Recently identified inflammatory disease VEXAS syndrome may be more common than thought, study suggests | CNN



CNN
— 

David Adams spent half a decade fighting an illness he couldn’t name. He was in and out of the hospital several times per year. His inflamed joints made his hands feel like they had been squeezed into gloves – and he could no longer play his beloved classical and jazz guitars.

He had constant fevers and fatigue. He even developed pain and swelling in his genitalia, which was his first sign that something was really wrong.

“At the turn of the year 2016, I started with some really painful effects in the male anatomy,” said Adams, now 70. “After that, again, a lot of fatigue – my primary care physician at that point had blood tests done, and my white blood cell count was very, very low.”

Next, Adams, who lives in Alexandria, Virginia, saw a hematologist, a pulmonologist, a urologist, a rheumatologist and then a dermatologist. Some of them thought he might have cancer.

Adams’ symptoms continued, with even more fatigue, pneumonia and a large rash below his waist. He tried at least a dozen medications, saw about two dozen doctors, and nothing helped.

In 2019, worsening symptoms forced him to retire early from his decades-long career in clinical data systems. But he remained in the dark about what was causing the problems.

Finally, in 2020, scientists at the National Institutes of Health discovered and named a rare genetic disorder: VEXAS syndrome, which wreaks havoc on the body through inflammation and blood problems.

Adams had an appointment with his rheumatologist at the time, and when he walked into the office, he saw that his physician “was giddy like a little kid.”

In his doctor’s hands was a copy of a paper in the New England Journal of Medicine detailing the discovery of VEXAS syndrome.

Adams had his answer.

“For the first time, there was a one-to-one correlation of symptoms,” he said. “It was quite a shock.”

An estimated 1 in about 13,500 people in the United States may have VEXAS syndrome, a new study suggests, which means the mysterious and sometimes deadly inflammatory disorder may be more common than previously thought.

In comparison, the genetic disorder spinal muscular atrophy affects about 1 in 10,000 people and Huntington’s disease occurs in about 1 in every 10,000 to 20,000 people.

Since its discovery, occasional VEXAS cases have been reported in medical research, but the study reveals new estimates of its prevalence.

The research, published Tuesday in the journal JAMA, suggests that about 1 in 13,591 people in the US have mutations in the UBA1 gene, which develop later in life and cause VEXAS syndrome.

“This study is demonstrating that there’s likely tens of thousands of patients in the US that have this disease, and the vast majority of them are probably not being recognized because physicians aren’t really considering this as a diagnosis more broadly,” said Dr. David Beck, an assistant professor in the Department of Medicine at NYU Langone Health and a lead author of the study.

VEXAS syndrome is not inherited, so people who have it don’t pass the disease to their children. But the UBA1 gene is on the X chromosome, so the syndrome is an X-linked disease. It predominantly affects men, who carry only one X chromosome. Women have two X chromosomes, so if they have a mutation in a gene on one X chromosome but not the other, they are generally unaffected.

“It’s present in 1 in 4,000 men over the age of 50. So we think it’s a disease that should be thought about in terms of testing for individuals that have the symptoms,” said Beck, who also led the federal research team that identified the shared UBA1 mutation among VEXAS patients in 2020.

“The benefit of VEXAS syndrome is that we have a test. We have a genetic test that can help directly provide the diagnosis,” he said. “It’s just a question of patients who meet the criteria – who are older individuals with systemic inflammation, low blood counts, who really aren’t responding to anything but steroids – then advocating to their doctors to get genetic testing to get a diagnosis.”

Adams, who became a patient of Beck’s, said that finally getting a diagnosis – and understanding the cause of his symptoms – was life-changing.

“It really was incredibly freeing to have the diagnosis,” he said.

“You can’t fight your enemy unless your enemy has a name,” he added. “We finally had something where we could point to and say, ‘OK, we understand what’s going on. This is VEXAS.’ “

For the new study, Beck and his colleagues at the NIH, New York University, Geisinger Research and other institutions analyzed data on 163,096 patients in a health system in central and northeastern Pennsylvania, from January 1996 to January 2022, including electronic health records and blood samples.

Eleven of the patients had a disease-causing UBA1 variant, and a 12th person had a “highly suspicious” variant.

Only three of the 12 are still alive. A five-year survival rate of 63% has been previously reported with VEXAS.

Among the 11 patients in the new study who had pathogenic variants in UBA1, only two were women. Seven had arthritis as a symptom, and four had been diagnosed with rheumatologic diseases, such as psoriasis of the skin or sarcoidosis, which causes swollen lumps in the body. All had anemia or low blood cell counts.

“None had been previously clinically diagnosed with VEXAS syndrome,” Beck said.

The finding “is emphasizing how it’s important to be able to pick these patients out, give them the diagnosis and start the aggressive therapies or aggressive treatments to keep their inflammation in check,” he said.

VEXAS – an acronym for five clinical characteristics of the disease – has no standardized treatment or cure, but Beck said symptoms can be managed with medications like the steroid prednisone or other immunosuppressants.

