Cannabis & Cannabinoids in the Treatment of Chronic Non-Cancer Pain

My 90 year old patient with spinal stenosis, diffuse osteoarthritis and now polycythemia vera was in for an office visit. He had been to see his hematologist and had been phlebotomized removing a unit of blood to control his overproducing bone marrow. He mentioned that the hematologist had sent him to a medical marijuana clinic run by a pain physician colleague of his.

The patient proudly showed me his marijuana registration license. “It doesn’t work you know. In fact I feel poorly after I take some. I have tried the oils and some edibles but it really doesn’t affect my pain in a positive way.”

Many of my patients now are licensed to receive medical marijuana for chronic pain. It’s a big business here in the state of Florida where senior citizens with chronic aches and pains are always looking for that magical pill to restore their vitality and youthfulness. His experience is unfortunately supported in the medical literature. In the May 25, 2018 issue of Pain magazine which looked at the pain relief of patients with rheumatoid arthritis, fibromyalgia, neuropathic pain and 48 other non-cancer pain conditions. The study was a literature review looking at the 104 studies published on this subject.

The findings were sobering and disappointing. They found that cannabinoids had no appreciable positive impact on pain relief. In addition it didn’t help sleep, there was no positive impression of change and there was no significant impact upon physical or emotional functioning.

I am not an anti-marijuana crusader. I see its positive impact in treating glaucoma. I see the studies citing it is more effective to deliver by smoking it than eating it or taking it in pill form.

The review studies included all forms of administration of cannabis. I just want to make sure that when authorities legalize a substance for use in pain control it is effective and not just profitable snake oil for a strong lobby of well-healed and crafty businesspeople.

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Tamsulosin and the Risk of Dementia

The journal Pharmacoepidemiology and Drug Safety published and reviewed in the online journal Primary Care which examines whether men with enlarged prostates and symptoms of prostatism develop dementia more frequently if they take the drug tamsulosin to relieve the symptoms. As men age, under the influence of male hormones, the three lobed prostate normally increases in size. As the prostate enlarges, it impedes the flow of urine as it attempts to leave the bladder. Patients feel urgency, hesitancy, dribbling, sometimes leaking and a diminished stream. Sleep-awakening night time urination becomes an issue as well as difficulty fully emptying the bladder.  Minimal night time urine production produces the urge to void.

There are many non-pharmacological surgical treatments for this normal, age related, condition. Medications have been used for years to try to prevent surgery or defer it to a later date. tamsulosin works by inhibiting certain receptors on the muscle in the prostate causing relaxation of smooth muscle and increased flow of urine. The study authors used Medicare data to look at men aged 66 and older taking tamsulosin to reduce symptoms of an enlarged prostate. They compared these men to others taking no medication for BPH and to those taking medications that work by a different mechanism of action including terazosin, doxazosin, alfuzosin, dutasteride and finesteride. The data was collected from years 2006 – 2012.

The results showed that men taking tamsulosin had a propensity for negative changes in cognitive function at a higher rate than men taking other products. This was clearly not a straight cause and effect study proving that tamsulosin causes cognitive dysfunction. The authors and reviewers in accompanying editorials point out the many variables and flaws which may have contributed to the conclusion but emphasize that further defining studies need to be started to clear up the doubt raised by this review.

A VA study done years ago comes to mind in which Veterans who ultimately switched from medications for an enlarged prostate underwent surgery and were interviewed one year later about their feelings about the results and function after surgery. Almost 100% of the study group felt better after surgery and relieved that the side effects of their medications for an enlarged prostate were a thing of the past. They wondered why they waited so long to have surgery and felt they would have asked for it sooner had they realized the many ill effects the medication was causing. It may be time for a more aggressive approach to prostate surgery as opposed to medical treatment?

Commercial Air Travel is Really Safe

For the last 25 years I have had the privilege of being a designated airman medical examiner by the Federal Aviation Administration. To earn that privilege, it required flying to FAA headquarters and taking a one week training course followed by refresher training material every three years.

The FAA grades medical examiners annually by our judgment and decision-making. The nature of the questions we are required to ask the pilot candidates, and the exam, have been dictated by the rigors of being a pilot and reflect the stresses unique to flying a plane safely. Many of them were created after a plane crash, fatality and the resulting National Transportation Safety Board (NTSB) investigation revealed a health reason involved in the crash.

