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Friday, July 3, 2020

Morning exercise is the key to a good night’s sleep after heart bypass surgery

Trouble sleeping after heart bypass surgery? Morning walks are the solution, according to research presented today on ACNAP Essentials 4 You, a scientific platform of the European Society of Cardiology (ESC).
“Many patients have trouble sleeping after heart bypass surgery,” said study author Dr. Hady Atef of Cairo University, Egypt. “When this persists beyond six months it exacerbates the heart condition and puts patients at risk of having to repeat the surgery. It is therefore of utmost importance to find ways to improve sleep after bypass surgery.”
Previous studies examining the effect of exercise on sleep after heart bypass surgery have failed to simultaneously assess the impact on functional capacity (the ability to do usual activities), which often declines after surgery.
This study investigated the effect of exercise on both sleep and functional capacity. The study enrolled 80 patients aged 45 to 65 years who had sleep disorders six weeks after heart bypass surgery and also had reduced functional capacity.
Three baseline measurements were performed. First, a six-minute walk test, which measures the distance patients are able to walk in six minutes on a hard, flat surface, and is a validated way to assess functional capacity. Second, participants completed the Pittsburgh sleep quality index (PSQI) questionnaire which asks about sleep disorders. Third, patients wore an actigraph watch for 96 hours to monitor rest and activity. Many of these patients have trouble staying awake during the day but have insomnia at night – the actigraph picks up both problems.
Patients were then randomly allocated to two exercise groups: aerobic exercise or a combination of aerobic and resistance exercise. Both groups did 30 exercise sessions in the morning over a 10-week period. During the aerobic exercise sessions, participants walked on a treadmill for 30 to 45 minutes. During the aerobic and resistance exercise sessions, participants walked on a treadmill for 30 to 45 minutes and did circuit weight training (a form of light resistance exercise).
After 10 weeks, patients completed the three assessments again: the six-minute walk test, the PSQI questionnaire, and wearing the actigraph watch for 96 hours. Changes in sleep and functional capacity were compared between the two exercise groups.
The researchers found that both exercise programmes (aerobic exercise alone and combined aerobic/resistance exercise) improved sleep and functional capacity over the 10-week period. But isolated aerobic exercise was much more beneficial on sleep and function than the combined programme.
Prior studies on sleep have used the PSQI questionnaire or an actigraph. A strength of this study was to use both methods of assessment, thereby providing a complete picture of the sleep disturbance. Together these measurements showed that exercise helped patients fall asleep, sleep continuously rather than waking up in the night, and sleep longer and more deeply.
“Our recommendation for heart bypass patients with difficulty sleeping and performing their usual activities is to do aerobic exercise only,” said Dr. Atef. “We think that resistance exercise requires a high level of exertion for these patients. This may induce the release of stress hormones which negatively affect sleep.”
“Aerobic exercise means physical activity that does not require a very high level of exertion,” he explained. “Choose an activity you enjoy like walking, cycling, or swimming. Aim for 30 to 45 minutes and do it in the morning because research shows this releases the hormone melatonin which helps us sleep well at night.”

Funding: The author acknowledges funding received from the European Society of Cardiology in the form of an ESC Nursing Grant.
Disclosures: None.

