Hope Vertrice Askew, PharmD

PGY-1 Pharmacy Resident

Parkland Health

JAMA Network Open. 2022;5(2):e220541. doi:10.1001/jamanetworkopen.2022.0541

• Study Questions •

Compare the potential value of alternative antibiotic treatment strategies

&

Estimate the impact of addiction care services among patients with IDU-IE

Increased number of

hospitalizations due to infective endocarditis (IE)

The increased trend in IE occurrences have been linked to the opioid pandemic

(especially heroin and fentanyl)

If this trend continues, estimated 250,000 people in the US alone will die of IDU-IE between

2020- 2030

Injection Drug Use-Associated Infective Endocarditis (IDU-IE) accounts for 1 in 10

IE hospitalizations

IV drug abusers are typically not discharged with IV abx. Leading to ~20% to be discharged AMA

In 2003

16 per 100,00

In 2016

22 per 100,000

vs.

Epidemiology

JAMA Network Open. 2022;5(2):e220541. doi:10.1001/jamanetworkopen.2022.0541

Standard Treatment & Guidelines

Full IV Antibiotic Therapy vs. Partial oral Antibiotic Therapy

Treatment of IE = 4-6 weeks of IV antibiotic therapy

OPAT is commonly utilized to treat infections that require prolonged abx therapy

US treatment guidelines: artial oral antibiotic therapy reasonable option for patients with IDU-IE associated with uncomplicated right-sided Staphylococcus aureus

infection but recommend that this approach only be used when parenteral antibiotic therapy is problematic.

JAMA Network Open. 2022;5(2):e220541. doi:10.1001/jamanetworkopen.2022.0541

Evaluation of Partial Oral Antibiotic Treatment for Persons Who Inject Drugs and Are Hospitalized With Invasive Infections

• Retrospective cohort study
• Those with IDU-IE who received a complete full course of IV abx had similar readmission rates to those who were given oral abx at the time the patient was discharge as AMA

Clin Infect Dis. 2020;71(10):e650-e656. doi:10.1093/cid/

ciaa365

2018 Systemic Review - Outpatient Parenteral Antimicrobial Therapy Among People Who Inject Drugs: A Review of the Literature

• OPAT may be safe and beneficial for treating IDU- IE when compared to those who are non-IDU
• 72% to 100% of PWID successfully completed OPAT
• Rate of 2% of misuse of PICC line
• Cost of the medical respite was $350 per day compared with $1500 for an acute care bed per day, leading to an estimated savings of $25 000 to their institution per episode of OPAT

Clinical impact, costs, and cost-effectiveness of hospital-based strategies for addressing the US opioid epidemic: a modelling study

• Combined interventions of expanding hospital-based prescribing of medications for opioid use disorder and implementing addiction consult services could improve
• life expectancy
• be cost-effective
• could be the basis for a comprehensive hospital-based strategy for addressing the opioid epidemic in the USA and countries with similar opioid epidemics

Lancet Public Health. 2022;7(1):e56-e64. doi: 10.1016/S2468-2667(21)00248-6

So how does this study differ from what we already know from previous literature and guidelines?

This is the FIRST study that is comparing the long-term impact and cost-effectiveness of OPAT with IV and partial oral antibiotic treatment strategies

Published February 28^th, 2022

Simulated Cost-effectiveness and Long-term Clinical Outcomes of Addiction Care and Antibiotic Therapy Strategies for Patients With Injection Drug Use Associated Infective Endocarditis

JoëllaW. Adams, PhD; Alexandra Savinkina, MSPH; James C. Hudspeth, MD; Mam Jarra Gai, MPH; Raagini Jawa,MD, MPH; Laura R. Marks, MD, PhD; Benjamin P. Linas, MD, MPH; Alison Hill, BA; Jason Flood, MBA; Simeon Kimmel, MD; Joshua A. Barocas, MDYour

Corresponding Author: Joshua A. Barocas, MD, Division of General Internal Medicine, Anschutz Medical Campus, University of Colorado

