How Will the COVID Pills Change the Pandemic?

In March, 2020, researchers at Emory University published a paper about a molecule called NHC/EIDD-2801. At the time, there were no treatments available for the coronavirus. But NHC/EIDD-2801, the researchers wrote, possessed “potency against multiple coronaviruses,” and could become “an effective antiviral against SARS-CoV-2.” A few days later, Emory licensed the molecule to Ridgeback Biotherapeutics, a Miami-based biotechnology company which had previously developed a monoclonal antibody for Ebola.

Ridgeback partnered with the pharmaceutical giant Merck to accelerate its development.The Emory researchers named their drug molnupiravir, after Mjölnir—the hammer of Thor. It turns out that this was not hyperbole. Last month, Merck and Ridgeback announced that molnupiravir could reduce by half the chances that a person infected by the coronavirus would need to be hospitalized. The drug was so overwhelmingly effective that an independent committee asked the researchers to stop their Phase III trial early—it would have been unethical to continue giving participants placebos.

None of the nearly four hundred patients who received molnupiravir in the trial went on to die, and the drug had no major side effects. On November 4th, the U.K. became the first country to approve molnupiravir; many observers expect that an emergency-use authorization will come from the U.S. Food and Drug Administration in December.

Oral antivirals like molnupiravir could transform the treatment of COVID-19, and of the pandemic more generally. Currently, treatments aimed at fighting COVID—mainly monoclonal antibodies and antiviral drugs like remdesivir—are given through infusion or injection, usually in clinics or hospitals. By the time people manage to arrange a visit, they are often too sick to receive much benefit. Molnupiravir, however, is a little orange pill.

A person might wake up, feel unwell, get a rapid COVID test, and head to the pharmacy around the corner to pick up a pack. A full course, which needs to start within five days of the appearance of symptoms, consists of forty pills—four capsules taken twice a day, for five days. Merck is now testing whether molnupiravir can prevent not just hospitalization after infection but also infection after exposure.

If that’s the case, then the drug might be taken prophylactically—you could get a prescription when someone in your household tests positive, even if you haven’t.Molnupiravir is—and is likely to remain—effective against all the major coronavirus variants. In fact, at least in the lab, it works against any number of RNA viruses besides SARS-CoV-2, including Ebola, hepatitis C, R.S.V., and norovirus. Instead of targeting the coronavirus’s spike protein, as vaccine-generated antibodies do, molnupiravir attacks the virus’s basic replication machinery. The spike protein mutates over time, but the replication machinery is mostly set in stone, and compromising that would make it hard for the virus to evolve resistance.

Once it’s inside the body, molnupiravir breaks down into a molecule called NHC. As my colleague Matthew Hutson explained, in a piece about antiviral drugs published last year, NHC is similar to cytosine, one of the four “bases” from which viral RNA is constructed; when the coronavirus’s RNA begins to copy itself, it slips into cytosine’s spot, in a kind of “Freaky Friday” swap. The molecule evades the virus’s genetic proofreading mechanisms and wreaks havoc, pairing with other bases, introducing a bevy of errors, and ultimately crashing the system.

A drug that’s so good at messing with viral RNA has led some to ask whether it messes with human DNA, too. (Merck’s trial excluded pregnant and breast-feeding women, and women of childbearing age had to be on contraceptives.) This is a long-standing concern about antiviral drugs that introduce genomic errors. A recent study suggests that molnupiravir, taken at high doses and for extended periods, can, in fact, introduce mutations into DNA. But, as the biochemist Derek Lowe noted, in a blog post for Science, these findings probably don’t apply directly to the real-world use of molnupiravir in COVID patients. The study was conducted in cells, not live animals or humans.

The cells were exposed to the drug for more than a month; even at the highest doses, it caused fewer mutations than were created by a brief exposure to ultraviolet light. Meanwhile, Merck has run a battery of tests—both in the lab and in animal models—and found no evidence that molnupiravir causes problematic mutations at the dose and duration at which it will be prescribed.With winter approaching, America is entering another precarious moment in the pandemic. Coronavirus cases have spiked in many European countries—including some with higher vaccination rates than the U.S.—and some American hospitals are already starting to buckle under the weight of a new wave. Nearly fifty thousand Americans are currently hospitalized with COVID-19.

