It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
Monday, April 27, 2020
Commonly used chemicals associated with miscarriage, study finds
Researchers at the Yale School of Public Health have found that maternal exposure to synthetic chemicals widely used in food packaging and commonly found in drinking water supplies is associated with a woman's risk for miscarriage in the second trimester.
Allwomenin the Danish cohort studied had detectable and multiple types of per- and polyfluoroalkyl substances (PFAS) in theirpregnancyserum. The study estimated a nearly 80% to 120% increased risk formiscarriagein women with the highest level of two common PFAS compounds, compared with those in the cohort with the lowest PFAS levels. Some positive associations, though in smaller magnitudes and less consistent, were also reported for exposure to other types of PFAS compounds evaluated.
TRUMP AND EPA PUSH BACK CLAIMING PFAS ARE NOT DANGEROUS!!!!
The association was stronger among women who had already borne children, and the researchers said that the results need to be replicated. The study is published in the journal Environmental Health Perspectives.
PFAS, introduced in the 1940s, are widely used in the manufacture of everyday products around the globe—from cookware, to clothing, carpets, and firefighting foam. PFAS are also used in industries such as aerospace, automotive, construction, electronics, and the military. Production of the two most common types of PFAS has been phased out by U.S. manufacturers over concerns about the impacts on the environment and human health, but other compounds in the PFAS family are being produced as replacements. PFAS usage in commercial products is not currently regulated in the United States.
"Policy regulation of PFAS exposure should consider adverse effects on maternal and child health, which have repeatedly suggested that these are vulnerable populations that need to be protected from exposure to these widespread chemicals," said Zeyan Liew, the study's lead author and an assistant professor in the department of Environmental Health Sciences at the Yale School of Public Health.
"More studies should follow up to investigate whether PFAS, widespread pollutants that are affecting nearly all pregnancies in the general population, are a modifiable risk factor for miscarriage," he said. Miscarriage is rather common and affects about 10% to 20% of all clinically recognized pregnancies.
Previous toxicological studies have suggested that high doses of PFAS exposure can cause pregnancy loss and infant deaths in rodents. However, whether PFAS exposure affects the risk of miscarriage in the general population was unclear. This is the largest epidemiological study based on pregnant women enrolled in the Danish National Birth Cohort and compared 220 women who carried their pregnancies through birth with 220 who experienced a miscarriage in the second trimester.
Maternal serum samples were collected in early gestations (around week eight) in the cohort, where the researchers measured the serum-level of several common PFAS compounds in these women. The PFAS exposure level in this pregnancy cohort in Denmark is similar to the exposure level reported in the studies of U.S. general population.
"Mechanistic studies are needed to elucidate the possible biological mechanisms that explain these associations," Liew said. "Moreover, larger epidemiological studies are needed to replicate our findings, evaluate the possible threshold or dose-dependent effects of PFAS exposure on pregnancy loss, and address confounding by pregnancy history."
More information:Zeyan Liew et al. Maternal Plasma Perfluoroalkyl Substances and Miscarriage: A Nested Case–Control Study in the Danish National Birth Cohort,Environmental Health Perspectives(2020).DOI: 10.1289/EHP6202
Shortage of hydroxychloroquine hits mothers with lupus
by Andrew J. Wight, SciDev.Net
Experts warn of babies being at risk over global shortage of hydroxychloroquine caused by COVID-19 panic. Credit: Marco Verch(CC BY 2.0)
Pregnant lupus sufferers and their babies are at risk as global supplies of an anti-malarial medicine used to treat the disease run dry due to COVID-19 panic.
Health experts in the global South warn that the shortage puts babies at more risk of being born with symptoms of the painful auto-immune disease lupus.
Hydroxychloroquine (HCQ), a less toxic derivative of chloroquine, has been approved for treating auto-immune diseases and malaria since the 1950s. US President Donald Trump promoted the drug as a potential COVID-19 treatment and US government departments made bulk purchases, even as studies began to emerge that the drug offered no protection from COVID-19.
The Indian Council of Medical Research has recommended HCQ as a preventative treatment for healthcare workers. Medical doctors voiced their concern in The Lancet that "in this environment of global panic, an endorsement by the highest scientific body of India (and also by the President of the U.S.) will create an overly optimistic perception of the effectiveness of hydroxychloroquine among the public," leading to self-medication and, ultimately, shortages.
Utibe Effiong, a physician at MidMichigan Health and assistant professor of medicine at Central Michigan University, tells SciDev.Net the resulting hoarding and diversion of HCQ is putting lupus patients—particularly pregnant women—at risk, citing the tens of thousands of lupus patients in his home country of Nigeria.
"Supply has reduced drastically due to air and land border closures in Nigeria as a result of COVID-19," Effiong says. "The manufacturing countries have temporarily shut exports to conserve the medications for their population and HCQ has jumped from 2000 Nigerian Naira (US$5.50) per pack of 30 tablets to N12,500 (US$34.70) per pack."
Effiong says the supply of HCQ in Nigeria and much of the developing world comes from Asia and those manufacturers are likely to prefer to sell to the highest bidder.
Ninety percent of the more than five million lupus patients worldwide are women, usually aged between 15 and 44, according to figures from the Lupus Foundation of America. These women tend to have higher maternal mortality, fewer live births, and more complications during pregnancy, a review of studies in the developing world found.
