Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults

BACKGROUND: There is no evidence-based guidance to facilitate design decisions for confirmatory trials or systematic reviews investigating treatment efficacy for adults with tinnitus. This systematic review therefore seeks to ascertain the current status of trial designs by identifying and evaluating the reporting of outcome domains and instruments in the treatment of adults with tinnitus. METHODS: Records were identified by searching PubMed, EMBASE CINAHL, EBSCO, and CENTRAL clinical trial registries (ClinicalTrials.gov, ISRCTN, ICTRP) and the Cochrane Database of Systematic Reviews. Eligible records were those published from 1 July 2006 to 12 March 2015. Included studies were those reporting adults aged 18 years or older who reported tinnitus as a primary complaint, and who were enrolled into a randomised controlled trial, a before and after study, a non-randomised controlled trial, a case-controlled study or a cohort study, and written in English. Studies with fewer than 20 participants were excluded. RESULTS: Two hundred and twenty-eight studies were included. Thirty-five different primary outcome domains were identified spanning seven categories (tinnitus percept, impact of tinnitus, co-occurring complaints, quality of life, body structures and function, treatment-related outcomes and unclear or not specified). Over half the studies (55 %) did not clearly define the complaint of interest. Tinnitus loudness was the domain most often reported (14 %), followed by tinnitus distress (7 %). Seventy-eight different primary outcome instruments were identified. Instruments assessing multiple attributes of the impact of tinnitus were most common (34 %). Overall, 24 different patient-reported tools were used, predominantly the Tinnitus Handicap Inventory (15 %). Loudness was measured in diverse ways including a numerical rating scale (8 %), loudness matching (4 %), minimum masking level (1 %) and loudness discomfort level (1 %). Ten percent of studies did not clearly report the instrument used. CONCLUSIONS: Our findings indicate poor appreciation of the basic principles of good trial design, particularly the importance of specifying what aspect of therapeutic benefit is the main outcome. No single outcome was reported in all studies and there was a broad diversity of outcome instruments. PROSPERO REGISTRATION: The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525. Registered on 12 March 2015 revised on 15 March 2016. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1399-9) contains supplementary material, which is available to authorized users

Polarization microscopy of picrosirius red stained sections. A useful method for qualitative evaluation of intestinal wall collagen

Collagen pattern in healing anastomosis of intestinal wall was compared with its normal pattern in the submucosal layer. Polarization colours were recorded for thin (0.8 pm or less) and thick (1.6-2.4 pm) collagen fibres. The polarization colours of thick collagen fibres in the anastomotic site were more greenish-yellow and yellow than those in normal intestine which were more yellowish-orange and orange. These findings indicate that the collagen in the anastomotic site 4 days after operation is less packed than the collagen of normal rat intestine. Examination of the polarization colours of Picrosirius red-stained sections is a useful procedure to follow healing of anastomotic sites or diagnosis of collagen pathology in different pathologic conditions in the intestinal wall

Temporal Integration at thresholds at very low and infrasonic frequencies

International audienceThe human ear can perceive sound well below 20 Hz, i.e. infrasound, provided that the levels involved are high enough to be heard. It is also known that below a critical duration, the shorter the sounds are, the higher their intensity must be to be detected. Furthermore, this duration seems to increase with decreasing frequency. While most studies about hearing at infrasonic frequencies mention the necessity to use stimuli of sufficient length to be above the critical duration, to our knowledge only one study has actually measured the critical duration for a couple frequencies below 20 Hz and showed that at 4 Hz, the critical duration would be above 4000 ms. The presented work aims at bringing more precision to the measurement of the critical duration. In this paper, we will present the experimental setup built in order to reproduce infrasound at audible levels and the test procedure that we will use to measure the critical duration at different durations and frequencies below 63 Hz