Common diabetes drug SGLT2i may trigger rare complications in COVID-19

 Diabetes is a known risk factor for morbidity and mortality related to COVID-19. In diabetes patients, rare but severe complications, like the potentially lethal condition diabetic ketoacidosis (DKA), can arise when illness or certain conditions prevent cells from receiving enough glucose to fuel their functioning. An uptick in a particular type of DKA called euDKA at Brigham and Women's Hospital during the COVID-19 pandemic has led researchers to hypothesize that diabetes patients on glucose-lowering drugs may be at increased risk for euDKA when they contract COVID-19. The observational case series was published in The American Association of Clinical Endocrinologists Clinical Case Reports.

EuDKA is a subset of the diabetes complication known as DKA, which occurs when the body's cells fail to absorb enough glucose and compensate by metabolizing fats instead, creating a build-up of acids called ketones. EuDKA differs from DKA in that it is characterized by lower blood sugar levels, making it more difficult to diagnose. The U.S. Food and Drug Administration has warned that the risk of DKA and euDKA may be increased for individuals who use a popular class of diabetes drugs called sodium-glucose cotransporter 2 inhibitors (SGLT2i), which function by releasing excess glucose in the urine. Underlying nearly all euDKA cases is a state of starvation that can be triggered by illnesses that cause vomiting, diarrhea, and loss of appetite and can be compounded by the diuretic effect of SGLT2i drugs.

Brigham researchers studied five unusual euDKA cases brought to the diabetes inpatient services within the span of two months, three of which occurred in one week, at the height of the pandemic in Boston in the spring of 2020. The five cases represented a markedly heightened incidence of euDKA compared to that of the previous two years, when inpatient services saw fewer than 10 euDKA cases. All five of the recent euDKA cases were observed in COVID-19 patients who were taking SGLT2i; three patients were discharged to rehabilitation facilities, one was discharged home, and one, a 52-year-old male with acute respiratory distress syndrome, died.

"We have the background knowledge of recognizing that SGLT2 inhibitors can cause DKA and euDKA," said corresponding author Naomi Fisher of the Division of Endocrinology, Diabetes, and Hypertension. "Our report reinforces that if patients are ill or have loss of appetite or are fasting, they should pause their medication and not resume until they are well and eating properly."

The authors of the study also suspect that COVID-19 may particularly exacerbate euDKA risks. When the virus infects a patient, it binds to cells on the pancreas that produce insulin and may exert a toxic effect on them. Studies of the earlier SARS-CoV-1 virus found that many infected patients had increased blood sugar. "It's been posited through other models that the virus may be preferentially destroying insulin-producing cells," Fisher said.

Moreover, the maladaptive inflammatory response associated with COVID-19, which produces high levels of immune-response-related proteins called cytokines, may increase DKA risks. "These high levels of cytokines are also seen in DKA, so these inflammatory pathways may be interacting," Fisher said. "It's speculative, but there may be some synergy between them."

Though these findings are observational, rather than the results of a randomized controlled trial, similar reports of heightened euDKA incidence have emerged from other institutions. The authors encourage patients and physicians to halt SGLT2i-use in the event of illness, which is already standard practice for the most common diabetes drug, metformin.

"Patients should continue to monitor their blood sugar, and if the illness is prolonged or if their blood sugar is very high, they can speak to their doctor about other forms of therapy," Fisher said. "But often it's a very short course off of the drug. We're hopeful that with widespread patient and physician education, we will not see another cluster of euDKA cases amid the next surge in COVID-19 infections."

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There was no funding organization for this study.

Paper cited: Vitale, RJ, Valtis, YK, et al. "Euglycemic Diabetic Ketoacidosis with Covid-19 Infection in Patients with Type 2 Diabetes Taking SGLT2 Inhibitors" The American Association of Clinical Endocrinologists Clinical Case Reports DOI:10.4158/ACCR-2020-0551

https://www.eurekalert.org/pub_releases/2020-12/bawh-cdd122420.php

In pandemic, new processes provide care to trauma patients, keep providers safe

 As the COVID-19 pandemic emerged, trauma centers faced unprecedented obstacles to providing care for injured patients. A look at steps taken by trauma centers in response to COVID-19 is provided by a survey in the January/February Journal for Healthcare Quality (JHQ), the peer-reviewed journal of the National Association for Healthcare Quality (NAHQ). The journal is published in the Lippincott portfolio by Wolters Kluwer.