“But the toxicities of prednisone over years is challenging. There are other anti-inflammatory medications that we use, but they’re only partially effective at the moment,” he said. “One treatment for individuals that we’ve seen that’s very effective is bone marrow transplantation. That comes with its own risks, but that’s just underscoring the severe nature of the disease.”

Although the new study helps provide estimates of the prevalence and symptoms of VEXAS syndrome, the data is not representative of the entire United States, and Beck said that more research needs to be done on a larger, more diverse group of people.

Some men might be hesitant to seek medical care for VEXAS symptoms, but Adams said that doing so could save their life.

“Eventually, it’s going to get so bad that you’ll end up like my first hospitalization, where you’re on death’s door,” Adams said. “You don’t want to be in that situation.”

Adams has been taking prednisone to ease his symptoms, and it’s helped. But because steroid use can have side effects such as cataracts and weight gain, he has been working with his doctors to find other therapies so he can reduce his intake of the medication.

Beck and his colleagues are studying targeted therapies for VEXAS syndrome, as well as conducting stem cell bone marrow transplant trials at the NIH.

“There are many different facets of the disease,” Dr. Bhavisha Patel, a hematologist and researcher in the National Heart, Lung and Blood Institute’s Hematopoiesis and Bone Marrow Failure Laboratory, said in an NIH news release last month.

“I believe that is what is challenging when we think about treatment, because it’s so heterogeneous,” said Patel, who was not involved in the new study.

“Both at NIH and worldwide, the groups that have dedicated themselves to VEXAS are looking for medical therapies to offer to other patients who don’t qualify for a bone marrow transplant,” she said. “We continue to collaborate on many projects in order to categorize this disease further and ultimately come up with the best treatment options.”

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Millions have the same ‘bendy body’ disease as my daughter. Why isn’t the medical profession paying more attention? | CNN



CNN
— 

One day in July 2021, my then 15-year-old daughter Poppy stumbled and fell while walking down some stairs, grazing her knee. It wasn’t a serious wound, but over the weeks it didn’t heal.

Around the same time, her wrists and knees became sore; her ankles started rolling when she walked; her hands began shaking; her headaches and stomach aches became more frequent and intensely painful. She was always exhausted.

Before her health declined, Poppy had enjoyed horse riding and gymnastics, she’d competed in cross country races and been a fearless goalkeeper for the school hockey team.

But within a couple of months, as walking became increasingly difficult, she asked me for a walking stick. We found one that folds up and fits neatly in her school bag.

I took Poppy to doctors who conducted tests, but they couldn’t find out what was wrong with her. Then, in October, a breakthrough.

A podiatrist who was measuring Poppy for insoles to support her aching feet asked if Poppy could bend her thumb to reach her forearm. She could. Could she pull her little finger back to form a 90-degree angle with the back of her hand? She could do that, too.

“Have you heard of Ehlers-Danlos syndrome?” the podiatrist asked me. I hadn’t – so as soon as I got home, I went looking on the internet.

There are 13 types of Ehlers-Danlos syndrome (EDS), according to research and advocacy organization The Ehlers-Danlos Society. Most types are very rare, and can be diagnosed using genetic tests. However, the genes that cause hypermobile EDS (hEDS) – the most common form, accounting for about 90% of cases – are unknown, so diagnosis is based on a checklist of symptoms. The list includes a hypermobility rating, known as the Beighton Score.

Poppy had enough symptoms to qualify for hEDS, and the diagnosis was confirmed by a doctor one year ago, on Christmas Eve. He told us that although we can do our best to alleviate some symptoms, there is no cure.

Poppy reacted to the news better than I did. She had known for some time that something was fundamentally wrong. The diagnosis was upsetting but identifying her illness also gave her a sense of relief. I felt shocked and overwhelmed, and I cried for weeks.

Reading about EDS was like a dreadful slow reveal.

I learned that it’s a genetic disorder that causes the body to make faulty connective tissue, and connective tissue is everywhere – in the tendons, ligaments, skin, heart, digestive system, eyes and gums.

Weak connective tissue leads to hypermobility, which may sound like a good thing, but some people with bendy bodies suffer a mind-boggling array of symptoms, including joint dislocations and subluxations (like a mini dislocation, when the joint partially slips out of place), soft stretchy skin, abnormal scarring, poor wound healing, gastrointestinal disorders, chronic pain and fatigue.

The severity of symptoms varies wildly. Patients with milder cases can lead relatively normal lives, while others become housebound, and some can’t digest food and must be fed through tubes.

What’s more, people with hEDS are prone to other conditions, including POTS (postural orthostatic tachycardia syndrome, which makes you dizzy when you stand up) and MCAS (mast cell activation syndrome, which gives you allergy-type symptoms).

I learned a lot of new acronyms and they all spelled bad news.

I initially thought hEDS was rare, because all forms of EDS are commonly referred to as rare. But within a few weeks, I felt like I was seeing references to hEDS everywhere. Actor, writer and director Lena Dunham; actor and presenter Jameela Jamil; and drag queen Yvie Oddly live with it. I deep dived into EDS Twitter and EDS Instagram, while Poppy found it comforting to watch TikTok videos made by teenagers with the condition.

