A Randomized Trial of Progesterone in Women with Recurrent Miscarriages

It is known that progesterone is an essential hormone for maintaining a pregnancy. Naturally, progesterone is secreted by the corpus luteum in the second half of the menstrual cycle. It is also secreted from the corpus luteum during early pregnancy. It prepares the endometrium for implantation. This study evaluated the effect of progesterone supplementation during the first trimester in women with a history of recurrent miscarriages.

Participants in the trial were recruited at 36 different hospitals across the U.K and the Netherlands. Eligible women were ages 18-39 years of age actively trying to conceive after receiving a diagnosis of unexplained recurrent miscarriage. This is defined as three or more pregnancy losses during the first trimester. A total of 1568 participants received 400 mg of progesterone twice daily or a matching placebo after testing positive for pregnancy. The primary outcome measure was birth. Overall, the trial demonstrated that vaginal progesterone supplementation did not significantly increase the rate of live births for women with a history of recurrent miscarriages. I am curious whether the outcomes would have changed if the progesterone was administered orally. Further studies should be conducted to evaluate various routes of administration.

Coomarasamy A, Williams H, Truchanowicz E, et al. A randomized trial of progesterone in women with recurrent miscarriages. N Engl J Med. 2015;373:2141-8.

Trimethoprim-Sulfamethoxazole vs Placebo for Uncomplicated Skin Abscess

Recently, U.S. emergency department visits for a methicillin-resistant MRSA have increased. Currently it is not clear what role antibiotics play for a drained abscess. The investigators conducting this randomized trial selected five emergency departments in the U.S. in order to figure out if trimethoprim-sulfamethoxazole (320 mg or 1600 mg twice daily) would be more effective than a placebo for an uncomplicated abscess. The primary outcome was curing the abscess. An assessment took place 7 to 14 days after the end of treatment. The participants in the study were outpatients older than 12 years old.

Overall, trimethoprim-sulfamethoxazole was more effective than placebo for increasing the cure rate for patients with a drained cutaneous abscess. This in turn resulted in a lower rate for surgical drainage procedures, skin infections at new sites, and infections among household members. I actually had a friend who recently had this condition and throughout the week had to get the abscess periodically drained, which was not a pleasant procedure. It is nice to see that research is progressing on this topic to prevent more people from having to go through this procedure often.

Talan DA, Mower WR, Krishnadasan A, et al. Trimethoprim-sulfamethoxazole versus placebo for uncomplicated skin abscess. N Engl J Med. 2016;374:823-32.

 

Synthesis of dihydropyrazole sulphonamide derivatives that act as anti-cancer agents through COX-2 inhibition

For years now, COX-2 inhibitors have been used to treat pain and inflammation. Recently, much research has suggested that they may potentially be able to reduce tumour processes. COX-2 can be upregulated by tumor promotors, revealing that it may be involved in pathological processes of various types of cancer. Currently, there are hundreds of clinical trials being conduced testing the anti-tumor properties of COX-2 inhibitors such as celecoxib.

The investigators in this study created new COX-2 inhibitors derived from an analysis of currently known COX-2 inhibitors. One of the dihydropyrazole sulphonamide derivatives developed, 4d, demonstrated high COX-2 selectivity and anticancer properties. Further, it was shown that 4d could stop the cell cycle at the G2/M phase. It also induced apoptosis in A549 (tumor cell-line) cells. Overall, it seems that compound 4d could potentially be utilized for cancer treatment.

Qiu H, Wang P, Zhen L, et al. Synthesis of dihydropyrazole sulphonamide derivatives that act as anti-cancer agents through COX-2 inhibition. Pharmacol Res. 2016;104:86-96.

 

Efficacy and safety of gelatine tannate for the treatment of acute gastroenteritis in children

Acute gastroenteritis causes increased mortality and morbidity in children. Currently, treatment for this illness focuses on treating and preventing dehydration, reducing severity and duration of diarrhea, and promoting weight gain following rehydration. Gelatine tannate has anti-inflammatory and astringent characteristics which gives it protective properties. It also inhibits growth of certain bacteria in the gut. In Europe recently, it has been advertised to treat gastroenteritis. However, currently there is only little evidence to demonstrate the efficacy of gelatine tannate to treat gastroenteritis in children or adults. The objective of this trial is determine the safety and efficacy of gelatine tannate for treating acute gastroenteritis in children.

This is a randomized, placebo-controlled, blind trial. A total of 158 children younger than 5 years old were recruited for the study. Children older than 3 years old will receive 500 mg per day, and children under 3 years old will receive 350 mg per day for 5 days. If not given the drug, they were given a matching placebo. The main outcome measured was duration of diarrhea. All participants were followed up for the 5 days of the intervention, as well as an additional 48 hours. This study has not been conducted yet. I am interested to see if this study finds gelatine tannate to be a potential treatment for this condition.

