Researchers Weigh Benefits, Risks of PPIs

Reviewed by Brunilda Nazario, MD on July 31, 2019

July 31, 2019 — Rebecca Hill thought she was having a heart attack. The 59-year-old Tennessee native, now living in Wasilla, AK, went straight to the ER.

“They did some tests and found out that I had reflux,” she says. “I’ve gone through very many PPIs to try to keep mine under control.”

She was 34. Since then, Hill has used most of the prescription PPIs available and several over-the-counter versions. She hasn’t had any side effects.

But not everyone has such positive experiences. PPIs, or proton pump inhibitors, are among the most common prescription drugs and are used to treat acid reflux, heartburn, indigestion, gastroesophageal reflux disease (GERD), and stomach ulcers. They include omeprazole, lansoprazole, esomeprazole, pantoprazole and rabeprazole, PPIs work by cutting the amount of acid the stomach makes.

There are numerous case studies of the popular prescription drugs causing myriad health problems. But research results are mixed. Some studies have warned of doctors being too quick to prescribe PPIs and patients staying on them for too long. Others have found little reason for concern.

LeighAnn Miller of Knoxville, TN, was on PPIs for years without any problems.
I had initially taken Prilosec probably about 10 years ago,” she says. “It was prescribed by my primary care physician. I Just had some random heartburn and he prescribed it to me, I took it, didn’t have any issues.”

The symptoms got better 3 years later, so she stopped taking it. But the symptoms came back last July, and she was prescribed a different PPI. This time, her experience was much different.

“I began to have what appeared to be bug bites on my forearm,” says Miller, 35. “And at first, it was just a few, then it began to multiply. … I was covered in a rash from head to toe with the exception of my face for 6 months. It did not resolve completely until March.”

She stopped taking the medication as soon as the symptoms began. After several visits to dermatologists and a rheumatologist, after extensive bloodwork and a battery of tests including a biopsy, everything came back normal. Miller says she and her rheumatologist did some research and found that it could be drug-induced lupus.

According to the Lupus Foundation of America, there is a possible but not definitive link between the condition and PPIs in some people.

The experience has soured Miller on PPIs. “I’m not saying that there are not benefits to these medications, but I do think that there is more risk involved than there is benefit.”

A Very Common Drug
Just how risky it is to take these popular drugs has become a source of debate.

While the benefits to patients are undeniable, the drugs’ safety has come into sharp focus, with studies and researchers both defending and questioning the drugs’ benefits, dangers, and widespread use.

In the last few years, thousands of lawsuits have been filed, with patients claiming side effects including kidney disease and bone fractures. According to Drug Watch, a consumer advocacy group, one of the first cases is set for trial in September 2020.

A study published in May in The BMJ, a British medical journal, looked at death rates associated with PPIs.

According to lead investigator Ziyad Al-Aly, MD, an assistant professor of medicine at Washington University School of Medicine in St. Louis, the study focused on 157,000 veterans who were prescribed PPIs for the first time, following them for 10 years.
“There is a very significant body of evidence that suggests that these drugs (PPIs), when used for a long period of time, especially when they are not medically indicated, are associated with serious side effects and also associated with increased dying from specific causes — namely dying from heart disease, kidney disease, and stomach cancer.”

“There may be other risks as well,” Al-Aly continued, “But, it is important to mention in this context that PPIs are not all evil drugs. They’re also beneficial drugs when used appropriately in the right patient and for the indicated duration of time. In the right patients, these drugs actually also save lives.”

Paul Moayyedi, MD, a professor of gastroenterology at McMaster University in Ontario, Canada, says his new research on PPIs, published in early June in the American Gastroenterology Association’s journal Gastroenterology, found no need for worry.

His study was a large trial of 17,598 people whom researchers followed for 3 years. They found no evidence to support claims that PPIs cause serious diseases like chronic kidney disease, pneumonia, diabetes, and dementia.

One group was put on a PPI, and the other was given a placebo. Moayyedi says they found similar rates “of everything” between the two groups, “The rates of heart disease, stroke, pneumonia, fracture, chronic renal disease, and dementia were very similar between the two groups. Cancer rates were also similar, and all cause mortality was almost identical between the two groups.”

Moayyedi says most of the studies of PPIs are observational and therefore less reliable. They only look to understand causes and effects of these medications. But studies like his test the impact of the drugs on patients against those simply given a placebo.

“In other words, they look at people who are on PPI and people who are not on PPI … and see what happens to them over time,” he says. “These have shown increases in risk of diseases such as pneumonia, fractures. However, on average, patients in these databases who are on PPI are sicker than those who are not, and sicker people get other illnesses.”

His message to patients: “There is no harm that we can see so far.”

Folasade May, MD, director of quality improvement in gastroenterology at UCLA Health, is working on a study of the overuse of PPIs. She feels more research is needed. It’s the only way, she says, to test whether a specific medication leads to a specific outcome.

“The reason why these questions and these studies are important is that there are millions of people on PPIs,” she says. “When a medication is this common, even rare adverse effects can impact a lot of individuals. And that’s why it’s important for scientists — those in the laboratory and those that conduct human studies — to expand our knowledge on if and how PPIs are affecting our bodies in ways that we don’t want them to.”