I discovered multiple patient groups on Facebook, each with tens of thousands of members, which turned out to be great sources of support. I asked questions (what kind of shoes are best for weak ankles? Which knee braces are easiest to pull on and off?) and kind strangers sent helpful advice. At the same time, scrolling through countless personal stories of pain, despair and shattered dreams made me feel terrified about what might lie ahead.

I noticed common themes. Many EDS patients had spent years seeking the correct diagnosis; others felt they’d been neglected and gaslit by doctors.

There was also a lot of talk of zebras.

Linda Bluestein, a Colorado-based physician who specializes in EDS and other hypermobility conditions, and has hEDS herself, explains why.

“I was told in medical school, ‘when you hear hoofbeats think horses, not zebras,’” she says. Many trainee doctors receive the same advice – when a patient presents with symptoms, “look for the common thing.” That’s why EDS patients commonly refer to themselves as zebras – and also use the fabulous collective noun “dazzle.” The name represents rarity and evokes the stripy stretch marks that are a common feature on EDS skin.

But if people with hEDS are medical zebras, why am I encountering so many of them?

Bluestein says that for many years it was thought that one in 5,000 people had Ehlers-Danlos syndrome. But she says the limited research that’s been carried out into the prevalence of hEDS suggests the true number of cases is “much, much higher” than that.

Dr. Linda Bluestein has treated hEDS patients  who have been searching for a diagnosis for decades.

Bluestein points me to a 2019 study carried out in Wales – a country of 3.1 million people. An examination of primary care and hospital records from 1990 to 2017 found that one in 500 people there has either hEDS or joint hypermobility syndrome (a similar condition with a slightly different set of symptoms). She says it’s “a good study” but believes it’s still an underestimate. The Ehlers-Danlos Society says more population studies need to be done to give a more accurate view of its incidence elsewhere.

But despite this possible prevalence, and how debilitating hypermobility disorders can be, the average time to diagnosis from the onset of symptoms is 10 to 12 years, according to The Ehlers-Danlos Society.

Bluestein has firsthand experience of this. Growing up, she wanted to become a ballet dancer and trained six days a week. When puberty hit, she started experiencing joint pain and migraines, and at 16 had her first orthopedic surgery. She realized she wouldn’t succeed in the ballet world and instead pursued her “back-up plan,” to become a doctor. But despite her career choice, Bluestein only received her hEDS diagnosis when she was 47 – more than 30 years later.

“I told my doctor on numerous occasions, ‘there is something wrong with me, I don’t heal well, I get injured more easily than other people’,” she says. “And he just never, never listened.”

Why, for so many patients, does it take so long to get diagnosed?

In 2014 a leading EDS expert, Professor Rodney Grahame, remarked at a conference that “no other disease in the history of modern medicine has been neglected in such a way as Ehlers-Danlos syndrome.”

Far more women than men are diagnosed with EDS, which could help to explain the neglect, because the medical profession has a long history of overlooking health complaints made by women.

A 2009 study, conducted by the European Organisation for Rare Diseases, surveyed 414 families of EDS patients from five countries and found that the average delay to an EDS diagnosis was four years for men – but 16 years for women.

The report states that women with EDS tend to be “diagnosed later because their pain and hypotonia (poor muscle tone) aren’t considered as physical symptoms but rather as psychological symptoms or common complaints.”

“We tend to get dismissed a lot more easily,” says Bluestein. “People jump to the conclusion that we’re histrionic females.”

Anxiety is very common in patients with hypermobility issues, says Bluestein, which can cloud the picture. “When people with anxiety present to a physician, it can suck all the air out of the room, so that the physician almost can’t see anything else.”

This can ramp up the patient’s anxiety further “because people aren’t validating our symptoms, and then we start to doubt ourselves,” she says.

What’s more, medicine is divided into silos which creates the “worst possible model” for EDS patients, says Bluestein.

VIDEO THUMBNAIL Ehlers-Danlos Syndrome 1

‘We’re born with this and will never be free:’ Hear stories from people with Ehlers-Danlos syndrome

She explains that undiagnosed patients might consult a neurologist for their migraines, a rheumatologist for joint pain, a cardiologist for palpitations, a gastroenterologist for digestive issues and a urologist for bladder symptoms. Each doctor focuses on the symptoms that fall within their specialty but doesn’t consider the other ailments. “Nowhere along the way does somebody realize that there are certain conditions that could tie all of these things together and explain everything,” says Bluestein.

The 2009 rare diseases study found that during the quest for a diagnosis, 58% of EDS patients consulted more than five doctors, and 20% consulted more than 20.

The consequences of not getting diagnosed for years can be devastating.

Melissa Dickinson, a psychotherapist in Atlanta, Georgia, says she experienced symptoms of a “mystery illness” since childhood. Then in 2013, she “went on honeymoon to Mexico, relatively healthy, and came back disabled and with a dislocated neck.”