It seems like molnupiravir is arriving just when we need it.It isn’t the only antiviral COVID pill, either. A day after the U.K. authorized Merck’s drug, Pfizer announced that its antiviral, Paxlovid, was also staggeringly effective at preventing the progression of COVID-19 in high-risk patients. The drug, when taken within three days of the onset of symptoms, reduced the risk of hospitalization by nearly ninety per cent. Only three of the nearly four hundred people who took Paxlovid were hospitalized, and no one died; in the placebo group, there were twenty-seven hospitalizations and seven deaths. Paxlovid is administered along with another antiviral medication called ritonavir, which slows the rate at which the former drug is broken down by the body.

Like Merck, Pfizer is now examining whether Paxlovid can also be used to prevent infections after an exposure. Results are expected early in 2022. (It’s not yet known how much of a difference the drugs will make for vaccinated individuals suffering from breakthrough infections; Merck’s and Pfizer’s trials included only unvaccinated people with risk factors for severe disease, such as obesity, diabetes, or older age. Vaccinated individuals are already much less likely to be hospitalized or die of COVID-19.)

Living in an Age of ExtinctionPaxlovid interrupts the virus’s replication not by messing with its genetic code but by disrupting the way its proteins are constructed. When a virus gets into our cells, its RNA is translated into proteins, which do the virus’s dirty work. But the proteins are first built as long strings called polypeptides; an enzyme called protease then slices them into the fragments from which proteins are assembled.
If you can’t cut the plywood, you can’t build the table, and Paxlovid blunts the blade. Because they employ separate mechanisms to defeat the virus, Paxlovid and molnupiravir could, in theory, be taken together. Some viruses that lead to chronic infections, including H.I.V. and hepatitis C, are treated with drug cocktails to prevent them from evolving resistance against a single line of attack. This approach is less common with respiratory viruses, which don’t generally persist in the body for long periods.
But combination antiviral therapy against the coronavirus could be a subject of study in the coming months, especially among immunocompromised patients, in whom the virus often lingers, allowing it the time and opportunity to generate mutations.

Merck will be producing a lot of molnupiravir. John McGrath, the company’s senior vice-president of manufacturing, told me that Merck began bolstering its manufacturing capacity long before the Phase III trial confirmed how well the drug worked. Normally, a company assesses demand for a product, then brings plants online slowly. For molnupiravir, Merck has already set up seventeen plants in eight countries across three continents. It now has the capacity to produce ten million courses of treatment by the end of this year, and at least another twenty million next year.

It expects molnupiravir to generate five to seven billion dollars in revenue by the end of 2022.How much will all these pills soften the looming winter surge? As has been true throughout the pandemic, the answer depends on many factors beyond their effectiveness. The F.D.A. could authorize molnupiravir within weeks, and Paxlovid soon afterward. But medications only work if they make their way into the body. Timing is critical. The drugs should be taken immediately after symptoms start—ideally, within three to five days. Whether people can benefit from them depends partly on the public-health infrastructure where they live. In Europe, rapid at-home COVID tests are widely available.

Twenty months into the pandemic, this is not the case in much of the U.S., and many Americans also lack ready access to affordable testing labs that can process PCR results quickly.Consider one likely scenario. On Monday, a man feels tired but thinks little of it. On Tuesday, he wakes up with a headache and, in the afternoon, develops a fever. He schedules a COVID test for the following morning. Two days later, he receives an e-mail informing him that he has tested positive. By now, it’s Friday afternoon. He calls his doctor’s office; someone picks up and asks the on-call physician to write a prescription. The man rushes to the pharmacy to get the drug within the five-day symptom-to-pill window.

Envision how the week might have unfolded for someone who’s uninsured, elderly, isolated, homeless, or food insecure, or who doesn’t speak English. Taking full advantage of the new drugs will require vigilance, energy, and access.Antivirals could be especially valuable in places like Africa, where only six per cent of the population is fully vaccinated. As they did with the vaccines, wealthy countries, including the U.S. and the U.K., have already locked in huge contracts for the pills; still, Merck has taken steps to expand access to the developing world.

