Heart Failure

Aim-High…and fail Part III

Who killed Kennedy?  Did we fake the moon landings?  Is that really President Obama’s birth certificate?  Is Fox News really true and accurate?  Some ideas just won’t go away no matter how many negative facts build up against it.

Such is the case with niacin and coronary disease.  In light of this latest news, there is a school of thought that researchers just keep looking in the wrong place for the right answer.  They point to an ongoing study: The Heart Protection Study 2 THRIVE.  This study is being run by a very prestigious study group and is utilizing a 25,000 participant cohort with atherosclerotic disease and statin.  This is an “all comer trial” and adds a drug that Merck developed and is approved for use in Europe. The compound is niacin combined with a prostaglandin agent laropiprant which supposedly controls the prominent side effects of niacin.

Perhaps, this will be the death knell for niacin.  It will have to show a significant benefit to be added to the regimen in use now.  Here is one mind blowing factoid about this trial: in 2008, this drug combination was turned down by the FDA, and they told Merck to submit again in 2013.  WOW, a 25,000 participant study with a drug we can’t even use here.  So much for the global nature of medicine.

As I have blogged about before, the cost of these studies is increasing, and the value is decreasing.  Medical management of coronary artery disease is so good now that researchers are having trouble proving anything works beyond aspirin, statins, beta blockers and angiotensin eliminating drugs.  The government will unfortunately have to be more and more involved if researchers want to answer some basic questions about how we treat people.  This is one of the goals of the new health care act.  Prove that what we do and take for granted actually works or are we just spending and earning money.

“First do no harm” has a corollary which is “If you do something, have at least some evidence that there is a benefit to patients."  That unfortunately is lacking in much of what is unquestioned but accepted as medical care.  Patients want more and more tests and more and more pills but get less and less benefit.  I feel the tide turning, slowly but turning nonetheless.

To those patients taking niacin, I would urge you to talk with your physicians and examine all of your drugs.  Seriously ask yourself whether you can do better on diet and exercise and strive to improve your own fitness.  Take ownership of a problem you likely didn’t cause but have not helped by your actions.  Take as much statin as possible to achieve the lowest LDL possible and for heavens sake do not let doctors tell you your LDL is too low.  Make them prove IT.

Finally, there is very little evidence that small doses of niacin do anything.  It will not hurt you, but it will not help you.  Instead of wasting your money, donate it to buy real medication for patients that cannot afford to.

I wish I had positive news for you.  Researchers and big Pharma will, I promise, keep trying.  One day our prince will come…

Aim-High…and fail. The failure of a system Part II

niacin

AccessMedicine © 1978-Present McGraw-Hill and/or its respective owners.

Aim-High was a study to determine if patients who had cardiovascular disease but persistently low HDL levels and high triglycerides would be benefited by adding slow release niacin to their drug therapy.

I have blogged about Niacin and it’s troubled past before.  It was the substance tested in the ARBITER6-Halts trial that I blogged about.  Niacin is Vitamin B3 and known as nicotinic acid.  A vitamin is a substance that is necessary for human health.  Niacin is involved in DNA repair and the production of steroid hormones.  Without niacin, the disease known as pellagra develops.

Niacin blocks the breakdown of fatty tissue in the body so it decreases very-low-density lipoprotein levels which are a precursor to LDL.  This process increases HDL to some extent.  In the past, trials of niacin vs. placebo were effective in lowering cardiovascular event rates.  ARBITER6 was a Frankenstein of a study using Zetia vs. 2000mgs of slow release niacin to effect the cholesterol levels in carotid arteries.  Zetia lost again but this was not an event trial and was piggybacked on statins.

Niacin is a very difficult substance to take as a drug.  Big Pharma is obsessed with finding a preparation of niacin which allows it to be used as a drug without the side effects of flushing, itching and nausea.  This takes the form of “slow releasing it” or covering the side effects up with a prostaglandin drug.  None of these attempts has been successful to date.  Further complicating this is the relatively acknowledged need to take about 2000 mgs a day.  This comes from early work when niacin was used without statins but seems to persist as a dream dose. Even at this dose it doesn’t seem to do anything but cause side effects.  All of this is propelled by the money earned on slow release niacin which amounts to just under a billion dollars a year.

