Assessing Stakeholder Engagement for Outcomes-Based Research Among Patients With Chronic Rhinosinusitis and Asthma: A Survey-Based Investigation.

BACKGROUND: Despite significant morbidity, there remains a critical need for prospective analyses to investigate the impact of comorbid chronic rhinosinusitis (CRS) with asthma (CRSwA) on patient centered outcomes. The objective of this study was to ascertain critical stakeholder feedback from patients that could inform future study design based on patient preferences, in an effort to optimize patient enrollment. METHODS: A prospective, descriptive study was performed in order to determine the importance of various factors on CRSwA treatment among critical stakeholders. A Likert-scale survey highlighting various aspects of treatment of CRSwA and elucidating patient enthusiasm for clinical enrollment was constructed and prospectively administered to patients with CRSwA. A univariate analysis was instituted to understand the significance of the different trial design preferences. RESULTS: Survey responses were collected from a total of 17 patients with CRSwA. With Likert scores >4/5, responses indicated significant stakeholder interest in research focused on understanding symptom triggers, including the impact of air quality and allergens. Importantly, the highest mean scores noted were for studies focused on improving (1) overall quality of life (4.8/5) and (2) lung function (4.8/5). Patients appeared least interested in participation in a randomized trial, whereas the greatest support was communicated for a purely observational trial (P = .08). CONCLUSION: Patients with CRSwA demonstrate enthusiasm for participation in research that focuses on improving patient centered outcomes-specifically quality of life and lung function. Stakeholder feedback also indicates a preference for observational study design over randomized control trials.

Electronic health record-derived outcomes in obstructive sleep apnea managed with positive airway pressure tracking systems.

STUDY OBJECTIVES: To assess the effectiveness of continuous positive airway pressure (CPAP) management guided by CPAP machine downloads in newly diagnosed patients with obstructive sleep apnea (OSA) using electronic health record-derived health care utilization, biometric variables, and laboratory data. METHODS: Electronic health record data of patients seen at the University of Utah Sleep Program from 2012-2015 were reviewed to identify patients with new diagnosis of OSA in whom CPAP adherence and residual apnea-hypopnea index as measured by a positive airway pressure adherence tracking device data for ≥ 1 year were available. Biometric data, laboratory data, and system-wide charges were compared in the 1 year before and after CPAP therapy. Subgroups were divided by whether patients met tracking criteria, mean nightly usage, and OSA severity. RESULTS: 976 consecutive, newly diagnosed participants with OSA (median age 55 years, 56.6% male) met inclusion criteria. There was a mean decrease of systolic blood pressure (BP) of 1.2 mm Hg and diastolic BP of 1.0 mm Hg within a year of initiation of CPAP therapy. BP improvements in the subgroup meeting CPAP tracking targets were 1.36 mmHg (systolic) and 1.37 mmHg (diastolic). No significant change was noted in body mass index, glycated hemoglobin, or serum creatinine values within a year of starting CPAP therapy, and health care utilization increased (mean acute care visits 0.22 per year to 0.53 per year; mean charges of $3,997 per year to $8,986 per year). CONCLUSIONS: An improvement in BP was noted within a year of CPAP therapy in newly diagnosed patients with OSA, with no difference in the magnitude of improvement between those meeting tracking system adherence targets. CITATION: Locke BW, Neill SE, Howe HE, Crotty MC, Kim J, Sundar KM. Electronic health record-derived outcomes in obstructive sleep apnea managed with positive airway pressure tracking systems. J Clin Sleep Med. 2022;18(3):885-894.

Transcriptional Changes in Chronic Rhinosinusitis with Asthma Favor a Type 2 Molecular Endotype Independent of Polyp Status.

