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Systematic Reviews
Published in: Systematic Reviews 1/2016

Open Access 01-12-2016 | Protocol

Efficacy and safety of pharmacological agents in the treatment of erythema migrans in early Lyme borreliosis—systematic review protocol

Authors: Gabriel Torbahn, Heidelore Hofmann, Roman Allert, Michael H. Freitag, Rick Dersch, Volker Fingerle, Harriet Sommer, Edith Motschall, Jörg J. Meerpohl, Christine Schmucker

Published in: Systematic Reviews | Issue 1/2016

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Abstract

Background

Erythema migrans represents an early cutaneous and most common manifestation of Lyme borreliosis. Recommendations regarding pharmacological agents, dose and duration of treatment are subject of intense debate. This review aims to explore differences in efficacy and safety between pharmacological treatments and control treatment.

Methods

To identify relevant studies, we will conduct a systematic literature search. We will include randomised controlled trials (RCTs) and non-RCTs. Eligible comparative studies need to (1) consider patients with a diagnosis of erythema migrans resulting from Lyme borreliosis and (2) compare different pharmacological agents against each other, against any other non-pharmacological treatment, placebo or no treatment. Two review authors will independently assess included studies for risk of bias according to the methods of the Cochrane Handbook for Systematic Reviews of Interventions and related to specific study designs. We will address patient-relevant outcomes including clinical remission of cutaneous symptoms, any treatment-related adverse events, quality of life and progressive symptoms such as neuroborreliosis or Lyme carditis and flu-like symptoms. Provided that the identified trials are comparable in terms of clinical issues, combined estimates will be provided. Estimations of treatment effects will be calculated based on a random effects model. Heterogeneity will be evaluated based on I 2 and chi-square test. In case of significant heterogeneity, a pooled estimate will not be provided, but heterogeneity will be investigated on the basis of methodological and clinical study aspects. We plan subgroup analysis to reveal potential differences in the effect estimates between patient populations and treatment specifications. We will consider risk of bias using sensitivity analyses to decide whether to rely on the pooled estimates. The quality of a body of evidence for individual outcomes will be assessed using the GRADE approach.

Discussion

Benefits and harms of pharmacological treatment in erythema migrans have not yet been adequately assessed. This systematic review will evaluate and summarise available evidence addressing benefits and harms of different pharmacological treatments. In addition, this summary of clinical evidence will inform decision-making between clinicians and patients and will play an important part in patient care.

