The value of tocainide in the treatment of tinnitus

Summary We assessed the value of tocainide in the treatment of tinnitus by performing a double-blind controlled trial in which each of 48 patients with annoying tinnitus received either tocainide HCl 900 mg/day or a placebo. Before the trial, the effect of intravenous lidocaine was evaluated in each patient so that both lidocaine and tocainide could be compared in altering tinnitus. We found that tocainide appeared to have no better effect than the placebo, whereas lidocaine suppressed tinnitus in 81% of the patients treated. The mechanisms of action of both drugs as well as their influence on tinnitus are discussed, as are the side effects of tocainide.     

A review of randomized clinical trials in tinnitus.

OBJECTIVES: Review reports of randomized clinical trials (RCTs) in tinnitus to identify well-established treatments, promising developments, and opportunities for improvement in this area of clinical research. STUDY DESIGN: Literature review of RCTs (1964-1998) identified by MEDLINE and OLD MEDLINE searches and personal files. METHODS: Studies were compared with the RCT criteria of Guyatt et al. for quality of design, performance, and analysis; "positive" results were critically examined for potential clinical relevance. RESULTS: Sixty-nine RCTs evaluated tocainide and related drugs, carbamazepine, benzodiazepines, tricyclic antidepressants, 16 miscellaneous drugs, psychotherapy, electrical/magnetic stimulation, acupuncture, masking, biofeedback, hypnosis, and miscellaneous other nondrug treatments. No treatment can yet be considered well established in terms of providing replicable long-term reduction of tinnitus impact, in excess of placebo effects. CONCLUSIONS: Nonspecific support and counseling are probably helpful, as are tricyclic antidepressants in severe cases. Benzodiazepines, newer antidepressants, and electrical stimulation deserve further study. Future tinnitus therapeutic research should emphasize adequate sample size, open trials before RCTs, careful choice of outcome measures, and long-term follow-up.     

Systematic review and meta-analyses of randomized controlled trials examining tinnitus management

Objectives/Hypothesis:

To evaluate the existing level of evidence for tinnitus management strategies identified in the UK Department of Health's Good Practice Guideline.

Study Design:

Systematic review of peer‐reviewed literature and meta‐analyses.

Methods:

Searches were conducted in PubMed, Cambridge Scientific Abstracts, Web of Science, and EMBASE (earliest to August 2010), supplemented by hand searches in October 2010. Only randomized controlled trials that used validated questionnaire measures of symptoms (i.e., measures of tinnitus distress, anxiety, depression) were included.

Results:

Twenty‐eight randomized controlled trials met our inclusion criteria, most of which provide moderate levels of evidence for the effects they reported. Levels of evidence were generally limited by the lack of blinding, lack of power calculations, and incomplete data reporting in these studies. Only studies examining cognitive behavioral therapy were numerous and similar enough to perform meta‐analysis, from which the efficacy of cognitive behavioral therapy (moderate effect size) appears to be reasonably established. Antidepressants were the only drug class to show any evidence of potential benefit.

Conclusions:

The efficacy of most interventions for tinnitus benefit remains to be demonstrated conclusively. In particular, high‐level assessment of the benefit derived from those interventions most commonly used in practice, namely hearing aids, maskers, and tinnitus retraining therapy needs to be performed.     

Radiofrequency treatment of turbinate hypertrophy in subjects using continuous positive airway pressure: a randomized, double-blind, placebo-controlled clinical pilot trial.

