RESUMO
Purpose: Triple therapy (long-acting muscarinic antagonist/long-acting ß2-agonist/inhaled corticosteroid) is recommended for patients with chronic obstructive pulmonary disease (COPD) who experience recurrent exacerbations. Multiple-inhaler triple therapy (MITT) is associated with poor adherence and persistence. This study assessed comparative adherence and persistence to single-inhaler triple therapy (SITT) versus MITT among patients with COPD in a real-world setting in Germany. Patients and Methods: This retrospective analysis using the WIG2 benchmark database identified patients with COPD newly initiating triple therapy with MITT or SITT (fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI] or formoterol/beclomethasone/glycopyrronium bromide [FOR/BDP/GLY]) November 2017-June 2019. Eligible patients were ≥35 years with 1 year's continual insurance prior to triple therapy initiation and no previous record of triple therapy. Inverse probability of treatment weighting was used to balance baseline characteristics. Adherence was measured using proportion of days covered (PDC) at 6, 12, and 18 months post-treatment initiation; persistence (time until treatment discontinuation) was measured at 6, 12, and 18 months, with a gap of >30 days used to define non-persistence. Results: Of 5710 patients included in the analysis (mean age 66 years), 71.4% initiated MITT and 28.6% initiated SITT (FF/UMEC/VI: 41.4%; FOR/BDP/GLY: 58.6%). Mean PDC was higher among SITT versus MITT users at all time points; at each time point, mean PDC was highest among FF/UMEC/VI users. During the first 6 months following treatment initiation, higher adherence was exhibited by FF/UMEC/VI (29%) and FOR/BDP/GLY (19%) users versus MITT users. Over the entire observation period, FF/UMEC/VI users had the highest proportion of persistent patients; at 18 months, 16.5% of FF/UMEC/VI users were persistent versus 2.3% of MITT users. Conclusion: Patients initiating SITT in Germany had significantly higher adherence and persistence compared with patients initiating MITT over 6 to 18 months following treatment initiation. Among SITT, FF/UMEC/VI users had the highest proportion of adherence and persistence.
Assuntos
Agonistas de Receptores Adrenérgicos beta 2 , Broncodilatadores , Combinação de Medicamentos , Adesão à Medicação , Antagonistas Muscarínicos , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Masculino , Feminino , Alemanha , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Administração por Inalação , Antagonistas Muscarínicos/administração & dosagem , Broncodilatadores/administração & dosagem , Resultado do Tratamento , Quinuclidinas/administração & dosagem , Fatores de Tempo , Bases de Dados Factuais , Clorobenzenos/administração & dosagem , Clorobenzenos/uso terapêutico , Demandas Administrativas em Assistência à Saúde , Quimioterapia Combinada , Álcoois Benzílicos/administração & dosagem , Álcoois Benzílicos/uso terapêutico , Nebulizadores e Vaporizadores , Glicopirrolato/administração & dosagem , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologiaRESUMO
BACKGROUND: In recent years, the incorporation of LAMAs into asthma therapy has been expected to enhance symptom control. However, a significant number of patients with asthma continue to experience poorly managed symptoms. There have been limited investigations on LAMA-induced airway alterations in asthma treatment employing IOS. In this study, we administered a LAMA to patients with poorly controlled asthma, evaluated clinical responses and respiratory function, and investigated airway changes facilitated by LAMA treatments using the IOS. METHODS: Of a total of 1282 consecutive patients with asthma, 118 exhibited uncontrolled symptoms. Among them, 42 switched their treatment to high-dose fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) (ICS/LABA/LAMA). The patients were then assessed using AHQ-33 or LCQ and ACT. Spirometry parameters (such as FEV1 or MMEF) and IOS parameters (such as R20 or AX) were measured and compared before and after exacerbations and the addition of LAMA. RESULTS: Of the 42 patients, 17 who switched to FF/UMEC/VI caused by dyspnea exhibited decreased pulmonary function between period 1 and baseline, followed by an increase in pulmonary function between baseline and period 2. Significant differences were observed in IOS parameters such as R20, R5-R20, Fres, or AX between period 1 and baseline as well as between baseline and period 2. Among the patients who switched to inhaler due to cough, 25 were classified as responders (n = 17) and nonresponders (n = 8) based on treatment outcomes. Among nonresponders, there were no significant differences in spirometry parameters such as FEV1 or PEF and IOS parameters such as R20 or AX between period 1 and baseline. However, among responders, significant differences were observed in all IOS parameters, though not in most spirometry parameters, between period 1 and baseline. Furthermore, significant differences were noted between baseline and period 2 in terms of FEV1, %MMEF, %PEF, and all IOS parameters. CONCLUSION: ICS/LABA/LAMA demonstrates superiority over ICS/LABA in improving symptoms and lung function, which is primarily attributed to the addition of LAMA. Additionally, IOS revealed the effectiveness of LAMA across all airway segments, particularly in the periphery. Hence, LAMA can be effective against various asthma phenotypes characterized by airway inflammation, even in real-world cases.
