Correlation between Proton Pump Inhibitor Use and the Development of Chronic Kidney Disease

Proton pump inhibitors, or PPIs, are a class of drugs commonly prescribed to treat GERD and that had over 15 million users in America in 2013.  These drugs have been known to cause adverse side effects, including acute kidney injury. Based on this potential for kidney damage, a group of researchers developed a study to test their hypothesis that the use of PPIs was correlated to an increase in kidney ailments, particularly chronic kidney disease, or CKD. The study compared 10,482 patients who received either PPI therapy, H2 Receptor Antagonist Therapy, or no therapy. These patients were selected from communities in four different states, and the trials were carried out by six different universities located in these communities who studied patients over a median of 13.9 years per patient. Patient medication use was determined primarily by an annual over the phone follow ups, with patients also being asked to visit researchers a total of five times with at least three years between each visit, starting in 1987 and ending in 2013.

This study determined that patients using PPIs were 1.45 times as likely to develop CKD as a patient who was taking H2 Receptor Antagonist therapy or no therapy. A second study was conducted by the Geisinger Health System, which examined 248,751 patients for a mean of about six years per patient. This study also determined that PPI use increased the likelihood of developing CKD, while neither study suggested that H2 Receptor Antagonist use was associated with an increased risk of CKD. These studies demonstrated a correlation between PPI use and CKD development, but further studies would be needed to determine if the cause of kidney damage is actually the PPI. However, these studies suggest caution may be appropriate when recommending PPI therapy, and may also necessitate further study and research into whether over the counter PPIs need additional regulation in order to cut down on the prevalence of CKD.

 

Lazarus B, Chen Y, et al. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med. doi:10.1001/jamainternmed.2015.7193 (Published 11 January 2016).

Battling increasing cases of multi-drug resistant tuberculosis by modifying current treatments

With the upcoming renewal of our TB tests, I thought this article was appropriate. Mycobacterium tuberculosis (Mtb) infects one-third of the world’s population and accounted for 1.5 million deaths in 2013. Recently, first line treatments of TB are decreasing as multidrug-resistant strains are increasing worldwide. Therefore it is imperative to begin researching how to alter and modify our current treatments to combat drug-resistant strains. Fluoroquinolone antibacterials, such as our top drug ciprofloxacin, target DNA gyrase and are used to treat tuberculosis. DNA gyrase alters the coiling of DNA by breaking its strands and then resealing them. Quinolones work by targeting tuberculosis gyrase and preventing the resealing of the DNA, therefore causing the bacteria to die.

In this study, researchers used x-ray crystallography to generate 3-D models of how TB’s gyrase interacts with various drugs. Through this modeling, researchers have discovered two different sites where drugs could potentially interact. However, they found that current drugs only interact with one of the sites, revealing the untapped potential of the other site, or even the possibility of altering current drugs to interact with both sites at once, therefore decreasing the risk of the bacteria developing resistance. Because of this study, researchers have more information on how quinolones work and have a direction to focus their attention on in an attempt to fight tuberculosis antibiotic resistance.

Blower TR, Williamson BH, Kerns RJ et al. Crystal structure and stability of gyrase-fluoroquinolone cleaved complexes from mycobacterium tuberculosis. PNAS. 2016; published ahead of print January 20, 2016.

Link to article

Genetics and Determination of Retinal Dystrophy Gene Mutations

In one study, Nicole Weisschuh and colleagues looked into how difference in genetics have a role in determining what retinal dystrophy patients may have. The idea behind the study was to use next generation sequencing to gain a better understanding of variability between patients and improve knowledge of what is causing the issue. The study used 89 independent cases and families with different forms of retinal dystrophy. There can be a lot of variability genetically that causes retinal dystrophy, and currently there are no cures. However, gene-replacement has become a promising direction. The study resulted in identification of mutations due to differences in sequences and found 39 new mutations. One issue with the study was that a gene could have been overlooked if it was not already identified as contributing to retinal dystrophy. In some of the cases, initial clinical diagnosis of the kind of retinal dystrophy had to be changed after the study.

I found this article to be interesting because with a better knowledge of what genetic mutations are causing retinal dystrophy, the better the chance of finding a treatment. If identification of genetic variability can be detected in retinal dystrophy, it could also likely be applied to other conditions. It would be a way to help identify what a patient will need to do or take to live a quality life.

Weisschuh N, Mayer A, Strom T, et al. Mutation Detection in Patients with Retinal Dystrophies Using Targeted Next Generation Sequencing. PLoS One. 2016; 11(1).

http://www-ncbi-nlm-nih-gov.pitt.idm.oclc.org/pubmed/26766544

Long-term Exposure to Antipsychotics in Youth and Type 2 Diabetes

Over the years, antipsychotic use in youth has become increasingly popular. Most youth are prescribed second generation antipsychotic or SGAs. When SGAs were first approved for youth they were restricted to those that were on the schizophrenia spectrum. Since then, they have been approved for diseases such as Tourette syndrome and some autistic characteristics such as bipolar mania and irritability. The issue with SGAs being prescribed to the youth now is that they are being prescribed for a broad range of off label indications. These indications are impulsivity, mood, aggression, depression, and anxiety.

