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1.
J Allergy Clin Immunol Pract ; 10(12): 3156-3162, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36028212

RESUMO

Allergic fungal rhinosinusitis (AFRS) is a noninvasive subtype of chronic rhinosinusitis with nasal polyps (CRSwNP) that usually develops in immunocompetent atopic individuals and is more common in geographic regions characterized by warm temperatures and high humidity, conducive to higher environmental fungal presence. Allergic fungal rhinosinusitis usually presents with unique computed tomography findings and significant polyp burden, yet patients often report minimal sinus symptoms. Patients with AFRS often have extremely elevated serum total and fungal-specific IgE levels. Treatment almost always requires surgery, in which adjuvant medical therapy is critical to success. However, until recently the choice of adjuvant therapy has consisted primarily of either oral and/or topical steroids. Although oral corticosteroids decrease recurrence after surgery, data for the effectiveness of other adjunctive pharmacologic agents, including topical and oral antifungal agents and immunotherapy, have remained unclear and hence are not recommended in recent guidelines including the International Consensus of Allergy and Rhinology. Three biologics, omalizumab, dupilumab, and mepolizumab, have recently been approved for treating CRSwNP in general, but clinical trials to date with these biologics did not involve AFRS patients. Recently published case reports and smaller prospective studies have shown good efficacy of these biologics on the AFRS subgroup of patients. This article provides an overview of the understanding of the pathophysiology of AFRS, implications of this understanding on the possible role of biologics, and clinical reports on the use of biologics in treating AFRS. Because biologics are indicated for treating CRSwNP, follow up real-world evidence studies are needed for AFRS.


Assuntos
Sinusite Fúngica Alérgica , Produtos Biológicos , Pólipos Nasais , Rinite , Sinusite , Humanos , Produtos Biológicos/uso terapêutico , Estudos Prospectivos , Sinusite/diagnóstico , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/cirurgia , Doença Crônica , Rinite/tratamento farmacológico
2.
J Allergy Clin Immunol Pract ; 10(10): 2570-2578, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35764285

RESUMO

Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is a condition characterized by the triad of chronic rhinosinusitis with nasal polyps, bronchial asthma, and hypersensitivity to nonsteroidal anti-inflammatory drugs. This article explores the current knowledge on the various pathological mechanism(s) of N-ERD-such as arachidonic acid metabolism, cysteinyl leukotrienes, prostaglandins, platelets, IgE, mast cells, eosinophils, basophils, and innate immune system-and the role of omalizumab in its management. The authors dive deep into the role of IgE in N-ERD and its potential as a therapeutic target. IgE plays a significant role in mediating allergic reactions, is intricately linked with mast cells, interacts with multiple immunopathological pathways involved in N-ERD, and tends to be elevated in patients with N-ERD. Multiple real-world studies, observational studies, and case series, as well as 2 phase III trials, have demonstrated the effectiveness of omalizumab in the management of N-ERD. For a disease with such a well-documented history, the pathophysiology of N-ERD and the most effective ways to manage it remain a mystery. With this background, the authors ask-is IgE a missing piece of the N-ERD puzzle, thus explaining the efficacy of omalizumab in the treatment of the disease?


Assuntos
Hipersensibilidade , Transtornos Respiratórios , Anti-Inflamatórios não Esteroides/efeitos adversos , Ácido Araquidônico , Humanos , Imunoglobulina E , Leucotrienos , Omalizumab/uso terapêutico , Prostaglandinas
3.
BMC Psychiatry ; 22(1): 428, 2022 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-35751076

