Sirolimus use in patients with subglottic stenosis in the context of granulomatosis with polyangiitis (GPA), suspected GPA, and immunoglobulin G4-related disease.

Objective: Subglottic stenosis (SGS) is a severe, life-threatening disease found in immune-mediated diseases such as granulomatosis with polyangiitis (GPA) and in rare cases of immunoglobulin G4 (IgG4)-related disease. It can result in persistent airway compromise due to the fibrotic response following inflammation. Standard management involves repeated endoscopic interventions to dilate the airway, and tracheostomy is occasionally required. In addition, immunosuppression remains a cornerstone of therapy aimed at controlling the underlying inflammatory disease; however, cumulative dosing leads to significant adverse effects. We present five cases of predominantly anti-neutrophil cytoplasmic antibody-negative GPA and a case of IgG4-related disease with SGS, in whom we evaluated the long-term utility of sirolimus, which has beneficial anti-proliferative and fibrotic effects, in the management of their disease. Method: We conducted a retrospective review of a cohort of patients with SGS at a tertiary vasculitis unit. These patients were treated with sirolimus, in addition to conventional medical and endoscopic treatment. Clinical symptoms, frequency and time to endoscopic intervention pre- and post-treatment, additional rescue therapy, and any adverse effects were recorded and analysed. Results: Six patients were treated with sirolimus and followed for up to 9 years; two discontinued the drug owing to adverse effects, early on. In the remaining four patients, glucocorticoids were withdrawn, and the frequency of endoscopic intervention was reduced. One patient on sirolimus required rituximab therapy for disease flare. Conclusion: Sirolimus may be a therapeutic option for some patients with severe SGS, allowing steroid withdrawal and resulting in a positive adverse effect profile.

A prospective randomized clinical trial to evaluate the impact of intraoperative ventilation with high oxygen content on the extent of postoperative pneumocephalus in patients undergoing craniotomies.

Purpose of the article: To determine whether intraoperative ventilation with pure oxygen during the last stage of surgery reduces the occurrence and volume of postoperative pneumocephalus when compared to conventional air/oxygen mixture in patients undergoing craniotomy. MATERIAL AND METHODS: prospective randomized single-blinded study to compare the rate of occurrence and volume of postoperative pneumocephalus in patients undergoing craniotomy receiving intraoperative ventilation with pure oxygen (Group B) versus a conventional air/oxygen 1:1 mixture (Group A) during the last stage of surgery. This trial was registered in ClinicalTrials.gov #NCT02722928, protocol number 2015H0032. RESULTS: One hundred patients were randomized into group 'A' and group 'B'. Seventy patients were included in the final analysis with 39 patients allocated in group 'A' and 31 patients in group 'B'. Median and IQR were used for postoperative penumocephalus volume. Group A: 9.65 [3.61-23.20]; Group B: 7.06 [2.70-20.1]. Our study showed no prophylactic effect on postoperative pneumocephalus volume when using mechanical ventilation with higher oxygen concentrations than the standard FiO2 during the last stage of surgery in patients undergoing craniotomy (p = .47). No statistical difference was found in SICU LOS between groups (median 1,380 min [group A] versus 1,524 min [group B]; p = .18). CONCLUSION: The use of intraoperative mechanical ventilation with pure oxygen was not associated with a prophylactic effect on the occurrence and extent of postoperative pneumocephalus in our patient setting. Published literature describing the extent of postoperative pneumocephalus is limited or highly variable among institutions.

Effects of competing news media frames of weight on antifat stigma, beliefs about weight and support for obesity-related public policies.

