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Meningitis

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Clinical Trials in Neurology

Part of the book series: Neuromethods ((NM,volume 138))

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Abstract

Although the development of conjugate vaccines has decreased meningitis’ incidence in developed countries, acute bacterial meningitis is still a life-threatening condition worldwide. Therefore, the aim of this chapter is to summarize and discuss methodological characteristics of the 100 most highly cited clinical trials in meningitis between 1995 and 2015. Based on the CONSORT guidelines, a review of the literature was conducted in order to discuss the main challenges involved in this field and guide researchers to develop future clinical trials.

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References

  1. World Health Organization (WHO) (2011) Health topics: meningitis. WHO, Geneva. https://doi.org/10.5860/CHOICE.41-4081

    Book  Google Scholar 

  2. Kasanmoentalib ES, Brouwer MC, van de Beek D (2013) Update on bacterial meningitis: epidemiology, trials and genetic association studies. Curr Opin Neurol 26:282–288. https://doi.org/10.1097/WCO.0b013e328360415c

    Article  PubMed  Google Scholar 

  3. World Health Organization (WHO) (1997) Control of epidemic meningococcal disease. WHO practical guidelines. Int Organ 17:82. https://doi.org/10.1017/S0020818300002071

    Article  Google Scholar 

  4. van de Beek D, de Gans J, Spanjaard L et al (2004) Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med 351:1849–1859. https://doi.org/10.1056/NEJMoa040845

    Article  PubMed  Google Scholar 

  5. Scheld WM, Koedel U, Nathan B, Pfister HW (2002) Pathophysiology of bacterial meningitis: mechanism (s) of neuronal injury. J Infect Dis 186:225–233. https://doi.org/10.1086/344939

    Article  Google Scholar 

  6. Desalermos A, Kourkoumpetis TK, Mylonakis E (2012) Update on the epidemiology and management of cryptococcal meningitis. Expert Opin Pharmacother 13:783–789. https://doi.org/10.1517/14656566.2012.658773

    Article  PubMed  CAS  Google Scholar 

  7. Park BJ, Wannemuehler K a, Marston BJ, et al (2009) Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 2009 23:525–530. doi: https://doi.org/10.1097/QAD.0b013e328322ffac

  8. Torok ME, Bang ND, Chau TTH et al (2011) Dexamethasone and long-term outcome of tuberculous meningitis in Vietnamese adults and adolescents. PLoS One 6:1–6. https://doi.org/10.1371/journal.pone.0027821

    Article  CAS  Google Scholar 

  9. Gleissner B, Chamberlain MC (2006) Neoplastic meningitis. Lancet Neurol 5:443–452. https://doi.org/10.1016/S1474-4422(06)70443-4

    Article  PubMed  Google Scholar 

  10. Herrlinger U, Förschler H, Küker W et al (2004) Leptomeningeal metastasis: survival and prognostic factors in 155 patients. J Neurol Sci 223:167–178. https://doi.org/10.1016/j.jns.2004.05.008

    Article  PubMed  Google Scholar 

  11. Roth P, Weller M (2015) Management of neoplastic meningitis. Chinese Clin Oncol 4:1–8. https://doi.org/10.3978/j.issn.2304-3865.2015.05.02

    Article  Google Scholar 

  12. Tamimi NA, Ellis P (2009) Drug development: from concept to marketing. Nephron Clin Pract 113:125–131. https://doi.org/10.1159/000232592

    Article  CAS  Google Scholar 

  13. Bomgaars L, Geyer JR, Franklin J et al (2004) Phase I trial of intrathecal liposomal cytarabine in children with neoplastic meningitis. J Clin Oncol 22:3916–3921. https://doi.org/10.1200/JCO.2004.01.046

    Article  PubMed  CAS  Google Scholar 

  14. Organization WM (2013) World Medical Association declaration of Helsinki. JAMA 310:2191. https://doi.org/10.1001/jama.2013.281053

    Article  CAS  Google Scholar 

  15. Jackson AT, Nussbaum JC, Phulusa J et al (2012) A phase II randomized controlled trial adding oral flucytosine to high-dose fluconazole, with short-course amphotericin B, for cryptococcal meningitis. AIDS 26:1363–1370. https://doi.org/10.1097/QAD.0b013e328354b419

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Tansuphaswadikul S, Maek-a-Nantawat W, Phonrat B et al (2006) Comparison of one week with two week regimens of amphotericin B both followed by fluconazole in the treatment of cryptococcal meningitis among AIDS patients. J Med Assoc Thai 89:1677–1685

    PubMed  Google Scholar 

  17. Jarvis JN, Meintjes G, Rebe K et al (2012) Adjunctive interferon-γ immunotherapy for the treatment of HIV-associated cryptococcal meningitis. AIDS 26:1105–1113. https://doi.org/10.1097/QAD.0b013e3283536a93

