Delta is more dangerous in many ways. It has an incubation period of four days, rather than six, making people contagious sooner.

This article was posted on Wednesday, July 28, 2021 in Kaiser Health News.

By Liz Szabo

Upon first inspection, the mutations in the highly contagious delta covid variant don’t look that worrisome.

For starters, delta has fewer genetic changes than earlier versions of the coronavirus.

“When people saw that the epidemic in India was driven by delta, they did not suspect it would be so bad or overtake other variants,” said Trevor Bedford, an evolutionary biologist at the Fred Hutchinson Cancer Research Center.

But those expectations were wrong.

Delta has kept some of the most successful mutations found in earlier variants, but also contains new genetic changes that enable it to spread twice as fast.

Delta is more dangerous in many ways. It has an incubation period of four days, rather than six, making people contagious sooner. When the pandemic began, people spread the original coronavirus to an average of two or three people. Today, people infected with delta infect six people, on average.

As of this week, the delta variant had caused at least 92% of the new infections in the United States, according to covariants.org, a research firm in Bern, Switzerland.

Although delta isn’t necessarily any more lethal than other variants, it can kill huge numbers of people simply because it infects so many more, said Dr. Eric Topol, founder and director of the Scripps Research Translational Institute.

Scientists have sequenced delta’s mutations but are still trying to understand their significance, said Angela Rasmussen, a virologist at the University of Saskatchewan’s Vaccine and Infectious Disease Organization. “When we see the same mutations appearing repeatedly and independently, that suggests they’re important,” Rasmussen said.

Scientists have the best understanding of mutations on the so-called spike protein — which sticks out from the surface of the virus like a club — and which have been studied the most intensely because of its serious ramifications, Rasmussen said. The coronavirus uses the spike protein to enter human cells, and changes in the spike can help the virus evade antibodies.

Scientists believe one of the most important areas of the spike is the receptor-binding domain, the specific part of the protein that allows the virus to latch onto a receptor on the surface of our cells, said Vaughn Cooper, a professor of microbiology and molecular genetics at the University of Pittsburgh. Receptors are like sockets or docking stations that allow proteins to interact with the cell. Once the virus gains entry to the cell, it can cause havoc, hijacking the cell’s genetic machinery and turning it into a virus-making factory.

Delta’s Worrisome Mix

Delta’s rapid spread is particularly surprising given it lacks two mutations that made earlier variants so scary.

Delta doesn’t have the N501Y spike mutation found in the alpha, beta and gamma variants, which enabled them to invade cells more successfully than the original virus. That mutation changed one amino acid — a building block of proteins — in the receptor-binding domain.

Delta also lacks the E484K mutation, which has made the gamma variant so worrisome. This genetic change, sometimes called “Eek,” allows the virus to spread even among vaccinated people.

(Scientists use the Greek alphabet to name variants of concern.)

“The ‘D’ in delta stands for ‘different’ and a ‘detour’ to a different genomic mutation path,” Topol said. “But it doesn’t mean ‘doom,’” he said, noting that existing covid vaccines remain mostly effective against the delta variant.

Vaccines protect people from covid by providing them with antibodies that attach themselves to the spike protein, preventing the virus from entering cells. By dramatically reducing the number of viruses that enter cells, vaccines can prevent people from developing severe disease and make them less infectious to others.

Delta does share mutations with other successful variants. Like all the identified variants in circulation, delta contains a spike mutation called D614G, sometimes known as “Doug,” which became ubiquitous last year.

Scientists think Doug increases the density of spike protein on the surface of viral particles and makes it easier for the virus to enter cells.

Delta also has a spike mutation called P681R, which closely resembles a mutation in the alpha variant that appears to produce higher viral loads in patients, Cooper said. People infected with delta have 1,000 times more virus in their respiratory tract, making them more likely to spread the virus when they sneeze, cough or talk.

The P681R mutation, also found in the kappa variant, is located at the beginning of a part of the genome called the furin cleavage site, Cooper said.

Furin is a naturally occurring human enzyme that gets hijacked by the coronavirus, which uses it to slice the spike protein into the optimal shape for entering the cell, Rasmussen said. The new mutation makes that sculpting more efficient, Rasmussen said.

Another delta mutation — also found in kappa and epsilon — is called L452R. Experiments suggest this mutation, which also affects the receptor-binding domain, acts to prevent antibodies from neutralizing the virus, Cooper said.

These mutations appear to be more formidable as a team than alone.

The genetic changes “are certainly doing something, but why that combination makes the delta variant more fit is not entirely obvious,” Bedford said. “Putting them together seems to matter.”