While on vacation, Dickinson says she got food poisoning and was prescribed ciprofloxacin, an antibiotic that can pose a serious risk of aortic aneurysm to people with EDS. Instead, she says it triggered significant nerve damage, digestive issues that almost made her go blind because her body wasn’t absorbing nutrients, and put her in a wheelchair.

Dickinson, who finally received her hEDS diagnosis in 2014, says taking the wrong medication “wrecked me from head to toe.” Now that she’s receiving treatment, “I can walk with mobility aids, but most of my body has to have constant support to function.”

Lara Bloom, president and CEO of The Ehlers-Danlos Society, who herself has hEDS, says many patients have “medicalized PTSD.”

“They have had to stop their careers, they’ve had to drop out of school, their relationships have broken down.” The delay inevitably results in worsening symptoms and a declining quality of life, she says. In worst-case scenarios, patients “are dying by suicide, they’re self-harming.”

Sometimes, the failure to diagnose EDS has led to children being taken away from their parents.

In 2010, Americans Rana Tyson and her husband Chad were falsely accused of harming their 4-week-old twin daughters, who had unexplained fractures in their legs.

Along with their older sister, the baby girls were taken by state authorities in Texas and sent to live with relatives. “It was the worst day of my life,” Tyson tells me in a phone call.

Five months later, a geneticist identified the twins as having a connective tissue disorder, and they were subsequently diagnosed with EDS and a vitamin D deficiency. The family was reunited but “12 years later, it still hurts,” says Tyson.

Bloom says some other parents of children with EDS have been wrongly accused of “fabricated or induced illness (FII)” – a rare form of abuse, formerly known as Munchausen’s syndrome by proxy, in which a parent or care giver deliberately causes symptoms or tries to convince doctors that a healthy child is ill.

Ellie Pattison, who has hEDS, has been repeatedly misdiagnosed as having an eating disorder.

Ellie Pattison, a 19-year-old student who lives in County Durham, England, suffers from severe digestive issues linked to hEDS.

Throughout her childhood, Ellie was repeatedly misdiagnosed as having an eating disorder, she says, while her mother Caroline was accused of FII on three separate occasions. Caroline successfully fought to keep her daughter at home, says Ellie, but the ordeal has left the whole family with “an unimaginable amount of trauma.” Ellie says she suffered from PTSD and endured years of horrific nightmares, triggered by living with the fear from a young age that she could be forcibly separated from her family.

This underlines why prompt diagnosis is so important, says Bloom. “Our hope and dream is for people to get diagnosed when their symptoms begin.”

In the case of hEDS, a crucial first step is to find out what causes it.

Cortney Gensemer, a biomedical scientist in the Norris Lab at the Medical University of South Carolina’s department of Regenerative Medicine and Cell Biology, is trying to solve this mystery. She and research mentor Russell Norris, head of the lab, have been studying a gene mutation they believe causes hEDS (the results of the study are currently under peer review).

Like Poppy, Gensemer was diagnosed with hEDS as a teenager. She says the disease affects every aspect of her work. Looking down a microscope is particularly painful at times – her neck is unstable because of her hEDS, and she’s had metal screws put into some of her neck vertebrae to fuse them.

Cortney Gensemer working in the Norris Lab and recovering from neck surgery earlier this year.

Norris kitted the lab out with special equipment, including motion sensor doors (standard lab doors are very heavy), adjustable chairs and ergonomic pipettes that are gentle on the hands. “If I didn’t have all that stuff, I don’t think I’d be able to do it,” says Gensemer.

To find a hEDS-causing gene, Gensemer says she and Norris sampled DNA from a large family with cases spanning four generations and looked for a mutation that appears only in relatives who have the disease. They identified a “strong candidate gene” and inserted it into mice using gene editing tools.

Gensemer and Norris found that the hEDS mice had significantly more lax tissues, and floppier tails than regular rodents. “You can tie a loose knot into the mutant mouse tail. With a normal mouse tail, you can (only) bend it into a circle,” Gensemer says.

The gene that Gensemer and Norris found won’t account for all hEDS cases, she says. They believe that eventually multiple genes will be identified, and hEDS may be split into different subtypes. This would help to explain why different patients have different symptoms. Crucially, if genetic information sheds light on how the connective tissue is “messed up,” it could lead to effective treatments, says Gensemer.

The Ehlers-Danlos Society is also looking for genes as well as blood markers, working with a team of experts to sequence and analyze the DNA of 1,000 hEDS patients from around the world. And at the UK’s University of Warwick, Ph.D. candidate Sabeeha Malek, another scientist with hEDS, has proposed that EDS might be caused by a fault in the way that collagen binds to cell membranes in connective tissue. If she’s right, she hopes her work will lead to a skin biopsy test that could identify all forms of the disease.

Sabeeha Malek is working to identify biomarkers that could make EDS diagnosis easier.

Progress is being made but on a very small scale. “If you look at any major academic institution, there are multiple labs studying cancer, multiple labs studying heart disease. When you look at a disease that affects one in 500 people, and probably more than that, there should be a lab studying it at every single academic institution,” says Gensemer.

Gensemer hopes that as more discoveries are made and data is accumulated it will “change the way the medical community looks at the disease” – and that it will be taken more seriously.