OBJECTIVES: In the popular news media, public health officials routinely emphasize the health risks of obesity and portray weight as under personal control. These messages may increase support for policies designed to reduce rates of obesity, but can also increase antifat stigma. Less often, the media cover 'Health at Every Size' or 'Fat Rights' perspectives that may have the opposite effects. We investigated how exposure to different 'fat frames' shifts attitudes about weight and support for obesity policies. METHODS: Across four experiments (n=2187), people read constructed news articles framing fatness as negative (unhealthy, controllable, acceptable to stigmatize) or positive (healthy, uncontrollable, unacceptable to stigmatize). RESULTS: Compared with people who read fat-positive frames, people who read fat-negative frames expressed more: belief in the health risks of being fat (d=0.95-1.22), belief weight is controllable (d=0.38-0.55), support for charging obese people more for health insurance (d=0.26-0.77), antifat prejudice (in three out of four experiments, d=0.28-0.39), willingness to discriminate against fat people (d=0.39-0.71) and less willingness to celebrate body size diversity (d=0.37-0.64). They were also less willing to say that women at the lower end of the obese range could be healthy at their weights. Effects on support for public policies, however, were generally small and/or nonsignificant. Compared with a control condition, exposure to fat-positive frames generally shifted attitudes more than fat-negative frames. In experiment 4, adding a message about the unacceptability of weight-based discrimination to unhealthy/controllable news articles only reduced antifat stigma on one of three measures compared with articles adding a discrimination-acceptable message. CONCLUSIONS: Exposure to different news frames of fat can shift beliefs about weight-related health risks and weight-based stigma. Shifting policy attitudes, however, is more challenging.

A Study of Clinical Coding Accuracy in Surgery: Implications for the Use of Administrative Big Data for Outcomes Management.

BACKGROUND: Clinical coding is the translation of clinical activity into a coded language. Coded data drive hospital reimbursement and are used for audit and research, and benchmarking and outcomes management purposes. METHODS: We undertook a 2-center audit of coding accuracy across surgery. Clinician-auditor multidisciplinary teams reviewed the coding of 30,127 patients and assessed accuracy at primary and secondary diagnosis and procedure levels, morbidity level, complications assignment, and financial variance. Postaudit data of a randomly selected sample of 400 cases were reaudited by an independent team. RESULTS: At least 1 coding change occurred in 15,402 patients (51%). There were 3911 (13%) and 3620 (12%) changes to primary diagnoses and procedures, respectively. In 5183 (17%) patients, the Health Resource Grouping changed, resulting in income variance of £3,974,544 (+6.2%). The morbidity level changed in 2116 (7%) patients (P < 0.001). The number of assigned complications rose from 2597 (8.6%) to 2979 (9.9%) (P < 0.001). Reaudit resulted in further primary diagnosis and procedure changes in 8.7% and 4.8% of patients, respectively. CONCLUSIONS: The coded data are a key engine for knowledge-driven health care provision. They are used, increasingly at individual surgeon level, to benchmark performance. Surgical clinical coding is prone to subjectivity, variability, and error (SVE). Having a specialty-by-specialty understanding of the nature and clinical significance of informatics variability and adopting strategies to reduce it, are necessary to allow accurate assumptions and informed decisions to be made concerning the scope and clinical applicability of administrative data in surgical outcomes improvement.

Reliability of OperaVOX against Multidimensional Voice Program (MDVP).

OBJECTIVE: To evaluate the agreement between OperaVOX and MDVP. DESIGN: Cross sectional reliability study. SETTING: University teaching hospital. METHODS: Fifty healthy volunteers and 50 voice disorder patients had supervised recordings in a quiet room using OperaVOX by the iPod's internal microphone with sampling rate of 45 kHz. A five-seconds recording of vowel/a/was used to measure fundamental frequency (F0), jitter, shimmer and noise-to-harmonic ratio (NHR). All healthy volunteers and 21 patients had a second recording. The recorded voices were also analysed using the MDVP. The inter- and intrasoftware reliability was analysed using intraclass correlation (ICC) test and Bland-Altman (BA) method. Mann-Whitney test was used to compare the acoustic parameters between healthy volunteers and patients. RESULTS: Nine of 50 patients had severe aperiodic voice. The ICC was high with a confidence interval of >0.75 for the inter- and intrasoftware reliability except for the NHR. For the intersoftware BA analysis, excluding the severe aperiodic voice data sets, the bias (95% LOA) of F0, jitter, shimmer and NHR was 0.81 (11.32, -9.71); -0.13 (1.26, -1.52); -0.52 (1.68, -2.72); and 0.08 (0.27, -0.10). For the intrasoftware reliability, it was -1.48 (18.43, -21.39); 0.05 (1.31, -1.21); -0.01 (2.87, -2.89); and 0.005 (0.20, -0.18), respectively. Normative data from the healthy volunteers were obtained. There was a significant difference in all acoustic parameters between volunteers and patients measured by the Opera-VOX (P < 0.001) except for F0 in females (P = 0.87). CONCLUSION: OperaVOX is comparable to MDVP and has high internal consistency for measuring the F0, jitter and shimmer of voice except for the NHR.

