The Incidental Economist

The following originally appeared on the Baker Institute Blog and is coauthored by Vivian Ho, Ph.D. (@healthecontx), James A. Baker III Institute Chair in Health Economics, Kirstin Matthews, Ph.D. (@stpolicy), Baker Institute Fellow in Science and Technology Policy and Heidi Russell, M.D., Ph.D., Associate Professor, Department of Pediatrics, Baylor College of Medicine and Associate Director, Center for Medical Ethics and Health Policy, Baylor College of Medicine.

By the Numbers

As of Friday, July 10, data from the Covid Tracking Project showed that the 7-day average (smoothed) number of new U.S. daily cases rose to 54,561, a 15% increase relative to 47,244 the previous Friday. The percent of cases testing positive rose to 8.4% from 7.4% one week earlier. The smoothed number of deaths in the U.S. rose 16%, from 529 a week earlier to 614 last Friday. Here in Texas, the growth in the number of smoothed daily cases rose 20% between July 3 and July 10, and the smoothed number of daily deaths increased from 36 to 63. The percent of people testing positive rose from 12.7% on July 3rd to 12.9% last Friday.

Risk Factors and Disease Effects

We are six months into the pandemic, and scientists still face multiple unresolved questions including: why people respond differently; is immunity achievable and how long will it last; is the virus developing worrisome mutations; how well will vaccines work; and where did the virus originate from.

Two distinct strains of SARS-CoV-2 are recognized – the D variant that originated in Wuhan and a G variant.  International tracking reported in Cell reveals that the newer G variant is currently the dominant strain in the US and is more infective.  A video depiction of spread by strain is viewable  online.

More than 650 coronavirus cases have been linked to nearly 40 churches and religious events across the United States since the beginning of the pandemic, with many of them occurring over the last month.

The personal protective gear that was in dangerously short supply during the early weeks of the coronavirus crisis in the U.S. is running low again as the virus resumes its rapid spread and the number of hospitalized patients climbs. Test shortages are also pervasive.

After an international group of 239 experts called on the World Health Organization to review the research on airborne transmission of the coronavirus, the W.H.O. finally acknowledged that the virus can linger in the air in crowded indoor spaces, spreading from one person to the next.

Vaccines and Treatments

So many coronavirus vaccines are nearing the pivotal testing phase, that researchers and companies are going to extraordinary lengths to recruit the tens of thousands of healthy volunteers needed for testing. Volunteers can sign up here.

An editorial co-authored by former FDA Commissioner Scott Gottlieb explains how antibody drugs that potentially could protect the elderly and the immune-compromised for months could be ready for use as early as this fall. However, the federal government must invest substantial funds to enable drug makers to ready these drugs for mass-production.

Policy Interventions

The US Centers for Disease Control and Prevention will not revise its guidelines for reopening schools despite calls from President Donald Trump and the White House to do so, agency Director Dr. Robert Redfield said Thursday. The president tweeted that the guidelines were “very tough” and “expensive,” while in another tweet threatened to cut off school funding if schools resisted opening.

Sweden, which never locked down during the pandemic, has suffered higher Covid-19 deaths per capita than other developed countries, and reaped no economic benefit from keeping their economy open.

The U.S. Department of Health and Human Services’ Office of the Assistant Secretary for Preparedness and Response is the top U.S. agency charged with preparing for a pandemic and overseeing the medical stockpile. ASPR had a $2.6 billion budget for fiscal 2020 and prioritized preparation for a possible bioweapon, chemical, or nuclear attack, and did little to prepare for a pandemic.

Young people in Tuscaloosa, Alabama, hometown of the University of Alabama, were reported to be throwing Covid-19 parties, where people who have coronavirus attend and the first person to get infected receives a payout, local officials said. Meanwhile, Tulane University warned students of suspensions or expulsions if they are found to have hosted parties or gatherings of more than 15 people.

The Texas Medical Board emailed members this week to remind them of emergency medical licensure changes making it easier for out-of-state or retired practitioners to practice in Texas. With the rise in Covid-19 patients in Texas, these providers are badly needed.

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On July 9th, I spent the day at the Cancer Centre meeting with my radiation oncologist, and I learned a lot. I’ll tell you about my cancer, what might have caused it, and what that tells us about how we can prevent cancers like this.