Aim-High enrolled 4,314 participants in the United States and Canada.  It was funded by the NHLBI and Abbott the present owner of Niaspan the slow release formulation used.  It was originally manufactured by Kos pharmaceuticals but they were gobbled up by Abbott.  More will be said about this source of funding later.  All of the participants were given simvastatin and the goal was to lower the LDL to 40-80 mg/dl.  The current recommendations are in this type of patient to lower the LDL level to 70 mg/dl or as low as possible.  However because simvastatin is not the most powerful statin available 515 participants were given Zetia also.  Did this cause a problem?  Would the results been different if they used a different statin?

As in most trials the end point was combined.  The end point simply can’t be mortality at this point as thankfully that happens relatively rarely even in this group of patients.  The end points were fatal or non-fatal myocardial infarction, stroke, hospitalizations for unstable angina or a revascularization procedure.

The majority of the endpoints were hospitalizations or revascularizations.  When the trial was stopped, 5.8% of the treatment group and 5.6% of the control group had an end point. The trial was stopped 18 months early because it was “futile." Of note, strokes were more common in the treatment group than the control group 1.6% vs. 0.7% this was total of 28 strokes in 32 months of follow up.

I should point out that the HDL increase was 20% and the triglycerides were lowered by close to 25% in the treatment group.  An example would be an HDL of 30 becoming 36.

In my next blog I will sum up the implications of all this.  They go beyond coronary disease.

An aside… this blog starts my third year of providing two blogs a week for this forum.  It remains a great pleasure to bring this information to you, and I hope it increases your understanding of cardiovascular disease and the controversies surrounding it.  I appreciate your continued viewing.

Aim-High…and Fail. The failure of a system Part I

What a mess.  We as physicians are faced with negative news about a beloved idea and everyone has an opinion.  The content of this blog is often similar not because there is little to blog about but because the topics are so vital to many people who seek solutions to their very real problems.  Many of my patients have undergone coronary artery bypass and angioplasty, yet the disease of atherosclerosis persists in spite of maximal statin use.  I guess you could use more than 40 mgs of Crestor but each up titration of dose yields smaller benefit. As I have often blogged about the reason statins work is not because the LDL goes down.  The decrease in LDL is a marker for a variety of processes which reflects endothelial health.  To paraphrase President Clinton (or more correctly James Carville), it’s the endothelium, stupid.  The endothelium is what disrupts and causes a myocardial infarction or unstable angina.  The endothelium is what is invaded by cholesterol and damaged.  The same process causes some strokes. The search has been on to address those patients “under the curve."  The question is why don’t more patients benefit from the same statin dose?  What are we missing?  The answer is unknown, but I believe it lies within us.  It is a very real combination of genetic factors plus environmental factors, and I do not believe that it will be solved in my lifetime by a drug or combination of drugs.  The unfortunate “truth” is that we must eat “right," lose weight and stop smoking.  Let me add in exercise.  All of these increase endothelial heath and have been shown over and over again to reduce event rates. At this point we as physicians have not been able to study another target substance i.e. HDL or triglycerides and produce benefit unless we do not use statins in the mix.  This however is not possible as it would be unethical to not use statins in this population as they reduce mortality. This problem is very vexing to those patients who for whatever reasons can not take statins.  It also vexes doctors who continue to prescribe an expensive, sometimes toxic, brew of medications instead of increasing statins to maximal dose which is at this date the only result necessary by the randomized clinical trails done to date.  We all can have opinions but we can not have our own facts. Medical researchers continue to try to affect targets other than LDL.  Ongoing are several large trials with HDL target drugs that raise HDL by inhibiting Cholesterol Enzyme Transport Protein metabolism (CETP inhibitors).  The first of these agents torcetrapib did not survive after a billion dollars of expense.  These studies are being done in the “new way” that is no one really cares how much HDL can be raised, we just care about when added to effective statin therapy, does the event rate go down?  The last drug approved under the “old way” was Zetia, and as I have blogged about in the past, we are still waiting for the results of the clinical trial regarding event rates to be completed.  At this time, they have more events in their trial than all of the patients enrolled in Aim-High. In my next blog I will explain how Aim-High was brought low.

If it doesn’t work on my stent, I’ll just drink it

stentdesigns

Coronary stents are the little engine that could.  They saved coronary angioplasty from the probable scrape heap as who really wants a procedure that only worked one half the time?  Stents now provide an almost unlimited opportunity to repair coronary anatomy with satisfying long term results.