OBJECTIVES: To estimate the treatment effect of temperature-controlled radiofrequency (TCRF) reduction of turbinate hypertrophy in patients with sleep-disordered breathing (SDB) treated with nasal continuous positive airway pressure (CPAP), and to assess the impact of study design on this estimate. STUDY DESIGN: Prospective, randomized, double-blind, placebo-controlled clinical pilot trial. METHODS: Twenty-two CPAP-treated patients with SDB with turbinate hypertrophy were randomly assigned to either TCRF turbinate treatment (mean energy 415 +/- 37 J/turbinate; n = 17) or placebo control (n = 5). Changes in nasal obstruction were evaluated between pretreatment and 4 weeks post-treatment. The primary outcome assessed changes in the blinded examiners' findings of nasal obstruction on a visual analogue scale (VAS). Secondary outcomes included blinded patients' and unblinded examiner assessments of nasal obstruction (VAS), nightly CPAP use, adherence, and tolerance, along with sleepiness and general health status scales. The treatment group findings were subtracted from the changes in the placebo group to yield treatment effect. RESULTS: The primary outcome treatment effect by VAS was -0.9 cm (95% confidence interval [CI], -2.4, 0.7), and beyond the placebo effect of -1.5 cm (95% CI: -3.4, 0.3). The secondary treatment effect of the unblinded examiner was -3.0 cm (95% CI, -4.9, -1.1). A beneficial treatment effect was also seen on every secondary outcome except general health status, but only self-reported CPAP adherence (P = .03) was statistically significant. CONCLUSIONS: TCRF turbinate treatment appears to benefit nasal obstruction and CPAP treatment for SDB. Placebo control and double blinding are critical for establishing the true treatment effect. A future definitive trial is feasible to establish statistical significance of these findings.     

耳鸣治疗仪联合银杏叶提取物注射液治疗突聋伴耳鸣的疗效分析

目的观察耳鸣治疗仪联合银杏叶提取物注射液对突聋伴耳鸣的疗效。方法选取108例突聋伴耳鸣患者,随机数表法分为观察组与对照组,各54例。对照组应用银杏叶提取物注射液治疗,观察组联合耳鸣治疗仪。比较两组患者的听力总有效率、耳鸣总有效率、治疗前后听阈值与血液流变学指标。结果两组患者听力总有效率比较,观察组(88.89%)高于对照组(66.67%);两组患者耳鸣总有效率比较,观察组(81.48%)高于对照组(61.11%)。治疗1周、2周、4周后,观察组的听阈值均低于对照组。治疗后观察组的全血高切黏度、全血中切黏度、全血低切黏度、血浆黏度、红细胞聚集指数均低于对照组;治疗后观察组的红细胞变形指数高于对照组。结论耳鸣治疗仪联合银杏叶提取物注射液可有效改善突聋患者血液流变,缓解耳鸣症状,提高患者听力。     

对我国耳鸣治疗文献的循证医学评价

目的复习我国近5年来有关耳鸣的文献资料,分析耳鸣的诊治现状。方法在中国生物医学文献数据库（cmcc）以“耳鸣”和“治疗”为关键词检索2002年～2006年发表的耳鸣文献。依据国际循证医学标准,在中国期刊网医学专题全文数据库（www.cnki.net）下载全文进行逐篇分析。结果以“耳鸣”为关键词共检出758篇文章,再用“治疗”为关键词二次检出496篇,以耳鸣为第一治疗目的的文献204篇,中医药治疗耳鸣文献多达176篇（86.3%）。说明耳鸣治疗例数的186篇（91.2%）,共治疗患者9731例。其中,设有对照试验的75篇（40.3%）,符合临床随机对照试验（randomized controlled trials,RCT）的53篇（28.5%）,应用随机分组的文献62篇（33.3%）,仅有19篇（10.2%）进行了组间均衡性检验;许多文献用“常规药物”治疗耳鸣,但“常规药物”包括的内容却各不相同;无1篇使用真正的安慰剂作对照,仅有2篇文献采用双盲方法,其它均为开放实验;无多中心的协作研究;仅17篇有不良反应记录,3篇文献涉及不良事件的干预措施,7篇文献说明了退出及失访情况,6篇有随访记录,最长随访3年。结论我国治疗耳鸣的文献很多,尤其中医药治疗耳鸣的文献更多,但绝大部分都没有严格按照随机、双盲、对照、多中心的原则进行实验设计,更没有统一的疗效标准,使得结果与结论不够客观、可靠,并且缺乏可比性,影响了国内外学术交流。我国耳鸣治疗研究论文的质量有待提高。     

Clinical trial on tinnitus patients with normal to mild hearing loss: broad band noise and mixed pure tones sound therapy

Background: Tinnitus treatments present a quandary for clinicians, but no thoroughly satisfactory medical treatments are offered to tinnitus patients.

