Mepolizumab has clinical benefits including oral corticosteroid sparing irrespective of baseline EGPA characteristics.

Background: The Mepolizumab in Relapsing or Refractory EGPA (MIRRA) trial (GSK ID: 115921/NCT02020889) demonstrated that mepolizumab increased remission time and reduced oral corticosteroid (OCS) use compared with placebo in patients with relapsing or refractory eosinophilic granulomatosis with polyangiitis (EGPA). The present analysis investigated the impact of baseline characteristics on clinical outcomes and characterised the OCS-sparing effect of mepolizumab. Methods: In a phase 3, randomised controlled trial for patients with EGPA (MIRRA), patients received standard of care plus mepolizumab 300 mg or placebo every 4 weeks for 52 weeks. The accrued duration of remission, the proportion of patients in remission at weeks 36 and 48, and the proportion of patients with clinical benefit (remission, OCS or relapse-related) were assessed according to baseline EGPA characteristic subgroups (post hoc). Mepolizumab-related OCS-sparing benefits were also quantified. Results: Accrued duration of remission and the proportion of patients in remission at weeks 36 and 48 were greater with mepolizumab than placebo across the baseline subgroups of refractory disease, immunosuppressant use, EGPA duration, relapse number and OCS use ≤20 mg·day-1. The proportion of patients with clinical benefit was greater with mepolizumab versus placebo (range 76-81% versus 25-39%), irrespective of immunosuppressant use or EGPA duration. Patients treated with mepolizumab versus placebo accrued significantly more weeks on OCS ≤4 mg·day-1 (OR 5.06, 95% CI 2.47-10.38) and had a mean of 1423.1 mg less per-patient OCS exposure over 52 weeks. Conclusions: Mepolizumab treatment provided benefits to patients with EGPA across varying baseline clinical characteristics and can be considered an OCS-sparing treatment in EGPA.

HES and EGPA: Two Sides of the Same Coin.

Elevated eosinophil counts are implicated in multiple diseases, from relatively prevalent organ-specific disorders such as severe eosinophilic asthma, to rare multisystem disorders such as hypereosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis (EGPA). Patients with these multisystem diseases, often associated with markedly elevated eosinophil counts, have a substantial risk of morbidity and mortality due to delayed diagnosis or inadequate treatment. A thorough workup of symptomatic patients presenting with elevated eosinophil counts is essential, although in some cases the differential diagnosis may remain difficult because of overlapping presentations between HES and EGPA. Notably, first- and second-line treatment options and response to therapy may differ for specific HES and EGPA variants. Oral corticosteroids are the first line of treatment for HES and EGPA, except when HES is the result of specific mutations driving clonal eosinophilia that are amenable to targeted treatment with a kinase inhibitor. Cytotoxic or immunomodulatory agents may be required for those with severe disease. Novel eosinophil-depleting therapies, such as those targeting interleukin 5 or its receptor, have shown great promise in reducing blood eosinophil counts, and reducing disease flares and relapses in patients with HES and EGPA. Such therapies could reduce the side effects associated with long-term oral corticosteroids or immunosuppressant use. This review provides a pragmatic guide to approaching the diagnosis and clinical management of patients with systemic hypereosinophilic disorders. We highlight practical considerations for clinicians and present cases from real-world clinical practice to show the complexity and challenges associated with diagnosing and treating patients with HES and EGPA.

What bothers severe asthma patients most? A paired patient-clinician study across seven European countries.

