant Leila R. Zelnick, PhD; Nicolae Leca, MD; Bessie Young, MD, MPH; et al Audio Race-Neutral Estimates of Kidney Function: Enhancing Equity Video

Join the conversation. Follow JAMA on Twitter.

Judge shopping for abortion rulings

 Justice (like politics, sausage and econometrics) is constructed in complex ways. The Washington Post has a story on the case against an anti-abortion drug, now being heard by federal judge Matthew Kacsmaryk in Amarillo Texas, which could result in a nationwide ban on that drug.  The case concerns medical issues about drug regulation, and isn't directly concerned with the legal controversy about abortion rights.

The Texas judge who could take down the abortion pill. A devout Christian, Matthew Kacsmaryk has been shaped by his deep antiabortion beliefs. By Caroline Kitchener and  Ann E. Marimow  February 25, 2023 

"The abortion pills lawsuit, which Kacsmaryk could rule on any day, is the latest in a long line of politically explosive cases to appear on the judge’s docket. In a practice known as “forum shopping,” conservative groups have zeroed in on the Amarillo division of the Northern District of Texas as a go-to place to challenge a wide range of Biden administration policies. Because Amarillo is a federal district with a single judge, plaintiffs know their arguments will be heard by Kacsmaryk — who, like any federal judge, is positioned to issue rulings with nationwide implications.

"Appeals from Kacsmaryk’s district follow a path that has regularly yielded favorable outcomes for conservatives — reviewed first by the U.S. Court of Appeals for the 5th Circuit, which upheld a strict Texas abortion ban long before Roe v. Wade was overturned, then ultimately by the conservative-controlled Supreme Court."

********

Here's a related story from Medpage Today:

A Ban on the Abortion Drug Mifepristone Is Looming— A Texas lawsuit may be disastrous for effective abortion access and FDA's authority by Lawrence O. Gostin, JD, LLD, and Sarah Wetter, JD, MPH, February 23, 2023

"In the most consequential and controversial attack on reproductive rights since the overturning of Roe v. Wade, a Texas judge could ban the safest, most effective, and most common method for abortion in all 50 states. The hyper-conservative anti-abortion group Alliance Defending Freedom  (ADF) is seeking to overturn the FDA's approval of mifepristone (Mifeprex), a medication in a two-pill regimen used to terminate pregnancies through the first 10 weeks gestation. The lawsuit does not target the other medication, misoprostol (Cytotec), which FDA approved to treat stomach ulcers, and can be prescribed off-label for abortion.

...

"Given the FDA's rigorous risk evaluation and mitigation strategy (REMS) for mifepristone and its safe use for 23 years, the case is utterly frivolous and political, but due to "judge shopping" the repercussions for reproductive health and equity are real. Perversely, a single federal trial judge has the power to block a federal law, rule, or action on a national scale. The case could make its way to the Supreme Court, with potentially disastrous consequences for safe, effective abortion access and the authority of the FDA."

opens in a new tab or windowfor mifepristone and its safe use for 23 years, the case is utterly frivolous and political, but due to "judge shopping" the repercussions for reproductive health and equity are real. Perversely, a single federal trial judge has the power to block a federal law, rule, or action on a national scale. The case could make its way to the Supreme Court, with potentially disastrous consequences for safe, effective abortion access and the authority of the FDA.

Compensation for participating in clinical trials

 Here's an opinion piece from Medpage Today:

It's Time to Pay Clinical Trial Participants More — Accelerating trial enrollment can catalyze access to much-needed medications  by Gunnar Esiason 

He writes:

"Most people I know with cystic fibrosis have participated in at least one, if not several clinical trials. 

...

"Participating in a trial can be like working for a company that hasn't invested in its employees in a long time. In this case, the employees are clinical trial participants. The pay is low despite the time required to participate in research and the growing number of trials that need participants.

"From 2019-2022, the number of registered clinical trials grew by 25%opens in a new tab or window globally -- yet participant pay remains arbitrary and inconsistentopens in a new tab or window between studies. It's almost like mismatched supply and demand curves, where participants are in high demand but unwilling to participate.

"Increasing trial participant pay might be a path toward alleviating the participant supply crunch in trials hungry for patients. One key benefit of increasing pay for patients could be substantial: namely, speeding up clinical trials through a more competitive enrollment process.

...

"More than 80% of clinical trials fail to enroll on time, leading to costs of anywhere from $600,000 to $8 million per dayopens in a new tab or window and making trials take up to twice as longopens in a new tab or window.

"And yet it has been shownopens in a new tab or window that moderately increasing pay can motivate participation without being an "unjust inducement." In other words, patients are encouraged to participate -- but not coerced to do so.

