Tagged Drugs (Pharmaceuticals)

Researchers Are Hatching a Low-Cost Coronavirus Vaccine

A new formulation entering clinical trials in Brazil, Mexico, Thailand and Vietnam could change how the world fights the pandemic.

A new vaccine for Covid-19 that is entering clinical trials in Brazil, Mexico, Thailand and Vietnam could change how the world fights the pandemic. The vaccine, called NVD-HXP-S, is the first in clinical trials to use a new molecular design that is widely expected to create more potent antibodies than the current generation of vaccines. And the new vaccine could be far easier to make.

Existing vaccines from companies like Pfizer and Johnson & Johnson must be produced in specialized factories using hard-to-acquire ingredients. In contrast, the new vaccine can be mass-produced in chicken eggs — the same eggs that produce billions of influenza vaccines every year in factories around the world.

If NVD-HXP-S proves safe and effective, flu vaccine manufacturers could potentially produce well over a billion doses of it a year. Low- and middle-income countries currently struggling to obtain vaccines from wealthier countries may be able to make NVD-HXP-S for themselves or acquire it at low cost from neighbors.

“That’s staggering — it would be a game-changer,” said Andrea Taylor, assistant director of the Duke Global Health Innovation Center.

First, however, clinical trials must establish that NVD-HXP-S actually works in people. The first phase of clinical trials will conclude in July, and the final phase will take several months more. But experiments with vaccinated animals have raised hopes for the vaccine’s prospects.

“It’s a home run for protection,” said Dr. Bruce Innes of the PATH Center for Vaccine Innovation and Access, which has coordinated the development of NVD-HXP-S. “I think it’s a world-class vaccine.”

2P to the rescue

The molecular structure of HexaPro, a modified version of the SARS-CoV-2 spike protein, with its six key alterations shown as red and blue spheres.
The molecular structure of HexaPro, a modified version of the SARS-CoV-2 spike protein, with its six key alterations shown as red and blue spheres.University of Texas at Austin

Vaccines work by acquainting the immune system with a virus well enough to prompt a defense against it. Some vaccines contain entire viruses that have been killed; others contain just a single protein from the virus. Still others contain genetic instructions that our cells can use to make the viral protein.

Once exposed to a virus, or part of it, the immune system can learn to make antibodies that attack it. Immune cells can also learn to recognize infected cells and destroy them.

In the case of the coronavirus, the best target for the immune system is the protein that covers its surface like a crown. The protein, known as spike, latches onto cells and then allows the virus to fuse to them.

But simply injecting coronavirus spike proteins into people is not the best way to vaccinate them. That’s because spike proteins sometimes assume the wrong shape, and prompt the immune system to make the wrong antibodies.

Jason McLellan, a structural biologist at the University of Texas at Austin. His research on coronavirus spike proteins aided the development of the Pfizer, Moderna, Johnson & Johnson and Novavax vaccines.Ilana Panich-Linsman for The New York Times

This insight emerged long before the Covid-19 pandemic. In 2015, another coronavirus appeared, causing a deadly form of pneumonia called MERS. Jason McLellan, a structural biologist then at the Geisel School of Medicine at Dartmouth, and his colleagues set out to make a vaccine against it.

They wanted to use the spike protein as a target. But they had to reckon with the fact that the spike protein is a shape-shifter. As the protein prepares to fuse to a cell, it contorts from a tulip-like shape into something more akin to a javelin.

Scientists call these two shapes the prefusion and postfusion forms of the spike. Antibodies against the prefusion shape work powerfully against the coronavirus, but postfusion antibodies don’t stop it.

Dr. McLellan and his colleagues used standard techniques to make a MERS vaccine but ended up with a lot of postfusion spikes, useless for their purposes. Then they discovered a way to keep the protein locked in a tulip-like prefusion shape. All they had to do was change two of more than 1,000 building blocks in the protein into a compound called proline.

The resulting spike — called 2P, for the two new proline molecules it contained — was far more likely to assume the desired tulip shape. The researchers injected the 2P spikes into mice and found that the animals could easily fight off infections of the MERS coronavirus.

The team filed a patent for its modified spike, but the world took little notice of the invention. MERS, although deadly, is not very contagious and proved to be a relatively minor threat; fewer than 1,000 people have died of MERS since it first emerged in humans.

But in late 2019 a new coronavirus, SARS-CoV-2, emerged and began ravaging the world. Dr. McLellan and his colleagues swung into action, designing a 2P spike unique to SARS-CoV-2. In a matter of days, Moderna used that information to design a vaccine for Covid-19; it contained a genetic molecule called RNA with the instructions for making the 2P spike.

Other companies soon followed suit, adopting 2P spikes for their own vaccine designs and starting clinical trials. All three of the vaccines that have been authorized so far in the United States — from Johnson & Johnson, Moderna and Pfizer-BioNTech — use the 2P spike.

Other vaccine makers are using it as well. Novavax has had strong results with the 2P spike in clinical trials and is expected to apply to the Food and Drug Administration for emergency use authorization in the next few weeks. Sanofi is also testing a 2P spike vaccine and expects to finish clinical trials later this year.

Two prolines are good; six are better

Dr. McLellan’s ability to find lifesaving clues in the structure of proteins has earned him deep admiration in the vaccine world. “This guy is a genius,” said Harry Kleanthous, a senior program officer at the Bill & Melinda Gates Foundation. “He should be proud of this huge thing he’s done for humanity.”

But once Dr. McLellan and his colleagues handed off the 2P spike to vaccine makers, he turned back to the protein for a closer look. If swapping just two prolines improved a vaccine, surely additional tweaks could improve it even more.

“It made sense to try to have a better vaccine,” said Dr. McLellan, who is now an associate professor at the University of Texas at Austin.

In March, he joined forces with two fellow University of Texas biologists, Ilya Finkelstein and Jennifer Maynard. Their three labs created 100 new spikes, each with an altered building block. With funding from the Gates Foundation, they tested each one and then combined the promising changes in new spikes. Eventually, they created a single protein that met their aspirations.

The winner contained the two prolines in the 2P spike, plus four additional prolines found elsewhere in the protein. Dr. McLellan called the new spike HexaPro, in honor of its total of six prolines.

The structure of HexaPro was even more stable than 2P, the team found. It was also resilient, better able to withstand heat and damaging chemicals. Dr. McLellan hoped that its rugged design would make it potent in a vaccine.

Dr. McLellan also hoped that HexaPro-based vaccines would reach more of the world — especially low- and middle-income countries, which so far have received only a fraction of the total distribution of first-wave vaccines.

“The share of the vaccines they’ve received so far is terrible,” Dr. McLellan said.

To that end, the University of Texas set up a licensing arrangement for HexaPro that allows companies and labs in 80 low- and middle-income countries to use the protein in their vaccines without paying royalties.

Meanwhile, Dr. Innes and his colleagues at PATH were looking for a way to increase the production of Covid-19 vaccines. They wanted a vaccine that less wealthy nations could make on their own.

With a little help from eggs

The first wave of authorized Covid-19 vaccines require specialized, costly ingredients to make. Moderna’s RNA-based vaccine, for instance, needs genetic building blocks called nucleotides, as well as a custom-made fatty acid to build a bubble around them. Those ingredients must be assembled into vaccines in purpose-built factories.

The way influenza vaccines are made is a study in contrast. Many countries have huge factories for making cheap flu shots, with influenza viruses injected into chicken eggs. The eggs produce an abundance of new copies of the viruses. Factory workers then extract the viruses, weaken or kill them and then put them into vaccines.

The PATH team wondered if scientists could make a Covid-19 vaccine that could be grown cheaply in chicken eggs. That way, the same factories that make flu shots could make Covid-19 shots as well.

In New York, a team of scientists at the Icahn School of Medicine at Mount Sinai knew how to make just such a vaccine, using a bird virus called Newcastle disease virus that is harmless in humans.

For years, scientists had been experimenting with Newcastle disease virus to create vaccines for a range of diseases. To develop an Ebola vaccine, for example, researchers added an Ebola gene to the Newcastle disease virus’s own set of genes.

The scientists then inserted the engineered virus into chicken eggs. Because it is a bird virus, it multiplied quickly in the eggs. The researchers ended up with Newcastle disease viruses coated with Ebola proteins.

At Mount Sinai, the researchers set out to do the same thing, using coronavirus spike proteins instead of Ebola proteins. When they learned about Dr. McLellan’s new HexaPro version, they added that to the Newcastle disease viruses. The viruses bristled with spike proteins, many of which had the desired prefusion shape. In a nod to both the Newcastle disease virus and the HexaPro spike, they called it NDV-HXP-S.

PATH arranged for thousands of doses of NDV-HXP-S to be produced in a Vietnamese factory that normally makes influenza vaccines in chicken eggs. In October, the factory sent the vaccines to New York to be tested. The Mount Sinai researchers found that NDV-HXP-S conferred powerful protection in mice and hamsters.

“I can honestly say I can protect every hamster, every mouse in the world against SARS-CoV-2,” Dr. Peter Palese, the leader of the research, said. “But the jury’s still out about what it does in humans.”

The potency of the vaccine brought an extra benefit: The researchers needed fewer viruses for an effective dose. A single egg may yield five to 10 doses of NDV-HXP-S, compared to one or two doses of influenza vaccines.

“We are very excited about this, because we think it’s a way of making a cheap vaccine,” Dr. Palese said.

A nurse administering the NDV-HXP-S  vaccine to a volunteer at Mahidol University in Bangkok during the country’s first human trial.Government Pharmaceutical Organization of Thailand, via Agence France-Presse — Getty Images

PATH then connected the Mount Sinai team with influenza vaccine makers. On March 15, Vietnam’s Institute of Vaccines and Medical Biologicals announced the start of a clinical trial of NDV-HXP-S. A week later, Thailand’s Government Pharmaceutical Organization followed suit. On March 26, Brazil’s Butantan Institute said it would ask for authorization to begin its own clinical trials of NDV-HXP-S.

Meanwhile, the Mount Sinai team has also licensed the vaccine to the Mexican vaccine maker Avi-Mex as an intranasal spray. The company will start clinical trials to see if the vaccine is even more potent in that form.

To the nations involved, the prospect of making the vaccines entirely on their own was appealing. “This vaccine production is produced by Thai people for Thai people,” Thailand’s health minister, Anutin Charnvirakul, said at the announcement in Bangkok.

From left, Dimas Covas, director of the Butantan Institute in Brazil; João Doria, governor of the state of São Paulo; and Jean Gorinchteyn, the state health secretary, announcing the ButanVac Covid-19 vaccine candidate against in São Paulo on March 26. Miguel Schincariol/Agence France-Presse — Getty Images

In Brazil, the Butantan Institute trumpeted its version of NDV-HXP-S as “the Brazilian vaccine,” one that would be “produced entirely in Brazil, without depending on imports.”

Ms. Taylor, of the Duke Global Health Innovation Center, was sympathetic. “I could understand why that would really be such an attractive prospect,” she said. “They’ve been at the mercy of global supply chains.”

Madhavi Sunder, an expert on intellectual property at Georgetown Law School, cautioned that NDV-HXP-S would not immediately help countries like Brazil as they grappled with the current wave of Covid-19 infections. “We’re not talking 16 billion doses in 2020,” she said.

Instead, the strategy will be important for long-term vaccine production — not just for Covid-19 but for other pandemics that may come in the future. “It sounds super promising,” she said.

In the meantime, Dr. McLellan has returned to the molecular drawing board to try to make a third version of their spike that is even better than HexaPro.

“There’s really no end to this process,” he said. “The number of permutations is almost infinite. At some point, you’d have to say, ‘This is the next generation.’”

Researchers Are Hatching a Low-Cost Covid-19 Vaccine

A new formulation entering clinical trials in Brazil, Mexico, Thailand and Vietnam could change how the world fights the pandemic.

A new vaccine for Covid-19 that is entering clinical trials in Brazil, Mexico, Thailand and Vietnam could change how the world fights the pandemic. The vaccine, called NVD-HXP-S, is the first in clinical trials to use a new molecular design that is widely expected to create more potent antibodies than the current generation of vaccines. And the new vaccine could be far easier to make.

Existing vaccines from companies like Pfizer and Johnson & Johnson must be produced in specialized factories using hard-to-acquire ingredients. In contrast, the new vaccine can be mass-produced in chicken eggs — the same eggs that produce billions of influenza vaccines every year in factories around the world.

If NVD-HXP-S proves safe and effective, flu vaccine manufacturers could potentially produce well over a billion doses of it a year. Low- and middle-income countries currently struggling to obtain vaccines from wealthier countries may be able to make NVD-HXP-S for themselves or acquire it at low cost from neighbors.

“That’s staggering — it would be a game-changer,” said Andrea Taylor, assistant director of the Duke Global Health Innovation Center.

First, however, clinical trials must establish that NVD-HXP-S actually works in people. The first phase of clinical trials will conclude in July, and the final phase will take several months more. But experiments with vaccinated animals have raised hopes for the vaccine’s prospects.

“It’s a home run for protection,” said Dr. Bruce Innes of the PATH Center for Vaccine Innovation and Access, which has coordinated the development of NVD-HXP-S. “I think it’s a world-class vaccine.”

2P to the rescue

The molecular structure of HexaPro, a modified version of the SARS-CoV-2 spike protein, with its six key alterations shown as red and blue spheres.
The molecular structure of HexaPro, a modified version of the SARS-CoV-2 spike protein, with its six key alterations shown as red and blue spheres.University of Texas at Austin

Vaccines work by acquainting the immune system with a virus well enough to prompt a defense against it. Some vaccines contain entire viruses that have been killed; others contain just a single protein from the virus. Still others contain genetic instructions that our cells can use to make the viral protein.

Once exposed to a virus, or part of it, the immune system can learn to make antibodies that attack it. Immune cells can also learn to recognize infected cells and destroy them.

