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MIT’s top research stories of 2021

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Despite the pandemic’s disruptions, MIT’s research community still found a way to generate a number of impressive research breakthroughs in 2021. In the spirit of reflection that comes with every new orbit around the sun, below we count down 10 of the most-viewed research stories on MIT News from the past year.

We’ve also rounded up the year’s top MIT community-related stories .

10. Giving cancer treatment a recharge . In October, researchers discovered a way to jump-start the immune system to attack tumors. The method combines chemotherapy and immunotherapy to spur immune cells into action. The researchers hope it could allow immunotherapy to be used against more types of cancer.

9. Generating 3D holograms in real-time . Computer scientists developed a deep-learning-based system that allows computers to create holograms almost instantly. The system could be used to create holograms for virtual reality, 3D printing, medical imaging, and more — and it’s efficient enough to run on a smartphone.

8. Creating inhalable vaccines . Scientists at the Koch Institute developed a method for delivering vaccines directly to the lungs through inhalation. The new strategy induced a strong immune response in the lungs of mice and could offer a quicker response to viruses that infect hosts through mucosal surfaces.

7. Assessing Covid-19 transmission risk . Two MIT professors proposed a new approach to estimating the risks of exposure to Covid-19 in different indoor settings. The guidelines suggest a limit for exposure based on factors such as the size of the space, the number of people, the kinds of activity, whether masks are worn, and ventilation and filtration rates.

6. Teaching machine learning models to adapt . Researchers in CSAIL developed a new type of neural network that can change its underlying equations to continuously adapt to new data. The advance could improve models’ decision-making based on data that changes over time, such as in medical diagnosis and autonomous driving.

5. Programming fibers . In June, a team created the first fabric fiber with digital capabilities. The fibers can sense, store, analyze, and infer data and activity after being sewn into a shirt. The researchers say the fibers could be used to monitor physical performance, to detect diseases, and for a variety of medical purposes.

4. Examining the limitations of data visualizations . A collaboration between anthropologists and computer scientists found that coronavirus skeptics have used sophisticated data visualizations to argue against public health orthodoxy like wearing a mask. The researchers concluded that data visualizations aren’t sufficient to convey the urgency of the Covid-19 pandemic because even the clearest graphs can be interpreted through a variety of belief systems.

3. Developing a Covid-detecting face mask . Engineers at MIT and Harvard University designed a prototype face mask that can diagnose the person wearing the mask with Covid-19 in about 90 minutes. The masks are embedded with tiny, disposable sensors that can be fitted into other face masks and could also be adapted to detect other viruses.

2. Confirming Hawking’s black hole theorem . Using observations of gravitational waves, physicists from MIT and elsewhere confirmed a major theorem created by Stephen Hawking in 1971. The theorem states that the area of a black hole’s event horizon — the boundary beyond which nothing can ever escape — will never shrink.

1. Advancing toward fusion energy . In September, researchers at MIT and the MIT spinout Commonwealth Fusion Systems ramped up a high-temperature superconducting electromagnet to a field strength of 20 tesla, the most powerful magnetic field of its kind ever created on Earth. The demonstration was three years in the making and is believed to resolve one of greatest remaining points of uncertainty in the quest to build the world’s first fusion power plant that produces more energy than it consumes.

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Top 10 research topics from 2021.

Find the answers to your biggest research questions from 2021. With collective views of over 3.7 million, researchers explored topics spanning from nutritional immunology and political misinformation to sustainable agriculture and the human-dog bond .

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5. Plant science

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HBR’s Most-Read Research Articles of 2021

by Dagny Dukach

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What will it take to make work better? Over the past year, HBR has published a wide array of research-backed articles that explore topics ranging from retaining employees to overcoming meeting overload to fostering gender equity in the workplace. In this end-of-year roundup, we share key insights and trends from our most-read research articles of 2021.

As the workplace rapidly transforms in the wake of the pandemic, social movements, and more, a fundamental question remains: How can we ensure we’re making work better — for employees, organizations, and society at large?

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Striking findings from 2021

As 2021 draws to a close, here are some of Pew Research Center’s most striking research findings from the past year. These 15 findings cover subjects ranging from extreme weather to the COVID-19 pandemic and ongoing demographic shifts in the United States. And they represent just a small slice of the year’s full list of research publications .

A growing share of childless Americans say it is unlikely they will ever have children, an October survey found. Some 44% of non-parents ages 18 to 49 say it is not too or not at all likely that they will have children someday, an increase from the 37% who said the same in 2018. Meanwhile, 74% of adults younger than 50 who are already parents say they are unlikely to have more kids, virtually unchanged since 2018.

What’s behind the growing share of non-parents younger than 50 who expect not to have children? A majority (56%) say a major reason is that they just don’t want to. Among those who point to some other reason, about two-in-ten (19%) say it’s due to medical reasons, 17% say it’s for financial reasons and 15% say it’s because they do not have a partner. Roughly one-in-ten point to their age or their partner’s age (10%), or to the state of the world (9%).

Around seven-in-ten U.S. adults (72%) said in an August survey that they personally know someone who has been hospitalized or died from COVID-19. As has been the case throughout the COVID-19 outbreak , larger shares of Black (82%) and Hispanic (78%) adults than White (70%) and English-speaking Asian adults (64%) said they personally know someone who had been hospitalized or died as a result of the coronavirus.

Across other major demographic groups, there were modest or no differences in the shares who say this. Democrats and Democratic-leaning independents, for example, were about as likely as Republicans and GOP leaners to say they know someone who had been hospitalized or died (74% and 71%, respectively).

More than 600,000 Americans had died from the virus at the time of the August survey. Since then, the death toll has risen to more than 800,000 .

Americans voted in record numbers in the 2020 presidential election, as turnout rose in every state, according to a January analysis by the Center. Nearly two-thirds of the estimated number of eligible voters and more than six-in-ten people of voting age cast ballots in the election.

Nationwide, presidential election turnout was about 7 percentage points higher than in 2016, regardless of which of three different turnout metrics we looked at. Turnout rates increased in every state compared with 2016, but of the 10 states where it rose the most, seven conducted the vote entirely or mostly by mail.

Minnesota had the highest turnout of any state, with 79.4% of estimated eligible voters casting ballots for the presidential election. Colorado, Maine and Wisconsin all followed close behind at about 75.5%; Washington state, at 75.2%, rounded out the top five. The lowest-turnout states were Tennessee (59.6% of estimated eligible voters), Hawaii and West Virginia (57% each), Arkansas (55.9%) and Oklahoma (54.8%).

About eight-in-ten Asian Americans say violence against them is increasing in the U.S., an April survey found. The survey was fielded after the  fatal shooting  of six Asian women and two other people in the Atlanta area in March, and following  other assaults on Asian Americans .

Amid widespread reports of discrimination and violence against Asian Americans during the coronavirus outbreak , 45% of Asian adults said they had experienced at least one of five specific types of incidents since the start of the pandemic.

Around a third (32%) said they had feared someone might threaten or physically attack them – a greater share than among people in other racial or ethnic groups who said this. Some 27% of Asian adults said people had acted as if they were uncomfortable around them. Another 27% said they had been subject to slurs or jokes. Lower shares said someone had made a remark that they should go back to their home country (16%) or that they were to blame for the coronavirus outbreak (14%).

At the same time, 32% said someone has expressed support for them since the start of the pandemic.

Across 16 publics surveyed in spring 2021 , a median of just 17% of adults said democracy in the U.S. is a good example for other countries to follow. A median of 57% said American democracy used to be a good example for other countries to follow but has not been in recent years. A median of 23% said American democracy has never been a good example for other countries to follow.

Americans largely shared the view that their country is no longer a good model of democracy: 72% said U.S. democracy used to be a good example for others to follow but has not been recently. Democrats and Democratic leaners were twice as likely as their Republican and GOP leaning counterparts to say the U.S. has never been a good model of democracy.

More broadly, the U.S. political system also received generally lukewarm ratings across the 16 advanced economies surveyed. People were split on how the  system is functioning , with a median of 50% saying it works well and 48% who disagreed.

In just five years, the percentage of Republicans with at least some trust in national news organizations has fallen by half – dropping from 70% in 2016 to 35% this year, a June survey found.  

Democrats remain far more likely than Republicans to say they have a lot or some trust in the information that comes from national news organizations (78% vs. 35%). The 43-point partisan gap is the widest measured since at least 2016. 

Women in the U.S. are now more likely than men to have a four-year college degree, according to a November analysis . Around four-in-ten women ages 25 and older (39%) have a bachelor’s degree, compared with a slightly smaller share of men in the same age group (37%). Among those ages 25 to 34 specifically, women are now 10 percentage points more likely than men to have a bachelor’s degree (46% vs. 36%).

The reasons for not completing a four-year degree differ for men and women, according to an accompanying survey of adults who do not have such a degree and are not currently enrolled in college. Men are more likely than women to point to factors that have more to do with personal choice. Roughly a third of men without a bachelor’s degree (34%), for example, say a major reason they didn’t complete college is that they just didn’t want to. Only one-in-four women say the same.

Most Democrats in the U.S. see voting as a fundamental right, while most Republicans view it as a privilege that comes with responsibilities, according to a July survey .

The vast majority of Democrats (78%) say voting is a “fundamental right for every adult U.S. citizen and should not be restricted in any way.” Two-thirds of Republicans say voting is “a privilege that comes with responsibilities and can be limited if adult U.S. citizens don’t meet some requirements.”

Overall, a majority of Americans (57%) say voting is a fundamental right that should not be restricted while 42% express the view that voting is a privilege that comes with responsibilities.

About three-in-ten Americans are religiously unaffiliated, a 10 percentage point rise from a decade ago, according to a survey conducted between May and August . Currently, 29% of U.S. adults are religious “nones” – those who describe themselves as atheists, agnostics or “nothing in particular.” By comparison, 16% described themselves this way when the Center first asked the question in 2007.

Christians continue to make up a majority of the U.S. population (63%), but their share is 12 points lower in 2021 than it was in 2011. Christians now outnumber religious “nones” by a ratio of a little more than two-to-one. In 2007, when the Center began asking its current question about religious identity, Christians outnumbered “nones” by almost five-to-one (78% vs. 16%).

Democrats and Republicans were deeply divided over former President Donald Trump’s role in the events of Jan. 6, according to a March survey .

The vast majority of Democrats (87%) said Trump’s conduct surrounding the riot at the U.S. Capitol was wrong and that senators should have voted to convict him during his impeachment trial, while just 11% of Republicans said the same. Around two-thirds of Republicans (65%) said Trump’s conduct was not wrong and that he should not have been impeached by the U.S. House of Representatives; just 4% of Democrats said the same.

Overall, about half of Americans (52%) said Trump’s conduct was wrong and that senators should have voted to convict him, while 31% said his conduct was not wrong and that he should not have been impeached by the U.S. House. Some Americans (15%) said Trump’s conduct was wrong but that senators should not have voted to convict him.

For the first time, the number of Americans who identify as non-Hispanic White declined between 2010 and 2020, according to the Center’s analysis of U.S. Census Bureau data. The White population of the United States declined by about 5.1 million people during that timespan.

In a related Pew Research Center survey in July , about six-in-ten U.S. adults (61%) said the decline in the White share of the U.S. population is neither good nor bad for society. About two-in-ten (22%) said it is bad, including 9% who said it is very bad. Slightly fewer (15%) said it is good, including 7% who said it is very good.

Only 34% of U.S. adults under the age of 30 now get TV through cable or satellite, down from 65% in 2015, according to a survey fielded in January and February . There were declines in other age groups, too, with decreases of 27 percentage points among those ages 30 to 49 and 14 points among those 50 to 64.

Adults under 30 who are nonsubscribers are also much more likely than older nonsubscribers to have never received TV at home via cable or satellite – and to say they don’t currently subscribe because they can find the content they want online instead.

Two-thirds of U.S. adults say extreme weather events across the country have been occurring more often than in the past, a September survey found. Far fewer Americans say they’re happening about as often (28%), and only 4% say they are happening less often.

Nearly half of Americans (46%) also say the area where they live has had an extreme weather event over the past 12 months, according to the same survey.

Nearly three-quarters of U.S. adults (73%) in the West South Central  census division , which includes Texas, Louisiana, Arkansas and Oklahoma, say they’ve experienced extreme weather within the past year. A majority of adults (59%) say the same in the Mid-Atlantic region, which includes Pennsylvania, New York and New Jersey. By contrast, far fewer say they’ve experienced extreme weather in other regions over the past year.

In most census regional divisions, Democrats are more likely than Republicans to report experiencing extreme weather within the past year. Overall, 51% of Democrats say the area where they live has experienced this, compared with 39% of Republicans.

A growing share of U.S. adults are neither married nor living with a partner , according to an October study . In 2019, roughly four-in-ten adults ages 25 to 54 (38%) were unpartnered – that is, neither married nor living with a partner, according to a Pew Research Center analysis of Census Bureau data for that year (the most recent available). This share was up sharply from 29% in 1990. Men were more likely to be unpartnered than women.

All of the growth in the unpartnered population since 1990 has come from a rise in the number who have never been married, although the unpartnered population does include some adults who were previously married (those who are separated, divorced or widowed).

Around the world, more people mention their family as a source of meaning in their lives than any other factor, according to an open-ended survey question the Center posed to people in 17 advanced economies in the spring.

In 14 of the 17 nations surveyed, more people mentioned their family as a source of meaning than anything else. Respondents highlighted their relationships with parents, siblings, children and grandchildren; quality time spent with their relatives; and the pride they get from family members’ accomplishments. Many also expressed the desire to live a life that leaves an improved world for their offspring.

Read the other posts in our striking findings series:

• 20 striking findings from 2020
• 19 striking findings from 2019
• 18 striking findings from 2018
• 17 striking findings from 2017
• 16 striking findings from 2016
• 15 striking findings from 2015
• Asian Americans
• Climate, Energy & Environment
• Coronavirus (COVID-19)
• Discrimination & Prejudice
• Donald Trump
• Election 2020
• Political & Civic Engagement
• Politics & Policy
• Racial & Ethnic Shifts
• Racial Bias & Discrimination
• Voter Participation

Katherine Schaeffer is a research analyst at Pew Research Center .

Người Mỹ Gốc Á: Tổng quan nhanh về dữ liệu khảo sát (All Asian Americans VI)

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ABOUT PEW RESEARCH CENTER  Pew Research Center is a nonpartisan fact tank that informs the public about the issues, attitudes and trends shaping the world. It conducts public opinion polling, demographic research, media content analysis and other empirical social science research. Pew Research Center does not take policy positions. It is a subsidiary of  The Pew Charitable Trusts .

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The Ten Most Significant Science Stories of 2021

Thrilling discoveries, hurdles in the fight against Covid and advancements in space exploration defined the past year

Associate Editor, Science

Covid-19 dominated science coverage again in 2021, and deservedly so. The disease garnered two entries on this list of our picks for the most important science stories of the year. But other key discoveries and achievements marked the year in science too, and they deserve more attention. NASA and private companies notched firsts in space. Scientists discovered more about the existence of early humans. And researchers documented how climate change has impacted everything from coral reefs to birds. Covid-19 will continue to garner even more attention next year as scientists work to deal with new variants and develop medical advances to battle the virus. But before you let stories about those topics dominate your reading in 2022, it’s worth it to take a look back at the biggest discoveries and accomplishments of this past year. To that end, here are our picks for the most important science stories of 2021.

The Covid Vaccine Rollout Encounters Hurdles

Last year the biggest science story of the year was that scientists developed two mRNA Covid vaccines in record time. This year the biggest Covid story is that the rollout of those vaccines by Pfizer and Moderna, and one other by Johnson and Johnson, haven’t made their way into a large proportion of the United States population and a significant portion of the world. As of this writing on December 21 , roughly 73 percent of the U.S. population has received one dose, and roughly 61 percent of the U.S. population has been fully vaccinated. An incomplete rollout allowed for a deadly summer surge, driven by the highly contagious Delta variant . Experts pointed out that vaccination rates lagged due to widespread disinformation and misinformation campaigns . It didn’t help that some popular public figures —like Packers’ quarterback Aaron Rodgers , musician Nick Minaj , podcast host Joe Rogan and rapper Ice Cube —chose not to get vaccinated. Luckily, by November, U.S. health officials had approved the Pfizer vaccine for children as young as five, providing another barrier against the deadly disease’s spread, and Covid rates declined. But while the wall against the disease in the U.S. is growing, it is not finished. As cases surge as the Omicron variant spreads around the country, building that wall and reinforcing it with booster shots is critically important. In much of the rest of the world, the wall is severely lacking where populations haven’t been given decent access to the vaccine. Only 8 percent of individuals in low-income countries have received at least one dose of the vaccine, and a WHO Africa report from this fall said that on that continent, less than 10 percent of countries would hit the goal of vaccinating at least 40 percent of their citizens by the end of the year. Globally, less than 60 percent of the population has been vaccinated. The holes in vaccination coverage will allow the virus to continue to kill a large number of individuals, and allow an environment where possibly other dangerous variants can emerge.

Perseverance Notches Firsts on Mars

NASA took a huge step forward in exploring the Red Planet after the rover Perseverance landed safely on Mars in February. Scientists outfitted the vehicle with an ultralight helicopter that successfully flew in the thin Martian atmosphere , a toaster-sized device called MOXIE that successfully converted carbon dioxide to oxygen , and sampling elements that successfully collected rocks from the planet’s floor. All of the achievements will lend themselves to a better understanding of Mars, and how to investigate it in the future. The flight success will give scientists clues on how to build larger helicopters, the oxygen creation will help scientists come up with grander plans for conversion devices, and the rocks will make their way back to Earth for analysis when they are picked up on a future mission. In addition to the rover’s triumphs, other countries notched major firsts too. The United Arab Emirates Hope space probe successfully entered orbit around the planet and is studying the Martian atmosphere and weather. China’s Zhurong rover landed on Mars in May and is exploring the planet’s geology and looking for signs of water. With these ongoing missions, scientists around the world are learning more and more about what the planet is like and how we might better explore it, maybe one day in person.

Is “Dragon Man” a New Species of Human?

The backstory of the skull that scientists used to suggest there was a new species of later Pleistocene human—to join Homo sapiens and Neanderthals—garnered a lot of ink. After the fossil was discovered at a construction site in China nearly 90 years ago, a family hid it until a farmer gave it to a university museum in 2018. Since then, scientists in China pored over the skull—analyzing its features, conducting uranium series dating, and using X-ray fluorescence to compare it to other fossils—before declaring it a new species of archaic human. They dubbed the discovery Homo longi , or “Dragon Man.” The skull had a large cranium capable of holding a big brain, a thick brow and almost square eye sockets—details scientists used to differentiate it from other Homo species. Some scientists questioned whether the find warranted designation as a new species. “It’s exciting because it is a really interesting cranium, and it does have some things to say about human evolution and what’s going on in Asia. But it’s also disappointing that it’s 90 years out from discovery, and it is just an isolated cranium, and you’re not quite sure exactly how old it is or where it fits,” Michael Petraglia of the Smithsonian Institution’s Human Origins Initiative told Smithsonian magazine back in June. Other scientists supported the new species designation, and so the debate continues, and likely will until more fossils are discovered that help to fill in the holes of human history.

Climate Change Wreaks Havoc on Coral Reefs

Increasing natural disasters—forest fires, droughts and heat waves—may be the most noticeable events spurred by climate change; a warming Earth has helped drive a five-fold uptick in such weather-related events over the last 50 years according the a 2021 report by the World Meteorological Organization . But one of the biggest impacts wrought by climate change over the past decade has occurred underwater. Warming temps cause coral reefs to discard the symbiotic algae that help them survive, and they bleach and die. This year a major report from the Global Coral Reef Monitoring Network announced that the oceans lost about 14 percent of their reefs in the decade after 2009, mostly because of climate change. In November, new research showed that less than 2 percent of the coral reefs on the Great Barrier Reef—the world’s largest such feature—escaped bleaching since 1998. That news came just two months after a different study stated that half of coral reefs have been lost since the 1950s , in part due to climate change. The reef declines impact fisheries, local economies based on tourism and coastal developments—which lose the offshore buffer zone from storms the living structures provide. Scientists say if temperatures continue to rise, coral reefs are in serious danger. But not all hope is lost—if humans reduce carbon emissions rapidly now, more reefs will have a better chance of surviving .

The Space Tourism Race Heats Up

This year the famous billionaires behind the space tourism race completed successful missions that boosted more than just their egos. They put a host of civilians in space. Early in July, billionaire Richard Branson and his employees flew just above the boundary of space—a suborbital flight—in Virgin Galactic’s first fully crewed trip. (But Virgin Galactic did delay commercial missions until at least late next year.) Just over a week after Branson’s mission, the world’s richest person, Jeff Bezos, completed Blue Origin’s first crewed suborbital flight with the youngest and oldest travelers to reach space. In October, his company Blue Origin repeated the feat when it took Star Trek actor William Shatner up. A month before that, a crew of four became the first all-civilian crew to circle the Earth from space in Elon Musk’s SpaceX Dragon capsule Resilience. More ambitious firsts for civilians are in the works. In 2022, SpaceX plans to send a retired astronaut and three paying passengers to the International Space Station. And beyond that, Bezos announced Blue Origin hopes to deploy a private space station fit for ten—called “Orbital Reef”—sometime between 2025 and 2030.

WHO Approves First Vaccine Against Malaria

In October, the World Health Organization approved the first vaccine against malaria. The approval was not only a first for that disease, but also for any parasitic disease. The moment was 30 years in the making, as Mosquirix—the brand name of the drug— cost more than $750 million since 1987 to develop and test. Malaria kills nearly a half million individuals a year, including 260,000 children under the age of five. Most of these victims live in sub-Saharan Africa. The new vaccine fights the deadliest of five malaria pathogens and the most prevalent in Africa, and is administered to children under five in a series of four injections. The vaccine is not a silver bullet; it prevents only about 30 percent of severe malaria cases. But one modeling study showed that still could prevent 5.4 million cases and 23,000 deaths in children under five each year. Experts say the vaccine is a valuable tool that should be used in conjunction with existing methods—such as drug combination treatments and insecticide-treated bed nets—to combat the deadly disease.

Discoveries Move Key Dates Back for Humans in the Americas

Two very different papers in two of the world’s most prestigious scientific journals documented key moments of human habitation in the Americas. In September, a study in Science dated footprints found at White Sands National Park to between 21,000 and 23,000 years ago. Researchers estimated the age of the dried tracks known as “ghost prints” using radiocarbon dating of dried ditchgrass seeds found above and below the impressions. Previously, many archaeologists placed the start of human life in the Americas at around 13,000 years ago, at the end of the last Ice Age, based on tools found in New Mexico. The new paper, whose results have been debated , suggests humans actually lived on the continent at the height of the Ice Age. A month after that surprising find, a study in Nature published evidence showing that Vikings lived on North America earlier than previously thought. Researchers examined cut wood left by the explorers at a site in Newfoundland and found evidence in the samples of a cosmic ray event that happened in 993 C.E. The scientists then counted the rings out from that mark and discovered the wood had been cut in 1021 C.E. The find means that the Norse explorers completed the first known crossing of the Atlantic from Europe to the Americas.

Humans Are Affecting the Evolution of Animals

New research published this year shows that humans have both directly and indirectly affected how animals evolve. In probably the starkest example of humans impacting animal evolution, a Science study found a sharp increase in tuskless African elephants after years of poaching. During the Mozambican Civil War from 1977 to 1992, poachers killed so many of the giant mammals with tusks that those females without the long ivory teeth were more likely to pass on their genes. Before the war, 20 percent were tuskless. Now, roughly half of the female elephants are tuskless. Males who have the genetic make-up for tusklessness die , likely before they are born. And killing animals isn’t the only way humans are impacting evolution. A large study in Trends in Ecology and Evolution found that animals are changing shape to deal with rising temps. For example, over various time periods bats grew bigger wings and rabbits sprouted longer ears—both likely to dissipate more heat into the surrounding air. More evidence along those lines was published later in the year in Science Advances . A 40-year-study of birds in a remote, intact patch of Amazon rainforest showed 77 species weighed less on average, and many had longer wings, than they used to. Scientists said the changes likely occurred due to rising temperatures and changes in rainfall.

Antiviral Pills That Fight Covid Show Promising Results

Almost a year after scientists released tests showing the success of mRNA vaccines in fighting Covid, Merck released promising interim test results from a Phase III trial of an antiviral pill. On October 1, the pharmaceutical giant presented data that suggested molnupiravir could cut hospitalizations in half. Ten days later, the company submitted results to the FDA in hopes of gaining emergency use. In mid-November, the U.K. jumped ahead of the U.S. and granted approval for the treatment. By late November, advisers to the FDA recommended emergency authorization of the pill, though it was shown by this time to reduce death or disease by 30—not 50—percent. The drug should be taken —four pills a day for five days—starting within five days of the appearance of symptoms. It works by disrupting SARS-CoV-2’s ability to replicate effectively inside a human cell.

