Objective Measures Of Disease Severity Research Articles

Impact of the COVID-19 pandemic on chronic disease management and patient reported outcomes in patients with pulmonary hypertension: The Pulmonary Hypertension Association Registry.

To better understand the impact of the COVID-19 pandemic on the care of patients with pulmonary hypertension, we conducted a retrospective cohort study evaluating health insurance status, healthcare access, disease severity, and patient reported outcomes in this population. Using the Pulmonary Hypertension Association Registry (PHAR), we defined and extracted a longitudinal cohort of pulmonary arterial hypertension (PAH) patients from the PHAR's inception in 2015 until March 2022. We used generalized estimating equations to model the impact of the COVID-19 pandemic on patient outcomes, adjusting for demographic confounders. We assessed whether insurance status modified these effects via covariate interactions. PAH patients were more likely to be on publicly-sponsored insurance during the COVID-19 pandemic compared with prior, and did not experience statistically significant delays in access to medications, increased emergency room visits or nights in the hospital, or worsening of mental health metrics. Patients on publicly-sponsored insurance had higher healthcare utilization and worse objective measures of disease severity compared with privately insured individuals irrespective of the COVID-19 pandemic. The relatively small impact of the COVID-19 pandemic on pulmonary hypertension-related outcomes was unexpected but may be due to pre-established access to high quality care at pulmonary hypertension comprehensive care centers. Irrespective of the COVID-19 pandemic, patients who were on publicly-sponsored insurance seemed to do worse, consistent with prior studies highlighting outcomes in this population. We speculate that previously established care relationships may lessen the impact of an acute event, such as a pandemic, on patients with chronic illness.

Identification of circulating metabolites associated with wooden breast and white striping.

Current diagnostic methods for wooden breast and white striping, common breast muscle myopathies of modern commercial broiler chickens, rely on subjective examinations of the pectoralis major muscle, time-consuming microscopy, or expensive imaging technologies. Further research on these disorders would benefit from more quantitative and objective measures of disease severity that can be used in live birds. To this end, we utilized untargeted metabolomics alongside two statistical approaches to evaluate plasma metabolites associated with wooden breast and white striping in 250 male commercial broiler chickens. First, mixed linear modeling was employed to identify metabolites with a significant association with these muscle disorders and found 98 metabolites associated with wooden breast and 44 metabolites associated with white striping (q-value < 0.05). Second, a support vector machine was constructed using stepwise feature selection to determine the smallest subset of metabolites with the highest categorization accuracy for wooden breast. The final support vector machine achieved 94% accuracy using only 6 metabolites. The metabolite 3-methylhistidine, which is often used as an index of myofibrillar breakdown in skeletal muscle, was the top metabolite for both wooden breast and white striping in our mixed linear model and was also the metabolite with highest marginal prediction accuracy (82%) for wooden breast in our support vector machine. Overall, this study identified a candidate set of metabolites for an objective measure of wooden breast or white striping severity in live birds and expanded our understanding of these muscle disorders.

A machine-learning based objective measure for ALS disease severity

Amyotrophic Lateral Sclerosis (ALS) disease severity is usually measured using the subjective, questionnaire-based revised ALS Functional Rating Scale (ALSFRS-R). Objective measures of disease severity would be powerful tools for evaluating real-world drug effectiveness, efficacy in clinical trials, and for identifying participants for cohort studies. We developed a machine learning (ML) based objective measure for ALS disease severity based on voice samples and accelerometer measurements from a four-year longitudinal dataset. 584 people living with ALS consented and carried out prescribed speaking and limb-based tasks. 542 participants contributed 5814 voice recordings, and 350 contributed 13,009 accelerometer samples, while simultaneously measuring ALSFRS-R scores. Using these data, we trained ML models to predict bulbar-related and limb-related ALSFRS-R scores. On the test set (n = 109 participants) the voice models achieved a multiclass AUC of 0.86 (95% CI, 0.85–0.88) on speech ALSFRS-R prediction, whereas the accelerometer models achieved a median multiclass AUC of 0.73 on 6 limb-related functions. The correlations across functions observed in self-reported ALSFRS-R scores were preserved in ML-derived scores. We used these models and self-reported ALSFRS-R scores to evaluate the real-world effects of edaravone, a drug approved for use in ALS. In the cohort of 54 test participants who received edaravone as part of their usual care, the ML-derived scores were consistent with the self-reported ALSFRS-R scores. At the individual level, the continuous ML-derived score can capture gradual changes that are absent in the integer ALSFRS-R scores. This demonstrates the value of these tools for assessing disease severity and, potentially, drug effects.

