Serum Vitamin D levels at admission predict the length of intensive care unit stay but not in-hospital mortality of critically ill surgical patients

Effects and benefits of vitamin D have been heavily studied, yet it seems as though we are only beginning to grasp just how influential vitamin D levels may be in certain medical situations.  A recent study sought to analyze the effects of vitamin D on length of stay in intensive care units, as well as in-hospital mortality, in patients who have recently had surgery.

The study was a prospective, cross-sectional, descriptive study that looked at 70 ICU patients over the course of a year at the Imam Khomeini Hospital in Iran. Basic demographic and health information was collected from the patients, as well as blood samples to determine serum levels. Of the 70 patients, 52 (74.3%) of them had serum vitamin D levels lower than 30 ng/mg. These patients had longer stays than patients with vitamin D levels greater than or equal to 30 ng/mL by roughly 3-4 days, and this was a statistically significant difference. The occurrence of hospital mortality, although higher in vitamin D deficient patients (25% vs. 22.2%), was not significantly different.

As hospital stays, especially in the ICU, require enormous amounts of money and resources, reducing the duration of stay would ease a great financial burden of the hospital, while also allowing patients to recover more quickly. I was very surprised by the findings of this study. We had recently learned about vitamin D and its transformation in the body, so I was surprised to find just how big of an impact it could have on length of hospital stays. I was aware that it was important for many things such as bone health and protecting the body from disease, but I would not have thought it could have such a significant impact on something like length of ICU hospital stays. I think that in the next few years we will continue to uncover many interesting effects and benefits of vitamin D, and we will hopefully be better educated as health professionals in suggesting vitamin D supplementation.

 

Alizadeh N, Khalili H, Mohammadi M, Abdullahi A. Serum Vitamin D levels at admission predict the length of intensive care unit stay but not in-hospital mortality of critically ill surgical patients. J Res Pharm Pract. 2015;4: 193–198.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4645131/

Evolving Therapeutic Strategies to Improve Nonsteroidal Anti-inflammatory Drug Safety

The question of how to treat chronic pain is one that seems to be drawing more and more attention. As people are living longer, more will eventually come to face chronic pain caused by osteoarthritis, diabetes neuropathy, or other chronic conditions. Additionally, increasing misuse of opioid pain medications and the dangerous side effects associated with medications like NSAIDs has pressed for development of alternative forms of pain management. This retrospective analysis of 2177 patient charts looked at the comparative effectiveness of three topical options for chronic pain management: two compounded creams and one NSAID based gel.

Cream I creams contained 20% Flurbiprofen, 5% Tramadol, 0.2% Clonidine, 4% Cyclobenzaprine, and 3% Bupivacaine. Cream II contained 20% Flurbiprofen, 2% Baclofen, 0.2% Clonidine, 10% Gabapentin, and 5% Lidocaine. The NSAID based gel, Voltaren, contains 1% diclofenac sodium. 1141 patients were given Cream I, 527 received Cream II, and 509 patients received Voltaren gel.  Voltaren gel caused a decrease in pain intensity score of 19%, which is statistically significant to be less than the pain intensity decrease caused by both Cream I (37% ) and Cream II (35%). It is hypothesized in the journal article that this increase in efficacy of the two compounded creams stems from the inclusion of multiple active ingredients with different mechanisms of action.

Use of a cream for chronic pain treatment is beneficial in many areas. It can be topically administered at the site of the pain and will have lower systemic bioavailability.  This will lead to less of the dose-limiting adverse effects commonly seen with oral medications such as NSAIDs and opioids. Do you think topical pain medication should always be an option for patients with chronic pain? Can you think of an example of when it may not be as effective as an oral medication?

