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Monday, June 29, 2020

COVID-19 Stay-at-Home Orders Negatively Impacted Patients With Obesity

Target Audience and Goal Statement: Endocrinologists, infectious disease specialists, primary care physicians
The goal of this study was to examine the impact of COVID-19 stay-at-home orders on weight-related behaviors among patients with obesity.
Question Addressed:
  • Did the stay-at-home orders affect the physical, mental, and financial health of people with obesity?
Study Synopsis and Perspective:
The fast-spreading SARS-CoV-2 virus has upended lives and economies worldwide. Broad and quick societal upheavals have been the norm, due to the mounting COVID-19 death toll (more than 450,000 worldwide at last count).
Although the “patchwork pandemic” may be “fraying” in the U.S. and elsewhere, one thing has become clear: deaths have not been distributed evenly. For example, obesity-related conditions seem to worsen the effect of COVID-19. Indeed, as U.S. states continue to reopen, a Kaiser Family Foundation study reported that almost one in four American adult workers could be vulnerable to severe illness from COVID-19.

Action Points

  • Patients with marked obesity reported more anxiety and depression, as well as less exercise and more stress eating, due to stay-at-home orders implemented to stop the spread of COVID-19, according to a University of Texas survey study.
  • Note that these results show that the COVID-19 pandemic is having a significant impact on patients with obesity regardless of infection status, and can help inform clinicians and healthcare professionals about effective strategies to minimize negative outcomes for this vulnerable population now and in post-COVID-19 recovery efforts.
Various strategies have been devised for jump-starting economies by ending social distancing or quarantine — two of the ways to slow the spread of COVID-19 in the absence of effective treatments or a vaccine. However, implicit in this approach is the supposition that vulnerable individuals may have to self-isolate longer than others or take additional precautions.
According to research led by Sarah Messiah, PhD, of the University of Texas (UT) Health Science Center at Houston School of Public Health in Dallas, people with obesity have been struggling to maintain their weight and mental health during the stay-at-home orders.
Results from their study of weight management patients at the UT Southwestern Weight Wellness Program and a community bariatric surgery practice were recently published in Clinical Obesity.
“Everyone was told to stay home to protect themselves from infection and this was especially important for people with severe obesity, who are more likely to have serious complications and higher risk of death with the coronavirus,” said Messiah in a statement. “But these are also patients who often have comorbidities such as heart disease and diabetes that need consistent care. This was the first assessment of this patient population to see the effects of the upheaval of their daily lives on their health behavior and well-being.”
The final analytic sample consisted of 123 patients (87% women, mean age 51.2 years, mean body mass index [BMI] 40.2 kg/m2, 49.2% non-Hispanic white); 33.1% had completed bariatric surgery. More than half of the patients (56.1%) had graduated college and an additional third had some education beyond high school. Most of the sample (53.6%) had an annual household income >$75,000. Frequent self-reported medical conditions were high blood pressure (67%), sleep apnea (51%), and diabetes (30%).
Patients responded to an online survey (non-anonymous) designed to obtain information about the pandemic’s impact on their lives. This was started on April 15 — about 2 weeks after the state’s governor issued a stay-at-home order. They also filled out a demographic questionnaire (Behavioral Risk Factor Surveillance System [BRFSS]). Depressive symptoms were assessed using the 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR).
Most patients reported only leaving their homes for necessities. While only two patients (1.7%) had tested positive for SARS-CoV-2, more patients (14.6%) reported COVID-19 symptoms.
Since the start of the stay-at-home orders, 72.8% reported increased anxiety and 83.6% reported increased depression.