Sebastián Herrera, a rheumatologist based at Medellín General Hospital and CES University in Colombia, says that despite Colombia having many manufacturing facilities for HCQ, the unexpected increased demand means that the medicine is no longer available via pharmacy websites and it has become difficult to obtain, especially outside Colombia's major cities.
The Latin American country has had nearly half a million cases of lupus reported in the past five years, mainly impacting women.
According to Herrera, the biggest impact of a HCQ shortage is going to be on pregnant lupus patients and their newborns, as HCQ is one of the few medicines that can reduce the risk of giving birth to children with lupus symptoms.
"In some women with certain types of antibodies that increase the risk of complications for the baby (neonatal lupus), hydroxychloroquine decreases the risk of this complication—if there is no availability, there would be no other option to reduce this risk," Herrera says, adding that switching to other drugs may increase the risk of infections by altering the function of the patient's immune system.
In addition, Herrera says the scarcity of HCQ could lead to disease relapses in other patients, which leads to increased fatigue, absenteeism from work, deterioration in mental health, as well as increased pain.
Akpabio Akpabio, a rheumatologist at the University of Uyo Teaching Hospital in Nigeria, says in his region of southern Nigeria, shortages are starting to bite.
"From my own personal experience, up to 60 percent of lupus patients are currently experiencing shortages in HCQ—some still have it but many of them are running out," he says.
One of the first major papers to discuss the impact of the COVID-19 crisis on lupus patients observed a few missed doses of HCQ may not be critical, but a prolonged shortage could lead to significant consequences.
This has led to some hard choices, Akpabio says, because there is no consensus in the literature on how far and for how long patients can reduce their dosages and still receive the protective effects of the medicine.
FDA warns of heart risks with Trump-promoted malaria drug by Matthew Perrone and Marilynn Marchione This Tuesday, April 7, 2020 file photo shows a bottle of hydroxychloroquine tablets in Texas City, Texas. On Friday, April 24, 2020, the U.S. Food and Drug Administration warned doctors against prescribing the malaria drug to treat COVID-19 outside of hospitals or research settings. (AP Photo/David J. Phillip)The U.S. Food and Drug Administration on Friday warned doctors against prescribing a malaria drug touted by President Donald Trump for treating the new coronavirus except in hospitals and research studies.
In an alert, regulators flagged reports of sometimes fatal heart side effects among coronavirus patients taking hydroxychloroquine or the related drug chloroquine. The decades-old drugs, also prescribed for lupus and rheumatoid arthritis, can cause a number of side effects, including heart rhythm problems, severely low blood pressure and muscle or nerve damage.
The warning comes as doctors at a New York hospital published a report that heart rhythm abnormalities developed in most of 84 coronavirus patients treated with hydroxychloroquine and the antibiotic azithromycin, a combo Trump has promoted.
Both drugs are known to sometimes alter the heartbeat in dangerous ways, and their safety or ability to help people with COVID-19 is unknown. A National Institutes of Health experts panel earlier this week recommended against taking that drug combo except in a formal study because of the side effects potential.
Last month, the FDA authorized limited use of the malaria drugs for hospitalized patients with COVID-19 who aren't enrolled in ongoing research. The FDA said the drugs' risks are manageable when patients are carefully screened and monitored by doctors. A number of studies are testing hydroxychloroquine as a treatment or for prevention of COVID-19.
Regulators said they are now investigating dangerous side effects and deaths reported with the malaria drugs to poison control centers and other health authorities. "It is important that health care providers are aware of the risks of serious and potentially life-threatening heart rhythm problems that can occur with these drugs," the FDA said in a statement. The agency did not specify the number of reports it has received of side effects or deaths.
Calls to U.S. poison control centers about the malaria drugs increased last month to 79, compared to 52 for March 2019, according to Dr. Christopher Hoyte of the Rocky Mountain Poison Center in Denver, Colorado.
The problems reported include abnormal heart rhythms, seizures, nausea and vomiting, Hoyte said.
Trump has repeatedly touted hydroxychloroquine during his regular coronavirus briefings, suggesting its skeptics would be proved wrong. He has offered patient testimonials that the drug is a lifesaver.
But a number of early coronavirus studies have suggested problems or no benefit.
In Friday's report in the journal Nature Medicine, doctors at New York University and NYU Langone Health found a significant prolonging of what's called the heart's QT interval two to five days after coronavirus patients were given usual doses of hydroxychloroquine and azithromycin. The drugs can alter the QT interval, or the time it takes the heart to charge between beats. When that time is too long, it can trigger a rhythm problem that can lead to sudden death.
Nine of the 84 patients had severe prolongation of this interval. Four patients died from organ failure but there was no evidence heart problems contributed. Severe disease or other health problems may play a role in whether the heartbeat abnormality develops, the researchers speculated.
The results show how important it is that these drugs only be used in a study where patients are closely tracked, said one independent expert, Dr. Rais Vohra, an emergency medicine specialist at the Fresno branch of the University of California, San Francisco.
"That combination really sets you up for having a problem with the heart," he said. "My colleagues and I are concerned. People are self-medicating and coming down with very predictable side effects on the heart."
Another recent analysis involving 368 patients in U.S. veterans hospitals found no benefit from hydroxychloroquine—and more deaths. The report was not a rigorous test of the drug and results have not yet been reviewed by other scientists but are the largest so far of its use in COVID-19 patients.