RESUMO

BACKGROUND: ADHD is common in psychiatric populations. This study aimed to compare clinical characteristics in adults with and without ADHD who presented with self-harm, and to compare later risk of suicidal behaviour within 6 months. METHODS: Eight hundred four adults presented with self-harm (with and without suicidal intent) at psychiatric emergency services at three Swedish hospitals. Persons with a discharge ICD-10 diagnosis F90.0-F90.9 or a prescription for ADHD medication were considered to have ADHD (n = 93). Medical records were reviewed for evidence of subsequent suicide attempts (SA) within 6 months; suicides were identified by national register. RESULTS: Recent relationship problems were more prevalent in the ADHD group. While the index episodes of those with ADHD were more often non-suicidal, and actual SAs more often rated as impulsive, medical lethality at presentation did not differ in attempters with and without ADHD. Subsequent SAs (fatal or non-fatal) were observed in 29% of the ADHD group and 20% in all others (P = .005). A logistic regression model showed elevated risk of suicidal behaviour during follow-up in the ADHD group (OR = 1.70, CI 1.05-2.76), although a final regression model suggested that this association was partly explained by age and comorbid emotionally unstable personality disorder. CONCLUSIONS: Findings highlight the need for clinicians to take self-harm seriously in adults with ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Comportamento Autodestrutivo , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Seguimentos , Humanos , Comportamento Autodestrutivo/epidemiologia , Comportamento Autodestrutivo/psicologia , Ideação Suicida , Tentativa de Suicídio/psicologia
4.
Allergy Asthma Clin Immunol ; 17(1): 55, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099035

RESUMO

BACKGROUND: The aim of this cross-sectional survey was to compare the health-economic consequences for allergic rhinitis (AR) patients treated with sublingual Immunotherapy (SLIT) in terms of direct and indirect costs with a reference population of patients receiving standard of care pharmacological therapy. METHODS: Primary objective was to analyse the health-economic consequences of SLIT for grass pollen allergy in Sweden vs reference group waiting for subcutaneous immunotherapy (SCIT). A questionnaire was mailed to two groups of AR patients. RESULTS: The questionnaire was distributed to 548 patients, 307 with SLIT and 241 in reference group (waiting for SCIT). Response rate was 53.8%. Mean annual costs were higher for reference patients than SLIT group; € 3907 (SD 4268) vs € 2084 (SD 1623) p < 0.001. Mean annual direct cost was higher for SLIT-patients, € 1191 (SD 465) than for reference, € 751 (SD 589) p < 0.001. Mean annual indirect costs for combined absenteeism and presenteeism were lower for patients treated with SLIT, € 912 (SD 1530), than for reference, € 3346 (SD 4120) p < 0.001, with presenteeism as main driver. CONCLUSIONS: SLIT seems to be a cost-beneficial way to treat seasonal AR. This information might be used to guide future recommendations.

5.
Respir Res ; 21(1): 93, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32321518

RESUMO

BACKGROUND: COPD is a heterogeneous disease and patients may respond differently to therapies depending on baseline symptom burden. METHODS: This post-hoc analysis from the 52-week FLAME study investigated the impact of baseline symptom burden in terms of health status, dyspnoea, bronchitis status, eosinophil levels and smoking status on the subsequent risk of moderate or severe exacerbations. Health status was measured by St. George's Respiratory Questionnaire (SGRQ) score (higher ≥46.6 and lower < 46.6) and COPD Assessment Test (CAT) score (higher ≥17 and lower < 17); dyspnoea and bronchitis were assessed via an electronic diary (eDiary). Differential response to once-daily indacaterol/glycopyrronium (IND/GLY) 110/50 µg versus twice-daily salmeterol/fluticasone (SFC) 50/500 µg was assessed. RESULTS: Data from 3354 patients was analysed. The risk of exacerbations was lower in patients who had less severe health impairment (rate ratio [RR] [95% CI]): SGRQ-C, (0.88 [0.78, 0.99]); CAT, 0.85 [0.75, 0.96]) and lower dyspnoea (0.79 [0.69, 0.90]) at baseline versus those with more severe health impairment and higher dyspnoea, respectively. Compared with SFC, IND/GLY led to better prevention of moderate-to-severe exacerbations in the majority of groups studied. CONCLUSION: Patients with more severe health status impairment and greater symptom burden at baseline subsequently experienced more exacerbations in the FLAME study. IND/GLY was overall more effective in preventing exacerbations versus SFC, regardless of baseline symptom burden. Our results suggest that future studies on novel exacerbation therapies should consider targeting patients with higher symptom burden at baseline. CLINICAL TRIAL IDENTIFIER: NCT01782326.