In the case of the coronavirus, the best target for the immune system is the protein that covers its surface like a crown. The protein, known as spike, latches onto cells and then allows the virus to fuse to them.

But simply injecting coronavirus spike proteins into people is not the best way to vaccinate them. That’s because spike proteins sometimes assume the wrong shape, and prompt the immune system to make the wrong antibodies.

Jason McLellan, a structural biologist at the University of Texas at Austin. His research on coronavirus spike proteins aided the development of the Pfizer, Moderna, Johnson & Johnson and Novavax vaccines.Ilana Panich-Linsman for The New York Times

This insight emerged long before the Covid-19 pandemic. In 2015, another coronavirus appeared, causing a deadly form of pneumonia called MERS. Jason McLellan, a structural biologist then at the Geisel School of Medicine at Dartmouth, and his colleagues set out to make a vaccine against it.

They wanted to use the spike protein as a target. But they had to reckon with the fact that the spike protein is a shape-shifter. As the protein prepares to fuse to a cell, it contorts from a tulip-like shape into something more akin to a javelin.

Scientists call these two shapes the prefusion and postfusion forms of the spike. Antibodies against the prefusion shape work powerfully against the coronavirus, but postfusion antibodies don’t stop it.

Dr. McLellan and his colleagues used standard techniques to make a MERS vaccine but ended up with a lot of postfusion spikes, useless for their purposes. Then they discovered a way to keep the protein locked in a tulip-like prefusion shape. All they had to do was change two of more than 1,000 building blocks in the protein into a compound called proline.

The resulting spike — called 2P, for the two new proline molecules it contained — was far more likely to assume the desired tulip shape. The researchers injected the 2P spikes into mice and found that the animals could easily fight off infections of the MERS coronavirus.

The team filed a patent for its modified spike, but the world took little notice of the invention. MERS, although deadly, is not very contagious and proved to be a relatively minor threat; fewer than 1,000 people have died of MERS since it first emerged in humans.

But in late 2019 a new coronavirus, SARS-CoV-2, emerged and began ravaging the world. Dr. McLellan and his colleagues swung into action, designing a 2P spike unique to SARS-CoV-2. In a matter of days, Moderna used that information to design a vaccine for Covid-19; it contained a genetic molecule called RNA with the instructions for making the 2P spike.

Other companies soon followed suit, adopting 2P spikes for their own vaccine designs and starting clinical trials. All three of the vaccines that have been authorized so far in the United States — from Johnson & Johnson, Moderna and Pfizer-BioNTech — use the 2P spike.

Other vaccine makers are using it as well. Novavax has had strong results with the 2P spike in clinical trials and is expected to apply to the Food and Drug Administration for emergency use authorization in the next few weeks. Sanofi is also testing a 2P spike vaccine and expects to finish clinical trials later this year.

Two prolines are good; six are better

Dr. McLellan’s ability to find lifesaving clues in the structure of proteins has earned him deep admiration in the vaccine world. “This guy is a genius,” said Harry Kleanthous, a senior program officer at the Bill & Melinda Gates Foundation. “He should be proud of this huge thing he’s done for humanity.”

But once Dr. McLellan and his colleagues handed off the 2P spike to vaccine makers, he turned back to the protein for a closer look. If swapping just two prolines improved a vaccine, surely additional tweaks could improve it even more.

“It made sense to try to have a better vaccine,” said Dr. McLellan, who is now an associate professor at the University of Texas at Austin.

In March, he joined forces with two fellow University of Texas biologists, Ilya Finkelstein and Jennifer Maynard. Their three labs created 100 new spikes, each with an altered building block. With funding from the Gates Foundation, they tested each one and then combined the promising changes in new spikes. Eventually, they created a single protein that met their aspirations.

The winner contained the two prolines in the 2P spike, plus four additional prolines found elsewhere in the protein. Dr. McLellan called the new spike HexaPro, in honor of its total of six prolines.

The structure of HexaPro was even more stable than 2P, the team found. It was also resilient, better able to withstand heat and damaging chemicals. Dr. McLellan hoped that its rugged design would make it potent in a vaccine.

Dr. McLellan also hoped that HexaPro-based vaccines would reach more of the world — especially low- and middle-income countries, which so far have received only a fraction of the total distribution of first-wave vaccines.

“The share of the vaccines they’ve received so far is terrible,” Dr. McLellan said.

To that end, the University of Texas set up a licensing arrangement for HexaPro that allows companies and labs in 80 low- and middle-income countries to use the protein in their vaccines without paying royalties.

Meanwhile, Dr. Innes and his colleagues at PATH were looking for a way to increase the production of Covid-19 vaccines. They wanted a vaccine that less wealthy nations could make on their own.

With a little help from eggs

The first wave of authorized Covid-19 vaccines require specialized, costly ingredients to make. Moderna’s RNA-based vaccine, for instance, needs genetic building blocks called nucleotides, as well as a custom-made fatty acid to build a bubble around them. Those ingredients must be assembled into vaccines in purpose-built factories.

The way influenza vaccines are made is a study in contrast. Many countries have huge factories for making cheap flu shots, with influenza viruses injected into chicken eggs. The eggs produce an abundance of new copies of the viruses. Factory workers then extract the viruses, weaken or kill them and then put them into vaccines.

The PATH team wondered if scientists could make a Covid-19 vaccine that could be grown cheaply in chicken eggs. That way, the same factories that make flu shots could make Covid-19 shots as well.

In New York, a team of scientists at the Icahn School of Medicine at Mount Sinai knew how to make just such a vaccine, using a bird virus called Newcastle disease virus that is harmless in humans.

For years, scientists had been experimenting with Newcastle disease virus to create vaccines for a range of diseases. To develop an Ebola vaccine, for example, researchers added an Ebola gene to the Newcastle disease virus’s own set of genes.

The scientists then inserted the engineered virus into chicken eggs. Because it is a bird virus, it multiplied quickly in the eggs. The researchers ended up with Newcastle disease viruses coated with Ebola proteins.

At Mount Sinai, the researchers set out to do the same thing, using coronavirus spike proteins instead of Ebola proteins. When they learned about Dr. McLellan’s new HexaPro version, they added that to the Newcastle disease viruses. The viruses bristled with spike proteins, many of which had the desired prefusion shape. In a nod to both the Newcastle disease virus and the HexaPro spike, they called it NDV-HXP-S.

PATH arranged for thousands of doses of NDV-HXP-S to be produced in a Vietnamese factory that normally makes influenza vaccines in chicken eggs. In October, the factory sent the vaccines to New York to be tested. The Mount Sinai researchers found that NDV-HXP-S conferred powerful protection in mice and hamsters.

“I can honestly say I can protect every hamster, every mouse in the world against SARS-CoV-2,” Dr. Peter Palese, the leader of the research, said. “But the jury’s still out about what it does in humans.”

The potency of the vaccine brought an extra benefit: The researchers needed fewer viruses for an effective dose. A single egg may yield five to 10 doses of NDV-HXP-S, compared to one or two doses of influenza vaccines.

“We are very excited about this, because we think it’s a way of making a cheap vaccine,” Dr. Palese said.

A nurse administering the NDV-HXP-S  vaccine to a volunteer at Mahidol University in Bangkok during the country’s first human trial.Government Pharmaceutical Organization of Thailand, via Agence France-Presse — Getty Images

PATH then connected the Mount Sinai team with influenza vaccine makers. On March 15, Vietnam’s Institute of Vaccines and Medical Biologicals announced the start of a clinical trial of NDV-HXP-S. A week later, Thailand’s Government Pharmaceutical Organization followed suit. On March 26, Brazil’s Butantan Institute said it would ask for authorization to begin its own clinical trials of NDV-HXP-S.

Meanwhile, the Mount Sinai team has also licensed the vaccine to the Mexican vaccine maker Avi-Mex as an intranasal spray. The company will start clinical trials to see if the vaccine is even more potent in that form.

To the nations involved, the prospect of making the vaccines entirely on their own was appealing. “This vaccine production is produced by Thai people for Thai people,” Thailand’s health minister, Anutin Charnvirakul, said at the announcement in Bangkok.

From left, Dimas Covas, director of the Butantan Institute in Brazil; João Doria, governor of the state of São Paulo; and Jean Gorinchteyn, the state health secretary, announcing the ButanVac Covid-19 vaccine candidate against in São Paulo on March 26. Miguel Schincariol/Agence France-Presse — Getty Images

In Brazil, the Butantan Institute trumpeted its version of NDV-HXP-S as “the Brazilian vaccine,” one that would be “produced entirely in Brazil, without depending on imports.”

Ms. Taylor, of the Duke Global Health Innovation Center, was sympathetic. “I could understand why that would really be such an attractive prospect,” she said. “They’ve been at the mercy of global supply chains.”

Madhavi Sunder, an expert on intellectual property at Georgetown Law School, cautioned that NDV-HXP-S would not immediately help countries like Brazil as they grappled with the current wave of Covid-19 infections. “We’re not talking 16 billion doses in 2020,” she said.

Instead, the strategy will be important for long-term vaccine production — not just for Covid-19 but for other pandemics that may come in the future. “It sounds super promising,” she said.

In the meantime, Dr. McLellan has returned to the molecular drawing board to try to make a third version of their spike that is even better than HexaPro.

“There’s really no end to this process,” he said. “The number of permutations is almost infinite. At some point, you’d have to say, ‘This is the next generation.’”

Teenage Brains May Be Especially Vulnerable to Marijuana and Other Drugs

Teenagers are more likely to get hooked on marijuana, stimulants and other recreational drugs than college-aged or older adults.

Adolescents and teenagers who experiment with marijuana and prescription drugs are more likely to get hooked on them than young people who try these drugs for the first time when they are college-aged or older, according to a new analysis of federal data.

The research suggests that young people may be particularly vulnerable to the intoxicating effects of certain drugs, and that early exposure might prime their brains to desire them. The findings have implications for public health policymakers, who in recent years have called for increased screening and preventive measures to reverse a sharp rise in marijuana vaping among teenagers.

The new study, published in JAMA Pediatrics and led by a team of scientists at the National Institute on Drug Abuse, sought to gain a better understanding of how adolescent brains respond to a variety of recreational drugs. Previous research suggested that early exposure to marijuana, nicotine and alcohol might lead to faster development of substance use disorders. But the new analysis cast a wider net, looking at the effects of nine different drugs, including opioid painkillers, stimulants, marijuana, alcohol, cigarettes, cocaine, heroin, methamphetamine and tranquilizers.

The researchers used data from the government’s National Survey on Drug Use and Health, a closely watched annual study that tracks substance use and mental health issues among Americans. The new research focused on two age groups: adolescents between the ages of 12 and 17, and young adults aged 18 to 25. Alcohol was by far the most commonly used substance in both groups: A quarter of adolescents and 80 percent of young adults said they had used it. About half of young adults said they had tried cannabis or tobacco. But among adolescents, that number was smaller: Roughly 15 percent said they had experimented with cannabis, and 13 percent said they had tried tobacco.

Most troubling to the authors of the new study was how many people went on to develop a substance use disorder, indicating that their experimentation had spiraled into an addiction. The researchers found that within a year of first trying marijuana, 11 percent of adolescents had become addicted to it, compared to 6.4 percent of young adults. Even more striking was that within three years of first trying the drug, 20 percent of adolescents became dependent on it, almost double the number of young adults.

Adolescents who tried prescription drugs were also more likely to become addicted. About 14 percent of adolescents who took prescription stimulants for recreational use went on to develop a substance use disorder within one year, compared to just 4 percent of young adults. And while 7 percent of young adults who tried opioid painkillers became addicted soon after taking them, that figure rose to 11.2 percent among younger users.

For alcohol and tobacco, however, there was not much of a difference between the two age groups: Both older and younger youth had a similar rate of developing a substance use disorder. And for illicit drugs such as cocaine and heroin, the number of adolescents using them was too small for the researchers to draw any meaningful conclusions.

One possible explanation for the findings is that young people who have a greater predisposition to developing an addiction may be more likely to seek out illicit drugs at an earlier age. But Dr. Nora Volkow, a senior author of the new study and the director of NIDA, said it is known that cannabis and other drugs can have a potent effect on adolescent brains because they are still developing. Younger brains exhibit greater plasticity, or ability to change, than the relatively static brains of older individuals. As a result, drugs like cannabis are more likely to alter synaptic connections in younger brains, leading to stronger memories of pleasure and reward.

“It’s a learning process when you become addicted,” said Dr. Volkow. “It’s a type of memory that gets hard-wired into your brain. That occurs much faster in an adolescent brain.”

Studies show that regularly using marijuana can affect cognition in adolescents, leading to impairments in parts of the brain that are involved in learning, reasoning and paying attention. Yet in recent years the booming popularity of e-cigarettes has led to a sharp increase in the number of adolescents who vape nicotine and marijuana, a trend that has alarmed public health officials. Some studies suggest that adolescents may also be more likely to try marijuana as more and more states legalize its recreational use.

Dr. Volkow said that as states implement new marijuana regulations, policymakers should work on measures aimed at protecting adolescents. She stressed that pediatricians and dentists should screen for drug use in their young patients by asking them about it. And she cautioned parents not to dismiss marijuana use in teens and adolescents as something that is harmless.

“As it relates to marijuana, the drugs that were available when parents today were teenagers are very different from the drugs that are available now,” she said. “The content of THC is much higher, and the higher the THC content, the greater the risk of adverse effects.”

European Countries Suspend Use of AstraZeneca Shots over Worries About Blood Clots

European Countries Suspend Use of AstraZeneca Shots Over Worries About Blood Clots

Millions of people have received the vaccine without safety problems, and there is no evidence of any causal link between the vaccine and blood clots.

