Publications by authors named "Robert Kern"

251 Publications

Publicly Reported Patient Satisfaction Scores in Academic Otolaryngology Departments.

Laryngoscope 2021 Apr 8. Epub 2021 Apr 8.

Department of Otolaryngology - Head and Neck Surgery, Northwestern University Feinberg, School of Medicine, Chicago, Illinois, U.S.A.

Objectives/hypothesis: Despite controversy regarding their impact and validity, there is a rising national focus on patient satisfaction scores (PSS). We describe the landscape of online PSS as posted by academic otolaryngology practices.

Study Design: Retrospective cross-sectional study.

Methods: Websites of academic otolaryngology programs were reviewed for PSS scores, provider type, and geographic location. Gender was determined by picture or profile pronouns. Years of experience were determined by year of initial American Board of Otolaryngology-Head and Neck Surgery certification. We defined PSS derived from Press-Ganey or Clinician and Group Consumer Assessment of Healthcare Providers and Systems surveys as "standardized PSS". We determined potential associations between provider characteristics and standardized PSS.

Results: Out of 115 Otolaryngology-Head and Neck Surgery academic programs, 40 (35%) posted a total of 64,638 online PSS surveys (nonstandardized plus standardized) of 507 unique otolaryngology care providers. Standardized PSS were posted for 473 providers (370 [78%] male; 446 physicians; 27 advanced practice providers). Median overall standardized PSS was 4.8 (interquartile range 4.7-4.9; range 3.8-5.0). PSS were similar between gender, provider type, and years of experience. Male providers had more surveys than female providers (149 vs. 93; P < .01). There was a linear relationship between number of surveys and years of experience (P < .01), but no relationship between number of surveys and overall standardized PSS.

Conclusions: Patient satisfaction with otolaryngology providers at academic institutions is consistently high, as demonstrated by high online PSS with little variability. The limited variation in PSS may limit their usefulness in differentiating providers and quality of care.

Level Of Evidence: NA Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29557DOI Listing
April 2021

Studies of the Role of Basophils in Aspirin Exacerbated Respiratory Disease Pathogenesis.

J Allergy Clin Immunol 2021 Apr 2. Epub 2021 Apr 2.

Division of Allergy and Immunology, Department of Medicine; Department of Otolaryngology Northwestern University Feinberg School of Medicine.

Background: Aspirin Exacerbated Respiratory Disease (AERD) is characterized by the triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and intolerance to cyclooxygenase-1 (COX-1) enzyme inhibitors. The underlying mechanisms contributing to AERD pathogenesis are not fully understood, but AERD is characterized by an enhanced type-2 inflammatory phenotype. Basophils are potent type 2 effector cells, but their involvement in AERD pathophysiology remains unclear.

Objective: To characterize the systemic and local basophil responses in AERD compared to CRSwNP patients.

Methods: Sinonasal tissues including inferior turbinate (IT) and/or nasal polyps (NP) and peripheral blood were collected from controls, AERD, and CRSwNP patients. Expression of cell surface (CD45, FcεRI, CD203c), activation (CD63) and intracellular (2D7) markers associated with basophils were characterized using flow cytometry. Clinical data including Lund-Mackay scores and pulmonary function were obtained.

Results: The mean number of basophils (CD45CD203cFcεRICD117) detected in AERD NP (147±28 cells/mg tissue) was significantly elevated compared to CRSwNP (69±20 cells/mg tissue; p=0.01). The number of circulating basophils was significantly elevated in AERD (p=0.04). Basophils in NP had significantly higher CD203c and CD63 MFI compared to blood in both conditions (p<0.01). Basophils from AERD NP had lower expression of the granule content marker 2D7 than matched blood (p<0.01) or NP of CRSwNP (p=0.06), suggesting ongoing degranulation. Basophil 2D7 MFI significantly correlated with pulmonary function (r=0.62, p=0.02) and inversely correlated with sinonasal inflammation (r=-0.56, p=0.004).

Conclusions: Increased basophil numbers and extent of ongoing degranulation in NP of patients with AERD compared to CRSwNP may contribute to the exaggerated disease pathogenesis and severity unique to AERD.
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http://dx.doi.org/10.1016/j.jaci.2021.02.045DOI Listing
April 2021

Awareness of illness is associated with better social and nonsocial cognition in recent-onset schizophrenia.

Schizophr Res 2021 Mar 23;231:51-53. Epub 2021 Mar 23.

Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States of America; Department of Psychology, University of California Los Angeles, Los Angeles, CA, United States of America; Semel Institute for Neuroscience and Human Behavior at UCLA, United States of America.

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http://dx.doi.org/10.1016/j.schres.2021.02.020DOI Listing
March 2021

Responsiveness and convergent validity of the chronic rhinosinusitis patient-reported outcome (CRS-PRO) measure in CRS patients undergoing endoscopic sinus surgery.

Int Forum Allergy Rhinol 2021 Mar 16. Epub 2021 Mar 16.

Department of Otolaryngology-Head and Neck Surgery, Northwestern University, Feinberg School of Medicine, Chicago, Illinois.

