Validation of the Airway-Dyspnoea-Voice-Swallow (ADVS) scale and Patient-Reported Outcome Measure (PROM) as disease-specific instruments in paediatric laryngotracheal stenosis.

OBJECTIVE: To validate the Airway-Dyspnoea-Voice-Swallow (ADVS) instrument as a disease-specific Patient-Reported Outcome Measure in paediatric laryngotracheal stenosis. DESIGN: Prospective observational study. SETTING: A quaternary referral centre for complex airway disease. PARTICIPANTS: Forty-eight patients (30 males) with a mean age of 49 ± 49 months who underwent laryngotracheal surgery or microlaryngoscopy and bronchoscopy (MLB) following laryngotracheal surgery. MAIN OUTCOME MEASURES: Airway-Dyspnoea-Voice-Swallow summary scale and Patient-Reported Outcome Measure (PROM), Paediatric Quality of Life (PedsQL) scale, Paediatric Voice Handicap Index (pVHI) and Lansky performance scale were administered to patients before and 6-8 weeks following airway examination/surgery. RESULTS: Most patients (73%) had intubation-related subglottic stenosis, and 60% of patients had prior airway treatments. The majority of patients (77%) had more than one major chronic morbidity, and the commonest procedures were diagnostic MLB (49%), followed by airway dilation (29%). Cronbach-α value for the ADVS PROM was 0.71 overall and 0.85, 0.86 and 0.64 for the dyspnoea, voice and swallow domains, respectively. Rank correlations between Dyspnoea, Voice and Swallow summary scale and PROM scores were 0.83, 0.71 and 0.81, respectively (P < 0.0001). For those patients undergoing diagnostic MLB, pre- and post-examination scores were highly correlated (intraclass correlations >0.75). There was a significant rank correlation between ADVS PROM score and Lansky performance score (r = -0.68; P < 0.0001). There were significant correlations between PROM score and PedsQL (r = -0.57; P < 0.0001) and between voice domain of the PROM and pVHI (r = 0.78; P < 0.0001). There were strong correlations between Myer-Cotton stenosis severity and dyspnoea scale and PROM score (r = 0.68; P < 0.0001). There were significant differences in voice and swallow ADVS scales and PROM scores between patients with and without concomitant laryngeal/oesophageal pathology. Patient age and presence of high dyspnoea and swallowing PROM scores were independently associated with poorer quality of life and performance status. CONCLUSIONS: These series of observations validate the ADVS instrument as a disease-specific outcome measure for paediatric laryngotracheal stenosis. Dyspnoea and swallowing dysfunction appear to have the greatest impact on quality of life. More widespread adoption of the ADVS instrument could help create a shared language for outcomes communication and benchmarking for children with this complex condition.

Advancing the framework for considering the effects of climate change on worker safety and health.

In 2009, a preliminary framework for how climate change could affect worker safety and health was described. That framework was based on a literature search from 1988-2008 that supported seven categories of climate-related occupational hazards: (1) increased ambient temperature; (2) air pollution; (3) ultraviolet radiation exposure; (4) extreme weather; (5) vector-borne diseases and expanded habitats; (6) industrial transitions and emerging industries; and (7) changes in the built environment. This article reviews the published literature from 2008-2014 in each of the seven categories. Additionally, three new topics related to occupational safety and health are considered: mental health effects, economic burden, and potential worker safety and health impacts associated with the nascent field of climate intervention (geoengineering). Beyond updating the literature, this article also identifies key priorities for action to better characterize and understand how occupational safety and health may be associated with climate change events and ensure that worker health and safety issues are anticipated, recognized, evaluated, and mitigated. These key priorities include research, surveillance, risk assessment, risk management, and policy development. Strong evidence indicates that climate change will continue to present occupational safety and health hazards, and this framework may be a useful tool for preventing adverse effects to workers.

Tissue-Engineered Tracheal Replacement in a Child: A 4-Year Follow-Up Study.

