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Is Vaping Safer than Smoking Cigarettes?

Laura Gottschalk, PhD, John-Anthony Fraga, Jared Hirschfield, Diana Zuckerman, PhD, National Center for Health Research


Electronic cigarettes, or e-cigarettes, are being marketed as the “safe” new alternative to conventional cigarettes. By November 7, 2019, reports of 39 deaths and more than 2,000 possible cases of serious lung injuries related to vaping have made it clear that vaping can be even more dangerous than smoking.23 Many of the patients report vaping marijuana products or marijuana and nicotine products, but others only vaped nicotine products. Based on what they know so far, doctors believe that the cause is chemical, not bacterial. But until these reports of hospitalized teens and adults are scrutinized in greater depth, we won’t know what types of vaping are most dangerous and under what circumstances.

E-cigarettes come in a variety of forms and include vape mods, Juuls, and vape pens. There are brand name products (Juul is the most widely used) and “home-made” versions.  Some contain high levels of nicotine, while others contain marijuana or just contain flavoring.  The focus of this article is on e-cigarettes because most of the research that exists has been done on them, but much of the information below is relevant to these other products as well.

The big questions are: Are they safe?  Will they reverse the decline in smoking—giving new life to an old habit—or can they help people quit smoking?  Here is what you need to know.

What are E-cigarettes?

E-cigarettes are battery-operated devices that were initially shaped like cigarettes, but now include vape mods, Juuls, and vape pens. The brand-name products contain nicotine, an addictive drug that stimulates, relaxes, and is naturally found in tobacco. It is the nicotine in cigarettes that makes smoking so addictive, and the same is true for most vaping and juuling. These electronic products allow nicotine to be inhaled, and they work by heating a liquid cartridge containing nicotine, flavors, and other chemicals into a vapor. Because e-cigarettes heat a liquid instead of tobacco, what is released is considered smokeless.1

Is Vaping Safer than Smoking Traditional Cigarettes?

The key difference between traditional cigarettes and e-cigarettes and related products is that the latter don’t contain tobacco.  But, it isn’t just the tobacco in cigarettes that causes cancer and other serious diseases. Traditional cigarettes contain a laundry list of chemicals that are proven harmful, and e-cigarettes have some of these same chemicals.

While smoking can cause lung cancer, breast cancer, emphysema, heart disease, and other serious diseases, those diseases usually develop after decades of smoking.  In contrast, in 2019 it became clear that vaping could cause seizures and serious lung damage after just a year, possibly less, based on CDC reports of almost 200 patients hospitalized for lung damage apparently caused by vaping.2,3   While there have been warnings about the possible risk of e-cigarettes for a decade, it was not expected that they could cause such severe damage in such a short period of time.

Since 2009, FDA has pointed out that e-cigarettes contain “detectable levels of known carcinogens and toxic chemicals to which users could be exposed.” For example, in e-cigarette cartridges marketed as “tobacco-free,” the FDA detected a toxic compound found in antifreeze, tobacco-specific compounds that have been shown to cause cancer in humans, and other toxic tobacco-specific impurities.4 Another study looked at 42 of these liquid cartridges and determined that they contained formaldehyde,  a chemical known to cause cancer in humans.5 Formaldehyde was found in several of the cartridges at levels much higher than the maximum EPA recommends for humans. In 2017, a study published in the Public Library of Science Journal showed that significant levels of benzene, a well-known carcinogen, were found in the vapor produced by several popular brands of e-cigarettes. 6

The body’s reaction to many of the chemicals in traditional cigarette smoke causes long-lasting inflammation, which in turn leads to chronic diseases like bronchitis, emphysema, and heart disease.7 Since e-cigarettes also contain many of the same toxic chemicals, there is no reason to believe that they will significantly reduce the risks for these diseases.

In fact, a preliminary study presented at the 2018 annual meeting of the American Chemical Society found that vaping could damage DNA.8 The study examined the saliva of 5 adults before and after a 15-minute vaping session. The saliva had an increase in potentially dangerous chemicals, such as formaldehyde and acrolein. Acrolein has been proven to be associated with DNA damage, for example, and DNA damage can eventually cause cancer. 9

A study of mice funded by the National Institutes of Health found that e-cigarette smoke could cause mutations in DNA that could increase the risk of cancer. These specific mutations have been shown to potentially contribute to the development of lung and bladder cancer in mice exposed to electronic cigarette smoke. The researchers claim that these chemicals could also induce mutations leading to cancer in humans. Although mice studies aren’t always relevant to human health, this study seems to confirm the studies of human health and e-cigarettes. 10

Because they are smokeless, many incorrectly assume that e-cigarettes are safer for non-smokers and the environment than traditional cigarettes. However, a study published in the International Journal of Hygiene and Environmental Health found that the use of e-cigarettes results in increased concentrations of volatile organic compounds (VOCs) and airborne particles, both of which are potentially harmful when inhaled.11 Although e-cigarette vapor may not result in the obvious smell and visible smoke of traditional cigarettes, it still has a negative impact on air quality, especially when vaping indoors.

There are no long-term studies to back up claims that the vapor from e-cigarettes is less harmful than conventional smoke. Cancer takes years to develop, and e-cigarettes were only very recently introduced to the United States. It is almost impossible to determine if a product increases a person’s risk of cancer or not until the product has been around for at least 15-20 years. Despite positive reviews from e-cigarette users who enjoy being able to smoke them where regular cigarettes are prohibited, very little is known about their safety and long-term health effects.

There is also danger from e-cigarettes exploding in the user’s mouth or face.  Last year, the British Medical Journal used data from several agencies to estimate that there were roughly 2,035 e-cigarette explosion and burn injuries in the U.S. just in a three-year period from 2015 to 2017.  One of the authors of the study stated that the number was likely higher as such incidents were not well tracked.  The report also said that e-cigarettes, commonly powered by a lithium-ion battery, could overheat to the point of catching fire or exploding, a phenomenon known as “thermal runway”.12

Can Vaping Help to Cut Down or Quit Smoking Regular Cigarettes?

