Why aren't there enough ventilators and hospital beds? Anti-trust laws have a lot to do with it.

by Khalida Sarwari, Northeastern University

Credit: CC0 Public Domain

Around the world, ventilators—a life-saving medical device that keeps air flowing into the lungs of a patient who is unable to breathe—are a scarce resource in hospitals and clinics where they're used to treat those infected with the COVID-19 virus.

The machines are expensive, complex, and they take a long time to make. They're also produced by only a handful of manufacturers, among them Medtronic, a medical equipment company that specializes in such devices. In response to the pandemic, the company has agreed to nearly double its production capacity, and recently offered to share its ventilator technology with other companies in order to accelerate production.

But if the antitrust laws regulating mergers and acquisitions by the Federal Trade Commission had been more stringent a few years ago, says economist John Kwoka, there wouldn't be such a limited number of suppliers dominating the ventilator market, which as a result has left us vulnerable to a shortage during a public health emergency.

"Everyone's concerned about how we got into this circumstance," says Kwoka, Neal F. Finnegan distinguished professor of economics at Northeastern. "And the answer is some of it was the result of planning too close to the margin, but some of it was the willful acts of companies seeking to prevent competition."

The Federal Trade Commission has shown a tendency over the past 20 years not to challenge mergers until the field of competition is smaller. The agency has also looked for benefits or reasons to approve mergers, says Kwoka, whereas in the old days, it took a more cautious approach, approving mergers only if they were clearly harmless or even beneficial.

One consequence of that has been a rapid consolidation in the medical equipment markets where a single company has ended up acquiring other relatively smaller companies that represented either competitive threats or overlapping possibilities.

"As a result of that process of consolidation, we have a much smaller number of very large companies with huge portfolios of products instead of a larger number of competitors in any single market," Kwoka says.

Similarly, the hospital industry has also undergone dramatic consolidation in the last 15 to 20 years—to the tune of close to 800 acquisitions, Kwoka says, many by hedge funds seeking to quickly maximize their bottom line.

This has left many communities, especially in rural areas, without a single hospital, and contributed to the steady decline and current shortage of beds across the country amid the pandemic.

"The Federal Trade Commission again has really not been active in challenging enough of these," says Kwoka. "They try to challenge some, to their credit, but with a tidal wave of mergers, it's been difficult for them to do anything other than take a look at the leading and largest examples."

The Medtronic case goes back to 2013 when, in an effort to supplement the national inventory, the U.S. Department of Health and Human Services contracted with Newport, a small startup supplier of ventilators. The department put out a series of specifications requiring a certain number of units and at one-third the price than the ones that were being produced by the major ventilator manufacturers in the country at the time, which included the Dutch firm Philips, and eventually a company called COVIDien (which was later acquired by Medtronic).

Newport had already produced some test models that met the specifications, says Kwoka. Nevertheless, the company was bought by COVIDien, which demanded a bigger contract from the government, and when the government only partially acquiesced, COVIDien withdrew from the contract and none of these new ventilators was produced.

"A number of observers at the time, and some government officials, thought—not surprisingly—that part of COVIDien's plan was simply to eliminate a lower cost potential competitor to its traditional ventilator operation," says Kwoka.

Consequently, he says, the effort to produce small, cheaper ventilators in large numbers to supplement the country's stockpile collapsed. The health and human services department eventually entered into a new contract with Philips, but years were wasted and that agreement still has yet to produce any ventilators.

"The long and short of it is that COVIDien wanted to keep a potential competitor—a cheaper substitute for its own equipment—off the market, and succeeded in doing so," Kwoka says.

The Federal Trade Commission, upon completing a cursory review of the COVIDien acquisition, deemed that it was not a competition issue, and therefore did not challenge it.

While it's "nearly impossible" to undo the existing acquisitions, Kwoka suggests that going forward, the Federal Trade Commission can be more vigilant about preventing similar mergers in the medical equipment area. And to address the shortage, he says that the major ventilator manufacturers can, as Medtronic has now agreed to do, disclose its designs to enable other companies to manufacture the devices.