It recently granted royalty-free licenses to the Medicines Patent Pool, a U.N.-backed nonprofit, which will allow manufacturers to produce generic versions of the drug for more than a hundred low- and middle-income countries. (Pfizer has reached a similar agreement with the Patent Pool; the company also announced that it will forgo royalties for Paxlovid in low-income countries, both during and after the pandemic.) As a result, a full course of molnupiravir could cost as little as twenty dollars in developing countries, compared with around seven hundred in the U.S. “Our goal was to bring this product to high-, middle-, and low-income countries at fundamentally the same time,” Paul Schaper, Merck’s executive director of global pharmaceutical policy, told me.

More than fifty companies around the world have already contacted the Patent Pool to obtain a sublicense to produce the drug, and the Gates Foundation has pledged a hundred and twenty million dollars to support generic-drug makers. Charles Gore, the Patent Pool’s executive director, recently said that, “for large parts of the world that have not got good vaccine coverage, this is really a godsend.” Of course, the same challenges of testing and distribution will apply everywhere.

Last spring, as a doctor caring for COVID patients, I was often dismayed by how little we had to offer. We tried hydroxychloroquine, blood thinners, and various oxygen-delivery devices and ventilator maneuvers; mostly, we watched as patients got better or got worse on their own. In the evenings, as I walked the city’s deserted streets, I often asked myself what kinds of treatment I wished we had. The best thing, I thought, would be a pill that people could take at home, shortly after infection, to halt the cascade of biological processes that sends them to the hospital, the I.C.U., or worse.

We will soon have not one but two such treatments. Outside of the vaccines, the new antiviral drugs are the most important pharmacologic advance of the pandemic. As the coronavirus becomes endemic, we’ll need additional tools to treat the inevitable infections that will continue to strike both vaccinated and unvaccinated people. These drugs will do that, reducing the damage that the coronavirus can inflict and, possibly, cordoning off avenues through which it can spread. Still, insuring that they are meaningfully and equitably used will require strength in the areas in which the U.S. has struggled: early and accessible testing; communication and coördination across health-care providers; fighting misinformation and building trust in rapid scientific advances. Just as vaccines don’t help without shots in arms, antivirals can’t work without pills in people.

 

Source: https://www.newyorker.com/

More on the Coronavirus

Seven Simple Steps To Sounder Sleep

Everything about our day impacts our sleep. How many minutes we spend outside, what and when we eat, what’s happening with our hormones, our habits, emotions, stress and thoughts – all this feeds into the sleep we end up with at night. All of which I was completely oblivious to when battling chronic insomnia for years on end.

Sleep anxiety can create a very real and vicious circle. I would spend hours lying in bed, increasingly wired, anxious and exhausted as time ticked by, with prescription sleeping pills within reach for those 3am nights when I had to be up first thing. The problem is that the more we worry about sleep, the higher our stress hormones go – and too much of the stress hormone cortisol, whatever the trigger, disturbs our sleep.

We’re left in a state of fight or flight, when we need to be in the opposite state of rest and digest. When my insomnia was at its worst, I’d start my day exhausted, running on empty, and have recurring burn-out days, where an overwhelming fatigue would stop me in my tracks, forcing me to lie down and recharge.

I realise now that the various sleep tips I tried over the years were like sticking plasters on a broken leg – there’s only so much that lavender, earplugs or herbal teas can do when your sleep is disrupted and out of control. Fortunately a eureka moment came along, when I was reading a book by my great great uncle, Richard Waters, a pioneer in cognitive therapy and clinical hypnosis and a protégé of the French pharmacist and self-help guru Emile Coué.

Waters wrote just a couple of pages about insomnia – how the words we use and having an understanding of sleep biology affects our mind, body and our sleep – but they were intriguing enough to set me thinking, researching and experimenting. I interviewed various experts and tried out all the sleep science and tactics I came across, while considering sleep in a much wider context than usual.

Waters also wrote a short, first-person sleep script, about what should be going on in the mind and body in the countdown to sleep. And I recorded myself reading this one-minute sleep script on my phone, which I listened to every day, when fixing my own insomnia and researching my book Teach Yourself to Sleep.