If a company makes a claim that its product can be used to treat a disease or addiction, like nicotine addiction, it must provide studies to the FDA showing that its product is safe and effective for that use. On the basis of those studies, the FDA approves or doesn’t approve the product. So far, there are no large, high-quality studies looking at whether e-cigarettes can be used to cut down or quit smoking long-term. Most of the studies have been either very short term (6 months or less) or the participants were not randomly assigned to different methods to quit smoking, including e-cigarettes. Many of the studies are based on self-reported use of e-cigarettes. For example, a study done in four countries found that e-cigarette users were no more likely to quit than regular smokers even though 85% of them said they were using them to quit.13 Other year-long studies, conducted in the U.S., had similar findings.  A study published in a prestigious medical journal in 2014 found that although smokers may believe they are vaping e-cigarettes to help them quit,  6-12 months after being first interviewed, nearly all of them are still smoking regular cigarettes.14 Similarly, a year-long study published in 2018 compared smokers who used e-cigarettes to traditional cigarette smokers, and concluded that e-cigarette users were more likely to say they were trying to quit but no more likely to successfully kick the smoking habit, with 90% of e-cigarette users still smoking regular cigarettes at the end of the study.  Until there are results from well-conducted studies, the FDA has not approved e-cigarettes for use in quitting smoking.15

Teenagers, Children, and Vaping

The percentage of teenagers who have tried e-cigarettes almost quadrupled over just four years, from 5% in 2011 to 19% in 2015.  Three million U.S. students in middle school and high school tried e-cigarettes in 2015, according to the National Youth Tobacco Survey.  And, 1 in 5 middle schoolers who said they had tried e-cigarettes also said they had never smoked conventional cigarettes.16

E-cigarette and juul use by young people is worrisome for a number of reasons:

  1. The younger people are when they begin smoking, the more likely it is they will develop the habit: nearly 9 out of 10 smokers started before they were 18.17
  2. Nicotine and other chemicals found in e-cigarettes, juuls, etc.  might harm brain development in younger people.18
  3. Vaping may introduce many more young people to smoking who might otherwise never have tried it, and once they are addicted to nicotine, some may decide to get their “fix” from regular cigarettes. Whether vaping or juuling is a “gateway” to regular cigarettes or not, young people who use them risk becoming addicted to nicotine and exposing their lungs to harmful chemicals.

The sharp rise in vaping among youth highlights the need to stop manufacturers from targeting teenagers with candy-like flavors and advertising campaigns.

Even children who are too young to smoke have been harmed by e-cigarettes and related products. The liquid is highly concentrated, so absorbing it through the skin or swallowing it is far more likely to require an emergency room visit than eating or swallowing regular cigarettes. In 2012, less than 50 kids under the age of six were reported to poison control hotlines per month because of e-cigarettes. In 2015, that number had skyrocketed to about 200 children a month, almost half of which were under the age of two!19

For more information about juuls, check out our article here.

How are these products regulated?

The FDA was given the power to regulate the manufacturing, labeling, distribution and marketing of all tobacco products in 2009 when President Obama signed into law the Family Smoking Prevention and Tobacco Control Act and in 2010 a court ruled that the FDA could regulate e-cigarettes as tobacco products.20

E-Cigarette Ad

It wasn’t until 2016 that the FDA finalized a rule to regulate e-cigarettes, which would ban the sale of e-cigarettes to anyone under the age of 18 and would require all e-cigarettes that hit shelves after February 15, 2007 to go through a “premarket review,” the process that the FDA uses to determine whether potentially risky products are safe.21 Companies were to be given from 18 months to two years to comply with this rule and prepare their applications. However, in 2017, the Trump administration appointed a new FDA Commissioner, Dr. Scott Gottlieb, who defended the safety of e-cigarettes and delayed implementing the rules until 2022.8 Nevertheless, as the epidemic of e-cigarette use among youth became obvious, in 2018, Commissioner Gottlieb threatened to crack down on the advertising of e-cigarettes to children under 18.22 Critics have questioned whether sales and ads can be effectively restricted. Moreover, Commissioner Gottlieb resigned in 2019, and it is unclear how the agency will respond to the growing evidence that vaping can cause serious harm.

In the meantime, individual states have always had the power to pass laws restricting the sale and use of e-cigarettes. Current laws pertaining to e-cigarettes are available on the Public Health Law Center website: https://www.publichealthlawcenter.org/resources/us-e-cigarette-regulations-50-state-review

The Bottom Line

E-cigarettes, juuls, and other similar products have not been around long enough to determine the harm they cause in the long run. Unfortunately, many people, including teenagers, are under the impression that e-cigarettes are safe or that they are effective in helping people quit smoking regular cigarettes. Studies by the FDA show that e-cigarettes contain some of the same toxic chemicals as regular cigarettes, even though they don’t have tobacco. There is evidence that some of these toxic chemicals can cause DNA damage that can cause cancer. More important, the reports of teens and adults who died or were hospitalized due to vaping are proof that vaping can be extremely dangerous even after just a few weeks, months, or years.

The big three tobacco companies—Lorillard, Reynolds American, and Altria Group—all have their own e-cigarette brands, so it’s not surprising that e-cigarettes are being marketed and advertised much the way regular cigarettes used to be. Here are the 7 Ways E-Cigarette Companies Are Copying Big Tobacco’s Playbook.

Although there are clearly serious dangers from vaping, more research is needed to confirm the impact of vaping on DNA damage, especially in children. Meanwhile, claims that e-cigarettes are an effective strategy to quit smoking are not supported by the evidence thus far. In addition, more toxicological studies and epidemiological studies are needed to understand the hundreds of reports of permanent lung damage and deaths from vaping.  It is essential to find out whether some types of vaping are more dangerous than others in the short-term and the long-term.  To understand the risks for everyone who vapes, research is needed to compare the risks of specific brands of e-cigarettes with tobacco products, as well as to neither smoking nor vaping.

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

The National Center for Health Research is a nonprofit, nonpartisan research, education and advocacy organization that analyzes and explains the latest medical research and speaks out on policies and programs. We do not accept funding from pharmaceutical companies or medical device manufacturers. Find out how you can support us here.