Molnupiravir isn’t the only viral drug with positive results. In November, Pfizer announced its antiviral pill, Paxlovid, was effective against severe Covid. By December, the pharmaceutical giant shared final results that it reduced the risk of hospitalization and death by 88 percent in a key group. News about both pills was welcome , as they are expected to work against all versions of the virus, including Omicron. Though the drugs aren’t as big of a breakthrough as the vaccines, a doctor writing for the New Yorker called them “the most important pharmacologic advance of the pandemic.” Many wealthy countries have already agreed to contracts for molnupiravir, and the Gates Foundation pledged $120 million to help get the pill to poor countries. If approved and distributed fast enough, the oral antivirals can be prescribed in places, like Africa, where vaccines have been lacking. The pills represent another crucial tool, in addition to masks and vaccines, in the fight against Covid.

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Joe Spring is the associate digital science editor for Smithsonian magazine.

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Nih research matters.

December 22, 2021

2021 Research Highlights — Promising Medical Findings

Results with potential for enhancing human health.

With NIH support, scientists across the United States and around the world conduct wide-ranging research to discover ways to enhance health, lengthen life, and reduce illness and disability. Groundbreaking NIH-funded research often receives top scientific honors. In 2021, these honors included Nobel Prizes to five NIH-supported scientists . Here’s just a small sample of the NIH-supported research accomplishments in 2021.

Printer-friendly version of full 2021 NIH Research Highlights

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Advancing COVID-19 treatment and prevention

Amid the sustained pandemic, researchers continued to develop new drugs and vaccines for COVID-19. They found oral drugs that could  inhibit virus replication in hamsters and shut down a key enzyme that the virus needs to replicate. Both drugs are currently in clinical trials. Another drug effectively treated both SARS-CoV-2 and RSV, another serious respiratory virus, in animals. Other researchers used an airway-on-a-chip to screen approved drugs for use against COVID-19. These studies identified oral drugs that could be administered outside of clinical settings. Such drugs could become powerful tools for fighting the ongoing pandemic. Also in development are an intranasal vaccine , which could help prevent virus transmission, and vaccines that can protect against a range of coronaviruses .

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Developments in Alzheimer’s disease research

One of the hallmarks of Alzheimer’s is an abnormal buildup of amyloid-beta protein. A study in mice suggests that antibody therapies targeting amyloid-beta protein could be more effective after enhancing the brain’s waste drainage system . In another study, irisin, an exercise-induced hormone, was found to improve cognitive performance in mice . New approaches also found two approved drugs (described below) with promise for treating AD. These findings point to potential strategies for treating Alzheimer’s. Meanwhile, researchers found that people who slept six hours or less per night in their 50s and 60s were more likely to develop dementia later in life, suggesting that inadequate sleep duration could increase dementia risk.

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New uses for old drugs

Developing new drugs can be costly, and the odds of success can be slim. So, some researchers have turned to repurposing drugs that are already approved for other conditions. Scientists found that two FDA-approved drugs were associated with lower rates of Alzheimer’s disease. One is used for high blood pressure and swelling. The other is FDA-approved to treat erectile dysfunction and pulmonary hypertension. Meanwhile, the antidepressant fluoxetine was associated with reduced risk of age-related macular degeneration. Clinical trials will be needed to confirm these drugs’ effects.

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Making a wireless, biodegradable pacemaker

Pacemakers are a vital part of medical care for many people with heart rhythm disorders. Temporary pacemakers currently use wires connected to a power source outside the body. Researchers developed a temporary pacemaker that is powered wirelessly. It also breaks down harmlessly in the body after use. Studies showed that the device can generate enough power to pace a human heart without causing damage or inflammation.

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Fungi may impair wound healing in Crohn’s disease

Inflammatory bowel disease develops when immune cells in the gut overreact to a perceived threat to the body. It’s thought that the microbiome plays a role in this process. Researchers found that a fungus called  Debaryomyces hansenii  impaired gut wound healing in mice and was also found in damaged gut tissue in people with Crohn’s disease, a type of inflammatory bowel disease. Blocking this microbe might encourage tissue repair in Crohn’s disease.

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Nanoparticle-based flu vaccine

Influenza, or flu, kills an estimated 290,000-650,000 people each year worldwide. The flu virus changes, or mutates, quickly. A single vaccine that conferred protection against a wide variety of strains would provide a major boost to global health. Researchers developed a nanoparticle-based vaccine that protected against a broad range of flu virus strains in animals. The vaccine may prevent flu more effectively than current seasonal vaccines. Researchers are planning a Phase 1 clinical trial to test the vaccine in people.

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A targeted antibiotic for treating Lyme disease

Lyme disease cases are becoming more frequent and widespread. Current treatment entails the use of broad-spectrum antibiotics. But these drugs can damage the patient’s gut microbiome and select for resistance in non-target bacteria. Researchers found that a neglected antibiotic called hygromycin A selectively kills the bacteria that cause Lyme disease. The antibiotic was able to treat Lyme disease in mice without disrupting the microbiome and could make an attractive therapeutic candidate.

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Retraining the brain to treat chronic pain

More than 25 million people in the U.S. live with chronic pain. After a treatment called pain reprocessing therapy, two-thirds of people with mild or moderate chronic back pain for which no physical cause could be found were mostly or completely pain-free. The findings suggest that people can learn to reduce the brain activity causing some types of chronic pain that occur in the absence of injury or persist after healing.

2021 Research Highlights — Basic Research Insights >>

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The Most Popular RAND Research of 2021

Dec 22, 2021

The year began with a deadly attack on American democracy. On January 6, a mob of insurrectionists, persuaded by falsehoods about the 2020 presidential election, laid siege to the U.S. Capitol, attacking law enforcement officers and calling for the sitting vice president to be hanged.

And while 2021 was the year of lifesaving COVID-19 vaccines , it was also the year the pandemic refused to end. Lingering vaccine hesitancy and costly global inequities in access, among other challenges, have prolonged the slog. The virus continues to disrupt daily life and kill thousands each day, having already led to the deaths of millions of people worldwide.

Meanwhile, countless other challenges loomed. For one, global security concerns are rising as the New Year approaches. U.S. rivalries with both China and Russia have become more and more fraught this year.

At RAND, we're not letting up in our efforts to inform evidence-based decisions to confront these and other critical issues. As another extraordinary year draws to a close, we continue to believe that objective, nonpartisan research and analysis has a key role to play in navigating what continues to be a difficult time.

Here are the 10 research projects that resonated most with rand.org readers in 2021.

Photo by NASA and RomoloTavani/Getty Images

China's Quest for Global Primacy

Several RAND reports published this year focus on a wide-ranging challenge that has become central to much of the Biden administration's foreign and economic policy: strategic competition with China.

The most popular of these studies aims to understand how Beijing thinks about its approach to competing with Washington and how China defines success.

The authors explore a strategy in which China aims to establish regional and global primacy by relying on economic prowess and diplomatic maneuvers. China's goal is to gain a competitive edge that the United States cannot undo.

Notably, China would pursue these goals through peaceful methods and attempt to avoid war. However, that doesn't rule out the possibility of militarized crises or even limited conflicts, such as proxy wars.

A Kindergarten teacher cleans and prepares her classroom, where she will begin the new school year teaching virtually because of the COVID-19 pandemic, in Boston, Massachusetts, September 18, 2020

Photo by Brian Snyder/Reuters

Teacher Stress Was a Problem Even Before the Pandemic

According to a RAND survey of former public school teachers, stress was the most common reason they quit their jobs before the pandemic hit. And as many American educators have likely experienced themselves by now, COVID-19 has made this problem even worse.

Three out of every four former teachers we surveyed said that work was “often” or “always” stressful during their most recent year in the classroom. They cited stress nearly twice as often as insufficient pay as their reason for quitting. Almost half of respondents who left the profession early and voluntarily since March 2020 said the pandemic was the main reason for their departure.

“Different COVID-19 stressors affected pandemic teachers differently,” said Melissa Diliberti, lead author of the report. “Insufficient pay and childcare responsibilities drove out younger teachers under 40, while older teachers were more likely to say health conditions made them leave.”

Our researchers continue to track and study this important issue. Elizabeth Steiner , author of another popular 2021 RAND study on this topic, recently noted on Twitter that the impact of teacher stress and burnout goes well beyond any effects on turnover. “Teachers are people; stress affects them just like anyone else,” she said. “Even if they aren't quitting their jobs, they may still experience related physical and mental health concerns.”

Photo by Ivana Cajina/Unsplash

How to Transform the U.S. Mental Health Care System

Now may be the time for major changes to America's mental health care system. That's the takeaway from a comprehensive RAND review of mental health care best practices and innovations, as well as interviews with mental health experts across the country.

Why might this be the moment? The authors note that relevant scientific advances, the growth of Medicaid, and political consensus on the importance of mental health have helped set the stage for transformative change to improve millions of Americans' lives.

Such a transformation would be timely, too, considering the widespread anxiety, depression, grief, anger, and loneliness caused by COVID-19. ( Another 2021 RAND study estimates that as many Americans experienced serious distress in just the first month of the pandemic as during the entire year beforehand.)

“Policymakers have the opportunity now to cut short the pandemic's long tail of mental illness by taking decisive action,” said lead author Ryan McBain .

F-16 Fighting Falcons in formation with two Royal Saudi Air Force F-15E Strike Eagles, after receiving fuel from a KC-135R Stratotanker

Photo by Staff Sgt. Taylor Harrison/U.S. Air Force

The Role of U.S. Airpower in Defeating ISIS

What happened during the air campaign against ISIS in Iraq and Syria? How was airpower employed? And what are some of the lessons the U.S. Air Force and joint force should learn?

In February, RAND released a detailed report that seeks to answer these questions, examining U.S. and coalition use of airpower during Operation Inherent Resolve from August 2014 to March 2019. At more than 500 pages, the report is a trove of information about U.S. airpower.

The authors find that the ISIS caliphate would not have been destroyed without airpower, which provided critical intelligence and firepower, while “put[ting] steel in the backbone of the Iraqi forces,” as one U.S. lieutenant general said. However, even if the coalition had adopted a more aggressive air campaign, it would have accelerated ISIS's defeat only slightly.

An aerial view of the Cave of the Patriarchs, a site sacred to Jews and Muslims, in the Palestinian city of Hebron in the Israeli-occupied West Bank, November 2, 2020

Photo by Ilan Rosenberg/Reuters

Alternatives in the Israeli-Palestinian Conflict

The two-state solution has dominated efforts to resolve the Israeli-Palestinian conflict for decades. But growing doubts about its viability have highlighted the potential importance of alternative approaches. Are there any other solutions that average Israelis and Palestinians would support?

To find out, RAND experts conducted focus groups with more than 270 West Bank Palestinians, Gazan Palestinians, Israeli Jews, and Israeli Arabs. Their findings were published in a February 2021 study.

The researchers asked participants about five options, including a two-state solution. None were acceptable to a majority of both Israelis and Palestinians. In short, Israelis do not believe that the status quo is a problem, while Palestinians do not believe that the status quo has a solution.

“The data highlight the deep distrust and profound animosity of each side for the other,” lead author Daniel Egel said. Unfortunately, these sentiments were on dramatic, deadly display shortly after the RAND report was published, when fighting erupted in Gaza in May.

“It is hard to imagine a departure from present trends and where they lead,” Egel and coauthors wrote, “unless and until strong, courageous leadership among Israelis, Palestinians, and the international community articulates a desire for a better future for all.”

The east front of the U.S. Capitol seen through a shattered door in Washington, D.C., January 7, 2021

Photo by Bill Clark/CQ Roll Call via AP Images

Violent Extremism in America

As the attack on the Capitol highlighted, violent extremism—and especially violent white extremism—is one of the greatest domestic threats facing the United States. To better understand this problem, RAND researchers interviewed former extremists and their loved ones.

What made these people leave extremist movements? For more than half of them, it was an encounter with someone they had been taught to hate, who showed them kindness. “I found myself in situations where I was faced…with my perceived enemy,” one former white supremacist recalled, “and my perceived enemy was treating me normal.”

Insights from the interviews also suggest that America's approach to countering extremism could be improved by focusing on preventing it—as if extremism were a virus—rather than responding only once it becomes a crisis.

“People can escape this; they can find their way out of these extreme ideologies,” said Todd Helmus, one of the study authors. “Those who are knee-deep in QAnon conspiracy theories or so radicalized by the notion that the election was stolen—they, too, can escape that. There's hope at the end of the tunnel.”

An ethnic Uyghur boy stands at the door of his home as Chinese security forces secure the area in Urumqi, China, July 10, 2009

Photo by Nir Elias/Reuters

China's Disappeared Uyghurs: What Satellite Images Reveal

At least one million Uyghurs and other ethnic minorities have vanished into a sprawling network of camps and prisons in western China. Beijing initially denied that these camps existed and then later claimed they were empty.

But open-source satellite data reviewed by RAND researchers showed that most of these facilities appeared to be active. The images revealed bright-lit compounds, cars in parking lots, walkways plowed of snow, walls of barbed wire, and a sudden rush to build what appear to be fortified preschools.

This imagery has provided a bird's-eye view of what's happening in the vast Uyghur homeland of Xinjiang, which Chinese officials have turned into one of the world's most sophisticated surveillance states.

“It's breathtaking how much satellite imagery is publicly available,” said RAND's Edmund Burke , who worked on the project. “You see stories about one particular camp, or hear one harrowing account from someone who got out of Xinjiang. We realized we could advance those stories and help provide a broader account of what is happening there.”

China's mistreatment of the Uyghur people is likely to remain center stage. Alleged Chinese human rights abuses in Xinjiang formed the basis of a recently announced U.S. diplomatic boycott of next year's Winter Olympics in Beijing.

Photo by Yuriy Panyukov/Adobe Stock

A U.S. Grand Strategy of Restraint

There is growing public interest in rethinking America's role in the world. And as the pandemic and the recession continue, some advocates are calling for the United States to reevaluate its national security strategy and spending.

One option is to adopt a grand strategy of restraint in which America takes a more cooperative approach toward other powers, reduces the size of its military, and ends or renegotiates some security commitments.

One of the most popular RAND reports of 2021 explores the policy implications of embarking down this path. Its conclusion: Those in favor of this approach need to provide more details.

“Advocates of restraint have offered a clear critique about recent U.S. grand strategy as well as broad policy proposals for key regions,” said lead author Miranda Priebe . “To generate more specific policy implications for each region, advocates of restraint need to expand on their logic and conduct additional analysis.”

A masked woman in surgical scrubs signs for personal protective equipment delivery

Photo by Marc A. Hermann/MTA New York City Transit/CC BY 2.0

The Pandemic and Lessons for Criminal Justice Reform

As COVID-19 swept through the United States in 2020, criminal justice entities—including law enforcement, court systems, and corrections facilities—had to adapt to slow the spread of disease. At the same time, national protests in response to the murder of George Floyd and other Black Americans created significant pressure for criminal justice reform.

How did this remarkable period affect the criminal justice system? And how might it shape the post-pandemic future? RAND researchers convened a series of workshops to find out and published their findings in a popular August 2021 report.

The pandemic forced the criminal justice system to adapt in unprecedented ways. Many of these changes, such as scaling back low-level arrests and releasing people who were serving minor sentences, also aligned with growing demands for reform. As a result, the authors conclude that it may be difficult or even impossible to fully separate the effects of the pandemic from the broader national environment created by calls for justice reform.

Whatever drove the many changes in America's criminal justice system, this dynamic time highlighted new possibilities for the future and identified critical questions still to be answered.

Photo by stevecoleimages/Getty Images

U.S. Prescription Drug Prices Are 2.5 Times Those in Comparison Countries

Prescription drug prices in the United States are, on average, 2.56 times those in 32 other countries. That's according to the most popular RAND research report of 2021.

Brand-name drugs are the primary driver of America's higher prescription drug prices, as this stop-motion animation highlights: For branded drugs, U.S. prices are 3.44 times those in other nations, on average. Prices for generic drugs, on the other hand, are slightly lower in the United States than in most other countries.

“For the generic drugs that make up a large majority of the prescriptions written in the United States, our costs are lower,” lead author Andrew Mulcahy said. “It's just for the brand-name drugs that we pay through the nose.”

Price transparency may help address the problem of rising U.S. prescription drug spending, which is estimated to account for more than 10 percent of the country's total health care spending.

— Pete Wilmoth

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RAND Video Highlights of 2021

Dec 20, 2021

RAND Commentary Highlights of 2021

Dec 21, 2021

MARK H. EBELL, MD, MS, AND ROLAND GRAD, MD, MSc

Am Fam Physician. 2022;106(1):61-69

Published online June 1, 2022.

Author disclosure: Dr. Ebell is cofounder and editor-in-chief of Essential Evidence Plus; see Editor’s Note. Dr. Grad has no relevant financial relationships.

This article summarizes the top 20 research studies of 2021 identified as POEMs (patient-oriented evidence that matters) that did not address the COVID-19 pandemic. Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists prevent adverse cardiovascular and renal outcomes in patients with type 2 diabetes mellitus and also reduce all-cause and cardiovascular mortality. Most older adults (mean age, 75 years) with prediabetes do not progress to diabetes. Among patients in this age group with type 2 diabetes treated with medication, an A1C level of less than 7% is associated with increased risk of hospitalization for hypoglycemia, especially when using a sulfonylurea or insulin. For patients with chronic low back pain, exercise, nonsteroidal anti-inflammatory drugs, duloxetine, and opioids were shown to be more effective than control in achieving a 30% reduction in pain, but self-discontinuation of duloxetine and opioids was common. There is no clinically important difference between muscle relaxants and placebo in the treatment of nonspecific low back pain. In patients with chronic pain, low- to moderate-quality evidence supports exercise, yoga, massage, and mindfulness-based stress reduction. For acute musculoskeletal pain, acetaminophen, 1,000 mg, plus ibuprofen, 400 mg, without an opioid is a good option. Regarding screening for colorectal cancer, trial evidence supports performing fecal immunochemical testing every other year. For chronic constipation, evidence supports polyethylene glycol, senna, fiber supplements, magnesium-based products, and fruit-based products. The following abdominal symptoms carry a greater than 3% risk of cancer or inflammatory bowel disease: dysphagia or change in bowel habits in men; rectal bleeding in women; and abdominal pain, change in bowel habits, or dyspepsia in men and women older than 60 years. For secondary prevention in those with established arteriosclerotic cardiovascular disease, 81 mg of aspirin daily appears to be effective. The Framingham Risk Score and the Pooled Cohort Equations both overestimate the risk of cardiovascular events. Over 12 years, no association between egg consumption and cardiovascular events was demonstrated. Gabapentin, pregabalin, duloxetine, and venlafaxine provide clinically meaningful improvements in chronic neuropathic pain. In patients with moderate to severe depression, initial titration above the minimum starting dose of antidepressants in the first eight weeks of treatment is not more likely to increase response. In adults with iron deficiency anemia, adding vitamin C to oral iron has no effect. In children with pharyngitis, rhinosinusitis, acute bronchitis, or acute otitis media, providing education combined with a take-and-hold antibiotic prescription results in 1 in 4 of those children eventually taking an antibiotic.

Annually for 23 years, a team of clinicians has systematically reviewed English-language medical journals to identify the research most likely to change and improve primary care. The team includes experts in family medicine, pharmacology, hospital medicine, and women’s health. 1 , 2

The goal of this process is to identify POEMs (patient-oriented evidence that matters). A POEM must report at least one patient-oriented outcome, such as improvement in symptoms, morbidity, or mortality. It should also be free of important methodologic bias, making the results valid and trustworthy. Finally, if the results were applied in practice, some physicians would change what they do by adopting a new practice or discontinuing an old one shown to be ineffective or harmful. Adopting POEMs in clinical practice should improve patient outcomes. Of more than 20,000 research studies published in 2021 in the journals reviewed by the POEMs team, only 260 met criteria for validity, relevance, and practice change. These POEMs are emailed daily to subscribers of Essential Evidence Plus (Wiley-Blackwell, Inc.).

The Canadian Medical Association purchases a POEMs subscription for its members, many of whom receive the daily POEM. As these physicians read each POEM, they can rate it using a validated questionnaire. This process is called the Information Assessment Method ( https://www.mcgill.ca/iam ). POEM ratings address the domains of clinical relevance, cognitive impact, use in practice, and expected health benefits if that POEM is applied to a specific patient. 2 , 3 In 2021, each of the 260 daily POEMs were rated by an average of 1,189 physicians.

In this article, the 11th installment of our annual series ( https://www.aafp.org/pubs/afp/content/top-poems.html ), we present the 20 most clinically relevant POEMs of 2021 as determined by Canadian Medical Association members. Looking beyond COVID-19, our patients continue to face the usual (and unusual) health problems of everyday life. Thus, we summarize the clinical questions and bottom-line answers for research studies about a variety of topics that were identified as top 20 POEMs, followed by a brief discussion. This set of 20 POEMs includes the most relevant practice guidelines of the year. The full POEMs are available online at https://www.aafp.org/pubs/afp/content/top-poems/2021.html .

The five most highly rated POEMs in 2021, and eight of the top 15, were about the COVID-19 vaccines and their effectiveness in different populations. Because of the emergence of variants and widespread endorsement of the vaccine by family physicians, these POEMs are not as likely to lead to practice changes as they were when originally published. One additional COVID-19 POEM reported the incidence of myocarditis following vaccination with the Pfizer BioNTech and Moderna mRNA vaccines in U.S. military personnel. The incidence of approximately 4 more cases than expected per 100,000 patients is significantly lower than the more than 300 per 100,000 patients seen among those with SARS-CoV-2 infection. 4 The rest of this article includes POEMs not related to the COVID-19 pandemic.

Type 2 Diabetes Mellitus

The first three POEMs in this category are about the management of type 2 diabetes ( Table 1 ) . 5 – 8 The first study identified 2,482 adults with a mean age of 75 years who had prediabetes (defined as an A1C level between 5.7% and 6.4%, a fasting glucose level between 100 and 125 mg per dL [5.55 and 6.94 mmol per L], or both). 5 Over an average of 6.5 years, only 8% to 9% of patients progressed to diabetes, many regressed to normoglycemia, and the remainder stayed at prediabetic levels. These results will help reassure physicians and avoid overtreatment of older patients with prediabetes. Of note, the U.S. Preventive Services Task Force does not recommend screening for prediabetes or type 2 diabetes beyond 70 years of age. 9

A study in the United Kingdom identified 6,288 people 70 years and older with type 2 diabetes and three consecutive A1C measurements of less than 7%. 6 Approximately 90% were taking a sulfonylurea. Compared with a similar group of people with type 2 diabetes who did not have A1C levels of less than 7% and were not taking a sulfonylurea, those with tight control were 2.5 times more likely to be hospitalized for severe hypoglycemia, with a 1 in 7 risk of hospitalization over 10 years. Use of a sulfonylurea or insulin was associated with severe hypoglycemia and death. A more relaxed A1C target of 7.0% to 8.0% is more appropriate, especially for older patients, and sulfonylureas should be used with caution.

A systematic review assessed the effectiveness of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes. 7 The authors did not receive pharmaceutical funding. Both classes of drugs reduced all-cause mortality, cardiovascular mortality, nonfatal myocardial infarction, and kidney failure. SGLT-2 inhibitors were more effective at reducing hospital admission, whereas GLP-1 receptor agonists were more likely to reduce nonfatal stroke. The absolute benefit of treatment increased with a patient’s cardiac risk. For example, over five years, there were 2 to 5 fewer deaths per 1,000 patients at low cardiac risk compared with 24 to 48 fewer deaths per 1,000 patients at the highest risk. A useful calculator that allows estimates of benefit at various risk levels is available at https://magicevidence.org/match-it/200820dist .

The final study is a meta-analysis that examined the effect of SGLT-2 inhibitors in patients with and without type 2 diabetes or heart failure. 8 These drugs similarly reduced all-cause and cardiovascular mortality in patients with or without type 2 diabetes and with or without heart failure (overall hazard ratio for all-cause mortality = 0.84 [95% CI, 0.78 to 0.91]). SGLT-2 inhibitors reduced the progression of renal disease in all patients.

Musculoskeletal Conditions

The next, and largest, category of POEMs addresses musculoskeletal conditions ( Table 2 ) . 10 – 14 The first three present research on low back pain, one of the most challenging conditions in primary care. The first POEM is a systematic review of a broad range of therapies for chronic low back pain. 10 The review included 63 randomized controlled trials (RCTs) reporting a clinical response, generally a reduction in pain of at least 30%, to any one of 15 interventions. Exercise was effective at reducing pain (number needed to treat [NNT] = 7) and had a sustained benefit. Although other medical therapies such as oral nonsteroidal anti-inflammatory drugs (NNT = 6), duloxetine (Cymbalta; NNT = 10), and opioids (NNT = 16) also reduced pain, they did not have sustained benefits and were associated with adverse effects. Lower-quality data suggest that manipulation and topical capsaicin are also effective.

Another systematic review, this time looking at muscle relaxants for nonspecific low back pain, found small reductions in pain intensity that were not clinically important and not seen when only the highest-quality studies were included. 11 We have said it before—it is inappropriate to routinely prescribe muscle relaxants for low back pain.

