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Background and Aims: Real-world analyses on burden of illness in patients with alpha-1 antitrypsin deficiency (AATD) are limited. We investigated the real-world burden of liver-related clinical events among adult and pediatric patients with AATD in the USA. Methods: This was a retrospective, observational analysis of administrative claims data from the IQVIA PharMetrics® Plus and Ambulatory Electronic Medical Records databases from 2011 to 2022. Patients had a diagnosis of liver and/or lung disease with ≥180 days of continuous enrollment in the IQVIA PharMetrics Plus database before and ≥90 days after their first diagnosis. Follow-up time was assigned to the AATD with liver disease health state or AATD with both liver and lung disease health state (for patients aged ≥18 years only). Baseline demographic characteristics and liver-related clinical events of interest were reported. Results: Of 5136 eligible patients, 771 adult and 123 pediatric patients contributed time to the AATD with liver disease health state; 541 adults contributed time to the AATD with both liver and lung disease health state. Among adults, patients with both liver and lung disease had higher rates of liver-related clinical events than patients with liver disease alone. Ascites was the most frequently observed clinical event among adults in both health states, and the median time to the composite of any liver-related clinical event was 26.5 days among all adults combined. Across all pediatric age groups, ascites, gastrointestinal bleed and hepatic encephalopathy were more common than spontaneous bacterial peritonitis and hepatocellular carcinoma, but median time to liver-related clinical event varied by age group at index date and type of event. No liver transplantations occurred in patients aged 6-17 years. Conclusion: Diagnosed AATD with liver disease carries a substantial burden on adult and pediatric patients; new treatment options are warranted to avoid disease progression to decompensating events.
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Aim: To evaluate all-cause and liver-associated healthcare resource utilization (HCRU) and costs among patients with alpha-1 antitrypsin deficiency (AATD) with liver disease (LD) and/or lung disease (LgD). Materials & methods: This was a retrospective analysis of linked administrative claims data from the IQVIA PharMetrics® Plus and the IQVIA Ambulatory Electronic Medical Records (AEMR) databases from 1 July 2021 to 31 January 2022. Patients with AATD in the IQVIA PharMetrics Plus database were included with ≥1 inpatient or ≥2 outpatient medical claims ≥90 days apart with a diagnosis of AATD, or with records indicating a protease inhibitor (Pi)*ZZ/Pi*MZ genotype in the IQVIA AEMR database with linkage to IQVIA PharMetrics Plus. For a patient's identified continuous enrollment period, patient time was assigned to health states based on the initial encounter with an LD/LgD diagnosis. A unique index date was defined for each health state, and HCRU and costs were calculated per person-year (PPY). Results: Overall, 5136 adult and pediatric patients from the IQVIA PharMetrics Plus and IQVIA AEMR databases were analyzed. All-cause and liver-associated HCRU and costs were substantially higher following onset of LD/LgD. All-cause cost PPY ranged from US $11,877 in the absence of either LD/LgD to US $74,015 in the presence of both LD and LgD. Among liver transplant recipients in the AATD with LD health state, liver-associated total costs PPY were US $87,329 1-year pre-transplantation and US $461,752 1-year post-transplantation. In the AATD with LgD and AATD with LD and LgD health states, patients who received augmentation therapy were associated with higher all-cause total costs PPY and lower liver-associated total costs PPY than their counterparts who did not receive augmentation therapy. Conclusion: Patients with AATD had increased HCRU and healthcare costs in the presence of LD and/or LgD. HCRU and healthcare costs were highest in the AATD with LD and LgD health state.