Stents, however humble appearing, are micro looking but macro engineered.  There are multiple issues with a stent that you might want to think about to appreciate the beauty of them.  They are no longer stainless steel for one thing.  The vast majority are now an alloy of cobalt and chromium.  This for one thing allows them to be subjected to MRI evaluation as they are not magnetic.

Another benefit is superior strength with superior flexibility.  At times stents need to be deployed down hard calcified arteries that are sometimes very unforgiving, so flexibility is at a premium. But then, stents need to scaffold up the artery so they need strength to resist recoil.

Drugs are then placed on the stent and the “adhesive” substance which applies the drug to the stent  must not “inflame” the artery or interact with the body in any way.  The drug must then block the abnormal proliferative response that sometimes occurs when a nondrug stent is implanted.

This introduction brings me to my topic.  Most of the drugs used today are from the sirolimus drug family.  I have blogged about them before.  The name of the original compound is rapamycin.  Rapamycin was the name given to the compound because the compound was found on Rapa Nui.  Do you know where Rapa Nui is?  To save you a trip to Wikipedia Rapa Nui is the ancient name of Easter Island in the Pacific Ocean.  The island is an ancient wonder because of the Moai or enormous statues that were carved and moved to a site around 1500 B.C., which are interesting as a wonder of a more primitive age.  The drug was found in a sample at the base of one of the Moai.  The largest Moai is 82 tons.

I digress.  The search is on for new and perhaps better drugs to put on stents, and one such compound was recently presented at the American Heart Association Arteriosclerosis, Thrombosis and Vascular Biology 2011 Scientific Session in Chicago this past week.  I have blogged about this compound in the past and it is of great interest for many reasons.  This work has only been done in rats, and it would be several years before trials would begin in humans if it makes it that far.

The compound is resveratrol a substance which is found in the skins of red grapes and in high concentrations in red wine.  This substance is chemically a polyphenol and has been synthesized and is undergoing study in many trials.  It was at one time felt to be the solution of the "French Paradox."  The French Paradox is why do the French eat, drink and smoke anything they want and have low rates of coronary heart disease than we do.  It was felt to be the consumption of red wine.  This has been set aside to some degree, and it is now felt that the paradox is best explained by consumption of moderate amounts of alcohol regardless of the type.  It is felt to be mechanistically involved with the lowering of blood pressure because you are more “relaxed” after some alcohol.

The drug was placed on a stent and then implanted in rat carotids.  High dose, low dose and no drug stents were implanted.  The results were that the drug in either dose caused a more rapid reendothelialization compared with bare metal stents.  The endothelium is the lining of the artery that is destroyed during angioplasty.  A faster more complete reendothelialization would, in theory, allow less of a need for clopidogrel if it proved to be the case in humans.

We are a long way from human studies, but it is intriguing that wine may be so useful.  Here’s to you health.

A good idea that is ignored. Until now.

lipitorPhoto Source: AccessMedicine © 1978-Present McGraw-Hill and/or its respective owners.

Medicine moves slowly and rarely in a straight line.  Change is hard to implement in particular if you are going to try to change an institution.  But, medicine and we who practice it, have an obligation to identify any institute changes that seem to improve patient care and provide little risk.

One such change that I have known about but have not instituted will be described below.  The time seems to have arrived for its wide spread implementation.  The data can no longer be ignored.

It involves my favorite type of drug: the statins.  Yes,  I’m proud to announce that they seem to have another action that screams out for attention and use.  They may be the MVD (most valuable drug) of cardiology.

As reported in Circulation (Journal of the American Heart Association) on April 4, 2011 (Circ 2011;123: 1622-1632), statins given before an angioplasty -- including those angioplasties that are emergencies -- reduce heart attacks by 44%.  What’s the down side? None.

The authors found 13 randomized studies and received the patient data from 12 them for a total of 3,341 patients.  The control groups received either low dose or no statins, and the active group received high dose statins.  The data was then combined and analyzed showing that there was no independent variable except the dose of statins.  There was a reduction of myocardial infarctions defined by the standard >3x increase in CKMB of 44% in the group taking high dose statins.

The rate of major adverse events (i.e. death, myocardial infarction and target vessel revascularization) were reduced by 44% mostly driven by the myocardial infarction rate.  If you exclude the myocardial infarction rate, the results were 0.6% versus 1.4%.