A health authority van arrives at a  school on a remote island in Denmark.
A health authority van arrives at a  school on a remote island in Denmark.Credit…Claus Fisker/Ritzau Scanpix, via Reuters
  • March 11, 2021, 7:11 p.m. ET

Health authorities in three European countries on Thursday suspended use of AstraZeneca’s vaccine because of concerns that it might increase the risk of blood clots, but emphasized that they were taking action as a precaution and that there is no evidence of any causal link.

Denmark acted after a 60-year-old woman who received a shot died after developing a blood clot. Several other European countries had recently stopped using doses from the same batch of the vaccine after some reports of severe blood clots, and European drug regulators are investigating.

In the flurry of suspensions on Thursday, Norway and Iceland followed Denmark’s lead. Italy and Romania also paused shots, but only from a different batch of the vaccine than the one that had raised concerns elsewhere.

Public health experts expect medical conditions to turn up by chance in some people after they get any vaccine, just by chance. In the vast majority of cases such illnesses have nothing to do with the shots. Most other countries where the vaccine has been given to many millions of people have not reported similar red flags.

The safety scare is a setback for AstraZeneca’s vaccine, which has already struggled with a perception that it is a less desirable shot because it had a lower overall efficacy rate in clinical trials than some others. There is, however, extensive data showing that the vaccine is safe and effective, and especially good at preventing severe illness and death. And in many places across the world, it is the only shot available.

As of Wednesday, 30 cases of obstructive blood clots had been reported among nearly five million people vaccinated with the AstraZeneca vaccine in the European Union and three other European countries — a rate no higher than in the general population, the European Medicines Agency said. The agency, Europe’s main drug regulator, said that the vaccine’s benefits outweigh any risks.

The agency also said that there is no indication the vaccine “has caused these conditions.”

Gonzalo Viña, a spokesman for AstraZeneca, said the company’s data have not turned up such safety issues. “An analysis of our safety data of more than 10 million records has shown no evidence of an increased risk of pulmonary embolism or deep vein thrombosis in any defined age group, gender, batch or in any particular country,” he said.

Blood clots, particularly if they are large, can damage tissue or organs like the lungs, heart or brain. Severe cases can be fatal, but people with small clots can often be treated outside of a hospital with prescription drugs.

Daniel Salmon, director of the Institute for Vaccine Safety at Johns Hopkins University, said that authorities noticing the cases and investigating them is a sign of the system working as it should. “I wouldn’t jump to any conclusions that because you saw some blood clots after vaccination that they’re causal,” he said. “It warrants looking at it more carefully.”

Dr. Salmon said he is worried that an unsubstantiated safety scare will cause public panic and deter people from taking a vaccine that is badly needed to end the pandemic.

“There is a possibility for a real problem. There’s a much higher probability that some coincidental event will scare people — and derail the program,” Dr. Salmon said.

AstraZeneca’s vaccine has already faced production lags that caused a slow and bumpy rollout in Europe. What’s more, some people in Germany and other countries have resisted the vaccine, saying they prefer shots that showed higher efficacy in trials.

At the center of the latest scrutiny is a specific batch of one million doses of the vaccine, which was delivered to 17 European Union countries. The European Medicines Agency said a quality defect in that batch was “unlikely” but that the possibility would be investigated further.

Denmark’s drug regulator halted all use of the vaccine for at least 14 days. Health officials have said they wanted to err on the side of safety.

Austria over the weekend suspended use of that same batch after severe blood clots turned up in several people who received those doses. One person died 10 days after vaccination. Another is now recovering after being hospitalized.

Estonia, Lithuania, Luxembourg and Latvia followed Austria’s lead in suspending use of that batch, though they will continue to inoculate their citizens with AstraZeneca doses from other batches.

Italy’s suspension of a different batch was tied to a man in Sicily who died after receiving his shot. It’s unclear whether a blood clot was involved.

More than 142,000 people in Denmark, which has a population of about six million, have been injected with the vaccine produced by AstraZeneca.

The Danish minister of health, Magnus Heunicke, said on Twitter that it is “currently not possible to conclude whether there is a connection.” He added. “We acted early, it needs to be thoroughly investigated.”

Denmark had already scaled back the target for finishing its immunization campaign in part because of delays in deliveries. The safety pause will delay it further.

AstraZeneca’s vaccine came under scrutiny over potential safety issues last year while it was being tested in clinical trials. Two vaccinated volunteers in Britain developed neurological symptoms consistent with transverse myelitis, an inflammatory syndrome that affects the spinal cord and is often caused by viral infections.

Those concerns temporarily shut down global trials of the vaccine, but investigations ultimately found no evidence linking the symptoms to the vaccine. One of the participants who fell ill was later found to have an undiagnosed case of multiple sclerosis.

More than 70 countries have since authorized the vaccine, with the notable exception of the United States, where regulators are waiting on data from a large clinical trial there expected in the next few weeks. A decision from the Food and Drug Administration on whether to authorize AstraZeneca’s vaccine is likely more than a month away.

The most extensive real-world data on the vaccine’s safety comes from Britain, which had administered 9.7 million doses through last month. The British drug regulator, the Medicines and Healthcare Products Regulatory Agency, said “the number and nature of suspected adverse reactions reported so far are not unusual in comparison to other types of routinely used vaccines.”

Rebecca Robbins reported from Bellingham, Wash., and Thomas Erdbrink from Amsterdam. Jason Horowitz and Emma Bubola contributed reporting from Italy, Benjamin Mueller from London and Denise Grady from New York.

Nobody Wants Cancer. But a ‘Big C’ Label Has Surprising Upsides.

Voices

Nobody Wants Cancer. But a ‘Big C’ Label Has Surprising Upsides.

Classifying a rare blood disorder as a cancer opened new doors for disease investigation, treatment and hope for a cure.

Credit…Paper Illustration by Reina Takahashi, photographed by Tony Cenicola/The New York Times

  • March 11, 2021, 5:00 a.m. ET

I have a rare blood disorder. When it was diagnosed 25 years ago, it was called an “orphan disease,” meaning the small number of people affected didn’t justify research investments by major pharmaceutical companies.

Enter the World Health Organization and its 2008 decision to classify the condition as a blood “cancer.” This opened new doors for disease investigation and understanding. It prompted a growing number of super specialist practitioners, and most important, hope for some 300,000 people living in the United States with what are now called myeloproliferative neoplasms, or MPNs.

Nobody likes to hear a cancer diagnosis, particularly for a disease they thought was benign. In fact, when I first saw my blood disorder referred to as a cancer, I wrote to the MPN Research Foundation, a nonprofit research and advocacy group, and suggested they remove the “Big C” word from their website. How, I thought, could they be so misleading?

That’s when I discovered I was behind the times. MPNs were indeed reclassified as a malignant condition of the bone marrow, affecting sometimes one, two or all three types of blood cells: white cells, red cells and platelets.

The average age people are diagnosed with an MPN is 60-something. My diagnosis came at age 38. For the next 15 years, I was treated for essential thrombocythemia, a type of MPN that caused my bone marrow to produce significantly higher than normal numbers of platelets. The proliferation of platelets put me at risk for dangerous clots and ultimately led to complete blockages of two important veins of the portal system, which carries blood to the liver.

The Big C label began to look like good news.

Once MPNs were classified as blood cancers — including essential thrombocythemia, polycythemia vera and myelofibrosis — interest grew from research laboratories, major medical centers, and small and mega pharmaceutical companies, which now saw these rare and poorly understood conditions as an opportunity. Perhaps pieces to the MPN puzzle could shed light on more common blood cancers, like leukemia and lymphoma. And perhaps treatments for those widely studied cancers could be used to treat MPNs.

“The cancer designation did open up significant new funding opportunities, for example from the National Cancer Institute,” said Barbara Van Husen, board chair of the MPN Research Foundation. “It has definitely accelerated research.” There are more than 200 clinical trials underway for various MPNs, as well as ongoing research into stem cell transplantation, currently the only potential cure for these rare cancers.

In my case, for reasons researchers are working to understand, my bone marrow flipped a switch. I was no longer making excessive platelets. Instead I was producing too many red cells and was given a revised diagnosis of polycythemia vera, a distinctly different MPN. I went for regular phlebotomies, the modern version of bloodletting in which pints of my blood were drained into a collection bag to reduce blood volume. Think blood transfusion, reversed.

Doctors increased the dose of the 30-year-old chemotherapy drug I had been taking since my blood clots first appeared. The drug is still considered standard of care “if well tolerated.” It effectively adjusted my red counts. Unlike newer, more targeted drugs, however, it does not discriminate, potentially killing off not just red cells but white cells and platelets as well.

I continued to live a full and largely unaffected life, though I often suffered symptoms such as debilitating headaches and bone pain.

The hallmark fatigue of these blood disorders was not yet on my radar. I hiked. I cycled. I traveled. I was a night owl typically functioning “well” on five to six hours of sleep.

Then, in September of 2019, my summer bike rides became an exhausting effort. By October, I was so fatigued that walking up a slightly inclined sidewalk had me leaning on a lamppost to catch my breath. Doctors identified scarring (“fibrosis”) in my bone marrow, elevating my diagnosis once again, to the third evolution of my MPN journey, myelofibrosis.

“You’re a poster child for exploring new drug therapies for MPNs,” Dr. Ellen Ritchie, of Weill Cornell Medical Center in Manhattan, recently told me. Just seven months into my participation in a global phase 2 clinical trial for a new combination drug therapy, tests indicated significant, measurable improvement. It appears my disease is beginning to reverse.

More than two decades after my first of many bone marrow biopsies, I have more energy than many of the “healthy” people I know.

We tend to think of cancer as acute. Get it out quickly, go through treatments, prevent it from spreading. But for those with a chronic cancer like an MPN, there isn’t a distinctive beginning, middle and end. It can be overwhelming, emotionally exhausting, and even as we learn more about the disease, full of uncertainty.

“Often, individuals with a chronic illness, like cancer, are more challenged to be hopeful about their future, while also needing to be focused on thriving on a daily basis,” says Laura Kaplan, a licensed clinical social worker whose Connecticut practice helps people navigate serious illness. “It is important for their identity and quality of life to try to keep a good perspective about living with the process of their disease.”

For years, I chose not to let my condition define me. I chose not to identify myself as someone living with cancer. I would simply live my life fully, day to day. I would work hard and play hard, enjoy raising my two boys, deal with whatever challenged my health, and keep on moving. That approach continues to serve me well.

Ruth Fein Revell, a health and environment writer, serves on a patient advisory board of the MPN Research Foundation.

Medical Marijuana Is Not Regulated as Most Medicines Are

Personal Health

Medical Marijuana Is Not Regulated as Most Medicines Are

The industry lacks randomized controlled clinical trials that can clearly establish benefits and risks.

Credit…Gracia Lam
Jane E. Brody

  • March 8, 2021, 5:00 a.m. ET

Dan Shapiro was the first person I knew to use medical marijuana. As a junior at Vassar College in 1987, he was being treated for Hodgkin’s lymphoma with potent chemotherapy that caused severe nausea and vomiting. When Dan’s mother learned that smoking marijuana could relieve the distressing side effect, to help her son, this otherwise law-abiding woman planted a garden full of the illegal weed in her Connecticut back yard.

Decades later, marijuana as medicine has become a national phenomenon, widely accepted by the public. Although the chemical-rich plant botanically known as Cannabis sativa remains a federally controlled substance, its therapeutic use is now legal in 36 states and the District of Columbia.

Yet experts in the many specialties in which medical marijuana is said to be helpful have only rarely been able to demonstrate its purported benefits in well-designed scientific studies. And they caution that what is now being legally sold as medicinal marijuana in dispensaries throughout the country is anything but the safe, pure substance Americans commonly expect when they are treated with licensed medications.

For example, in Oregon, where both recreational and medicinal marijuana can be sold legally, all recreational marijuana must be tested for pesticides and solvents, but such tests are not required for most medical marijuana, an audit by the Secretary of State published in January 2019 showed. The Oregon Health Authority does not require tests for heavy metals and microbes that might sicken users.

Indeed, most of the same health concerns raised decades ago about using marijuana therapeutically are still unresolved, even as the potency of the plant’s intoxicating ingredient, tetrahydrocannabinol, best known as THC, has increased fivefold. Furthermore, exclusive medical use is uncommon; in a Canadian study of 709 medical users, 80.6 percent also reported using marijuana recreationally.

“People are using a medical excuse for their recreational marijuana habit,” said Dr. Kenneth Finn, a pain management specialist in Colorado Springs and editor of a new, 554-page professional book on the subject, “Cannabis in Medicine: An Evidence-Based Approach.”

Proponents of medical marijuana argue that cannabis is relatively safe and less expensive than licensed pharmaceuticals and is often used for conditions for which effective therapies are lacking or inadequate. Opponents say that what is most lacking are standardized marijuana products and randomized controlled clinical trials that can clearly establish benefits and risks.

The evidence — or lack thereof — of health benefits that can be reliably attributed to smoking, vaping or ingesting marijuana, even in its purest form, is described in great detail in Dr. Finn’s book. “Components of the cannabis plant can help in various conditions, but that’s not what people are buying in stores,” he said in an interview. “Let’s do the research on purified, natural, noncontaminated cannabinoids,” as the various potentially therapeutic chemicals in marijuana are called.

Three such substances have been approved by the Food and Drug Administration. One, Epidiolex, a cannabidiol-based liquid medication, is approved to treat two forms of severe childhood epilepsy. The others, dronabinol (Marinol, Syndros) and nabilone (Cesamet), are pills used to curb nausea in cancer patients undergoing chemotherapy and to stimulate appetite in AIDS patients with wasting syndrome.

Another marijuana-based drug, nabiximols (Sativex), is available in Canada and several European countries to treat spasticity and nerve pain in patients with multiple sclerosis.