BACKGROUND: Data regarding the inflammatory profile of patients with asthma and chronic rhinosinusitis (CRS-A) with (CRSwNP-A) and without (CRSsNP-A) nasal polyposis remain limited. OBJECTIVE: Define and compare systemic transcriptional changes in patients with CRS-A to those with non-asthma-related CRS with (CRSwNP) and without nasal polyposis (CRSsNP). METHODS: Thirty-four patients with CRS-A (n=19) and CRS (n=15) were prospectively enrolled into an observational study. Demographic information and subjective and objective disease severity measures were recorded. Multiplex gene expression analysis of mRNA extracted from peripheral blood was performed. A total of 594 genes associated with innate/adaptive immunity were analyzed using NanoString technology. Gene expression ratios were reported for genes that were differentially expressed among these cohorts. Linear regression analysis was used to compare the mRNA transcript copy numbers for each gene with disease severity. RESULTS: There was no significant difference in age, gender, nasal polyposis, or health-related quality of life measures between the two groups (p>0.05). HLA class II histocompatibility antigen, DRB3-1 beta chain (HLA-DRB3) was significantly upregulated in the peripheral blood of patients with CRSsNP-A compared to CRSsNP, whereas chemokine (C-C motif) ligands 4 (CCL4) and zinc finger protein helios (IKZF2) were significantly upregulated in CRSwNP-A compared to CRSwNP (p<0.05). CONCLUSION: Patients with CRSsNP-A demonstrate a molecular endotype associated with a Th2-dominant inflammatory profile compared to CRSsNP. Patients with CRSwNP-A similarly demonstrate an overrepresentation of genes associated with Th2-driven inflammation compared to patients with CRSwNP.

Asthma increases long-term revision rates of endoscopic sinus surgery in chronic rhinosinusitis with and without nasal polyposis.

BACKGROUND: Chronic rhinosinusitis with asthma (CRS-A) has a significant impact on patient morbidity and quality of life. Nevertheless, little is known about the natural history of endoscopic sinus surgery (ESS) in this cohort. The objective of this study was to evaluate revision rates of ESS in CRS-A and identify risk factors associated with increased likelihood for revision surgery compared to those with CRS without asthma (CRS-alone). METHODS: The Utah Population Database was queried for patients age >18 years with CRS who underwent at least 1 ESS between 1996 and 2018. Demographic information and history of ESS were collected and compared between CRS-A and CRS-alone using chi-square tests for categorical variables and t tests for continuous variables. Risk factors for revision surgery were analyzed using Cox proportional hazard models. RESULTS: A total of 33,090 patients (7693 CRS-A and 25,397 CRS-alone) were included in the final analysis. Mean follow up was 9.8 years in CRS-A and 9.1 years in CRS-alone (p < 0.001). The revision rate among patients with CRS-A (21.5%) was twice that of CRS-alone (10.8%) (p < 0.001). Among patients with CRS, a history of allergy (p < 0.001), asthma (p < 0.001), and nasal polyposis (p < 0.001) was independently associated with increased risk of revision ESS. Patients with CRS-A and nasal polyposis were 6 times more likely to require revision surgery than those with CRS-alone (p < 0.010). CONCLUSION: The rate of revision ESS in CRS-A was twice that of CRS-alone; patients with CRS-A and nasal polyposis were 6 times more likely to require revision than those with CRS-alone. ©2021 ARSAAOA, LLC.

The impact of intestinal transplantation on quality of life.