The next study showed the power of language on health outcomes. 12 Patients with low back pain and no red flags on magnetic resonance imaging (MRI) or indications for surgery were randomized to receive their MRI results in one of two ways: by stating that all findings were normal and incidental or age-related or by stating that all findings were normal and incidental or age-related but also including words such as degeneration, tears, ruptures, and neural compression. Patients receiving the easily misinterpreted version of the report that used alarming words had more pain, lower self-efficacy, and less function over six weeks of follow-up compared with patients who were essentially told their findings were normal. Physicians should develop their own script for sharing results that avoids catastrophizing language.

The next POEM studied several types of musculoskeletal pain other than back pain. 13 Patients presenting in the emergency department with acute musculoskeletal pain were randomized to one of five single-dose pain regimens: (1) acetaminophen, 1,000 mg, with ibuprofen, 400 mg; (2) acetaminophen, 1,000 mg, with ibuprofen, 800 mg; (3) acetaminophen, 300 mg, with codeine, 30 mg; (4) acetaminophen, 300 mg, with hydrocodone, 5 mg; or (5) acetaminophen, 325 mg, with oxycodone, 5 mg. Pain scores decreased by about 3 points on a 10-point scale in all five groups at one hour and by about 4.5 points at two hours, with no significant difference between groups. About 1 out of 4 patients in each group required rescue pain medication, again with no difference. Nausea and vomiting were more common in patients receiving an opioid. Thus, a good choice is acetaminophen, 1,000 mg, plus ibuprofen, 400 mg, or even acetaminophen alone, without an opioid. 15

A large systematic review asked the question: Which nondrug therapies are effective for chronic musculoskeletal pain? 14 For chronic low back pain, exercise, massage, yoga, cognitive behavior therapy, mindfulness-based stress reduction, acupuncture, spinal manipulation, low-level laser therapy, and rehabilitation all reduced pain and/or improved function. There was evidence for the use of exercise, massage, low-level laser therapy, acupuncture, and Pilates in the treatment of chronic neck pain. Only exercise and cognitive behavior therapy were helpful for knee osteoarthritis. There is evidence only for the use of exercise and manual therapies for the treatment of hip osteoarthritis. Patients with fibromyalgia benefited from cognitive behavior therapy, myofascial release massage, tai chi, qi gong, acupuncture, rehabilitation, and exercise.

Gastrointestinal

The next set of POEMs addresses colorectal cancer screening, constipation treatment, and vague abdominal symptoms ( Table 3 ) . 16 – 18 Most countries screen for colorectal cancer using fecal immunochemical testing (FIT) as the initial method. Canada includes flexible sigmoidoscopy as an option, and the United States most commonly uses colonoscopy. The first POEM on gastrointestinal conditions is a Norwegian RCT that invited previously unscreened adults 50 to 74 years of age to undergo flexible sigmoidoscopy (52% had the procedure) or FIT every two years (68% had at least one test). 16 Although flexible sigmoidoscopy initially identified more cancers and advanced adenomas, FIT surpassed it over time, with a cancer detection rate of 0.49% after three rounds of FIT testing vs. 0.27% with flexible sigmoidoscopy. This is a very important point—screening programs must be compared over time, not just after a single round, using different tests. RCTs comparing FIT with colonoscopy over time are underway.

In a systematic review of over-the-counter treatments for chronic constipation, polyethylene glycol (Miralax) and senna were the most effective initial options. 17 Fiber supplements, other stimulant laxatives, magnesium-based products, and fruit-based products were also effective.

The final POEM evaluated the predictive value of common abdominal symptoms for cancer or inflammatory bowel disease. 18 Combinations of symptoms, such as change in bowel habits with rectal bleeding, were more predictive but varied by age and sex. Dysphagia or changes in bowel habits in men and rectal bleeding in women should prompt referral for further workup to exclude cancer or inflammatory bowel disease. Dyspepsia was largely unhelpful, except in patients older than 60 years. The severity and duration of gastrointestinal symptoms and whether they appear to be progressive were not part of this study but are important additional factors.

Cardiovascular Disease

Four POEMs about cardiovascular disease made the top 20 list ( Table 4 ) . 19 – 22 The first two addressed prevention. One was a large pragmatic trial that randomized 15,076 patients with established arteriosclerotic cardiovascular disease to 81 mg or 325 mg of aspirin daily and evaluated the likelihood of death, nonfatal myocardial infarction, or nonfatal stroke after a median of two years. 19 There was no difference between groups for these outcomes (7.3% for 81 mg and 7.5% for 325 mg) and no difference in hospitalization for major bleeding. The trial was a bit messy, with 7% in the 81-mg group switching to 325 mg and 42% in the 325-mg group switching to the lower dose. It is not clear why so many switched to the lower dose, but, for whatever reason, there is no advantage with the higher dose.

U.S. guidelines for cardiovascular prevention all begin with an assessment of cardiovascular risk using the Pooled Cohort Equations. The second cardiovascular POEM warns us that this score significantly overestimates risk. The Canadian researchers identified more than 80,000 people 40 to 79 years of age and estimated their risk using the Framingham Risk Score and the Pooled Cohort Equations. 20 Cardiovascular risk estimates from both tools were about twice as high as the real-world risk. The overestimates occurred in all groups regardless of age and sex but tended to be larger in younger patients. This is important for shared decision-making. For example, an estimated risk of 10% based on the Pooled Cohort Equations might lead to prescribing a statin, but the true cardiovascular risk may be significantly lower.

The U.S. Preventive Services Task Force draft guidelines recommend prescribing a statin for adults 40 to 75 years of age with at least one cardiovascular risk factor (dyslipidemia, diabetes, hypertension, or smoking) and an estimated 10-year cardiovascular risk of 10% or greater. Statins should be selectively offered to those with a risk factor and a risk between 7.5% and 10% because the benefits are smaller than those at higher risk. 23

Another calibration issue was addressed by the third POEM. The researchers compared the blood pressure measurements used by researchers in SPRINT (Systolic Blood Pressure Intervention Trial) with those recorded by the patients’ regular primary care physicians. 21 The physician-recorded systolic blood pressure measurements were about 5 to 7 mm Hg higher; therefore, the SPRINT recommendations to lower systolic blood pressure to less than 120 mm Hg need to be interpreted accordingly—in the real world, achieving a level of 130 mm Hg is probably similar to 120 mm Hg in the trial setting.

The next POEM made our day, as egg lovers. This systematic review included 23 observational studies with nearly 1.4 million patients. 22 Eating more eggs was not shown to increase the risk of cardiovascular events. In fact, compared with eating one or no eggs per day, those eating more than one egg per day had a decreased risk of coronary disease (hazard ratio = 0.89; 95% CI, 0.86 to 0.93).

Miscellaneous

Four top POEMs do not fall easily into a single category ( Table 5 ) . 24 – 27 A systematic review addressed treatment of chronic pain caused by diabetic neuropathy or postherpetic neuralgia. 24 It included only studies reporting an outcome of clinically meaningful response, defined as a 30% improvement on a pain or function score. Moderate-quality evidence supported the use of the anticonvulsants gabapentin (Neurontin) and pregabalin (Lyrica) and the serotonin-norepinephrine reuptake inhibitors duloxetine and venlafaxine, and low-quality evidence supported the use of rubefacients (usually salicylates). The NNT was 7 or 8 for all the identified therapies. Opioid studies were of low quality and also showed more harms (number needed to harm = 12). Only a few trials with low-certainty evidence studied acupuncture and tricyclic antidepressants.

A systematic review identified RCTs that compared treatment of moderate to severe depression using the minimum licensed dose of a selective serotonin reuptake inhibitor, venlafaxine, or mirtazapine (Remeron) with a dosing regimen that allowed titration to higher doses. 25 There was no improvement in the balance of effectiveness and harms between taking the minimum dose and titrating to higher doses, although patients taking venlafaxine may respond to a higher dose if they show no response to the minimum dose.

The next POEM identified 436 children with pharyngitis, rhinosinusitis, acute bronchitis, or acute otitis media whose treating physician had reasonable doubts about the need for an antibiotic. 26 Patients were randomized to no antibiotics; an immediate antibiotic; or an antibiotic prescription to be filled only if the child had fever, felt much worse after 24 hours, or was not improving after a longer period (varied by type of infection). Only 25% of children in the delayed antibiotic group and 12% in the no antibiotic group ultimately filled a prescription, and there was no difference between these groups and the immediate antibiotic group in the duration of symptoms (eight days) or complications. Gastrointestinal symptoms and cost were higher in those receiving an antibiotic.

Finally, clinicians have long recommended that people taking iron supplements also take vitamin C because it theoretically improves absorption. A study tested the theory by randomizing 440 adults with iron deficiency anemia to ferrous succinate, 100 mg, plus vitamin C, 200 mg, or to ferrous succinate alone, each given every eight hours. There was no difference in hemoglobin or serum ferritin levels at three months. 27

Practice Guidelines

POEMs sometimes summarize high-impact clinical practice guidelines. Key messages from the three highest-rated guidelines, which address antibiotics for common infections, non–low back musculoskeletal injuries, and tobacco screening and cessation, are summarized in Table 6 . 28 – 30

Editor's Note: This article was cowritten by Dr. Mark Ebell, deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell, Inc. Because of Dr. Ebell’s dual roles and ties to Essential Evidence Plus, the concept for this article was independently reviewed and approved by a group of AFP ’s medical editors. In addition, the article underwent peer review and editing by four of AFP ’s medical editors. Dr. Ebell was not involved in the editorial decision-making process.—Sumi Sexton, MD, Editor-in-Chief

The authors thank Wiley-Blackwell, Inc., for giving permission to excerpt the POEMs; Drs. Allen Shaughnessy, Henry Barry, David Slawson, Nita Kulkarni, and Linda Speer for selecting and writing the original POEMs; the academic family medicine fellows and faculty of the University of Missouri–Columbia for their work as peer reviewers; Canadian Medical Association Joule for supporting the POEMs CME program in Canada; Pierre Pluye, PhD, for codeveloping the Information Assessment Method; and Maria Vlasak for her assistance with copyediting the POEMs.

Shaughnessy AF, Slawson DC, Bennett JH. Becoming an information master: a guidebook to the medical information jungle. J Fam Pract. 1994;39(5):489-499.

Ebell MH, Barry HC, Slawson DC, et al. Finding POEMs in the medical literature. J Fam Pract. 1999;48(5):350-355.

Grad RM, Pluye P, Mercer J, et al. Impact of research-based synopses delivered as daily e-mail: a prospective observational study. J Am Med Inform Assoc. 2008;15(2):240-245.

Montgomery J, Ryan M, Engler R, et al. Myocarditis following immunization with mRNA COVID-19 vaccines in members of the US military. JAMA Cardiol. 2021;6(10):1202-1206.

• Rooney MR, Rawlings AM, Pankow JS, et al. Risk of progression to diabetes among older adults with prediabetes [published correction appears in JAMA Intern Med . 2021;181(4):570]. JAMA Intern Med. 2021;181(4):511-519.

Ling S, Zaccardi F, Lawson C, et al. Glucose control, sulfonylureas, and insulin treatment in elderly people with type 2 diabetes and risk of severe hypoglycemia and death: an observational study. Diabetes Care. 2021;44(4):915-924.

• Palmer SC, Tendal B, Mustafa RA, et al. Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials [published correction appears in BMJ . 2022;376:o109]. BMJ. 2021;372:m4573.
• Salah HM, Al'Aref SJ, Khan MS, et al. Effect of sodium-glucose cotransporter 2 inhibitors on cardiovascular and kidney outcomes. Systematic review and meta-analysis of randomized placebo-controlled trials. Am Heart J. 2021;232:10-22.

U.S. Preventive Services Task Force. Final recommendation statement. Prediabetes and type 2 diabetes: screening. August 24, 2021. Accessed March 15, 2022. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/screening-for-prediabetes-and-type-2-diabetes

Kolber MR, Ton J, Thomas B, et al. PEER systematic review of randomized controlled trials: management of chronic low back pain in primary care. Can Fam Physician. 2021;67(1):e20-e30.

Cashin AG, Folly T, Bagg MK, et al. Efficacy, acceptability, and safety of muscle relaxants for adults with non-specific low back pain: systematic review and meta-analysis. BMJ. 2021;374:n1446.

Rajasekaran S, Dilip Chand Raja S, Pushpa BT, et al. The catastrophization effects of an MRI report on the patient and surgeon and the benefits of ‘clinical reporting’: results from an RCT and blinded trials. Eur Spine J. 2021;30(7):2069-2081.

Bijur PE, Friedman BW, Irizarry E, et al. A randomized trial comparing the efficacy of five oral analgesics for treatment of acute musculoskeletal extremity pain in the emergency department. Ann Emerg Med. 2021;77(3):345-356.

Skelly AC, Chou R, Dettori JR, et al. Noninvasive nonpharmacological treatment for chronic pain: a systematic review update. Comparative Effectiveness Review no. 227. Agency for Healthcare Research and Quality; 2020. Accessed May 13, 2022. https://www.ncbi.nlm.nih.gov/books/NBK556229/

Gong J, Colligan M, Kirkpatrick C, et al. Oral paracetamol versus combination oral analgesics for acute musculoskeletal injuries. Ann Emerg Med. 2019;74(4):521-529.

Randel KR, Schult AL, Botteri E, et al. Colorectal cancer screening with repeated fecal immunochemical test versus sigmoidoscopy: baseline results from a randomized trial. Gastroenterology. 2021;160(4):1085-1096.e5.

Rao SSC, Brenner DM. Efficacy and safety of over-the-counter therapies for chronic constipation: an updated systematic review. Am J Gastroenterol. 2021;116(6):1156-1181.

Herbert A, Rafiq M, Pham TM, et al. Predictive values for different cancers and inflammatory bowel disease of 6 common abdominal symptoms among more than 1.9 million primary care patients in the UK: a cohort study. PLoS Med. 2021;18(8):e1003708.

Jones WS, Mulder H, Wruck LM, et al.; ADAPTABLE Team. Comparative effectiveness of aspirin dosing in cardiovascular disease. N Engl J Med. 2021;384(21):1981-1990.

Ko DT, Sivaswamy A, Sud M, et al. Calibration and discrimination of the Framingham Risk Score and the Pooled Cohort Equations. CMAJ. 2020;192(17):E442-E449.

Drawz PE, Agarwal A, Dwyer JP, et al. Concordance between blood pressure in the systolic blood pressure intervention trial and in routine clinical practice. JAMA Intern Med. 2020;180(12):1655-1663.

Krittanawong C, Narasimhan B, Wang Z, et al. Association between egg consumption and risk of cardiovascular outcomes: a systematic review and meta-analysis. Am J Med. 2021;134(1):76-83.e2.

U.S. Preventive Services Task Force. Draft recommendation statement. Statin use for the primary prevention of cardiovascular disease in adults: preventive medication. February 22, 2022. Accessed March 10, 2022. https://www.uspreventiveservicestaskforce.org/uspstf/draft-recommendation/statin-use-primary-prevention-cardiovascular-disease-adults

Falk J, Thomas B, Kirkwood J, et al. PEER systematic review of randomized controlled trials: management of chronic neuropathic pain in primary care. Can Fam Physician. 2021;67(5):e130-e140.

Furukawa TA, Salanti G, Cowen PJ, et al. No benefit from flexible titration above minimum licensed dose in prescribing antidepressants for major depression: systematic review. Acta Psychiatr Scand. 2020;141(5):401-409.

Mas-Dalmau G, Villanueva López C, Gorrotxategi PG, et al.; DAP Pediatrics Group. Delayed antibiotic prescription for children with respiratory infections: a randomized trial. Pediatrics. 2021;147(3):e20201323.

Li N, Zhao G, Wu W, et al. The efficacy and safety of vitamin C for iron supplementation in adult patients with iron deficiency anemia: A randomized clinical trial. JAMA Netw Open. 2020;3(11):e2023644.

Lee RA, Centor RM, Humphrey LL, et al. Appropriate use of short-course antibiotics in common infections: best practice advice from the American College of Physicians. Ann Intern Med. 2021;174(6):822-827.

Qaseem A, McLean RM, O'Gurek D, et al. Nonpharmacologic and pharmacologic management of acute pain from non–low back, musculoskeletal injuries in adults: a clinical guideline from the American College of Physicians and American Academy of Family Physicians. Ann Intern Med. 2020;173(9):739-748.

Krist AH, Davidson KW, Mangione CM, et al. Interventions for tobacco smoking cessation in adults, including pregnant persons. US Preventive Services Task Force recommendation statement. JAMA. 2021;325(3):265-279.

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The 10 Most Significant Education Studies of 2021

From reframing our notion of “good” schools to mining the magic of expert teachers, here’s a curated list of must-read research from 2021.

It was a year of unprecedented hardship for teachers and school leaders. We pored through hundreds of studies to see if we could follow the trail of exactly what happened: The research revealed a complex portrait of a grueling year during which persistent issues of burnout and mental and physical health impacted millions of educators. Meanwhile, many of the old debates continued: Does paper beat digital? Is project-based learning as effective as direct instruction? How do you define what a “good” school is?

Other studies grabbed our attention, and in a few cases, made headlines. Researchers from the University of Chicago and Columbia University turned artificial intelligence loose on some 1,130 award-winning children’s books in search of invisible patterns of bias. (Spoiler alert: They found some.) Another study revealed why many parents are reluctant to support social and emotional learning in schools—and provided hints about how educators can flip the script.

1. What Parents Fear About SEL (and How to Change Their Minds)

When researchers at the Fordham Institute asked parents to rank phrases associated with social and emotional learning , nothing seemed to add up. The term “social-emotional learning” was very unpopular; parents wanted to steer their kids clear of it. But when the researchers added a simple clause, forming a new phrase—”social-emotional & academic learning”—the program shot all the way up to No. 2 in the rankings.

What gives?

Parents were picking up subtle cues in the list of SEL-related terms that irked or worried them, the researchers suggest. Phrases like “soft skills” and “growth mindset” felt “nebulous” and devoid of academic content. For some, the language felt suspiciously like “code for liberal indoctrination.”

But the study suggests that parents might need the simplest of reassurances to break through the political noise. Removing the jargon, focusing on productive phrases like “life skills,” and relentlessly connecting SEL to academic progress puts parents at ease—and seems to save social and emotional learning in the process.

2. The Secret Management Techniques of Expert Teachers

In the hands of experienced teachers, classroom management can seem almost invisible: Subtle techniques are quietly at work behind the scenes, with students falling into orderly routines and engaging in rigorous academic tasks almost as if by magic. 

That’s no accident, according to new research . While outbursts are inevitable in school settings, expert teachers seed their classrooms with proactive, relationship-building strategies that often prevent misbehavior before it erupts. They also approach discipline more holistically than their less-experienced counterparts, consistently reframing misbehavior in the broader context of how lessons can be more engaging, or how clearly they communicate expectations.

Focusing on the underlying dynamics of classroom behavior—and not on surface-level disruptions—means that expert teachers often look the other way at all the right times, too. Rather than rise to the bait of a minor breach in etiquette, a common mistake of new teachers, they tend to play the long game, asking questions about the origins of misbehavior, deftly navigating the terrain between discipline and student autonomy, and opting to confront misconduct privately when possible.

3. The Surprising Power of Pretesting

Asking students to take a practice test before they’ve even encountered the material may seem like a waste of time—after all, they’d just be guessing.

But new research concludes that the approach, called pretesting, is actually more effective than other typical study strategies. Surprisingly, pretesting even beat out taking practice tests after learning the material, a proven strategy endorsed by cognitive scientists and educators alike. In the study, students who took a practice test before learning the material outperformed their peers who studied more traditionally by 49 percent on a follow-up test, while outperforming students who took practice tests after studying the material by 27 percent.

The researchers hypothesize that the “generation of errors” was a key to the strategy’s success, spurring student curiosity and priming them to “search for the correct answers” when they finally explored the new material—and adding grist to a 2018 study that found that making educated guesses helped students connect background knowledge to new material.

Learning is more durable when students do the hard work of correcting misconceptions, the research suggests, reminding us yet again that being wrong is an important milestone on the road to being right.

4. Confronting an Old Myth About Immigrant Students

Immigrant students are sometimes portrayed as a costly expense to the education system, but new research is systematically dismantling that myth.

In a 2021 study , researchers analyzed over 1.3 million academic and birth records for students in Florida communities, and concluded that the presence of immigrant students actually has “a positive effect on the academic achievement of U.S.-born students,” raising test scores as the size of the immigrant school population increases. The benefits were especially powerful for low-income students.

While immigrants initially “face challenges in assimilation that may require additional school resources,” the researchers concluded, hard work and resilience may allow them to excel and thus “positively affect exposed U.S.-born students’ attitudes and behavior.” But according to teacher Larry Ferlazzo, the improvements might stem from the fact that having English language learners in classes improves pedagogy , pushing teachers to consider “issues like prior knowledge, scaffolding, and maximizing accessibility.”

5. A Fuller Picture of What a ‘Good’ School Is

It’s time to rethink our definition of what a “good school” is, researchers assert in a study published in late 2020.⁣ That’s because typical measures of school quality like test scores often provide an incomplete and misleading picture, the researchers found.

The study looked at over 150,000 ninth-grade students who attended Chicago public schools and concluded that emphasizing the social and emotional dimensions of learning—relationship-building, a sense of belonging, and resilience, for example—improves high school graduation and college matriculation rates for both high- and low-income students, beating out schools that focus primarily on improving test scores.⁣

“Schools that promote socio-emotional development actually have a really big positive impact on kids,” said lead researcher C. Kirabo Jackson in an interview with Edutopia . “And these impacts are particularly large for vulnerable student populations who don’t tend to do very well in the education system.”

The findings reinforce the importance of a holistic approach to measuring student progress, and are a reminder that schools—and teachers—can influence students in ways that are difficult to measure, and may only materialize well into the future.⁣

6. Teaching Is Learning

One of the best ways to learn a concept is to teach it to someone else. But do you actually have to step into the shoes of a teacher, or does the mere expectation of teaching do the trick?

In a 2021 study , researchers split students into two groups and gave them each a science passage about the Doppler effect—a phenomenon associated with sound and light waves that explains the gradual change in tone and pitch as a car races off into the distance, for example. One group studied the text as preparation for a test; the other was told that they’d be teaching the material to another student.

The researchers never carried out the second half of the activity—students read the passages but never taught the lesson. All of the participants were then tested on their factual recall of the Doppler effect, and their ability to draw deeper conclusions from the reading.

The upshot? Students who prepared to teach outperformed their counterparts in both duration and depth of learning, scoring 9 percent higher on factual recall a week after the lessons concluded, and 24 percent higher on their ability to make inferences. The research suggests that asking students to prepare to teach something—or encouraging them to think “could I teach this to someone else?”—can significantly alter their learning trajectories.

7. A Disturbing Strain of Bias in Kids’ Books

Some of the most popular and well-regarded children’s books—Caldecott and Newbery honorees among them—persistently depict Black, Asian, and Hispanic characters with lighter skin, according to new research .

Using artificial intelligence, researchers combed through 1,130 children’s books written in the last century, comparing two sets of diverse children’s books—one a collection of popular books that garnered major literary awards, the other favored by identity-based awards. The software analyzed data on skin tone, race, age, and gender.

Among the findings: While more characters with darker skin color begin to appear over time, the most popular books—those most frequently checked out of libraries and lining classroom bookshelves—continue to depict people of color in lighter skin tones. More insidiously, when adult characters are “moral or upstanding,” their skin color tends to appear lighter, the study’s lead author, Anjali Aduki,  told The 74 , with some books converting “Martin Luther King Jr.’s chocolate complexion to a light brown or beige.” Female characters, meanwhile, are often seen but not heard.

Cultural representations are a reflection of our values, the researchers conclude: “Inequality in representation, therefore, constitutes an explicit statement of inequality of value.”

8. The Never-Ending ‘Paper Versus Digital’ War

The argument goes like this: Digital screens turn reading into a cold and impersonal task; they’re good for information foraging, and not much more. “Real” books, meanwhile, have a heft and “tactility”  that make them intimate, enchanting—and irreplaceable.

But researchers have often found weak or equivocal evidence for the superiority of reading on paper. While a recent study concluded that paper books yielded better comprehension than e-books when many of the digital tools had been removed, the effect sizes were small. A 2021 meta-analysis further muddies the water: When digital and paper books are “mostly similar,” kids comprehend the print version more readily—but when enhancements like motion and sound “target the story content,” e-books generally have the edge.

Nostalgia is a force that every new technology must eventually confront. There’s plenty of evidence that writing with pen and paper encodes learning more deeply than typing. But new digital book formats come preloaded with powerful tools that allow readers to annotate, look up words, answer embedded questions, and share their thinking with other readers.

We may not be ready to admit it, but these are precisely the kinds of activities that drive deeper engagement, enhance comprehension, and leave us with a lasting memory of what we’ve read. The future of e-reading, despite the naysayers, remains promising.

9. New Research Makes a Powerful Case for PBL

Many classrooms today still look like they did 100 years ago, when students were preparing for factory jobs. But the world’s moved on: Modern careers demand a more sophisticated set of skills—collaboration, advanced problem-solving, and creativity, for example—and those can be difficult to teach in classrooms that rarely give students the time and space to develop those competencies.