A year has passed since Poppy’s diagnosis. The initial shock has subsided, and while I’m still grieving the loss of her health, we’ve both learned to accept our new reality and have adjusted to living with EDS.

I’ve assembled a team of supportive doctors and therapists and acquired an arsenal of paraphernalia to fight pain and manage symptoms, including braces and kinesiology tape to hold her joints in place; ice packs, heat pads, tiger balm and arnica gel for sore muscles; and a cupboard full of medications and supplements.

With Poppy often stuck at home, I also got her a giant kitten that she calls Bagel, and he provides the best therapy.

Poppy with Bagel.

Writing this article has taught me a lot more about EDS: It’s been upsetting to report on the terrible experiences some have suffered, but I’ve been awestruck by the dedication of people, many with the condition themselves, who are working to find solutions.

I don’t know what the future holds for Poppy. Some patients’ symptoms improve with age; others experience an increase in pain and a loss of mobility. I’ve learned there’s a limit to what we can control but there’s a lot we can do, to tackle symptoms and make life easier. And I believe that change is coming.

With a better understanding of the condition and diagnostic tools on the horizon, my biggest hope is that there will be a cure one day – and that it will come in time for Poppy.

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Study shows convalescent plasma works for immune-compromised Covid-19 patients, but it can be hard to find | CNN



CNN
— 

Convalescent plasma – a once-celebrated treatment for Covid-19 that has largely fallen out of favor – does work well for people who are immune-compromised, according to a study published Thursday.

The report in the journal JAMA Network Open analyzed the results of nine studies and found that immune-compromised Covid-19 patients were 37% less likely to die if they got convalescent plasma, an antibody-rich blood product from people who’d recovered from the virus.

Although it’s legal to use convalescent plasma to treat Covid patients who are immune-compromised, as inpatients or outpatients, government guidelines are neutral about whether the treatment works, so some hospitals offer it but others do not.

“Our concern is that many patients who need [convalescent plasma] are not getting it,” said Dr. Arturo Casadevall, an infectious disease expert at Johns Hopkins University and a co-author of the new study. “This is really important because these people can be treated, and they could have better outcomes with this material if we can just get the word out.”

He said it’s to everyone’s advantage to treat immune-compromised patients quickly.

Immune-compromised people sometimes have “smoldering Covid” for months because they lack the antibodies to fight it off, which gives the virus plenty of opportunities to mutate in the person’s body.

“These immune-compromised patients are essentially variant factories,” said Dr. Michael Joyner, an anesthesiologist at the Mayo Clinic and another study co-author. “And you do not want a bunch of people running around out there making weird variants.”

There are about 7 million immune-compromised people in the US, and treating them if they contract Covid-19 has proved challenging.

Many of them can’t take the antiviral drug Paxlovid because it interferes with other medicines they take.

Monoclonal antibodies, once popular for prevention and treatment for this group, aren’t used anymore because coronavirus variants have changed over time. One of the advantages of convalescent plasma is that as long as it’s been donated recently, there’s a high likelihood it will have antibodies to currently circulating variants, according to advocates for the treatment.

But the National Institutes of Health’s Covid-19 treatment guidelines say there’s not enough evidence to recommend either for or against the use of convalescent plasma in people with compromised immune systems.

Three times last year – in May, August and December – Casadevall, Joyner and dozens of other doctors from Harvard, Stanford, Mayo, Columbia and other academic medical centers wrote emails to scientists at the National Institutes of Health, sending them research materials and urging them to revise the guidelines. They say they have not received a response.

Joyner said he’s “frustrated” with the NIH’s “bureaucratic rope-a-dope,” calling the agency’s guidelines a “wet blanket” that discourages doctors from trying convalescent plasma on these people.

Some patient advocates say they’re angry.

“This lack of response to the researchers is infuriating,” said Janet Handal, co-founder of the Transplant Recipient and Immunocompromised Patient Advocacy Group.

Several large randomized clinical trials on the general population, including one in India and one in the UK, have found that convalescent plasma did not reduce Covid-19 deaths or prevent severe illness, and the treatment is no longer authorized in the US for people who have healthy immune systems.

The nine studies analyzed in the new report are much smaller and looked only at immune-compromised patients.

Dr. Peter Horby, a professor at the University of Oxford and the co-principal investigator of the large UK study, said that a large randomized clinical trial should be done on immune-compromised patients before clinical practice guidelines for this group are changed.

He said that support for convalescent plasma to treat Covid-19 has been based on “an emotional feeling that something had to be done.”

“We’ve seen time and again that people’s beliefs and emotions about what works can be wildly wrong, and so the best thing to do is to evaluate these things properly in trials,” he said.

At the beginning of the pandemic, there was great enthusiasm for convalescent plasma as Covid-19 survivors sought to save lives, donating antibodies against the virus to people who were sometimes at death’s door.

In August 2020, the US Food and Drug Administration granted emergency use authorization for the treatment, but some questioned whether it was politically motivated and whether the data really showed that it worked.

Then, the large clinical trials suggested convalescent plasma didn’t work.

