Younger persons who developed colorectal cancer (CRC) were more and more likely to present with distant-stage disease in recent years, researchers found.
From 2000 to 2016, people in their 20s and 30s experienced the sharpest increases in distant-stage early-onset colorectal adenocarcinomas out of various age groups — with young Black and Hispanic patients disproportionately affected, reported Jordan Karlitz, MD, of University of Colorado School of Medicine, Denver, and colleagues.
“Optimizing earlier screening initiatives and risk-stratifying younger patients by symptoms and family history are critical to counteract rising distant stage disease,” they wrote in Cancer Epidemiology, Biomarkers & Prevention.
The results “support the benefits of shifting the average-risk screening age from 50 to 45 for all patients and assuring that real-world screening rates are optimized,” they said. “Furthermore, the results underscore that in patients younger than screening age, vigilant attention to concerning symptoms must be paid so that earlier diagnostic testing can be undertaken and … comprehensive family history assessments must take place so that earlier screening can be offered.”
For their study, Karlitz’ group analyzed data on 103,975 patients with CRC who were included in the U.S. Surveillance Epidemiology and End Results 18 cancer registry. In situ adenocarcinomas decreased in most age groups and sites from 2000-2002 to 2014-2016.
But over this time period, distant-stage cancers rose significantly, both when looking at colorectal tumors and colon- or rectal-only adenocarcinomas:
Colorectal: up 57% for the 20-29 age group, up 66% for 30-39, up 41% for 40-49, and up 15% for ages 50-54
Rectal-only: up 133%, 97%, 48%, and 33%, respectively
Colon-only: up 19%, 49%, 38%, and 7%, respectively
Distant-stage disease comprised an increasing proportion of CRCs from 2000-2002 to 2014-2016, with the steepest increases observed in the rectal subsite. For example, the burden of distant-stage cancers in patients 20-29 years old presenting with rectal-only adenocarcinoma increased from 18% to 31% between the two time periods, while it increased from 20% to 29% in those 30-39 years old.
In rectal-only adenocarcinoma, non-Hispanic Blacks (0% to 46%) and Hispanics (28% to 41%) in the 20-29 year age group had the greatest rise in distant-stage disease. Non-Hispanic Blacks ages 20-29 also had a substantial jump in distant-stage colon-only adenocarcinoma (20% to 34%).
Study authors cautioned that their work was limited by its observational nature and said that more research is needed to determine why younger patients are increasingly presenting with distant-stage colorectal adenocarcinoma.
The COVID-19 pandemic has been hard on so many people in so many ways. For babies born during this pandemic, a study published in JAMA Pediatrics suggests that the damage has potential to be lifelong.
The first three years of life are crucial for brain development. And it’s not just the health of babies that matters, but the interactions between babies and their caregivers. Babies need to be touched, held, spoken to, smiled at, played with. As they receive and respond to those interactions, in a “serve and return” kind of way, neural connections are built in the brain. When babies don’t have those interactions, or enough of them, their brains don’t develop as they should — and can even be literally smaller.
When you are a stressed or depressed parent or caregiver, it can be hard to find the time, let alone the energy or interest, to talk to and play with your infant. There are multiple studies showing that maternal depression, poverty, and other family stressors can change the development of a child forever.
How was the study done?
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In this study, part of an ongoing study of mothers and babies, researchers from Columbia University looked at the development of three groups of 6-month-old babies. Two of the groups were born during the COVID-19 pandemic; the mothers of one group had COVID-19, while the mothers of the other did not. The third group was a historical cohort (a group of babies who were born before the pandemic).
Mothers participating in the study used an Ages and Stages Questionnaire (ASQ-3) to record their babies’ development. The researchers noted no difference in the development of the two groups of babies born during the pandemic, suggesting that prenatal exposure to COVID-19 doesn’t affect development, which is great news. But the babies born during the pandemic scored lower in gross motor, fine motor, and social-emotional development than the babies born before the pandemic. Examples of developmental tasks for infants this age are rolling from back to tummy (gross motor), reaching for or grasping a toy with both hands (fine motor), and acting differently to strangers than to parents or familiar people (social-emotional development).
What does it suggest about infant development during the pandemic?
It’s just one study, and we need to do more research to better understand this, but the findings are not really surprising given what we know about infant development. The COVID-19 pandemic has caused a lot of stress — emotional, financial, and otherwise — for so many families. It has also markedly affected the number and kind of interactions we have with other people. Babies are on average interacting with fewer people (and seeing fewer faces because of masking) than they did before the pandemic.
Even though we need to do more research, this study should serve as an alarm bell for us as a society. The children of this pandemic may carry some scars forever if we don’t act now. We’ve been seeing the emotional and educational effects on children; we need to be aware of the developmental effects on babies, too. All of these could permanently change their lives.
What can we do to address these challenges?
We need to find ways to support families with young children, financially and emotionally. We need to be energetic and creative, and work every angle we can. While our government should play a role, communities and individuals can help too.
We need to refer families to and fund early intervention programs around the country that support the development of children from birth to 3 years of age. Because of the pandemic, many of these programs have moved to virtual visits, which can make them less effective. So we need to get creative here, too. We can’t just wait for the pandemic to be over.
And parents and caregivers of infants and toddlers need to know about this research — and ask for help. It’s understandable and natural for parents to think that babies are too small and unaware to be affected by the pandemic. But they are affected, in ways that could be long-lasting. Talk to your doctor about what you can do to help yourself, your family, and your baby’s future.
More Americans seem to be heeding the latest scientific evidence pointing to COVID-19 booster shots as a boon to our immune systems and as protection against serious illness from SARS-CoV-2 infection, especially as the virus continues to mutate.
But while some surveys show the number of people getting boosters is rising, the U.S. Centers for Disease Control and Prevention has said that less than 40 percent of fully vaccinated Americans eligible for a booster shot have received one, despite mounting evidence of the effectiveness of booster shots in fighting the contagion.
