The 1920s was a thriving time for scientific discoveries and innovations. It was especially instrumental in the world of medicine, as countless drug discoveries were made which have impacted pharmaceutical processes since then. Read More
Developing new drugs is a long and complex process. It requires years of research and testing, waiting on approvals by the regulatory bodies, and close monitoring of the post-approval marketing being done for the drug to receive the green light. Read More
Often touted for the long-term health benefits, fasting has come in vogue these last few years for treating several negative health states while improving lifespan.
There are as many kinds of fasting as ideological differences between people. Still, all of them share the general principle that eating is restricted to specific days of the week or hours of the day. Intermittent fasting is believed to increase insulin sensitivity , potentially helping reverse type II diabetes. There are multiple side-benefits: decreased blood pressure, reduced night-time hunger, slower aging, and a superior lipid profile. Some of these claims are substantiated more thoroughly than others, but an increasing number of them are quantitatively demonstrated in clinical studies.
Although seemingly unrelated, the subject of SIBO may prove to fall among those side-benefits – or for sufferers of the disease, it could easily become the main focus. SIBO, itself only recently under the attention of the medical profession, is short for Small Intestinal Bacterial Overgrowth. SIBO is a condition that usually involves relentless, stabbing, motile stomach pains, often exacerbated during eating. Adding insult to injury, the syndrome frequently features gas, bloating, sleep disturbances, diarrhea or constipation, as well as other gastrointestinal problems. All of this is thought to be caused by an out of control overgrowth of bacteria in the small intestine, “bad bacteria” that has run amok or bacteria that are not typically found in the human digestive tract.
Diet plays a considerable role in SIBO, either by initiating and fueling the bacterial overgrowth or tamping it down during treatment. As the ancient polymath Maimonides once said, “No disease that can be treated by diet should be treated with any other means.” SIBO is believed to be brought on by a combination of factors, two of which are strictly relevant to this discussion. The first is the kinds of foods that cause illness: simple carbohydrates that tend to fuel the overgrowth, including sugars, and a few complex carbs that bacteria inside the human body are unable to process. The second point of concern is timing. SIBO often strikes people who have frequent, sudden, and dramatic changes to eating patterns.
Intermittent fasting can target each of these issues. The emphasis on restricted times for eating is a strong central point that might help the body prune the overgrowth. By maximizing the time between feedings, the gut is afforded more opportunity to clean itself. Time for extra waves of peristalsis means we might be able to manually remove more bacteria along with the chyme, and time with an empty small intestine could mean that we have more time to starve whatever microbes are still hanging around.
The other point is diet, insofar as it relates to not feeding the bacteria that are present. Intermittent fasting is often coupled with other, healthful changes in the diet, but it is separable from those influences. After all, some people entirely refrain from eating two days a week, or even every other day of the week, and many of these people eat whatever they want on non-fasting days. Could this provide relief for those with SIBO?
More research needs to be done, but the preliminary, anecdotal evidence provided by doctors shows that it works. By increasing the rate of the MMC – the migrating motor complex, a series of electromechanical waves that serve to “sweep house” during the long periods between meals – extended fasting helps the gut to reduce the bacterial overgrowth.. The MMC is so heavily bound up with SIBO that impairment in this area is considered a known cause of SIBO. Conversely, SIBO itself tends to reduce the duration of peak MMC activity, or eliminate the peak phase, so fasting may help initiate a positive-feedback boost where our gut health spirals upward.
Another important mechanism by which bacterial overgrowth might be attenuated by fasting is the regulation of the type of flora present. This, too, is the subject of ongoing research and not just for SIBO. One paper, studying the effects on patients with MS, examined the relationship between beneficial gut microorganisms and the brain. Several of their observations hint at myriad possibilities:
“A mechanism through which diet can influence immune responses is the gut microbiome, which is emerging as a critical contributor in numerous human diseases. Here we show that intermittent fasting (IF) ameliorated clinical course and pathology of the MS animal model, experimental autoimmune encephalomyelitis (EAE), leading to less inflammation, demyelination, and axonal damage. IF changed the gut microbiome resulting in increased bacteria richness and enrichment of the Lactobacillaceae, Bacterioidaceae, and Prevotellaceae families.”
Healthier gut microbiota is what is needed for SIBO. The improved balance of microorganisms, the drop in markers of inflammation, and neurological damage signal a truly enormous scope of benefits. Although the diet may not be suitable for everyone, it’s time for many more of us to try it. Friendlier bacteria and a healthier gut await.