Last month, the federal government accepted more than 30 million doses of hydroxychloroquine and chloroquine donated to the national stockpile by drugmakers Sandoz and Bayer. Since then, more than 20 million doses have been distributed to state and local health officials, according to the Department of Health and Human Services.
Accepting the donation required sign off by both the FDA and the Biomedical Advanced Research and Development Authority, or BARDA, a unit of HHS that obtains treatments to combat bioterrorism and infectious diseases.
Earlier this week, former BARDA director, Rick Bright, said he was demoted from his job leading the agency because he resisted political pressure to allow widespread use of hydroxychloroquine. He has called for a federal investigation and reinstatement to his original job.
More information: Ehud Chorin et al. The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin, Nature Medicine (2020). DOI: 10.1038/s41591-020-0888-
EULAR: Hydroxychloroquine use in lupus patients 'does not seem to prevent COVID-19'
by European League Against Rheumatism (EULAR)
Credit: CC0 Public Domain
The current outbreak of COVID-19 represents a source of concern for the management of systemic
lupus erythematous, SLE, patients. These patients have an increased risk of severe infections due to their underlying disease, the use of immunosuppressive drugs, as well as the potential presence of organ damage associated with their disease.
Hydroxychloroquine, HCQ, a drug that is currently part of the long-term care treatment for SLE, has been reported to possess anti-viral activity in vitro and recent publications have suggested a beneficial effect on COVID-19.
The Annals of the Rheumatic Diseases has published a letter this week regarding the impact of COVID-19 on SLE patients taking hydoxychloroquine: "Clinical course of Coronavirus Disease 2019 (COVID-19) in a series of 17 systemic lupus erythematous patients under long-term treatment with hydroxychloroquine."
EULAR Past-President Professor Johannes W. Bijlsma says, "This gives a first clinical picture of the course of COVID-19 in SLE patients treated with HCQ. It paves the way for a larger observational study to identify the risk factors associated with the occurrence of a severe form of COVID-19 in patients with SLE. Our preliminary conclusion, based on the observation that most of the SLE patients in this study received long-term treatment with HCQ, having blood concentrations of the drug within therapeutic range, is that HCQ does not seem to prevent COVID-19, at least its severe forms, in patients with SLE."
Medicine shortages are a significant challenge for people with rheumatic and musculoskeletal diseases in the ongoing situation around COVID-19. Data collected by EULAR shows that a majority of countries in Europe have encountered and are still encountering serious shortages of hydroxychloroquine (HCQ), and that shortages in essential medicines were also encountered before the COVID-19 pandemic. EULAR advises that the unrestricted access to HCQ for a possible COVID-19 prophylaxis in the absence of evidence from clinical trial data should be avoided and the drug rather continue to be available for those who are in need of it, for example for use in the case of a disease in which it has already been long approved.
Systemic Lupus Erythematous is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary from mild to severe and can include painful and swollen joints among other factors. There are often periods of illness, called flares, as well as remission in which there are fewer symptoms.
EULAR has launched the COVID-19 rheumatic and musculoskeletal diseases reporting database, a European paediatric and adult database to monitor and report outcomes of COVID-19 occurring in patients with rheumatic and musculoskeletal diseases with the support of the Global Rheumatology Alliance: https://www.eular.org/eular_covid19_database.cfm
EULAR has released guidance for patients in the context of the COVID-19 outbreak.The guidance addresses typical questions that patients with RMDs have and recommends protective measures both for patients and the health care workforce.More information and a video can be found here:
More information: Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine. Annals of the Rheumatic Diseases, 24 April 2020. DOI: 10.1136/annrheumdis-2020-217566
Provided by European League Against Rheumatism (EULAR)
U.S. states build stockpiles of malaria drug touted by Trump
by Brady McCombs and Lindsay Whitehurst
This Monday, April 6, 2020, file photo shows an arrangement of Hydroxychloroquine pills in Las Vegas. At least 13 states have obtained a total of more than 10 million doses of malaria drugs to treat COVID-19 patients despite warnings from doctors that more tests are needed before the medications that President Trump once fiercely promoted should be used to help people with the coronavirus. (AP Photo/John Locher,File)
State and local governments across the United States have obtained more than 30 million doses of a malaria drug touted by President Trump to treat patients with the new coronavirus, despite warnings from doctors that more research is needed.
At least 22 states and Washington, D.C. secured shipments of the drug, hydroxychloroquine, according to information compiled from state and federal officials by The Associated Press. Sixteen of those states were were won by Trump in 2016, although five of them including North Carolina and Louisiana are now led by Democratic governors.
Supporters say having a supply on hand makes sense in case the drug is shown to be effective against the pandemic that's devastated the global economy and killed nearly 200,000 people worldwide, and to ensure a steady supply for people who need it for other conditions like lupus.
But health experts worry that having the drug easily available at a time of heightened public fear could make it easier to misuse it. The U.S. Food and Drug Administration on Friday warned doctors against prescribing the drug, hydroxychloroquine, for treating the new coronavirus outside of hospitals or research settings, because of reports of serious side effects, including dangerous irregular heart rhythms, and death among patients.
It's the latest admonition against the drug that Trump mentioned 17 times in various public appearances, touting its potential despite his own health advisors telling him it is unproven.