Introduction: Severe asthma is a complex, multidimensional disease. Optimal treatment, adherence and outcomes require shared decision-making, rooted in mutual understanding between patient and clinician. This study used a novel, patient-centred approach to examine the most bothersome aspects of severe asthma to patients, as seen from both perspectives in asthma registries. Methods: Across seven countries, 126 patients with severe asthma completed an open-ended survey regarding most the bothersome aspect(s) of their asthma. Patients' responses were linked with their treating clinician who also completed a free-text survey about each patient's most bothersome aspect(s). Responses were coded using content analysis, and patient and clinician responses were compared. Finally, asthma registries that are part of the SHARP (Severe Heterogeneous Asthma Research collaboration, Patient-centred) Clinical Research Collaboration were examined to see the extent to which they reflected the most bothersome aspects reported by patients. Results: 88 codes and 10 themes were identified. Clinicians were more focused on direct physical symptoms and were less focused on "holistic" aspects such as the effort required to self-manage the disease. Clinicians accurately identified a most bothersome symptom for 29% of patients. Agreement was particularly low with younger patients and those using oral corticosteroids infrequently. In asthma registries, patient aspects were predominantly represented in questionnaires. Conclusions: Results demonstrated different perspectives and priorities between patients and clinicians, with clinicians more focused on physical aspects. These differences must be considered when treating individual patients, and within multidisciplinary treatment teams. The use of questionnaires that include multifaceted aspects of disease may result in improved asthma research.

Clinical Benefit of Mepolizumab in Eosinophilic Granulomatosis With Polyangiitis for Patients With and Without a Vasculitic Phenotype.

OBJECTIVE: To evaluate mepolizumab's efficacy in eosinophilic granulomatosis with polyangiitis (EGPA) with and without a vasculitic phenotype. METHODS: The MIRRA study (NCT02020889/GSK ID: 115921) included adults with relapsing/refractory EGPA and 4 or more weeks of stable oral glucocorticoids (OG). Patients received mepolizumab (300 mg subcutaneously every 4 weeks) or placebo, plus standard of care for 52 weeks. This post hoc analysis assessed EGPA vasculitic phenotype using antineutrophil cytoplasmic antibody (ANCA) history, baseline Birmingham Vasculitis Activity Score (BVAS), and Vasculitis Damage Index (VDI) score. Coprimary endpoints included accrued remission over 52 weeks and proportion in remission at Week 36 and Week 48. Remission was defined as a BVAS equal to 0 and an OG dose of 4 or more mg/day of a prednisone equivalent. Types of relapses (vasculitis, asthma, and sino-nasal) and EGPA vasculitic characteristics (by study remission status) were also assessed. RESULTS: A total of 136 patients were included (n = 68, mepolizumab and placebo). Irrespective of history of ANCA positivity status, baseline BVAS, or baseline VDI, the accrued remission duration and the proportion of patients in remission at Weeks 36 and 48 were greater with mepolizumab compared with placebo. With mepolizumab, remission at both Week 36 and Week 48 was achieved by 54% of patients with and 27% of patients without a history of ANCA positivity compared with 0% and 4%, respectively (placebo); 45% of patients with a BVAS of 0 and 22% of patients with BVAS of greater than 0 compared with 5% and 2%, respectively (placebo); and 29% of patients with a VDI score of less than 5 and 37% of patients with a VDI score of 5 or more compared with 6% and 0%, respectively (placebo). Mepolizumab reduced all types of relapses as compared with placebo. Baseline vasculitic characteristics (neuropathy, glomerulonephritis, alveolar hemorrhage, palpable purpura, and ANCA positivity) were generally similar among patients with and without remission. CONCLUSION: Mepolizumab is associated with clinical benefits for patients with and without a vasculitic EGPA phenotype.

Mepolizumab therapy improves the most bothersome symptoms in patients with hypereosinophilic syndrome.

Background: Hypereosinophilic syndrome (HES) is characterized by persistent elevated blood and/or tissue eosinophil levels and eosinophil-mediated organ damage. Presentation is highly heterogenous; patients may experience symptoms affecting multiple organ systems. Objectives: To assess the effects of mepolizumab, which targets interleukin-5, on HES-related symptom burden, based on HES daily symptoms (HES-DS) questionnaire data collected during the Phase III (ClinicalTrials.gov ID: NCT02836496) study of mepolizumab in patients with HES. Methods: Each of the six HES-related symptoms were rated (0-10) daily by patients, recalling worst symptom experience in the prior 24 hours; change from baseline at Week 32 was also calculated for mepolizumab versus placebo. Results: Mepolizumab versus placebo reduced HES-related symptom burden severity in patients with HES at Week 32. Improvements in the median change from baseline scores were seen across all symptom groups except skin for patients treated with mepolizumab; greatest improvement from baseline was observed for breathing symptoms. Conclusion: These data highlight the considerable symptom burden associated with HES and further support the clinical benefits of mepolizumab treatment for these patients.

