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Saturday, April 4, 2020

Zentalis pulls off speedy $165M IPO amid pandemic-driven uncertainty

The new coronavirus has injected all kinds of uncertainty into the biotech world, leading companies to delay clinical trials, reorganize their pipelines and hold off on their IPOs. Not so for Zentalis Pharmaceuticals, which priced its IPO at $165 million, eclipsing the $100 million goal it laid out in early March.
Zentalis will use the proceeds to develop ZN-c5, a selective estrogen receptor degrader, for the treatment of ER-positive, HER2-negative breast cancer. The company teamed up with Pfizer in May 2018 to test it alongside Pfizer’s CDK4/6 inhibitor Ibrance and expects to report data from a phase 1/2 study of the combo, as well as ZN-c5 as a single agent, later this year.
It has two other programs in the clinic: ZN-c3, which targets the WEE1 kinase to treat solid tumors, and an EGFR drug for lung cancer. The company aims to move its fourth program, which targets BCL-2 in blood cancers, into clinical trials by the middle of this year.

Zentalis spent its first few years under the radar, officially launching in December with an $85 million series C round. Just three months later—and two days before the World Health Organization (WHO) officially declared COVID-19 a pandemic—it filed to raise $100 million in its Nasdaq debut. By Bloomberg’s count, Zentalis is the second biotech company to go public in the U.S. since WHO’s declaration.

It joins Imara, a biotech working on a treatment for sickle cell disease, which began trading March 12, the day after the pandemic was declared. Unlike Zentalis, which outraised its goal by more than half, Imara took a bit of a hit, pricing its IPO at $75.2 million after taking aim at an $86 million listing.
Toward the end of 2019, industry watchers listed a number of factors that might affect the U.S. IPO market in 2020, ranging from the presidential election and changes in interest rates to Brexit and trade tensions between the U.S. and China. A pandemic was not one of them. Now, COVID-19 has “thrown a wrench in what would have been the most active period of the 2020 IPO market,” Renaissance Capital said in a report last month.
It has all but “shut down the spring IPO market,” Renaissance wrote. It now expects a “narrower IPO window in the summer, for companies relatively unaffected by the virus” and for more companies to aim for fall IPOs.
https://www.fiercebiotech.com/biotech/zentalis-pulls-off-speedy-165m-ipo-amid-pandemic-driven-uncertainty

