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Meta-Analysis: Cysticidal Drugs for Neurocysticercosis: Albendazole and Praziquantel

Oscar H. Del Brutto, MD; Karen L. Roos, MD; Christopher S. Coffey, PhD; and Héctor H. García, MD, PhD
[+] Article and Author Information

From Hospital-Clínica-Kennedy, Guayaquil, Ecuador; Indiana University School of Medicine, Indianapolis, Indiana; University of Alabama at Birmingham, Birmingham, Alabama; and Instituto de Ciencias Neurológicas and Universidad Peruana Cayetano Heredia, Lima, Peru.


Grant Support: None.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Oscar H. Del Brutto, MD, Air Center 3542, PO Box 522970, Miami, FL 33152-2970; e-mail, odb@gye.satnet.net.

Current Author Addresses: Dr. Del Brutto: Department of Neurological Sciences, Hospital-Clíníca-Kennedy, Seccion Delta, Sotano, Oficina 7, Cuidadela Nueva Kennedy, Calle 9 na s/n y Avenue San Jorge, Guayaquil, Ecuador.

Dr. Roos: Department of Neurology, Indiana University School of Medicine, 550 North University Boulevard, Suite 4411, Indianapolis, IN 46202.

Dr. Coffey: Department of Biostatistics, University of Alabama at Birmingham, Ryals Public Health Building, Room 327M, Birmingham, AL 35294.

Dr. García: Department of Microbiology, Universidad Peruana Cayetano Heredia, Avenue H. Delgado 430, SMP, Lima 31, Peru.


Ann Intern Med. 2006;145(1):43-51. doi:10.7326/0003-4819-145-1-200607040-00009
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Background: Conflicting reports have caused controversy on whether cysticidal drugs modify the natural course of neurocysticercosis.

Purpose: To perform a meta-analysis of randomized trials assessing the effect of cysticidal drugs on neuroimaging and clinical outcomes of patients with neurocysticercosis.

Data Sources: Search of MEDLINE, Cochrane Database of Systematic Reviews, and Literatura Latino-Americana y del Caribe en Ciencias de la Salud (LILACS) between 1979 and 2005. There were no language restrictions.

Study Selection: Randomized trials of cysticidal drug therapy for neurocysticercosis that met predefined criteria designed to allow characterization of the disease and objective evaluation of therapy.

Data Abstraction: The authors independently reviewed articles. Abstracted data included study design, number of randomly assigned patients and withdrawals, intervention, adverse events, timing of neuroimaging studies, and outcomes.

Data Synthesis: Eleven studies met the inclusion criteria. Six trials randomly assigned 464 patients with cystic lesions (vesicular cysticerci), and 5 trials randomly assigned 478 patients with enhancing lesions (colloidal cysticerci). Parasites were located in the brain parenchyma or subarachnoid space at the convexity of the cerebral hemispheres. Cysticidal drug therapy was associated with complete resolution of cystic lesions (44% vs. 19%; P = 0.025). Trials on enhancing lesions showed a trend toward lesion resolution favoring the use of cysticidal drugs (72% vs. 63%; P = 0.38) that became statistically significant when an outlier trial was excluded from the analysis (69% vs. 55%; P = 0.006). Risk for seizure recurrence was lower after cysticidal treatment in patients with enhancing lesions (14% vs. 37%; P < 0.001). The single trial evaluating the frequency of seizures in patients with cystic lesions showed a 67% reduction in the rate of generalized seizures with treatment (P = 0.006).

Limitations: Not all studies focused on the control of seizures as an outcome.

Conclusions: Cysticidal drug therapy results in better resolution of colloidal and vesicular cysticerci, lower risk for recurrence of seizures in patients with colloidal cysticerci, and a reduction in the rate of generalized seizures in patients with vesicular cysticerci.

Figures

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Figure 1.
Study flow diagram.

LILACS = Literatura Latino-Americana y del Caribe en Ciencias de la Salud.

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Figure 2.
Forest plot showing the effects of cysticidal drugs on lesion resolution in trials of patients with parenchymal brain-enhancing lesions.
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Figure 3.
Forest plot showing the effects of cysticidal drugs on lesion resolution in trials of patients with intracranial cystic lesions.
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Figure 4.
Forest plot showing the effects of cysticidal drugs on seizure recurrence in patients with parenchymal brain-enhancing lesions.
Grahic Jump Location

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Making Difficult Choices
Posted on July 27, 2006
Susan Galandiuk
Price Institute of Surgical Research, University of Louisville, ,KY 40202
Conflict of Interest: None Declared

TO THE EDITOR: Del Brutto and colleagues (1) provide a well thought out meta-analysis, in which they state clear inclusion criteria and three authors independently reviewed articles. Over the past decade, meta- analyses have been increasingly used in medicine. In addition to providing a more precise estimate of the effect of a treatment or exposure, properly conducted meta-analyses combine studies to show a less biased estimate than traditional reviews (2). One way of achieving this less biased estimate is by utilizing multiple databases when searching for studies that meet meta-analysis inclusion criteria (3). Failure to search multiple health databases can result in missing up to half of the relevant literature (4).

Embase and Medline are the two most comprehensive databases used in meta-analyses. Embase contains over 18 million records, including an index of over 7,000 journals from 70 countries. It is recognized as an important source of pharmacological and biomedical literature. It is also a relevant source of negative studies, since European and non-English journals are said to be more likely to publish negative findings. Despite the recognized importance of searching Embase, many meta-analysts [including Del Brutto et al. (1)] neglect it in their search for relevant articles.

We believe that cost is an important reason for this lack of use. While Medline is free of charge and available to anyone by internet, Embase is more difficult to access and considerably more expensive. Meta- analysts have to make the difficult choice of whether they should use funding to access Embase.

For researchers without the necessary funding to access pay-for-view databases, several options remain. An important source for obtaining negative studies is by hand searching gray literature (defined as abstracts in major meetings and symposiums, newsletters, theses, etc.). It has been estimated that omitting gray literature from meta-analyses can affect analysis outcome by as much as 15% (5).

Searching multiple databases is an important step in retrieving relevant articles for meta-analyses. Utilizing as many sources of information as possible reduces bias. Pay-for-view databases make it more difficult for researchers to acquire relevant information and, in turn, may compromise meta-analyses.

Suhal S. Mahid, MRCS

Kyle S. Minor, BA

Susan Galandiuk, MD

Price Institute of Surgical Research, University of Louisville, Louisville, KY 40202

References

1. Del Brutto OH, Roos KL, Coffey CS, Garcia HH. Meta-analysis: Cysticidal drugs for Neurocysticercosis: Albendazole and Praziquantel. Ann Intern Med. 2006;145:43-51. [PMID: 16818928]

2. Mahid SS, Hornung CA, Minor KS, Turina M, Galandiuk S. Quality assessment of systematic reviews and meta-analysis for the surgeon scientist. Br J Surg. 2006 (in press).

3. Sampson M, Barrowman NJ, Moher D, Klassen TP, Pham B, Platt R, et al. Should meta-analysts search Embase in addition to Medline? J Clin Epidemiol. 2003;56:943-55. [PMID: 14568625]

4. Dickersin K, Scherer R, Lefebvre C. Identifying relevant studies for systematic reviews. BMJ. 1994;309:1286-91. [PMID: 7718048]

5. McAuley L, Pham B, Tugwell P, Moher D. Does the inclusion of grey literature infleunce estimates of intervention effectiveness reported in meta-analyses? Lancet. 2000;356:1228-31. [PMID: 11072941]

Conflict of Interest:

None declared

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