HSC Section 8_April 2017

investigations. The standard for high-quality studies is a

well-executed randomized controlled trial (RCT).

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

; 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,

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).

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:

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.

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

Crowson et al