Assuntos
Progressão da Doença , Combinação Fluticasona-Salmeterol/administração & dosagem , Volume Expiratório Forçado/efeitos dos fármacos , Glicopirrolato/análogos & derivados , Nível de Saúde , Indanos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinolonas/administração & dosagem , Idoso , Broncodilatadores/administração & dosagem , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Volume Expiratório Forçado/fisiologia , Glicopirrolato/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Inquéritos e Questionários
6.
Respirology ; 25(4): 393-400, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31339215

RESUMO

BACKGROUND AND OBJECTIVE: Indacaterol/glycopyrronium (IND/GLY) 110/50 µg once daily (q.d.) has demonstrated greater improvements in lung function, patient-reported outcomes and lower exacerbation rates versus mono long-acting muscarinic antagonists (LAMA) in chronic obstructive pulmonary disease (COPD) patients. However, data are limited on initial treatment with IND/GLY 110/50 µg q.d. versus mono LAMA in COPD patients, not previously on maintenance treatment with long-acting bronchodilators (LABD). METHODS: A pooled analysis of ARISE, SHINE and SPARK trials was conducted to evaluate the efficacy of IND/GLY 110/50 µg q.d. versus open-label (OL) tiotropium (TIO) 18 µg q.d. and GLY 50 µg q.d. in COPD patients, not on maintenance treatment with LABD at study entry (LABD-naïve). Efficacy was assessed after 24/26 weeks of treatment. RESULTS: In total, 998 LABD-naïve patients were included (IND/GLY: 353; OL TIO: 328; GLY: 317). Patients treated with IND/GLY 110/50 µg q.d. experienced greater improvements in trough forced expiratory volume in 1 s (FEV1 ) versus OL TIO 18 µg q.d. (least squares mean treatment difference (Δ): 0.086 L) and GLY 50 µg q.d. (Δ: 0.080 L) after 24/26 weeks. Improvements in electronic diary (eDiary) symptom scores, transition dyspnoea index (TDI) focal score, St George's Respiratory Questionnaire (SGRQ) total score and rescue medication use were also greater with IND/GLY versus OL TIO and GLY. Greater proportion of patients achieved minimal clinically important difference in trough FEV1 , TDI and SGRQ with IND/GLY versus OL TIO and GLY. CONCLUSION: LABD-naïve patients treated with IND/GLY 110/50 µg q.d. achieved improvements in lung function, daily symptoms, dyspnoea, health-related quality of life and rescue medication use versus those who received single LAMA.


Assuntos
Glicopirrolato/uso terapêutico , Indanos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinolonas/uso terapêutico , Brometo de Tiotrópio/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Idoso , Broncodilatadores/uso terapêutico , Combinação de Medicamentos , Dispneia/etiologia , Dispneia/fisiopatologia , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Int J Chron Obstruct Pulmon Dis ; 14: 995-1008, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190785

RESUMO

Purpose: Assess the clinical and economic consequences associated with an early versus late diagnosis in patients with COPD. Patients and methods: In a retrospective, observational cohort study, electronic medical record data (2000-2014) were collected from Swedish primary care patients with COPD. COPD indicators (pneumonia, other respiratory diseases, oral corticosteroids, antibiotics for respiratory infections, prescribed drugs for respiratory symptoms, lung function measurement) registered prior to diagnosis were applied to categorize patients into those receiving early (2 or less indicators) or late diagnosis (3 or more indicators registered >90 days preceding a COPD diagnosis). Outcome measures included annual rate of and time to first exacerbation, mortality risk, prevalence of comorbidities and health care utilization. Results: More patients with late diagnosis (n=8827) than with early diagnosis (n=3870) had a recent comorbid diagnosis of asthma (22.0% vs 3.9%; P<0.0001). Compared with early diagnosis, patients with late diagnosis had a higher exacerbation rate (hazard ratio [HR] 1.89, 95% confidence interval [CI]: 1.83-1.96; P<0.0001) and shorter time to first exacerbation (HR 1.61, 95% CI: 1.54-1.69; P<0.0001). Mortality was not different between groups overall but higher for late versus early diagnosis, after excluding patients with past asthma diagnosis (HR 1.10, 95% CI: 1.02-1.18; P=0.0095). Late diagnosis was also associated with higher direct costs than early diagnosis. Conclusion: Late COPD diagnosis is associated with higher exacerbation rate and increased comorbidities and costs compared with early diagnosis. The study highlights the need for accurate diagnosis of COPD in primary care in order to reduce exacerbations and the economic burden of COPD.