Assuntos
Asma , Antagonistas Muscarínicos , Oscilometria , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/administração & dosagem , Asma/tratamento farmacológico , Asma/fisiopatologia , Asma/diagnóstico , Resultado do Tratamento , Oscilometria/métodos , Adulto , Idoso , Combinação de Medicamentos , Quinuclidinas/administração & dosagem , Clorobenzenos/administração & dosagem , Broncodilatadores/administração & dosagem , Antiasmáticos/administração & dosagem , Antiasmáticos/uso terapêuticoRESUMO
Molecular interaction fields (MIFs) are three-dimensional interaction maps that describe the intermolecular interactions expected to be formed around target molecules. In this paper, a method for the fast computation of MIFs using the approximation functions of quantum mechanics-level MIFs of small model molecules is proposed. MIF functions of N-methylacetamide with chlorobenzene, bromobenzene, and iodobenzene probes were precisely approximated and used to calculate the MIFs on protein surfaces. This method appropriately reproduced halogen-bond-formable areas around the ligand-binding sites of proteins, where halogen bond formation was suggested in a previous study.
Assuntos
Halogênios , Modelos Moleculares , Proteínas , Proteínas/química , Proteínas/metabolismo , Halogênios/química , Acetamidas/química , Teoria Quântica , Clorobenzenos/química , Conformação Proteica , Propriedades de Superfície , Iodobenzenos/química , Sítios de Ligação , Bromobenzenos/química , LigantesRESUMO
Objective: To evaluate the safety of umeclidinium/vilanterol in Chinese participants in a real-world setting. Methods: This was a 24-week, prospective, multicenter, single-arm, observational study that enrolled participants treated with umeclidinium/vilanterol in real-world settings from 14 sites in China from 14 December 2020 to 30 January 2022. The primary outcomes were the incidence of adverse events (AEs) and serious adverse events (SAEs) at week 24. Results: A total of 887 participants on umeclidinium/vilanterol were enrolled. The mean (±SD) age of these participants was 67.5 (±9.6) years, with more men (77.7%) enrolled. The majority of the participants (98.1%) had been diagnosed with chronic obstructive pulmonary disease, and 67.6% of them reported comorbidities. More than half of the participants (52.8%) were taking concomitant medication in addition to the study treatment. AEs were reported in 59 (6.7%) participants and were predominantly mild to moderate in severity. SAEs were reported in 21 (2.4%) participants, including 9 fatal SAEs, 10 reported non-fatal SAEs, and 2 reported both non-fatal and fatal SAEs. None of the SAEs, including the fatal events, were considered by the investigators to be related to umeclidinium/vilanterol. Adverse drug reactions (ADRs) were reported in 6 (0.7%) participants with 4 preferred terms (PTs), all of which were considered mild in severity. Of these PTs, 2 were known ADRs of umeclidinium/vilanterol. Three participants (0.3%) reported AEs that were part of serious identified/potential hazards, all of which were considered by the investigators to be unrelated to umeclidinium/vilanterol. Conclusion: The results of this study showed that umeclidinium/vilanterol was well tolerated in Chinese participants in a real-world setting and no new drug-related safety signals were observed.
Assuntos
Álcoois Benzílicos , Clorobenzenos , Quinuclidinas , Humanos , Álcoois Benzílicos/administração & dosagem , Álcoois Benzílicos/efeitos adversos , Estudos Prospectivos , Clorobenzenos/efeitos adversos , Clorobenzenos/administração & dosagem , Quinuclidinas/efeitos adversos , Quinuclidinas/administração & dosagem , Idoso , Masculino , Feminino , China , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Pessoa de Meia-Idade , Povo Asiático , População do Leste AsiáticoRESUMO
BACKGROUND: Previous studies have reported reduced acute exacerbation rates and improved symptom control in asthma patients treated using inhaled corticosteroids plus formoterol maintenance and reliever therapy (MART). Fluticasone furoate (FF) and vilanterol (VIL) also provide rapid bronchodilation and sustained anti-inflammatory effects, however no studies have investigated FF/VIL as MART for asthma control. METHODS: From October 1, 2021 to September 30, 2023, this retrospective study included asthma patients classified as step 3 or 4 according to the Global Initiative for Asthma guidelines, who were then divided into two groups. One group received BUD/FOR as MART, while the other received FF/VIL as MART. Pulmonary function tests, exacerbation rates, Asthma Control Test (ACT), fractional exhaled nitric oxide (FeNO) levels, and blood eosinophil counts were measured before and after 12 months of treatment. RESULTS: A total of 161 patients were included, of whom 36 received BUD/FOR twice daily as MART, and 125 received FF/VIL once daily as MART. After 12 months of treatment, the FF/VIL group showed a significant increase in ACT scores by 1.57 (p < 0.001), while the BUD/FOR group had an increase of 0.88 (p = 0.11). In terms of FeNO levels, the BUD/FOR group experienced a decline of -0.2 ppb (p = 0.98), whereas the FF/VIL group had a mild increase of + 0.8 ppb (p = 0.7). Notably, there was a significant difference in the change of FeNO between the two groups (∆ FeNO: -0.2 ppb in BUD/FOR; + 0.8 ppb in FF/VIL, p < 0.001). There were no significant alterations observed in FEV1, blood eosinophil count, or acute exacerbation decline in either group. CONCLUSIONS: In the current study, patients treated with FF/VIL as MART showed improvements in ACT scores, while those treated with BUD/FOR as MART exhibited a reduction in FeNO levels. However, the difference between the two treatment groups did not reach clinical significance. Thus, FF/VIL as MART showed similar effectiveness to BUD/FOR as MART.
