| Selection
of Dr. Cameron's presentations
Primary
changes in ILADS Evidence-Based Practice Treatment Guidelines
Cameron
DJ, Gaito A, Harris N, Bach G, Bellovin S, Bock K, Bock S, Burrascano
J, Dickey CE, Horowitz R, Phillips S, Merr-Sherrer L, Raxlen B, Sherr
V, Smith H, Smith P, Stricker R. International Lyme and Associated Diseases
Society (ILADS), Bethesda Maryland
Objective: These guidelines build upon the Infectious Diseases
Society of America (IDSA) 2000 Practice Treatment Guidelines for Lyme
disease to incorporate the growing body of evidence of the complexity
of persistent and recurrent Lyme disease.
Limitations of IDSA guidelines: The IDSA Lyme Disease Practice
Guidelines concluded there was no evidence that chronic Lyme disease existed
as a separate diagnostic entity and there is no data to support prolonged
and repeated treatment.
Data Sources: English-language articles published 1975 to 2002
identified through MEDLINE and bibliographies.
Major Additions in the ILADS Guidelines:
1. Laboratory testing is meant to contribute to rather than to supersede
physicians' judgment.
2. Clinical judgment is necessary to identify individuals who may benefit
from antibiotics to avoid preventable persistent, recurrent, and refractory
Lyme disease.
3. Empiric treatment should be considered as routine treatment of patients
for whom Lyme disease is a likely diagnosis.
4. The previously recommended practice of stopping antibiotics to allow
for a delayed recovery is no longer recommended for patients with persistent,
recurrent and refractory Lyme disease.
5. Duration of therapy should be guided by clinical response rather than
any arbitrary 30-day treatment course.
6. A reasonable course would be to continue therapy to treat Lyme disease,
after clinical and laboratory abnormalities are resolving and symptoms
have resolved.
7. Indications for retreatment should be broadened from meningitis, heart
block, and arthritis to include symptomatic presentations.
Conclusions: The ILADS Practice Treatment Guidelines revises and
expand use of clinical judgment and empiric treatment.
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The
Consequence of Underdiagnosing and Undertreating Lyme Disease: The Lyme
Disease Surveillance Database Study
Cameron
DJ, Glushanok G, McCoy K. Mt. Kisco, New York, USA, board member, International
Lyme and Associated Diseases Society (ILADS)
Background: Recent recommendations focused on avoiding overdiagnosis
and overtreatment of Lyme disease. The consequences of underdiagnosing
and undertreating Lyme disease have not been adequately assessed.
Study design: A Lyme Disease Surveillance Database was used to
identify 100 consecutively evaluated Lyme disease patients from 1997
to 2001 confirmed with a positive IgG Western blot subset of the Centers
for Disease Control and Prevention (CDC) two-tier serologic criteria.
Results: Treatment was delayed for 34 of the 100 Lyme disease
patients, 21 (62%) due to the physician alone, 11 (32%) due to the patient
alone, and 2 (6%) due to both the physician and patient. The mean treatment
delays for physicians and patients were 2.2 years and 6 months respectively,
p = .016. Delays in treatment were significantly associated with poor
outcome of initial treatment for physician delay (52% vs 15%, p <
.001) and a trend toward a poor outcome for patient delay (27% vs 15%,
NS). The higher failure rate for physician delay than patient delay
(52% vs 27%) could have been explained by the more – than - 2
year physician delay.
The diagnosis of Lyme disease was associated with objective findings
in half of the delayed patients including erythema migrans, disseminated
erythema migrans, Bell’s palsy, and arthritis of the knee. Other
patients were inappropriately diagnosed with shoulder pain, streptococcal
infection, sinus infection, and Epstein Barr syndrome. In addition,
unnecessary investigations were often carried out that resulted in delays
of treatment for Lyme disease. The study could not address the degree
of physicians’ concern with overdiagnosis and overtreatment and
the degree of patients’ delaying treatment to avoid a label of
“Lyme anxiety”.
Conclusions: Lyme disease patients in this sample were significantly
underdiagnosed and undertreated. The present findings emphasize that
timely treatment of chronic Lyme disease is crucial for outcome. Physicians
are encouraged to become involved in initiatives to reduce underdiagnosis
and undertreatment.
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Selection
Bias in Clinical Trials of Lyme Disease
Cameron
DJ, Mt. Kisco, New York, USA, board member, International Lyme and Associated
Diseases Society (ILADS)
Objective: To assess the prevalence of biases from selection of
patients in a recently completed randomized placebo-controlled clinical
trial.