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Hepatopatías , Enfermedades Pulmonares , Deficiencia de alfa 1-Antitripsina , Humanos , Deficiencia de alfa 1-Antitripsina/economía , Deficiencia de alfa 1-Antitripsina/complicaciones , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Hepatopatías/economía , Estados Unidos , Adulto , Estudios Longitudinales , Enfermedades Pulmonares/economía , Aceptación de la Atención de Salud/estadística & datos numéricos , Costos de la Atención en Salud/estadística & datos numéricos , Anciano , Adulto Joven , Adolescente , Recursos en Salud/estadística & datos numéricos , Recursos en Salud/economíaRESUMEN
BACKGROUND: This retrospective cohort study compared patient characteristics and burden of infection in patients with mature B cell malignancies with and without secondary immunodeficiency disease (SID). PATIENTS AND METHODS: Data were extracted from the Humedica database (H-DB) and Guardian Research Network (GRN) database from October 1, 2015 to March 10, 2020, including a 6-month pre-index period (PIP) and 12-month follow-up. Patients aged ≥18 years diagnosed with chronic lymphocytic leukemia/small lymphocytic lymphoma, multiple myeloma, or non-Hodgkin's lymphoma in the PIP were stratified into 2 cohorts: SID (hypogammaglobulinemia [using ICD-10-CM codes] or serum IgG levels <5.0 g/L, both with signs and symptoms of SID or at least 1 infection) and no-SID. Patients with SID or primary immunodeficiency diseases in the PIP were excluded. RESULTS: Overall, 2221 patients with SID (H-DB/GRN: n = 1959/262), and 19,141 patients without SID (n = 17,598/1543) were included. Baseline characteristics were similar across cohorts. At 12-month follow-up, significantly more patients with SID had experienced ≥1 infection and ≥1 severe bacterial infection than those without SID (both P < .001). H-DB/GRN mean (standard deviation) number of severe bacterial infections was 7.6 (9.9)/2.9 (2.7) for the SID cohort versus 5.2 (6.8)/2.4 (2.2) for the no-SID cohort. CONCLUSION: This study confirms that patients with mature B cell malignancies and SID face a significantly higher burden of infections than those without SID.
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Infecciones , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Infecciones/etiología , Infecciones/diagnóstico , Síndromes de Inmunodeficiencia/complicaciones , Síndromes de Inmunodeficiencia/diagnóstico , Adulto , Anciano de 80 o más Años , Leucemia Linfocítica Crónica de Células B/complicaciones , Leucemia Linfocítica Crónica de Células B/diagnósticoRESUMEN
OBJECTIVES: To characterize the impact of prior exposure and refractoriness to lenalidomide or proteasome inhibitors (PIs) on the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in relapsed/refractory multiple myeloma (RRMM). METHODS: INSURE is a pooled analysis of adult RRMM patients who had received IRd in ≥2 line of therapy from three studies: INSIGHT MM, UVEA-IXA, and REMIX. RESULTS: Overall, 391/100/68 were lenalidomide-naïve/-exposed/-refractory and 37/411/110 were PI-naïve/-exposed/-refractory. Median duration of therapy (DOT) was 15.3/15.6/4.7 months and median progression-free survival (PFS) was 21.6/25.8/5.6 months in lenalidomide-naïve/exposed/refractory patients. Median DOT and PFS in PI-naïve/exposed/refractory patients were 20.4/15.2/6.9 months and not reached/19.8/11.4 months, respectively. The proportion of lenalidomide-naïve/exposed/refractory patients in INSIGHT and UVEA-IXA who discontinued a study drug due to adverse events (AEs) was ixazomib, 31.6/28.2/28.0% and 18.6/6.7/10.5%; lenalidomide, 21.9/28.2/16.0% and 16.1/6.7/10.5%; dexamethasone, 18.4/20.5/16.0% and 10.6/0/10.5%, respectively. The proportion of PI-naïve/exposed/refractory patients in INSIGHT and UVEA-IXA who discontinued a study drug due to AEs was: ixazomib, 44.4/28.8/27.8% and 22.2/16.7/15.7%; lenalidomide, 33.3/22.0/19.4% and 16.7/15.9/11.8%; dexamethasone, 33.3/17.4/16.7% and 16.7/9.5/7.8%, respectively. REMIX AE discontinuation rates were unavailable. CONCLUSION: IRd appeared to be effective in RRMM patients in routine clinical practice regardless of prior lenalidomide or PI exposure, with better outcomes seen in lenalidomide- and/or PI-nonrefractory versus refractory patients.