This Monday, April 6, 2020 file photo shows an arrangement of hydroxychloroquine pills in Las Vegas.At least 13 states have obtained a total of more than 10 million doses of malaria drugs to treat COVID-19 patients despite warnings from doctors that more tests are needed before the medications that President Trump once fiercely promoted should be used to help people with the coronavirus. (AP Photo/John Locher,File)
Oklahoma spent $2 million to buy the drugs and Utah and Ohio have spent hundreds of thousands on purchases. The rest of the cities and states have received free shipments from drug companies or the U.S. government in the last month. Ohio also received a large donation from a local company.
Several states including New York, Connecticut, Oregon, Louisiana, North Carolina and Texas received donations of the medication from a private company based in New Jersey called Amneal Pharmaceutical. Florida was given 1 million doses from Israeli company Teva Pharmaceutical.
And the Federal Emergency Management Agency has sent 19 million doses of hydroxychloroquine to 14 cities including Washington, D.C., Philadelphia and Baltimore from the federal government's national stockpile, a source that also provided South Dakota and California with supplies. The U.S. government received a donation of 30 million doses from Swiss drugmaker Novartis on March 29 to build up the stockpile.
"If he (Trump) hadn't amplified the early and inappropriate enthusiasm for the drug, I doubt if the states would have even been aware of it," said Dr. Kenneth B. Klein, a consultant from outside of Seattle who has spent the last three decades working for drug companies to design and evaluate their clinical trials.
Klein said it's understandable that government and health officials looked into hydroxychloroquine—which is approved for treating malaria, rheumatoid arthritis and lupus—as a possible remedy during a frightening pandemic, but the time and energy has been misspent. The potential side effects are worrisome, especially because many coronavirus patients already have underlying health conditions, he said.
In this April 21, 2020 file photo Utah Gov. Gary Herbert speaks during a news conference in South Jordan, Utah. Herbert, a Republican, acknowledged that hydroxychloroquine for COVID-19, is "not without controversy," but said an $800,000 purchase from a local company whose CEO appeared alongside GOP lawmakers touting the drugs last month was part of the state's effort to make rational decisions based on "good science and good data." (AP Photo/Rick Bowmer,File)
"The states and the federal government are reacting in light of that fear but it's not a rational response," Klein said.
Doctors can already prescribe the malaria drug to patients with COVID-19, a practice known as off-label prescribing, and many do. Medical and pharmacy groups have warned against prescribing it for preventative purposes. The FDA has allowed it into the national stockpile, but only for narrowly defined purposes as studies continue.
Utah Gov. Gary Herbert, a Republican, acknowledged that the drug is "not without controversy," but said an $800,000 purchase from a local company was part of the state's effort to make rational decisions based on "good science and good data."
The Utah health department said earlier this week it planned to spend $8 million more to buy 200,000 additional treatments from the company, but said Thursday after media inquiries about the deal that those plans are on hold as the state researches FDA requirements for compounding and distribution of the drugs.
South Dakota, with a population of 885,000 people, received 1.2 million doses from the federal government and is using the drug for a trial as well as doctor-approved prescriptions for COVID-19 positive patients. South Dakota Gov. Kristi Noem, a Republican and Trump ally, said earlier this month she pushed the White House to provide enough hydroxychloroquine to give it to every hospitalized person, others who are vulnerable to the coronavirus and "front line" health care workers. As of Tuesday, 200 people in South Dakota were being treated with the drug, according to Sanford Health.
In this March 23, 2020 file photo Dr. Lee Norman, Kansas secretary of health and environment, answers questions about the coronavirus pandemic as Gov. Laura Kelly watches during a news conference in Topeka, Kan. Norman said of hydroxychloroquine that the state has no intention of buying the drug because there's not enough evidence it helps treat COVID-19. "It's just not been shown to be worthwhile," Norman said. "It hasn't been shown to be effective for COVID-19 patients in any disciplined professional study." (AP Photo/John Hanna,File)
Many states, however, have opted to steer clear over concerns about side effects and lingering questions about the effectiveness. At least one of those states is led by a Republican governor, Tennessee, where the state's Department of Health sent a letter warning against using the drug, or hoarding it.
"We were seeing a flood of inappropriate prescribing and hoarding, quite frankly," Health Commissioner Lisa Piercey told reporters.
Kansas health director Dr. Lee Norman said the state has no intention of buying the drug because there's not enough evidence it helps treat COVID-19.
Most states aren't paying for the drug, and it's not clear why Utah didn't get it from the federal reserve or a donation from a business like Amneal Pharmaceutical. News releases from state governments show the New Jersey-based company has sent millions of doses of the drug free of cost to states, including 2 million to New York and 1 million to Texas. A company spokesperson declined to provide a list of donations or answer other questions from The Associated Press
Pharmaceutical companies can often manufacture pills they already make fairly cheaply and the donations may have been done to earn good publicity while setting it up to make future sales if hydroxychloroquine ends up being a reliable treatment for the virus, Klein said.
In this April 22, 2020 file photo President Donald Trump watches as Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, speaks about the coronavirus in the James Brady Press Briefing Room of the White House in Washington. After weeks of near-daily plugs for the use of hydroxychloroquine to help treat COVID-19 patients, Trump and the White House abruptly stopped discussing the drug a week ago. His promotion of the drug, based on isolated reports and instinct, frequently put him at odds with medical professionals, including Fauci, the nation's top infectious disease expert, who said evidence for the efficacy of the drug for COVID-19 patients was "anecdotal." (AP Photo/Alex Brandon,File) Controversy has swirled around the drug since Trump started promoting it from the podium in the White House briefing room on March 19.