CDC director Redford on coronavirus, masks, and an agency gone quiet

Robert Redfield, director of the Centers for Disease Control and Prevention, describes the coronavirus pandemic as the greatest public health crisis in a century.
And yet the storied agency that Redfield leads — one that has been used as a model by countries around the world, including the China CDC — has played a largely invisible role in the nation’s response since the White House took over communications about the outbreak last month.
CDC experts, who held regular briefings to update the public about previous health threats such as the H1N1 flu pandemic and the Zika outbreak, have been silenced. It has been nearly a month since the last CDC media briefing, which took place March 9.
STAT asked Redfield about the agency’s role, whether he was satisfied with it, the agency’s evolving thinking about whether people should wear cloth masks in public, and how he sees the pandemic unfolding. The conversation has been lightly edited for length and clarity.
How are you? It’s a very challenging time.
I’m doing fine.
I would like to ask you a bit about the mask issue. [After this interview with Redfield, the CDC issued guidance urging the public to wear cloth masks in public to slow spread of the disease. President Trump announced the new recommendation at a press briefing.]
We strongly continue to recommend that N95 masks and surgical masks really be committed to the health care workers that are on the frontlines. Our nation owes them all a great gratitude as they continue to confront what you and I now know is the greatest public health crisis that’s hit this nation in more than a century.
But we actually have one of the most powerful weapons that we need to defeat the spread of this virus. And I know a lot of people may not see it as a powerful weapon, but it is. And that’s social distancing. This virus cannot jump 6 feet. So this is why the president’s recommendation is to slow the spread of the coronavirus.
I want to constantly thank the American public that have taken these social distancing recommendations and operationalized them into action with vigor and vigilance. And I just want to petition the remainder to have everybody go all in. That big, powerful weapon that we have is just to stay 6 feet apart.
Now that said, there’s probably greater numbers of individuals that are without symptoms, and have this virus and can shed this virus than I think was originally appreciated. So we are discussing in detail whether a face covering, a face barrier, whether that would modify the ability of those of us that may be infected and don’t know it to actually infect others. It’s not a decision to try to protect me from getting coronavirus. It’s to help modify spreading. And there is scientific data to show that when you aerosolized virus through a cloth barrier, you have a reduction in the amount of virus that gets through the other side.
Kind of a homemade, make-it-yourself barrier, whether it’s a bandana or a scarf.
Are you going to give people some advice on what kind of fabric? Because all fabrics are not created equal. 
Obviously, there will be guidance on the fabrics, guidance on how to make them.
You mentioned earlier that the biggest tool that we have is social distancing. But it is being applied in a patchwork manner across the country. Some states have been more aggressive. Others are not. Do you think it’s time for a national stay-at-home order?
I think ultimately in these things it’s, how do you get full participation? I think you have to get the hearts and minds of people behind this. And so I think, you know, different jurisdictions will approach it in different ways. I will say what I’ve seen is the American public is embracing these strategies.
Dr. [Deborah] Birx says not enough of them. 
I think people can decide independently in these states, the governors, and the mayors, how they think they’re best going to motivate their individuals to adhere to the social distancing. My own personal view is the best way to motivate is to have them shut their eyes and see their parents’ faces, their grandparents’ faces, their neighbors that have chronic illness, children that are suffering from cancer and say, “I need you to do it for them.”
What is the next year, the next 18 months going to look like in your estimation? 
I think there’s a reasonable probability that this virus is going to have a seasonality to it. And that means that there’s a potential global catastrophe that may, in fact, be on its way to the Southern Hemisphere, particularly sub-Saharan Africa. And we need to prepare for that.
Related to us, that means that we may, in fact, get through in the weeks ahead, the months ahead into a lull. But I would say [if] we’re lucky enough to have that we need to get very prepared because next late fall and early winter, like most respiratory viruses, coronavirus 19 will be an enemy that we’re going to have to face again. Now we’re going to have time to prepare. We’re going to have, I think, hopefully time to reinforce our public health capacity in many parts of the nation so that we can do early diagnosis, isolation, contact tracing, prevent large community clusters, prevent what we call sustained community transmission. Just one of our challenges next season is going to be two simultaneous outbreaks: coronavirus 19, second wave, and our regular flu season. And they both compete for the same hospital resources.
The CDC hasn’t had a briefing in almost one month. That is extraordinary. Don’t you fear that your agency has been sidelined in this? 
No, I wouldn’t say that at all. I think we’re fully engaged in all of the decisions. If you look at CDC’s website and what we’re doing constantly in our communications …
People are not going to dive through the website and read hundreds of words. 
CDC is at the table in every decision. We’re at the task force meeting every single day. We’re giving our public health guidance and our recommendations.
We’ve got literally thousands of people working 24/7 gathering data all over this nation, not to mention sending people across this country to help with outbreak responses. So I think we’re fully engaged in the operations of the response. You know, if others seem to communicate some of that, that’s a decision that the administration can make. But I will guarantee you we’re 100% engaged 24/7 in operationalizing the response throughout this nation.
So you’re OK with the fact that the CDC hasn’t briefed for a month? 
I’m saying that we’re giving our recommendations at the highest level on a daily basis and on a daily basis we’re working 24/7 to actually operationalize the day-to-day response throughout this nation.
In this incredibly polarized time something that should be pretty basic — a virus is looking for throats to infect and it doesn’t care which way those throats vote — has become utterly polarized. Having the messaging come from the CDC, which is completely agnostic on a political basis, could strip out some of that politicalization that is just really not helpful.
I don’t think there’s any way you can even overstate how aggressively the CDC is involved throughout this nation in operationalizing the response. You know, we do think that we have a calming effect in being viewed as being basically …
But you’re invisible now, sir. Your agency is invisible.
You may see it as invisible on the nightly news, but it’s sure not invisible in terms of operationalizing this response. And all you have to do to find that is go talk to your state and territorial health departments. Go out and look at the outbreaks. Go look in the field. So I guess it depends on how you define visibility.
Who is in charge of the outbreak response at the CDC now? 
Anne Schuchat [CDC’s principal deputy director] is running the day-to-day response down at CDC.
So was Nancy Messonnier, director of the CDC’s Center for Immunization and Respiratory Diseases, sidelined? 
It was an evolution. Nancy really activated her center for the response in very early January when China probably still had less than 50 cases. But it was clear that this was going to be a broader agency wide response. Nancy is a very important technical person involved in the response.
So this has nothing to do with the fact that it was felt that she was contradicting the messaging from the White House? 
I think Nancy Messonnier is a gift to this nation. She’s a great talent. She continues to provide those talents and recommendations to the agency. She continues to run one of our most important centers for respiratory disease and immunization.
I did mean to ask you, have you had Covid-19? 
Not to my knowledge.
Have you been tested for it? 
No.
An interview with the CDC director on coronavirus, masks, and an agency gone quiet