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Protocolos de Quimioterapia Combinada Antineoplásica , Compuestos de Boro , Dexametasona , Resistencia a Antineoplásicos , Glicina , Lenalidomida , Mieloma Múltiple , Inhibidores de Proteasoma , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Mieloma Múltiple/diagnóstico , Compuestos de Boro/administración & dosificación , Compuestos de Boro/efectos adversos , Compuestos de Boro/uso terapéutico , Glicina/análogos & derivados , Glicina/administración & dosificación , Glicina/efectos adversos , Glicina/uso terapéutico , Lenalidomida/administración & dosificación , Lenalidomida/efectos adversos , Lenalidomida/uso terapéutico , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Masculino , Inhibidores de Proteasoma/administración & dosificación , Inhibidores de Proteasoma/uso terapéutico , Inhibidores de Proteasoma/efectos adversos , Anciano , Femenino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto , Anciano de 80 o más Años , Recurrencia , RetratamientoRESUMEN
In the study of surface-enhanced Raman scattering (SERS) processes, a simple and fast approach is needed to ensure the large-scale preparation of SERS substrates. This article uses anodic aluminum oxide (AAO) as a template to assemble gold nanoparticles (Au NPs) into an ordered array. By changing the pore size of AAO and silanizing the pores, the number and density of Au NPs entering the pores through liquid-liquid two-phase self-assembly (LLSA) can be effectively regulated. Using Rh6G (Rhodamine 6G) and CV (Crystal Violet) molecules as probe molecules, substrate sensitivity was evaluated with an enhancement factor of up to 6.34 × 107. In addition, the uniformity of the substrate is good, with a relative standard deviation (RSD) of 9.94%, and the logarithmic concentration and the Raman signal presented significant linear correlations R2 was 0.997 and 0.985, respectively. The detection limit of the substrate for APM (aspartame) as a solvent is as low as 0.0078 g/L. Finally, the substrate was subjected to high sensitivity testing on two types of beverages containing APM sold, proving the practicality of the substrate. It is expected to achieve simple and rapid detection in food additive trace detection in the future.
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Aim: We pooled data from three observational studies (INSIGHT MM, UVEA-IXA and REMIX) to investigate the real-world effectiveness of ixazomib-lenalidomide-dexamethasone (IRd) in relapsed/refractory myeloma. Materials & methods: INSIGHT MM was a prospective study conducted in countries across Europe, Asia and North/Latin America while UVEA-IXA and REMIX were multicenter, retrospective/prospective studies conducted in Europe. Patients who had received IRd as ≥2nd line of therapy were analyzed. Primary outcomes were time-to-next treatment (TTNT) and progression-free survival (PFS). Results: Overall, 564 patients were included (median follow-up: 18.5 months). Median TTNT and PFS were 18.4 and 19.9 months; both outcomes were numerically longer for earlier versus later lines. Median treatment duration was 14.0 months. Overall response rate was 64.6%. No new safety concerns were noted. Conclusion: The effectiveness of IRd in routine practice appears similar to the efficacy observed in TOURMALINE-MM1. IRd benefit in earlier versus later lines was consistent with previous reports.
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Glicina , Mieloma Múltiple , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Compuestos de Boro/uso terapéutico , Dexametasona/uso terapéutico , Glicina/análogos & derivados , Lenalidomida/uso terapéutico , Estudios Multicéntricos como Asunto , Mieloma Múltiple/tratamiento farmacológico , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
Aim: To compare the effectiveness of in-class transition to all-oral ixazomib-lenalidomide-dexamethasone (IRd) following parenteral bortezomib (V)-based induction versus continued V-based therapy in US oncology clinics. Patients & methods: Non-transplant eligible patients with newly diagnosed multiple myeloma (MM) receiving in-class transition to IRd (N = 100; US MM-6), or V-based therapy (N = 111; INSIGHT MM). Results: Following inverse probability of treatment weighting, overall response rate was 73.2% with IRd versus 57.5% with V-based therapy (p < 0.0001). Median duration of treatment was 10.8 versus 5.3 months (p < 0.0001). Overall, 18/24% of patients discontinued IRd/V-based therapy due to adverse events. Conclusion: IRd after V-based induction was associated with significantly improved overall response rate and duration of treatment than continued V-based combination therapy. Clinical Trial Registration: US MM-6: NCT03173092; INSIGHT MM: NCT02761187 (ClinicalTrials.gov).