Assuntos
Custos de Cuidados de Saúde , Atenção Primária à Saúde/economia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/economia , Idoso , Comorbidade , Progressão da Doença , Diagnóstico Precoce , Registros Eletrônicos de Saúde , Feminino , Nível de Saúde , Humanos , Masculino , Valor Preditivo dos Testes , Prognóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/mortalidade , Estudos Retrospectivos , Fatores de Risco , Suécia/epidemiologia , Fatores de Tempo
8.
Respir Res ; 19(1): 172, 2018 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-30200965

RESUMO

BACKGROUND: Inhaled corticosteroids (ICS) are associated with an increased risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD). Other factors such as severity of airflow limitation and concurrent asthma may further raise the possibility of developing pneumonia. This study assessed the risk of pneumonia associated with ICS in patients with COPD. METHODS: Electronic Medical Record data linked to National Health Registries were collected from COPD patients and matched reference controls in 52 Swedish primary care centers (2000-2014). Levels of ICS treatment (high, low, no ICS) and associated comorbidities were assessed. Patients were categorized by airflow limitation severity. RESULTS: A total of 6623 patients with COPD and 48,566 controls were analyzed. Patients with COPD had a more than 4-fold increase in pneumonia versus reference controls (hazard ratio [HR] 4.76, 95% confidence interval [CI]: 4.48-5.06). ICS use increased the risk of pneumonia by 20-30% in patients with COPD with forced expiratory volume in 1 s ≥ 50% versus patients not using ICS. Asthma was an independent risk factor for pneumonia in the COPD population. Multivariate analysis identified independent predictors of pneumonia in the overall population. The highest risk of pneumonia was associated with high dose ICS (HR 1.41, 95% CI: 1.23-1.62). CONCLUSIONS: Patients with COPD have a greater risk of pneumonia versus reference controls; ICS use and concurrent asthma increased the risk of pneumonia further.


Assuntos
Registros Eletrônicos de Saúde/tendências , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Sistema de Registros , Idoso , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde/tendências , Estudos Retrospectivos , Fatores de Risco , Suécia/epidemiologia
9.
Respirology ; 23(12): 1152-1159, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30074294

RESUMO

BACKGROUND AND OBJECTIVE: Combination long-acting ß2 -agonist/long-acting muscarinic antagonist (LABA/LAMA) has demonstrated superior clinical outcomes over LABA/inhaled corticosteroid (ICS) in chronic obstructive pulmonary disease (COPD) patients; however, data from blinded randomized controlled trials on direct switching from LABA/ICS to LABA/LAMA are lacking. FLASH (Assessment of switching salmeterol/Fluticasone to indacateroL/glycopyrronium in A Symptomatic COPD patient coHort) investigated if direct switch, without a washout period, from salmeterol/fluticasone (SFC) to indacaterol/glycopyrronium (IND/GLY) in COPD patients improves lung function and is well tolerated. METHODS: In this 12-week, multicentre, double-blind study, patients with moderate-to-severe COPD and up to one exacerbation in previous year, receiving SFC for ≥3 months, were randomized to continue SFC 50/500 µg twice daily (bd) or switch to IND/GLY 110/50 µg once daily (od). Primary endpoint was pre-dose trough forced expiratory volume in 1 s (FEV1 ) at Week 12. RESULTS: In total, 502 patients were randomized (1:1) to IND/GLY or SFC. Patients switched to IND/GLY demonstrated superior lung function (pre-dose trough FEV1 ) versus SFC at Week 12 (treatment difference (Δ) = 45 mL; P = 0.028). IND/GLY provided significant improvements in pre-dose trough forced vital capacity (FVC; Δ = 102 mL; P = 0.002) and numerical improvements in transition dyspnoea index (TDI; Δ = 0.46; P = 0.063). Rescue medication use and COPD assessment test (CAT) scores were comparable between groups. Both treatments had similar safety profiles. CONCLUSION: FLASH demonstrated that a direct switch to IND/GLY from SFC improved pre-dose FEV1 and FVC in COPD patients with up to one exacerbation in the previous year. No new safety signals were identified.