Medicinal cannabis is hardly a new therapeutic agent. It was widely used as a patent medicine in the United States during the 19th and early 20th centuries and was listed in the United States Pharmacopoeia until passage of the Marijuana Tax Act in 1937 rendered it illegal.

Then a federal law in 1970 made it a Schedule 1 controlled substance, which greatly restricted access to marijuana for legitimate research. Also complicating attempts to establish medical usefulness is that plants like marijuana contain hundreds of active chemicals, the amounts of which can vary greatly from batch to batch. Unless researchers can study purified substances in known quantities, conclusions about benefits and risks are highly unreliable.

That said, as recounted in Dr. Finn’s book, here are some conclusions reached by experts about the role of medical marijuana in their respective fields:

Pain Management

People using marijuana for pain relief do not reduce their dependence on opioids. In fact, Dr. Finn said, “patients on narcotics who also use marijuana for pain still report their pain level to be 10 on a scale of 1 to 10.” Authors of the chapter on pain, Dr. Peter R. Wilson, pain specialist at the Mayo Clinic in Rochester, Minn., and Dr. Sanjog Pangarkar of the Greater Los Angeles V.A. Healthcare Service, concluded, “Cannabis itself does not produce analgesia and paradoxically might interfere with opioid analgesia.” A 2019 study of 450 adults in the Journal of Addiction Medicine found that medical marijuana not only failed to relieve patients’ pain, it increased their risk of anxiety, depression and substance abuse.

Multiple Sclerosis

Dr. Allen C. Bowling, neurologist at the NeuroHealth Institute in Englewood, Colo., noted that while marijuana has been extensively studied as a treatment for multiple sclerosis, the results of randomized clinical trials have been inconsistent. The trials overall showed some but limited effectiveness, and in one of the largest and longest trials, the placebo performed better in treating spasticity, pain and bladder dysfunction, Dr. Bowling wrote. Most trials used pharmaceutical-grade cannabis that is not available in dispensaries.

Glaucoma

The study suggesting marijuana could reduce the risk of glaucoma dates back to 1970. Indeed, THC does lower damaging pressure inside the eye, but as Drs. Finny T. John and Jean R. Hausheer, ophthalmologists at the University of Oklahoma Health Sciences Center, wrote, “to achieve therapeutic levels of marijuana in the bloodstream to treat glaucoma, an individual would need to smoke approximately six to eight times a day,” at which point the person “would likely be physically and mentally unable to perform tasks requiring attention and focus,” like working and driving. The major eye care medical societies have put thumbs down on marijuana to treat glaucoma.

Allison Karst, a psychiatric pharmacy specialist at the V.A. Tennessee Valley Healthcare System, who reviewed the benefits and risks of medical marijuana, concluded that marijuana can have “a negative effect on mental health and neurological function,” including worsening symptoms of PTSD and bipolar disorder.

Dr. Karst also cited one study showing that only 17 percent of edible cannabis products were accurately labeled. In an email she wrote that the lack of regulation “leads to difficulty extrapolating available evidence to various products on the consumer market given the differences in chemical composition and purity.” She cautioned the public to weigh “both potential benefits and risks,” to which I would add caveat emptor — buyer beware.

Which Covid Vaccine Should You Get? Experts Weigh the Effect Against Severe Disease

Which Covid Vaccine Should You Get? Experts Cite the Effect Against Severe Disease

Infectious disease doctors say getting a shot of the J&J vaccine, which has a lower efficacy against the virus than other vaccines, would still be well worthwhile.

Covid vaccinations in Santa Barbara County, Calif., this week.
Covid vaccinations in Santa Barbara County, Calif., this week.Credit…Daniel Dreifuss for The New York Times

  • Jan. 29, 2021, 5:32 p.m. ET

At first glance, the results reported on Friday from the long-awaited trial of Johnson & Johnson’s coronavirus vaccine might have seemed disappointing. Its overall efficacy — the ability to prevent moderate and severe disease — was reported at 72 percent in the United States, 66 percent in Latin American countries and 57 percent in South Africa.

Those figures appear far below the high bar set by Pfizer-BioNTech and Moderna, the first two vaccines authorized for emergency use in the United States, which reported overall efficacy from 94 to 95 percent.

Dr. Anthony S. Fauci, the nation’s leading infectious disease expert and now the lead medical adviser to President Biden on the coronavirus pandemic, acknowledged the striking difference at a briefing on Friday.

“If you woke up and you say, ‘Well, go to the door on the left and you get 94 or 95 percent, go to the door on the right and you get 72 percent,’ which door do you want to go to?” he asked.

But Dr. Fauci said that the more crucial measure was the ability to prevent severe disease, which translates to keeping people out of the hospital and preventing deaths. And that result, for Johnson & Johnson, was 85 percent in all of the countries where it was tested, including South Africa, where a rapidly spreading variant of the virus had shown some ability to elude vaccines.

More important than preventing “some aches and a sore throat,” Dr. Fauci said, is to fend off severe disease, especially in people with underlying conditions and in older adults, who are more likely to become seriously ill and to die from Covid-19.

“If you can prevent severe disease in a high percentage of individuals, that will alleviate so much of the stress in human suffering and death in this epidemic that we’re seeing, particularly now,” Dr. Fauci said, “as we well know, over the last several weeks, our health care system has been stressed by the number of people that require hospitalization, as well as intensive care.”

Dr. Francis Collins, director of the National Institutes of Health, compared the ability to prevent severe disease to the effects of flu shots, which do not always prevent influenza entirely but can make it less severe.

“The same thing seems to be applying here, in a circumstance where this variant is clearly making it a little tougher to get the most vigorous response that you would want to have,” Dr. Collins said. “But still, for severe disease, it’s looking really good.”

The Moderna vaccine also showed high efficacy, 100 percent, against severe disease. The Pfizer-BioNTech one appeared to as well, but the overall number of severe cases in the study was too small to be sure.

But researchers warn that trying to compare effectiveness between new studies and earlier ones may be misleading, because the virus is evolving quickly and to some extent the trials have studied different pathogens.

A participant in the Johnson & Johnson vaccine trial in Cape Town, South Africa, last month.
A participant in the Johnson & Johnson vaccine trial in Cape Town, South Africa, last month.Credit…Joao Silva/The New York Times

“You have to recognize that Pfizer and Moderna had an advantage,” Dr. William Schaffner, an infectious disease expert at Vanderbilt University, said in an interview. “They did their clinical trials before the variant strains became very apparent. Johnson & Johnson was testing its vaccine not only against the standard strain but they had the variants.”

The best way to stop the spread of mutants and to prevent more new ones from emerging is to vaccinate as many people as quickly as possible, Dr. Fauci and other researchers say. Viruses cannot mutate unless they are replicating, and they cannot replicate unless they can get into cells. Keeping them out by immunizing people can shut down the process.

In addition to the Pfizer-BioNTech and Moderna vaccines already in use in the United States, three more may soon become available: those made by Novavax, Johnson & Johnson and AstraZeneca. AstraZeneca’s vaccine has already been authorized in Britain and other countries.

Globally, the Johnson & Johnson vaccine is expected to play an important role, especially in low and middle-income countries, because it works after just one shot, is relatively inexpensive and is easier to store and distribute than the vaccines made by Pfizer-BioNTech and Moderna since it does not share their stringent requirements for freezing and refrigerating.

People waiting to be vaccinated may wonder if they will be able to pick and choose among vaccines, and if they should hold out and wait until the one that looks best to them becomes available.


Covid-19 Vaccines ›


Answers to Your Vaccine Questions

Currently more than 150 million people — almost half the population — are eligible to be vaccinated. But each state makes the final decision about who goes first. The nation’s 21 million health care workers and three million residents of long-term care facilities were the first to qualify. In mid-January, federal officials urged all states to open up eligibility to everyone 65 and older and to adults of any age with medical conditions that put them at high risk of becoming seriously ill or dying from Covid-19. Adults in the general population are at the back of the line. If federal and state health officials can clear up bottlenecks in vaccine distribution, everyone 16 and older will become eligible as early as this spring or early summer. The vaccine hasn’t been approved in children, although studies are underway. It may be months before a vaccine is available for anyone under the age of 16. Go to your state health website for up-to-date information on vaccination policies in your area

You should not have to pay anything out of pocket to get the vaccine, although you will be asked for insurance information. If you don’t have insurance, you should still be given the vaccine at no charge. Congress passed legislation this spring that bars insurers from applying any cost sharing, such as a co-payment or deductible. It layered on additional protections barring pharmacies, doctors and hospitals from billing patients, including those who are uninsured. Even so, health experts do worry that patients might stumble into loopholes that leave them vulnerable to surprise bills. This could happen to those who are charged a doctor visit fee along with their vaccine, or Americans who have certain types of health coverage that do not fall under the new rules. If you get your vaccine from a doctor’s office or urgent care clinic, talk to them about potential hidden charges. To be sure you won’t get a surprise bill, the best bet is to get your vaccine at a health department vaccination site or a local pharmacy once the shots become more widely available.

Probably not. The answer depends on a number of factors, including the supply in your area at the time you’re vaccinated. Check your state health department website for more information about the vaccines available in your state. The Pfizer and Moderna vaccines are the only two vaccines currently approved, although a third vaccine from Johnson & Johnson is on the way.

That is to be determined. It’s possible that Covid-19 vaccinations will become an annual event, just like the flu shot. Or it may be that the benefits of the vaccine last longer than a year. We have to wait to see how durable the protection from the vaccines is. To determine this, researchers are going to be tracking vaccinated people to look for “breakthrough cases” — those people who get sick with Covid-19 despite vaccination. That is a sign of weakening protection and will give researchers clues about how long the vaccine lasts. They will also be monitoring levels of antibodies and T cells in the blood of vaccinated people to determine whether and when a booster shot might be needed. It’s conceivable that people may need boosters every few months, once a year or only every few years. It’s just a matter of waiting for the data.

Employers do have the right to compel their workers to be vaccinated once a vaccine is formally approved. Many hospital systems, for example, require annual flu shots. But employees can seek exemptions based on medical reasons or religious beliefs. In such cases, employers are supposed to provide a “reasonable accommodation” — with a coronavirus vaccine, for example, a worker might be allowed to work if they wear a mask, or to work from home.

If you have other questions about the coronavirus vaccine, please read our full F.A.Q.

Dr. Paul Offit, a vaccine expert at Children’s Hospital of Philadelphia, told CNN that if there was an abundant supply of the Pfizer-BioNTech and Moderna vaccines, they would be his first choices because of their higher overall efficacy.

But for now, there is not enough of those vaccines.

If he could not get either the Pfizer-BioNTech vaccine or the Moderna one, he would take the Johnson & Johnson shot, Dr. Offit said — as long as the data that the company will be presenting to the Food and Drug Administration looks as good as what the company reported on Friday.

He said Johnson & Johnson’s report of the reduction in severe disease was a powerful selling point.

“That’s what you want,” Dr. Offit said. “You want to stay out of the hospital, and stay out of the morgue.”

He noted that the company was also studying a two-shot regimen, which might raise its efficacy.

People who take the Johnson & Johnson vaccine should be able to safely receive a Pfizer-BioNTech or Moderna vaccine later if a booster shot is needed, he said.

Dr. Schaffner said he had just attended a meeting with other public health experts, and they had asked one another what they would tell their spouses or partners to do if they could get the Johnson & Johnson vaccine tomorrow, or had to wait three weeks for Pfizer-BioNTech’s or Moderna’s.

“All of us said, ‘Get the one tomorrow,’” Dr. Schaffner said. “The virus is bad. You’re risking three more weeks of exposure as opposed to getting protection tomorrow.”

He said Johnson & Johnson’s 85 percent efficacy against severe disease was a bit lower than those reported by Moderna and Pfizer-BioNTech, “but it’s still pretty darn high.”

It is not yet known whether it would be safe to take one type of vaccine now and then another later, Dr. Schaffner said, adding, “We haven’t studied this.”

Pregnant Women Get Conflicting Advice on Covid-19 Vaccines

The W.H.O. and the C.D.C. provide differing views, and experts partly blame a lack of data because expectant mothers have been excluded from clinical trials.

U.S. Vaccine Supply: What to Know

U.S. Covid Vaccine Supply: How to Make Sense of Those Confusing Numbers

Can President Biden really boost production? Why are governors trying to buy directly from Pfizer? And when will supply exceed demand?

New Yorkers lined up at a  vaccine hub set up by the city’s Health Department in Jamaica, Queens, this month.
New Yorkers lined up at a  vaccine hub set up by the city’s Health Department in Jamaica, Queens, this month.Credit…Hiroko Masuike/The New York Times

  • Jan. 21, 2021, 12:23 p.m. ET

Demand for vaccines is skyrocketing as the United States grapples with a record death toll from Covid-19 and the threat of new, more contagious variants. After a slow start in December, many states and cities have quickly ramped up vaccine delivery, widening access to larger groups of people and setting up mass testing sites.

But now there’s a new wrinkle: Some mayors and governors say they have run out of available vaccines, and have had to cancel appointments.

The Biden administration has promised to overhaul the country’s faltering vaccine effort, but there’s only so much it can do to increase the available supply.

Here’s what you need to know.

How many doses are available?

There are simply not enough doses of authorized vaccines to meet the enormous demand. And that is not likely to change for the next few months.

The two companies with authorized vaccines, Moderna and Pfizer, have each promised to provide the United States with 100 million vaccine doses by the end of March, or enough for 100 million people to get the necessary two shots.

But that doesn’t mean those 200 million doses are sitting in a factory warehouse somewhere, waiting to be shipped. Both companies are manufacturing the doses at full capacity, and are collectively releasing about 12 million doses each week, a number expected to gradually increase.

As of Wednesday, nearly 36 million doses of the Pfizer and Moderna vaccines had been distributed to state and local governments. However, only about 16.5 million shots had been administered to patients.