Project-based learning (PBL) would seem like an ideal solution. But critics say PBL places too much responsibility on novice learners, ignoring the evidence about the effectiveness of direct instruction and ultimately undermining subject fluency. Advocates counter that student-centered learning and direct instruction can and should coexist in classrooms.

Now two new large-scale studies —encompassing over 6,000 students in 114 diverse schools across the nation—provide evidence that a well-structured, project-based approach boosts learning for a wide range of students.

In the studies, which were funded by Lucas Education Research, a sister division of Edutopia , elementary and high school students engaged in challenging projects that had them designing water systems for local farms, or creating toys using simple household objects to learn about gravity, friction, and force. Subsequent testing revealed notable learning gains—well above those experienced by students in traditional classrooms—and those gains seemed to raise all boats, persisting across socioeconomic class, race, and reading levels.

10. Tracking a Tumultuous Year for Teachers

The Covid-19 pandemic cast a long shadow over the lives of educators in 2021, according to a year’s worth of research.

The average teacher’s workload suddenly “spiked last spring,” wrote the Center for Reinventing Public Education in its January 2021 report, and then—in defiance of the laws of motion—simply never let up. By the fall, a RAND study recorded an astonishing shift in work habits: 24 percent of teachers reported that they were working 56 hours or more per week, compared to 5 percent pre-pandemic.

The vaccine was the promised land, but when it arrived nothing seemed to change. In an April 2021 survey  conducted four months after the first vaccine was administered in New York City, 92 percent of teachers said their jobs were more stressful than prior to the pandemic, up from 81 percent in an earlier survey.

It wasn’t just the length of the work days; a close look at the research reveals that the school system’s failure to adjust expectations was ruinous. It seemed to start with the obligations of hybrid teaching, which surfaced in Edutopia ’s coverage of overseas school reopenings. In June 2020, well before many U.S. schools reopened, we reported that hybrid teaching was an emerging problem internationally, and warned that if the “model is to work well for any period of time,” schools must “recognize and seek to reduce the workload for teachers.” Almost eight months later, a 2021 RAND study identified hybrid teaching as a primary source of teacher stress in the U.S., easily outpacing factors like the health of a high-risk loved one.

New and ever-increasing demands for tech solutions put teachers on a knife’s edge. In several important 2021 studies, researchers concluded that teachers were being pushed to adopt new technology without the “resources and equipment necessary for its correct didactic use.” Consequently, they were spending more than 20 hours a week adapting lessons for online use, and experiencing an unprecedented erosion of the boundaries between their work and home lives, leading to an unsustainable “always on” mentality. When it seemed like nothing more could be piled on—when all of the lights were blinking red—the federal government restarted standardized testing .

Change will be hard; many of the pathologies that exist in the system now predate the pandemic. But creating strict school policies that separate work from rest, eliminating the adoption of new tech tools without proper supports, distributing surveys regularly to gauge teacher well-being, and above all listening to educators to identify and confront emerging problems might be a good place to start, if the research can be believed.

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• v.37(16); 2022 Apr 25

A Practical Guide to Writing Quantitative and Qualitative Research Questions and Hypotheses in Scholarly Articles

Edward barroga.

1 Department of General Education, Graduate School of Nursing Science, St. Luke’s International University, Tokyo, Japan.

Glafera Janet Matanguihan

2 Department of Biological Sciences, Messiah University, Mechanicsburg, PA, USA.

The development of research questions and the subsequent hypotheses are prerequisites to defining the main research purpose and specific objectives of a study. Consequently, these objectives determine the study design and research outcome. The development of research questions is a process based on knowledge of current trends, cutting-edge studies, and technological advances in the research field. Excellent research questions are focused and require a comprehensive literature search and in-depth understanding of the problem being investigated. Initially, research questions may be written as descriptive questions which could be developed into inferential questions. These questions must be specific and concise to provide a clear foundation for developing hypotheses. Hypotheses are more formal predictions about the research outcomes. These specify the possible results that may or may not be expected regarding the relationship between groups. Thus, research questions and hypotheses clarify the main purpose and specific objectives of the study, which in turn dictate the design of the study, its direction, and outcome. Studies developed from good research questions and hypotheses will have trustworthy outcomes with wide-ranging social and health implications.

INTRODUCTION

Scientific research is usually initiated by posing evidenced-based research questions which are then explicitly restated as hypotheses. 1 , 2 The hypotheses provide directions to guide the study, solutions, explanations, and expected results. 3 , 4 Both research questions and hypotheses are essentially formulated based on conventional theories and real-world processes, which allow the inception of novel studies and the ethical testing of ideas. 5 , 6

It is crucial to have knowledge of both quantitative and qualitative research 2 as both types of research involve writing research questions and hypotheses. 7 However, these crucial elements of research are sometimes overlooked; if not overlooked, then framed without the forethought and meticulous attention it needs. Planning and careful consideration are needed when developing quantitative or qualitative research, particularly when conceptualizing research questions and hypotheses. 4

There is a continuing need to support researchers in the creation of innovative research questions and hypotheses, as well as for journal articles that carefully review these elements. 1 When research questions and hypotheses are not carefully thought of, unethical studies and poor outcomes usually ensue. Carefully formulated research questions and hypotheses define well-founded objectives, which in turn determine the appropriate design, course, and outcome of the study. This article then aims to discuss in detail the various aspects of crafting research questions and hypotheses, with the goal of guiding researchers as they develop their own. Examples from the authors and peer-reviewed scientific articles in the healthcare field are provided to illustrate key points.

DEFINITIONS AND RELATIONSHIP OF RESEARCH QUESTIONS AND HYPOTHESES

A research question is what a study aims to answer after data analysis and interpretation. The answer is written in length in the discussion section of the paper. Thus, the research question gives a preview of the different parts and variables of the study meant to address the problem posed in the research question. 1 An excellent research question clarifies the research writing while facilitating understanding of the research topic, objective, scope, and limitations of the study. 5

On the other hand, a research hypothesis is an educated statement of an expected outcome. This statement is based on background research and current knowledge. 8 , 9 The research hypothesis makes a specific prediction about a new phenomenon 10 or a formal statement on the expected relationship between an independent variable and a dependent variable. 3 , 11 It provides a tentative answer to the research question to be tested or explored. 4

Hypotheses employ reasoning to predict a theory-based outcome. 10 These can also be developed from theories by focusing on components of theories that have not yet been observed. 10 The validity of hypotheses is often based on the testability of the prediction made in a reproducible experiment. 8

Conversely, hypotheses can also be rephrased as research questions. Several hypotheses based on existing theories and knowledge may be needed to answer a research question. Developing ethical research questions and hypotheses creates a research design that has logical relationships among variables. These relationships serve as a solid foundation for the conduct of the study. 4 , 11 Haphazardly constructed research questions can result in poorly formulated hypotheses and improper study designs, leading to unreliable results. Thus, the formulations of relevant research questions and verifiable hypotheses are crucial when beginning research. 12

CHARACTERISTICS OF GOOD RESEARCH QUESTIONS AND HYPOTHESES

Excellent research questions are specific and focused. These integrate collective data and observations to confirm or refute the subsequent hypotheses. Well-constructed hypotheses are based on previous reports and verify the research context. These are realistic, in-depth, sufficiently complex, and reproducible. More importantly, these hypotheses can be addressed and tested. 13

There are several characteristics of well-developed hypotheses. Good hypotheses are 1) empirically testable 7 , 10 , 11 , 13 ; 2) backed by preliminary evidence 9 ; 3) testable by ethical research 7 , 9 ; 4) based on original ideas 9 ; 5) have evidenced-based logical reasoning 10 ; and 6) can be predicted. 11 Good hypotheses can infer ethical and positive implications, indicating the presence of a relationship or effect relevant to the research theme. 7 , 11 These are initially developed from a general theory and branch into specific hypotheses by deductive reasoning. In the absence of a theory to base the hypotheses, inductive reasoning based on specific observations or findings form more general hypotheses. 10

TYPES OF RESEARCH QUESTIONS AND HYPOTHESES

Research questions and hypotheses are developed according to the type of research, which can be broadly classified into quantitative and qualitative research. We provide a summary of the types of research questions and hypotheses under quantitative and qualitative research categories in Table 1 .

Research questions in quantitative research

In quantitative research, research questions inquire about the relationships among variables being investigated and are usually framed at the start of the study. These are precise and typically linked to the subject population, dependent and independent variables, and research design. 1 Research questions may also attempt to describe the behavior of a population in relation to one or more variables, or describe the characteristics of variables to be measured ( descriptive research questions ). 1 , 5 , 14 These questions may also aim to discover differences between groups within the context of an outcome variable ( comparative research questions ), 1 , 5 , 14 or elucidate trends and interactions among variables ( relationship research questions ). 1 , 5 We provide examples of descriptive, comparative, and relationship research questions in quantitative research in Table 2 .

Hypotheses in quantitative research

In quantitative research, hypotheses predict the expected relationships among variables. 15 Relationships among variables that can be predicted include 1) between a single dependent variable and a single independent variable ( simple hypothesis ) or 2) between two or more independent and dependent variables ( complex hypothesis ). 4 , 11 Hypotheses may also specify the expected direction to be followed and imply an intellectual commitment to a particular outcome ( directional hypothesis ) 4 . On the other hand, hypotheses may not predict the exact direction and are used in the absence of a theory, or when findings contradict previous studies ( non-directional hypothesis ). 4 In addition, hypotheses can 1) define interdependency between variables ( associative hypothesis ), 4 2) propose an effect on the dependent variable from manipulation of the independent variable ( causal hypothesis ), 4 3) state a negative relationship between two variables ( null hypothesis ), 4 , 11 , 15 4) replace the working hypothesis if rejected ( alternative hypothesis ), 15 explain the relationship of phenomena to possibly generate a theory ( working hypothesis ), 11 5) involve quantifiable variables that can be tested statistically ( statistical hypothesis ), 11 6) or express a relationship whose interlinks can be verified logically ( logical hypothesis ). 11 We provide examples of simple, complex, directional, non-directional, associative, causal, null, alternative, working, statistical, and logical hypotheses in quantitative research, as well as the definition of quantitative hypothesis-testing research in Table 3 .

Research questions in qualitative research

Unlike research questions in quantitative research, research questions in qualitative research are usually continuously reviewed and reformulated. The central question and associated subquestions are stated more than the hypotheses. 15 The central question broadly explores a complex set of factors surrounding the central phenomenon, aiming to present the varied perspectives of participants. 15

There are varied goals for which qualitative research questions are developed. These questions can function in several ways, such as to 1) identify and describe existing conditions ( contextual research question s); 2) describe a phenomenon ( descriptive research questions ); 3) assess the effectiveness of existing methods, protocols, theories, or procedures ( evaluation research questions ); 4) examine a phenomenon or analyze the reasons or relationships between subjects or phenomena ( explanatory research questions ); or 5) focus on unknown aspects of a particular topic ( exploratory research questions ). 5 In addition, some qualitative research questions provide new ideas for the development of theories and actions ( generative research questions ) or advance specific ideologies of a position ( ideological research questions ). 1 Other qualitative research questions may build on a body of existing literature and become working guidelines ( ethnographic research questions ). Research questions may also be broadly stated without specific reference to the existing literature or a typology of questions ( phenomenological research questions ), may be directed towards generating a theory of some process ( grounded theory questions ), or may address a description of the case and the emerging themes ( qualitative case study questions ). 15 We provide examples of contextual, descriptive, evaluation, explanatory, exploratory, generative, ideological, ethnographic, phenomenological, grounded theory, and qualitative case study research questions in qualitative research in Table 4 , and the definition of qualitative hypothesis-generating research in Table 5 .

Qualitative studies usually pose at least one central research question and several subquestions starting with How or What . These research questions use exploratory verbs such as explore or describe . These also focus on one central phenomenon of interest, and may mention the participants and research site. 15

Hypotheses in qualitative research

Hypotheses in qualitative research are stated in the form of a clear statement concerning the problem to be investigated. Unlike in quantitative research where hypotheses are usually developed to be tested, qualitative research can lead to both hypothesis-testing and hypothesis-generating outcomes. 2 When studies require both quantitative and qualitative research questions, this suggests an integrative process between both research methods wherein a single mixed-methods research question can be developed. 1

FRAMEWORKS FOR DEVELOPING RESEARCH QUESTIONS AND HYPOTHESES

Research questions followed by hypotheses should be developed before the start of the study. 1 , 12 , 14 It is crucial to develop feasible research questions on a topic that is interesting to both the researcher and the scientific community. This can be achieved by a meticulous review of previous and current studies to establish a novel topic. Specific areas are subsequently focused on to generate ethical research questions. The relevance of the research questions is evaluated in terms of clarity of the resulting data, specificity of the methodology, objectivity of the outcome, depth of the research, and impact of the study. 1 , 5 These aspects constitute the FINER criteria (i.e., Feasible, Interesting, Novel, Ethical, and Relevant). 1 Clarity and effectiveness are achieved if research questions meet the FINER criteria. In addition to the FINER criteria, Ratan et al. described focus, complexity, novelty, feasibility, and measurability for evaluating the effectiveness of research questions. 14

The PICOT and PEO frameworks are also used when developing research questions. 1 The following elements are addressed in these frameworks, PICOT: P-population/patients/problem, I-intervention or indicator being studied, C-comparison group, O-outcome of interest, and T-timeframe of the study; PEO: P-population being studied, E-exposure to preexisting conditions, and O-outcome of interest. 1 Research questions are also considered good if these meet the “FINERMAPS” framework: Feasible, Interesting, Novel, Ethical, Relevant, Manageable, Appropriate, Potential value/publishable, and Systematic. 14

As we indicated earlier, research questions and hypotheses that are not carefully formulated result in unethical studies or poor outcomes. To illustrate this, we provide some examples of ambiguous research question and hypotheses that result in unclear and weak research objectives in quantitative research ( Table 6 ) 16 and qualitative research ( Table 7 ) 17 , and how to transform these ambiguous research question(s) and hypothesis(es) into clear and good statements.

a These statements were composed for comparison and illustrative purposes only.

b These statements are direct quotes from Higashihara and Horiuchi. 16

a This statement is a direct quote from Shimoda et al. 17

The other statements were composed for comparison and illustrative purposes only.

CONSTRUCTING RESEARCH QUESTIONS AND HYPOTHESES

To construct effective research questions and hypotheses, it is very important to 1) clarify the background and 2) identify the research problem at the outset of the research, within a specific timeframe. 9 Then, 3) review or conduct preliminary research to collect all available knowledge about the possible research questions by studying theories and previous studies. 18 Afterwards, 4) construct research questions to investigate the research problem. Identify variables to be accessed from the research questions 4 and make operational definitions of constructs from the research problem and questions. Thereafter, 5) construct specific deductive or inductive predictions in the form of hypotheses. 4 Finally, 6) state the study aims . This general flow for constructing effective research questions and hypotheses prior to conducting research is shown in Fig. 1 .

Research questions are used more frequently in qualitative research than objectives or hypotheses. 3 These questions seek to discover, understand, explore or describe experiences by asking “What” or “How.” The questions are open-ended to elicit a description rather than to relate variables or compare groups. The questions are continually reviewed, reformulated, and changed during the qualitative study. 3 Research questions are also used more frequently in survey projects than hypotheses in experiments in quantitative research to compare variables and their relationships.

Hypotheses are constructed based on the variables identified and as an if-then statement, following the template, ‘If a specific action is taken, then a certain outcome is expected.’ At this stage, some ideas regarding expectations from the research to be conducted must be drawn. 18 Then, the variables to be manipulated (independent) and influenced (dependent) are defined. 4 Thereafter, the hypothesis is stated and refined, and reproducible data tailored to the hypothesis are identified, collected, and analyzed. 4 The hypotheses must be testable and specific, 18 and should describe the variables and their relationships, the specific group being studied, and the predicted research outcome. 18 Hypotheses construction involves a testable proposition to be deduced from theory, and independent and dependent variables to be separated and measured separately. 3 Therefore, good hypotheses must be based on good research questions constructed at the start of a study or trial. 12

In summary, research questions are constructed after establishing the background of the study. Hypotheses are then developed based on the research questions. Thus, it is crucial to have excellent research questions to generate superior hypotheses. In turn, these would determine the research objectives and the design of the study, and ultimately, the outcome of the research. 12 Algorithms for building research questions and hypotheses are shown in Fig. 2 for quantitative research and in Fig. 3 for qualitative research.

EXAMPLES OF RESEARCH QUESTIONS FROM PUBLISHED ARTICLES

• EXAMPLE 1. Descriptive research question (quantitative research)
• - Presents research variables to be assessed (distinct phenotypes and subphenotypes)
• “BACKGROUND: Since COVID-19 was identified, its clinical and biological heterogeneity has been recognized. Identifying COVID-19 phenotypes might help guide basic, clinical, and translational research efforts.
• RESEARCH QUESTION: Does the clinical spectrum of patients with COVID-19 contain distinct phenotypes and subphenotypes? ” 19
• EXAMPLE 2. Relationship research question (quantitative research)
• - Shows interactions between dependent variable (static postural control) and independent variable (peripheral visual field loss)
• “Background: Integration of visual, vestibular, and proprioceptive sensations contributes to postural control. People with peripheral visual field loss have serious postural instability. However, the directional specificity of postural stability and sensory reweighting caused by gradual peripheral visual field loss remain unclear.
• Research question: What are the effects of peripheral visual field loss on static postural control ?” 20
• EXAMPLE 3. Comparative research question (quantitative research)
• - Clarifies the difference among groups with an outcome variable (patients enrolled in COMPERA with moderate PH or severe PH in COPD) and another group without the outcome variable (patients with idiopathic pulmonary arterial hypertension (IPAH))
• “BACKGROUND: Pulmonary hypertension (PH) in COPD is a poorly investigated clinical condition.
• RESEARCH QUESTION: Which factors determine the outcome of PH in COPD?
• STUDY DESIGN AND METHODS: We analyzed the characteristics and outcome of patients enrolled in the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) with moderate or severe PH in COPD as defined during the 6th PH World Symposium who received medical therapy for PH and compared them with patients with idiopathic pulmonary arterial hypertension (IPAH) .” 21
• EXAMPLE 4. Exploratory research question (qualitative research)
• - Explores areas that have not been fully investigated (perspectives of families and children who receive care in clinic-based child obesity treatment) to have a deeper understanding of the research problem
• “Problem: Interventions for children with obesity lead to only modest improvements in BMI and long-term outcomes, and data are limited on the perspectives of families of children with obesity in clinic-based treatment. This scoping review seeks to answer the question: What is known about the perspectives of families and children who receive care in clinic-based child obesity treatment? This review aims to explore the scope of perspectives reported by families of children with obesity who have received individualized outpatient clinic-based obesity treatment.” 22
• EXAMPLE 5. Relationship research question (quantitative research)
• - Defines interactions between dependent variable (use of ankle strategies) and independent variable (changes in muscle tone)
• “Background: To maintain an upright standing posture against external disturbances, the human body mainly employs two types of postural control strategies: “ankle strategy” and “hip strategy.” While it has been reported that the magnitude of the disturbance alters the use of postural control strategies, it has not been elucidated how the level of muscle tone, one of the crucial parameters of bodily function, determines the use of each strategy. We have previously confirmed using forward dynamics simulations of human musculoskeletal models that an increased muscle tone promotes the use of ankle strategies. The objective of the present study was to experimentally evaluate a hypothesis: an increased muscle tone promotes the use of ankle strategies. Research question: Do changes in the muscle tone affect the use of ankle strategies ?” 23

EXAMPLES OF HYPOTHESES IN PUBLISHED ARTICLES

• EXAMPLE 1. Working hypothesis (quantitative research)
• - A hypothesis that is initially accepted for further research to produce a feasible theory
• “As fever may have benefit in shortening the duration of viral illness, it is plausible to hypothesize that the antipyretic efficacy of ibuprofen may be hindering the benefits of a fever response when taken during the early stages of COVID-19 illness .” 24
• “In conclusion, it is plausible to hypothesize that the antipyretic efficacy of ibuprofen may be hindering the benefits of a fever response . The difference in perceived safety of these agents in COVID-19 illness could be related to the more potent efficacy to reduce fever with ibuprofen compared to acetaminophen. Compelling data on the benefit of fever warrant further research and review to determine when to treat or withhold ibuprofen for early stage fever for COVID-19 and other related viral illnesses .” 24
• EXAMPLE 2. Exploratory hypothesis (qualitative research)
• - Explores particular areas deeper to clarify subjective experience and develop a formal hypothesis potentially testable in a future quantitative approach
• “We hypothesized that when thinking about a past experience of help-seeking, a self distancing prompt would cause increased help-seeking intentions and more favorable help-seeking outcome expectations .” 25
• “Conclusion
• Although a priori hypotheses were not supported, further research is warranted as results indicate the potential for using self-distancing approaches to increasing help-seeking among some people with depressive symptomatology.” 25
• EXAMPLE 3. Hypothesis-generating research to establish a framework for hypothesis testing (qualitative research)
• “We hypothesize that compassionate care is beneficial for patients (better outcomes), healthcare systems and payers (lower costs), and healthcare providers (lower burnout). ” 26
• Compassionomics is the branch of knowledge and scientific study of the effects of compassionate healthcare. Our main hypotheses are that compassionate healthcare is beneficial for (1) patients, by improving clinical outcomes, (2) healthcare systems and payers, by supporting financial sustainability, and (3) HCPs, by lowering burnout and promoting resilience and well-being. The purpose of this paper is to establish a scientific framework for testing the hypotheses above . If these hypotheses are confirmed through rigorous research, compassionomics will belong in the science of evidence-based medicine, with major implications for all healthcare domains.” 26
• EXAMPLE 4. Statistical hypothesis (quantitative research)
• - An assumption is made about the relationship among several population characteristics ( gender differences in sociodemographic and clinical characteristics of adults with ADHD ). Validity is tested by statistical experiment or analysis ( chi-square test, Students t-test, and logistic regression analysis)
• “Our research investigated gender differences in sociodemographic and clinical characteristics of adults with ADHD in a Japanese clinical sample. Due to unique Japanese cultural ideals and expectations of women's behavior that are in opposition to ADHD symptoms, we hypothesized that women with ADHD experience more difficulties and present more dysfunctions than men . We tested the following hypotheses: first, women with ADHD have more comorbidities than men with ADHD; second, women with ADHD experience more social hardships than men, such as having less full-time employment and being more likely to be divorced.” 27
• “Statistical Analysis
• ( text omitted ) Between-gender comparisons were made using the chi-squared test for categorical variables and Students t-test for continuous variables…( text omitted ). A logistic regression analysis was performed for employment status, marital status, and comorbidity to evaluate the independent effects of gender on these dependent variables.” 27

EXAMPLES OF HYPOTHESIS AS WRITTEN IN PUBLISHED ARTICLES IN RELATION TO OTHER PARTS

• EXAMPLE 1. Background, hypotheses, and aims are provided
• “Pregnant women need skilled care during pregnancy and childbirth, but that skilled care is often delayed in some countries …( text omitted ). The focused antenatal care (FANC) model of WHO recommends that nurses provide information or counseling to all pregnant women …( text omitted ). Job aids are visual support materials that provide the right kind of information using graphics and words in a simple and yet effective manner. When nurses are not highly trained or have many work details to attend to, these job aids can serve as a content reminder for the nurses and can be used for educating their patients (Jennings, Yebadokpo, Affo, & Agbogbe, 2010) ( text omitted ). Importantly, additional evidence is needed to confirm how job aids can further improve the quality of ANC counseling by health workers in maternal care …( text omitted )” 28
• “ This has led us to hypothesize that the quality of ANC counseling would be better if supported by job aids. Consequently, a better quality of ANC counseling is expected to produce higher levels of awareness concerning the danger signs of pregnancy and a more favorable impression of the caring behavior of nurses .” 28
• “This study aimed to examine the differences in the responses of pregnant women to a job aid-supported intervention during ANC visit in terms of 1) their understanding of the danger signs of pregnancy and 2) their impression of the caring behaviors of nurses to pregnant women in rural Tanzania.” 28
• EXAMPLE 2. Background, hypotheses, and aims are provided
• “We conducted a two-arm randomized controlled trial (RCT) to evaluate and compare changes in salivary cortisol and oxytocin levels of first-time pregnant women between experimental and control groups. The women in the experimental group touched and held an infant for 30 min (experimental intervention protocol), whereas those in the control group watched a DVD movie of an infant (control intervention protocol). The primary outcome was salivary cortisol level and the secondary outcome was salivary oxytocin level.” 29
• “ We hypothesize that at 30 min after touching and holding an infant, the salivary cortisol level will significantly decrease and the salivary oxytocin level will increase in the experimental group compared with the control group .” 29
• EXAMPLE 3. Background, aim, and hypothesis are provided
• “In countries where the maternal mortality ratio remains high, antenatal education to increase Birth Preparedness and Complication Readiness (BPCR) is considered one of the top priorities [1]. BPCR includes birth plans during the antenatal period, such as the birthplace, birth attendant, transportation, health facility for complications, expenses, and birth materials, as well as family coordination to achieve such birth plans. In Tanzania, although increasing, only about half of all pregnant women attend an antenatal clinic more than four times [4]. Moreover, the information provided during antenatal care (ANC) is insufficient. In the resource-poor settings, antenatal group education is a potential approach because of the limited time for individual counseling at antenatal clinics.” 30
• “This study aimed to evaluate an antenatal group education program among pregnant women and their families with respect to birth-preparedness and maternal and infant outcomes in rural villages of Tanzania.” 30
• “ The study hypothesis was if Tanzanian pregnant women and their families received a family-oriented antenatal group education, they would (1) have a higher level of BPCR, (2) attend antenatal clinic four or more times, (3) give birth in a health facility, (4) have less complications of women at birth, and (5) have less complications and deaths of infants than those who did not receive the education .” 30

Research questions and hypotheses are crucial components to any type of research, whether quantitative or qualitative. These questions should be developed at the very beginning of the study. Excellent research questions lead to superior hypotheses, which, like a compass, set the direction of research, and can often determine the successful conduct of the study. Many research studies have floundered because the development of research questions and subsequent hypotheses was not given the thought and meticulous attention needed. The development of research questions and hypotheses is an iterative process based on extensive knowledge of the literature and insightful grasp of the knowledge gap. Focused, concise, and specific research questions provide a strong foundation for constructing hypotheses which serve as formal predictions about the research outcomes. Research questions and hypotheses are crucial elements of research that should not be overlooked. They should be carefully thought of and constructed when planning research. This avoids unethical studies and poor outcomes by defining well-founded objectives that determine the design, course, and outcome of the study.