“We didn’t see a benefit,” said Horby, director of Oxford’s Pandemic Sciences Institute.

But there was one exception.

Horby said his study did find “some evidence of some benefit” in Covid-19 patients who had not developed antibodies against the virus. This would most likely include immune-compromised patients because their faulty immune systems don’t always generate antibodies the way they should, even after infection.

When this group of patients received convalescent plasma, Horby said, they had a slightly shortened hospital stay and a slightly lower risk of ending up on a ventilator compared with similar patients who did not receive convalescent plasma.

Joyner and Casadevall, the Mayo and Hopkins doctors, point to that finding – and a similar one in a large trial in Australia, Canada, the UK and the US, as well as results of smaller studies – as an indication that convalescent plasma is worth trying in immune-compromised patients.

Immune-compromised patients who catch Covid-19 can get convalescent plasma relatively easily if they’re patients at Hopkins, Mayo or several other medical centers.

But many other people might have a difficult time accessing it.

It took Bernadette Kay of Manhattan Beach, California, months to get it, and she had to be “relentless” and call in the help of several “angels” in New York, Maryland, Minnesota and California to finally make it work.

Kay, 64, who has a compromised immune system because of a drug she takes for rheumatoid arthritis, got Covid-19 in July. She took two monoclonal antibodies, as well as remdesivir and Paxlovid – twice. But she still tested positive on and off for months and had fatigue, congestion and headaches.

“I felt like half a person,” she said. “I was not an able-bodied person. I was disabled because of lack of energy. It feels dark – a heavy feeling in your forehead and your face.”

Kay said she saw several doctors and none of them suggested convalescent plasma. That’s where her first angel came in: her daughter, who had signed her up for the Transplant Recipient and Immunocompromised Patient Advocacy Group.

That group, as well as the CLL Society, an advocacy organization for cancer patients, have been helping immune-compromised people when they get infected with Covid-19, connecting them with experts and offering guidance on how to arrange to have the plasma ordered.

Kay says Handal, the co-founder of the immune-compromised patients’ group, was her second angel, because she pointed her to angels No. 3 and 4: Joyner, the Mayo doctor, and Dr. Shmuel Shoham, an infectious disease expert at Hopkins.

Joyner and Shoham pointed Kay to her fifth angel: Chaim Lebovits, a businessman, leader in the New York’s Hasidic Jewish community and co-founder of the Covid Plasma Initiative.

Lebovits reached out to a hospital and blood bank near Kay that could procure the plasma once a doctor ordered it. Kay then reached out to six local doctors, most of them infectious disease experts, inquiring about convalescent plasma, but she didn’t make any progress.

“I think they thought it was quack medicine,” she said.

By this time, it was November, four months after she initially tested positive for Covid. She sought out a seventh doctor, sending him information from plasma experts, including a slide presentation by Joyner and Casdevall. She said that doctor, after conferring with someone at the blood bank that Libovits had suggested, agreed to order the plasma.

That’s where her sixth angel came in: Robert Simpson, vice president for hospital services at the San Diego Blood Bank, who arranged to have the blood flown in from Stanford University Medical Center.

“Robert watched the flight on Flight Tracker and had a courier waiting to bring it to the hospital,” Kay said, adding that she calls her angels collectively her “circle of love.”

Two to three weeks after her infusion, she began to feel better. She tested negative on January 4 and has continued to feel well and test negative since then.

“My energy level is back to normal. I don’t feel like half a person,” she said.

She said she’ll never know for sure exactly what spurred her recovery, but “I think it was plasma that made the difference, because in six months, nothing else made a difference.”

Kay, who works in health care, said most other people wouldn’t have known how to navigate the system like she did or might have given up in frustration.

“With the help of Janet [Handal] and her team of scientists, I’ve been able to get where I am today,” she said. “But it was not easy. This was driven by my bullheaded advocacy, because that’s who I am. I think I’m a total anomaly. No one has the persistence that I have.”

Joyner said that while he and his colleagues wait for a response from their emails to the NIH, they’ve formed the National Covid-19 Convalescent Plasma Project, and they have a phone meeting every Thursday night to discuss their progress.

“We’ve encountered many roadblocks,” said Dr. Liise-anne Pirofski, chief of the Division of Infectious Diseases at the Albert Einstein College of Medicine. “It’s just not viewed as part of the Covid-19 treatment armamentarium, and it should be.”

Pirofski, Joyner and Casadevall say they receive no financial benefit from convalescent plasma. They think one reason convalescent plasma isn’t more widely used is that there isn’t a pharmaceutical company spending money to advocate for it.

Handal, who runs the Facebook group for people who are immune-compromised, said that after she sent several emails to the NIH, agency scientists wrote back, inviting her and other leaders of her group to a meeting next week.

She plans to tell them that they need to review their Covid-19 plasma guidelines and fund more research on the coronavirus and the immune-compromised, as they have few treatment options and so often isolate at home with their families to avoid the virus.

