Severe pain hurts a lot.

By: Matt Smith M.D. with Alabama Pain Physician's

Severe pain hurts a lot. This is a tautology, but sometimes it behooves us doctors to remind ourselves how unpleasant severe pain really is. When someone hurts, it becomes tremendously more difficult for her or him to do all of the things necessary to maintain a healthy, vibrant life. Recall the characteristics of someone who is depressed or who has generalized anxiety disorder. They are frequently the same behaviors we all take on when we hurt. We frequently want to be alone. We stay in bed. Highly palatable, highly processed, nutrient-poor food seems ever more attractive. It is nigh impossible to exercise. We stop seeing much sunlight. Our sleep is disrupted. Watching the Kardashians bicker and the 24 hour news cycle seem somewhat less onerous.

Not only do all these things frequently cause a downward spiral of eventually worse pain, but they also are a surefire recipe for getting the metabolic syndrome, or that cluster of diseases associated with insulin resistance, systemic inflammation, obesity, dyslipidemia, and oftentimes diabetes type two. Eat bad food. Don't move. Get poor sleep. Never get sunshine. That'll do it.

Thus it should be no surprise that chronic pain is tied to the metabolic syndrome, if only for common sense reasons.

And while everyone’s story is different, and every vicious cycle has its own character and history, there are often common denominators between chronic pain and such a host of other physiological and psychological pathologies.

Many of these vicious cycles are relatively simple and can be boiled down to simple maladaptive behavior. Acute pain becomes chronic. Chronic pain leads to bad habits like poor diet and no exercise. These maladaptive behaviors lead to more health problems and usually worse pain.

Yet, here’s where things get really interesting and here’s why the treatment of pain requires more than just advanced procedures and analgesics. There is now a tremendous amount of evidence that changes in behavior are only the tip of the iceberg relating severe pain to other pathologies. It is now incontrovertible that there is also a complicated web of physiology that causes various vicious cycles, making pain ever worse.

For example, consider the sympathetic nervous system, or that part of our bodies responsible for the “fight or flight” response. The sensation of pain, both conscious and unconscious, strongly stimulates the sympathetic response. When pain continues unchecked, the hypothalamic-pituitary-adrenal (HPA) axis becomes dysregulated. Cortisol soars and the so-called neurosteroids, or a class of hormones that attenuate the HPA axis, cannot compensate. Eventually, physiological exhaustion kicks in. While cortisol declines somewhat, many of these neurosteroids decline even more. As cortisol plummets, more generalized aches and pains start to ensue.

As HPA axis dysregulation and the metabolic syndrome kick in, the sex hormones also become affected. Chronic pain is strongly associated with sex hormone dysregulation and there are multiple reasons why this is. Visceral and subcutaneous adiposity tends to increase. Aromatase - an enzyme in the adrenal glands and adipose tissue that turns testosterone into estrogen - goes up. Systemic inflammation goes up. There is a greater preponderance now for increased damage to the initially injured area, as well as everywhere else in the body.

Perpetually elevated fight and flight. Lack of a compensatory response. Drops in the hormones that are associated with well-being. This picture of course looks very similar to the same pathophysiology behind depression and anxiety. And it is. Hence the extraordinarily high comorbidity of major depressive disorder and chronic pain. Fibromyalgia is a prototype of this interrelationship. Fibromyalgia is strongly associated with low cortisol, obesity, sleep disorders, and, of course, systemic inflammation. True to the nature of a vicious cycle, one causes the other, which causes the one.

But it gets worse. Not only is this self-reinforcing nature of chronic pain often inadequately understood, but oftentimes physicians and other clinicians misunderstand exactly what pain is. Pain is often like described as merely nociception, or the signals that peripheral nerves send to the spinal cord and brain that sometimes get translated to the conscious experience of pain. But pain is so much more. Pain also involves an immensely complicated cascade of processing at the dorsal root ganglia, spinal cord, brainstem, thalamus, cortex, and elsewhere. All of these other pathways and signaling mechanisms may act for good or ill in making pain better or worse, short lived or chronic.

To complicate matters even more, one must differentiate not just between nociception and pain, but between pain and suffering. While pain may be described as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”, suffering also involves the broad contexts in which pain occurs. Suffering is thus not just nociception and it is not just pain. Suffering is the experience of pain in the context of family, vocation, society, cultural norms, met and unmet personal goals and expectations, and a myriad other factors.

And this is the real challenge with pain medicine. Chronic, severe pain and suffering often a complicated web of vicious cycles of aberrant physiology, damaged anatomy, and maladapted psychology all couched in a myriad social contexts.

Fortunately, while this web of pathology is complex, realizing its complexity gives us a more nuanced ability to care for our patients more fully. It also explains why severe and chronic pain often does not respond adequately to just one intervention.

Realizing the complexity and nuances of pain and suffering also allows us to treat pain in a comprehensive manner. “Comprehensive care” is somewhat of a modern buzzword, oftentimes with little meaning besides a nod towards marketing. Yet when dealing with chronic pain, it is absolutely essential.