The CDC data, for example, showed that in December unvaccinated Americans 50 years and older were about 45 times more likely to be hospitalized than those who were vaccinated and got a third shot.
Questions remain on which vaccine type to get, whether to mix and match types, and how soon after a breakthrough infection to get boosted.
To untangle some of these uncertainties, Harvard Medicine News spoke with Jonathan Li, associate professor of medicine at Harvard Medical School and Brigham and Women’s Hospital. Li is also a member of the NIH COVID-19 Treatment Guidelines Panel and the HMS-led Massachusetts Consortium on Pathogen Readiness (MassCPR).
HMNews: One person is fully vaccinated and has received a booster, while another is fully vaccinated but has not received a booster. What level of protection does each now have?
Li: It’s becoming clear that against the omicron variant, you really need three vaccine doses in order to achieve the best level of protection. Two doses are not enough. This is why the CDC now states that a third vaccine dose is needed in order to be considered up to date for COVID-19 vaccinations.
HMNews: How soon after a breakthrough infection should a person get a booster shot?
Li: Great question. Breakthrough infections will no doubt boost antibody titers and immune responses, even beyond levels achieved from two shots of an mRNA vaccine. However, the extent of immunity conferred by natural infection really varies person to person. The vaccines provide high-level immune responses that are dependable and the immunity is longer lasting. This is why we recommend that our patients go ahead and receive their next shot as soon as they feel confident that they have recovered from their COVID-19 infection.
HMNews: What about mixing and matching vaccines?
Li: We know that the mRNA vaccines Moderna and Pfizer work great as a booster dose regardless of the initial vaccine used. This is what most people should use, unless they had a severe reaction or have another reason to prefer the J&J vaccine.
HMNews: Is there a scenario under which clinicians might suggest that a vaccinated individual should not get a booster?
Li: Individuals need to wait at least five months since their initial shots, and those who had a severe allergic reaction should talk to their doctor before attempting to get another shot.
HMNews:There are indicators that omicron is reaching its peak. Does this change the calculus on the importance of getting a booster?
Li: While it’s certainly great news that the omicron wave appears to be peaking and declining across the U.S., now is not the time to let our guard down. I expect that just as many people are going to be infected on the downslope as were infected on the upslope of the omicron wave. Receiving the booster dose of the vaccine is still the best way to protect yourself from severe disease.
HMNews: What does the virus’s continued evolution mean for the future of vaccines?
Li: This virus continues to surprise us. It’s hard to know what the future holds, but making sure that everyone is up to date on their vaccines is the best way to prevent new variants from emerging.
Once overshadowed by antibodies, T cells begin to take center stage in the fight against COVID-19
Since the start of the COVID-19 pandemic, antibodies have dominated the attention of both physician-scientists and the public. They have been the object of intense research across scientific labs. They formed the basis of SARS-CoV-2 vaccines and antibody-based therapies, acquiring household-name status in the process.
This fame is well-deserved.
Churned out by the immune system when it encounters a pathogen, or made in response to vaccines that mimic one, these tiny proteins glom onto SARS-CoV-2 to gum up its cell-entry machinery, preventing the virus from invading cells and turning them into virus-making factories that cause widespread infection. Vaccines designed to elicit antibodies against SARS-CoV-2 are a feat of modern science and remain the most critical tool in taming the contagion.
If antibodies are the rampart around the castle, then T cells are the elite guards inside it that disable intruders should they manage to sneak in.
But for all their virtues, antibodies may have overshadowed another part of the immune system that has played a critical role in shielding us from the worst ravages of COVID-19: T cells. When antibodies fail to stop the virus from getting into our cells, T cells come to the rescue. They kill virus-infected cells, limiting the spread of the disease and halting tissue damage. If antibodies are the rampart around the castle, then T cells are the elite guards inside it that disable intruders should they manage to sneak in. In people who do get infected with SARS-CoV-2, it’s T cells that are responsible for preventing severe symptoms, hospitalizations, and deaths from COVID-19.
COVID-19 vaccines excel at inducing antibody response, but studies have shown that antibodies tend to decline within several months of immunization, requiring booster doses to prod the immune system to make more of them.
T cells, on the other hand, may represent an underutilized target for vaccines, not only against SARS-CoV-2 but against myriad other infections.
“Antibodies are extremely valuable, but if we can further bolster the immune response on the T cell side, it’ll just provide further benefit and augment those good antibodies,” said Gaurav Gaiha, assistant professor of medicine at Harvard Medical School and an immunologist at the Ragon Institute of MGH, MIT and Harvard, whose lab is focused on developing T cell-based vaccines for SARS-CoV-2, HIV, and cancer.
Powerful, not infallible
It is important not to reduce antibodies to mere neutralizers of viruses, researchers point out. Their roles in immune protection are diverse. They engage in a complex interplay with other parts of the immune system to signal the presence of pathogens, they help other immune cells devour microbes and clean up microbial debris and infected cells, and they assist other parts of the immune system in forming long-term memory of previously seen pathogens, ensuring the immune system can spring into action quickly to defend against any subsequent encounters with a past invader.
Yet, antibodies are not a foolproof defense mechanism. Like any wily pathogen, SARS-CoV-2 has developed workarounds that bypass our immune defenses. Mutations—changes to parts of the virus that render it less recognizable to antibodies—are one such workaround. SARS-CoV-2 variants have sprouted multiple mutations, most of them on the spike protein—the very part of the virus that antibodies target and neutralize. Omicron—the latest, but certainly not the last, variant of concern—has some 30 such alterations on its spike alone, allowing the variant to evade antibodies better than its predecessors. Omicron’s immune evasiveness has dramatically upped the number of breakthrough infections among individuals once deemed immune, either because of vaccination or because of prior infection.