Evaluation of real-world mepolizumab use in severe asthma across Europe: the SHARP experience with privacy-preserving federated analysis.

Background: An objective of the Severe Heterogeneous Asthma Registry, Patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking nonstandardised, patient-level registry data. Mepolizumab has shown clinical efficacy in randomised controlled trials and prospective real-world studies and could therefore serve as a proof of principle for this novel approach. The aim of the present study was to harmonise data from 10 national severe asthma registries and characterise patients receiving mepolizumab, assess its effectiveness on annual exacerbations and maintenance oral glucocorticoid (OCS) use, and evaluate treatment patterns. Methods: In this observational cohort study, registry data (5871 patients) were extracted for harmonisation. Where harmonisation was possible, patients who initiated mepolizumab between 1 January 2016 and 31 December 2021 were examined. Changes of a 12-month (range 11-18 months) period in frequent (two or more) exacerbations, maintenance OCS use and dose were analysed in a privacy-preserving manner using meta-analysis of generalised estimating equation parameters. Periods before and during the coronavirus disease 2019 pandemic were analysed separately. Results: In 912 patients who fulfilled selection criteria, mepolizumab significantly reduced frequent exacerbations (OR 0.18, 95% CI 0.13-0.25), maintenance OCS use (OR 0.75, 95% CI 0.61-0.92) and dose (mean -3.93 mg·day-1, 95% CI -5.24-2.62 mg·day-1) in the pre-pandemic group, with similar trends in the pandemic group. Marked heterogeneity was observed between registries in patient characteristics and mepolizumab treatment patterns. Conclusions: By harmonising patient-level registry data and applying federated analysis, SHARP demonstrated the real-world effectiveness of mepolizumab on asthma exacerbations and maintenance OCS use in severe asthma patients across Europe, consistent with previous evidence. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof manner.

Hypereosinophilic syndrome in Europe: Retrospective study of treatment patterns, clinical manifestations, and healthcare resource utilization.

BACKGROUND: The burden of hypereosinophilic syndrome (HES) in Europe is not well characterized. OBJECTIVE: To evaluate real-world patient characteristics, treatment patterns, clinical manifestations, and healthcare resource utilization for patients with HES from France, Germany, Italy, Spain, and the United Kingdom. METHODS: In this retrospective, noninterventional study, data for patients with a physician-confirmed diagnosis of HES were abstracted from medical chart reviews. Patients were aged 6 years or older at the time of HES diagnosis and had 1 or more years of follow-up from the index date (first clinic visit between January 2015 and December 2019). Data on treatment patterns, comorbidities, clinical manifestations, clinical outcomes, and healthcare resource utilization were collected from diagnosis or index date to end of follow-up. RESULTS: Data for 280 patients were abstracted from medical charts by 121 physicians treating HES, with multiple specialties. Most patients (55%) had idiopathic HES, and 24% had myeloid HES; the median number (interquartile range [IQR]) of diagnostic tests per patient was 10 (6-12). The most common comorbidities were asthma (45%) and anxiety or depression (36%). Most patients (89%) used oral corticosteroids; 64% used immunosuppressants or cytotoxic agents, and 44% used biologics. Patients had a median (IQR) of 3 clinical manifestations (1-5), most commonly constitutional (63%), lung (49%), and skin (48%). Twenty-three percent of patients experienced a flare, and 40% had a complete treatment response. Some patients (30%) were hospitalized with a median (IQR) stay of 9 days (5-15) for HES-related issues. CONCLUSION: Patients with HES across 5 European countries had a substantial disease burden despite extensive oral corticosteroids treatment, highlighting the need for additional targeted therapies.

Insights from Social Media on the Patient Experience of Living With Rare Eosinophil-Driven Diseases.

Eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES) are driven by persistently high eosinophil numbers, causing damage to tissues and organs. As rare diseases, they are often underappreciated by healthcare professionals. Using a social listening analysis, we collected patient and caregiver comments relating to EGPA and HES made on online social platforms between 1 January 2019 and 31 May 2020, in English, French, and German. Results were classified into key areas of interest. In total, 746 comments with consent to publish were collected mentioning EGPA, and 39 were identified mentioning HES. The most common theme was sharing of personal experiences (EGPA: 77%; HES: 100%). Diagnosis, including diagnosis delays and misdiagnosis, was mentioned in 33% of comments for EGPA, and 82% for HES. Other common themes included seeking and giving advice, symptoms, and treatments. These insights highlight the views and unmet needs of people living with EGPA and HES. Further work should improve disease awareness and effective communications among healthcare professionals and patients with these conditions.

Characterization of disease flares and impact of mepolizumab in patients with hypereosinophilic syndrome.

In patients with hypereosinophilic syndrome (HES), mepolizumab reduces the incidence of HES-related clinical signs and symptoms (flares). However, reports characterizing flare manifestations are limited. The double-blind, parallel-group 200622 trial (NCT02836496) enrolled patients ≥12 years old with HES for ≥6 months, ≥2 flares in the previous year, and screening blood eosinophil count ≥1000 cells/µL. Patients maintained ≥4 weeks stable HES therapy, before randomization (1:1) to 4-weekly subcutaneous mepolizumab (300 mg) or placebo, plus baseline HES therapy, for 32 weeks. This post hoc analysis investigated flare manifestations and duration by re-examining the Core Assessments form and narrative recorded for each flare during the study. Flare symptoms were retrospectively categorized into constitutional, dermatological, respiratory, nasal, gastrointestinal, neurologic and other. The most frequently reported flare symptoms were constitutional (94% of flares), dermatological (82% of flares) and respiratory (72% of flares); flares reported in patients receiving mepolizumab compared with placebo were generally similar in terms of the frequency of symptoms reported. Mepolizumab was associated with a shorter median (range) duration of flares (10.0 [4, 126] days) versus placebo (26.0 [1, 154] days). In patients with HES, flares were associated with symptoms linked to multiple organ systems highlighting the challenges faced for treating flares. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT02836496, identifier NCT02836496.

Association Between Baseline Therapy and Flare Reduction in Mepolizumab-Treated Patients With Hypereosinophilic Syndrome.

Background: Current standard-of-care treatments for hypereosinophilic syndrome (HES) include oral corticosteroids (OCS) and immunosuppressive/cytotoxic (IS/CT) therapies. The anti-IL-5 monoclonal antibody mepolizumab has also recently been approved for patients with this disease. The objective of this analysis was to assess the relationship between baseline therapy and flare reduction in patients with HES treated with mepolizumab, using data from the Phase III 200622 study (NCT02836496). Methods: In the double-blind, parallel-group 200622 study, eligible patients were ≥12 years old and had HES for ≥6 months, ≥2 flares in the previous 12 months, blood eosinophils ≥1000 cells/µL at screening and ≥4 weeks' stable HES therapy. Patients were randomised (1:1) to receive mepolizumab 300 mg subcutaneously or placebo every 4 weeks for 32 weeks plus their existing HES therapy. This post hoc, descriptive analysis assessed the effect of baseline HES therapy [IS/CT (± OCS), OCS No IS/CT, and No IS/CT/OCS] on the proportion of patients with ≥1 flare during the study period, the annualised rate of flares, time to first flare, and the proportion of patients with ≥1 flare during Weeks 20─32, with mepolizumab versus placebo. Results: Mepolizumab treatment was associated with a decrease in the proportion of patients who experienced ≥1 flare during the study period in all baseline therapy groups versus placebo (32-96% reduction). Similarly, the probability of a flare was lower with mepolizumab (14.3-31.4%) than placebo (35.7-74.1%) in all baseline therapy groups, as was the annualised flare rate (0.22-0.68 vs 1.14-1.62). The proportion of patients who experienced ≥1 flare during Weeks 20-32 was reduced with mepolizumab versus placebo for all baseline therapy groups (55-85% reduction). For all endpoints, the greatest effect of mepolizumab treatment was seen in the IS/CT (± OCS) group. Conclusions: Patients with poorly controlled HES are likely to achieve clinical benefit with mepolizumab in terms of flare reduction, regardless of their baseline therapy. Clinical Trial Registration: (https://clinicaltrials.gov/ct2/show/NCT02836496).

