News on Newer Oral Anticoagulants (NOAC)

For most of my adult medical career, warfarin or Coumadin has been the gold standard for achieving anticoagulation to prevent deep vein thrombosis, pulmonary embolism, embolic strokes and other hypercoaguable conditions. Taking warfarin required monitoring your INR or Prothrombin Time by taking blood from a vein or puncturing your finger and using the finger stick blood on a strip to calculate the INR. Our goal was to keep the INR level therapeutic between 2 and 3. The safe dose of warfarin (Coumadin) is affected by dietary intake of foods containing Vitamin K (green leafy vegetables and fruits) and medications that either makes the warfarin more or less potent. These dietary and medication interferences either made your blood more coaguable increasing your risk of an embolic event, or made the blood less coaguable and contributed to bleeding events. These could include intracranial bleeds leading to permanent neurological damage and or death or gastrointestinal or retroperitoneal bleeding which could be life threatening. Warfarin or Coumadin’s anticoagulant effect could be reversed quickly by administering an antidote, fresh frozen plasma (FFP) and or replacing Vitamin K.

Within the last decade, pharmaceutical manufacturers developed and released newer oral anticoagulants such as Pradaxa (dabigatran), Xarelto (rivaroxaban) and Eliquis (apixaban). These medications were advertised as safe and did not require blood tests to monitor their effectiveness while eliminating interactions with healthy foods and most medicines. They were embraced by cardiologists trying to prevent embolic strokes in patients with the arrhythmia atrial fibrillation. The major drawback was that if you started to bleed, there was no antidote to stop the bleeding available. In the introductory period the drug could only be reversed by removing the drug via hemodialysis. There were additional questions about whether the drug was actually as or more effective than warfarin when the warfarin dosage was monitored and regulated at reputable and established medical centers in the United States.

At the European Society of Cardiology meetings in Rome, Italy, Stuart J Connelly, MD, from McMaster University in Hamilton, Ontario Canada reported this week on the results of the ANNEXA – 4 Study. They reported being able to reverse the effects of Xarelto and Eliquis using a newly created chemical. According to their report they had achieved a safe and effective antidote for these two drugs which would complement another product already approved by the FDA and in use to reverse the anticoagulant effects of Pradaxa. Their presentation of the data was accompanied by the simultaneous publication of the results in the New England Journal of Medicine. Despite the papers presentation and warm reception and publication in a respected peer review journal, the FDA has yet to approve this medication for use in the United States.

At the same meeting, Dutch researchers presented data showing that the NOAC’s (Pradaxa, Xarelto, Eliquis) provide at least the same degree of embolic stroke prevention as warfarin with less chance of intracranial bleeding. Clearly if this study is reproducible and if the antidote for bleeding with Xarelto and Eliquis receives FDA approval, it will be far easier for patients and clinicians to work with these NOAC’s then to continue treatment with Coumadin. The NOAC’s are far more expensive than warfarin (Coumadin) but their ease of use and reversibility with the newly approved agents, will make them the drugs of choice when an oral anticoagulant is required.

To Floss or Not To Floss? Making Recommendations Without Data

The U.S. Department of Health has announced that there is no data that flossing your gums has any benefit.  This has led to an Associated Press review of the paucity of randomly controlled trials with evidence that flossing is beneficial. The result is a new recommendation that flossing daily is not necessary. We are living in an era where the only justification for research and observational studies seems to be to justify saving money by not teaching patients something or encouraging them not to do something. Cost containment is the key as the US Government tries to lower the percentage of dollars spent on health care as a percentage of the Gross National Product.

Experts at the Cleveland Clinic spurred on by the “Bale and Doneen” philosophy that inflammation in arterial vessels leads to acute heart attacks and strokes have pushed for greater periodontal care and health. Flossing is part of that philosophy. Cleaning in-between your teeth with hand held pics or water pics provides cleaning of the gums and spaces between teeth as well.  There are few or any studies on this subject because the benefit is so obvious that there has been no need to perform them.  Dentists assure me that proper tooth and gum care is essential to your general health and wellbeing.  This is common sense like not crossing a busy street against the light, not drinking alcohol and driving a car or truck or not jumping out of an airplane without a parachute. It’s time for our dental schools to organize and perform these studies but I suggest you keep caring for your gums and teeth while the data is being accumulated.