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Mieloma Múltiple , Humanos , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Bortezomib/efectos adversos , Lenalidomida/uso terapéutico , Dexametasona , Glicina , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Compuestos de Boro/efectos adversosRESUMEN
BACKGROUND: Alpha-1 antitrypsin deficiency is a rare genetic disease and a leading cause of inherited alterations in plasma protein metabolism (APPM). AIM: To understand the prevalence, burden and progression of liver disease in patients with APPM including alpha-1 antitrypsin deficiency. METHODS: We conducted a retrospective analysis of anonymized patient-level claims data from a German health insurance provider (AOK PLUS). The APPM cohort comprised patients with APPM (identified using the German Modification of the International Classification of Diseases-10th Revision [ICD-10-GM] code E88.0 between 01/01/2010-30/09/2020) and incident liver disease (ICD-10-GM codes K74, K70.2-3 and K71.7 between 01/01/2012-30/09/2020). The control cohort comprised patients without APPM but with incident liver disease. Outcomes were incidence/prevalence of liver disease in patients with APPM, demographics/baseline characteristics, diagnostic procedures, progression-free survival (PFS), disease progression and mortality. RESULTS: Overall, 2680 and 26299 patients were included in the APPM (fibrosis, 96; cirrhosis, 2584) and control (fibrosis, 1444; cirrhosis, 24855) cohorts, respectively. Per 100000 individuals, annual incidence and prevalence of APPM and liver disease was 10-15 and 36-51, respectively. In the APPM cohort, median survival was 4.7 years [95% confidence interval (CI): 3.5-7.0] and 2.5 years (95%CI: 2.3-2.8) in patients with fibrosis and cirrhosis, respectively. A higher proportion of patients in the APPM cohort experienced disease progression (92.0%) compared with the control cohort (67.2%). Median PFS was shorter in the APPM cohort (0.9 years, 95%CI: 0.7-1.1) compared with the control cohort (3.7 years, 95%CI: 3.6-3.8; P < 0.001). Patients with cirrhosis in the control cohort had longer event-free survival for ascites, hepatic encephalopathy, hepatic failure and esophageal/gastric varices than patients with cirrhosis in the APPM cohort (P < 0.001). Patients with fibrosis in the control cohort had longer event-free survival for ascites, cirrhosis, hepatic failure and esophageal/gastric varices than patients with fibrosis in the APPM cohort (P < 0.001). In the APPM cohort, the most common diagnostic procedures within 12 mo after the first diagnosis of liver disease were imaging procedures (66.3%) and laboratory tests (51.0%). CONCLUSION: Among patients with liver disease, those with APPM experience substantial burden and earlier liver disease progression than patients without APPM.
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Citric acid is the most important organic acid in melon and has a great influence on fruit flavor quality. ATP-citrate (pro-S) lyase (ACL) is a key regulator in the acetyl-CoA pathway and plays an important role in citric acid metabolism. In this study we analyzed the structure and phylogenetics of CmACL genes and their functions in sugar and acid accumulation in melon. A total of four CmACL genes were identified in the melon genome, and phylogenetic analysis assigned these genes into the α subfamily (CmACLα1 and CmACLα2) and the ß subfamily (CmACLß1 and CmACLß2). Conserved motif and gene structure analyses showed that members of the same subfamily shared identical conserved motifs and gene structures, and probably have similar biological functions. Analysis of cis-acting elements revealed that CmACL promoter sequences contained regulatory elements related to light, stress, phytohormones, and growth and development, indicating that CmACL genes may be involved in melon growth and stress responses. The prediction of protein interaction network showed that CmACL proteins were closely related to the proteins belonging to tricarboxylic acid cycle, glyoxylic acid cycle and glycolytic pathway, suggesting that CmACL proteins may play an important role in sugar and acid metabolism. The expression of CmACLß1 was significantly and positively correlated with sucrose content, and CmACLß2 expression was significantly positively correlated with citric acid content, suggesting that CmACLß1 and CmACLß2 have important roles in sugar and acid accumulation in melon. Our results offer novel insights and avenues for the regulation of sugar and acid levels in melon and provide a theoretical foundation for breeding high-quality melon cultivars.