Background: The chronic rhinosinusitis patient-reported outcome (CRS-PRO) measure is a 12-item measure with previously demonstrated validity in chronic rhinosinusitis (CRS) patients receiving medical therapy. This study establishes the factor structure, responsiveness, and convergent validity of the CRS-PRO following endoscopic sinus surgery (ESS).

Methods: Northwestern CRS Subject Registry patients had pre-ESS, 3-month (n = 111; CRS without nasal polyps [CRSsNP] = 60, CRS with nasal polyps [CRSwNP] = 51), and 6-month (n = 86; CRSsNP = 47, CRSwNP = 39) post-ESS assessments where patients completed the CRS-PRO, 22-item Sino-Nasal Outcome Test (SNOT-22), and four Patient-Reported Outcomes Measurement (PROM) Information System (PROMIS) short forms (general health measures). Patients had pre-ESS objective testing (endoscopic and radiographic assessment). Factor analysis was conducted using principal axis factoring with varimax rotation on the baseline CRS-PRO. The clinically important difference (CID) was estimated using both distribution-based and anchor-based methods.

Results: Factor analysis found the CRS-PRO comprised the "rhino-psychologic," "facial discomfort," and "cough" factors, which were responsive to ESS and correlated with the other PROMs. The changes observed in the CRS-PRO at 3 months had strong correlation with the corresponding changes in SNOT-22 (r = 0.792, p < 0.0001) and moderate correlations with changes in PROMIS fatigue and sleep domains. These changes had a very large effect size (Cohen's d 1.44) comparable to the longer SNOT-22 (Cohen's d 1.41) with slightly larger effect sizes observed in CRSwNP compared to CRSsNP patients. Similar convergent validity and responsiveness were observed in the 6-month data. The CRS-PRO CID was estimated to be between 5.0 and 7.5 (midpoint 6.0) using distribution-based and anchor-based methods.

Conclusion: This study demonstrates the validity and responsiveness of the CRS-PRO in subjects receiving ESS.
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http://dx.doi.org/10.1002/alr.22782DOI Listing
March 2021

Self-stigma in psychotic disorders: Clinical, cognitive, and functional correlates in a diverse sample.

Schizophr Res 2021 Feb 11;228:145-150. Epub 2021 Jan 11.

Desert Pacific Mental Illness Research, Education and Clinical Center, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, United States of America; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, United States of America.

Self-stigma in mental illness is linked to negative clinical and functional outcomes, but little is known about its correlates specifically in psychotic disorders. Here we investigated the role of clinical symptoms, cognition, and vocational status as correlates of self-stigma in 98 individuals with psychotic disorders (36 Black American, 32 White Hispanic, 11 White Non-Hispanic, 11 Asian American). A principal component analysis of the Internalized Stigma of Mental Illness scale yielded three components: Experiential Stigma, Stereotype Endorsement, and Stigma Resistance. Higher Experiential Stigma was associated with greater severity of affective symptoms and lower vocational status. Higher Stigma Resistance was associated with higher social and non-social cognition, and higher vocational status. Stereotype Endorsement did not significantly correlate with any predictor variable. Linear regression models showed that 13% of the variance in Experiential Stigma was explained by affective symptoms and vocational status, and 20% of the variance in Stigma Resistance was explained by non-social cognition and vocational status. These findings provide new information about the correlates of self-stigma in an ethnically and racially diverse psychotic disorder sample. Such information may lead to a better understanding of self-stigma mechanisms in this population.
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http://dx.doi.org/10.1016/j.schres.2020.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987768PMC
February 2021

Valuing diversity, equity, and inclusion.

Int Forum Allergy Rhinol 2021 Jan;11(1)

Oregon Health and Science University, Portland, OR.

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http://dx.doi.org/10.1002/alr.22751DOI Listing
January 2021

Mechanisms and biomarkers of inflammatory endotypes in chronic rhinosinusitis without nasal polyps.

J Allergy Clin Immunol 2021 Apr 14;147(4):1306-1317. Epub 2020 Dec 14.

Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill. Electronic address:

Background: Chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) is a common disease that is characterized by multiple inflammatory endotypes. However, the molecular mechanisms in CRSsNP are poorly understood compared with those of polypoid CRS.

Objective: Our aim was to identify mechanisms and biomarkers associated with inflammatory endotypes underpinning CRSsNP.

Methods: Ethmoid tissues and nasal lavage fluids (NLFs) were obtained from control patients and patients with CRS. The gene expression profiles were determined by microarray analysis and quantitative RT-PCR, and expression of proteins was measured by ELISA and Luminex analysis.

Results: Microarray found that compared with their levels of expression in control tissue, the levels of expression of 126, 241, and 545 genes were more than 3-fold and significantly elevated in CRSsNP with type 1 (T1) endotype, type 2 (T2) endotype, and type 3 (T3) endotype, respectively. Selected identified genes were confirmed by RT-PCR. Gene set enrichment analysis suggested that T1 CRSsNP was associated with IFN-γ signaling and antiviral immunity controlled by T cells (T1 and CD8), natural killer cells, and antigen-presenting cells; T2 CRSsNP was associated with STAT6 signaling and IgE-mediated activation controlled by eosinophils, mast cells, T2 cells, group 2 innate lymphoid cells, and antigen-presenting cells; and T3 CRSsNP was associated with IL-17 signaling, acute inflammatory response, complement-mediated inflammation, and infection controlled by neutrophils, T17 cells, B cells, and antigen-presenting cells. The results suggest that T1 (CXCL9 and CXCL10), T2 (eosinophilic proteins and CCL26), and T3 (CSF3) endotypic biomarkers in NLF may be able to distinguish tissue endotypes in CRSsNP.