A significantly higher proportion of non-Hispanic white patients reported increased anxiety compared with other racial and ethnic groups, though there were no significant differences in those reporting depression. After adjustment, Hispanic patients were less likely to report anxiety than non-Hispanic whites.
Those with obesity already have a 25% higher risk of developing mood and anxiety disorders.
Almost 70% of the participants reported having more difficulty in achieving their weight loss goals since the order, while 48% had less exercise time, and 56% had less intensity in exercise.
Half of the sample reported an increase in stockpiling food, while slightly more than a third (39.6%) of the sample reported grocery shopping once a week. Well over half reported cooking more often (63.8%), and 61.2% reported stress eating. Although most respondents were not food insecure (78.3%), some of them did skip meals (12.1%). Almost 10% lost their jobs during the pandemic, and 20% said they could not afford a balanced meal.
This was a convenience sample, and thus prone to selection bias. Furthermore, participants had established weight management goals and secured health insurance, which is not representative of the average American challenged with obesity, in which <2% receive anti-obesity medications. This limits the generalizability of the findings and may not accurately reflect the burden of COVID-19 on obesity-related health and behaviors in those of lower socioeconomic status and/or ethnic minority populations who are disproportionately more affected by obesity and COVID-19. Other study limitations included the self-reported perception of patient behavioral changes at the time of the survey, rather than quantified behaviors.
Source Reference: Clinical Obesity 2020; DOI: 10.1111/cob.12386
Study Highlights and Explanation of Findings:
Stay-at-home orders mandated in many states plus efforts to isolate vulnerable populations and people with diagnosed or suspected COVID-19 have had serious effects on health behaviors and well-being for patients with obesity.
“Public health strategies to control the outbreak that focused on social distancing have led to an increase in loneliness and social isolation, which play a significant role in behaviors that influence body weight,” Messiah and team wrote.
Most of the patients followed the stay-at-home orders, and as a result 87% left their homes only for necessities. Overall, nearly 70% of patients reported that their weight loss goals were harder to achieve.
There were substantial decreases in physical activity duration and intensity. Patients also reported negative impacts on food access and consumption behaviors. Even more troubling, according to the researchers, were the increased anxiety, depression, and job loss.
“You don’t have to contract the virus to be adversely affected by it. The major strength of this study is that it is one of the first data-driven snapshots into how the COVID-19 pandemic has influenced health behaviors for patients with obesity,” said first author Jaime Almandoz, MD, MBA, an assistant professor of internal medicine at UT Southwestern, in a press release.
Almandoz highlighted the point that some patients may reside in food deserts lacking grocery stores, where their choices may be limited to fast food and processed foods from convenience stores.
“Unchecked diabetes, hypertension, and other obesity-related comorbidities will create a huge backlog of needs that will come back to haunt us. When you throw in disruptions like social isolation, coupled with losing your job and insurance coverage, a potential disaster is waiting to unfold,” he added.
Lost health insurance due to lost jobs and missed non-COVID-19 medical appointments because of the pandemic might add to lives lost.
The researchers emphasized that due to the “increase in obesogenic behavior” found in this study, healthcare access should not be interrupted for patients with obesity.
“In addition to asking about diet and exercise patterns, screening for indicators of mental health, loneliness, financial stressors and behaviors that may influence body weight should be implemented by healthcare teams” to prevent “exacerbating the negative health and economic consequences of excess body weight,” the team wrote.
Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College