"If increasing participant pay can accelerate trial enrollment, then a safe and effective drug can reach the market faster and therefore reduce the amount of time products remain in the pre-revenue stage. The return on investment for study sponsors who increase participant pay should be clear from a business perspective.

"From a patient perspective, even a marginal improvement in time to accessing new drugs is something worth celebrating. For patients, we pay the cost of delays with our health."

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Some earlier related posts:

Monday, February 22, 2021

Ethical Payment in Human Infection Challenge Studies in the American Journal of Bioethics

Monday, March 1, 2021

Compensating challenge vaccine trial participants: further discussion in the American Journal of Bioethics

Thursday, October 29, 2020

Paying participants in challenge trials of Covid-19 vaccines, by Ambuehl, Ockenfels, and Roth

"we note that increasing hourly pay by a risk-compensation percentage as proposed in the target article provides compensation proportional to risk only if the risk increases proportionally with the number of hours worked. (Some risky tasks take little time; imagine challenge trials to test bulletproof vests.) "

Sunday, November 1, 2020

What do we know about the effects of payments to participants in challenge trials for vaccines, and other public spirited activities?

Euthanasia in Canada

 The NYT columnist Ross Douthat considers the medical aid in dying policies in Canada, and warns us that conservative politics is what protects us against the slippery slope that might lead us down the Canadian path.

 What Euthanasia Has Done to Canada

"In recent years, Canada has established some of the world’s most permissive euthanasia laws, allowing adults to seek either physician-assisted suicide or direct euthanasia for many different forms of serious suffering, not just terminal disease. In 2021, over 10,000 people ended their lives this way, just over 3 percent of all deaths in Canada. A further expansion, allowing euthanasia for mental-health conditions, will go into effect in March 2023; permitting euthanasia for “mature” minors is also being considered.

...

"The rules of civilization necessarily include gray areas. It is not barbaric for the law to acknowledge hard choices in end-of-life care, about when to withdraw life support or how aggressively to manage agonizing pain.

"It is barbaric, however, to establish a bureaucratic system that offers death as a reliable treatment for suffering and enlists the healing profession in delivering this “cure.” And while there may be worse evils ahead, this isn’t a slippery slope argument: When 10,000 people are availing themselves of your euthanasia system every year, you have already entered the dystopia.

"Indeed, according to a lengthy report by Maria Cheng of The Associated Press, the Canadian system shows exactly the corrosive features that critics of assisted suicide anticipated, from health care workers allegedly suggesting euthanasia to their patients to sick people seeking a quietus for reasons linked to financial stress.

...

"in the Canadian experience you can see what America might look like with real right-wing power broken and a tamed conservatism offering minimal resistance to social liberalism. And the dystopian danger there seems not just more immediate than any right-authoritarian scenario, but also harder to resist — because its features are congruent with so many other trends, its path smoothed by so many powerful institutions.

...

"without a potent conservatism, the cultural balance tilts too much against these doubts. And the further de-Christianization proceeds, the stronger the impulse to ... rationalize the new order with implicit reassurances that it’s what some higher power wants.

"It’s often treated as a defense of euthanasia that the most intense objections come from biblical religion. But spiritual arguments never really disappear, and the liberal order in a dystopian twilight will still be infused by some kind of religious faith.

"So I remain a conservative, unhappily but determinedly, because only conservatism seems to offer a stubborn obstacle to that dystopia"

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Update, January 14: in a followup column, Douthat responds to supporters of Canada's euthanasia policies,* and summarizes his position with this concluding sentence: 

"And if euthanasia is kept within limits or rolled back from its advances, I suspect it will be the old taboos and Christian prohibitions that make the difference, not a libertarianism that so quickly and easily yields to pagan destinations."

*See in particular

Canadian Euthanasia as Moral Progress. Individual liberty, the common good, and human dignity. by Richard Hanania

Here's a summary paragraph:

"First, I will show that the MAID program is currently small, and likely represents cases of the most extreme suffering given the data that we have. I then go on to refute arguments against MAID that have appeared in the popular press. Sometimes, these arguments are simply false, as when it is claimed that it will eventually lead to large numbers of healthy young adults killing themselves with state sanction. Other times, the arguments may be correct but actually make the case for euthanasia. It is true, for example, that some people might feel “pressured” to commit suicide because they don’t want to be burdens on their families or the government. I don’t think there’s anything wrong with this — in practically every other kind of situation, it is usually considered pro-social to care about the impact your life has on others. This gets to the point that my support for euthanasia does not simply rest on libertarian and utilitarian grounds, but also on the idea that people should behave in ways that consider the common good and that, yes, preserve human dignity. The state’s interest in saving costs, as long as it’s going to pay for healthcare, is also legitimate, although I won’t dwell on that here."