Conclusions: Inflammatory endotypes in CRSsNP were controlled by different molecular mechanisms. NLF biomarker assays may allow for more precise and personalized medical treatments in CRS.
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http://dx.doi.org/10.1016/j.jaci.2020.11.037DOI Listing
April 2021

International consensus statement on allergy and rhinology: rhinosinusitis 2021.

Int Forum Allergy Rhinol 2021 Mar;11(3):213-739

Capital Medical University, Beijing, China.

I.

Executive Summary: BACKGROUND: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR-RS-2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence-based findings of the document.

Methods: ICAR-RS presents over 180 topics in the forms of evidence-based reviews with recommendations (EBRRs), evidence-based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary.

Results: ICAR-RS-2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence-based management algorithm is provided.

Conclusion: This ICAR-RS-2021 executive summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS.
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http://dx.doi.org/10.1002/alr.22741DOI Listing
March 2021

Array programming with NumPy.

Nature 2020 09 16;585(7825):357-362. Epub 2020 Sep 16.

Quansight, Austin, TX, USA.

Array programming provides a powerful, compact and expressive syntax for accessing, manipulating and operating on data in vectors, matrices and higher-dimensional arrays. NumPy is the primary array programming library for the Python language. It has an essential role in research analysis pipelines in fields as diverse as physics, chemistry, astronomy, geoscience, biology, psychology, materials science, engineering, finance and economics. For example, in astronomy, NumPy was an important part of the software stack used in the discovery of gravitational waves and in the first imaging of a black hole. Here we review how a few fundamental array concepts lead to a simple and powerful programming paradigm for organizing, exploring and analysing scientific data. NumPy is the foundation upon which the scientific Python ecosystem is constructed. It is so pervasive that several projects, targeting audiences with specialized needs, have developed their own NumPy-like interfaces and array objects. Owing to its central position in the ecosystem, NumPy increasingly acts as an interoperability layer between such array computation libraries and, together with its application programming interface (API), provides a flexible framework to support the next decade of scientific and industrial analysis.
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http://dx.doi.org/10.1038/s41586-020-2649-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759461PMC
September 2020

Effects of aerobic exercise on cardiorespiratory fitness and social functioning in veterans 40 to 65 years old with schizophrenia.

Psychiatry Res 2020 09 3;291:113258. Epub 2020 Jul 3.

UCLA Semel Institute for Neuroscience & Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, Los Angeles, California, United States of America; Department of Veterans Affairs Desert Pacific Mental Illness Research, Education, and Clinical Center, VA Greater Los Angeles Healthcare System, Los Angeles, California, United States of America.

The usual physical activity level of people with chronic histories of schizophrenia is very low. In this pilot study, we examined the effects of an easy to implement aerobic exercise (AE) program on cardiorespiratory fitness and social functioning in 54 Veterans aged 40-65 years old with schizophrenia. Participants were randomized 2:1 to AE (36 forty-minute sessions conducted 3 times per week over 12 weeks) versus a non-aerobic stretching exercise condition conducted under the same regimen and timeframe. Cardiorespiratory fitness improved significantly within the AE group (p<.0001), and differed significantly from the comparison group (p<.02; Cohen's d=.41). Trend-level improvements were seen in social functioning within the AE group (p<.09) and showed a similar trend level difference in the between-group comparison (p<.06; Cohen's d=.35). Improvements in social functioning were significantly related to gains in cardiorespiratory fitness (r=.42; p<.01). AE effects on other physical and mental health indices were also examined. Overall, the AE intervention was well-tolerated, safe, and showed low rates of attrition after the commencement of training. Our findings indicate it is feasible to improve cardiorespiratory fitness in this clinical population, and there is suggestive evidence that the interventions aimed to do so may also benefit social functioning.
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http://dx.doi.org/10.1016/j.psychres.2020.113258DOI Listing
September 2020

Should Oral Corticosteroids be Used in Medical Therapy for Chronic Rhinosinusitis? A Risk Analysis.

Laryngoscope 2021 03 7;131(3):473-481. Epub 2020 Jul 7.

Department of Otolaryngology-Head & Neck Surgery, University of Toronto, Toronto, Ontario, Canada.

Objectives: Oral corticosteroid (OCS) as a part of appropriate medical therapy (AMT) (formerly maximal medical therapy) in chronic rhinosinusitis remains controversial. While the risks of OCS are well known, the benefit remains unclear due the absence of a standardized prescribing regimen. Consequently, it is difficult to characterize whether the risks of OCS and its ability to avert endoscopic sinus surgery (ESS) are helpful in AMT. When OCS is highly effective at averting surgery, the lesser risks of OCS would be justified because it can avoid the greater risks of ESS. When OCS is poorly effective at averting ESS, the risks of OCS would not be justified because many patients will be exposed to both risks. This study seeks to identify the threshold effectiveness of OCS at averting ESS that would minimize risk exposure to patients.