But as local health authorities become more adept at vaccine distribution, they will eventually catch up to the limited supply. Some local officials, including those in New York City, have said they are already reaching that point, and have had to cancel appointments because they said they do not have enough.

President Biden said he would use the Defense Production Act to increase supply. Will that help?

Vaccine experts and the companies themselves have said that at least in the short term, using the Defense Production Act will not significantly increase supply, although every little bit could help. That’s because manufacturing facilities are already at or near capacity, and there is a worldwide race to develop vaccines that use a finite amount of resources.

Although the Trump administration was criticized for not using the Defense Production Act more aggressively to ramp up production of testing supplies and protective gear, it did use the act many times to give vaccine manufacturers priority access to suppliers of raw ingredients and equipment.

In a plan released on Thursday, the Biden administration indicated it would continue to use the act to boost supplies needed for vaccine manufacturing, as well as other materials that are required to immunize tens of millions of people. Although the plan provided few details, one example cited is increasing production of a special syringe that can squeeze six doses out of Pfizer vials that were originally intended to contain five.

A drive-through vaccination center in Napa, Calif., earlier this month.
A drive-through vaccination center in Napa, Calif., earlier this month.Credit…Max Whittaker for The New York Times

What about the federal stockpile of vaccines?

There is no significant reserve of vaccines to speak of. For the most part, vaccines are being shipped out each week as they are manufactured. (The exception is a small emergency stockpile that the Biden administration has said will continue.)

Last week, Alex M. Azar II, the outgoing secretary of health and human services, stirred confusion when he announced that the federal government would be releasing a reserve of vaccine doses. Many states said they were told that this meant an influx of vaccines was on the way, which could be used to inoculate more people.

In his news conference, Mr. Azar urged states to open up their immunization policies, and said they had been moving too slowly to use the doses they had already been sent. As a result, several governors, including Andrew Cuomo in New York, changed eligibility rules to allow people 65 and older to get the vaccine.


Covid-19 Vaccines ›


Answers to Your Vaccine Questions

While the exact order of vaccine recipients may vary by state, most will likely put medical workers and residents of long-term care facilities first. If you want to understand how this decision is getting made, this article will help.

Life will return to normal only when society as a whole gains enough protection against the coronavirus. Once countries authorize a vaccine, they’ll only be able to vaccinate a few percent of their citizens at most in the first couple months. The unvaccinated majority will still remain vulnerable to getting infected. A growing number of coronavirus vaccines are showing robust protection against becoming sick. But it’s also possible for people to spread the virus without even knowing they’re infected because they experience only mild symptoms or none at all. Scientists don’t yet know if the vaccines also block the transmission of the coronavirus. So for the time being, even vaccinated people will need to wear masks, avoid indoor crowds, and so on. Once enough people get vaccinated, it will become very difficult for the coronavirus to find vulnerable people to infect. Depending on how quickly we as a society achieve that goal, life might start approaching something like normal by the fall 2021.

Yes, but not forever. The two vaccines that will potentially get authorized this month clearly protect people from getting sick with Covid-19. But the clinical trials that delivered these results were not designed to determine whether vaccinated people could still spread the coronavirus without developing symptoms. That remains a possibility. We know that people who are naturally infected by the coronavirus can spread it while they’re not experiencing any cough or other symptoms. Researchers will be intensely studying this question as the vaccines roll out. In the meantime, even vaccinated people will need to think of themselves as possible spreaders.

The Pfizer and BioNTech vaccine is delivered as a shot in the arm, like other typical vaccines. The injection won’t be any different from ones you’ve gotten before. Tens of thousands of people have already received the vaccines, and none of them have reported any serious health problems. But some of them have felt short-lived discomfort, including aches and flu-like symptoms that typically last a day. It’s possible that people may need to plan to take a day off work or school after the second shot. While these experiences aren’t pleasant, they are a good sign: they are the result of your own immune system encountering the vaccine and mounting a potent response that will provide long-lasting immunity.

No. The vaccines from Moderna and Pfizer use a genetic molecule to prime the immune system. That molecule, known as mRNA, is eventually destroyed by the body. The mRNA is packaged in an oily bubble that can fuse to a cell, allowing the molecule to slip in. The cell uses the mRNA to make proteins from the coronavirus, which can stimulate the immune system. At any moment, each of our cells may contain hundreds of thousands of mRNA molecules, which they produce in order to make proteins of their own. Once those proteins are made, our cells then shred the mRNA with special enzymes. The mRNA molecules our cells make can only survive a matter of minutes. The mRNA in vaccines is engineered to withstand the cell’s enzymes a bit longer, so that the cells can make extra virus proteins and prompt a stronger immune response. But the mRNA can only last for a few days at most before they are destroyed.

However, senior administration officials clarified last Friday that all of those reserve doses were already earmarked as booster shots for people who had gotten the vaccine, and that Mr. Azar was just spelling out the logical extension of a distribution policy that had been established by top federal officials in December, when shipments began. The release of the reserve doses would go to people who needed their second dose, not new pools of people who were getting their first shot.

Going forward, Mr. Azar said, the government would shift to a new model: rather than holding onto a reserve of booster shots, each weekly shipment from the manufacturers would include doses for new people as well as second doses for those due for their booster shots. President Biden echoed that policy in announcing his vaccine plan last week.

Will there be enough vaccine supply to give everyone a second dose?

Federal officials have previously said they were working with states to track who has gotten a vaccine, and when they are due for their booster shots, which is three weeks later for the Pfizer vaccine and four weeks later for the Moderna one.

They have said that each weekly shipment will give priority to people who need their second dose that week, and whatever is left will go to vaccinating new people.

But the plan relies on state and federal governments working together and accurately reporting who has received a vaccine, and what is needed from week to week. Many state governments have complained they do not have the resources to carry out the vaccine distribution plan, and the next few weeks will demonstrate how well the system works.

The incoming Biden administration has vowed to overhaul distribution to the states, providing more transparency to local officials about how much vaccine they can expect, in the hopes of allowing states to better plan.

Doses of Moderna’s vaccine were prepared at the Sonoma County Fairgrounds in Santa Rosa, Calif.Credit…Jim Wilson/The New York Times

Some Democratic governors have asked to buy vaccines directly from Pfizer. Is that possible?

No, it’s not likely to happen.

Last week, Gov. Gretchen Whitmer of Michigan asked the federal government for permission to buy 100,000 doses of vaccine directly from Pfizer. And on Monday, Gov. Cuomo wrote a letter to Pfizer asking for the state to buy vaccines directly.

Pfizer and Moderna’s supply has been fully claimed for at least the first quarter of this year, meaning it’s unlikely there will be any spare vaccine to sell to individual states.

In addition, the emergency use authorizations for the Pfizer and Moderna vaccines stipulate that the federal government oversees distribution.

In a statement, a Pfizer spokeswoman said the company “is open to collaborating with the U.S. Department of Health and Human Services on a distribution model that gives as many Americans as possible access to our vaccine as quickly as possible.” But she noted that “before we can even consider direct sales to state governments, H.H.S. would need to approve that proposal.”

A state official said on Tuesday that the governor felt it was important to exhaust all his options, no matter how unlikely they would be succeed, and pointed to his efforts in March to directly buy ventilators from manufacturers — setting up a bidding war among states that he later criticized the federal government for fueling.

But advisers to the Biden administration have indicated that they are not in favor of such a move. On Monday, Dr. Celine Gounder, a pandemic adviser to Mr. Biden during his presidential transition, said allowing states to reach separate deals would cause more problems than it would solve.

In an interview on CNBC, Dr. Gounder noted Mr. Cuomo’s previous criticism of bidding over ventilators. “I think this kind of an approach to vaccine allocation is going to result, frankly, in the same kind of situation that he, himself, was criticizing last spring,” she said.

Vaccinations underway in Minneapolis on Tuesday.Credit…Octavio Jones for The New York Times

Are we going to get more vaccines anytime soon?

Yes, most likely.

At least three other vaccines are in late-stage clinical trials, and the success of any one of them could mean millions of more doses for U.S. residents by this spring.

Johnson & Johnson is expected to announce the results of its vaccine trial any day now, and if it is successful, the first doses could become available in the United States by February. Although early production of the vaccine has lagged, the company has signed a deal to provide 100 million doses of its one-dose vaccine by the end of June.

By March and April, results from trials testing two-dose vaccines by AstraZeneca and Novavax could also be made public. AstraZeneca has an arrangement with the U.S. government to provide 300 million doses, and Novavax to provide 110 million.

What’s more, both Pfizer and Moderna say their factories are ramping up and expanding capacity each week. They have signed deals to supply an additional 100 million doses each of their vaccines in the second quarter of this year.

When will we have enough vaccines for everybody in the country?

It’s still not clear, although conservatively, there could be enough vaccines by the summer.

If no other vaccines are authorized, the United States has signed deals with Pfizer and Moderna for a total of 400 million doses to be delivered by summer, or enough for 200 million people.

That’s pretty close to the American population of 260 million adults (the vaccines are not approved yet for children although studies are underway).

But if other vaccines do prove safe and effective — which experts say is likely — millions more people could be vaccinated more quickly, possibly by late spring.

Don’t Let the Pandemic Stop Your Shots

the new old age

Don’t Let the Pandemic Stop Your Shots

Even as older adults await the coronavirus vaccine, many are skipping the standard ones. That’s not wise, health experts say.

Credit…Chris Lyons

  • Dec. 28, 2020, 12:12 p.m. ET

Peggy Stein, 68, a retired teacher in Berkeley, Calif., skipped a flu shot this year. Her reasoning: “How could I get the flu if I’m being so incredibly careful because of Covid?”

Karen Freeman, 74, keeps meaning to be vaccinated against shingles, but hasn’t done so. A retired college administrator in St. Louis, she quipped that “denial has worked well for me these many years.”

Sheila Blais, who lives on a farm in West Hebron, N.Y., has never received any adult vaccine. She also has never contracted the flu. “I’m such an introvert I barely leave the farm, so where’s my exposure?” said Ms. Blais, 66, a fiber artist. “If it’s not broke, don’t fix it.”

While older adults await vaccination against Covid-19, public health officials also worry about their forgoing, forgetting, fearing or simply not knowing about those other vaccines — the ones recommended for adults as we age and our immune systems weaken.

“There’s a lot of room for improvement,” said Dr. Ram Koppaka, associate director for adult immunization at the Centers for Disease Control and Prevention.

Every year, campaigns urge older adults to protect themselves against preventable infectious diseases. After all, influenza alone has killed 12,000 to 61,000 Americans annually over the past decade, most of them 65 or older, and has sent 140,000 to 810,000 people a year to hospitals.

The coronavirus pandemic has introduced another imperative. Those hospitals are filling fast with Covid-19 patients; in many places they are already swamped, their staffs overworked and exhausted.

“Knowing how stressed the health care system is, prevention is key,” said Dr. Nadine Rouphael, a vaccine researcher and infectious disease specialist at Emory University. “When we have record numbers of deaths, why would you go to a hospital for a vaccine-preventable illness?”

Yet the nation has long done a better job of vaccinating its children than its elders. The most recent statistics, from 2017, show that about one-third of adults over 65 had not received a flu shot within the past year. About 30 percent had not received the pneumococcus vaccine.

The proportion receiving the shingles vaccine, a fairly recent addition to the list, has inched up, but by 2018 only 34.5 percent of people over 60 had been vaccinated.

Moreover, Dr. Koppaka pointed out: “When you look deeper, there are longstanding, deep, significant differences in the proportion of Black and Hispanic adults getting vaccines compared to their white counterparts. It’s really unacceptable.”

Close to 40 percent of non-Hispanic whites had been vaccinated against shingles, for instance, compared with fewer than 20 percent of Blacks and Hispanics.

One might expect a group who can recall polio fears and outbreaks of whooping cough to be less hesitant to get vaccinated than younger cohorts. “You’ll probably have a different concept of vaccination from someone who never experienced what a serious viral illness can do,” Dr. Koppaka said.

When it comes to the Covid-19 vaccine, for instance, only 15 percent of those over 65 say they would definitely or probably not get it, compared with 36 percent of those 30 to 49, a Kaiser Family Foundation tracking poll showed earlier this month. (Ms. Stein, Ms. Blais and Ms. Freeman all said they would happily accept the Covid vaccine.)

But for other diseases, vaccination rates lag. Given that older people are more vulnerable to severe illness from them, why the gaps in coverage?

Internists and other doctors for adults don’t promote vaccines nearly as effectively as pediatricians do, said Dr. William Schaffner, an infectious disease specialist at Vanderbilt University. Older patients, who often see a variety of doctors, may also have trouble keeping track of when they got which shot.

Experts fear that vaccination rates may have fallen further during the pandemic, as they have among children, if older people wary of going to doctors’ offices or pharmacies skipped shots.

Financial and bureaucratic obstacles also thwart vaccination efforts. Medicare Part B covers three vaccines completely: influenza, pneumococcus and, when indicated, hepatitis B.

The Tdap and shingles vaccines, however, are covered under Part D, which can complicate reimbursement for doctors; the vaccines are easier to obtain in pharmacies. Not all Medicare recipients buy Part D, and for those who do, coverage varies by plan and can include deductibles and co-pays.

Still, older adults can gain access to most recommended vaccines for no or low cost, through doctors’ offices, pharmacies, supermarkets and local health departments. For everyone’s benefit, they should.

Here’s what the C.D.C. recommends:

Influenza An annual shot in the fall — and it’s still not too late, because flu season peaks from late January into February. Depending on which strain is circulating, the vaccine (ask for the stronger versions for seniors) prevents 40 to 50 percent of cases; it also reduces illness severity for those infected.

Thus far this year, flu activity has remained extraordinarily low, perhaps because of social distancing and masks or because closed schools kept children from spreading it. Manufacturers shipped a record number of doses, so maybe more people got vaccinated. In any case, fears of a flu/Covid “twindemic” have not yet been realized.