SGAs differ from first generation antipsychotics (FGAs) because of their fewer neuromotor side effects. Although SGAs do not cause many neuromotor adverse effects they do cause cardiometabolic side effects. These side effects include weight gain and other disease states that can lead to type 2 diabetes mellitus (T2DM). The article focuses on the concern that these cardiometabollic adverse effects are present at low dosages, and are more severe in the youth, concerning   that long-term expose can only worsen the adverse effects.

The study concluded that the highest risk for development of T2DM was in the antipsychotic exposed group of approximately 1000 patients. The mean age of the patients was 14 years old with almost two-thirds being males. The patients were The incidence rate of developing T2DM from exposure to SGAs was found to be 0.5% , and is very statistically significant. This shows that long-term exposure of the youth to antipsychotics increased the possible development of T2DM and that antipsychotics should be monitored and used for as short of a duration as possible in the youth.

I find this study to be very interesting because it calls into question not only the adverse effects that can develop in the antipsychotic exposed youth, but also the control in prescribing these medications. Specifically, I wonder what we can do to better control the prescribing of antipsychotics to youth, who present with more side effects? Or what other changes in diet or exercise we can supplement the youth with who are on antipsychotic treatment long-term?

 

Galling B, Roldan A, Nielsen R, et al. Type 2 Diabetes Mellitus in Youth Exposed to Antipsychotics. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2015.2923(published January 20, 2016)

Link to Article

Utilizing Brain Waves to Predict Dosing of Anesthesia

A conflicting issue today is that there is no direct way to measure the sedative effects of anesthesia administered by anesthesiologists other than the patient’s level of awareness.  Concentrations in the brain cannot be determined.  A study conducted by Chennu et al., utilized an EEG to experiment a better way to study dose administration of sedative-hypnotics.

It is difficult for scientists to quantitatively measure the consciousness of the brain.  When utilizing anesthetics, measuring level of sedation and the ability to track this parameter is difficult by the variability between individuals and their susceptibility to anesthetics.  Within this study conducted by Chennu et. al., the researchers utilize high-density electroencephalography in tandem with propofol  (a sedative-hypnotic), and the changes in the brain were measured.  An EEG can easily measure brain waves from the surface of the scalp, but it is not universally utilized.  This change could solve the need for reliable anesthesia monitoring during use of a sedative.  The researchers conducted assessments prior to, during and after the administration of the sedative.  The participant’s behavioral responsiveness and the drug concentrations in the blood were measured within these assessments.  All of these experiments were conducted on healthy volunteers.  When administering the propofol, key changes in the brain waves were observed.

The researchers highlight that the alpha waves are compromised during sedation.  There is a spectral connectivity when considering the alpha waves in sedated participants.  This is an indicator of susceptibility to propofol which varies between individuals.  The concentration of drug was measured at each level of sedation.  Correlations were also found between the alpha waves and behavioral impairment.  These results can assist in dosing the patient correctly instead of injecting medication until unconscious.

Chennu S, O’Connor S, Adapa R, Menon DK, Bekinschtein TA. Brain Connectivity Dissociates Responsiveness from Drug Exposure during Propofol-Induced Transitions of Consciousness. PLOS Computational Biology. 2016.

Given the advanced technology present in the medical world, I was surprised that EEGs are not universally utilized when sedating patients for surgery.  The variability between individual patients’ susceptibility to anesthetics such as propofol has been observed in the past.  This article highlights the need that individuals should be receiving different doses of this drug to sedate them accordingly.  This has me thinking of other procedures conducted within the hospital that potentially conducts dosing based on behavioral assessment.

What should pharmacists do if a drug is dosed based on bias or strictly behavioral results?  What is the responsibility of the pharmacist within this type of scenario?

Pediatrics: Synbiotics for Prevention and Treatment of Atopic Dermatitis

Chang and colleagues conducted a meta-analysis of all published randomized clinical control trials that have been reviewed to study the use of synbiotics in the prevention/treatment of atopic dermatitis (AD) in pediatric patients. AD is a common condition in children and is more commonly referred to as eczema. It is characterized by dry and scaly red patches, usually occurring on the face of children. Chang and colleagues also describe AD as creating an environment that increases a child’s susceptibility to allergic diseases. Synbiotics are OTC medications that are a mixture of both prebiotics and probiotics. The clinical control trials must have met certain criteria in order to be included in the analysis. 8 of the 257 studies met the criteria of an oral administration intervention of synbiotics, and included the severity of the AD in the children within the trial. Of the studies used, 6 were for treatment of AD and 2 were the prevention. After a complete analysis of the 8 studies, evidence was found that synbiotics can be used to treat AD for children 1 year and older, but no significant evidence was found to support the use of synbiotics for AD primary prevention.