 

Somberg JC, Molnar J. Retrospective Evaluation on the Analgesic Activities of 2 Compounded Topical Creams and Voltaren Gel in Chronic Noncancer Pain. Am J Ther. 2015;22:342-349.

http://ovidsp.tx.ovid.com/sp-3.18.0b/ovidweb.cgi?&S=BLBGFPDBADDDKCBDNCJKKDDCAJPEAA00&Link+Set=S.sh.13512_1456860318_56.13512_1456860318_68.13512_1456860318_76.13512_1456860318_78.13512_1456860318_82.13512_1456860318_106%7c3%7csl_10

Macrolide antibiotics and the risk of ventricular arrhythmia in older adults

Macrolides are a kind of antibiotic often prescribed to combat respiratory tract infections.  In the past the FDA has included a warning with these medications suggesting increased risk of arrhythmia development, especially in older adults.  This warning was based on a previous observational study.  This journal article includes a study that contradicts previous results and could lead to a change in warnings listed on the medication label.

This study, a population-based retrospective cohort study, looked at records of adults over 65 who had been prescribed a macrolide to determine incidence of hospitalization within the following 30 days for a ventricular arrhythmia.  They also looked for any mortality within those 30 days as a secondary parameter.  Patients taking macrolides were compared on a 1:1 ratio with patients taking nonmacrolide medications.  The results were analyzed and particular attention was payed to four subgroups including patients with CKD, CHF, CAD, and concurrent use of a QT prolonging drug.

After comparing charts of 260 patients, the study determined that readmission for ventricular arrhythmia was not statistically different between macrolides and nonmacrolides, and use of macrolides was actually associated with lower rates of mortality within the 30-day period.

These results demonstrate that the previous observational study and associated warnings may not be the best information to guide prescribing of antibiotics.  As this study showed, macrolides may actually be safer in general.  This demonstrates why new research looking at old questions is essential to understanding medications.  We would miss out on a lot of medical opportunities if we remained certain of preliminary drug studies.  Do you agree that it is important to re-examine potential adverse effects and efficacy of medications?

 

Trac MH, McArthur E, Jandoc R, et al. Macrolide antibiotics and the risk of ventricular arrhythmia in older adults. Can Med Assoc Jdoi:10.1503/cmaj.150901 (published 22 February 2016).

http://www.cmaj.ca/content/early/2016/02/22/cmaj.150901

Does celecoxib improve the efficacy of chemotherapy for advanced non-small cell lung cancer?

Lung cancer is the most common culprit of cancer-related death globally. Currently, treatment for this type of cancer can only help patients so much.  The American Cancer Society estimates that 158,080 patients will die from lung cancer in 2016.  Thus, looking for new forms of treatment is a crucial focus of current research.  This study, knowing of a newfound relationship between cancer and inflammation, decided to look into the efficacy of celecoxib, as COX-2 inhibitor, as an add-on therapy to current chemotherapeutics.  This study was a meta-analysis of previous clinical trials that were on their own somewhat inconsistent.

The researchers performed a literature search and analyzed data from all published randomized controlled trials that had studied celecoxib as adjunct treatment to chemotherapy in patients with non-small cell lung carcinoma.  Eventually they narrowed the group of 206 such studies down to six trials that met their criteria for closer review.  The investigational treatment was celecoxib plus chemotherapy, and chemotherapy alone served as the control.  They looked at toxicity and efficacy, and determined that improved efficacy of the group with added-on celecoxib therapy was statistically significant.  Although they found an increased overall response rate with celecoxib, they could not determine how it affected overall survival due to lack of data.  They call for further randomized clinical trials to better determine the best treatment course.

I think that completion of meta-analyses such as this one are important because it sums up what different researchers have found recently in regards to one specific problem, and can then use that condensed information to direct future research on the topic.  For example, researchers trying to determine whether it is worth it to study celecoxib and chemotherapy treatment further can look to this review article and see that it is an area that has potential as a solution, as well as room for new data.  What are your thoughts on how meta-analyses play into future research studies?

 

Hou LCHuang F, Xu HB.  Does celecoxib improve the efficacy of chemotherapy for advanced non-small cell lung cancer?.  Br J Clin Pharmacy. 2016;81:2332.

http://onlinelibrary.wiley.com/doi/10.1111/bcp.12757/full

Emergency Procedural Sedation With Propofol in Older Teenagers: Any Cause for Concern?