Listening to a sleep script allows us to harness the power of suggestion, using self-talk and clinical hypnosis to change our habitual thoughts, physiology and behaviour. I discussed this at length with clinical hypnosis expert Professor Peter Whorwell, whose hospital department at Manchester University NHS Foundation Trust creates bespoke scripts to help treat a wide range of disorders, including insomnia, phobias, pain and debilitating IBS symptoms, with a 75-80% success rate, where other treatments have failed.

Following the thread from Waters and Coué to now, and exploring the fascinating world of sleep, light and habit science, experimental psychology and more, it became clear that it pays to have a basic grasp of the biology and science of sleep and to appreciate the extraordinary power of the mind-body loop. Getting results that last makes life easier on so many levels – quality sleep not only improves our physical and mental health but also our energy levels, cognitive function and overall wellbeing.

I now instinctively remove obstacles that will get in the way of my sleep and set up sleep habit cues throughout my day. This means I can go to sleep without being up half the night, and wake up refreshed and able to get the most out of the following day. Here are seven sleep tips I used to dismantle my insomnia.

1) Stop calling yourself a bad sleeper!

Our words have an immediate effect on us physically and mentally – and you can see this in action if you consciously choose diametrically opposed words to describe the same situation. The words we choose alter our feelings, perceptions, hormones and behaviour, including our sleep.

There are some astounding studies on this and the mind-body loop, and how this can be manipulated to improve our health. As Professor Brooks of the Harvard Business School told me: “Our words codify and solidify our thoughts” – and, in turn, they change how we feel.

2) Embrace the biological fact that your body responds to too much light

Our body is hard-wired to line itself up with the light and dark of nature’s 24-hour clock. As with everything that influences your sleep, it makes all the difference if you’re aware of the simple biology taking place. In this instance, it’s understanding that the extremely light-sensitive cells in your eyes help keep your sleep-wake cycle turning as it should.

I use a light box on certain mornings, to give my office light some extra clout. At the other end of the day, a screen break before bed, moving away from bright, stay-wake signals and towards the darkness of night, helps boost sleep-inducing melatonin levels.

3) Weaken the negative fallout from stress

Stress is a huge sleep disrupter with nearly 50% of sleep issues blamed on stress. To help balance the body’s chemical cocktail in favour of sleep, it’s invaluable if we lean on science-based stress busters, to bring down our cortisol levels, which the pace, anxiety and overstimulation of modern life is forever increasing.

Effective stress busters I’ve found include “forest bathing”, aka walking among trees, as well as reframing my emotions and changing my perception of stress to weaken its hold. I regularly make use of these tactics among others if I feel my stress levels spiking during the day.

4) Know your DIY sleep habit science

Bad sleep habits, like any other, can be systematically intercepted and replaced with good ones, once you know how they take shape in the brain. Our bedroom is our sleep habit context, and making certain changes here, behavioural and content-wise, helps to break automatic sleep behaviour. Displacing negative rumination by listing the things you’re grateful for gets measurable results.

Another thing you can do is remove sleep-sabotaging cues from your bedroom (eg, work and screens), while loading in sleep-promoting cues (eg, sleep-inducing scents), to help new, desirable sleep habits stick.

5) Listen to a sleep script

Habitual thoughts set off a chain reaction that changes your emotions, body chemicals, behaviour, expectations and your sleep. A sleep script, which is a positive affirmation of how well your mind and body are preparing you for sleep, helps with this by gradually shifting your habitual sleep-related thoughts. This taps into the power of self-talk and clinical hypnosis, which are increasingly being explored by scientists, neuroscientists and medics.

Also, by listening to a sleep script during the day, you give yourself a moment to pause, creating a window for any stress to subside. I listened to myself reading a short sleep script daily, when sorting out my chronic insomnia and still rely on one as a very potent sleep habit cue.

6) Have an armchair offload

If your mind is full of worries, or all the jobs you need to do tomorrow/this week, have an armchair offload some time before bed, to let your mind think about it all and perhaps write it down. Ideally this would involve sitting in a relaxed space that isn’t your bedroom, giving you time to reflect before heading to bed, once the rush of the day, and/or TV shows are over.