“If anything, omicron was able to beat a lot of antibodies, so leveraging this other wonderful side of our immune response on the T cell side to provide further protection against variants is something we should seriously consider as this pandemic evolves and as new pathogens emerge,” Gaiha said.
T cell tenacity
A spate of new studies, many of them not yet peer-reviewed, have brought reassuring news about the durability and reliability of T cells in response to omicron.
“We have found that T cell responses are highly cross-reactive against variants, including omicron,” said Dan Barouch, professor of medicine at HMS and Beth Israel Deaconess Medical Center and co-lead of the vaccine research working group of the HMS-led Massachusetts Consortium on Pathogen Readiness. “In contrast, antibody responses are drastically reduced against omicron, and only partially restored with boosting.”
T cells, which arise in the bone marrow as immature white blood cells and get “trained” in the thymus to become T cells, come in many forms, each highly specialized to perform different functions. Two kinds of T cells are particularly important in responding to infections. T cells called CD8, or cytotoxic T cells (literally cell-killing cells), destroy virus-infected cells in COVID-19 and other infectious diseases. Another type of T cell called CD4 works as a helper. Both CD4 and CD8 T cells recognize tiny bits of the virus—or any other pathogen—loaded on top of infected human cells. These small viral chunks act as a beacon to draw the attention of T cells.
A not yet-peer-reviewed study led by Barouch suggests that vaccines elicit reliable T cell defense against omicron. Research out of South Africa—also not peer-reviewed—shows that T cell immunity remains robust against omicron, even as the variant escapes neutralizing antibodies. Work by an Italian team of investigators also points to preserved T cell responses among vaccinated individuals against omicron.
This T cell protection also appears to be vaccine-agnostic, meaning that it is present across recipients of different vaccines as well as among individuals with prior SARS-CoV-2 infections. A 2021 study led by Barouch comparing antibody and T cell responses across recipients of Pfizer, Moderna, and Johnson & Johnson vaccines showed that antibodies tend to rise and decline fairly quickly (within six to eight months) among mRNA vaccine recipients. By contrast, antibodies never quite reached the same levels with the vector-based J & J vaccine, yet remained relatively stable over time. The study, however, also showed that T cell responses across all vaccines remained robust and that individuals who got the vector-based J & J vaccine had somewhat higher T cell levels compared with those who got mRNA vaccines (Moderna and Pfizer).
“The rapid waning of vaccine protection from antibodies has been discouraging, but the good news is that T cell responses persist across vaccines,” said Barouch, who is also the director of the Center for Virology and Vaccine Research at Beth Israel Deaconess.
The researchers say that although these findings have yet to be peer-reviewed, they are nonetheless encouraging because multiple teams converge on the same findings: Protective T cells induced by current SARS-CoV-2 vaccines recognize the omicron variant and offer considerable protection against severe disease despite the substantial reduction of neutralizing antibody response. This is the reason why vaccinated individuals—even when the virus breaks through their immune defenses—get milder infections than unvaccinated people.
The reason for this enduring response despite viral mutations is the ability of T cells to recognize the entire length of the spike protein and generate a protective effect, not just the highly specific and mutable portions targeted by neutralizing antibodies. T cells developed following natural infection can also recognize non-spike parts of the virus because the immune system has been exposed to the entire viral genome.
Indeed, from the perspective of T cells, omicron is not a variant, Barouch said, it’s a very similar pathogen to kill.
“Whether induced by vaccine or natural infection, T cells are far better able to maintain their recognition and response than antibodies,” Gaiha said.
But the obvious advantage of vaccine-induced immunity over natural immunity, Gaiha added, is that vaccines generate an immune response without any of the inherent risks of natural infection.
But SARS-CoV-2 is an ever-surprising pathogen, and even T cells may not remain forever impervious to the virus’s shapeshifting tricks. New research led by Gaiha—currently undergoing peer review—found that T cells lost half of their reactivity against omicron in one of five people with prior immunity to SARS-CoV-2. Overall, the study is still encouraging because it shows that 80 percent of people retained T-cell response even against the heavily mutated omicron. It also showed that individuals who received vaccine boosters had enhanced antibody and T cell responses against the variant. However, it is an surprising observation, Gaiha said, which may signal that T cells could eventually lose some of their ability to recognize future variants if the virus continues to mutate.
Exploiting T cells’ potential
T cell engagement was not an explicit part of the original SARS-CoV-2 vaccine design. Optimizing current and subsequent vaccines to specifically stimulate T cells by giving the immune system exposure to the non-spike proteins of the virus would offer an important hedge against COVID-19 in the face of a rapidly mutating virus that may continue to escape antibodies.
“I think T cells offer such a tremendous opportunity to enhance current vaccines, and there hasn’t been a dedicated effort towards their induction by vaccines,” Gaiha said. “In the span of two years, we’ve seen the emergence of all these variants, so augmenting vaccines to specifically engage T cells would further solidify that backstop against severe illness.”
Such vaccines would still include spike components but also non-spike components. Even if these vaccines turn out not to lead to sterilizing immunity, which would prevent the virus from infecting our cells, they would go a long way toward ensuring that an infection with SARS-CoV-2 remains minimally symptomatic, on par with the common cold.
“I think we’ve reached a point where we understand we’ll be living with this virus for a long time, but if we can make it a mild illness that doesn’t cause severe disease that may be a tenable goal,” Gaiha said.
Another important benefit of targeted T cell stimulation would be enhancing their function in older people, whose T cells tend to lose potency and diversity with age, as well as among people who are immunocompromised, or have chronic infections or cancer, conditions that can lead to T cell exhaustion.