I attended my refresher course in Washington, D.C. this past week over a three-day period. Physicians designated by the FAA fly to the event and stay at their own expense. By law, the FAA is not permitted to pay for food, coffee or any expenses. Over 50% of the attendee physicians are pilots who fly to the conference in their own private planes. There are about 2,800 physicians performing these exams around the world and, judging by the grey hairs, and canes in the crowd; they are getting significantly older reflecting the same process in the physician population in our country.

This was the first time I attended this meeting and I saw a significant number of women physicians in the audience which makes me believe there is diversity in the physician examining population as well. The speakers on medical topics are first rate. We heard from leading doctors at the best places, all leaders in aerospace medicine and research in cardiology, neurology, psychiatry, otolaryngology, ophthalmology, fatigue and sleep medicine. I learn a great deal of general medicine to bring back to my medical practice medicine at these sessions.

Performing FAA exams for pilots is not a particularly lucrative proposition. You see 3 classes of candidates including the commercial pilots for class 1 exams, navigators for class 2 exams and general aviation or civilian private pilots for class 3.

As our pilot population continues to age, domestic airlines are now retiring them at age 65. If perfectly healthy, a class 1 pilot starts getting EKGs annually at age 39 and they are then seen every six months at a minimum. The exam and paperwork takes 45 minutes at least and must be transmitted back to the FAA by computer. If you detect a problem either by your taking a history, or performing an exam, there is a further investment of time and research to provide the FAA safety experts with the medical records they need to determine if the pilot is healthy enough to safely fly a plane.

I would say the vast majority of examiners charge only $175 or less for these exams. Try getting that time, attention and value when you go to most physicians for an exam.

The reward for being a designated airman medical examiner is being part of a team that keeps the skies safe for the flying public. Seeing accident and mortality rates decrease year after year brings an extraordinary sense of satisfaction. I get to work with extraordinarily talented and dedicated employees of the FAA, from the staff at my Regional Flight Surgeons headquarters in Atlanta, and the professionals in Oklahoma City and D.C. who read, train and study so when I fly from place to place, I arrive there intact after an uneventful flight. There you have it. Commercial air travel is really safe.

Consumerism and Convenience Gone Wild in Health Care

I have received several phone calls in the last few weeks from young adults requesting information about their last vaccinations. They are travelling to areas of the world that suggest or require certain vaccines and do not remember if they had them or not. Others are applying for positions of employment which require travel and the employer’s human resources department needs the patient’s updated vaccination records.

When we tell them that we only have a record of the vaccinations we have given them in the office they act surprised. “You mean XXX hasn’t sent you a copy of my tetanus booster shot?” Others inquire if the travel health service they went to sends us a record of the vaccines they administered. The answer is “sometimes”.

The State of Florida instituted a website called Florida Shots for immunization records a few years back which is incomplete at best. At one time you received all your vaccinations and immunizations in the doctor’s office and a record was then maintained.

In the new world of consumer convenience first, pharmacies are paid by insurers for administering vaccines while the same shot given in your doctor’s office is not a covered service. In some cases, we have the childhood vaccination records from a pediatrician and a college health form updating us on meningitis and hepatitis A and B vaccines. Those adults out of college for more than seven years who do not have a copy of that form are just out of luck. This is a prime example of consumerism and convenience gone wild for no good reason

Another example is the creation of the BasicMed program allowing non-commercial pilots to obtain a medical certification to fly instead of going to a highly trained certified FAA Airmen Medical Examiner Physician (AME). If you have a driver’s license and pilot a plane for 6 or less passengers, which will not fly faster than 250 knots, or ascend above an altitude of 18,000 feet; you can go to any doctor with your driver’s license and be certified to fly.

Why would a pilot go to BasicMed rather than to a trained and certified and recertified physician in aerospace medicine? Probably because they are concerned that the trained physician will not pass them based on their health and the non-certified doctor will either go easier on them or just miss the problems that an AME might investigate.

 

This law was the result of lawsuits against the FAA by pilots not meeting the standards and resulted in Congress passing this private pilot friendly law. In recent years, expensive private flight schools have become the pathway for a student to eventually become a commercial airline pilot. They are replacing the previous pathway of hiring former military pilots who are more experienced, more disciplined and usually older and more mature than flight school candidates. This new breed of air transport pilot will now be sharing the skies with private civilian pilots receiving their medical clearance from less physicians with less aerospace medical knowledgeable. Is this not also convenience and consumerism gone wild?

