New Cancer Drug Vermurfenib Treats BRAF V600 Mutation in Both Melanoma and Nonmelanoma

The BRAF V600 mutation occurs in almost 50% of melanomas and results in activation of a MAPK pathway. Vemurafenib, a new cancer, is an inhibitor of the BRAF V600 kinase and is associated with a 50% response rate and improved survival in patients with the BRAF V600 mutation who also have metastatic melanoma. The efficacy of vermurafenib in nonmelanoma cancers has not been heavily studied. Thus to treat nonmelanoma cancer patients with the BRAF V600 gene, Hyman and his colleagues designed a study to test the efficacy of vermurafenib in other various types of cancer.

 

The study included patients with the following nonmelanoma cancers: non-small-cell lung cancer, ovarian cancer, colorectal cancer, cholangiocarcinoma, and breast cancer. The primary outcomes was to measure the response rate of the drug, progression of the tumor, and overall survival rate. In the group with the non-small-cell lung cancer, the response rate was 42% and the survival rate extended 7.3 months. There were positive responses in the drug treating the other variations of cancer, but this was the most significant one. Therefore the BRAF V600 gene is a good target gene for some nonmelanoma cancers, especially non-small-cell lung cancer. In addition, vemurafenib is a drug that can treat both melanoma and nonmelanoma cancer.

 

It is always encouraging when a new cancer drug is developed and proven to be effective. What is so remarkable about this drug is that although it treats a very specific gene mutation, it treats a significant amount of different outcomes from this mutation. Non-small cell lung cancer is a type of lung cancer that causes death in 50% of its patients so finding a drug that can prolong life and decrease tumor growth is a great accomplishment.

 

Hyman D, Puzannov I, Subbiah V, et al. Vermurfenib in multiple nonmelanoma cancers with BRAFV600 Mutations. N Engl J Med. 2015; 373:726-736.

 

 

Different Levels of Oxygen Saturation in Premature Infants

It has been a long-standing debate on how to treat premature infants with oxygen. Most neonatal intensive care units either treat these babies with either 85 to 89% oxygen saturation or 91 to 95% oxygen saturation. While both of these ranges show therapeutic effect, a research trial conducted in Australia and the United Kingdom compared the two different saturations to see which one was safer and more effective for infants born before 28 weeks gestation.

 

In the trial the infants were randomly assigned to either the lower range group (85-89%) oxygen saturation or the higher range group (91 to 95%) oxygen saturation. The researchers were studying death or disability at the age of 2 years old to see which infants had less negative outcomes. The results showed that death or disability occurred in 247 of 549 infants (45%) in the group that received the lower saturated oxygen. In addition, 217 of 545 infants (39.8%) in the higher saturation group either died or were diagnosed with disability at 2 years old. Thus those premature infants that received the more saturated oxygen had more positive outcomes as they aged.

 

It will be interesting to see if the results of this study are put in to everyday practice in the NICU. The results seem to really favor a higher amount of oxygen saturation. If these results of this new study are implemented into everyday practice, hundreds of infants lives could be saved each year.

The BOOST-II Australia and United Kingdom Collaborative Groups. Outcomes of two trials of oxygen-saturation target in preterm infants. N Engl J Med 2016; 374:749-760.

 

 

Cellular Clutter May Cause Aging and Death

As we discussed in Dr. Johnson’s biochemistry lecture, cellular senescence is when cells go into a state of growth arrest due to stress. This cellular senescence stops damaged cells from going and was seen as a beneficial cell function. It is believed that some cancers develop when senescence stops or cells that were once in a period of senescence are able to grow again. However, new research is showing that cells entering senescence may have something to do with causing death and aging. Senescence is expressed in cells when a specific gene p16lnk4a is expressed. When this gene is expressed and certain cells enter into a state of senescence, they begin to build up in organ and various tissues; it is this build up in unwanted places that is believed to cause aging and death.

 

Researchers explored the consequences of senescent cells building up by examining mice. The researchers gave the mice a gene that caused all cells that expressed the p16lnk4a gene and were senescent to enter apoptosis and die. They began treating the mice in this manner when the mice reached one year old. After years of observing the mice, they discovered that by removing these senescent cells tumorigenesis was delayed and the weakening organs that is associated with age was slowed as well. In fact, the kidney and heart were some senescent cells make their home aged at a much slower rate when compared to normal mice that did not receive this treatment. If senescent cells in humans build up and cause aging like they do in mice, there might be some therapeutic use in removing these cells to improve and elongate lifespan.

 

I believe that if humans also respond to this treatment the same way that mice do, we may be able to slow the process of aging. However, with most drugs I believe that there will be significant side effects in deleting these senescent cells, especially in humans who have a more complex genome. I will be interesting to see if this research is continued and if these methods are ever performed on humans.