Methods: A probabilistic risks-based decision analysis was constructed from literature reported incidences and impacts of adverse events of OCS and ESS. Monte Carlo analysis was performed to identify the minimum effectiveness required to avoid further intervention (MERAFI) for chronic sinusitis without nasal polyp (CRSsNP) and chronic sinusitis with nasal polyp (CRSwNP).

Results: The analysis showed MERAFI results of 20.8% (95% CI 20.7-20.9%) for CRSsNP and 16.8% (95% CI 16.7-16.9%) for CRSwNP.

Conclusions: Given reported OCS effectiveness in the range of 34-71% in CRSsNP and 46-63% in CRSwNP, this analysis suggests that the inclusion of OCS in AMT may be the lower risk strategy.

Level Of Evidence: N/A Laryngoscope, 131:473-481, 2021.
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http://dx.doi.org/10.1002/lary.28843DOI Listing
March 2021

The Impact of Anticholinergic Burden on Functional Capacity in Persons With Schizophrenia Across the Adult Life Span.

Schizophr Bull 2021 Jan;47(1):249-257

Centre for Addiction and Mental Health, Toronto, ON, Canada.

Anticholinergic burden (ACB) from medications impairs cognition in schizophrenia. Cognition is a predictor of functional capacity; however, little is known about ACB effect on functional capacity in this population. This study assesses the relationship between ACB and functional capacity across the life span in individuals with schizophrenia after controlling for ACB effect on cognition. A cross-sectional analysis was performed with data collected from 6 academic tertiary health centers. Two hundred and twenty-three community-dwelling participants with schizophrenia or schizoaffective disorder were included in this study. Main variables were ACB, antipsychotic olanzapine equivalents, functional capacity, cognition, and negative symptoms. Simultaneous linear regression analyses were performed to assess the association between ACB, functional capacity, and cognition and then between ACB and cognition. A mediation analysis was then performed to examine whether cognition mediated ACB effect on functional capacity if there was an association between ACB and cognition. Mean age of participants was 49.0 years (SD = 13.1, range 19-79), and 63.7% of participants had severe ACB, ie, a total score of 3 or above. Regression analyses revealed that ACB, age, education, and cognition independently predicted functional capacity and that ACB predicted cognition among those aged 55 years and older. Mediation analysis showed that cognition did partially mediate the effect of ACB on functional capacity in this older cohort. In conclusion, people with schizophrenia are exposed to severe ACB that can have a direct negative impact on functional capacity after controlling for its impact on cognition. Reducing ACB could improve functional capacity and potentially real-world function in schizophrenia.
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http://dx.doi.org/10.1093/schbul/sbaa093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825090PMC
January 2021

A new approach to categorization of radiologic inflammation in chronic rhinosinusitis.

PLoS One 2020 29;15(6):e0235432. Epub 2020 Jun 29.

Department of Environmental Health and Engineering, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States of America.

Chronic rhinosinusitis (CRS) is a prevalent condition. Clinical diagnosis requires subjective evidence (i.e. symptoms) and objective evidence of inflammation (e.g. sinus computed tomography [CT]). Few studies have assessed differences in common CT scoring approaches for CRS, the Lund-Mackay (LM) system and its modified version (mLM); none in a general population sample. The aims of this study were to answer the following: (1) Is mLM superior to LM? (2) Should nasal cavity opacification be included in scoring? (3) How should location-specific scores be utilized? (4) If location-specific scores are summed, what should be the cutoff? (5) Are associations of opacification with symptoms observed when using different measurement approaches? We scored sinus CTs using LM and mLM from 526 subjects selected from a larger CRS study. Exploratory factor analysis (EFA) assessed similarity of mLM and LM. Latent class analysis (LCA) identified subgroups of sinus opacification patterns. Factors associated with group membership and relations with nasal and sinus symptoms (NSS) guided clinical relevance. EFA suggested no differences between LM and mLM, or after addition of nasal cavity opacification. LCA identified three opacification groups: no/mild, localized, and diffuse. Males were 2.7x more likely to have diffuse opacification than females, as were those with asthma or hay fever. A LM cutoff of 3 had similar performance to the currently used 4. Diffuse opacification was associated with nasal blockage and smell loss. Differing patterns of opacification may be clinically relevant, improving measurement of objective evidence in studies of CRS and sinus diseases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235432PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323942PMC
September 2020

Motivational and cognitive factors linked to community integration in homeless veterans: study 1 - individuals with psychotic disorders.

Psychol Med 2020 Jun 10:1-9. Epub 2020 Jun 10.

Department of Psychiatry and Biobehavioral Sciences, Jane and Terry Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, CA90024-1759, USA.

Background: Little is known about the determinants of community integration (i.e. recovery) for individuals with a history of homelessness, yet such information is essential to develop targeted interventions.