 Peterson, C. et. al. Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes. Cell Metabolism, 2018. 27: 6. DOI: <https://doi.org/10.1016/j.cmet.2018.04.010>.
 Tello, M. Intermittent fasting: Surprising update. Harvard Health Blog. 2020. <https://www.health.harvard.edu/blog/intermittent-fasting-surprising-update-2018062914156>. This blog contains several important primary references.
 Palikuca, S. Intermittent fasting: Can we fast our way to better health? The Do. Jan 30, 2019. <https://thedo.osteopathic.org/2019/01/intermittent-fasting-can-we-fast-our-way-to-better-health/>.
 Pimental, et. al. Lower frequency of MMC is found in IBS subjects with abnormal lactulose breath test, suggesting bacterial overgrowth. Dig. Dis. Sci. 2002 Dec;47(12):2639-43. doi: 10.1023/a:1021039032413.
 Hasler, W. Physiology of the Gastrointestinal Tract (Fourth ed.) 2006.
 Cignarella, F. Intermittent fasting confers protection in CNS autoimmunity by altering the gut microbiota. Cell Metab. 2018. 27(6): 1222–1235.e6. doi: 10.1016/j.cmet.2018.05.006
There’s an enormous “Godzilla Dust Cloud” from the Sahara Desert that moving across the land. It has penetrated deep into the U.S. mainland, and worse, appears to be followed by a second wave of dust, billowing and roiling its’ way to Texas. How did this happen, and how dangerous is it?The how is the easy part.
Hot, raging convection-driven winds blowing over the dessert create plumes of dust up to 20,000 feet high, loading it into the aptly named Saharan Air Layer (SAL). The mix of dust in the SAL, buoyed by hot, dry air, can remain aloft thanks to high-altitude anticyclonic eddies that continually blow it around at heights of about 4 km above the surface, keeping the dust aloft for many thousands of kilometers. The third-largest desert (largest, if you don’t count frozen wastelands like Antarctica) sends forth about 60-200 million tons of mineral dust every year, which is more than all human activities combined. It’s enough to attenuate some hurricane seasons because the dust blocks out enough sunlight to cool the Atlantic Ocean’s surface.
The danger to human health is a different matter, trickier to pin down. Moreover, it’s something that people are accustomed to since the dust cloud is a regular occurrence on the U.S. East Coast, particularly the Southeast. Our familiarity is not necessarily helpful in this case. Large particles typically settle out before the clouds reach the U.S., so we don’t get the kind of clouds that usually block out the sky and make shutting down the economy necessary (this happens during the Saharan dust season in the Canary Islands, near the coast of Africa). Instead, the particles that reach us are much too small to see, as the results of an eight-year study published in the journal Epidemiology show:
“This multiyear analysis clearly shows that the contribution of Saharan dust to size classes <2.5 μm is dominant in terms of numbers and substantial in terms of mass. Over the entire particle size range, 99.5% of the number and 38% of the mass are <2.5 μm during Saharan dust events. ”
Airborne particles smaller than 2.5 um are a huge problem, and most of the time, we’re not aware that we’re breathing them. For most people, in small doses, the effects set in gradually and unnoticed: a little coughing is seen as usual, for example, during the wintertime, with so many suffering from the seasonal illnesses that go around. They’re too small to see, cannot usually be tasted or smelled, and irritate our lungs very severely, but the effects come on slowly and usually slip below our radar. The consequences from the Saharan dust inhalation are probably worse than we imagined; the more general implications of breathing in particles of this size range are devastating for humankind.
The first thing to know about inhaling these microscopic particles, which are just a tad larger than the optical limits of a compound light microscope, is that they don’t just get into your lungs. Of course, they penetrate the lungs deeply, and some of them may sit there, but others manage to enter your bloodstream. They contribute to irritation of the blood vessels, where they are strongly linked to non-fatal heart attacks. These might not kill you, but you probably wouldn’t want one, and anyway, the research is at an inchoate stage, and it would be unsurprising if soon we found out that fatal heart attacks could be provoked as well. They also are linked to cardiac arrhythmias, even in otherwise healthy people.