Disclosure: The authors have no potential conflicts of interest to disclose.

Author Contributions:

• Conceptualization: Barroga E, Matanguihan GJ.
• Methodology: Barroga E, Matanguihan GJ.
• Writing - original draft: Barroga E, Matanguihan GJ.
• Writing - review & editing: Barroga E, Matanguihan GJ.

The top 10 journal articles of 2020

In 2020, APA’s 89 journals published more than 5,000 articles—the most ever and 25% more than in 2019. Here’s a quick look at the 10 most downloaded to date.

Vol. 52 No. 1 Print version: page 24

1. Me, My Selfie, and I: The Relations Between Selfie Behaviors, Body Image, Self-Objectification, and Self-Esteem in Young Women

Veldhuis, j., et al..

Young women who appreciate their bodies and consider them physical objects are more likely to select, edit, and post selfies to social media, suggests this study in Psychology of Popular Media (Vol. 9, No. 1). Researchers surveyed 179 women, ages 18 to 25, on how often they took selfies, how they selected selfies to post, how often they used filters and editing techniques, and how carefully they planned their selfie postings. They also assessed participants’ levels of body appreciation and dissatisfaction, self-objectification, and self-esteem. Higher levels of self-objectification were linked to more time spent on all selfie behaviors, while body appreciation was related to more time spent selecting selfies to post, but not frequency of taking or editing selfies. Body dissatisfaction and self-esteem were not associated with selfie behaviors. DOI: 10.1037/ppm0000206

2. A Closer Look at Appearance and Social Media: Measuring Activity, Self-Presentation, and Social Comparison and Their Associations With Emotional Adjustment

Zimmer-gembeck, m. j., et al..

This Psychology of Popular Media (online first publication) article presents a tool to assess young people’s preoccupation with their physical appearance on social media. Researchers administered a 21-item survey about social media to 281 Australian high school students. They identified 18 items with strong inter-item correlation centered on three categories of social media behavior: online self-presentation, appearance-related online activity, and appearance comparison. In a second study with 327 Australian university students, scores on the 18-item survey were found to be associated with measures of social anxiety and depressive symptoms, appearance-related support from others, general interpersonal stress, coping flexibility, sexual harassment, disordered eating, and other factors. The researchers also found that young women engaged in more appearance-related social media activity and appearance comparison than did young men. DOI: 10.1037/ppm0000277

3. The Novel Coronavirus (COVID-2019) Outbreak: Amplification of Public Health Consequences by Media Exposure

Garfin, d. r., et al..

Repeated media exposure to the COVID-19 pandemic may be associated with psychological distress and other public health consequences, according to this commentary in Health Psychology (Vol. 39, No. 5). The authors reviewed research about trends in health behavior and psychological distress as a response to media coverage of crises, including terrorist attacks, school shootings, and disease outbreaks. They found that repeated media exposure to collective crises was associated with increased anxiety and heightened acute and post-traumatic stress, with downstream effects on health outcomes such as new incidence of cardiovascular disease. Moreover, misinformation can further amplify stress responses and lead to misplaced or misguided health-protective and help-seeking behaviors. The authors recommended public health agencies use social media strategically, such as with hashtags, to keep residents updated during the pandemic. They also urged the public to avoid sensationalism and repeated coverage of the same information. DOI: 10.1037/hea0000875

4. Barriers to Mental Health Treatment Among Individuals With Social Anxiety Disorder and Generalized Anxiety Disorder

Goetter, e. m., et al..

This study in Psychological Services (Vol. 17, No. 1) indicates that 3 in 4 people who suffer from anxiety do not receive proper care. Researchers recruited 226 participants in the United States who were previously diagnosed with social anxiety disorder or generalized anxiety disorder and assessed their symptom severity and asked them to self-report any barriers to treatment. Shame and stigma were the highest cited barriers, followed by logistical and financial barriers and not knowing where to seek treatment. Participants with more severe symptoms reported more barriers to treatment than those with milder symptoms. Racial and ethnic minorities reported more barriers than racial and ethnic majorities even after controlling for symptom severity. The researchers called for increased patient education and more culturally sensitive outreach to reduce treatment barriers. DOI: 10.1037/ser0000254

5. The Construction of “Critical Thinking”: Between How We Think and What We Believe

This History of Psychology (Vol. 23, No. 3) article examines the emergence of “critical thinking” as a psychological concept. The author describes how, between World War I and World War II in the United States, the concept emerged out of growing concerns about how easily people’s beliefs could be changed and was constructed in a way that was independent of what people believed. The author delves into how original measurements of critical thinking avoided assumptions about the accuracy of specific real-world beliefs and details how subsequent critical thinking tests increasingly focused on logical abilities, often favoring outcome (what we believe) over process (how we think). DOI: 10.1037/hop0000145

6. Treatment of Alcohol Use Disorder: Integration of Alcoholics Anonymous and Cognitive Behavioral Therapy

Breuninger, m. m., et al..

This article in Training and Education in Professional Psychology (Vol. 14, No. 1) details how to work with alcohol use disorder patients who are participating in both cognitive behavioral therapy (CBT) and Alcoholics Anonymous (AA). The authors point to distinctions between AA and CBT: The goal of AA is total abstinence and the primary therapeutic relationship is with a peer in recovery, while CBT takes a less absolute approach and the primary relationship is with a psychotherapist. The authors also point to commonalities: both approaches emphasize identifying and replacing dysfunctional beliefs and place value in social support. The authors recommend clinicians and trainees become more educated about AA and recommend a translation of the 12-step language into CBT terminology to bridge the gap. DOI: 10.1037/tep0000265

7. Positivity Pays Off: Clients’ Perspectives on Positive Compared With Traditional Cognitive Behavioral Therapy for Depression

Geschwind, n., et al..

Positive cognitive behavioral therapy, a version of CBT focused on exploring exceptions to the problem rather than the problem itself, personal strengths, and embracing positivity, works well to counter depressive symptoms and build well-being, according to this study in Psychotherapy (Vol. 57, No. 3). Participants received a block of eight sessions of traditional CBT and a block of eight sessions of positive CBT. Researchers held in-depth interviews with 12 of these participants. Despite initial skepticism, most participants reported preferring positive CBT but indicated experiencing a steeper learning curve than with traditional CBT. Researchers attributed positive CBT’s favorability to four factors: feeling empowered, benefiting from effects of positive emotions, learning to appreciate baby steps, and rediscovering optimism as a personal strength. DOI: 10.1037/pst0000288

8. Targeted Prescription of Cognitive-Behavioral Therapy Versus Person-Centered Counseling for Depression Using a Machine Learning Approach

Delgadillo, j., & gonzalez salas duhne, p..

Amachine learning algorithm can identify which patients would derive more benefit from cognitive behavioral therapy (CBT) versus counseling for depression, suggests research in this Journal of Consulting and Clinical Psychology (Vol. 88, No. 1) article. Researchers retrospectively explored data from 1,085 patients in the United Kingdom treated with either CBT or counseling for depression and discovered six patient characteristics—age, employment status, disability, and three diagnostic measures of major depression and social adjustment—relevant to developing an algorithm for prescribing the best approach. The researchers then used the algorithm to determine which therapy would work best for an additional 350 patients with depression. They found that patients receiving their optimal treatment type were twice as likely to improve significantly. DOI: 10.1037/ccp0000476

9. Traumatic Stress in the Age of COVID-19: A Call to Close Critical Gaps and Adapt to New Realities

Horesh, d., & brown, a. d..

This article in Psychological Trauma: Theory, Research, Practice, and Policy (Vol. 12, No. 4) argues that COVID-19 should be examined from a post-traumatic stress perspective. The authors call for mental health researchers and clinicians to develop better diagnoses and prevention strategies for COVID-related traumatic stress; create guidelines and talking points for the media and government officials to use when speaking to an anxious, and potentially traumatized, public; and provide mental health training to professionals in health care, education, childcare, and occupational support in order to reach more people. DOI: 10.1037/tra0000592

10. Emotional Intelligence Predicts Academic Performance: A Meta-Analysis

Maccann, c., et al..

Students with high emotional intelligence get better grades and score higher on standardized tests, according to the research presented in this article in Psychological Bulletin (Vol. 146, No. 2). Researchers analyzed data from 158 studies representing more than 42,529 students—ranging in age from elementary school to college—from 27 countries. The researchers found that students with higher emotional intelligence earned better grades and scored higher on achievement tests than those with lower emotional intelligence. This finding was true even when controlling for intelligence and personality factors, and the association held regardless of age. The researchers suggest that students with higher emotional intelligence succeed because they cope well with negative emotions that can harm academic performance; they form stronger relationships with teachers, peers, and family; and their knowledge of human motivations and socialinteractions helps them understand humanities subject matter. DOI: 10.1037/bul0000219

5 interviews to listen to now

Psychology’s most innovative thinkers are featured on APA’s Speaking of Psychology podcast , which highlights important research and helps listeners apply psychology to their lives. The most popular episodes of 2020, as measured by the number of downloads in the first 30 days, were: 

• How to have meaningful dialogues despite political differences , with  Tania Israel, PhD
• Canine cognition and the survival of the friendliest , with  Brian Hare, PhD  
• The challenges faced by women in leadership , with  Alice Eagly, PhD
• How to choose effective, science-based mental health apps , with  Stephen Schueller, PhD  
• Psychedelic therapy , with Roland Griffiths, PhD  

Listen to all of the Speaking of Psychology episodes .

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• Introduction
• Conclusions
• Article Information

A symptom was included if at least 5% of infected or uninfected participants reported experiencing that symptom. Adjusted odds ratios and risk differences were estimated from models that included infection status as the exposure and the presence of each prolonged symptom as the outcome, with adjustment for sex assigned at birth and race and ethnicity (see eMethods in Supplement 3 ).

A, Least absolute shrinkage and selection operator (LASSO) was used to fit a logistic regression model to identify which symptoms could be used to identify individuals likely to have PASC. Estimated log odds ratios were divided by 0.10 and rounded up to the nearest 0.5 to calculate symptom scores. An individual’s PASC research index is calculated by summing the scores for each prolonged symptom a participant reported (ie, the participant experienced the symptom for 4 weeks since the beginning of the pandemic and is currently experiencing it at the time of the survey). B, The optimal index threshold for PASC was selected using bootstrapping to estimate standard error bars. An approximation of the “elbow” method was used to identify the cutoff where the number of uninfected participants misclassified as PASC-probable stabilized (eMethods in Supplement 3 ). The threshold (index of at least 5.5) can be used to identify school-age children with PASC for research purposes. Using this threshold, the percentage of infected PASC-probable school-age children with each symptom was as follows: headache, 55%; trouble with memory or focusing, 45%; trouble sleeping, 44%; stomach pain, 43%; nausea or vomiting, 34%; back or neck pain, 30%; itchy skin or skin rash, 29%; fear about specific things, 26%; feeling lightheaded or dizzy, 26%; and refusing to go to school, 23%. C, Participant responses to 3 questions from the Patient-Reported Outcomes Measurement Information System (PROMIS) Global 10 survey, stratified into 7 groups: participants with a zero PASC research index and no prolonged symptoms, zero PASC research index but at least 1 prolonged symptom, and participants with nonzero PASC index, divided into quintiles. The dark vertical line indicates the index threshold for PASC. Each cell is shaded according to the frequency of each response within each column, ranging from 0% to 100%.

A, Least absolute shrinkage and selection operator (LASSO) was used to fit a logistic regression model to identify which symptoms could be used to identify individuals likely to have PASC. Estimated log odds ratios were divided by 0.10 and rounded up to the nearest 0.5 to calculate symptom scores. An individual’s PASC research index is calculated by summing the scores for each prolonged symptom a participant reported (ie, the participant experienced the symptom for 4 weeks since the beginning of the pandemic and is currently experiencing it at the time of the survey). B, The optimal index threshold for PASC was selected using 95% CIs to estimate error bars. An approximation of the “elbow” method was used to identify the cutoff where the number of uninfected participants misclassified as PASC-probable stabilized (eMethods in Supplement 3 ). The threshold (index of at least 5) can be used to identify adolescents with PASC for research purposes. Using this threshold, the percentage of infected PASC-probable adolescents with each symptom was as follows: daytime tiredness/sleepiness or low energy, 80%; body, muscle, or joint pain, 61%; headache, 56%; trouble with memory or focusing, 47%; tired after walking, 42%; back or neck pain, 40%; feeling lightheaded or dizzy, 39%; and change or loss in smell or taste, 34%. C, Participant responses to 3 questions from the Patient-Reported Outcomes Measurement Information System (PROMIS) Global 10 survey, stratified into 7 groups: participants with a zero PASC research index and no prolonged symptoms, zero PASC research index but at least 1 prolonged symptoms, and participants with nonzero PASC index, divided into quintiles. The dark vertical line indicates the index threshold for PASC (to the left is PASC-unspecified, to the right is PASC-probable). Each cell is shaded according to the frequency of each response within each column, ranging from 0% to 100%.

Symptoms, sorted from most to least common in the study population overall, are in the center column. Left columns correspond to school-age children in 3 groups: uninfected, infected and not meeting the PASC research index threshold (infected, PASC-unspecified), and infected and meeting the PASC research index threshold (infected, PASC-probable). The columns on the right correspond to adolescents with columns in the reverse order. Note that school-age children were not asked about panic attacks. Frequency of each prolonged symptom is indicated by shading, from 0% to 100%.

A and B, Subgroups formed using consensus clustering to group participants with similar symptom profiles (based on prolonged symptoms contributing to the PASC research index only). Four clusters were identified in PASC-probable school-age children and 3 clusters among adolescents. C and D, Frequencies of each prolonged symptom are shown for each cluster, where shading indicates frequency from 0%-100%. Symptoms that contribute to the PASC research index are above the dark horizontal line, and those below do not contribute to the PASC research index, sorted in decreasing frequency among all PASC-probable participants. Symptoms present in <5% of participants in every cluster were omitted. The full set of symptoms is in eFigure 6 in Supplement 3 .

Trial protocol

Statistical analysis plan

Nonauthor contributors

Data sharing statement

• Uncovering Pediatric Long COVID JAMA Editorial August 21, 2024 Suchitra Rao, MBBS, MSCS

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Gross RS , Thaweethai T , Kleinman LC, et al. Characterizing Long COVID in Children and Adolescents. JAMA. Published online August 21, 2024. doi:10.1001/jama.2024.12747

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Characterizing Long COVID in Children and Adolescents

• 1 Division of General Pediatrics, Department of Pediatrics, NYU Grossman School of Medicine, New York
• 2 Department of Biostatistics, Massachusetts General Hospital, Boston
• 3 Department of Medicine, Harvard Medical School, Boston, Massachusetts
• 4 Division of Population Health, Quality, and Implementation Sciences (PopQuIS), Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey
• 5 Bristol Myers Squibb Children’s Hospital, New Brunswick, New Jersey
• 6 Division of Infectious Diseases, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock
• 7 Division of Pediatric Cardiology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York
• 8 Division of Pediatric Allergy, Immunology and Rheumatology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York
• 9 Division of Respiratory Medicine, Department of Pediatrics, UC San Diego School of Medicine, Rady Children’s Hospital, San Diego, California
• 10 Division of Child and Community Health, Department of Pediatrics, UC San Diego School of Medicine, Rady Children’s Hospital, San Diego, California
• 11 Departments of Cognitive Science, Psychiatry, and Radiology, UC San Diego School of Medicine, Rady Children’s Hospital, San Diego, California
• 12 School of Nursing, Virginia Commonwealth University, Richmond
• 13 Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles
• 14 Division of Infectious Diseases, Department of Pediatrics, Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles
• 15 Division of Cardiology, Department of Pediatrics, Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles
• 16 Department of Cardiology, Harvard Medical School, Boston, Massachusetts
• 17 Boston Children’s Hospital, Boston, Massachusetts
• 18 Division of Pediatric Cardiology, Department of Pediatrics, University of Utah, Primary Children’s Hospital, Salt Lake City
• 19 Division of General Pediatrics, Department of Pediatrics, University of California, San Francisco
• 20 Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah Health, Salt Lake City
• 21 Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Massachusetts General Hospital, Boston
• 22 Brigham and Women’s Hospital, Boston, Massachusetts
• 23 Division of Neurology, Department of Neurology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
• 24 Massachusetts General Hospital, Boston
• 25 Division of Child Study Center, Department of Child and Adolescent Psychiatry, NYU Grossman School of Medicine, New York
• 26 Department of Medicine, NYU Grossman School of Medicine, New York
• 27 Division of Pediatric Critical Care Medicine, Department of Pediatrics, NYU Grossman School of Medicine, New York
• 28 Division of Cardiology, Department of Medicine, NYU Grossman School of Medicine, New York
• 29 NYU Grossman School of Medicine, Bellevue Hospital Center, New York
• 30 Division of Developmental and Behavioral Pediatrics, Department of Pediatrics, NYU Grossman School of Medicine, New York
• 31 RECOVER Patient, Caregiver, or Community Advocate Representative, New York, New York
• 32 Long Covid Families, Charlotte, North Carolina
• 33 Division of Long COVID, Department of Pandemic Equity, Vermont Center for Independent Living, Montpelier
• 34 Patient Led Research Collaborative, Washington, DC
• 35 CORe Community, Inc (COVID Recovery through Community, a 501c3), New York, New York
• 36 Division of Community Impact, Department of Health Strategies, American Heart Association, Atlanta, Georgia
• 37 Division of Biostatistics, Department of Medicine, Massachusetts General Hospital, Boston
• 38 Division of Child and Adolescent Health, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York
• 39 Department of Population and Family Health, Mailman School of Public Health, New York-Presbyterian Hospital, New York
• Editorial Uncovering Pediatric Long COVID Suchitra Rao, MBBS, MSCS JAMA

Question   What prolonged symptoms experienced by youth are most associated with SARS-CoV-2 infection?

Findings   Among 5367 participants in the RECOVER-Pediatrics cohort study, 14 symptoms in both school-age children (6-11 years) and adolescents (12-17 years) were more common in those with vs without SARS-CoV-2 infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. Empirically derived indices for PASC research and associated clustering patterns were developed.

Meaning   This study developed research indices for characterizing pediatric PASC. Symptom patterns were similar but distinguishable between school-age children and adolescents, highlighting the importance of characterizing PASC separately in different age groups.

Importance   Most research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed to characterize pediatric PASC to enable studies of underlying mechanisms that will guide future treatment.

Objective   To identify the most common prolonged symptoms experienced by children (aged 6 to 17 years) after SARS-CoV-2 infection, how these symptoms differ by age (school-age [6-11 years] vs adolescents [12-17 years]), how they cluster into distinct phenotypes, and what symptoms in combination could be used as an empirically derived index to assist researchers to study the likely presence of PASC.

Design, Setting, and Participants   Multicenter longitudinal observational cohort study with participants recruited from more than 60 US health care and community settings between March 2022 and December 2023, including school-age children and adolescents with and without SARS-CoV-2 infection history.

Exposure   SARS-CoV-2 infection.

Main Outcomes and Measures   PASC and 89 prolonged symptoms across 9 symptom domains.

Results   A total of 898 school-age children (751 with previous SARS-CoV-2 infection [referred to as infected ] and 147 without [referred to as uninfected ]; mean age, 8.6 years; 49% female; 11% were Black or African American, 34% were Hispanic, Latino, or Spanish, and 60% were White) and 4469 adolescents (3109 infected and 1360 uninfected; mean age, 14.8 years; 48% female; 13% were Black or African American, 21% were Hispanic, Latino, or Spanish, and 73% were White) were included. Median time between first infection and symptom survey was 506 days for school-age children and 556 days for adolescents. In models adjusted for sex and race and ethnicity, 14 symptoms in both school-age children and adolescents were more common in those with SARS-CoV-2 infection history compared with those without infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. These symptoms affected almost every organ system. Combinations of symptoms most associated with infection history were identified to form a PASC research index for each age group; these indices correlated with poorer overall health and quality of life. The index emphasizes neurocognitive, pain, and gastrointestinal symptoms in school-age children but change or loss in smell or taste, pain, and fatigue/malaise–related symptoms in adolescents. Clustering analyses identified 4 PASC symptom phenotypes in school-age children and 3 in adolescents.

Conclusions and Relevance   This study developed research indices for characterizing PASC in children and adolescents. Symptom patterns were similar but distinguishable between the 2 groups, highlighting the importance of characterizing PASC separately for these age ranges.

Long COVID, or postacute sequelae of SARS-CoV-2 infection (PASC), has been broadly defined as symptoms, signs, and conditions that develop, persist, or relapse over time after SARS-CoV-2 infection. 1 , 2 These symptoms can last weeks, months, or years after the acute infection resolves and can have debilitating effects. Some experts believe that worldwide, an estimated 65 million people are living with PASC, 3 with impacts on population-level health anticipated to last for decades. Most research characterizing PASC has focused on adults, 4 leading to misperception that pediatric PASC is rare or presents similarly to PASC in adults. 5 , 6 This may lead clinicians to miss symptoms or misdiagnose children. Consistent with the life course framework in which developmental stage influences health outcomes, 7 PASC may present in both similar and different ways compared with adults.

Studies of pediatric PASC have documented a wide range of symptoms involving every organ system. 8 - 11 Most pediatric research has focused on individual symptoms and either pooled data from different ages or focused on adolescents. Little is known about differences in PASC symptoms between school-age children (6-11 years) and adolescents (12-17 years). 12 , 13 The absence of a consistent analytic approach to objectively identify children with PASC hinders the research needed to identify underlying mechanisms of disease and treatment targets. The National Institutes of Health–funded Researching COVID to Enhance Recovery ( RECOVER ) Initiative aims to fill these gaps by bringing together researchers, clinicians, communities, and families in a comprehensive study of PASC in children. 14 The aims of this analysis of the RECOVER-Pediatrics cohort were to identify (1) common prolonged symptoms experienced by children (6 to 17 years old) after SARS-CoV-2 infection, (2) how these symptoms differ by age (school-age vs adolescents), (3) how symptoms cluster into phenotypes, and (4) what symptoms in combination could be used as an empirically derived index to help researchers consistently assess the likely presence of PASC. These indices, like the one previously developed for the RECOVER-Adult cohort (18 years or older), 15 were intended to be used to identify factors that distinguish children who likely have developed PASC from those who may not have and to help evaluate risk factors for developing PASC, elucidate its pathophysiology, and enable follow-up to analyze recovery and relapse.

The RECOVER Pediatric Observational Cohort Study (RECOVER-Pediatrics) 14 is a combined retrospective and prospective longitudinal study including 4 cohorts. Data presented are from 2 cohorts: the de novo RECOVER cohort, including participants from birth through 25 years with and without SARS-CoV-2 infection history newly recruited from health care and community settings, and the extant National Institutes of Health–funded Adolescent Brain Cognitive Development cohort, 16 - 18 the largest long-term US study of brain development in adolescence. The protocol and statistical analysis plan for RECOVER-Pediatrics were previously described 19 (see Supplements 1 and 2 ). Data were obtained from more than 60 sites (eTable 1 in Supplement 3 ). The study received institutional review board approval from NYU Grossman School of Medicine (de novo cohort) or UC San Diego Human Research Protections Program (Adolescent Brain Cognitive Development cohort), with other institutions relying on these single institutional review boards. Caregiver-child pairs provided informed consent and age-appropriate assent. Strengthening and Reporting of Observational Studies in Epidemiology (STROBE) guidelines were followed.

The analytic sample included individuals aged 6 to 17 years enrolled between March 16, 2022, and December 16, 2023, with and without known SARS-CoV-2 infection history ( infected and uninfected , respectively). Child age was recorded at symptom survey completion.

