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. 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. 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. 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. 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.

Summary: Polymorphic membrane protein (Pmp)21 otherwise known as PmpD is the longest of 21 Pmps expressed by Chlamydophila pneumoniae. Recent bioinformatical analyses annotated PmpD as belonging to a family of exported Gram‐negative bacterial proteins designated autotransporters. This prediction, however, was never experimentally supported, nor was the function of PmpD known. Here, using 1D and 2D PAGE we demonstrate that PmpD is processed into two parts, N‐terminal (N‐pmpD), middle (M‐pmpD) and presumably third, C‐terminal part (C‐pmpD). Based on localization of the external part on the outer membrane as shown by immunofluorescence, immuno‐electron microscopy and immunoblotting combined with trypsinization, we demonstrate that N‐pmpD translocates to the surface of bacteria where it non‐covalently binds other components of the outer membrane. We propose that N‐pmpD functions as an adhesin, as antibodies raised against N‐pmpD blocked chlamydial infectivity in the epithelial cells. In addition, recombinant N‐pmpD activated human monocytes in vitro by upregulating their metabolic activity and by stimulating IL‐8 release in a dose‐dependent manner. These results demonstrate that N‐PmpD is an autotransporter component of chlamydial outer membrane, important for bacterial invasion and host inflammation.

Tinnitus is the conscious perception of a sound without a corresponding external acoustic stimulus, usually described as a phantom perception. One of the major challenges for tinnitus research is to understand the pathophysiological mechanisms triggering and maintaining the symptoms, especially for subjective chronic tinnitus. Our objective was to synthesize the published literature in order to provide a comprehensive update on theoretical and experimental advances and to identify further research and clinical directions. We performed literature searches in three electronic databases, complemented by scanning reference lists from relevant reviews in our included records, citation searching of the included articles using Web of Science, and manual searching of the last 6 months of principal otology journals. One-hundred and thirty-two records were included in the review and the information related to peripheral and central mechanisms of tinnitus pathophysiology was collected in order to update on theories and models. A narrative synthesis examined the main themes arising from this information. Tinnitus pathophysiology is complex and multifactorial, involving the auditory and non-auditory systems. Recent theories assume the necessary involvement of extra-auditory brain regions for tinnitus to reach consciousness. Tinnitus engages multiple active dynamic and overlapping networks. We conclude that advancing knowledge concerning the origin and maintenance of specific tinnitus subtypes origin and maintenance mechanisms is of paramount importance for identifying adequate treatment.

Tinnitus disturbs lives and negatively affects the quality of life of about 2% of the adult world population. Research has shown that the main cause of tinnitus is hearing loss. To analyze a possible association of the degree of hearing loss with the severity of tinnitus, we have performed a retrospective study using admission data on 531 patients suffering from chronic tinnitus. We have found that 83% of our tinnitus patients had a high frequency hearing loss corresponding to a noise-induced hearing loss (NIHL). There was a significant correlation between the mean hearing loss and the tinnitus loudness (p < 0.0001). Interestingly, patients suffering from decompensated chronic tinnitus had a greater degree of hearing loss than the patients with compensated form of tinnitus. In addition, we demonstrate that the degree of hearing loss positively correlates with the two subscales (“intrusiveness” and “auditory perceptional difficulties”) of the Tinnitus Questionnaire. Our retrospective study provides indirect evidence supporting the hypothesis that the degree of noise-induced hearing loss influences the severity of tinnitus.

Conflicting data about the role of gender in tinnitus distress exist in the literature. In addition, little is known about gender differences regarding age and duration of tinnitus. Tinnitus was shown to be related to stress and impairment of coping, sense of coherence, and personal resources. There are known differences in the aforementioned psychological parameters between man and women or among different age groups. The authors hypothesized that this may also be true for patients with chronic tinnitus in addition to gender- and age-related differences in tinnitus annoyance. Therefore, using a large number of patients with chronic tinnitus, the authors analyzed pretherapeutic scores of tinnitus annoyance, perceived stress, proactive coping strategies, sense of coherence, and personal resources in addition to hearing loss and tinnitus pitch and loudness in respect to gender and age of the patients as well as duration of tinnitus. The study group included 607 female and 573 male patients who reported tinnitus for longer than 3 months. The age of the patients ranged from 17 to 81 years in both gender groups. Pretherapeutic scores of tinnitus annoyance, perceived stress, proactive coping strategies, sense of coherence, and personal resources as well as the degree of hearing loss and tinnitus pitch and loudness were analyzed. Irrespective of age and tinnitus duration, women were more annoyed by tinnitus and perceived more stress than men did. In addition, women scored lower than men in proactive coping, sense of coherence, and personal resources but had lower levels of hearing loss and tinnitus loudness than men did. The differences were small, but statistically significant. Analysis of three age groups revealed significant differences between older female and male patients. Tinnitus annoyance was stronger in the middle-age groups of women and men (45-59 years of age) than in younger patients and decreased again in older men (≥60 years of age), but not in older women. Women, but not men, had cognitive distress scores that progressed with age. Older women (≥60 years of age) reported more sleep disturbances than older men. Women had more somatic complaints and coped less efficiently than men, except for younger patients (<45 years of age). The scores of perceived stress decreased whereas scores of sense of coherence and self-efficacy increased in older men and women (≥60 years of age). However, women scored worse than men did in this age group. Hearing loss was found to be correlated with tinnitus loudness and age in both gender groups. The duration of tinnitus affected subjective hearing problems, intrusiveness of tinnitus, and proactive coping. This association was in part age-dependent. The authors found gender differences regarding tinnitus-related distress in patients with chronic tinnitus; however, these differences depended on age and in part on duration of tinnitus. Addressing these differences could result in improved, tailored therapy approaches. For instance, applying physical exercise and relaxation techniques could be of special help for older women to reduce their somatic complaints and sleep disturbances. Similarly, cognitive behavioral therapy could reduce their cognitive distress. Therapy for younger patients should in particular include stress management.