The Consumer Healthcare Products Association represents leading manufacturers and marketers of over-the-counter medicines. In a statement to WebMD, it stands by the safety of these drugs based on years of data and use.
“More than 60 authors from 29 countries recently published results from a large randomized clinical trial confirming the safety of PPIs. Addressing a number of less rigorous studies which have raised concerns that PPIs may be associated with various health risks, the Authors concluded, ‘It is reassuring that there was no evidence for harm for most of these events other than an excess of enteric [intestinal] infections.’ ” According to the American Gastroenterological Association, which published the study in its official journal, this “new research puts safety concerns to rest.”

For 20 years, John Pandolfino, MD, has been prescribing PPIs to his patients. The division chief of gastroenterology and hepatology at Northwestern University told WebMD he’s never had a patient complain about side effects.

“In the grand scheme of things, I do think PPIs are safe, but there are studies that suggest an association between PPIs and some adverse outcomes. However, I think we have to be careful when we look at those particular studies so as to not over exaggerate the cause-and-effect potential, but also to not completely discount them.

“We know that patients that take PPIs are inherently sicker than those who do not take PPIs, and this confounder may bias studies and explain many of these associations.”

Pandolfino thinks doctors who prescribe these medicines must be more vigilant in their follow-up.

“I think this is an important conversation to be having because right now, we’re seeing new studies every week about PPIs. And since they are very similar studies, we see the same results and the same potential bias in the outcomes. This is a wake-up call for all of us to do a better job of educating patients about the risks and benefits of medicines, because all medicines have risks.”

Risks that patients are trying to process as they make decisions about whether to remain on these drugs — or not.

As Melanoma Rises, Doctors Challenge Some Early Testing

May 6, 2019 — As melanoma cases continue to rise sharply, Americans are being urged to get screened early for this deadliest of skin cancers. But some dermatologists question whether screening people without symptoms has resulted in overdiagnosing melanoma, bringing unnecessary anxiety and treatments.

They note that while the number of invasive melanoma cases diagnosed in the U.S. doubled from 1982 to 2011 and continue to rise, death rates have only dropped slightly. From 2007 to 2016, deaths from melanoma decreased by 2% in adults 50 and older and by 4% in people younger than 50.

“A huge increase in diagnosed melanomas should be associated with a steep decline in mortality,” says Ade Adamson, MD, a dermatologist and assistant professor at Dell Medical School at the University of Texas at Austin. “This is a very delicate discussion in my field because we want to believe so badly that screening healthy people and early detection is going to save lives, regardless of the cancer.”

Adamson says advances in technology contribute to overdiagnoses, including skin scanning tools that pick up tiny changes the eye can’t see. He says it is difficult, sometimes impossible, for a doctor or pathologist to tell a malignant melanoma lesion from a benign mole in the earliest stages of skin cancer.

He says the United States Preventive Services Task Force — a group of independent experts that use evidence to guide decision making — cites overdiagnosis as one of the reasons it doesn’t endorse routine skin cancer screening. The task force said it didn’t have enough data to determine if screening helps save lives. This recommendation is for people without a history or skin cancer who do not have any suspicious moles or other spots.

“The potential for harm clearly exists,” according to a statement the task force released in 2016, although “current evidence is insufficient to assess the balance of benefits and harms of visual skin examination by a clinician to screen for skin cancer in adults.”

It says potential harms include misdiagnosis, overdiagnosis, cosmetic effects from biopsy (where a doctor removes a small amount of tissue to examine it for cancer cells), and overtreatment. For instance, surgical removal of moles can leave scars, and medications can have side effects.

A Controversial Topic

Overdiagnosis is controversial in the field of dermatology, where the prevailing wisdom is that greater exposure to ultraviolet (UV) radiation from the sun and tanning salons has led to higher melanoma rates over the years. Dermatology organizations urge Americans to use sunscreen, avoid tanning salons, and regularly get screened for skin cancer, especially if they sunburn easily or have a family history of the disease.

Since 1985, the American Academy of Dermatology has offered free skin cancer screening clinics around the country in May, which is melanoma awareness month.

A spokesman for the academy, Joel Cohen, MD, says the rise in melanoma cases may be related to better technology in the field that helps detect cancer early, screening programs that find melanoma early, and public education campaigns about how to recognize the early signs of skin cancer. When caught early, melanoma doesn’t have to be a death sentence, he says.

“Early diagnosis is absolutely essential when it comes to melanoma,” says Cohen, director of AboutSkin Dermatology in Greenwood Village, CO. “When we catch something tiny, believe me, it’s something to celebrate about. You’ve actually given this person a chance at life.”

Five-year survival rates for people whose melanoma is detected early is 92%, according to data provided by the American Society of Clinical Oncology. If the cancer has spread to other part of the body, that rate drops to 23%.

A recent study examined the American Academy of Dermatology’s SPOTme skin cancer screening program from 1986 to 2014. It said the data suggest that the program “detected thousands of skin cancers that may have gone undetected or experienced a delay in detection.”

It also said that people who went on to be diagnosed with skin cancer were more likely to be uninsured.