PD06-10 URINARY ATP LEVELS: A POTENTIAL BIOMARKER OF OVERACTIVE BLADDER TREATMENT RESPONSE FOLLOWING ONABOTULINUM TOXIN-A INJECTIONS

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I (PD06)1 Sep 2021PD06-10 URINARY ATP LEVELS: A POTENTIAL BIOMARKER OF OVERACTIVE BLADDER TREATMENT RESPONSE FOLLOWING ONABOTULINUM TOXIN-A INJECTIONS Samantha Freeman, Laura Tellechea, Ilir Agalliu, Melissa Laudano, Nitya Abraham, and Sylvia Suadicani Samantha FreemanSamantha Freeman More articles by this author , Laura TellecheaLaura Tellechea More articles by this author , Ilir AgalliuIlir Agalliu More articles by this author , Melissa LaudanoMelissa Laudano More articles by this author , Nitya AbrahamNitya Abraham More articles by this author , and Sylvia SuadicaniSylvia Suadicani More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001974.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Overactive bladder (OAB) is diagnosed clinically based on symptoms. However, a biomarker may help provide objective measurement of disease severity and improvement after treatment. ATP is released from the urothelium and levels tend to be higher in animal models and patients with OAB. Bladder onabotulinum toxin-A (BTX-A) injections decrease stretch-induced ATP release in animal models, yet little is known about the effect of BTX-A on human urine ATP levels. The objective of this study is to quantify changes in voided urine ATP levels and correlate with OAB-V8 symptom improvement in women treated with BTX-A injection. METHODS: Urine samples were collected and frozen on dry ice from women prior to and after 100 units of BTX-A treatment. Urine ATP levels were quantified using the luciferin-luciferase luminescent assay. OAB-V8 questionnaires were administered at time of urine collection. Women with positive urine cultures or neurogenic bladder were excluded. Degree of OAB-V8 score improvement was used to categorize participants: non-responders (change<8), mild responders (change 8-16), moderate responders (change 17-24), and marked responders (change>24). Percent change in ATP level was compared based on OAB-V8 score improvement and statistical significance was determined using the Mann-Whitney test. RESULTS: Urine was collected from 23 female patients (OAB-V8 scores 2 to 40); 7 were excluded. Median age was 53.5 years (49.5-61.5). 8 patients had chronic pain disorders, 2 patients had Type 2 diabetes, and 6 patients had prior pelvic surgery. After BTX-A injections, responders had significantly lower median ATP levels compared to non-responders at 2 weeks (p=0.0268). When patients were classified according to OAB-V8 score improvement (non-responder, mild, moderate, marked responders), the improvement directly correlated with a decrease in ATP levels (Figure 1). CONCLUSIONS: Decreases in urine ATP levels after BTX-A injections were associated with clinical improvement in OAB symptoms. This may be the result of a direct or indirect effect of BTX-A on mechanisms of urothelial ATP release and signaling. Quantification of urine ATP may provide a valuable tool to assess treatment response and guide further management. Source of Funding: N/A © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e103-e104 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Samantha Freeman More articles by this author Laura Tellechea More articles by this author Ilir Agalliu More articles by this author Melissa Laudano More articles by this author Nitya Abraham More articles by this author Sylvia Suadicani More articles by this author Expand All Advertisement Loading ...