Objective: We compared sound therapy effects of the broad band noise (BBN) and the mixed pure tones on tinnitus patients with normal to mild hearing loss, and the possible mechanisms were discussed.

Material and methods: This study was a double-blinded randomized controlled trial. The patients in two groups were followed up for three months. We used a BBN in group A, and mixed pure tones of nine different frequencies in group B. The Tinnitus Handicap Inventory (THI) and Visual Analog Scale (VAS) measuring were used to evaluate the handicap, loudness and anxiety of tinnitus.

Results: The THI, VAS scores of group B after 3 months were lower than those at baseline. The VAS scores of group B were lower than those of group A at 8 and 12 weeks.

Conclusions: The mixed pure tones were more advantageous than BBN as the sound therapy for tinnitus patients with normal to mild hearing loss.

Significance: This trial provides a special and effective sound therapy method. Tinnitus patients with normal to mild hearing loss will experience more positive effects.

Trial registration: Chinese Clinical Trial Registry identifier: ChiCTR1800015554.     

The effect of beta-blocker premedication on the surgical field during endoscopic sinus surgery

OBJECTIVES/HYPOTHESIS: A number of previous studies have tried to assess the effects of hypotension on the surgical field during endoscopic sinus surgery. These studies have been limited by inadequate sample sizes, lack of a control group, and limited data collection. The aim of the present study was to determine whether the routine use of beta-blockers as a pre-medication could improve the operative field in endoscopic sinus surgery. STUDY DESIGN: A prospective, randomized, double-blinded, placebo-controlled trial. METHODS: Eighty patients undergoing endoscopic sinus surgery who fit the inclusion and exclusion criteria were randomly assigned to receive either a beta-blocker, Metoprolol (group 1), or a placebo tablet (group 2) 30 minutes before surgery. A standard anesthetic protocol was followed. At the commencement of surgery and at regular 15-minute intervals the surgical field, blood loss, heart rate, blood pressure, and isoflurane concentration were assessed. RESULTS: There was a significant difference in overall mean heart rate between the placebo and beta-blocker groups (P <.0001). In the entire group, surgical grade correlated with heart rate (r = 0.36, P <.05) but not with mean arterial blood pressure. Mean surgical grade was similar between the placebo and beta-blocker groups, but early in the study a significantly better surgical field was recorded in the beta-blocker group (P <.001). Surgical grade was significantly better in those with a mean heart rate of less than 60 beats per minute (P <.02). CONCLUSION: Although "optimum" conditions were present in the patients receiving beta-blocker, the authors thought that the grading system was not discriminating enough to demonstrate a significant difference between the groups. The crucial finding in the study was the correlation between heart rate and surgical grade in the entire group. During endoscopic sinus surgery surgery, anesthetic manipulations should be directed at maintaining a low heart rate.     

Lidocaine test in patients with tinnitus: rationale of accomplishment and relation to the treatment with carbamazepine