That is why with Alabama Pain Physicians, we have pioneered a model of comprehensive care that addresses all of the involved issues as described above, along with many more.

For instance, inherent to any adequate treatment of pain is an identification of any anatomical or physiological issue that may be addressed with an advanced procedure, whether that be neuroablation, injection of stem cells, or something equally sophisticated.

In the vast majority of cases of chronic pain, there is also muscle atrophy, loss of mobility, and changes in biomechanics that demand some type of physiotherapy and a lifelong regimen of appropriate exercises. That is why we work closely with numerous therapists and have our own specific training protocols.

Inherent in most patients with chronic pain, for hopefully now obvious reasons, are also depression, anxiety disorder, and many other psychological pathologies. That is why we incorporate mental healthcare extensively in our treatments.

And, of course, in almost all of our patients there are metabolic abnormalities that have resulted from some of the vicious cycles described. That is why we do advanced laboratory testing, advanced physical metrics, and tailored treatments to address these issues.

Because of this expanded view of the many overlapping and self-reinforcing cycles that cause chronic pain, adequate treatment requires looking at the whole person. This approach is something that must be done to adequately treat severe chronic pain. It is not optional.

When treating severe chronic pain, comprehensive care must be the standard of care. For more information on pain management and our Alabama Pain Physicians’ comprehensive treatments, visit Bamapain.com or call (205) 332-3160

Tips for Spotting Phishing Attacks

By: TekLinks staff

More than 100 Billion spam emails are sent each day, with email filters blocking only 10% of them. Of those, nearly half are opened. It’s clear to see how phishing has become a multi-billion dollar industry. Protect your organization’s data by using these 5 easy tips for spotting phishing attacks.

1. Linked URLs are different from the one shown.

Often the URL in a phishing message will appear to be valid. However, if you hover your mouse over top of the URL, you will see the actual hyperlinked address. If the hyperlinked address is different from the address that is displayed then the message is likely a phish. This is more difficult to see and validate on a phone or tablet.

2. Look for URLs that contain misleading domain names.

Criminals use this phishing technique to trick victims that the message came from a company like Microsoft, EBay or the FBI. The phisher creates a child domain bearing the name for a well-known company like Amazon or Apple. The resulting domain name looks something like this: amazon.criminalphishingdomainname.com. It is the last part of the domain name that gives it away – in the previous example criminalphishingdomainname.com. Anything before this is meaningless or just misleading.

3. Beware of messages that ask for personal information.

Regardless of how official or convincing the email message looks if it is asking for confidential information you should be on high alert. Your bank doesn’t need you to send them your account number. Similarly, your credit card company should never send an email asking for your password, credit card number, or the answer to a security question.

4. If it seems too good to be true …

You know the old familiar saying and it is especially true when it is an email message. If you receive a message from someone who is making big promises, then the message is probably a con.

5. Watch out for messages demanding you to take immediate action.

Another phishing technique is to trick you into clicking a link urging you to take immediate action – the message may state that your account has been closed or put on hold, or that there’s been fraudulent activity that requires your immediate attention. It is conceivable to receive a legitimate message informing you to take action on your account. But to be safe don’t click the link in the email, no matter how genuine it appears to be. Instead, log into the account in question directly by visiting the appropriate website, then check your account status.


Interested in helping your business stay more secure? Email us at info@teklinks.com.

Medical Association Past President Receives National Award

Dr. George C. Smith Sr., has been a role model for countless physicians in Alabama, including his son and granddaughter. For more than 50 years, Dr. Smith has practiced medicine in the small community of Lineville, and his years of service and dedication to patient care have garnered him national recognition.

The Federation of State Medical Boards recently honored Dr. Smith with the John H. Clark, M.D., Leadership Award, which recognizes outstanding and exemplary leadership, commitment and contributions to advancing the public good at the state medical board level.

“I’m very honored,” Dr. Smith said. “It was very much a surprise. I didn’t know I was nominated.”

Medicine is a family affair for the Smith family. Dr. Smith said he is a fourth-generation Smith from his hometown of Lineville, which has a population of about 2,500 residents. He and his son, Dr. Buddy Smith Jr., work together at the Clay County Medical Clinics. When Dr. Smith Jr.’s daughter, Ashley, receives her medical degree, she will join the clinic later this fall.

“That’s special and I’m so proud,” Smith said. “Three generations of doctors, that’s pretty rare,” Dr. Smith said.

As a past member and chairman of the Alabama Board of Medical Examiners and the Board of Censors of the Medical Association of the State of Alabama, and through his current service on the Medical Licensure Commission of Alabama and the Interstate Medical Licensure Compact Commission, Dr. Smith has worked selflessly to ensure the safety, protection and welfare of patients. In 2011 Dr. Smith received the Paul W. Burleson Award from the Medical Association in recognition of a medical career encompassing not only high ethical and professional standards in patient care, but also extraordinary service to physician organizations. His exceptional work has been recognized by his induction into the Alabama Healthcare Hall of Fame in 2014, and by the naming of the Clay County Public Health building in his honor. Dr. Smith has been a member of the Clay County Medical Society and the Medical Association since 1966.