Impact of unilateral vocal fold mobility impairment on laryngopulmonary physiology.

OBJECTIVE: To examine the impact of unilateral vocal fold mobility impairment (UVFMI) on airway physiology. STUDY DESIGN: Cross-sectional observational study. PARTICIPANTS: There were 21 patients with UVFMI and 53 controls. MAIN OUTCOME MEASURES: All patients and patient controls underwent a maximum-effort flow-volume loop examination. Forced expiratory flow in one second (FEV1 ), forced expiratory volume (FVC), peak inspiratory flow rate and peak expiratory flow rate (PIFR and PEFR, respectively) and area under the inspiratory and expiratory flow-volume loops (AUCI nspiratory and AUCE xpiratory, respectively) were measured. The ratio of PEFR to PIFR and AUCE xpiratory to AUCI nspiratory was derived. RESULTS: There were 48 males and 26 females. Mean age at measurement was 39 ± 11 years. Patients and controls were matched for age, sex, height and weight. None of the expiratory variables were significantly different between the groups. PIFR was significantly lower in UVFMI patients compared with controls (3.4 ± 1.2 versus 5.3 ± 1.8; P < 0.0001), as was AUCI nspiratory (11.5 ± 6.3 versus 17.5 ± 8.5; P = 0.0002). PEFR/PIFR provided the best differentiation between patients with UVFMI and controls with an area under the Receiver Operating Characteristic (ROC) curve of 0.96 and at a threshold of 1.9, and PEFR/PIFR had sensitivity and specificity of 95.2% and 90.6%, respectively. CONCLUSIONS: Flow-volume loops are a non-invasive method of studying vocal abduction and could compliment voice assessment and laryngoscopy in UVFMI. With further research, they could provide an outcome measure for laryngeal rehabilitative procedures, and a shared physiological language for screening and surgical quality assurance.

Biomarkers and Cognition Study, Singapore (BIOCIS): Protocol, Study Design, and Preliminary Findings.

BACKGROUND: The focus of medicine is shifting from treatment to preventive care. The expression of biomarkers of dementia and Alzheimer's disease (AD) appear decades before the onset of observable symptoms, and evidence has emerged supporting pharmacological and non-pharmacological interventions to treat modifiable risk factors of dementia. However, there is limited research on the epidemiology, clinical phenotypes, and underlying pathobiology of cognitive diseases in Asian populations. OBJECTIVES: The objectives of the Biomarkers and Cognition Study, Singapore(BIOCIS) are to characterize the underlying pathobiology of Cognitive Impairment through a longitudinal study incorporating fluid biomarker profiles, neuroimaging, neuropsychological and clinical outcomes in a multi-ethnic Southeast Asian population. DESIGN, SETTING, PARTICIPANTS: BIOCIS is a 5-year longitudinal study where participants are assessed annually. 2500 participants aged 30 to 95 will be recruited from the community in Singapore. To investigate how pathology presents with or without minimal clinical symptoms and vice versa, CI and unimpaired individuals will be recruited. Participants will undergo assessments to characterise biomarkers of dementia through neuroimaging, fluid biomarkers, cognitive assessments, behavioural and lifestyle profiles, retinal scans and microbiome indicators. RESULTS: Since commencement of recruitment in February 2022, 1148 participants have been enrolled, comprising 1012 Chinese, 62 Indian, and 35 Malay individuals. Mean age and education is 61.32 years and 14.34 years respectively with 39.8% males. 47.9 % of the cohort are employed and 32.06% have a family history of dementia. The prevalence of cerebral small vessel disease is 90.2% with a mean modified Fazekas white matter hyperintensity score of 4.1. CONCLUSION: The BIOCIS cohort will help identify novel biomarkers, pathological trajectories, epidemiology of dementia, and reversible risk factors in a Southeast Asian population. Completion of BIOCIS longitudinal data could provide insights into risk-stratification of Asians populations, and potentially inform public healthcare and precision medicine for better patient outcomes in the prevention of Alzheimer's disease and dementia.

An audit of the nature and impact of clinical coding subjectivity variability and error in otolaryngology.