Delta also has developed genetic changes not seen in other variants.

One such spike mutation is called D950N. “This might be unique,” Cooper said. “We don’t see that anywhere else.”

The D950N mutation is different than other mutations because it’s located outside the receptor-binding domain in an area of the coronavirus genome that helps the virus fuse with human cells, Cooper said. Fusing with human cells allows the coronavirus to dump its genetic material into those cells.

This mutation could affect which types of cells the virus infects, potentially allowing it to harm different organs and tissues. Mutations in this region are also associated with higher viral loads, Cooper said.

Delta also contains mutations in a part of the spike protein called the N-terminal domain, which provides a “supersite” for antibodies to latch onto the virus and prevent it from entering cells, said Dr. Hana Akselrod, an infectious diseases specialist at the George Washington University School of Medicine & Health Sciences.

Mutations in this region make monoclonal antibodies less effective in treating covid and increases the delta variant’s ability to escape vaccine-generated antibodies, Akselrod said. That may explain why vaccinated people are slightly more likely to become infected with delta, causing mostly mild illness but allowing them to transmit the virus.

Delta’s Future Course

Scientists say it’s impossible to predict exactly how delta will behave in the future, although Topol said, “It’s going to get worse.”

Topol noted that delta outbreaks tend to last 10 to 12 weeks, as the virus “burns through” susceptible populations.

If the United States continues to follow a pattern seen in the United Kingdom and the Netherlands, infections could rise from the current seven-day moving average of 42,000 cases to 250,000 a day. Yet Topol said the United States is unlikely to suffer the high death rates seen in India, Tunisia and Indonesia because nearly half the population here is fully vaccinated.

While some studies have concluded that the Johnson & Johnson vaccine stimulates strong and persistent antibodies against delta, a new report found that antibodies elicited by one shot may not be enough to neutralize delta. Authors of that study, from the New York University Grossman School of Medicine, suggested a second dose may be needed.

Two doses of the Pfizer-BioNTech vaccine protect 94% of people from any symptomatic infection by the alpha variant, compared with 88% against the delta variant, according to a new study in the New England Journal of Medicine. Two doses of the AstraZeneca vaccine protect 75% of people from alpha and 67% from delta.

Cooper said covid vaccines offer remarkably good protection. “I will always celebrate these vaccines as the scientific achievements of my lifetime,” he said.

The best way to slow down the evolution of variants is to share vaccines with the world, vaccinating as many people as possible, Bedford said. Because viruses undergo genetic changes only when they spread from one host to another, stopping transmission denies them a chance to mutate.

Whether the coronavirus evolves more deadly variants “is totally in our hands,” Cooper said. “If the number of infections remains high, it’s going to continue to evolve.”

By failing to contain the virus through vaccination, wearing masks and avoiding crowds, people are allowing the coronavirus to morph into increasingly dangerous forms, said Dr. William Haseltine, a former Harvard Medical School professor who helped design treatments for HIV/AIDS.

“It’s getting better, and we’re making it better,” he said. “Having half the population vaccinated and half unvaccinated and unprotected — that is the exact experiment I would design if I were a devil and trying to design a vaccine-busting virus.”

However, California's new law has been hailed by advocates as a national model for mental health reform.

This article was posted on Wednesday, July 28, 2021 in Kaiser Health News.

By April Dembosky, KQED

When Miriam McDonald decided she wanted to have another baby at age 44, her doctor told her she had a better chance of winning the lottery. So when she got pregnant right away, she and her husband were thrilled. But within three days of giving birth to their son, in September 2019, everything shifted.

"I was thinking, 'Oh my God, what did I do?' I just brought this baby into this world and I can barely take care of myself right now," she recalled. "I feel exhausted. I haven't slept in three days. I haven't really eaten in three days."

As the weeks went by, her depression got worse. She felt sad, but also indifferent. She didn't want to hold her baby, she didn't want to change him. She says she felt no connection with him.

This confused her — she never felt anything like this after her first two kids — and she worried her mood might hurt her son. Untreated postpartum depression can affect babies' cognitive and social development. For the mother, it can be life or death. Suicide accounts for up to 20% of maternal deaths.

"Every day, I was crying. Every day, I felt like I just wanted to die. Every day, I thought about ending my life," said McDonald, who lives in Vacaville, California, and works as an IT professional at the University of California-Davis.