Author Affiliations: Section of Infectious Diseases, Boston Medical Center, Boston, Massachusetts (Adams,

Savinkina, Hudspeth, Gai, Jawa, Linas, Kimmel); RTI International, Research Triangle Park, North Carolina (Adams);

Department of Medicine, Boston University School of Medicine, Boston, Massachusetts (Jawa, Linas, Kimmel);

Division of Infectious Diseases, School of Medicine,Washington University in St Louis, St Louis, Missouri (Marks);

Population Health Analytics Division, Boston Medical Center, Boston, Massachusetts (Hill, Flood); Section of

General Medicine, Boston Medical Center, Boston, Massachusetts (Kimmel); Division of General Internal Medicine,

Anschutz Medical Campus, University of Colorado, Aurora (Barocas); Division of Infectious Diseases, Anschutz

Medical Campus, University of Colorado, Aurora (Barocas).

Conflict of Interest Disclosures: Dr Kimmel reported receiving personal fees from Abt Associates and the

American Academy of Addiction Psychiatry outside the submitted work

Funding/Support: This work was supported by grants

JAMA Network Open. 2022;5(2):e220541. doi:10.1001/jamanetworkopen.2022.0541

• Methods •

Analysis

• CHEERS (Consolidated Health Economic Evaluation Reports Standards) utilized as the reporting guideline for economic evaluations of health interventions
• REDUCE (Reducing Infection Related to Drug Use Cost-Effectiveness) Model used to simulate the natural history of injection opioid use and compare the 4 treatment strategies used for IDU-IE
• Deterministic Sensitivity Analysis conducted to evaluate the extent of uncertainty in the input parameters
• Threshold Analysis to assess which values to include for the population parameters

(both analysis: included over 500,000 individuals over a lifetime)

• C++ programming was used to construct the model
• No significance test were performed for this stimulation study

MOUD = Medication for Opioid Use Disorder

Reduce Model Overview

• Simulated a closed cohort experiencing natural history of injection opioid drug use
• > 1,000 simulations completed
• “Patients” moved through time in weekly steps from start of model/ trial until death
• 5 million patients over a lifetime included
• Each week there was a pre-determined probability of developing complications from injecting drugs (ie. overdose, IDU-IE) that would lead to hospitalization and receiving outpatient addiction care
• Assumptions:
• high frequency injection of drugs = higher probability of BOTH overdose & IDU-IE
• Sharing of needles or practice nonsterile injection techniques = higher probability of IDU-IE

​

• Stratified by:
• Sex (female vs. male)
• Age (0-99 yrs)
• Injection behavior profile
• frequency of injection (high vs. low vs. not currently using)
• sharing needles (yes vs. no vs. never)
• sterile injection techniques (cleaning vs. not cleaning vs. never cleaned)

REDUCE Model – Simulation Assumptions

1. High frequency injection of drugs = higher probability of BOTH overdose & IDU-IE
2. Sharing of needles or practice nonsterile injection techniques = higher probability of IDU-IE
3. If MOUD and addiction care services was received while admitted = higher probability of linking to an outpatient MOUD and addiction care service = decrease frequency of injection drug use
4. Not ALL patients who received addiction care services received MOUD
5. While hospitalized still a probability of leaving before treatment completion
6. If left prior to completion of therapy of IDU-IE, would remain infected until they were readmitted to the hospital or died
7. OPAT and partial oral antibiotic strategy groups incorporation of weekly probability to discontinue treatment for IDU-IE prior to full therapy completed
8. Individuals had a probability of dying from overdose, IDU-IE in addition ot age, sex, drug-use 🡪 adjusted mortality from competing causes of death
9. At hospitalization, accrued an additional mortality risk applied to reflect inpatient mortality
10. Each pt occurs cost associated with opioid use, hospitalization, and outpatient services (varies depending on which opioid is used)
11. Cost analysis accounted for healthcare services and were stratified by age, sex that was NOT associated with opioid use

IDU-IE Treatment Strategy Groups

​

4-6 weeks of inpatient IV antibiotic therapy along with opioid detoxification

4-6 weeks of inpatient IV antibiotic therapy along with inpatient addiction care services that offered MOUD

