In June 2016, Baptist Health, Arkansas’s largest not-for-profit, full-service hospital and CareLink, a non-profit that serves homebound and active older people, and family caregivers, combined to sponsor Complete Health with PACE. Their goal was to improve care for the elderly population in Little Rock. The Program of Allinclusive Care for the Elderly (PACE) enables nursing home-eligible adults with the option to live at home as long as possible while receiving the highest quality of care. Valerie Dunn, Executive Director, and Delbra Valerie Dunn, Executive Director Caradine, MD, Medical Director, found that being new to PACE contained a unique set of challenges that their partnership with CareKinesis greatly aided in addressing. “As a startup, there were many obstacles—most notable was the fact that every member of the team was new to the PACE model,” said Dunn. Among the challenges that Complete Health with PACE faced as a start-up was familiarizing staff with the PACE Model and with CMS regulations. This required some re-education and defining what the PACE care model meant for the team and guiding staff and participants on the difference between needs and wants. According to Dunn, “this required tweaking the tools used for resource allocation.” An additional learning curve: the staff had to become comfortable with the use of an Electronic Health Record (EHR).
“Being new to PACE,” said Caradine, “we were naive and unsure about process and operations. CareKinesis offers an array of PACE-specific services and expertise which is just what we needed.” Very quickly, Complete Health with PACE maximized efficiency and accuracy, using an integration between EireneRx and Cognify’s Greenway (PrimeSuite) EHR. They also appreciate the comprehensive services that support participant needs: prospective, personalized medication management; reminder packaging; 28-day medication cycle deliveries to participant homes or the PACE center; and same-day medication access with the on-site cabinet or contracted local pharmacies. Dunn has appreciated the support, stating that “partnering with CareKinesis has enabled us to provide medication care with few medicationrelated interruptions.” Caradine appreciates how CareKinesis has supported Complete Health with more than just medication management: “CareKinesis is always very helpful and responsive when I have questions related to medication therapy, technical support, same-day medication access with our on-site medication cabinet, or just a general PACE question. I can always rely on timely assistance from CareKinesis.” Visit www.CareKinesis.com to read the full case study.
Opioid Quality Program This quarter, CareKinesis pharmacists reviewed all participants who were taking both an SSRI and an opioid analgesic that use Bob Alesiani, PharmD, CGP the same genetic pathway for activation in the body. While not detected in common pharmacy or EMR software, these occurrences are serious drug-drug interactions which can cause major, negative downstream effects. CareKinesis pharmacists verified that these interactions had been discussed with the PACE clinicians, and that recommendations had been made.
Recommended interventions included:
Switch the participant to a non-CYP 2D6 antidepressant (e.g., sertraline, citalopram, escitalopram). NOTE: if choosing this path, opioid effects may increase after elimination of competitive inhibition. Patients on high dose opioids (e.g., OxyContin®) could risk dangerous overconversion and accidental overdose, so concurrent reduction in the opioid should be considered. Fastacting breakthrough (“rescue”) medication should then be made available (e.g., morphine).
If the antidepressant can’t be switched, switch the 2D6-opioid (e.g., OxyContin®) to morphine, which does not require the enzyme to be activated. NOTE: if choosing this path, the equi-analgesic conversion must be conservative to prevent accidental overdose.
Discontinue the opioid. When and why was the pain medication initiated; does the participant actually take it; and does it still need to be on the profile? Explore other ways to control the participant’s pain.
Taper and discontinue the antidepressant. When and why was the SSRI started, and does the patient still need it? If Prozac® was initiated 5 years ago for situational depression, perhaps the participant is ready for a taper with the goal of discontinuation.
Leave the medication profile as-is, and monitor the participant for status changes.
In many cases, ‘taper and discontinue the antidepressant’ was our recommendation, because participants’ drug combinations were already adjusted to account for these drug-drug interaction effects. A critical clinical note is this: these SSRI-opioid combinations make the opioid LESS effective. Thus, risk of overdose is only a consideration if the antidepressant is suddenly decreased/discontinued—especially in cases where the combination precipitated the need for a stronger opioid combination (e.g.: HC/APAP 10/325 vs HC/APAP 5/325).
