Cigna: COVID-19 leads to deferred ped care for conditions like epilepsy, asthma

COVID-19 is leading many parents to defer acute care for their children, new data from Cigna show.
Building on an analysis released in April that examined adults pushing off acute needs amid the pandemic, the insurer released a second study that tracks those trends in a set of six potentially serious conditions: acute appendicitis, diabetes, sickle cell, feeding difficulties or failure to thrive, epilepsy and seizure, and asthma.
Based on claims data for 2.5 million children covered in Cigna’s commercial plans, the researchers found that overall hospitalization rates per 100,000 members were down by 30.8% in March and April 2020 compared to March and April of 2019.

The largest decline was for asthma, where the hospitalization rate decreased by 68.7%.
“The reason we’re trying to highlight the data is to surface the fact that this is not just a phenomenon for adults,” Saif Rathore, M.D., head of data and analytic innovation at Cigna and one of the report’s authors, told Fierce Healthcare.

Hospitalization rates were down across all the conditions included in the analysis, with declines of 47.8% for epilepsy and seizure and 37.2% for feeding difficulties or failure to thrive. Hospitalization rates for sickle cell were down by 35.5% in March and April 2020 compared to the same months in 2019.
Hospitalization rates for diabetes were down by 23.2%, and rates for acute appendicitis were down by 17.2%, according to the study.
The findings track with Cigna’s previous study, which found large declines in hospitalization rates among adults for seven conditions including appendicitis, atrial fibrillation and transient ischemic attacks, or “mini-strokes.”
Glen Stettin, M.D., senior vice president and chief innovation officer at Express Scripts and another of the report’s authors, told Fierce Healthcare that it is important to consider that the conditions included in the study can vary in severity quite significantly.
He cautioned that though the declines are dramatic, it’s not likely that large numbers of parents are ignoring their children’s severe asthma attacks out of fear of contracting COVID-19.

“While hospitalizations do occur, it may very well be that the more mild cases or the cases that ultimately would have been diagnosed as something else are the ones that are missing,” Stettin said.
For parents who may be leery at the idea of taking their children to the hospital in the middle of a pandemic, he said that in many cases with these conditions, barring a severe emergency, there’s time to call ahead to the emergency department or to speak with the child’s pediatrician to get their perspective.
Rathore said the message in the latest data is similar to the previous study: Don’t put off a potentially serious need because of COVID-19.
Parents should also make sure that they’re wearing protective equipment, including a mask, if they do go to the hospital and give their children and idea of how the trip may be different from a typical visit to the doctor. Young children, for example, may find the masked clinical staff scary, Stettin said.
“Give them a sense of what they might expect there,” he said.
https://www.fiercehealthcare.com/payer/cigna-covid-19-leading-to-deferred-pediatric-care-for-conditions-like-epilepsy-asthma

Trump administration pushes for healthcare facilities to reopen

Healthcare facilities in states that have seen enough of a decline in COVID-19 cases to reach the Phase II criteria for reopening their economies should begin offering nonemergent, non-COVID-19 care, the Trump administration said Monday.
According to new guidance released by the Centers for Medicare & Medicaid Services (CMS), even as those healthcare facilities open access they should continue taking precautions to prevent the spread of the virus and optimize telehealth services to reduce the need for in-person services. Patients at higher risk for severe COVID-19 illness should continue to be advised to shelter in place.
Facilities should also ensure they have the ability to quickly respond to a surge in COVID-19 cases, if necessary.

“Those needing operations, vaccinations, procedures, preventive care, or evaluation for chronic conditions should feel confident seeking in-person care when recommended by their provider,” said CMS Administrator Seema Verma in a statement.
Health systems and physicians practices closed their doors to elective procedures and nonemergent care in the midst of shelter-in-place orders due to the COVID-19 pandemic. Since mid-April when CMS issued its Phase 1 recommendations, healthcare facilities have begun slowly testing the waters by reopening elective procedures on a state-by-state basis. Last month, CMS issued further recommendations to nursing homes telling them they should be among the last to reopen.