Assuntos
Asma , Álcoois Benzílicos , Clorobenzenos , Combinação de Medicamentos , Humanos , Masculino , Feminino , Álcoois Benzílicos/administração & dosagem , Álcoois Benzílicos/uso terapêutico , Estudos Retrospectivos , Asma/tratamento farmacológico , Pessoa de Meia-Idade , Clorobenzenos/administração & dosagem , Clorobenzenos/uso terapêutico , Adulto , Broncodilatadores/administração & dosagem , Broncodilatadores/uso terapêutico , Administração por Inalação , Androstadienos/administração & dosagem , Androstadienos/uso terapêutico , Budesonida/administração & dosagem , Budesonida/uso terapêutico , Antiasmáticos/uso terapêutico , Antiasmáticos/administração & dosagem , Idoso , Fumarato de Formoterol/administração & dosagem , Resultado do Tratamento , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Combinação Budesonida e Fumarato de Formoterol/administração & dosagem , Combinação Budesonida e Fumarato de Formoterol/uso terapêutico , Testes de Função Respiratória , Eosinófilos/efeitos dos fármacosRESUMO
Microbial fuel cell (MFC) is a promising device for water decontamination and energy generation. However, the correlation between power generation and pollutant degradation has not been clarified. Herein, a ruthenium-activated carbon (Ru-AC) bioanode was constructed for chlorobenzenes (CBs) treatment. The pollutant tolerance was improved by Ru-AC anode, and the minimum removal efficiencies of CB and ortho-dichlorobenzene (o-DCB) reached 75.1 % and 69.3 %, respectively, which were considerably higher than those of other MFCs (16.3 %-39.7 %). Correspondingly, the maximum output voltage reached 360.7 mV for the Ru-AC anode, whereas the values obtained from others reached 45.2-149.6 mV. Interaction models were introduced to quantify the relationship between power generation and pollutant degradation. The conversion of highly toxic chlorophenols to organic acids could be accelerated by boosting the mass and electron transfer, thereby simultaneously enhancing CBs removal and power generation. This work provided important insights into pollutant-powered MFC development.
Assuntos
Fontes de Energia Bioelétrica , Clorobenzenos , Eletrodos , Cinética , Poluentes Químicos da Água , Rutênio/química , Carvão Vegetal/química , Carvão Vegetal/farmacologia , Biodegradação Ambiental , Purificação da Água/métodosRESUMO
BACKGROUND: This cost-utility analysis assessed the long-term clinical and economic benefits of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy vs FF/VI or UMEC/VI from a Quebec societal perspective in patients with chronic obstructive pulmonary disease (COPD) with ≥1 moderate/severe exacerbation in the previous year. METHODS: The validated GALAXY disease progression model was utilized, with parameters set to baseline and efficacy data from IMPACT. Treatment costs (2017 Canadian dollars [C$]) were estimated using Quebec-specific unit costs. Costs and health outcomes were discounted at 1.5 %/year. A willingness-to-pay threshold of C$50,000/quality-adjusted life year (QALY) was considered cost-effective. Outcomes modeled were exacerbation rates, QALYs, life years (LYs), costs and incremental cost-effectiveness ratios (ICERs). Subgroup analyses were performed according to prior treatment, exacerbation history in the previous year, and baseline lung function. RESULTS: Over a lifetime horizon, FF/UMEC/VI resulted in more QALYs and LYs gained, at a small incremental cost compared with FF/VI and UMEC/VI. From a societal perspective, the estimated ICER for the base case was C$18,152/QALY vs FF/VI, and C$15,847/QALY vs UMEC/VI. For the subgroup analyses (FF/UMEC/VI compared with FF/VI and UMEC/VI), ICERs ranged from: C$17,412-25,664/QALY and C$16,493-18,663/QALY (prior treatment); C$15,247-19,924/QALY and C$15,444-28,859/QALY (exacerbation history); C$14,025-34,154/QALY and C$16,083-17,509/QALY (baseline lung function). INTERPRETATION: FF/UMEC/VI was predicted to improve outcomes and be cost-effective vs both comparators in the base case and all subgroup analyses, and based on this analysis would be an appropriate investment of health service funds in Quebec. CLINICAL TRIAL REGISTRATION NUMBER: IMPACT trial NCT02164513.
Assuntos
Androstadienos , Álcoois Benzílicos , Clorobenzenos , Análise Custo-Benefício , Doença Pulmonar Obstrutiva Crônica , Anos de Vida Ajustados por Qualidade de Vida , Quinuclidinas , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/economia , Quebeque , Álcoois Benzílicos/economia , Álcoois Benzílicos/administração & dosagem , Álcoois Benzílicos/uso terapêutico , Quinuclidinas/economia , Quinuclidinas/administração & dosagem , Quinuclidinas/uso terapêutico , Masculino , Feminino , Clorobenzenos/economia , Clorobenzenos/administração & dosagem , Clorobenzenos/uso terapêutico , Androstadienos/economia , Androstadienos/administração & dosagem , Androstadienos/uso terapêutico , Pessoa de Meia-Idade , Combinação de Medicamentos , Nebulizadores e Vaporizadores/economia , Administração por Inalação , Idoso , Pirrolidinas/economia , Pirrolidinas/uso terapêutico , Pirrolidinas/administração & dosagem , Broncodilatadores/economia , Broncodilatadores/administração & dosagem , Broncodilatadores/uso terapêutico , Progressão da Doença , Quimioterapia Combinada , Resultado do TratamentoRESUMO
Environmental exposures may have endocrine disruptor (ED) effects, e.g., a role for halogenated hydrocarbon chlorobenzenes in increasing vasopressin (AVP), oxytocin (OT) secretion and, in association, anxiety and aggression in male rats has been shown. Our aim is to investigate whether 1,2,4-trichlorobenzenehexachlorobenzene= 1:1 (mClB) treatment of female rats also shows ED effects and reproductive biology differences, and whether AVP may have a mediator role in this? Female Wistar rats were treated (0.1; 1.0; 10.0 µg/bwkg/day) with mClB (by gastrictube) and then 30; 60; 90 days after treatment anxiety (open field test) and aggressive (resident intruder test) behaviors AVP, OT concentrations from blood plasma samples were detected by radioimmunoassay on 30; 60; 90 days. Treated female rats were mated with untreated males. Mating success, number of newborn and maternal aggression on the neonates were monitored. Results showed that AVP, OT levels; and anxiety, aggressive behaviors; and mothers' aggression towards their offspring increased significantly in relation to the duration and the dose of mClB treatment. But mating propensity and number of offspring decreased. Patterns of AVP, OT release and anxiety, aggression behaviors, and reproductive-related behaviors were correlated. Consistent with the literature, our studies confirmed the role of AVP and OT in different behavioral effects.