5 ways to cope when masks run low

With hospitals in coronavirus hotspots struggling to preserve personal protective equipment (PPE), MedPage Today spoke with experts in engineering, medicine, and infection prevention on ways to extend their supply and use.
Infection preventionists spend their days “frantically searching” for PPE, teaching clinicians how to reuse masks and gowns or how to create their own, said Ann Marie Pettis, RN, BSN, president-elect of the Association for Professionals in Infection Control and Epidemiology (APIC) during a press briefing last week.
“This goes against everything we have known from the scientific evidence and what we have always taught our staff,” Pettis said.
An APIC survey released on March 27 found that among 1,140 infection preventionists across the U.S., 20% reported that their facilities have no respirators and another 28% are almost out of them. Roughly half of respondents were also almost or completely out of face shields.
That has prompted healthcare professionals and the agencies offering guidance to look hard at ways to make available supplies last longer and, in extreme situations, for workers to fabricate their own gear. In many facilities, it’s simply impossible to put on a new, fresh-from-the-box mask for every patient encounter. That means wearing them longer and/or decontaminating them.
Option 1: Extended Wear, Reuse
The CDC recommendations around optimizing the use of N95s fall into three categories: conventional, contingency, and crisis.
Already many hospitals in the contingency and crisis stages are implementing policies of extended use or limited reuse.
Kathleen Aumann Morales, PhD, RN, CNE, of Berry College in Georgia, said on a webinar hosted by The Infection Prevention Strategy (TIPS) that she has heard of nurses getting one mask per day, per week, or even every 2 weeks. Some nurses wear surgical masks over their N95 respirators to make them last longer, she noted.
In CDC guidance issued Tuesday, the agency pointed to studies demonstrating that the virus that causes COVID-19 can live on plastic, stainless steel, and cardboard surfaces for up to 72 hours.
The agency then suggested a passive decontamination strategy of sorts: issuing five respirators to each healthcare worker seeing COVID-19 patients. The worker wears each mask in the same order and places it in a paper bag at the end of the day. If done correctly, there should be a minimum of 5 days between each respirator’s repeat use, the guidance notes.
But reuse, a “contingency capacity strategy,” is not without risks: “There is perhaps something worse than no mask, and that would be self-inoculation,” said Larry Chu, MD, MS, director of the Anesthesia Informatics and Media (AIM) Lab at Stanford University Medical Center in California.
It’s easy to imagine a clinician unknowingly placing a mask that’s been stuffed in a pocket or bag and become contaminated with the COVID-19 virus up against his or her face, Chu told MedPage Today. “If we remove a mask … it may be safest to only replace it with a clean or disinfected mask,” he said. (Chu emphasized that healthcare workers should always comply with their hospitals’ policies and that his views are not necessarily those of Stanford Medicine.)
“Extended use is probably the safest way to go,” particularly for those in a designated COVID unit, Pettis told MedPage Today.
In its guidance, CDC reminds workers who reuse masks to treat respirators as though they are contaminated. Wearers should wash their hands with soap and water, use clean gloves when donning and performing seal checks, and inspect the respirator to ensure there’s no damage, particularly to the straps, nose bridge, and nose foam material, and to always avoid touching the inside of the respirator.
Pettis also noted that unused respirators that have passed the expiration dates on their labels can be used, per the CDC.
“Realistically, a lot of times expiration dates are over-cautious,” she said.
But if a respirator is “compromised” or if a seal check fails, the respirator should be discarded and replaced, the CDC advised.
Decontamination
Decontamination is in a kind of “Wild, Wild West” phase, Pettis said.
Despite there being no CDC-approved method for decontamination, the agency said ultraviolet germicidal irradiation (UVGI), vaporous hydrogen peroxide (VHP), and moist heat have shown “the most promise” as methods for decontaminating respirators.
The CDC warned that decontamination and subsequent reuse is a “crisis capacity strategy” because it may diminish a respirators’ level of protection, a CDC spokesperson told MedPage Today via email.
Changes to the respirator could reduce its filtration efficiency, its breathability, or “degrade the straps, nose bridge material, or strap attachments,” which could in turn affect how well a respirator fits, the spokesperson noted.
There isn’t specific data to support the efficacy of decontamination against the COVID-19 virus right now on respirators, and more research will be needed to confirm that the virus is “inactivated,” noted the CDC.
The FDA issued new guidance on March 29 explaining that during this public health emergency, the agency “does not intend to object to the distribution and use of sterilizers, disinfectant devices, and air purifiers that are intended to be effective at killing SARS-CoV-2 [the virus that causes COVID-19] … FDA believes such devices will not create such an undue risk, when performance and labeling criteria are met.”
Option 2: Ultraviolet Light
John Lowe, PhD, of the University of Nebraska Medical Center College in Omaha, designed a method for decontaminating N95 respirators using ultraviolet light.
The process works like this: Bags of used masks are transported to a room inside the university’s medical center fitted with two ultraviolet light towers. The respirators are labeled with the wearer’s first initial, last name, and the date of first use, and the paper bags are similarly labeled with the wearer’s full name and the unit to which the respirators should be returned.