Depending on the mode of delivery, it is feasible that some T cell-based vaccines may go beyond disease mitigation and achieve actual viral clearance to prevent infection. For example, research in animals has shown that intranasal, rather than injectable, vaccines can induce a T cell response at the nasopharynx, the site of initial infection where the virus enters the body, and achieve clearance promptly on the spot by killing off infected cells in that region, thus preventing further spread, Gaiha said.
Lessons from HIV
One way to overcome the ongoing challenge of viral mutation in SARS-C0V-2 is to design vaccines that are variant-resistant, Gaiha said. These vaccines would target stable parts of the virus—those that remain unchanged in all variants, no matter how much the virus evolves.
This approach is informed by insights from HIV, another daunting pathogen, arguably the greatest shapeshifter among viruses, whose maneuvers Gaiha has studied for years.
As a postdoc in the lab of leading HIV researcher Bruce Walker, Gaiha teamed up with Elizabeth Rossin, HMS instructor in ophthalmology at Mass Eye and Ear, to elucidate mechanisms by which some people’s immune systems are capable of suppressing and controlling the virus.
“In HIV, it is apparent that a good CD8 T cell response targeted to the mutation-resistant parts of the virus can lead to successful suppression of the virus,” Gaiha said.
It is those sine-qua-non regions of any pathogenic virus that researchers should be incorporating as targets of future vaccines, Gaiha said.
Gaiha and colleagues have already mapped these structurally critical regions on SARS-CoV-2 and published their work in the summer of 2020. Using network theory, they predicted which parts of SARS-CoV-2 would remain unchanged due to their integral role in the viral structure and function. The pandemic has since then affirmed the accuracy of the team’s predictions: The variants have exploded, but the very regions they predicted would not change still haven’t mutated.
“The question in front of us now,” Gaiha said, “is how can we focus the immune response specifically on those regions of SARS-CoV-2.”
More traditional technology may sway the vaccine hesitant
It is often said that we are at war with COVID-19. The universal elements are all there. International leaders like Xi Jinping, Boris Johnson, and Scott Morrison have all invoked wartime rhetoric. The U.S. mobilized a “war effort” with unprecedented industrial and human resources to combat an enemy virus. Both sides of this conflict continue to evolve and learn. One recursive of prolonged battle is that an enemy can adapt to its opponent through new behaviors or technologies. When the U.S. embarked upon WWII, we had inferior training, battleships, and aircraft. By the end, the allies dominated the seas and the skies. During the late middle ages, the French and English battled for 116 years. This tumultuous period witnessed the evolution of new tactics, the longbow, and eventually gunpowder.
Our protracted war with COVID-19 is no different. Despite early losses, both self-inflicted and from a largely indefensible enemy we have advanced on all fronts. Our generals are preparing for another push forward with armamentaria to be used alongside first-generation mRNA weaponry. The newest battlefield intervention soon to debut: the Novavax vaccine.
Our time with COVID-19 has been nothing short of a grind. It is, in fact, easier to compare our experience to pitched battle as opposed to modern, technologically driven warfare. After the initial shock of worldwide spread eased, we hunkered down in our respective cities and towns, awaiting transmission of the virion particle like barbarians at the gate. When the time came to counterattack, we did so on the back of vaccines. The vaccines were our heavy mounted cavalry providing the shock tactics necessary for victory. These relatively new constructs containing encoded information were superb, slashing through enemy hordes by gutting infection, transmission, and poor outcomes. Now, some 2 years in, the cavalry is exhausted. And the enemy evolves.
Omicron is a cunning foe whose manifest destiny has unfolded before us in the crucible of the human body. A kind of hyper-speed Darwinian evolution has rendered it supremely able to infect, though less able to kill. It has learned from us how to optimize itself for maximum fitness. It is now able to partially side-step our cavalry, but that cavalry is more important than ever.
Approximately 87% of U.S. adults have had at least one COVID-19 vaccination. When this is viewed in context with the natural immunity imparted by the rapid spread of Omicron, the totality of immunity has rarely looked more sanguine. But there still is, and may always be, an element of stochasticity with this virus. While people with significant comorbidities are at highest risk for severe outcomes, every once in a while, it comes for the healthy. And still, millions of Americans refuse to be vaccinated.
Given the historical scope of vaccine hesitancy and our natural predilection for certain freedoms, we really deserve a collective pat on the back for a job well done rather than the de rigueur self-flagellation. But this is not the time for complacency.
We have yet another opportunity to drive vaccination that should not be squandered. Novavax will be looking for their U.S. emergency use authorization in short order. With international authorizations from the World Health Organization and European Medicines Agency, key partnerships with the Coalition for Epidemic Preparedness Innovations and the Serum Institute of India, and pending applications with the remaining Anglosphere, the company is well positioned worldwide. Novavax produces a recombinant protein subunit vaccine that reconstitutes spike without the need for genetic materials. The upshot here is that this construct has a significant history of use for diseases like pertussis, hepatitis B, and pneumococcus. In trials, the vaccine showed similar protection to currently available vaccines, and none of the participants experienced severe clotting, anaphylaxis, or myocarditis.
Novavax has disappointed many with an oft-delayed regulatory path and manufacturing difficulties, but they have a following that should not be underestimated. Social media and Reddit groups maintain a cult-like fanaticism for their marketed vaccine product known as Nuvaxovid or Covovax. The stock, caught up in this fever but simultaneously throttled by a souring vaccine landscape, is as wild as a Yellowstone bucking bronco. But its real value may be in giving the un-jabbed another chance. Many unvaccinated do not see themselves as vaccine hesitant — this label merely reflects the lens through which they are viewed in this highly politicized environment. In their defense, it has been egregiously unfair to brand the millions up to date with their schedules as “anti-vax” because of a one-time offense. This is their chance to square up.