The guidance released Monday covered a range of topics to ensure patient and clinician safety including facility considerations, testing and sanitation protocols, personal protective equipment and supplies, and workforce availability. When it comes to the reopening, CMS advises health facilities to continue to follow federal, state and local orders as well as Centers for Disease Control and Prevention recommendations.
A new patient guide was also released Monday, advising patients to continue utilizing telehealth but not to feel unsafe if they need to seek in-person care.
https://www.fiercehealthcare.com/hospitals/trump-administration-releases-reopening-guide-for-healthcare-facilities

White House works to move stalled airline contact tracing plan

The White House wants a plan in place by Sept. 1 for airlines to collect contact tracing information from U.S.-bound international passengers, but will not immediately implement a Centers for Disease Control and Prevention (CDC) proposal, three people briefed on the matter said on Wednesday.

The Trump administration convened a high-level White House meeting on Tuesday that included Homeland Security Secretary Chad Wolf, Transportation Secretary Elaine Chao, and other senior officials. The White House tasked a interagency working group with adopting an interim solution by June 30 and ahead of any potential coronavirus second wave.
A debate over how data should be collected from passengers in order to quickly identify and contact people exposed to the coronavirus has dragged on for months without resolution.
In February, the CDC issued an internal final rule that aimed to require airlines to collect five contact data elements from international passengers and electronically submit them to Customs and Border Protection to facilitate contact tracing.

That has not been enforced. Airlines strongly protested, saying it was unworkable. They argued they could not provide such information, especially from passengers booking tickets through third-party websites.
Airline groups instead backed the setting up of a website and mobile application for passengers to send their contact information directly to the CDC.
The interagency group will work with technical experts at industry association Airlines for America, the CDC and others on an interim solution that could take effect by Sept. 1 and will consider the airline proposal, the sources said.
If no workable plan is identified, the administration will likely move ahead with the existing CDC plan, sources said.

Airlines for America, a group representing American Airlines, United Airlines, Delta Air Lines and others, said earlier this week airlines “strongly support a contract tracing solution that will provide the most secure data to the U.S. government in a timely and efficient manner.”
https://www.reuters.com/article/us-health-coronavirus-airlines-tracing/white-house-works-to-move-stalled-airline-contact-tracing-plan-sources-idUSKBN23H3J7

From Reinfection to Persistent Positives: COVID Testing FAQs Answered

Only months into the COVID-19 pandemic, confusion remains on the topic of testing for SARS-CoV-2, with many physicians grappling with similar types of questions.
“My patient is still positive for COVID-19 a month and a half later. Why?”
“Has my patient been reinfected, or is this just delayed recovery?”
Most of these questions revolve around what these tests are looking for, the nuances of interpreting test results, and persistent positive results in asymptomatic patients. Medscape spoke with Paul Auwaerter, MD, to get the answers to our readers’ frequently asked questions about coronavirus testing. This interview has been edited for length and clarity.

What types of diagnostic and serologic/antibody tests are currently available, and how are they different? How reliable is each type of test?

The most commonly available tests are the molecular assays that use PCR technology to detect parts of the novel coronavirus RNA. Samples of the upper respiratory tract are taken using a swab that is inserted into the nostril to the nasopharynx. Some labs have also validated tests that may use swabs of the oropharynx, sputum, or even saliva. A positive result is highly accurate, indicating presence of SARS-CoV-2 RNA.
The number of false-negative results for these tests is not well known. One analysis of seven studies suggested that the rate may be approximately 20%, but it depends on when the sample is acquired relative to the timing of illness. For patients with a high suspicion of COVID-19, a negative test should not rule out the infection. There is also variability among manufacturers and in-house assays, as well as issues related to whether specimens were procured properly.

Serological tests determine if antibodies thought to be specific to the novel coronavirus are detected. Studies suggest that antibodies are starting to be produced about 7 days after onset of symptoms, and that by day 14-28, most patients have developed detectable antibodies. What is not yet well understood is whether these antibodies offer protective immunity and whether they genuinely reflect a history of having had the infection in someone who has not had symptoms of COVID-19.
The Centers for Disease Control and Prevention uses purified spike protein of the novel coronavirus in an ELISA [enzyme-linked immunosorbent] assay. They feel this test offers a 99% specificity and 96% sensitivity. Other manufacturers may cite accuracy results, but they may not have been validated on a large number of clinical samples.