“It is unconscionable that the NIH has let stand for months its guideline on Covid convalescent plasma, which says there is not enough information to make a recommendation, while we who are immune-compromised see our treatments dwindle,” she said. “The NIH needs to speak to the clinician researchers who are experts, prioritize the immune-compromised and fund the research needed to keep us safe.”

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New treatment for nightmares holds promise, study finds | CNN


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CNN
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Heart pounding, I sit bolt upright in bed, flushed, sweaty and utterly panicked. My brain has snatched me from a nightmare — a dream so alarming I wake up.

I’ve only had one or two such night terrors, but for people suffering from trauma, post-traumatic stress disorder, depression or anxiety, frightening dreams may come night after night, ruining their sleep and ultimately their health.

Visions from nightmares can also creep like dark shadows into the light of the next day, disrupting a person’s ability to focus and think. Mood plummets, and anxiety rises. Days may be filled with an intense fear of falling asleep and trigger yet another terrifying dream.

Such symptoms can lead to a diagnosis of nightmare disorder, a sleep condition that affects about 4% of adults, according to the American Academy of Sleep Medicine.

Treatment can include stress reduction, counseling, gradual desensitization and medications, but the gold standard is imagery rehearsal therapy, a form of cognitive behavioral training that teaches people to reimagine their nightmares with positive endings. Still, not everyone with nightmare disorder responds to the treatment, experts say.

Now a new study has added a twist — playing a sound the person’s memory has associated with a more positive outcome during REM (rapid eye movement) or the dream stage of sleep. The result was a fourfold reduction in nightmares over the basic therapy alone.

“As far as I know, this is the first clinical and therapeutic study that uses target memory activation to accelerate and enhance therapy,” said lead author Dr. Lampros Perogamvros, a psychiatrist at the Sleep Laboratory of the Geneva University Hospitals and the University of Geneva.

“This is a promising development. It does appear that adding a well-timed sound during REM sleep augments the effect of image rehearsal therapy … which is a standard and perhaps one of the most effective non-pharmacologic therapies at this time,” said Dr. Timothy Morgenthaler, lead author of the most recent American Academy of Sleep Medicine guidelines on nightmares.

“The result should be replicated,” said Morgenthaler, who was not involved in the study. “But I was a bit excited at this new possibility.”

Imagery rehearsal therapy has four basic steps that can be taught in one day, experts say. First, people are asked to write down every detail of their nightmare. Next, each person rewrites the nightmare with a positive arch, making sure that it ends with a pleasant or empowering solution or resolution.

Now the practice begins. The reworked dream must be rehearsed five to 20 minutes each day until it’s woven into the memory circuits of the brain. Once that is in place, it’s time to put it into action by rehearsing the new dream just before bed.

In the new study, published Thursday in the journal Current Biology, researchers added a twist to the therapy. Eighteen people with nightmare disorder heard a neutral sound — a piano cord — while they reinvented their nightmares in more positive ways. A control group of 18 people who also had nightmare disorder heard no additional sound, while they reworked their dreams.

All 36 people were given a headband called an actimeter to wear at night for two weeks. In addition to monitoring the stages of sleep, the device delivered sound in a way that would not wake the sleeper — via bone conduction.

“One of the significant things about this study’s intervention is the use of relatively new technology that can more accurately time the stimulus to true REM sleep,” said Morgenthaler, a professor of medicine at Mayo Clinic School of Medicine.

“Most wearable devices do not accurately measure actual REM sleep,” he added. “Of course, further study might find that the timing is not that critical — but that remains to be determined.”

The sound was delivered to both groups every 10 seconds during the dream stage of sleep over a two-week period. In this case, “imagery rehearsal therapy worked for all of the participants, including the control group,” Perogamvros said.

“But in the experimental group, where the sound was positively associated, the decrease was significantly bigger — they had nearly four times fewer nightmares,” he added.

Imagery rehearsal therapy also lessened overall distress, measures of mood and sleep quality in both groups, but nightmare reduction happened faster in the experimental group and persisted at a three-month follow-up, Perogamvros said. In addition, members of the group who heard the sound reported more joyful dream experiences during their dreams than those in the control group.

Additional research is needed to verify these results and expand upon the concept, but Perogamvros said he hoped the technique might lead to breakthroughs for the about 30% of patients who are unresponsive to imagery rehearsal therapy, also called IRT.

“The ideas underpinning the hypothesis that targeted memory reactivation might boost the effects of IRT have merit,” Morgenthaler said, “and this elegant test of that hypothesis strengthens that theory.”



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1 in 10 Americans over 65 have dementia, study finds | CNN





CNN
— 

One in 10 Americans over 65 had dementia, while 22% experienced mild cognitive impairment, the earliest stage of the slow slide into senility, according to a new study conducted between 2016 and 2017.

The research, which the authors said is the first nationally representative examination of cognitive impairment prevalence in more than 20 years, was able to measure prevalence of dementia and mild cognitive impairment by age, education, ethnicity, gender and race.

The results showed older adults who self-identified as Black or African American were more likely to have dementia, while those who identify as Hispanic were more likely to suffer from mild cognitive impairment. People who had less than a high school education were more likely to have both conditions.