Often in emergency departments there is a need for fast, short-term sedation so that necessary procedures can be performed.  A common sedative used for this purpose is propofol, which is delivered intravenously and can be adjusted to varying doses to provide the appropriate level of sedation.  Use of propofol in youth has been uncommon; emergency departments typically utilize ketamine in these cases.  This study sought to find out whether propofol would be appropriate for use in 16-19 year olds because ketamine becomes less favorable as patients grow older.

The study looked at 4,063 emergency department procedural sedations, including 230 teenagers, 2,835 adults, and 980 senior citizens.  The study concluded that the teenage group was in fact less likely to experience hypotension as a side effect when compared to the other age groups, and all groups had a similar satisfaction with treatment.  The study also confirmed, “there were no recorded episodes of arrhythmias or of apnea lasting longer than 30 seconds.”

These results demonstrate that propofol is safe and effective in patients ages 16-19; however, the journal article notes that “drugs and therapeutics committees frequently restrict access to propofol to the operating room in pediatric facilities.”  The results from this study could have a large impact in patient care and emergency department regulations and procedures.  It opens the possibility of a very favorable sedation mechanism for use in a new age range of patients.  It will be interesting to see how the restrictions of pediatric emergency departments change in response to this new data.

 

Campbell SG, MacPhee S, Butler, M, et al.  Emergency Procedural Sedation With Propofol in Older Teenagers: Any Cause for Concern?  Pediatr Emerg Care.  2015;31:762-765.

http://ovidsp.tx.ovid.com/sp-3.18.0b/ovidweb.cgi?&S=OCGOFPNKJBDDEEIINCJKLGFBMPILAA00&Link+Set=S.sh.21833_1455116825_21.21833_1455116825_33.21833_1455116825_41.21833_1455116825_43.21833_1455116825_47.21833_1455116825_51%7c6%7csl_10

Perimenopause and Menopause Are Associated With High Frequency Headache in Women With Migraine

Migraine headaches can seriously affect a person’s day-to-day life.  A recent study looked at the incidence of these headaches at different times in a woman’s life to determine at which points risk for frequent headaches (defined as at least 10 headache days per month) would be highest.  The research study was a cross-sectional observational study, relying on data from a 2006 American Migraine, Prevalence and Prevention study survey. It looked at women between the ages of 35-65, and looked at incidence of frequent headaches in premenopause (normal loss of ovary function before 40), perimenopause (years immediately prior to menopause), and postmenopuse.

After adjusting for other factors, the study concluded, “risk for high frequency headache is increased by 1.4-fold during the perimenopause as compared to the pre menopause.”  The study also found that, contrary to previous epidemiological studies, incidence of high frequency headaches were higher in menopause.  Previous studies seem to have indicated that headache frequency would decrease postmenopause.  The authors are not entirely sure why their results do not match this common assumption, but they suspect it may be due to a different focus: they focused on high frequency headaches rather than migraine prevalence.

Personally, as someone with a mother who suffers from severe and debilitating migraines, this data is important because it may influence how physicians expect to treat their patients.  With the expectation that their patients who have suffered from headaches and migraines in the past may experience more frequent headaches through there perimenopausal, physicians will be prepared to provide preventative treatment for their patients.  Do you think this expectation would benefit patients, or would you worry that physicians might overcompensate and prescribe unneeded medication?

Martin VT, Pavlovic J, Fanning KM, et al. Perimenopause and Menopause Are Associated With High Frequency Headache in Women With Migraine: Results of the American Migraine Prevalence and Prevention Study. Headache: The Journal of Head and Face Pain. doi: 10.1111/head.12763. (published 21 January 2016).

http://onlinelibrary.wiley.com/doi/10.1111/head.12763/full

Effect of Opioids vs NSAIDs and Larger vs Smaller Chest Tube Size on Pain Control and Pleurodesis Efficacy Among Patients With Malignant Pleural Effusion

Pleural effusion is a condition in which fluid collects between tissues lining the lung and chest.  This condition can be painful and may lead to infection.  It can often be treated with antibiotics or diuretics, but sometimes it is necessary to physically deplete the space between the tissue via a surgical procedure known as pleurodesis.  This randomized clinical trial compared the efficacy of pain treatment for the procedure between opioids, which are the current go-to treatment, and NSAIDs.