COVID Trials Threatened by Shifting Surges

While COVID-19 has delayed and disrupted clinical trials across specialties, the trials aimed at disrupting the pandemic have struggled to keep up with the wild swings in epidemiology.
That was the experience in New York City.
“We went from a blank piece of paper to our first patient randomized who had COVID in a little over 2 weeks. Those timelines are almost impossible,” said Alex Spyropoulos, MD, primary investigator on the HEP-COVID trial comparing anticoagulation doses in a planned 308 severe COVID-19 patients at Northwell Health’s Feinstein Institutes for Medical Research there.
“Northwell touched over 100,000 COVID-positive patients. And yet despite being in the epicenter of the epicenter, the pandemic passed us and we were only able to get few patients into our randomized trials.”
“Investigators were quick to design trials, but the disease epidemiology curve got ahead of us,” agreed Behnood Bikdeli, MD, of NewYork-Presbyterian Hospital/Columbia University Irving Medical Center in New York City.
His group’s 100-patient IMPROVE-COVID trial comparing anticoagulant doses in the ICU fell short of 50% enrollment before the surge moved on to other cities.
Antithrombotic trials were especially on the back foot because the issue came as a surprise for a “respiratory infection,” Bikdeli noted.
“Everyone went in the direction of thinking, ‘Let’s try to use antiviral agents’ and some people, ‘Let’s try to use some of the anti-inflammatory agents.’ People started to think of them a little earlier, and that’s part of the reason we got more patients enrolled in those trials, and now we have some informative results,” he said.
But at least two high-profile COVID-19 treatment trials out of Wuhan, China, suffered from the same phenomenon: A study of severe COVID-19 patients suggested no clinical benefit with remdesivir but was inconclusive due to lack of statistical power. Even though the trial began on February 6, patients meeting eligibility criteria became too difficult to find after March 12 and the trial was stopped after enrolling just 237 of the planned 453 patients.
A second study of convalescent plasma for hospitalized COVID-19 patients again showed no statistically significant benefit in time to clinical improvement, but was underpowered for many of the intended analyses with only 103 patients of the originally planned 200 treated before the outbreak petered out in Wuhan.
What’s the Problem?
Academic centers, and the U.S. more broadly, are poorly set up to get trials running in a pandemic situation, noted Spyropoulos. “Every hospital has their legal oversight, regulatory oversight, informatics oversight, HIPAA [Health Insurance Portability and Accountability Act] oversight. By the time all those hurdles are passed, it’s already gone.”
A steep spike is also a research deterrent, said Chris Amos, MD, director of the Institute of Clinical and Translational Medicine at Baylor College of Medicine in Houston, which appears to be well underway with just such a spike.
“A benefit that we’ve had was that the impact was not felt immediately, so we’ve had some time to plan and prepare for increasing numbers of patients affected by COVID-19 and develop our approach to conducting clinical research,” he told MedPage Today.
“The biggest stress for us will be as the number of cases increase, the demands on the clinical faculty and staff also increases, and that in general makes it harder to find the staffing to engage in as many trials as we would like,” he said. “We really like any patient that is willing and eligible to participate to be involved in clinical study, but if the surge is too intense you have trouble with that.”
Another logistical problem for locally-run trials at a single health system or region: “There was not even time to get funding. All of us volunteered our own time,” said Bikdeli about his group’s IMPROVE COVID trial.
So far, the key successes in COVID-19 have come from national-level trials — by the National Institute of Allergy and Infectious Diseases in the case of remdesivir and by the University of Oxford for dexamethasone’s pragmatic U.K. trial.
“We need to tack away from single center studies, particularly trials, and embrace collaboration across the country so we can ensure that we are doing adequately powered studies with strong protocols, vetted broadly,” argued Harlan Krumholz, MD, director of the Center for Outcomes Research and Evaluation at Yale-New Haven Hospital in Connecticut.
“My hope is that the pandemic will spark greater efforts to partner — there is no reason to have large numbers of small trials,” he told MedPage Today. “We need to get into virtual rooms together and collaborate vigorously.”
Small trials raise the risk of type 1 error that could misdirect the search for effective clinical treatments, noted Barbara Bierer, MD, faculty director of the Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard in Boston, a research and policy center trying to improve clinical research practices.
She pointed to remdesivir’s ACTT trial as a good example of fast-moving adaptive design and the proliferation of small hydroxychloroquine trials as a bad example. Hundreds of the latter are still listed as open on ClinicalTrials.gov, “despite the evidence being available that they should be closed,” Bierer said.
Having clinical trial networks in place beforehand to speed broad multisite collaborations is really ideal, she suggested.
What Can Be Done?
All isn’t lost for trials stymied by quick cycles of spikes and lockdowns, though.
There is a possibility that a second wave of COVID-19 could buoy some of the foundering trials, Spyropoulos noted. “As a clinical trialist, I’m hoping to get that spike so we can get the answers, but as doctor and father I hope we don’t.”
Otherwise, the only solution to make any sense of such data is pooling patient-level meta-analytic data, he suggested.
For that reason, Bierer’s center, along with collaborators at Johns Hopkins University in Baltimore, created the COVID-19 Collaboration Platform for sharing clinical trial protocols; adding like-minded clinical sites to turn a single-site trial into a multisite trial; and even sharing data that’s already been collected from similar protocols.
“We will host deidentified data and, on the back end after the fact, see whether and how we can harmonize the data so we can draw inferences from the universe of data that’s been collected at these different sites,” she said. “It’s much harder to do that on the back end…but it can be done.”
They’re currently reaching out to some of the hydroxychloroquine studies — particularly those with controls — to see if there’s anything they should learn from that, she said. “Same for convalescent plasma, both pediatric and adult, because frankly no single site is likely to have enough that we can learn what we need to learn and be published.”
For observational data, there’s the Observational Health Data Sciences and Informatics (OHDSI) program for large-scale analytics, run out of Columbia University in New York City, Bikdeli noted.
Regulators have been responsive, flexible, and supportive of trials — it’s up to clinicians and centers now, Bierer said.
“There is nothing that is standing in our way of doing a better job than we’re currently doing, other than we’ve never been in a situation like this in the last century,” she added.