She went to Kaiser Permanente, her healthcare provider, for help. (KHN is not affiliated with Kaiser Permanente.) She said doctors there put her on a merry-go-round of medication trial and error. The first drug her doctor prescribed made her anxious. Upping the dose of a second drug gave her horrific nightmares. A third drug gave her auditory and visual hallucinations that took seven weeks to go away after she stopped taking it.

Then, her psychiatrist retired. And when McDonald complained to her new psychiatrist that she was still depressed, four months after giving birth, the physician suggested more medications.

"I was desperate," McDonald said. "I was like, 'I'm trying to help myself, but things are just getting worse. So what am I left with?'"Bottom of Form

She did her own research and learned about a new treatment, brexanolone. It's the first and only drug approved by the Food and Drug Administration specifically to treat postpartum depression, which affects 1 in 8 new mothers in the United States. Instead of targeting the serotonin system in the brain, like many antidepressants, brexanolone replenishes a hormone metabolite that gets depleted after childbirth: allopregnanolone. Some doctors call allopregnanolone, which is produced by progesterone, "nature's Valium" because it helps regulate neurotransmitters that affect mood. After giving birth, natural levels of estrogen, progesterone and allopregnanolone all plummet rapidly, making some women vulnerable to postpartum depression. Brexanolone is a synthetic version of allopregnanolone, delivered through an IV infusion over the course of 60 hours. It costs $34,000 per treatment.

In clinical trials, 75% of women who got brexanolone started to feel better immediately after the three-day treatment. Half the women went into remission. In the placebo group, 56% of women responded and a quarter went into remission. In practice, doctors are seeing that the effectiveness of the drug in the field mirrors the trial results.

"People walk out of the hospital, wanting to be with their child, wanting to return home," said Dr. Riah Patterson, who has been treating women with brexanolone at the University of North Carolina-Chapel Hill since it became available in summer 2019. "There is a hopefulness, a brightness. You can really see that transformation in the hospital room over those 60 hours. It's pretty miraculous."

McDonald wanted to try it.

But when she asked her doctor for brexanolone, she was told no. In an email, the doctor wrote that the existing studies were "not very impressive." She added that McDonald did not meet Kaiser Permanente's criteria for the drug: She would first have to try — and fail to improve with — four medications and electroconvulsive therapy (ECT) before she could try brexanolone. And she had to be six months or less postpartum to try it at all. For Miriam, the clock had run out. She wondered, How could anyone qualify?

"This is crazy. By the time you even try one drug, that's like four weeks out," she said, noting that traditional antidepressants take weeks to become effective and weeks to taper off from. "There's just no way."

'Unacceptable Burden' on New Moms

Kaiser Permanente's guidance is an outlier. An analysis of guidelines from a dozen health plans revealed that three of them require women to fail treatment with at least one other medication before trying brexanolone. One plan, California's Medicaid program for low-income women, requires two fails. But KP is the only system analyzed that recommends women first fail four drugs, as well as ECT.

"That's absurd. So I'm assuming no woman will ever have the opportunity to try brexanolone?" said UNC's Patterson, one of several experts on postpartum depression who questioned KP's guidance.

"Asking someone to fail four oral antidepressants is an unacceptable burden that will undoubtedly create more harm than good," said Bethany Sasaki, who runs the Midtown Birth Center in Sacramento, California, and is licensed to administer brexanolone.

Psychiatrist Dr. Shannon Clark, who's been administering brexanolone at UC Davis Medical Center for the past two years, seeing positive results, said there are a lot of reasons new moms may not be candidates for one medication, let alone four: taking pills while breastfeeding could be too anxiety-provoking; some women may not be able to adhere to a daily pill regimen; or they may have a liver condition that contraindicates those medications. Clark called Kaiser Permanente's guidance "terrible."

It could also be illegal, according to some California lawmakers and mental health advocates. Under a California state law that took effect this January, health plans must conform to generally accepted standards of care, including scientific literature and expert consensus, when making decisions about mental health treatment.

"If Kaiser is making it effectively impossible to get a particular, important mental health treatment, that could definitely be a violation of our parity law," said state Sen. Scott Wiener (D-San Francisco), the bill's author.

KP officials responded by saying they always follow the law. They also say its integrated structure — as both the health insurer and the health provider — makes it different from traditional insurers. At KP, a patient's doctor determines whether a medication is appropriate, not the health plan, and the criteria doctors use are recommendations, not requirements or prerequisites that patients need to "exhaust," said Dr. Maria Koshy, KP's chair of psychiatry for Northern California.

"At the end of the day, this is an individual clinical decision by both the provider — the physician — and the patient," she said.