Know More Hepatitis C

By: Rishi K. Agarwal, MD
Birmingham Gastroenterology Associates

Hepatitis C (HCV) is the most common viral hepatitis in the US with an estimated 3.5 million individuals with chronic HCV. There were an estimated 29,718 new cases of HCV in 2013 (per the CDC). Many of these people are living with chronic viral hepatitis and do not know they are infected. The CDC has designated May “Hepatitis Awareness Month” to increase awareness about this hidden disease. The CDC has also recommended that all people born from 1945-1965 to get tested for Hepatitis C.

Hepatitis C is classically known as a chronic disease though there is a phase of acute HCV which occurs during the first 6 months of exposure. In the vast majority of cases, this acute phase will lead to chronic Hepatitis C. Why is the chronicity of this disease so important? It is because until recently Hepatitis C was considered a lifelong illness and one of the leading causes of cirrhosis and liver cancer. Different patient populations are considered to be at high risk for Hepatitis C. Those are namely current or former injection drug users, recipients of blood transfusions or solid organ transplants prior to 1992, chronic hemodialysis patients, persons with known exposure to HCV (healthcare workers after needle sticks with HCV-positive blood), persons with HIV, and children born to HCV-positive mothers. Hepatitis C can be transmitted sexually, but the risk is significantly lower compared to those listed above.

Given how common hepatitis C is in our population, the next obvious question is: "what symptoms should we be looking for?" That is a bit more challenging since approximately 70-80% of patients with acute Hepatitis C and a large percentage of patients with chronic Hepatitis C do not have any symptoms. For acute Hepatitis C, some patients may have mild to severe symptoms including fever, fatigue, loss of appetite, nausea, vomiting, abdominal pain, joint pain, and jaundice. For chronic Hepatitis C, the majority of patients will not have symptoms until they begin to have liver damage, even in the setting of normal liver function tests. With this being said, asymptomatic patients can still spread the virus to other individuals.

Chronic Hepatitis C is a serious disease than can lead to long-term health problems. Of every 100 people infected with Hepatitis C, 75-85 people will develop chronic Hepatitis C. Of those, 60-70 people will go on to develop chronic liver disease, 5-20 will go on to develop cirrhosis over a 20-30 year period, and 1-5 people will die from cirrhosis or liver cancer. With this data, approximately 15,000 people die every year from Hepatitis C related liver disease.

Because HCV infection is frequently asymptomatic, screening patients who may have an increased likelihood of being infected with HCV is an important step toward improving the detection and ultimately the treatment of infected individuals. Screening for HCV generally focuses on testing those who have an individual risk factor for exposure, who have evidence of liver disease, and who belong to certain demographic groups that have a high-prevalence of infection-including individuals born in the United States between 1945 and 1965. Several organizations have provided guidelines for who should be tested/screened for HCV infection.

Screening is performed initially via a Hepatitis C antibody test. A positive antibody test is followed by an RNA test. If positive, it is important to discern the genotype, as treatment regimens are tailored to the genotype the patient has. It is important to avoid alcohol if diagnosed with Hepatitis C as alcohol and Hepatitis C can have a synergistic effect on disease progression. Vaccinations are very important as well, thus patients should be vaccinated against Hepatitis A and B, as well as against the flu (once a year), pneumonia (at least once), diphtheria and tetanus (once every 10 years) and pertussis (once during adulthood).

Treatment for Hepatitis C has come a long way from where we started. Approximately 20% of patients with Hepatitis C will spontaneously clear the virus; however, the remaining 80% of patients will be looking for treatment options. In the early days, our options were limited, typically committing patients to 2-drug (and even 3-drug) therapy from anywhere between 6 and 12 months with the primary medications being interferon and ribavirin. In some cases, we were only able to offer successful treatment ~50% of the time. These medications were noted to have multiple side effects ranging from anemia, to fatigue, to depression, which decreased compliance. Over the last few years, great strides have been made in the treatment of Hepatitis C to the point that, depending on the genotype, we can potentially offer non-interferon treatment regimens (i.e. an all-oral regimen) and have a near 90% chance of clearing the virus – thus providing not only treatment but a cure.

In summary, Hepatitis C is a global health problem that can progress to cirrhosis and end stage liver disease in a substantial proportion of patients. Screening can play a major role in identifying patients and ultimately treating them with ever-evolving and improving therapies.

Five Common MISperceptions about the Care of a Dry Eye Patient

By: Jillian F. Meadows, OD, MS, FAAO with UAB Eye Care

Do you see patients who complain of dry eyes? Or perhaps you personally experience dry eyes? Regardless of whether you are a provider or a patient, you likely hold at least one, if not all, of these common misperceptions about dry eye disease (DED).

1. Dry eye is not important.

Up to 1 out of every 3 individuals has DED.1 Although highly prevalent as is, these values are thought to be increasing due to the aging population and the surge in smartphone, tablet, and computer use. On a yearly basis, $3.84 billion are spent on dry eye alone. 2 Beyond economic burden, the quality of life of those with severe dry eye has been reported to be equivalent to moderate to severe angina.3 Patients with the most severe forms of dry eye disease (requiring surgery) were affected more than those who reported a disabling hip fracture.3 In other words, dry eye is a prevalent disease, is costly to manage, and is often associated with a poor quality of life. This is why UAB Eye Care is committed to providing focused care to all dry eye patients.