In 2010, a tissue-engineered trachea was transplanted into a 10-year-old child using a decellularized deceased donor trachea repopulated with the recipient's respiratory epithelium and mesenchymal stromal cells. We report the child's clinical progress, tracheal epithelialization and costs over the 4 years. A chronology of events was derived from clinical notes and costs determined using reference costs per procedure. Serial tracheoscopy images, lung function tests and anti-HLA blood samples were compared. Epithelial morphology and T cell, Ki67 and cleaved caspase 3 activity were examined. Computational fluid dynamic simulations determined flow, velocity and airway pressure drops. After the first year following transplantation, the number of interventions fell and the child is currently clinically well and continues in education. Endoscopy demonstrated a complete mucosal lining at 15 months, despite retention of a stent. Histocytology indicates a differentiated respiratory layer and no abnormal immune activity. Computational fluid dynamic analysis demonstrated increased velocity and pressure drops around a distal tracheal narrowing. Cross-sectional area analysis showed restriction of growth within an area of in-stent stenosis. This report demonstrates the long-term viability of a decellularized tissue-engineered trachea within a child. Further research is needed to develop bioengineered pediatric tracheal replacements with lower morbidity, better biomechanics and lower costs.

Cardiovascular MRI predicts 5-year adverse clinical outcome in heart transplant recipients.

Imaging recommendations for the follow-up of heart transplant recipients (HTRs) lack evidence justifying their prognostic value. Cardiovascular magnetic resonance imaging (CMRI) can characterize heart structure and function and has prognostic value in many myocardial diseases. We hypothesized that CMRI evaluation of cardiac allografts would predict adverse events. We performed CMRI on 60 HTRs evaluating biventricular size, function and myocardial scar. We performed survival analysis to identify independent predictors of cardiovascular (CV) death or hospitalization. Participants had a mean age of 51 ± 14 years, mean graft age of 3.5 years (±4) and 75% are male. Median follow-up time was 4.9 years with 22 CV hospitalizations and 7 CV deaths. A multivariable survival analysis of imaging and clinical variables identified myocardial scar (hazard ratio [HR] of 10.7, p = 0.005), right ventricular end- diastolic volume index (RVEDVI; 1.1/mL/m(2) , p = 0.001), graft age (HR = 1.2/year, p = 0.004) and previous allograft rejection (HR = 4.4, p = 0.006) as predictive of time to CV death or hospitalization. CMRI-derived myocardial scar and RVEDVI are independently associated with CV outcomes in HTRs.

The neural correlates of everyday recognition memory.

We used a novel automatic camera, SenseCam, to create a recognition memory test for real-life events. Adapting a 'Remember/Know' paradigm, we asked healthy undergraduates, who wore SenseCam for 2 days, in their everyday environments, to classify images as strongly or weakly remembered, strongly or weakly familiar or novel, while brain activation was recorded with functional MRI. Overlapping, widely distributed sets of brain regions were activated by recollected and familiar stimuli. Within the medial temporal lobes, 'Remember' responses specifically elicited greater activity in the right anterior and posterior parahippocampal gyrus than 'Know' responses. 'New' responses activated anterior parahippocampal regions. A parametric analysis, across correctly recognised items, revealed increasing activation in the right hippocampus and posterior parahippocampal gyrus (pPHG). This may reflect modulation of these regions by the degree of recollection or, alternatively, by increasing memory strength. Strong recollection elicited greater activity in the left posterior hippocampus/pPHG than weak recollection indicating that this region is specifically modulated by the degree of recollection.

An fMRI study of long-term everyday memory using SenseCam.