OBJECTIVES: To audit the accuracy of clinical coding in otolaryngology, assess the effectiveness of previously implemented interventions, and determine ways in which it can be further improved. DESIGN: Prospective clinician-auditor multidisciplinary audit of clinical coding accuracy. PARTICIPANTS: Elective and emergency ENT admissions and day-case activity. MAIN OUTCOME MEASURES: Concordance between initial coding and the clinician-auditor multi-disciplinary teams (MDT) coding in respect of primary and secondary diagnoses and procedures, health resource groupings health resource groupings (HRGs) and tariffs. RESULTS: The audit of 3131 randomly selected otolaryngology patients between 2010 and 2012 resulted in 420 instances of change to the primary diagnosis (13%) and 417 changes to the primary procedure (13%). In 1420 cases (44%), there was at least one change to the initial coding and 514 (16%) health resource groupings changed. There was an income variance of £343,169 or £109.46 per patient. The highest rates of health resource groupings change were observed in head and neck surgery and in particular skull-based surgery, laryngology and within that tracheostomy, and emergency admissions, and specially, epistaxis management. A randomly selected sample of 235 patients from the audit were subjected to a second audit by a second clinician-auditor multi-disciplinary team. There were 12 further health resource groupings changes (5%) and at least one further coding change occurred in 57 patients (24%). These changes were significantly lower than those observed in the pre-audit sample, but were also significantly greater than zero. Asking surgeons to 'code in theatre' and applying these codes without further quality assurance to activity resulted in an health resource groupings error rate of 45%. The full audit sample was regrouped under health resource groupings 3.5 and was compared with a previous audit of 1250 patients performed between 2007 and 2008. This comparison showed a reduction in the baseline rate of health resource groupings change from 16% during the first audit cycle to 9% in the current audit cycle (P < 0.001). CONCLUSIONS: Otolaryngology coding is complex and susceptible to subjectivity, variability and error. Coding variability can be improved, but not eliminated through regular education supported by an audit programme.

Automatic conformal prescription of very selective saturation bands for in vivo 1H-MRSI of the prostate.

An important step in the implementation of three-dimensional in vivo proton magnetic resonance spectroscopic imaging ((1)H-MRSI) of the prostate is the placement of spatial saturation pulses around the region of interest (ROI) for the removal of unwanted contaminating signals from peripheral tissue. The present study demonstrates the use of a technique called conformal voxel magnetic resonance spectroscopy (CV-MRS). This method automates the placement, orientation, timing and flip angle of very selective saturation (VSS) pulses around an irregularly-shaped, user-defined ROI. The method employs a user adjustable number of automatically positioned VSS pulses (20 used in the present study) which null the signal from periprostatic lipids while closely conforming the shape of the excitation voxel to the shape of the prostate. A standard endorectal coil in combination with a torso-phased array coil was used for all in vivo prostate studies. Three-dimensional in vivo prostate (1)H-MRSI data were obtained using the proposed semi-automated CV-MRS technique, and compared with a standard point resolved spectroscopy (PRESS) technique at TE = 130 ms using manual placement of saturation pulses. The in vivo prostate (1)H-MRSI data collected from 12 healthy subjects using the CV-MRS method showed significantly reduced lipid contamination throughout the prostate, and reduced baseline distortions. On average there was a 50 ± 17% (range 12% - 68%) reduction in lipids throughout the prostate. A voxel-by-voxel benchmark test of over 850 voxels showed that there were 63% more peaks fitted using the LCModel when using a Cramer-Rao Lower Bound (CRLB) cut-off of 40% when using the optimized conformal voxel technique in comparison to the manual placement approach. The evaluation of this CV-MRS technique has demonstrated the potential for easy automation of the graphical prescription of saturation bands for use in (1)H-MRSI.

The menthol and cold sensation receptor TRPM8 in normal human nasal mucosa and rhinitis.

BACKGROUND: Menthol and cold sensation trigger symptoms and reflex responses in the upper airway, but the underlying molecular mechanisms are unknown. We have therefore studied nerve fibres expressing the menthol and cold receptor TRPM8 in normal human mucosa, and in rhinitis. TRPM8 nerve fibres were compared with those expressing other TRP receptors including TRPV1 (capsaicin and heat receptor), and TRPA1 (mechano-cold receptor). METHODS: Immunohistology and image-analysis were used to study TRP receptors in biopsies of nasal turbinate from control subjects, patients with allergic rhinitis, and non-allergic rhinitis. RESULTS: TRPM8-immunoreactive nerve fibres were observed in the sub-epithelium, and were profuse around blood vessels in deeper regions, where they were markedly greater in number than TRPV1+ fibers. Image analysis of TRPM8 in sub-epithelial and vascular regions showed no significant differences between control and the rhinitis patient groups. TRPA1-immunoreactivity was weak and seen rarely in nerve fibres. CONCLUSION: We show that TRPM8 nerve fibres are abundant in nasal mucosa particularly around blood vessels, and may mediate neurovascular reflexes. TRPM8 antagonists deserve consideration for therapeutic trial in rhinitis.