He mentioned the drug in briefings through April 14, and the White House distributed press releases praising Trump's efforts to stockpile it for use in areas of the country hard-hit by the virus. But for the past week, as studies have shown mixed or even harmful results, Trump has gone silent on the drug.
Asked about it Thursday, Trump said he hadn't heard of the a study done at U.S. veterans hospitals with preliminary results that showed no benefit, and rejected the notion he had stopped promoting hydroxychloroquine as a cure.
"I haven't at all. I haven't at all," Trump said. "We'll see what happens."
In early April, the Centers for Disease Control and Prevention revised its guidance to recommend that in addition to social distancing measures, all Americans should wear masks when leaving the house for essential trips such as going to the grocery store or the pharmacy. Thursday, Brigham and Women's Hospital in Boston reported that new COVID-19 infections among hospital staff dropped by half after instituting a universal masking policy.
Asbest practicesfor limiting the spread of thecoronaviruscontinue to evolve, the Hub spoke with Johns Hopkins Associate Professor Kirsten Koehler and Assistant Professor Ana Rule, both of the Department of Environmental Health and Engineering at the Bloomberg School of Public Health. They helped clarify how the "hierarchy of controls"—a prioritized method of controlling workplace hazards through actions such associal distancingand masks—can limit spread of the coronavirus. They also discussed the CDC's recent guidance and other questions related to mask use. This conversation has been edited for length and clarity.
Why did the CDC change its guidance to recommend that everyone wear a mask or face covering when leaving home?
Koehler: The CDC is concerned, in part, that there's a reasonably large portion of the population that are asymptomatic carriers of COVID-19 and are propagating the virus. For the general public, compliance will likely mean relying on a homemade mask, but it's important to do so with the mindset that we're wearing these masks to protect others, not necessarily to protect ourselves. The best self-protection is still the same: to stay home.
Rule: The CDC made the decision to encourage everyone to wear non-medical-grade masks, and we know that part of the rationale for that guidance was because of a concern that, without these guidelines, there could be hoarding of precious resources. In the past couple of weeks, we've seen how the stockpiles of essential medical personal protective equipment like N95 and surgical masks have dwindled greatly. The people who need these most are certainly the point of contact providers—those in hospitals and working with patients who are generating the aerosols that potentially contain the coronavirus. For those providers, PPE is their main protection.
Do homemade masks still offer adequate protection? What should people know about how best to approach the use of protective masks?
Koehler: To be clear, staying at home is the best option to protect yourself and others. If you can't do that, making a homemade mask is better than nothing. More broadly, my concern is that the general public has no training or guidance in the safe and proper way to use a homemade mask. If you use PPE as part of your job, you receive training about putting on and taking off this equipment. This training includes precautions like hand-washing whenever you put on or take off the mask. You should wash hands whenever you touch the mask and be careful about what you do whenever you take off the mask when you get home. A mask that you wear outside could potentially be covered in virus, and it's essential that when you take it off, you put it somewhere safe and out of the way, like where you keep laundry, and put on a different, clean mask whenever you have to go outside next.
Rule: In terms of the science, the bigger particles, which are the ones most likely to be filtered by a homemade mask, are going to fall quickly to the ground, anyway. The smaller particles will pass right through the mask. So, the mask will stop those larger particles from depositing on surfaces and potentially being picked up by the next person that touches that surface, for example at the supermarket. There's not a lot of science out there yet about tests to determine how a homemade mask protects the environment and people around you if you are contagious and shedding viruses. This is important, especially with so many asymptomatic people having this particular virus.
There are many different types of masks available, from the medical-grade N95 to surgical procedure masks to homemade masks and scarves. What is most preferable for non-medical workers? What types of materials from home might make for an effective mask?
Rule: There are a couple of papers that have actually tested different materials for filtration efficiencies against the most concerning and smallest particles, which are the ones that are the hardest to filter out. A couple of studies have shown that the materials that filter these particles the best are materials that are also the hardest to breathe through—thicker fabrics like hand towels or vacuum cleaner filters—but since it's really hard to breathe through them, they don't make for viable mask materials. Plus, none of them can provide a seal around the face. The smaller particles then go right around the filter. So there's no real protection from inhaling particles that might have virus. But any material will stop the bigger particles that could create contact points for the virus (such as on a hand railing or a table).
Koehler: For the small particles, I think there isn't a lot of difference in the various materials. Almost all of them remove less than 10% of really small particles.
Rule: But, and this is really important, even if you can get an N95 or surgical mask, please leave those for people who need to interact with patients. People who are actually caring for patients need to have those the most—we see people outside with these masks on and it's a problem since there's such a critical shortage for medical providers.
For those who decide to wear a mask, how can they do so effectively?
Koehler: Some people don't necessarily have a choice anymore—some states and cities have implemented mask requirements when in public. I do think that if people are going outside, whether required to or wearing a mask by choice, they should have the mindset that, "I'm wearing this to protect someone else, not to protect myself." Essentially, assuming that you are the contagious one, even if you feel perfectly healthy. If you think this way, it can lead to safer choices—for example, you might choose to limit your exposure by going to fewer stores and going outside less and maintaining social distancing standards of at least six feet of distance as much as possible, even if you are wearing a homemade mask.