NeoGenomics launches solid tumor liquid biopsy tests

NeoGenomics (NEO +5.3%launches three liquid biopsy tests for advanced non-small cell lung cancer, all solid tumor types (pan-cancer), and certain breast cancer cases.
These new tests provide a peripheral blood option for detection of therapeutic targets and prognostic markers, and the three new assays have a turnaround time of seven days or less.

FDA OKs Roche combo injection for type of breast cancer

June 29, 2020

The FDA approves Roche (OTCQX:RHHBY -0.6%) unit Genentech’s subcutaneously administered Phesgo (pertuzumab, trastuzumab and hyaluronidase- zzxf) for adults with metastatic HER2-positive breast cancer and adults with early-stage HER2-positive breast cancer.
HER-positive tumors comprise ~20% of total breast cancer cases.
The company markets the intravenous (IV) formulation of pertuzumab as Perjeta and the IV formulation of trastuzumab as Herceptin.
Subcutaneous administration is enabled by the addition of hyaluronidase, branded as Enhanze by Halozyme Therapeutics (HALO +3.3%). Roche in-licensed the drug delivery technology in 2017.

Sell-siders opine on Gilead’s remdesivir ROI after price announcement

Sell-side analysts are busy updating their spreadsheets and investor notes after Gilead Sciences (GILD +0.7%) announced its government price of $390/vial price for antiviral remdesivir, implying a typical cost per treatment course of $2,340 (six vials). Commercially insured patients will pay a bit more, $520 per vial or $3,120 per course.
Analysts expected a U.S. cost/course in the neighborhood of $5,000 after drug cost watchdog ICER published a cost/benefit analysis that determined a price of $4,500 to be cost-effective.
In his open letter, CEO Dan O’Day stated that earlier hospital discharge would save ~$12K per patient.
SunTrust’s Robyn Karnauskas (HOLD/$73) has trimmed her fair value target on the company by $3 saying it is “unclear” how Gilead will recoup its $1B investment in the near term since cost of goods sold (COGS) is unknown as is the number of patients who will be treated in H2.
RBC’s Brian Abrahams (OUTPERFORM/$88) remains a cheerleader, projecting that remdesivir will generate $2.3B in sales this year which should add $1/share in valuation and ~$1 to 2020 EPS.
SVB Leerink’s Geoffrey Porges (OUTPERFORM/$94) is revisiting his sales forecast although he believes the pricing is “reasonable.”
Piper Sandler’s Tyler Van Buren (OVERWEIGHT/$90) believes the pricing is “in line” with ICER’s assessment based on the mortality benefit.
Jefferies’ Michael Yee (BUY/$97) also regards the pricing as “in line” although the company could certainly charge more considering the $12,000 savings for early discharge. He would not be surprised if the company conservatively guides 2020 sales of ~$1B although investors are most likely expecting sales as high as $2B this year.