2. All dry eye is the same.

Many think that dry eye is as simple as it sounds—dryness of the eyes. In reality, there are many different types of DED. There could be deficiency of the lacrimal glands that make the watery portion of the tears or dysfunction of the meibomian glands that make the oily portion of the tears. There could be anomalous blink patterns, excessive exposure and drying of the eyes, microbial build-up along the eyelids, or systemic immunologic disease. Due to the broad possibilities, all patients reporting dry eyes deserve a dry eye work-up to rule out systemic immunologic diseases and medication-induced dry eye. Only through a targeted dry eye work-up, one of the services we offer at UAB Eye Care, can the exact type of DED be diagnosed and a personalized treatment plan developed.

3. Only severe complaints of dry eye need to be evaluated by an eye care provider (ECP).


Symptoms of DED have been shown to progress throughout the lifetime,4 and severe disease can often be recalcitrant to treatment. It is important to intervene in DED early to stay ahead of the natural history of the disease. While patients with severe DED will benefit from a dry eye work-up, those with milder versions likely will too.

4. A dry eye exam is the same as a routine eye examination.

Although routine eye examinations are important for everyone, those with dry eye need an additional type of evaluation, a “dry eye work-up.” This series of non-invasive testing helps ECPs rule out systemic diseases, determine a patient’s type of dry eye, determine the severity level, and develop a personalized treatment plan. During a dry eye work-up at UAB Eye Care, medical history will be thoroughly reviewed, paying attention to possible undiagnosed conditions. The osmolarity of the tears can be measured to assess severity, and InflammaDry® may be used to test for inflammation on the eye’s surface. Many additional dry eye tests, including specialty imaging of the blinking patterns, oily portion of the tears, and meibomian glands with either the Keratograph or LipiView II, can aid in assessing dry eye type and severity. These evaluations are critical for understanding a patient’s specific type of DED and how to best manage his or her condition.

5. There are no good treatment options for dry eye. Over a decade ago, this statement may have been true, but many advancements have improved existing options or led to the development of new ones. Lubrication with artificial tears, thermal therapy with warm compresses, and eyelid hygiene with specialty products often help with many forms of mild dry eye. Moderate to severe dry eye, however, typically requires medical intervention, such as topical steroids or cyclosporine (Restasis®, Allergan). There may even be a new pharmaceutical for DED being released this year! Details to come.

A plethora of in-office treatments are also now available. Punctal plugs can be inserted to reduce drainage of the tears and prolong contact time on the eye. Microblepharoexfoliation can be performed to remove eyelid debris that is often associated with DED. Amniotic membrane grafts can be applied to the eye to promote health and regeneration of the eye’s surface. Further, LipiFlow can be used as a soothing, in-office treatment that targets the meibomian glands, one of the major problems in DED, to promote better production of the oily component of the tears. Excitedly, we have more treatment options now than we have ever had before.

While it may be common to have dry eye, it is definitely not normal to have dry eyes. Help your patients (or yourself) get to a state where they feel better. To schedule a dry eye work-up, call UAB Eye Care at 975-2020.



References:

1. Gayton JL. Etiology, prevalence, and treatment of dry eye disease. Clin Ophthalmol. 2009; 3: 405-12.
2. McDonald M, Patel DA, Keith MS, Snedecor SJ. Economic and humanistic burden of dry eye disease in Europe, North America, and Asia: a systematic literature review. Ocul Surf. 2016; 14(2):144-67.
3. Schiffman RM, Walt JG, Jacobsen G, Doyle JJ, Lebovics G, Sumner W. Utility assessment among patients with dry eye disease. Ophthalmology. 2003; 110(7): 1412-9.
4. Lienert JP, Tarko L, Uchino M, Christen WG, Schaumberg DA. Long-term natural history of dry eye disease from the patient’s perspective. Ophthalmology. 2016; 123(2): 425-33.

Tennis elbow? But I don’t even play tennis

By: Julian Carlo, M.D. with The Brookwood Orthopedic Sports Medicine Institute

Despite the name, only a small fraction of those afflicted with tennis elbow actually play tennis. This very common condition, also called lateral epicondylitis, causes elbow pain and typically affects those between the ages of 30 and 50, with men and women equally affected. It is a notorious condition that is one of the more difficult orthopedic conditions to treat.
The cause of tennis elbow is thought to be a breakdown of the normal tendon origin of the wrist and finger extensor muscles on the lateral epicondyle of the elbow. Repetitive forceful firing of these muscles is thought to result in microtrauma to the tendon. Reinjury from repeated overuse disrupts the normal healing process, resulting in abnormal, pain-generating tissue.

Although overuse is a common factor, many patients may not recall any particular overuse activities leading to their symptoms. Patients typically present with sharp pain on the outside of the elbow associated with gripping, lifting, or squeezing. Pain can radiate down the forearm, and the elbow may be sore to move.