Tired of Being Ignored: Fatigue as a Presenting Symptom in Primary Hyperparathyroidism

BackgroundFatigue is a common presenting symptom in primary hyperparathyroidism (PHPT). Although fatigue alone is not currently an indication for parathyroidectomy, it can have a significant detrimental effect on quality of life. The purpose of this study was to determine if there are underlying differences in demographic or disease characteristics in patients with PHPT who present with fatigue compared with those who do not. MethodsWe reviewed a prospective database of 2197 patients undergoing parathyroidectomy for PHPT by three endocrine surgeons from 2001 to 2019. Patients were divided into two groups based on the presence or absence of fatigue as a presenting symptom. Objective measures of disease severity were then compared between groups. ResultsA total of 1379 (63%) patients presented with fatigue. Patients presenting with fatigue were more likely to be female and to have a prior fracture, lower preoperative serum calcium (Ca), and normocalcemic PHPT. There were no statistically significant differences between groups in age, body mass index, history of nephrolithiasis, or preoperative serum parathyroid hormone levels. Patients presenting with fatigue were also more likely to have smaller parathyroid glands and multiglandular disease. No statistically significant differences were detected in postoperative serum Ca and parathyroid hormone levels, or cure or recurrence rates. ConclusionsPatients with PHPT who report fatigue as a presenting symptom present with more complex disease as manifested by a higher incidence of multiglandular disease and normocalcemic PHPT. Despite this, surgical cure is equivalent to other patients. Therefore, fatigue should be a discrete indication for parathyroidectomy in PHPT.

Multisite Study of Evoked Potentials in Rett Syndrome.

The aim of the current study was to evaluate the utility of evoked potentials as a biomarker of cortical function in Rett syndrome (RTT). As a number of disease-modifying therapeutics are currently under development, there is a pressing need for biomarkers to objectively and precisely assess the effectiveness of these treatments. Yearly visual evoked potentials (VEPs) and auditory evoked potentials (AEPs) were acquired from individuals with RTT, aged 2 to 37 years, and control participants across 5 sites as part of the Rett Syndrome and Related Disorders Natural History Study. Baseline and year 1 data, when available, were analyzed and the repeatability of the results was tested. Two syndrome-specific measures from the Natural History Study were used for evaluating the clinical relevance of the VEP and AEP parameters. At the baseline study, group level comparisons revealed reduced VEP and AEP amplitude in RTT compared to control participants. Further analyses within the RTT group indicated that this reduction was associated with RTT-related symptoms, with greater severity associated with lower VEP and AEP amplitude. In participants with RTT, VEP and AEP amplitude was also negatively associated with age. Year 1 follow-up data analyses yielded similar findings and evidence of repeatability of EPs at the individual level. The present findings indicate the promise of evoked potentials (EPs) as an objective measure of disease severity in individuals with RTT. Our multisite approach demonstrates potential research and clinical applications to provide unbiased assessment of disease staging, prognosis, and response to therapy. ANN NEUROL 2021;89:790-802.

Predictors of disease severity in children presenting from the community with febrile illnesses: a systematic review of prognostic studies

IntroductionEarly identification of children at risk of severe febrile illness can optimise referral, admission and treatment decisions, particularly in resource-limited settings. We aimed to identify prognostic clinical and laboratory factors...

Does Stem Cell Implantation Have an Effect on Severity of Retinitis Pigmentosa: Evaluation with a Classification System?

Background: Cell replacement therapies have been evaluated in recent years as an alternative for various retinal pathologies to evaluate the therapeutic efficacy of cell therapy, it is important to measure the severity of the disease. The aim of this study was to evaluate the effect of umbilical cord derived Mesenchymal Stem Cell (UC-MSC) implantation on severity of Retinitis Pigmentosa (RP). Methods: This single-center, clinical study included data of 138 eyes of 92 patients who had a confirmed diagnosis of RP and received stem cell implantation to the suprachoroidal area with a surgical procedure. Patients were evaluated before and 1 year after the surgery regarding to the outcome measures of Best Corrected Visual Acuity (BCVA), Optical Coherence Tomography (OCT) and Visual Field (VF) tests. BCVA, VF width and ellipsoid zone (EZ) width on OCT were recorded for each patient and a scoring criterion was established for each variable varying from 0 to 5 depending on its distribution. The cumulative score (from 0 to 15) was used to classify disease severity from grade 0 to 5. Results: All of the patients completed 12-month follow-up period. The median age of the patients was 40.8 years, 46% were female, 77% had been diagnosed within 10 years and 41% had a family history. 79% of the patients with family history had autosomal recessive inheritance pattern. There were statistically significant improvements in the mean BCVA and VF scores during the study (p < 0.05). The mean score and the mean grade of the disease also improved after the treatment (p < 0.05). There was a negative correlation between BCVA improvement and scoring and grading of the disease. Conclusions: This study demonstrated beneficial effect of suprachoroidally applied UC-MSCs on BCVA, VF and the severity score and grade of the disease during 12-month follow-up period. Cell mediated therapy based on the secretion of Growth Factors (GFs) seems to be an effective and safe option for the treatment of degenerative retinal diseases. This classification is simple, produces objective measure of disease severity and gives opportunity to compare the results of different treatment modalities.