Assuntos
Agressão , Ansiedade , Disruptores Endócrinos , Ocitocina , Animais , Feminino , Masculino , Gravidez , Ratos , Agressão/efeitos dos fármacos , Agressão/fisiologia , Animais Recém-Nascidos , Arginina Vasopressina/sangue , Clorobenzenos/administração & dosagem , Relação Dose-Resposta a Droga , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Hexaclorobenzeno/sangue , Comportamento Materno/efeitos dos fármacos , Comportamento Materno/fisiologia , Ocitocina/sangue , Ratos Wistar , Reprodução/efeitos dos fármacos , Reprodução/fisiologia , Comportamento Sexual Animal/efeitos dos fármacos , Comportamento Sexual Animal/fisiologiaRESUMO
BACKGROUND: Real-world data assessing characteristics of patients with asthma initiating inhaled corticosteroid/long-acting muscarinic antagonist/long-acting ß2-agonist (ICS/LAMA/LABA) triple therapy in Japan are limited. METHODS: Descriptive, observational study of patients with asthma aged ≥15 years newly initiating single- or multiple-inhaler triple therapy (SITT: fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI], SITT: indacaterol/glycopyrronium bromide/mometasone furoate [IND/GLY/MF] or MITT) or ICS/LABA using JMDC/Medical Data Vision (MDV) health insurance databases from February 2021-February 2022 (first prescription date: index date). Patients were assigned to three non-mutually exclusive cohorts: A) new FF/UMEC/VI initiators; B) new FF/UMEC/VI, IND/GLY/MF, or MITT initiators; C) new FF/UMEC/VI, IND/GLY/MF, MITT or ICS/LABA initiators as initial maintenance therapy (IMT). Patient characteristics were assessed descriptively for 12-months pre-treatment initiation (baseline period). RESULTS: Cohort A: among new FF/UMEC/VI initiators, 12.8% and 0.1% (JMDC) and 21.7% and 0.9% (MDV) of patients had ≥1 moderate and severe exacerbation; 52.0% (JMDC) and 79.2% (MDV) had ICS/LABA use. Cohort B: most patients initiated FF/UMEC/VI and IND/GLY/MF over MITT (JMDC: 91.3% vs 8.7%; MDV: 67.8% vs 32.2%), with fewer exacerbations and lower rescue medication use. Cohort C: a greater proportion of FF/UMEC/VI initiators as IMT experienced a moderate exacerbation at index versus ICS/LABA initiators as IMT (JMDC: 17.8% vs 10.7%; MDV: 8.0% vs 5.1%). CONCLUSIONS: Patient characteristics were generally similar between treatment groups; SITT initiators had fewer exacerbations and lower rescue medication use than MITT initiators, represented by the greater proportion of IMT among SITT versus MITT initiators. Physicians may have prescribed triple over dual therapy as IMT in response to an exacerbation.
Assuntos
Androstadienos , Asma , Álcoois Benzílicos , Clorobenzenos , Quinuclidinas , Humanos , Álcoois Benzílicos/administração & dosagem , Clorobenzenos/administração & dosagem , Asma/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Quinuclidinas/administração & dosagem , Japão , Adulto , Administração por Inalação , Androstadienos/administração & dosagem , Idoso , Combinação de Medicamentos , Antagonistas Muscarínicos/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Nebulizadores e Vaporizadores , Adolescente , Adulto Jovem , Quimioterapia Combinada , Glicopirrolato/administração & dosagem , Quinolonas/administração & dosagemRESUMO
INTRODUCTION: Treatment with LABA/LAMA is recommended in GOLD B patients. We hypothesized that triple therapy (LABA/LAMA/ICS) will be superior to LABA/LAMA in achieving and maintaining clinical control (CC), a composite outcome that considers both impact and disease stability in a subgroup of GOLD B patients (here termed GOLD B+ patients) characterized by: (1) remaining symptomatic (CAT≥10) despite regular LABA/LAMA therapy; (2) having suffered one moderate exacerbation in the previous year; and (3) having blood eosinophil counts (BEC) ≥150cells/µL. METHODS: The ANTES B+ study is a prospective, multicenter, open label, randomized, pragmatic, controlled trial designed to test this hypothesis. It will randomize 1028 B+ patients to continue with their usual LABA/LAMA combination prescribed by their attending physician or to begin fluticasone furoate (FF) 92µg/umeclidinium (UMEC) 55µg/vilanterol (VI) 22µg in a single inhaler q.d. for 12 months. The primary efficacy outcome will be the level of CC achieved. Secondary outcomes include the clinical important deterioration index (CID), annual rate of exacerbations, and FEV1. Exploratory objectives include the interaction of BEC and smoking status, all-cause mortality and proportion of patients on LABA/LAMA arm that switch therapy arms. Safety analysis include adverse events and incidence of pneumonia. RESULTS: The first patient was recruited on February 29, 2024; results are expected in the first quarter of 2026. CONCLUSIONS: The ANTES B+ study is the first to: (1) explore the efficacy and safety of triple therapy in a population of B+ COPD patients and (2) use a composite index (CC) as the primary result of a COPD trial.