“Dementia research in general has largely focused on college-educated people who are racialized as white,” lead study author Jennifer Manly said in a statement.

“This study is representative of the population of older adults and includes groups that have been historically excluded from dementia research but are at higher risk of developing cognitive impairment because of structural racism and income inequality,” said Manly, professor of neuropsychology at the Gertrude H. Sergievsky Center and the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain at Columbia University.

“If we’re interested in increasing brain health equity in later life, we need to know where we stand now and where to direct our resources,” Manly said.

The study, published Monday in the journal JAMA Neurology, analyzed data from in-depth neuropsychological tests and interviews with nearly 3,500 people over age 65 enrolled in the Health and Retirement Study, a long-term research project sponsored by the National Institute on Aging and the Social Security Administration.

The research was based on a randomly selected sample of people from the study that completed the core survey and underwent neurological testing between June 2016 and October 2017.

Fifteen percent of people who identified as Black tested positive for dementia, while 22% had mild cognitive decline, the study found. Ten percent of people who identified as Hispanic had dementia, but the rate of milder issues was higher — 28% tested positive for mild cognitive impairment. Nine percent of White people had dementia, while 21% had mild cognitive impairment.

Educational achievement, which experts consider to be protective against cognitive decline, showed a significant divide: Nine percent of people with a college degree tested positive for dementia, compared with 13% of those who never received a high school diploma. Twenty-one percent of people over 65 with college degrees had mild cognitive decline, compared with 30% of those with less than a high school degree.

The extreme elderly had the highest rates of dementia and mild cognitive impairment. Only 3% of adults between 65 and 69 tested positive for dementia, compared with 35% of those 90 and older.

In fact, every five-year increase in age was associated with higher risk of dementia and mild cognitive impairment, the report said. The study, however, found no differences between men and women in rates of either condition

Symptoms of mild cognitive impairment can include losing items, forgetting to do things or go to appointments, or struggling to come up with words. A loss of smell and taste and movement issues can also be symptoms, according to the National Institute on Aging.

People with mild cognitive impairment are fully capable of taking care of themselves, “but what they have to go through to do so is exhausting,” Laura Baker, a professor of gerontology and geriatric medicine at Wake Forest University School of Medicine in Winston-Salem, North Carolina, told CNN in an earlier interview. She was not involved in the current study.

People with mild cognitive impairment may not remember where they are supposed to be, Baker said. ” ‘Let me check my calendar. Oh, I forgot to write on this calendar. Let’s check another calendar. Oh, I can’t find that calendar. I’ve lost my phone. Where is the key? I can’t find the key.’ They’re able to regroup in the early stages and accomplish things, but the toll is immense.”

Not everyone with mild cognitive impairment goes on to develop dementia, although many do, experts say. Lifestyle changes may be a key to reversing mental decline. A 2019 study found personalized lifestyle interventions -— such as diet, exercise, stress reduction and sleep hygiene — not only stopped cognitive decline in people at risk for Alzheimer’s, but actually increased their memory and thinking skills over 18 months. Women responded better than men, a follow-up study found.

A February study found about a third of women 75 years or older with mild cognitive impairment reversed their progression to dementia at some point during follow-up. All of the women, however, had high levels of education and academic performance and excellent written language skills, or what experts call “cognitive reserve.”

Signs of dementia can differ from one person to the next, and can include memory loss and confusion, difficulty speaking, understanding and expressing thoughts, or reading and writing, according to the National Institutes of Health.

People with dementia can act impulsively or show poor judgment, and they can have trouble paying bills or handling money responsibly. They may repeat questions, use strange words to refer to familiar objects and take longer than usual to complete daily tasks.

Wandering and getting lost in a familiar neighborhood is another sign of dementia, as is losing interest in daily activities or events or acting as if they don’t care about other people’s feelings. They may lose their balance or have other problems with movement. At times, people with dementia can hallucinate or experience delusions or paranoia.

Alzheimer’s disease is the most well-known cause of dementia, but cognitive issues can be caused by vascular problems that block the flow of blood to the brain or via ministrokes caused by tiny blood clots traveling to the brain. Frontal lobe dementia, a rare form thought to be associated with abnormal amounts of the proteins tau and TDP-43, often begins in people younger than 60. Another type of decline, called Lewy body dementia, is thought to be caused by abnormal deposits of the protein alpha-synuclein, which are called Lewy bodies.

A person with signs of cognitive decline or dementia needs a full workup by a neurologist to determine the underlying cause, the NIH said. Side effects from a number of medications can mimic dementia, as can certain diseases, such as Huntington’s disease.

If you’ve just been diagnosed with dementia, continue to meet with doctors and specialists and consider asking for a referral to a memory clinic, according to the National Institutes of Health. Reach out to your local Alzheimer’s Disease Research Center and consider joining a clinical trial.

The Alzheimer’s Association has detailed information on the differences between dementia and Alzheimer’s, and it offers many levels of support for both patients and caregivers.

Work on staying healthy — exercise helps with mood, balance and thinking, while eating a well-balanced diet and getting quality sleep can improve the brain’s ability to function.



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