The most obvious target is even more badly compromised. Lung function is decreased, with an absolute risk of premature for people who have heart or lung disease. Lung disease sufferers can also expect to have trouble breathing, shortness of breath, and irritation of the airways. Asthma suffers have been shown to have aggravated symptoms, and now with Covid-19 affecting sufferers’ lung function, even more people are going to have acute problems with PM 2.5.
But the most significant risk of all associated with PM 2.5 is probably cancer. Probably, because there isn’t enough data yet – but what information do exist show a relationship to many different kinds of cancer. Lung cancer is strongly associated, but its mortality risk increased less than many other cancers – and the range of cancers impacted is enormous. According to the AACR, in a massive three-year study of over 66,000 residents of Hong Kong, for every ten ug increase in exposure, the combined risk of dying from any form of cancer rose 22%, and lung cancer specifically rose 36%. But even more surprisingly, the risk of breast cancer increased 80%, and fatal upper G.I. tract cancers rose 42%. Shocking, but the numbers don’t lie, they merely highlight that the bloodborne particulates wreak inflammatory havoc throughout the whole organism (after all, although it’s beyond the scope of this blog, it’s not just humans that are affected).
The best thing that can be said about this problem is that we’re not powerless to stop it. Inside the home, HEPA air purifiers can make a considerable impact in removing PM 2.5. As a consequence of Brownian motion, they release incredibly tiny PM 0.3 and under particles more easily than they do the somewhat larger particles. A true HEPA filter can remove 99.97% of particles 0.3 um in diameter, but even the so-called “HEAP-type” air filters can remove 99% of um 2.0. Outside the home, we need to work on ways to decrease air pollution. We might not be able to stop the Sahara from coughing forth dust every year, but 30% of the world’s dust is anthropogenic, and that dust is made by humans, where humans live.
Cleaning up that 30% could have a considerable impact, and go a long way towards improving human health.
 Wikipedia, accessed June 2020.
 Sajani, et al 2010 Only Coarse Particles from the Sahara? doi: 10.1097/EDE.0b013e318258c23f, < https://journals.lww.com/epidem/fulltext/2012/07000/Only_Coarse_Particles_From_the_Sahara_.18.aspx#:~:text=Over%20the%20entire%20particle%20size,range%20of%201%E2%80%932.5%20%CE%BCm.>.
 US EPA website. Accessed June 2020 Health and Environmental Effects of Particulate Matter (PM). < https://www.epa.gov/pm-pollution/health-and-environmental-effects-particulate-matter-pm>.
 American Association for Cancer Research website.
Getting through Covid-19 seems to be easy for some of us. Although the long-term effects aren’t known yet, few people seem worried about long-lasting damage, especially if they never had severe symptoms. Maybe people should be concerned: a hill of evidence is starting to accumulate, pointing to long-lasting damage from Covid-19. While it is not surprising that Covid-19 could infect any tissue throughout the body, given the ubiquitous distribution of ACE-II receptors, the real surprise might lie in how and why it pops out again
A likely place to find long-term damage is the brain, since there are many ACE-II receptors in critical areas such as the hypothalamus. Troubling reports of confusion, delirium, memory loss, fatigue, and depression, are some of the long-lasting effects patients are reporting. The viral fatigue can be the only symptom some people ever experience, and for others, it has proven to last for months after their other symptoms went away. For others, biochemical changes leading to chronic depression and anxiety might linger for weeks or months, potentially much longer. The delirium and confusion associated with the brain damage caused by Covid-19 can remain: in the words of one patient, “Covid has killed me” – a reference to the fact that she suffers debilitating confusion, can no longer walk, and suffers from soul-crushing depression.
Perhaps one of the most interesting ways that Covid-19 intersects the brain and at the same time underscores the complex interconnection of the body’s systems concerns how it affects our breathing. In what has called “happy hypoxia” – or more accurately, silent hypoxia – nearly asymptomatic patients have had stunning, profound levels of oxygen deficit. While SPO2 levels below 80% can result in impaired cognition for most people, and below 75% typically results in loss of consciousness, some Covid-19 patients present with far lower levels – as low as 50% – yet seem fine. Fine as in, they’re happily texting away, oblivious to any danger they might be in, and reporting no discomfort related to their breathing. It’s thought that this constellation of symptoms might be due to a lack of communication from the brain centers responsible for breathing. Although more research is needed to support the hypothesis, it could explain the profound hypoxia – and the utter lack of awareness that suffers have.