Nevertheless, infectious disease experts urge older adults (and everyone over six months old) to get flu shots now. “Flu is fickle,” Dr. Schaffner said. “It could take off like a rocket in January.”

Tetanus, diphtheria, pertussis. A booster of TD vaccine every 10 years, to prevent tetanus and diphtheria. If you’ve never had the Tdap vaccine — which adds prevention against pertussis — that’s the one you want. Although pertussis, better known as whooping cough, occasionally shows up in adults, newborns are particularly at risk. Pregnant women will ask expectant grandparents to get a Tdap shot. Because it is covered under Part D, a pharmacy is the best bet.

Pneumococcus. “It’s a pneumonia vaccine, but it also prevents the most serious consequences of pneumonia, including meningitis and bloodstream infections,” Dr. Koppaka said.

People over 65 should get the polysaccharide formula — brand name Pneumovax — but there are certain circumstances, such as immune-compromising conditions, to discuss with a health care provider.

Those over 65 may choose, again in consultation with a provider, to also get the conjugate pneumococcal vaccine (brand name Prevnar), which provides some additional protection. If so, C.D.C. guidelines specify which vaccine to take when.

Shingles. Social distancing won’t ward off this disease; anyone who had chickenpox, which is just about every senior, still carries the virus.

“If you live to be 80, you stand a 35 to 50 percent chance of having an episode,” Dr. Schaffner said. “And the older you are when you get it, the more apt you are to get the most serious complication” — lingering nerve pain called post-herpetic neuralgia.

The C.D.C. recommends Shingrix, the highly effective shingles vaccine the F.D.A. approved in 2017, for everyone over 50. The previous shingles vaccine has been discontinued. Get Shingrix even if you had the earlier vaccine, Zostavax, and even if you’ve had shingles — it can recur.

The two required shots, given two to six months apart, can total $300 out of pocket. But Medicare Part D beneficiaries will pay an average of $50 for the pair, said a spokesman for the manufacturer GlaxoSmithKline, and people with private insurance even less.

Hepatitis A and hepatitis B. These aren’t age-related; the vaccines are recommended for people with certain health conditions, including chronic liver disease and H.I.V. infection, or for travelers to countries where the diseases are widespread.

The hepatitis B vaccine is also recommended, at a provider’s discretion, for diabetics over 60 who haven’t been previously vaccinated. Talk to a health care professional about your risks.

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The Risks of Using Steroids for Respiratory Infections

Personal Health

The Risks of Using Steroids for Respiratory Infections

Doctors often prescribe them for sore throats and the common cold, even though evidence of benefit is sorely lacking.

Credit…Gracia Lam
Jane E. Brody

  • Dec. 28, 2020, 5:00 a.m. ET

“Steroid Shots and the Culture of Instant Gratification,” an editorial published Oct. 8 in JAMA Otolaryngology-Head & Neck Surgery online, highlights a chronic ailment in American medical care: a frequent failure to practice evidence-based medicine. Maybe I’ve been living under a rock, but I was surprised to learn that doctors often prescribe oral or injected corticosteroids for acute respiratory tract infections like sore throat, sinusitis, bronchitis and the common cold even though evidence of benefit is sorely lacking and risks of the drugs are widely known.

Yet a recent analysis of nearly 10 million outpatient medical visits in the United States showed that nearly 12 percent of patients with acute respiratory infections were prescribed oral or injected steroids, and this dubious practice is on the rise. The analysis found that prescriptions for steroids like prednisone to treat acute respiratory ailments nearly doubled from 2007 to 2016.

Although steroids can be invaluable, even lifesaving, medications often vital to treating asthma, autoimmune conditions, and chronic pulmonary disease and preventing transplant rejection, their misuse can result in a treatment that is worse than the disease.

The editorial writer, Dr. Edward D. McCoul, otolaryngologist at the Ochsner Clinic Foundation, described a scenario that is apparently replicated hundreds of thousands of times a year in the United States among patients given steroid injections for acute respiratory infections: “Within moments of receiving the intramuscular injection your congestion wanes, the headache vanishes, and your energy level skyrockets.”

Sure, Dr. McCoul told me, you feel better, at least temporarily — steroids, after all, counter inflammation and have a euphoric, energizing effect. But at what price?

The answer to that question is addressed in another commentary published in the Annals of Internal Medicine. Dr. Beth I. Wallace at Michigan Medicine and Dr. Akbar K. Waljee of the V.A. Ann Arbor Healthcare System listed three serious risks that can follow as few as three days of treatment with corticosteroids taken orally even by relatively young, otherwise healthy patients: gastrointestinal bleeding, sepsis and heart failure.

A Danish study found an elevated risk of diabetes and osteoporosis among patients who had received one or more steroid shots a year for three or more years to treat allergic rhinitis, another use of steroids lacking evidence of benefit.

Dr. Evan L. Dvorin, internist at the Ochsner Health System and Dr. Mark H. Ebell of the University of Georgia, writing in the journal American Family Physician, added several other frightening side effects linked to the brief use of steroids: low blood sugar, elevated blood pressure, mood and sleep disturbances, fracture and blood clots.

Dr. Wallace, a rheumatologist whose patients often depend on long-term steroid therapy, said with regard to short bursts of steroids for respiratory infections, “A very large number of young, otherwise healthy patients are receiving a treatment that we know can be harmful for a condition where steroids just aren’t indicated.”

In an interview, Dr. Dvorin said that although steroids may make people euphoric, they can also “make some people feel pretty bad by causing anxiety, jitteriness and manic-like behavior.” In people with pre-existing psychosis, short-term steroid shots can trigger a psychotic episode, Dr. McCoul said.

Drs. Dvorin and Ebell wrote, “Physicians might assume that short-term steroids are harmless and free from the widely known long-term effects of steroids. However, even short courses of systemic corticosteroids are associated with many possible adverse effects.” (“Systemic” refers to both oral and injected steroids, as opposed to topical uses on the skin.)

Furthermore, there is no credible evidence to justify such risks when treating a condition like a cold or sinus infection, the Michigan doctors noted. When any treatment is prescribed, it’s the practitioner’s job to first weigh its expected benefits against possible risks. However, Drs. Wallace and Waljee reported that “corticosteroid bursts are frequently prescribed for self-limited conditions, where evidence of benefit is lacking.” Leading the list of such inappropriate uses of steroids are acute respiratory tract infections that usually resolve without specific treatment within a week or two.

As with antibiotics and opiates, short-term use of injected or oral steroids have “well-defined indications but can cause net harm when used — as they frequently are — when evidence of benefit is low,” they concluded.

In Louisiana, where Dr. McCoul practices, steroid shots for upper respiratory infections are shockingly common, he said. “Patients may go to urgent care five or six times a year to get a steroid shot.” Although the drugs themselves are not addictive, getting these shots “is like a behavioral addiction,” he said.

“It’s a pervasive practice for which there’s practically zero evidence of benefit,” Dr. McCoul added. “It’s important for the public to understand that most upper respiratory infections are self-limited; no intervention is required. They resolve on their own if you don’t seek care.”

However, when patients do go to the doctor, they expect something to happen, and doctors are often happy to oblige. They are reimbursed by insurance if they administer an injection but not if they hand patients a prescription for oral steroids.

A single steroid shot provides the equivalent of six days of oral prednisone at 20 milligrams a day, Dr. Dvorin said. But unlike pills that patients can stop taking, once an injection is administered, the drug can’t be removed from the body if it causes an adverse effect or confers no benefit.

Asked how to avoid inappropriate use of steroids, Dr. Dvorin suggested that patients look providers in the eye and ask, “Is this evidence-based? Is it something that’s really going to help me? What are the possible side effects? Are steroids really needed? What else can I do or take to relieve my symptoms?”

Less hazardous options abound, Dr. Wallace said. They include over-the-counter drugs like ibuprofen, acetaminophen (Tylenol and its store brands), and a nighttime cough syrup. Dr. McCoul suggested using an over-the-counter decongestant to reduce mucus production and relieve pressure in the head. Alternatively, try a saline nasal spray, which he said is “one of the best things a person can do for any acute or chronic upper respiratory condition in which inflammation plays a role.”

You can purchase a salt mixture or make your own to use in a nasal irrigation device like a Neti pot. Mix 3 teaspoons of noniodized salt with 1 teaspoon of baking soda. Add 1 teaspoon of the mixture to 8 ounces of distilled (or boiled and cooled) water in the device. Tilt your head over the sink at a 45-degree angle, place the spout in one nostril and gently pour in the salt solution. Repeat in the other nostril.

What People With Allergies Should Know About Covid Vaccines

Here’s What People With Allergies Should Know About Covid Vaccines

Four people so far have had allergic reactions after getting the Pfizer-BioNTech vaccine. Experts say that shouldn’t deter most people from getting a jab.

Vaccinations underway in Orange, Calif., on Wednesday.
Vaccinations underway in Orange, Calif., on Wednesday.Credit…Jenna Schoenefeld for The New York Times
Katherine J. Wu

  • Dec. 18, 2020, 12:27 p.m. ET

Allergic reactions reported in two health workers who received a dose of Pfizer’s vaccine in Alaska this week have reignited concerns that people with a history of extreme immune flare-ups might not be good candidates for the newly cleared shots.

The two incidents follow another pair of cases in Britain. Three of the four were severe enough to qualify as anaphylaxis, a severe and potentially life-threatening reaction. But all four people appear to have recovered.

Health officials on both sides of the pond are vigilantly monitoring vaccinated people to see if more cases emerge. Last week, British drug regulators recommended against the use of Pfizer’s vaccine in people who have previously had anaphylactic reactions to food, medicines or vaccines.

And on Thursday, Dr. Doran Fink, deputy director of the Food and Drug Administration’s clinical division of vaccines and related products applications, addressed the issue during a meeting about the vaccine made by Moderna that contains similar ingredients and is expected to soon receive emergency use authorization, or E.U.A., from the agency.

“We anticipate that there may be additional reports, which we will rapidly investigate,” Dr. Fink said, adding that robust surveillance systems were in place to detect these rare events.

Still, Dr. Fink said that “the totality of data at this time continue to support vaccinations under the Pfizer E.U.A., without new restrictions.”

The F.D.A., he added, would work with Pfizer to revise fact sheets and prescribing information for the vaccine so that the public would understand the risk of allergic reactions and know how to report them.

What do we know about the people who had bad reactions?

The first two confirmed cases of allergic reactions came from two health care workers in Britain. Both had a medical history of serious allergic reactions, but had not previously been known to have trouble with any of the vaccine’s ingredients. After an injection of epinephrine — the typical treatment for anaphylaxis — both recovered.

(A third British incident described as a “possible allergic reaction” was also reported and appears to have been minor.)

On Wednesday, two health workers in Alaska experienced reactions as well. One was too mild to be deemed anaphylaxis. But the other, which occurred in a middle-aged woman with no history of allergies, was serious enough to warrant hospitalization, even after she got a shot of epinephrine.

“What is happening does seem really unusual to me,” said Dr. Kimberly Blumenthal, an allergist, immunologist and drug allergy researcher at Massachusetts General Hospital. Vaccine-related allergic reactions are typically rare, occurring at a rate of about one in a million.

Dr. Blumenthal also pointed out that it was a bit bizarre to see allergic reactions clustering in just two locations: Britain and Alaska. Zeroing in on the commonalities between the two hot spots, she said, might help researchers puzzle out the source of the problem.

Do we know for sure that their reactions were caused by the vaccine?

British and U.S. agencies are investigating the causes, but no official has declared a direct link.

But Dr. Blumenthal suspects they were connected to the shots, because the reactions were immediate, occurring within minutes of injection.

“We have to think it was related because of the timing,” she said.

Nor is it known if a particular ingredient might have been the cause. Pfizer’s vaccine contains just 10 ingredients. The most important is a molecule called messenger RNA, or mRNA — genetic material that can instruct human cells to make a coronavirus protein called spike. Once manufactured, spike teaches the immune system to recognize the coronavirus so it can be fought off in the future. Messenger RNA, which is naturally found in human cells, is unlikely to pose a threat, and degrades within about a day of being injected.

The other nine ingredients are a mix of salts, fatty substances and sugars that stabilize the vaccine. None are common allergens. The only chemical with a history of causing allergic reactions is polyethylene glycol, or PEG, which helps package the mRNA into an oily sheath, protecting it as it goes into human cells.

But PEG is, generally speaking, inert and widespread. It’s found in ultrasound gel, laxatives like Miralax and injectable steroids, among other drugs and products, Dr. Blumenthal said. Despite the chemical’s ubiquity, she said, “I’ve only seen one case of a PEG allergy — it’s really, really uncommon.”

It’s still possible that something else could be causing the reactions — perhaps a factor related to how the vaccines are transported, thawed or administered, Dr. Blumenthal said.

Did the volunteers in Pfizer’s clinical trials have any bad reactions?

A small number of volunteers in Pfizer’s clinical trials experienced allergic reactions. Just one of the 18,801 participants who received the vaccine in a late-stage trial had anaphylaxis, and the incident was deemed unrelated to the vaccine, said Steven Danehy, a spokesman for Pfizer. No severe reactions were found in people who got a placebo shot.

Pfizer excluded people with a history of anaphylaxis to vaccines from its clinical trials.

What does the F.D.A. say about these reactions?

Several experts raised concerns about the allergic reactions in meetings convened to discuss both Pfizer’s and Moderna’s vaccines. The agency has advised caution, noting that health care providers should not administer the vaccine to anyone with a “known history of a severe allergic reaction” to any component of the vaccine — a standard warning for vaccines.

Should people with mild allergies wait to get vaccinated?

There’s no evidence that people with mild allergies, which are quite common, need to avoid the vaccine. Allergies are, simply put, the product of an inappropriate immune response against something harmless — pollen, peanuts, cat dander and the like. In many cases, the results of this overreaction are mild symptoms such as a runny nose, coughing or sneezing.