 

Baker DJ, Bennet CG, Durik M, et al. Naturally occurring p16lnk4a- positive cells shorten healthy lifespan. Nature International Weekly Journal of Science. 2016;530:184-189.

 

 

Actually Beneficial to Treat Hepatitis C Positive Prisoners

Ever since the extremely expensive Hepatitis C medications like Harvoni ® hit the market, there has been an ongoing struggle with what types of patients should receive this medication due to its cost. These medications cost about $90,000 per patient, but have a great success rate and completely cure about 90% of people from Hepatitis C. And this has raised multiple questions like: should private insurances cover the cost? Should Medicare and Medicaid pay for this medication? If people want this medication should they have to pay out of pocket? But one of the most highly debated questions is whether we should cure inmates of their Hepatitis C medication despite the fact that they have broken the law? However, a new study shows that treating these prisoners is a good investment in the long run.

 

Statistics state that about 15% of people in U.S. prisons have Hepatitis C. The reason that so many people are pushing for inmates to receive this treatment is because once these people are released back into the general public, they often highly contribute to the spread of this disease and continue to infect the general population. A study published in the Annals of Internal Medicine, conducted a research and mathematical study to assess the number of people that would be effected by Hepatitis C in the future with and without the new treatment interventions. They analyzed numbers based on current statistics and concluded that in the next 30 years, 41,900 to 122,700 prisoners could develop Hepatitis C. However, if these prisoners are properly screened and treated with the new medications on the market, 5,500 to 12,700 cases of Hepatitis C could be prevented. Furthermore, about 90% of these prevented infections include non-inmates who were infected by an inmate after her/she left prison. Additionally, screening and treatment could prevent 4,200 to 11,700 liver-related deaths outside of prisons. In conclusion, the study shows that despite the expensive of these new drugs, the benefits clearly out weight the cost and thousands of lives could be saved.

 

I was excited to read a controversial topic like this. Not only is the topic of the cost of the Hepatitis C medication controversial, but the topic of helping inmates who have committed federal crimes also a hot topic. When I first opened the article, I was totally against giving prisoners expensive drugs like this, especially when the means to pay for this medication was likely going to come from my tax dollars. However, the research really supports and shows the benefits to this methodology. Once again, by paying a little extra up front we can cut health care costs down the line and attempt to cure the U.S. of Hepatitis C all together.

 

He T, Li K, Roberts MS, Spaulding AC, et al. Prevention of Hepatitis C by Screening and Treatment in U.S. Prisons. Ann Intern Med. 2016;164:84-92.

 

 

Winter Months Call for Extra Vitamin D in Minority Youth

People, especially teenagers who have dark colored skin and who live in the Northern areas of the world, often lack normal levels of Vitamin D in their blood during the long winter months. This lack of Vitamin D is due to the fact that their skin’s pigmentation reduces their natural production of Vitamin D. Recent research has shown that changes in diet are still not getting these children enough vitamin D. So turning to prescription strength vitamin D is the most efficient way to get their levels up.

 

An 8 week study was conducted in 183 vitamin D deficient teenagers. These teenagers were given 3 different doses, one being prescription strength and the others being OTC strength. The results show that more than 80% of the patients that were taking the Rx strength dose were no longer Vitamin D deficient after the 8 week period. Furthermore, 60% of the patients on the OTC doses were still vitamin D deficient. This leads the researchers to believe that Vitamin D deficiency is a serious condition and something that requires prescription strength medication. The study also showed that both African American’s and Hispanics respond to this treatment in a similar manner. And that the heavier the patient is the more frequent dose they will need.

 

I found this article to be very interesting. I like the fact that the study was large and studied different minorities, it gave the study some depth. In addition, I think it is important to consider prescription strength vitamins like this. People are all too often looking for quick fixes for their ailments and immediately turn to prescription strength medications that are not naturally found in the body. I believe that prescribers should consider natural substances like this when treating patients as there are often fewer side effects associated.

 

Tabil HT, Ponnapakkam T, Gensure R, et al. Treatment of Vitamin D Deficiency in Predominantly Hispanic and Black Adolescents: A Randomized Clinical Trial. The Journal of Pediatrics. 2015.  

 

 

Atropine and Nearsightedness

Unfortunately, nearsightedness is extremely common in today’s youth. In fact, more than 80% of children in China are diagnosed with nearsightedness. And the nearsightedness only worsens as we age. A study in Asia has recently shown that an extremely common medication, when used as an eye drop, is an effective treatment for this disease state.

 

Atropine is the drug of choice in question. Although atropine is known for its strange side effects on the eye, like blurred vision and dilation researchers and drug developers are looking to create the correct dose so that these side effects are not experienced and the nearsightedness is cured. Tan and his colleagues, tested multiple atropine doses on nearly 400 children over a two year period. Those who began experiencing negative side effects had their dose lowered effectively. It was found that the most effective dose was 0.1% atropine. In this dose, more than 50% of the patients slowed the development of their nearsightedness. This dose gave the majority of the children no side effects either!