Trauma centers introduced new processes to optimize use of personal protective equipment (PPE), ICU beds, ventilators, and other limited resources, according to the report by David Bar-Or, MD, of ION Research, Englewood, Colo., and colleagues. "This information will be of value as trauma centers continue to respond and adapt to the pandemic, focusing on meeting the need for critical trauma services while protecting the health of trauma care teams," Dr. Bar-Or comments.

New processes to provide care at U.S. trauma centers, despite scarce resources

As the pandemic took hold in the spring of 2020, hospitals struggled to provide care not only for patients with COVID-19, but also for other groups of patients in need of care that couldn't be delayed. While the American College of Surgeons Committee on Trauma provided initial guidance on maintaining trauma center access, it was up to individual trauma centers to work out detailed processes for providing patient care.

"Trauma centers have a unique situation in that admissions for traumatic injuries are not scheduled and therefore cannot be cancelled or postponed," Dr. Bar-Or and colleagues point out. "Accordingly, they must prepare for an influx of patients with acute respiratory symptoms and continue care for patients with traumatic injuries."

To gain insights into how they met these challenges, Dr. Bar-Or and colleagues surveyed directors of six level I trauma centers in four states: Colorado, Kansas, Missouri, and Texas. The responses provided insights into changes in key areas, including:

• N-95 respirators. Trauma centers faced shortages of essential N-95 respirator masks. Four of the six trauma centers surveyed reported reusing respirators after employing various methods of sanitization or sterilization. At some centers, trauma team members received only one mask per day or per week.
• PPE. Most trauma centers clustered patient contacts, with the aim of minimizing need for personal protective equipment (masks, gowns, respirators, etc). Four hospitals increased PPE use for all patients on arrival, while two provided PPE to symptomatic patients. One hospital had to request PPE from local government due to regional shortages.
• ICU beds. Five hospitals added ICU beds, while three designated a specific ICU for COVID-19 patients. All hospitals isolated COVID-19 patients in negative pressure rooms. In some cases, rooms or entire floors were converted to negative pressure.
• Mechanical ventilation. Two trauma centers created ventilator allocation protocols. Three centers reported daily tracking of ventilator use, while three requested additional ventilators in anticipation of a surge. The trauma centers reported varying changes to intubation protocols, and in the use of noninvasive ventilation approaches (CPAP or BiPAP).

The survey was conducted in the latter half of May 2020, as U.S. Coronavirus deaths passed the 100,000 mark. At that time, none of the trauma centers had experienced an overwhelming surge of COVID-19 patients. "This could be due to the actions taken to allow for additional treatment beds," the researchers write.

The survey provides a snapshot of how trauma teams and hospitals met the need for essential trauma care through the first months of the Coronavirus crisis. "This study summarized the processes that participating trauma centers developed to protect the trauma patient and trauma care providers while providing optimal trauma care for patients--without specific guidance from professional organizations," Dr. Bar-Or and colleagues conclude. "This was possible even when faced with scarce resources."

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Click here to read "Processes for Trauma Care at Six Level I Trauma Centers During the COVID-19 Pandemic." DOI: 10.1097/JHQ.0000000000000285

https://www.eurekalert.org/pub_releases/2020-12/wkh-hdt123020.php

Existing chemo med pralatrexate outperforms remdesivir against SARS-CoV-2

 A novel computational drug screening strategy combined with lab experiments suggest that pralatrexate, a chemotherapy medication originally developed to treat lymphoma, could potentially be repurposed to treat Covid-19. Haiping Zhang of the Shenzhen Institutes of Advanced Technology in Shenzhen, China, and colleagues present these findings in the open-access journal PLOS Computational Biology.

With the Covid-19 pandemic causing illness and death worldwide, better treatments are urgently needed. One shortcut could be to repurpose existing drugs that were originally developed to treat other conditions. Computational methods can help identify such drugs by simulating how different drugs would interact with SARS-CoV-2, the virus that causes Covid-19.