Depressive symptoms and insecure attachment predict disability and quality of life in psoriasis independently from disease severity

Psoriasis is a multisystemic inflammatory disease with a significant burden in terms of disability and reduced quality of life. The interrelations between disease severity, psychological well-being, and disability and/or health-related quality of life (HRQOL) of psoriatic patients are not fully understood. The aim of the study was to assess the relative role of disease severity, depressive symptoms, and insecure attachment in predicting disability and HRQOL in 105 patients with psoriasis. Objective measures of disease severity included the Body Surface Area (BSA), the Psoriasis Area and Severity Index (PASI), and the Pain Visual Analog Scale (pain-VAS). The Sheehan Disability Scale (SDS). The Dermatology Life Quality Index (DLQI). Multivariate hierarchical regression analysis showed that a preoccupied style of attachment and the presence of depressive symptoms were predictors of disability and HRQOL over and above the contribution of demographic and clinical variables. The inclusion of attachment and depression into multivariate regression models improved substantially the prediction of disability and HRQOL. Conversely, the predictive utility of objective indicators of disease severity was scarce and only the pain-VAS emerged as a significant predictor of disability whereas there were no significant correlations between HRQOL and any of the objective indicators of disease severity. Measures capturing patients’ perspectives of the functional impact of disease should be routinely included in the clinical assessment of psoriasis.

Disease control after surgery for chronic rhinosinusitis: prospective, multi-institutional validation of the Sinus Control Test.

The Sinus Control Test (SCT) is a 4-question, patient-reported questionnaire that assesses disease control in chronic rhinosinusitis (CRS). This prospective, multicenter study examines SCT outcomes following endoscopic sinus surgery (ESS), further validating its use as a control instrument for CRS. Adults with CRS undergoing ESS were prospectively enrolled from 5 centers across North America. The SCT was administered at baseline and once 6 months after surgery. Quality of life and disease burden were evaluated using the 22-item Sino-Nasal Outcome Test (SNOT-22) and Lund-Kennedy endoscopy scores. Linear regression was used to determine whether specific demographic, comorbidity, or disease severity measures were independently associated with changes in SCT scores postoperatively. A total of 218 patients, 111 females (50.9%) and 107 males (49.1%), were enrolled, with mean ± standard deviation age of 50.1 ± 15.6 years. Mean SCT score improved from 8.9 ± 3.5 to 4.3 ± 3.7 postoperatively (p < 0.001). Preoperatively, 21.6% were uncontrolled, 71.5% partially controlled, and 6.9% controlled. Postoperatively, 6.0% were uncontrolled, 42.6% partially controlled, and 51.4% controlled (p < 0.001). Change in SCT score correlated independently with change in SNOT-22 (r = 0.500, p < 0.001) and endoscopy scores (r = 0.310, p < 0.001). Endoscopy scores did not correlate with control status among patients with CRS without nasal polyposis (CRSsNP) nor between uncontrolled and partially controlled patients. Demographics and comorbidities were not associated with changes in SCT. Improvement in disease control following ESS as measured by the SCT correlated with improvements in SNOT-22 and endoscopy scores. The SCT is an easily administered instrument that provides information complementary to existing patient-reported and objective measures of disease severity.

Selection criteria to palliative care implementation in advanced heart failure

Early palliative care (PC) integration in advanced and end-stage heart failure has shown to improve quality of life and spiritual well-being and to reduce physical symptoms. Barriers to implementation exist: perception that PC is opposite to "life-prolonging" therapies or is involved only in cancer disease and in end of life, prognostic difficulties in advanced heart failure, comorbidities, discrepancy between patient-reported symptom burden and objective measures of disease severity. This is why it is necessary to focus on patient and caregivers "needs" instead of exclusively numerical-objective measures, in order to emphasize clinical but also psychological, assistential and spiritual elements contributing to quality of life. The most appropriate instruments are "patient-reported outcome measures" (PROMs) or, better, "patient-centered outcome measures" (PCOMs), such as the Needs Assessment Tool: Progressive Disease-Heart Failure (NAT: PD-HF), Integrated Palliative Outcome Scale (IPOS), NECPAL and Supportive and Palliative Care Indicators Tool (SPICT). Finally, it is important to recognize triggers to initiate a PC approach (important changes in disease trajectory, difficult or refractory symptoms, frequent defibrillator shocks or transplant/mechanical support prevision, functional capacity decline, severe comorbidities, communication needs also for advanced care planning).