New journal to vet Covid preprints, tag misinformation, highlight credible data

The wild, wild west of Covid-19 preprints is about to get a new sheriff. On Monday, the MIT Press is announcing the launch of an open access journal that will publish reviews of preprints related to Covid-19, in an effort to quickly and authoritatively call out misinformation as well as highlight important, credible research.
“Preprints have been a tremendous boon for scientific communication, but they come with some dangers, as we’ve seen with some that have been based on faulty methods,” said Nick Lindsay, director of journals at the MIT Press, which will publish Rapid Reviews: Covid-19. “We want to debunk research that’s poor and elevate research that’s good.”
The Covid-19 pandemic has produced a fire hose of preprints (papers posted to servers such as bioRxiv and medRxiv without peer review), many of questionable validity. The poster child for that is a bioRxiv preprint that suggested the new coronavirus had somehow been engineered from HIV; it was quickly withdrawn. But many other preprints, while not clearly wrong, used weak methodology, such as small numbers of patients or inadequate controls, as in an experiment concluding that a commercially available immunoglobulin might protect against the disease.
“There have definitely been some crummy preprints,” said Richard Sever, a co-founder of both bioRxiv, in 2013, and medRxiv, whose methodical rollout a year ago accelerated to warp speed with the pandemic and has now posted some 5,000 papers about it. “Quite a lot of people are talking about doing something like [the MIT Press effort]. Their challenge is getting people to do the reviews quickly. It’s a great idea but might be easier said than done.”
The editor-in-chief of Rapid Reviews: Covid-19, Stefano Bertozzi of the University of California, Berkeley, thinks this project has a secret sauce that similar efforts do not. It will use an artificial intelligence system developed at Lawrence Berkeley National Laboratory to categorize new preprints by discipline (such as epidemiology or clinical care) and degree of novelty.
“There is such a huge volume of material every day, our goal is to do rapid reviews on preprints that are most interesting,” Bertozzi said. “Interesting” means studies that might influence public health officials, clinicians, and the public, he said, “as well as those that need to be validated or debunked, especially if they’re getting a lot of attention in the media or social media.”
That attention can come almost instantly, posing a challenge for a journal with “rapid” in its name. The AI sifter should speed up the process at the front end. Humans will also weigh in, with about 100 volunteer graduate students from around the world scanning preprints for those that most need review.
Once a preprint has been flagged, Bertozzi and his editors will ask up to three experts to review its strengths and limitations, with or without their name attached to the review.
Both medRxiv and bioRxiv would “absolutely” indicate whether a preprint has been given a Rapid Review, Sever said, just as it does when a preprint is published in a journal. “One of our missions is to alert readers to relevant conversations,” he said.
The first reviews should be up by mid-July, with an aim of posting them within seven to 10 days of a preprint appearing.
The closest similar effort went live in April at Johns Hopkins University, where epidemiologist Emily Gurley and pathologist Kate Grabowski launched the 2019 Novel Coronavirus Research Compendium. Its 50 volunteers, mostly from Hopkins, include experts in mathematical modeling, diagnostics, vaccines, and related fields. Using keyword searches, they select new studies, both preprints and those published in journals, that they think contain important information for clinicians and policymakers. Postdoctoral fellows and graduate students summarize the paper’s findings, and flag its strengths and limitations. Two Hopkins faculty members vet and edit the reviews, which recently passed 220.
“Our objective is to be sure folks, especially clinicians on the frontlines, can find the information they need,” Gurley said. “No one has time to go through all the papers that are coming out” on Covid-19.
Rapid Reviews: Covid-19 plans to tap a pool of 1,600 potential reviewers from hundreds of institutions, and will analyze papers on the economics and anthropology of the pandemic as well as biomedicine. If it lives up to its founders’ hopes, it would be the largest formal effort to ride herd on Covid-19 preprints. It also plans to publish original research from areas of the world that have been underrepresented in Western journals.
Praising the Hopkins project, Lindsay said, “The reality is, there’s so much Covid-19 research out there, there’s going to be plenty for all of us to examine.”

Planet Fitness down on report of COVID+ member in West Virginia

Planet Fitness (PLNT -5.9%) is down sharply after health officials in West Virginia warn hundreds of people about a Planet Fitness member who tested positive for COVID-19.
Media reports indicate about 205 people visited the gym in Monongalia County during a six-hour period that included the visit by the COVID+ member. Those people are being asked to quarantine for two weeks.
PLNT was set up to have a good day after a strong note was poured out by Wedbush earlier in the day on the long-term upside.