Why does this work?  It clearly is not by lipid lowering as that does not have time to occur so quickly.  It seems to be related to effects at the cellular level which protect the heart from ischemia or lack of blood flow.  It works even better if your C reactive protein level is elevated as many patients who have myocardial infarctions are.

It is important to point out that the majority of these studies used the highest dose of the most potent statins.  As most of my patients know, I favor the highest dose of statin that a patient can take, but I am often limited by insurance company interference.   In November of this year, atorvastatin (or Lipitor) will be generic and hopefully its use will be more widespread.  Even if you are taking high dose simvastatin you will be receiving another statin for the purposes of this data and the procedure.

I suspect that more and more patients will be asked to take these drugs before angioplasty.  The down side is none, and the upside great.  Angioplasty is far and away the leading procedure to revascularize a blocked coronary artery, and it appears to have just gotten safer.

I thought I was doing a great job at 150 (Part 2)

The use of guidelines has become a valuable resource for all practicing physicians.  They serve as a measure of how we are doing and add insight into why we physicians do things and how to improve our patient care.

One problem with them is that they often run into 100 or more pages.  The material is dense and often esoteric.  Very few of us ever read the end in  which the authors of the document reveal their “relationships” that may represent conflicts of interest.

This conflict of interest issue, like so many other PC issues, is often misconstrued, but it is particularly important with the passing of scientific information that proposes to change the way we as physicians do things.

As reported in the blog CardioBrief on April 21, 2011 by Dr. Allan Brett who is at the University of South Carolina Medical School and is the editor in chief of the Journal Watch General Medicine, six of the twelve authors of the guidelines have important financial ties to the makers of expensive drugs that are touted in the guidelines.

The question asked and I repeat here is, “Is it not possible to write these guidelines with people who have “nothing to report” as far as conflicts of interest?  Do we have that great a lack of uninvolved physicians who have this expertise?”

If you study these guidelines, the same people commonly show up.  Part of this is that they are heavily involved with the AHA and ACC the other part I suppose is that they obviously like the work and have the time to spend on it.  It is very time consuming, and you have to have many meetings.  It is impossible to actually have an active practice and do this work.  You would have to expand the number of hours in a day or just not sleep.  Neither is practical.

It is, however, off putting when the level of triglycerides is lowered and basically the only way to do it is to add a drug and to find out that one half of the writers have heavy sponsorship from industry.

This is an important piece of work and an important topic.  We have an epidemic of atherosclerosis in this country and need all the help we can get.  I believe that these individuals are not making these distinctions based upon anything but the best observations and experience that they bring to the table.  It would just smell better if the issue wasn’t there at all.

At the end, we still are left with diet, exercise, statins and other drugs to lower triglycerides.  Do the best you can with diet and exercise because in the end, these are the most important for overall health.  Statins will lower some patients' risks of disease and events including death.  The rest may not matter so much.

Time and more research will tell.

Rest in Peace

One of the unique realities of being a physician is the integration of your life with others.  At times that integration is quite close as you come to know patients over a lengthy period of their life.  I may be part of the last generation of physicians who have this opportunity as the practice of medicine is becoming much more impersonal and the presence of doctors that truly know you is becoming rarer and rarer.  I consider myself fortunate to have many patients who I have gotten to know over a greater than twenty year period. One such patient died on March 10th.  His story is important in many regards.  His name is not important but what he did and what happened to him is.  We were almost the same age.  He was about one year older than I.  He went to war, and I went to college after drawing 253 as my number in the draft lottery the first year it occurred.  He went into the Navy, became a Navy Seal and was deployed to Vietnam.  He spent the war doing what Seals do.  Most of it classified, all of it dangerous.  He was in Laos and Cambodia and all the places “we” never were.  One of his problems was that most of his service record was redacted whenever he went to the VA, and he was never afforded the respect that his service and rank deserved. He didn’t bring back much from the war but carried with him a visual reminder as he was tattooed across his forehead with a gunpowder stain that looked like a lightning bolt.  The souvenir of a failed execution attempt on his life while on a mission in Laos.  He returned to the Navy Seal base in Coronado, California and was made a Seal instructor.  There probably is not a higher training job in the military than that. Soon after, at age 41, he suffered his first heart attack and underwent bypass surgery.  He was discharged from the military life he so loved.  He went to work for IBM, and I met him when he began to have angina again.  He underwent the first of several angioplasties and eventually underwent his second bypass operation.  It was not very successful in relieving his symptoms as his bypass targets were poor. 