Experimental Drug Stops Parkinson’s Disease Progression in Mice

Researchers at Johns Hopkins University School of Medicine published an article in Nature Medicine Journal outlining how administration of a drug called NLY01 stopped the progression of Parkinson’s disease in mice specially bred to develop this illness for research purposes. The medication is an alternative form of several diabetic drugs currently on the market including Byetta, Victoza and Trulicity. Those drugs penetrate the blood brain barrier poorly. NLY01 is designed to penetrate the blood brain barrier.

In one study, researchers injected the mice with a protein known to cause severe Parkinsonian motor symptoms. A second group received the protein plus NLY01. That group did not develop any motor symptoms of Parkinson’s disease. The other group developed profound motor impairment.

In a second experiment, they took genetically engineered mice who normally succumb to the disease in slightly more than a year of life. Those mice, when exposed to NLY01, lived an extra four months.

This is positive news in the battle to treat and prevent disabling symptoms in the disease that affects over 1 million Americans. Human trials will need to be established with questions involving whether the drug is even safe in humans? If safety is proven then finding the right dosage where the benefits outweigh the risks is another hurdle. The fact that similar products are currently being used safely to treat Type II Diabetes is noteworthy and hopefully allows the investigation to occur at a faster pace.

Parkinson’s disease is a progressive debilitating neurologic disorder which usually starts in patient’s 60 years of age or greater. Patients develop tremors, disorders sleeping, constipation and trouble moving and walking. Over time the symptoms exacerbate with loss of the ability to walk and speak and often is accompanied by dementia.

More Good News for Coffee Drinkers

When I first started practicing, fresh out of my internal medicine residency and board certification, we were taught that consuming more than five cups of coffee per day increased your chances of developing pancreatic cancer. Thankfully that theory has been proven to be false.

Last week I reviewed a publication in a peer reviewed journal which showed that if you infused the equivalent of four cups of coffee into the energy producing heart cell mitochondria of older rodents, those mitochondria behaved like the mitochondria found in very young healthy rats. The authors of that article made the great leap of faith by suggesting that four cups of caffeinated coffee per day was heart healthy.

This week’s Journal of the American Medical Association Internal Medicine published a study which said if you drank eight cups of coffee per day your mortality from all causes diminished inversely. Their study included individuals who were found to be fast and slow metabolizers of caffeine. It additionally made no distinction between ground coffee, instant coffee or decaffeinated coffee.

The research study investigated 498,134 adults who participated in the UK Biobank study. The mean age of the group was 57 years with 54% women and 78% coffee drinkers. The study participants filled out questionnaires detailing how much coffee they drank and what kind. During a 10 year follow-up there were 14,225 deaths with 58% due to cancer and 20% due to cardiovascular disease. As coffee consumption increased, the risk of death from all causes decreased. While instant coffee and decaffeinated coffee showed this trend, ground coffee showed the strongest trend of lowering the mortality risk.

This is an observational study and, by design, observational studies do not prove cause and effect. It is comforting to know however that having an extra cup or two seems to be protective rather than harmful. At some point a blinded study with true controls will need to be done to prove their point. If the caffeine doesn’t keep you up or make you too jittery, and the coffee itself dehydrate you or give you frequent stools, then drink away if you enjoy coffee in large volume.

Shared Decision Making. Science versus Art of Medicine.

My 80 year old patient presented with symptoms and signs of kidney failure. I hospitalized him and asked for the assistance of a kidney specialist. We notified his heart specialist as a courtesy. A complicated evaluation led to a diagnosis of an unusual vasculitis with the patient’s immune system attacking his kidney as if it was a foreign toxic invader.

Treatment, post kidney biopsy, involved administering large doses of corticosteroids followed by a chemotherapy agent called Cytoxan. Six days later it was clear that dialysis was required at least until the patient’s kidneys responded to the therapy and began working again.

You need access to large blood vessels for dialysis, so a vascular surgeon was consulted. He placed a manufactured vascular access device in the patient’s lower neck on a Monday in the operating room. The access was used later that day for a cleansing filtration procedure called plasma exchange. The patient returned to his room at dinner time with a newly swollen and painful right arm and hand on the same side as the surgical vascular access procedure.

The nurses were alarmed and paged the vascular surgeon. His after-hours calls are taken by a nurse practitioner. She was unimpressed and suggested elevating the arm. The floor nurses were not happy with that answer since they had seen blood clots form downstream from vascular access devices. They next called the nephrologist. He suggested elevation of the arm plus heat. This did not satisfy the charge nurse who requested a diagnostic Doppler ultrasound to look for a clot. The nephrologist acquiesced and it was done quickly revealing a clot or deep vein thrombosis (DVT) in an arm vein.