But allergies are specific: A reaction to one substance does not guarantee a reaction to another. On Monday, the American College of Allergy, Asthma and Immunology released guidance stating that people with common allergies “are no more likely than the general public to have an allergic reaction to the Pfizer-BioNTech Covid-19 vaccine.”

William Amarquaye, a clinical pharmacist at Brandon Regional Hospital, said he wouldn’t let his asthma or allergies stop him from taking the vaccine when it is offered to him in the next few weeks. He’s also never had trouble with other vaccines he has taken in the past.

“It should still be OK to take the vaccine,” Dr. Amarquaye said. “I’m actually excited about it.”

What about people with a history of severe allergies?

Most people in this category should be good to go, too, said Dr. Eun-Hyung Lee, an expert in allergy and immunology at Emory University.

Guidelines released by the Centers for Disease Control and Prevention identify only one group of people who might not want to get Pfizer’s vaccine: those with a known history of severe allergic reactions to an ingredient in the injection.

People with a history of anaphylaxis to any other substance, including other vaccines or injectable drugs, can still get the vaccine, but should consult their health care providers and be monitored for 30 minutes after getting their shots. Everyone else, like people with mild or no allergies, need to wait only 15 minutes before leaving the vaccination site.

“In general, the immediate reactions that require epinephrine are those that happen within the first 30 minutes,” said Dr. Merin Kuruvilla, an allergist and immunologist at Emory University.

Some people will understandably be concerned. Dr. Taison Bell, a critical care physician at UVA Health in Charlottesville, Va., said he worried about his 7-year-old son, Alain, who is severely allergic to several foods, including wheat, peanuts and cow’s milk. Alain has about two bouts of anaphylaxis each year.

It’s a bit of a relief that Alain is “later in the prioritization schema,” Dr. Bell said. By the time a vaccine is ready for him, he said, “we’ll get a better sense for how serious this is.” The family plans to discuss their situation with Alain’s doctor.

Ultimately, it’s unlikely that any of the ingredients in a coronavirus vaccine would cause Alain any issues. Alain has tolerated other vaccines, including the flu shot, in previous years, and is looking forward to his own shot at immunization to the coronavirus, said Dr. Bell, who received his first dose of Pfizer’s vaccine on Tuesday.

What about Moderna’s vaccine?

Two volunteers in Moderna’s late-stage clinical trial developed anaphylactic reactions, the company reported at the F.D.A. committee meeting on Thursday. Neither was deemed to be linked to the company’s vaccine, which also contains mRNA, because they occurred weeks or months after the participants received their shots. One of these volunteers also had a history of asthma and a shellfish allergy.

Moderna, unlike Pfizer, did not exclude people with a history of anaphylaxis from its trials.

Dr. Tal Zaks, the company’s chief medical officer, said that while Moderna’s vaccine recipe was similar to Pfizer’s, key molecular differences existed that could set the two products on different paths. He said that bad reactions to Pfizer’s vaccine did not guarantee that similar events would happen in relation to the Moderna shots.

Both vaccines do, however, include a version of PEG.

Dr. Blumenthal and others said that anyone concerned about having an allergic reaction to a vaccine should seek the advice of a health care provider.

For anyone getting the vaccine, it’s all about “balancing out the risks,” Dr. Lee, of Emory, said. Allergic reactions can be dangerous. But they are rare and treatable, and the tools to combat them should be available at all vaccination sites. The coronavirus, on the other hand, can have far graver consequences.

“When it’s my turn in line, I think weighing these odds is what I would do,” Dr. Lee said.

Moderna to Begin Testing Its Coronavirus Vaccine in Children

Moderna Plans to Begin Testing Its Coronavirus Vaccine in Children

The company said the trial would involve children ages 12 through 17.

The study will include 3,000 children, with half receiving two shots of the vaccine four weeks apart.
The study will include 3,000 children, with half receiving two shots of the vaccine four weeks apart.Credit…Cody O’Loughlin for The New York Times

By

  • Dec. 2, 2020, 2:13 p.m. ET

The drugmaker Moderna said on Wednesday that it would soon begin testing its coronavirus vaccine in children ages 12 through 17. The study, listed Wednesday on the website clinicaltrials.gov, is to include 3,000 children, with half receiving two shots of vaccine four weeks apart, and half getting placebo shots of salt water.

But the posting says the study is “not yet recruiting,” and Colleen Hussey, a spokeswoman for Moderna, said it was not certain when the testing sites would be listed or start accepting volunteers. A link on the website to test centers is not yet working, and Ms. Hussey said she was not sure when it would become active.

Moderna announced on Monday that data from its study in 30,000 adults had found its vaccine to be 94.1 percent effective, and that it had applied to the Food and Drug Administration for emergency authorization to begin vaccinating adults. If approval is granted, certain groups of high-risk adults, including people in nursing homes, could receive shots late in December.

But no vaccine can be widely given to children until it has been tested in them. Vaccines meant for both adults and children are generally tested first in adults to help make sure they are safe for pediatric trials.

Moderna’s vaccine has not yet been studied in children or pregnant women. In the new clinical trial in adolescents, girls past puberty will be tested before each injection to make sure they are not pregnant.

“Everyone anticipates that when we test this first in adolescents, then older children, then the real small kids, that the Covid vaccine will work,” said Dr. William Schaffner, an infectious disease specialist at Vanderbilt University and an adviser on vaccines to the Centers for Disease Control and Prevention.

But children have more active immune systems than adults, and may have stronger reactions, including more fever, muscle and joint aches, and fatigue, Dr. Schaffner said.

“They may be more out of sorts than adults for a day or two,” he said. “You really do want to know, if it’s given in adolescents, what can parents expect? You really want to be able to tell them clearly how you might feel for 24 or 48 hours after you receive the vaccine. And obviously, we really want to be able to tell parents it works.”

If a child had intense side effects and parents were not prepared for it, they might be reluctant to go back for the second shot, Dr. Schaffner said.

Dr. Paul A. Offit, a vaccine expert at Children’s Hospital of Philadelphia, said that vaccines “for the most part” work equally well in children and adults. Occasionally, as with the hepatitis B vaccine, different doses are required, he said. Moderna will study the same dose in children that it has tested in adults.

Pfizer began testing its coronavirus vaccine in children as young as 12 in October. A large clinical trial found its vaccine to be 95 percent effective in adults, and the company has requested emergency authorization from the F.D.A. Britain approved the Pfizer vaccine for adults on Wednesday, the first country to do so.

AstraZeneca has also tested its vaccine in children, but not in the United States.

As vaccine studies have moved forward, rumors have spread on social media, particularly among people who oppose vaccines in general, that President-elect Joseph R. Biden Jr. plans to require vaccination for everyone, including children. His team has denied those claims, and Mr. Biden has said that he will rely on scientists’ advice for the best way to end the pandemic.

Who Will Get the Coronavirus Vaccine First?

After months of deliberation and debate, a panel of independent experts advising the Centers for Disease Control and Prevention is set to decide on Tuesday which Americans it will recommend to get the coronavirus vaccine first, while supply is still short.

The panel, the Advisory Committee on Immunization Practices, will vote in a public meeting on Tuesday afternoon, and it is expected to advise that health care workers be first in line, along with residents of nursing homes and other long-term care facilities. If the C.D.C. director, Dr. Robert R. Redfield, approves the recommendations, they will be shared with states, which are preparing to receive their first vaccine shipments as soon as mid-December, if the Food and Drug Administration approves an application for emergency use of a vaccine developed by Pfizer.

States don’t have to follow the C.D.C.’s recommendations, but most probably will, said Dr. Marcus Plescia, the chief medical officer for the Association of State and Territorial Health Officials, which represents state health agencies. The committee will meet again soon to vote on which groups should be next to receive priority.

Here are answers to some common questions about the vaccine and its distribution.

Who will get the vaccine first?

Based on its recent discussions, the C.D.C. committee will almost certainly recommend that the nation’s 21 million health care workers be eligible before anyone else, along with three million mostly elderly people living in nursing homes and other long-term care facilities.

A staggering 39 percent of deaths from the coronavirus have occurred in long-term care facilities, according to the committee. But there won’t be enough doses at first to vaccinate everyone in these groups; Pfizer and Moderna, the two companies closest to gaining approval for their vaccines, have estimated that they will have enough to vaccinate no more than 22.5 million Americans by January. So each state will have to decide which health care workers go first.

They may choose to prioritize critical care doctors and nurses, respiratory therapists and other hospital employees, including cleaning staff, who are most likely to be exposed to the coronavirus. Or they may offer the vaccine to older health care workers first, or those working in nursing homes, who are at higher risk of contracting the virus. Gov. Andy Beshear of Kentucky said on Monday that most of his state’s initial allocation would go to residents and employees of long-term care facilities, with a smaller amount going to hospital workers.

It’s important to remember that everyone who gets a vaccine made by Pfizer or Moderna will need a second shot — three weeks later for Pfizer’s, four weeks for Moderna’s.

Who gets it next?

The C.D.C. committee hinted last week that it would recommend essential workers be next in line. About 87 million Americans work in food and agriculture, manufacturing, law enforcement, education, transportation, corrections, emergency response and other sectors. They are at increased risk of exposure to the virus because their jobs preclude them from working from home. And these workers are disproportionately Black and Hispanic, populations that have been hit especially hard by the virus.

Individual states may decide to include in this group employees of industries that have been particularly affected by the virus. Arkansas, for example, has proposed including workers in its large poultry industry, while Colorado wants to include ski industry workers who live in congregate housing.

After essential workers, the priority groups likely to be recommended by the C.D.C. committee are adults with medical conditions that put them at high risk of coronavirus infection, and people over 65. But again, some states might diverge to an extent, choosing, for example, to vaccinate residents over 75 before some types of essential workers. All other adults would follow. The vaccine has not yet been thoroughly studied in children, so they would not be eligible yet.

If the C.D.C. director, Dr. Robert R. Redfield, approves the panel’s recommendations, they will be shared with states.
If the C.D.C. director, Dr. Robert R. Redfield, approves the panel’s recommendations, they will be shared with states.Credit…Stefani Reynolds for The New York Times

Who will make state-level decisions about priority groups?

Each state has a working group, composed largely of public health officials, that has been planning for months and making decisions about vaccination campaigns. Each state’s top health official and governor will probably sign off on final plans.

How long will states focus on one priority group before moving to the next in line?

States don’t need to reach everyone in one priority group before moving on to the next, according to the C.D.C. advisory committee. But more federal guidance is expected on the subject.

When will the first doses of a vaccine be shipped, and where will they go?

Federal officials have said they plan to ship the first 6.4 million doses within 24 hours after the F.D.A. authorizes a vaccine, and the number each state receives will be based on a formula that considers its adult population. Pfizer will ship special coolers, each containing at least 1,000 doses, directly to locations determined by each state’s governor. At first, almost all of those sites will probably be hospitals that have confirmed they can store shipments at minus 94 degrees Fahrenheit, as the Pfizer vaccine requires, or use them quickly.

When will a vaccine be available to the general public, and where will people receive it?

Federal officials have repeatedly suggested that people who are not in the priority groups — healthy adults under 65 who don’t work in health care or otherwise qualify as essential workers — should have access to the vaccine by May or June, because there will be enough supply by then. But a lot will have to go right for that to happen. One factor is whether, or when, other vaccines besides Pfizer’s and Moderna’s are approved.

Can employers like hospitals or grocery stores require their employees to be vaccinated?

Employers do have the right to compel their workers to be vaccinated. Many hospital systems, for example, require annual flu shots. But employees can seek exemptions based on medical reasons or religious beliefs. In such cases, employers are supposed to provide a “reasonable accommodation”; with a coronavirus vaccine, a worker might be allowed to wear a mask in the office instead, or to work from home.

Three companies have announced preliminary data indicating their vaccines are effective, and there are dozens of additional candidates in clinical trials. Can I choose which vaccine I get?

This depends on a number of factors, including the supply in your area at the time you’re vaccinated and whether certain vaccines are found to be more effective in certain populations, such as older adults. At first, the only choice is likely to be Pfizer’s vaccine, assuming it is approved. Moderna asked the F.D.A. for emergency authorization on Monday; if approved, it would most likely become available within weeks after Pfizer’s.

Are there any side effects from the shot?

Some participants in both Pfizer’s and Moderna’s trials have said they experienced symptoms including fever, muscle aches, bad headaches and fatigue after receiving the shots, but the side effects generally did not last more than a day. Still, preliminary data suggests that, compared with most flu vaccines, the coronavirus shots have a somewhat higher rate of such reactions, which are almost always normal signs that the body’s immune response is kicking in. At the meeting of the C.D.C. advisory committee last week, some members said it would be important for doctors to warn their patients about possible side effects and assure them of the vaccines’ safety.

How do I know it’s safe?

Each company’s application to the F.D.A. includes two months of follow-up safety data from Phase 3 of clinical trials conducted by universities and other independent bodies. In that phase, tens of thousands of volunteers get a vaccine and wait to see if they become infected, compared with others who receive a placebo. By September, Pfizer’s trial had 44,000 participants; no serious safety concerns have been reported.

The F.D.A. will also review the data for each vaccine seeking authorization and share it with its advisory committee, which will meet publicly — in the case of the Pfizer vaccine, on Dec. 10 — to ask questions and make a recommendation to the agency. The F.D.A. will then decide whether to approve the vaccine for emergency use.

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New Guidelines Cover Opioid Use After Children’s Surgery

Opioids are very effective drugs for managing pain, but they can also be scary drugs, with their potential for misuse and abuse. Given the current opioid epidemic in the United States, some parents worry about whether they are safe for children, while many pain experts worry that fear of opioids among parents and among physicians may contribute to the undertreatment of pediatric pain.