Background: A recently completed clinical trial by Klempner et
al (N Engl J Med 2001;345(2):85-92.) found no difference in outcome between
3 months of antibiotics (1 month ceftriaxone and 2 months doxycycline)
and placebo. The authors described a population of Lyme disease patients
ill for 4.7 years who had been treated a mean of 3.2 times before enrollment
in their clinical trial.
Method: To evaluate the potential for bias in selection, patients
in the clinical trials were compared with those treated in a surveillance
database. Only surveillance database patients evaluated from 1997 to 2001
confirmed by at least 5 bands on an IgG Western blot were considered.
To help control for baseline differences in the groups, patients in the
clinical trial were matched with the 36 patients in the surveillance database
who had been treated with antibiotics at least 3 times. Outcomes were
compared between the two groups.
Result: The surveillance database patients were less likely to
fail treatment than the clinical trials patients (33% vs 73%). Selection
of patients from the surveillance database without treatment delay and
with successful initial treatment would have led to a failure rate as
low as 14%. Selection of surveillance database patients with either a
treatment delay or failed initial treatment would have led to a failure
rate of 47%. Selection of patients with both treatment delays and failed
initial treatment would have led to failure rates of as high as 66%. Although
the matching was between two differing designs, these data provide some
evidence that Lyme disease patients who enroll in clinical trials do have
different characteristics than patients who do not.
Conclusion: Using an ongoing surveillance database as a control,
these results confirm the potential for bias associated with differential
selection of subjects. Delays in treatment and failed previous treatment
apparently were not considered when enrolling patients in the clinical
trial. Further clinical trials are needed to evaluate the outcome of prolonging
intravenous antibiotics longer than 4 weeks, raising the dose of doxycycline
from 200 mg to 400 mg, and evaluation for co-infections for Lyme disease
patients with delayed treatment or failing initial treatment.
Lyme
Disease International Surveillance Project (LDISP)
Cameron DJ, Gaito
A, Harris N, Bach G, Bellovin S, Bock K, Bock S, Burrascano J, Dickey
CE, Horowitz R, Phillips S, Merr-Sherrer L, Raxlen B, Sherr V, Smith H,
Smith P, Stricker R. International Lyme and Associated Diseases Society
(ILADS), Bethesda, Maryland
Background: Clinicians face a rise in the number of persistent,
recurrent, and refractory Lyme disease cases and growing controversy in
treatment.
Design: The world’s largest Lyme disease database - Lyme
Disease Surveillance Database (LDSP) – consisting of 2575 consecutively
evaluated individuals with Lyme disease will be expanded to multiple international
sites to further examine the emerging problems of persistent, recurrent,
and refractory Lyme disease.
Setting: Geographic areas on an international scale will be selected
for inclusion in the LDISP Program based on their ability to operate and
maintain a high quality Lyme disease reporting system and for their epidemiologically
significant population subgroups. Training courses for surveillance sites
will be arranged during professional meetings that include hands-on use
of the international LDISP software.
Measurement: Data include regular assessments of the broad spectrum
of factors that may influence outcomes, including demographics, history
of a tick bite or rash, serologic testing, co-morbidity, and specific
antibiotic treatments. The database looks to uncover new facts, which
may help clinicians choose the best treatment options including the impact
of different antibiotics on outcome of individuals with persistent, recurrent
and refractory Lyme disease.
Conclusion: The ILADS-sponsored LDISP brings together a database
for clinicians and community members to produce a timely resource for
Lyme disease, significantly influencing the understanding of Lyme disease.
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Integrating
Intramuscular Benzathine Penicillin into the Treatment of Chronic Lyme
Disease
Cameron
DJ, Mt. Kisco, New York, USA, board member, International Lyme and Associated
Diseases Society (ILADS)
Purpose: To assess the safety, tolerance, and efficacy of integrating
intramuscular benzathine penicillin in patients with chronic Lyme disease.
This article provides an overview of the clinical trial results using
this treatment for Lyme disease and discusses the initiation of a Phase
II clinical trial.
Method: Human studies of intramuscular benzathine penicillin were
identified from MEDLINE (1975 to 2002), and references in pertinent articles.
Results: Intramuscular Benzathine penicillin was a long-acting
agent that exploits the prolonged slow division of the spirochete. Intramuscular
benzathine penicillin was the first antibiotic proven efficacious for
chronic Lyme disease. A randomized clinical trial demonstrated that 4
weeks of intramuscular penicillin was more effective than placebo (35%
vs 0%) for Lyme arthritis (Steere et al. NEJM 1985;312:869-874). The concept
of treating Bb spirochete with prolonged blood levels had been introduced
(Luft Ann N Y Acad of Sci 1988;539:352-61). Weekly infusion schedule for
a minimum of 6 months appears very promising in the two case reports (Cimmino
Ann Rheum Dis. 1992;51(8):1007-8) and two case series (Corsaro L et al.