Michałek D, Kołodziej M, Konarska Z, Szajewska H. Efficacy and safety of gelatine tannate for the treatment of acute gastroenteritis in children: protocol of a randomised controlled trial. BMJ Open. 2016;6(2):e010530. doi:10.1136/bmjopen-2015-010530.

Mobile App Features Sought by Patients of Giant Eagle

This purpose of this study was to gain information about what features patients look for in a mobile application for pharmacy services provided by Giant Eagle pharmacies. Giant Eagle has 218 locations across western Pennsylvania, West Virginia, Ohio, Maryland and Indiana. At the time of the study, the company had a mobile app for grocery service and a pharmacy services app in development that had not yet been launched. Services provided by Giant Eagle pharmacists include providing medication therapy management (MTM), immunizations, counseling on specialty medications and diabetes self-management.

Participant interviews for the study took place at 5 different Giant Eagle pharmacies in Pittsburgh, PA. Eligible participants included patients older than 35 years old who use and own a smartphone on a daily basis. They also had to have received a prescription from the pharmacy on a monthly basis to be eligible. Participants were recruited to the study at the pharmacy counter when they dropped off or picked up prescriptions. Before the interview about preferred features in a mobile app, demographic information was collected. A total of 24 interviews were conducted with participants at the different locations. All participants interviewed stated a need for an app to be “user friendly,” meaning an app that requires few steps to reach a certain function. There were a few different themes for an app that participants desired. The first theme being an app meant to foster an improved and convenient pharmacy experience. The second theme described features designed to help patients with self-management of their medications. The third theme involves features to increase timely and personalized access to pharmacists.

This study showed that patients desire more information from a mobile app for convenience and ease of access. This could have a positive impact on the workflow for pharmacists. An app that provides patients with comprehensive services, medication lists, and drug and disease state information could reduce the frequency of patient calls for simple requests. By reducing the number of phone calls for simple requests such as drug identification questions or checking on checking if an order is ready, pharmacists would have more time to focus on patient care services like MTM. Patients expressed that they want an app that makes it easy to communicate to a pharmacists via instant messaging, video chat, or email. This could improve patient outcomes, as it has been demonstrated before that outcomes improve when pharmacists interact directly with patients. Overall, the study showed that patient desires should be considered when creating a mobile pharmacy app. This study could be helpful for community pharmacies across the country when they design mobile applications.

McCartney E, Bacci JL, Ossman KL, et al. Mobile application features sought after by patients of a regional grocery store chain pharmacy. J Am Pharm Assoc. 2016;56(1):62-66.

Effectiveness of a pharmacist-physician collaborative program to manage influenza-like illness

This study was designed to examine the effectiveness of a collaborative agreement between physicians and community pharmacists to treat influenza-like illness (ILI). Every year in the US, there are at least 48,000 deaths and 226,000 hospitalizations resulting from influenza. Normally neuraminidase inhibitors are used to treat it by preventing the cleavage of virions from infected cells, therefore halting the spread of the virus within the body. However, this does not eradiate the virus. Studies found that early detection of the disease if critical to achieving optimal outcomes for treatment, but this is challenging. Many people use OTC products to alleviate symptoms instead of seeking immediate medical attention, delaying actual treatment of the infection. When patients come into the pharmacy to obtain OTC products, this is an opportunity for pharmacist intervention. A study conducted during the 2007-2008 and 2008-2009 flu seasons found that a pharmacist-physician collaborative program resulted in more immediate identification and treatment for patients with ILI. This study conducted from October 2013 to May 2014 and examined clinical outcomes and healthcare utilizations.

The study took place across fifty-five pharmacies in Michigan, Minnesota, and Nebraska. The pharmacists screened adult patients that came to pharmacies presenting symptoms of ILI. Then, they carried point-of-care rapid influenza diagnostic test (RIDT), completed a brief physical examination, and provided a corresponding treatment or referral through an established collaborative practice agreement (CPA) with a local licensed prescriber. After the encounter, pharmacists followed up 24 to 48 hours afterwards with the patient to assess their status and if any further intervention is needed. The outcomes measured were the number of patients screened, tested, and treated for ILI.

There were 121 patients screened overall. Of these patients, 75 were eligible for participation, and 8 had a positive RIDT and were managed accordingly. Of the tested patients 38.7% visited a pharmacist outside of normal office hours and 34.6% did not have a primary care physician. Just 3% said they felt worse at the follow-up. This study found that using a CPA enabled pharmacists to provide timely treatment to patients with and without influenza. One limitation of this study is that it did not use confirmatory testing of the RIDT results. Therefore, there was a possibility that patients were misclassified of having or not having influenza. This study demonstrated that the improved performance of CLIA-waved RIDTs and increased clinical training for pharmacists have made an opportunity for pharmacists and physicians to use a CPA to improve early detected and treatment for patients with influenza. Overall, a CPA could improve the number of patients visiting a physician for causes that only require management of symptoms. If more studies regarding this topic are conducted, hopefully this will lead to better management of patients presenting ILI.