The pain is often severe in comparison to the inciting stimulus. For example, seemingly minor acts such as lifting a cup of coffee can cause debilitating pain. As a result, patients often have functional limitations and interference with their work, hobbies, and domestic activities.

A physical exam usually reveals an elbow with normal range of motion, tenderness on and just distal to the lateral epicondyle, and reproduction of pain with resisted finger or wrist extension. Radiographs are typically normal. Advanced imaging studies are not required for diagnosis.

Tennis elbow can be a frustrating condition to treat, both for patient and physician. The condition can last months or even extend beyond a year, so patience is required. Despite the availability of multiple treatment options, there is no strong evidence supporting the efficacy of any treatment. Approaches to treating tennis elbow also vary considerably. Some consider it a benign, self-limiting condition that should “burn itself out” with time, and therefore advocate benign neglect.

I feel there is a benefit to treatment and that a multimodal approach is most helpful. Modification of activities is important. I find it difficult for patients to improve if they continue to aggravate the injury on a daily basis. I recommend that use of a wrist splint at night, and if possible, during the day to protect and rest the involved muscles. Other wearable options include a tennis elbow strap or taping of the elbow. Oral over the counter medication such as acetaminophen and NSAIDS can help improve pain. A therapist can help by devising a stretching and conditioning program and by employing other pain-reducing modalities such as iontophoresis or ultrasound. A steroid injection to the lateral epicondyle area may help provide short-term pain relief, but studies tend to show no long term benefit. Platelet-rich plasma injections have shown promise in some studies, though they are generally expensive. I find it helpful to initiate treatment with a few of these options, while keeping others ready in the back pocket should escalation of care be necessary.

The majority of cases resolve with conservative management. If severe symptoms continue after six or more months of treatment, surgery can be considered. The typical surgery involves debridement of abnormal tissue at the origin of the extensor muscles. This can be performed on an outpatient basis in an open, arthroscopic, or percutaneous fashion. Another surgical option is denervation of the lateral epicondyle area. It is unclear which, if any, of these procedures is best. A surgeon will tend to choose the procedure he is most comfortable with and that gives him the best results. Most patients improve after surgery, though some may need additional therapy or treatment.

Tennis elbow is a common overuse injury. Although the best treatment is uncertain, many find relief with treatment options available. In the future, we hope that well-designed trials can help refine the management of this condition.


Julian Carlo, M.D. is an orthopedic hand and upper extremity surgeon at The Brookwood Orthopedic Sports Medicine Institute. For appointments, please call 205-877-BONE (2663) or visit brookwoodorthosports.com .

Healthy Salad Recipe Perfect for Spring

By: Chef John Hall Post Office Pies

Spring is finally here and that means swimsuit season and healthy eating. Luckily this is made easier with a plethora of in-season greens, fruits, and veggies we love! Here at Post Office Pies, we are currently offering our Shaved Fennel and Spicy Arugula Salad, which inspired us to use Arugula in another way for our blog series with Birmingham Medical News.

Arugula is an interesting green that falls into the cabbage family and has a bitter, peppery, mustard flavor. Peak season for this radish leaf looking green is spring and fall so it’s the perfect green to add to a salad this time of year! It pairs well with vinaigrettes, which if you know Post Office Pies then you know vinaigrettes are our specialty. It can also add freshness to pizza, pastas, and even stir-fries. Things we’re also pretty good at, if we do say so ourselves!

Arugulas are packed full of health benefits including vitamins A and C along with 14 percent of your daily vitamin K requirements. It also contains antioxidants to help the eyes, skin, and hair so it’s healthy and tasty! It is such a versatile green that you are sure to find a way to add it to your meals to make the perfect healthy bite.

We fell in love with this recipe because it uses Arugula, Mushrooms, and a Lemon Vinaigrette that pairs great with a pizza pie! Make this recipe at home if you can’t get in to try our Arugula salad in Avondale or Tuscaloosa. Or give us a call, order your favorite pizza to go, and then go home and enjoy this tasty salad with your pizza pie!

Ingredients

1 tablespoon white wine vinegar

1 tablespoon fresh lemon juice

2 teaspoons extra-virgin olive oil

1/4 teaspoon kosher salt

1/4 teaspoon freshly ground black pepper

1 cup quartered mushrooms

6 ounces baby arugula

1 tablespoon shaved Parmigiano-Reggiano cheese

Combine vinegar, lemon juice, olive oil, salt, and pepper in a medium bowl, stirring with a whisk. Add mushrooms and arugula; toss gently to coat. Top with shaved Parmigiano-Reggiano cheese.

First disease-modifying treatment should be approved for Duchenne

By: Michael Staley

Twelve young men in America hope to celebrate the five-year anniversary of their participation in a clinical trial for a drug called Eteplirsen on July 18th. They also hope that, by then, over 1000 other patients—or about 13 percent of the entire Duchenne Muscular Dystrophy population—will get a green light from the U.S. Food and Drug Administration (FDA) to begin receiving treatments as soon as enough of the drug can be manufactured.