  1. O’Connor RJ. Non-cigarette tobacco products: What have we learned and where are we headed? Tobacco Control. 2012;21(2): 181–190. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3716250/
  2. Hauck G.  CDC reports 153 possible cases of vaping-related illnesses, many involving THC. USA TODAY. August 22, 2019. https://news.yahoo.com/cdc-reports-153-possible-cases-180325194.html
  3. Sum LH. He went from hiking enthusiast to ‘on death’s door’ within days. Doctors blamed vaping. Washington Post. August 24, 2019. https://www.washingtonpost.com/health/one-mans-near-death-experience-with-vaping-related-lung-failure/2019/08/24/ca8ce42c-c5b4-11e9-9986-1fb3e4397be4_story.html 
  4. Food and Drug Administration. Summary of Results: Laboratory analysis of electronic cigarettes conducted By FDA. FDA News & Events. July 22 2009.
  5. Varlet V,  Farsalinos K, Augsburger M, et al. Toxicity of refill liquids for electronic cigarettes. International Journal for Environmental Research and Public Health. 2015;12:4796-4815. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4454939/
  6. Pankow JF, Kim K, McWhirter KJ, et al. Benzene formation in electronic cigarettes. PLOS ONE. 2017;12(3),e0173055. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/28273096/
  7. Centers for Disease Control and Prevention. Overviews of Diseases/Conditions. February 2019.  https://www.cdc.gov/tobacco/campaign/tips/diseases/index.html
  8. McGinley, L. FDA sued for delaying e-cigarette, cigar regulations. Washington Post. March 27 2018.  https://www.washingtonpost.com/news/to-your-health/wp/2018/03/27/fda-sued-for-delaying-e-cigarette-cigar-regulations/?utm_term=.f92695720619.
  9. Lee HW, Park SH, Weng MW, et al. E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells. Proceedings of the National Academy of Sciences of the United States of America. 2018;115(7), E1569. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816191/
  10. Kaisar MA, Prasad S, Liles T, et al. A decade of e-cigarettes: Limited research & unresolved safety concerns. Toxicology. 2016;365: 67–75. http://doi.org/10.1016/j.tox.2016.07.020
  11. Schober W, Szendrei K, Matzen W, et al. Use of electronic cigarettes (e-cigarettes) impairs indoor air quality and increases FeNO levels of e-cigarette consumers. International Journal of Hygiene and Environmental Health. 2014;217(6):628-637.  https://www.sciencedirect.com/science/article/pii/S1438463913001533
  12. Kaplan S. E-Cigarette exploded in a teenager’s mouth, damaging his jaw.  The New York Times. June 19 2019.  https://www.nytimes.com/2019/06/19/health/ecigarettes-explosion.html
  13. Adkison SE, O’Connor RJ, Bansal-Travers M, et al. Electronic nicotine delivery systems: International tobacco control four-country survey. American Journal of Preventive Medicine. 2013;44(3):207-215. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23415116/
  14. Grana RA, Popova L, Ling PM. A longitudinal analysis of electronic cigarette use and smoking cessation. JAMA Internal Medicine. 2014;174(5):812–813. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122246/
  15. Food and Drug Administration. Electronic Cigarettes. FDA News & Events. 25 July 2013.
  16. Singh T, Arrazola RA, Corey CG, et al. Tobacco use among middle and high school students – United States, 2011-2015. CDC Morbidity and Mortality Weekly Report. 2016. 65(14);361-367. https://dx.doi.org/10.15585/mmwr.mm6514a1
  17. Centers for Disease Control and Prevention. Fact sheets: Youth and tobacco use. Updated 2019. http://www.cdc.gov/tobacco/data_statistics/fact_sheets/youth_data/tobacco_use/
  18. Centers for Disease Control and Prevention. Preventing tobacco use among youth and young adults. 2012. http://www.cdc.gov/tobacco/data_statistics/sgr/2012/index.htm
  19. Kamboj A, Spiller HA, Casavant MJ, et al. Pediatric exposure to e-cigarettes, nicotine, and tobacco products in the United States. Pediatrics. 2016;137(6). pii: e20160041. https://pediatrics.aappublications.org/content/137/6/e20160041.long
  20. Food and Drug Administration. Regulation of E-Cigarettes and Other Tobacco Products. FDA News & Events. April 25, 2011.
  21. Food and Drug Administration. Deeming Tobacco Products To Be Subject to the Federal Food, Drug, and Cosmetic Act, as Amended by the Family Smoking Prevention and Tobacco Control Act; Restrictions on the Sale and Distribution of Tobacco Products and Required Warning Statements for Tobacco Products. 21 CFR Parts 1100, 1140, and 1143. 2016;81(90):28973-29106. https://www.govinfo.gov/content/pkg/FR-2016-05-10/pdf/2016-10685.pdf 
  22. Saltzman J, Freyer F. The FDA issues a warning: Teen vaping is ‘an epidemic.’ Boston Globe. September 13 2018. https://www.bostonglobe.com/metro/2018/09/12/fda-cracks-down-vaping-orders-makers-address-sales-minors/JaiqQYzZAl4CINLufnkKlL/story.html.
  23. Knowles H, Sun LH. What we know about the mysterious vaping-linked illness and deaths. Washington Post. November 7, 2019. https://www.washingtonpost.com/health/2019/09/07/what-we-know-about-mysterious-vaping-linked-illnesses-deaths/  

Can Belly Fat Cause Cancer?

Ammu Dinesh and Claire Viscione, National Center for Health Research


Belly fat is common among men and women. However, when a person’s body shape looks more like an apple than a pear, that could increase their likelihood of developing cancer. 

More than two-thirds of adult Americans are overweight or obese.1 Most people know that obesity increases the risk of diabetes, heart disease, and high blood pressure. But did you know that being overweight increases your chances of developing cancer, and that having an “apple” body shape due to belly fat can increase your chances of developing cancer even if you are not overweight?

Why is belly fat dangerous?

Whether your body fat is located at your waist (giving you an apple shape) or hips (giving you a pear shape) makes a difference to your health. Women tend to gain more belly fat as they get older. Regardless of their weight, white, black, and Latina women with a waistline measurement of 35 inches or more have higher health risks. This is also true for Asian women with a waistline of 31 inches or more. Although it is important to get rid of excess fat in general, belly fat is the most threatening to your health.

Physicians use often use body mass index (BMI) to estimate whether you are overweight or obese. However, determining your waist circumference is just as important. Even if you are not overweight or obese, if you have a lot of belly fat, you are more likely to develop cancer.