Methods: We recruited homeless Veterans with a history of psychotic disorders and evaluated four domains of correlates of community integration: perception, non-social cognition, social cognition, and motivation. Baseline assessments occurred after participants were engaged in supported housing services but before they received housing, and again after 12 months. Ninety-five homeless Veterans with a history of psychosis were assessed at baseline and 53 returned after 12 months. We examined both cross-sectional and longitudinal relationships with 12-month community integration.

Results: The strongest longitudinal association was between a baseline motivational measure and social integration at 12 months. We also observed cross-sectional associations at baseline between motivational measures and community integration, including social, work, and independent living. Cross-lagged panel analyses did not suggest causal associations for the motivational measures. Correlations with perception and non-social cognition were weak. One social cognition measure showed a significant longitudinal correlation with independent living at 12 months that was significant for cross-lagged analysis, consistent with a causal relationship and potential treatment target.

Conclusions: The relatively selective associations for motivational measures differ from what is typically seen in psychosis, in which all domains are associated with community integration. These findings are presented along with a partner paper (Study 2) to compare findings from this study to an independent sample without a history of psychotic disorders to evaluate the consistency in findings regarding community integration across projects.
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http://dx.doi.org/10.1017/S0033291720001889DOI Listing
June 2020

Motivational and cognitive factors linked to community integration in homeless veterans: Study 2 - clinically diverse sample.

Psychol Med 2020 May 29:1-8. Epub 2020 May 29.

Department of Veterans Affairs, Desert Pacific Mental Illness Research, Education, and Clinical Center, Los Angeles, USA.

Background: In an initial study (Study 1), we found that motivation predicted community integration (i.e. functional recovery) 12 months after receiving housing in formerly homeless Veterans with a psychotic disorder. The current study examined whether the same pattern would be found in a broader, more clinically diverse, homeless Veteran sample without psychosis.

Methods: We examined four categories of variables as potential predictors of community integration in non-psychotic Veterans: perception, non-social cognition, social cognition, and motivation at baseline (after participants were engaged in a permanent supported housing program but before receiving housing) and a 12-month follow-up. A total of 82 Veterans had a baseline assessment and 41 returned for testing after 12 months.

Results: The strongest longitudinal association was between an interview-based measure of motivation (the motivation and pleasure subscale from the Clinical Assessment Interview for Negative Symptoms) at baseline and measures of social integration at 12 months. In addition, cross-lagged panel analyses were consistent with a causal influence of general psychiatric symptoms at baseline driving social integration at 12 months, and reduced expressiveness at baseline driving independent living at 12 months, but there were no significant causal associations with measures of motivation.

Conclusions: The findings from this study complement and reinforce those in Veterans with psychosis. Across these two studies, our findings suggest that motivational factors are associated at baseline and at 12 months and are particularly important for understanding and improving community integration in recently-housed Veterans across psychiatric diagnoses.
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http://dx.doi.org/10.1017/S0033291720001609DOI Listing
May 2020

Development and Preliminary Validation of a New Patient-Reported Outcome Measure for Chronic Rhinosinusitis (CRS-PRO).

J Allergy Clin Immunol Pract 2020 Jul - Aug;8(7):2341-2350.e1. Epub 2020 May 4.

Department of Otolaryngology-Head and Neck Surgery, Northwestern University, Feinberg School of Medicine, Chicago, Ill; Division of Allergy and Immunology, Northwestern University, Feinberg School of Medicine, Chicago, Ill. Electronic address:

Background: Patient-reported outcome (PRO) measures developed and validated on patients with the currently defined phenotypes of chronic rhinosinusitis (CRS) are needed to support clinical trials in CRS.

Objective: This study developed and examined the initial reliability and validity of the CRS-PRO, a new PRO measure of CRS.

Methods: Instrument development was performed through structured interviews and focus groups with clinical experts and 45 patients with CRS meeting current definitions of disease, 21 patients with CRS without nasal polyps (CRSsNP), and 24 patients with CRS with nasal polyps (CRSwNP) to identify items important to patients. Then another 50 patients (32 with CRSsNP and 18 with CRSwNP) with stable CRS symptoms were enrolled to evaluate the reliability of the instrument. Each patient completed the CRS-PRO, Sinonasal Outcome Test-22 (SNOT-22), and 4 Patient-Reported Outcome Measurement Information System short forms at the baseline visit and then at least 7 days later.

Results: After the development process, 21 items were identified from the conceptual domains of physical symptoms, sensory impairment, psychosocial effects, and life impact. Using the responses of the 50 patients with CRS, 21 draft items were further refined to 12 items by eliminating conceptually similar or highly correlated items or those with low mean symptom severity. The 12-item questionnaire was shown to have excellent internal consistency (Cronbach α, 0.86) and test-retest reliability with a high intraclass correlation coefficient (0.89) and Pearson's correlation (r = 0.82, P < .0001). The 12-item CRS-PRO correlated highly with the longer SNOT-22 (r = 0.83, P < .0001) demonstrating its concurrent validity. We also demonstrated validity and reliability in a separate analysis for patients with CRSsNP and CRSwNP.

