Lansoprazole for persistent throat symptoms in secondary care: the TOPPITS RCT.

BACKGROUND: Persistent throat symptoms are commonly attributed to 'laryngopharyngeal reflux'. Despite a limited evidence base, these symptoms are increasingly being treated in primary care with proton pump inhibitors. OBJECTIVE: To assess the value of proton pump inhibitor therapy in patients with persistent throat symptoms. DESIGN: This was a double-blind, placebo-controlled, randomised Phase III trial. SETTING: This was a multicentre UK trial in eight UK ear, nose and throat departments. PARTICIPANTS: A total of 346 participants aged ≥ 18 years with persistent throat symptoms and a Reflux Symptom Index score of ≥ 10, exclusive of the dyspepsia item, were recruited. INTERVENTION: Random allocation (1 : 1 ratio) to either 30 mg of lansoprazole twice daily or matched placebo for 16 weeks. MAIN OUTCOME MEASURE: Symptomatic response (i.e. total Reflux Symptom Index score after 16 weeks of therapy). RESULTS: A total of 1427 patients were screened and 346 were randomised. The mean age was 52 years (standard deviation 13.7 years, range 20-84 years); 150 (43%) participants were male and 196 (57%) were female; 184 (53%) participants had a mild Reflux Symptom Index minus the heartburn/dyspepsia item and 162 (47%) had a severe Reflux Symptom Index minus the heartburn/dyspepsia item. A total of 172 patients were randomised to lansoprazole and 174 were randomised to placebo. MAIN OUTCOMES: A total of 267 participants completed the primary end-point visit (lansoprazole, n = 127; placebo, n = 140), of whom 220 did so between 14 and 20 weeks post randomisation ('compliant' group); 102 received lansoprazole and 118 received placebo. The mean Reflux Symptom Index scores at baseline were similar [lansoprazole 22.0 (standard deviation 8.0), placebo 21.7 (standard deviation 7.1), overall 21.9 (standard deviation 7.5)]. The mean Reflux Symptom Index scores at 16 weeks reduced from baseline in both groups [overall 17.4 (standard deviation 9.9), lansoprazole 17.4 (standard deviation 9.9), placebo 15.6 (standard deviation 9.8)]. Lansoprazole participants had estimated Reflux Symptom Index scores at 16 weeks that were 1.9 points higher (worse) than those of placebo participants (95% confidence interval -0.3 to 4.2; padj = 0.096), adjusted for site and baseline severity. SECONDARY OUTCOMES: Ninety-five (43%) participants achieved a Reflux Symptom Index score in the normal range (< 12) at 16 weeks: 42 (41%) in the lansoprazole group and 53 (45%) in the placebo group. A total of 226 participants completed the end-of-trial follow-up visit (lansoprazole, n = 109; placebo, n = 117), of whom 181 were 'compliant'. The mean Reflux Symptom Index scores at 12 months reduced from baseline in both groups [lansoprazole 16.0 (standard deviation 10.8), placebo 13.6 (standard deviation 9.6), overall 14.7 (standard deviation 10.2)]. A total of 87 (48%) participants achieved a Reflux Symptom Index score in the normal range at 12 months: 33 (40%) in the lansoprazole group and 54 (55%) in the placebo group. Likewise, the Comprehensive Reflux Symptom Score and Laryngopharyngeal Reflux - Health Related Quality of Life total scores and subscales all showed very similar changes in the lansoprazole and placebo cohorts at both 16 weeks and 12 months. LIMITATIONS: Drop-out rate and compliance are issues in pragmatic clinical trials. The Trial Of Proton Pump Inhibitors in Throat Symptoms (TOPPITS) aimed to detect clinically relevant difference with 90% power. The 346 randomised participants reduced to 283 at the primary end point; 267 completed the primary outcome measure, 220 within the protocol time scale. Despite this, the powers to detect the clinically relevant difference in Reflux Symptom Index score at 16 weeks were 82% (compliant comparison) and 89% (pragmatic comparison). The lack of difference between lansoprazole and placebo is generalisable across NHS clinics. CONCLUSIONS: Participants on lansoprazole did not report significantly better outcomes than participants on placebo on any of the three patient-reported outcome tools (Reflux Symptom Index, Comprehensive Reflux Symptom Score and Laryngopharyngeal Reflux - Health Related Quality of Life). This multicentre, pragmatic, powered, definitive Phase III trial found no evidence of benefit for patients by treating persistent throat symptoms with lansoprazole. TRIAL REGISTRATION: Current Controlled Trials ISRCTN38578686 and EudraCT number 2013-004249-17. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 3. See the NIHR Journals Library website for further project information.