California goes from COVID-19 success story to cautionary tale

California was once a coronavirus success story, a national example of how other states could battle the virus and win.
The most populous state in the country was the first to issue a stay-at-home order, and rapidly built up a robust contact-tracing operation. While the virus was devastating hot spots on the East Coast, California managed to dodge a major catastrophe.
In the spring, as other states began lifting their stay-at-home orders, Gov. Gavin Newsom (D) repeatedly stressed a cautious, science-based approach to reopening.
But now California is in trouble. As the state joins Arizona, Texas and Florida as one of the worst coronavirus hot spots in the country, state leaders and public health experts say it should be viewed as a cautionary tale.
“We flattened the curve in California. What we didn’t do was turn it downward,” state Sen. Richard Pan (D) said in an interview. “Then started opening things up again, and then of course now we have an upward swing again.”
Daily coronavirus cases have spiked, with an average of 6,000 new infections a day in the past week. The percentage of positive tests is the highest in months, with the biggest increase in just the last two weeks.
Hospitalizations have jumped 51 percent in the past two weeks, and ICU admissions are up 47 percent over the same period.
After being proactive in issuing a statewide stay-at-home order, Newsom let the 58 individual counties make their own reopening decisions, beginning in early May.
His plan initially allowed for limited retail stores to open with capacity and physical distancing requirements, but in a matter of weeks quickly allowed counties to open dine-in restaurants, gyms, nail salons and religious services.
In many instances, experts said, that flexibility likely allowed local governments to rush ahead and reopen before they were ready.
Pan, a practicing pediatrician, said when the messaging shifted from the importance of staying at home to safely reopening businesses, people took it as a green light to reopen no matter what the local conditions were like.
“And now we’re recognizing, unfortunately, the consequences of that,” Pan said. “You don’t need huge numbers of people to get complacent. All it takes is a small percentage of people, whether it’s politics or for other reasons, and they’re not following the guidelines, then the disease is going to spread.”
Local epidemiologists said reopening likely contributed to some of the case spikes, but there are other reasons as well. California has the world’s fifth-largest economy, and the sheer size of the state means each county comes with its own unique challenges in handling the virus.
George Rutherford, a professor of epidemiology at UC San Francisco, said the problems with California’s large, diverse population are a window into what’s happening throughout the country: virus outbreaks in San Quentin prison, Latino essential workers living in shared housing units in Imperial County and young people in Los Angeles flooding the bars and beaches on Memorial Day weekend.
Rutherford said because of that size and diversity, Newsom had to let counties make their own decisions.
“What goes on in the far northern-tier counties in California, and what goes on on the Mexican border are completely different,” Rutherford said. “So you really have to … approach this, at least, regionally. There’s a lot of territory to cover.”
Still, Rutherford said the surge has taken people by surprise.
“We knew that there would be cases when we reopened. We knew that there’d be a trade-off between the economy and disease. I don’t think anybody realized it would be this pronounced during June,” he said.
Art Reingold, head of the Epidemiology and Biostatistics division at the UC Berkeley School of Public Health, said the tailored approach to reopening was the best option, but also the most complicated.
“I think that the governor didn’t have terribly good options in terms of trying to mandate statewide goals and enforcing them equally across very different counties and situations,” Reingold said. “You know, I don’t know that any governor could have successfully done that.”
Newsom has begun cracking down and re-imposing restrictions, but there’s concern he may be too late.
On June 18, Newsom imposed a statewide mask requirement. On July 1, he took the strictest steps yet and ordered all indoor nonessential businesses to close in 19 counties across the state — a move that affects more than 75 percent of the state’s population.
As a way to control crowds during the July 4 weekend, Newsom will close all the parking lots at state-run beaches throughout Southern California and the Bay Area.
“I deeply respect people’s liberty, their desire to go back to the way things were, but I cannot impress upon you more, our actions have an impact on other people,” Newsom said.
The restrictions will remain in place for at least three weeks.
Reingold said the restrictions can help, but the ultimate impact is limited because the virus is so widespread.
“The value of these measures are much more likely to be successful when there are relatively few infections, and much less likely to be successful when there are a lot more infections,” Reingold said.
“And so unfortunately we’re now at a stage where we’ve got an awful lot of people infected with this virus in the United States and California. So I’m not sure how much we can expect in the way of a successful intervention at this point,” he added.

