Laryngeal reinnervation: feasibility studies and development of trial outcome measures

The unifying theme of this thesis is a series of research studies that collectively amount to a feasibility study for clinical trials of laryngeal reinnervation for the treatment of vocal fold paralysis. The question ‘Does laryngeal reinnervation or thyroplasty give better voice results for patients with unilateral vocal fold paralysis (UVFP)?’ remains outstanding; a question that ideally requires a randomised control trial. However, randomised control trials in surgery face inherent surgeons’ equipoise and recruitment issues that may lead to its failure. I performed a national survey of UK ENT consultants exploring their perception and obtaining crude numbers of eligible UVFP patients under their care for such trial, which revealed that the majority of ENT surgeons are receptive to the trial and the size of the potential patient pool is promising. I interviewed eligible UVFP patients to explore issues around the recruitment process, and this suggested that the proposed trial is feasible. Some phraseology used during recruitment that needed changing was identified, which may optimise the recruitment process for a trial. In voice surgery trials, outcome measures should be multidimensional and standardised. Acoustic analysis has been proposed but has limitations. OperaVOX is a potential new acoustic analysis software developed to resolve some of these factors. I demonstrated that OperaVOX is statistically comparable to the ‘gold standard’, Multidimensional Voice Programme, for most principal phonatory outcome measures. Another outcome measure- video-laryngostroboscopy, allows visual evaluation of characteristics and vibratory pattern of vocal folds. It is typically subjective that requires inter- and intra-rater reliability study. Here, I demonstrated that certain parameters depicted substantial inter- and intra-rater reliability. However, I showed that rater training is required to improve the reliability of other parameters. I investigated MRI as a potential non-invasive method to evaluate vocal muscles’ denervation and reinnervation. I found that signal changes on the T2-weighted MRI larynx images correlated with electrophysiological results with good repeatability. Another MRI sequence, dynamic contrast enhanced- and diffusion weighted MRI, suggested reduced perfusion in paralysed muscles, whilst cine-MRI for vocal fold mobility assessment demonstrated considerable potential as a method to grade vocal fold mobility. Finally, I present a small prospective case series of non-selective and selective laryngeal reinnervation in UVFP and unilateral vagal paralysis following vagal tumour excision respectively concomitant with injection laryngoplasty. Voice improvement was demonstrated by voice handicap index-10 and other multidimensional outcome measures, and these were supported by laryngeal electromyography and T2-weighted MRI outcomes. To my knowledge, this is the first multidimensional prospective study of laryngeal reinnervation and also the first to suggest that 3T MRI may be a promising outcome measure for future reinnervation trials. In summary, I have shown that a randomised trial of laryngeal reinnervation versus thyroplasty is feasible in the UK, and have validated patient- and observer-rated outcome measures. I have also shown that MRI may offer an alternative to electromyography in the assessment of laryngeal neuromuscular function in future trials and the clinic

A survey of voice pathology surveillance systems based on internet of things and machine learning algorithms

The incorporation of the cloud technology with the Internet of Things (IoT) is significant in order to obtain better performance for a seamless, continuous, and ubiquitous framework. IoT has many applications in the healthcare sector, one of these applications is voice pathology monitoring. Unfortunately, voice pathology has not gained much attention, where there is an urgent need in this area due to the shortage of research and diagnosis of lethal diseases. Most of the researchers are focusing on the voice pathology and their finding is only to differentiating either the voice is normal (healthy) or pathological voice, where there is a lack of the current studies for detecting a certain disease such as laryngeal cancer. In this paper, we present an extensive review of the state-of-the-art techniques and studies of IoT frameworks and machine learning algorithms used in the healthcare in general and in the voice pathology surveillance systems in particular. Furthermore, this paper also presents applications, challenges and key issues of both IoT and machine learning algorithms in the healthcare. Finally, this paper highlights some open issues of IoT in healthcare that warrant further research and investigation in order to present an easy, comfortable and effective diagnosis and treatment of disease for both patients and doctors

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Data for: Validity and reliability study of Bahasa Malaysia version of Voice Handicap Index-10

these data base in the excel for which include patient with various voice disorder , their voice assessment was asses via subjective voice assessment with Bahasa Malaysia version of voice handicap index-10 and the objective voice assessment with acoustic analysi

The reliability of vocal intensity and pitch range measurements in unilateral vocal fold palsy patients.

FINAL RESULTS FOR STUDY 1ST STAG

Myeloid sarcoma: An unusual and rare laryngeal presentation

Introduction: Myeloid Sarcoma (MS) or Granulocytic Sarcoma is an uncommon laryngeal malignancy. It may arise from myelodysplastic syndromes, malignancy or de novo. Presentation in the larynx is rare and some may present with Acute Myeloid Leukaemia (AML) whereby the later may be asymptomatic. Case Presentation: A 44-year-old South East Asian lady presented with a six months history of hoarseness, shortness of breath, reduced exercise tolerance, weight loss and laryngeal irritation. Symptoms progressed to coughing with liquids two months prior. On examination, she had a resting biphasic stridor and laryngoscopy revealed right immobile vocal cord with a firm right ventricle mass extending into the right paraglottic space. She was pale and haematology investigations revealed microcytic hypochromic anaemia. Magnetic Resonance Imaging (MRI) of the neck and thorax showed thickening of the right false cord, true cord and aryepiglottic fold. A biopsy taken during endolaryngeal microsurgery (ELMS) confirmed myeloid sarcoma of the right ventricle and para glottic mass. Further investigation revealed a background of AML and she then underwent chemotherapy. Discussion: MS is a rarity with only nine reported cases between the years of 1954 until 2015. Immunohistochemistry and immunophenotyping are definite for diagnosis confirmation as MS cells often exhibit myeloperoxidase (MPO), lymphocyte common antigen (LCA) and CD117 markers. MS is treated with are chemotherapy (either systemic or intrathecal), radiotherapy, surgical excision or in combination. Systemic chemotherapy has better efficacy and prognosis as compared to localised treatment of radiotherapy or surgical excision. However, there has yet to be a definitive chemotherapy protocol. Prognosis is poor with a 5-year survival rate of 48%. Conclusion: Although laryngeal MS is a rare phenomenon, early recognition is key and patients should always be investigated for an underlying myeloproliferative or dysplastic disease