The CDC urges that only tests approved under the FDA Emergency Use Act (EUA) be used. CDC guidance suggests only testing people who have a reasonable probability of having had COVID-19 or using two different serological tests to help minimize the chance of false positives. The serological tests are most helpful in securing a late diagnosis of COVID-19 when molecular swab tests may be negative.

Does a positive COVID-19 PCR test result indicate that the individual is infectious?

Because the COVID-19 PCR tests only detect a fragment of the viral RNA, a positive test does not mean that infectious virus is present. In one small study of people who had mild or asymptomatic novel coronavirus infection, virus was not cultured from the upper airway after day 10 of illness, but detection of viral carriage by the molecular assay has been seen more than 80 days after the initial infection.
A study carried out by the Korean CDC (KCDC) examined patients who had been hospitalized for COVID-19 but subsequently tested negative by PCR testing and were discharged home. Of 285 people who later retested positive, no instances of infection were found in 790 household family members and other close contacts. This strongly suggests that when there is detection of viral RNA at this stage, people are no longer infectious. The KCDC, therefore, now no longer requires isolation in such cases.
In general, people who have had the infection for 10 to 14 days are probably no longer infectious; however, this is not yet fully understood for all populations, such as immunosuppressed people or those who are severely ill in hospital.

There are reports that this virus is unable to be cultured after day 8 or 9 of infection. Is it because the material is bound to neutralizing antibodies, or only fragments are left?

The adaptive immune system is thought to play a major role in viral clearance. Production of neutralizing antibodies plays a role, but they are probably not the only players. T-cell responses, such as CD8 (cytotoxic T cells) and CD4, help clear infected cells or coordinate immune responses. Robust generation of T-cell epitopes to viral proteins highly suggests that T cells play a significant role in dealing with this pathogen. The detection of viral RNA after day 10 in people who are less ill doesn’t yield virus by culture, suggesting that only fragments of the RNA are found or that they are produced in cells but not yielding productive, intact virus.

Can the available tests differentiate between SARS-CoV-2 and other coronaviruses that may be similar? How would that affect test accuracy and reliability?

Commercially available multiplex PCR panels for respiratory viruses, such as the BioFire^®, do not detect SARS-CoV-2. Many companies have in development new panels that incorporate the novel coronavirus, but they are not yet FDA-approved.
SARS-CoV-2 PCR tests do not pick up routine respiratory coronaviruses (HCoV-OC43, HCoV-229E, HCoV-NL63, and HCoV-HKU1) or MERS-CoV.
Commercially available antibody tests have shown significant variability. Moreover, even if a test is 96% to 98% specific, if the pretest probability of COVID-19 is < 5%, it is more likely that the result is a false-positive than a true positive — and one of the key reasons mass serologic testing is not recommended, as it may give people a false sense of security.

Causes for false-positives include cross-reactivity with other coronaviruses, generation of antibodies due to other mechanisms, or poor test performance.

An Annals of Internal Medicine study describes how false-negative rates vary across the disease course, from 100% 4 days before symptom onset to 20% 3 days after symptom onset. With such high variability, how should doctors interpret results? What if a patient misses the window during which the false-negative rate is lowest?

If there is high clinical suspicion for COVID-19, repeat testing is suggested. If the patient has evaluation later in the illness, perhaps in the second or third week, serologic testing may help yield an answer if PCR testing on respiratory specimens is negative.

Is there a difference in false-negative rates in asymptomatic (lower viral load) vs symptomatic patients (higher viral load)?

There are probably more false-negatives in asymptomatic people with this coronavirus; however, no large definitive studies have been carried out yet that look at both seroconversion and respiratory PCR sample assessments.

The CDC urges that only tests approved under the FDA Emergency Use Act (EUA) be used. CDC guidance suggests only testing people who have a reasonable probability of having had COVID-19 or using two different serological tests to help minimize the chance of false positives. The serological tests are most helpful in securing a late diagnosis of COVID-19 when molecular swab tests may be negative.

Does a positive COVID-19 PCR test result indicate that the individual is infectious?

