|Otitis media with effusion and s-carboxymethylcysteine and/or its lysine salt: a critical overview
|Pignataro O, Pignataro L D, Gallus G, Calori G, Cordaro C I
To evaluate the therapeutic relevance of the medical treatment with S-carboxymethylcysteine (SCMC) and its monohydrate lysine salt (SCMC-LYS) in patients with otitis media with effusion (OME).
EMBASE, BIOSIS Previews and MEDLINE were searched from 1972 to 1993 using the keywords 'carbocysteine', 'S-carboxymethylcysteine', 'double blind controlled' and 'otitis media'. No other restrictions or sources are discussed.
Study designs of evaluations included in the review
Only randomised placebo-controlled trials with double-blinded outcome assessment and complete follow-up were included. Studies had to provide details of inclusion criteria and treat patients with SCMC or SCMC-LYS.
Specific interventions included in the review
SCMC and SCMC-LYS.
Participants included in the review
Children aged 3 to 12 years with OME of the middle ear, as per otoscopy and per continuous or intercurrent subjective deafness.
Outcomes assessed in the review
Outcome was assessed through measures of overall clinical improvement, specifically the numbers of patients with complete resolution of clinical signs and symptoms and no need for surgical intervention. Clinical improvement was assessed through results of tympanogram at baseline and post treatment for assessment of middle ear function, evaluation of hearing level by audiometry and Rinne test, reversion to normal of otoscopy findings, or subjective improvement referred to by the patient.
How were decisions on the relevance of primary studies made?
The authors do not state how the papers were selected for the review, or how many of the authors performed the selection.
Assessment of study quality
Nine items of methodology were assessed, specifically, publication date, number of patients and drop-outs, patients' age, hospitalisation status, diagnosis, posology, type of study, blindness and outcome measure. The papers were assessed for validity by one independent reviewer, blinded to the study results.
The data were extracted using a standardised data abstract form including publication date, number of patients and drop-outs, patients' age, hospitalisation status, diagnosis, posology, type of study, blindness and outcome measure. No mention is made of the number of reviewers extracting the data.
Methods of synthesis
How were the studies combined?
Efficacy results were reported as odds ratios (ORs) with 95% confidence intervals (CIs) using random-effects and fixed-effect models. The quality weighting was excluded from the analysis due to the arbitrariness of the weighting procedure.
How were differences between studies investigated?
Subgroup analysis was performed on two groups depending upon their adherence to the inclusion criteria, specifically, overall clinical efficacy and effectiveness by tympanogram.
Results of the review
Six studies (430 patients) for overall clinical efficacy analysis and 4 studies (340 patients) for evaluation of effectiveness by tympanogram.
Baseline disease characteristics (severity and chronicity) and duration of treatment were not thought to affect results, since duration was adjusted to disease characteristics and the scope of the intervention was unique. Patients age (range 3 to 12 years) may confound results due to it's influence on the method of assessment. In addition, the results of the review note the variation in drop-outs (8 to 20.9%), inclusion and exclusion criteria and outcome measures, but does not incorporate it further in the review, or consider it's effect on the results.
Tympanograms reversed to normal for 49.7% of patients (80 out of 161 patients) with active drug treatment, compared to 35.5% (54 out of 152 patients) of those on placebo, but the OR of 2.25 (95% CI: 0.97, 5.22, P=0.058) was not significant. In addition, only one study showed evidence of a superior drug effect over placebo. Overall clinical efficacy, not undergoing surgical intervention, was statistically significant for active drug treatment (119 out of 228 patients) compared to placebo (80 out of 127 patients), resulting in an OR of 2.31 (95% CI: 1.28, 4.20, P<0.01).
The authors note the lack of comparability of studies of interventions for children with OME, with variability in disease characteristics, host factors, concurrent illness, duration of OME and clinical end points.
However, the authors conclude that pharmacological treatment with carbocysteine, either as SCMC or as SCMC-LYS, is effective on the overall clinical improvement in OME.
The review provides a good discussion of its objective, participants, interventions, outcomes, search strategy, criteria for inclusion, quality criteria and process of quality assessment. Limited information is provided on the procedure for assessing study relevance or data extraction, as well as cost analysis. The methods for pooling the results though mentioned, are not clearly discussed. Problems are evident with confounding effects and the heterogeneity of studies included in the review. Although referring to the weakness, the review takes limited account of patient characteristics with diversity in patient age, disease characteristics, comorbidities and duration of treatment. In addition, outcomes or end points, loosely termed clinical improvement in the review, cover a wide variety of definitions. Limitations such as these weaken the strength of the evidence provided in the review and the authors' conclusions.
Implications of the review for practice and research
Improvements are necessary in the conduct of research into children with OME.
Pignataro O, Pignataro L D, Gallus G, Calori G, Cordaro C I. Otitis media with effusion and s-carboxymethylcysteine and/or its lysine salt: a critical overview. International Journal of Pediatric Otorhinolaryngology 1996; 35(3): 231-241
Subject indexing assigned by NLM
Adolescent; Adult; Aged; Anti-Infective Agents, Local /administration & Carbocysteine /administration & Child; Child, Preschool; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Lysine /administration & Otitis Media with Effusion /drug therapy; Treatment Outcome; dosage /therapeutic use; dosage /therapeutic use; dosage /therapeutic use
Date bibliographic record published
Date abstract record published
This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.