Once again, it’s more impactful if you have an inkling of the biology and science going on. By giving yourself this time to think, or jot down any notes, what you’re really doing is moving worries or preoccupations from your brain’s emotional HQ, the amygdala, to your problem-solving pre-frontal cortex. What’s more, your brain will look for solutions while you dream.

7) Stare into the darkness of a pitch-black bedroom

Staring into the darkness last thing, while lying in bed, will help to increase your sleep-promoting melatonin levels, as the “hormone of sleep” is released at night when those light-sensitive photoreceptors in your eyes see that it’s dark out there.

Among other things, melatonin is also an immune system booster, so allowing your body to release as much of it as possible throughout your evening by avoiding too much bright light the closer you get to bed, is a plus in more ways than just enjoying easier, more restorative sleep.

By:

Source: Seven simple steps to sounder sleep | Life and style | The Guardian

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The IRS Goes Undercover As A Bitcoin Trader In $180,000 Sting

On the hunt for tax cheats, fraudsters, money launderers and dark web drug dealers, the Internal Revenue Service (IRS) has sent an undercover agent to work on a market for trading bitcoin, ether and other cryptocurrency.

In a search warrant reviewed by Forbes, the undercover IRS agent went by the name of “Mr. Coins” on LocalCryptos.com, a platform exchanging cryptocurrency for dollars and other fiat currencies. Mr. Coins’ profile, still live at the time of publication, had 100% positive feedback after shifting up to $200,000 in digital money.

But his biggest success may have been to take down an alleged dark web drug dealer, tricking him into sending more than $180,000 in cash to the IRS in exchange for cryptocurrencies, according to the warrant.

In June of last year, Mr. Coins put up an advertisement offering to buy bitcoin via cash by mail and above market prices. All sellers had to do was get in touch over encrypted messaging apps Wickr or WhatsApp.

Shortly afterward, a person going by the name “Lucifallen21” got in touch to inquire about the ad, according to the search warrant. The IRS, without saying how, determined that Lucifallen21 was actually Evansville, Indiana, resident Chase Hite. By July, he’d agreed to buy from Mr. Coins, wrapping up $15,040 in cash in clothes, putting the money in a box and posting it to the agent in exchange for approximately 1.59 bitcoin, according to the government’s account.

More payments came in, with nearly $20,000 posted in August, in exchange for approximately 1.34 bitcoin and 45.2 monero, another cryptocurrency that promises better privacy protections than its rivals, the government said, adding that nearly $65,000 was sent to the agent over following months.

Come March this year, investigators were getting ready to home in on the conclusion to the sting operation. A $28,000 cash package from Hite was intercepted and marked as lost by the Postal Service, according to the IRS, which then monitored calls to the post office, waiting for the suspect to call and complain. Investigators linked this call with a phone number that was paid for by Hite.

Further messages over Wickr indicated Hite was involved in dark web drug sales, claiming to sell “pills and opioids,” as well as cocaine and marijuana, the IRS claimed. As they deepened their relationship, the undercover officer agreed to provide Hite with a loan, by which the suspect would send $54,000 in cash and get $79,000 worth of cryptocurrency in return, according to the search warrant. When that last package arrived, forensics took fingerprints and linked them to Hite, the government added.

Hite was arrested in July and has not yet filed a plea. The charges were filed in the Eastern District of New York. His lawyer declined to comment. LocalCryptos hadn’t responded to requests for comment. The IRS declined to provide more information than what had been filed in court.

The tax collecting agency has a track record of going undercover to snare cryptocurrency-using criminals. Earlier this year, it was revealed that the agency had organized a payment to a service called Bitcoin Fog, which offered to launder money.

The agents said they wanted to launder cryptocurrency they’d earned by selling Ecstasy, according to a criminal complaint, first reported by Wired, in which a Russian-Swedish administrator was charged. And in March, the IRS pretended to be a seller of counterfeit Gucci products sourced from China, asking the defendant in that case to convert bitcoin that they claimed to have acquired in selling the merchandise.

But this latest sting is a rare case where the IRS set up a profile on a cryptocurrency trading platform and created what amounts to a watering hole, with agents just waiting for criminals to dive in.