To aid virtual screening of existing drugs, Zhang and colleagues combined multiple computational techniques that simulate drug-virus interactions from different, complimentary perspectives. They used this hybrid approach to screen 1,906 existing drugs for their potential ability to inhibit replication of SARS-CoV-2 by targeting a viral protein called RNA-dependent RNA polymerase (RdRP).

The novel screening approach identified four promising drugs, which were then tested against SARS-CoV-2 in lab experiments. Two of the drugs, pralatrexate and azithromycin, successfully inhibited replication of the virus. Further lab experiments showed that pralatrexate more strongly inhibited viral replication than did remdesivir, a drug that is currently used to treat some Covid-19 patients.

These findings suggest that pralatrexate could potentially be repurposed to treat Covid-19. However, this chemotherapy drug can prompt significant side effects and is used for people with terminal lymphoma, so immediate use for Covid-19 patients is not guaranteed. Still, the findings support the use of the new screening strategy to identify drugs that could be repurposed.

"We have demonstrated the value of our novel hybrid approach that combines deep-learning technologies with more traditional simulations of molecular dynamics," Zhang says. He and his colleagues are now developing additional computational methods for generating novel molecular structures that could be developed into new drugs to treat Covid-19.

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Peer-reviewed; Simulation/modelling

Citation: Zhang H, Yang Y, Li J, Wang M, Saravanan KM, Wei J, et al. (2020) A novel virtual screening procedure identifies Pralatrexate as inhibitor of SARS-CoV-2 RdRp and it reduces viral replication in vitro. PLoS Comput Biol 16(12): e1008489.

https://doi.org/10.1371/journal.pcbi.1008489

Funding: This work was partly supported by the National Key Research and Development Program of China under Grant No. 2018YFB0204403 (Y.W.) and 2019YFA0906100 (X.W.); Strategic Priority CAS Project XDB38000000 to Y.W., National Science and Technology Major Project under Grant No. 2018ZX10101004 (Y.Y.), National Science Foundation of China under Grant no. U1813203 (Y.W.); the National Natural Youth Science Foundation of China (Grant no. 31601028: Y.P.); the Shenzhen Basic Research Fund under Grant no. JCYJ20190807170801656 (J.L.), JCYJ20180507182818013 (Y.W.), JCYJ20170413093358429 (Y.W.), and the SIAT Innovation Program for Excellent Young Researchers (J.L.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1008489

HHS Overturns Plan To Impose $14,000 Fee On Distilleries That Made Hand Sanitizer

 Health officials this week overturned fees that were being imposed on distilleries that made hand sanitizer early last year amid the COVID-19 pandemic.

Two different fees, including a $14,000 one, were included in the COVID 19 relief package that was signed into law in March. That package made distilleries that produced hand sanitizer “over-the-counter drug monograph facilities” and forced them to pay fees.

COVID-19 is the disease caused by the CCP (Chinese Communist Party) virus. Distilleries made hand sanitizer because there was a nationwide shortage of the product last year.

The fees were due on Feb. 12. The Food and Drug Administration alerted distilleries this week that the fees needed to be paid. In a public notice, the administration noted it was authorized to collect fees by the CARES Act.

However, a Health and Human Services spokesperson said Thursday that the fees are being reversed.

“Small businesses who stepped up to fight COVID-19 should be applauded by their government, not taxed for doing so,” Brian Harrison, chief of staff for the agency, said in a statement.

“I’m pleased to announce we have directed FDA to cease enforcement of these arbitrary, surprise user fees. Happy New Year, distilleries, and cheers to you for helping keep us safe!”

HHS lawyers found that the fees were issued in a manner that has the force and effect of a legislative rule, which only the HHS secretary has the authority to issue.

The Distilled Spirits Council had reacted to the fees with surprise, issuing a press released urging the Food and Drug Administration to waive them for hundreds of distillers who helped by making hand sanitizer amid the pandemic.

“This incredibly frustrating news comes as a complete shock to the more than 800 distilleries across the country that came to the aid of their local communities and first responders. This unexpected fee serves to punish already struggling distilleries who jumped in at a time of need to do the right thing,” said Distilled Spirits Council President and CEO Chris Swonger in a statement.