Association of marital status with access to renal transplantation.

In this report we evaluated the association of marital status with access to renal transplantation. We analyzed data from the USRDS. In patients with ESRD aged ≥ 27 (mean age of first marriage in the US), we analyzed the association of marital status with two outcomes: (1) likelihood of being placed on the waiting list for renal transplantation or first transplant, (2) likelihood of receiving kidney transplant in patients already listed. We analyzed marital status as a categorical variable: (1) not married (including never been married and widowed); (2) divorced or separated; and (3) currently married. Subgroups based on age, race, sex, donor type and diabetic status were also analyzed. After adjustments for the included independent variables and compared to individuals never married or widowed, those who were divorced/separated (HR 1.55, p < 0.001) and currently married (HR 1.54, p < 0.001) had a higher likelihood of being placed on the transplant waiting list. Once listed, married individuals had higher chances of getting transplanted as well (HR 1.28, p = 0.033). This trend was consistent in most of the subgroups studied. We demonstrated that being married is associated with better access to renal transplantation compared to those who were never married/widowed.

Advances in volume monitoring in dialysis patients.

Estimating volume status in patients on chronic dialysis is of great clinical value. Both hypervolemia and hypovolemia are associated with serious short term and long term complications, and volume status is often difficult to assess due to multiple factors affecting intravascular and extravascular volume compartments, as well as variability between patients in baseline blood pressures and physical exams. Traditional methods such as estimated dry weight (EDW) and physical exams are often not accurate because of the subjective nature of these indicators and variability between patients' baselines. This can lead to inaccurate volume status estimation and the associated complications. Furthermore, the concept of estimated dry weight is often defined based on measurements of blood pressure which may not accurately reflect volume status. In this review we describe several methods of measuring volume status in dialysis patients that may be more accurate than traditional measurements of blood pressure and dry weight estimation. These methods include dilutional techniques, imaging of vascular structures, use of biomarkers, bioimpedance analysis and online monitoring of biochemical variables during dialysis itself. We also discuss the clinical applicability and comparisons between these methods including the benefits and drawbacks of these methods and areas for future research.

A Metabolic Intravascular Platform to Study FDG Uptake in Vascular Injury.

PURPOSE: Metabolic alterations underlie many pathophysiological conditions, and their understanding is critical for the development of novel therapies. Although the assessment of metabolic changes in vivo has been historically challenging, recent developments in molecular imaging have allowed us to study novel metabolic research concepts directly in the living subject, bringing us closer to patients. However, in many instances, there is need for sensors that are in close proximity to the organ under investigation, for example to study vascular metabolism. METHODS: In this study, we developed and validated a metabolic detection platform directly in the living subject under an inflammatory condition. The signal collected by a scintillating fiber is amplified using a photomultiplier tube and decodified by an in-house tunable analysis platform. For in vivo testing, we based our experiments on the metabolic characteristics of macrophages, cells closely linked to inflammation and avid for glucose and its analog 18F-fluorodeoxyglucose (18F-FDG). The sensor was validated in New Zealand rabbits, in which inflammation was induced by either a) high cholesterol (HC) diet for 16 weeks or b) vascular balloon endothelial denudation followed by HC diet. RESULTS: There was no difference in weight, hemodynamics, blood pressure, or heart rate between the groups. Vascular inflammation was detected by the metabolic sensor (Inflammation: 0.60 ± 0.03 AU vs. control: 0.48 ± 0.03 AU, p = 0.01), even though no significant inflammation/atherosclerosis was detected by intravascular ultrasound, underscoring the high sensitivity of the system. These findings were confirmed by the presence of macrophages on ex vivo aortic tissue staining. CONCLUSION: In this study, we validated a tunable very sensitive metabolic sensor platform that can be used for the detection of vascular metabolism, such as inflammation. This sensor can be used not only for the detection of macrophage activity but, with alternative probes, it could allow the detection of other pathophysiological processes.

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.