Fever checks are a flawed way to flag Covid-19 cases; smell tests might help

Workplaces do it. Newly reopened public libraries do it. LAX does it. Some restaurants, bars, and retail stores started doing it when governors let them serve customers again: Use temperature checks — almost always with “non-contact infrared thermometers” — to identify people who might have, and therefore spread, the infectious disease.
Unfortunately, temperature checks could well join the long list of fumbled responses to the pandemic, from the testing debacle to federal officials’ about-face on masks.
Because many contagious people have no symptoms, using temperature checks to catch them is like trying to catch tennis balls in a soccer net: way too many can get through. On Tuesday, the head of the Transportation Security Administration told reporters, “I know in talking to our medical professionals and talking to the Centers for Disease Control … that temperature checks are not a guarantee that passengers who don’t have an elevated temperature also don’t have Covid-19.” The reverse is also true: Feverish travelers might not have Covid-19.
In this case, however, a growing body of science suggests a simple fix: make smell tests another part of routine screenings.
Of all the nose-to-toes symptoms of Covid-19, the loss of the sense of smell — also known as anosmia — could work particularly well as an add-on to temperature checks, significantly increasing the proportion of infected people identified by screening in airports, workplaces, and other public places.
“My impression is that anosmia is an earlier symptom of Covid-19 relative to fever, and some infected people can have anosmia and nothing else,” said physician Andrew Badley, who heads a virus lab at the Mayo Clinic. “So it’s potentially a more sensitive screen for asymptomatic patients.”
In a recent study, Badley and colleagues found that Covid-19 patients were 27 times more likely than others to have lost their sense of smell. But they were only 2.6 times more likely to have fever or chills, suggesting that anosmia produces a clearer signal and may therefore be a better Covid-catching net than fever.
There is no definitive study on the predictive value of temperature checks for Covid-19. But there are clues from when that strategy was used during the SARS epidemic of 2003. Deployed at airports, especially in Asia, the devices fell far short of the ideal, an analysis found. Although contactless thermometers are quite accurate if used correctly, many other conditions (including medications and inflammatory disease) can cause fever. As a result, the likelihood that someone with a fever had SARS ranged from 4% to 65%, depending on the underlying prevalence of the disease.
The likelihood that someone with a normal temperature reading was SARS-free was at least 86%. That suggests SARS fever checks didn’t miss many infected people. Unlike SARS, unfortunately, Covid-19 can be contagious even before an infected person runs a fever, which makes missed cases more likely.
As experts have cast around for other screening tools, some have zeroed in on smell tests, which could be as simple asking people to identify a particular scent from a scratch-and-sniff card. Though not a universal symptom, loss of smell is one of the earliest signs of Covid-19 because of how the virus acts. Support cells in the olfactory epithelium, the tissue that lines the nasal cavities, are covered with the receptors that SARS-CoV-2 uses to enter cells. They become infected very early in the disease process, often before the body has mounted the immune response that causes fever.
“These support cells either secrete molecules that shut down the olfactory receptor neurons, or stop working and starve the neurons, or somehow fail to support the neurons,” said Danielle Reed, associate director of Monell Chemical Senses Center, a world leader in the science of taste and smell. As a result, “the [olfactory neurons] either stop working or die.”
In an analysis of 24 individual studies, with data from 8,438 test-confirmed Covid-19 patients from 13 countries, 41% reported that they had lost their sense of smell partly or completely, researchers reported in Mayo Clinic Proceedings. But in studies that used objective measurements of smell rather than simply asking patients, the incidence of anosmia was 2.3 times higher.
A Monell analysis of 47 studies finds that nearly 80% of Covid-19 patients have lost their sense of smell as determined by scratch-and sniff tests, Reed said. But only about 50% include that in self-reported symptoms. In other words, people don’t realize they have partly or even completely lost their sense of smell. That may be because they’re suffering other, more serious symptoms and so don’t notice this one, or because smell isn’t something they focus on.
In a recent study of 1,480 patients led by otolaryngologist Carol Yan of UC San Diego Health, someone with anosmia was “more than 10 times more likely to have Covid-19 than other causes of infection,” she said. Nasal inflammation from some 200 cold, flu, and other viruses can cause it, she said, but especially during the summer, when those infections are pretty rare, the chance that anosmia is the result of Covid-19 rises.
“Anosmia was quite specific to Covid-19,” she said.
Fever, in contrast, has many possible causes. Temperature checks will therefore flag more people as potentially infected with Covid-19 than smell tests will. The likelihood that anosmia indicates Covid-19, called a test’s positive predictive value, increases as the prevalence of Covid-19 increases, as it is in many areas of the U.S.
A key unanswered question is a smell test’s “negative predictive value”: If someone has a normal sense of smell, the chance that he or she is nevertheless infected and likely contagious. Because at least some people infected with SARS-CoV-2 will have a normal sense of smell, especially early on, even experts who believe that anosmia screening can be widely beneficial — “I hope it will be used as a screening measure for the virus across the world,” Yan said — say it should be added to fever checks or other screening tools, but shouldn’t replace them.
“There is value in evaluating anosmia screening as a way to identify asymptomatic spreaders,” said Badley, the Mayo Clinic researcher.
UC San Diego Health is doing that. It asks about loss of smell (and taste) when it screens visitors and staff before allowing them to enter its buildings.
Because many people are unaware of their anosmia, testing would be even better than asking, Reed said.
The gold-standard test is the University of Pennsylvania Smell Identification Test, called UPSIT. It uses 40 microencapsulated scents — including dill pickle, turpentine, banana, soap, licorice, and cedar — released by scratching with a pencil. The test taker has a choice of four answers for each, and the whole thing takes 10 to 15 minutes.
A screening test for anosmia in the context of Covid-19 could be much simpler, experts say, especially since the idea is to identify whether individuals can smell or not, rather than whether they can discriminate different scents.
“I can see several practical ways is to have people check their sense of smell as a routine matter when entering public areas,” Reed said. Medical offices could “ask people to smell a scratch-and-sniff card and pick the correct odor out of four choices. For workplaces and schools, one way is to ask people to ‘stop and smell the roses’ as they enter buildings and report abrupt reductions in their ratings of odor intensity.”
To avoid cultural bias (not everyone knows what bubblegum or grass smells like), a test for anosmia in Covid-19 could have a standard amount of phenyl-ethyl alcohol (which smells like roses) on a swab or stick and have people sniff it, Reed said. A second stick could have less, testing for diminished sense of smell. A third stick could be a blank, to identify people who falsely claim they can smell.