“Everyone was totally blindsided by FDA’s announcement,” added Phil McDaniel, CEO of St. Augustine Distillery.

In a statement after the rollback of the fees, Swonger said the move “is such a relief to hundreds of distillers.”

“We want to thank HHS leadership for quickly intervening and protecting distillers from these unwarranted fees,” he said.

“Distillers were proud to help make hand sanitizer for their communities and first responders during their time of need.”

https://www.zerohedge.com/political/hhs-overturns-plan-impose-14000-fee-distilleries-made-hand-sanitizer 

Hospitals To Publish Secret Prices On Over 300 Procedures For 1st Time

 President Trump's health-care policy ambitions didn't receive much attention from the mainstream media, but as we head into the new year, some of his market-based reforms are starting to become reality.

One of the most important is a directive requiring the nation's biggest hospital chains to publish the rates they've agreed to charge various insurers. As WSJ explains, after a failed attempt at an appeal, the major hospital operators are saying they will comply with the new rules and make their prices public starting on Friday.

Suddenly, America's hospital operators, a $1.2 trillion industry comprising some 6% of the country's economy, will be subjected to more transparency than they've seen in decades. And the Trump Administration policy wonks he pushed the idea are hoping that good ol' fashioned market dynamics will kick in, and help lower prices across the board.

Per WSJ, the nation's largest hospital chains, including publicly traded giants HCA Healthcare, Universal Health Services and Community Health Systems, and national nonprofit chains CommonSpirit Health and Ascension, are planing to comply with new requirements to post pricing. Tenet Healthcare declined to comment.

Within a week, hospitals will disclose prices for 300 common procedures.

This is how the system has worked for years: Hospital pricing is negotiated confidentially between hospitals and the employer groups and insurance companies that pay for care.

Many criticized this system for obscuring market rates and helping drive up the cost of health insurance premiums paid by employers and workers. Rising hospital prices accounted for about one-fifth of the nation’s health spending growth over the last 50 years.

While groups like the American Hospital Association insist that their members have responsibly shared price information related to health-care premiums and medical bills, others insist that they were long left in the dark about the potentially wide disparities charged among hospitals for the same services.

Hilariously, the AHA has claimed that the publishing of prices would "confuse" patients. Now that the issue has been settled, the organization's general counsel tells WSJ: “The AHA continues to believe that the disclosure of privately negotiated rates does nothing to help patients understand what they will actually pay for treatment and will create widespread confusion for them.”

A wave of consolidation in the hospital space has reportedly caused price growth to accelerate, as the more dominant players exert their newfound market and pricing power.

Economists who spoke with WSJ said it's not clear how this transparency will impact the market.

Michael McWilliams, a Harvard University professor of health-care policy, argues that the transparency won't do much to change pricing: "So we should not believe that we can fix health-care markets simply by providing more information to consumers. There are many reasons why health-care markets do not function well."

But for better or worse, we will learn soon enough.

https://www.zerohedge.com/political/americas-hospitals-prepare-publish-long-secret-prices-charged-insurers

Caution urged in using remdesivir to treat COVID-19

 While the world has its eyes on vaccines to stop the spread of coronavirus, therapeutics are still necessary to treat hospitalized patients. One of these treatments, remdesivir, is the first and only antiviral agent of its kind that the U.S. Food and Drug Administration (FDA) has approved so far for COVID-19.

Research at the University of Cincinnati, however, contends that this antiviral drug is being used too indiscriminately when treating patients hospitalized with the virus. The study is published in the journal Fundamental & Clinical Pharmacology.

The FDA approved remdesivir, marketed as Veklury, for emergency use authorization in May 2020 to treat COVID-19 and granted full approval for treatment in October 2020. The World Health Organization came out in November 2020 with a conditional recommendation advising against its use entirely citing: "More research is needed, especially to provide higher certainty of evidence for specific groups of patients."

In the UC study, lead author Bingfang Yan, a pharmaceutical scientist, and his UC graduate students Yue Shen and William Eades, found that the drug permanently stops the activity of an enzyme called CES-2, which is found in the intestine, liver and kidney and is needed for the breakdown of many medications.