Systematic review registration

PROSPERO: CRD42016037932
Appendix
Available only for authorised users
Literature
1.
Altpeter E et al. Tick related diseases in Switzerland, 2008 to 2011. Swiss Med Wkly. 2013;143:w13725.PubMed
2.
Bacon RM, Kugeler KJ, Mead PS. Surveillance for Lyme disease—United States, 1992-2006. MMWR Surveill Summ. 2008;57(10):1–9.PubMed
3.
Berglund J et al. An epidemiologic study of Lyme disease in southern Sweden. N Engl J Med. 1995;333(20):1319–27.CrossRefPubMed
4.
5.
Huppertz HI et al. Incidence of Lyme borreliosis in the Wurzburg region of Germany. Eur J Clin Microbiol Infect Dis. 1999;18(10):697–703.CrossRefPubMed
6.
Ni XB et al. Lyme borreliosis caused by diverse genospecies of Borrelia burgdorferi sensu lato in northeastern China. Clin Microbiol Infect. 2014;20(8):808–14.CrossRefPubMed
7.
Eriksson P et al. The many faces of solitary and multiple erythema migrans. Acta Derm Venereol. 2013;93(6):693–700.CrossRefPubMed
8.
Hofmann H. The variable spectrum of cutaneous Lyme borreliosis. Diagnosis and therapy. Hautarzt. 2012;63(5):381–9.CrossRefPubMed
9.
10.
Stanek G et al. Lyme borreliosis: clinical case definitions for diagnosis and management in Europe. Clin Microbiol Infect. 2011;17(1):69–79.CrossRefPubMed
11.
12.
13.
Nadelman RB, Wormser GP. Recognition and treatment of erythema migrans: are we off target? Ann Intern Med. 2002;136(6):477–9.CrossRefPubMed
14.
Smith RP et al. Clinical characteristics and treatment outcome of early Lyme disease in patients with microbiologically confirmed erythema migrans. Ann Intern Med. 2002;136(6):421–8.CrossRefPubMed
15.
Auwaerter PG, Aucott J, Dumler JS. Lyme borreliosis (Lyme disease): molecular and cellular pathobiology and prospects for prevention, diagnosis and treatment. Expert Rev Mol Med. 2004;6(2):1–22.CrossRefPubMed
16.
17.
Strle F, Stanek G. Clinical manifestations and diagnosis of lyme borreliosis. Curr Probl Dermatol. 2009;37:51–110.CrossRefPubMed
18.
Wormser GP et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43(9):1089–134.CrossRefPubMed
19.
20.
Cameron DJ, Johnson LB, Maloney EL. Evidence assessments 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;12(9):1103–35.CrossRefPubMedPubMedCentral
21.
22.
Dattwyler RJ et al. Amoxycillin plus probenecid versus doxycycline for treatment of erythema migrans borreliosis. Lancet. 1990;336(8728):1404–6.CrossRefPubMed
23.
Luft BJ et al. Azithromycin compared with amoxicillin in the treatment of erythema migrans. A double-blind, randomized, controlled trial. Ann Intern Med. 1996;124(9):785–91.CrossRefPubMed
24.
IOM. Critical needs and gaps in understanding prevention, amelioration, and resolution of lyme and other tick-borne diseases: the short-term and long-term outcomes: workshop report. Washington: National Academies Press (US). National Academy of Sciences; 2011.
25.
Dersch R et al. Efficacy and safety of pharmacological treatments for acute Lyme neuroborreliosis—a systematic review. Eur J Neurol. 2015;22(9):1249–59.CrossRefPubMed
26.
27.
Shamseer L et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015;349:g7647.CrossRefPubMed
28.
Gartlehner G. Assessment of adverse effects and applicability—two areas not (yet) covered adequately in Cochrane reports. Z Evid Fortbild Qual Gesundhwes. 2008;102(8):497–502.CrossRefPubMed
29.
Chou R et al. AHRQ series paper 4: assessing harms when comparing medical interventions: AHRQ and the effective health-care program. J Clin Epidemiol. 2010;63(5):502–12.CrossRefPubMed
30.
Ware Jr JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30(6):473–83.CrossRefPubMed
31.
Turner-Stokes L et al. The Neurological Impairment Scale: reliability and validity as a predictor of functional outcome in neurorehabilitation. Disabil Rehabil. 2014;36(1):23–31.CrossRefPubMed
32.
van Swieten JC et al. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988;19(5):604–7.CrossRefPubMed
33.
Review manager (RevMan) [Computer program]. Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration; 2014.
34.
Higgins JPT, Altman DG, Sterne JAC. Chapter 8: assessing risk of bias in included studies. In: Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 (updated March 2011). Available from: http://​handbook.​cochrane.​org/​. Accessed 16 Nov 2015.
35.
Sterne JAC, Higgins JPT, Reeves BC, on behalf of the development group for ACROBAT-NRSI. A Cochrane Risk Of Bias Assessment Tool: for Non-Randomized Studies of Interventions (ACROBAT-NRSI), Version 1.0.0, 24 September 2014. Available from: http://​www.​riskofbias.​info. Accessed 16 Nov 2015.
36.
Friedrich JO, Adhikari NK, Beyene J. The ratio of means method as an alternative to mean differences for analyzing continuous outcome variables in meta-analysis: a simulation study. BMC Med Res Methodol. 2008;8(1):32.CrossRefPubMedPubMedCentral
37.
Guyatt GH et al. GRADE guidelines: 13. Preparing summary of findings tables and evidence profiles—continuous outcomes. J Clin Epidemiol. 2013;66(2):173–83.CrossRefPubMed
38.
39.
Ebrahim S et al. Addressing continuous data for participants excluded from trial analysis: a guide for systematic reviewers. J Clin Epidemiol. 2013;66(9):1014–1021.e1.CrossRefPubMed
40.
Ebrahim S et al. Addressing continuous data measured with different instruments for participants excluded from trial analysis: a guide for systematic reviewers. J Clin Epidemiol. 2014;67(5):560–70.CrossRefPubMed
41.
42.
Deeks JJ, Higgins JPT, Altman DG. Chapter 9: analysing data and undertaking meta-analyses. In: Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions. The Cochrane Collaboration, 2011; Version 5.1.0 (updated March 2011). Available from: http://​handbook.​cochrane.​org/​. Accessed 16 Nov 2015.
43.
Sterne JA et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ. 2011;343:d4002.CrossRefPubMed
44.
45.
Balshem H et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64(4):401–6.CrossRefPubMed
46.
47.
Evison J et al. Lyme disease Part 2: clinic and treatment. Rev Med Suisse. 2006;2(60):925–8. 930-4.PubMed
48.
Loewen PS, Marra CA, Marra F. Systematic review of the treatment of early Lyme disease. Drugs. 1999;57(2):157–73.CrossRefPubMed
Metadata
Title
Efficacy and safety of pharmacological agents in the treatment of erythema migrans in early Lyme borreliosis—systematic review protocol
Authors
Gabriel Torbahn
Heidelore Hofmann
Roman Allert
Michael H. Freitag
Rick Dersch
Volker Fingerle
Harriet Sommer
Edith Motschall
Jörg J. Meerpohl
Christine Schmucker
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Systematic Reviews / Issue 1/2016
Electronic ISSN: 2046-4053
DOI
https://doi.org/10.1186/s13643-016-0251-3

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