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Dr. Bain Appointed to BPS The Board of Pharmacy Specialties® (BPS), the premiere post-licensure certification agency serving the pharmacy profession, has announced the appointment of Kevin T. Bain, PharmD, MPH, BCPS, BCGP, CPH, FASCP to its Employer Advisory Committee (EAC). Kevin T. Bain, PharmD
As a member of this Committee, Dr. Bain’s duties include providing strategic direction; informing communication activities about the value of BPS certification; and identifying tools and services to offer employers. Dr. Bain is Vice President of Medication Risk Mitigation for CareKinesis / TRHC. He also serves as the Director, Pharmacy Practice Residency at TRHC. He was appointed Chair-Elect of the Commission for Certification in Geriatric Pharmacy (CCGP) Board of Commissioners prior to its merger with BPS. “Dr. Bain’s appointment to the EAC will call on his extensive background in inpatient, community, and federal pharmacy as well as outcomes research, clinical support and performance improvement,” said EAC Chair Beth Chester, PharmD, MPH, FCCP, BCPS. BPS board certification is recognized as the gold standard for determining which pharmacists are qualified to contribute at advanced practice levels. All 100% of eligible clinical CareKinesis PACE pharmacists are board certified, as are 100% of TRHC pharmacists—who provide medication management services to health plans.
Clinical Analysis: Probiotics & Antibiotics Occurring in up to 25% of older adults receiving antibiotics,1 antibioticassociated diarrhea (AAD) is a relatively common and potentially significant complication of antibiotic therapy for PACE participants. Furthermore, if inoculated with Clostridium difficile Sabina Bukowska, PharmD (C. diff), AAD can result PGY1 Pharmacy Resident in in hospitalization and even Geriatric Personalized Medicine death among PACE participants. The purpose of this article is to provide the reader with an overview of the importance of a healthy and natural balance of gastrointestinal (GI) microflora and explain how antibiotics pose a threat to the GI system. Additionally, this article aims to shed light on the mechanism of action of probiotics and evidence supporting their co-administration with antibiotics for the prevention of AAD and C. diff.
What is the role of gastrointestinal microflora? Microorganisms, including bacteria, archaea, viruses, and unicellular eukaryotes, colonize every surface of the human body. Of these microorganisms, approximately 70% colonize the GI tract, and most of the GI-colonizing microorganisms are bacteria.2 Gastrointestinal bacteria supply the human body with nutrients, synthesize vitamin K, assist in the digestion of cellulose, and promote angiogenesis and enteric nerve function.3 Bacteria that comprise normal flora help permit adequate digestion and overall maintenance of the GI tract. In return, the symbiotic relationship with the human body allows microorganisms to benefit from GI resources.
What causes disruptions in gastrointestinal microflora? The human body hosts microorganisms using a system of checks and balances that is typically harmonious; however, host and environmental factors, such as diet and medications (e.g., antibacterials, otherwise known as antibiotics), can influence and disrupt the microenvironment of the GI tract. Disruptions in the balance of normal GI flora can alter the diversity and composition of the microorganisms, which can negatively impact health.4
Sometimes these disruptions can be serious or lifethreatening, such as diarrhea induced by disruption of the GI flora in older adults whom are susceptible to dehydration.
What are antibiotic-associated diarrhea and Clostridium difficile (C. diff)? When antibiotics are orally ingested, they are immediately presented to the GI tract. As they pass through the GI tract, they become [partially] absorbed into the blood stream and subsequently distributed to their site(s) of action. The portion of the antibiotic that is not completely absorbed gets incorporated into fecal matter. As they pass through the GI tract, all antibiotics, and especially those of the broad spectrum variety, disrupt the delicate balance between the human host and the normal GI flora.5 Perturbation of normal GI flora caused by oral ingestion of antibiotics can result in diarrhea, which is referred to as AAD. Antibiotic-associated diarrhea is defined as a change in normal bowel habits, with a stool frequency of 3 or more watery stools per day for several days. Symptoms can present as soon as 24 hours after the initial administration of an antibiotic, and remain for up to 8 weeks after the antibiotic therapy is complete.1 Further, evidence suggests that antibiotic use causes long-lasting shifts in microorganism composition. In one example, the administration of ciprofloxacin or clindamycin consequently altered the balance of microorganisms for up to 12 months before returning to the pre-antibiotic state.6 Thus, for some individuals who receive antibiotics, the risk of AAD may be prolonged (i.e., exceed the duration of antibiotic therapy). It is well appreciated that all antibiotics cause an imbalance in normal GI flora, and it is believed that this alone at least contributes to symptoms of diarrhea.7 One postulated, and likely contributing, cause to AAD is a suppression of normal GI flora that results in alterations in intestinal carbohydrate and bile acid metabolism, leading to osmotic diarrhea.2,7 Suppression of normal GI flora may also cause or contribute to the overgrowth or overexpression of other microorganisms, such as C. diff. Thus, differences between the incidence and severity of AAD may be related to the propensity of antibiotics to suppress microorganisms in the GI tract.
