HSC Section 8_April 2017

Crowson et al

investigations. The standard for high-quality studies is a well-executed randomized controlled trial (RCT). 6 Planning and executing an RCT with sufficient power is an expensive and time-consuming undertaking. As a result, a significant proportion of the medical literature evaluating therapy effi- cacy takes the form of retrospective or prospective cohort analyses. These studies are ranked lower in evidence qual- ity 6 ; however, they may represent the only data available. Considering the historical lack of RCTs in the evaluation of diuretics for MD with no additional systematic review available for data since the Cochrane Review update in 2010, 5 we saw an opportunity to further investigate the use of diuretics in MD. The goal of this systematic review is to evaluate the reported efficacy of oral diuretic therapy in the treatment of MD for adult patients as reported over the past 10 years. Specifically, we aim to determine if diuretic therapy produces improvement in hearing and vestibular outcomes. Methods This study was reviewed by the Duke University Medical Center Institutional Review Board (IRB) and deemed to be exempt from full review. Our systematic review protocol was designed in accordance with the PRISMA-P 2015 guidelines (Preferred Reporting Items for Systematic Review and Meta- analysis Protocols). 7 The core search question for this systematic review was to evaluate the reported efficacy of diuretic therapy in the treatment of MD in the past 10 years. We sought to examine studies including any oral diuretic in adult patients, includ- ing reported hearing outcomes, vestibular symptom out- comes, diuretic side effects, and complications of therapy. Inclusion criteria were ‘‘Meniere’s disease’’ or ‘‘endolym- phatic hydrops,’’ with ‘and’ Boolean logic to combine with ‘‘diuretics-osmotic,’’‘‘diuretics,’’ and ‘‘diuretics-potassium sparing.’’ No restrictions were placed on publication country origin or language. Exclusion criteria included studies with medical therapy other than diuretics, as well as review, guideline, commentary, and letter publication types. On December 16, 2014, a search of EBSCOhost, EMBASE, Web of Science, and the Cochrane Reviews Database was completed with inclusion keywords of ‘‘Meniere Disease’’ or ‘‘Endolymphatic hydrops,’’ with ‘and’ or ‘or’ Boolean logic as appropriate to combine with ‘‘Diuretics- Osmotic,’’‘‘Diuretics,’’ and ‘‘Diuretics-Potassium Sparing.’’ Exclusion criteria were set to exclude review, guidelines, commentary, and letter publication types. A PubMed search was also completed with the strategy of ‘‘Therapy/ Broad[filter] AND ((‘‘diuretics’’[Pharmacological Action] OR ‘‘diuretics’’[MeSH Terms] OR ‘‘diuretics’’[All Fields]) AND (‘‘meniere disease’’[MeSH Terms] OR (‘‘meniere’’[All Fields] AND ‘‘disease’’[All Fields]) OR ‘‘meniere disease’’[All Fields] OR (‘‘meniere’s’’[All Fields] AND ‘‘disease’’[All Fields]) OR ‘‘meniere’s disease’’[All Fields])) AND Clinical Trial[ptyp]. Publication types: clinical trial, comparative study, controlled clinical trial, multi-center study, observational study, randomized controlled trial.’’

With the assistance of a Canadian Medical Association reference librarian, an OVID MEDLINE (1946 to November [week 3] 2014) search was completed on December 17, 2014, with the following search strategy: 1) endolymphatic hydrops/ or meniere disease/ or vertigo/; 2) ((labyrinth * or aural or endolymphatic) adj3 (syndrome or vertigo or hydrop * )).mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier]; 3) exp Diuretics/ or diure * .mp. [mp=title, abstract, original title, name of substance word, subject heading word, key- word heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier; 4) (1 or 2) and 3; 5) limit 4 to yr=‘‘2004 –Current.’’ Study entries from the above searches were consolidated into one spreadsheet and duplicates removed. Entries were then systematically screened to remove entries with no abstract available, letter or correspondence publication type, or irrelevance to the core search question. Full text articles were obtained, and 2 independent reviewers (M.G.C., A.P.) appraised the articles to exclude review, case report, qualita- tive survey, basic science, or diagnostic testing publication types. A data extraction spreadsheet was created with head- ings for title, author, year of publication, country of origin, size of study patient population, study type, diagnosis, diag- nostic criteria, intervention, follow-up duration, outcome measures, hearing outcomes, vestibular symptom outcomes, diuretic side effects, complications of therapy, and study conclusion. The studies were appraised according to the Oxford Centre for Evidence-Based Medicine’s Level of Evidence grading system. 6 As the outcome measurements were heterogeneous, a meaningful quantitative analysis was impossible. We per- formed a qualitative analysis of hearing and vestibular out- comes described for each study to determine if clinical benefit was evident, and we aggregated these results to gen- erate an overall impression. Results In sum, 439 studies were identified with our search strategy and subsequently analyzed for possible inclusion ( Figure 1 ); 122 duplicate studies were removed. Eleven abstracts were excluded, as no abstract body was available; 1 was a letter to the editor; and 1 was not related to diuretics in the treatment of MD. The full-text articles for the 306 remaining studies were obtained. A total of 287 full texts were excluded, including review articles, case reports, qualitative surveys, and basic science study designs. Thirty-five articles described the use of diuretics with MD; however, the discussion was in the context of the development of new diagnostic tests and not treatment related. Nineteen studies qualified for inclusion in our systematic review ( Table 1 ). Twelve (63.2%) were retrospective case series; 4 (21.1%), RCTs; 2 (10.5%), case-control; and 1 (5.3%), prospective case series. According to the Oxford Centre for Evidence-Based Medicine’s Level of Evidence

24