‘We’re Ramping Up Health Anxiety’

David J. Elpern, MD, a dermatologist in Williamstown, MA., says that overdiagnosis — not exposure to the sun — has contributed to rising melanoma rates. He believes dermatologists are finding more cases of melanoma early because of “diagnostic drift,” a growing tendency to diagnose and treat benign lesions as malignant cancers.

“You’re picking up tumors that probably never would have amounted to anything,” says Elpern, who has spoken out about changes in the field of dermatology that promote care that’s wasteful and not needed.

Overdiagnosis is not without consequences, he says. Once a patient is labeled with cancer, they’re launched into the health care system, where they’re subjected to excessive and expensive treatments, including biopsies, that are profitable for dermatologists.

“We’re ramping up health anxiety,” he says. Some dermatologists argue that these lowest-risk conditions shouldn’t be labeled as cancers at all. Instead, they should be watched.

But Stephanie Gardner, MD, a dermatologist in suburban Atlanta, says they are vigilant for a reason.

“Patient education and self-exams, appropriate timing of skin exams by dermatologists, and removal and surveillance of suspicious lesions all help to prevent advanced disease,” she says. “I would much rather be overdiagnosed than have a cancer missed, along with all of those ramifications.”

Prevention Tips

Prevention is the first step to avoid skin cancer. The American Academy of Dermatology urges everyone to take these steps:

  • Seek shade when needed. The sun’s strongest rays are between 10 a.m. and 2 p.m.
  • Wear protective clothing when possible: a wide-brimmed hat, sunglasses, long pants, and long-sleeved shirts.
  • Generously apply a broad-spectrum, water-resistant sunscreen with SPF 30 or higher. Use it whenever you are outside, even on cloudy days.
  • Reapply sunscreen every 2 hours.
  • Avoid tanning beds.
  • Do regular skin self-exams to look for new or suspicious spots on your skin.

People at higher risk of skin cancer include those who have:

  • Light skin
  • Skin that burns or freckles easily
  • Blue or green eyes
  • Blond or red hair
  • Certain types and a large number of moles
  • A family history of skin cancer
  • A personal history of skin cancer

How does bereavement impact the immune system?

Losing a loved one is, of course, incredibly traumatic; it may also shorten lifespan. A recent paper reviews decades’ worth of research into bereavement and its effects on the immune system.

For years, researchers and laypeople alike have noted that when someone loses a partner, their risk of mortality increases significantly.

In days gone by, we might have referred to this as a death from a broken heart.

The phenomenon has been under investigation for decades.

For instance, researchers using data from a Finnish population published their findings in 1987. They found that “For all natural causes, mortality during the first week [following the death of a spouse] was over two-fold, compared to expected rates.”

Another study, published in 1995, concluded that, following the death of a spouse, mortality “was significantly elevated in both men and women.” This elevation was most pronounced 7–12 months after the bereavement.

Although scientists have collected a fair amount of evidence demonstrating this effect, there is less information about the biological mechanism that drives it.

Bereavement and the immune system

Now, a literature review has attempted to tie previous findings together to create a clearer picture of this phenomenon. Specifically, the authors were interested in how bereavement and grief might negatively influence the immune system, thereby increasing mortality risk.

The authors, from the University of Arizona, in Tucson, recently published their paper in the journal Psychosomatic Medicine.

The researchers conducted a systematic review of published research from 1977 to now. In all, 33 studies met the grade to be considered for analysis and the scientists focused on 13, which were of the highest quality.

When asked why they conducted the research, one of the authors, Lindsey Knowles, explained that “There is strong evidence that spousal bereavement increases morbidity and risk for early mortality in widows and widowers; however, we have yet to discover how the stress of bereavement impacts health.”

It was in the late 1970s that scientists started looking to the immune system’s role in increased mortality risk after bereavement.

A paper published in The Lancet in 1977 claims to be the first to measure an abnormality in immune function following bereavement.

A new review of the evidence

Knowles explains that she wanted to create a document that includes “all published data on the association between bereavement and immune function — to establish a knowledge base and suggest specific directions for future research.”

The paper outlines the primary findings from studies that have been carried out to date.

In particular, they identify that people who are bereaved have increased levels of inflammation, faulty immune cell gene expression, and reduced antibody responses to immune challenges.

These changes are all significant when trying to understand why people who are bereaved have a higher risk of death; for instance, scientists already know that chronic inflammation plays a part in a range of conditions, including obesity, heart disease, and diabetes.

The authors also conclude that there is a link between the psychological impacts of bereavement — such as grief and depression — and how severely bereavement impacts immune function.

A study published in 1994, for instance, found that, overall, individuals who had been bereaved did not have significant differences in their immune profiles. However, those who also met the diagnostic criteria for depression did have impaired immune function.

This type of research is important; there is still an air of mystery around the topic, so any new insight is vital. Scientists know that grief increases the risk of an earlier death, so understanding what is happening on a physiological basis could help guide how doctors treat these people in the future.

Another of the paper’s authors, associate professor Mary-Frances O’Connor, explains how, “Someday, clinicians may be able to track changes in patients’ immunity and prevent medical complications after this difficult experience.”

When asked about the contribution that this paper lends to the field, O’Connor says:

“This systematic review gives researchers a resource to read all that research in one place, with a modern perspective on how the field has changed and a visual model to help move the field forward in a more organized way.”