Kwoka's forthcoming book, Controlling Mergers and Market Power: A Program for Reviving Antitrust in America, addresses the question of how to reform and revitalize antitrust policy, and merger control in particular, in the U.S, and provides a comprehensive roadmap for rebuilding the necessary policies, institutions, and practices of a vigorous merger control poli

---

Provided by Northeastern University

• 
  

The coronavirus was in the US in January: We need to understand how we missed it

by Laura Castañón, Northeastern University

Credit: CC0 Public Domain

Back in January, the "novel coronavirus" that had sprung up in the Chinese city of Wuhan was at most a distant worry for many people in the United States.

But SARS-CoV-2, the coronavirus that causes COVID-19, was already circulating in major U.S. cities, according to Alessandro Vespignani, Sternberg Family distinguished university professor, who directs Northeastern's Network Science Institute. And if we want to keep our communities safe going forward, we need to understand how we missed a virus that was right under our noses.

"We don't want to fall into this trap in the future," Vespignani says.

The discovery that the virus was already circulating in the U.S in January comes from a model that Vespignani and his colleagues have been using to study and predict the global spread of the virus. The model relies on human mobility and patterns of interaction, as well as the infection dynamics of the virus.

"The model allows us to go into what we call the invisible stage of the epidemic in the United States," Vespignani says. "We can simulate the arrival of infected people that were starting local transmission chains."

Research that the group released last month shows that the cordoning off of cities within China, as well as travel restrictions implemented by countries around the globe, came too late. The coronavirus was already out.

But how did we miss it? Why didn't we notice people getting sick?

"There was no large scale testing capacity in the US and Europe, and the guidelines were to test only people with a travel history," Vespignani says. "But when you get an infection from somebody who is already in the United States, you don't have a travel history."

It was January—the height of flu season, winter colds, and other respiratory illnesses. Even the few people with severe cases would not have drawn much attention without a history of recent travel to China.

"So what happened is that for a month and a half, the epidemic had gone unnoticed," Vespignani says. "Until you have a critical mass of cases. Then, at that point, you start to see the tip of the iceberg."

Cities that are hubs for international travel from China—New York, Seattle, San Francisco, Los Angeles—saw the earliest cases in the U.S. But similar chains of infection were beginning all over the world. By the time the U.S. was turning away or quarantining travelers from China, the coronavirus was already spreading through U.S. cities, and new cases were coming from Europe and other areas.

Given the amount of change our lives have undergone in the past few months, looking back to January may feel like ancient history. But understanding how and when these outbreaks started can help researchers make predictions down the line.

"If I have an epidemic that starts in early January, I can project a certain trajectory; if I have an epidemic that starts in early March, everything is shifted by two months," Vespignani says. "That's an infinite time for a disease like this one. So you really want to be as sharp as possible, down to the level of a single week, to have the right timeline now to inform what we will see in the next weeks or months."

And what the researchers are learning will also help us make smart decisions when the number of infections has dropped off and we begin to lift physical-distancing measures.

It wasn't enough to only test for the virus based on travel history to national or international hotspots, Vespignani says. If we don't have more extensive testing, and the ability to trace the contacts of each infected person, a second wave of infection could be building without our knowledge.

"We don't want to find ourselves in the same situation," Vespignani says. "We need to have all that so that we can make visible what, in principle, could be invisible."

Provided by Northeastern University 

Lithium may treat behavior linked to autism gene
by Peter Hess, Brandeis University

Altered responses: Neurons in mice missing a gene called SHANK3 do not respond well to changes in sensory input. Credit: Brandeis University

The mood-stabilizing drug lithium eases repetitive behaviors seen in mice missing SHANK3, an autism gene, according to a new study1.

The findings suggest lithium merits further study as a treatment for some people with autism, even though the drug has troublesome side effects, including tremors and impaired memory.

"Lithium is, of course, a rather difficult, non-ideal treatment," says lead investigator Gina Turrigiano, professor of vision science at Brandeis University in Waltham, Massachusetts. "It's really hard to get people on a lithium regimen that they can tolerate well." But understanding why lithium works may set the stage for better treatments, she says.

About 1 percent of people with autism have mutations in SHANK3. Deletion or mutation of the gene can also lead to Phelan-McDermid syndrome, which is characterized by intellectual disability, delayed speech and, often, autism.

Case studies of people with Phelan-McDermid syndrome also suggest that lithium eases behavior problems associated with the condition2.

Previous work has shown that SHANK3 helps stabilize neuronal circuits by adjusting excitatory and inhibitory signaling like a thermostat. This process, called homeostatic plasticity, allows neurons to respond to changes in sensory input.