But inside KP, the workplace culture is such that doctors are expected to follow these recommendations, according to former KP clinicians who spoke on background — as well as legislative experts familiar with KP's model. They say that when KP doctors deviate from the recommendations, they can get questioned or face other consequences.

"These physicians know that if they start routinely ignoring these bad recommendations, that that could have impacts on them professionally," said Wiener, who has worked on several bills aimed at regulating KP and other insurers in California. "Whether it's couched as a recommendation or a requirement is almost irrelevant. It has the same effect."

To McDonald, her physician seemed to follow the recommended criteria as if they were requirements when she declined to prescribe brexanolone. Another patient, Yesenia Muñoz, got a similar response when she sought brexanolone treatment. KP's grievance department sent her a letter denying the request because she had not failed enough medications.

"When I talked to the caseworker at Kaiser that had denied the medication, he said that Zulresso was very expensive," said Muñoz, referring to brexanolone's brand name.

In addition to the $34,000 cost for brexanolone, the three-day hospital stay can tack on another $30,000 to a patient's bill. Another complicating factor is the FDA requirement that health centers obtain special certification to infuse brexanolone, because of the risks of excessive sedation or fainting from the drug. KP doesn't have the certifications yet to administer the treatment at its own hospitals, so it must pay outside hospitals to provide it for its patients. KP officials say they have plans to eventually open three of their own certified centers in Northern California.

Muñoz, 35, was devastated by the denial. She was overwhelmed by postpartum depression and anxiety shortly after her daughter was born in August 2020. But none of the medications or therapies KP offered her worked. Four months after giving birth, she still felt suicidal.

"I could get out the door sometimes and take the stroller and go walk, and my mind kept on saying, 'If you just step in front of the car, it's all going to go away," she remembered.

Muñoz got help from family members and co-workers to appeal KP's decision to the state, and after reviewing her medical records, regulators ordered KP to pay for the brexanolone treatment.

Muñoz received the treatment at UC Davis Medical Center, and she started feeling better within the first day.

"The nurse came in and she said something funny and I laughed," Muñoz said. "It was the first time I had laughed in so long."

She started looking through photos and videos of her daughter on her phone and she said it was like she was experiencing those moments for the first time. She started making plans for the future.

"It was like a switch flicked and it made me happy enough to want to live," she said. "It saved my life."

Sage Therapeutics, the maker of brexanolone, said KP's approach to the new drug reflects "a lack of a sense of urgency for treating mental health." Dr. Steve Kanes, Sage's chief medical officer, said the company is working on making the treatment more accessible. Its biggest challenge has been getting enough health centers certified, across a wide enough geography, to reach women who need it. The company is studying a pill form of allopregnanolone that could eliminate the need for a hospital stay, but Kanes said that is still not close to being commercially available.

Stitching Up Legal Loopholes

In 2008, Congress passed a landmark federal law aimed at correcting disparities between how insurers pay for mental health treatments compared with care for physical health. The Mental Health Parity and Addiction Equity Act was later reinforced by provisions in the Affordable Care Act in 2010. But insurers found loopholes, creating overly restrictive or self-serving criteria that made it easy to deny services for mental healthcare and, as a result, save money.

California's new law, SB 855, aimed to tighten those loopholes and has been hailed by advocates as a national model for mental health reform. It requires health plans to use clinically based, expert-recognized criteria and guidelines in making medical decisions, with the goal of limiting arbitrary or cost-driven denials for treatments of mental health or substance use disorders.

KP operates in eight states and Washington, D.C. In California, it is the largest insurer, and in 2011 held a 40% share of the market, covering 9.2 million patients. KP officials have questioned how the new state law applies to the Kaiser system, given its unique integrated structure as both health insurer and medical provider. For example, Koshy, the KP psychiatrist, said that SB 855's requirement to comply with generally accepted standards of care "does not apply" to its brexanolone recommendations because they were developed and are used by the doctors, not the health plan administrators. When a reporter asked KP to provide the brexanolone policy its health plan uses for grievances or appeals, it said it didn't have one.

"We 100% intended this law to apply to the care people get at Kaiser," said Julie Snyder, government affairs director at the Steinberg Institute, which co-sponsored the law. "There is no place where we say Kaiser is exempt" because of its integrated structure.

Doctors at Kaiser have historically been "gatekeepers" for services in the system, more so than doctors who work with traditional insurers, said Meiram Bendat, an attorney and licensed psychotherapist who also advised legislators as the law was being drafted. It doesn't matter if practice recommendations for brexanolone were written by doctors or administrators, or whether the recommendations are mandatory or optional, Bendat said, they must be in compliance with the law.