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BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is caused by mutations in SERPINA1, which encodes alpha-1 antitrypsin, a protease inhibitor (Pi). Individuals with AATD and the homozygous Pi*ZZ genotype have variable risk of progressive liver disease but the influence of comorbid lung disease is poorly understood. AIMS: To characterise patients with AATD Pi*ZZ and liver disease (AATD-LD-Pi*ZZ) with or without lung disease and describe liver disease-related clinical events longitudinally. METHODS: This was an observational cohort study of patients in the Mayo Clinic Healthcare System (January 2000-September 2021). Patients were identified using diagnosis codes and natural language processing. Fibrosis stage (F0-F4) was assessed using a hierarchical approach at baseline (90 days before or after the index date) and follow-up. Clinical events associated with liver disease progression were assessed. RESULTS: AATD-LD-Pi*ZZ patients with lung disease had a longer median time from AATD diagnosis to liver disease diagnosis versus those without lung disease (2.2 vs. 0.2 years, respectively). Compared to those without lung disease, patients with lung disease had a longer time to liver disease-related clinical events (8.5 years and not reached, respectively). AATD-LD-Pi*ZZ patients without lung disease were more likely to undergo liver transplantation compared with those with lung disease. CONCLUSION: In patients with AATD and lung disease, there is a delay in the diagnosis of comorbid liver disease. Our findings suggest that liver disease may progress more rapidly in patients without comorbid lung disease.
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Enfermedades Pulmonares , Deficiencia de alfa 1-Antitripsina , Humanos , Deficiencia de alfa 1-Antitripsina/complicaciones , Deficiencia de alfa 1-Antitripsina/diagnóstico , Deficiencia de alfa 1-Antitripsina/genética , Enfermedades Pulmonares/complicaciones , Genotipo , Progresión de la Enfermedad , Inhibidores de ProteasasRESUMEN
BACKGROUND: Infections are a common reason for hospitalization and death in multiple myeloma (MM). Although pneumococcal vaccination (PV) and influenza vaccination (FV) are recommended for MM patients, data on vaccination status and outcomes are limited in MM. MATERIALS AND METHODS: We utilized data from the global, prospective, observational INSIGHT MM study to analyze FV and PV rates and associated outcomes of patients with MM enrolled 2016-2019. RESULTS: Of the 4307 patients enrolled, 2543 and 2500 had study-entry data on FV and PV status. Overall vaccination rates were low (FV 39.6%, PV 30.2%) and varied by region. On separate multivariable analyses of overall survival (OS) by Cox model, FV in the prior 2 years and PV in the prior 5 years impacted OS (vs. no vaccination; FV: HR, 0.73; 95% CI, 0.60-0.90; Pâ¯=â¯.003; PV: HR, 0.51; 95% CI, 0.42-0.63; P < .0001) when adjusted for age, region, performance status, disease stage, cytogenetics at diagnosis, MM symptoms, disease status, time since diagnosis, and prior transplant. Proportions of deaths due to infections were lower among vaccinated versus non-vaccinated patients (FV: 9.8% vs. 15.3%, Pâ¯=â¯.142; PV: 9.9% vs. 18.0%, Pâ¯=â¯.032). Patients with FV had generally lower health resource utilization (HRU) versus patients without FV; patients with PV had higher or similar HRU versus patients without PV. CONCLUSION: Vaccination is important in MM and should be encouraged. Vaccination status should be recorded in prospective clinical trials as it may affect survival. This trial was registered at www. CLINICALTRIALS: gov as #NCT02761187.