Unlike the fat that sits just beneath the skin, the fat that sits around internal organs is called visceral fat.2 This fat is the most dangerous, and it is typically what shows up as belly fat. If you measure your waistline, you can get a good idea of whether you have a dangerous amount of belly fat. 

Women Men
Low health risk 31.5 inches or less 37 inches or less
Intermediate health risk 31.6 – 34.9 inches 37.1 – 39.9 inches
High health risk 35 inches or more 40 inches or more

Table 1. What does your waistline measurement mean? 2

Several studies have looked at the relationship between belly fat and cancer. One study followed over 150,000 post-menopausal women ages 50-79 for about 20 years.3 This study found that women who have extra belly fat are at higher risk of death regardless of their weight. Causes of death in the study included cardiovascular disease and cancer. The women of normal weight who had extra belly fat tended to be older, nonwhite, and with less education and income. They were also less likely to use menopausal hormones and to exercise. 

To figure out your BMI for the chart below, enter your height and weight into this calculator.

Apple Shape (Extra Belly Fat) Not “Apple Shape”
Not Overweight (BMI below 25) 20% more likely to die from cancer within 20 years
Overweight (BMI of 25-29.9) 19% more likely to die from cancer within 20 years 4% less likely to die from cancer within 20 years
Obese (BMI of 30 or higher) 26% more likely to die from cancer within 20 years 4% less likely to die from cancer within 20 years

Table 2. Likelihood of death due to cancer in women based on BMI.3

Women who were not overweight or obese but had extra belly fat were just as likely to die from cancer as overweight women with extra belly fat.

A different study followed over 3,000 men and women for 7 years.4 They used CT scans and physical exams to look at the fat throughout the body. Over the course of the study, the men and women developed 141 cases of cancer, 90 heart-related incidents, and 71 deaths from various causes. The study found that people with more belly fat, specifically visceral fat, were about 44% more likely to develop cancer and heart disease, even when adjusting for waist circumference. 

What can you do?

As you can see, belly fat can be very dangerous, especially for women, even if they are not overweight. Losing weight or preventing weight gain can lower health risks. By exercising regularly, you can get rid of unhealthy belly fat. It is also important to change your diet to eat foods that are high in nutrients and essential vitamins. You can do this by eating more fresh vegetables, nuts, and whole-grain breads instead of processed meat, red meat, candy, pasta, and white bread. These few changes can help you lose belly fat and improve the quality and length of your life.

Learn more about how extra body fat can increase your risk for developing cancer, and how you can make a commitment to your health and reduce risky belly fat:

 

All articles on our website have been approved by Dr. Diana Zuckerman and other senior staff.

 

References:

  1. Center for Disease Control and Prevention. FastStats- Overweight Prevalence. CDC.gov. https://www.cdc.gov/nchs/fastats/obesity-overweight.htm. Updated June 13, 2016.
  2. Harvard Health Publishing. Abdominal obesity and your health. Health.Harvard.edu. https://www.health.harvard.edu/staying-healthy/abdominal-obesity-and-your-health. September 2005. Updated January 20, 2017.
  3. Sun Y, Liu B, Snetselaar LG, Wallace RB, Caan BJ, Rohan TE, et al. Association of Normal-Weight Central Obesity With All-Cause and Cause-Specific Mortality Among Postmenopausal Women. JAMA Network Open. 2019;2(7):e197337. https://www.ncbi.nlm.nih.gov/pubmed/31339542.
  4. Britton KA, Massaro JM, Murabito JM, Kreger BE, Hoffmann U, Fox CS. Body Fat Distribution, Incident Cardiovascular Disease, Cancer, and All-Cause Mortality. Journal of the American College of Cardiology. 2013; 62(10): 921-925. http://www.onlinejacc.org/content/62/10/921.

NCHR Comments on FDA’s Draft Guidance on Enhancing the Diversity of Clinical Trial Populations

National Center for Health Research; August 6, 2019


National Center for Health Research’s Public Comments on
Enhancing the Diversity of Clinical Trial Populations-Eligibility Criteria,
Enrollment Practices, and Trial Designs; Draft Guidance for Industry; Availability
[FDA-2019-D-1264]

Thank you for the opportunity to express our views on the critical issue of increasing diversity in clinical trials, and how FDA should be addressing this longstanding issue through guidance to its Centers and broadening clinical trial eligibility requirements.

The National Center for Health Research (NCHR) is a non-profit think tank that conducts, analyzes, and scrutinizes research, policies, and programs on a range of issues related to health and safety.  We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.

For many years, NCHR has been strongly encouraging FDA to expand the diversity of clinical trials for drugs and medical devices to include more elderly patients, women, children, and individuals from a broad variety of racial and ethnic groups.  Too frequently, trials of drugs and devices which lead to FDA approval are still conducted mainly on white adults under the age of 65.  In some cases, treatments intended for men and women are primarily tested on one or the other, and not analyzed separately by sex.   In 2012, Congress passed a law urging the FDA to do a better job of expanding clinical trial participants to take into account the factors of age, race and ethnicity, and sexual differences.

There are reasons why a drug or device may be less safe or less effective for women, children, older patients, or certain ethnic or racial subgroups.  These differences in results for under-represented subgroups may not be minor or trivial.  According to a review of 167 new molecular entities approved by FDA between 2008 and 2013, approximately 20% had differences in exposure or response across racial or ethnic groups, or both.1

Lack of diversity in clinical trials has real world consequences on the knowledge about the effectiveness and safety of medical products.  Our research has identified several products that were less effective for certain subpopulations, which have important implications for clinicians and patients in choosing appropriate care.  In addition, the lack of age-related data has enormous consequences for Medicare, which is required to cover substantial costs for medical products that have not been studied on more than a few patients who were over 65.  Such lack of meaningful age-related testing results in the waste of many millions of taxpayer dollars on ineffective or even adverse medical outcomes.

In its proposed draft guidance, FDA has recognized the need to broaden eligibility criteria in order to increase diversity in enrollment.  However, there has not been sufficient incentive for drug and device sponsors to actively recruit more women, minority patients, children, and older patients.  In the past, FDA focused on the need for patient groups to encourage under-represented demographic groups to apply to clinical trials, rather than focusing on what companies should do to recruit under-represented patients to participate.  What is needed is an incentive for companies to ensure diversity, and the most effective incentive is if the FDA makes it clear that the agency will not approve medical products for all populations if the product was not tested for safety and efficacy on sufficient numbers of patients representing major demographic subgroups.