"If it's inconsistent with generally accepted standards of care, then it has no place in California," he said.

Some of KP's recommended criteria for brexanolone are aligned with generally accepted standards of care; for example, reserving the drug for women who are six months or less postpartum, which was a criterion used in the clinical trials the FDA relied on when approving the drug.

But the recommendation that patients first try four or five alternative depression treatments before considering brexanolone conflicts with the judgment of half a dozen women's health experts interviewed for this story. They say there just isn't enough time to do that in the postpartum period — and too much is at stake.

Not only are babies at risk of developmental and emotional problems if their mother is depressed, husbands and partners are also at higher risk for depression and anxiety. And because new moms are learning to breastfeed, and figuring out what's part of the new normal and what's not, it can take months just to realize there's a problem, said UNC's Patterson.

"It takes so long for this illness to come to recognition and for someone to actually get into an appointment and actually be seen by a provider," she said.

Despite Run-Around, a Quick Turnaround

Indeed, the FDA fast-tracked the approval of brexanolone, in part, because of how well and how quickly it worked, allowing women to feel better and get back to their families in three days.

"It's new, it's promising," said KP's Koshy, adding that "it's not a benign medication." Six women in the clinical trials felt faint or fainted, which is why the FDA requires women to be continuously monitored in certified health centers when getting the medication.

Also, the safety and efficacy data is limited, Koshy said. The clinical trials compared brexanolone only to placebo, not to alternative treatments. So while the data shows brexanolone works better than nothing, there's no data on whether it works better than drugs like Zoloft, or better than electroconvulsive therapy.

Women who received the placebo in the trials also showed improvement in depressive symptoms — which is common in studies of depression treatments — but more women who received brexanolone showed improvement, and their improvement was more substantial and lasted longer, especially if their depression was more severe before treatment. Women with moderate depression who received the placebo did just as well, 30 days after treatment, as those who received brexanolone, which could be because they felt better on their own, or because other antidepressants they were allowed to take during the trial finally kicked in.

Koshy said KP is always reviewing practice recommendations as new evidence becomes available, but also acknowledged that KP's recommendations for brexanolone have not been updated since they were developed two years ago, in July 2019.

Two weeks after this story first aired in Northern California, Koshy said KP is now reviewing the recommendations.

It is unclear what role California's Department of Managed Healthcare, the state agency that regulates KP, might play in resolving issues of access to the infusion. In a statement, department officials said they will review any criteria or guidelines the KP health plan uses for brexanolone, but the department does not have jurisdiction over physician decisions.

The department also monitors patient complaints when new medications or treatments begin to be used, in order to identify problems with access to care. So far, the department has received two complaints about brexanolone — both filed by KP patients.

One was Yesenia Muñoz. The other was Miriam McDonald.

Before going to the state, McDonald called KP's grievance department to complain about her treatment and the denial of brexanolone. KP responded by sending the cops to her house for a welfare check.

The officers were calm and nice, McDonald said, but when she closed the door, she cried her eyes out.

"It just brought me to a whole new low," she said. "Why didn't my doctor call me and talk to me first? I mean, this is how you treat postpartum mental health? How dare you!"

KP declined to comment on any individual cases, but said that, generally, "we feel deep compassion for any patient experiencing the difficult and serious effects of postpartum depression, and our goal is always to support every patient's safe return to a healthy mental state."

McDonald never got brexanolone; by the time her appeals were heard, she was past the six-month postpartum window.

Still, she continued to fight for relief and eventually got KP to cover a different treatment for severe depression, transcranial magnetic stimulation, which uses an electromagnetic coil to stimulate nerve cells in the brain that control mood. That typically costs about $300 per session, and McDonald went in for the treatment five days a week, for three months. Now she is finally feeling like herself again.

"I can remember I woke up one day and I was excited. I had actual joy," she said. "I got up and I walked into his room and I was like, 'Hey, Nico! Hi! Hey, baby!' And he jumped up from his crib and giggled and put his arms out. And I just swooped him up in my arms and cried. Because I was like, 'I am so proud to be your mom.'"

Now when her son smiles at her, she genuinely smiles back. But it took more than 18 months to feel better. She can't help but grieve all the smiles she didn't return in that time, and how she felt like she was barely present at crucial times, like when her son took his first steps.

"I felt like I've been robbed of all those moments," she said, "of those little milestones, that I'm never going to get back."

