Long-term outcome of patients with chronic thromboembolic pulmonary hypertension

A rare complication of acute pulmonary embolism is chronic thromboembolic pulmonary hypertension which is characterized by fibrothrombotic obstructions of large pulmonary arteries in conjunction with small-vessel arteriopathy. The usual treatment for this is a surgery, pulmonary endarterectomy, but in patients who cannot be operated on, they can be treated with medicine. This study compares the effects and outcomes between two groups, one including pateints who receive an operation for their chronic thromboembolic pulmonary hypertension while the other group was only treated medicinally. This is the first study to take a prospective, large-scale, international registry of newly diagnosed patients with CTEPH and include patients who are operated on and those who are not. The most significant thing about it is how that it was long-term.

It turned out that sixty percent of patients were operated on and forty percent were not operated on either by their own decision or for medical reasons. In total, 143 patients died, 51 of which were operated on and 92 that were not operated on. The significant find was the fact that patients that were operated on had a significantly better long-term survival than not-operated patients. Patients were eight years younger, had higher six minutes walking distance and higher cardiac index for those who were operated on. Survival for not-operated patients at 3 years was on seventy percent compared to eighty-nine percent for those who were operated on. One of the biggest determinants of survival was actually the presence of comorbidities such as cancer, coronary disease, left heart failure, and chronic obstructive pulmonary disease. It is important to note that medically treated patients were sicker than the other patients. Another significant note is that patients were treated off-label with endothelin receptor antagonist or phosphodiesterase-5 inhibitor. The long-term effects of the recently improved drug needs to be further evaluated to see if this could lead to more problems down the road.

While reading this it made me realize that it is very difficult to tell what a medication will do to people over a very long period of time, and it is hard to find this out before many people are already taking it. I wonder what other medications could potentially lead to major problems for patients down the road that we do not know about yet.

Delcroix M, Lang I, Pepke-Zaba J, et al. Long-term outcome of patients with chronic thromboembolic pulmonary hypertension. Circulation. 2016;133:859-71.

Preoperative Narcotic Use in Patients with Crohn’s Disease

Crohn’s disease is an immune disorder that often causes people to experience chronic abdominal pain. To treat this chronic pain, many patients are given narcotics, which can cause immunosuppression, depression, anxiety, decreased quality of life, and increased disease activity in patients with Crohn’s disease. Another common feature of Crohn’s disease is that it comes with a high probability of needing surgery at some point in a patient’s life. Because there has not been much research done on the topic, this study examined the effects of preoperative narcotic use in patients who had an abdominal surgery for Crohn’s disease.

There were 1331 patients who received abdominal surgeries for Crohn’s disease between 1998 and 2014 in this retrospective study. Preoperative narcotic use, defined as electronic documentation of use of narcotics within the month before surgery, was identified in 267 of the patients. The end points studied were overall morbidity, length of stay in the hospital, and hospital readmission within 30 days of discharge.

The results showed that patients who had preoperative narcotic use had an average length of stay in the hospital of 11.2 days while those who did not use narcotics before the surgery had an average length of stay of 7.7 days. The results also showed that preoperative narcotic use was associated with an increased risk 30 day hospital readmission. A multivariable analysis was performed to show that preoperative narcotic use was an independent factor in both of these outcomes. Additionally, the risk of hospital readmission and longer length of stay was even higher when the use of preoperative narcotics was done in an outpatient setting rather than an inpatient setting.

The study concluded that preoperative narcotic use is associated with a longer length of stay in the hospital and a higher hospital readmission rate following abdominal surgeries for Crohn’s disease. It also added that, due to these findings, other options, like surgery, should be considered before narcotics for patients with Crohn’s disease. The fact that the use of narcotics as an outpatient was associated with a higher risk of adverse outcomes makes these findings more relevant to community pharmacists. The pharmacist has the potential to be an additional checkpoint for patients with Crohn’s disease who are starting to use narcotics. Knowing that preoperative narcotic use is associated with adverse postoperative outcomes could give pharmacists the opportunity to intervene and help investigate other treatment options before patients begin to use and rely on narcotics.


JAMA Surg. doi: 10.1001/jamasurg.2015.5558 (published February 24, 2016).