3 weeks of inpatient IV antibiotic therapy along with addiction care services followed by OPAT

MOUD = Medication for Opioid Use Disorder

3 weeks IV antibiotic therapy along with addiction care services followed by partial oral antibiotic therapy

Eligible to receive addiction care services while hospitalized

Strategy groups are based on the assumption:

​

When addiction care services were implemented, hospitalized IDU would have an increased probability of receiving MOUD plus addiction counseling, opioid withdrawal management, long-term medication titration, and referral and linkage to outpatient addiction care at the end of hospitalization

Simulated Study Timeline

Week #1

All groups, start inpatient IV antibiotics

Week #3

OPAT Strategy Group*:

Transition from hospital to either home-based or OPAT clinic infusions PLUS offered addiction care services

*assumption: 50% = home infusion and 50% OPAT clinic

🡪 suggesting ~1/2 were homeless so no dispo to “home”

Week #3

Partial Oral Antibiotic Strategy Group:

Only non-MRSA IDU-IE were transitioned to oral antibiotic PLUS ALL eligible for addiction services

Week #4

Usual Care Strategy Group:

If applicable, discontinue IV antibiotics therapy , continue opioid detox while in patient

Week #4

Usual + Addiction Care Strategy Group:

If applicable, discontinue IV antibiotics therapy PLUS eligible for addiction services

Week #6

Discontinuation of all IV antibiotics for all groups except Usual Care Strategy Group, may continue with addiction services

• Results •

MOUD = Medication for Opioid Use Disorder

Estimates for Model Parameters to Characterize Outcomes of People who Inject Drugs over a Lifetime

Cohort = 5 million individuals who reflected the age/sex of US population who inject drugs per the US census

Average Study Populations:

42 years old (18-64 yrs)

70% = Male

​

​

​

​

53% high freq. individuals

11% low-freq. drug users

36% no current IVDU

​

​

​

66% practicing unsterile injection

45% sharing needles

​

MOUD = Medication for Opioid Use Disorder

Estimates for Model Parameters to Characterize Outcomes of People who Inject Drugs over a Lifetime (continued)

*REDUCE model performed using a weekly time cycle, so all probabilities are weekly

Selected Cost and Clinical Outcomes

• Life expectancy was extended in all groups
• All groups showed lower % of IDU-IE associated deaths compared with usual care strategy
• Usual care/ addiction care (usual care + inpt addiction care services that offered

MOUD = cost more and had worse clinical outcomes

Abbreviations: CrI, credible interval; ICER, incremental cost-effectiveness ratio; IDU-IE,injection drug use–associated infective endocarditis; LY, life-year; NA, not applicable; OPAT, outpatient parenteral antimicrobial therapy; POA, partial oral antibiotic

Selected Cost and Clinical Outcomes

Selected Cost and Clinical Outcomes

• Clinicians have expressed concern over the possibility of overdose while receiving outpatient antibiotic therapy
• Despite quadrupling the rate of overdose in the community 🡪 found improved outcomes with partial oral antibiotic and OPAT regimens did not qualitatively change.

Threshold Values for Treatment Completion

3 threshold analyses examining which value of treatment discontinuation per week changed the major findings

• Brown Bar = OPAT threshold of 6% per week of pts discontinuing OPAT and the point where there were no longer a gain in life years (Lys) compared to usual care
• Orange POA A = threshold value of 2.65% of patients who stopped POA per week and when POA was not not cost effective compared to OPAT @ 100,000 per Lys
• Orange POA b = threshold of 7% of pts stopping POA per week and there is no longer a gain of Lys compared with the UC group

Cost-effectiveness Acceptability Curve for Injection Drug Use–Associated Infective Endocarditis Antibiotic Treatment Strategies

• partial oral antibiotic or OPAT strategy yielded the greatest net monetary benefit 100% of the time
• Up to a willingness-to-pay threshold of $60 000, the OPAT strategy was preferred
• willingness-to-pay threshold higher than $60 000, the partial oral antibiotic strategy was preferred

