Adult-Type Rhabdomyoma of the Larynx in Birt-Hogg-Dubé Syndrome: Evidence for a Real Association.

The autosomal dominant Birt-Hogg-Dubé syndrome is known to be associated with skin, lung and kidney lesions. It is caused by heterozygous germline mutations in the folliculin gene and has a high penetrance. We report the case of a 51 year old woman with Birt-Hogg-Dubé syndrome who presented with a laryngeal mass. Imaging confirmed a mass centered on the piriform sinus and following excision histological examination confirmed the lesion was composed of polygonal cells with abundant eosinophilic cytoplasm consistent with a rhabdomyoma. Laryngeal rhabdomyoma is rare condition and has not been previously described in association with Birt-Hogg-Dubé. In patients with Birt-Hogg-Dubé syndrome who develop upper aerodigestive tract symptoms secondary to mass lesion an adult-type rhabdomyoma might be considered as a differential, with endoscopic excision being the treatment of choice.

Developing a one-stop tinnitus service: outcomes of a joined up management strategy: a retrospective observational cohort study.

RATIONALE, AIMS AND OBJECTIVES: The pressure to deliver quality care with finite resources means that dealing with single-symptom conditions like tinnitus in an efficient and individualized manner has never been more important. Both primary and secondary care practitioners have an obligation to explore efficient delivery of simple management pathways. Commissioners of health care are in a unique position to affect evidence-based strategic change in the management of uncomplicated tinnitus. This study is an attempt to explore one such option. We present the outcomes of a tinnitus patient pathway designed for one-stop management, thereby minimizing unnecessary additional appointments. METHOD: A retrospective observational cohort study of 452 patients referred to a NHS one-stop tinnitus clinic from 2008 to 2012. Clinical care guided was through the use of a structured approach to history taking, neurotological examination and management. RESULTS: 294 out of 452 (65%) of patients referred had unilateral tinnitus. The most common associated complaints were hearing loss (387/452, 86%) and hyperacusis (329/452, 73%). 210 (46%) of patients had their presenting complaint dealt with in a single clinic visit. CONCLUSION: A structured system for referral and management of tinnitus within the health system ensures patients have timely access to evidence-based investigation and treatment. A consistent approach to imaging aimed at identifying retrocochlear pathology can benefit patients through early diagnosis of central pathology and the reassurance provided by a negative scan.