The impending release of another vaccine offers a critical opportunity for institutions like the CDC and the media to get their messaging right. In order to do so, it is useful to understand that there exists a spectrum of “vaccine hesitancy,” ranging from vaccine apathy to outright conspiracy. The extremes of the spectrum, and the shades of gray within, require precise messaging, communicated with empathy and compassion. The media, in order to avoid accusations of preference bias or worse, should deliver the same pomp and circumstance for this vaccine as it did for the likes of Pfizer and Moderna. Up to this point it has been eerily quiet.
If we are indeed still waging a pitched battle against this virus then it is time to refresh some of our chargers and give other beasts in the stable a chance. Vaccines will continue to be our best means to fight the enemy no matter how many therapeutics are advanced. Adding a protein subunit construct to the melee finally gives us the much needed, traditional option available for both the immunologically naïve and those hesitant to get boosted. It may provide a path forward for some who are pro-vaccine, but who drew the line at novel mRNA products. This is especially important given the disconnect that can exist between COVID-19 advocacy, science, and the manner in which this plays out in the realm of public policy. The Novavax option may indeed act as a compromise for some vaccine hesitant who are cornered by policies that squeeze healthcare workers, disregard naturally acquired immunity, require young and healthy adolescents to be boosted, or prevent children from leading more normal lives. Having another vaccine option just makes sense. It’s just a shame it didn’t arrive sooner.
The Omicron variant of SARS-CoV-2 has renewed attention on Covid-19 antigen test kits. They are in high demand across the United States, and many Americans are having trouble getting them, prompting President Biden to announce that the White House will buy and ship 500 million rapid tests for free beginning in January.
The untold backstory here is that many people are growing accustomed to simultaneously serving as doctor and patient. Before the pandemic struck, the idea that millions of people would administer tests on themselves at home to determine whether they had a life-threatening illness seemed difficult to imagine. Today, it’s part of daily life.
While home-based antigen tests have made a questionable epidemiological contribution to tracking and confronting the pandemic, the real value they present goes far beyond Covid-19. If people trust their results, the ultimate outcome of the U.S. government investing an expected $50 billion to subsidize at-home testing may spark movement on many fronts that radically decentralizes health care and changes what Americans expect from and how they access care.
The current discussion around antigen testing is naturally focused on the availability, cost, and efficacy of tests. Trust is another big issue. The rush for Food and Drug Administration approval may have backfired, undermining trust in the tests for some and creating a false sense of security for others.Related: Scientists try to pinpoint why rapid Covid tests are missing some cases
Still, as Americans come to value rapid home testing for Covid-19, I believe this will usher in a new era of health care in which people feel comfortable testing for a variety of conditions at home because of their positive experiences during the pandemic.
Just a few years ago, trying to engineer a shift like this would have seemed like a far-off dream requiring years of education, billions of dollars, and a dramatic change in mindset. It is astounding that this transformation appears to be taking place with relative ease.
Antigen tests are just the start. The public is increasingly familiar with — and has come to expect — tools that allow access to health care on their own terms, such as at-home tests for everything from strep throat to food sensitivities, FaceTime calls with their physicians, and prescription medicines delivered to their doors. That expectation is not going away anytime soon. The dilemma that health tech companies now face is finding ways to take advantage of the positive aspects of this trend while guarding against the challenges created in its wake.
My company, Healthy.io is, for example, working on applying this approach to chronic kidney disease. We call it “health care at the speed of life” because it means people will be able to take lifesaving medical tests in their own homes, when it is most convenient for them, without having to find their way to a lab or clinic or doctor’s office
This is consistent with the key lessons of the U.S.’s massive experiment with at-home antigen testing. Specifically, everyone should have access to key tests, not just those who can afford upfront costs. Otherwise, the new system will only reinforce the shortcomings of the one it replaces.
At-home tests must adhere to high clinical-grade standards. To have any diagnostic value, patients and practitioners alike need to believe that the tests are as effective and as reliable as those used in medical offices.
For the at-home testing revolution to truly benefit patients, it must also tackle systemic issues confronting the health care system. As Covid-19 home testing has shown, if a test exists but is too expensive for the people who need it most, it will simply reinforce existing inequities in health care.
The pandemic has forced Americans to address their health care needs in new and innovative ways. To their credit, they’ve done so with gusto and determination. We now have a golden opportunity to rewrite the rules of the game in health care. That must be done today, and in the right way, or it will be lost tomorrow.
The severity of fatigue that comes with Lyme and other tick-borne illnesses can be difficult to describe because Lyme disease fatigue is a whole different story
When I was sick with COVID-19 in 2020, I continued working (remotely) despite my mild fatigue, shortness of breath, low-grade fever, loss of taste and smell, and persistent cough. Though these symptoms were no walk in the park, they weren’t completely debilitating. For some COVID-19 patients, symptoms have rendered them bedridden, hospitalized, or worse. I was lucky not only to survive early COVID-19, but to have a moderate case.
For me, the fatigue of COVID-19 was nothing compared to the fatigue of Lyme disease. Lyme disease fatigue has become the barometer by which I measure all other fatigue, whether it’s general tiredness or illness-related. The severity of fatigue that comes with Lyme and other tick-borne illnesses can be difficult to describe, because fatigue can be defined many ways. It can mean muscle soreness after a workout, burnout after a long week, or yawns that come when you just didn’t sleep well. Fatigue can also mean general malaise from the pandemic, or sleepiness from any number of stressors. Then there’s feeling like your head is spinning after staying up all night finishing an assignment or tending to a crying baby.
All of these types of fatigue are uncomfortable. No one likes to be tired. But this level of fatigue generally can be solved with a few good nights of rest, a break, or even some caffeine. That’s because the fatigue is caused by external factors, not by illness. Your body has the resources to recover.