Although this line of inquiry has a long history, there are still many gaps that scientists need to fill with fresh research.

As the authors explain, there is a great need for large longitudinal studies; for instance, if researchers could assess an individual’s immune profile before bereavement occurs and throughout the aftermath, this would provide a much-needed depth of information. Of course, this approach would require a great many resources.

Hopefully, this review will ignite a fascination in the next generation of researchers who are destined to tackle this topic.

Type 2 diabetes: Work stress may raise risk in women

A new review featuring in the European Journal of Endocrinology suggests that a stressful work environment may increase the risk of developing type 2 diabetes in women.

A stressful work environment may increase the likelihood of type 2 diabetes in women, suggests new research.

More than 100 million people in the United States have diabetes or prediabetes, according to the latest statistics.

Over 9 percent of the U.S. population is living with diabetes, and more than 84 million people are living with prediabetes — a condition that is bound to develop into full-blown type 2 diabetes without treatment.

Risk factors for type 2 diabetes include a lack of physical activity, being overweight or having obesity, being aged 45 years or older, having high cholesterol and high blood pressure, or having a family history of diabetes, heart disease, or stroke.

Psychological factors may also play a role in the development of type 2 diabetes. Living with depression may make the risk higher, and a new study now suggests that work-related stress may also increase the likelihood of developing the condition, at least for women.

Guy Fagherazzi, a senior research scientist at the Centre for Research in Epidemiology and Population Health at the research institute Inserm in Paris, France, led the new study.

Mentally tiring work raises risk by 21 percent

Fagherazzi and his colleagues set out to examine whether there was a link between “mentally tiring work” and the incidence of type 2 diabetes in more than 70,000 women over a period of 22 years between 1992 and 2014.

About 75 percent of the women in the study were teachers, and 24 percent of them said at the start of the study that their work was “very mentally tiring.”

Throughout the study period, 4,187 women developed type 2 diabetes. The analysis revealed that the prevalence of diabetes was considerably higher among women who deemed their job to be more mentally draining.

Specifically, those who said that their job was “very” mentally taxing at the start of the study were 21 percent more likely to develop the condition than women with “little or not mentally tiring work.”

When the researchers adjusted for other factors, including unhealthful lifestyle habits and cardiometabolic risk factors, such as high blood pressure or a high body mass index, the association between work and diabetes risk stayed the same. Fagherazzi and colleagues conclude:

“These observational results suggest the importance of taking into consideration the potential long-term metabolic impact of work-related stress for women working in a demanding environment.”

The study’s senior author comments: “Although we cannot directly determine what increased diabetes risk in these women, our results indicate it is not due to typical type 2 diabetes risk factors. This finding underscores the importance of considering mental tiredness as a risk factor for diabetes among women.”

He goes on, “Both mentally tiring work and type 2 diabetes are increasingly prevalent phenomena. What we do know is that support in the workplace has a stronger impact on work-related stress in women than men.”

“Therefore, greater support for women in stressful work environments could help to prevent chronic conditions such as type 2 diabetes,” concludes the researcher.

In the near future, he and his team plan to examine the effect of mentally tiring work on people who are already living with type 2 diabetes. The researchers hope that their findings will aid the development of new ways to manage the condition.

Flu Season Far From Over, CDC Says

By Steven Reinberg

HealthDay Reporter

FRIDAY, Feb. 8, 2019 (HealthDay News) — Though much of the United States is in the grip of the flu, the season hasn’t peaked yet, health officials said Friday.

As of Feb. 2, flu is widespread in 47 states, and 24 states are experiencing high levels of the disease. In addition, hospitalizations are increasing, according to the U.S. Centers for Disease Control and Prevention.

“Flu activity has continued to increase this week,” said Lynnette Brammer, the lead of CDC’s domestic influenza surveillance team.

The most common type of flu around is still the influenza A strain H1N1. But it may be waning, Brammer said, as the level of influenza A H3N2 has increased.

Both of these flu strains are in this year’s vaccine, but while the H1N1 component is up to 65 percent effective, the effectiveness of the H3N2 is far less, according to the CDC.

Even though it is nearly mid-February, the flu season is expected to continue for several more weeks, probably well into March, Brammer said.

“There’s still a lot more flu season to come,” she said. “I expect activity to continue for several more weeks.”

That’s why she’s urging anyone who hasn’t yet been vaccinated to get a flu shot. “It’s not too late,” Brammer said.

An underrated benefit of the vaccine is that even if you get sick, your flu will be milder than if you haven’t been vaccinated. A milder flu can prevent complications like pneumonia that can be deadly, especially to the very young and very old.

Brammer also stressed that getting vaccinated not only protects you, but those around you, as well.

According to the CDC, flu activity is high in New York City, Alabama, Alaska, Arkansas, Colorado, Connecticut, Georgia, Indiana, Kansas, Kentucky, Massachusetts, Mississippi, Nebraska, New Jersey, New Mexico, North Carolina, Oklahoma, Rhode Island, South Carolina, South Dakota, Texas, Utah, Vermont, Virginia and West Virginia.