Mepolizumab Reduces Hypereosinophilic Syndrome Flares Irrespective of Blood Eosinophil Count and Interleukin-5.

BACKGROUND: Mepolizumab, an anti-interleukin-5 (IL-5) antibody, reduces disease flares in patients with hypereosinophilic syndrome (HES). Factors predicting treatment response are unknown. OBJECTIVE: To assess mepolizumab efficacy by baseline blood eosinophil count (BEC) and serum IL-5 level in patients with HES. METHODS: This post hoc analysis used data from the phase III study assessing mepolizumab in patients with HES (NCT02836496). Patients 12 years old or older, with HES for 6 or more months, 2 or more flares in the previous year, and BEC ≥1,000 cells/µL at screening were randomized (1:1) to 4-weekly subcutaneous mepolizumab (300 mg) or placebo, plus baseline HES therapy, for 32 weeks. The proportion of patients experiencing 1 or more flares (wk 32), annualized flare rate, and proportion of patients with change from baseline in Brief Fatigue Inventory (BFI) item 3 (wk 32), were analyzed by baseline BEC (<1500/≥1500 to <2500/≥2500 cells/µL). Flare outcomes were assessed by baseline serum IL-5 (<7.81/≥7.81 pg/mL). RESULTS: Across baseline BEC subgroups, mepolizumab reduced the proportion of patients experiencing 1 or more flares by 63% to 90% and flare rate by 58% to 84% (treatment-by-eosinophil interaction P = .76 and P = .90, respectively); patients had improved BFI item 3 score with mepolizumab versus placebo (cells/µL: <1,500: 54% vs 37%; ≥1,500 to <2,500: 47% vs 31%; ≥2,500: 61% vs 0%; treatment-by-eosinophil interaction P = .42). Most patients had undetectable baseline serum IL-5 levels; among these, mepolizumab versus placebo reduced the proportion of patients with 1 or more flares (77%) and flare rate (67%). CONCLUSIONS: Mepolizumab was efficacious in the patients with HES studied, irrespective of baseline BEC. Undetectable IL-5 levels should not preclude mepolizumab treatment.

Clinical Profile and Treatment in Hypereosinophilic Syndrome Variants: A Pragmatic Review.

BACKGROUND: Hypereosinophilic syndrome (HES) is a group of rare hematologic disorders leading to eosinophil-driven tissue damage and dysfunction. Better understanding of HES variants may facilitate improved patient management. OBJECTIVE: To describe disease characteristics, treatment, and outcomes of patients with idiopathic (I-HES), myeloproliferative (M-HES), lymphocytic (L-HES), and chronic eosinophilic leukemia, not otherwise specified (CEL-NOS) among HES case reports and aggregate data where available. METHODS: Relevant articles published between January 1, 2000, and March 20, 2020, were retrieved via PubMed; those reporting secondary, associated/reactive, overlap/single-organ, or familial HES were excluded. RESULTS: Of 188 articles included, 171 contained data on 347 separate HES cases (152 I-HES, 121 M-HES, 62 L-HES, 12 CEL-NOS). Based on individual data, mean age at diagnosis was 43 to 48 years for patients with all HES variants. Males accounted for 90% to 91% of M-HES/CEL-NOS and 55% to 65% of I-HES/L-HES cases. Cardiac symptoms were frequently observed for all HES variants (13%-22% of patients). Respiratory symptoms (I-HES), splenomegaly (M-HES and CEL-NOS), and skin conditions (L-HES) were also frequently observed. Bone marrow, heart, lung, spleen, liver, skin, and lymph nodes were commonly involved. Most patients with I-HES, L-HES, and CEL-NOS received corticosteroids (65%-85%), whereas most with M-HES received imatinib (81%); those with CEL-NOS also received interferon alpha (42%). CONCLUSIONS: Collective analysis of HES case reports supports and extends current understanding of HES variants, highlighting differences in signs and symptoms, organ involvement, and treatment approaches. Improved characterization of HES variants may facilitate the development of novel treatments.