Lyme disease fatigue, like the fatigue that comes with many other serious illnesses, is another story. In a survey of over 3,000 chronic Lyme disease patients conducted by lymedisease.org, 59% of patients described their fatigue as “severe” or “very severe.” At my lowest point of illness—which lasted years—that severity meant I was almost completely bedridden. I could walk around my house and go out for a few errands on good days, but sometimes it was too tiring to walk to the mailbox, or to sit up at the dinner table. My body screamed with exhaustion. It felt heavy, as if I was weighted to the bed, and all I wanted to do was sleep. And sleep. And sleep.
The problem was, I could not actually rest. Overrun with Lyme disease bacteria as well as babesiosis, ehrlichiosis, and possible bartonella, my nervous system could not turn off. At one point, I was literally awake for weeks. And while sleep medication, neurofeedback, and cognitive behavioral therapy did help me fall asleep, it took months to catch up on rest. In addition to recovering from severe sleep deprivation, my body was also busy fighting infections. I also had chronic active Epstein-Barr virus, which meant that the shackling fatigue I experienced when I had acute mononucleosis held on during my worst years of tick-borne illness.
My body was so worn out from doing battle that when I did sleep, I often dreamed about how tired I was. I’d be lying in the middle of my college campus too exhausted to get up, or I’d collapse on a ski run while others zoomed past me. In these dreams I craved sleep as desperately as I did when I was awake. In my waking hours, I suffered from brain fog and other neurological complications. I felt like I had skied all day, partied all night, written an entire thesis, and then gotten the flu. For years.
For many Lyme disease patients, fatigue persists during and after treatment, but the good news is that it does get better. Years after feeling shackled to my bed, I am now out living a normal life. I work. I write. I exercise. I socialize. I still keep a strict sleep schedule, and I nap every afternoon. This rest allows me to maintain my restored health, so that hopefully, I will never feel the unbearable fatigue of Lyme disease again.
Belly fat is usually unwelcome, but new research suggests it may actually be good for something: relief from foot pain.
A small pilot study suggests that an injection of a patient’s own fat cells can help ease the often-excruciating heel pain brought on by a condition known as plantar fasciitis.
“We take a small amount of fat from an area of excess — like the belly, inner thigh or love handles — and then inject the fat into the bottom of the foot near where the fascia inserts into the heel bone,” explained study co-author Dr. Jeffrey Gusenoff. The arch-supporting fascia is a ligament that runs from the heel to the toes.
The minimally invasive outpatient procedure is performed under local anesthesia, said Gusenoff, a professor of plastic surgery at the University of Pittsburgh School of Medicine, in Pennsylvania.
Plantar fasciitis is a common inflammatory condition, affecting more than 2 million Americans, said Beth Gusenoff, study co-author and wife of Jeffrey Gusenoff.
“About one in every 10 people will develop plantar fasciitis in their lifetime,” added the clinical assistant professor of plastic surgery at the university
There are many triggers, she said. Those include: excessive foot stretching; routinely putting too much weight on the inside edge of the foot; weight gain; overuse; excess exercise; pregnancy; and/or tight tendons.
For people with a seriously inflamed plantar fascia, the result is often “a searing, sharp-type pain like a ‘nail’ or ‘needle’ going right through their heel bone when they first rise from a seated position, or when they first wake in the morning,” Beth Gusenoff said. “As they walk and warm up the plantar fascia, and make it more flexible, the pain eases, but will begin throbbing again by the end of day.”
About nine in 10 patients will do well with standard treatments, she noted. Those include shoe orthotics, cortisone injections, stretching techniques, shockwave therapy, laser treatment and, in some cases, a small surgical incision aimed at “releasing” the fascia.
But sometimes surgery can prove destabilizing and/or give rise to painful scar tissue, she noted. And for the 10% of patients who develop a chronic condition — called “plantar fasciosis” — standard interventions often fail to provide relief.
So the husband-wife team set out to fashion a less risky and more effective intervention focused on fat.
First, they use a blunt needle to pierce the fascia. Then they inject the patient’s own fat into the injury site.
Why fat?
Fat is packed with stem cells and growth factors that can prompt a “regenerative” in-flow of fresh blood, the Gusenoffs explained. That, in turn, can speed up the healing process, with minimal pain-inducing scarring.
To test their approach, the duo split their 14 patients into two groups. One group underwent a single fat injection before being tracked for a year; the other underwent six months of observation before getting the injection, and was then tracked for six months.
Each group saw reduced plantar fascia thickness and was better able to engage in sports activity, both six and 12 months after the injection.
However, significant pain reduction was only seen in the 12-month post-injection group, not among the six-month group.
“It is possible that if we followed these participants out further, they would have had results similar to the one-year group,” said Jeffrey Gusenoff. “The regenerative process of the fat on the tissue likely takes a long time, so the results continue to get better with time.”
The procedure is still considered experimental, while the team prepares to conduct larger studies.
Wenjay Sung, a Los Angeles-based podiatrist, expressed enthusiasm for the study findings.
“This condition is the second-most common reason to see a doctor in the United States, the first being cold/flu symptoms,” said Sung, a physician spokesperson for the American Podiatric Medical Association.
“It’s great to recognize newer treatments and effective approaches when dealing with a chronic condition such as heel pain,” Sung said.
Still, he cautioned that the findings will need to be repeated by other researchers. “And increasing the pool of patients will give it more credibility,” Sung said. “I look forward to future studies and their results.”
There’s more on plantar fasciitis at the Cleveland Clinic.
SOURCES: Jeffrey Gusenoff, MD, professor, plastic surgery, University of Pittsburgh School of Medicine; Beth R. Gusenoff, DPM, FACFAS, clinical assistant professor, plastic surgery, University of Pittsburgh; Wenjay Sung, DPM, podiatrist and physician spokesperson, American Podiatric Medical Association, Los Angeles; Plastic and Reconstructive Surgery, February 2022
Flavan-3-ols and anthocyanins consistently linked to lower mortality
A diet higher in flavonoid-rich foods like berries, apples, tea, and red wine was tied to lower mortality risk in people with Parkinson’s disease.