Assuntos
Combinação Fluticasona-Salmeterol , Glicopirrolato , Indanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinolonas , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Idoso , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Método Duplo-Cego , Combinação de Medicamentos , Monitoramento de Medicamentos/métodos , Substituição de Medicamentos/métodos , Feminino , Combinação Fluticasona-Salmeterol/administração & dosagem , Combinação Fluticasona-Salmeterol/efeitos adversos , Glicopirrolato/administração & dosagem , Glicopirrolato/efeitos adversos , Humanos , Indanos/administração & dosagem , Indanos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Quinolonas/administração & dosagem , Quinolonas/efeitos adversos , Testes de Função Respiratória/métodos , Resultado do Tratamento
10.
Int J Chron Obstruct Pulmon Dis ; 13: 1125-1134, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29692607

RESUMO

BACKGROUND: The FLAME study compared once-daily indacaterol/glycopyrronium (IND/GLY) 110/50 µg with twice-daily salmeterol/fluticasone (SFC) 50/500 µg in symptomatic patients with moderate to very severe COPD and a history of exacerbations in the previous year. METHODS: This prespecified and post hoc subgroup analysis evaluated treatment efficacy on 1) moderate/severe exacerbations according to prior exacerbation history and treatment, and 2) types of exacerbations according to health care resource utilization (HCRU) during 1-year follow-up. RESULTS: IND/GLY reduced the rate of moderate/severe exacerbations versus SFC in patients with a history of 1 exacerbation (rate ratio [RR]: 0.83, 95% CI: 0.75-0.93), ≥2 exacerbations (RR: 0.85, 95% CI: 0.70-1.03) and ≥2 exacerbations or ≥1 hospitalization in the previous year (RR: 0.86, 95% CI: 0.74-1.00). Prolonged time-to-first exacerbation was observed in all the groups according to exacerbation history. Moderate/severe exacerbations decreased with IND/GLY versus SFC, independent of previous treatment. IND/GLY significantly reduced rates of moderate/severe exacerbations treated with antibiotics (RR: 0.79, 95% CI: 0.67-0.93) and systemic corticosteroids and antibiotics (RR: 0.80, 95% CI: 0.70-0.91); rates of exacerbations treated with systemic corticosteroids alone were comparable (RR: 0.99, 95% CI: 0.80-1.22). CONCLUSION: Overall, IND/GLY demonstrated consistent beneficial effects versus SFC on moderate/severe exacerbations, independent of prior exacerbation history or treatment. The efficacy of IND/GLY on exacerbation prevention was superior to SFC for exacerbations treated with antibiotics with/without systemic corticosteroids and was similar for exacerbations treated with systemic corticosteroids alone.


Assuntos
Corticosteroides/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Broncodilatadores/administração & dosagem , Combinação Fluticasona-Salmeterol/administração & dosagem , Glicopirrolato/administração & dosagem , Indanos/administração & dosagem , Pulmão/efeitos dos fármacos , Antagonistas Muscarínicos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinolonas/administração & dosagem , Corticosteroides/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Idoso , Broncodilatadores/efeitos adversos , Progressão da Doença , Método Duplo-Cego , Esquema de Medicação , Combinação de Medicamentos , Feminino , Combinação Fluticasona-Salmeterol/efeitos adversos , Volume Expiratório Forçado , Glicopirrolato/efeitos adversos , Hospitalização , Humanos , Indanos/efeitos adversos , Estimativa de Kaplan-Meier , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/efeitos adversos , Razão de Chances , Modelos de Riscos Proporcionais , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Quinolonas/efeitos adversos , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Capacidade Vital
12.
Respir Res ; 18(1): 206, 2017 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-29228950

RESUMO

BACKGROUND: This study assessed the cost-effectiveness of indacaterol/glycopyrronium (IND/GLY) versus salmeterol/fluticasone (SFC) in chronic obstructive pulmonary disease (COPD) patients with moderate to very severe airflow limitation and ≥1 exacerbation in the preceding year. METHODS: A previously published and validated patient-level simulation model was adapted using clinical data from the FLAME trial and real-world cost data from the ARCTIC study. Costs (total monetary costs comprising drug, maintenance, exacerbation, and pneumonia costs) and health outcomes (life-years (LYs), quality-adjusted life-years (QALYs)) were projected over various time horizons (1, 5, 10 years, and lifetime) from the Swedish payer's perspective and were discounted at 3% annually. Uncertainty in model input values was studied through one-way and probabilistic sensitivity analyses. Subgroup analyses were also performed. RESULTS: IND/GLY was associated with lower costs and better outcomes compared with SFC over all the analysed time horizons. Use of IND/GLY resulted in additional 0.192 LYs and 0.134 QALYs with cost savings of €1211 compared with SFC over lifetime. The net monetary benefit (NMB) was estimated to be €8560 based on a willingness-to-pay threshold of €55,000/QALY. The NMB was higher in the following subgroups: severe (GOLD 3), high risk and more symptoms (GOLD D), females, and current smokers. CONCLUSION: IND/GLY is a cost-effective treatment compared with SFC in COPD patients with mMRC dyspnea grade ≥ 2, moderate to very severe airflow limitation, and ≥1 exacerbation in the preceding year.