To add to his misery, his sternum never healed and was a constant source of pain.  Throughout it all he never complained.  He was disabled and incapacitated, unable to even walk his dogs. I tried everything without success.  He did everything he was told including undergoing gastric bypass so he would ease the burden on his heart.  He lost 120 pounds but still no relief from his angina.  He was evaluated and turned down for a heart transplant as he had no support system.  He was not a candidate for another bypass operation.  When a stem cell trial came along, he was the first in line, but again he had no luck.  I eventually found out he was in the placebo arm of the study. One day he brought me something special.  I never knew what he brought me existed until he showed me.  It seems that most servicemen have little use for medals.  They figure that anyone of them would do the same thing in the same position.  What he gave me was what they really want.  It seems that each branch of the service has a coin.  The Seals have one with their logo on it.  They give the coins to themselves when they think that one of them does something extraordinary, and these coins are what are valued.  Along with his Seal insignia pin, he gave me the coin.  I keep both in my desk. His pain was unrelenting, and he became dependent on narcotics for relief.  It broke my heart every time he came in for his monthly visit.  He became more and more debilitated, and I worried that he would harm himself as he certainly had the means.  He died peacefully, naturally.  He is finally at rest. My friend taught me about medicine.  He taught me the limits of what I could do.  He taught me how much a human being can suffer without any hope of relief.  He taught me courage in the face of adversity. A Seal never rings the bell…

A sign of the times...Everyone says sleep longer

As far back as Benjamin Franklisleepn, sleep has been a topic of interest.  You will remember that Franklin -- who published Poor Richard’s Almanac -- said, “Early to bed and early to rise makes a man healthy, wealthy and wise."  Interesting that Franklin said healthy first.  There is a growing body of research that seems to indicate that not only the amount of sleep but the quality of sleep is important.

Recently, enough acts of Air Traffic Controllers asleep on the job got the division director fired, and the rules changed so that controllers couldn’t stack shifts.  In my own profession, it seems that residents in training must only work 80 hours a week and take “uninterrupted naps” during certain parts of their day.  (Can I sign up?)  I for one could have told you that sleeping more doesn’t make you smarter or a better doctor.  Published recently was a study that the new work schedule of residents is not making for a safer patient environment.  The answer to that problem is better supervision, but no one asked me.  It doesn’t matter anymore, the die is cast.  Recently, another paper suggested that surgeons who do not have enough sleep should inform their patients during the informed consent process.  I don’t think that this suggestion is very likely to get much traction.

This week in the New York Times, an article that provided many answers to the how-long-do-I-need-to-sleep question was published. The answer, however unfortunate, is that most people need 8 hours of good sleep.  Some more, some less.  Very few can get by on six hours although we think we can.  These subjects were all studied in a very strict way, and the ability to score well on the test dropped off considerably at six hours.  You can force yourself awake, but performance suffers.  Coffee and cigarettes do not substitute for sleep.

At the EuroPRevent 2011 meeting in Geneva -- remember I told you about the European meetings -- an article was presented stating that amount is not enough; it needs to be “good sleep."  Short sleepers (those that slept six or less hours, who had poor quality sleep, defined as not feeling “rested “ when they awoke) had a 65% higher risk of cardiovascular disease and an 85% higher risk of  cardiac heart disease than those with a normal (8 hours) and good sleep quality.  I guess I’m doomed.

Is this a sign of the times?  Is there really a penalty for burning the candle at both ends?  Since many of us aren’t working, is the answer sleeping longer?  There is no question that sleep is important.  Short of water boarding, the best form of torture is sleep deprivation.  Most people have at one time in their lives been awake so long that they know that they can not function let alone see straight.  The really bad news is that it doesn’t seem that you can make up the deficit easily.

Franklin had two other sayings: “He that rises late must trot all day, and shall scarce overtake his business at night”  and  “If you would not be forgotten as soon as you are dead and rotten, either write things worth reading or do things worth the writing.”
He was a very great man.  I’m going to bed.

What’s the true cost of Pradaxa?