Objectives: There is strong evidence in the literature about the effect of local anesthetics such as lidocaine in controlling tinnitus; these agents act by stabilizing hair cell membrane and cochlear nerve fibers. However, the effect of intravenous lidocaine is transient, and its oral analog (tocainide) does not have the same efficacy for long-term treatment in patients with tinnitus. Some oral anti-epileptic drugs (carbamazepine, for instance) have been used alternatively in several studies. The aim of this work is to evaluate the response to intravenous lidocaine in patients with intractable tinnitus and the effect of oral carbamazepine in long-term maintenance of tinnitus relief. Patients and methods: We studied prospectively 50 patients (28 females and 22 males; mean age 50.9 years) who underwent the lidocaine test, performed by a 3-min intravenous infusion of 2% lidocaine chloridrate. The patients who experienced any relief after the test started treatment with oral carbamazepine in ascending dosages (50–600 mg/day). Results: The results were classified as tinnitus abolition (18%), marked relief (32%), partial relief (26%), unchanged (22%), or worsening (2%). The lidocaine test showed favorable results in 76% of patients, especially those with bilateral tinnitus (P<0.001). Afterwards, 50% of patients treated with carbamazepine maintained the improvement of tinnitus (P=0.0034). Conclusion: The authors conclude that intravenous lidocaine is effective in reducing intractable tinnitus and that there is a close association between lidocaine and oral carbamazepine effects. Therefore, carbamazepine can be used for the treatment of tinnitus when the patient achieves improvement of symptom after the lidocaine test.     

The application of direct current electrical stimulation of the ear and cervical spine kinesitherapy in tinnitus treatment

Objective

The aim of the study was to evaluate the effectiveness of electrical stimulations of the hearing organ in tinnitus treatment adapting the frequency of stimulation according to tinnitus frequency, to assess the influence of cervical spine kinesitherapy on tinnitus, as well as to evaluate hearing after electrical stimulations alone and together with cervical spine kinesitherapy.

Methods

The study comprised 80 tinnitus, sensorineural hearing loss patients (119 tinnitus ears) divided into two groups. In group I (n – 58 tinnitus ears) electrical stimulation of the hearing organ was performed, in group II (n – 61 tinnitus ears) electrical stimulation together with cervical spine kinesitherapy. Hydrotransmissive, selective electrical stimulations were conducted using direct, rectangular current. The passive electrode was placed on the forehead, the active – a silver probe – was immersed in the external ear canal in 0.9% saline solution. The treatment involved fifteen applications of electrical stimulations (each lasted for 4 min) administered three or four times a week (whole treatment lasted approximately 30 days). The evaluation of the results considered a case history (change from permanent to temporary tinnitus), questionnaires (the increase/decrease of the total points) and the audiometric evaluation of hearing level.

Results

Before the treatment, group I comprised 51 ears (87.93%) with permanent, and 7 ears (12.07%) with temporary tinnitus; group II – 55 ears (90.17%) with permanent and 6 ears (9.83%) with temporary tinnitus. After the treatment, in both groups the number of ears with permanent tinnitus decreased considerably obtaining the pauses or disappearing of tinnitus. Directly after the treatment, group I comprised 25 ears (43.11%) with permanent, and 10 ears (17.24%) with temporary tinnitus, in 23 ears (39.65%) tinnitus disappeared; group II – 33 ears (54.1%) with permanent and 11 ears (18.03%) with temporary tinnitus, in 17 ears (27.87%) tinnitus disappeared.Regarding questionnaires, improvement was observed in group I – in 43.11% of ears, in group II – 32.8%. In both groups audiometric improvement of hearing was recognized.

Conclusions

(1) Electrical stimulation of the hearing organ, with the application of current frequencies according to tinnitus frequencies (selective electrical stimulation), was an efficient method in severe tinnitus treatment. (2) Cervical spine kinesitherapy in the treatment of tinnitus, using electrical stimulation, did not have any supporting influence.     