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Whitty CJM, French N et al (2007) Corticosteroids for bacterial meningitis in adults in sub-Saharan Africa. N Engl J Med 357:2441–2450

    Article  PubMed  PubMed Central  Google Scholar 

  19. Bahr NC, Boulware DR (2014) Methods of rapid diagnosis for the etiology of meningitis in adults. Biomark Med 8:1085–1103. https://doi.org/10.2217/bmm.14.67

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Gray LD, Fedorko DP (1992) Laboratory diagnosis of bacterial meningitis. Clin Microbiol Rev 5:130–145. https://doi.org/10.1128/CMR.5.2.130

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Boulware DR, Meya DB, Muzoora C et al (2014) Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis. N Engl J Med 370:2487–2498. https://doi.org/10.1056/NEJMoa1312884

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Marais S, Thwaites G, Schoeman JF et al (2010) Tuberculous meningitis: a uniform case definition for use in clinical research. Lancet Infect Dis 10:803–812. https://doi.org/10.1016/S1473-3099(10)70138-9

    Article  PubMed  Google Scholar 

  23. Montezuma-Rusca JM, Powers JH (2014) Outcome assessments in clinical trials of cryptococcal meningitis: considerations on use of early fungicidal activity as a potential surrogate endpoint for all-cause mortality. Curr Treat Options Infect Dis 6:326–336. https://doi.org/10.14440/jbm.2015.54.A

    Article  PubMed  PubMed Central  Google Scholar 

  24. Ravina B, Cummings J, Mcdermott M, Poole RM (2012) Selecting outcome measures. In: Clinical trials in neurology: design, conduct, analysis, 1st edn. Cambridge University Press, Cambridge, pp 69–77

    Chapter  Google Scholar 

  25. Atkinson AJJ, Colburn WA, DeGruttola VG et al (2001) Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 69:89–95. https://doi.org/10.1067/mcp.2001.113989

    Article  Google Scholar 

  26. Walton MK, Iii JHP, Hobart J et al (2015) Clinical outcome assessments: conceptual foundation — report of the ISPOR clinical outcomes assessment – emerging good practices for outcomes research task force. Value Health 18:741–752

    Article  PubMed  PubMed Central  Google Scholar 

  27. Ross S (2007) Composite outcomes in randomized clinical trials: arguments for and against. Am J Obstet Gynecol 196:119.e1–119.e6. https://doi.org/10.1016/j.ajog.2006.10.903

    Article  Google Scholar 

  28. Nathan N, Borel T, Djibo A et al (2005) Ceftriaxone as effective as long-acting chloramphenicol in short-course treatment of meningococcal meningitis during epidemics: a randomised non-inferiority study. Lancet 366:308–313. https://doi.org/10.1016/S0140-6736(05)66792-X

    Article  PubMed  CAS  Google Scholar 

  29. Kim J (2012) Survival analysis. Pediatr Rev 33:621–643. https://doi.org/10.1016/B978-0-12-802387-7.00035-4

    Article  Google Scholar 

  30. George B, Seals S, Aban I (2014) Survival analysis and regression models. J Nucl Cardiol 21:686–694. https://doi.org/10.1007/s12350-014-9908-2

    Article  PubMed  PubMed Central  Google Scholar 

  31. Kanra GY, Ozen H, Secmeer G et al (1995) Beneficial effects of dexamethasone in children with pneumococcal meningitis. Pediatr Infect Dis J 14:490–494

    Article  CAS  PubMed  Google Scholar 

  32. Gijwani D, Kumhar MR, Singh VB et al (2002) Dexamethasone therapy for bacterial meningitis in adults: a double blind placebo control study. Neurol India 50:63

    PubMed  CAS  Google Scholar 

  33. Sankar J, Singhi P, Bansal A, Ray P, Singhi S (2007) Role of dexamethasone and oral glycerol in reducing hearing and neurological sequelae in children with bacterial meningitis. Indian Pediatr 44:649–656. https://doi.org/10.1301/nr.2006.sept.385

    Article  PubMed  Google Scholar 

  34. Peltola H, Roine I, Ferna J et al (2007) Adjuvant glycerol and/or dexamethasone to improve the outcomes of childhood bacterial meningitis: a prospective, randomized, double-blind, placebo-contreolled trial. Clin Infouctious Dis Am 45:1277–1286. https://doi.org/10.1086/522534

    Article  CAS  Google Scholar 

  35. Kapoor R et al (2003) Blockers of sodium and calcium entry protect axons from nitric oxide-mediated degeneration. Ann Neurol 53(2):174

    Article  CAS  PubMed  Google Scholar 

  36. Schulz KF, Altman DG, Moher D, Group C (2010) Academia and clinic annals of internal medicine CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials OF TO. Ann Intern Med 1996:727–732. https://doi.org/10.7326/0003-4819-152-11-201006010-00232