It’s still too early to tell how severe this season will be, Brammer said. So far, the season has been much less severe than last year when the H3N2 virus predominated. Last year, flu sent nearly 1 million Americans to the hospital and killed about 80,000.

This season is still classified as a less severe season, Brammer said. “But we’re not finished yet,” she said. “We’ll have to see how it plays out.”

The CDC doesn’t track adult deaths from flu, but they do keep tabs on pediatric deaths. This week, four more children died from flu, bringing the total to 28.

The best way to protect yourself and those around you is to get a flu shot, and there’s still time to get vaccinated, Brammer said.

The CDC recommends that everyone aged 6 months and older get vaccinated.

Getting a flu shot should be at the top of the list for those at high risk for flu, including the elderly, people with heart disease or lung disease, and pregnant women.

Brammer added that this year’s vaccine is well matched to the circulating strains of flu, and vaccine is still available. “I haven’t heard of any shortages,” she said.

As long as flu is circulating, it’s not too late to get vaccinated. “And right now, flu is circulating at a pretty high level,” Brammer said.

If you get the flu, antiviral drugs such as Tamiflu and Relenza can make your illness less severe. But if you’re sick, the CDC recommends that you stay home so you don’t infect others.

Brammer wouldn’t be surprised if the flu season doesn’t peak for several more weeks. It also wouldn’t surprise her if the H1N1 virus peaks before the H3N2 virus.

In any case, even when the season peaks, there’s still a long way to go before it’s over, she said.

Diabetes: Are you over-monitoring your blood sugar?

Many people living with type 2 diabetes monitor their blood sugar levels on a daily basis, but does that really make a difference to health? A new study suggests that they may be over-monitoring.

According to a recent Centers for Disease Control and Prevention (CDC) report, about 30.3 million people in the United States live with diabetes, which equates to almost one in 10 individuals.

The most commonly diagnosed form of diabetes is type 2 diabetes, which, more often than not, does not require insulin injections.

Instead, people with type 2 diabetes can manage their condition by taking the appropriate medication.

A drug that doctors often prescribe for this form of diabetes is metformin, which helps people keep their blood sugar levels under control.

As keeping blood sugar in check is so important in diabetes, endocrinologists advise people with this condition to perform regular, simple blood tests that they can do at home with the appropriate devices.

However, emerging evidence suggests that many people living with type 2 diabetes may be erring too much on the side of caution and taking these tests too often, without deriving any real benefits from doing so.

A new study by researchers from the University of Michigan in Ann Arbor suggests that a significant percentage of people with type 2 diabetes test their blood sugar levels at least twice a day.

These findings, which appear in the journal JAMA Internal Medicine, indicate that U.S. citizens or, in some cases, their insurance plans may pay excessive amounts of money for the supplies they require for unnecessary testing.
Too many prescriptions for test strips

Dr. Kevin Platt, who is in the Department of Internal Medicine at the University of Michigan, led a team who looked at the insurance data of 370,740 people with type 2 diabetes. The researchers specifically assessed how these individuals had been filling test-strip prescriptions for blood sugar tests following the updated guidelines that the Endocrine Society and Society of General Internal Medicine issued in 2013.

These guidelines recommended that people with type 2 diabetes reduced the frequency of at-home blood sugar level tests.

In their analysis, the researchers only looked at people with diabetes who did not require insulin or take medication that increases hypoglycemia (low sugar levels) risk. However, they did include people who took no medicine for the regulation of blood sugar, as well as those who took medicine that did not require them to check their blood sugar levels frequently.

The researchers found that “86, 747 (23.4 percent) of [the people in the study cohort] filled three or more claims for test strips during the course of the year.” They also noted that “more than half of these individuals,” equivalent to 51,820 people or 14 percent of the study population, were “potentially using the supplies inappropriately.”

Of these people, “32,773 individuals were taking agents not considered to be a risk for causing hypoglycemia (e.g., metformin hydrochloride) and 19,047 had no claims for any antidiabetic medications,” the authors write.
‘Reducing the use of unnecessary care’

Dr. Platt and team explain that once a person taking blood sugar medication has determined the dosage that works best for them, they no longer have to test their sugar levels on a daily basis.

However, the study findings indicate that even the people who did not need to take daily blood tests were still using an average of two test strips per day.

The researchers believe that people may keep on taking the tests to allow them to keep a log of their blood sugar levels and feel more in control of their condition.

However, they are spending a lot of money in doing so, whether it be on insurance plans or out of their own pocket in the absence of insurance.

“The median claims cost for test strips was $325.54 […] per person per year” in the case of people with an insurance plan, the researchers write, and the cost is likely to be even greater for those without insurance.

“Healthcare costs and access to care are an important issue for many Americans,” says Dr. A. Mark Fendrick, the study’s senior author.

Preventing sudden cardiac death with genome editing

Each year, at least 3 million people worldwide die of sudden cardiac death. In the U.S., this number reaches up to 450,000 people. Although sudden cardiac death is more common in older adults, younger people also are significantly affected. In the 1 to 40 age group, up to 9 per 100,000 people are affected each year. In this group, inherited cardiac diseases, including inherited cardiac arrhythmia disorders, cause a substantial proportion of sudden cardiac death.