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Gripe Humana , Mieloma Múltiple , Humanos , Gripe Humana/prevención & control , Estudios Prospectivos , Hospitalización , VacunaciónRESUMEN
INTRODUCTION: This observational study describes the real-world economic burden in patients with anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) receiving a first-line ALK inhibitor, and the economic impact of brain metastases (BM). METHODS: Administrative claims data (Truven Health MarketScan® Commercial Claims and Encounters database and Medicare Supplemental and Coordination of Benefits database; January 1, 2015-March 31, 2020) for adult patients with ALK+ NSCLC who received a first-line ALK inhibitor were retrospectively reviewed. Healthcare costs and resource utilization were calculated on a per-patient-per-month (PPPM) basis and stratified by the presence or absence of BM prior to first-line ALK inhibitor. Factors associated with costs were identified. RESULTS: A total of 496 patients were eligible for analysis. Mean PPPM total healthcare costs were $21,961 for all patients receiving up to 1 year of a first-line ALK inhibitor. Patients were significantly more likely to have higher mean PPPM total costs if they had BM prior to first-line ALK inhibitor (vs. no BM; odds ratio: 1.11; 95% confidence interval: 1.02, 1.21; p = 0.013). Mean PPPM days of hospital stay (p = 0.0056), and inpatient hospital visits (p = 0.0030) were significantly higher for patients with BM compared to no BM. The main cost drivers for non-inpatient procedures for all patients were medications, radiation therapy, and other diagnostic procedures. CONCLUSIONS: The economic burden in patients with ALK+ NSCLC receiving a first-line ALK inhibitor was high. Patients with ALK+ NSCLC and BM had higher healthcare costs and resource utilization than patients without BM.
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Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adulto , Humanos , Anciano , Estados Unidos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Quinasa de Linfoma Anaplásico , Estudios Retrospectivos , Estrés Financiero , Medicare , Inhibidores de Proteínas Quinasas/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/secundarioRESUMEN
In this paper, we report a flexible wavelength-, pulse-controlled mode-locked all-fiber laser based on a novel fiber optic Lyot filter. The wavelength, pulse duration and spectral bandwidth of passive mode-locked lasers can be tuned by controlling the polarization controller. The proposed Lyot filter was constructed by a single-mode fiber insertion between two polarization-maintaining fibers. The filter bandwidth and laser output tunability were based on the birefringence characteristics of the polarization-maintaining fibers. This all-fiber laser is simple and stable and can be used for various applications where width-tunable or wavelength-tunable pulses are necessary.
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Based on the dual-resonance principle around the dispersion turning point, a scheme of chiral long-period fiber gratings (CLPGs) formed by twisting a high-birefringence (Hi-Bi) fiber is herein proposed to realise ultra-broadband flat-top circular polarizers. The coupling bandwidth is approximately seven times larger than that of traditional CLPGs. In addition, by introducing chirp characteristics in these CLPGs, an ultra-broadband flat-top circular polarizer with â¼200â nm@3â dB was conveniently achieved. Subsequently, by optimising the chirped CLPGs, a circular polarizer with a bandwidth extinction ratio of approximately 30â dB and a high level of â¼100â nm at 1â dB was realised. It was shown that the mode-controlling performances of the CLPGs can be remarkably improved, which has significant applications in light-field regulation. Finally, for the first time, it was proved that the CLPG cannot generate a vortex beam.
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Oriental melon (Cucumis melo var. acidulus) is one of the most economically important fruit crops worldwide. To elucidate the molecular basis related to soluble sugar and organic acid metabolism in the fruits of two oriental melon cultivars with different sweetness, we performed integrated metabolomic and transcriptomic analyses of the fruits of 'Tianbao' (A) with high sweetness and 'Xiaocuigua' (B) with low sweetness at different ripening stages. The high accumulation of sucrose, D-glucose, D-(+)-raffinose, and the relatively lower citric acid and malic acid might contribute to the sweet taste of A. By screening the differentially expressed genes (DEGs) and correlation analysis of the DEGs and differentially accumulated metabolites, we deduced that the B cultivar might promote the conversion of glucose and fructose into intermediate compounds for downstream processes such as glycolysis. The tricarboxylic acid (TCA) cycle might also be enhanced compared to A, thus resulting in the differential accumulation of soluble sugars and organic acids, ultimately causing the taste difference between the two oriental melon cultivars. Our finding provides important information for further exploring the metabolic mechanisms of soluble sugars and organic acids in oriental melon.