Assuntos
Análise Custo-Benefício/métodos , Combinação Fluticasona-Salmeterol/economia , Glicopirrolato/economia , Indanos/economia , Modelos Econômicos , Vigilância da População/métodos , Doença Pulmonar Obstrutiva Crônica/economia , Quinolonas/economia , Idoso , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Combinação Fluticasona-Salmeterol/administração & dosagem , Glicopirrolato/administração & dosagem , Humanos , Indanos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Quinolonas/administração & dosagem , Suécia/epidemiologia
14.
Am J Respir Crit Care Med ; 195(9): 1189-1197, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28278391

RESUMO

RATIONALE: Post hoc analyses suggest that blood eosinophils have potential as a predictive biomarker of inhaled corticosteroid efficacy in the management of chronic obstructive pulmonary disease (COPD). OBJECTIVES: We prospectively investigated the value of blood eosinophils as a predictor of responsiveness to an inhaled corticosteroid/long-acting ß2-agonist combination versus a long-acting ß2-agonist/long-acting muscarinic antagonist combination for exacerbation prevention. METHODS: We conducted prespecified analyses of data from the FLAME (Effect of Indacaterol Glycopyronium vs Fluticasone Salmeterol on COPD Exacerbations) study, which compared once-daily long-acting ß2-agonist/long-acting muscarinic antagonist indacaterol/glycopyrronium 110/50 µg with twice-daily long-acting ß2-agonist/inhaled corticosteroid salmeterol/fluticasone combination 50/500 µg in patients with one or more exacerbations in the preceding year. Subsequent post hoc analyses were conducted to address further cutoffs and endpoints. MEASUREMENTS AND MAIN RESULTS: We compared treatment efficacy according to blood eosinophil percentage (<2% and ≥2%, <3% and ≥3%, and <5% and ≥5%) and absolute blood eosinophil count (<150 cells/µl, 150 to <300 cells/µl, and ≥300 cells/µl). Indacaterol/glycopyrronium was significantly superior to salmeterol/fluticasone for the prevention of exacerbations (all severities, or moderate or severe) in the <2%, ≥2%, <3%, <5%, and <150 cells/µl subgroups, and at no cutoff was salmeterol/fluticasone superior to indacaterol/glycopyrronium. Furthermore, the rate of moderate or severe exacerbations did not increase with increasing blood eosinophils. The incidence of pneumonia was higher in patients receiving salmeterol/fluticasone than indacaterol/glycopyrronium in both the <2% and ≥2% subgroups. CONCLUSIONS: Our prospective analyses indicate that indacaterol/glycopyrronium provides superior or similar benefits over salmeterol/fluticasone regardless of blood eosinophil levels in patients with COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01782326).


Assuntos
Eosinófilos , Doença Pulmonar Obstrutiva Crônica/sangue , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Idoso , Biomarcadores/sangue , Método Duplo-Cego , Quimioterapia Combinada , Eosinófilos/efeitos dos fármacos , Feminino , Combinação Fluticasona-Salmeterol/uso terapêutico , Humanos , Indanos/uso terapêutico , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinolonas/uso terapêutico , Resultado do Tratamento
15.
Acta Otolaryngol ; 136(8): 852-9, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27052839