I am the patient’s admitting physician and attending physician (it is unclear to me what the difference is) but I was surprised I did not receive the first or second call regarding the swollen arm. I was the first however to receive a call with the result. My first knowledge that a problem was occurring came when an RN called, “Dr. Reznick, the patient in 803 came back from dialysis with a painful swollen right arm and hand. The vascular surgeon was called but his covering nurse practitioner wasn’t concerned. The nephrologist ordered the test after we encouraged him to. There is a clot in the right brachial vein. What should we do?”

This was a new complication occurring to a frightened patient just returning from surgery, plasma exchange and hemodialysis for the first time to treat a rare aggressive disease he and his children had never heard of. One of my cardinal rules of practice is when in doubt listen to the patient, take a thorough history of the events, examine the involved body parts, look at the diagnostic studies with the radiologist and explain it all to the patient and family. I changed my leisure clothes to my doctor clothes and headed to the hospital delaying dinner, something my wife is incredibly understanding and tolerant of.

One of the perks of teaching medical students is being provided free and total access to the medical literature using the school’s library and subscription access. I searched for anything related to upper extremity deep vein thrombosis after establishing vascular access and related to his vasculitis. Three items popped up including recommendations and guidelines for diagnosis and treatment from the American College of Cardiology and the American College of Thoracic Surgeons all within the last six months. They both suggested the same things, use intravenous blood thinners for five to seven days then oral anticoagulants for three to six months or until the vascular access is removed. The risk of the blood clot traveling to the lungs is lower than in leg and pelvic DVTs but it is still 5 – 6%.

I read this while the radiologist accessed the films and reviewed them with me. Next stop was the eighth floor where the patient and his out of town visiting adult child were. I asked them what happened. They showed me the warm swollen arm and hand. I checked for pulses which were present and then color and neurological sensation which were normal. I explained that when vascular access is inserted in the large neck veins it can increase the risk of a clot forming in the arm veins resulting in arm and hand swelling. I explained that the chances of a clot traveling back to his heart and out to his lung were 5 – 6% and significantly less than DVTs in leg or pelvic veins. The treatment was explained. His nephrologist concurred as did the cardiologist. Heparin was begun.

With elevation and soaks the swelling was down by morning. He returned from dialysis that afternoon with his chin and neck all black and blue. He was bleeding profusely from the upper portion of the surgical access site. Nurses were applying compression to the area after the blood thinner was stopped and it continued to bleed. Vascular surgery was furious that heparin or any blood thinner was used for the clot.

Repeated phone calls to the vascular surgeon resulted in him angrily arriving much later placing six sutures to stop the bleeding. Heparin can lower platelet counts when antibodies to heparin cross react with platelets. His platelet count of 80,000 was sufficient to prevent bleeding. A blood test for heparin induced thrombocytopenia was drawn and he received two more units of blood products to replace what he lost. After stabilizing the patient, we realized his drop in platelets was due to the Cytoxan having its peak effect not heparin.

The patient had no further bruising or bleeding. He was dialyzed or had plasma exchange on alternating days for another week. The nephrologist wanted this done in the hospital not as an outpatient. It took one week for the reference lab to return the negative HIT (heparin induced thrombocytopenia) results clearing the heparin of causing the bleeding and bruises.

Prior to discharge I reviewed the long term oral anticoagulation recommendations of the American College of Cardiology and Thoracic Surgeons with the patient, nephrologist, cardiologist and hematologist. The nephrologist was comfortable with administering a kidney failure lower dose of eliquis. The vascular surgeon and cardiologist felt it was not necessary. The hematologist initially agreed then changed his mind. I asked each of the naysayers to explain to me how this patient differed from the patients in the many studies who comprised the data for the recommendations? They said he did not. They said they had a feeling and discussed “the art of medicine in addition to the science”.

In a rare vasculitis disease which few of us have seen frequently, I prefer the data in multiple studies to one’s clinical intuition. At discharge, I prescribed the oral blood thinner. I reviewed the pros and cons of the drug. The patient and daughter told me that based on the ambivalence of the hematologist he would stick with his aspirin rather than the oral anticoagulant.

Shared decision making appropriately allows patients to decide for themselves. If the patient develops pleuritic chest pain coughing up blood with shortness of breath from a pulmonary embolus, I will be called to provide care not my colleagues because specialists don’t admit.