For these analyses, the infected group included participants who completed their survey about prolonged symptoms at least 90 days after their first infection, reported by their caregivers (eMethods in Supplement 3 ). SARS-CoV-2 antibodies were not required. The uninfected group was defined by caregiver report and required confirmation of negative nucleocapsid antibodies at enrollment. Those thought to be uninfected but found to be antibody-positive (Ab+) within 30 days of survey completion were analyzed separately to understand asymptomatic infection. 20 Throughout, uninfected refers strictly to uninfected participants who were confirmed to be nucleocapsid antibody–negative.

Infected participants with an unknown date for their first infection, participants with history of multisystem inflammatory syndrome in children (because this is a well-characterized entity), 21 - 25 uninfected participants without antibody testing, and participants with missing symptom surveys (defined as <50% of questions completed) were excluded.

Caregivers completed a comprehensive symptom survey remotely (interviewer-administered if needed) assessing 89 prolonged symptoms across 9 domains, using health literacy–informed principles and plain-language descriptions (eTable 2 in Supplement 3 ). 19 , 26 Some symptoms describing a similar phenotype were combined into composites, resulting in 75 symptoms (eMethods in Supplement 3 ): general (12 symptoms), eyes/ears/nose/throat (15 symptoms), heart/lungs (10 symptoms), gastrointestinal (6 symptoms), dermatologic (5 symptoms), musculoskeletal (3 symptoms), neurologic (6 symptoms), behavioral/psychological (14 symptoms), and menstrual (4 symptoms). The same symptoms were assessed in both age groups (except panic attacks, which were assessed in adolescents only). Menstrual symptoms were assessed in those assigned female or intersex at birth and who started menstruating (reported only among adolescents).

The primary outcome was a prolonged symptom lasting for more than 4 weeks that started or became worse since the beginning of the pandemic and was present at the time of survey completion (at least 90 days after infection). If a symptom lasted for more than 4 weeks but was absent at survey completion, it was not counted as a prolonged symptom.

Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Scales were assessed, measuring caregiver perception of the child’s overall health, physical health, and quality of life. 27

The main exposure variable was SARS-CoV-2 infection. Other variables included sex, race and ethnicity, geographic origin, time since SARS-CoV-2 infection, calendar time of enrollment, and SARS-CoV-2 vaccination status (eMethods in Supplement 3 ). Like other variables, race and ethnicity were collected via caregiver report based on prespecified categories and measured to enhance understanding of racial and ethnic differences in PASC. Caregiver variables included relationship to child and educational attainment.

Statistical analyses were modeled after those published for RECOVER-Adult and were age-stratified. 15 The analysis calculated the proportion of participants who reported each prolonged symptom and who reported experiencing at least 1 prolonged symptom among infected and uninfected participants separately (eTable 3 in Supplement 3 ). For symptoms present in at least 5% of infected participants (candidate symptoms), the risk difference, odds ratio, and relative risk for infected vs uninfected participants were estimated using linear, logistic, and Poisson regression, respectively, adjusting for sex and race and ethnicity (eMethods in Supplement 3 ). Second, to identify combinations of symptoms that could be used for research, a penalized logistic regression approach (least absolute shrinkage and selection operator [LASSO]) 28 was used to identify what candidate symptoms (predictors) were best at differentiating participants with or without an infection history (outcome). 15 Because all sexes were combined for this analysis, menstrual symptoms were excluded. Based on the model fit, each symptom was assigned a score corresponding to the estimated log odds ratio, where a higher symptom score indicated a stronger association with infection. A total index was calculated for each participant by summing the individual scores for each symptom reported. An optimal index threshold for identifying PASC was selected based on the proportion of uninfected participants who were likely misclassified as having PASC (eMethods in Supplement 3 ). Participants meeting the index threshold were categorized as PASC-probable and others were categorized as PASC-unspecified . PASC rates were reported among infected and uninfected participants separately. Among infected participants, these rates were also reported by whether they were infected by December 1, 2021 (when the Omicron variant became the dominant US strain).

Third, the analysis examined correlations between PASC indices and caregiver-reported overall child health, quality of life, and physical health and symptoms selected by LASSO. Further, the frequency of all symptoms was reported in infected PASC-probable, infected PASC-unspecified, and uninfected participants separately. Fourth, symptom patterns were investigated among infected participants categorized as PASC-probable. Correlations between symptoms contributing to the PASC index among infected PASC-probable participants were calculated. K-means consensus clustering was performed based on symptoms contributing to the PASC index to identify distinct PASC symptom profiles. 29 The number of different systems affected among infected PASC-probable participants was then summarized by counting the systems in which at least 1 prolonged symptom was reported. Fifth, we summarized the characteristics and symptomatology of uninfected participants found to be Ab+.

This study included 751 infected and 147 uninfected school-age children and 3109 infected and 1369 uninfected adolescents (see cohort identification details in eFigure 1 in Supplement 3 ). The Table and eTable 4 in Supplement 3 contain demographic and infection history characteristics, respectively. eTable 5 in Supplement 3 contains demographic characteristics for the adolescent cohort, stratified by recruiting cohort (Adolescent Brain Cognitive Development vs de novo).

Overall, 45% of infected (338/751) and 33% of uninfected (48/147) school-age children and 39% of infected (1219/3109) and 27% of uninfected (372/1369) adolescents reported having at least 1 prolonged symptom. Twenty-six symptoms in infected school-age children and 18 symptoms in infected adolescents were prolonged in at least 5% of participants ( Figure 1 ). The lower 95% confidence bound of the adjusted odds ratio exceeded 0 for 14 symptoms in both school-age children and adolescents, with 4 additional symptoms in school-age children only and 3 in adolescents only ( Figure 1 ). The frequency of each symptom among infected participants did not differ after stratification into quintiles based on time between first infection and symptom survey date (eFigure 2 in Supplement 3 ).

The LASSO analysis identified 10 symptoms in school-age children and 8 in adolescents that were most associated with infection history ( Figures 2 A and 3 A). Optimal index thresholds of 5.5 in school-age children and 5.0 in adolescents were identified ( Figures 2 B and 3 B). Overall, 152 infected (20%) and 6 uninfected (4%) school-age children and 445 infected (14%) and 44 uninfected (3%) adolescents met or exceeded this index threshold (eTable 6 in Supplement 3 ). This percentage was higher for participants infected before vs after the emergence of Omicron (21% vs 14% for school-age children; 17% vs 7% for adolescents). Correlations between symptoms that contributed to the index are shown in eFigure 3 in Supplement 3 . Correlations between these symptoms and those that did not contribute to the index are shown in eTable 7 in Supplement 3 . Some uninfected participants may have met the index threshold due to misclassification or due to having other symptoms.

In both age groups, higher PASC research indices were correlated with worse PROMIS scores ( Figures 2 C and 3 C). The number of systems affected among infected PASC-probable participants (eFigure 4 in Supplement 3 ) indicated substantial multisystem burden.

Figure 4 shows the percentage of participants in each age group experiencing each symptom after stratification into 3 subgroups: infected PASC-probable, infected PASC-unspecified, and uninfected. The most common prolonged symptom among PASC-probable school-age children that also contributed to the PASC research index ( Figures 2 B and 4 ) was headache (57%), followed by trouble with memory/focusing and trouble sleeping (44%) and stomach pain (43%). Among symptoms that did not contribute to the index, body/muscle/joint pain (51%), daytime tiredness/sleepiness or low energy (49%), and feeling anxious (47%) were the most common ( Figure 4 ). The distribution of symptoms was similar between PASC-unspecified and uninfected school-age children.

Among PASC-probable adolescents, the most common prolonged symptoms contributing to the index ( Figures 3 B and 4 ) were daytime tiredness/sleepiness or low energy (80%), body/muscle/joint pain (60%), headaches (55%), and trouble with memory/focusing (47%). Among symptoms that did not contribute to the index, trouble sleeping (47%), feeling anxious (47%), and feeling sad/depressed (38%) were the most common ( Figure 4 ). The distribution of symptoms was similar between PASC-unspecified and uninfected adolescent participants.

Among school-age children, 4 symptom clusters were identified ( Figure 5 ). Cluster 1 had high rates of many symptoms and the highest symptom burden. Cluster 2 was characterized by high rates of headache (95%), body/muscle/joint pain (60%), and daytime tiredness/sleepiness or low energy (52%). Cluster 3 was characterized by higher rates of trouble sleeping (64%) and trouble with memory/focusing (62%). Cluster 4 was characterized predominantly by stomach pain (100%) and nausea/vomiting (61%). Among adolescents, 3 clusters were identified ( Figure 5 ). Cluster 1 had high rates of many symptoms, similar to the first school-age cluster. Cluster 2 was characterized by high rates of daytime tiredness/sleepiness or low energy (89%) and body/muscle/joint pain (87%). Cluster 3 was characterized by having change/loss in smell or taste (100%), with relatively low rates of all other symptoms. The clusters with the most symptoms in both school-age children and adolescents (cluster 1) had the highest mean number of systems affected (eTable 8 in Supplement 3 ) and were correlated with poorer overall health and quality of life (eFigure 5 in Supplement 3 ).

Overall, 64 school-age children and 781 adolescents enrolled as uninfected but were Ab+ (ie, asymptomatically infected; eFigure 1 and eTable 9 in Supplement 3 ). Among school-age children, 6 (9%) met the index threshold whereas 18 (28%) reported experiencing at least 1 prolonged symptom. Among adolescents, 29 (4%) met the index threshold and 175 (22%) reported at least 1 prolonged symptom.

Symptom frequencies for all groups (infected, uninfected, and uninfected Ab+), including estimated risk ratios and odds ratios, are shown in eTable 10 in Supplement 3 .

In this large-scale study, children with probable PASC experienced prolonged symptoms in almost every organ system, with the majority having multisystem involvement. A clear pattern of symptom differences was identified between school-age children and adolescents, underscoring the importance of characterizing PASC separately in these 2 age groups.

This study developed an empirically derived index that can be used to help researchers identify children likely to have PASC, which was associated with overall health, physical health, and quality of life. This PASC research index, distinct for each age group, used combinations of 10 symptoms in school-age children and 8 symptoms in adolescents to indicate the likelihood of PASC. Although many other symptoms were more common in infected compared with uninfected participants, symptoms selected for the index were those that were most associated with infection history. Because these other symptoms were highly associated with the symptoms selected for the index (eTable 7 in Supplement 3 ), it was rare for participants not meeting the index threshold to have these other symptoms ( Figure 4 ). In this cohort, 20% of infected school-age children exceeded the PASC symptom threshold, while 14% of adolescents exceeded the threshold. PASC symptoms clustered into 4 distinct clusters in school-age children and 3 in adolescents.

The PASC research index presents a framework for future studies and can be used as a continuous or binary outcome variable (based on derived thresholds) to determine risk factors for developing PASC and the trajectory of PASC and its resolution (or relapse). Although this provisional index may be used for research, it is not intended for clinical practice, and 1 symptom may be sufficient to indicate PASC in any given child.

This study makes a substantial contribution to the understanding of pediatric PASC. Most research to understand PASC symptoms has focused on adults, potentially due to the misperception that children were not severely affected by COVID-19, leaving childhood symptoms less understood. Most prior pediatric studies have relied on electronic health records. 30 , 31 The current study had the advantage of comprehensively assessing caregiver-reported symptoms across every organ system, examining them in combination, and comparing them directly to an uninfected seronegative control group. The symptoms identified as being related to PASC were associated with infection, not only symptoms that became more common during the pandemic.

This study identified separate PASC research indices for school-age children and adolescents based on symptoms most likely to differentiate between those with and without an infection history. Higher indices were correlated with worse functional outcomes, and those with indices meeting the PASC threshold reported many prolonged symptoms, not just those selected by LASSO. 28 The strongest differentiators of infection history in adults (RECOVER-Adult study) 15 and adolescents overlapped considerably. There was less overlap between adults and school-age children. These findings underscore the need for separate assessments in different age groups. This may be one reason that younger children with PASC are being undercounted in studies and/or undiagnosed clinically, although undercounting may also be due to younger children being less able to recognize and report symptoms. The pathophysiology behind these age-related differences warrants future study, given substantial changes in growth, development, immunological factors, and pubertal hormones that occur across the life course. 11

Among infected participants, there was a wide range of time elapsed between infection and survey completion (median [IQR] time was 501 [297-801] days for school-age children and 518 [333-810] days for adolescents). However, symptom frequency did not change meaningfully when comparing different times between infection and survey completion, underscoring the usefulness of the PASC index for any child in the postacute phase of SARS-CoV-2 infection.

Four symptom clusters in school-age children and 3 in adolescents were identified. In both age groups, there was a single cluster with high symptom burden (as in adults) and a cluster predominated by fatigue and pain symptoms. Other clusters differed by age. School-age children had a cluster with neuropsychological and sleep impacts and another with gastrointestinal predominance. Adolescents had a cluster that was primarily loss of taste and smell, 32 similar to that found in adults, which was not noted in the school-age clusters. Clusters predominated by respiratory symptoms were not identified, possibly related to community recruitment or few participants with severe acute illness. Future research should evaluate whether these pediatric clusters are associated with different pathophysiology from adults, 33 - 35 which will be critical for identifying the treatment targets needed for clinical trials. 36 - 40

This study has limitations. First, the research index is not intended for use in clinical practice to diagnose PASC. Rather it must be considered with clinical judgement because children may have PASC without meeting the index threshold. There are many prolonged symptoms that differ between those previously infected and uninfected with SARS-CoV-2 that are not part of this index. It remains unknown how many children with other diagnoses would have similar prolonged symptoms. This index may evolve over time with changing variants and population immunity. Although children with higher PASC indices report worse quality of life, the cross-sectional analyses preclude causal inference. If a symptom lasted more than 4 weeks but was absent at survey completion, it was not included as a prolonged symptom because this index was not meant to describe incidence. However, it can be used for longitudinal follow-up of recovery and relapse, which would not be possible if resolved symptoms were used in the calculations.

Second, the population prevalence of pediatric PASC cannot be determined with the current design because participants with more prolonged symptoms may have been more inclined to enroll. To mitigate differences that may have resulted from having an extant adolescent cohort, community outreach within the school-age group was encouraged.

Third, some participants in the infected and uninfected groups could have been misclassified. Infected participants were not required to have evidence of SARS-CoV-2 infection; this study relied on caregiver-reported COVID-19 infection history, given variable access to testing. Uninfected children were confirmed to not have SARS-CoV-2 antibodies, but it is possible that some may have been unknowingly infected without developing antibodies or their immunity waned. 41 Uninfected participants may have another postviral syndrome or other conditions that may have symptoms and even pathophysiology that overlaps with PASC. 42 Despite this uncertainty, important differences between infected and uninfected groups were detected.

Fourth, given that symptoms were caregiver-reported, recall bias is possible. In addition, caregiver perceptions of their adolescents’ symptoms may differ from those of the adolescents themselves. However, to enable valid comparisons across age groups, data collection methods were standardized. Future analyses will combine caregiver-reported surveys with objective measures collected during the in-person longitudinal study phase. 19

Fifth, this empirically derived index is a framework that identified commonalities for research purposes. Iterative adaptation of how PASC is assessed may occur as more RECOVER data are collected and as children are followed up. Future analyses will examine PASC symptoms in early childhood (birth to 5 years) and the effects of SARS-CoV-2 on worsening underlying conditions and increasing new conditions, 43 - 45 such as diabetes, 46 autoimmune diseases, 47 neurocognitive disorders, and postinfectious syndromes. 11

In this large-scale study, symptoms that characterized pediatric PASC differed by age group, and several distinct phenotypic PASC presentations were described. The research indices developed here will help researchers identify children and adolescents with high likelihood of PASC. Although these indices will require further research and validation, this work provides an important step toward a clinically useful tool for diagnosis with the ultimate goal of supporting optimal care for youth with PASC.

Accepted for Publication: June 4, 2024.

Published Online: August 21, 2024. doi:10.1001/jama.2024.12747

Corresponding Author: Rachel S. Gross, MD, MS, NYU Grossman School of Medicine, 462 First Ave, New York, NY 10016 ( [email protected] ).

RECOVER-Pediatrics Group Authors: Venkataraman Balaraman, MD; Amanda Bogie, MD; Hulya Bukulmez, MD; Allen J. Dozor, MD; Daniel Eckrich, MS; Amy J. Elliott, PhD; Danielle N. Evans, DHSc, MHA; Jonathan S. Farkas, MD; E. Vincent S. Faustino, MD, MHS; Laura Fischer, MPH; Sunanda Gaur, MD; Ashraf S. Harahsheh, MD; Uzma N. Hasan, MD; Daniel S. Hsia, MD; Gredia Huerta-Montañez, MD; Kathy D. Hummel, MSN; Matt P. Kadish, MD; David C. Kaelber, MD, MPH; Sankaran Krishnan, MD, MPH; Jessica S. Kosut, MD; Jerry Larrabee, MD; Peter Paul C. Lim, MD; Ian C. Michelow, MD; Carlos R. Oliveira, MD, PhD; Hengameh Raissy, PharmD; Zaira Rosario-Pabon, MS; Judith L. Ross, MD; Alice I. Sato, MD, PhD; Michelle D. Stevenson, MD, MS; Maria M. Talavera-Barber, DO; Ronald J. Teufel, MD, MSCR; Kathryn E. Weakley, MD, MSc; Emily Zimmerman, PhD, CCC-SLP; Marie-Abele C. Bind, PhD; James Chan, MA; Zoe Guan, PhD; Richard E. Morse, BA; Harrison T. Reeder, PhD; Natascha Akshoomoff, PhD; Judy L. Aschner, MD; Rakesh Bhattacharjee, MD; Lesley A. Cottrell, PhD; Kelly Cowan, MD; Viren A. D'Sa, MD; Alexander G. Fiks, MD, MSCE; Maria L. Gennaro, MD; Katherine Irby, MD; Manaswitha Khare, MD; Jeremy Landeo Guttierrez, MD, MPH; Russell J. McCulloh, MD, MS; Shalu Narang, MD; Manette Ness-Cochinwala, MD; Sheila Nolan, MD; Paul Palumbo, MD; Julie Ryu, MD; Juan C. Salazar, MD, MPH; Rangaraj Selvarangan, PhD; Cheryl R. Stein, PhD; Alan Werzberger, MD; William T. Zempsky, MD, MPH; Robin Aupperle, PhD; Fiona C. Baker, PhD; Marie T. Banich, PhD; Deanna M. Barch, PhD; Arielle Baskin-Sommers, PhD; James M. Bjork, PhD; Susan Y. Bookheimer, PhD; Sandra A. Brown, PhD; BJ Casey, PhD; Linda Chang, MD; Duncan B. Clark, MD, PhD; Anders M. Dale, PhD; Mirella Dapretto, PhD; Thomas M. Ernst, PhD; Damien A. Fair, PA-C, PhD; Sarah W. Feldstein Ewing, PhD; John J. Foxe, PhD; Edward G. Freedman, PhD; Naomi P. Friedman, PhD; Hugh Garavan, PhD; Dylan G. Gee, PhD; Raul Gonzalez, PhD; Kevin M. Gray, MD; Mary M. Heitzeg, PhD; Megan M. Herting, PhD; Joanna Jacobus, PhD; Angela R. Laird, PhD; Christine L. Larson, PhD; Krista M. Lisdahl, PhD; Monica Luciana, PhD; Beatriz Luna, PhD; Pamela A.F. Madden, PhD; Erin C. McGlade, PhD; Eva M. Müller-Oehring, PhD; Bonnie J. Nagel, PhD; Michael C. Neale, PhD; Martin P. Paulus, PhD; Alexandra S. Potter, PhD; Perry F. Renshaw, MD, PhD; Elizabeth R. Sowell, PhD; Lindsay M. Squeglia, PhD; Susan Tapert, PhD; Lucina Q. Uddin, PhD; Sylia Wilson, PhD; Deborah A. Yurgelun-Todd, PhD.

Affiliations of RECOVER-Pediatrics Group Authors: Department of Biostatistics, Massachusetts General Hospital, Boston (Chan, Guan, Morse, Reeder); Division of Respiratory Medicine, Department of Pediatrics, UC San Diego School of Medicine, Rady Children’s Hospital, San Diego, California (Bhattacharjee, Guttierrez, Ryu); Division of Biostatistics, Department of Medicine, Massachusetts General Hospital, Boston (Bind); Department of Pediatrics, Kapi'olani Medical Center for Women and Children, University of Hawaii, John A. Burns School of Medicine, Honolulu, Hawaii (Balaraman, Kosut); Department of Pediatrics, Oklahoma University Health Science Center, Oklahoma City (Bogie); Division of Pediatric Rheumatology, Department of Pediatrics, MetroHealth System, Cleveland, Ohio (Bukulmez); Division of Pediatric Pulmonology, Allergy, and Sleep Medicine, Department of Pediatrics, Boston Children's Health Physicians, New York Medical College, Valhalla (Dozor, Krishnan); Department of Biomedical Research Informatics Center, Nemours Children's Hospital Delaware, Wilmington (Eckrich); Avera Research Institute, Sioux Falls, South Dakota (Elliott); Division of Research, Department of Research Administration, Arkansas Children's Hospital, Little Rock (Evans, Hummel); Department of Pediatrics, NYU Grossman School of Medicine, New York City Health and Hospitals Bellevue, New York (Farkas); Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut (Faustino); Pediatric Research Office, University of Nebraska Medical Center, Omaha (Fischer); Division of Allergy, Immunology, and Infectious Diseases, Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey (Gaur); Division of Cardiology, Department of Pediatrics, Children's National Hospital, The George Washington University School of Medicine & Health Sciences, Washington, DC (Harahsheh); Division of Infectious Diseases, Department of Pediatrics, Cooperman Barnabas Medical Center, Livingston, New Jersey (Hasan); Department of Clinical Trials Unit, Pennington Biomedical Research Center, Baton Rouge, Louisiana (Hsia); Division of Puerto Rico Testsite for Exploring Contamination Threats, Northeastern University, Boston, Massachusetts (Huerta-Montañez); Division of General Pediatrics, Department of Pediatrics, University of New Mexico School of Medicine, Albuquerque (Kadish, Larrabee); Departments of Pediatrics, Internal Medicine, and Population and Quantitative Health Sciences, MetroHealth System, Cleveland, Ohio (Kaelber); Division of Infectious Diseases, Department of Pediatrics, University of South Dakota Sanford School of Medicine, Avera Research Institute, Sioux Falls (Lim); Division of Infectious Diseases, Department of Pediatrics, Connecticut Children's Medical Center, University of Connecticut School of Medicine, Hartford (Michelow, Salazar); Division of Infectious Diseases, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut (Oliveira); Division of Pulmonary, Department of Pediatrics, University of New Mexico School of Medicine, Albuquerque (Raissy); Division of Puerto Rico Testsite for Exploring Contamination Threats, Department of Civil and Environmental Engineering, Northeastern University, Boston, Massachusetts (Rosario-Pabon); Division of Pediatrics Administration, Department of Pediatrics, Thomas Jefferson University, Nemours Children's Hospital Delaware, Philadelphia, Pennsylvania (Ross); Division of Infectious Disease, Department of Pediatrics, University of Nebraska Medical Center, Omaha (Sato); Division of Norton Children's Emergency Medicine, Department of Pediatrics, University of Louisville School of Medicine, Louisville, Kentucky (Stevenson); Department of Pediatrics, University of South Dakota Sanford School of Medicine, Avera Research Institute, Sioux Falls (Talavera-Barber); Department of Pediatrics, Medical University of South Carolina, Charleston (Teufel); Division of Norton Children's Infectious Diseases, Department of Pediatrics, University of Louisville School of Medicine, Louisville, Kentucky (Weakley); Division of Puerto Rico Testsite for Exploring Contamination Threats, Department of Communication Sciences & Disorders, Northeastern University, Boston, Massachusetts (Zimmerman); Department of Psychiatry, UC San Diego School of Medicine, Rady Children's Hospital, San Diego, California (Akshoomoff, Jacobus, Tapert); Center for Discovery and Innovation, Department of Pediatrics, Hackensack Meridian School of Medicine, Nutley, New Jersey (Aschner); Department of Pediatrics, West Virginia University, Morgantown (Cottrell); Division of Pediatric Pulmonology, Department of Pediatrics, University of Vermont, Burlington (Cowan); Department of Developmental Pediatrics, Rhode Island Hospital, Providence (D'Sa); Division of General Pediatrics, Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (Fiks); Public Health Research Institute, Departments of Medicine, Rutgers Robert Wood Johnson Medical School, Newark, New Jersey (Gennaro); Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock (Irby); Division of Hospital Medicine, Department of Pediatrics, UC San Diego School of Medicine, Rady Children's Hospital, San Diego, California (Khare); Division of Pediatric Hospital Medicine, Department of Pediatrics, University of Nebraska Medical Center, Omaha (McCulloh); Cooperman Barnabas Medical Center, Livingston, New Jersey (Narang); Nicklaus Children's Hospital, Division of Population Health, Quality, and Implementation Sciences (PopQuIS), Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, Miami, Florida (Ness-Cochinwala); Division of Infectious Diseases, Department of Pediatrics, Boston Children's Health Physicians, New York Medical College, Valhalla (Nolan); Divisions of Infectious Disease and International Health, Departments of Pediatrics and Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire (Palumbo); Department of Pediatrics, Children's Mercy Hospital and Clinics, Kansas City, Missouri (Selvarangan); Department of Child and Adolescent Psychiatry, NYU Grossman School of Medicine, New York (Stein); Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, Best Healthcare Inc, Monroe, New York (Werzberger); Department of Pediatrics, Connecticut Children's Medical Center, University of Connecticut School of Medicine, Hartford (Zempsky); Laureate Institute for Brain Research, Tulsa, Oklahoma (Aupperle, Paulus); Center for Health Sciences, SRI International, Menlo Park, California (Baker, Müller-Oehring); Institute of Cognitive Science and Department of Psychology and Neuroscience, University of Colorado Boulder (Banich); Departments of Psychological & Brain Sciences, Psychiatry, and Radiology, Washington University in St Louis, St Louis, Missouri (Barch); Department of Psychology, Yale University, New Haven, Connecticut (Baskin-Sommers, Gee); Institute for Drug and Alcohol Studies, Virginia Commonwealth University, Richmond (Bjork); Department of Psychiatry and Biobehavioral Sciences, University of Southern California, Children's Hospital Los Angeles (Bookheimer, Dapretto, Uddin); Department of Psychology and Psychiatry, UC San Diego School of Medicine, Rady Children's Hospital, San Diego, California (Brown); Department of Psychology, Barnard College - Columbia University, New York, New York (Casey); Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland Baltimore (Chang, Ernst); Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania (Clark, Luna); Departments of Neurosciences, Radiology, and Psychiatry, UC San Diego School of Medicine, Rady Children's Hospital, San Diego, California (Dale); Institute of Child Development, Department of Pediatrics, Masonic Institute for the Developing Brain, University of Minnesota, Oregon Health & Science University, Minneapolis (Fair); Department of Psychology, University of Rhode Island, Kingston (Feldstein Ewing); Deptartment of Neuroscience, Del Monte Institute for Neuroscience, University of Rochester School of Medicine, Rochester, New York (Foxe, Freedman); Institute for Behavioral Genetics and Department of Psychology and Neuroscience, University of Colorado Boulder (Friedman); Department of Psychiatry, University of Vermont, Burlington (Garavan); Department of Psychology, Florida International University, Miami (Gonzalez); Division of Addiction Sciences, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston (Gray, Squeglia); Department of Psychiatry, University of Michigan, Ann Arbor (Heitzeg); Department of Population and Public Health Sciences, University of Southern California, Children's Hospital Los Angeles (Herting); Department of Physics, Florida International University, Miami (Laird); Department of Psychology, University of Wisconsin-Milwaukee (Larson, Lisdahl); Department of Psychology, University of Minnesota, Minneapolis (Luciana); Department of Psychiatry, Washington University in St Louis, St Louis, Missouri (Madden); Departments of Psychiatry and Veteran Affairs, MIRECC, University of Utah School of Medicine, Salt Lake City (McGlade, Renshaw, Yurgelun-Todd); Department of Psychiatry, Oregon Health & Science University, Portland (Nagel); Virginia Institute for Psychiatric & Behavioral Genetics, Virginia Commonwealth University, Richmond (Neale); Division of Clinical Neuroscience Research Unit, Department of Psychiatry, University of Vermont, Burlington (Potter); Department of Pediatrics, University of Southern California, Children's Hospital Los Angeles (Sowell); Institute of Child Development, University of Minnesota, Minneapolis (Wilson).