RESUMO

CONCLUSIONS: The potential effects of KOS are still uncertain regarding the most effective air pressure to be used as well as the physiological effects on the nasal mucosa. The results of the study do not support a convincing treatment effect by KOS on IR. OBJECTIVES: Idiopathic rhinitis (IR) is a common disorder, affecting ∼10-20% of the population. A new method for treating IR, Kinetic Oscillation Stimulation (KOS), has been reported to have beneficial effects on total vasomotor symptom scores (TVRSS). The primary objective with this study was to evaluate if a mean pressure of 65 mbar, pressure amplitude of 100 mbar, and 68 Hz treatment with KOS had a positive effect on total vasomotor symptom scores (TVRSS), as compared with a mean pressure of 65 mbar, pressure amplitude of 4 mbar, and 68 Hz treatment in patients with idiopathic rhinitis. METHODS: Two hundred and seven patients were randomized (Full Analysis Set, FAS) in the study, including five visits and lasting for ∼25 weeks. All patients had two treatment episodes, and all patients had at least one treatment, meant as active, with high amplitude pressure for 10 min in each nostril. Group 1 had two such treatments, and Group 2 had one treatment with low amplitude pressure, initially meant as placebo, on one occasion. Because of numerical improvements in these two groups, a new control group, Group 3, was introduced. They had one new control treatment where the balloon was inserted into the nose, without any air inflation and without oscillations. RESULTS: KOS treatment with high amplitude pressure did not have significant beneficial effects as compared to low amplitude pressure on TVRSS. Numerical improvements in TVRSS and SNOT 22 were found when comparing high and low amplitude pressure treatments with uninflated balloon treatment. However, this part of the study was initially single-blinded, and these results were secondary objectives.


Assuntos
Rinite Vasomotora/terapia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pressão , Rinite/terapia , Adulto Jovem
16.
NPJ Prim Care Respir Med ; 26: 15082, 2016 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-26845513

RESUMO

Allergic rhinitis is a global illness with a well-recognised impact on quality of life and work performance. Comparatively little is known about the extent of its economic impact on society. The TOTALL study estimates the total cost of allergic rhinitis using a sample representing the entire Swedish population of working age. A questionnaire focused on allergic rhinitis was mailed out to a random population of Swedish residents, aged 18-65 years. Health-care contacts, medications, absenteeism (absence from work) and presenteeism (reduced working capacity at work) were assessed, and the direct and indirect costs of allergic rhinitis were calculated. Medication use was evaluated in relation to the ARIA guidelines. In all, 3,501 of 8,001 (44%) answered the questionnaire, and 855 (24%) of these reported allergic rhinitis. The mean annual direct and indirect costs because of allergic rhinitis were €210.3 and €750.8, respectively, resulting in a total cost of €961.1 per individual/year. Presenteeism represented 70% of the total cost. Antihistamines appear to be used in excess in relation to topical steroids, and the use of nasal decongestants was alarmingly high. The total cost of allergic rhinitis in Sweden, with a population of 9.5 million, was estimated at €1.3 billion annually. These unexpectedly high costs could be related to the high prevalence of disease, in combination with the previously often underestimated indirect costs. Improved adherence to guidelines might ease the economic burden on society.


Assuntos
Absenteísmo , Custos de Medicamentos , Serviços de Saúde/economia , Presenteísmo/economia , Rinite Alérgica/economia , Corticosteroides/economia , Corticosteroides/uso terapêutico , Adulto , Idoso , Efeitos Psicossociais da Doença , Dessensibilização Imunológica/economia , Feminino , Serviços de Saúde/estatística & dados numéricos , Antagonistas dos Receptores Histamínicos/economia , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Descongestionantes Nasais/economia , Descongestionantes Nasais/uso terapêutico , Rinite Alérgica/tratamento farmacológico , Inquéritos e Questionários , Suécia , Adulto Jovem
17.
J Geriatr Psychiatry Neurol ; 29(3): 133-41, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26810564

RESUMO

OBJECTIVE: The aim was to compare cognitive function in older suicide attempters with a population-based comparison group. METHODS: Hospitalized suicide attempters aged 70 years and older were assessed cognitively at baseline (n = 99) and 1-year follow-up (n = 59). Depression symptoms were rated with the Montgomery-Åsberg Depression Rating Scale (MADRS). Results of cognitive assessments in attempters were compared with results in nonattempter comparison subjects (n = 115) selected among participants in our population-based health studies to yield a similar distribution of MADRS scores. RESULTS: Suicide attempters scored lower on Mini-Mental State Examination (MMSE) than comparison persons. Among attempters, the mean MMSE score was lower in those with medically serious attempts. Attempters displayed poorer performance on tests of pentagon drawing and abstract thinking compared to comparison persons, and the results remained also after exclusion of those with medically serious attempts. At 1-year follow-up, significant improvement in MADRS scores was observed in the attempters. No evidence of improvement could be shown regarding cognitive deficits. CONCLUSION: Older suicide attempters may have cognitive deficits, which may in part be related to the attempt itself. This needs to be taken into account when designing intervention strategies.