BACKGROUND: One of the commonest reasons for patients attending hospital throat or voice clinics is persistent throat symptoms, which include a feeling of a lump in the throat, a cough or a hoarse voice. Over time, more of these patients are being treated with proton pump inhibitors to suppress stomach acid in the belief that stomach acid entering the throat causes the symptoms, but there is little evidence that these medications work. STUDY AIM: The aim of this study is to explore whether or not having a 16-week course of proton pump inhibitors has any impact on throat symptoms. We also tested the usefulness of three different questionnaires in measuring throat symptoms, explored side effects and whether or not patients adhere to treatment, and measured patients' quality of life. METHODS: Patients with persistent (lasting for more than 6 weeks) throat symptoms who agreed to participate were randomised to receive either the proton pump inhibitor lansoprazole or a placebo. Participants took lansoprazole or placebo for 16 weeks. Symptoms and quality of life were measured before patients were randomised and at 4 and 12 months after randomisation. RESULTS: The total number of participants was 346. The mean Reflux Symptom Index outcome score (higher scores meaning worse symptoms) was 22 before the 4-month course of capsules, 16 after 4 months and 15 after 12 months. Participant-reported throat symptoms and quality of life in all participants improved over the 12 months of the study. There was no difference in the symptom improvement experienced by proton pump inhibitor and placebo participants. CONCLUSIONS: This study shows that proton pump inhibitors do not benefit patients with persistent throat symptoms. Future research should focus on other available therapies.

Validation of an operating room immersive microlaryngoscopy simulator.

OBJECTIVES/HYPOTHESIS: To assess the face and construct validity of two assessment tools for a microlaryngoscopy simulator-a Checklist Assessment for Microlaryngeal Surgery and Global Rating Assessment for Microlaryngeal Surgery. STUDY DESIGN: Blinded experimental simulator-based study. METHODS: There were 15 candidates divided into a novice (≤50 procedures performed) or experienced (>50 procedures) group depending on their previous microlaryngoscopy experience. Each candidate undertook a 10-minute simulation of a microlaryngoscopy and excision biopsy, and two blinded experts rated their performance live on each of the two assessment tools. To assess face validity, each candidate subsequently completed a questionnaire about the simulator. RESULTS: The model demonstrated good face validity across all levels of experience. The global rating assessment demonstrated excellent interrater reliability (0.9) compared to the checklist assessment (0.7). The checklist assessment was able to differentiate experienced and novice candidates and therefore demonstrated construct validity. The global rating tool, however, was unable to differentiate candidates. There was a significant correlation between the two assessment tools (correlation coefficient = 0.624). CONCLUSIONS: This study is the first reported study of a high-fidelity microlaryngoscopy simulator with task-specific rating tools. Use of these tools is recommended within otolaryngology training programs, with the global rating assessment for use as a frequently used feedback tool, and the checklist assessment as a confirmatory evaluation of competency at transitions of professional training.

Objective dysphonia quantification in vocal fold paralysis: comparing nonlinear with classical measures.

Clinical acoustic voice-recording analysis is usually performed using classical perturbation measures, including jitter, shimmer, and noise-to-harmonic ratios (NHRs). However, restrictive mathematical limitations of these measures prevent analysis for severely dysphonic voices. Previous studies of alternative nonlinear random measures addressed wide varieties of vocal pathologies. Here, we analyze a single vocal pathology cohort, testing the performance of these alternative measures alongside classical measures. We present voice analysis pre- and postoperatively in 17 patients with unilateral vocal fold paralysis (UVFP). The patients underwent standard medialization thyroplasty surgery, and the voices were analyzed using jitter, shimmer, NHR, nonlinear recurrence period density entropy (RPDE), detrended fluctuation analysis (DFA), and correlation dimension. In addition, we similarly analyzed 11 healthy controls. Systematizing the preanalysis editing of the recordings, we found that the novel measures were more stable and, hence, reliable than the classical measures on healthy controls. RPDE and jitter are sensitive to improvements pre- to postoperation. Shimmer, NHR, and DFA showed no significant change (P>0.05). All measures detect statistically significant and clinically important differences between controls and patients, both treated and untreated (P<0.001, area under curve [AUC]>0.7). Pre- to postoperation grade, roughness, breathiness, asthenia, and strain (GRBAS) ratings show statistically significant and clinically important improvement in overall dysphonia grade (G) (AUC=0.946, P<0.001). Recalculating AUCs from other study data, we compare these results in terms of clinical importance. We conclude that, when preanalysis editing is systematized, nonlinear random measures may be useful for monitoring UVFP-treatment effectiveness, and there may be applications to other forms of dysphonia.