Pneumococcal Vaccine in Development May Fight All Strains of the Disease

Community acquired pneumonia (CAP) plus other infections attributable to the Pneumococcus bacteria account for 15 million infections per year including pneumonia, meningitis and bronchitis. The organism is the leading cause of death in children less than five years old.  Over the last 30 years pharmaceutical companies have developed Pneumovax 23 which covers 23 unique bacteria that cause CAP in adults and Prevnair 13 which covers 13 pneumococcal bacterial strains.  Twelve of the bacteria in Prevnair 13 are identical to the Pneumovax 23 with only one unique bacterial type included.

A group at the State University of New York at Buffalo led by Blaine Pfeifer, specializing in chemical and bacterial engineering; has developed a new approach to pneumococcal vaccination. Working with computer modeling and animals to this point, they have developed a successful vaccine that attacks pathogenic pneumococcal bacteria while leaving the beneficial and non-pathogenic subtypes alone. The vaccine reads proteins on the surface of the bacterial cells and destroys only those that show aggressive activity. The vaccine has been 100% effective against the 12 most virulent pneumococcal bacterial strains existing in animal studies.    The vaccine is being prepared for human testing in the near future.  The preliminary work was discussed in the medical magazine Medical Economics

Telomeres and Healthy Aging. The Tufts Perspective

Telomeres are bits of DNA genetic material that sit atop DNA strands and keep vital genetic material intact when cells divide or replicate. Think of them as the little plastic piece on top of the shoe laces. When they fall off or become damaged the shoelaces get damaged or frayed. Healthier older individuals have longer DNA strands with intact telomeres compared to people with shorter life spans and chronic diseases who have smaller and shorter telomeres. Whether the shorter telomeres are the “chicken or egg” is unclear but clearly those with shorter telomeres are more likely to die from heart disease or infectious processes.

There does seem to be a relationship between telomere size and nutritional and vitamin levels. Ligi Paul Pottenplackel is a researcher at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts New England Medical Center. She has looked extensively at the humans’ intake and concentration of folate and telomere length and health. She found that those with an exceptionally high folate level and intake have shorter telomeres and worse health. While many researchers believe that folate being water soluble is flushed out if you don’t need it and causes no cumulative toxicity, she believes the short telomeres may be the result of excessive folate intake.

Physical exercise seems to keep telomeres from eroding. In an article in the journal Medicine & Science in Sports and Exercise, researchers showed that telomeres were longer in those who were active. Over time, all participants telomeres shortened but less so in the physically active groups.

While Tufts takes a closer look at nutrition and healthy aging we urge all to stay physically active while eating a balanced diet

Zika Update

Zika is an infectious virus introduced to Florida by individuals who traveled to South and Central America plus the Caribbean Islands and were infected by the bite of an aegypti mosquito or a close relative of that mosquito. They then brought the infection back to the USA. The disease has an incubation period of less than two weeks and generally produces a mild illness that most adults do not even know they have. Fever, aches and pains, a fleeting rash, headache and conjunctivitis are common symptoms. Once infected the disease can be transmitted from human to human by body fluids during sexual activity. It can additionally be transmitted when an infected individual is bitten by a mosquito and then it bites a human being. Fortunately the mosquitoes have a flight range of about 100 yards. It is the mobility of infected human beings causing the geographical spread of the virus more than mosquitoes. The virus infects a male’s semen and can remain infectious for about six months. This has led to the suggestion that infected men use condoms when having sex for six months post infection.

The disease is mild in adults but the body’s response to infection has produced a neurological ascending paralysis known as Guillan Barre Syndrome (GBS) at three times the expected rate of this diseases occurrence.  GBS is painful and can affect our respiratory muscles necessitating the use of mechanical respirators and ICU care for survival. The disease is most dangerous in pregnant women causing permanent brain and developmental damage and death in developing fetuses.

At the current time treatment is supportive. There are lab tests to detect an infection using blood and urine specimens. A vaccine to prevent infection is under development with early success noted in rhesus monkeys. Prevention at this point involves practicing safe sex, avoiding mosquito bites using repellant and appropriate clothing.  The mosquito spreading Zika bites during daylight hours. Spraying to reduce the mosquito population is an ongoing strategy being hampered by poor funding. An experimental project to introduce sterile genetically engineered female mosquitoes is being hampered by lack of funding and citizen concern about potential dangers of releasing mutated mosquitoes.

President Obama asked Congress last spring for 1.9 billion dollars to fight Zika but Congress adjourned without providing any funds. The CDC used other funds to begin the research and fight against Zika but is rapidly running out of funds.