In his lab at Baylor College of Medicine, Dr. Xander Wehrens and his colleagues study cardiac conditions, including inherited cardiac arrhythmia disorders. In addition to being often associated with a high incidence of sudden cardiac death, these disorders can be difficult to treat.

“For this particular study, we were inspired by a young patient who has been affected by an inherited cardiac arrhythmia disorder called catecholaminergic polymorphic ventricular tachycardia (CPVT). Our patient has recurring arrhythmias — irregular and fast heartbeats — and fainting episodes,” said Wehrens, who is professor of molecular physiology and biophysics, the Juanita P. Quigley Endowed Chair in Cardiology and director of the Cardiovascular Research Institute at Baylor. “Several family members had near fatal arrhythmias or sudden cardiac death. Current treatment options including anti-arrhythmic drugs and an implantable defibrillator — a device to correct certain irregular heartbeats — are not optimal for this patient.”

Genetic studies have shown that the cause of the young patient’s arrhythmia is a mutation in gene RYR2. Mutations in this gene account for nearly 60 percent of all CPVT cases. This gene encodes proteins that form a channel that regulates calcium flow in heart muscle cells called cardiomyocytes. Cardiomyocytes require proper calcium flow to contract and relax in a coordinated manner.

Gene mutations that produce defective RYR2 proteins lead to defective calcium channels that promote uncontrolled calcium leak. During exercise or emotional stress, a heart with defective RYR2 proteins will not regulate calcium flow properly, and this can lead to potentially life-threatening arrhythmias.

Designing a permanent treatment for CPVT

Wehrens teamed up with Dr. William Lagor, associate professor of molecular physiology and biophysics, who is an expert in gene therapy using Adeno-Associated Viral (AAV) vectors. These viruses can be used to deliver the CRISPR/Cas9 genome editing machinery directly into the heart.

The long-term goal of this collaborative project is to develop a permanent treatment for CPVT in humans by editing the patient’s own DNA.

Wehrens and Lagor engineered AAV vectors to deliver CRISPR/Cas9 (AAV-CRISPR) into the hearts of live animals. They reasoned that eliminating the disease-causing copy of the RYR2 gene, called R176Q, could correct this lethal arrhythmia disorder in mice. To test this new approach, AAV-CRISPR was used to selectively disrupt the mutant RYR2 gene in the R176Q mouse model of CPVT.

Ten days after birth, mice carrying the R176Q mutation and normal mice received a single injection of AAV-CRISPR or placebo treatment. Five to six weeks later, the researchers evaluated the mice, and found very encouraging results.

None of the mice carrying the disease-causing R176Q mutation that were treated with AAV-CRISPR developed arrhythmias. In contrast, 71 percent of the mice that carried the mutation and received a placebo virus did develop arrhythmias. Editing of the defective copy of the gene using AAV-CRISPR greatly reduced the abundance of the dysfunctional RYR2 proteins. Furthermore, the single ‘healthy copy’ of the RYR2 gene that remained was enough to support proper heart function. No adverse events linked to treatments were observed in the groups of normal or affected mice.

“We are particularly excited that we were able to selectively disrupt the disease-causing R176Q mutated gene without adversely affecting the healthy gene variant in the genome,” Wehrens said.

“We are now testing the same approach in stem cells from patients with the same condition, to analyze efficacy and safety in human cells. This may enable us to develop this approach for future therapeutic studies in patients with this arrhythmia syndrome,” said Wehrens.

Lagor also is optimistic about this new therapeutic approach.

“There are many diseases that are unsuitable for additive gene therapy, either because the gene is too large to deliver or a defective copy of the gene acts in a dominant way. For many mutations in RYR2 that cause CPVT, both of these are the case,” Lagor said. “We believe that precision genome editing is the future for tissue-directed gene therapies, and severe cardiac diseases are an ideal place to start.”

It Takes an Army to Manage a Medical Tragedy

Broken-out windows (lower right in image) on the 32nd floor of Mandalay Bay Resort and Casino on Las Vegas Boulevard from which a shooter rained bullets down on innocent concert-goers, killing 58 and injuring nearly 500.

By Dr. Sudip Bose, MD, FACEP, FAAEM

“The worst act imaginable often brings out the best of people.”

You’ve likely heard that phrase, probably often repeated, during the news coverage of the horrific mass shooting at the Route 91 Harvest Festival outdoor concert on the Strip in Las Vegas on Sunday, Oct. 1, as well as during the aftermath of hurricanes Harvey, Irma and Maria.

As a physician and especially as an emergency department doctor, we train for mass casualty situations on a routine basis, always hoping we never have to experience such an incident in reality. It’s a concept I accepted as a medical officer on the front lines of Iraq in the Army: We prepare in peacetime for wartime. When a mass casualty situation happens, that’s exactly what it’s like – you get thrust into a war zone immediately.

And it takes an Army to carry out the mission needed to try to keep casualties as low as possible.