Conclusion: The CRS-PRO is a concise, valid, and reliable measure that was developed with extensive input from patients with CRS with current disease definitions.
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http://dx.doi.org/10.1016/j.jaip.2020.04.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448958PMC
May 2020

Activation of the 15-lipoxygenase pathway in aspirin-exacerbated respiratory disease.

J Allergy Clin Immunol 2021 Feb 1;147(2):600-612. Epub 2020 May 1.

Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.

Background: Aspirin-exacerbated respiratory disease (AERD) is characterized by asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and an intolerance of medications that inhibit cyclooxygenase-1. Patients with AERD have more severe upper and lower respiratory tract disease than do aspirin-tolerant patients with CRSwNP. A dysregulation in arachidonic acid metabolism is thought to contribute to the enhanced sinonasal inflammation in AERD.

Objective: Our aim was to utilize an unbiased approach investigating arachidonic acid metabolic pathways in AERD.

Methods: Single-cell RNA sequencing (10× Genomics, Pleasanton, Calif) was utilized to compare the transcriptional profile of nasal polyp (NP) cells from patients with AERD and patients with CRSwNP and map differences in the expression of select genes among identified cell types. Findings were confirmed by traditional real-time PCR. Lipid mediators in sinonasal tissue were measured by mass spectrometry. Localization of various proteins within NPs was assessed by immunofluorescence.

Results: The gene encoding for 15-lipooxygenase (15-LO), ALOX15, was significantly elevated in NPs of patients with AERD compared to NPs of patients with CRSwNP (P < .05) or controls (P < .001). ALOX15 was predominantly expressed by epithelial cells. Expression levels significantly correlated with radiographic sinus disease severity (r = 0.56; P < .001) and were associated with asthma. The level of 15-oxo-eicosatetraenoic acid (15-Oxo-ETE), a downstream product of 15-LO, was significantly elevated in NPs from patients with CRSwNP (27.93 pg/mg of tissue) and NPs from patients with AERD (61.03 pg/mg of tissue) compared to inferior turbinate tissue from controls (7.17 pg/mg of tissue [P < .001]). Hydroxyprostaglandin dehydrogenase, an enzyme required for 15-Oxo-ETE synthesis, was predominantly expressed in mast cells and localized near 15-LO epithelium in NPs from patients with AERD.

Conclusions: Epithelial and mast cell interactions, leading to the synthesis of 15-Oxo-ETE, may contribute to the dysregulation of arachidonic acid metabolism via the 15-LO pathway and to the enhanced sinonasal disease severity observed in AERD.
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http://dx.doi.org/10.1016/j.jaci.2020.04.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606335PMC
February 2021

Responsiveness and Convergent Validity of a New Patient-Reported Outcome Measure for Chronic Rhinosinusitis (CRS-PRO).

J Allergy Clin Immunol Pract 2020 Jul - Aug;8(7):2351-2359.e2. Epub 2020 Apr 30.

Department of Otolaryngology - Head and Neck Surgery, Northwestern University, Feinberg School of Medicine, Chicago, Ill; Division of Allergy-Immunology, Northwestern University, Feinberg School of Medicine, Chicago, Ill. Electronic address:

Background: The CRS-PRO is a new patient-reported outcome measure (PROM) for chronic rhinosinusitis (CRS) that was developed using extensive patient input per Food and Drug Administration guidance on PROMs acceptable for use as end points in clinical trials.

Objective: To assess the responsiveness and convergent validity of the CRS-PRO following standard-of-care medical therapy.

Methods: This was a prospective study of 51 patients (21 with nasal polyps and 30 without) with newly diagnosed CRS or having an acute CRS exacerbation who were initiated on appropriate medical therapy. At the baseline visit each patient completed the CRS-PRO questionnaire, the 22-item Sino-Nasal Outcome Test, the EuroQol 5-dimensional questionnaire, and 4 Patient-Reported Outcome Measure Information System short forms along with objective testing including endoscopic and radiographic scores, smell discrimination, and nasal inspiratory flow testing. This same battery of questionnaires and testing was administered at a follow-up visit 4 to 8 weeks later.

Results: We verified that shortening the 21-item CRS-PRO to 12 items as previously described maintains its psychometric properties. The 12-item CRS-PRO was responsive with a large effect size (Cohen's d, 0.94) comparable to the longer 22-item Sino-Nasal Outcome Test (Cohen's d, 0.93). The instrument was slightly more responsive to medically treated patients with CRS without nasal polyps compared with patients with CRS with nasal polyps (Cohen's d, 1.1 vs 0.89, respectively). The change in 12-item CRS-PRO total score has moderate correlation with change in Lund-Mackay computed tomography scores.

Conclusions: The CRS-PRO is a 12-item rigorously developed, responsive, and valid PROM that was developed using extensive input from patients with current definitions of CRS, including its 2 major phenotypes.
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http://dx.doi.org/10.1016/j.jaip.2020.04.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448959PMC
April 2020

Airway Epithelial Dynamics in Allergy and Related Chronic Inflammatory Airway Diseases.

Front Cell Dev Biol 2020 27;8:204. Epub 2020 Mar 27.

Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.