Certainly FDA’s draft guidance recommendation to make trial participation less burdensome for participants is a positive step, but that in itself will not result in the recruitment of a broader section of demographic subgroups who have been too often largely excluded in the past.  However, advising potential trial participants of possible reimbursement of travel and other trial expenses, as FDA’s draft guidance also recommended, may well help recruit older patients, parents of young children and caretakers of family members, and others who may otherwise lack the financial resources to enable them to participate in clinical trials.

We agree that measures to adopt enrollment and retention practices that enhance inclusiveness as outlined in the draft guidance should have a positive impact on the recruitment of broader demographic subgroups.  However, these should be “strongly encouraged” and not simply “considered.” The same is true for the recommendations for trial design and methodological approaches, which are also intended to broaden clinical trial participation.  The lack of meaningful incentives for sponsors to broaden clinical trial eligibility and recruitment has been a primary cause of why these various subgroups have remained under-represented for so long.

FDA issued a 1993 guidance for the inclusion of women trial participants in the clinical evaluation of drugs, and that situation has improved although more needs to be done in terms of using the data to restrict labeled indications when appropriate.  NCHR was critical of the 2014 FDA Action Plan for efforts to include more elderly patients in clinical trials as lacking in specificity.  This latest draft guidance is a chance for the agency to rectify these clearly identified and longstanding shortcomings.

The agency’s work with the Office of Minority Health, the HHS Office for Human Research Protections, and NIH, as well as the FDA Consumer page, indicates progress in improving enrollment diversity practices in clinical trials.  But our research indicates that much remains to be done.

We also point out that while this guidance pertains to CDER and CBER, diversity in clinical trials is also essential for medical devices, particularly implants.  Our research on devices approved through the PMA pathway following Advisory Committee consideration in 2014-2017 found numerous devices were tested primarily on white patients.2  For devices that included information about race, white participants made up 69%-99% of participants.  Most devices did not include information about the number of participants over the age of 65 years and many did not specify the range of ages of participants in trial(s).

In addition, of devices intended for both men and women, 45% (9/20) of devices were approved based on pivotal trials where less than 35% of participants were of the minority gender.  The implications of lack of diversity in clinical trials for high-risk medical devices are important.  For example, Lutonix, a drug-coated balloon catheter used to open a blocked artery, was found to be beneficial for men but not women; women’s outcomes were better with of the control balloon catheters.  A colorectal cancer test, Epi proColon, was, even though it was less accurate for patients older than 69 years of age than for patients less than 60 years old.  It was also found to be less accurate for black patients compared to white.

Thank you for the opportunity to comment on this important medical and patient issue.

National Center for Health Research can be reached at info@center4research.org or at (202) 223-4000.

References

  1. Ramamoorthy A, Pacnowski MA, Bull J, Zhang L. Racial/ethnic differences in drug disposition and response: Review of recently-approved drugs. Clinical Pharmacology & Therapeutics. 2015;97(3):263-273. https://www.ncbi.nlm.nih.gov/pubmed/25669658
  1. Fox-Rawlings SF, Gottschalk L, Doamekpor LA, Zuckerman D. Diversity in Medical Device Clinical Trials: Do We Know What Works for Which Patients? Milbank Quarterly.2018;96(3):499-529. https://onlinelibrary.wiley.com/doi/abs/10.1111/1468-0009.12344

 

Dr. Diana Zuckerman’s Statement on FDA’s Request for Recall of Allergan Breast Implants and Expanders


Statement of Dr. Diana Zuckerman, President, National Center for Health Research on July 24 Announced Recall of Allergan Biocell Breast Implants and Expanders

“The FDA announced today that at its request, Allergan is implementing a worldwide recall of their Biocell textured breast implants and expanders.  This recall is an important step toward reducing the risk of a type of cancer of the immune system called Anaplastic Large Cell Lymphoma (ALCL) caused by breast implants.  Many other countries had already banned this type of Allergan textured breast implant, but the FDA had previously stated that such a ban was premature.  However, it was inevitable that either the company would voluntarily decide to withdraw them from the market to protect from lawsuits, or the FDA would persuade Allergan to do so.  It is a little surprising that the FDA is taking credit for the recall, since most recalls of medical devices are described by the companies as voluntary.

“When women decide to get breast implants for reconstruction after mastectomy or for breast augmentation, they should not be putting their lives at risk for lymphoma.  This recall will reduce that risk but it won’t eliminate it.”

For more information, see the FDA’s Press Release here.

Cancer Prevention and Treatment Funds’ Comments On USPSTF Draft Recommendation Statement for BRCA-Related Cancer: Risk Assessment, Genetic Counseling, and Genetic Testing

March 18th, 2019


We are pleased to have the opportunity to express our strong concerns about the draft recommendations for risk assessment, genetic counselling, and genetic testing for BRCA-related breast cancer. The Cancer Prevention and Treatment Fund is a nonprofit program that conducts, analyzes, and reviews research, with a particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from pharmaceutical companies and have no financial ties to this issue.

We have concerns about the familial risk prediction methods and the baseline mutation probability threshold being used to refer large numbers of women for genetic counselling and potentially genetic testing.

According to the CDC[1], 1 in 40 Ashkenazi Jewish women have the BRCA mutation. Based on most of these models, most 30-year-old Jewish women with any first- or second-degree family history of breast cancer would likely be referred for genetic counseling, and yet 90% will not have a BRCA mutation.  This will clearly raise anxiety levels and we question whether the benefits outweigh those concerns.

Studies have shown that applying a seemingly universal mutation probability threshold of 10% for almost all risk prediction models will lead to a phenomenon called ‘over-dispersion.’  This means that those who are most likely to be carriers will have a very high probability prediction and those who are least likely to be carriers will have very low probability estimation.[2] Statistically, this often provides misleading and conflicting results to physicians.