Disease Severity and Quality of Life in Patients With Idiopathic Pulmonary Fibrosis: A Cross-Sectional Analysis of the IPF-PRO Registry

Limited data are available on the association between clinically measured disease severity markers and quality of life (QOL) in idiopathic pulmonary fibrosis (IPF). The study examined the associations between objective disease severity metrics and QOL in a contemporary IPF population. This study evaluated baseline data from patients enrolled in the multicenter, US-based Idiopathic Pulmonary Fibrosis Prospective Outcomes Registry between June 2014 and July 2018. Disease severity metrics included FVC %predicted, diffusing capacity for carbon monoxide (Dlco) %predicted, supplemental oxygen use with activity, supplemental oxygen use at rest, and two summary scores (the Gender-Age-Lung Physiology index, based on gender, age, and %predicted values for Dlco and FVC; and the Composite Physiologic Index, based on %predicted values for Dlco, FVC, and FEV1). Multivariable adjusted regression models were used to examine cross-sectional associations between each severity measure and St. George's Respiratory Questionnaire (SGRQ) total score. Among 829 patients with complete SGRQ data, the median (interquartile range) SGRQ score at enrollment was 40 (26-53), with higher scores indicating worse QOL. Modest SGRQ impairments were observed with increasing Gender-Age-Lung Physiology score (2.9 [1.8-4.0] per 1-point increase] and with increasing Composite Physiologic Index scores (3.0 [2.4-3.6] per 5-point increase). Substantial SGRQ impairments were observed for oxygen use with activity (15.6 [12.9-18.2]), oxygen use at rest (16.2 [13.0-19.4]), and decreasing Dlco (5.0 [4.0-6.1] per 10%decrease in %predicted). Objective measures of disease severity, including severity scores, physiologic parameters, and supplemental oxygen use, are associated with worse QOL in patients with IPF. ClinicalTrials.gov; No.: NCT01915511; URL: www.clinicaltrials.gov.

Tossing and Turning in Bed: A Wearable Sensor Documents Abnormal Nocturnal Movements in Parkinson's Disease