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OBJECTIVES: To examine the temporal patterns of patient characteristics, treatments used and outcomes associated with COVID-19 in patients who were hospitalised for the disease between January and 15 November 2020. DESIGN: Observational cohort study. SETTING: COVID-19 subset of the Optum deidentified electronic health records, including more than 1.8 million patients from across the USA. PARTICIPANTS: There were 51 510 hospitalised patients who met the COVID-19 definition, with 37 617 in the laboratory positive cohort and 13 893 in the clinical cohort. PRIMARY AND SECONDARY OUTCOME MEASURES: Incident acute clinical outcomes, including in-hospital all-cause mortality. RESULTS: Respectively, 48% and 49% of the laboratory positive and clinical cohorts were women. The 50- 65 age group was the median age group for both cohorts. The use of antivirals and dexamethasone increased over time, fivefold and twofold, respectively, while the use of hydroxychloroquine declined by 98%. Among adult patients in the laboratory positive cohort, absolute age/sex standardised incidence proportion for in-hospital death changed by -0.036 per month (95% CI -0.042 to -0.031) from March to June 2020, but remained fairly flat from June to November, 2020 (0.001 (95% CI -0.001 to 0.003), 17.5% (660 deaths /3986 persons) in March and 10.2% (580/5137) in October); in the clinical cohort, the corresponding changes were -0.024 (95% CI -0.032 to -0.015) and 0.011 (95% CI 0.007 0.014), respectively (14.8% (175/1252) in March, 15.3% (189/1203) in October). Declines in the cumulative incidence of most acute clinical outcomes were observed in the laboratory positive cohort, but not for the clinical cohort. CONCLUSION: The incidence of adverse clinical outcomes remains high among COVID-19 patients with clinical diagnosis only. Patients with COVID-19 entering the hospital are at elevated risk of adverse outcomes.
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COVID-19 , Adulto , COVID-19/epidemiología , Estudios de Cohortes , Femenino , Mortalidad Hospitalaria , Hospitalización , Humanos , SARS-CoV-2RESUMEN
The objective of this retrospective cohort study was to describe pre-treatment characteristics, treatment patterns, health resource use, and clinical outcomes among adults hospitalized with COVID-19 in the United States (US) who initiated common treatments for COVID-19. The Optum® COVID-19 electronic health records database was used to identify patients >18 years, diagnosed with COVID-19, who were admitted to an inpatient setting and received treatments of interest for COVID-19 between September 2020 and January 2021. Patients were stratified into cohorts based on index treatment use. Patient demographics, medical history, care setting, medical procedures, subsequent treatment use, patient disposition, clinical improvement, and outcomes were summarized descriptively. Among a total of 26,192 patients identified, the most prevalent treatments initiated were dexamethasone (35.4%) and dexamethasone + remdesivir (14.9%), and dexamethasone was the most common subsequent treatment. At day 14 post-index, <10% of patients received any treatments of interest. Mean (standard deviation [SD]) patient age was 65.6 (15.6) years, and the most prevalent comorbidities included hypertension (44.8%), obesity (35.4%), and diabetes (25.7%). At the end of follow-up, patients had a mean (SD) 8.1 (6.6) inpatient days and 1.4 (4.1) days with ICU care. Oxygen supplementation, non-invasive, or invasive ventilation was required by 4.5%, 3.0%, and 3.1% of patients, respectively. At the end of follow-up, 84.2% of patients had evidence of clinical improvement, 3.1% remained hospitalized, 83.8% were discharged, 4% died in hospital, and 9.1% died after discharge. Although the majority of patients were discharged alive, no treatments appeared to alleviate the inpatient morbidity and mortality associated with COVID-19. This highlights an unmet need for effective treatment options for patients hospitalized with COVID-19.