Is it OK to reuse a mask, whether homemade or otherwise, and if so, how can one ensure that the mask is clean and safe to use again?
Koehler: To clean a homemade mask, throwing it in the washer and dryer is really fine. Make at least a couple of masks so that you can wash them between uses and, hopefully, since people should not be going out that much anyway, only having several masks should be enough.
Rule: I saw a video yesterday of someone making a mask made out of a sock—if it's that simple, really, you can have five or so around, and put them in the laundry after every use.
Koehler: I've seen bandanas folded up many times and held together with hair ties and looped over the ears—you could have several of those and keep putting them in the wash. You don't need to be a master seamstress to do this effectively. N95 and surgical masks should not be washed. To reuse these kinds of masks, it is best to place them in a paper bag in a warm place for at least 7 days before reusing them. This will give enough time for the virus to no longer be infectious.
For those without easy access to laundry facilities, storing homemade masks in paper bags is also an option. Recent data suggests the virus will lose infectivity after about 2 days from cloth masks.
When going to the pharmacy or grocery store for essentials, what can people do to minimize the risk of transmission? Should they wear other forms of PPE, like gloves?
Koehler: I don't recommend the use of gloves—if you're not a medical provider, they aren't helpful and, like with masks, people are likely using them incorrectly. If you were going to wear gloves, to do so effectively would mean never using your phone, wallet, or purse because as soon as you touch any of those high-touch surfaces then the gloves aren't effective anymore. They're also a huge environmental waste and it's not worth the effort and pollution and wastefulness to wear them.
Rule: Not only that, gloves can likely give you a false sense of security because someone might think they are protected when they're really just as susceptible and distracted from other important prevention steps—like washing your hands. Plus, if you don't dispose of gloves properly they could be another source of contamination in the environment. Really, we need to remember that, in the hierarchy of controls, PPE is the last resort—it's been shown for many years that wearing things like masks and gloves is the least effective factor at controlling exposure. That's why social distancing, cleaning, and washing hands are the best ways to protect yourself from the virus.
Study challenges reports of low fatality rate for COVID-19
A comparison of daily deaths in Italy since January 2020 with those over the previous five years there indicates that the fatality rate in that country for those infected with the new coronavirus is at least 0.8%, far higher than that of the seasonal flu and higher than some recent estimates.
Extrapolating from the Italian data, University of California, Berkeley, and Lawrence Berkeley National Laboratory data scientists estimate that the fatality rate in New York City and Santa Clara County in California can be no less than 0.5%, or one of every 200 people infected.
These conclusions contrast with those of a study posted online last week by Stanford University epidemiologists, who pegged the fatality rate at between 0.1% and 0.2%. An affiliated team from the University of Southern California (USC) this week reported a similar fatality rate in Los Angeles.
"Their final number is much lower than our estimate," said senior author Uros Seljak, a UC Berkeley professor of physics, faculty scientist at Berkeley Lab and member of the Berkeley Institute for Data Science. He also is co-director of the Berkeley Center for Cosmological Physics (BCCP).
Seljak says that getting COVID-19 doubles your chance of dying this year.
"If you want to know what are the chances of dying from COVID-19 if you get infected, we observed that a very simple answer seems to fit a lot of data: It is the same as the chance of you dying over the next 12 months from normal causes," said Seljak.
Current uncertainties can push this number down to 10 months or up to 20 months, he added. His team discovered that this simple relation holds not only for the overall fatality rate, but also for the age stratified fatality rate, and it agrees with the data both in Italy and in the U.S.
"Our observation suggests COVID-19 kills the weakest segments of the population," Seljak said.
The paper was posted online Monday on MedRxiv in advance of peer review and submission to a journal.
Italy's deaths twice the official count
The study by Seljak and his colleagues predicts that the true number of deaths in Italy from COVID-19 is more than twice the official figure: around 50,000 people, as of April 18. The country's official statistics listed more than 150,000 confirmed cases, as of that date, and more than 20,000 attributed deaths.
The difference, the researchers say, is likely due to many deaths among older people that have not been counted in the official Italian statistics. The team found a much higher fatality rate for those over 70 years of age: In Lombardy, a region hit hard by the pandemic, those between 70 and 79 had a 2.3% infection fatality rate, while those 80 to 89 had an almost 6% fatality rate. Nearly 13% of those over 90 died.
In comparison, those 40 to 49 had a 0.04% fatality rate.
These differing fatality rates can explain the observed higher number of deaths among younger people in New York City. Because the population there is younger than in Italy, more deaths among young people are expected, despite their lower fatality rate. The researchers predict that about 26% of all deaths from COVID-19 in New York City will be among those younger than 65.
The population of Italy, on the other hand, is older, yielding a higher overall fatality rate for the country's population: 0.8%, versus 0.5% for New York. Only 10% of Italian deaths will be younger than 65.
The team also estimated, based on the predicted fatality rate for those infected with the new coronavirus and the positivity rate for those tested for COVID-19 in New York City, that about one-quarter of that city's population has been infected with the virus. This agrees with the recent announcement by New York Gov. Andrew Cuomo of 21% infection.
The team's predicted infection rate for Santa Clara is around 1%, while that for Los Angeles is around 2%, based on current mortality rates.
Given known infection and fatality rates on the Diamond Princess cruise ship, the team also calculated an upper limit on the fatality rate for those infected: about twice the lower limit, or 1%, for New York City and Santa Clara County.