The respirators are hung on wires across the room and decontaminated when the UV light towers are turned on. Afterwards, the respirators are returned to the original wearer.
Chu and Amy Price, DPhil, of Stanford Medicine, who recently tested five different methods of decontaminating respirators, confirmed that UVGI was “safe and effective” in the models tested. (Chu noted that Stanford’s AIM Lab COVID-19 Evidence Service Report is not intended to advocate for any product or service.)
But Pettis said that while ultraviolet germicidal irradiation may be relatively “tried and true,” it’s not an easy process: Light must reach every part of the mask and absorption levels have to be monitored, she explained, noting that her hospital, Highland Hospital of the University of Rochester in New York, has chosen hydrogen vapor peroxide instead.
“Process-wise, it was just easier and we had more confidence in the hydrogen peroxide vapor getting into everything that needed to be decontaminated,” Pettis said.
William Anderson, of the University of Waterloo Faculty of Engineering in Ontario, said on the TIPS webinar that UV radiation doesn’t appear to harm the respirator’s capacity for filtration.
Still, he said, the buildup of material as masks are used and reused could potentially make breathing more difficult.
Anderson said he was not sure how many decontamination cycles the process would allow per respirator, but Morales guessed an upper limit of five.
Option 3: Vaporous Hydrogen Peroxide
Battelle Labs, a Columbus, Ohio-based nonprofit, received an emergency use authorization from the FDA on March 28 to decontaminate N95 respirators for reuse using a VHP procedure that calls for 2.5 hours of exposure to concentrated gases and a maximum of 20 decontamination cycles per respirator.
VHP decontamination showed “minimal effect” on filtration efficacy and demonstrated “99.9999% efficiency in killing bacterial spores” and similar efficacy against bacteriophage viruses, the CDC noted in its guidance.
But the elastic bands themselves can degrade after about 30 cycles, Anderson pointed out, citing an earlier FDA report on the Bioquell HPV Decontamination system.
Anderson said that although some studies note concerns of hydrogen peroxide residue on respirators, as long as enough time is allotted for off-gassing, he does not anticipate a problem.
Overall, he called it a “feasible approach,” but expressed concerns about throughput for VHP systems that hospitals already have on site, which may take “multiple hours per batch.”
Battelle’s system, a “scaled-up version of VHP,” can handle “quite a few masks, but deployment may take a while,” he added in a follow-up email. Battelle is currently processing N95 respirator masks for OhioHealth. In addition, Stony Brook University Hospital in New York has plans to begin using Battelle’s Critical Care Decontamination System, which can disinfect up to 80,000 masks in a day, a spokesperson for the university said in an email.
Option 4: Heat
A third method of decontamination, moist heat, has been studied at 60°C and 80% relative humidity. In one study, it only minimally reduced filtration and fit of the respirator, according to the CDC, while in a second it led to a “99.99% reduction” in H1N1 influenza virus. One drawback from this method is the uncertainty around its ability to disinfect different pathogens, the agency noted.
In addition, Yi Cui, PhD, of Stanford University, and colleagues have experimental data suggesting that, although different, use of dry heat around 75°C for 30 minutes can also decontaminate N95 respirators and maintain filtration efficiency over several cycles.
But that process will require more research before it can be confirmed, he noted.
The CDC’s guidance found that decontamination with 160° C dry heat reduced the efficacy of the N95 filter and “did not meet the levels that NIOSH [the National Institute for Occupational Safety and Health] would allow for approval,” but this is twice the temperature Cui’s team studied.
The CDC guidance also noted that decontamination with an autoclave, 70% isopropyl alcohol, microwave irradiation, and soap and water resulted in “significant filter degradation.”
What Not to Do
While the PPE shortages have encouraged clinicians to be innovative, experts shared certain do’s and don’ts:
  • Do not bake a respirator in a home oven, Chu warned, as it could expose the wearer and others to the virus
  • Do not use tanning lamps or nail dryers as a source of UV radiation, Anderson said, explaining that those lamps typically use UVA radiation that have a longer wavelength and do less damage to pathogens
  • Do not randomly redistribute decontaminated respirators; clinicians should write their names on their masks and each hospital should have a system to ensure they are returned to the appropriate owner, said Chu. Masks are disinfected but not cleaned. Not only is it “disconcerting” to receive a mask with someone else’s lipstick on it, the process may have eliminated the COVID-19 virus without inactivating all other microbes
Option 5: Homemade Substitute
As a last resort, homemade masks are “better than nothing,” Morales said, but they’re more effective at “keeping the germ in than keeping the germ out.”
Chu and his colleagues assessed the filtration efficiency of different homemade materials using everything from vacuum cleaner bags to cotton T-shirts.
But as Cui pointed out, it would be impossible for a layperson to make “a high efficiency mask” with these materials.
At Pettis’ hospital, homemade masks are given to outsiders visiting patients or confirmed COVID-19 patients who are being sent home. The masks are laundered, of course, and could in the future be used by clinicians to make their own N95s last longer.
“Could we get to the point where we do have to use them for the staff? We could,” she admitted. “After this is all over, I think there will be a lot of soul-searching to figure out how to improve and prevent some of the issues that we’re facing right now.”
https://www.medpagetoday.com/infectiousdisease/covid19/85799