My cancer is an ~80 cubic centimetres, p16 positive, oropharyngeal, squamous cell carcinoma (p16+ OPSCC). Carcinoma means that this cancer originated from epithelial cells. Epithelial cells form the surface of your throat and mouth. Squamous cell indicates the type of epithelial cells; squamous cells are flat, like tiles or plates. Oropharyngeal tells us that the carcinoma is in the middle of my throat. P16+ means that when the pathologist stained the biopsy sample in a certain way, it revealed that a high-risk variant of the human papillomavirus (HPV) helped cause this cancer. 80 cc ( = ~5 inches³) indicates that the carcinoma is, unfortunately, large.

The radiation oncologist inserted a thin tube with a camera and an LED into my nostril and threaded it down into my mouth. This felt weird, but not painful. The camera showed us the inside of my throat. And there was the tumour: an irregularly surfaced lump, vast on a big screen.

Radiation oncologist: “That’s why you can’t swallow well. I’m amazed that the air can get around it. Actually, how do you even breathe?”

<Me: [silent] Like I’m supposed to know?>

RO: “If your throat swells from the radiation, you won’t be able to breathe. Maybe we’ll need to do a tracheotomy before we start.”

<Me: [silent, but SHOUTING] SAY WHAT?>

If it wasn’t clear already, this game is played for real money.

So what caused this cancer? Tobacco and alcohol are the principal risk factors for throat and mouth cancers, but I have never smoked, and I don’t drink that much.

However, the staining of the biopsy sample showed that I was at some time infected with a strain of HPV that can cause this type of cancer (not all strains do). HPV can cause cancer not only in the pharynx but also in the cervix, vulva, vagina, penis, or anus. In the US in 2019, there were 52,840 new cases of these cancers and 12,100 deaths.

So how does HPV cause cancer? When a virus infects a cell, the genes in the virus use materials in the cell to make proteins that eventually replicate the virus. However, these proteins can have additional consequences. In the dangerous strains of HPV, we call some of the viral genes oncogenes, because they influence the cell to transition to unrestrained growth, that is, cancer.

How HPV infection can lead to throat cancer. From Liu et al., The molecular mechanisms of increased radiosensitivity of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC): an extensive review. J Otolaryngol – Head Neck Surg 2018;47:59. Available from: https://doi.org/10.1186/s40463-018-0302-y

The HPV oncogenes produce oncoproteins, in this case, the E6 and E7 oncoproteins. The oncoprotein E7 leads to a cascade of events, one of which is the overproduction of the p16 protein. When the pathologist stained my biopsy sample, the overproduction of p16 became visible, and he or she used this marker to diagnose the carcinoma as HPV+ ( = p16+). E7 also damages the brakes on the cell reproduction cycle, which helped set the stage for uncontrolled proliferation.

The E6 oncoprotein interferes with the action of the p53 protein, a famous molecule that is essential in DNA repair. P53 is also critical to safety mechanisms in cells that trigger apoptosis — cell death — when dangerous problems develop in cell reproduction. E6 also helps preserve telomere length in the cell’s chromosomes. Diminishing telomere lengths are part of the cellular ageing processes. By keeping them long, E6 helps make the cell immortal.

The transition from healthy to cancerous cells takes a long time following HPV infection.  Nevertheless, the upshot of these sequences of events is that the cell becomes long-lived, and it reproduces in an uncontrolled way, which is to say it becomes an HPV+ OPSCC, like the tumour I saw on the screen.

But how, you ask, did I get infected with HPV in the first place? Let’s not be coy:

Human papilloma viruses are… spread through vaginal, oral and anal sex. HPV is the most common sexually transmitted infection in the United States, affecting more than half of sexually active individuals at some point during their lives… The time lag between an oral HPV infection and the development of HPV-related oropharyngeal cancer is estimated at between 15 and 30 years. As such, the rise in [OPSCC] seen since the 1990s in large part reflects changes in sexual practices in the 1960s and 1970s.

I was infected as part of a viral epidemic. It most likely happened while I was giving oral sex during college.

I regret nothing. Tell it like it is, Edith!

Be advised that the HPV epidemic has never gone away. However, HPV+ OPSCC and cancers of the penis, anus, vulva, vagina are preventable with HPV vaccines. Cervical cancer — the biggest killer — is almost entirely preventable. The vaccines are cost-effective and exceptionally safe. Sixty-seven million doses were administered from 2006 to 2014. Those doses resulted in 25,000 reports of adverse events (< 4 per 10,000 doses). However, only 8% of those reports were serious (~3 in 100,000 doses). Importantly, a report of an adverse event just means that it happened; it does not necessarily mean that the vaccination caused that event. For example, the serious adverse events included 85 deaths, but the deaths had no typical pattern, as would be expected if the vaccine caused them.

