RESUMO
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
Although carboplatin (CBDCA) is classified as a moderately emetogenic agent, the majority of guidelines recommend the use of a neurokinin-1 receptor antagonist in addition to a 5-hydroxytryptamine type 3 receptor antagonist with dexamethasone (DEX) for CBDCA-containing chemotherapy because of its higher emetogenic risk. However, the additional efficacy of aprepitant (APR) in CBDCA-containing treatment remains controversial, and data on multiple-day treatments are limited. Etoposide (ETP) was administered on days 1-3 in the CBDCA + ETP regimen, and it is important to evaluate suitable antiemetic therapy for the regimen. Therefore, we evaluated the efficacy of additional APR in CBDCA + ETP. Patients were divided into two groups and retrospectively evaluated. One was the control group, which was prophylactically administered palonosetron (PALO) and DEX, and the other was the APR group, which received APR orally with PALO and DEX. The primary endpoint was complete response (CR) between the groups. The overall CR rates were 75.0 and 76.4% in the control and APR groups, respectively, with no significant difference (p = 1.00). In the acute phase, it was 88.9 and 97.2%, respectively, and 86.1 and 79.2% in the delayed phase, respectively, without significant differences (p = 0.10 and 0.38, respectively). The incidence and severity of nausea, vomiting, and anorexia were not significantly different between the two groups in the acute and delayed phases. Our findings suggest that combining APR with PALO and DEX does not improve the CR rate in CBDCA + ETP therapy.
Assuntos
Antieméticos , Aprepitanto , Carboplatina , Dexametasona , Etoposídeo , Náusea , Palonossetrom , Vômito , Aprepitanto/uso terapêutico , Aprepitanto/administração & dosagem , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Carboplatina/efeitos adversos , Humanos , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Palonossetrom/administração & dosagem , Palonossetrom/uso terapêutico , Masculino , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Antieméticos/administração & dosagem , Antieméticos/uso terapêutico , Feminino , Pessoa de Meia-Idade , Vômito/induzido quimicamente , Vômito/prevenção & controle , Idoso , Náusea/induzido quimicamente , Náusea/prevenção & controle , Estudos Retrospectivos , Adulto , Quimioterapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quinuclidinas/administração & dosagem , Quinuclidinas/uso terapêutico , Morfolinas/administração & dosagem , Morfolinas/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Isoquinolinas/administração & dosagem , Isoquinolinas/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVE: To assess whether adding metoclopramide to a protocol of maropitant and pantoprazole would reduce incidence of ptyalism, vomiting and regurgitation in brachycephalic dogs undergoing thoracolumbar spinal surgery. STUDY DESIGN: Randomized blinded controlled trial. ANIMALS: A total of 43 brachycephalic dogs undergoing thoracolumbar spinal surgery. METHODS: In addition to a standardized anaesthetic regimen, dogs were randomized to be administered either a 2 mg kg-1 day-1 metoclopramide constant rate infusion (CRI) or a saline solution at an equivalent infusion rate, started after anaesthetic induction and discontinued 5 hours after tracheal extubation. The presence of vomiting, regurgitation and pytalism, and short form of the Glasgow Composite Pain Scale pain scores were assessed by a blinded observer hourly for 4 hours, starting 1 hour postextubation. RESULTS: Regurgitation occurred in six dogs postoperatively; three dogs were in the placebo group and three in the metoclopramide group. The odds ratio (OR) of regurgitation after surgery did not differ between groups [OR: 0.76, 95% confidence interval (CI): 0.13-4.3, p = 0.76]. The odds of observing ptyalism at 3 and 4 hours was approximately 15 times less than 1 hour postoperatively (both OR: 15.4, 95% CI: 1.8-130.7, p = 0.012) and did not differ based on the addition of metoclopramide (OR: 0.73, 95% CI: 0.07-8.0, p = 0.79). The odds of observing pain did not change over time and did not differ based on the addition of metoclopramide (OR: 0.71, 95% CI: 0.12-4.2, p = 0.71). Vomiting did not occur during the study (0.0%, 95% CI: 0.0-8.2%). No adverse effects were observed during the study period in either group. CONCLUSIONS AND CLINICAL RELEVANCE: The addition of a metoclopramide CRI to maropitant and pantoprazole did not result in a significant reduction in ptyalism or regurgitation in brachycephalic dogs undergoing thoracolumbar spinal surgery.