Allergic rhinitis, chronic rhinosinusitis, and asthma are highly prevalent, multifactorial chronic airway diseases. Several environmental and genetic factors affect airway epithelial dynamics leading to activation of inflammatory mechanisms in the airways. This review links environmental factors to host epithelial immunity in airway diseases. Understanding altered homeostasis of the airway epithelium might provide important targets for diagnostics and therapy of chronic airway diseases.
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http://dx.doi.org/10.3389/fcell.2020.00204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118214PMC
March 2020

The Rationale for Multidisciplinary Management of Chronic Rhinosinusitis with Nasal Polyposis.

J Allergy Clin Immunol Pract 2020 05 12;8(5):1565-1566. Epub 2020 Mar 12.

Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic, Scottsdale, AZ. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2020.03.001DOI Listing
May 2020

Analysis of Sinus Balloon Catheter Dilation Providers Based on Medicare Provider Utilization and Payment Data.

Am J Rhinol Allergy 2020 Jul 9;34(4):463-470. Epub 2020 Mar 9.

Department of Otolaryngology-Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

Background: The use of balloon catheter dilation (BCD) to treat chronic rhinosinusitis has increased dramatically since its conception, necessitating further characterization of BCD providers and trends in its usage. Medicare data on BCD providers have made it possible to study recent demographic patterns. There has also been an increase in mid-level providers' scope of otolaryngologic practice that is not well defined.

Objective: To better understand BCD adoption by studying volume of BCD procedures as well as training, geography, and practice socioeconomic characteristics of BCD providers for Medicare beneficiaries.

Methods: We reviewed Medicare Provider Utilization and Payment Data Public Use Files for 2014 and 2015 for providers with claims for BCD of the sinuses. We extracted provider zip code, state, gender, and number of services per BCD code. We obtained median household income by zip code and geographic region based on US Census Bureau data. Providers were classified using an Internet search to determine practice setting and type of specialty training/certification.

Results: In 2014 and 2015, 428 providers performed 42 494 BCDs billed to Medicare beneficiaries. Among BCD providers, 5.1% were female, 98.1% had Doctor of Medicine/Doctor of Osteopathic Medicine credentials, and 1.9% had nurse practitioner/physician assistant credentials. Over the 2-year period, the median number of BCDs was 63 for physicians and 37 for mid-level providers. Fellowship-trained rhinologists performed a median of 38 BCDs over 2 years. The most common subspecialty certification/training was in facial plastics and reconstructive surgery. The majority of providers (63.8%) performed 1 to 99 BCDs over the 2 years. In the South, there were 21.9 BCD procedures performed per 100 000 people compared to 7.3 in the Northeast, 9.3 in the Midwest, and 8.5 in the West.

Conclusion: There is a large range in total BCD procedures performed by individual providers, and this varies by certain provider characteristics. Mid-level providers have emerged as a significant population performing BCD.
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http://dx.doi.org/10.1177/1945892420905250DOI Listing
July 2020

Common fibrin deposition and tissue plasminogen activator downregulation in nasal polyps with distinct inflammatory endotypes.

J Allergy Clin Immunol 2020 09 26;146(3):677-681. Epub 2020 Feb 26.

Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2020.02.010DOI Listing
September 2020

SciPy 1.0: fundamental algorithms for scientific computing in Python.

Nat Methods 2020 03 3;17(3):261-272. Epub 2020 Feb 3.

Google LLC, Cambridge, MA, USA.

SciPy is an open-source scientific computing library for the Python programming language. Since its initial release in 2001, SciPy has become a de facto standard for leveraging scientific algorithms in Python, with over 600 unique code contributors, thousands of dependent packages, over 100,000 dependent repositories and millions of downloads per year. In this work, we provide an overview of the capabilities and development practices of SciPy 1.0 and highlight some recent technical developments.
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http://dx.doi.org/10.1038/s41592-019-0686-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056644PMC
March 2020

Current and Future Treatments of Rhinitis and Sinusitis.

J Allergy Clin Immunol Pract 2020 05 28;8(5):1522-1531. Epub 2020 Jan 28.

Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill. Electronic address:

Advances in understanding the pathogenic mechanisms of both rhinitis and chronic rhinosinusitis have resulted in new treatment options, especially for chronic rhinosinusitis. A review of relevant medical and surgical clinical studies shows that intranasal corticosteroids, antihistamines, and allergen immunotherapy continue to be the best treatments for chronic rhinitis. Dupilumab is the first biologic approved for chronic rhinosinusitis with polyps. Omalizumab, mepolizumab, and benralizumab may have a future role in the treatment of chronic rhinosinusitis. Novel corticosteroid delivery devices such as an exhalation delivery system for fluticasone and bioabsorbable sinus implants provide enhanced and localized distribution of corticosteroids. Surgical management tailored to the underlying disease process improves clinical outcomes in chronic rhinosinusitis with or without nasal polyposis. Advances in the understanding of the heterogeneous nature of rhinitis and rhinosinusitis have resulted in more precise treatments. Improving the understanding of different endotypes should provide better knowledge to determine appropriate current and new therapies to treat these diseases.
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http://dx.doi.org/10.1016/j.jaip.2020.01.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416524PMC
May 2020

Clinical factors associated with acute exacerbations of chronic rhinosinusitis.