Assuntos
Álcoois Benzílicos , Combinação de Medicamentos , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Estudos Prospectivos , Álcoois Benzílicos/uso terapêutico , Álcoois Benzílicos/administração & dosagem , Clorobenzenos/uso terapêutico , Clorobenzenos/administração & dosagem , Quinuclidinas/uso terapêutico , Quinuclidinas/administração & dosagem , Quimioterapia Combinada , Antagonistas Muscarínicos/uso terapêutico , Antagonistas Muscarínicos/administração & dosagem , Androstadienos/uso terapêutico , Androstadienos/administração & dosagem , Resultado do Tratamento , Corticosteroides/uso terapêutico , Broncodilatadores/uso terapêutico , Broncodilatadores/administração & dosagem , Administração por Inalação , Masculino , Feminino , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Eosinófilos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Compared with multiple-inhaler triple therapy (MITT), single-inhaler triple therapy (SITT) with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) demonstrated improved lung function and meaningful improvements in chronic obstructive pulmonary disease (COPD) Assessment Test score. This real-world study compared the effectiveness of switching patients with COPD in England from MITT to once-daily SITT with FF/UMEC/VI by evaluating rates of COPD exacerbation, healthcare resource use (HCRU) and associated direct medical costs. METHODS: Retrospective cohort pre-post study using linked primary care electronic health record and secondary care administrative datasets. Patients diagnosed with COPD at age ≥35 years, with smoking history, linkage to secondary care data and continuous GP registration for 12 months pre-switch and 6 months post-switch to FF/UMEC/VI were included. Index date was the first initiation of an FF/UMEC/VI prescription immediately following MITT use from 15 November 2017 to 30 September 2019. Baseline was 12 months prior to index, with outcomes assessed 6/12 months pre-switch and post-switch, and stratified by prior COPD exacerbation status. RESULTS: We included 2533 patients (mean [SD] age: 71.1 [9.9] years; 52.1% male). In the 6 months post-switch, there were significant decreases in the proportion of patients experiencing ≥1 moderate-to-severe (36.2%-28.9%), moderate only (24.4%-19.8%) and severe only (15.4%-11.8%) COPD exacerbation (each, p<0.0001) compared with the 6 months pre-switch. As demonstrated by rate ratios, there were significant reductions in exacerbation rates of each severity overall (p<0.01) and among patients with prior exacerbations (p<0.0001). In the same period, there were significant decreases in the rate of each COPD-related HCRU and total COPD-related costs (-24.9%; p<0.0001). CONCLUSION: Patients with COPD switching from MITT to once-daily SITT with FF/UMEC/VI in a primary care setting had significantly fewer moderate and severe exacerbations, and lower COPD-related HCRU and costs, in the 6 months post-switch compared with the 6 months pre-switch.
Assuntos
Álcoois Benzílicos , Broncodilatadores , Clorobenzenos , Combinação de Medicamentos , Nebulizadores e Vaporizadores , Atenção Primária à Saúde , Doença Pulmonar Obstrutiva Crônica , Quinuclidinas , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Masculino , Estudos Retrospectivos , Feminino , Idoso , Pessoa de Meia-Idade , Álcoois Benzílicos/administração & dosagem , Clorobenzenos/administração & dosagem , Inglaterra , Administração por Inalação , Broncodilatadores/administração & dosagem , Quinuclidinas/administração & dosagem , Resultado do Tratamento , Antagonistas Muscarínicos/administração & dosagem , AndrostadienosRESUMO
Development of efficient catalysts for non-thermal plasma (NTP) assisted catalysis to mitigate the formation of harmful by-products is a significant challenge in the degradation of chlorinated volatile organic compounds (Cl-VOCs). In this study, catalytically active Pt nanoparticles supported on non-porous SiO2 and silicalite-1 zeolites (S1) with different pore structure were comparatively investigated for catalytic chlorobenzene degradation under NTP condition. It was shown that the pore structure could significantly impact the metal size and metal dispersion rate. Pt supported on modified S1 hierarchical meso-micro-porous silicalite-1 (Pt/D-S1) exhibited the smallest particle size (â¼6.19 nm) and the highest dispersion rate (â¼1.87). Additionally, Pt/D-S1 demonstrated superior catalytic performance compared to the other catalysts, achieving the highest chlorobenzene conversion and COx selectivity at about 80% and 75%, respectively. Furthermore, the pore structure also affected the formation of by-products according to the findings from GC-MS analysis. Pt/SiO2 generated a total of 18 different species of organic compounds, whereas only 12 species of organic by-products were identified in the Pt/D-S1 system (e.g. polychlorinated compounds like 3,4 dichlorophenol were exclusively identified in Pt/SiO2). Moreover, dioxin-like polychlorinated biphenyl and other chlorinated organic compounds, which have potential to form highly toxic dioxins, were detected in the catalysts. HRGC-HRMS confirmed and quantified the 17 different dioxin/furans formed on Pt/SiO2 (25,100 ng TEQ kg-1), Pt/S1 (515 ng TEQ kg-1) and Pt/D-S1 (367 ng TEQ kg-1). The correlation between synthesis-structure-performance in this study provides insights into the design of catalysts for deep oxidation of Cl-VOCs in NTP system.