Nevertheless, in 2013, less than 40% of female patients and less than 15% of male patients had been vaccinated. There are at least two reasons. First, there has been political resistance to HPV vaccination.

Vaccine coverage is hindered by public perceptions regarding HPV’s status as a sexually transmitted infection and dissent over the recommended age of vaccination. Social conservatives have countered vaccine mandates with the argument that they infringe upon parental rights to discuss the topic of sex on their own terms. Pro-abstinence activists raise similar concerns that HPV vaccination may increase teenage promiscuity, though there is no evidence for this claim… Finally, several studies have shown that parents fail to vaccinate due to misperceptions about the risk of HPV infection.

Some of these misperceptions about vaccine risk stem from false claims spread by Michelle Bachman during her failed presidential campaign in 2011.

The second reason relatively few youths are vaccinated is that getting vaccinated is a bother. It requires three shots to prevent an adverse health outcome that won’t occur, if it ever does, for decades. That feels, I imagine, like too much trouble.

We need to cultivate the norm that there is a duty, part of our solidarity with our neighbours, that we should endure the mild risks and inconveniences and get vaccinated for HPV. We could save even more lives by accepting a collective duty to get vaccinated for the flu, and, we must hope, soon for the coronavirus. Doing these things would save many tens of thousands of lives each year.

To read the Cancer Posts from the start, please begin here. The next post, about how we decided on a treatment, is here.

@Bill_Gardner

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In this episode, Aaron Carroll talks with Dr. Chandy John about his experiences as an infectious disease researcher and pediatrician. Dr. John’s research focuses on global health, and he’s involved in programs in both Kenya and Uganda.

Available wherever you get your podcasts, including iTunes!

The Healthcare Triage podcast is sponsored by Indiana University School of Medicine whose mission is to advance health in the state of Indiana and beyond by promoting innovation and excellence in education, research and patient care.

IU School of Medicine is leading Indiana University’s first grand challenge, the Precision Health Initiative, with bold goals to cure multiple myeloma, triple negative breast cancer and childhood sarcoma and prevent type 2 diabetes and Alzheimer’s disease.

@DrTiff_PhD

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Me, writing in an Ottawa ED waiting room. And, yes, I am a Utes fan. It’s a long story.

It’s 3:00 AM, July 3rd, 2020, in the Ottawa Hospital Civic Campus emergency department. I have been here since 3:00 PM, July 2nd. The journey began in mid-January when I started to experience occasional difficulty swallowing my food. Come early March, the swallowing problem is recurring, and there is now a soreness in my throat. My wife notices that the register of my voice seems to be changing. OK, time to do something. 

Getting a problem looked at in Canada requires one to go through your family physician. By US standards, the Canadian health care system is conservative in its use of diagnostic procedures. The bigger problem, though, is the pandemic. All non-urgent care is postponed.

I get a chest x-ray and standard bloodwork, but they reveal nothing. I try to get a videofluoroscopic study of my swallowing problem, but I can’t get through the waiting list. Weeks pass. My PCP pleads with the diagnostic clinics. They promise to get back to me for a phone appointment to evaluate whether I need a diagnostic procedure. It doesn’t happen.

Then, on July 2nd, I start coughing blood. A quick conference with my PCP, the only course is to go to the ED. I get there at 3:00, and it’s standing room only. This is Canada, so the crowd is orderly and cooperative, but it’s not a good scene. Five hours of waiting and I see a resident. I tell him my story. He responds using medical words that translate to “uh oh,” and he sends me to get a CT scan. I get scanned at about 11:00 PM. And then I wait.

Which brings us to 3:00 AM. I am called to an exam room. An attending physician comes in. She says, directly but gently and gracefully, “I have serious news.” 

There is a moment in Alan Furst’s The Polish Officer in which the title character, a WW2 resistance fighter, is woken by gunfire in the night. It’s the Wehrmacht, assaulting the barn where his unit is hiding. He looks at a comrade, and in the glance, they exchange the recognition that “The time that we always knew would happen has happened.” I have been through this with friends and family. Now it’s my turn.

The CT scan shows that I have a mass in my oropharynx, the middle component of the throat. Later that morning, I see an ENT surgeon who had the same view as the ED doc, “This is an oropharyngeal squamous cell carcinoma [OPSCC] until proven otherwise.” He did a biopsy with a needle through the side of my neck. 