Opioids and pain management: revised CDC guidelines

 Concerned over the opioid addiction epidemic in the U.S., and the increasing number of overdose related deaths, the CDC issued the 2016 CDC Opioid Prescribing Guideline, which led to reduced opioid prescriptions by doctors. Sometimes this led to the undertreatment of pain, which in turn may have led to patients accessing opioids on the black market, where they are less safe. It may also have led to suicides of patients with unbearable pain.

The CDC has now issued some updated guidelines that appear aimed at balancing concerns with over-prescription against concerns with under-treatment.

Here are the updated guidelines:

CDC Clinical Practice Guideline for Prescribing Opioids for Pain — United States, 2022

"This guideline provides recommendations for clinicians providing pain care, including those prescribing opioids, for outpatients aged ≥18 years. It updates the CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016 (MMWR Recomm Rep 2016;65[No. RR-1]:1–49) and includes recommendations for managing acute (duration of <1 month), subacute (duration of 1–3 months), and chronic (duration of >3 months) pain.

...

"CDC recommends that persons with pain receive appropriate pain treatment, with careful consideration of the benefits and risks of all treatment options in the context of the patient’s circumstances. Recommendations should not be applied as inflexible standards of care across patient populations. This clinical practice guideline is intended to improve communication between clinicians and patients about the benefits and risks of pain treatments, including opioid therapy; improve the effectiveness and safety of pain treatment; mitigate pain; improve function and quality of life for patients with pain; and reduce risks associated with opioid pain therapy, including opioid use disorder, overdose, and death.

A central tenet of this clinical practice guideline is that acute, subacute, and chronic pain needs to be appropriately and effectively treated regardless of whether opioids are part of a treatment regimen. 

...

"To avoid unintended consequences for patients, this clinical practice guideline should not be misapplied, or policies derived from it, beyond its intended use (67). Examples of misapplication or inappropriate policies include being inflexible on opioid dosage and duration, discontinuing or dismissing patients from a practice, rapidly and noncollaboratively tapering patients who might be stable on a higher dosage, and applying recommendations to populations that are not a focus of the clinical practice guideline (e.g., patients with cancer-related pain, patients with sickle cell disease, or patients during end-of-life care)

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Earlier post:

Tuesday, March 15, 2022

Opioid prescription reductions and suicides

Why is it so easy to get drugs, and so hard to get drug abuse treatment? Overdose deaths continue to climb.

 Here's an update on drug abuse in the U.S., from the WSJ. One quote particularly struck me, from a mom whose child died: "it’s so easy to get drugs,”  “It’s so much more available than treatment.”

How Meth Worsened the Fentanyl Crisis. ‘We Are in a Different World.’ Methamphetamine fatalities are rising, increasingly in combination with opioids  By Jon Kamp and Arian Campo-Flores.

"One in five of the total fatal overdoses last year involved an opioid and a psychostimulant, a drug class dominated by meth, preliminary federal data show. A decade earlier, about 2% of drug deaths involved such combinations.

...

"The rise in fatalities involving stimulants, often combined with opioids, has created a fourth wave of the decadeslong U.S. overdose-death crisis, according to Dr. Daniel Ciccarone, a professor of addiction medicine at the University of California, San Francisco. Deaths from combinations of opioids and cocaine, another stimulant, are also climbing.

...

"Fentanyl drove U.S. overdose deaths to a record-breaking tally of more than 108,000 last year, according to the federal data.

"Now, the combination of meth and opioids—especially fentanyl—is supercharging those numbers. Meth-related deaths, though smaller in number, are increasing at a faster rate than opioid and overall drug fatalities.

"About 33,400 deaths last year involved psychostimulants such as meth, up more than 340% from roughly 7,500 five years earlier, the federal data show. In the same time span, deaths involving synthetic opioids like fentanyl rose about 270% to around 72,000, and overall drug fatalities rose about 71%.

...

"it’s so easy to get drugs,” said Mr. Ryan’s mother, Alicia Vigil-Ryan. “It’s so much more available than treatment.”

Black markets in abortion pills

 Americans differ in their opinions about whether American women have a right to end a pregnancy, or whether state legislators have the right to decide the issue for residents of their state.  Six American Supreme Court justices hold the latter opinion, and so overturned the constitutional right defined 50 years ago by the same court in Roe v. Wade.

This means that different states are going to have different laws about abortion. But medical technology is such that abortion pills exist, and can arrive in the mail. So even State laws criminalizing that may not stop it, when abortion and abortion pills remain legal in other states. That is, we're about to see a situation ripe for black markets. We may also see a legal conflict among the states.