This story is part of The Wire IRL feature in my newsletter, The Wiretap. Out every Monday, it’s a mix of strange true crime and real-world surveillance, with all the relevant search warrants and court documents for you to pore over. There’s also all the cybersecurity and privacy news you need to read. Sign up here.

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I’m associate editor for Forbes, covering security, surveillance and privacy. I’m also the editor of The Wiretap newsletter, which has exclusive stories on real-world

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AstraZeneca’s Calquence Showed Improvement In Small Group Of Hospitalized Covid-19 Patients

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Late in the afternoon on the first Friday of April, Andrew Monticelli, an oncologist at Rocky Mountain Cancer Centers, got a phone call from Jeff Sharman, the medical director of hematology research for McKesson’s U.S. Oncology. Sharman said that a blood cancer drug Monticelli knew well, AstraZeneca’s Calquence, could potentially help later-stage Covid-19 patients.

“Can you find patients because we can get you the drug under compassionate use?” asked Sharman, who had come to believe Calquence could potentially tamp down the overzealous immune system responses of hospitalized Covid-19 patients and shared the rational with Monticelli.

Early the next morning, Saturday April 4, Monticelli was riding shotgun as Timothy Murphy, president of Rocky Mountain Cancer Centers, raced like a Formula One driver from Colorado Springs to Denver, where the cancer care provider’s central pharmacy had two bottles of available Calquence, which costs about $14,000 for a 30-day supply. The two doctors then raced back for an hour to Penrose Hospital in Colorado Springs, where they had coordinated with doctors caring for later-stage Covid-19 patients. They had enough Calquence, which is also known by its generic name acalabrutinib, for six people.

“As we’re driving back down by phone, I was arranging a meeting to have in the Penrose doctors lounge,” said Monticelli, who was in touch with in an infectious disease specialist and two other doctors there. “We decided on patients that were clinically deteriorating, trying to find the sicker patients, or patients who had just recently been placed on the ventilator.”

With Monticelli’s help, seven Covid-19 patients at Penrose Hospital and St. Francis Medical Center, including two who were on ventilators, were given Calquence in April. They were part of a study of 19 extremely sick Covid-19 patients suffering from acute respiratory distress syndrome who received the AstraZeneca drug that showed promising results. A majority of those patients experienced improving oxygenation, often within one to three days, with no toxicity, researchers said in a paper published Friday by Science Immunology.

Covid-19 patients who were on supplemental oxygen did better with Calquence than those on ventilators, the study showed. After being treated with Calquence for 10 to 14 days, 9 out of 11, or 82%, of patients who were receiving supplemental oxygen had been discharged from the hospital and no longer required supplemental oxygen; while four out of eight patients on mechanical ventilation had been successfully extubated and no longer required supplemental oxygen. Five patients who were given Calquence, including four who had been on ventilators, died.

The results are promising enough for British drug giant AstraZeneca to launch two phase 2 clinical trials of Calquence involving 200 hospitalized Covid-19 patients. But the early promising indications in Colorado and a handful of other U.S. sites do not prove the effectiveness of Calquence, which requires data from the trials that have yet to enroll patients. There was no comparison group in the initial small study, making it even more difficult to decipher the data.

“The beneficial effect of acalabrutinib was clearly different between patients who were on supplemental oxygen, 9 (82%) showed major improvement in oxygenation including 8 who achieved normal oxygenation on room air and/or were discharged from the hospital,” the authors of the paper said.

“Though the benefit of acalabrutinib was less dramatic in patients on ventilators, half of these patients were extubated after receiving acalabrutinib. This group, however, was quite heterogeneous clinically and included patients who had been ventilated for prolonged periods of time and had major organ dysfunction.”

The Science Immunology paper does provide hope that Calquence and maybe other Bruton’s tyrosine kinase (BTK) inhibitor drugs like AbbVie ABBV ’s Imbruvica could calm the cytokine storm of the human immune system that has become a lethal problem for COVID-19 patients with immune systems overreacting to the virus.

The paper was co-written by officials from the federal government’s National Cancer Institute, AstraZeneca researchers, and doctors at medical sites where patients received Calquence. Researchers detailed the experiences of 19 hospitalized Covid-19 patients who were given Calquence off label. AstraZeneca’s drug is approved in the U.S. for the treatment of mantle cell lymphoma and chronic lymphocytic leukemia.