Additionally, further research on the validation of risk prediction models has shown that the decision threshold should be derived from “diagnostic accuracy measures rather than defined directly by any breast cancer risk.”[3] Science has shown that tests in clinical settings with a high sensitivity are more likely to detect a higher number of carriers ultimately reducing the burden of unnecessary medical expense.3

Therefore, we urge the USPSTF to reconsider its assessment of the risk prediction models by employing a universal standardized sensitivity threshold instead of a universal standard mutation probability threshold. A universal sensitivity for all predication models will yield varying but statistically relevant mutation thresholds for different models. This will more accurately identify mutation carriers in need of genetic counselling and reduce the overall number of non-carriers who are sent for genetic counselling.

For questions or more information, please contact Dr.Varuna Srinivasan, MBBS, MPH at vs@center4research.org.

[1] Center for Disease Control and Prevention,  Jewish Women and BRCA Gene Mutations, www.cdc.org, https://www.cdc.gov/cancer/breast/young_women/bringyourbrave/hereditary_breast_cancer/jewish_women_brca.htm, November 5th 2018

[2] Lindor, N. M., Lindor, R. A., Apicella, C., Dowty, J. G., Ashley, A., Hunt, K., Mincey, B. A., Wilson, M., Smith, M. C., … Hopper, J. L. (2007). Predicting BRCA1 and BRCA2 gene mutation carriers: comparison of LAMBDA, BRCAPRO, Myriad II, and modified Couch models. Familial cancer, 6(4), 473-82.

[3] Schneegans, S. M., Rosenberger, A., Engel, U., Sander, M., Emons, G., & Shoukier, M. (2011). Validation of three BRCA1/2 mutation-carrier probability models Myriad, BRCAPRO and BOADICEA in a population-based series of 183 German families. Familial cancer, 11(2), 181-8.

NCHR Comments on USPSTF’s Draft Research Plan for Colorectal Cancer: Screening

National Center for Health Research: January 30, 2019

National Center for Health Research’s Public Comments on
the USPSTF’s Draft Research Plan for Colorectal Cancer: Screening

Thank you for the opportunity to share our views regarding U.S. Preventive Services Task Force (USPSTF)’s draft research plan regarding screening for colorectal cancer. The National Center for Health Research is a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.

The USPSTF last reviewed the literature in 2016 and provided an “A” grade for colorectal cancer screenings in adults aged 50 to 75 at average risk.1 It did not provide recommendations for particular stool-based, direct visualization, or serum screening tests, leaving the choice to be based on the balance of benefits, risks and preferences of the clinician and patient. However, recent studies based on the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program indicates that the rates of colorectal cancer are increasing among adults in their 40s.2  In response to that research, in 2018 the American Cancer Society released new guidelines recommending that adults at average risk for colorectal cancer begin screening at 45 years of age.3 In addition, the U.S Multi-Society Task Force on Colorectal Cancer supports screening African Americans for colorectal cancer beginning at age 45.4

We support the efforts of the USPSTF to carefully draft a research plan to guide the systematic review of available evidence for colorectal cancer screenings to reduce rates of colorectal cancer mortality. We also strongly support the efforts of the USPSTF to review the evidence regarding the harms and benefits of specific types of colorectal cancer screenings, and how they vary by age, sex, and race/ethnicity.

The draft research plan is specifically for average-risk adults, with adults at higher risk intentionally excluded. It is essential that the USPSTF always clearly specify whether recommendations are aimed only at individuals at average-risk.

We commend inclusion of the proposed contextual questions to determine what tools exist to assess the risk of colorectal cancer in the average-risk population. However, we strongly urge that these tools also be explicit regarding the impact of race/ethnicity, sex, and age, because those traits can affect the development of colorectal cancer as well as mortality.

While we understand that screening recommendations for high-risk individuals might differ from those for average-risk individuals, it is not clear why the draft research plan excludes all studies based on high-risk individuals.  Such studies could have important implications for the effectiveness or safety of screening methods for average-risk individuals.  This decision should be clarified or reconsidered.

We disagree with the plan to exclude the analysis of minor harms that affect screening behaviors and compliance with screening guidelines, such as physical discomfort and convenience.  Preparation for colonoscopy is the subject of considerable criticism and even derision.  As a result, it is essential to consider avoidance behaviors that result from minor harms.

We also urge that the analyses include studies of the potential harms of false positives that result in unnecessary colonoscopies or polypectomy.

We commend the inclusion of demographic subgroup analyses for screening program effectiveness, screening test accuracy, and harms.  We urge that these be analyzed in terms of whether the screening tests have benefits that outweigh the risks for each subgroup, rather than compare which subgroup has the best outcomes compared to other subgroups.  What matters to patients is whether the screening test is safe and effective for patients like them, not whether there are other types of patients for whom some tests are better.

In conclusion, we strongly support the USPSTF’s efforts to update recommendations for different types of colorectal cancer screening for different demographic subgroups, as well as their broader efforts to improve the health of all Americans by making evidence-based recommendations about clinical preventive services.

Thank you for the opportunity to comment on this issue.

The National Center for Health Research can be reached through Stephanie Fox-Rawlings, PhD at sfr@center4research.org.

References

  1. Final Recommendation Statement: Colorectal Cancer: Screening. U.S. Preventive Services Task Force. June 2017. https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/colorectal-cancer-screening2
  2. Siegel RL, Fedewa SA, Anderson WF, et al. Colorectal cancer incidence patterns in the United States, 1974–2013. JNCI: Journal of the National Cancer Institute. 2017. 109(8). https://doi.org/10.1093/jnci/djw322
  3. Smith RA, Andrews KS, Brooks D, et al. Cancer screening in the United States, 2018: A review of current American Cancer Society guidelines and current issues in cancer screening. CA: A Cancer Journal for Clinicians. 68(4):297-316. https://onlinelibrary.wiley.com/doi/full/10.3322/caac.21446
  4. Rex DK, Boland CR, Dominitz JA, et al. Colorectal cancer screening: Recommendations for physicians and patients from the US Multi-Society Task Force on Colorectal Cancer. The American Journal of Gastroenterology. 112(7):1016-1030. https://www.nature.com/articles/ajg2017174

NCHR Comment on FDA’s 510(k) Third Party Review Program Draft Guidance

National Center for Health Research: December 13, 2018


Comment of the National Center for Health Research Regarding the
510(k) Third Party Review Program:
Draft Guidance for Industry, FDA Staff, and Third Party Review Organizations.
OMB Control Number 0910-0375

The National Center for Health Research (NCHR) is a non-profit organization which conducts original research to better inform policy makers, health professionals, and patients.   NCHR accepts no funding from any entity which manufactures or distributes medical products.