Long-term quantitative results of an Isshiki type 4 thyroplasty-a case study.

OBJECTIVE: We believe that we have described the first instance of long-term follow-up of a bilateral Isshiki type IV thyroplasty in a 58-year-old woman after bilateral superior laryngeal nerve (SLN) damage. METHOD: Comparison of voice handicap index-10 (VHI-10) questionnaire and electrolaryngographic measurements pre- and post-thyroplasty (type IV). RESULTS: VHI-10 scores reduced from 25 pre-thyroplasty to seven and five at 6 and 34 months, respectively. Mean, mode, and median dynamic frequency range (DFx-1) scores increased from 118, 125, and 124 Hz preoperatively to 144, 172, and 163 Hz at 6 months and 167, 167, and 169 Hz, at 34 months, respectively (a subjectively higher voice). Range of tones produced while speaking reduced from an 80% range of 2.48 octaves and 90% range of 3.52 octaves to scores of 1.46 and 2.75 octaves for 80% and 90%, respectively at 6 months and 0.82 and 1.73 octaves at 34 months (a more defined voice). Ninety percent spectrum of single tone production increased from 0.17 octaves preoperatively to 0.55 octaves at 6 months and 0.49 octaves at 34 months. DISCUSSION: Type IV thyroplasty is most commonly performed for the male-to-female transsexual patient. Bilateral SLN palsy can be effectively treated with this approach with good long-term results. CONCLUSION: Three-year follow-up for bilateral type IV thyroplasty reveals increased pitch, definition, and clarity but decreased range overall.

The management of otitis externa: a randomised controlled trial of a glycerol and icthammol ribbon gauze versus topical antibiotic and steroid drops.

We compared the use of glycerol and icthammol (G&I) ribbon gauze versus topical antibiotic and steroid drops in the management of otitis externa. Patients presenting with acute otitis externa were systematically recruited from attendance in the ENT emergency clinic. Exclusion criteria were age <18 years, diabetic patients, and those who had been previously treated for otitis externa by the department within the last month. A total of 43 patients were recruited with 48 infected ears, the mean patient age was 47 years, (range 18-80 years). Patients were randomised to either insertion of a G&I ribbon gauze or topical ear drops by means of a ballot with no stratification. All patients were reviewed 5 days later. Patients were asked to comment on their pain using the ten point visual analogue pain score. Oedema of the canal wall, presence of debris and visibility of the tympanic membrane were graded on microscopy. Patient satisfaction and return to work were assessed. There was a statistically significant decrease in the pain score between each visit for the entire group of patients and decrease in canal wall swelling (P < 0.001). There was no significant difference between drops and ribbon gauze in terms of pain relief, canal wall oedema, or aural discharge. Following microbiological analysis, 27.8% of bacteria were resistant to neomycin. The cost of treatment with G&I is less than a third of that for topical antibiotic-steroid drops and requires less patient compliance. Patient concerns with the ribbon gauze included its cosmetic appearance and loss of hearing and with drops included frequency of application. We recommend the use of G&I ribbon gauze as first-line treatment, particularly for those who have had allergies to carriers of drops, those that are poorly compliant or with poor manual dexterity, for example patients with rheumatic hands.

"Hot potato voice" in peritonsillitis: a misnomer.

The "hot potato voice" is widely recognized as a symptom of peritonsillar cellulitis or abscess; yet there have been no studies assessing the resonance characteristics of the vocal tract in peritonsillitis. Analysis was undertaken of formant frequencies in the articulation of the vowels /i:/. /a:/ and /u:/ in six subjects with peritonsillitis and compared with articulation once the peritonsillitis had settled. Significant variation was found in F1 when articulating /i:/ and in F2 when articulating /a:/, which are explainable by dyskinesis of the peritonsillar musculature. These findings were compared with six subjects articulating the same vowels with and without a hot potato in their mouth. Variation was found in both F1 and F2 when articulating /i:/, which can be related to interference of the potato with movement of the anterior tongue. The changes in the vocal tract differ in these two cases and the title "hot potato voice" in peritonsillitis is a misnomer.