"This enzyme normally breaks down and activates medicines in certain antivirals or inactivates other medicines such in certain anticoagulants," says Yan, professor at the James L. Winkle College of Pharmacy. On the other hand, he says this breakdown increases the toxicity of many more medications such as with heart medicines and anticancer drugs.

An antiviral is a drug against viruses and an anticoagulant is a drug that hinders the clotting of blood.What further complicates the issue, Yan says, is that when delivered through an IV, remdesivir does not treat the virus unless the body has additional specific enzymes, which are not found in all patients. It can also cause other antiviral drugs, such as those used for HIV/AIDS and hepatitis C, to not work properly.

Remdesivir is only administered through the veins in a hospital setting, with the FDA typically recommending a dose of once a day, for approximately 10 days, and "intravenous injection of remdesivir can cause safety concerns because of high initial concentrations of the drug in the system," says Yan, noting, "If physicians use it, they have to use it with caution."

He adds, "Clearly, the treatment should be used for the right patients and in the proper dosages with care when used in combination with other medications."

Explore further

Gilead Sciences reports almost $900 mn in Q3 remdesivir sales

More information: 

Yue Shen et al, Remdesivir potently inhibits carboxylesterase‐2 through covalent modifications: signifying strong drug‐drug interactions, Fundamental & Clinical Pharmacology (2020). DOI: 10.1111/fcp.12643

https://medicalxpress.com/news/2020-12-urges-caution-remdesivir-covid-.html

Long lines as Florida's COVID vaccination drive picks up pace

 The lines are endless and hospital telephones are ringing off the hook since coronavirus vaccines became available this week for the elderly in retiree-rich Florida.

The state government gave the green light Monday for inoculating those aged 65 and above—a group that makes up nearly 20 percent of the Sunshine State's population, the largest such proportion in America.

So ever since, it has been mayhem, as tens of thousands try to get a shot they hope will protect them against the potentially deadly COVID-19.

Governor Ron DeSantis has asked for patience, admitting that at least for now, there are not enough doses for every elderly Floridian.

"The COVID vaccine supply is limited," he told a press conference on Wednesday in a retirement community in Palm Beach.

"We don't have enough vaccine on hand for all four million-plus senior citizens. We will get there."

The Jackson Health System said that this week, it hopes to vaccinate 10,000 of its 65-plus patients and individuals at high risk due to pre-existing conditions. Next week, it will help patients outside its system.

It kicked off its campaign with a few local celebrities getting the jab—musician Emilio Estefan (husband of Gloria), 67, and former Miami Dolphins player Nat Moore, who is 69.

Estefan defended the need for people to get inoculated, amid ongoing speculation about how effective it is.

"I think there's a lot of misinformation out there," Estefan told reporters at the headquarters of the Jackson Health System, the largest hospital network in Miami.

North of Miami, in Fort Lauderdale, Broward Health got such a flood of calls that it said its appointments for vaccinations are now filled up until February.

The Broward County webpage for making a vaccination appointment has been down since Wednesday.

Things are just as frantic in central Florida: in Orange County, which includes Orlando, home to Disney World, officials said they have scheduled 30,000 vaccinations and can make no more appointments for now.

'I can't wait'

So far, more than 175,000 people have received their shots, according to the state health department.

But for some, after nearly a year of various lockdown restrictions, the wait feels unbearably long.

"I can't wait to see my grandkids. I can't wait to hug those little guys. It's just been so long," Candice Seltzer, a retiree who has been vaccinated, told CNN.

Since vaccines were first distributed in mid-December, from Pfizer-BioNTech and then from Moderna, the majority of doses went to health care workers, and nursing home residents and staff.

Last week, DeSantis extended the campaign to include everyone aged 65 and above, and patients with serious health complications.

So far, Florida has recorded more than 1.3 million coronavirus cases and more than 21,500 deaths. It has recently been notching up as many cases each day as it did at its previous worst moment of the pandemic, in July.

https://medicalxpress.com/news/2021-01-lines-florida-covid-vaccination-pace.html