JAMA Pediatr. doi:10.1001/jamapediatrics.2015.3943 (published online 25 January 2016).

Parents have the most concern about newborns and what medications that they are receiving. They are also concerned about any disease that may affect their young children, and are willing to do anything in order to treat their children. This analysis shows that there is an effective oral treatment for AD in children, but do you think that this analysis alone is enough for a parent to agree to use as a treatment for their child’s AD? Pediatric medication use also has very strict guidelines in order to ensure the safety of children. In my opinion, I would be more inclined to give a child a topical medication that only interacts with the affected area before I would suggest an over the counter oral medication.

Cardiovascular Risks and Clarithromycin

After reviewing some inconclusive data regarding a correlation between clarithromycin and cardiovascular outcomes, the Hospital Authority of Hong Kong decided to carry out an observational study to determine the presence or lack of a correlation. Patient’s data was collected anonymously from a database containing more than seven million residents’ personal characteristics and health information. Adults eighteen and over that had been prescribed either clarithromycin or amoxicillin between January 1, 2005 and December 31, 2009 were selected. Patients taking clarithromycin were then matched up with one or two patients taking amoxicillin based on age, sex, and time when it was used. Patients were excluded if they had a previous cardiac episode but those included had a primary outcome of the first reported heart attack. Patients were also excluded if they had received inpatient treatment with clarithromycin, which would suggest a more serious problem.

Heart attacks and arrhythmia were identified among the patients and a cardiologist reviewed the records and determined that 95% of the reported cases were in fact verified episodes. Poisson regression was then used to compare the rate of heart incidents in amoxicillin versus clarithromycin users.

Results of the study found that clarithromycin users were more likely to have diagnoses of COPD, obesity, hepatic problems, and heart failure. They were also more likely to be prescribed insulin, oral corticosteroids, proton pump inhibitors, and H2 receptor blockers. Despite increased rate ratios, the study concluded that the increases were not statistically significant in comparing clarithromycin and amoxicillin use. Long term, no increased cardiovascular risks were associated with clarithromycin but there may be a short term risk of heart attack, arrhythmia, and cardiac death in the Hong Kong population while taking clarithromycin. Basically, caution should be taken when prescribing clarithromycin, especially to those that may be at increased risk of heart problems. So should clarithromycin even be considered as a possible therapy treatment when other options, such as amoxicillin exist?

http://www.bmj.com/content/352/bmj.h6926

Citation: Wong AW, Root A, Douglas IJ, et al. Cardiovascular outcomes associated with use of clarithromycin: population based study. BMJ 2016;352:h6926.

 

Pharmacists Help Encourage Short Term Antibiotic Regimines

This study aimed to reduce the duration of antibiotics prescribed to children with uncomplicated skin and skin structure infections. Uncomplicated skin and skin structure infections, or uSSTIs, usually are treated with antibiotic therapy and include simple abscesses, cellulitis, impetiginous lesions, and furuncles. Complicated skin structure and skin structure infections (cSSTIs) affect deeper skin or are considered complicated in an immune-deficient patient. These include major abscesses, infected burns and ulcers, other infected wounds, and diabetic foot infections. The guidelines from Infectious Diseases Society of America for the management of SSTIS suggest a 5 day course of antibiotic treatment for uSSTIs, and can be extended if improvement is not made. The short antibiotic courses can help prevent antibiotic resistant bacteria from forming, lower costs, and reduce adverse effects. This study took place at the Cincinnati Children’s Hospital Medical Center, and aimed to increase short course antibiotic treatment (less than 7 days) in patients who came in with uSSTIs, compared to the previously used long-course therapy which lasts 7 to 14 days. At the beginning of this study 23% of patients with uSSTIs were prescribed short course antibiotic treatment.

To accomplish the study’s goal, they used a few methods. First, they had two 15-minute information sessions with residents and attendants. They also attached information cards about optimal antibiotic regimens for SSTIs to medical personnel’s identification badges. Pharmacists identified the third intervention as part of a multidisciplinary team, who noted that the order set default for uSSTIs was a 14-day course of therapy. The last intervention method was having a team member from the study contacting the physicians attending to SSTI patients and reiterating that short term antibiotic therapies can be used for uSSTIs, and to contact them with any questions. 5 months after the project began, 74% of patients with uSSTIs were discharged with the short term antibiotic therapies, and there was no significant difference in the amount of readmissions or recurrence for those who received the short term antibiotic treatment.