Background: Sleep interruptions and nocturnal hypokinesia are common in Parkinson's disease (PD). Pilot work using wearable technologies showed fewer nocturnal movements in patients with advanced PD compared to controls. However, the prevalence of these impairments in early stage of the disease and the influence of non-motor symptoms, and dopaminergic medication are unknown. Methods: This study evaluated wearable sensor data collected in 305 patients with PD at different Hohen and Yahr disease stages (HY HY H&Y3=77) and 205 healthy controls (HC). Subjects wore a tri-axial accelerometer continuously (24/7) on the lower back for at least 2 days. Percent upright-time and nighttime walking were defined based on the vertical axis of the acceleration signal and were classified as sleep interruptions. The number, velocity, time, side, and degree of rotations in bed during the night evaluated nocturnal movements. Findings: Nocturnal lying-time was similar between PD and controls (p=0.501), however, the number of turns and the turn velocity significantly decreased (p<0.001) with H&Y stage. Advanced patients (H&Y3) had more upright periods during the night while the number and velocity of their turns were reduced (p<=0.021). Recently diagnosed patients (<1 year from diagnosis) were similar to controls in number of nocturnal turns (p=0.148) but showed longer turning time (p=0.001) and reduced turn magnitude (p=0.002). Nocturnal movements were significantly correlated with non-motor symptoms, cognition, and dopaminergic medication. Interpretation: Reduced nocturnal movements are already detectable in recently diagnosed patients and are associated with increased PD motor severity and dysautonomia. Using wearable sensors for continuous monitoring at night may offer an unbiased, objective measure of disease severity that could enhance optimal nighttime dopaminergic treatment and utilization of turning strategies. Funding Statement: European Commission (FP7 project V-TIME-278169), The Michael J Fox Foundation for Parkinson's research, a grant from Biogen Inc and by the NIHR/Wellcome Trust Clinical Research Facility (CRF). Declaration of Interests: Anat Mirelman, Jeff Hausdorff and Nir Giladi report having submitted a patent for assessment of mobility using wearable sensors in Parkinson's disease. The intellectual property rights are held by the Tel Aviv Medical Center. Prof. Mirelman and Hausdorff also serve as consultants for the Michael J Fox Foundation, Biogen, Sanofi (JH) and Neuroderm (AM) in areas relating to the use of wearable sensors to assess mobility in PD. JMH and AM have received grant funding from the European Commission and MJFF. Lynn Rochester reports no conflict of interests pertaining to the manuscript. She receives grants from the Medical Research Council, European Commission, NIHR, Wellcome Trust, EPSRC, Parkinson's UK, and the Stroke Association. Alice Nieuwboer reports no conflict of interest pertaining to the manuscript. She has received grant funding from the European Commission. Bastiaan R Bloem currently serves on the editorial of Practical Neurology and Digital Biomarkers, has received honoraria from serving on the scientific advisory board for Abbvie, Biogen, UCB and Walk with Path, has received fees for speaking at conferences from AbbVie, Zambon, Roche, GE Healthcare and Bial, and has received research support from the Netherlands Organization for Scientific Research, the Michael J Fox Foundation, UCB, Abbvie, the Stichting Parkinson Fonds, the Hersenstichting Nederland, the Parkinson’s Foundation, Verily Life Sciences, Horizon 2020, the Topsector Life Sciences and Health, and the Parkinson Vereniging. Jesse Cederbaum and Mirek Brys are shareholders in Biogen, Inc. Nir Giladi reports reports counseling for: Neuroderm, Intec Pharma, Teva, Genzyme-Sanofi, Biogen, Lysosomal Therapeutics, Denali, Cellanis, GaitBetter, Vibrant and Sionara; that he holds shares or options in Lysosomal Therapeutics, Cellanis, GaitBetter and Vibrant; that he has received royalties from Lysosomal Therapeutics; that he received honorarium from UCB, Teva, Novartis, Abbvie, Genzyme-Sanofie, Neuroderm, Bial, Shire, MDS; that he has chaired the DSMBs for Teva and Pharma2B; that he is a PI on a Center Grant given by Biogen to TLVMC. Inbar Hillel, Silvia Sel Din, Laura Avanzino, Inbal Maidan, Talia Herman, Meir Kestenbaum, Avner Thaler, Tanya Gurevich and Avi Orr Urtreger report no disclosures pertaining to the manuscript. Ethics Approval Statement: The studies were approved by local ethical committees and were performed according to the principles of the Declaration of Helsinki. All participants gave their informed written consent prior to participation.

Validation of exercise testing and laryngeal auscultation for grading brachycephalic obstructive airway syndrome in pugs, French bulldogs, and English bulldogs by using whole-body barometric plethysmography.

To determine whether the sensitivity of clinical examination for assessing upper airway disease severity in 3 breeds of brachycephalic dogs can be improved by incorporating an exercise test (ET) or by auscultation of a laryngeal stridor to predict laryngeal collapse. Prospective clinical study. Client-owned brachycephalic dogs (n = 44 ET; n = 57 laryngeal stridor assessment). In the first part of the study, clinical examinations were performed at rest and after 5-minute walk and 3-minute trot tests, and a grade reflective of brachycephalic obstructive airway syndrome (BOAS) severity was assigned. Whole-body barometric plethysmography was used as a comparative, objective measure of disease severity. In the second part of the study, the degree of laryngeal collapse present in dogs undergoing BOAS surgery was compared to pre-exercise and postexercise laryngeal stridor detected during functional testing. The sensitivity of clinical examination for BOAS diagnosis was 56.7% pre-ET, 70% after a 5-minute walk test, and 93.3% after a 3-minute trot test. The sensitivity of laryngeal stridor as a predictor of laryngeal collapse was improved after exercise (70%) compared with before exercise (60%). Specificity of laryngeal stridor for laryngeal collapse was 100% (pre-exercise and postexercise). The sensitivity of clinical examination for BOAS diagnosis was improved by inclusion of an ET, particularly the 3-minute trot test. Audible laryngeal stridor was highly specific but only moderately sensitive for laryngeal collapse. Inclusion of a 3-minute trot test and careful auscultation for laryngeal stridor are recommended during BOAS assessment of brachycephalic dogs.