三七通舒胶囊治疗常见耳源性眩晕的多中心随机对照临床研究

目的:探讨三七通舒胶囊治疗常见耳源性眩晕疾病的疗效及安全性。方法:采用多中心随机对照试验方法,将206例常见耳源性眩晕(突发性聋伴眩晕、梅尼埃病和良性阵发性位置性眩晕)患者随机分为三七通舒组(155例)和敏使朗组(51例),治疗期为14d。治疗前后使用眩晕障碍量表(DHI)进行生活质量评估。结果:采用全分析集(FAS)分析三七通舒组和敏使朗组有效率,结果分别为84.86%和90.92%(P>0.05);采用符合方案集(PPS)分析的结果分别为84.76%和90.92%(P>0.05)。治疗14d后,FAS和PPS分析表明:2组DHI评分均较治疗前降低,且各分项(包括身体、情绪、功能)的评分也较治疗前降低,差异有统计学意义(P<0.01);2组间治疗前后DHI评分的差值,以及各分项(包括身体、情绪、功能)评分的差值,差异均无统计学意义(均P>0.05)。安全性分析表明:三七通舒组不良反应发生率为3.29%,敏使朗组为7.84%,2组间比较差异无统计学意义(P>0.05)。结论:三七通舒胶囊是一种安全、有效的治疗常见耳源性眩晕疾病的药物。     

A double-blind, randomized, placebo-controlled trial of macrolide in the treatment of chronic rhinosinusitis

OBJECTIVES: The antiinflammatory effect of macrolide antibiotics has been well-established, as has their role in the treatment of certain disorders of chronic airway inflammation. Several studies have suggested that long-term, low-dose macrolides may be efficacious in the treatment of chronic rhinosinusitis; however, these studies have lacked a control group. To date, this effect has not been tested in a randomized, placebo-controlled study. METHOD: The authors conducted a double-blind, randomized, placebo-controlled clinical trial on 64 patients with chronic rhinosinusitis. Subjects received either 150 mg roxithromycin daily for 3 months or placebo. Outcome measures included the Sinonasal Outcome Test-20 (SNOT-20), measurements of peak nasal inspiratory flow, saccharine transit time, olfactory function, nasal endoscopic scoring, and nasal lavage assays for interleukin-8, fucose, and a2-macroglobulin. RESULTS: There were statistically significant improvements in SNOT-20 score, nasal endoscopy, saccharine transit time, and IL-8 levels in lavage fluid (P<.05) in the macrolide group. A correlation was noted between improved outcome measures and low IgE levels. No significant improvements were noted for olfactory function, peak nasal inspiratory flow, or lavage levels for fucose and a2-macroglobulin. No improvement in any outcome was noted in the placebo-treated patients. CONCLUSION: These findings suggest that macrolides may have a beneficial role in the treatment of chronic rhinosinusitis, particularly in patients with low levels of IgE, and supports the in vitro evidence of their antiinflammatory activity. Additional studies are required to assess their place in clinical practice.     

Randomized trial of neomycin/dexamethasone spray vs drop preparation for the treatment of active chronic mucosal otitis media

Active mucosal chronic otitis media (COM) is notoriously difficult to treat. A randomized, non-blind trial of a drop vs spray preparation of neomycin sulphate (3250 units/ml) and dexamethasone 0.1% (Otomize) has been performed. The spray was significantly better than drops (91% vs 44%) in the resolution of activity in simple perforations P = 0.002 χ² test, with continuity correction). In ears with an open mastoid cavity, 68% of those on the spray preparation became inactive compared with 42% on drops, a difference which just failed to achieve statistical significance P = 0.06). It is concluded that the spray delivery system is a significant improvement over drops for the treatment of active mucosal COM particularly in the absence of a mastoid cavity.     

Pre-market version of a commercially available hearing instrument with a tinnitus sound generator: feasibility of evaluation in a clinical trial

Objective: This report considers feasibility of conducting a UK trial of combination devices for tinnitus, using data from the study which evaluated different listener programmes available within the pre-market version of Oticon Alta with Tinnitus Sound Generator. Design: Open and closed questions addressed the following feasibility issues: (1) Participant recruitment; (2) Device acceptability; (3) Programme preferences in different self-nominated listening situations; (4) Usability; (5) Compliance; (6) Adverse events. Study sample: Eight current combination hearing aid users (all males) aged between 62–72 years (mean age 67.25 years, SD?=?3.8). Results: All eight participants reported the physical aspects and noise options on the experimental device to be acceptable. Programmes with amplification and masking features were equally preferred over the basic amplification-only programme. Individual preferences for the different programme options varied widely, both across participants and across listening situations. Conclusions: A set of recommendations for future trials were formulated which calls for more “real world” trial design rather than tightly controlling the fitting procedure.     