Uncertainty fueled by lack of diagnostic tests
Uncertainty about the fatality rate for those infected by the new virus, dubbed SARS-CoV-2, resulted from delays in testing, due to a shortage of test kits and testing labs. This left public health officials in the dark about the true rate of infection in the general population, which is needed to calculate what percentage of infected people die.
The Stanford study estimated an infection rate in Santa Clara County of between 2.5% and 4.2% of residents, whereas the USC study estimated an infection rate in Los Angeles between 2.8% and 5.6%. Both are much higher than previous estimates, which means the number of confirmed COVID-positive deaths relative to those infected dropped to a low of 0.2%.
Based on these studies, some of the Stanford authors have argued that COVID-19 is little worse than the seasonal flu, casting doubt on decisions to mandate shelter-in-place and the closing of many businesses.
"Of course, it (the infection fatality rate) matters, for policy decisions," Seljak said. "Is this just a bad case of flu, as they would like to claim, or is it something much more serious?"
To answer that question, Seljak and his colleagues mined a previously untapped source of data: the daily death rate for 1,688 towns in Italy between Jan. 1 and April 4 for the years 2015 through 2020, provided by the Italian Institute of Statistics. The excess deaths between January and April of this year, presumably due to COVID-19, can be used to calculate a lower limit for the death rate from the virus.
"The dataset is a treasure trove for statistical analysis of COVID-19 mortality," Seljak said. "For example, it can give mortality rate as a function of age better than any other data out there, a sad consequence of tens of thousands of deaths from COVID-19 in Italy. With this data, we established that if one gets infected and is above 90 years of age, the probability of dying is at least 10%, because that is the fraction of the entire population of Bergamo province in this age group that died. In contrast, the corresponding number for ages 40 to 49 is 0.04%, far lower than previous estimates."
The Lombardy region of Italy, for example, was a viral hotspot, with the province of Bergamo hardest hit: The infection spread to so many people in Bergamo—likely two-thirds of the population, if not the entire population—that it is possible that so-called herd immunity has set in, Seljak said. That means that enough people are immune, at least temporarily, to stanch the spread of the virus among the the uninfected.
With essentially everyone in Bergamo infected, and the known deaths since January—predicted to be more than 6,000 out of a population of 1 million—it was easy to calculate the lowest possible infected fatality rate: 0.56%.
For Lombardy, the researchers estimated that the lowest possible fatality rate was even higher: about 0.84%. They also estimated that 23% of the population of Lombardy was infected, as of April 18—on average, 35 times the number of positive tests in the province.
The team conducted an analysis for all Italian towns that reported daily death data and for all age groups, using a counterfactual analysis: estimating the expected number of deaths daily between January and April 2020, based on the previous five years, and comparing those numbers with reported deaths. The excess is assumed to be due to COVID-19. The researchers employed statistical methods often used in analyzing large sets of data: the Conditional Mean with a Gaussian process (CGP) and a Synthetic Control Method (SCM).
In nearly all towns, the excess deaths in early 2020 exceeded the official count attributed to COVID-19.
The numbers the team came up with are lower limits, the researchers emphasize, since deaths in many Italian towns are not fully up to date.
"Some of my colleagues think that we have been overly conservative, which might be true," Seljak said. "We have just accounted for the people who have died up until today, but people are still dying."
More information:Chirag Modi et al. Total COVID-19 Mortality in Italy: Excess Mortality and Age Dependence through Time-Series Analysis,(2020).DOI: 10.1101/2020.04.15.20067074
A microinjection device (red) is attached to a citrus tree, providing a way of injecting pesticide or other materials directly into the plant's circulatory system. Credit: Massachusetts Institute of Technology
While the human world is reeling from one pandemic, there are several ongoing epidemics that affect crops and put global food production at risk. Oranges, olives, and bananas are already under threat in many areas due to diseases that affect plants' circulatory systems and that cannot be treated by applying pesticides.
A new method developed by engineers at MIT may offer a starting point for delivering life-saving treatments to plants ravaged by such diseases.
These diseases are difficult to detect early and to treat, given the lack of precision tools to access plant vasculature to treat pathogens and to sample biomarkers. The MIT team decided to take some of the principles involved in precision medicine for humans and adapt them to develop plant-specific biomaterials and drug-delivery devices.
The method uses an array of microneedles made of a silk-based biomaterial to deliver nutrients, drugs, or other molecules to specific parts of the plant. The findings are described in the journal Advanced Science, in a paper by MIT professors Benedetto Marelli and Jing-Ke-Weng, graduate student Yunteng Cao, postdoc Eugene Lim at MIT, and postdoc Menglong Xu at the Whitehead Institute for Biomedical Research.
The microneedles, which the researchers call phytoinjectors, can be made in a variety of sizes and shapes, and can deliver material specifically to a plant's roots, stems, or leaves, or into its xylem (the vascular tissue involved in water transportation from roots to canopy) or phloem (the vascular tissue that circulates metabolites throughout the plant). In lab tests, the team used tomato and tobacco plants, but the system could be adapted to almost any crop, they say. The microneedles can not only deliver targeted payloads of molecules into the plant, but they can also be used to take samples from the plants for lab analysis.
