Download Lyme Borreliosis and Related Tick-borne Disorders: Challenges in

Beatrice M. Szantyr, MD, FAAP
Women in Government
Annual Southern and Eastern Regional Conferences
Bar Harbor, Maine
September 30, 2016
 ~ 30,000 surveillance cases of Lyme reported yearly in US
• Doesn’t capture all diagnosed cases
 CDC work to estimate actual incidence
• Project 1: Tests by large commercial US labs
• Estimated incidence: 288,000
• Project 2: claims from large insurance database.
• Estimated Incidence: 329,000
 CDC estimates annual US incidence >300,000
 CDC estimates in untreated patients:
 5% develop persistent neurological
complaints months to years after infection
 60% begin to have intermittent bouts of
arthritis with severe joint pain and swelling
http://www.cdc.gov/lyme/signs_symptoms/index.html
August 3, 2015
 “Approximately 10 to 20% of patients experience fatigue,
muscle aches, sleep disturbance, or difficulty thinking
even after completing a recommended course of
antibiotic treatment.”

http://www.cdc.gov/lyme/faq/index.html March 4, 2015
• Shadick 1994: 34% had long-term sequelae
• Population-based retrospective cohort study
• Aucott 2015: 36% had post treatment symptoms
• Prospective cohort study
Quality of life survey:
3,090 patients with Lyme disease
and
symptoms for > 6 mos after a
minimum of 21 days of abx
7.9% not diagnosed until at least 3 months after onset sx
16.6% not diagnosed for at least 6 months
61.7% not diagnosed for at least 2 years
Johnson et al. (2014), PeerJ, DOI 10.7717/peerj.322
Fair or Poor Health as a Function of
Duration of Illness
Johnson L, et al 2014
Fair or Poor Health
Lyme vs Other Chronic Illnesses
Johnson L, et al 2014.
 Vanderhoof 1993
 survey: 503 physician-dxd patients
 assess: medical and non-medical costs (lost income)
 Findings
 average total cost ~ $60,000
 delay of diagnosis associated with higher cost
 cost if dx delayed >12 months 3x cost if dx <6 months
 Lowest cost subgroup:
rash and (+) test = less time to dx
 Largest cost cases averaged 31 months to diagnosis and
cost ~$250K
Vanderhoof, IT and Vanderhoof-Forschner K Lyme disease: cost to society. Contingencies 1993
Jan/Feb: 42-48
method
$ direct
/ pt
$ indirect
/other /pt
Total
avg/pt
TOTAL
estimate
Vanderhoof
1993
Survey
support
group pts.
na
na
$61,688
$12 million$1.3 billion/yr.
Maes
1998
CDC incid. $731-$3,445
+claims + early Lyme
panel+
survey
$2,740$8,270 late
$356-$3,152
na
derm/”flu” v
card/neuro
Zhang
2006
Med
record
data +
survey
$2,970
$5,202
$8,172/
yr
Aucott
2015
Data:
claims &
enrollment
$2968 >
cost/yr
than not
Lyme
*if dx Lyme,
$3,798 >/ yr
if 1 or more
PTLD rel. dx
+$2,968- $712 million+3,798yr $1.3 billion/yr
above
no Lyme
$89-$214
parent time
$2.5 million/yr
$2.5 billion/5yr to
prevent 55,626
late sequelae
$203 million/yr
 Complex microbiology of B. burgdorferi
 Slow growth characteristics (similar to TB and Leprosy)
 Adaptable (many different species as host)
 Survival strategies:
 multiple forms
 intra-and extra-cellular
 privileged sites
 immune modulation
 Strain variations
 Presence of co-infections may complicate diagnosis
and treatment
 History:
 No tick; no rash
• Multiple complaints: unrecognized symptom patterns or
clusters
• The new “great imitator”
• Exam:
 Physical findings may be subtle or absent
 Lab:
 Poor test reliability, sensitivity, reproducibility
 Impact of co-infection on testing uncertain
12
 No laboratory tests definitively rule in or rule out
 Culture not readily available: slow growth characteristics
limit utility
 PCR specific but not sensitive
 Serology - antibodies
 Early: not useful – not measurable til 2-6 wks after infection
 Late: variable performance better for arthritis than for neurologic
 Persistent: difficult to interpret; may persist or wan
 Tests may be supportive
 Which antibiotic(s)?
 Failures documented for every trial regimen
 Individual differences among patients
 Combinations- very little research
 For how long?
 Duration of treatment not well-established
 Varies by disease stage
 Conflicting recommendations
 What about side effects and complications of treatment?
 What about consequences of non-treatment?
•
~50% of infectious disease recommendations based on
low quality evidence.
Khan et al Clin Inf Dis
2010;51(10):1147-1156
• GRADE-based evaluation that evidence quality is very
low.
Hayes and Mead Clin Evid 2004(12)1115-24
 the quality of evidence is very low.
“…the evidence base for treating Lyme disease is best
described as sparse, conflicting and emerging.”
Cameron, Maloney, and Johnson Expert Rev Anti Infect Ther. 2014 Sep; 12(9): 1103–
1135.
Institute of Medicine called for the development of treatment
guidelines to assist clinicians
-assemble recommendations to optimize patient care
-informed by
-systematic review of research evidence
-assessment of benefit and harms of alternatives
This information should enable healthcare providers to
select the best care for a unique patient, based on best
evidence and considering individual patient’s preferences.
-IOM Clinical Practice Guidelines We Can Trust
2011
 IOM explains this occurs most often when
 Evidence is weak
 Developers differ in their approach to evidence
reviews
 Developers differ in their evidence synthesis
 Developers have varying assumptions about
intervention benefits and harm
 Stakeholders:



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Patients, doctors/clinicians, insurers, employers- provider and patient
public health departments, researchers, funding organizations
professional boards
pharmaceutical companies
 Clinician Pressures: Practice setting and time constraints
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
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Complicated patients
Complex diagnostic possibilities
Careful follow-up requirements
Controversial illness
Concern about lack of expertise and experience
 Guidelines




Used as if they are laws
Used as performance measures
Used to determine payment
Used for disciplinary purposes
 Evidence based medicine is the integration of high
quality (best available) trial evidence, clinical
expertise and patient values.
 When evidence is poor, clinical judgment guides
decision-making.
 Patient –centered
 Review of best evidence.
 Clinical experience
 We tend to measure what is readily measurable:
 Is that the best assessment of quality?
 We tend to provide funding based on numbers:
 Which numbers? Case numbers? Costs? Whose costs?
 We regulate insurers:
 Do we regulate insurers?
 We establish rules and regulations in medicine:
 Do they enhance the physician-patient relationship?
 Do they support physician autonomy?
 Do they support patient autonomy and right to choose?
 Do no harm.
 Do good.
 Women in Government Foundation, Inc.
 Katie Lanzarotto
 Representative Deb Sanderson
 Fellow panelists
 Colleagues who influenced and edited this work
 Patients and their families who share their stories
 YOU.
 Hinckley A, Connolly N, Meek J, Johnson B, et al Lyme disease testing by large
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commercial laboratories in the United States. Clin Inf Dis. 2014; 59(5):676-681.
Nelson C, Saha S, Kugler K, Delorey M, Shankar M, Hinckley A, Mead P
Incidence of clinician-diagnosed Lyme disease, United States, 2005-20010. EID
2015; 21(9):1625-1631.
www.cdc.gov/lyme/signs_symptoms/index.html August 3, 2015
www.cdc.gov/lyme/stats/humancases.html March 4, 2015
www.cdc.gov/lyme/faq/index.html March 4, 2015
Shadick N, Phillips C, Logigian E, Steere A, Kaplan R, Berardi V, Duray P,
Larson M, Wright E, Ginsburg K, Katz J, Liang M The long-term clinical
outcomes of Lyme disease: a population-based retrospective cohort study. Ann
Intern Med 1994; 121: 560-567.
Aucott J, Rebman A, Crowder L, Kortte K Post-treatment Lyme disease
syndrome symptomotology and impact on life functioning: is there something
here? Qual Life Res (2013) 22: 75-84.
Johnson L, Wilcox S, Mankoff J, Stricker R (2014), Severity of chronic Lyme
disease compared to other chronic conditions: a quality of life survey. PeerJ
2:e322; DOI 10.7717/peerj.322
Vanderhoof IT, Vanderhoof-Forschner K Lyme disease: cost to society.
Contingencies 1993; Jan/Feb: 42-48.
 Maes E, Lacomte P, Ray N A cost of illness study of Lyme disease in the United
States. Clin Ther 1998; 20(5):993-1008
 Zhang X, Meltzer M, Pena C, Wroth L, Fix A Economic impact of Lyme disease.
EID 2006; 12(4): 653-660.
 Adrion ER, Aucott J, Lemke KW, Weiner JP (2015) Health care costs, utilization
and patterns of care following Lyme disease. PLoS ONE 10(2):
e0116767.doi:10.137/journalpone.0116767.
 Khan A, Khan S, Zimmerman V, Baddour L, Tleyjeh I Quality and strength of
evidence of the Infectious Diseases Society of America clinical practice
guidelines. Clin Infect Dis 2010; 51(10): 1147-1156.
 Hayes E, Mead P Lyme disease Clin Evid 2004; 08: 910.
 Cameron D, Maloney E, Johnson L Evidence assessment and guideline
recommendations in Lyme disease: the clinical management of known tick
bites, erythema migrans rashes and persistent disease. Expert Rev Anti Infect
Ther 2014 Sep; 12(9): 1103-1135.
 Graham R, Mancher M, Wolman DM et al. eds. Clinical Practice Guidelines We
can trust. Washington, D.C.: National Academies Press, 2011.
 Scott I, Guyatt G Suggestions for improving guideline utility and
trustworthiness. Evid Based Med April 2014; 19(2): 41-46.