Street shifts bets to big pharma as COVID-19 vaccine race progresses

Wall Street is moving some bets on COVID-19 vaccines to large pharmaceutical companies with robust manufacturing capabilities, signaling that a love affair with small biotech firms might be ending after the sector’s best quarter in almost 20 years.
Early signs of the shift came Wednesday, when positive data for one of Pfizer Inc’s COVID-19 vaccine candidates sent shares of the large U.S. drugmaker up more than 3%. Shares of its partner on the vaccine, Germany’s BioNTech SE, have been flat on the data.
Although the news had little effect on shares of Pfizer’s large rivals in the vaccine race, smaller peers Moderna Inc and Inovio Pharmaceuticals Inc, both of which have previously shown promising COVID-19 data of their own, ended down more than 4% and 25%, respectively. Inovio partially rebounded Thursday.
For the week so far, shares of bigger players in the vaccine race, such as Johnson & Johnson and Merck, have also outperformed Inovio and Moderna.
Some of the selling was likely driven by end-of-quarter profit-taking, locking in dizzying gains in an otherwise turbulent market. Moderna and Inovio shares have risen nearly 200 percent and 540 percent in the year-to-date, respectively, greatly eclipsing gains for large pharmaceutical companies.
Analysts say investors are changing their strategy to focus on companies that can make, as well as discover, a vaccine and that the risk reward profile for some biotechs is less favorable after their stunning gains so far this year.
“I would certainly say success by Pfizer, AstraZeneca, or Johnson & Johnson could make it more challenging for smaller companies, given size and scale and manufacturing capability,” said Vamil Divan, a biotechnology analyst at Mizuho.
Smaller biotechnology companies with promising COVID-19 vaccines pose a special challenge for investors, said Justin Onuekwusi, a portfolio manager at Legal & General Group Plc.
Because of their limited manufacturing capabilities, investors in those stocks are effectively betting that the company or its drug will be bought by larger companies, he said.
“In smaller cap stocks like biotech, it all tends to be quite binary so fundamental or detailed analysis don’t always work,” Onuekwusi said.
Medical manufacturers have never faced a challenge like that of producing a global COVID-19 vaccine.
Companies including Pfizer and Johnson & Johnson have said they each aim to produce as many as 1 billion doses by the end of 2021.
There are more than 17 vaccine candidates being tested on humans in a frantic global race to end a pandemic that has infected 10 million people and killed more than half a million. Drugmakers have released early stage human trial data for five vaccine candidates so far.
Bernstein Research analyst Vincent Chen said COVID-19 vaccines could generate in excess of $10 billion in annual revenue, but many investors are struggling to determine their value.
“In the near term, they are not going make a ton of money on” the vaccines, said Evan Seigerman, an analyst at Credit Suisse. “The initial round of vaccines are going to be given away or sold at cost. Where people will start making money is if COVID-19 vaccine becomes something like the flu shot and people need to constantly protect against it.”