Psychiatric (Axis I) and personality (Axis II) disorders and subjective psychiatric symptoms in chronic tinnitus

Objective: Chronic tinnitus has been associated with several psychiatric disorders. Only few studies have investigated these disorders using validated diagnostic interviews. The aims were to diagnose psychiatric and personality disorders with structured interviews, to assess self-rated psychiatric symptoms and elucidate temporal relations between psychiatric disorders and tinnitus. Design: Current and lifetime DSM-IV diagnoses of axis-I (psychiatric disorders) and axis-II (personality disorders) were assessed using structured clinical interviews (SCID-I and -II). Current subjective psychiatric symptoms were evaluated via self-rating instruments: the Symptom Check List-90 (SCL-90), the Beck Depression Inventory, and the Dissociative Experiences Scale (DES). Study sample: 83 patients (mean age 51.7, 59% men) with chronic, disturbing tinnitus and a median Tinnitus Handicap Inventory score of 32. Results: The rates of lifetime and current major depression were 26.5% and 2.4%. The lifetime rate of obsessive-compulsive personality disorder (type C) was 8.4%. None of the patients had cluster B personality disorder or psychotic symptoms. The SCL-90 subscales did not differ from the general population, and median DES score was low, 2.4. Conclusions: Tinnitus patients are prone to episodes of major depression and often also have obsessive-compulsive personality features. Psychiatric disorders seem to be comorbid or predisposing conditions rather than consequences of tinnitus. Clinical trial reference: ClinicalTrials.gov (ID NCT 01929837).     

听力正常高调耳鸣患者药物治疗前后畸变产物耳声发射变化分析

目的 通过对急性耳鸣、亚急性耳鸣和慢性耳鸣3组高调耳鸣患者药物治疗前后畸变产物耳声发射(DPOAE)反应幅值变化及3组不同发病时长高调耳鸣患者药物治疗前后DPOAE反应幅值差值结果的分析,了解药物治疗对高调耳鸣患者DPOAE反应幅值的影响及分析药物疗效与疾病发病时长的关系。方法 按发病时长将收治的68例(77耳)听力正常高调耳鸣患者分为3组,急性耳鸣组(病程≤3个月)25例(27耳),亚急性耳鸣组(3﹤病程≤12个月)23例(26耳),慢性耳鸣组(病程>12个月)20例(24耳),对3组患者检测其DPOAE反应幅值。通过药物治疗2周后,再次测量3组患者DPOAE反应幅值,初步评估药物治疗对耳鸣患者DPOAE反应幅值的影响和药物疗效与疾病发病时长的关系。结果 3组患者在药物治疗2周后,其在0.5~1 kHz频点DPOAE反应幅值的变化以及DPOAE反应幅值变化差值比较均无统计学意义,但在2～8 kHz频点,除第3组患者在6、8 kHz治疗前后DPOAE反应幅值的变化无统计学意义外,其余每组患者经药物治疗后,DPOAE反应幅值的改变均具有统计学意义(P<0.05),且3组患者治疗前后DPOAE反应幅值的差值比较具有统计学意义(P<0.05)。3组患者在治疗前后DPOAE引出率变化,在0.5~1.5 kHz频点无明显差异;在2～8 kHz频点有明显差异,但第3组患者在6、8 kHz频点除外。3组患者经药物治疗后,第1组患者有效率100%,第2组患者有效率65.38%,第3组患者有效率29.17%。3组间治疗有效率比较差异具有统计学意义(χ²=19.38,P<0.01)。结论 高调耳鸣患者给予改善内耳微循环等药物治疗是一种有效的治疗方法,发病时长越短,治疗后DPOAE反应幅值提高越大,且治疗后有效率越高,表明病程越短、疗效越佳,让其早发现、早干预,提高治愈率,以改善患者的生活质量。