Patiently waiting in the background are thousands of Duchenne patients who have most of their short-term hope invested in the underlying technology called exon skipping. Basically, the same technology used to develop Eteplirsen can be tweaked slightly to help different subsets of Duchenne patients.

Duchenne Muscular Dystrophy is a terrible genetic condition that leads to a complete loss of mobility and premature death. Complications from the associated cardiac and respiratory muscle weakness steal life from children as young as ten years old. Eteplirsen is designed to stop the progression of the condition by inducing the production of a vital protein—called dystrophin—that helps worked muscles recover.

In a 2015 interview, Scott Griffin of Birmingham candidly described the nightmarish reality his son Gabe will face without access to a drug to slow the progression of Gabe’s form of Duchenne.

  “But my son is going to have tubes coming in and out all part of his body, with a steel rod shoved in his back, his Achilles heel cords cut, not being able to roll over, not being able to lift his head up. I don’t think it gets much worse than that.”1

Scott Griffin holds his son, Gabe, in Iowa on July 19, 2014 during Ride4Gabe. (www.ride4gabe.com)

In the late 1980’s, President Ronald Reagan spoke eloquently about how first generation treatments for AIDS could slow the progression of the condition until scientific doors could be opened for the development of more advanced and more effective treatments in the future.

  “It makes no sense, and in fact it’s cruel, to keep the hope of new drugs from dying patients. And I don’t blame those who are out marching and protesting…I sympathize with them, and we’ll supply help and hope as quickly as we can.”

  “Science is clearly capable of breathtaking advances, but it’s not capable of miracles…tests require time, and this is a problem money cannot overcome. We will not have a vaccine on the market until the mid-to late 1990’s, at best. Since we don’t have a cure for the disease and we don’t have a vaccine against it, the question is how do we deal with it in the meantime.”2

Announcing the first therapeutic agent for AIDS patients in 1986, Department of Health and Human Services Assistant Secretary Robert E. Windom called the results of the tests on the drug AZT “exciting” and said AZT was “the first therapeutic agent that seems to hold some promise for some AIDS patients.” According to The Washington Post, he also cautioned that the drug was not a cure and noted that, while promising tests triggered the release of the drug, it was still possible that the positive results would not persist and that unexpected side effects could appear.3

Dr. Janet Woodcock is the current FDA Director of the Center for Drug Evaluation and Research. Fortunately for Duchenne patients, Dr. Woodcock is well aware of the promise and hope found in the words President Reagan and Assistant Secretary Windom spoke about HIV/AIDS in the 1980’s.

In a 2012 hearing before the U.S. House Committee on Energy and Commerce, Dr. Woodcock reminded the committee of the important role the government played enabling doctors to transform AIDS from what was essentially a 10 year death sentence to a condition that people can live long and full lives with if managed properly.

   “I have had several people who are involved in the AIDS epidemic say to me if we had treated that as business as usual, we would never have solved this epidemic, we would have never gotten effective drugs available.”4

The FDA sometimes convenes advisory committees to collect independent expert advice on a range of complex scientific, technical, and policy issues. The FDA appoints experts who have “experience interpreting complex data” and are “able to analyze detailed scientific data and understand its public health significance.”5

Inside a Maryland convention center on April 25—about twenty miles outside of Washington, D.C.—a nearly twelve-hour public meeting of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee was held to evaluate Eteplirsen.6 As expected, the panelists spent most of their time debating the design of the Eteplirsen trials and whether 1 percent of a vital protein is better than none.

Above: April 25, 2016 FDA  Peripheral and Central Nervous Systems Drugs Advisory Committee (Photo Credit: Parent Project Muscular Dystrophy)

Then a series of things happened that are not “business as usual.”

First, Duchenne patients—including most of the Eteplirsen trial participants—took to the microphone during the Open Public Hearing portion of the meeting to provide their own expert testimony about how the drug is working for them. Patients described decreases in or absence of spontaneous falls. Others talked about being able to walk again after recovering from lower limb fractures attributable to brittle bones caused by heavy doses of steroids they are prescribed as Duchenne patients. Others noted a decrease, stabilization or smaller increase than would be expected in the use of mobility devices like wheelchairs or scooters. Finally, several even disclosed their increased ability to participate in activities of daily living such as using the restroom independently or getting in and out of bed. They presented all of this information to the FDA in a first-of-its-kind Patient Centered Outcomes Report detailing patient and caregiver outcomes of those enrolled in clinical trials of Eteplirsen.7

Next, Congressman Mike Fitzpatrick from Pennsylvania read a letter signed by 108 of his colleagues in the U.S. House of Representatives. The letter reminded the Advisory Committee members that Congress has a clear view about how the agency should apply the Accelerated Approval standard and flexibilities in the law to rare conditions like Duchenne.