Assuntos
Transtornos Cognitivos/psicologia , Cognição/fisiologia , Tentativa de Suicídio/psicologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Transtornos Cognitivos/diagnóstico , Depressão/diagnóstico , Depressão/psicologia , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica
18.
Geriatrics (Basel) ; 1(3)2016 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31022816

RESUMO

High rates of suicide are observed among older adults in many countries worldwide. In clinical settings, those who make a medically serious suicide attempt are generally considered to be at higher risk of subsequent suicide than those who make less serious attempts. Medically serious attempts in older clinical cohorts are, however, relatively understudied. The aim was to compare older adult suicide attempters (70+) who did or did not make medically serious attempts. We hypothesized, in line with the Interpersonal Model of suicide, that social problems and feelings of being a burden would be associated with medical seriousness. Participants (n = 101) were recruited in hospitals in the aftermath of a suicide attempt; they took part in an interview with a research psychologist. Attempters with (n = 28) and without (n = 73) medically serious attempts were compared. Major depression was common in both groups, and scores on the Geriatric Depression Scale did not differ. However, older adults who made medically serious attempts scored higher on the Brief Scale of Anxiety and lower on the Mini Mental State Examination than their peers who made less serious attempts. Medically serious attempters more often attributed the attempt to social problems as well as problems with functioning and autonomy, but perceived burdensomeness was not associated with seriousness. Findings may help to inform clinicians who meet and treat older suicidal persons.

19.
J Chromatogr A ; 1369: 105-15, 2014 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-25441077

RESUMO

This paper reports a simple chromatographic system to separate lipids classes as well as their molecular species. By the use of phenyl coated silica as stationary phase in combination with a simple mobile phase consisting of methanol and water, all tested lipid classes elute within 30 min. Furthermore, a method to accurately predict retention times of specific lipid components for this type of chromatography is presented. Common detection systems were used, namely evaporative light scattering detection (ELSD), charged aerosol detection (CAD), electrospray mass spectrometry (ESI-MS), and UV detection.


Assuntos
Cromatografia de Fase Reversa/métodos , Lipídeos/isolamento & purificação , Cromatografia Líquida de Alta Pressão/instrumentação , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa/instrumentação , Espectrometria de Massas por Ionização por Electrospray
20.
J Chromatogr A ; 1360: 39-46, 2014 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-25108767

RESUMO

The retention characteristics of the major lipid components in biodiesels and edible oils as well as representative polycyclic aromatic compounds (PAHs) have been investigated on five different normal phase HPLC stationary phases, in order to optimize class separation for an automatized online HPLC cleanup of PAHs prior GC-MS analysis. By stepwise comparison of different hexane/MTBE compositions as mobile phases on cyano-, phenyl-, pentabromobenzyl-, nitrophenyl- and amino-modified silica columns, the capacity and selectivity factors for each analyte and column could be calculated. It was concluded that the most suitable column for backflush isolation of PAHs in biodiesel and edible oil matrices was the pentabromobenzyl-modified silica (PBB). A previously described online HPLC-GC-MS system using the PBB column was then evaluated by qualitative and quantitative analysis of a biodiesel exhaust particulate extract and a vegetable oil reference material. The GC-MS full scan analysis of the biodiesel particulate extract showed that the lipids had been removed from the sample and a fraction containing PAHs and oxygenated derivatives thereof had been isolated. Quantified mass fractions of PAHs of the reference material BCR-458 agreed well for most of the certified PAH mass fractions in the spiked coconut oil reference material.


Assuntos
Biocombustíveis/análise , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Lipídeos/isolamento & purificação , Óleos de Plantas/química , Hidrocarbonetos Policíclicos Aromáticos/isolamento & purificação , Emissões de Veículos/análise , Óleo de Coco
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