C. diff, an anaerobic, spore-forming microorganism, causes 10-20% of cases of AAD.8 In such cases, it is referred to as C. difficile-associated diarrhea (CDAD). The microorganism is acquired exogenously, and the spores of the toxigenic C. diff are able to survive on surfaces and can withstand the low pH of the stomach upon ingestion. The spores are carried in the stool by both symptomatic and asymptomatic patients.9 In colonized patients whose balance of normal GI flora has been disturbed, such as those receiving antibiotics, C. diff acts as an opportunistic microorganism and can release cytotoxins and enterotoxins from its spores—causing symptoms that range from mild diarrhea to life-threatening pseudomembranous colitis.8 With CDAD on the rise, there is increasing concern for at-risk individuals.9
Being confined to the same space as pathogenic bacteria, probiotics compete for invasion of the epithelium and mucus. They compete both for space and for limited resources, such as elemental iron. Finally, probiotics can enhance mucosal immunity by producing protective cytokines such as interleukin-10, which have the potential to inhibit epithelial cell apoptosis and enhance epithelial cell regeneration. Certain probiotic strains also affect intestinal dendritic cells, which function to present antigens and help shape T-cell response, participate in anti-inflammatory effects, and modulate immune response via B-lymphocyte and antibody production.11
What is the role of probiotics in antibiotic-associated diarrhea?
Probiotic production processes vary among manufacturers, and there is a lack of quality control oversight of the process by regulatory agencies, such as the U.S. Food and Drug Administration. Because probiotics are manufactured from live microorganisms, their enumeration may be complicated by mechanisms of mass production and they are often subjected to environmental stressors. It also can be difficult to accurately quantify the amount of colony forming units (CFUs) within a given probiotic product. Evidence has shown that commercial products often do not contain the exact CFUs stated on the product label.12 Further, stability and viability—critical factors to effectiveness—are not always guaranteed by the manufacturer.13 Few wellconducted clinical trials exist that demonstrate effectiveness of specific probiotic products, and often the diversity of the strains and formulations commercially available makes it difficult to create standardized rules for manufacturing and testing effectiveness.8 Therefore, there is marked uncertainty about the quality and effectiveness of some commercially available probiotic products.
The World Health Organization (WHO) defines probiotics as, “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.” A literature review of 420 randomized controlled trials found that prevention of AAD is the most common indication for probiotic use.10 To understand the use of probiotics for AAD, it is helpful to understand their mechanisms of action. Probiotics exert antimicrobial effects and enhance both epithelial protection and mucosal immunity.11 The lumen, or innermost part of the intestines, is surrounded by the mucosa. Certain probiotic strains stimulate the production of hydrolytic enzymes that ultimately increase acid production within the lumen. The production of acid results in a reduction in luminal pH, which functions to inhibit the colonization and growth of pathogenic bacteria. Probiotics can also produce antibacterial chemicals, such as bacteriocins, hydrogen peroxide, and organic acids, which further function to inhibit pathogenic bacterial growth.11
Is one probiotic better than another for the prevention of antibiotic-associated diarrhea?
Probiotics most studied for the prevention of AAD are the Lactobacillus and Saccharomyces genera. The majority of trials have shown benefits of Lactobacillus GG and Saccharomyces boulardii in both children and adults.14 Although there are few individual, robust randomized controlled trials that assess the efficacy of probiotics, several systematic reviews and meta-analysis have shown promising results.15,16 Most recently, a 2012 systematic review and meta-analysis analyzed trials with interventional probiotics containing microorganisms from the genera Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and Bacillus for the prevention or treatment of AAD.17 Pooled evidence from these mostly small, randomized controlled clinical trials revealed that probiotics (Continued next page)
are associated with a reduction in AAD, with a relative risk of 0.58.17 Due to limitations of the trials, such as poor documentation of probiotic strains and unexplained diversity, more research is needed to determine which strains are most effective, but results encourage further research.17
Conclusion In an effort to reduce the consequences of AAD, experts suggest that administering probiotics concomitantly with antibiotic therapy may restore balance to GI flora and prevent the onset of diarrhea and associated infections. Despite acknowledged limitations of clinical trials, probiotics have a long history of safety and tolerability, allowing for their careful consideration as an addition to a participant’s antibiotic therapy to help prevent AAD.
References 1. McFarland LV. Antibiotic-associated diarrhea: epidemiology, trends and treatment. Future Microbiol. 2008;3(5):563-78. 2. Sekirov I, Russell SL, Antunes LC, Finlay BB. Gut microbiota in health and disease. Physiol Rev. 2010;90(3):859-904. 3. Zhang YJ, Li S, Gan RY, Zhou T, Xu DP, Li HB. Impacts of gut bacteria on human health and diseases. Int J Mol Sci. 2015;16(4):7493-519. 4. Iqbal S, Quigley EM. Progress in our understanding of the gut microbiome: implications for the clinician. Curr Gastroenterol Rep. 2016;18(9):49. 5. Dethlefsen L, Relman DA. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci U S A. 2011;108 Suppl 1:4554-61.
