October 2017

www.CareKinesis.com 888-9-PharmD

In this Issue: page

Opioid Quality Initiative 2

BPS Appointment 3

Probiotics/Antibiotics 4

Team Member Recognition 6

Data Driving Value 7

Calendar 8

Copyright © 2017 by CareKinesis, Inc.

All rights reserved

Personalizing medication management • Advancing pharmacy knowledge • Promoting participant safety

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 All-

inclusive 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

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 medication-

related 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.

Who are we?

CareKinesis is a comprehensive pharmacy

solution for PACE providers.

The CareKinesis model improves medication-related outcomes and PACE clinic

operational efficiency.

Partner Spotlight: Complete Health with PACE (AR)

How antibiotics pose a threat to the GI system? Pg 4

Valerie Dunn, Executive Director

Looking for Comprehensive Pharmacy Services?

Prescriber support with PACE-experienced clinicians Medication Risk Mitigation and e-prescribing platform

customized for PACE Multiple adherence packaging options Technology solutions for on-site medication access Part D plan management resources Documented improved outcomes, including quality and costs

Medication Risk Stratification & Score analysis

Call us today! 888-974-2763

Page 2 www.CareKinesis.com

This quarter, CareKinesis pharmacists reviewed all participants

who were taking both an SSRI and an opioid analgesic that use

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 over-

conversion and accidental overdose, so concurrent reduction in the opioid should be considered. Fast-

acting 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).

Opioid Quality Program

Medication Safety by the Numbers

How does your PACE stack up?

Let us evaluate your PACE population

to show you how your participants’

Medication Risk Scores stack up

and where interventions will

have the greatest impact!

info@CareKinesis.com

Bob Alesiani, PharmD, CGP

www.CareKinesis.com 888-9-PharmD

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).

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.

Kevin T. Bain, PharmD

Occurring in up to 25% of

older adults receiving

antibiotics,1 antibiotic-

associated diarrhea

(AAD) is a relatively

common and potentially

significant complication

of antibiotic therapy for

PACE participants.

Furthermore, if inoculated

with Clostridium difficile

(C. diff), AAD can result

in hospitalization and even

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 gastro-

intestinal (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 micro-

organisms 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 microenviron-

ment 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 life-

threatening, 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 micro-

organism 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.

www.CareKinesis.com 888-9-PharmD Page 4

Clinical Analysis: Probiotics & Antibiotics

Sabina Bukowska, PharmD PGY1 Pharmacy Resident in

Geriatric Personalized Medicine

Copyright © 2017 by CareKinesis, Inc. All rights reserved Page 5

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 micro-

organism 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 micro-

organism 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

What is the role of probiotics in antibiotic-associated diarrhea?

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 bacteri-

ocins, hydrogen peroxide, and organic acids, which further

function to inhibit pathogenic bacterial growth.11

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

Is one probiotic better than another for the prevention of 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 well-

conducted 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.

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)

Page 6 Page 6 www.CareKinesis.com

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. Fu-ture 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 hu-man 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. Fre-quency 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, placebo-controlled 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 pro-biotics. 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, placebo-controlled trials. Lancet Infect Dis. 2006;6(6):374-82.

16.McFarland LV. Meta-analysis of probiotics for the prevention of antibiotic associated di-arrhea 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.

(Continued from page 5)

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.

www.CareKinesis.com 888-9-PharmD

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.

Report Portal data includes:

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!!

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!

Data Driving Value for CareKinesis Partners

In EireneRx, data is also provided in a variety of outputs.

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