Patient Reported Outcomes After Pneumatic Dilation for Achalasia

Introduction: Patient reported outcomes (PRO) and quality of life (QOL) in achalasia patients are an emerging determinants of achalasia treatment success. We examined PRO after pneumatic dilation (PD) in treatment naive patients to assess correlation with the Eckardt score, an objective measurement of disease severity. We also explored PPI use and GERD symptoms before and after PD as a measure of QOL. Methods: An IRB approved retrospective cross-sectional study was conducted at a tertiary care university clinic. 51 treatment naive patients seen between 2002-2014 with manometric diagnosis of idiopathic achalasia were included. Patients with confounding esophageal or autoimmune pathology were excluded. Patients responded to a telephone questionnaire based on the Achalasia Severity Questionnaire regarding pre- and post-PD metrics including QOL, perception of disease severity, GERD symptoms, PPI use, and willingness to undergo repeat PD. Descriptive statistics, Wilcoxon sign rank test for matched pairs, and Spearman correlation were used for statistical analysis. Results: Eckardt score, QOL, and perception of disease severity improved after PD (p<0.001). Associations between improvements in Eckardt score and QOL (r2= -0.429, p<0.01); Eckardt score and perception of disease severity (r2=0.389, p<0.01); and perception of disease severity and QOL (r2=0.561, p<0.01) were found. There was a weak correlation between improved QOL and decreased PPI use (r2= -0.141, p<0.05). There was no significant association between PD failure and worsening of QOL, perception of disease severity, or Eckardt score (p=0.41). 22/51 patients reported pre-PD reflux symptoms compared to 14/51 post-PD. 31/51 reported pre-PD PPI use compared to 19/51 post-PD. Reported reflux symptoms decreased after PD (X2, p=0.017). Conclusion: PD improves Eckardt scores, QOL, and perception of disease severity in treatment naive achalasia patients. Improvements in QOL and perception of disease severity are associated with improved Eckardt scores, and are therefore reasonable metrics for gauging PD success. PD failure did not result in worsening of QOL, perception of disease severity, or Eckardt scores. Though post-procedural GERD is commonly reported, we found that reported reflux symptoms and PPI use decreased after PD. We conclude that patient reported outcomes are important factors in a holistic treatment approach to achalasia.

Mucus T helper 2 biomarkers predict chronic rhinosinusitis disease severity and prior surgical intervention.

Chronic rhinosinusitis (CRS) is a diverse clinical syndrome with a heterogeneous pathophysiology. Early attempts to identify CRS endotypes and biomarkers have largely relied on analysis of surgically obtained tissue, thus limiting their practical utility. This study examined the ability of mucus T helper 2 (Th2) biomarkers to predict CRS disease severity and clinical characteristics. CRS (n = 90) and healthy control subjects (n = 17) were prospectively enrolled prior to surgical intervention and mucus levels of interleukin (IL)-4, IL-5, and IL-13 were determined using a multiplex cytometric bead assay. Data for relevant cytokines was then scaled, normalized, and later combined to develop standardized metrics indicative of Th2-associated inflammation. Th2-high and Th2-low subgroups were consequently identified and validated against factors associated with disease severity and clinical outcomes. Mucus levels of IL-5 and IL-13 were elevated in CRS subjects compared to controls, while no significant difference was noted for IL-4. IL-5 and IL-13 high CRS were associated with worse objective measures of disease severity and greater rates of revision surgery. Similar relationships were noted for both cytokines when CRS with nasal polyps (CRSwNP) patients were analyzed separately. Th2-high CRS and Th2-low CRS were then categorized using a scaled IL-5/IL-13 metric. Th2-high CRS was characterized by an increased number of subjects with nasal polyps and comorbid asthma, and worse symptom and computed tomography (CT) scores. The Th2-associated cytokines, IL-5 and IL-13, are detectable in sinonasal mucus and their levels can be used to define Th2-high and Th2-low CRS. Identification of Th2-high and Th2-low endotypes using mucus-based biomarkers could facilitate stratification of CRS subgroups and guide personalized therapies.