This story comes from NPR's health reporting partnership with KQED and Kaiser Health News (KHN).

This story was produced by KHN (Kaiser Health News), a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Healthcare Foundation.

April Dembosky, KQED: @adembosky

Recent polling shows that no matter which tactics are used, a strong majority of unvaccinated people are unlikely to budge on getting a shot.

This article was published on Tuesday, July 27, 2021 in Kaiser Health News.

By Anna Almendrala

SAN BERNARDINO, Calif. — A few months ago, the boxy, teal truck parked outside a McDonald's in this Inland Empire city might have drawn hundreds of people willing to stand in line for hours under the scorching sun.

The truck is San Bernardino County's mobile vaccine unit, which brings COVID-19 vaccines directly to people. But on July 15, only 22 people got a COVID shot during the four hours it sat there.

Roughly 12 feet away, more people were often seen waiting by a red canopy for free, government-subsidized smartphones, intended for low-income people, than were stepping up for the potentially lifesaving shots.

Barry Luque, a 37-year-old car wash worker who visited the red canopy that day for a free phone, was lured by the truck. He had been eligible for a COVID vaccine since April but never got around to making an appointment. Had he not seen the truck in the parking lot on his day off, "this wouldn't have gotten done," he said.

It's Luque's job to guide drivers into the car wash, but his boss won't let him take his mask off unless he can show proof he's vaccinated.

"People come in from different lives, different styles, different moods at different times," he said after getting his first dose of the Pfizer-BioNTech vaccine. "I've got to guide them carefully and gently, and it's kinda hard for them to see the smile on my face."

Luque and the other 21 people who got vaccinated that day — in addition to the scores of others who drove by or waited in the McDonald's drive-thru line without seeking a shot — offer a snapshot of California's stalling vaccination effort.

Some who finally got the shot, like Luque, were motivated by mandates from employers or are tired of wearing masks. Others want to visit other countries, and vaccinations may help ease travel or quarantine requirements. Some were persuaded, at long last, by family and friends.

Those who continued to hold out primarily cited potential side effects and distrust of the medical system.

About 61% of Californians age 12 and up were fully vaccinated by then, according to the U.S. Centers for Disease Control and Prevention, ranking the state 18th among other states and the District of Columbia.

But the overall rate masks deep disparities among, and even within, regions. In geographically and ethnically diverse San Bernardino County, about 47% of eligible residents were fully vaccinated as of Wednesday, with the lowest rates among young people, men, Latinos, Blacks and those who live in the poorest and unhealthiest communities. Statewide, the profile of unvaccinated people is largely the same.

One way local and state leaders are trying to get shots into residents' arms is by hosting pop-up clinics that make COVID vaccines more convenient and accessible for those who can't or won't sign up for an appointment.

San Bernardino County is organizing pop-up events at supermarkets, schools, churches and community centers. The state is also funding vaccine clinics, including 155 events at more than 80 McDonald's restaurants in 11 counties as of Wednesday.

The pop-ups require significant resources and are showing diminishing returns. About 2,500 doses have been administered at the McDonald's clinics so far — an average of 16 shots per event. The California Department of Public Health declined to say how much these events cost, saying it varies.

At the McDonald's in San Bernardino, a city of more than 200,000 that serves as the county seat, eight staffers were on hand to check people in, administer shots and watch for side effects from 9 a.m. to 1 p.m. They also scheduled the necessary second dose for another local pop-up event.

Jeisel Estabillo, 36, hadn't been vaccinated, even though she is a registered nurse who sometimes cares for COVID patients at a hospital. She was one of the first people in the county to become eligible for vaccines, in December, but avoided getting a shot because she wanted to wait and see how it would affect others. She also tested positive for COVID during the winter surge.

But Estabillo changed her mind and visited the vaccine clinic with her father and teenage son because they plan to vacation in the Philippines next year and hope vaccination will reduce travel restrictions or quarantines.

Estabillo also likes that vaccinated people can forgo masks in most public places, although that perk may slip away as more California counties respond to the delta surge by calling on residents to mask up again indoors.

But Jasmine Woodson continued to hold out against the vaccine even though she was hired to provide security and direct traffic for the clinic. Woodson, 24, is studying to become a pharmacy technician and has been tracking vaccine news. She said she was alarmed by the brief pause in the administration of the one-shot Johnson & Johnson vaccine over concern about blood clots, and reports of rare heart inflammation linked to the Moderna and Pfizer vaccines. She also knows that no COVID vaccine has been fully approved by the Food and Drug Administration, which puts her on high alert.