Because the COVID-19 PCR tests only detect a fragment of the viral RNA, a positive test does not mean that infectious virus is present. In one small study of people who had mild or asymptomatic novel coronavirus infection, virus was not cultured from the upper airway after day 10 of illness, but detection of viral carriage by the molecular assay has been seen more than 80 days after the initial infection.
A study carried out by the Korean CDC (KCDC) examined patients who had been hospitalized for COVID-19 but subsequently tested negative by PCR testing and were discharged home. Of 285 people who later retested positive, no instances of infection were found in 790 household family members and other close contacts. This strongly suggests that when there is detection of viral RNA at this stage, people are no longer infectious. The KCDC, therefore, now no longer requires isolation in such cases.
In general, people who have had the infection for 10 to 14 days are probably no longer infectious; however, this is not yet fully understood for all populations, such as immunosuppressed people or those who are severely ill in hospital.

There are reports that this virus is unable to be cultured after day 8 or 9 of infection. Is it because the material is bound to neutralizing antibodies, or only fragments are left?

The adaptive immune system is thought to play a major role in viral clearance. Production of neutralizing antibodies plays a role, but they are probably not the only players. T-cell responses, such as CD8 (cytotoxic T cells) and CD4, help clear infected cells or coordinate immune responses. Robust generation of T-cell epitopes to viral proteins highly suggests that T cells play a significant role in dealing with this pathogen. The detection of viral RNA after day 10 in people who are less ill doesn’t yield virus by culture, suggesting that only fragments of the RNA are found or that they are produced in cells but not yielding productive, intact virus.

Can the available tests differentiate between SARS-CoV-2 and other coronaviruses that may be similar? How would that affect test accuracy and reliability?

Commercially available multiplex PCR panels for respiratory viruses, such as the BioFire^®, do not detect SARS-CoV-2. Many companies have in development new panels that incorporate the novel coronavirus, but they are not yet FDA-approved.
SARS-CoV-2 PCR tests do not pick up routine respiratory coronaviruses (HCoV-OC43, HCoV-229E, HCoV-NL63, and HCoV-HKU1) or MERS-CoV.
Commercially available antibody tests have shown significant variability. Moreover, even if a test is 96% to 98% specific, if the pretest probability of COVID-19 is < 5%, it is more likely that the result is a false-positive than a true positive — and one of the key reasons mass serologic testing is not recommended, as it may give people a false sense of security.

Causes for false-positives include cross-reactivity with other coronaviruses, generation of antibodies due to other mechanisms, or poor test performance.

An Annals of Internal Medicine study describes how false-negative rates vary across the disease course, from 100% 4 days before symptom onset to 20% 3 days after symptom onset. With such high variability, how should doctors interpret results? What if a patient misses the window during which the false-negative rate is lowest?

If there is high clinical suspicion for COVID-19, repeat testing is suggested. If the patient has evaluation later in the illness, perhaps in the second or third week, serologic testing may help yield an answer if PCR testing on respiratory specimens is negative.

Is there a difference in false-negative rates in asymptomatic (lower viral load) vs symptomatic patients (higher viral load)?

There are probably more false-negatives in asymptomatic people with this coronavirus; however, no large definitive studies have been carried out yet that look at both seroconversion and respiratory PCR sample assessments.
https://www.medscape.com/viewarticle/932105#vp_1

Amazon puts one year moratorium on police use of its facial recognition tech

Amazon on Wednesday announced that it is placing a one year moratorium on police use of its facial recognition technology, Rekognition.
“We’ve advocated that governments should put in place stronger regulations to govern the ethical use of facial recognition technology, and in recent days, Congress appears ready to take on this challenge,” the company wrote in a blog post.
“We hope this one-year moratorium might give Congress enough time to implement appropriate rules, and we stand ready to help if requested.”

Amazon said it will still allow organizations to use Rekognition for work tracking human trafficking victims and finding missing children.
The company’s decision to block police use of its facial recognition comes amid concern from activists and civil rights groups that law enforcement may be using the technology to identify individuals participating in the anti-police brutality demonstrations that have erupted across the nation since the death of George Floyd.
It also comes on the heels of IBM ending its facial recognition business.