We appreciate the opportunity to comment on this draft guidance.  We note that this draft guidance applies to low-to-medium risk medical devices, which concerns us because many Class II devices are permanent implants that have the potential to cause permanent harm to patients.  In fact, our research indicates that even Class I devices have been subjected to high-risk recalls by the FDA due to the potential for causing death or permanent harm.1 2 3

We have several serious concerns about the draft guidance.  First, Original Equipment Manufacturers (OEM) are accountable for the efficacy and safety of their medical devices.  FDA standards require that devices manufactured by OEM’s comply with relevant regulatory standards.  OEMs are required to track, monitor, and report product issues to FDA.  Overseeing the OEMs and their reporting are FDA’s responsibility to ensure patient safety.

Second, in the past FDA has had the opportunity to review the work of any third party reviewer, and reject it if deemed inadequate or shoddy.  In fact, the agency has often found problems with the third party reviews.  The proposed guidance would sharply reduce the agency’s oversight of third party reviews, which will clearly compromise safety.  Even if certified as qualified, third party review companies have an inherent conflict of interest: If their standards are too high, no device company will hire them and they will go out of business.  The system is similar to the EU regulation of medical devices, which has resulted in very harmful decisions, such as the clearance of the PIP breast implants that were found to use non-medical grade silicone.4  In addition, investigative reporters recently obtained CE clearance for a “surgical” mesh that was made out of a plastic mesh bag used for oranges.

Transparency is also a crucial factor.  Currently, third party review companies are not required to clearly label an OEM device indicating that a critical repair has been completed by someone other than the OEM.  Once that repair is made, the device is no longer the same device that was approved or cleared by FDA.  It is important that this chain of accountability is not broken or interrupted.

While we understand the desire of FDA officials to reduce medical device review times and reduce the burden on FDA staff and industry, the 510(k) program already is a quick way to get devices to market and the device industry has clearly benefitted from it.  The 510(k) pathway has been widely criticized by the Institute of Medicine, physicians, patients, and the media for its lack of clinical trials and lack of scientific evidence.5  Despite its weaknesses, the 510(k) pathway is considered superior to the EU regulatory system, however.  By reducing the “burden” for FDA staff and industry, the proposed guidance increases the burden on patients and doctors to figure out which devices are safe and which are not.  This would clearly put U.S. patients at greater risk.

FDA has not demonstrated that its proposed changes to the third party review pathway of Class I and Class II devices will benefit patients.  By definition, 510(k) devices only rarely are substantially superior to recent predicates.  Speeding up the process of clearance is not demonstrated to benefit patients.  Moreover, with registries, NEST, and other planned efforts to improve post-market surveillance still far from effectively implemented, any loosening of 510(k) regulations is very premature.

Finally, we note that Commissioner Gottlieb responded to recent media criticism of CDRH regulations by promising improvements to the 510(k) pathway to ensure patient safety.  The third party review program clearly moves in the opposite direction, reducing patient safety, rather than protecting patients from potentially harmful devices.   We strongly oppose it for that reason.

 

References

  1. Zuckerman, D.M., Brown, P, and Nissen, S.E.  (2011) Medical Device Recalls and the FDA Approval Process, Archives of Internal Medicine, 117, 1006-11.
  2. Zuckerman D.M., Brown P., Nissen S.E. (2011). In Reply, Archives of Internal Medicine, 171(11), 1045.
  3. Zuckerman D.M., Brown P., Nissen S.E. (2011). In Reply, Archives of Internal Medicine, 171(21), 1963.
  4. Zuckerman, D., Booker, N, and Nagda, S. (2012) Public Health Implications of Difference in US and European Union Regulatory Policies for Breast Implants, Reproductive Health Matters, 20 (40),102-111.
  5. Zuckerman D.M., Brown P. & Das A. (2014) Lack of Publicly Available Scientific Evidence on the Safety and Effectiveness of Implanted Medical Devices,  JAMA Internal Medicine, 174(11): 1781-1787.

 

After Years of Complaints, U.S. and U.K. Officials Say They Want to Reform the Medical Device Industry

Amy Martyn, ConsumerAffairs: November 29, 2018.


The official who oversees medical device safety for the Food and Drug Administration (FDA) recently said he wants the United States to be the “first” to approve medical devices, raising concerns among public health advocates that the agency isn’t taking efforts to reform the device industry seriously enough.

Dr. Jeffrey Shuren, the director of the FDA’s medical devices division under both the Obama and Trump administrations, earlier this year agreed to speak at a conference attended by medical device executives, according to a new report by the Associated Press.

At the conference, which cost executives $1,000 a head to attend, Shuren reportedly said that the FDA’s goal was to be “first in the world” to approve new devices. He also said he wanted the agency to remove “unnecessary burdens” for companies hoping to get their devices approved.

Such a goal may be at odds with what public health advocates say is a need to reform medical device regulation. Dr. Peter Lurie, a former FDA official who now heads the watchdog the Center for Science in the Public Interest, told the Associated Press that Shuren’s comments essentially offered device executives “an invitation to a race to the bottom for scientific standards.”

“Fatally flawed” system

The medical device industry already faces lower barriers for approval than the drug industry does, despite the fact that many medical devices are intended to be permanent implants or can leave lifelong impacts on a person’s body.

“If you’re going to have something implanted in your body for potentially the rest of your life, wouldn’t you like it to be really well-tested beforehand? Is that really too much to ask?” Dr. Diana Zuckerman, a health policy analyst and head of the National Center of Health Research, told ConsumerAffairs earlier this year.

Independent researchers for years have said that the medical device approval process in the U.S. is “fatally flawed.”

More recently, a Netflix documentary called The Bleeding Edge exposed the tragic, life-long effects that four failed medical implants had on nearly 70 patients interviewed for the film.

Looking for improvement

Regulators in the United States and abroad are now promising to put safety at the forefront of medical device regulation.

Shortly before Thanksgiving, FDA Commissioner Scott Gottlieb, who was portrayed in the Netflix film as being in the industry’s pocket, announced new plans for the agency to “create a more robust medical device safety net for patients through better data.”