Other problems also occur and never go away – or they do so in such an asymmetrical fashion that sufferers can be held hostage by symptoms, even when they remit for the occasional good day. A special kind of post-traumatic stress disorder, post-intensive care syndrome, seems to haunt a great many survivors. Some of the condition is psychological: being treated in isolation and breathing with a mechanical ventilator can be extremely traumatic. But other components may be physical: sufferers complain of chest tightness and shortness of breath. Since many will have alveolar damage, and perhaps permanent scarring in their lungs, the seemingly reasonable question of whether these symptoms are primarily psychological becomes a chicken-or-the-egg type of ordeal. Furthermore, post-intensive care syndrome presents commonly as a hospital-acquired delirium. As one critical care fellow at UCSD reported, “I had one patient who came to our ICU recovery clinic, who told me that he was in a half-conscious state the whole time. He thought the nurses were hooking up poisonous snakes to his arms.”  About half of long-term (20 days or more) ICU patients seem to have some long-term affliction following their time in the hospital.
Regardless of the differences in manifestation, early March Covid-19 survivors are still showing the symptoms, in some cases, over 100 days later. For many people, the most enduring symptom is intense bouts of viral fatigue. The fatigue often (but not necessarily) presents as irregularly occurring, sudden attacks of body-draining bone-weariness that make it impossible to do anything, sometimes even making it difficult to leave the house. Some sufferers report that it intensifies throughout the day, with milder morning symptoms that give way to debilitating fatigue, usually the afternoon or the evening. Sleeping provides only a brief respite, followed by day after day repetition of the cycle.
Nobody knows how long these things will go on, nor do we know who will get better and who will not. It bears repeating that most cases don’t result in serious disease, and many of us may never even know that we had it. In other words, Covid-19 is not worth panicking over. But it is worth taking seriously.
 Cormier, Z. June 22, 2020. Future. How Covid-19 Can Damage the Brain. https://www.bbc.com/future/article/20200622-the-long-term-effects-of-covid-19-infection. https://www.nytimes.com/2020/04/20/opinion/sunday/coronavirus-testing-pneumonia.html.
 Edwards, E. March 28, 2020. Post intensive-care syndrome’: Why some COVID-19 patients may face problems even after recovery < https://www.nbcnews.com/health/health-news/post-intensive-care-syndrome-why-some-covid-19-patients-may-n1166611>.
 From testimony on Good Morning Britain. June 24, 2020. <https://www.youtube.com/watch?v=nMbQlzqZZKs>.
This time it’s the lies that bind.In recent news, which has garnered some attention from the media but not nearly enough, hundreds of Chinese suppliers of medical equipment to U.S. have been discovered using false, faulty, or utterly implausible registration with the FDA. That would not be good any day of the week, but it gets comically worse. Some thirteen hundred plus companies were found using the same address to pawn their wares off on the U.S. FDA. The house is a three-bedroom brick shelter in Wilmington, Delaware, and neither the occupants nor landlord knew anything about any Chinese companies when they were interviewed. The edifice was little more than a ruse for these companies to import their goods into the U.S. using an agency known as CCTC, while the FDA has deemed it has “probable cause to believe CCTC is a fictitious corporation.”
Previous to the medical equipment debacle, federal health officials revoked U.S. authorization for masks made by over 60 Chinese manufacturers that failed to meet standards for the safety of health care workers. Due to shortages caused by the influx of patients with Covid-19, the U.S. accepted donations of masks, gloves and protective equipment from China. The Food and Drug Administration allowed the imports based on testing data from the companies, but new U.S. testing revealed the masks to fall far short of the reported test results. The Chinese were modified N95 masks, which filter at least 95% of particles. U.S. testing showed dozens of the Chinese masks failed to meet that 95% level, with some masks filtering as little as 20% of particles, according to the CDC. More than masks and protective equipment are at stake, China is the world’s leading manufacturer for a multitude of products worldwide, from shoes and buttons to Christmas lights.
The fabricated figures from Luckin and FDA shenanigans with the CCTC both serve to underscore the sad state of oversight in China. A backlash against the falsification of data is informing calls for stricter regulatory oversight of securities when companies go public, and for a more rigorous auditing process to ensure that published data from Chinese companies are truthful. Domestic Chinese investors, no less than their international counterparts, want to have confidence that their holdings can weather audits without withering at the slightest inquiry.
