Automated Voice Pathology Discrimination from Continuous Speech Benefits from Analysis by Phonetic Context

In contrast to previous studies that look only at discriminating pathological voice from the normal voice, in this study we focus on the discrimination between cases of spasmodic dysphonia (SD) and vocal fold palsy (VP) using automated analysis of speech recordings. The hypothesis is that discrimination will be enhanced by studying continuous speech, since the different pathologies are likely to have different effects in different phonetic contexts. We collected audio recordings of isolated vowels and of a read passage from 60 patients diagnosed with SD (N=38) or VP (N=22). Baseline classifiers on features extracted from the recordings taken as a whole gave a cross-validated unweighted average recall of up to 75% for discriminating the two pathologies. We used an automated method to divide the read passage into phone-labelled regions and built classifiers for each phone. Results show that the discriminability of the pathologies varied with phonetic context as predicted. Since different phone contexts provide different information about the pathologies, classification is improved by fusing phone predictions, to achieve a classification accuracy of 83%. The work has implications for the differential diagnosis of voice pathologies and contributes to a better understanding of their impact on speech

Use of proton pump inhibitors to treat persistent throat symptoms: Multicentre, double blind, randomised, placebo controlled trial

Objective. To assess the use of proton pump inhibitors (PPIs) to treat persistent throat symptoms. Design. Pragmatic, double blind, placebo controlled, randomised trial. Setting. Eight ear, nose, and throat outpatient clinics, United Kingdom. Participants. 346 patients aged 18 years or older with persistent throat symptoms who were randomised according to recruiting centre and baseline severity of symptoms (mild or severe): 172 to lansoprazole and 174 to placebo. Intervention. Random blinded allocation (1:1) to either 30 mg lansoprazole twice daily or matched placebo twice daily for 16 weeks. Main outcome measures. Primary outcome was symptomatic response at 16 weeks measured using the total reflux symptom index (RSI) score. Secondary outcomes included symptom response at 12 months, quality of life, and throat appearances. Results. Of 1427 patients initially screened for eligibility, 346 were recruited. The mean age of the study sample was 52.2 (SD 13.7) years, 196 (57%) were women, and 162 (47%) had severe symptoms at presentation; these characteristics were balanced across treatment arms. The primary analysis was performed on 220 patients who completed the primary outcome measure within a window of 14-20 weeks. Mean RSI scores were similar between treatment arms at baseline: lansoprazole 22.0 (95% confidence interval 20.4 to 23.6) and placebo 21.7 (20.5 to 23.0). Improvements (reduction in RSI score) were observed in both groups—score at 16 weeks: lansoprazole 17.4 (15.5 to19.4) and placebo 15.6 (13.8 to 17.3). No statistically significant difference was found between the treatment arms: estimated difference 1.9 points (95% confidence interval −0.3 to 4.2 points; P=0.096) adjusted for site and baseline symptom severity. Lansoprazole showed no benefits over placebo for any secondary outcome measure, including RSI scores at 12 months: lansoprazole 16.0 (13.6 to 18.4) and placebo 13.6 (11.7 to 15.5): estimated difference 2.4 points (−0.6 to 5.4 points). Conclusions. No evidence was found of benefit from PPI treatment in patients with persistent throat symptoms. RSI scores were similar between the lansoprazole and placebo groups after 16 weeks of treatment and at the 12 month follow-up

A randomised, placebo controlled trial of extra-oesophageal reflux treatment in the management of upper respiratory symptoms [TOPPITS:Trial of Proton Pump Inhibitors in Throat Symptoms]