Assuntos
Antieméticos , Doenças do Cão , Metoclopramida , Animais , Cães , Metoclopramida/administração & dosagem , Metoclopramida/uso terapêutico , Antieméticos/administração & dosagem , Antieméticos/uso terapêutico , Masculino , Feminino , Doenças do Cão/cirurgia , Doenças do Cão/prevenção & controle , Craniossinostoses/cirurgia , Craniossinostoses/veterinária , Náusea e Vômito Pós-Operatórios/veterinária , Náusea e Vômito Pós-Operatórios/prevenção & controle , Refluxo Laringofaríngeo/veterinária , Refluxo Laringofaríngeo/prevenção & controle , Quinuclidinas/administração & dosagem , Quinuclidinas/uso terapêutico , Pantoprazol/administração & dosagem , Pantoprazol/uso terapêutico , Pantoprazol/farmacologiaRESUMO
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: 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
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
BACKGROUND: Cough is a common clinical complaint in small animal practice with limited treatment options for chronic underlying conditions. OBJECTIVES: The present study aimed to evaluate the efficacy of three antitussive drugs in a novel, minimally invasive canine acute cough model. METHODS: Five clinically healthy Beagles were used to create an acute cough model by administering sterile saline via a transtracheally placed central venous catheter. Single-dose antitussive effects of butorphanol, maropitant and Danpron were assessed. Cough frequency was measured before and at hourly intervals up to 3 h post-administration of each drug, with a linear mixed model used for statistical analysis. RESULTS: Butorphanol (0.3 m/kg, IM) significantly reduced cough frequency at 1 and 3 h post-administration. Danpron (0.1 mL/kg, IM) also significantly reduced cough frequency 1 h post-administration; however, this effect was not sustained at 3 h. Maropitant (1 mg/kg, IM) did not significantly reduce cough frequency. The cough induction method was effective and minimally invasive, with no adverse effects. CONCLUSION: The present study demonstrated that butorphanol has a potent and prolonged antitussive effect in an acute canine cough model, whereas Danpron shows a transient effect. These findings provide valuable insights into the comparative efficacy of commonly used antitussive drugs in dogs.
Assuntos
Antitussígenos , Butorfanol , Tosse , Doenças do Cão , Animais , Cães , Tosse/veterinária , Tosse/tratamento farmacológico , Tosse/etiologia , Antitussígenos/uso terapêutico , Antitussígenos/farmacologia , Antitussígenos/administração & dosagem , Doenças do Cão/tratamento farmacológico , Butorfanol/administração & dosagem , Butorfanol/uso terapêutico , Quinuclidinas/uso terapêutico , Quinuclidinas/farmacologia , Quinuclidinas/administração & dosagem , Masculino , Feminino , Modelos Animais de Doenças , Doença AgudaRESUMO
Background: In the absence of head-to-head comparative data from randomized controlled trials, indirect treatment comparisons (ITCs) may be used to compare the relative effects of treatments versus a common comparator (either placebo or active treatment). For acute pain management, the effects of oliceridine have been compared in clinical trials to morphine but not to fentanyl or hydromorphone. Aim: To assess the comparative safety (specifically differences in the incidence of nausea, vomiting and opioid-induced respiratory depression [OIRD]) between oliceridine and relevant comparators (fentanyl and hydromorphone) through ITC analysis. Methods: A systematic literature review identified randomized clinical trials with oliceridine versus morphine and morphine versus fentanyl or hydromorphone. The ITC utilized the common active comparator, morphine, for the analysis. Results: A total of six randomized controlled trials (oliceridine - 2; hydromorphone - 3; fentanyl - 1) were identified for data to be used in the ITC analyses. The oliceridine data were reported in two studies (plastic surgery and orthopedic surgery) and were also reported in a pooled analysis. The ITC focused on nausea and vomiting due to limited data for OIRD. When oliceridine was compared with hydromorphone in the ITC analysis, oliceridine significantly reduced the incidence of nausea and/or vomiting requiring antiemetics compared with hydromorphone (both orthopedic surgery and pooled data), while results in plastic surgery were not statistically significant. When oliceridine was compared with hydromorphone utilizing data from Hong, the ITC only showed a trend toward reduced risk of nausea and vomiting with oliceridine that was not statistically significant across all three comparisons (orthopedic surgery, plastic surgery and combined). An ITC comparing oliceridine with a study of fentanyl utilizing the oliceridine orthopedic surgery data and combined orthopedic and plastic surgery data showed a trend toward reduced risk that was not statistically significant. Conclusion: In ITC analyses, oliceridine significantly reduced the incidence of nausea and/or vomiting or the need for antiemetics in orthopedic surgery compared with hydromorphone and a non-significant trend toward reduced risk versus fentanyl.