Inadequate housing and pulmonary tuberculosis: a systematic review.

BACKGROUND: Tuberculosis (TB) is a global health issue that has long threatened and continues to threaten human health. While previous studies are important in the search for a cure for TB, to eradicate the disease it is also crucial to analyze environmental influences. Therefore, this study determined the potential effect of inadequate housing on TB and the magnitude of the effect. METHODS: This is a systematic review of the effects of inadequate housing on TB. Between Jan 1, 2011 and Oct 25, 2020, we searched four electronic databases using the search terms "housing AND tuberculosis" or "housing AND TB". The target population comprised residents of inadequate housing and the homeless. RESULTS: We found 26 eligible studies. The distribution of the studies across continents was uneven, and the housing issues of interest seemed to vary depending on the economic level of the country. The eight steps identified in TB development and the consequences thereof were more strongly associated with housing affordability than with housing quality. CONCLUSIONS: This is the first systematic review to identify the effects of inadequate housing on TB and to categorize inadequate-housing-related exposure to TB in terms of affordability and quality. The steps identified in TB development and the consequences thereof had a greater association with housing affordability than with housing quality. Therefore, public health interventions regarding housing affordability could be more diverse, and interventions that support affordable housing for residents of inadequate housing and the homeless should proceed simultaneously to improve housing quality.

Methylammonium Compensation Effects in MAPbI3 Perovskite Solar Cells for High-Quality Inorganic CuSCN Hole Transport Layers.

Recent studies have demonstrated that copper (I) thiocyanate (CuSCN) has huge potential as a hole extraction material (HEM) for perovskite solar cells. Here, we used CuSCN as a HEM and analyzed its relationships with a methylammonium lead iodide (MAPbI3) perovskite layer. The CuSCN dissolved in diethyl sulfide (DES) was spin-coated on the MAPbI3 layer. For high-quality and dense CuSCN layers, post-annealing was carried out at various temperatures and times. However, the unwanted dissociation of MAPbI3 to PbI2 was observed due to the post-annealing for a long time at elevated temperatures. In addition, DES, which is used as a CuSCN solvent, is a polar solvent that damages the surface of MAPbI3 perovskites and causes poor interfacial properties between the perovskite layer and HEM. To solve this problem, the effect of the molar ratio of methylammonium iodide (MAI) and PbI2 in the MAPbI3 precursor solution was investigated. The excess MAI molar ratio in the MAPbI3 precursor solution reduced MAPbI3 surface damage despite using DES polar solvent for CuSCN solution. In addition, dissociation of MAPbI3 to PbI2 following an adequate post-annealing process was well suppressed. The excess MAI molar ratio in the MAPbI3 precursor could be compensated for the MA loss and effectively suppress phase separation from MAPbI3 to MAI + PbI2 during post-annealing. The efficiency based on the normal planar structure of CuSCN/MAPbI3 (using excess MAI)/TiO2 was approximately 17%. The CuSCN-based MAPbI3 device shows more optimized stability than the conventional spiro-OMeTAD under damp heat (85 °C and 85% relative humidity) conditions because of the robust inorganic HEM.

Blood eosinophil counts in the general population and airways disease: a comprehensive review and meta-analysis.