Covid-19: four fifths of cases are asymptomatic, China figures indicate

Michael Day
Author affiliations
New evidence has emerged from China indicating that the large majority of coronavirus infections do not result in symptoms.
Chinese authorities began publishing daily figures on 1 April on the number of new coronavirus cases that are asymptomatic, with the first day’s figures suggesting that around four in five coronavirus infections caused no illness. Many experts believe that unnoticed, asymptomatic cases of coronavirus infection could be an important source of contagion.
A total of 130 of 166 new infections (78%) identified in the 24 hours to the afternoon of Wednesday 1 April were asymptomatic, said China’s National Health Commission. And most of the 36 cases in which patients showed symptoms involved arrivals from overseas, down from 48 the previous day, the commission said.
China is rigorously testing arrivals from overseas for fear of importing a fresh outbreak of covid-19.
Tom Jefferson, an epidemiologist and honorary research fellow at the Centre for Evidence-Based Medicine at the University of Oxford, said the findings were “very, very important.” He told The BMJ, “The sample is small, and more data will become available. Also, it’s not clear exactly how these cases were identified. But let’s just say they are generalisable. And even if they are 10% out, then this suggests the virus is everywhere. If—and I stress, if—the results are representative, then we have to ask, ‘What the hell are we locking down for?’”
Jefferson said that it was quite likely that the virus had been circulating for longer than generally believed and that large swathes of the population had already been exposed.
Users of Chinese social media have expressed fears that carriers with no symptoms could be spreading the virus unknowingly, especially now that infections have subsided and authorities have eased curbs on travel for people in previous hotspots in the epidemic.
Zhong Nanshan, a senior medical adviser to the Chinese government, said that asymptomatic infections would not be able to cause another major outbreak of covid-19 if such people were kept in isolation. Officials have said this is usually for 14 days.
Nanshan said that once asymptomatic infected people were identified, they and their contacts would be isolated and kept under observation.
Citing classified data, the South China Morning Post said that China had already found more than 43 000 cases of asymptomatic infection through contact tracing.
The latest findings seem to contradict a World Health Organization report in February that was based on covid-19 in China. This suggested that “the proportion of truly asymptomatic infections is unclear but appears to be relatively rare and does not appear to be a major driver of transmission.”1
But since that WHO report other researchers, including Sergio Romagnani, a professor of clinical immunology at the University of Florence, have said they have evidence that most people infected by the virus do not show symptoms. Romagnani led the research that showed that blanket testing in a completely isolated village of roughly 3000 people in northern Italy saw the number of people with covid-19 symptoms fall by over 90% within 10 days by isolating people who were symptomatic and those who were asymptomatic.2
In an article on the website of the Centre for Evidence-Based Medicine, Jefferson and Carl Heneghan, director of the centre and editor of BMJ EBM, write, “There can be little doubt that covid-19 may be far more widely distributed than some may believe. Lockdown is going to bankrupt all of us and our descendants and is unlikely at this point to slow or halt viral circulation as the genie is out of the bottle.
“What the current situation boils down to is this: is economic meltdown a price worth paying to halt or delay what is already amongst us?”3