Klepser ME, Klepser DG, Dering-Anderson AM, et al. Effectiveness of pharmacist-physician collaborative program to manage influenza-like illness. J Am Pharm Assoc. 2016;56(1):14-21.

Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study

A study investigated the use of benzodiazepines the risk of it causing dementia or rapid cognitive decline. Benzodiazepines are used among 9-12% of older adults in the United States to treat anxiety and insomnia. Drugs that fall into this class are not recommended for long term use in older adults due to the associated increased risk of falls and delirium. Single dose studies found that benzodiazepines impair memory and attention span, but its effect in long term use is still uncertain. One problem with determining if long term benzodiazepine use increases the risk of dementia is that dementia is often preceded by anxiety and insomnia: symptoms often treated with benzodiazepines. Two out of three known studies that considered early dementia symptoms and potential for reverse causation reported an increased risk of dementia with benzodiazepine use.

The investigators hypothesized that cumulative, heavier benzodiazepine exposure over a long period of time was the most likely mechanism to cause an increased risk of dementia. The study was conducted within an integrated healthcare delivery system in the North West US. There were 3434 randomly selected participants in the study aged 65 or older who did not have dementia at the start of the study. Every two years, the cognitive abilities screening instrument (CASI) was administered to test for dementia. It was also used to assess cognitive trajectory. Computerized pharmacy data was use to define benzodiazepine exposure associated with risk of dementia. This consisted of the total standardized daily doses (TSDDs) over a 10 year period. The date of onset dementia was made the midpoint between the visit triggering the dementia evaluation and the visit before that.

While the study found a slightly higher risk of dementia associated with the lowest use of benzodiazepine, it did not find an increased risk in those using the highest level. Therefore, the findings do not support the theory that cumulative use of benzodiazepines at levels used in our population has a causal relationship to increased risk of cognitive decline or dementia. However, the study did not investigate acute adverse cognitive effects that can occur upon starting benzodiazepine treatment in older adults. Healthcare providers should still avoid benzodiazepine use in older adults to prevent other important adverse effects. Considering that other studies did report a causal relationship, it seems that this is a topic that still requires more investigation.

Gray GL, Dublin S, Yu O, et al. Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study. BMJ. 2016;352:90.

Community Pharmacists’ Experience with Pharmacogenetic Testing

This aim of this study was to investigate the experience and perfection of pharmacogenetic (PGx) testing in the community pharmacy setting. PGx testing has had a significant impact on many different health fields such as psychiatry and oncology. The dosing of several drugs now rely on a patient’s genetic profile. For example, it has been found that up to 30% of people of European descent experience a lack of therapeutic effect from clopidogrel. This is due to a variant in the CYP2C19 gene. Also, a variant in the SLOC1B1 gene is associated with reduced efficacy of simvastatin. The PGx services are most commonly utilized in a clinic or in a hospital setting. However, it is only just beginning to be utilized in a community pharmacy setting.

The study focused on patient interest in PGx testing, amount of time pharmacists take to administer PGx testing, patient comprehension of results, pharmacist interactions with the patient’s physician after PGx testing and how the PGx testing affected the patient’s prescriptions. For each patient in the study, pharmacists completed surveys at two different time points that PGx. The participating pharmacies then offered testing for the CYP2C19 for patients who take clopidogrel and/or SLCO1B1 gene for those taking simvastatin. A buccal test was collected using the Harmonyx test kits. Within 1 week, results were sent to the patient’s healthcare provider and pharmacist. Testing took place across 5 independent community pharmacies in North Carolina. Of the patients offered, 81% agreed to the testing. The main reason patients declined was they felt there were no problems with their medications and thought testing was uncessary. 54% of pharmacists reported their patients understood the results “very well”. The amount of time to discuss results was normally brief, and 73% of patients had no questions or concerns about their results. Most results didn’t indicate a need to change a prescription or dose.

The findings of the study suggest that PGx testing is not too time-consuming in the community pharmacy setting. Patients also are interested and have very little concerns about the testing. It possible that so many patients agreed to the testing due to their trust in pharmacists and that the testing was relatively non-invasive. Pharmacists have expressed interest in the PGx testing, but also acknowledge they need more education in that area. This means that additional PGx testing education for pharmacists would be beneficial. This could be a potential limitation for companies that may not want to pay for additional training. Perhaps PGx courses could be added in pharmacy school curricula to avoid this problem. Additional studies could also be useful to further determine patient satisfaction and understanding of the testing. Overall, PGx testing in a community pharmacy setting seems to be feasible. What are some ways we can work towards making pharmacogenetic testing more available in community pharmacies?

 

Moaddeb J, Mills R, Haga SB. Community pharmacists’ experience with pharmacogenetic testing. J Am Pharm Assoc. 2015;55:587-94.