I really thought that this article showed the importance of pharmacists as part of a healthcare team, and how pharmacists can contribute innovative practices to medication changes. While changing the automatic duration of therapy in the prescribing system may seem simple, it can remind and alert the physician about the benefits of short term antibiotics and lead to less human error and increased savings. Also, this was the first time I had heard about short-term antibiotic regimens. While at first it seemed a little strange to me since I’ve been taught a lot about the importance of finishing antibiotic treatments to avoid resistance, it makes sense that shorter term antibiotic regimens would lead to increased patient adherence. Do you think that any of these methods could be implemented into a community pharmacy setting? Could pharmacists have played a more important role in this study, perhaps by educating pharmacists as well so that they can perform interventions when filling out prescriptions?

 

Citation: Schuler CL, Courter JD, Conneely SE, et al. Decreasing Duration of Antibiotic Prescribing for Uncomplicated Skin and Soft Tissue Infections. Pediatrics. doi: 10.1542/peds.2015-1223 (published 18 January 2016).

 

Link: http://pediatrics.aappublications.org/content/early/2016/01/15/peds.2015-1223

Prebiotics and the Importance of Defining them Correctly

Paul Stangl

In this article published in Elsevier, researchers from several US and international universities collaborated to expand on the scientific definition of prebiotics and then make a case for the use of a universal, consistent definition. Prebiotics are substances usually taken in tablet, powder or capsule form that are indigestible and provide probiotics (beneficial bacteria in our gut) with a food source. Examples include Fructo-oligosaccarides (FOS) and Galacto-oligosaccardes (GOS). The benefits from prebiotics have been observed to positively impact digestive health and there is a variety of prebiotic supplements on pharmacy shelves and online.

According to the article, the problem with prebiotics occurs when different specialties have varying definitions of what a prebiotic is and does. Scientists define that prebiotics should improve host health or otherwise provide a beneficial physiological effect. Regulators, such as the FDA classify prebiotics in the same category as vitamins and mineral supplements and have different standards for use in the market. In the same vein, the food industry does not have any set definition and therefore there are inconsistencies with what regulators determine for the industry and what the scientific definitions are. This confusion escalates further when consumers and even healthcare providers have little understanding of what prebiotics actually are. The article states some surprisingly negative statistics about the understanding of even the basic definitions of prebiotics, which includes the difference between prebiotics and probiotics.

 

The main point of this study is to highlight the confusion between disciplines when the definition of a term is not well defined.

What steps could pharmacists take to promote proper understanding and use of prebiotics in the patient population?

View the article here: Prebiotics: why definitions matter

 

Hutkins RW, Krumbeck JA, Bindels BL, et al.

Prebiotics: why definitions matter:

Elsevier. 2016;37:1-7.

Quantity and Quality of Life

A vast amount of evidence is now available to help health care professionals make the best possible decisions for patients facing life-threatening illnesses.  Evidence has shown that the amount of suffering people endure in their last year of life is considerable.  A study found that 51% of patients during their last year suffered moderate to severe pain.  Additionally, among people who died between 1998 and 2010, symptoms were still observed during the last year of life and the occurrence of pain, depression and periodic confusion actually increased.  The article shows that incorporating palliative care specialists early on in a patient’s treatment can produce increased survival.

One of the biggest issues facing end of life care is that patients are often cognitively impaired by their illnesses and are unable to make decisions about their care.  The decisions are often left up to family members and health care professionals and the decisions made often do not line up with the preferences of the patient.  This creates the opinion that palliative care or hospice care is equivalent to “giving up.”  This opinion leads people to believe that palliative care or hospice care is only relevant to people who are out of options for disease-based therapy.

I found this article very interesting because it brought up many points that I had previously never considered.  I never realized how public opinion about certain aspects of health care can influence the decisions made by both patients and health care professionals.  End of life care is an extremely controversial discussion and I believe that the patient’s interests should be at heart regardless of cost.  This is where I believe the pharmacist comes in; pharmacists can be palliative care specialists or hospice care pharmacists.  In these roles, I believe pharmacists have the most access to the patients and are able to develop a personal connection that is beyond the role of the physician.  This means that the pharmacist can learn the patient’s attitudes and their goals of treatment and thus personalize their therapy according to exactly what the patient wants.

The discussion also makes me consider things from a financial standpoint:  Are financial costs a deciding factor for family members when making medical decisions?  Is hospice care or palliative care covered by most insurances?  When a medical decision is left up to a patient’s health care team do they make a decision based on what is more cost effective for the hospital?

Gawande A. Quantity and Quality of Life: Duties of Care in Life-Limiting Illness. JAMA.2016;315(3):267-269. doi:10.1001/jama.2015.19206.

JAMA. 2016;315(3):267-269. doi:10.1001/jama.2015.19206.