At 10:05 pm Sunday night, shots rang out from the upper floors of the Mandalay Bay Resort and Casino on Las Vegas Boulevard. Initially most people thought what they heard might be fireworks associated with the concert. But all too soon, concert-goers realized that they were being fired upon as hundreds of rounds of bullets rained down on them. It didn’t take long for that “Army” to swing into action on the ground to start treating the wounded. First responders, as well as concert-goers themselves, immediately started do what they could to stop the bleeding of those hit. They had to get the injured stabilized and transported to hospitals. Las Vegas area hospital emergency departments quickly became saturated with patients. Victims – 5, 6, 7, 8 at a time – were piled into ambulances at the scene of the shooting and rushed away for treatment. Eyewitnesses to the shooting event also reported that gunshot victims were loaded into pickup trucks and civilian cars in some cases and transported to hospitals.

Continue reading “It Takes an Army to Manage a Medical Tragedy”

Coping With Disaster: A Medical Overview

NASA Earth Observatory

By Dr. Sudip Bose, MD, FACEP, FAAEM

First there was Harvey, then Irma and, most recently, Maria. Hurricanes have hit Texas and the Gulf Coast, have torn through Florida, and have raked across the Caribbean, devastating Puerto Rico and the Virgin Islands. These disastrous power punches have left scores dead, millions uprooted and much physical and emotional devastation in their wake.

As of this writing, Hurricane Harvey has been reported to have caused 82 deaths; Hurricane Irma’s U.S. death toll stands at 75; and so far, Hurricane Maria has claimed 27 lives and likely will go higher. Some of those killed as a result of Irma involved nursing home patients.

How can that happen, you ask? Shouldn’t these kinds of victims have been our top priorities for keeping safe? Of course. But sometimes, all the planning and precaution in the world can’t overcome the unpredictability of Mother Nature, a disabled infrastructure and the failure of emergency backup power.

Every natural disaster, such as hurricanes Harvey, Irma and Maria, also becomes a looming public health disaster. As the storms approach, each hospital, nursing home and medical facility that houses patients must make difficult decisions between evacuating patients and staff and battening down to ride out the storm. Evacuations pose major logistical issues as patients, staff, equipment and medications all have to be transitioned from one location to another. An evacuation for a chronically or critically ill patient can be life-threatening. During the height of the storms, hospitals and other medical facilities face critical issues in trying to keep their patients not only alive, but also well cared for. Shortages of food, water, medicine and power can turn very bad very quickly.

After the Storm

After the brunt of hurricanes like Harvey, Irma and Maria push through, health resources re-focus on fighting infections, both from bacteria in floodwaters and from mosquitoes. Physicians scramble to contain potential epidemics that might arise after flooding. Based on the health problems that arose after Hurricane Katrina, medical professionals have to prepare to try to avert major public-health emergencies, environmental illnesses, and outbreaks, which could intensify in the aftermath of the devastating blows dealt by these hurricanes. Sewage that has overflowed its containment can pose a major health issue, as can spilled fuel and chemicals from tanks and pipelines torn apart during the hurricanes.

And not only that, but for hospitals and other facilities that made the decision to move patients, those same patients have to be transitioned back home to their original facilities at some point, assuming those facilities are able to open and operate again.

As you can see, there is much to consider when preparing for a natural disaster like hurricanes Harvey, Irma and Maria. In fact, the Centers for Medicare and Medicaid Services have established an Emergency Preparedness Rule that all hospitals and health care facilities must have a plan in place and be in compliance by Nov. 16, 2017. This emergency preparedness plan, by CMS guidelines, must address an all-hazards risk assessment and contain four core elements:

Four Core Elements of Emergency Preparedness
RISK ASSESSMENT AND EMERGENCY PLANNING (include but not limited to):

  • Hazards likely in geographic area
  • Care-related emergencies
  • Equipment and power failures
  • Interruption in communications, including cyber attacks
  • Loss of all/portion of facility
  • Loss of all/portion of supplies
  • Plan is to be reviewed and updated at least annually

COMMUNICATION PLAN

  • Complies with federal and state laws
  • System to contact staff, including patients’ physicians, other necessary persons
  • Well-coordinated within the facility, across health care providers, and with state and local public health departments and emergency management agencies.

POLICIES AND PROCEDURES

  • Complies with federal and state laws

TRAINING AND TESTING

  • Complies with federal and state laws
  • Maintain and at a minimum update annually

The plan must also consider those individuals locally who may be deemed “at risk.” To quote from the CMS guidelines:

“At-risk populations are individuals who may need additional response assistance, including … [those] from diverse cultures, [who] have limited English proficiency, or are non-English speaking.”

In addition to shelters, hospitals are often a focal point of their communities during a crisis. In addition to patients already admitted to a hospital, during a natural disaster like a hurricane, new patients are very likely to seek medical assistance by coming to the emergency department either on their own or after being rescued by a first responder. And first responders need to know the status of a hospital to ensure they’re transporting patients to an open, operating, safe medical facility. Hospitals need to work with other hospitals to know where to send or receive patients if any of the open facilities become overwhelmed. And as always, hospitals need to remain HIPAA-compliant regarding patient information; just because a hospital might be operating within a disaster doesn’t mean it can be casual or careless with personal patient information.

Once hurricanes like Harvey, Irma and Maria have passed and done their damage, the next challenge is keeping the most critically ill patients cared for. We’re seeing that now, and especially so, in Puerto Rico, which is an island. You just can’t drive trucks there loaded with food, fuel, water and medical supplies. All that has to be flown in or shipped in.