Woodson, who is Black, is also wary because these mobile vaccine events seem to take place only in low-income Black and Latino neighborhoods — a tactic public health officials say is meant to increase uptake in these communities.

"Every day there's always something new. You're not meant to live that long, so if you get it, you get it, and if you don't, you don't," Woodson said of COVID.

Maxine Luna, 69, who came to the nearby red canopy to get a phone, also was not swayed. A longtime smoker whose doctor has been pleading with her to get a COVID shot, she fears side effects, mentioning a friend who battled two weeks of headaches, diarrhea and vomiting after getting vaccinated.

To mitigate her risk, Luna sticks close to her home, which she shares with her brother, who is vaccinated, and her sister and brother-in-law, who are not.

"We're not out and about, we don't go to shows, and we don't go to crowded places," she said.

Concern about side effects is the most common reason holdouts cite for not getting a COVID vaccine, said Ashley Kirzinger, associate director of public opinion and survey research for KFF. (The KHN newsroom is an editorially independent program of KFF.) This is followed by fear that the vaccine is too new or hasn't been tested enough.

Kirzinger said it's important to acknowledge that some people simply can't be persuaded.

"They don't see themselves at risk for COVID, they think that the vaccine is a greater risk to their health than the virus itself, and there's really no incentive, no stick, no message, no messenger that's going to convince these populations," she said. "It's going to be really hard to reach the goals set by public health officials, with the decreasing enthusiasm around the vaccine that we have seen in the past several weeks."

This story was produced by KHN (Kaiser Health News), a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

This story was produced by KHN, which publishes California Healthline, an editorially independent service of the California Healthcare Foundation.

Anna Almendrala: aalmendrala@kff.org, @annaalmendrala

Some in public health now argue that monitoring programs to cut off prescription opiate misuse, will push addicts to use heroin and fentanyl.

This article was published on Monday, July 26, 2021 in Kaiser Health News.

By Eric Berger

Kathi Arbini said she felt elated when Missouri finally caught up to the other 49 states and approved a statewide prescription drug monitoring program this June in an attempt to curb opioid addiction.

The hairstylist turned activist estimated she made 75 two-hour trips in the past decade from her home in Fenton, a St. Louis suburb, to the state capital, Jefferson City, to convince Republican lawmakers that monitoring how doctors and pharmacists prescribe and dispense controlled substances could help save people like her son, Kevin Mullane.

He was a poet and skateboarder who she said turned to drugs after she and his dad divorced. He started "doctor-shopping" at about age 17 and was able to obtain multiple prescriptions for the pain medication OxyContin. He died in 2009 at 21 from a heroin overdose.

If the state had had a monitoring program, doctors might have detected Mullane's addiction and, Arbini thinks, her son might still be alive. She said it's been embarrassing that it's taken Missouri so long to agree to add one.

"As a parent, you would stand in front of a train; you would protect your child forever — and if this helps, it helps," said Arbini, 61. "It can't kill more people, I don't think."

But even though Missouri was the lone outlier, it had not been among the states with the highest opioid overdose death rates. Missouri had an average annual rank of 16th among states from 2010 through 2019, as the country descended into an opioid epidemic, according to a KHN analysis of Centers for Disease Control and Prevention data compiled by KFF.

Some in public health now argue that when providers use such monitoring programs to cut off prescription opiate misuse, people who have an addiction instead turn to heroin and fentanyl. That means Missouri's new toll could cause more people to overdose and leave the state with buyer's remorse.

"If we can take any benefit from being last in the country to do this, my hope would be that we have had ample opportunity to learn from others' mistakes and not repeat them," said Rachel Winograd, a psychologist who leads NoMODeaths, a state program aimed at reducing harm from opioid misuse.

Before Missouri's monitoring program was approved, lawmakers and health and law enforcement officials warned that the absence made it easier for Missouri patients to doctor-shop to obtain a particular drug, or for providers to overprescribe opiates in what are known as pill mills.

State Sen. Holly Rehder, a Republican with family members who have struggled with opioid addiction, spent almost a decade pushing legislation to establish a monitoring program but ran into opposition from state Sen. Rob Schaaf, a family physician and fellow Republican who expressed concerns about patient privacy and fears about hacking.

In 2017, Schaaf agreed to stop filibustering the legislation and support it if it required that doctors check the database for other prescriptions before writing new ones for a patient. That, though, sparked fresh opposition from the Missouri State Medical Association, concerned the requirement could expose physicians to malpractice lawsuits if patients overdosed.