    Article  Google Scholar 

  37. Schulz KF, Grimes DA (2005) Sample size calculations in randomised trials: mandatory and mystical. Lancet 365:1348–1353. https://doi.org/10.1016/S0140-6736(05)61034-3

    Article  PubMed  Google Scholar 

  38. Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd edn. Lawrence Erlbaum Associates, Mahwah, NJ

    Google Scholar 

  39. Schulz KF (1995) Subverting randomization in controlled trials. JAMA 274:1456–1458

    Article  CAS  PubMed  Google Scholar 

  40. Vickers AJ (2008) How to randomize. J Soc Integr Oncol 4:194–198

    Article  Google Scholar 

  41. Schulz KF, Grimes DA (2002) Allocation concealment in randomised trials: defending against deciphering. Lancet 359:614–618

    Article  PubMed  Google Scholar 

  42. Pildal J, Chan A-W, Hrobjartsson A et al (2005) Comparison of descriptions of allocation concealment in trial protocols and the published reports: cohort study. BMJ 330:1049–1040. https://doi.org/10.1136/bmj.38414.422650.8F

    Article  PubMed  PubMed Central  Google Scholar 

  43. Schulz KF, Grimes DA (2002) Generation of allocation sequences in randomised trials: chance, not choice. Lancet 359:515–519

    Article  PubMed  Google Scholar 

  44. Schulz KF, Grimes DA (2002) Blinding in randomised trials: hiding who got what. Lancet 359:696–700

    Article  PubMed  Google Scholar 

  45. Schulz KF (2002) The landscape and lexicon of blinding in randomized trials. Ann Intern Med 136:254–259

    Article  PubMed  Google Scholar 

  46. Singhi S, Jarvinen A, Peltola H (2008) Increase in serum osmolality is possible mechanism for the beneficial effects of glycerol in childhood bacterial meningitis. Pediatr Infect Dis J 27:892–896. https://doi.org/10.1097/INF.0b013e318175d177

    Article  PubMed  Google Scholar 

  47. Mfinanga S, Chanda D, Kivuyo SL et al (2015) Cryptococcal meningitis screening and community-based early adherence support in people with advanced HIV infection starting antiretroviral therapy in Tanzania and Zambia: an open-label, randomised controlled trial. Lancet 385:2173–2182. https://doi.org/10.1016/S0140-6736(15)60164-7

    Article  PubMed  Google Scholar 

  48. Lasagna L (1979) Problems in publication of clinical trial methodology. Clin Pharmacol Ther 25:751–753

    Article  CAS  PubMed  Google Scholar 

  49. Robiner WN (2005) Enhancing adherence in clinical research. Contemp Clin Trials 26:59–77. https://doi.org/10.1016/j.cct.2004.11.015

    Article  PubMed  Google Scholar 

  50. Thoma A, Farrokhyar F, Mcknight L, Bhandari M (2010) How to optimize patient recruitment. Can J Surg 53:205–210

    PubMed  PubMed Central  Google Scholar 

  51. Molyneux E, Walsh A, Forsyth H et al (2002) Dexamethasone treatment in childhood bacterial meningitis in Malawi: a randomised controlled trial. Lancet 360:211–218. https://doi.org/10.1016/S0140-6736(02)09458-8

    Article  PubMed  CAS  Google Scholar 

  52. Haukoos JS, Newgard CD (2007) Advanced statistics: missing data in clinical research-part 1: an introduction and conceptual framework. Acad Emerg Med 14:662–668. https://doi.org/10.1197/j.aem.2006.11.037

    Article  PubMed  Google Scholar 

  53. Yusuf S, Wittes J, Probstfield J, Tyroler HA (1991) Analysis and interpretation of treatment effects in subgroups of patients in randomized clinical trials. JAMA 266:93–98

    Article  CAS  PubMed  Google Scholar 

  54. Pocock SJ, Assmann SE, Enos LE, Kasten LE (2002) Subgroup analysis, covariate adjustment and baseline comparisons in clinical trial reporting: current practice and problems. Stat Med 21:2917–2930. https://doi.org/10.1002/sim.1296

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Laboratory of Neuromodulation, Center of Clinical Research Learning, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA

    Felipe Jones & Felipe Fregni

  2. Spaulding Research Institute, Spaulding Rehabilitation Hospital, Harvard Medical School, Charlestown, MA, USA

    Felipe Fregni

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  1. Felipe Jones
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  2. Felipe Fregni
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Correspondence to Felipe Fregni .

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Editors and Affiliations

  1. Laboratory of Neuromodulation, Center of Clinical Research Learning, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Felipe Fregni

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Jones, F., Fregni, F. (2018). Meningitis. In: Fregni, F. (eds) Clinical Trials in Neurology. Neuromethods, vol 138. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7880-9_7

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  • DOI: https://doi.org/10.1007/978-1-4939-7880-9_7

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7879-3

  • Online ISBN: 978-1-4939-7880-9

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