We used a novel automatic camera, SenseCam, to investigate recognition memory for real-life events at a 5-month retention interval. Using fMRI we assessed recollection and familiarity memory using the remember/know procedure. Recollection evoked no medial temporal lobe (MTL) activation compared to familiarity and new responses. Instead, recollection activated diverse regions in neocortex including medial prefrontal cortex. We observed decreased activation in anterior hippocampus/ anterior parahippocampal gyrus (aPHG) at 5 months compared to a 36-hour retention interval. Familiarity was associated with greater activation in aPHG and posterior parahippocampal gyrus (pPHG) than recollection and new responses. Familiarity activation decreased over time in anterior hippocampus/aPHG and posterior hippocampus/pPHG. The engagement of neocortical regions such as medial prefrontal cortex at a 5-month delay, together with the reduced MTL activation at 5 months relative to at 36 hours is in line with the assumptions of Consolidation theory. SenseCam provides a valuable technique for assessing the processes that underlie remote everyday recognition memory.

Transient epileptic amnesia: regional brain atrophy and its relationship to memory deficits.

Transient epileptic amnesia (TEA) is a recently recognised form of epilepsy of which the principle manifestation is recurrent, transient episodes of isolated memory loss. In addition to the amnesic episodes, many patients describe significant interictal memory difficulties. Performance on standard neuropsychological tests is often normal. However, two unusual forms of memory deficit have recently been demonstrated in TEA: (i) accelerated long-term forgetting (ALF): the excessively rapid loss of newly acquired memories over a period of days or weeks and (ii) remote autobiographical memory loss: a loss of memories for salient, personally experienced events of the past few decades. The neuroanatomical bases of TEA and its associated memory deficits are unknown. In this study, we first assessed the relationship between subjective and objective memory performance in 41 patients with TEA. We then analysed MRI data from these patients and 20 matched healthy controls, using manual volumetry and voxel-based morphometry (VBM) to correlate regional brain volumes with clinical and neuropsychological data. Subjective memory estimates were unrelated to performance on standard neuropsychological tests but were partially predicted by mood, ALF and remote autobiographical memory. Manual volumetry identified subtle hippocampal volume loss in the patient group. Both manual volumetry and VBM revealed correlations between medial temporal lobe atrophy and standard anterograde memory scores, but no relation between atrophy and ALF or remote autobiographical memory. These results add weight to the hypothesis that TEA is a syndrome of mesial temporal lobe epilepsy. Furthermore, they suggest that although standard anterograde memory test performance is related to the degree of mesial temporal lobe damage, this is not true for ALF and autobiographical amnesia. It is possible that these unusual memory deficits have a more diffuse physiological basis rather than being a consequence of discrete structural damage.

Recent insights into the impairment of memory in epilepsy: transient epileptic amnesia, accelerated long-term forgetting and remote memory impairment.

Complaints of memory difficulties are common among patients with epilepsy, particularly with temporal lobe epilepsy where memory-related brain structures are directly involved by seizure activity. However, the reason for these complaints is often unclear and patients frequently perform normally on standard neuropsychological tests of memory. In this article, we review the literature on three recently described and interrelated forms of memory impairment associated with epilepsy: (i) transient epileptic amnesia, in which the sole or main manifestation of seizures is recurrent episodes of amnesia; (ii) accelerated long-term forgetting, in which newly acquired memories fade over days to weeks and (iii) remote memory impairment, in which there is loss of memories for personal or public facts or events from the distant past. Accelerated long-term forgetting and remote memory impairment are common amongst patients with transient epileptic amnesia, but have been reported in other forms of epilepsy. Their presence goes undetected by standard memory tests and yet they can have a profound impact on patients' lives. They pose challenges to current theoretical models of memory. We discuss the evidence for each of these phenomena, as well as their possible pathophysiological bases, methodological difficulties in their investigation and their theoretical implications.

A multidisciplinary audit of clinical coding accuracy in otolaryngology: financial, managerial and clinical governance considerations under payment-by-results.