 

I think it is really interesting that a well-known ancient medication like atropine is being used and further developed to cure diseases today. I think that it was genius of these researchers to turn to medications of the past. In addition, I thought that it was interesting that they used multiple doses in their clinical trials with the patients. This seems much more effective and less costly than just testing one dose and I hope that this tool is utilized when developing new drugs.

 

 

Saw SM, Shih-Yen EC, Koh A, Tan D. Interventions to retard myopia progression in children: an evidence-based update. PubMed. 2002; 109(3) 415-21.

 

Tylenol is Not As Effective as It Seems When Treating the Flu

In the midst of Flu season people are always looking for a quick remedy to cure their symptoms and stop the flu as quickly as possible. One of the most common flu symptoms is a fever and often to combat the fever people are told to take antipyretics like acetaminophen or Tylenol. A research group in New Zeland studied the effectiveness of antipyretics like paracetamol on treating the flu. They chose this study because creating a fever is a natural and physiological adaptation that happens in the body that is actually a survival benefit. In addition, they chose to do this study because many antipyretics are actually harmful to animals and increase their chances of infection and even mortality.

 

The study conducted was both double blind and randomized and the participants were between the ages of 18 and 65. Half of the patients were given a placebo and the other half of the patients were given 1 gram of paracetamol four times a day. After a full week of recording the patients symptoms and examining the area under the curve of a PCR viral load it was found that there were 22 participants in the placebo group that were found to have influenza positive-PCR. In addition, 24 participants in the paracetamol group tested positive for PCR influenza. Based on these results, the research study concluded that antipyretics like paracetamol were not effective in treating the flu/flu-like symptoms. Thus the researchers recommended other treatments as no real benefit was seen.

 

I feel as if studies like this are extremely helpful for all health care professionals to know about. Whether you are a pharmacist, a nurse, a doctor, or just a patient, the flu is so common that it is important that we know how to treat it. I truly believe that many people think treating the flu with medications like this is helpful. Therefore, assignments like this blog show how important it is to keep up on new research and literature so that we can give our patients the best care possible.

 

Jefferies, S., Braithwaite, I., Walker, S., Weatherall, M., Jennings, L., Luck, M., Barrett, K., Siebers, R., Blackmore, T., Beasley, R., Perrin, K. and Pi Study Group (2016), Randomized controlled trial of the effect of regular paracetamol on influenza infection. Respirology, 21: 370–377.

 

 

 

 

Antibiotic Effectiveness in Treating Pediatric Appendicitis

When most people think of Appendicitis, they think of a surgical procedure to remove the appendix, one that includes both pre and postoperative pain. In fact, this procedure is fairly common considering 11.4% of child hospitalizations are due to acute uncomplicated appendicitis. This disease is defined as a form of appendicitis in which the appendix has not yet rupture and there are not yet impacted feces, but there is a relatively low white blood cell count and there is still abdominal pain associated with it. Previous to this study, the only way to treat this form of appendicitis was to remove the appendix in an invasive surgery. This surgery is associated with children missing 2 to 3 weeks of school and activities after, complications occurring in 5 to 10% of procedures, and serious complications occurring in 1 to 7% of patients.

 

A recent study suggested treating these pediatric patients with antibiotics instead of choosing the surgery option. The study took place over a six-month period in which 102 patients between the age of 7 and 17 were enrolled. This unique study allowed the patients and their families to choose which form of treatment they were to receive, either the antibiotic treatment or the operative treatment. 37 of these patients chose to take short-term antibiotics in order to avoid some of the complications associated with the surgery. This antibiotic treatment includes receiving an intravenous antibiotic for approximately 24 hours or until symptoms have improved. Following this inpatient treatment, the patient is then given a 10-day oral antibiotic treatment that they can receive at home while they continue on with their day-to-day lives. After just 30 days of treatment 89.2% patients had success and were cured. The nonoperative group also showed a lower incidence of the appendicitis turning complicated. 2.7% of the nonoperative group developed complicated appendicitis while 12.3% of patients in the operative group developed complicated appendicitis. Furthermore, after 1 year the antibiotic group was associated with lower health care costs and experienced fewer disability days.

 

After analyzing this article I think that it is extremely interesting and advanced that we are looking to treatment options other than operations. With the increasing cost of health care I think that it is extremely important to consider these cheaper and less invasive options. The only question I had that the article did not answer was the potential of antibiotic resistance, which I think would be something to consider in the future. I believe that if this antibiotic treatment method is further studied and the results continue to show its effectiveness that this could become the most important and best option for treating acute uncomplicated appendicitis.

 

Minneci PC, Mahida JB, Lodwick DL, et al. Effectiveness of Patient Choice in Nonoperative vs Surgical Management of Pediatric Uncomplicated Acute Appendicitis. JAMA Surg. 2015: 1-8