  “FDA has been successful at applying flexibility in oncology and HIV/AIDS to speed patient access to apparently safe treatments, and the need and opportunity to adopt innovative and flexible approaches to the review of rare disease drugs has never been greater than it is today. Patients are waiting.” Mr. Fitzpatrick’s letter also notes that “it is critical the FDA take into account the views and experiences of patients as part of the review process. It is our understanding that the community worked collaboratively with regulators and benefit-risk experts to ascertain quantifiable patient-preference data…We urge the FDA to consider…the testimony and experiences of…patient representatives on the advisory committee and patients and expert clinicians who treat them as they testify during the open public hearing portion of the upcoming advisory committee.” 8

The FDA is considering Eteplirsen approval under its Accelerated Approval pathway for serious and life-threatening conditions. To be approved, the drug needs to demonstrate a “meaningful advantage over available therapies” and “demonstrate an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit.”9

The predominant media message following the Advisory Committee Meeting focused on the fact that the panel delivered a split recommendation to the FDA—one favoring non-approval. One panelist who voted negatively noted his confusion in the record. Dr. Bruce I. Ovbiagele, chairman of neurology at the Medical University of South Carolina, said “Based on all I heard, the drug definitely works, but the question was framed differently.”

Dr. Janet Woodcock summed things up nicely in her comments during the Advisory Committee meeting on Eteplirsen. She said there is “an inherent presumption” under accelerated approval that “more uncertainty is going to be tolerated, at least at the beginning.” She also said that “Often there is never consideration of another error—that of not approving a drug that works.” 10

Duchenne Muscular Dystrophy is not “business as usual.” Anyone interested in advancing promising therapies to terminally ill patients with rare conditions should be focused on the FDA this month. If you are so inclined to reach out to the FDA with your own comments, you should encourage Dr. Woodcock to open the floodgates on Duchenne and approve the first disease-modifying treatment without further delay.


Michael Staley is a Senior Policy Advisor at Waller Landsen Dortch & Davis. He served as chief of staff to former U.S. Representative Spencer Bachus from 2007-2014. Michael advises clients on a range of issues including federal drug approval policy. He is active on the board of the Birmingham-based Hope for Gabe Foundation and an avid cyclist. For more information about Ride4Gabe, go to www.ride4gabe.com


1
http://www.washingtontimes.com/news/2015/jun/7/family-behind-new-ala-right-to-try-looks-beyond-th/?page=all

2
http://www.pbs.org/wgbh/pages/frontline/aids/docs/amfar.html

3
https://www.washingtonpost.com/archive/politics/1986/09/20/results-of-preliminary-tests-prompt-aids-drugs-release/97bfae9a-2fe0-4be0-aa02-432d4eb94693/

4
https://energycommerce.house.gov/hearings-and-votes/hearings/fda-user-fees-2012-hearing-issues-related-accelerated-approval-medical  

5
http://www.fda.gov/AdvisoryCommittees/AboutAdvisoryCommittees/CommitteeMembership/ucm117646.htm

6
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PeripheralandCentralNervousSystemDrugsAdvisoryCommittee/UCM497064.pdf

7
http://www.tucsonnewsnow.com/story/31806339/jett-foundation-to-present-patient-centered-outcomes-report-to-fda-advisory-committee-on-duchenne-treatment

8
http://media.wix.com/ugd/653359_27d7b196c26042e3b3496ea4be574277.pdf

9
http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf

10
http://www.bizjournals.com/boston/blog/bioflash/2016/04/fda-chief-lays-out-rationale-for-duchenne-drug-to.html

One in two Americans has a Musculoskeletal Condition

By: C J Talbert, MD
Southlake Orthopaedics Sports Medicine and Spine Center, PC

In March, I was fortunate to attend our annual AAOS (American Academy of Orthopaedic Surgeons) meeting in Orlando this year. Being in the midst of the entire hubbub is always a bit overwhelming. There is no way to see or do everything available in courses, symposia, poster displays, and then the exhibits and running into old friends. I came home with a sense of pride having been involved with this medical industry for so long and a secure feeling that I have been a cog in the wheels that make it all work.

I also learned some interesting facts worth sharing: [The information is from The United States Bone and Joint Initiative (USBJI).]

 ●One in two Americans has a musculoskeletal condition costing an estimated $213 billion each year. An estimated 126.6 million Americans are affected by a musculoskeletal condition—comparable to the total percentage of Americans living with a chronic lung or heart condition.

●Arthritis is the most common cause of disability, with 51.8 million—half of U.S. adults age 65 and older—suffering from the disease. With the aging of the American population, the report projects arthritis prevalence to increase to 67 million people, or 25 percent of the adult population, by 2030. Arthritis is not just a disease for older Americans, with two-thirds of arthritis sufferers under age 65.

●Back and neck pain affects nearly one in three or 75.7 million adults.

●Osteoporosis affects 10 million Americans, with 19 million more (mostly women) at risk for the disease. One in two women and one in four men over the age of 50 will have an osteoporosis-related fracture, and 20 percent of hip fracture patients over age 50 will die within one year of their injury.

●Among children and adolescents, musculoskeletal conditions are surpassed only by respiratory infections as a cause of missed school days.