Author Contributions: Drs Thaweethai and Foulkes had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Gross and Thaweethai contributed equally as co–first authors and Drs Foulkes and Stockwell contributed equally as co–senior authors.

Concept and design: Gross, Thaweethai, Kleinman, Snowden, Milner, Tantisira, Rhee, Jernigan, Kinser, Salisbury, Warburton, Mohandas, Flaherman, Metz, Karlson, Chibnik, Pant, Gallagher, Gennaro, Lamendola-Essel, Katz, Yin, Dreyer, Carmilani, Coombs, Fitzgerald, Taylor, Evans, Huerta-Montanez, Kaelber, Oliveira, Raissy, Reeder, Baker, Brown, Dale, D'Sa, Fair, Lisdahl, Luna, McGlade, Renshaw, Foulkes, Selvarangan, Stockwell, Yurgelun-Todd.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Gross, Thaweethai, Snowden, Kinser, Warburton, Mohandas, Krishnamoorthy, Gallagher, Katz, Carmilani, Coombs, Fitzgerald, Taylor, Eckrich, Raissy, Ross, Sato, Feldstein Ewing, Paulus, Stockwell, Squeglia.

Critical review of the manuscript for important intellectual content: All authors.

Statistical analysis: Fischer, Thaweethai, Chibnik, Pant, Krishnamoorthy, Letts, Sato, Reeder, Teufel, Neale, Bind, Chan, Foulkes.

Obtained funding: Gross, Thaweethai, Kleinman, Rosenzweig, Tantisira, Rhee, Jernigan, Kinser, Salisbury, Warburton, Katz, Elliott, Raissy, Aschner, Baker, Barch, Baskin-Sommers, Bjork, Bookheimer, Casey, Chang, Clark, Dale, Dapretto, Ernst, Fair, Feldstein Ewing, Foxe, Friedman, Gee, Gonzalez, Gray, Herting, Jacobus, Laird, Lisdahl, Luciana, Muller-Oehring, Nagel, Neale, Paulus, Renshaw, Salazar, Selvarangan, Stockwell, Tapert, Wilson.

Administrative, technical, or material support: Fischer, Gross, Hasan, Hsia, Kadish, Kleinman, Kosut, Snowden, Milner, Rhee, Jernigan, Warburton, Wood, Truong, Flaherman, Karlson, Gallagher, Lamendola-Essel, Hasson, Katz, Taylor, Teufel, Eckrich, Evans, Farkas, Faustino, Huerta-Montanez, Jacobus, Kaelber, Krishnan, Raissy, Morse, Cottrell, Fiks, Landeo Guttierrez, Ness-Cochinwala, Ryu, Stein, Baskin-Sommers, Aupperle, Brown, Bukulmez, Chan, Chang, Clark, Dale, Dozor, Ernst, Foxe, Freedman, Garavan, Gee, Laird, Lisdahl, McGlade, Paulus, Renshaw, Salazar, Stevenson, Squeglia, Uddin, Werzberger.

Supervision: Gross, Hsia, Thaweethai, Kleinman, Snowden, Rhee, Jernigan, Kinser, Warburton, Mohandas, Wood, Chibnik, Lamendola-Essel, Katz, Kaelber, Krishnan, Oliveira, Cottrell, Ness-Cochinwala, Akshoomoff, Aschner, Banich, Baskin-Sommers, Brown, Bukulmez, Chan, Chang, Clark, Dozor, Gee, Heitzeg, Herting, Hummel, Larrabee, Lisdahl, McGlade, Nolan, Renshaw, Fiks, Foulkes, Jacobus, Larson, Luciana, Salazar, Sowell, Stockwell, Teufel, Werzberger, Yurgelun-Todd.

Other - discussions of findings: Gallagher.

Other - communication of scientific findings: Fitzgerald.

Other - Contributed experience and knowledge from the patient/caregiver, and Infection Associated Chronic Condition community, perspective: Letts.

Conflict of Interest Disclosures: Dr Kleinman reported receiving grants from New York University via subcontract of NIH during the conduct of the study; owning shares in Amgen, Regeneron, Sanofi, and GLAXF; and being a member of the board of Dartnet Institute and member of the board of health of Borough of Metuchen, Quality Matters, Inc . Dr Snowden reported serving on a Pfizer COVID-19 advisory board, which ended in November 2023. Dr Milner reported serving on a scientific advisory board for Blueprint Medicine and receiving grants from Pharming. Dr Jernigan reported receiving grants from University of California San Diego OTA during the conduct of the study. Dr Salisbury reported receiving grants from NIH and HRSA and donated funds from Anthem outside the submitted work. Dr Newburger reported receiving grants from Pfizer for an observational study on COVID-19 associated myocarditis, serving on a data and safety monitoring committee for BMS, and serving on an independent events adjudication committee for pediatric apixiban study outside the submitted work. Dr Truong reported being co–principal investigator on a Pfizer-funded study to assess long-term sequalae of vaccine-associated myocarditis. Dr Metz reported being a site principal investigator for Pfizer studies of SARS-CoV-2 vaccination in pregnancy, RSV vaccination in pregnancy, and Paxlovid in pregnancy. Dr Dreyer reported receiving grants from NYU Grossman School of Medicine during the conduct of the study. Dr Aschner reported being a stockholder in Gilead Sciences. Dr Bhattacharjee reported serving on an advisory board for Jazz Pharmaceuticals. Dr Werzberger reported receiving funding from Merck for a hepatitis A vaccine immunology study. Dr Zempsky reported affiliations with OmmioHealth, Lundbeck Pharmacueticals, and Editas. Dr Banich reported receiving grants from University of Colorado Boulder during the conduct of the study. Dr Barch reported receiving grants from NIMH and NIDA during the conduct of the study. Dr Bhattacharjee reported consulting for Jazz Pharmaceuticals and Avadel Pharmaceuticals outside the submitted work. Dr Dale reported being a founder of and holding equity in CorTechs Labs, Inc; serving on a scientific advisory board for CorTechs Labs, Inc, Human Longevity, Inc, and the Mohn Medical Imaging and Visualization Centre; and receiving funding through a research agreement with General Electric Healthcare (GEHC). Dr Fair reported being a patent holder for the Framewise Integrated Real-Time Motion Monitoring (FIRMM) software and a cofounder of Turing Medical, Inc. Dr Fiks reported receiving personal fees from Rutgers and salary support from AAP during the conduct of the study; receiving support from American Medical Association for travel and honorarium from Atlantic Health Systems and Boston Medical Center, PCORI, and Emory University; and having a patent for decision support software known as Care Assistant pending. Dr Foulkes reported receiving grants from NIH/NHLBI during the conduct of the study. Dr Gray reported receiving grants from Aelis Farma and personal fees from Indivior and Jazz Pharmaceuticals outside the submitted work. Dr McCulloh reported receiving grants from University of Arkansas for Medical Sciences sub-awardee for the NIH RECOVER grant during the conduct of the study and grants from Merck Foundation for vaccine communication research through the Merck Investigator Studies Program outside the submitted work. Dr McGlade reported receiving salary support from Department of Veteran Affairs outside the submitted work. Dr Neale reported receiving grants from NIH/NIDA during the conduct of the study. Dr Palumbo reported being a member of a data and safety monitoring committee for Gilead and Janssen outside the submitted work. Dr Paulus reported receiving grants from National Institute on Drug Abuse during the conduct of the study, receiving royalties from an article on methamphetamine in UpToDate, and having compensated consulting agreement with Boehringer Ingelheim International GmbH. Dr Ross reported receiving grants from Nemours Children’s Health-DE NIH RECOVER STUDY during the conduct of the study. Dr Stockwell reported receiving grants from CDC to Trustees of Columbia related to SARS-CoV-2 infection and vaccination research and service agreement paid to trustees of Columbia for being associate director of pediatric research in office settings from American Academy of Pediatrics outside the submitted work. Dr Teufel reported receiving grants from HRSA and Duke outside the submitted work. No other disclosures were reported.

Funding/Support: This research was funded by NIH agreements OT2HL161841, OT2HL161847, and OT2HL156812, with additional support from grant R01 HL162373.

Role of the Funder/Sponsor: The NIH had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The RECOVER-Pediatrics Consortium appear listed in Supplement 4 .

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the RECOVER Program or the NIH.

Data Sharing Statement: See Supplement 5 .

Additional Contributions: We would like to thank the National Community Engagement Group, all patient, caregiver, and community representatives, and all the participants enrolled in the RECOVER Initiative.

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Gun violence was leading cause of death for US kids and teens in 2021, study finds

This story discusses suicide. If you or someone you know is in crisis, call or text 988 to reach the Suicide and Crisis Lifeline. You can also text HOME to 741741 or visit  SpeakingOfSuicide.com/resources  for additional resources.  

Gun-related deaths among children in the U.S. reached a distressing peak in 2021 , claiming 4,752 young lives and surpassing the  record total  seen during the first year of the pandemic, a new analysis of Centers for Disease Control and Prevention data found. 

The alarming statistic clearly indicated that America’s gun violence epidemic has gotten worse, experts say. 

More than 80% of the gun deaths were among males 19 and younger. Black male children were more likely to die from homicide. White males 19 and younger were more likely to kill themselves with guns.

“This is undoubtedly one of our chief public health crises in this country,” said Dr. Chethan Sathya, a pediatric trauma surgeon at Northwell Health in New York and the lead author of the study, which was published Monday in the journal Pediatrics. “The most likely reason that your child will die in this country is at the hands of a firearm. That’s not acceptable.”

This grim reality marks the second consecutive year in which gun-related injuries have solidified their position as the leading cause of death among children and adolescents, surpassing motor vehicles, drug overdoses and cancer. 

There are no signs of this trend slowing, Sathya said.

Nearly two-thirds of the deaths in 2021 were homicides, although unintentional shootings have killed many children. No matter how young the victims, pediatric gun-related deaths have left their mark on nearly every corner of the U.S. 

In recent months, a 3-year-old in  Florida  died after shooting himself with a handgun. In  California , a 3-year-old killed his 1-year-old sister with a handgun. A 2-year-old in  Michigan  died after finding an “unsecured firearm.” Just last week, a 6-year-old in Florida  was fatally shot  by a 9-year-old. 

Black children continue to be disproportionately affected.

From 2018 to 2021, there was a nearly 42% increase in the rate of children killed by guns, according to the analysis. The fatalities continued to increase in 2021, with more than 4,700 reported gun-related child deaths, an almost 9% increase in the rate compared with 2020.

Researchers had expected to see a decrease in gun-related deaths among children in 2021, following their sharp increase in 2020, which had been believed to be driven by pandemic-induced lockdowns and children being confined at home. 

Those projections, however, were not realized.

“This was surprising to many of us,” Sathya said, adding that the country has potentially entered an “alarming new baseline” in which it will continue to see more gun deaths in children.

Out of those 2021 fatalities, 64.3% were homicides, 29.9% were suicides and 3.5% resulted from unintentional injury, according to the analysis. 

The burden of gun homicides among children has disproportionately affected communities of color. 

Black children accounted for 67.3% of gun-related homicides, with a nearly twofold death rate increase from 2020. White children accounted for 78.4% of gun-related suicides. 

Overall, Black children represented half of all gun-related deaths.

The disparities between Black and white children match what has been found in earlier research, according to Nirmita Panchal, a senior policy analyst at KFF, formerly known as the Kaiser Family Foundation. 

“Communities of color have seen a stark increase in these deaths compared to their white peers,” she said. Furthermore, young survivors of gun-related injuries may face additional challenges that extend beyond their physical trauma, she added. They are also more susceptible to developing mental health problems and substance use disorders.

When examining gun-related deaths among children geographically, southern states — such as Louisiana, Mississippi, Alabama and South Carolina — and Montana bore a greater burden of fatalities, although researchers are beginning to see increasing rates in the Midwest, according to the analysis.

Older adolescents, ages 15 to 19, accounted for 82.6% of gun-related deaths in 2021. Across the U.S., higher poverty levels correlated with higher death rates from guns.

“Structural inequity, structural racism, social determinants of health, food insecurity are all root drivers of violence,” including gun violence, Sathya said.

Dr. Emily Lieberman, a pediatrician with Lurie Children’s Hospital, survived the  Highland Park Shooting in Chicago  last year, along with her husband and two children.

“I was not a hero that day. I saved no one, I helped no one but my family, and when I did leave that day alive, I knew that I was changed forever,” she said.

Lieberman said she wished she had been surprised by the latest statistics on pediatric gun deaths. But because of a lack of legislation from lawmakers targeting guns, she believes the death toll will only be higher next year.

“We are seeing every day countless children dying, perishing from gun violence,” she said. “It is affecting everyone, everywhere and only getting worse.”

Panchal noted members of Congress have focused on youth mental health, including expanding school-based mental health services and providing trauma care.

Sathya said he has advocated for better background checks and safer storage of weapons. He also said there needed to be more research into the root causes of gun violence.

“Although we can say this is an issue that might not affect everybody, it really does,” he said. “If you look at the spikes in gun injuries, it’s hitting all communities. It doesn’t matter where you live.”

This story originally appeared on NBCNews.com .

Berkeley Lovelace Jr. is a health and medical news reporter for NBC News.

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Identification and molecular characterization of a novel Babesia orientalis rhoptry neck protein 4 (BoRON4)

• Published: 29 August 2024
• Volume 123 , article number  310 , ( 2024 )

Cite this article

• Fangjie Li 1 , 2   na1 ,
• Jiaying Guo 4   na1 ,
• Sen Wang 1 , 2 ,
• Zhen Han 1 , 2 ,
• Zheng Nie 1 , 2 ,
• Long Yu 1 , 2 ,
• Xiang Shu 1 , 2 ,
• Yingjun Xia 1 , 2 ,
• Lan He 1 , 2 , 3 &
• Junlong Zhao 1 , 2 , 3  

B abesia orientalis , a protozoan parasite transmitted by the tick Rhipicephalus haemaphysaloides , holds significant economic importance along the Yangtze River. Key factors in the host invasion process include rhoptry neck proteins (RON2, RON4, and RON5) and apical membrane antigen 1 (AMA1). However, the intricacies of the interaction between AMA1 and RONs remain incompletely elucidated in B. orientalis . To better understand these crucial invasion components, the RON4 gene of B. orientalis (BoRON4) was cloned and sequenced. RON4 is 3468 base pairs long, encodes 1155 amino acids, and has a predicted molecular weight of 130 kDa. Bioinformatics analysis revealed a unique region (amino acid residues 109–452) in BoRON4, which demonstrates higher sensitivity to epitope activity. The BoRON4 gene was strategically truncated, amplified, and cloned into the pGEX-6p-1 vector for fusion expression. We successfully used the mouse polyclonal antibody to identify native BoRON4 in B. orientalis lysates. Furthermore, the corresponding BoRON4 protein band was detected in the water buffalo serum infected with B. orientalis , while no such band was observed in the control. Additionally, I-TASSER and Discovery Studio software were used to predict the tertiary structures of BoRON4 and its ligands, CH-PKA and CH-complex. These ligands can serve as lead compounds for the development of anti-babesiosis drugs. In conclusion, BoRON4 emerges as a promising candidate antigen for distinguishing water buffalo infected with B. orientalis from their normal counterparts. This study positions BoRON4 as a potential diagnostic antigen for babesiosis in water buffalo, contributing valuable insights to the field of parasitology.

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This study was supported by grant 31930108 from the National Natural Science Foundation of China, grant 2022YFD1800200 from the National Key Research and Development Program of China, and the Fundamental Research Funds for the Central Universities in China (Project 2662020DKPY016 and 2262022DKYJ001).

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Fangjie Li and Jiaying Guo did the equal work. Fangjie Li was responsible for the whole process of experimental design and experimental operation, and Jiaying Guo was responsible for the experimental scheme design.

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State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, Hubei, China

Fangjie Li, Sen Wang, Zhen Han, Zheng Nie, Long Yu, Xiang Shu, Yingjun Xia, Lan He & Junlong Zhao

Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, Hubei, China

Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People’s Republic of China, Wuhan, 430070, Hubei, China

Lan He & Junlong Zhao

Heilongjiang Provincial Key Laboratory of Zoonosis, College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, China

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FL, LH, and JZ designed the study and drafted the manuscript. FL and JG performed the experiments. ZH and SW participated in the data analysis. All authors read and approved the final manuscript.

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• Published: 07 December 2020

2021: research and medical trends in a post-pandemic world

• Mike May 1  

Nature Medicine volume  26 ,  pages 1808–1809 ( 2020 ) Cite this article

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Goodbye 2020, a year of arguably too many challenges for the world. As tempting as it is to leave this year behind, the biomedical community is forever changed by the pandemic, while business as usual needs to carry on. Looking forward to a new year, experts share six trends for the biomedical community in 2021.

Summing up 2020, Sharon Peacock, director of the COVID-19 Genomics UK Consortium, says “we’ve seen some excellent examples of people working together from academia, industry, and healthcare sectors...I’m hopeful that will stay with us going into 2021.” Nonetheless, we have lost ground and momentum in non-COVID research, she says. “This could have a profound effect on our ability to research other areas in the future.”

The coronavirus SARS-CoV-2 has already revealed weaknesses in medical research and clinical capabilities, as well as opportunities. Although it is too soon to know when countries around the world will control the COVID-19 pandemic, there is already much to be learned.

To explore trends for 2021, we talked to experts from around the world who specialize in medical research. Here is what we learned.

1. The new normal

Marion Koopman, head of the Erasmus MC Department of Viroscience, predicts that emerging-disease experts will overwhelmingly remain focused on SARS-CoV-2, at least for the coming year.

“I really hope we will not go back to life as we used to know it, because that would mean that the risk of emerging diseases and the need for an ambitious preparedness research agenda would go to the back burner,” Koopman says. “That cannot happen.”

Scientists must stay prepared, because the virus keeps changing. Already, Koopman says, “We have seen spillback [of SARS-CoV-2] into mink in our country, and ongoing circulation with accumulation of mutations in the spike and other parts of the genome.”

Juleen R. Zierath, an expert in the physiological mechanisms of metabolic diseases at the Karolinska Institute and the University of Copenhagen, points out that the pandemic “has raised attention to deleterious health consequences of metabolic diseases, including obesity and type 2 diabetes,” because people with these disorders have been “disproportionally affected by COVID-19.” She notes that the coupling of the immune system to metabolism at large probably deserves more attention.

2. Trial by fire for open repositories

The speed of SARS-CoV-2’s spread transformed how scientists disseminate information. “There is an increased use of open repositories such as bioRxiv and medRxiv, enabling faster dissemination of study and trial results,” says Alan Karthikesalingam, Research Lead at Google Health UK. “When paired with the complementary — though necessarily slower — approach of peer review that safeguards rigor and quality, this can result in faster innovation.”

“I suspect that the way in which we communicate ongoing scientific developments from our laboratories will change going forward,” Zierath says. That is already happening, with many meetings going to virtual formats.

Deborah Johnson, president and CEO of the Keystone Symposia on Molecular and Cellular Biology, notes that while virtual events cannot fully replace the networking opportunities that are created with in-person meetings, “virtual events have democratized access to biomedical research conferences, enabling greater participation from young investigators and those from low-and-middle-income countries.” Even when in-person conferences return, she says, “it will be important to continue to offer virtual components that engage these broader audiences.”

3. Leaps and bounds for immunology

Basic research on the immune system, catapulted to the frontlines of the COVID-19 response, has received a boost in attention this year, and more research in that field could pay off big going forward.

Immunobiologist Akiko Iwasaki at the Yale School of Medicine hopes that the pandemic will drive a transformation in immunology. “It has become quite clear over decades of research that mucosal immunity against respiratory, gastrointestinal, and sexually transmitted infections is much more effective in thwarting off invading pathogens than systemic immunity,” she says. “Yet, the vast majority of vaccine efforts are put into parenteral vaccines.”

“It is time for the immunology field to do a deep dive in understanding fundamental mechanisms of protection at the mucosal surfaces, as well as to developing strategies that allow the immune response to be targeted to the mucosal surfaces,” she explains.

“We are discovering that the roles of immune cells extend far beyond what was previously thought, to play underlying roles in health and disease across all human systems, from cancer to mental health,” says Johnson.

She sees this knowledge leading to more engineered immune cells to treat diseases. “Cancer immunotherapies will likely serve as the proving ground for immune-mediated therapies against many other diseases that we are only starting to see through the lens of the immune system.”

4. Rewind time for neurodegeneration

Oskar Hansson, research team manager of Lund University’s Clinical Memory Research, expects the trend of attempting to intervene against neurodegenerative disease before widespread neurodegeneration, and even before symptom onset, to continue next year.

This approach has already shown potential. “Several promising disease-modifying therapies against Alzheimer’s disease are now planned to be evaluated in this early pre-symptomatic disease phase,” he says, “and I think we will have similar developments in other areas like Parkinson’s disease and [amyotrophic lateral sclerosis].”

Delving deeper into such treatments depends on better understanding of how neurodegeneration develops. As Hansson notes, the continued development of cohort studies from around the world will help scientists “study how different factors — genetics, development, lifestyle, etcetera — affect the initiation and evolution of even the pre-symptomatic stages of the disease, which most probably will result in a much deeper understanding of the disease as well as discovery of new drug targets.”

5. Digital still front and center

“As [artificial intelligence] algorithms around the world begin to be released more commonly in regulated medical device software, I think there will be an increasing trend toward prospective research examining algorithmic robustness, safety, credibility and fairness in real-world medical settings,” says Karthikesalingam. “The opportunity for clinical and machine-learning research to improve patient outcomes in this setting is substantial.”