Fixed-dose combination therapy for the prevention of cardiovascular disease.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death and disability worldwide, yet CVD risk factor control and secondary prevention rates remain low. A fixed-dose combination of blood pressure and cholesterol lowering and antiplatelet treatments into a single pill, or polypill, has been proposed as one strategy to reduce the global burden of CVD by up to 80% given its potential for better adherence and lower costs. OBJECTIVES: To determine the effectiveness of fixed-dose combination therapy on reducing fatal and non-fatal CVD events and on improving blood pressure and lipid CVD risk factors for both primary and secondary prevention of CVD. We also aimed to determine discontinuation rates, adverse events, health-related quality of life, and costs of fixed-dose combination therapy. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 6), MEDLINE Ovid (1946 to week 2 July 2013), EMBASE Ovid (1980 to Week 28 2013), ISI Web of Science (1970 to 19 July 2013), and the Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database (HTA), and Health Economics Evaluations Database (HEED) (2011, Issue 4) in The Cochrane Library. We used no language restrictions. SELECTION CRITERIA: We included randomised controlled trials of a fixed-dose combination therapy including at least one blood pressure lowering and one lipid lowering component versus usual care, placebo, or a single drug active component for any treatment duration in adults ≥ 18 years old with no restrictions on presence or absence of pre-existing cardiovascular disease. DATA COLLECTION AND ANALYSIS: Three review authors independently selected studies for inclusion and extracted the data. We evaluated risk of bias using the Cochrane risk of bias assessment tool. We sought to include outcome data on all-cause mortality, fatal and non-fatal CVD events, adverse events, changes in systolic and diastolic blood pressure, total and low density lipoprotein (LDL) cholesterol concentrations, discontinuation rates, quality of life, and costs. We calculated risk ratios (RR) for dichotomous data and weighted mean differences (MD) for continuous data with 95% confidence intervals (CI) using fixed-effect models when heterogeneity was low (I(2) < 50%) and random-effects models when heterogeneity was high (I(2) > 50%). MAIN RESULTS: We found nine randomised controlled trials with a total of 7047 participants. Seven of the nine trials evaluated the effects of fixed-dose combination therapy on primary CVD prevention, and the trial length ranged from six weeks to 15 months. We found a moderate to high risk of bias in the domains of selection, performance, detection, attrition, and other types of bias in five of the nine trials. Compared with the comparator groups, the effects of the fixed-dose combination treatment on mortality (1.2% versus 1.0%, RR 1.26, 95% CI 0.67 to 2.38,  N = 3465) and cardiovascular events (4.0% versus 2.9%, RR 1.38, 95% CI 0.91 to 2.10, N = 2479) were uncertain (low quality evidence). The low event rates for these outcomes, limited availability of data as only two out of nine trials reported on these outcomes, and a high risk of bias in at least one domain suggest that these results should not be viewed with confidence. Adverse events were common in both the intervention (30%) and comparator (24%) groups, with participants randomised to fixed-dose combination therapy being 20% (95% CI 9% to 30%) more likely to report an adverse event. Notably, no serious adverse events were reported. Compared with placebo, the rate of discontinuation among participants randomised to fixed-dose combination was higher (14% versus 11%, RR 1.26 95% CI 1.02 to 1.55). The weighted mean differences in systolic and diastolic blood pressure between the intervention and control arms were -7.05 mmHg (95% CI -10.18 to -3.87) and -3.65 mmHg (95% CI -5.44 to -1.85), respectively. The weighted mean differences (95% CI) in total and LDL cholesterol between the intervention and control arms were -0.75 mmol/L (95% CI -1.05 to -0.46) and -0.81 mmol/L (95% CI -1.09 to -0.53), respectively. There was a high degree of statistical heterogeneity in comparisons of blood pressure and lipids (I(2) ≥ 70% for all) that could not be explained, so these results should be viewed with caution. Fixed-dose combination therapy improved adherence to a multi-drug strategy by 33% (26% to 41%) compared with usual care, but this comparison was reported in only one study. The effects of fixed-dose combination therapy on quality of life are uncertain, though these results were reported in only one trial. No trials reported costs. AUTHORS' CONCLUSIONS: Compared with placebo, single drug active component, or usual care, the effects of fixed-dose combination therapy on all-cause mortality or CVD events are uncertain; only few trials report these outcomes and the included trials were primarily designed to observe changes in CVD risk factor levels rather than clinical events. Reductions in blood pressure and lipid parameters are generally lower than those previously projected, though substantial heterogeneity of results exists. Fixed-dose combination therapy is associated with modest increases in adverse events compared with placebo, single drug active component, or usual care but may be associated with improved adherence to a multidrug regimen. Ongoing trials of fixed-dose combination therapy will likely inform key outcomes.

Allograft tympanoplasty: a historical perspective.

OBJECTIVE: To present the rise and decline of allograft tympanoplasty and investigate how the challenges it has faced may inform us of its future. DATA SOURCES: Articles and books published over the last 48 years that refer to allograft tympanoplasty or its historical roots. HISTORY: The first published account of allograft tympanoplasty is by Ned Chalat in 1964; however, whether he was the first to use the technique is controversial. In 1966, Jean Marquet published the first clinically successful use of allograft tympanic membranes. Since that time, a number of surgeons have trialed both en bloc tympano-ossicular techniques and tympanomeatal techniques with separate ossicle interposition or columellar reconstruction, often with considerable success. The advent of the human immunodeficiency virus and Creutzfeldt-Jakob's disease resulted in a reduction in its application; however, a number of centers are still successfully using the technique in their current practice. CONCLUSION: Whether allograft tympanoplasty will have a place in the future of otology remains to be seen, but an understanding of the history of this technique is essential in evaluating its merit.

Cautery of the tympanic membrane: the lesser known history of myringoplasty.

OBJECTIVE: To present the fascinating, controversial, and tumultuous history of tympanic cautery as a form of myringoplasty and describe the relevance of work more than 150 years old to modern practice and research. DATA SOURCES: More than 70 English, French, and German articles and books published over the last 400 years, which refer to some aspect of tympanic membrane cautery. HISTORY: The first recorded use of silver nitrate to stimulate closure of tympanic membrane perforations is by William Wilde in 1848. Since then, numerous modifications of this technique have been used, and its significance has waxed and waned in response to events within the speciality of otology and the wider world. CONCLUSION: There are lessons to be learned from the rise and fall of this once widely practiced technique. There exists a school of thought that believes that the significance of cautery lies not only in the history of otology but also in its future.