Assuntos
Clorobenzenos , Platina , Dibenzodioxinas Policloradas , Dióxido de Silício , Clorobenzenos/química , Catálise , Platina/química , Dióxido de Silício/química , Dibenzodioxinas Policloradas/química , Gases em Plasma/química , Zeolitas/química , Compostos Orgânicos Voláteis/química , Nanopartículas Metálicas/química , Benzofuranos/químicaRESUMO
Purpose: To assess patient characteristics of users and new initiators of triple therapy for chronic obstructive pulmonary disease (COPD) in Germany. Patients and Methods: Retrospective cohort study of patients with COPD and ≥1 prescription for single-inhaler triple therapy (SITT; fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI] or beclomethasone dipropionate/glycopyrronium bromide/formoterol [BDP/GLY/FOR]) or multiple-inhaler triple therapy (MITT), using data from the AOK PLUS German sickness fund (1 January 2015-31 December 2019). The index date was the first date of prescription for FF/UMEC/VI or BDP/GLY/FOR (SITT users), or the first date of overlap of inhaled corticosteroid, long-acting ß2-agonist, and long-acting muscarinic antagonist (MITT users). Two cohorts were defined: the prevalent cohort included all identified triple therapy users; the incident cohort included patients newly initiating triple therapy for the first time (no prior use of MITT or SITT in the last 2 years). Patient characteristics and treatment patterns were assessed on the index date and during the 24-month pre-index period. Results: In total, 18,630 patients were identified as prevalent triple therapy users (MITT: 17,945; FF/UMEC/VI: 700; BDP/GLY/FOR: 908; non-mutually exclusive) and 2932 patients were identified as incident triple therapy initiators (MITT: 2246; FF/UMEC/VI: 311; BDP/GLY/FOR: 395; non-mutually exclusive). For both the prevalent and incident cohorts, more than two-thirds of patients experienced ≥1 moderate/severe exacerbation in the preceding 24 months; in both cohorts more BDP/GLY/FOR users experienced ≥1 moderate/severe exacerbation, compared with FF/UMEC/VI and MITT users. Overall, 97.9% of prevalent triple therapy users and 86.4% of incident triple therapy initiators received maintenance treatment in the 24-month pre-index period. Conclusion: In a real-world setting in Germany, triple therapy was most frequently used after maintenance therapy in patients with recent exacerbations, in line with current treatment recommendations.
Triple therapy (a combination of three different respiratory inhaled medications) is recommended for patients with chronic obstructive pulmonary disease (COPD) who experience repeated short-term symptom flare-ups when taking dual therapy (a combination of two different respiratory medications). Previously, patients had to take triple therapy using two or three separate inhalers. More recently, single-inhaler triple therapies have been developed, meaning patients can take all three different medications at the same time via one single inhaler. This study assessed the characteristics of patients who were already receiving triple therapy, or who started triple therapy (either via multiple inhalers or a single inhaler), in Germany between January 2015 and December 2019. In total, 18,630 patients who were already receiving triple therapy during the study period, and 2932 patients who newly started using triple therapy were included. The study reported that more than two-thirds of included patients had experienced at least one flare-up of COPD symptoms in the 2 years before starting triple therapy. Most patients had also received another therapy for COPD before starting triple therapy. A small proportion of patients started taking triple therapy after receiving no other therapy for COPD in the previous 2 years. The results of the study suggest that triple therapy for COPD in Germany is most often used in accordance with recommendations (patients already receiving therapy and experiencing repeated symptom flare-ups).
Assuntos
Agonistas de Receptores Adrenérgicos beta 2 , Broncodilatadores , Combinação de Medicamentos , Glicopirrolato , Antagonistas Muscarínicos , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Feminino , Estudos Retrospectivos , Alemanha , Idoso , Administração por Inalação , Pessoa de Meia-Idade , Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/efeitos adversos , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Glicopirrolato/administração & dosagem , Glicopirrolato/efeitos adversos , Clorobenzenos/administração & dosagem , Clorobenzenos/efeitos adversos , Quinuclidinas/administração & dosagem , Quinuclidinas/efeitos adversos , Resultado do Tratamento , Álcoois Benzílicos/administração & dosagem , Álcoois Benzílicos/efeitos adversos , Beclometasona/administração & dosagem , Beclometasona/efeitos adversos , Fumarato de Formoterol/administração & dosagem , Quimioterapia Combinada , Fatores de Tempo , Idoso de 80 Anos ou maisRESUMO
The development of efficient technologies for the synergistic catalytic elimination of NOx and chlorinated volatile organic compounds (CVOCs) remains challenging. Chlorine species from CVOCs are prone to catalyst poisoning, which increases the degradation temperature of CVOCs and fails to balance the selective catalytic reduction of NOx with the NH3 (NH3-SCR) performance. Herein, synergistic catalytic elimination of NOx and chlorobenzene has been originally demonstrated by using phosphotungstic acid (HPW) as a dechlorination agent to collaborate with CeO2. The conversion of chlorobenzene was over 80% at 270 °C, and the NOx conversion and N2 selectivity reached over 95% at 270-420 °C. HPW not only allowed chlorine species to leave as inorganic chlorine but also enhanced the BroÌ·nsted acidity of CeO2. The NH4+ produced in the NH3-SCR process can effectively promote the dechlorination of chlorobenzene at low temperatures. HPW remained structurally stable in the synergistic reaction, resulting in good water resistance and long-term stability. This work provides a cheaper and more environmentally friendly strategy to address chlorine poisoning in the synergistic reaction and offers new guidance for multipollutant control.