The new study suggests the gene controls this thermostat by regulating how frequently neurons fire and how they adjust the electrical currents flowing through them. SHANK3 loss or mutation prevents neurons from adapting to changes in sensory input.

"What we've shown is there's this cellular mechanism, and loss of that mechanism is a direct result of a loss of SHANK3," Turrigiano says.

Firepower

The team first recorded electrical activity in rat neurons in which SHANK3 expression was partially disrupted. They artificially blocked the neurons' ability to fire. The mutant neurons' rate of firing did not return to its original range afterward as it did in control cells, the team found.

The neurons also responded with less electrical activity than controls did when the researchers blocked and then restarted electrical currents. This suggests the mutant neurons had lost their ability to adjust the current flowing through them.


Excitatory neurons in the cortex called pyramidal cells are most strongly affected. Lithium restored the cells' ability to adjust both their firing rates and how much current they carry.

To examine how neurons in mice lacking SHANK3 respond to changes in sensory input, the team implanted electrode arrays into the visual cortex of the mutant mice and controls and glued one eye shut in each mouse.

Over the following three or four days, the neurons in both groups of mice decreased how frequently they fired. But the decrease in the mutant mice was more gradual, suggesting that they take longer to adjust.

Neurons in the control mice returned to their typical firing rate two days after the rate had slowed to its lowest level, presumably because the mice's brains had adapted to the loss of vision in one eye. But in the mutant mice, the neurons never returned to their original firing rates, indicating that without the gene, their brains could not adapt.

The mutant mice also groom themselves excessively, a behavior that is thought to align with obsessive or repetitive behaviors in people. To the researchers' surprise, lithium stopped this behavior entirely. The work appeared in March in Neuron.

Treatment potential

The findings support the idea that lithium may help treat people with SHANK3 mutations, and perhaps those with other forms of autism as well, says Jean Martin Beaulieu, associate professor of psychiatry and neurosciences at the University of Toronto in Canada, who was not involved in the study.

However, he says, the study does not prove that the problems with homeostatic plasticity cause the repetitive behavior. Overgrooming is a complex behavior involving multiple brain areas, he says, whereas the study examined only the visual cortex.

It is also unclear whether lithium acts directly on SHANK3 or on some other target in the circuit, says Thomas Bourgeron, professor of genetics at the Institut Pasteur in Paris, France, who was not involved in the study.

Turrigiano says the loss of SHANK3 may be just the first step in a process that leads to neurons' inability to adapt to sensory input. Identifying which part of that process lithium corrects may point to new targets for treatment, she says.

Turrigiano's team is studying how SHANK3 helps balance excitatory and inhibitory activity of neurons, to better understand its role in maintaining homeostatic plasticity.

New study may explain why people with autism are often highly sensitive to light and noise

More information: Vedakumar Tatavarty et al. Autism-Associated Shank3 Is Essential for Homeostatic Compensation in Rodent V1, Neuron (2020). DOI: 10.1016/j.neuron.2020.02.033

Sylvie Serret et al. Lithium as a rescue therapy for regression and catatonia features in two SHANK3 patients with autism spectrum disorder: case reports, BMC Psychiatry (2015). DOI: 10.1186/s12888-015-0490-1

Journal information: Neuron


Provided by Brandeis University

Commonly used chemicals associated with miscarriage, study finds

by Michael Greenwood, Yale University

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.

All women in the Danish cohort studied had detectable and multiple types of per- and polyfluoroalkyl substances (PFAS) in their pregnancy serum. The study estimated a nearly 80% to 120% increased risk for miscarriage in 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."

Fecal excretion of PFAS by pets

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

Journal information: Environmental Health Perspectives 

 by Yale University 

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.

Journal information: The Lancet 

Provided by SciDev.Net

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 deaths, no benefit from malaria drug in VA virus study (Update)

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-

Journal information: Nature Medicine

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: 

EULAR launches COVID-19 RMD reporting database as part of Global Rheumatology Alliance

---

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

Journal information: Annals of the Rheumatic Diseases 

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."

Understanding changing guidance on mask use

by Johns Hopkins University

Credit: CC0 Public Domain

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.

As best practices for limiting the spread of the coronavirus continue 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 as social distancing and 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.