• Discussion •

Discussion

• Compared to usual care, partial oral antibiotics therapy or OPAT was associated with similar or improved long term clinical outcomes and was cost-effective
• Given MRSA IDU-IE not allowed to receive oral antibiotics, OPAT was preferred and most const-effective 🡪 if no exclusion then partial antibiotic strategy was optimal
• IDU-IE has high levels of mortality within 1 year of diagnosis, desire to discharge as soon as possible.
• This study showed: OPAT and POA regimens are beneficial clinically and less costly compared to usual standard of care 🡪 support expanding opportunities for in-vivo study’s
• Concern for PICC placement in IVDU’s
• This study accounted for this and looked at POA’s role
• 80% or more of the patients receiving partial oral antibiotic therapy successfully completed treatment(83% = OPAT)
• Showing improvement in life expectancy compared to usual care

Limitations

• Not real- world data, simulation data gathered from various sources
• Can we extrapolate findings to all metropolitan areas? Non-metropolitan areas? 🡪 Maybe? no changes in qualitative findings despite changes in sensitivity analyses when different assumptions were made
• What if IVDU is non-opioids? Same findings?
• Took into consideration many real-world factors but unable to account for all variables and confounders (ie availability in OPAT clinic to receive abx)

Final Thoughts

Even with a high probability of overdose after leaving the hospital, alternative antibiotic regimens were associated with improved outcomes compared with the usual care regimen.

​

Suggesting that the opportunity to complete treatment and link to MOUD through addiction care services may prevent more overdose fatalities than an extended hospital stay.

​

These results can be used as an advocacy tool for agencies such as Medicaid to work with post acute care facilities to improve access to OPAT (and addiction services)

​

Possible longitudinal project for the ID, Psych, and Admin PGY-2 Residents to work on? Longitudinally?

​

Given no true prospective data looking at these finds! But has a lot of of benefit both for patient life but hospital/taxpayer cost-savings!!

hope.askew@phhs.org

Questions?

Hope Vertrice Askew, PharmD

PGY-1 Pharmacy Resident

Parkland Health

• Adams JW, Savinkina A, Hudspeth JC, et al. Simulated Cost-effectiveness and Long-term Clinical Outcomes of Addiction Care and Antibiotic Therapy Strategies for Patients With Injection Drug Use–Associated Infective Endocarditis. JAMA Netw Open. 2022;5(2):e220541. doi:10.1001/jamanetworkopen.2022.0541
• Marks LR, Liang SY, Muthulingam D, et al. Evaluation of partial oral antibiotic treatment for persons who inject drugs and are hospitalized with invasive infections. Clin Infect Dis. 2020;71(10):e650-e656. doi:10.1093/cid/Ciaa365
• Mitchell ED, Czoski Murray C, Meads D, Minton J,Wright J, Twiddy M. Clinical and cost-effectiveness, safety and acceptability of community intravenous antibiotic service models: CIVAS systematic review. BMJ Open. 2017;7 (4):e013560. doi:10.1136/bmjopen-2016-013560
• Suzuki J, Johnson J, MontgomeryM, Hayden M, Price C. Outpatient parenteral antimicrobial therapy among people who inject drugs: a review of the literature. Open Forum Infect Dis. 2018;5(9):ofy194. doi:10.1093/ofid/ ofy194

​

References

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Strength

Weakness

Opportunities

Threat

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REDUCE Model Assumptions

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The function of education is to teach one to think intensively and to think critically. Intelligence plus character - that is the goal of true education.

Dr. Martin Luther King, Jr.

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CONTENTS

Content Option 01

Content Option 02

Content Option 03

Content Option 04

Content Option 05

Content Option 06

Content Option 07

Content Option 08

Content Option 09

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James Sager

Developer

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Jimmy Sager

CEO

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Morgan Sager

CFO

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Lori Sager

Customer Service

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Copyright Notice

Allowed Actions:

You are free to use for school, personal or business presentations. Just delete this slide and edit or delete other slides to fit your needs. No fees, no royalties, just free PowerPoint Templates for you to use as you wish. If you are an educator and would like to have your classes use our templates, we have a PowerPoint you can use to guide them through usage of our site, and modification of our templates. This PowerPoint is available for download on all our templates pages, in the right sidebar (scroll down about halfway).