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Clorobenzenos , Catálise , Clorobenzenos/química , Compostos Orgânicos Voláteis/química , Cloro/química , Cério/química , HalogenaçãoRESUMO
In order to study the degradation process of dioxins in industrial flue gas, the decomposition of o-dichlorobenzene (o-DCB) in a DBD plasma catalytic reactor was investigated. The results showed that an NTP-catalyzed system, especially using the CuMnTiOx catalyst, had better o-DCB degradation performance compared to plasma alone. The combination of the CuMnTiOx catalyst with NTP can achieve a degradation efficiency of up to 97.2% for o-DCB; the selectivity of CO and CO2 and the carbon balance were 40%, 45%, and 85%, respectively. The dielectric constant and electrical property results indicated that the surface discharge capacity of the catalysts played a major role in the degradation of o-DCB, and a higher dielectric constant could suppress the plasma expansion and enhance the duration of the plasma discharge per discharge cycle. According to the O1s XPS and O2-TPD results, the conversion of CO to CO2 follows the M-v-K mechanism; thus, the active species on the catalyst surface play an important role. Moreover, the CuMnTiOx and NTP mixed system exhibited excellent stability, which is probably because Cu doping improved the lifetime of the catalyst. This work can provide an experimental and theoretical basis for research in the degradation of o-DCB by plasma catalyst systems.
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Poluentes Atmosféricos , Clorobenzenos , Titânio , Clorobenzenos/química , Catálise , Titânio/química , Poluentes Atmosféricos/química , Modelos Químicos , Gases em Plasma/químicaAssuntos
Aminofenóis , Benzodioxóis , Fibrose Cística , Combinação de Medicamentos , Indóis , Pirazóis , Quinolonas , Humanos , Benzodioxóis/uso terapêutico , Fibrose Cística/tratamento farmacológico , Fibrose Cística/fisiopatologia , Aminofenóis/uso terapêutico , Indóis/uso terapêutico , Quinolonas/uso terapêutico , Pirazóis/uso terapêutico , Masculino , Criança , Adolescente , Feminino , Piridinas/uso terapêutico , Pirróis/uso terapêutico , Quinolinas/uso terapêutico , Agonistas dos Canais de Cloreto/uso terapêutico , Clorobenzenos/uso terapêutico , Testes de Função Respiratória , PirrolidinasRESUMO
OBJECTIVE: A study has analyzed the long-term cost-effectiveness of fluticasone furoate/umeclidinium bromide/vilanterol combination therapy (FF/UMEC/VI) versus umeclidinium bromide/vilanterol dual therapy (UMEC/VI) in the treatment of moderate or severe chronic obstructive pulmonary disease (COPD), providing evidence for decision-making in COPD treatment. METHODS: From the perspective of the whole society, a Markov model based on the severity of COPD was established, consisting of four states: moderate, severe, very severe, and death. The cycle of the model is three months, and the time frame of the study is 20 years. Data such as initial states, transition probabilities, costs, and utilities were collected from published literature, the National Institute for Health and Care Excellence (NICE) COPD economic report, Yaozh database, and the National Statistics Office. The discount rate is 5 %, and the willingness to pay threshold is set at three times the per capita GDP of China in 2022. TreeAge Pro 2011 was used to obtain the results of multiplication analyses, and one-way factor analysis and probability sensitivity analysis were conducted. RESULTS: The study findings demonstrate that for patients treated with FF/UMEC/VI and UMEC/VI, the 20-year treatment costs amount to $10,126.46 and $10,685.74, respectively. Similarly, the effectiveness is 32.94 quality-adjusted life years (QALYs) and 32.19 QALYs, respectively. The incremental cost-effectiveness ratio is $-745.70/QALY, which is lower than the willingness to pay threshold. The tornado plot from one-way factor analysis indicates that the first two factors impacting the results are the utility values for severe COPD of UMEC/VI and FF/UMEC/VI. Probability sensitivity analysis indicates that FF/UMEC/VI compared to UMEC/VI can be considered a more cost-effective treatment at the willingness to pay threshold of $35,806.96. CONCLUSION: The triple therapy (FF/UMEC/VI) is more affordable than dual therapy (UMEC/VI) when compared to China's three times GDP per capita criterion.