References

https://www.bmj.com/content/369/bmj.m1375

Proposed Rule Could Mean Cuts in Federal Medicaid Funds to States

A proposal to change the way the federal government pays some states under the Medicaid program is causing headaches for healthcare groups and Medicaid directors, even though it hasn’t actually been enacted yet.
The Medicaid Fiscal Accountability Rule (MFAR), released last November by the Centers for Medicare & Medicaid Services (CMS), would reduce the amount of money that CMS gives to states as part of their Medicaid matching funds when the money is generated through various supplemental means.
“CMS is aware of numerous schemes states have used that are not consistent with federal statute,” the agency said in a press release. “Some examples include states that generate extra payments for private nursing facilities that enter into arrangements with local governments to bypass tax and donation rules, and the use of a loophole to tax managed care entities 25 times higher for Medicaid business than for similar commercial business. States can then use that tax revenue to generate additional payments, with no commensurate increase in state spending.”
“Many of the vulnerabilities in Medicaid financing arise from high-risk financing mechanisms that states have used, or sought to use, to finance the state portion of Medicaid payments,” the release continued. “These include intergovernmental fund transfers … provider taxes, and provider donations that provide additional payments to institutions with no clear link to improving care for patients. The proposed rule would provide clearer guidance on the law to states and other stakeholders, help close regulatory loopholes, and improve reporting to help CMS ensure that states fund their share of payments to providers through only permissible sources and with methodologies that comport with statutory requirements.”
Concerns About Payment Cuts
But critics of the proposed rule say that it would mean a cut in federal Medicaid funds that states have come to rely on.
“Through the proposed rule, CMS outlines a number of changes that reduce states’ ability to generate state share to finance their Medicaid program,” wrote Margaret Murray, CEO of the Association for Community Affiliated Plans (ACAP), which represents safety-net health plans, in a Jan. 31 letter to CMS. “ACAP is concerned that these changes will limit state flexibility to generate state share, which will have downstream effects on state Medicaid funding and ultimately reduce access to critical services for Medicaid beneficiaries.”
States could lose $37 billion to $49 billion annually under the rule, according to a report from Manatt Health and the American Hospital Association.
The agency gave two justifications for developing the rule, explained Edwin Park, JD, a research professor at Georgetown University’s Center for Children and Families, in a phone interview. First, “they document problems where states have violated existing federal requirements, and they say, ‘We don’t have enough data on what states and providers are doing,'” he said.
Two Justifications
In the rule’s preamble, CMS gives some examples of states violating current rules; however, “What’s not clear from that preamble is that they found these problematic arrangements under existing rules and … there are existing enforcement arrangements to prevent them. The rule changes really have nothing to do with those examples; they’re using the examples to make a very broad change to rules that have been in place for almost three decades.”
The other justification for the rule is a need for more transparency about these miscellaneous financing mechanisms like intergovernmental transfers and provider taxes; the rule would require more reporting from states. “There is general acceptance that there should be more known about these arrangements,” Park agreed. “But the reporting is only one small portion of the proposed rule, and the large majority of the rule is about prohibiting existing arrangements.”
As the COVID-19 pandemic advanced on the U.S., healthcare groups were encouraged that several of the stimulus bills passed by Congress addressed states’ healthcare funding needs. For example, the Families First Coronavirus Response Act, which President Trump signed into law on March 18, provides enhanced Medicaid matching funds to states to help them through the pandemic. But if there is less state money on the table because the federal government has disallowed some of these financing mechanisms, “you draw down less federal dollars, including the enhanced matching rate that Family First provides,” said Park.
“If you add on the COVID 19 crisis, as revenues fall and program costs rise, states are going to be cash-strapped,” he continued. That will mean Medicaid cuts, “and one of the obvious places states would go would be provider rates, as was done in previous economic downturns.”
Push for Delay or Rescission
During the debate over the most recent stimulus bill, Democratic legislators presented alternative legislation that included a provision that would delay the implementation of MFAR, but it didn’t get included in the final bill. The only possible good news on the MFAR front, according to Matt Salo, executive director of the National Association of Medicaid Directors, “is that CMS is telling us that all non-COVID-19 work is on the back burner. That’s good, but what does that really mean? Back burner until 6 weeks from now? Eighteen months from now? We of course don’t know.”
“There are assurances that when they do get back around to MFAR, two things will have happened — a lot of people commented, including us, and it sounds like they’re going to take those comments into consideration, which is good, and they also said everything they do post-COVID will be in light of the fact that they’re post-COVID,” so maybe the final MFAR rule won’t be as bad as people fear, Salo said in a phone interview. “But you can’t bank on any of that.”
In an ideal world, Congress would rescind MFAR entirely, the rule’s critics say, but that hasn’t happened yet. “We sent a letter to Congress recently calling for Congress to rescind the regulation, and sent a letter to the administration asking for the same thing,” Murray, of ACAP, said in a phone interview. “Ideally, they would rescind it, but if they can’t do that, could they at least delay it?”
With the comment period for the rule now closed, CMS is now in a period of finalizing the rule. The agency did not respond by press time to a request for comment on this story.
With the comment period for the rule now closed, CMS is now in a period of finalizing the rule. Asked to comment on this story, a spokesperson responded in an email that “in light of the 2019 Novel Coronavirus outbreak, CMS is looking closely at all its policies and across all its programs to see where we can strengthen the nation’s response.” Since MFAR is only a proposed rule, “no current regulations have been changed” yet, the spokesperson added.
https://www.medpagetoday.com/publichealthpolicy/medicaid/85798