As of Monday, IBM will no longer release software packages or develop, create, research or sell facial recognition software itself.
Even before the protests, facial recognition technology has been criticized as a tool for unwarranted surveillance, while multiple studies have found that it tends to misidentify women and people of color at comparatively higher rates than men and white people.
The National Institute of Standards and Technology, a federal agency within the Department of Commerce, released an expansive study in December finding that the majority of facial recognition systems have “demographic differentials” that can worsen their accuracy based on a person’s age, gender or race.
https://thehill.com/policy/technology/502160-amazon-puts-one-year-moratorium-on-police-use-of-its-facial-recognition

With Adult Acne, You Are What You Eat

Dietary habits — particularly fats and carbs — were associated with risk of acne in adults, a French study found.
Looking at daily dietary records of nearly 25,000 individuals, consumption of one portion of fatty and sugary food per day was tied to a 54% higher odds of currently suffering from acne (adjusted odds ratio 1.54, 95% CI 1.09-2.16), Laetitia Penso, MSc, of the University of Paris in France, and colleagues reported in JAMA Dermatology.

In particular, drinking one glass of a sugary beverage a day was tied to moderately higher odds of current acne (aOR 1.18, 95% CI 1.01-1.38). And similarly, each daily glass of milk was tied to a bump in risk of current acne (aOR 1.12, 95% CI 1.00-1.25).
And just generally adhering to an “unhealthy” diet rich in energy-dense foods was associated with higher odds of currently suffering from acne (aOR 1.13, 95% CI 1.05-1.18).
These associations were dose-dependent as well:

• 5 glasses of milk/1 liter: aOR 1.76 (95% CI 1.00-3.05)
• 5 glasses of sugary beverages/1 liter: aOR 2.29 (95% CI 1.05-5.00)
• Complete meal of fatty and sugary products: aOR 8.38 (95% CI 1.54-47.02)

As for other notable offenders, consumption of carbohydrates (aOR 1.43, 95% CI 1.06-1.93), as well as saturated fatty acid intake (aOR 3.90, 95% CI 1.02-15.00), were also both tied to a significantly higher odds of currently having acne.
“Our results may support the hypothesis that the Western diet (rich in animal products and fatty and sugary foods) is associated with the presence of acne in adulthood,” Penso’s group wrote.

Part of the ongoing NutriNet-Santé study, this cross-sectional analysis pooled data on 24,452 adults in France who completed an online self-questionnaire including their experiences with acne in the past and present. Among these individuals, nearly half reported either having suffered from past or current acne. About 60% of this cohort was comprised of adults age 55 and older.
Participants also completed dietary intake assessments, which consisted of a series of 24-hour dietary recalls, each 6 months apart. Only individuals who completed at least three dietary recalls were included in the analysis.
Data were collected on average daily intake across several food groups, including fruit, vegetables, meat, fish, milk, dark chocolate, milk chocolate, refined cereals, snacks, and fast foods, as well as fatty and sugary products, in addition to nutrient intake of vitamins, zinc, fibers, carbohydrates, lipids, proteins, and saturated fatty acids.
The study’s findings don’t come as much of a surprise, said John Barbieri, MD, MBA, of the University of Pennsylvania in Philadelphia, in an accompanying editorial. “These findings are largely in line with prior observational studies suggesting an association between milk consumption and high glycemic-load diet with acne,” he wrote.

However, he pointed out that the study failed to take note of milkfat percentage or whey protein consumption in the data collection, which could hold further insight into these associations.
“[B]efore we can confidently make dietary recommendations for patients with acne, trials are needed to evaluate whether dietary interventions can improve or prevent acne and how the effect size of such interventions compares with other standard treatment modalities,” Barbieri concluded.

Disclosures

Penso and co-authors reported no disclosures.
Barbieri reported being supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health and partial salary support through a Pfizer Fellowship grant to the Trustees of the University of Pennsylvania.

Primary Source

JAMA Dermatology

Source Reference: Penso L, et al “Association Between Adult Acne and Dietary Behaviors: Findings From the NutriNet-Santé Prospective Cohort Study” JAMA Dermatol 2020; DOI: 10.1001/jamadermatol.2020.1602.