In the U.S. it is becoming apparent that the FDA needs to up its game to ensure that it is doing an adequate job of protecting its constituents. While it is true that the companies that exploited regulatory weaknesses in the American marketplace need to be held accountable for their actions, our laxity paved the way for them to find those weaknesses. The FDA’s relaxed enforcement in the wake of Covid-19 is one factor that has negatively affected the quality of goods in the American marketplace, but certainly not the only one. How many people know where their drugs are manufactured? In an age where the ins and outs of API manufacture are proprietary and concealed with trade secrets, how can we know where the medicines on our shelves come from – and more importantly, how do we ensure that our supplies are safe?
There are two different kinds of safety involved here: freedom from defects and impurities (i.e., product quality) and reliability of sourcing (i.e., supply chain robustness). These issues raise questions about both. The cGMP paradigm is not about quality “tested into” a product, which might miss things. The paradigm is about quality built into a product, which according to the FDA website, “…includes establishing strong quality management systems, obtaining appropriate quality raw materials, establishing robust operating procedures, detecting and investigating product quality deviations, and maintaining reliable testing laboratories.”
Over the years an enormous amount of both scientific and pseudo-scientific speculation has been aimed at explaining prevailing trends in the lifespan of animals,and how we might apply those lessons to humans.
Since clear, observable trends exist with respect to various groups of animals and lifespan, if we can understand the underlying processes behind those trends, we might be able to extend and maximize our own lifespans. The most obvious trend is body size versus lifespan, which is robust and repeatable, yet has some outliers that offer tantalizing grounds for speculation.
Figure 1 shows the trend between size and lifespan. The trend lines, both of which have significant scatter, clearly show two trends, with the data broken down to illustrate the difference between flying and non-flying species. The striking difference between species who can and cannot fly will be immediately available to anyone who has ever kept a parrot – some species can reliably outlive their human owners.
A number of theories exist to explain the differences between these groupings – and why bats and birds live so much longer. The authors of the study behind Figure 1  point to the differences in predation vulnerability and argue that flying reduces predation and vulnerability to food shortages. In that respect, flight offers some of the same advantages as large body size, resulting in the anomalously longer lifespans enjoyed by bats and birds. The only problem with this hypothesis is that a Malthusian distribution should ensue, and when these populations explode to the very limits of their ecological carrying capacity, one would expect that these advantages would be nullified. Yet the differences persist.
An alternative view is that animals adapted for flight have a chemical advantage related to flying. Their tissues express larger quantities of mitochondrial uncoupling proteins, which allow the “leak” of H+ without producing ATP in the mitochondria. This means that they can “throw away” excess energy produced when they are at rest, necessary because their cellular machinery is designed to process huge amounts of energy during periods of flight. Tossing the protons made by oxidative respiration has the side benefit that reactive oxygen species (ROS) are destroyed, preventing cellular damage that accumulates over time and causes aging. Birds therefore age slowly and maintain their youthful function throughout the vast majority of their years.
Other animals, including humans, might be able to benefit from research that targets these proteins. A growing body of research aimed at treating obesity has a similar goal, and gene therapies that are aimed at stimulating “brown fat” promise to kill two birds with one stone. Brown fat, a vascular active form of adipose tissue, burns fats rapidly in the presence of oxygen and uncoupling proteins to generate heat. This is the fat that allows long-lived walruses and cetaceans to keep warm even with wet skin in freezing climates by using fat as nothing more than fuel for the furnace. Through gene regulation to stimulate brown fat we might be able to reduce obesity and inflammation caused by ROS.
Current research is promising, with the side benefits that gene therapies that increase the activity of the brown fat also cause marked increase in muscle mass and strength, at least in lab mice. Scientists at Virginia Tech have recently identified a small mitochondrial uncoupler, named BAM15, that decreases the body fat mass of mice without affecting food intake and muscle mass or increasing body temperature. The research of Santos and colleagues, published in Nature Communications on May 14, 2020, are especially promising for the treatment of obesity and diseases characterized by inflammation.
Although research on mitochondrial decoupling proteins is ongoing, recent progress is promising, and the implications for medicine are sky-high.
 Healy, et. al. 2014 Ecology and mode-of-life explain lifespan variation in birds and mammals. Proc. Royal Soc. B. DOI: https://doi.org/10.1098/rspb.2014.0298 or visit https://royalsocietypublishing.org/doi/10.1098/rspb.2014.0298.