Diets with the highest quartile of total flavonoid intake before Parkinson’s diagnosis were associated with lower future risk for all-cause mortality in men (HR 0.53, 95% CI 0.39-0.71, P trend<0.001), but not in women (HR 0.93, 95% CI 0.68-1.28, P trend=0.69), compared with the lowest quartile, after adjusting for age, smoking status, total energy intake, and other covariates, reported Xiang Gao, MD, PhD, of Pennsylvania State University in University Park, and co-authors.
After Parkinson’s disease diagnosis, higher intakes of total flavonoid and several subclasses including flavonols, anthocyanins, flavan-3-ols, and flavonoid polymers were associated with lower mortality risk (pooled adjusted HR 0.78, 0.66, 0.59, 0.75, and 0.65, respectively, P<0.05 for all), they wrote in Neurology.
Anthocyanins (found in berries and red wine) and flavan-3-ols (found in apples, tea, and red wine) were consistently associated with lower risk of death, both before and after Parkinson’s diagnosis.
For flavonoid-rich foods, a higher intake of berries and red wine after Parkinson’s diagnosis was associated with lower mortality risk (pooled HR comparing three or more servings/week versus less than one serving per month 0.74 and 0.60, respectively, P<0.05 for both).
“This is the first study to examine the risk of mortality among individuals with Parkinson’s disease in relation to the habitual diet,” Gao and co-authors noted. “Although direct comparison with other studies cannot be made, our results are in line with those from previous studies on related topics, e.g., an association between flavonoids intake and risk of developing Parkinson’s disease, and flavonoids intake and mortality in general populations.”
“Oxidative stress can lead to alpha synuclein aggregation found in Lewy bodies, a hallmark of Parkinson’s disease,” noted Thomas Holland, MD, of Rush University in Chicago, who wasn’t involved with the study. “Further, inflammation from microglial activation in response to an immune reaction can lead to dopaminergic neuronal loss,” he told MedPage Today.
“Flavonoids, as we know them, have antioxidant and anti-inflammatory properties,” Holland said. “Thus, a higher dietary intake of flavonoids through a diet diverse in fruits and vegetables has the potential to be protective and perhaps slow disease progression.”
“It’s currently understood that most, if not all, neurodegenerative disease processes involve a degree of inflammation and oxidative stress, to some extent,” he added. “Given the inherent properties of flavonoids, it’s important to ensure our diets are rich in foods that have a diverse quantity and quality of nutrients and bioactives. Additional lifestyle factors like physical activity, cognitive activity, and appropriate sleep quality have the capability to bolster these protective aspects.”
The analysis was based on participants in two longstanding, ongoing cohorts — 599 women from the Nurses’ Health Study and 652 men from the Health Professionals Follow-Up Study — who were newly diagnosed with Parkinson’s disease during follow-up.
The researchers assessed dietary intake of total flavonoid and its subclasses and major flavonoid-rich foods using food frequency questionnaires every 4 years until June 2018. They determined mortality through the National Death Index and state vital statistics records.
Mean ages at Parkinson’s diagnosis were 73 for men and 72 for women. In both groups, people who consumed more flavonoids were more likely to never smoke, have higher physical activity levels, and higher intake of vitamin C, vitamin E, and beta-carotene.
Adjusting for vitamin C, vitamin E, and beta-carotene intake did not substantially alter overall findings in both pre- and post-diagnosis analyses, Gao and co-authors said.
People in the highest quartile consumed an average of 673 mg of flavonoids each day; the lowest quartile consumed 134 mg.
During 34 years of follow-up, 944 people (528 men and 416 women) died. Overall, 513 people died from Parkinson’s, 112 died from cardiovascular diseases, and 69 died from cancer.
The study had several limitations, the researchers acknowledged. Severity of Parkinson’s disease was unknown, which may confound results. Both cohorts included predominantly white healthcare professionals, and findings may not apply to others. In addition, food frequency questionnaires may not have captured flavonoid intake accurately.
Feds lead investment in antimicrobial resistance, but more private help is needed, BARDA says
In an editorial published Saturday, The Lancet noted that strategies to improve antimicrobial resistance (AMR) “have been consistently recommended.”
However, “[i]nnovation has been extremely slow,” the editorial continued. “Vaccines are available for only one of the six leading pathogens … The clinical pipeline for antibiotics is too small to tackle the increasing emergence and spread of AMR.”
“National leaders now have an obligation to move AMR to a higher position in their political agendas,” the editorialists argued. “Research efforts should be accelerated to address knowledge and innovation gaps and to inform policy and practices.”
The day before the editorial’s publication, MedPage Today spoke with Chris Houchens, PhD, director of the division of Chemical, Biological, Radiological, and Nuclear (CBRN) Medical Countermeasures for the Biomedical Advanced Research and Development Authority (BARDA). We discussed BARDA’s investments in addressing AMR, the potential of vaccines for AMR, and why private investment in this space lags, among other issues.
The following is an edited version of our conversation:
Give me your assessment on the AMR issue. I’ve heard it referred to as the next big pandemic; I’m wondering if you agree about that.
Houchens: I would agree it is the next pandemic. In fact, it’s a pandemic that’s already occurring [and] responsible for, I think, close to 23,000 deaths every year in the United States.
It’s going to be very challenging to ever develop that definitive antibiotic that addresses bacterial infection, all the different indications which the bug is not going to figure out how to get around.
Is it a pandemic of COVID-19 proportions? Or is it ever going to be as transmissible as Ebola? Probably not.
You’re in a very, very precarious state, that there is very limited private equity support. There is not a return on investment, because … people that are taking these drugs, they take them for 2 or 3 weeks at a time, rather than for the rest of their lives. It’s a small population that takes them, there’s generics on the market, and these drugs are going to fail in 4 or 5 years. [But] likely at some point you or somebody you know, somebody that’s close to you, is going to be impacted by this. It’s almost like global warming.