OBJECTIVES: To audit the accuracy of otolaryngology clinical coding and identify ways of improving it. DESIGN: Prospective multidisciplinary audit, using the 'national standard clinical coding audit' methodology supplemented by 'double-reading and arbitration'. SETTINGS: Teaching-hospital otolaryngology and clinical coding departments. PARTICIPANTS: Otolaryngology inpatient and day-surgery cases. MAIN OUTCOME MEASURES: Concordance between initial coding performed by a coder (first cycle) and final coding by a clinician-coder multidisciplinary team (MDT; second cycle) for primary and secondary diagnoses and procedures, and Health Resource Groupings (HRG) assignment. RESULTS: 1250 randomly-selected cases were studied. Coding errors occurred in 24.1% of cases (301/1250). The clinician-coder MDT reassigned 48 primary diagnoses and 186 primary procedures and identified a further 209 initially-missed secondary diagnoses and procedures. In 203 cases, patient's initial HRG changed. Incorrect coding caused an average revenue loss of 174.90 pounds per patient (14.7%) of which 60% of the total income variance was due to miscoding of a eight highly-complex head and neck cancer cases. The 'HRG drift' created the appearance of disproportionate resource utilisation when treating 'simple' cases. At our institution the total cost of maintaining a clinician-coder MDT was 4.8 times lower than the income regained through the double-reading process. CONCLUSIONS: This large audit of otolaryngology practice identifies a large degree of error in coding on discharge. This leads to significant loss of departmental revenue, and given that the same data is used for benchmarking and for making decisions about resource allocation, it distorts the picture of clinical practice. These can be rectified through implementing a cost-effective clinician-coder double-reading multidisciplinary team as part of a data-assurance clinical governance framework which we recommend should be established in hospitals.

Validation of the Clinical COPD Questionnaire as a psychophysical outcome measure in adult laryngotracheal stenosis.

OBJECTIVES: To validate the Clinical Chronic Obstructive Pulmonary Disease Questionnaire (CCQ), a patient-administered instrument developed for bronchopulmonary disease as a disease-specific psychophysical outcome measure for adult laryngotracheal stenosis. DESIGN: Prospective observational study. SETTINGS: Tertiary/National referral airway reconstruction centre. PARTICIPANTS: Thirty-three tracheostomy-free patients undergoing endoscopic laryngotracheoplasty. MAIN OUTCOME MEASURES: CCQ and the Medical Research Council (MRC) Dyspnoea scale, a previously validated but more limited scale, were administered to patients 2 weeks before surgery, preoperatively, and 2 weeks after endoscopic laryngotracheoplasty. Pulmonary function was assessed preoperatively. Internal consistency was assessed with Cronbach alpha statistics and test-retest reliability was determined using intraclass correlation. Correlations between CCQ and MRC scale, and pulmonary function were used to assess convergent and divergent validity respectively. Instrument responsiveness was assessed by correlating total and domain-specific CCQ scores with anatomical disease severity and post-treatment effect size. RESULTS: There were 12 males and 21 females. Mean age was 44 +/- 15 years. Cronbach alpha coefficient and intraclass correlation coefficient were 0.88 and 0.95 respectively. Total and domain-specific CCQ scores significantly correlated with the MRC scores (P < 0.001) and significant correlations between CCQ and peak expiratory flow rate and FEV(1) were identified (P < 0.03). There were statistically significant changes in total and domain-specific CCQ scores when different stenosis severities were compared. Clinical COPD Questionnaire scores also changed significantly and congruently following surgery (P < 0.05 in both cases). DISCUSSION: Clinical COPD Questionnaire is a valid and sensitive instrument for assessing symptom severity and levels of function and well-being in adult patients with laryngotracheal stenosis and can be used as a patient-centred disease-specific outcome measure for this condition.

Avian agnosia: A window into auditory semantics.