BACKGROUND: The clinical context for using blood eosinophil (EOS) counts as treatment-response biomarkers in asthma and COPD requires better understanding of EOS distributions and ranges. We describe EOS distributions and ranges published in asthma, COPD, control (non-asthma/COPD) and general populations. METHODS: We conducted a comprehensive literature review and meta-analysis of observational studies (January 2008 to November 2018) that included EOS counts in asthma, severe asthma, COPD, control and general populations. Excluded studies had total sample sizes <200, EOS as inclusion criterion, hospitalised population only and exclusively paediatric participants. RESULTS: Overall, 91 eligible studies were identified, most had total-population-level data available: asthma (39 studies), severe asthma (12 studies), COPD (23 studies), control (seven studies) and general populations (14 studies); some articles reported data for multiple populations. Reported EOS distributions were right-skewed (seven studies). Reported median EOS counts ranged from 157-280 cells·µL-1 (asthma, 22 studies); 200-400 cells·µL-1 (severe asthma, eight studies); 150-183 cells·µL-1 (COPD, six studies); and 100-160 cells·µL-1 (controls, three studies); and 100-200 cells·µL-1 (general populations, six studies). The meta-analysis showed that observed variability was mostly between studies rather than within studies. Factors reportedly associated with higher blood EOS counts included current smoking, positive skin-prick test, elevated total IgE, comorbid allergic rhinitis, age ≤18 years, male sex, spirometric asthma/COPD diagnosis, metabolic syndrome and adiposity. CONCLUSION: EOS distribution and range varied by study population, and were affected by clinical factors including age, smoking history and comorbidities, which, regardless of severity, should be considered during treatment decision-making.

Depression Severity Detection Using Read Speech with a Divide-and-Conquer Approach.

We propose a divide-and-conquer approach to detect depression severity using speech. We divide speech features based on their attributes, i.e., acoustic, prosodic, and language features, then fuse them in a modeling stage with fully connected deep neural networks. Experiments with 76 clinically depressed patients (38 severe and 38 moderate in terms of Montgomery-Asberg Depression Rating Scale (MADRS)), we obtain 78% accuracy while patients' self-reporting scores can classify their own status with 79% accuracy.

Near-Infrared Self-Powered Linearly Polarized Photodetection and Digital Incoherent Holography Using WSe2/ReSe2 van der Waals Heterostructure.

Polarization-sensitive photodetection has attracted considerable attention as an emerging technology for future optoelectronic applications such as three-dimensional (3D) imaging, quantum optics, and encryption. However, traditional photodetectors based on Si or III-V InGaAs semiconductors cannot directly detect polarized light without additional optical components. Herein, we demonstrate a self-powered linear-polarization-sensitive near-infrared (NIR) photodetector using a two-dimensional WSe2/ReSe2 van der Waals heterostructure. The WSe2/ReSe2 heterojunction photodiode with semivertical geometry exhibits excellent performance: an ideality factor of 1.67, a broad spectral photoresponse of 405-980 nm with a significant photovoltaic effect, outstanding linearity with a linear dynamic range wider than 100 dB, and rapid photoswitching behavior with a cutoff frequency up to 100 kHz. Strongly polarized excitonic transitions around the band edge in ReSe2 lead to significant 980 nm NIR linear-polarization-dependent photocurrent. This linear polarization sensitivity remains stable even after exposure to air for longer than five months. Furthermore, by leveraging the NIR (980 nm)-selective linear polarization detection of this photodiode under photovoltaic operation, we demonstrate digital incoherent holographic 3D imaging.