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Androstadienos , Álcoois Benzílicos , Clorobenzenos , Combinação de Medicamentos , Doença Pulmonar Obstrutiva Crônica , Anos de Vida Ajustados por Qualidade de Vida , Quinuclidinas , Feminino , Humanos , Masculino , Androstadienos/economia , Androstadienos/uso terapêutico , Álcoois Benzílicos/uso terapêutico , Álcoois Benzílicos/economia , Broncodilatadores/economia , Broncodilatadores/uso terapêutico , China , Clorobenzenos/uso terapêutico , Clorobenzenos/economia , Análise de Custo-Efetividade , Quimioterapia Combinada , Cadeias de Markov , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/economia , Quinuclidinas/economia , Quinuclidinas/uso terapêutico , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: Despite the introduction of improved drug eluting stents (DES), the rate of repeat revascularization procedures following percutaneous coronary interventions (PCI) in coronary chronic total occlusions (CTO) remains high. By leaving vessels uncaged and limiting length of stented segments, drug-coated balloons (DCB) represent an appealing alternative to DES for CTO-PCI. Since data supporting the use of DCBs in CTO-PCI is scarce, we compared the outcomes of patients undergoing CTO-PCI involving DCBs vs DES only. METHODS: From 2 prospective registries, outcomes of patients undergoing CTO-PCI involving DCBs and those undergoing PCI with DES only were compared. Outcomes included major adverse cardiac and cerebrovascular events (MACCE) and cardiovascular death (CV-death). RESULTS: Overall, 157 patients were studied; 112 (71%) underwent CTO-PCI involving DCBs and 45 (29%) were treated with DES only. Mean J-CTO score was 1.84 ± 0.7. Most CTO-lesions involved the right coronary artery, 88 (56%), and 26 (17%) cases were in-stent occlusions. In the DCB group, 46 (41%) lesions were treated with DCBs alone. Mean lengths of the stented segments in the DCB vs DES cohorts were 59 ± 28 mm vs 87 ± 37 mm (P less than .001), respectively. After 12 months, the MACCE rate was higher in the DES only vs DCB group (26% vs 11%, P=.03). Length of the stented segment was an independent predictor for MACCE (HR 1.15 [95% CI, 1.05-1.26] per 10-mm stent length). CONCLUSIONS: Revascularization of CTO lesions involving DCBs appears safe and potentially lowers MACCE rates compared to treatment with DES alone. Importantly, using DCBs for CTO treatment may reduce total stent length, which determines PCI outcomes.
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Clorobenzenos , Oclusão Coronária , Intervenção Coronária Percutânea , Humanos , Oclusão Coronária/diagnóstico , Oclusão Coronária/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , Estudos Prospectivos , Coração , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgiaRESUMO
A highly efficient chlorobenzene-degrading strain was isolated from the sludge of a sewage treatment plant associated with a pharmaceutical company. The strain exhibited a similarity of over 99.9% with multiple strains of Paenarthrobacter ureafaciens. Therefore, the strain was suggested to be P. ureafaciens LY. This novel strain exhibited a broad spectrum of pollutant degradation capabilities, effectively degrading chlorobenzene and other organic pollutants, such as 1, 2, 4-trichlorobenzene, phenol, and xylene. Moreover, P. ureafaciens LY co-metabolized mixtures of chlorobenzene with 1, 2, 4-trichlorobenzene or phenol. Evaluation of its degradation efficiency showed that it achieved an impressive degradation rate of 94.78% for chlorobenzene within 8 h. The Haldane-Andrews model was used to describe the growth of P. ureafaciens LY under specific pollutants and its concentrations, revealing a maximum specific growth rate (µmax ) of 0.33 h-1 . The isolation and characterization of P. ureafaciens LY, along with its ability to degrade chlorobenzene, provides valuable insights for the development of efficient and eco-friendly approaches to mitigate chlorobenzene contamination. Additionally, investigation of the degradation performance of the strain in the presence of other pollutants offers important information for understanding the complexities of co-metabolism in mixed-pollutant environments.
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Clorobenzenos , Poluentes Ambientais , Micrococcaceae , Biodegradação Ambiental , Clorobenzenos/metabolismo , Fenol , Preparações FarmacêuticasRESUMO
As the wide use of pesticides, they could form combined pollution with heavy metals, which would affect their environmental behaviors and toxic effects. Particularly, the effects would be more intricate for chiral pesticides. In this study, the accumulation and dissipation trends of tetraconazole enantiomers in zebrafish were investigated by individual and combined exposure of cadmium (Cd) and tetraconazole (including racemate and enantiomers) after confirming the absolute configuration of tetraconazole enantiomer. For the enantiomer treatments, Cd enhanced the accumulation of S-(+)-tetraconazole, but declined the concentrations of R-(-)-tetraconazole in zebrafish. The dissipation half-lives of tetraconazole enantiomers were extended by 1.65-1.44 times after the combined exposure of Cd and enantiomers. The community richness and diversity of intestinal microbiota were reduced in all treatments, and there were significant differences in R + Cd treatment. There was synergistic effect between Cd and S-(+)-tetraconazole for the effects on the relative abundances of Fusobacteria, Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes. For R-(-)-tetraconazole, Cd mainly exhibited antagonistic effects. In the combined exposure of Cd and S-(+)-tetraconazole, the relative abundance changes of Cetobacterium (Fusobacteria, increase) and Edwardsiella (Proteobacteria, decrease) might affect the carbohydrate metabolism and energy metabolism, and led to the increase of S-(+)-tetraconazole bioaccumulation concentration. In the combined exposure of Cd and R-(-)-tetraconazole, Cd could increase the relative abundance of Edwardsiella (Proteobacteria), and affect the amino acid metabolism, which might reduce the bioaccumulation concentration of R-(-)-tetraconazole. This study reported for the first time that the abundance of intestinal microbiota in zebrafish might affect the bioaccumulation and dissipation of tetraconazole enantiomers, and would provide new insight for the study of combined pollutions.