The NY Times has a story on that:

Risking Everything to Offer Abortions Across State Lines. Doctors and midwives in blue states are working to get abortion pills into red states — setting the stage for a historic legal clash.  By Emily Bazelon

"When the landscape settles, abortion is likely to be illegal or severely restricted in at least 20 states — where just two years ago, in 2020, about 250,000 people had abortions. It is clear that clinicians in those states will face imminent prosecution if they continue to provide abortions. What is much less clear is what happens if providers in blue states offer telemedicine abortions to women in states where that’s against the law. These clinicians, too, could be arrested or sued or lose their medical licenses. To protect themselves, they may have to give up traveling to certain parts of the country — and it’s still no guarantee.

"In the face of so much uncertainty and an invigorated anti-abortion movement, large organizations and most clinicians are loath to gamble. But Aid Access providers think that the end of Roe calls for doctors to take bold action. Their answer is to mail many more pills to women who otherwise may be forced to carry pregnancies they don’t want.

"The court’s decision overturning Roe last June, Dobbs v. Jackson Women’s Health Organization, polarized the public while opening the door to a new threat — a direct clash among the states over abortion law. In jettisoning the single national standard Roe established, the court invited states to pass or enforce their own laws, which could be diametrically opposed to those of neighboring states."

"Sitting in her office in New York, hundreds of miles from states that could go after her, Prine, at 71, was close to retirement and willing to take chances. “I don’t want younger physicians to be embroiled in lawsuits or criminally charged,” she said. “I’m the one that should happen to. Doctors like me who are at the end of our careers, we should be the ones to step up.”

"Article IV of the Constitution, which addresses the relationships among states, says that if a person charged with a crime in one state flees to another, she must be “delivered up,” or extradited, to the first state. If a doctor from Connecticut, for example, went to Texas, performed an illegal abortion there and then went home, Connecticut would have to send that doctor to Texas for prosecution. But courts have held in the past that if the person never set foot in the state that is prosecuting her, then she didn’t flee, and her state of residence has no constitutional obligation to extradite her. 

...

"But there’s a catch. If a provider travels outside her home state while Texas has a warrant for her arrest, another state without a shield law could follow the customary practice of interstate cooperation — and extradite her to Texas. In addition, if an abortion provider in a pro-access state like Connecticut is sued in Texas rather than prosecuted, Article IV requires the states to help enforce a civil judgment. Connecticut would probably be obligated to comply in collecting damages, for example, if a family member of a woman who had an abortion won a lawsuit for the wrongful death of a fetus. To deter these sorts of suits, Cohen, Donley and Rebouché suggest that states that want to shield their abortion providers could authorize them to countersue for interfering with legally protected health care. “If you’re hoping for a $1 million judgment in Alabama, but you know New York will let someone try to get it back from you, maybe you don’t sue in the first place,” Cohen says.

"The closest historical analogy, however imperfect, for the coming clash may be the conflict between Southern and Northern states over fugitive slave laws in the 19th century. “There are genuinely significant differences between slavery and abortion, morally and legally,” says Jamal Greene, a law professor at Columbia University. “But it’s a reasonable starting point for understanding why it’s a problem, in a nation that wants to hold itself together, when individual states are allowed to make policy about basic rights that people feel extremely strongly about, on both sides.”

"Tensions among the states can become corrosive. The framers of the Constitution gave enslavers the power to recapture enslaved people who escaped to free states. As the cause of abolition gained support, some free states passed personal liberty laws that protected Black people from kidnapping. In 1842, in Prigg v. Pennsylvania, the Supreme Court weighed in on the side of the South, striking down the conviction in Pennsylvania of a slave catcher for kidnapping a mother and her children."

Kidney news from Cambridge on possibility of removing blood type barriers

 Here's some very preliminary kidney news (a press release) in The Guardian and at Cambridge, that could have the potential to have an impact sooner rather than later in helping potential transplant recipients with blood type O, who can only receive blood type O kidneys (which can be received by patients of any blood type)...  

Researchers change blood type of kidney in transplant breakthrough University of Cambridge team’s work could significantly increase supply of organs for people with rarer blood types

"University of Cambridge researchers used a normothermic perfusion machine – a device that connects with a human kidney to pass oxygenated blood through the organ to better preserve it for future use – to flush blood infused with an enzyme through the deceased donor’s kidney.

"The enzyme removed the blood type markers that line the blood vessels of the kidney, which led to the organ being converted to type O."

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https://www.cam.ac.uk/stories/kidneybloodtype

The scientists mentioned are Professor Michael  Nicholson and PhD student Serena MacMillan .