In my world, back here at home, I treat adult degenerative conditions, mainly spine. We joke in my office about “Stamping out back pain - One patient at a time”. Most of these conditions do not require surgery. I try to keep things simple. I was recently asked, “Patients usually do what you tell them, don’t they?’ My answer was, “No, I ask patients many times every day to stop smoking and lose weight.” Nicotine has been proven without a doubt to be detrimental to the health of intervertebral discs and tissue healing. BMI over 40 has been shown to cause adverse joint problems and increase operative complications 4-5 fold.

If you are seeing patients who suffer from spine problems, my general advice is:

─avoid nicotine products,

─try to achieve reasonable body weight (bariatric advice may be helpful),

─stay active and fit (at a minimum, try to walk 30-45 minutes every other day),

─avoid heavy lifting (over 30-50 pounds),

─avoid prolonged sitting (shift positions or stand at work),

─do housework or yardwork in intervals (work 20-30 minutes, take a 15-20 minute break and then return to your work).

I have found that in many situations a 6-8 month course of body reconditioning and fitness can be more effective than surgery in some cases. I have also come to realize in some difficult cases multimodal pain management can be lifesaving. I encourage elderly patients to work on core strengthening and on balance. I also feel it is important they have evaluation for osteopenia and Vitamin D. 

Potentially Life-Changing Changes Afoot for Children with Food Allergies

By: Dr. Prescott Atkinson, Director of Pediatric Allergy and Immunology at Children’s of Alabama and a Professor of Pediatrics at UAB.


New medical research is ushering in big changes in how doctors think about food allergies and the way they will be treated in the near future.

The turning point came last year with the LEAP (Learning Early About Peanut) Study published in the New England Journal of Medicine. This five-year study showed that avoidance of food allergens by children at risk for food allergy is often the wrong strategy, which, of course, is contrary to something doctors had been advising for decades.

Data in the study were so powerful that doctors have already changed the advice they are giving to parents with children pre-disposed to food allergies. Meanwhile, the American Academy of Allergy and Immunology together with the American College of Allergy and Immunology are working with the National Institutes of Health to firm up a position paper to formalize these new recommendations.

Researchers with the Immune Tolerance Network conducted the LEAP Study by enrolling hundreds of infants from 4 to 11 months old who were predisposed toward peanut allergy. Children in the study were not yet sensitized to peanuts, but they had the family history plus a strong sign of developing food allergies—severe eczema. It is likely that eczema is associated with food allergies because breaks in the skin allow allergens to sensitize children.

Children in the study were divided into two groups. One group was fed peanuts daily, and the other group strictly avoided peanuts. After five years, researchers looked at which children had become allergic to peanuts and which had not. Only about 2 percent in the group that was exposed repeatedly to peanuts developed a peanut allergy. By contrast, nearly 14 percent of the children in the peanut avoidance group developed allergies. We seldom see differences like that in human studies. It was striking and statistically significant.

So there’s a new recommendation for infants at risk for food allergies. We can do testing, of course, and if they are not already allergic and are able to tolerate the food allergen, we are recommending that they should be fed the food frequently. That is the opposite of the previous recommendation, which warned parents to avoid exposing children to potentially allergenic foods for as long as possible.

For children who have already developed food allergies, some hopeful trials are underway that may offer protocols for desensitization. This approach would be similar to how allergists desensitize people who are allergic to pollen. Pollen desensitization is usually done with injections, but that’s dangerous for people with food allergies. With food allergies, the desensitization would be attempted with a graded, oral protocol. These are being developed for egg, nut and peanut allergens.

Patients would be challenged in clinic to see how much of an allergen they can tolerate. Then, a patient will consume that amount daily, possibly increasing that amount according to how they fared in subsequent challenges. Researchers have found that food tolerance gradually increases in most patients. In about a third of cases, patients can become completely desensitized, even those who had severe allergic reactions. A majority of patients are desensitized to the point that they can tolerate a small amount of allergens safely. That substantially lowers risks for severe, life-threatening allergic reactions.

Obviously, there is great interest in these protocols since about 5 percent of children have food allergies. We expect to have the new protocols available in general clinical use in the not-too-distant future.

This changing paradigm about food allergies is making doctors take a second look at why food allergies have been increasing. Most likely doctors have been contributing to this pattern by giving new mothers the wrong advice. Until the LEAP Study, we just didn’t have the data to make a good scientific recommendation, so we depended upon logic and common sense. We turned out to be wrong.

I strongly suspect that the incidence of food allergies in children will begin to subside after new recommendations take effect.

It’s also worth mentioning that there are some new biologic drugs in the pipeline that are promising for children with severe allergic asthma. We’ve been using one of these injection drugs, Xolair (omalizumab), for about a decade. Now, new ones will be available soon and some are effective at controlling severe asthma and even severe hives.

These new drugs will be expensive, but for people who are often hospitalized with severe asthma, they may be cost-effective and could certainly improve their quality of life.


Dr. Prescott Atkinson is Director of Pediatric Allergy and Immunology at Children’s of Alabama and a Professor of Pediatrics at UAB. He is board certified in pediatrics, as well as allergy and immunology. He received his MD/PhD from Emory University in 1987, completed his pediatric residency at Georgetown University and completed a fellowship in allergy and immunology in 1992 at the National Institutes of Health. He joined the UAB faculty in 1992.