Secondary Source

JAMA Dermatology

Source Reference: Barbieri JS “Diet and Acne — Challenges of Translating Nutritional Epidemiologic Research Into Clinical Practice” JAMA Dermatol 2020; DOI: 10.1001/jamadermatol.2020.1601.

https://www.medpagetoday.com/dermatology/generaldermatology/86997

Genmab brings on Abbvie for bispecific boost

Abbvie pays handsomely to join the CD20 bispecific brawl, handing over $750m to Genmab for access to a project that is behind the competition.
Genmab has been promising a deal on its lead R&D project, epcoritamab, for some time now and today unveiled Abbvie as its new partner. The CD20-targeting bispecific sits in a field where Roche and Regeneron are ahead with similar agents, so the Danish biotech was always going to need help competing.
With its big presence in haematological cancers thanks to Imbruvica and Venclexta, partnering with Abbvie certainly makes sense. The deal terms point to the promise seen with bispecifics in this area: $750m up front and up to $3.2bn in milestones for Genmab, which also gets to keep a healthy portion of the profits should help epcoritamab make it to market.
The broad development and commercialisation deal also involves two other clinical-stage bispecifics and potentially four other projects down the road, so some of the fees will relate to progress elsewhere. A big proportion will be linked to epcoritamab, however, which Genmab will jointly market with Abbvie in the US and Japan.
Profits will be shared equally in these countries; elsewhere Genmab will receive 22-26% royalties. The terms are broadly similar for the other two projects: CD3 bispecifics targeting CD37, GEN3009, which is in a phase I trial; and 5T4, a target expressed on a wide variety of solid tumours. This is much earlier in development, with an IND having only just been filed.
On a call with investors this afternoon the deal was repeatedly described as a “50:50 partnership” and “transformational” by Genmab executives, although Abbvie’s management team are also probably hoping for pretty big things. The company has fired several blanks in oncology – think Rova-T and velaparib – and shares in the company opened up almost 2% today.
With an $18bn market cap Genmab can hardly be described as a small biotech anymore, though this valuation is largely thanks to a substantial rally over the past few months. The stock touched a record high in late May and has surged 64% so far this year, which probably explains a relatively muted response to the deal: shares were trading 5% higher on the news.
The bispecific promise
Highly encouraging response rates with Regeneron’s REGN1979 and Roche’s mosunetuzumab across various lymphomas have raised hopes that using a bispecific to hit CD20 might boost the effectiveness of this well established mechanism. The nearest term hope is that these agents might offer a more tolerable and convenient option than Car-T in later-stage settings.
While there are several CD20 bispecific projects in development, Roche and Regeneron are considered out in front. Both presented substantial data sets at Ash last year, which seems to show what REGN1979 gained in efficacy over mosunetuzumab, it lost in safety (Ash 2019 – Regeneron takes the bispecific baton and runs, December 10, 2019).
As a huge player in the CD20 space with Rituxan and Gazyva Roche should not be ruled out here, of course, but this is a race that is far from over.
Genmab presented the latest cut from an ongoing trial of epcoritamab at Asco this year, which appeared to show competitive efficacy. And on safety, which is more easily stacked up at this stage, epcoritamab certainly holds it own, with a much lower rate of more severe cytokine release seen, albeit in fewer patients to date.

CD20 bispecific safety comparison
	REGN1979 (Regeneron)	Mosunetuzumab (Roche)	Epcoritamab (Genmab/Abbvie)
N	110	270	58
CRS	59%	29%	57%
CRS grade 3-4	6.40%	1.10%	0%
CRS=cytokine release syndrome. Source: Ash 2019, Asco 2020.

Both Regeneron and Roche have already started much larger phase II programmes with their respective candidates, and on today’s call Genmab and Abbvie executives said they were keeping specific plans for epcoritamab “close to their chests”. While they acknowledged that they are behind, plans are afoot to catch up, they insisted, and hinted that a huge pivotal programme is on the cards.
A “Darzalex type development programme” should be expected, they revealed, involving multiple thousands of patients; combinations with Imbruvica and Venclexta are also likely. Considering that epcoritamab data in only 58 patients has been published to date, some might find this talk premature.
And of course if this comes to pass much of Genmab’s new-found wealth will be earmarked for such studies. However it is clear that in Abbvie a motivated and ambitious partner has been found.
https://www.evaluate.com/vantage/articles/news/deals/genmab-brings-abbvie-bispecific-boost