6. Rashid MU, Zaura E, Buijs MJ, Keijser BJ, Crielaard W, Nord CE, et al. Determining the long-term effect of antibiotic administration on the human normal intestinal microbiota using culture and pyrosequencing methods. Clin Infect Dis. 2015;60 Suppl 2:S77-84. 7. Wistrom J, Norrby SR, Myhre EB, Eriksson S, Granstrom G, Lagergren L, et al. Frequency of antibiotic-associated diarrhoea in 2462 antibiotic-treated hospitalized patients: a prospective study. J Antimicrob Chemother. 2001;47(1):43-50. 8. Beausoleil M, Fortier N, Guenette S, L'Ecuyer A, Savoie M, Franco M, et al. Effect of a fermented milk combining Lactobacillus acidophilus Cl1285 and Lactobacillus casei in the prevention of antibiotic-associated diarrhea: a randomized, double-blind, placebocontrolled trial. Can J Gastroenterol. 2007;21(11):732-6. 9. Gerding DN, Johnson S. Clostridium difficile Infection, Including Pseudomembranous Colitis. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson JL, Loscalzo J, editors. Harrison's Principles of Internal Medicine, 19e. New York, NY: McGraw-Hill Education; 2015. 10.McFarland LV. From yaks to yogurt: the history, development, and current use of probiotics. Clin Infect Dis. 2015;60 Suppl 2:S85-90. 11.Patel R, DuPont HL. New approaches for bacteriotherapy: prebiotics, new-generation probiotics, and synbiotics. Clin Infect Dis. 2015;60 Suppl 2:S108-21. 12.Davis C. Enumeration of probiotic strains: review of culture-dependent and alternative techniques to quantify viable bacteria. J Microbiol Methods. 2014;103:9-17. 13.Johnson S, Maziade PJ, McFarland LV, Trick W, Donskey C, Currie B, et al. Is primary prevention of Clostridium difficile infection possible with specific probiotics? Int J Infect Dis. 2012;16(11):e786-92. 14.Sánchez B, Delgado S, Blanco-Miguez A, Lourenco A, Gueimonde M, Margolles A. Probiotics, gut microbiota, and their influence on host health and disease. Mol Nutr Food Res. 2017;61(1).[Epub 2016 Oct 10]. 15.Sazawal S, Hiremath G, Dhingra U, Malik P, Deb S, Black RE. Efficacy of probiotics in prevention of acute diarrhoea: a meta-analysis of masked, randomised, placebocontrolled trials. Lancet Infect Dis. 2006;6(6):374-82. 16.McFarland LV. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol. 2006;101 (4):812-22. 17.Hempel S, Newberry SJ, Maher AR, Wang Z, Miles JN, Shanman R, et al. Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. :1959-69.
CareKinesis RIDES! The CareKinesis team is proud to support the Bike MS: City to Shore Ride 2017 which took place September 23/24. Participating team members rode at least 75 miles, and participated in fundraising for MS research.
CareKinesis GIVES! On August 18, CareKinesis hosted a blood drive at TRHC headquarters (our third in 12 months), and broke yet another record with 47 donations—that makes 117 donations since September of 2016. More than 90% of donors were CareKinesis and TRHC staff members.
CareKinesis SHARES! CareKinesis has delivered medications to a pharmacy in Puerto Rico and remains available to assist as hurricane clean-up continues.
Data Driving Value for CareKinesis Partners Who owns participant data? The PACE, of course! PACE data is incredibly valuable for helping you understand how to enhance care, improve quality, and control costs. We deliver your data to you in different ways. Through EireneRx, clients have complete access to clinical reports. Using Report Portal, clients have a host of administrative and financial reports, viewable and downloadable in many formats.
The CareKinesis Report Portal is an extremely valuable tool.
Executive Report Dashboard Medical Director Dashboard Antipsychotic Drug Utilization Billing Detail (and local pharmacy detail) ESRD Drugs & Drug Utilization OMS Acetaminophen, Opioids Participant Data (demographics, status, allergies, etc.) PDE Reports Psychotherapeutic Drug Utilization Medication Changes New Medications And more!!
In EireneRx, data is also provided in a variety of outputs. PACE-Level Reports include: Participant Data Controlled Substances Drug Therapy Expiring Meds/Refills Remaining MAR Prescribed, Dispensed Meds Participant Reports include: Med Profile Med Schedule for Participants MAR, eMAR Order & Dispense History Monitoring Parameters QA Reports are routinely provided to clients, and we’re always happy to deliver custom reports!
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