A similar call to reform medical device regulations is also currently taking place in Europe. In the United Kingdom, the Royal College Of Surgeons recently called for “drastic regulatory changes” after an investigative report by a group of European journalists published yesterday linked 83,000 deaths and 1.7 million injuries to faulty medical devices.

But while medical devices face low scrutiny from European regulators, the socialized healthcare systems abroad are at least more hesitant about allowing such devices to actually be used in surgery, experts say.

“In Europe, it’s very easy to get something on the market, but the national health plans won’t pay for it if it’s not proven to be safe and effective,” Zuckerman of the National Center for Health Research previously told ConsumerAffairs.

It’s not that Europeans aren’t reporting injuries from faulty devices. However, those who do tend to be wealthier people who opted for private insurance over the public plans.

See the original story here.

Here’s What We Know About Breast Implants and This Rare Type of Cancer

Daisy Melamed Sanders, Survivornet: November 2018.

A series of new stories are examining the potential health risks that both silicone- and saline-filled breast implants may carry. The most serious of these is the possibility of developing a type of blood cancer. What’s not yet clear is if the evidence is significant enough for the government to issue a warning.

The blood cancer that implants may cause, called Breast Implant-Associated Anaplastic Large Cell Lymphoma or BIA-ALCL, is a type of non-Hodgkins lymphoma that is not breast cancer. It is rare, and symptoms include pain, redness and swelling around the implant or breast area.

And while getting breast implants certainly does not definitively mean you’ll definitely get this type of lymphoma, it’s a dangerous illness for those who do get it. “ALCL is rare, but for those who get ALCL from their breast implants, it is very frightening and potentially fatal,” says Diana Zuckerman, PhD, President of the National Center for Health Research.

Here’s what we do know: The Food and Drug Administration—responsible for regulating medications and medical devices—has acknowledged that it has known of a potential relationship between breast implants and increased risk of ALCL since 2011. The risk involves both textured and smooth implants but the FDA’s position is that the textured kind may have a higher likelihood of causing the disease. The FDA also notes that incomplete or inefficient monitoring of, and reporting on, these health issues on a national level has meant that many women do not know all the facts when choosing to have implants for either cosmetic or reconstructive reasons.

According to the FDA, “In most cases, BIA-ALCL is found in the scar tissue and fluid near the implant, but in some cases, it can spread throughout the body. Precise risks are difficult to determine due to lack of information about how many patients have received breast implants in the US and worldwide.”

In an interview conducted prior to recent news, Dr. Andrea Pusic, Chief of Plastic Surgery at Brigham and Women’s Hospital, told SurvivorNet that breast implants are generally considered safe—but they do require monitoring by a doctor. The FDA also states that breast implants are “not lifetime devices,” and that the longer a patient has them, the more likely they are to rupture or experience other complications.

With regards to the safety of implants, Dr. Darrick Antell, a private practice plastic surgeon in New York City, cites the rarity of these instances as part of the reason implants are not excessively dangerous. “Textured surface implants have rarely been noted to develop ALCL, at a rate of 1 in 30,000—I would even recommend them to a family member,” he says. “Multiple leading institutions from around the world have shown them to be safe.”

But, as Dr. Zuckerman urges, it’s important to discuss the risk with your doctor before getting implants, because some women felt blindsided and uninformed about the disease possibility. “We know women who, when they developed ALCL, felt betrayed because their doctors hadn’t warned them of the risks.”

Breast implants also have the possibility of causing other health or physical issues. These issues have not been fully studied, but Zuckerman and the NCHR recently released a paper that discusses some of the possible side effects.

The risks that come with implants are real for all women, Dr. Zuckerman tells SurvivorNet, but these risks increase with a personal or family history of autoimmune or connective tissue symptoms or diseases. They can happen soon after getting implants or years later, and are especially likely when a silicone gel implant breaks—most likely after three years. Another issue is that leaking silicone can migrate into the lymph nodes, and, “from there, the silicone can get into the lungs, liver, or other organs.” Broken saline implants, she continues, offer less risk when they leak, but can cause health issues from the silicone shell, other chemicals, as well as from bacteria, fungus and mold issues that develop over time.

This isn’t the first time instance of concern regarding breast implants and potential health risks. Throughout the 1980’s and early 1990’s, a company called Dow Corning was named in a number of class-action lawsuits claiming that their breast implants were the cause of a number of health issues.

In 1992, the FDA mandated that silicone implants be removed from the market, but they were re-introduced in 2006 following stricter regulations around tracking patients for at least 10 years after their surgeries. However, because monitoring the implants and patients with them is not always thorough nor properly reported, it is difficult to know for sure what side effects implants are having in the long term.

The best idea, as always, is to discuss all the possible risks and benefits of implants with your doctor before any procedures, and be on alert for any symptoms that indicate a medical issue, suggests Dr. Zuckerman. “If a woman with implants starts to have any of the autoimmune symptoms that we’ve described in our report, she should consider having her implants removed.”

See the original story here.

Doctors, Patients Raise Alarms About Cancer Linked to Breast Implants

Lauren Dunn and Maggie Fox, NBC News: November 26, 2018.


When Michelle Forney’s breast started swelling and itching, doctors told her she had mastitis, a common infection, and treated her with antibiotics. When she discovered that she, in fact, had a rare form of lymphoma and that it was probably caused by her breast implant, she was both furious and frightened.

Forney is just one of hundreds of breast-implant recipients who have developed a rare blood cancer called anaplastic large cell lymphoma (ALCL). The Food and Drug Administration has been investigating reports linking breast implants with the cancer, and now has more than 400 reports about patients who developed ALCL after having a breast implant, including nine who died.

“I had my breast implants for about 19 years. And everything was fine for many of those years until about three years ago,” when she developed major itching and pain in her breast, said Forney, who is 46 and lives in Sacramento.

“Come December of last year, I woke up one day and my breast was the size of a volleyball. Within a day it grew and just engorged,” Forney told NBC News. “So I immediately went back to the doctor, saw my OB-GYN and she brought in a breast specialist. And they said: ‘Oh, breast mastitis. You have an infection.’”

But a 10-day course of antibiotics did nothing to help.