However, more trials are needed to prove which artificial intelligence works in medicine and which does not. Eric Topol, a cardiologist who combines genomic and digital medicine in his work at Scripps Research, says “there are not many big, annotated sets of data on, for example, scans, and you need big datasets to train new algorithms.” Otherwise, only unsupervised learning algorithms can be used, and “that’s trickier,” he says.

Despite today’s bottlenecks in advancing digital health, Topol remains very optimistic. “Over time, we’ll see tremendous progress across all modalities — imaging data, speech data, and text data — to gather important information through patient tests, research articles or reviewing patient chats,” he says.

He envisions that speech-recognition software could, for instance, capture physician–patient talks and turn them into notes. “Doctors will love this,” he says, “and patients will be able to look a doctor in the eye, which enhances the relationship.”

6. ‘Be better prepared’ — a new medical mantra

One trend that every expert interviewed has emphasized is the need for preparation. As Gabriel Leung, a specialist in public-health medicine at the University of Hong Kong, put it, “We need a readiness — not just in technology platforms but also business cases — to have a sustained pipeline of vaccines and therapies, so that we would not be scrambling for some of the solutions in the middle of a pandemic.”

Building social resilience ahead of a crisis is also important. “[SARS-CoV-2] and the resulting pandemic make up the single most important watershed in healthcare,” Leung explains. “The justice issue around infection risk, access to testing and treatment — thus outcomes — already make up the single gravest health inequity in the last century.”

One change that Peacock hopes for in the near future is the sequencing of pathogens on location, instead of more centrally. “For pathogen sequencing, you need to be able to apply it where the problem under investigation is happening,” she explains. “In the UK, COVID-19 has been the catalyst for us to develop a highly collaborative, distributed network of sequencing capabilities.”

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Trends in the integration of medical corporation hospitals in Japan: a national wide longitudinal study between 2017 and 2021

• Satoshi Funada 1 ,
• Yan Luo 2 ,
• Hirotaka Kato 3 ,
• Takashi Yoshioka 1 , 4 ,
• Shunsuke Uno 1 , 5 ,
• Kimiko Honda 6 ,
• Yoko Akune 6 &
• Rei Goto 6 , 7  

BMC Health Services Research volume  24 , Article number:  1005 ( 2024 ) Cite this article

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Medical corporations, which are non-profit organizations that aim to operate hospitals, clinics, or long-term care facilities, account for more than half of all hospital beds and play a central role in the health care system in Japan. However, limited analysis of hospital integration has been performed. Examining the hospital integration trends of medical corporations can provide valuable insights for optimizing health care delivery and resource allocation in Japan. This study conducted a comprehensive analysis of trends in the hospital integration of medical corporations and market concentration in Japan using nationwide longitudinal data.

This longitudinal study evaluated the hospital integration of medical corporations in Japan between 2017 and 2021 using medical corporation financial data provided by the Neostage Company. The target population was medical corporations that own hospitals in Japan. The primary outcomes were the horizontal and vertical integration of medical corporation hospitals. Horizontal integration was defined as the integration of two or more hospitals within the same corporation, while vertical integration was defined as the integration of a hospital with different types of health care facilities, such as clinics or long-term care facilities, within a single medical corporation. The Herfindahl–Hirschman Index (HHI) was calculated to measure hospital market concentration using hospital bed data for medical corporations in all prefectures.

The number of hospitals and hospital beds within medical corporations decreased from 5,670 to 848,174 in 2017 to 5,486 and 814,462 in 2021, respectively. Both horizontal and vertical integration among medical corporation facilities showed a gradual upward trend, increasing from 24.92% to 55.75% in 2017 to 26.92% and 59.42% in 2021, respectively. The mean (standard deviation [SD]) HHI increased slightly from 262.7 (178.6) in 2017 to 275.2 (187.9) in 2021, with rural areas being more concentrated than urban areas, although both remained unconcentrated.

Conclusions

This longitudinal study revealed a gradual downward trend in the number of hospitals and hospital beds owned by medical corporations, while horizontal and vertical integration gradually progressed without any particular medical corporation dominating the market. These findings are expected to contribute to policymaking efforts aimed at providing optimal health care services in Japan.

Peer Review reports

Medical corporations (“Iryohoujin” in Japanese) are non-profit organizations established under the Medical Care Act (“Iryou Hou” in Japanese) [ 1 ]. These entities are founded with private capital but operate as strictly non-profit organizations. Their primary purpose is to own and manage various healthcare facilities, including hospitals, clinics, and long-term care facilities [ 1 ]. Since its establishment in 1950, the number of medical corporations has grown, and they have played an important role in supporting Japan’s health care system. Japan achieved universal health coverage in 1961, a milestone that significantly reduced the financial burden of medical costs on the population and greatly improved access to hospital care [ 2 ]. This led to a surge in demand for medical services, outpacing supply. Consequently, the number of hospitals increased dramatically from 6,094 in 1960 to 9,608 in 1985, with the majority of this growth occurring within medical corporations [ 3 ]. However, the rapid expansion of hospital beds soon led to concerns about oversupply in many regions and rising medical expenditures. To address these issues, the Japanese government implemented several key policy changes. The first revision of the Medical Care Act in 1985 introduced restrictions on opening new hospital beds, which were implemented at the prefectural level in 1989 [ 4 ]. As a result, policies were established to calculate a standard number of hospital beds per prefecture, aiming to control the uneven distribution of hospital beds across regions. These regulatory measures have contributed to a gradual downward trend in the number of hospital beds nationwide, while simultaneously encouraging more efficient use of existing healthcare resources.

In 2022, medical corporations owned 5,658 hospitals (69.4% of the total) and 834,330 hospital beds (55.9% of the total) [ 3 ]. In contrast, national and public hospitals accounted for 18.6% of the total number of hospitals (3.9% national, 14.7% public) and 29.0% of the total number of hospital beds (8.3% national, 20.7% public), indicating that these three types of entities dominate the hospital landscape in Japan [ 3 ]. While the management of national and public hospitals is determined by government policy, the same authority does not work for medical corporations, which would need to be guided by policy. To contain health care costs and optimize resource allocation in the face of a declining birth rate and an aging population in Japan, adjustments to the entire health care system, including medical corporations, are crucial [ 5 ]. Therefore, understanding the management trends within medical corporations is essential for policymaking.

Hospital integration has become an important strategy for hospital management to reduce costs and standardize care through horizontal integration between hospitals and vertical integration between hospitals and different levels of health care facilities [ 6 ]. In recent decades, both horizontal and vertical integration have accelerated rapidly in the United States [ 7 , 8 , 9 ], leading to the emergence of giant health care systems and “Integrated Delivery Networks” [ 10 ]. On the other hand, concerns have been raised about reduced competition due to market dominance by integrated health care hospitals [ 11 ]. In Japan, where the opening of new hospital beds is legally regulated by the first revision of the Medical Care Act in 1985 [ 1 ], integration becomes necessary for medical corporations to increase their scale and bed capacity. According to the Organization for Economic Co-operation and Development (OECD), Japan has one of the highest numbers of hospitals and hospital beds in the world [ 12 ], and reducing these numbers through integration is a major policy goal to promote health care cost reduction and optimal resource allocation [ 5 ].

To evaluate the effectiveness of past policies and develop the next policy to establish an optimal health care system in Japan, it is essential to understand current trends in the hospital integration of medical corporations. The Ministry of Health, Labour and Welfare (MHLW) reports aggregate data on hospitals by entity, which shows a decline in the number of hospitals and hospital beds owned by medical corporations after peaking in 2017. This could be due to a combination of factors: a simple reduction in the total number of hospitals and hospital beds and integration leading to aggregation. However, the Ministry’s publicly available data lack individual-level data for medical corporations, making it difficult to assess integration and market concentration. A previous nationwide study reported that horizontal integration accounted for 22.1% of hospitals and 28.1% of beds in 2011, with increases of 4.7% and 5.1%, respectively, over the 10-year period [ 13 ]. Another study showed that 23.1% of medical corporation hospitals were integrated with long-term care facilities in 1996 [ 14 ]. These previous studies conducted up to the 2010s demonstrated a steady progression of both horizontal and vertical integrations among medical corporations from the 1990s to the early 2010s. The Japanese healthcare landscape has undergone significant changes since these studies were conducted, including the Long-Term Care Insurance System in 2000 [ 15 ], the Community-based Integrated Care System around 2010 [ 16 ], and the revisions to medical and nursing fees in 2018 [ 17 , 18 ]. These policy changes have likely influenced the strategies and operations of medical corporations. However, no comprehensive analysis of medical corporation hospital integration has been conducted since the early 2010s, leaving a significant gap in our understanding of recent trends.

The present study aimed to analyze horizontal and vertical integration among medical corporation hospitals using individual hospital-level data. By examining the most recent five-year period, we tried to understand recent trends and make predictions about future integration. We also measured the market concentration of medical corporation hospitals and observed competition among them.

Study design

This longitudinal study examined trends in the integration of hospitals owned by medical corporations in Japan. Given that this study solely utilized medical corporation data, it was exempt from institutional review board approval and participant consent requirements, in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects that belongs to the MHLW in Japan. This study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines [ 19 ].

This study was conducted in Japan and focused on the landscape of medical corporation hospitals between 2017 and 2021.

Data source

The data for this study were derived from Medical Corporate Financial Data provided by The Neostage Company, a company that supports the collection and analysis of corporate information and data processing [ 20 ]. Under the Medical Care Act, medical corporations are required to submit annual financial statements and details of the owned facilities to each prefectural government [ 1 ], and the reports are compiled annually into a database by The Neostage Company. This database covers 95% of all medical corporations in Japan and provides comprehensive information on various characteristics of medical corporations, including facility types (hospital/clinic/long-term care facility/other), board of directors and executive officers, geographic address, number of beds, and financial statements, including balance sheets and profit and loss statements. The database does not contain information except for medical corporations, such as national, public, or individual hospitals. We collected data from this database for five years, from 2017 to 2021.

Study population

The target population of the study was medical corporations operating hospitals in Japan. According to the Medical Care Act, a medical corporation is an non-profit association or foundation that incorporates the relevant facility that aims to establish a hospital, clinic, or long-term care facility [ 1 ]. The types of facilities owned by medical corporations were classified into four categories according to the Medical Care Act [ 1 ] and Long-Term Care Insurance Act [ 21 ] as follows:

Hospital: a place where physicians provide health care, with inpatient facilities for 20 or more patients.

Clinic: a place where physicians provide health care, with no inpatient facilities or with inpatient facilities for 19 or fewer patients.

Long-term care facility: a place that provides medical care, including nursing and medical supervision and assistance with activities of daily living, for elderly persons in need of care, with a resident physician required on staff.

Other: a place that does not fall into any of the three categories above but provides services related to health and social welfare. Examples include community-based residential services, short-term stay service facilities, day care service centers and in-home service providers.

Of the medical corporations, we narrowed the target population to medical corporations that own hospitals and examined how they own hospitals, clinics, long-term care facilities, and others within their corporations.

Outcome measures and definitions

The following variables were extracted from the database: the name of the medical corporation, the classification of the facility (including hospitals, clinics, long-term care facilities, and others), the name of the facility, the geographic address of the facility, and the number of hospital beds. According to the OECD definition, hospital beds are all available beds, including psychiatric and special beds, but excluding operating tables, stretchers, closed beds, temporary beds or beds in long-term care facilities [ 22 ]. Horizontal integration was defined as the integration of two or more hospitals under a single medical corporation, while maintaining their individual operational structures (Fig.  1 ) [ 10 ]. Vertical integration, on the other hand, was defined as the integration of a hospital with different types of health care facilities, including clinics, long-term care facilities, or others, under a single medical corporation (Fig.  1 ) [ 10 ]. We assessed the integration status of each medical corporation annually over the five-year study period.

Schema of horizontal and vertical integration

Statistical analysis

We described the integration of hospitals within medical corporations each year over the period from 2017 to 2021 using numerical counts and percentages (%). We categorized medical corporation hospitals into horizontal and vertical integration groups and analyzed trends in the number of hospitals and hospital beds within each integration type annually. In addition, the Herfindahl–Hirschman Index (HHI) [ 23 ] was calculated to measure hospital market concentration using hospital bed data for medical corporations in all prefectures, such as Tokyo and Hokkaido. We calculated the HHI at the prefecture level because new hospital openings and bed restrictions are determined at the prefecture level by the Medical Care Act and prefectural governments play a significant role in healthcare planning and resource allocation in Japan [ 1 ]. This variable is the sum of the squared market share of each medical corporation in each prefecture multiplied by 10,000. According to the guidelines, markets were classified as highly concentrated if their HHI exceeded 2500, moderately concentrated if their HHI fell between 1500 and 2500, unconcentrated if their HHI fell between 100 and 1500, and highly competitive if their HHI was below 100 [ 24 ]. An increase in the HHI of less than 100 points is also classified as a small change in concentration [ 24 ]. All analyses were conducted between December 2023 and March 2024 using R (version 4.3.1; R Foundation for Statistical Computing, Vienna, Austria).

Medical corporation trends

Supplementary Fig.  1 shows the study flow diagram. The total number of medical corporations included in hospitals was 4,791 in 2017, 4,748 in 2018, 4,692 in 2019, 4,623 in 2020 and 4,545 in 2021. Table  1 shows the owned facilities and hospital beds of medical corporations with hospitals. Both the number of hospitals and the number of hospital beds owned by medical corporations exhibited a downward trend from 5,670 to 848,174 in 2017 to 5,486 and 814,462 in 2021, respectively.

Horizontal and vertical integration of medical corporation hospitals

Table  2 illustrates the trends in horizontal integration of hospitals within medical corporations from 2017 to 2021. In 2017, 4,257 medical corporations operated without horizontal integration, while 534 engaged in horizontal integration (as shown in the top column of Table  2 ). Among these 534 corporations, 389 owned two hospitals, and 82 owned three hospitals. While the absolute number of medical corporations with non-horizontal integrations decreased from 4,257 in 2017 to 4,009 in 2021, their proportion remained relatively constant at approximately 88% throughout the five-year period. Among horizontal integrations, medical corporations comprising two hospitals constituted the dominant group. Notably, corporations with more than ten hospitals remained scarce, representing less than 0.2% of the total. The proportion of hospitals and hospital beds covered by horizontal integrations increased steadily from 24.92% to 31.55% in 2017 to 26.92% and 33.75% in 2021, respectively (in the middle and bottom column of Table  2 ).

Table  3 demonstrates the trends in vertical integration. In 2017, 2,509 medical corporations operated without vertical integration, while 2,282 implemented vertical integration (as indicated in the top column of Table  3 ). Of these 2,282 corporations, 763 integrated hospitals with clinics, and 859 combined hospitals with long-term care facilities. The proportion of medical corporations without vertical integrations declined from 52.37% in 2017 to 48.98% in 2021. Looking at the types of vertical integration, the most common configurations were combinations of hospitals and long-term care facilities, hospitals and clinics, and a trifecta of hospitals, clinics, and long-term care facilities. Similar to horizontal integration, the share of hospitals and hospital beds within vertically integrated entities showed a gradual upward trend from 55.75% to 60.79% in 2017 to 59.42% and 63.76% in 2021, respectively (in the middle and bottom column of Table  3 ).

Hospital market concentration

Figure  2 and Supplementary Table 1 show the trend of hospital market concentration in medical corporations between 2017 and 2021, by prefecture. The mean (standard deviation [SD]) HHI increased slightly from 262.7 (178.6) in 2017 to 275.2 (187.9) in 2021 (Supplementary Table 1 ). Regional areas such as Tottori, Shimane, Ishikawa, and Yamagata had higher HHIs (dark red in Fig.  2 ) than did urban areas such as Tokyo, Fukuoka, Osaka, and Saitama (light red in Fig.  2 ). The HHIs in all regions remained below 1,000, indicating moderate market concentration according to the HHI thresholds (unconcentrated; 100 to 1500). Only Yamagata showed an increase in HHI above 100 from 2017 to 2021, and the average change in HHI across all regions during this period was 12.5 (27.2).

Hospital concentration in medical corporations across Japan between 2017 and 2021. Abbreviation: HHI, Herfindahl-Hirschman Index

Principal findings

This study provides a comprehensive analysis of the five-year trends in the integration of medical corporation hospitals in Japan based on a nationwide dataset. While the number of hospitals and hospital beds owned by medical corporations has declined, both horizontal and vertical integration have increased slightly as a percentage of the total. The horizontal integration rates remain relatively modest, with the majority of medical corporations operating only one or two hospitals. In contrast, vertical integration accounts for approximately half of the total, indicating a more pronounced presence. While hospital market competition within medical corporations is somewhat more concentrated in rural areas than in urban areas, the overall level of concentration is not significant.

Comparison with other studies

Previous studies on the integration of medical corporation hospitals in Japan are very limited. According to a comprehensive national survey of medical corporations, 17.4% of the total 5,533 hospitals and 23.6% of the total 811,961 hospital beds in medical corporations were horizontally integrated in 2002, which increased to 22.1% of the total 5,712 hospitals and 28.7% of the total 851,918 hospital beds in 2011 [ 13 ]. Although the databases were different, our study showed that 26.92% of the total 5,486 hospitals and 33.75% of the total 814,462 hospital beds in 2021, suggesting that horizontal integration has progressed very slowly but steadily over these 20 years. On the other hand, regarding vertical integration, a national survey of prefectures, hospitals, and long-term care facilities by telephone and letters in 1996 reported that 23.1% of the total 4,367 medical corporation hospitals were integrated with long-term care facilities [ 14 ]. Although the databases and definitions were different, our study showed the total integration including hospitals and long-term care facilities 31.3% of all 4,545 corporations in 2021 (Table  3 ), suggesting that the type of vertical integration has been increasing from about 20–30% for 25 years.

Assuming that health care systems are different, we compared the trends in health care systems in the U.S. with the results of the present study. The United States stands out as having the most extensive reports on trends in health care systems. Over the past few decades, health care in the United States has undergone rapid integration [ 7 , 8 ], with vertical integration reportedly outpacing horizontal integration in recent years [ 9 ]. The extent of integration is substantial, with nearly half of the hospital referral regions in the United States reported to be in a highly concentrated state, with HHI values exceeding 2,500 in 2011, indicating highly concentrated conditions [ 7 ]. Comparing the level of integration of the health care system in the U.S. with our study, both horizontal and vertical integration have developed very slowly in Japan, and the HHI is less than 1000 in all regions, indicating a much lower level of integration than in the U.S. When comparing integration trends internationally, it’s crucial to consider how vertical integration is defined in each context, particularly regarding which facility types are included. This study, similar to previous comparisons between the United States and England [ 25 ], demonstrates that the differences between healthcare systems can be so substantial that direct comparisons may not yield meaningful insights for policymaking in either country. Instead, these comparisons serve to highlight the extent to which healthcare systems are shaped by country-specific factors. Moving forward, discussions on healthcare integration should focus on the unique aspects of its system, including the role of medical corporations, regulatory frameworks, and cultural factors that influence healthcare delivery and management. This approach will likely yield more relevant and actionable insights for policymakers and healthcare leaders in each country.

Mechanisms and implications

Based on the findings of this analysis, it is evident that Japan’s health care system stabilized four decades after the initial revision of the Medical Care Act in 1985, which imposed restrictions on hospital beds [ 1 ]. While the total number of hospitals and hospital beds has gradually declined, there has been steady progress in horizontal and vertical integration. This trend toward integration, especially vertical integration, can be largely attributed to changes in the delivery system for medical and long-term care services for elderly people due to population aging and low birth rates, as well as to policy implementation. The 1985 amendment to the Medical Care Act prohibited the establishment of new hospital beds [ 1 ], compelling medical corporations to pursue horizontal integration as the only means of expanding their scale. Subsequently, the revision of the Health and Medical Service Act for the Aged (now Retitled Act on Assurance of Medical Care for Elderly People) in 1986 led to the establishment of geriatric health care facilities [ 26 ], and the Ten-Year Strategy to Promote Health Care and Welfare for the Elderly (the so-called “Gold Plan”) policy of the 1990s promoted the establishment of welfare facilities [ 27 ], marking the beginning of vertical integration unique to Japan. With the introduction of the Long-Term Care Insurance System in 2000, the integration of medical and nursing care services began, leading to the development of vertical integration involving hospitals and long-term care facilities [ 15 ]. In approximately 2010, the Community-based Integrated Care System, which aimed at providing “housing, medical care, nursing care, prevention, and life support” at the regional level, was introduced, further promoting vertical integration [ 16 ]. Moreover, the 2018 revisions to medical and nursing fees provided incentives for collaboration between medical and nursing services, further encouraging vertical integration [ 17 , 18 ]. These developments are believed to have led to the distinctive patterns of horizontal and vertical integration observed in Japan.

As the aging population and low birth rate are expected to continue, gradual progress in the integration of medical corporation hospitals is expected in the future. These findings can serve as a valuable reference point for policymakers when considering desirable health care delivery systems for medical corporations in the future. If further integration is deemed beneficial, a re-evaluation of existing policies and the implementation of new initiatives may be warranted.

Strengths and limitations of the study

This study has several notable strengths. First, this study used a comprehensive database of Japanese medical corporations to conduct a thorough analysis of recent trends, indicating for the first time that such research has been disseminated in English. This facilitates the global dissemination of trends within Japan’s health care system, enables comparative analysis with health care systems in other countries, and promotes seamless academic communication with researchers and policymakers worldwide. Second, the study used individual-level data from medical corporations to analyze health care services at the corporate level. The existing data from the MHLW are aggregated data that only show trends in the number of hospitals and hospital beds for medical corporations as a whole. By analyzing at the level of medical corporations, horizontal and vertical integration among medical corporations can be identified, allowing for microlevel trend analysis.

This study has several limitations. First, although our data have a coverage rate of approximately 95%, they do not include all medical corporations for analysis. However, since the trend in the number of hospitals and beds is almost consistent with the publicly available data from the MHLW, the dataset is considered sufficient for conducting broad trend analyses. Second, since the data are not derived from public sources, the reliability of the data is not guaranteed due to possible cases of missing data or errors. Nevertheless, because the data have been used by universities and financial institutions [ 20 ], despite their limitations, they are currently the most relevant data for analyzing medical corporations in Japan. Third, although the analysis is conducted at the level of individual medical corporations, it does not extend to larger groups of medical corporations. For example, although the top two companies, “Iryohojin Tokushukai” and “Iryohojin Okinawa Tokusyukai,” are different medical corporations, they both belong to the same conglomerate. For a more detailed examination of interfirm cooperation in the health care sector, future research may require analysis at a broader conglomerate level. Fourth, the HHI calculated in this study solely examines the concentration among medical corporations, not including national and public hospitals. As a result, it does not capture the entire hospital market in Japan. Although this measure may not strictly represent the overall market concentration, the interpretation that it reflects a certain level of concentration within the market occupied by medical corporations, which account for approximately 55% of the market share and have remained relatively stable over the past five years, can be considered valid. Fifth, this study did not evaluate the potential impact of integration on outcomes such as quality of care or improvements in health care costs. To fully assess the advantages and disadvantages of integration, an analysis of the associated changes in relevant outcomes is needed. In this regard, future research plans include incorporating quality of care and financial performance data into the existing database for further analysis.

In this longitudinal study to examine trends in hospitals owned by medical corporations in Japan, we have observed a gradual downward trend in the number of hospitals and hospital beds, while horizontal and vertical integration is gradually progressing without any particular medical corporation occupying the market. These results are expected to contribute to policymaking for providing optimal health care services.

Data availability

Data are available to appropriate academic parties upon reasonable request to the corresponding author.

Abbreviations

Herfindahl–Hirschman Index

Ministry of Health, Labour and Welfare

Organisation for Economic Co-operation and Development

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Acknowledgements

We would like to thank the Institute for Health Economics and Policy for its support in the research grant and the National Institute for Public Health for its support in article publishing.

We would thank the Institute for Health Economics and Policy for the support in the research grant and the National Institute for Public Health for their support in language editing fees and article publishing charges.

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Satoshi Funada, Takashi Yoshioka & Shunsuke Uno

Population Health and Policy Research Unit, Medical Education Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan

School of Economics and Business Administration, Yokohama City University, Kanagawa, Japan

Hirotaka Kato

Institute of Clinical Epidemiology (iCE), Showa University, Tokyo, Japan

Takashi Yoshioka

Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan

Shunsuke Uno

Graduate School of Health Management, Keio University, Tokyo, Japan

Kimiko Honda, Yoko Akune & Rei Goto

Graduate School of Business Administration, Keio University, Tokyo, Japan

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SF and RG conceived and designed the experiments. SF designed the analytical strategy and analyzed the data. SF prepared the draft manuscript. SF coordinated the whole experiment and was responsible for the overall content as the guarantor. All authors edited and reviewed the manuscript and approved the final version of the manuscript.

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Funada, S., Luo, Y., Kato, H. et al. Trends in the integration of medical corporation hospitals in Japan: a national wide longitudinal study between 2017 and 2021. BMC Health Serv Res 24 , 1005 (2024). https://doi.org/10.1186/s12913-024-11463-5

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DOI : https://doi.org/10.1186/s12913-024-11463-5

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