Background. Persistent throat symptoms, such as throat clearing, globus sensation, voice change and catarrh are extremely common. On very limited evidence, they are increasingly attributed to “laryngopharyngeal reflux (LPR)” and treated with proton pump inhibitors (PPIs) in primary and secondary care. Methods. A double blind placebo controlled UK multicentre phase III trial randomly allocated adults with persistent throat symptoms 1:1 to either 30 mg of Lansoprazole or matched placebo twice daily for 16 weeks, stratified by centre and symptom severity. The primary outcome was patient-reported symptomatic response, measured by the total Reflux Symptom Index (RSI) score at the end of therapy. Secondary outcomes included safety, further symptoms and quality of life measures at 12-months. Results. 346 participants were randomised from 8 UK centres: mean (sd) age 52 (13), 196 (57%) female, 162 (47%) severe symptoms, balanced across randomised groups. Mean RSI scores (95% CI) were similar at baseline- Lansoprazole: 22.0 (20.4, 23.6), placebo: 21.7 (20.5, 23.0). Improvements (reduction in score) were observed in both groups at 16-weeks: Lansoprazole: 17.4 (15.5, 19.4), placebo: 15.6 (13.8, 17.3) (p=0.096 adjusted by site, severity). There was no statistically significant difference between randomised groups. No significant differences were observed in the secondary outcome measures. Conclusions. TOPPITS is the largest, definitive trial to assess PPI effectiveness for persistent throat symptoms. It found no advantage of Lansoprazole over placebo in a range of outcomes. The near routine use of PPIs for throat symptoms should be discontinued

Intra-tracheal multiplexed sensing of contact pressure and perfusion

Incorrect endotracheal tube (ETT) cuff inflation pressure causes significant problems for intubated patients. The technical development and first in vivo use of a smart ETT for measurements at the cuff-trachea interface during mechanical ventilation are described. The intra-tracheal multiplexed sensing (iTraXS) ETT contains integrated optical fibre sensors to measure contact pressure and blood perfusion. The device is tested during mechanical ventilation in a porcine model (N=6). For contact pressure, signals were obtained in all 30 measurements. For perfusion, data could be obtained in all 33 measurements. In the 3 cases where the cuff was inflated to an artificially high-level, blood occlusion is observed

Packages of Care for Schizophrenia in Low- and Middle-Income Countries

In the third in a series of six articles on packages of care for mental disorders in low- and middle-income countries, Jair Mari and colleagues discuss the treatment of schizophrenia

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

A mixed-method feasibility study of the use of the Complete Vocal Technique (CVT), a pedagogic method to improve the voice and vocal function in singers and actors, in the treatment of patients with muscle tension dysphonia: a study protocol

Abstract Background Muscle tension dysphonia (MTD) results from inefficient or ineffective voice production and is the cause of voice and throat complaints in up to 40% of patients presenting with hoarseness. Standard treatment is voice therapy (SLT-VT) delivered by specialist speech therapists in voice disorders (SLT-V). The Complete Vocal Technique (CVT) is a structured, pedagogic method which helps healthy singers and other performers optimise their vocal function enabling them to produce any sound required. The aim of this feasibility study is to investigate whether CVT administered by a trained, non-clinical CVT practitioner (CVT-P) can be applied to patients with MTD before progressing to a pilot randomised control study of CVT voice therapy (CVT-VT) versus SLT-VT. Methods/design In this feasibility study, we use a mixed-method, single-arm, prospective cohort design. The primary aim is to demonstrate whether CVT-VT can improve the voice and vocal function in patients with MTD in a pilot study using multidimensional assessment methods. Secondary aims are to assess whether (1) a CVT-VT study is feasible to perform; (2) is acceptable to patients, the CVT-P and SLT-VTs; and (3) whether CVT-VT differs from existing SLT-VT techniques. A minimum of 10 consecutive patients with a clinical diagnosis of primary MTD (types I–III) will be recruited over a 6-month period. Up to 6 video sessions of CVT-VT will be delivered by a CVT-P using a video link. The primary outcome will be a change in pre-/post-therapy scores of a self-reported patient questionnaire (Voice Handicap Index (VHI)). Secondary outcomes include changes in throat symptoms (Vocal Tract Discomfort Scale), acoustic/electroglottographic and auditory-perceptual measures of voice. Acceptability of the CVT-VT will be assessed prospectively, concurrently and retrospectively both quantitatively and qualitatively. Differences from SLT-VT will be assessed by performing a deductive thematic analysis of CVT-P transcripts of therapy sessions. Conclusion This feasibility study will provide important data to support whether to proceed with a randomised controlled pilot study focusing on the effectiveness of the intervention compared to standard SLT-VT. Progression criteria will be based on demonstrating a positive outcome in treatment, successful delivery of the pilot study protocol, acceptability to all stakeholders and satisfactory recruitment rates. Trial registration ClinicalTrials.gov website ( NCT05365126 Unique Protocol ID: 19ET004). Registered on 06 May 2022