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Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Antiinflamatorios/uso terapéutico , Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Dexametasona/uso terapéutico , Hipertensión/epidemiología , Obesidad/epidemiología , Alta del Paciente , SARS-CoV-2/genética , SARS-CoV-2/inmunología , Adenosina Monofosfato/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alanina/uso terapéutico , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/virología , Comorbilidad , Quimioterapia Combinada/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/genética , Estudios Retrospectivos , Resultado del Tratamiento , Estados Unidos/epidemiología , Adulto JovenRESUMEN
OBJECTIVE: To examine age, gender, and temporal differences in baseline characteristics and clinical outcomes of adult patients hospitalised with COVID-19. DESIGN: A cohort study using deidentified electronic medical records from a Global Research Network. SETTING/PARTICIPANTS: 67 456 adult patients hospitalised with COVID-19 from the USA; 7306 from Europe, Latin America and Asia-Pacific between February 2020 and January 2021. RESULTS: In the US cohort, compared with patients 18-34 years old, patients ≥65 had a greater risk of intensive care unit (ICU) admission (adjusted HR (aHR) 1.73, 95% CI 1.58 to 1.90), acute respiratory distress syndrome(ARDS)/respiratory failure (aHR 1.86, 95% CI 1.76 to 1.96), invasive mechanical ventilation (IMV, aHR 1.93, 95% CI, 1.73 to 2.15), and all-cause mortality (aHR 5.6, 95% CI 4.36 to 7.18). Men appeared to be at a greater risk for ICU admission (aHR 1.34, 95% CI 1.29 to 1.39), ARDS/respiratory failure (aHR 1.24, 95% CI1.21 to 1.27), IMV (aHR 1.38, 95% CI 1.32 to 1.45), and all-cause mortality (aHR 1.16, 95% CI 1.08 to 1.24) compared with women. Moreover, we observed a greater risk of adverse outcomes during the early pandemic (ie, February-April 2020) compared with later periods. In the ex-US cohort, the age and gender trends were similar; for the temporal trend, the highest proportion of patients with all-cause mortality were also in February-April 2020; however, the highest percentages of patients with IMV and ARDS/respiratory failure were in August-October 2020 followed by February-April 2020. CONCLUSIONS: This study provided valuable information on the temporal trends of characteristics and outcomes of hospitalised adult COVID-19 patients in both USA and ex-USA. It also described the population at a potentially greater risk for worse clinical outcomes by identifying the age and gender differences. Together, the information could inform the prevention and treatment strategies of COVID-19. Furthermore, it can be used to raise public awareness of COVID-19's impact on vulnerable populations.
Asunto(s)
COVID-19 , Adolescente , Adulto , Estudios de Cohortes , Femenino , Salud Global , Hospitalización , Humanos , Unidades de Cuidados Intensivos , Masculino , Pandemias , Respiración Artificial , SARS-CoV-2 , Adulto JovenRESUMEN
By rationally choosing Pd as an active metal and Cu as a promoting metal, we developed Cu-rich CuPd bimetallic aerogels as a self-supported electrocatalyst for nitrate electroreduction. The spongy aerogel structure provides abundant catalytically active sites, while the synergistic benefit of the CuPd binary composition increases their reactivity, helping to achieve efficient nitrate-to-ammonia conversion.
RESUMEN
A novel method to control the parameters of a chiral fiber grating structure is proposed. Mode couplings are controlled in real time during the twisting fabrication process. This chiral grating structure can satisfy the phase-matching condition for generating high-quality orbital angular momentum (OAM) beams, with an order mode of conversion efficiency over 99.9%. Both theoretical analysis and experimental results of this OAM mode conversion have been investigated, with good agreement. The results demonstrate a dual-OAM beam converter with a charge of ±1 for the right- and left-handed CLPGs, respectively. The high-quality OAM beam generated in this twisted single-mode fiber process may find excellent applications in optical communications.