The new law does not include such a requirement for prescribers. Pharmacists who dispense controlled substances will be required to enter prescriptions into the database.

Dr. Silvia Martins, an epidemiologist at Columbia University who has studied monitoring programs, said it's important to mandate that prescribers review a patient's information in the database. "We know that the ones that are most effective are the ones where they check it regularly, on a weekly basis, not just on a monthly basis," she said.

But Stephen Wood, a nurse practitioner and visiting substance abuse bioethics researcher at Harvard Law School, said the tool is often punitive because it cuts off access to opioids without offering viable treatment options.

He and his colleagues in the intensive care unit at Carney Hospital in Boston don't use the Massachusetts monitoring program nearly as often as they once did. Instead, he said, they rely on toxicology screens, signs such as injection marks or the patients themselves, who often admit they are addicted.

"Rather than pulling out a piece of paper and being accusatory, I find it's much better to present myself as a caring provider and sit down and have an honest discussion," Wood said.

When Kentucky in 2012 became the first state to require prescribers and dispensers to use the system, the number of opioid prescriptions and overdoses from prescription opioids initially decreased slightly, according to a state study.

But the number of opioid overdose deaths — with the exception of a slight dip in 2018 and 2019 — has since consistently ticked upward, according to a KFF analysis of CDC data. In 2020, Kentucky was estimated to have had the nation's second-largest increase in drug overdose deaths.

When efforts to establish Missouri's statewide monitoring program stalled, St. Louis County established one in 2017 that 75 local jurisdictions agreed to participate in, covering 85% of the state, according to the county health department. The county now plans to move its program into the state one, which is scheduled to launch in 2023.

Dr. Faisal Khan, director of the county department, said he has no doubt that the St. Louis program has "saved lives across the state." Opioid prescriptions decreased dramatically once the county established the monitoring program. In 2016, Missouri averaged 80.4 opioid prescriptions per 100 people; in 2019, it was down to 58.3 prescriptions, according to the CDC.

The overall drug overdose death rate in Missouri has steadily increased since 2016, though, with the CDC reporting an initial count of 1,921 people dying from overdoses of all kinds of drugs in 2020.

Khan acknowledged that a monitoring program can lead to an increase in overdose deaths in the years immediately following its establishment because people addicted to prescription opioids suddenly can't obtain them and instead buy street drugs that are more potent and contain impurities.

But he said a monitoring program can also help a physician intervene before someone becomes addicted. Doctors who flag a patient using the monitoring program must then also be able to easily refer them to treatment, Khan and others said.

"We absolutely are not prepared for that in Missouri," said Winograd, of NoMODeaths. "Substance use treatment providers will frequently tell you that they are at max capacity."

Uninsured people in rural areas may have to wait five weeks for inpatient or outpatient treatment at state-funded centers, according to PreventEd, a St. Louis-based nonprofit that aims to reduce harm from alcohol and drug use.

For example, the waiting list for residential treatment at the Preferred Family Healthcare clinic in Trenton is typically two weeks during the summer and one month in winter, according to Melanie Tipton, who directs clinical services at the center, which mostly serves uninsured clients in rural northern Missouri.

Tipton, who has worked at the clinic for 17 years, said that before the COVID-19 pandemic, people struggling with opioid addiction mainly used prescription pills; now it's mostly heroin and fentanyl, because they are cheaper. Fentanyl is a synthetic opioid that is 50 to 100 times more potent than morphine, according to the National Institute on Drug Abuse.

Still, Tipton said her clients continue to find providers who overprescribe opiates, so she thinks a statewide monitoring program could help.

Inez Davis, diversion program manager for the Drug Enforcement Administration's St. Louis division, also said in an email that the program will benefit Missouri and neighboring states because "doctor shoppers and those who commit prescription fraud now have one less avenue."

Winograd said it's possible that if the state had more opioid prescription pill mills, it would have a lower overdose death rate. "I don't think that's the answer," she said. "We need to move in the direction of decriminalization and a regulated drug supply." Specifically, she'd rather Missouri decriminalize possession of small amounts of hard drugs, even heroin, and institute regulations to ensure the drugs are safe.

State Rep. Justin Hill, a Republican from St. Charles and former narcotics detective, opposed the monitoring program legislation because of his concerns over patient privacy and evidence that the lack of a program has not made Missouri's opioid problem any worse than many other states'. He also worries the monitoring program will lead to an increase in overdose deaths.

"I would love the people that passed this bill to stand by the numbers," Hill said. "And if we see more deaths from overdose, scrap the monitoring program and go back to the drawing board."