Burden of illness associated with eosinophilic granulomatosis with polyangiitis: a systematic literature review and meta-analysis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease associated with vascular inflammation and multisystem organ damage. The literature reporting EGPA incidence or prevalence is limited. We performed a systematic literature review and meta-analysis to describe the incidence, prevalence, and disease burden associated with EGPA. Real-world, observational, English-language studies in MEDLINE, MEDLINE In-Process, and Embase up to 6 June, 2019, were included. A single investigator screened all identified titles/abstracts and extracted data; an additional, independent investigator repeated the screening and validated the extracted data. A random-effects meta-analysis was conducted to generate pooled estimates for EGPA incidence and prevalence. Data from 100 eligible publications were extracted (32 with incidence/prevalence data, 65 with morbidity/healthcare resource data; 3 with both types of data). Significant evidence of between-study heterogeneity for reported incidence (p = 0.0013-0.0016) and prevalence (p = 0.0001-0.0006) estimates was observed. Global and European pooled estimates (95% confidence interval) of EGPA incidence were 1.22 (0.93, 1.60) and 1.07 (0.94, 1.35) cases per million person-years, respectively; global and European pooled estimates (95% confidence interval) for EGPA prevalence were 15.27 (11.89, 19.61) and 12.13 (6.98, 21.06) cases per million individuals, respectively. The proportions of patients experiencing relapses, or who had nasal polyps or severe asthma, varied considerably across studies. EGPA healthcare resource use was high, with inpatient admissions and emergency department visits reported for 17-42% and 25-42% of patients, respectively. Our results indicate that although global and European EGPA incidence and prevalence is low, the associated disease burden is substantial. Key points • We performed a systematic literature review and meta-analysis of real-world, observational studies describing the incidence, prevalence, and disease burden associated with eosinophilic granulomatosis with polyangiitis (EGPA). • Based on meta-analysis data from 35 eligible studies reporting incidence and prevalence, the incidence and prevalence of EGPA were low (globally 1.22 cases per million person-years and 15.27 cases per million individuals, respectively). • Among the 49 studies with morbidity and/or healthcare resource data, most reported a large proportion of patients with EGPA relapses and comorbidities of nasal polyps and severe asthma. • Healthcare resource use was also high among patients with EGPA in these studies, with inpatient admissions and emergency department visits reported for 17-42% and 25-42% of patients, respectively. Taken together, these data indicate the substantial disease burden associated with EGPA.

Efficacy and safety of mepolizumab in Korean patients with severe eosinophilic asthma from the DREAM and MENSA studies.

BACKGROUND/AIMS: The efficacy and safety of mepolizumab in patients with severe eosinophilic asthma has been evaluated in a global clinical trial programme. This post hoc analysis assesses the efficacy and safety of mepolizumab in Korean patients. METHODS: Data from Korean patients in the Phase III, placebo-controlled, randomised DREAM (MEA112997/NCT01000506) and MENSA (MEA115588/ NCT01691521) studies were included. Patients ≥ 12 years old with severe eosinophilic asthma received mepolizumab (DREAM: 75, 250 or 750 mg intravenously [IV]; MENSA: 75 mg IV or 100 mg subcutaneously [SC]), or placebo every 4 weeks for 52 weeks (DREAM) or 32 weeks (MENSA). The primary outcome was the rate of clinically significant asthma exacerbations. Secondary outcomes included forced expiratory volume in 1 second (FEV1), Asthma Control Questionnaire (ACQ) and St George's Respiratory Questionnaire (SGRQ) scores (MENSA only). Blood eosinophil counts (BEC) and safety were assessed throughout. RESULTS: Reductions in the rate of clinically significant asthma exacerbations were observed with the approved (100 mg SC) and bioequivalent (75 mg IV) doses of mepolizumab in Korean patients who participated in DREAM and MENSA. In MENSA, trends for improvements from baseline at week 32 in pre-bronchodilator FEV1 (75 mg IV group), ACQ-5 and SGRQ scores (in both treatment groups) were seen versus placebo in Korean patients. Incidence of on-treatment adverse events was similar in Korean patients versus non-Korean patients as were observed reductions from baseline in BEC. CONCLUSION: Mepolizumab treatment provided clinical benefits for Korean patients with severe eosinophilic asthma; the safety profile is consistent with the overall population.

"How are you?" Estimation of anxiety, sleep quality, and mood using computational voice analysis.

We developed a method of estimating impactors of cognitive function (ICF) - such as anxiety, sleep quality, and mood - using computational voice analysis. Clinically validated questionnaires (VQs) were used to score anxiety, sleep and mood while salient voice features were extracted to train regression models with deep neural networks. Experiments with 203 subjects showed promising results with significant concordance correlation coefficients (CCC) between actual VQ scores and the predicted scores (0.46 = anxiety, 0.50 = sleep quality, 0.45 = mood).