The functional and neural organisation of auditory knowledge is relatively poorly understood. The breakdown of conceptual knowledge in semantic dementia has revealed that pre-morbid expertise influences the extent to which knowledge is differentiated. Whether this principle applies to a similar extent in the auditory domain is not yet known. Previous reports of patients with impaired auditory vs. intact visual expert knowledge suggest that expertise may have differential effects upon the organisation of auditory and visual knowledge. An equally plausible alternative, however, is that auditory knowledge is simply more vulnerable to deterioration. Thus, expertise effects in the auditory domain may not yet have been observed because knowledge of auditory expert vs. non-expert knowledge has yet to be compared. We had the opportunity to address this issue by studying SA, a patient with semantic dementia and extensive pre-morbid knowledge of birds. We undertook a systematic investigation of SA's auditory vs. visual knowledge from matched expert vs. non-expert categories. Relative to a group of 10 age, education and IQ matched bird experts, SA showed impaired auditory vs. intact visual avian knowledge, despite intact basic auditory perceptual abilities. This was explained by independent effects of modality and expertise. Thus, he was also disproportionately impaired for auditory vs. visual knowledge of items from non-expert categories. In both auditory and visual modalities, his performance was relatively more impaired on tests of non-expert vs. expert knowledge. These findings suggest that, while auditory knowledge may be more vulnerable to deterioration, expertise modulates visual and auditory knowledge to a similar extent.

Sensitivity and responsiveness of the Medical Research Council dyspnoea scale to the presence and treatment of adult laryngotracheal stenosis.

OBJECTIVES: To assess the sensitivity and responsiveness of the Medical Research Council (MRC) scale, a psychophysical dyspnoea assessment instrument to the presence and treatment of adult laryngotracheal stenosis. DESIGN: Prospective observational study. SETTINGS: Tertiary/National referral airway reconstruction centre. PARTICIPANTS: Fourty tracheostomy-free patients undergoing endoscopic airway examination/laryngotracheoplasty. MAIN OUTCOME MEASURES: Demographic and clinical information, obtained from patient records, lesion severity, which was recorded intraoperatively, standard spirometry, which was measured preoperatively, and the MRC dyspnoea scale, which was administered preoperatively and at the first outpatient visit 4-6 weeks later. RESULTS: There were 16 males and 24 females. Mean age at presentation was 44 +/- 14 years (+/- SD). Postintubation stenosis was the commonest aetiology (73%) followed by idiopathic subglottic stenosis and Wegener's Granulomatosis. Six patients were examined post-treatment and had minimal residual stenosis and the remaining patients had glottic stenosis (n = 11) or Myer-Cotton Grade I (n = 8), II (n = 7) or III (n = 8) tracheal stenoses. Pre-treatment MRC dyspnoea scores and the degree of change in the MRC score following treatment strongly correlated with pre-treatment stenosis severity (r = 0.75 and r = -0.71 respectively; P < .001). Moreover statistically significant correlations existed between preoperative peak expiratory flow and forced expiratory volume in 1 s and preoperative MRC dyspnoea scores (r = -0.34 and r = -0.35 respectively; P < 0.05). DISCUSSION: Exertional dyspnoea is the hallmark symptom of laryngotracheal stenosis and for many patients it is the primary cause of disability. These findings confirm that the MRC dyspnoea scale is an appropriate outcome instrument for assessing dyspnoea associated with this condition.

An optimized non-destructive protocol for testing mechanical properties in decellularized rabbit trachea.