 Weintraub, Arlene. 2020 Gene therapy cuts fat and builds muscle in sedentary mice on unhealthy diets. Fierce Biotech. May 11. https://www.fiercebiotech.com/research/gene-therapy-cuts-fat-and-builds-muscle-sedentary-mice-unhealthy-diets.
 Tang et. al. 2020 Gene therapy for follistatin mitigates systemic metabolic inflammation and post-traumatic arthritis in high-fat diet–induced obesity. Science Adv. 08 May 2020:Vol. 6, no. 19. DOI: 10.1126/sciadv.aaz7492 or https://advances.sciencemag.org/content/6/19/eaaz7492. https://www.sciencedaily.com/releases/2020/06/200608132539.htm?utm_content=131524119&utm_medium=social&utm_source=twitter&hss_channel=tw-463200485
The need to reshore American products has been recognized on a federal level for many decades, with legislation such as the original Buy American Act, dated to 1933.
The urgency has grown in recent years, with the burgeoning dependence of the United States on foreign medicines and medical equipment now constituting a huge strategic burden. The issue has recently come to forefront because of renewed distrust in supply chain stability thanks to Covid-19, however, and current legislation is upping the ante by including Big Pharma among the list of key players that need to be reformed.
The imperative to return American products home is primarily being addressed through legislation offering incentives aimed at making American businesses more competitive, imposing tariffs on foreign goods and offering tax benefits for American manufacturers. Although 28% of registered worldwide pharmaceutical API manufacturing sites are located within the US, according to government statistics when we consider the sourcing of raw materials, various estimates suggest that the true foreign dependence is even higher. Indeed, it is surprisingly difficult for consumers to determine the origin of their drugs and medicines, and many pharmaceutical companies are reticent about their suppliers given the proprietary nature of the information.
President Trump’s proposed “Buy America” Executive Order, spearheaded by White House trade adviser Peter Navarro, was sidelined by the National Security Council before it could be signed last Friday. Although the exact details of the order are under negotiation, it is clear that the future of the pharmaceutical industry is at a major crossroads: what happens when the order is signed will shape the manufacturing of pharmaceuticals worldwide.
While this situation underscores the necessity for re-shoring American manufacturing of pharmaceuticals, the biggest opposition to the movement is coming from pharmaceutical lobbyists on Capitol Hill. Perhaps this is unsurprising, given the enormous disruptions that changing the system would cause, and the fact that many of the losers would be large, powerful corporations with pronounced sourcing from overseas. Nevertheless, the Pharmaceutical Research and Manufacturers of America (PhRMA), which is the largest pharma lobbying group present, has proffered an argument that re-shoring proposals will “… not only overestimate the potential feasibility and underestimate the time and effort it would take to make such changes, but also misunderstand that a diverse pharmaceutical supply chain is precisely what enables the industry to respond quickly and make adjustments in its supply chain sourcing during natural emergencies and global public health crises.”
Some of this rhetoric is true: the process will definitely be expensive and difficult. Some of this is false: parallel supply chains increases the robustness of the worldwide supply. In fact, redundancy is a key element to airplane safety, and by analogy, it’s plain to see that parallel sources are far more secure than relying on a potentially distant source in an emergency. This resistance is troubling, since the truth is staring us in the face: global supply chains are not always reliable. Imports from China for critical medicines and pharmaceuticals are being cut off entirely due to Covid-19. This dependence has placed lives at risk since 90 percent of the generic medications that Americans use daily are imported.
The reluctance of Big Pharma to reduce an unhealthy and greedy dependence on cheap labor and materials will have serious consequences for American healthcare as well as national security. China’s dominance of the pharma supply chain is highly dangerous to the United States. Pharmaceutical production must be reshored and even expanded in order to develop secure and safe supply chains for medications, vaccines and medical devices. This crossroads brings us to a critical question: will the United States commit its financial might to developing American pharmaceutical manufacturing capabilities, or will pharma itself stand in the way?
According to the CDC, heart disease is the leading cause of death in the U.S., killing more than 600,000 Americans each year.
- More than five million Americans are diagnosed with heart valve disease annually.
- Heart valve disease can occur in any single valve or a combination of the four valves, but diseases of the aortic and mitral valves are the most common.
- Calcific aortic stenosis is the most common form of aortic stenosis (AS).