On the 7th, I got a call from my PCP with the results from the biopsy. “I am going to be straightforward. This is bad news.” The mass is indeed an OPSCC, with lymph node involvement to boot. The report also included word salad about the staining of cells on the slides. I’m sure it’s crucial, but it made no sense to either of us, which we found hilarious. Thank God that my PCP speaks my native tongue, which is Black Humour. The other good news is that OPSCC can often be treated with success. 

The upshot is that I am now a cancer patient during the COVID-19 pandemic.

With your permission, dear reader, I plan to blog through this experience. There is a genre of health professionals narrating their experience as patients. That’s not quite what I want to do. I’m going to mostly avoid making this about me, partly because I’m not the writer that, say, Paul Kalinithi was. Instead, being a cancer patient provides a point of view to analyze the global crisis. The pandemic is obstructing the care of many other conditions. I may end up becoming collateral damage of the coronavirus because COVID-19 delayed my diagnosis. Or was that a fault of Canadian medicine? If so, how ought we address it? Or I might become a direct casualty of the pandemic because my age and illness place me in a high-risk category for COVID-19. You — meaning now the young and healthy population — have a role to play here: please wear your masks.

I have spent much of my career studying health care systems, often from an ethics framework. Perhaps we can learn something from this.

The next cancer post, about how my tumour was diagnoses, is here.

@Bill_Gardner

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By the Numbers

As of Friday, July 3, data from the Covid Tracking Project showed that the 7-day average (smoothed) number of new U.S. daily cases rose to 47,244, a 37% increase relative to 34,476 the previous Friday. The percent of cases testing positive rose to 7.5% from 6.4% one week earlier. The smoothed number of deaths in the U.S. fell 36%, from 825 a week earlier to 530 last Friday. Here in Texas, the growth in the number of smoothed daily cases rose 34% between June 26 and July 3, and the smoothed number of daily deaths increased from 26 to 36. The percent of people testing positive rose from 10.9% on June 26^th to 12.7% last Friday.

Risk Factors and Disease Effects

Scientists analyzing non-influenza-like illnesses in March 2020 suggest that more than 8 million people in the US during that time could have been infected with Covid-19 but undiagnosed due to limited and unreliable testing at the time.

Two economic studies suggest that African-Americans may be dying at higher rates than white people in part because of black people’s heavier reliance on public transportation for commuting.

Reports from populations in Atlanta (CDC) and Louisiana (Oschner Health) support older age, black race, male sex, lack of commercial insurance, smoking, obesity, and diabetes as risk factors for being hospitalized because of Covid-19. Race was not a risk factor for death after comorbidities and other socio-demographics were considered. The comorbidities that were more prevalent among black patients included fever, higher markers of inflammation, and/or poor kidney function than white patients.

Recent reports have described individuals who developed type 1 diabetes following a Covid-19 infection. While previous reports have linked diabetes with Covid-19 infection, these new cases as well as a series of patients admitted with high blood sugar and ketones (produced by the liver when insulin levels are low) suggest that the virus might cause an autoimmune reaction which impacts a patient’s ability to regulate insulin.

Vaccines and Treatments

Labs are turning to pooled testing for more efficient Covid-19 surveillance. The approach will be used by Cornell University when it reopens to students in the fall.

The FDA will require any Covid-19 vaccine to prevent disease in 50 percent of recipients to win approval.

Moderna’s vaccine candidate phase 3 trial, which was expected to start on July 9^th, has been delayed. It’s unclear when the trial will begin, as the company is revising its protocol or plan, although many are still optimistic it will be this month.

Giliad Pharmaceuticals announced pricing of remdesivir, the antiviral agent with FDA emergency use authorization to treat hospitalized patients with Covid-19. For governments in developed countries the price will be $390 per vial, or $2,340 for a 5-day course. The price for U.S private insurance will be 33% higher – $520 per vial for U.S.

Policy Interventions

Conflicting Covid-19 messages are creating a cloud of confusion around public health and prevention. NewsGuard has identified 217 websites in Europe and the United States that publish “materially false” information about COVID-19. A separate study of 225 pieces of online misinformation found that misinformation spread by political figures and celebrities made up only 20% of the sample but accounted for 69% of engagement.

Public health departments play a crucial role in controlling the pandemic around the world. But in the U.S., since 2010, spending for state public health departments has dropped by 16% per capita and spending for local health departments has fallen by 18%.

Airports, hospitals, and other locales are checking temperatures to reduce the spread of Covid-19, but now experts are suggesting using a smell test. Several reports already identified loss of smell as a common early symptom of the disease. A recent study found that Covid-19 patients were 27 times more likely to lose their sense of smell but only 2.6 times as likely to have a fever or chills.

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