Quality-of-Life Metrics Correlate With Disease Severity in Idiopathic Subglottic Stenosis.

Idiopathic subglottic stenosis (ISGS) can have significant impacts on quality of life (QOL), but it remains unclear how patients' subjective responses correlate with objective measurement of disease severity. Peak expiratory flow percentage (PEF%) has been shown to be an effective measure of disease severity in subglottic stenosis. This study aims to identify the key QOL questions correlated with PEF% and proposes a statistical model for prediction of disease severity. Patients with ISGS presenting to an academic laryngologist were included retrospectively from 2012 to 2016. Peak expiratory flow percentage (age, sex, and height adjusted) was recorded for each visit, along with four validated QOL instruments (European QOL-Five Dimensions; RAND 36-Item Health Survey; Clinical COPD [Chronic Obstructive Pulmonary Disease] Questionnaire; and the Airway, Dyspnea, Voice, and Swallowing Summary Assessment). A stepwise multiple linear regression was used to identify statistically significant independent variables correlated with PEF%, and a model was built with these variables. Thirty-two patients were included, with a total of 271 patient encounters. Overall scores from each of the four QOL instruments were correlated with PEF% values recorded each visit (P < 0.05). Question responses correlating most positively included overall breathlessness, difficulty catching breath, cough within the past week, dyspnea with moderate activity, perception that voice changes are restricting social life, and overall general health (all P < 0.01). A model constructed using six nonoverlapping questions yielded an adjusted R2 of 0.58. Quality of life is correlated to PEF% in ISGS. Using a limited number of QOL questions, clinicians can predict objective worsening or improvement of disease severity, as measured by spirometry. 2b. Laryngoscope, 2017.

058. How school attendance relates to perceived and objective measures of disease severity in paediatric rheumatological conditions – a service evaluation project

058. How school attendance relates to perceived and objective measures of disease severity in paediatric rheumatological conditions – a service evaluation project

EASI p-EASI: Utilizing a combination of serum biomarkers offers an objective measurement tool for disease severity in atopic dermatitis patients

EASI p-EASI: Utilizing a combination of serum biomarkers offers an objective measurement tool for disease severity in atopic dermatitis patients

Examination of high-antibiotic users in a multi-institutional cohort of chronic rhinosinusitis patients.

In addition to known concerns regarding antibiotic overuse, recent research indicates that excessive antibiotic use is associated with poorer long-term health. Given that rhinosinusitis is the leading condition accounting for antibiotic prescriptions in the ambulatory setting, we aimed to evaluate characteristics associated with greater antibiotic use in chronic rhinosinusitis (CRS). Adult CRS patients enrolled in a prospective, multi-institutional, observational cohort study evaluating treatment outcomes were included in this analysis. Study participants were asked to report the number of days out of the previous 90 days that systemic antibiotics were taken for sinus disease. Patient demographics, disease characteristics, and measures of disease severity were evaluated. A total of 561 patients from 4 institutions were included in the analysis, with mean antibiotic use of 17.4 ± 22.4 out of the prior 90 days. No differences between antibiotic-use groups were found for objective measures of disease severity (computed tomography [CT], endoscopy, Brief Smell Identification Test [BSIT] scores), however, increased patient-reported symptom burden (22-item Sino-Nasal Outcome Test [SNOT-22], Rhinosinusitis Disability Index [RSDI]) was associated with more antibiotic use. Patients reporting the most antibiotic use were older (p = 0.004) but no ethnic or gender differences were seen. Comorbid diagnoses of allergy, asthma, diabetes, depression, or fibromyalgia were not associated with increased antibiotic use. In accordance with literature recommendations, CRS with nasal polyps (CRSwNP) patients were less likely to have used antibiotics. Endoscopic sinus surgery (ESS) significantly decreased antibiotic use. Variability in antibiotic use in CRS appears to be driven by symptom burden, independent of objective measures of disease severity, patient demographics, and presence of comorbid disease. Clear guidelines are essential to define appropriate antibiotic use in CRS.