Finding Comfort

“The other challenge that we face, is unfortunately because of the severity of the hit [from Hurricane Maria] there is diminished capacity of local governments and state government to respond similar to what we saw with Texas and Florida,” said Brock Long, FEMA Administrator. “So therefore, it is requiring us to push forward a lot of resources, including the USS [sic] Comfort, which is on the way.”

The USNS Comfort is a Navy hospital ship that sails to points of distress when needed to assist medical personnel on the ground with there most dire patients and circumstances. It is heading to Puerto Rico. It has one of the largest trauma facilities in the United States. It has a supply of 5,000 units of blood, according to a U.S. Navy fact sheet about the vessel, and is equipped with a full spectrum of surgical and medical services including X-ray machines, CAT scan units, a dental office, an optometry facility, a physical therapy center and a pharmacy. The 1,000-bed ship was sent to Haiti in 2010 after a large earthquake killed upwards of 300,000 people. In 2005, the ship sailed to the Gulf Coast after Hurricane Katrina hit and more than 1,500 people were treated aboard the vessel. In 2003, the hospital ship spent two months in the Persian Gulf during the invasion of Iraq, and it also was deployed to New York in the aftermath of 9-11.

Getting medical support to areas ravaged by these hurricanes and other natural disasters can be formidable. The news media may leave these areas after the initial news is reported and the days march on; however, the support needed for medical personnel, supplies and treatment carries on for months until the area stabilizes.

Right now in Puerto Rico, according to a report by Reuters, “For hospitals across this region, the challenges are mounting. After the power went out, back-up generators at some hospitals failed quickly. Other hospitals are running critically low on diesel. Fuel is so precious that deliveries are made by armed guards to prevent looting, according to Dr. Ivan Gonzalez Cancel, a cardiovascular surgeon and director of the heart transplant program at Centro Cardiovascular,” the report said.

People line up for blocks trying to get enough fuel to power generators and vehicles, waiting for sometimes up to seven hours. Everything else there is in a shambles as well, adding to the urgency and stress. Food is scarce. The island’s electrical grid has gone down and may stay that way for months.

“Cellular service, internet, and email have virtually disappeared, hurling a modern society into a bygone era,” Reuters reported. “Radio has become a primary source of information.”

For hospitals that need to transfer critical patients because they can’t support them due to lack of electricity, the situation is dire. For them, the USNS Comfort can’t arrive fast enough. If necessary, the most critical patients can be evacuated via medevac and transferred to the USNS Comfort while it’s still underway and sailing towards Puerto Rico.

And in the meantime, if medical staff on the island can’t get gasoline for their cars, how can they even get to work to care for the sick and injured?

FEMA’s Twitter feed has been carrying photos of ongoing efforts in Puerto Rico: The American Red Cross is on the scene, as is the Salvation Army, U.S. state urban search and rescue teams, the National Guard, Customs and Border Protection is assisting, the U.S. Coast Guard, the U.S. Navy, Veterans Administration medical centers are supporting by taking in evacuated patients … it goes on and on. The effort is just massive and won’t end anytime soon. (Also see, The Guardian: Photos After Hurricane Maria)

Getting Help

All these areas – Texas with Hurricane Harvey, Florida with Hurricane Irma, and Puerto Rico with Hurricane Maria – need our continued help and support on a variety of fronts. And we also should not forget those suffering in Mexico, which was hit recently with major earthquakes resulting in a death toll of at least 333 people and counting. Here are some links and suggestions for ways you can donate, if you are moved to do so, culled from relief websites and media:

Those are just a handful of entry points for support and donations and sources for helping victims. Use your discretion for any donation should you decide to help out. Let’s hope these areas get the continued support they desperately need.


To learn more about Dr. Sudip Bose, MD, please go to SudipBose.com and visit his nonprofit TheBattleContinues.org where 100 percent of donations go directly to injured veterans.

The High Cost of Prescription Drugs in the United States

By Dr. Sudip Bose, MD, FACEP, FAAEM

Spending on prescription medications is higher in the US, per capita, than in any other country in the world, according to a recent Journal of the American Medical Association study. And, the report said, those costs are “largely driven by brand-name drug prices that have been increasing in recent years at rates far beyond the consumer price index.”

An NBC News report noted that, “Paying for medicine can be the most expensive out-of-pocket health cost for Americans.”

Why?

If you look at the landscape of prescription drugs in America, you’ll notice there is nothing in place to keep drug prices low. There are no specific regulations to keep a ceiling on costs. The pharmaceutical manufacturers have the very tempting opportunity to charge whatever they think a drug’s demand and the market will bear. It’s simply possible for a drug company to charge high prices if they want to, just because they can. There’s nothing regulating whatever cost they want to charge. So the opportunity to charge more exists.

Drug companies will tell you immediately that their costs to research, develop and bring a drug to market are astronomical, and they have to cover those costs and make a profit to continue to stay in business and develop even more innovative prescription medications that will help save more lives. That’s a primary reason pharmaceutical companies will point to as a reason for escalating prices on all the medications they manufacture. And that’s true – to a degree.

Continue reading “The High Cost of Prescription Drugs in the United States”