“Upon treatment with acalabrutinib, what they observed is an early indicator that they were shutting down very quickly the inflammatory pathway and patients’ improvement occurred very rapidly,” said José Baselga, the head of oncology research and development at AstraZeneca, in an interview. “I think the story is coming together, these patients have increased BTK activation and in patients with respiratory distress if you block BTK these patients get better.”

BTK inhibitor drugs like Calquence block the BTK protein that is key to the signaling and mobilization of white blood B cells of the human immune system. While they have been proven very effective in treating certain blood cancers, BTK inhibitors also have an anti-inflammatory benefit and are considered safe, with Calquence in particular causing few side effects.

While Baselga cautioned the study reflected only a cohort of patients and was far from a randomized clinical trial, it did show that Calquence could hit a central key pathway that regulates many of the pro-inflammatory cytokines that marshal an out-of-control immune response to the virus.

“The fact that you see a decrease in some of the markers that are related to this inflammatory response such as C-reactive protein and (pro-inflammatory cytokine) IL-6, and improving neutrophils, is telling us this is a mechanistic based activity,” Baselga said. “It’s very refreshing because at a time when many people have been doing a lot of clinical trials based on need and desperation, when somebody comes in with a proposal and a clinical trial based on a mechanism, it’s really the way to go forward. And I think that’s what this shows.”

One of the complicated issues facing doctors and nurses has been how to administer Calquence, which is a capsule, through nasogastric tubes to patients who are on ventilators. The Science Immunology paper advises doctors on how to mix the capsule’s powder in a slurry made up of Coca-Cola KO , which has the right acidity to dissolve the drug properly.

Baselga pointed out that the four patients on ventilators who died after taking Calquence were very sick and that AstraZeneca was not sure if the absorption of medication in their cases was optimal. AstraZeneca is now conducting a healthy-volunteer study to measure how exactly to treat patients using the nasogastric tubes.

While the study followed the patients who took Calquence until April 23, the authors did go back and check how those patients were doing after stopping to take the drug as recently as May 28. Forbes first reported in April that the federal government’s National Cancer Institute had given Calquence to a small number of hospitalized Covid-19 patients at Walter Reed Army Medical Center and that the drug showed early promise.

With AstraZeneca’s support, the NCI effort was expanded to other sites like Penrose Hospital, partially through McKesson’s U.S. Oncology, the large cancer services company. In Colorado Springs’ Penrose Hospital, Calquence was initially given on the weekend of April 4 to two patients on ventilators using Diet Coke. The diet soda was shaken by a hospital pharmacist three times to reduce the carbonization because otherwise the drug would aerosolize. A third patient, an elderly man with stage four prostate cancer in the intensive care unit who was not on a ventilator, was also treated with the drug. In each case, the treating physician got patient or family consent.

By Sunday evening, the elderly man reported feeling better. The next day, laboratory work came back showing the two patients on ventilators had stabilized. Hospital staff were able to take one of the patients off the ventilator on Tuesday. The other patient on a ventilator was severely ill and obese. Still, the patient was able to come off the ventilator and went home within days like the other two initial patients.

“I am just really proud of the crew here, everybody jumped in right away,” said Monticielli, who is one of the authors of the study. “We were handed the ball and had to put the ball in the end zone and I think we did the best we could.”

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Polyphasic Sleep: When Productivity Becomes Madness – Ben Mulholland

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It sounds like a miracle pill or silver bullet. Polyphasic sleep. How to rest for two hours a day with no ill effects.Imagine everything you could get done with that free time! No more rushing for work deadlines, wishing you could read that book that’s been haunting your bag for a year, or trying to find time to just relax.

Unfortunately, as with most miracle solutions, polyphasic sleep has major associated health risks and little in the way of proven benefits. Most of its good press is down to urban myths and overestimating the positives.

We don’t sleep just for the hell of it – humans need solid rest to process the information gained in waking hours and properly order memories. Unfortunately, the idea of periodically napping throughout the day to replace regular sleep is consistently brought up in productivity discussions.

Source: https://www.process.st/polyphasic-sleep/

 

 

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