Successful tissue-engineered tracheal transplantation relies on the use of non-immunogenic constructs, which can vascularize rapidly, support epithelial growth, and retain mechanical properties to that of native trachea. Current strategies to assess mechanical properties fail to evaluate the trachea to its physiological limits, and lead to irreversible destruction of the construct. Our aim was to develop and evaluate a novel non-destructive method for biomechanical testing of tracheae in a rabbit decellularization model. To validate the performance of this method, we simultaneously analyzed quantitative and qualitative graft changes in response to decellularization, as well as in vivo biocompatibility of implanted scaffolds. Rabbit tracheae underwent two, four and eight cycles of detergent-enzymatic decellularization. Biomechanical properties were analyzed by calculating luminal volume of progressively inflated and deflated tracheae with microCT. DNA, glycosaminoglycan and collagen contents were compared to native trachea. Scaffolds were prelaminated in vivo. Native, two- and four-cycle tracheae showed equal mechanical properties. Collapsibility of eight-cycle tracheae was significantly increased from -40cm H2O (-3.9kPa). Implantation of two- and four-cycle decellularized scaffolds resulted in favorable flap-ingrowth; eight-cycle tracheae showed inadequate integration. We showed a more limited detergent-enzymatic decellularization successfully removing non-cartilaginous immunogenic matter without compromising extracellular matrix content or mechanical stability. With progressive cycles of decellularization, important loss of functional integrity was detected upon mechanical testing and in vivo implantation. This instability was not revealed by conventional quantitative nor qualitative architectural analyses. These experiments suggest that non-destructive, functional evaluation, e.g. by microCT, may serve as an important tool for mechanical screening of scaffolds before clinical implementation. STATEMENT OF SIGNIFICANCE: Decellularization is a front-running strategy to generate scaffolds for tracheal tissue-engineering. Preservation of biomechanical properties of the trachea during this process is paramount to successful clinical transplantation. In this paper, we evaluated a novel method for biomechanical testing of decellularized trachea. We detected important loss of functional integrity with progressive cycles of decellularization. This instability was not revealed by our quantitative nor qualitative analyses. These experiments suggest that the technique might serve as a performant, non-destructive tool for mechanical screening of scaffolds before clinical implementation.

Accelerated forgetting of real-life events in Transient Epileptic Amnesia.

Transient Epileptic Amnesia (TEA) is a form of temporal lobe epilepsy associated with ictal and interictal memory disturbance. Some patients with TEA exhibit Accelerated Long-term Forgetting (ALF), in which memory for verbal and non-verbal material is retained normally over short delays but fades at an unusually rapid rate over days to weeks. This study addresses three questions about ALF in TEA: (i) whether real-life events undergo ALF in a similar fashion to laboratory-based stimuli; (ii) whether ALF can be detected within 24h; (iii) whether procedural memories are susceptible to ALF. Eleven patients with TEA and eleven matched healthy controls wore a novel, automatic camera, SenseCam, while visiting a local attraction. Memory for images of events was assessed on the same day and after delays of one day, one week, and three weeks. Forgetting of real-life events was compared with forgetting of a word list and with performance on a procedural memory task. On the day of their excursion, patients and controls recalled similar numbers of primary events, associated secondary details (contiguous events, thoughts and sensory information) and items from the word list. In contrast, patients showed ALF for primary events over three weeks, with ALF for contiguous events, thoughts and words over the first day. Retention on the procedural memory task was normal over three weeks. The results indicate that accelerated forgetting in TEA: (i) affects memory for real-life events as well as laboratory stimuli; (ii) is maximal over the first day; and (iii) is specific to declarative memories.

Inflammatory myofibroblastic tumour of the tonsil: case report and literature review.

OBJECTIVE: We present the first reported case in the English language literature of an inflammatory myofibroblastic tumour of the right tonsil in a young, pregnant woman, and we report a management strategy for this enigmatic entity. CASE REPORT: A 28-year-old, pregnant woman presented with a 10-day history of odynophagia despite a course of antibiotics. Examination revealed a grade II, erythematous right tonsil with ulceration on the upper pole. A biopsy was arranged, and initial evaluation was suggestive of spindle cell carcinoma. However, this diagnosis was reviewed after immunohistochemical staining confirmed an inflammatory myofibroblastic tumour. Subsequent complete excision was undertaken using CO2 laser. CONCLUSION: Clinically, inflammatory myofibroblastic tumour of the tonsil is known to be locally aggressive and can present in a manner not dissimilar to a high grade carcinoma of the tonsil. As a result, the recommended treatment is complete local excision with careful follow up.