Concentration Accuracy of Mitomycin C for Ophthalmic Surgery

Patients with glaucoma may undergo trabeculectomy surgery. This surgery is an operation that reduces pressure in the eye through a small hole in the sclera which allows the aqueous humor to drain out slowly. After this procedure, there is a potential risk of scarring. To prevent scarring, surgeons will use mitomycin C (MMC) during the procedure. At the right concentration, this medication can have a very beneficial effect on healing after surgery. The concentration of MMC used for each patient is different and dependent on the age of the patient, ethnicity/race, and if they have had past operations or conditions of concern. The normal concentration range of the drug is 0.20 – 0.40 mg/mL.

This particular study wanted to show the accuracy in the concentrations being compounded. Is the concentration they are expecting to compound accurate with the actual concentration of the final product? There were 60 samples taken from a few different pharmacy settings: academic/community hospitals and an independent pharmacy compounding accreditation board. These settings were to use normal procedure when compounding and storing MMC at a 0.4 mg/mL dose. Typically, MMC is refrigerated, frozen, or made as a dry powder for compounding. To test the samples, high accuracy (92-100%) C18 reversed-phase high-performance liquid chromatography and a calibration curve were used. The samples concentrations were surprising. The average measured concentration for the samples was 0.35 mg/mL; this is 12.5% lower than the expected concentration of 0.4 mg/mL. Among the 60 samples, the range of concentrations was 0.26 – 0.46 mg/mL. A range this large with an average concentration of 12.5% less than anticipated concentration could be caused by a number of reasons such as compounding techniques or degradation of the drug. The study concluded that this is one of the reasons glaucoma surgeries could be inconsistent. Attempting to predict the scarring risk of a patient is almost worthless if the compounded product is not accurate.

It is scary to think that many invasive procedures can be so inconsistent. It’s one thing to have inconsistency based on a patient’s genetics or personal ability to handle a drug or surgery, but another to be dispensing the incorrect concentration of a medication. Patients put their health on the line by trusting healthcare professionals to be accurate and precise. One small mistake or inconsistency could greatly affect a patient. For example, a compounding pharmacy may be mixing a suspension and add the wrong amount of water. This could severely affect a patient’s health and there are not many checks and balances set in place to catch these small mistakes. How do you think errors in compounding should be handled or minimized?

Kinast R, Akula K, Mansberger S, et al. Concentration Accuracy of Compounded Mitomycin C for Ophthalmic Surgery. JAMA Ophthalmol. 2016;134(2):191-195.


Selective COX-2 inhibitors significantly reduce the occurrence of heterotopic ossification after hip arthroscopic surgery

A well known complication after hip arthroscopic surgery is heterotopic ossification (HO), the presence of bone in soft tissue. This complication can be as prevalent as 44% of patients when no prophylactic intervention is given. Although it is not totally understood how HO occurs, it is known that mesenchymal cells provide the origin for this, and they are activated by inflammatory mediated response in injured tissues. Low-dose irradiation and nonsteroidal anti-inflammatory drugs are the two most commonly used interventions for this problem of reducing and preventing HO. This study hypothesized that postoperative HO prophylaxis using 600 mg of etodolac once daily for two weeks would significantly reduce risk of HO in patients after surgery in comparison with a groups of patients who were treated by the same surgeon who did not receive NSAID prophylaxis. Their ultimate goal of the study was to evaluate the effectiveness of short-term selective COX-2 inhibitors (specific NSAID) when they are being used prophylactically for HO.

In this retrospective analysis of data gathered from a cohort of patients who underwent surgery by the same surgeon for the same reason, femoroacetabular impingement.  Although the study started out with 263 patients patients, 163 were included in the final analysis because 100 of them had to be excluded for various reasons including lost to follow-up, previous hip surgery or HO, and not meeting inclusion criteria. 100 patients were assigned to the control group and 63 were included in the group that received COX-2 inhibitor prophylaxis. In the control group, 35 of 100 patients developed HO. The patients were tested for HO 2 weeks, 6 months, and 1 year after surgery. The data did exhibit a significant difference between the control and study groups, as there were no patients in the study group who developed HO. This is the first study to ever look at a dose this low, half of the maximum, in attempting to prevent HO with this specific medication. It is significant that this research is able to show a short-term, selective NSAID can be used to effectively prevent HO in this patient population because it gives the patients much less of a risk of developing the GI side effects that are so closely associated with traditional NSAIDs.

It is interesting how choosing between medications in the same class can often be very significant when treating a patient and trying to keep them as healthy and happy as possible. In what other classes of drugs can this be significant?
Rath E, Warschawski Y, Maman E, et al. Selective COX-2 inhibitors significantly reduce the occurrence of heterotopic ossification after hip arthroscopic surgery. Sports Med. 2016;44:677-81.