NSAIDs had previously been avoided for this type of procedure due to fear that they might decreases the efficacy of pleurodesis; however, this study found that not only did the NSAIDs result in similar pain scores, but they also resulted in noninferior pleurodesis efficacy.  These results demonstrate that NSAIDs are essentially equivalent to opioids in effective pain management following pleurodesis, while also not negatively affecting the efficacy of pleurodesis itself.

These results offer an interesting and favorable pain management option. The growing incidence rates of opioid abuse and opioid-related death have led health professionals to look for other viable pain management options when possible.  Recently, an emergency department in New York successfully attempted to run a whole shift without giving opioids to patients (http://www.ashpintersections.org/2016/02/pharm-d-m-d-team-successfully-enacts-opioid-free-ed-shift/).

Personally, I am excited to see the results of this clinical trial.  I believe we will need to begin looking for other viable methods of pain management following surgery or injury to combat the growing opioid epidemic in the US.  Hospitals can begin to use this kind of data to try prescribing alternative medications such as NSAIDs when safe.  Although NSAIDs come with their own set of problems and are especially unsafe in older patients, there are many cases in which it could be a superior option to opioids.

Do you think it is feasible to significantly reduce prescription and usage of opioids for pain management, or do you believe will it be near impossible to make this transition in the near future?

Rahman NM, Pepperell J, Rehal S, et al. Effect of Opioids vs NSAIDs and Larger vs Smaller Chest Tube Size on Pain Control and Pleurodesis Efficacy Among Patients With Malignant Pleural Effusion: The TIME1 Randomized Clinical Trial. JAMA. 2015;314:2641-2653.

http://jama.jamanetwork.com/article.aspx?articleid=2478201

Host gene expression classifiers diagnose acute respiratory illness etiology

Antibiotic resistance is becoming an increasingly hot topic in the news.  The drugs we have been using in the last few decades are starting to face some serious problems with the development of various antibiotic-resistant super bugs.  A great deal of research has been conducted lately regarding ways we can curb this trend to ensure the medications we have will be able to work long into the future.

One cause of growing antibiotic resistant is the mis-diagnosis and subsequent mis-treatment of common respiratory infections.  Often when a patient visits the doctor with this kind of illness, the doctor will prescribe antibiotics without determining if the infection is actually bacterial based or viral based.  A recent article looked at a possible test that could distinguish between the two types of infections, therefore leading to more accurate treatment and curbing inappropriate use of antibiotics.

The researchers analyzed host RNA looking for identifiers that would indicate whether the host, or patient, was responding to a bacterial or viral infection.  It analyzed data on what genes are expressed or over-expressed during each kind of infection to set classifications by which they would be able to analyze the subject’s genetics.

Using these new classifications the prediction of infection type overall in subjects was 87% accurate.

I feel like this could be an extremely impactful test if it becomes implemented in the community setting.  I know so many friends who simply expect antibiotics from their physician when they have a cough.  This puts pressure on the physician to prescribe even if they are not sure of the diagnosis.  With this test it would aid physicians in making a firm diagnosis that they could explain to the patients, curbing inappropriate antibiotic use for viral respiratory infections.

Overall, it seems like this would be a worthwhile test to implement. What problems could arise with the implementation of such a test in a physician’s office?

Tsalik EL, Henao R, Nichols M, et al. Host gene expression classifiers diagnose acute respiratory illness etiology. Sci Transl Med. 2016;8:1-11.

http://stm.sciencemag.org/content/8/322/322ra11