J Allergy Clin Immunol 2020 06 29;145(6):1598-1605. Epub 2020 Jan 29.

Department of Medicine, Division of Allergy and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Ill; Department of Otolaryngology-Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Ill. Electronic address:

Background: Chronic rhinosinusitis (CRS) is complicated by frequent acute exacerbations leading to significant health care burden and impaired quality of life.

Objective: The objective of this study was to identify clinical factors associated with frequent acute exacerbation of CRS (AECRS).

Methods: This is a retrospective cohort study of patients with CRS from January 1, 2014, to May 31, 2016. Frequent AECRS was defined as at least 4 episodes over a 12-month period in which an antibiotic was prescribed for worsening sinus symptoms, and infrequent AECRS was defined as 0 to 3 episodes. Clinical factors, including asthma, allergic rhinitis, eosinophil count of at least 150 cells per microliter, and autoimmune disease, were evaluated for associations between the 2 groups.

Results: Of the 3109 patients with CRS who were identified, 600 (19.3%) were classified as having frequent exacerbation. Asthma, allergic rhinitis, eosinophil count of at least 150 cells per microliter, and autoimmune disease were associated with frequent AECRS with statistically significant adjusted odds ratios (aORs) after controlling for age, race, and sex in multivariate analysis (asthma aOR = 2.61 [95% CI = 2.14-3.18]; allergic rhinitis aOR = 1.96 [95% CI = 1.58-2.42]; eosinophil count of at least 150 cells per microliter aOR = 1.54 [95% CI = 1.21-1.97]; and autoimmune disease aOR = 1.68 [95% CI = 1.36-2.07]). Antibody deficiency, antibiotic allergy, lower FEV, radiographic sinus disease severity, nasal polyposis, and systemic corticosteroid use were also associated with frequent AECRS.

Conclusion: Patients with frequent episodes of AECRS were characterized by a higher prevalence of asthma, allergic rhinitis, eosinophil count of at least 150 cells per microliter, autoimmune disease, and other allergic and immunologic diseases. These findings identify a high-risk phenotype of patients with CRS for preventive interventions to reduce exacerbation frequency.
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http://dx.doi.org/10.1016/j.jaci.2020.01.023DOI Listing
June 2020

The characteristics of cognitive neuroscience tests in a schizophrenia cognition clinical trial: Psychometric properties and correlations with standard measures.

Schizophr Res Cogn 2020 Mar 31;19:100161. Epub 2019 Oct 31.

Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, United States of America.

In comparison to batteries of standard neuropsychological tests, cognitive neuroscience tests may offer a more specific assessment of discrete neurobiological processes that may be aberrant in schizophrenia. However, more information regarding psychometric properties and correlations with standard neuropsychological tests and functional measures is warranted to establish their validity as treatment outcome measures. The N-back and AX-Continuous Performance Task (AX-CPT) are two promising cognitive neuroscience tests designed to measure specific components of working memory and contextual processing respectively. In the current study, we report the psychometric properties of multiple outcome measures from these two tests as well as their correlations with standard neuropsychological measures and functional capacity measures. The results suggest that while the AX-CPT and N-back display favorable psychometric properties, they do not exhibit greater sensitivity or specificity with functional measures than standard neurocognitive tests.
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http://dx.doi.org/10.1016/j.scog.2019.100161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889798PMC
March 2020

Radiologic sinus inflammation and symptoms of chronic rhinosinusitis in a population-based sample.

Allergy 2020 04 2;75(4):911-920. Epub 2019 Dec 2.

Department of Population Health Sciences, Geisinger, Danville, Pennsylvania.

Background: Chronic rhinosinusitis (CRS) epidemiology has been largely studied using symptom-based case definitions, without assessment of objective sinus findings.

Objective: To describe radiologic sinus opacification and the prevalence of CRS, defined by the co-occurrence of symptoms and sinus opacification, in a general population-based sample.

Methods: We collected questionnaires and sinus CT scans from 646 participants selected from a source population of 200 769 primary care patients. Symptom status (CRS ) was based on guideline criteria, and objective radiologic inflammation (CRS ) was based on the Lund-Mackay (L-M) score using multiple L-M thresholds for positivity. Participants with symptoms and radiologic inflammation were classified as CRS . We performed negative binomial regression to assess factors associated with L-M score and logistic regression to evaluate factors associated with CRS . Using weighted analysis, we calculated estimates for the source population.

Results: The proportion of women with L-M scores ≥ 3, 4, or 6 (CRS ) was 11.1%, 9.9%, and 5.7%, respectively, and 16.1%, 14.6%, and 8.7% among men. The respective proportion with CRS was 1.7%, 1.6%, and 0.45% among women and 8.8%, 7.5%, and 3.6% among men. Men had higher odds of CRS compared to women. A greater proportion of men (vs women) had any opacification in the frontal, anterior ethmoid, and sphenoid sinuses.

Conclusion: In a general population-based sample in Pennsylvania, sinus opacification was more common among men than in women and opacification occurred in different locations by sex. Male sex, migraine headache, and prior sinus surgery were associated with higher odds of CRS .
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http://dx.doi.org/10.1111/all.14106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176524PMC
April 2020