The work started in response to a request from the U.S. Department of Agriculture for ideas on how to address the citrus greening crisis, which is threatening the collapse of a $9 billion industry, Marelli says. The disease is spread by an insect called the Asian citrus psyllid that carries a bacterium into the plant. There is as yet no cure for it, and millions of acres of U.S. orchards have already been devastated. In response, Marelli's lab swung into gear to develop the novel microneedle technology, led by Cao as his thesis project.
The disease infects the phloem of the whole plant, including roots, which are very difficult to reach with any conventional treatment, Marelli explains. Most pesticides are simply sprayed or painted onto a plant's leaves or stems, and little if any penetrates to the root system. Such treatments may appear to work for a short while, but then the bacteria bounce back and do their damage. What is needed is something that can target the phloem circulating through a plant's tissues, which could carry an antibacterial compound down into the roots. That's just what some version of the new microneedles could potentially accomplish, he says.
"We wanted to solve the technical problem of how you can have a precise access to the plant vasculature," Cao adds. This would allow researchers to inject pesticides, for example, that would be transported between the root system and the leaves. Present approaches use "needles that are very large and very invasive, and that results in damaging the plant," he says. To find a substitute, they built on previous work that had produced microneedles using silk-based material for injecting human vaccines.
"We found that adaptations of a material designed for drug delivery in humans to plants was not straightforward, due to differences not only in tissue vasculature, but also in fluid composition," Lim says. The microneedles designed for human use were intended to biodegrade naturally in the body's moisture, but plants have far less available water, so the material didn't dissolve and was not useful for delivering the pesticide or other macromolecules into the phloem. The researchers had to design a new material, but they decided to stick with silk as its basis. That's because of silk's strength, its inertness in plants (preventing undesirable side effects), and the fact that it degrades into tiny particles that don't risk clogging the plant's internal vasculature systems.
They used biotechnology tools to increase silk's hydrophilicity (making it attract water), while keeping the material strong enough to penetrate the plant's epidermis and degradable enough to then get out of the way.
Sure enough, they tested the material on their lab tomato and tobacco plants, and were able to observe injected materials, in this case fluorescent molecules, moving all they way through the plant, from roots to leaves.
"We think this is a new tool that can be used by plant biologists and bioengineers to better understand transport phenomena in plants," Cao says. In addition, it can be used "to deliver payloads into plants, and this can solve several problems. For example, you can think about delivering micronutrients, or you can think about delivering genes, to change the gene expression of the plant or to basically engineer a plant."
"Now, the interests of the lab for the phytoinjectors have expanded beyond antibiotic delivery to genetic engineering and point-of-care diagnostics," Lim adds.
For example, in their experiments with tobacco plants, they were able to inject an organism called Agrobacterium to alter the plant's DNA—a typical bioengineering tool, but delivered in a new and precise way.
So far, this is a lab technique using precision equipment, so in its present form it would not be useful for agricultural-scale applications, but the hope is that it can be used, for example, to bioengineer disease-resistant varieties of important crop plants. The team has also done tests using a modified toy dart gun mounted to a small drone, which was able to fire microneedles into plants in the field. Ultimately, such a process might be automated using autonomous vehicles, Marelli says, for agricultural-scale use.
Meanwhile, the team continues to work on adapting the system to the varied needs and conditions of different kinds of plants and their tissues. "There's a lot of variation among them, really," Marelli says, so you need to think about having devices that are plant-specific. For the future, our research interests will go beyond antibiotic delivery to genetic engineering and point-of-care diagnostics based on metabolite sampling."
More information: Yunteng Cao et al. Precision Delivery of Multiscale Payloads to Tissue‐Specific Targets in Plants, Advanced Science (2020). DOI: 10.1002/advs.201903551
A new study led by McGill University has found that tectonic plates beneath the Earth's surface can show varying degrees of roughness and could help explain why certain earthquakes are stronger than others.
Earthquakes happen when the rocks beneath the Earth's surface break along geological fault lines and slide past each other. The properties of these faults—such as the roughness of their surface—can have an influence on the size of seismic events, however their study has been challenging because they are buried deep beneath the Earth's surface.
In order to have a better understanding of the characteristics of these faults, researchers from McGill University, the University of California Santa Cruz and Ruhr University Bochum in Germany used high-resolution seismic reflection data to map and measure the roughness of 350 km2 of a plate boundary fault located off the Pacific coast of Costa Rica.
"We already knew that the roughness of a fault was an important factor, but we did not know how rough faults in the subsurface truly are, nor how variable the roughness is for a single fault," says James Kirkpatrick, a professor in McGill's Department of Earth and Planetary Sciences.
Rougher surfaces of faults may explain earthquake magnitude
In a recently published study in Nature Geoscience, Kirkpatrick and his colleagues were able to show that some parts of the studied fault have a rougher surface than others.
Historically, the earthquakes that have occurred in this part of the world have been moderately large (M7) and Kirkpatrick, who is also the study's first author, believes the rough patches they found might be the reason why.
"These rough patches are stronger and more resistant to earthquake slip," he says. "The historical record of earthquakes is relatively short, so we can't say with certainty that larger ones have not occurred. Future seismic events in the area, which will be recorded with modern equipment, should help us determine if they show the same limited magnitude."
Kirkpatrick and his colleagues also hope to apply their methods to other subduction zones where similar geophysical data is available to start to evaluate whether their conclusions are generally applicable.
"This connection between the fault roughness and earthquake magnitude might one day help us understand the size and style of earthquakes most likely to occur a given fault."