In new guidelines published in November in the journal JAMA Surgery, a panel convened by the American Pediatric Surgical Association Outcomes and Evidence-based Practice Committee set out some guidelines for how to think about — and prescribe — opioids for children to relieve pain after surgery. “It’s important to understand that children undergo a lot of painful procedures,” said Dr. Lorraine Kelley-Quon, a pediatric surgeon at Children’s Hospital Los Angeles, who was the lead author on the guidelines. “They have real pain; opioids can help.”

Matthew Kirkpatrick, an addiction expert who is an assistant professor in the department of preventive medicine at the Keck School of Medicine at the University of Southern California, and who was one of the authors of the new guidelines, said, “We don’t want to contribute to scaring parents and to scaring physicians about undertreating pain.” From the data they reviewed, he said, “kids that use these medications as prescribed are at very low risk for abuse and dependence either in the short term or the long term.”

However, the first six statements in the guidelines discuss the risks of adolescents misusing prescription opioids (misuse is anything other than use exactly as directed by the prescriber, or use without a prescription), diverting them (giving them away or selling them), and possibly having a higher risk of problems with opioids in the future. Dr. Kelley-Quon pointed out that many health care practitioners may not be familiar with the addiction literature. But some pain experts warn that heavy emphasis on that risk as a way of framing the issue may frighten both parents and doctors.

Dr. Elliot Krane, the chief of pediatric pain management at Stanford Children’s Health, who was not an author of the new guidelines, said, “the concern is that the paper is going to discourage the appropriate use of opioids, though I know that wasn’t the intent of the authors — the reason I think that’s the risk is they set up their recommendations with a premise which I think is untrue, that kids are dying and becoming addicts” at an increasing rate.

Dr. Krane disputed some of the statements about the risk: “I think the evidence that opioid abuse is increasing in children is very weak; I think the evidence in children that prescription opioids lead to later abuse isn’t there at all.”

Dr. Scott Hadland, a pediatrician and addiction specialist at Boston Medical Center, who was not involved with the guidelines, said, “While I agree with the recommendations, I agree also with the concern from the pain community that risk may be overstated — may not be as large as some of the earlier studies have suggested.”

The guidelines recommend non-opioid medications as first-line postoperative drugs, including the use of regional anesthesia.

But when opioids are used, the guidelines stress careful supervision. “It all boils down to access,” Dr. Kirkpatrick said, and the imperative is to make sure that parents and physicians get the right information “to manage the dispensing of the medication to their kids and the access that their kids have to the medication.” Parents should not be afraid of managing the child’s pain with opioids when they are needed, but should understand the importance of controlling that access in children and through adolescence.

“The parent should be highly engaged in managing the child’s pain, in making sure the child gets the medication to manage the pain, but the child does not have access to the drug on their own.”

Dr. Kirkpatrick said that overprescribing by physicians has contributed to opioid use and misuse in adults. In data from a national survey on drug use and health, he said, kids were most likely to get medication they had misused from friends or family members, but when they were asked where that person had gotten it, it was often from a doctor.

Dr. William Zempsky, the division head of pain and palliative medicine at Connecticut Children’s Medical Center, who was not an author of the guidelines, said that while opioids have been prescribed inappropriately to adults in some settings, there is no clear evidence that it has been a problem in pediatrics.

“We need to do things right, but we don’t need to scare people,” Dr. Zempsky said. “Kids continually are at risk for lack of appropriate postoperative surgical management because of fear of opioid addiction.”

Dr. Eugene Kim, the chief of the division of pain medicine at Children’s Hospital Los Angeles, who was one of the authors of the guidelines, said, “I am aware of the caution that certain pain management experts have,” regarding the dangers of underprescribing and undertreating pain. The guidelines should be the basis for ongoing conversations, he said, as well as for responsible prescribing.

“Parents of children who are undergoing surgeries should be educated as to when to use the medications, how to use the medications, and we, as providers, should be involved in that process from the get-go as far as the education process, as far as responsible prescribing, as far as follow up.”

Some adolescents may be particularly at risk for problems with opioids, especially those who have had substance use problems in the past, and those who have mental health problems.

With patients at higher risk, Dr. Hadland said, such as those with anxiety or depression or those who have had substance abuse issues, opioids can still be prescribed when they’re needed, but “we should take great care.”

When a patient of his, a young adult who had alcohol use disorder, needed surgery, Dr. Hadland said, “I and the patient themselves were both concerned about the potential misuse of opioids because of the history of addiction.” He and the surgeon partnered, he said, and agreed that Dr. Hadland would do the postoperative pain management because he was more readily available and more comfortable working with a patient who had this history. He prescribed very small amounts of oxycodone, he said, discussing at every stage with the patient how it felt to be taking the medication. “We had open communication around it and things went really well.”

The guidelines go beyond the discussion of when opioids should be used and cover the importance of educating both children and their parents and caregivers about the possible side effects of opioids (oversedation and respiratory depression), about the importance of following medical instructions carefully, about the need for storing these medications securely (that is, in a locked area) and getting any unused doses out of the home in a safe and secure way (they should be returned to a secure opioid disposal bin).

None of the other specialists I spoke with suggested changing the specific recommendations for multimodal pain relief, for using opioids when other drugs are insufficient for effective pain control, and for good parent education leading to careful oversight, locked storage and safe disposal of unused doses.

“The spirit behind these guidelines is correct,” Dr. Hadland said. “Prescribing the lowest effective dose for the shortest period of time, use only short acting formulations, and talk to families about risks and monitoring dosing and locking up medication.”

Parents and physicians can feel safe that if kids are using these medications as prescribed to manage their pain, Dr. Kirkpatrick said, they are “not at significantly greater risk for developing opioid use related problems.”

“If your child needs surgery, talk to your doctor, ask questions about what pain should be expected,” Dr. Kelley-Quon said. Ask if opioids will be used, and if so, how should they be used, and how can they be safely disposed of, she said. “We want to be at the sweet spot, treating pain appropriately, maximizing benefit and minimizing risk.”

Can Statins Cause Diabetes?

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Drug Company Lunches Have Big Payoffs

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A free lunch may be all it takes to persuade a doctor to prescribe a brand-name drug instead of a cheaper generic, a new study suggests.

Using Medicare’s Open Payments data, researchers collected information on 279,669 doctors who received 63,524 payments reported by drug companies. They concentrated on specific drugs in four categories: cholesterol lowering statins, two types of blood pressure drugs and antidepressants.

The study, in JAMA Internal Medicine, found that 95 percent of the payments were for meals sponsored by drug companies, worth about $12 to $18 each.

Doctors who were treated to a single meal, where drug companies present information about their medications, were 18 percent more likely to prescribe Crestor, a brand-name cholesterol-lowering medicine. They were 70 percent more likely to prescribe Bystolic, a brand-name beta blocker for high blood pressure, and 52 percent more likely to prescribe Benicar, also for hypertension.

The more meals doctors had, the more likely they were to prescribe the promoted drug.

Think Like a Doctor: Drowning on Dry Land Solved

On Thursday we challenged Well readers to unravel the case of a 67-year-old healthy retiree who suddenly developed knife-like chest pain and a worsening cough. Maybe this case was too easy because more than a quarter of you figured it out.

The correct diagnosis is:

Eosinophilic pneumonia, caused by the antibiotic daptomycin (brand name Cubicin)

The first reader to make this not-quite-as-tough-as-I-thought diagnosis was Francis Graziano, a second-year medical student at Georgetown University School of Medicine. He had just learned about daptomycin and recalled that there were some pretty dramatic side effects linked to it. And the time course seemed right. So he went to the Wikipedia page on the drug and saw that this type of pneumonia was a known adverse reaction to it. Francis is another two-time winner, having solved another tough case two years ago. Well done, Francis.

The Diagnosis

Daptomycin is an antibiotic used primarily to treat drug-resistant staph infections. It was approved by the Food and Drug Administration in 2003.

The first report suggesting a link between this antibiotic and pneumonia was made in 2007. An 87-year-old man who, like this patient, was being treated with daptomycin for an infection after knee surgery lost 15 pounds over the course of just a few weeks and became increasingly fatigued. A CT scan of his chest revealed multiple nodules, and when these nodules were biopsied, the patient was found to have a pneumonia.

But it was an unusual pneumonia. Instead of finding bacteria or the usual infection-fighting white blood cells in the lungs, the sample showed a handful of eosinophils (or eos), a type of white blood cell that normally fights off parasites (like intestinal worms) but can also be seen in allergic reactions. The doctors suspected that the pneumonia was an allergic reaction to the daptomycin. They stopped the drug, and the pneumonia resolved.

As a result of this case report, the F.D.A. put eosinophilic pneumonia on the list of possible adverse reactions. By 2011, 11 cases had been reported, enough to convince the F.D.A. that the link was real.

Eosinophilic pneumonia is an unusual disorder and is usually caused by exposure to certain drugs or toxins or radiation therapy. The most common trigger is cigarette smoke, and the illness may occur in those who recently started or restarted smoking. More than 300 different medications have been linked to eosinophilic pneumonia; antibiotics and nonsteroidal anti-inflammatory drugs such as ibuprofen are most commonly cited.

How or why this pneumonia develops is not clear. Men are more likely to be affected than women. In the cases of eosinophilic pneumonia associated with daptomycin, patients were all over age 60.

How the Diagnosis Was Made

Dr. Robert Centor was the doctor on call when the patient was admitted to the hospital. The patient was seen by the resident on his team, who called to tell him about the 67-year-old man with the infected knee and a week-long pneumonia.

Dr. Centor was intrigued. Why would a pretty healthy guy on antibiotics for one infection develop a second infection? He was getting his antibiotics through an intravenous catheter than ran from a vein in his arm into his heart. Could some type of skin bug have traveled up the catheter into his heart, and from there into his lungs?

He asked the resident to make sure that the patient had a CT scan of his chest to look for tiny pieces of infection, known as septic emboli, which might be clogging up the blood vessels in his lungs. The patient got the scan, which showed only the fluffy clouds dotted throughout his lungs.

The next morning, Dr. Centor went to the radiology suite to review the chest X-ray and CT scan with the radiologist. No septic emboli were present. After confirming what he’d already heard the night before, the internist headed up to see the patient with his team.

Looking for Answers

After talking to the patient and examining him, Dr. Centor was certain of two things. First, that the patient was seriously ill. Second, that he wasn’t sure why. It didn’t make any sense at all that this youthful 67-year-old retiree should suddenly develop a whopping double pneumonia.

Certainly bad things can happen to healthy people, but Dr. Centor liked to understand why. In this case, “I was completely befuddled,” Dr. Centor told me in his thoughtful Southern twang. We were old friends; he had been a wonderful teacher and mentor to me. “But whenever I am befuddled, I just talk to other people,” he told me.

I know from my own experience that often enough, just posing a case to a colleague as a question can prompt you to see it in a different light and reveal an answer you hadn’t considered. And if you’re really lucky, the answer comes from asking someone who has previously come across a similar case. So Dr. Centor, who was the dean of his residency program, headed to the cafeteria, where he grabbed a cup of coffee and scanned the room for familiar faces. He settled down at a table full of doctors and residents and quickly outlined the case.

The Right Place, the Right Time

Mohamed Raja, a resident in his second year of training, listened carefully to the case. “It was a matter of being in the right place at the right time,” he told me. Because as soon as Dr. Centor mentioned the name of the antibiotic the patient had been getting, the resident realized with a jolt that he knew the diagnosis.

Well, he said to Dr. Centor, he had been reading up on Cubicin just the week before. And there was this rare complication associated with the drug that had caught his attention. It was an allergic reaction that manifests itself as a terrible and painful pneumonia, caused not by an infection but by the patient’s own white blood cells, the eosinophils.

Hearing of this unusual reaction, Dr. Centor quickly pulled out his cellphone and looked up Cubicin and eosinophilic pneumonia. Sure enough, this unusual side effect, first described just a few years earlier, seemed to fit his patient exactly.

The only way to know for certain was to get a lung doctor to put a scope into the patient’s lungs and see if these specialized cells, the eosinophils, were there. They shouldn’t be. But first he had to stop the medication.

Dr. Centor called the nurses to make certain the patient didn’t get his next scheduled dose. Then he went upstairs to tell his team and the patient.

Waiting for Watson

It is the nature of medical knowledge that no one knows everyone. We doctors all learn the same basics, and what we add depends on the patients we see and the interests we pursue. One of the key skills all doctors must hone is how to recognize and supplement these almost inevitable gaps.

The Internet has made this kind of supplementation much, much easier. For example, when Dr. Centor first told me about this case, he gave me the outline and asked what I thought was going on – a game we often play. I didn’t know, but what I call “test logic” told me that if he was telling me the name of the antibiotic, it had to be part of the answer. So I Googled the terms “daptomycin” and “pneumonia” and whammo, I got the answer immediately.

Last fall, IBM announced that it is developing a health care business based on its supercomputer, Watson. Using the same data-accumulating skills that allowed Watson to conquer “Jeopardy!” in 2011, the goal is to master all medical knowledge – new and old – so that we won’t have to. But until then, doctors must continue to rely on their own data accumulating skills.

Dr. Centor turned first to the traditional method, the who-wants-to-be-a-millionaire option of phoning a friend, before turning to other sources. Will Watson – or any of the other emerging databases – fully replace human recall and thought? They haven’t so far.

How the Patient Fared

The patient had the bronchoscopy the next day. He had eosinophils and no signs of infection. He was started on high-dose steroids to calm the allergic reaction, and the Cubicin was replaced with another antibiotic for the last weeks of treatment.

It’s been four months since his scary pneumonia episode, and the patient tells me he feels just fine. He’s resigned to the fact that his knee may never be perfect. But breathing? No problem.

As for his fishing camp, it’s closed for the winter. But he’ll be back as soon as the weather, and his knee, allow.