IX International Conference on Lyme Borreliosis & Other Tick-borne
Disorders, 1999., Héctor R. JSTD 2000;7(1):22-25). The data suggest
that 1.2 or 2.4 million units of intramuscular penicillin has efficacy
comparable to many oral and intravenous antibiotics. Patients with meningitis
from Lyme disease should NOT be administered intramuscular antibiotics
due to proven efficacy of intravenous antibioitics. Characteristics of
patients that might predict a benefit from intramuscular benzathine penicillin
are not being identified.
Conclusion: Clinical data favors the use of intramuscular benzathine
penicillin in chronic Lyme disease patients for whom oral and intravenous
antibiotics have failed. These promising results have led to the initiation
of a phase II study that is evaluating the safety, tolerability, and efficacy
of a minimum of 6 months of intramuscular benzathine penicillin for chronic
Lyme disease. top
Feasibility
of Randomized Double-Blind Placebo-Controlled Clinical Trials in Lyme
Disease: Lyme Disease Retreatment Study.
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Cameron DJ, McCoy
K, Glushanok G. Mt. Kisco, New York, USA, board member, International
Lyme and Associated Diseases Society (ILADS)
Objective: To advance knowledge about the treatment of Lyme disease
investigators must adhere to the requirements of a strict experimental
research design while concurrently providing clinical services. The inherent
difficulties are compounded when the trial is to enroll patients with
a recurrence of symptoms of Lyme disease who are concerned with potential
persistent infection, who view enrollment in a placebo-controlled design
with suspicion. We present our experiences in attempting to recruit and
retain patients with chronic Lyme disease in a double-blind randomized
placebo-controlled clinical trial.
Design/setting: A double-blind randomized placebo-controlled clinical
trial in a community setting. The intervention comprised of 2 groups -
3 months of oral Amoxicillin and placebo – in a 2 to 1 ratio.
Results: Of 57 subjects enrolled to date, 19 (33%) were dropped
during follow-up. The most frequent problems subjects reported who withdrew
were persistence of symptoms (10), positive IgM Western blot (4), adverse
events (2), new tick bite (1), non-compliance (1), and concurrent illness
with diabetes (1). The two adverse events were moderate and consisted
of hives and gastric problems. The subject with hives was unblinded and
found to be placebo. Patients were unblinded if additional antibiotics
were considered after treatment failure. Dropouts for treatment failure
were three times more likely to be placebo than treated patients.
Conclusions: The high attrition rate in this trial of Lyme disease
represents a major difficulty in conducting studies of patients with persistent
multi-organ symptomatology who have benefited from antibiotics previously.
Given these difficulties, there is a crucial need to augment clinical
trials with other designs including a surveillance database.
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Psychiatric
aspects of Lyme disease in children and adolescents
Brian A. Fallon,
MD, MPH, Hector Bird, MD, Christina Hoven, DrPH, Daniel Cameron, MD,
MPH, Michael R. Liebowitz, MD, and David Shaffer, MD. Psychiatric
aspects of Lyme disease in children and adolescents: A community epidemiologic
study in Westchester, New York. Journal of Spirochetal and Tick-Borne
Diseases. Vol. 1, No. 4, 1994. pp. 98-100.
To date, no community study has examined the psychiatric aspects and or
sequelae of Lyme disease (LD) among children. As part of a community epidemilogic
study of psychiatric disorders among children ages 9 through 17 in a Lyme
endemic county, parents were asked whether their child had ever been diagnosed
as having LD, and 10.1% (36/357) responded yes to the LD question. Of
the 36, 29 also agreed to take part in a follow-up interview. Sixteen
of the 29 children had had physician-diagnosed LD as well as either an
erythema migrans rash or a positive serology. Fifteen of these 16 received
treatment within 1 month of symptom onset; none of these 15 children were
symptomatic longer than 4 months. Only one child had physical symptoms
at the time of the interview; she was not treated until 4 months after
symptom onset. The child experienced 5 years of intermittent arthritis,
cognitive deficits, emotional problems, severe fatigue, and a deterioration
in school performance. Courses of oral antibiotics were at first associated
with a good response, followed by a resurgence of symptoms months later.
The lifetime prevalence of LD by history among children ages 9 through
17 in an endemic area may be at least 44.8/1000. In general, when LD is
diagnosed early, it responds well to treatment. Delayed diagnosis and
treatment may lead to a chronic course.
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