At the recent American College of Cardiology meeting in New Orleans, an analysis was done on the patients who were studied in two trials: the RE-LY and the RECOVER.  The RE-LY study or Randomized Evaluation of Long-Term Anticoagulation Therapy was the trial that enrolled 18,000 patients and served as the pivotal study which the FDA used to approve Pradaxa.  RECOVER is a study about using Pradaxa in the treatment of acute venous thrombosis instead of warfarin.

They studied 1774 patients.  If warfarin was chosen, the cost was $1,385,494, and the majority of the cost is labor and laboratory expense.  If treated with Pradaxa, the cost would be $4,371,136 made up mostly of the cost for the drug.

This study is a good example of what I would consider an extremely flawed study and yet is presented as “factual." Not taken into account is the very real cost of the patient having to come for a blood draw, being scheduled for that blood draw, finding the patient to give them the results and discussing and changing the dose of warfarin commonly with the same conversation of, "What are you doing and are you taking the pills properly?"  This also doesn’t take into the account the fairly constant phone calls concerning the multiple drug interactions and the need to stop the drug for procedures.  These now include calls from pharmacists who do not want to dispense medication that “they” don’t think is correct and the required phone call to solve the problem... This does not only involve the doctor but many other staff members, and the chance of error is great.  None of this is reimbursed to the physician.

Further, the authors seem to be using the retail cost of the drug, and cost breaks are often given in this setting to the larger companies.  The amount of time that needs to be spent at the begging of treatment is considerable but no more than the beginning of any drug therapy.  After that, it is pretty smooth sailing as the off the drug discussion is simple: stop three doses, and you are there.

Also, not included in this analysis is the frequency that patients enter the hospital because they are wildly anti-coagulated because of some error or change in their condition.  This cost is extensive and sometimes fatal.  Pradaxa does not change in this way.

In our new health care environment, my time and the time of my staff seems to be an ever increasing free commodity.  Phone calls, letters, discussions are not charged the $450 going rate of lawyers at this time or anytime in the past.  I for one am happy that I have a drug that is good for the patient and good for my time and effort.  If it costs the system money, I would suggest that they do a better analysis and consider the intangibles here.  It is money well spent.

Yawn. The American College of Cardiology meeting and why we are in trouble

researchEarly this month, the American College of Cardiology meeting was held in New Orleans.  I am here to tell you that nothing new was presented.  As discussed in my blog posts, one of the things that has been shipped overseas is research, so most studies are now presented at the European Society of Cardiology meeting.  One advantage is that they are in more interesting cities.  London, Paris, Barcelona.  This year it’s in Paris at the end of August.

At one point, the ACC meeting was the high point of the year.  It was at the ACC in 1976 that Dr. Gruentzig presented his first poster about the feasibility of coronary angioplasty (no one cared), and the next year, electrified the audience with the first human case.  I have been present in many standing room only auditoriums where doctors banged on the door to be let in.  We are impatient.

This year nothing, nada, zilch.  We got to hear about TAVI again, and I do say again.  The Germans have been doing it for five years now.  All you have to do is go to Canada, and there is no hassle; first come first served.  What are we waiting for?

Oh, I forgot.  NAGOYA was presented.  Never heard of it?  Amlodipine and Valsartan were compared in hypertension patients with glucose intolerance.  You can’t beat that for excitement.  The study EXCELLENT was presented.  The Xience stent, is the one 98% of patients now get.  It was compared to the Cypher stent, the one that 98% of the people used to get.  Someone should have told them that Cordis dropped the stent and the division.

RIVAL was presented in an attempt to again change the habits of Interventional Cardiologists and make them use the radial artery in the arm instead of the femoral artery in the leg.  I guess they don’t care that a large percentage of the arm cases end up closing the artery.  (Don’t worry you have another.)

If we don’t snap out of it no one will want to go to these meetings.  That would be a shame.  Where else can you see practically everyone wearing the same Blue Blazer and Khaki pants?  Yes, we are spiffy dressers.  The Italian doc’s look pretty sharp though.

We are in a rut in this country, and I don’t see much of a way out.  I’m going to San Francisco next month to the Heart Rhythm Society meeting, and I figure if the meeting is not enlightening at least the food is good.  I will blog from there about new devices that we have yet to see and new concepts in treatment.

If I can work it in, I’m going to Paris in August…