INTRODUCTION: Intestinal failure (IF) and intestinal transplant (ITx) are associated with poor quality of life (QoL). Disease-specific assessment of QoL for IF and ITx is challenging, owing to the different problems encountered. We have sought to compare QoL pre-ITx with post-ITx and have compared generic QoL with a stable IF population. METHODS: Two prospectively maintained databases of patients referred for and undergoing ITx and a chronic (Type 2 & 3) IF cohort were interrogated. QoL instruments used were generic (EQ-5D-5L and SF-36) and disease-specific (HPN-QOL and ITx-QOL). Analysis used Student's t-test and one-way ANOVA with Bonferroni correction for multiple comparisons. Data were collected pre- and post-ITx at 3, 6, 12-months and yearly thereafter. RESULTS: All QoL instruments improved following ITx to levels comparable with a cohort of stable IF patients not requiring ITx. Both the visual analogue score component (EQ-5D-5L) and the effect of underlying illness on QoL (HPN-QOL/ITx-QOL) were higher following ITx than either pre-ITx or when compared with the IF cohort. Effects on general health, ability to eat and drink, to holiday and travel were improved as early as 3 months post-ITx. Other components did not before 6-12 months following ITx, but were maintained to at least 24 months. Patient personal financial pressures are greater following ITx, even in a publicly funded healthcare system. CONCLUSION: ITx has beneficial effects on QoL compared to those assessed for or awaiting ITx. QoL following ITx is similar to patients with IF not requiring ITx. A QoL instrument that covers the journey of patients from IF through ITx would assist longitudinal analysis of the value and timing of ITx at an individual level.

Massive panniculectomy results in improved functional outcome.

BACKGROUND: Panniculus morbidus is a large abdominal apron found in morbidly obese patients. This condition creates a vicious cycle of weight gain and functional incapacity. Our study assessed the functional improvement in patients undergoing massive panniculectomy. METHODS: A retrospective review of panniculectomies performed from 1994 to 2012 was conducted. Twenty-seven patients with resections >20 lbs were selected. Data on demographics, operative details, complications, and pre- and postoperative functional capacity (using the Steinbrocker Functional Classification) were collected. RESULTS: The preoperative mean body mass index was 58 kg/m(2), with a mean resection weight of 33 lbs. The overall complication rate was 74%. A statistically significant improvement in functional capacity (preop mean 3.7 vs postop mean 2.0; P < .0001) was identified. CONCLUSIONS: Panniculus morbidus is a functionally debilitating condition and massive panniculectomy is often the only treatment available. Our data suggest that massive panniculectomy is a viable option for patients functionally incapacitated by panniculus morbidus.

Role of neurokinin 3 receptors in supraoptic vasopressin and oxytocin neurons.

Neurokinin 3 receptors (NK3-Rs) are expressed in the supraoptic nucleus (SON), and SON is innervated by substance P (SP)-expressing A1 neurons in the medulla. Because SP stimulates vasopressin (VP) and oxytocin release from explants of the hypothalamo-neurohypophyseal system (HNS), two hypotheses were tested: (1) SP-stimulated VP release is mediated by NK3-Rs, and (2) stimulation of the A1 pathway by hypotension activates SON NK3-Rs. Senktide, an NK3-R agonist, stimulated VP release from HNS explants, but neither a neurokinin 1 receptor antagonist [L732,138 (N-acetyl-L-tryptophan 3,5-bis(tri-fluoromethyl)benzyl ester)] nor two NK3-R antagonists (SB222200 and SB235375) prevented SP-stimulated VP release. Because the affinity of these antagonists for rat NK-Rs may limit their efficacy, NK3-R internalization was used to assess the ability of SP to activate SON NK3-Rs. Senktide, SP, or vehicle was microinjected above SON. The brain was perfused 5 min after injection and stained for NK3-R immunoreactivity. Using confocal microscopy, the number of NK3-R-immunoreactive (-IR) endosomes was counted in a 5.6(2) mu region of cytoplasm in SON neurons. Senktide, but not SP or vehicle, significantly increased the number of NK3-R-IR endosomes in the cytoplasm. When hypotension was induced with hydralazine, NK3-R internalization was observed within 5 min (p < 0.005). A decrease in cytoplasmic NK3-R immunoreactivity was observed within 15 min of hypotension. Unexpectedly, both senktide and hypotension resulted in translocation of NK3-R-IR immunoreactivity to the nucleus. Thus, although these studies do not identify SP as the NK3-R ligand, they do provide evidence for hypotension-induced release of an endogenous tachykinin in SON and evidence suggesting a role for NK3-Rs in transcription regulation.