What do you think it would take? Or is it even possible to get more pharmaceutical investment in the space?
Houchens: There are a lot of private equity investors who are happy to invest in technologies and products and things like that, that serve a public good. They don’t have to make a lot of money doing it, but they don’t want to lose money doing it, either. A new antibiotic, it’s going to require $1 billion in investment to get it to the market, then those investors are going to want to see at least $2 billion in return in sales.
It’s going to require that antibiotics are appropriately priced or reimbursed, whether it’s through changes in how CMS reimburses [or] another possibility is that companies that develop products, they receive a payment from the government, companies getting a payment for the delivery of an approved antibiotic that would be commensurate with the value of that antibiotic and [investments] the company have made.
I have to make clear: I’m not endorsing the policies. I’m talking about some of the policies that have been discussed.
Give me a high-level summary of the major programs BARDA are working on within the space.
Houchens: There are three major investment areas. One is CARB-X. This is a partnership that we established in 2016 with Boston University. And it brought in other funders like NIH, the Wellcome Trust, the governments of the United Kingdom and Germany, and also the Gates Foundation.
CARB-X was established to support the early-stage research and development of antibiotics … up through phase 1 development — at which point then we transition to the BARDA portfolio, where we support all the way to product licensure. Then we have a third area that we use that’s called Project BioShield. That is to support the post-licensure activities.
We’re actually 6 years now since we established CARB-X. We’ve invested $200 million. Our other partners have provided an additional $300 million. Other investors have provided another $2.2 billion. Nine of those [funded products] have graduated from CARB-X. Nine other products have also entered phase 1 development. … Right now the project has 54 active programs [out of 92 programs over the last 6 years]. Our bet was a 5-year project, and the U.S. government has made a commitment to continue CARB-X for another 10 years. Nine [products] entered clinical trials. We picked two up into our BARDA portfolio, into our clinical development portfolio.
So, does that mean we can expect those to be on the market at some point in the near future?
Houchens: At some point? Absolutely. The genesis of CARB-X was … gaps between discovery of a new antibiotic and getting it into clinical development, where there wasn’t a lot of accessibility. So, you did not see a lot of candidates coming through that early phase of development.
That brings us to the BARDA clinical portfolio. We have had that [since] 2010. We also recognized that there’s a critical need for developments for … bacteria that are responsible for the majority of hospital infections. They’re responsible for secondary bacterial infections that are often going to accompany any sort of health emergency. And also, at the end of the day, the real goal is to make sure that we are making antibiotics available.
And over the past 11 years, 12 years, we’ve invested $1.6 billion in product development for AMR. We support 18 [novel candidates] in advanced development. Seven of those are in phase 3. We anticipate that we’ll probably get two new approvals in the next year. We have one product in phase 2 and we have five products in phase 1. We also have a number of products that are already out and available now in preclinical development.
We supported the development of three drugs backed by the FDA over the last few years. The problem is these companies that got [the] products went bankrupt soon after product approval.
[Note: BARDA has helped cultivate 33 AMR candidates, resulting in three FDA approvals, a spokesperson told MedPage Today in an email following the interview.]
The post-approval phase for antibiotics is very, very cost-intensive. So, the third phase of our investment [is] to buy a drug and put it into the stockpile. And that is company revenue that they can use in turn to go back and build their skills and build a margin. It allows the company to gain the ability to market that drug for the new diseases, these new indications.
We anticipate that we’re going to put out a call for proposals pretty soon that’s going to look for two new antibiotics that we can support as a target for BioShield.
How much can BARDA really do? And how much will these efforts really help when it comes to addressing the problem of AMR? How about outside of government? Are we relying almost entirely on government to end this problem?
Houchens: I’m sorry to say, but yeah. Until an antibiotic can be valued appropriately for the health system on the delivery of healthcare, I just don’t see that any other entity is going to put their money on the line. And that’s the state that we play in, which is addressing market failures.
When we were at the World Anti-Microbial Resistance Congress, there was a lot of talk about vaccines. Not a lot of information was shared there. So, I’m wondering what you know about the potential for a vaccine?
Houchens: I think that there’s value in vaccines. Now, there are not a lot of indications where you could [have] patient populations that are at very high risk for specific bacterial infections. There are some cases for the elderly population in healthcare settings, long-term care settings, that are more susceptible to Pseudomonas infections, for example.
You’re not going to have the same patient population as you do for a cardiovascular drug or diabetes drug. You’d have to conduct a study with maybe 50,000 to 100,000 individuals, just to ensure that you have enough patients who are likely to go on to get a bacterial infection. So, all those are the economic forces that are pushing against the development of vaccines. Now, there may be some situations where you could see the use of a vaccine and the evaluation of a vaccine, in a post-exposure prophylaxis study.
[One] way that we could evaluate new vaccines for bacterial infections is looking at situations where you have likely exposures and vaccinating those individually. But again, they’re very challenging studies, very expensive studies to conduct, on a very limited patient population.
Right. So, do you have any idea as to why some of these companies are looking at this?
Houchens: They’re hoping to be able to demonstrate some value that’s going to differentiate their vaccine. They’re really invested, it doesn’t cost a lot of money to do that clinical research and development. We’re talking tens of millions of dollars compared to hundreds of millions or a billion dollars for the clinical development [of new drugs]. So, it’s easier for you to get smaller investment from venture capital for some of these, what could be very transformational vaccines.
What you saw at the World Anti-Microbial Resistance Congress, you’re seeing early-stage research and development of the vaccines that is not very capital intensive.
Is there anything that you wanted to add, anything important you feel like I didn’t cover?
Houchens: It’s going to continue to collapse [baring major change]. And those healthcare providers are going to lose access to these life-saving drugs.
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