Not Allowed:

You are not authorized to redistribute in any manner. Even if you edit this document, it will still contain our hidden copyright watermark. As long as any product contains our hidden watermark, it is considered our intellectual property, with full protections under the law. If you are an educator, you are free to download and provide to your class as needed, at your discretion.

Image Usage Rights:

Most of our images are licensed through Shutterstock, for use within our PowerPoint Templates only. You are free to modify and transfer photos between our templates, but use outside our templates could constitute a copyright violation. By providing these PowerPoint Templates to you, we are not transferring any of our licensing of images to be used outside these templates.

© 2015-2017 sage-fox.com

Image Tips

Background Images:

Many of our slides have background images, which you may want to replace or remove to fit your needs. To modify, right click the slide (in the left preview panel) and choose “format background” from the dropdown menu. A “format background” screen will open to the right of the slide. To replace image, choose “file” from the insert section to browse your computer, or “online” to search the internet.

Changing Image Elements :

Simply right click the image and choose the “change picture” option, and it will give you options to browse your computer or search online. Some images will not allow the “change picture” option, for these right click anywhere within the image, then choose “format picture” from the drop down menu. Click the “fill” icon in the right screen, then click the File button to browse and find your image.

Color Transparency Screen:

Many of our slides have colored screen with varying transparency levels to allow a background image to be used, and still allow page content to be easily seen. Without this screen, background images could be too distracting, making content harder to discern, taking the focus away from the presentation. To modify color, change transparency, or remove this screen, you will have to go to the master screen, then edit or delete this screen on the first Master Slide.

On the first master slide, right click the screen. Then choose ‘format shape” from the dropdown box. You will now see a color selector box and transparency options to the right. Make changes to get the desired results you are looking for. If you want to just remove this screen, choose “cut” from the dropdown menu when you right click it.

Transition & Animation Tips

Animations:

Many of our slides have animations. You can edit properties of each by navigating to the “Animations” tab, then selecting each object and modifying to your desired effects. To completely REMOVE all animations on a slide, navigate to a slide and click anywhere within that slide, then on your keyboard hit CTRL + A (this will highlight all elements). Now click the “none” option from the animation menu, and all animations will now be gone.

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Slide Pause:

Sometimes you may want a slide pause… example, you want each bullet point to load, and be able to talk about before moving to the next. To do this, select the element that you want delayed, then in the toolbar above change “ After previous” to “on click”. Now the slide will stop before that element, and will not proceed until you hit the next button.

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Animation Changes:

To speed up, slow down, or change animation effect, click the element you want changed. In the toolbar above change the duration up or down, or select the desired transition. This must be completed for each element on the page that you want changed.

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Transitions:

Some of our templates have transitions (graphic effects on slide change). To see if a template has transitions or how it would look in presentation mode, click the View>Reading View options on the menu above. If you want to add, remove or modify transitions, click the slide, then click the Transitions tab at top of page. Select “none” to remove, or select the appropriate effect to add/modify. This must be done to each slide, as changes only affect the slide you are currently working on.

Please Support SageFox Free PowerPoint

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We are a free service, and we will never ask for money. We do however ask that you support us by letting others know about our free service. We maintain operations through advertisements on the site, so the more people who visit our site, the easier it will be for us to maintain costs for servers, continue new development, etc.

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There are many ways to help get the word out:

1. Social media likes and shares.
2. Forum posts in communities you are already members (please do not spam).
3. Telling classmates, teachers, coworkers about our PowerPoint Templates.
4. Placing one of our banners on your website, blog, etc.

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Note: If you click the “site pages” menu on our website, you will see a “link to us” page, which contains various banners and codes for you to easily insert text or image links into forums, websites, etc.

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