COVID-19 lockdown will take its own toll on health

As governments race to stem the spread of coronavirus through an unprecedented closing of schools, businesses and travel, some specialists fear the long term public health impacts of a depressed economy and shuttered society.
It’s the most dramatic government intervention into our lives since World War II. To fight the coronavirus outbreak, governments across the globe have closed schools, travel and businesses big and small. Many observers have fretted about the economic costs of throwing millions of people out of work and millions of students out of school.
Now, three weeks after the United States and other countries took sweeping suppression steps that could last months or more, some public health specialists are exploring a different consequence of the mass shutdown: the thousands of deaths likely to arise unrelated to the disease itself.
The longer the suppression lasts, history shows, the worse such outcomes will be. A surge of unemployment in 1982 cut the life spans of Americans by a collective two to three million years, researchers found. During the last recession, from 2007-2009, the bleak job market helped spike suicide rates in the United States and Europe, claiming the lives of 10,000 more people than prior to the downturn. This time, such effects could be even deeper in the weeks, months and years ahead if, as many business and political leaders are warning, the economy crashes and unemployment skyrockets to historic levels.
Already, there are reports that isolation measures are triggering more domestic violence in some areas. Prolonged school closings are preventing special needs children from receiving treatment and could presage a rise in dropouts and delinquency. Public health centers will lose funding, causing a decline in their services and the health of their communities. A surge in unemployment to 20% – a forecast now common in Western economies – could cause an additional 20,000 suicides in Europe and the United States among those out of work or entering a near-empty job market.
None of this is to downplay the chilling death toll COVID-19 threatens, or to suggest governments shouldn’t aggressively respond to the crisis.
“Depressions are deadly for people, poor people especially.”
Dr. Jay Bhattacharya, Stanford University health policy researcher
A recent report by researchers from Imperial College London helped set the global lockdown in motion, contending that coronavirus could kill 2 million Americans and 500,000 people in Great Britain unless governments rapidly deployed severe social distancing measures. To truly work, the report said, the suppression effort would need to last, perhaps in an on-again, off-again fashion, for up to 18 months.
In the United States, the White House this week said the final toll could rise to 240,000 dead. States have responded to the dire warnings, and the escalating number of cases revealed each day, by extending stay-at-home shutdowns.
The medical battle against COVID-19 is developing so rapidly that no one knows how it will play out or what the final casualty count will be. But researchers say history shows that responses to a deep and long economic shock, coupled with social distancing, will trigger health impacts of their own, over the short, mid and long term.
Here is a look at some.
Domestic Violence
Trapped at home with their abusers, some domestic violence victims are already experiencing more frequent and extreme violence, said Katie Ray-Jones, the chief executive officer of the National Domestic Violence Hotline.
Domestic violence programs across the country have cited increases in calls for help, news accounts reported – from Cincinnati to Nashville, Portland, Salt Lake City and statewide in Virginia and Arizona. The YWCA of Northern New Jersey, in another example, told Reuters its domestic violence calls have risen up to 24%.
“There are special populations that are going to have impacts that go way beyond COVID-19,” said Ray-Jones, citing domestic violence victims as one.
Vulnerable Students
Students, parents and teachers all face challenges adjusting to remote learning, as schools nationwide have been closed and online learning has begun.
Some experts are concerned that students at home, especially those living in unstable environments or poverty, will miss more assignments. High school students who miss at least three days a month are seven times more likely to drop out before graduating and, as a result, live nine years less than their peers, according to a Robert Wood Johnson Foundation report.
Among the most vulnerable: the more than 6 million special education students across the United States. Without rigorous schooling and therapy, these students face a lifetime of challenges.
Special needs students “benefit the most from highly structured and customized special education,” said Sharon Vaughn, executive director of the The Meadows Center for Preventing Educational Risk at the University of Texas. “This means that they are the group that are most likely to be significantly impacted by not attending school both in the short and long term.”
In New Jersey, Matawan’s Megan Gutierrez has been overwhelmed with teaching and therapy duties for her two nonverbal autistic sons, eight and 10. She’s worried the boys, who normally work with a team of therapists and teachers, will regress. “For me, keeping those communications skills is huge, because if they don’t, that can lead to behavioral issues where they get frustrated because they can’t communicate,” Gutierrez said.
Soaring Suicides
In Europe and the United States, suicide rates rise about 1% for every one percentage point increase in unemployment, according to research published by lead author Aaron Reeves from Oxford University. During the last recession, when the unemployment in the United States peaked at 10%, the suicide rate jumped, resulting in 4,750 more deaths. If the unemployment rate increases to 20%, the toll could well rise.
“Sadly, I think there is a good chance we could see twice as many suicides over the next 24 months than we saw during the early part of the last recession,” Reeves told Reuters. That would be about 20,000 additional dead by suicide in the United States and Europe.
Less than three weeks after extreme suppression measures began in the United States, unemployment claims rose by nearly 10 million. Treasury Secretary Steven Mnuchin warned the rate could reach 20% and Federal Reserve economists predicted as high as 32%. Europe faces similarly dire forecasts.
Some researchers caution that suicide rates might not spike so high. The conventional wisdom is that more people will kill themselves amid skyrocketing unemployment, but communities could rally around a national effort to defeat COVID-19 and the rates may not rise, said Anne Case, who researches health economics at Princeton University. “Suicide is hard to predict even in the absence of a crisis of Biblical proportions,” Case said.
This week, the Air Force Academy in Colorado Springs, Colorado, relaxed its strict social isolation policies after the apparent suicides of two cadet seniors in late March, The Gazette, a Colorado Springs newspaper, reported. While juniors, sophomores and freshmen had been sent home, the college seniors were kept isolated in dorms, and some had complained of a prison-like setting. Now, the seniors will be able to leave campus for drive-thru food and congregate in small groups per state guidelines.
Public Health Crippled
Local health departments run programs that treat chronic diseases such as diabetes. They also help prevent childhood lead poisoning and stem the spread of the flu, tuberculosis and rabies. A severe loss of property and sales tax revenue following a wave of business failures will likely cripple these health departments, said Adriane Casalotti, chief of government affairs with the National Association of County and City Health Officials, a nonprofit focused on public health.
After the 2008 recession, local health departments in the U.S. lost 23,000 positions as more than half experienced budget cuts. While it’s become popular to warn against placing economic concerns over health, Casalotti said that, on the front lines of public health, the two are inexorably linked. “What are you going to do when you have no tax base to pull from?” she asked.
Carol Moehrle, director of a public health department that serves five counties in northern Idaho, said her office lost about 40 of its 90 employees amid the last recession. The department had to cut a family planning program that provided birth control to women below the poverty line and a program that tested for and treated sexually transmitted diseases. She worries a depression will cause more harm.
“I honestly don’t think we could be much leaner and still be viable, which is a scary thing to think about,” Moehrle said.
Job-loss Mortality
Rises in unemployment during large recessions can set in motion a domino effect of reduced income, additional stress and unhealthy lifestyles. Those setbacks in income and health often mean people die earlier, said Till von Wachter, a University of California Los Angeles professor who researches the impact of job loss. Von Wachter said his research of past surges in unemployment suggests displaced workers could lose, on average, a year and a half of lifespan. If the jobless rate rises to 20%, this could translate into 48 million years of lost human life.
Von Wachter cites measures he believes could mitigate the effects of unemployment. The Coronavirus Aid, Relief, and Economic Security Act approved by the White House last week includes emergency loans to businesses and a short-time compensation program that could encourage employers to keep employees on the payroll.
Young People Suffer
Young adults entering the job market during the coronavirus suppression may pay an especially high price over the long term.
First-time job hunters seeking work during periods of high unemployment live shorter and unhealthier lives, research shows. An extended freeze of the economy could shorten the lifespan of 6.4 million Americans entering the job market by an average of about two years, said Hannes Schwandt, a health economics researcher at Northwestern University, who conducted the study with von Wachter. This would be 12.8 million years of life lost.
Thousands of college graduates will enter a job market at a time global business is frozen. Jason Gustave, a senior at William Paterson University in New Jersey who will be the first in his family to graduate from college, had a job in physical therapy lined up. Now his licensure exam is postponed and the earliest he could start work is September.
“It all depends on where the economy goes,” he said. “Is there a position still available?”
In the weeks ahead, a clearer picture of the disease’s devastation will come into focus, and governments and health specialists will base their fatality estimates on a stronger factual grounding.
As they do, some public health experts say, the government should weigh the costs of the suppression measures taken and consider recalibrating, if necessary.
Dr. Jay Bhattacharya, who researches health policy at Stanford University, said he worries governments worldwide have not yet fully considered the long term health impacts of the impending economic calamity. The coronavirus can kill, he said, but a global depression will, as well. Bhattacharya is among those urging government leaders to carefully consider the complete shutdown of businesses and schools.
“Depressions are deadly for people, poor people especially,” he said.
https://www.reuters.com/investigates/special-report/health-coronavirus-usa-cost/