- While up to 1.5 million people in the U.S. suffer from AS, approximately 500,000 within this group of patients suffer from severe AS. An estimated 250,000 patients with severe AS are symptomatic.
- Without an aortic valve replacement (AVR), as many as 50 percent of patients with severe AS will not survive more than two years after the onset of symptoms.
Aortic valve stenosis — or aortic stenosis — occurs when the heart’s aortic valve narrows. This narrowing prevents the valve from opening fully, which reduces or blocks blood flow from your heart into the aorta and onward to the rest of your body.
Recent advances in the treatments for aortic valve stenosis seem to be tipping doctors and patients increasingly towards xenografts for treatment. Traditional treatment regimes have involved open heart surgery, focused on the replacement of the damaged aortic valve with a mechanical replacement. The move away from these highly invasive operations has been prompted largely by a single, increasingly attractive development: Transcatheter Aortic Valve Replacement, or TAVR.
The new method of TAVR was only approved as recently as August 2019 for low-risk patients, as new research began to overturn the idea that mechanical heart valves were superior for patients with significant post-operative life expectancy. The old thinking went like this: since mechanical heart valves do last longer, these valves could provide patients with a lower risk of failure, complications or repeat surgery. The problem is that some of these assumptions are no longer true, and in many cases, “biologic valves are better even in the young patient.”
The only true representation of the above claims is the fact that mechanical heart valves last longer. That’s absolutely true; a valve made from titanium or other high-strength, highly impervious material can last for decades. Unfortunately, these materials increase the risks of blood-clots since platelets have an affinity for collecting on non-biogenic surfaces. These blood clots can result in thromboses, heart attacks and strokes.
The current treatment regimen is at best an uneasy compromise, because patients are assigned a life-long regimen of anti-coagulants that must balance the risks of clots against the risks of fatal bleeding, hemorrhagic stroke and other complications from the anti-coagulants. The mortality and morbidity due to surgical complications and failure of the mechanical valves are complicating factors as well.
TAVR addresses some of these problems with short-term mortality by significantly reducing the risks of open heart surgery. The minimally-invasive procedure begins by inserting a catheter into the femoral artery (or another blood vessel) and threading it up into the aorta. Once there, in the increasingly common valve-in-valve (VIV) procedure, a collapsible replacement valve can be delivered right inside the aortic valve and then expanded. Once it’s inside the valve, the new valve holds everything open during systole, meaning output resistance drops and the heart doesn’t have to work as hard. The new valve will also close more effectively, so blood doesn’t continually wash back and forth, which further eases stress on the heart.
TAVR heart valves are typically made from cow pericardium, which also eliminates the platelet adhesion problems seen with mechanical valves. Some people can go off of blood thinners, and not have to worry about their potential side effects. The primary disadvantage of TAVR valves is their limited lifespan of 10 to 12 years. New refinements are addressing this problem: recent studies have shown the chances of having problems with repeat surgeries and TAVR for failed bio-prosthesis valves are either the same, or slightly better for redo TAVR. In another study of approximately 50 patients who had redo TAVR due to failing bio-prosthetic valves, every patient survived to discharge, with only one serious bleed and one minor, non-disabling stroke. In fact, the lower risk of early- and mid-term morbidity associated with TAVR means that for many people, the procedure offers the best chance to live their best lives – living with the highest quality and lowest risk of disability.
 Source for stenosis diagram: Michigan Medicine, Frankel Cardiovascular Center. https://www.umcvc.org/conditions-treatments/aortic-stenosis.
 Expert Analysis. 2015 Surgical Aortic Valve Replacement: Biologic Valves Are Better Even in the Young Patient. American College of Cardiology.
 Source for TAVR diagram: TCTMD.com
 Maxwell, Y.R. 2018. Valve-in-Valve TAVR: Mortality, Adverse Events Similar to Redo Surgery at 30 Days. TCTMD/the heart beat. < https://www.tctmd.com/news/valve-valve-tavr-mortality-adverse-events-similar-redo-surgery-30-days>.
 Barbanti, et al. 2016. Circ. Cardiovasc. Interv. (9):e003930. Outcomes of Redo Transcatheter Aortic Valve Replacement for the Treatment of Postprocedural and Late Occurrence of Paravalvular Regurgitation and Transcatheter Valve Failure. < https://pubmed.ncbi.nlm.nih.gov/27578840/>. DOI: 10.1161/CIRCINTERVENTIONS.116.003930