Assuntos
Dor Aguda , Analgésicos Opioides , Fentanila , Hidromorfona , Náusea , Ensaios Clínicos Controlados Aleatórios como Assunto , Compostos de Espiro , Tiofenos , Vômito , Humanos , Hidromorfona/administração & dosagem , Hidromorfona/efeitos adversos , Hidromorfona/uso terapêutico , Fentanila/efeitos adversos , Fentanila/administração & dosagem , Fentanila/uso terapêutico , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Analgésicos Opioides/administração & dosagem , Dor Aguda/tratamento farmacológico , Vômito/induzido quimicamente , Vômito/prevenção & controle , Vômito/tratamento farmacológico , Náusea/prevenção & controle , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Administração Intravenosa , Insuficiência Respiratória/induzido quimicamente , Manejo da Dor/métodos , Quinuclidinas/uso terapêutico , Quinuclidinas/administração & dosagem , Quinuclidinas/efeitos adversosRESUMO
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: Findings from CAPTAIN (NCT02924688) suggest that treatment response to fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) differs according to baseline type 2 inflammation markers in patients with moderate to severe asthma. Understanding how other patient physiologic and clinical characteristics affect response to inhaled therapies may guide physicians toward a personalized approach for asthma management. OBJECTIVE: To investigate, using CAPTAIN data, the predictive value of key demographic and baseline physiologic variables in patients with asthma (lung function, bronchodilator reversibility, age, age at asthma onset) on response to addition of the long-acting muscarinic antagonist UMEC to inhaled corticosteroid/long-acting ß2-agonist combination FF/VI, or doubling the FF dose. METHODS: Prespecified and post hoc analyses of CAPTAIN data were performed using categorical and continuous variables of key baseline characteristics to understand their influence on treatment outcomes (lung function [trough FEV1], annualized rate of moderate/severe exacerbations, and asthma control [Asthma Control Questionnaire]) following addition of UMEC to FF/VI or doubling the FF dose in FF/VI or FF/UMEC/VI. RESULTS: Adding UMEC to FF/VI led to greater improvements in trough FEV1 versus doubling the FF dose across all baseline characteristics assessed. Doubling the FF dose was generally associated with numerically greater reductions in the annualized rate of moderate/severe exacerbations compared with adding UMEC, independent of baseline characteristics. Adding UMEC and/or doubling the FF dose generally led to improvements in Asthma Control Questionnaire scores irrespective of baseline characteristics. CONCLUSIONS: Unlike previous findings with type 2 biomarkers, lung function, bronchodilator reversibility, age and age at asthma onset do not appear to predict response to inhaled therapy.
Assuntos
Corticosteroides , Agonistas de Receptores Adrenérgicos beta 2 , Asma , Álcoois Benzílicos , Antagonistas Muscarínicos , Quinuclidinas , Humanos , Asma/tratamento farmacológico , Asma/fisiopatologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Álcoois Benzílicos/uso terapêutico , Álcoois Benzílicos/administração & dosagem , Quinuclidinas/uso terapêutico , Quinuclidinas/administração & dosagem , Corticosteroides/uso terapêutico , Corticosteroides/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Antagonistas Muscarínicos/uso terapêutico , Antagonistas Muscarínicos/administração & dosagem , Clorobenzenos/uso terapêutico , Clorobenzenos/administração & dosagem , Administração por Inalação , Resultado do Tratamento , Combinação de Medicamentos , Androstadienos/uso terapêutico , Androstadienos/administração & dosagem , Idoso , Antiasmáticos/uso terapêutico , Antiasmáticos/administração & dosagem , Broncodilatadores/uso terapêutico , Broncodilatadores/administração & dosagem , Adulto JovemRESUMO
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
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: 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.
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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 TratamentoAssuntos
Procedimentos Cirúrgicos em Ginecologia , Laparoscopia , Náusea e Vômito Pós-Operatórios , Quinuclidinas , Humanos , Método Duplo-Cego , Laparoscopia/efeitos adversos , Feminino , Quinuclidinas/administração & dosagem , Náusea e Vômito Pós-Operatórios/prevenção & controle , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Anestesia por Inalação/efeitos adversos , Antieméticos/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Anestesia IntravenosaRESUMO
This article reports orthodontic treatment of a case of hypodontia of five premolars in an 11-year-old female patient with a positive tooth size-arch length discrepancy in both dental arches. The patient had a straight profile with balanced facial growth. Setup manufacture revealed the possibility of achieving ideal occlusion by mesializing permanent molars up to 15 mm, in addition to keeping a primary molar in the dental arch. With the aid of absolute anchorage, the proposed mechanics was performed and the occlusion predicted in the setup was achieved, while profile and facial growth pattern were maintained. The use of miniscrews for extensive orthodontic movements was successful. Furthermore, one primary molar was extensively mesialized. The indication of gingivoplasty to correct gingival smile proved effective. This is considered a useful technique for orthodontists.
Este artigo apresenta o tratamento ortodôntico de um caso com hipodontia de cinco pré-molares, em uma paciente, de 11 anos de idade, com discrepância positiva de modelo em ambas as arcadas. A paciente apresentava perfil reto, com crescimento facial equilibrado. Por meio da confecção de set-up, verificou-se a possibilidade de se estabelecer uma oclusão ideal por meio da mesialização, de até 15mm, dos molares permanentes e manutenção de um molar decíduo no arco. Com o auxílio de ancoragem absoluta, foi realizada a mecânica proposta, alcançando-se a oclusão prevista em set-up, além da manutenção do perfil e do padrão de crescimento facial. A utilização de mini-implantes para grandes movimentos ortodônticos foi favorável, incluindo a extensa mesialização de um molar decíduo. A indicação da gengivoplastia para correção do sorriso gengival se mostrou acertada, sendo essa uma técnica de grande auxílio à Ortodontia.