A call to honesty in pandemic modeling

Recently there has been a proliferation of modeling work which has been used to make the point that if we can stay inside, practice extreme social distancing, and generally lock-down nonessential parts of society for several months, then many deaths from COVID-19 can be prevented.
For example, a new study by Christopher J.L. Murray at the University of Washington models hospital and ICU utilization and deaths over a 4 month period of mitigations, and estimates that “Total deaths” can be kept under 100,000.
Murray’s study estimates hospital and ICU utilization in addition to deaths.
Like other recent studies considering short-term mitigations, he estimates fewer than 100,000 deaths.
A similar story is told by a recent model developed by a group of researchers and publicized by Nicholas Kristof of the New York Times. Their basic message? Social distancing for 2 months instead of 2 weeks could dramatically drop the number of COVID-19 infections:
The model publicized by Nicholas Kristof presents a dramatic benefit from 2 months of social distancing instead of 2 weeks.
The same narrative appears in recent study in the Lancet, whose authors modeled the effects of mitigations continuing in Wuhan through the beginning of March or the beginning of April. In their findings, the authors write that continuing mitigations until the beginning of April instead of the beginning of March “reduced the median number of infections by more than 92% (IQR 66–97) and 24% (13–90) in mid-2020 and end-2020, respectively.”.

Hiding infections in the future is not the same as avoiding them

A keen figure-reader will notice something peculiar in Kristof’s figure. At the tail end of his “Social distancing for 2 months” scenario, there is an intriguing rise in the number of infections (could it be exponential?), right before the figure ends. That’s because of an inevitable feature of realistic models of epidemics; once transmission rates return to normal, the epidemic will proceed largely as it would have without mitigations, unless a significant fraction of the population is immune (either because they have recovered from the infection or because an effective vaccine has been developed), or the infectious agent has been completely eliminated, without risk of reintroduction. In the case of the model presented in Kristof’s article, assumptions about seasonality of the virus combined with the longer mitigation period simply push the epidemic outside the window they consider.
For example, in our work studying the possible effects of heterogeneous measures, we presented examples of epidemic trajectories for COVID-19 assuming no mitigations at all, or assuming extreme mitigations which are gradually lifted at 6 months, to resume normal levels at 1 year.
With no mitigations we see nearly 500,000 deaths relatively quickly.
With mitigations which let up between 6 months and a year we still see nearly 500,000 deaths, just later.
Unfortunately, extreme mitigation efforts which end (even gradually) reduce the number of deaths only by 1% or so; as the mitigation efforts let up, we still see a full-scale epidemic, since almost none of the population has developed immunity to the virus.
In the case of Kristof’s article, the epidemic model being employed is actually implemented in Javascript, and run — live — in a users web browser. This means that it is actually possible to hack their model to run past the end of October. In particular, we can look into the future, and see what happens in their model after October, assuming mitigations continue for 2 months. In particular, instead of the right-hand figure here:
Kristof’s original figure, with the effects of 2-months of mitigations shown on the right.
The truth for their Social distancing for 2 months scenario is this:
This is exactly the same model for “2 months of mitigations” from the Kristof column, but extended past October
Two months of mitigations have not improved the outcome of the epidemic in this model, it has just delayed its terrible effects. In fact, because of the role of weather in the model presented in the Kristof article, two months of mitigations actually results in 50% more infections and deaths than two weeks of mitigations, since it pushes the peak of the epidemic to the winter instead of the summer, whose warmer months this model assumes causes lower transmission rates.
The same thing plays out in other papers modeling a low number of infections or deaths from short-term suppression efforts. For example, Murray’s paper models 4 months of mitigations, but only models the epidemic over a 4 month period, ending in July. He concludes that less than 100,000 people will die in his model. But what happens in August? He obtains improvement in death rates in his model precisely because a small minority of the population becomes infected in his mitigation window. (In fact, because his approach is based on fitting a model to current data, it is unable to model a world in which transmission levels have returned to normal.) In fact, as soon as transmission levels increase, a large epidemic will follow, which he would detect if he did model the epidemic past 4 months. Similarly, in the Lancet study modeling mitigations in Wuhan, the only effect of delaying the end of mitigations is to delay the epidemic; infections are “reduced” in “mid-2020” and “end-2020”, but increased at later time-points.

For two months of containment to be better than two weeks of containment, the situation on the ground has to change

There is a simple truth behind the problems with these modeling conclusions. The duration of containment efforts does not matter, if transmission rates return to normal when they end, and mortality rates have not improved. This is simply because as long as a large majority of the population remains uninfected, lifting containment measures will lead to an epidemic almost as large as would happen without having mitigations in place at all.
This is not to say that there are not good reasons to use mitigations as a delay tactic. For example, we may hope to use the months we buy with containment measures to improve hospital capacity, in the hopes of achieving a reduction in the mortality rate. We might even wish to use these months just to consider our options as a society and formulate a strategy. But mitigations themselves are not saving lives in these scenarios; instead, it is what we do with the time that gives us an opportunity to improve the outcome of the epidemic.

What makes an honest model?

There can be value in modeling short-term effects of mitigations. For example, Murray’s study of ICU utilization over the next 4 months may have obvious relevance for planning in the short term — and his paper is clear that his model only models deaths over a 4 month period. But we take issue with models which study the effects of mitigations over a limited time-frame, when most of the impact of the epidemic would occur outside of that time-frame.
We should say that all the papers we quote here are clear about what they model, and none claimed explicitly to model the number of infections or deaths that would happen over the entire course of the epidemic. If one reads all of Kristof’s column, an honest disclaimer is eventually encountered:
But by this point, after figures with “total infections” labeled in bold have been tweeted to millions of followers, the model has already played its role in misleading the public. Moreover, the fixed time window they choose for their model — one of the only parameters of the model a user cannot tinker with in the app on Kristof’s column — means that users can’t discover this basic truth for themselves.
In particular, we suggest that no model whose purpose is to study the overall benefits of mitigations should end at a time-point before a steady-state is reached. This is not the same as saying that modelers must assume that the epidemic remains a threat until herd immunity is reached. Indeed, it is perfectly reasonable to model the effects of mitigation strategies if we assume that a vaccine will be available in 18 months, or that mortality 6 months from now could be reduced by new treatments, or that hospital capacity might be increased with the time bought by mitigations. But these are all assumptions that can and should be made explicit and quantitative in a model that attempts to estimate effects on overall mortality. Without making assumptions explicit, it is impossible to debate whether they are reasonable, or to estimate the sensitivity of the model’s conclusions.

Where we are now

Nations around the world are staring down a host of terrible options. Business-as-usual means overrun hospitals, and large numbers of preventable deaths. One or two years of suppression measures in wait for a vaccine means a global shutdown whose full ramifications will require input from experts across multiple domains to fully understand. The viability of middle roads, which might attempt to replace suppression efforts with contact tracing while allowing normal social and economic activity, is still debated by experts.
What should be absolutely clear is that hard decisions lie ahead, and that there are no easy answers. The team at Imperial, which recently released a new study currently serving as the basis for the U.K’s new efforts at containment, summarize it this way:
Regardless of which strategies various governments will eventually turn to in the fight against COVID-19, their success will hinge in large part on the cooperation of the public — maintaining effective suppression on a timescale of years, for example, would require extraordinary levels compliance from citizens. The public should not be misled by presenting false stories of hope to motivate behavior in the short-term. Public health depends on public trust. If we claim now that our models show that 2 months of mitigations will cut deaths by 90%, why will anyone believe us 2 months from now when the story has to change?