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1.
Clin Res Cardiol ; 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31325043

RESUMO

BACKGROUND: Inflammation drives atherosclerosis and its complications. Anti-inflammatory therapy with interleukin 1 beta (IL-1ß) antibody reduces cardiovascular events in patients with elevated high-sensitive C-reactive protein (hsCRP). This study aims to identify the share of patients with coronary heart disease (CHD) and residual inflammation who may benefit from anti-inflammatory therapy. METHODS: hsCRP and low-density lipoprotein (LDL) levels were determined in 2741 all-comers admitted to the cardiological ward of our tertiary referral hospital between June 2016 and June 2018. Patients without CHD, with acute coronary syndrome, chronic or recurrent systemic infection, use of immunosuppressant or anti-inflammatory agents, chronic inflammatory diseases, chemotherapy, terminal organ failure, traumatic injury and pregnancy were excluded. RESULTS: 856 patients with stable CHD were included. 42.7% of those had elevated hsCRP ≥ 2 mg/l. Within the group of patients with LDL-cholesterol < 70 mg/dl, 30.9% shared increased hsCRP indicating residual inflammation. After multivariate adjusted backward selection elevated Lipoprotein (a) (OR 1.61, p = 0.048), elevated proBNP (OR 2.57, p < 0.0001), smoking (OR 1.70, p = 0.022), and obesity (OR 2.28, p = 0.007) were associated with elevated hsCRP. In contrast, the use of ezetimibe was associated with normal hsCRP (OR 0.51, p = 0.014). In the subgroup of patients with on-target LDL-cholesterol < 70 mg/dl, backward selection identified elevated proBNP (OR 3.49, p = 0.007) as independent predictor of elevated hsCRP in patients with LDL-cholesterol < 70 mg/dl. CONCLUSION: One-third of all-comers patients with CHD showed increased levels of hsCRP despite a LDL-cholesterol < 70 mg/dl potentially qualifying for an anti-inflammatory therapy. Elevated proBNP is an independent risk factor for hsCRP elevation.

2.
Chest ; 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31103696

RESUMO

BACKGROUND: Historically, COPD has been considered to affect mostly older men with a history of smoking; however, in recent times, its prevalence and mortality rates have steadily increased among women. OBJECTIVES: The goal of this study was to systematically assess differences in COPD expression between women and men in UK primary care clinics who were newly diagnosed with COPD. METHODS: This retrospective cohort study compared women and men with an incident diagnosis of COPD by using electronic medical records data from the Clinical Practice Research Datalink and linked Hospital Episode Statistics data. The overall study period was between January 1, 2006, and February 28, 2016; patients with an incident diagnosis of COPD between January 1, 2010, and February 28, 2015, were analyzed. RESULTS: A cohort of 22,429 patients were identified as incident patients and included in the study; 48% of patients with COPD were women. The risk of first moderate or severe exacerbation was 17% greater in women than in men (hazard ratio, 1.17; 95% CI, 1.12-1.23), with a median time to first exacerbation of 504 days for women and 637 days for men. These differences were more prominent in the younger age group (≥ 40 years to < 65 years), as well as in Global Initiative for Chronic Obstructive Lung Disease 2016 groups B, C, and D and in individuals with moderate to severe airflow obstruction. The annual rate of moderate or severe exacerbations was higher in women compared with men in the first, second, and third year of follow-up. CONCLUSIONS: These results highlight the unmet need for appropriate identification and management of women with COPD in clinical practice.

3.
Contemp Clin Trials ; 80: 34-39, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30904595

RESUMO

BACKGROUND: Ranibizumab and aflibercept are anti-vascular endothelial growth factor therapies for diabetic macular edema (DME) but have only been directly compared in one study: the Protocol T study, a 24-month randomized controlled trial which compared the safety and efficacy of three anti-VEGF agents (ranibizumab 0.3 mg, aflibercept 2.0 mg and bevacizumab 1.25 mg). The ranibizumab dose used in Protocol T is not licensed for use outside of the US, where a higher ranibizumab dose of 0.5 mg is approved. Therefore, the relevance of the head-to-head Protocol T study findings to healthcare providers in Europe is limited. The purpose of this research was to predict the visual outcomes that may have been achieved in Protocol T with ranibizumab 0.5 mg. METHODS: A simplified dose-response model was constructed to describe the relationship between average monthly dose and one-year best corrected visual acuity (BCVA) change from baseline. A linear mixed effects model was evaluated and Bayesian Monte-Carlo Markov chains method was used to estimate the model parameters. RESULTS: If ranibizumab 0.5 mg PRN had been studied in Protocol T, it would have resulted in a BCVA gain of 14-15 early treatment diabetic retinopathy study (ETDRS) letters; 3-4 letters more than the actual BCVA gain reported with ranibizumab 0.3 mg PRN. In Protocol T patients with poor baseline BCVA (<69 letters), a similar additional letter gain would have been achieved. CONCLUSION: The relevance of the Protocol T study findings are limited due to the use of ranibizumab 0.3 mg PRN which, based on the modelling approach reported herein, resulted in sub-optimal visual gains.

4.
CPT Pharmacometrics Syst Pharmacol ; 7(10): 660-669, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30043524

RESUMO

Intravitreal ranibizumab is a first-line therapy for neovascular age-related macular degeneration (nAMD), but there is a need to optimize patient outcomes while minimizing treatment burden. Here, we developed an indirect response, nonlinear, mixed effects model of disease progression and drug effect in anti-vascular endothelial growth factor (VEGF) treatment-naïve patients. A total of 1,524 treatment-naïve patients and 29,754 visual acuity observations from the ANCHOR, MARINA, PIER, and EXCITE clinical trials informed the model. The model accurately described natural nAMD disease progression and predicted mean visual acuity gains in the HARBOR study, notably with a 2.0 mg ranibizumab dose not used for model development. Furthermore, individualized treatment regimens were shown by simulation to be a viable alternative to the commonly used pro re nata or fixed monthly dosing regimen approaches. Therefore, this model could be a useful tool to predict the outcomes of different, more patient-tailored treatment regimens in nAMD.

5.
Cell Death Dis ; 9(5): 510, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29724998

RESUMO

Binding of allergen-specific IgE to its primary receptor FcεRI on basophils and mast cells represents a central event in the development of allergic diseases. The high-affinity interaction between IgE and FcεRI results in permanent sensitization of these allergic effector cells and critically regulates their release of pro-inflammatory mediators upon IgE cross-linking by allergens. In addition, binding of monomeric IgE has been reported to actively regulate FcεRI surface levels and promote survival of mast cells in the absence of allergen through the induction of autocrine cytokine secretion including interleukin-3 (IL-3). As basophils and mast cells share many biological commonalities we sought to assess the role of monomeric IgE binding and IL-3 signaling in FcεRI regulation and cell survival of primary human basophils. FcεRI cell surface levels and survival of isolated blood basophils were assessed upon addition of monomeric IgE or physiologic removal of endogenous cell-bound IgE with a disruptive IgE inhibitor by flow cytometry. We further determined basophil cell numbers in both low and high serum IgE blood donors and mice that are either sufficient or deficient for FcεRI. Ultimately, we investigated the effect of IL-3 on basophil surface FcεRI levels by protein and gene expression analysis. Surface levels of FcεRI were passively stabilized but not actively upregulated in the presence of monomeric IgE. In contrast to previous observations with mast cells, monomeric IgE binding did not enhance basophil survival. Interestingly, we found that IL-3 transcriptionally regulates surface levels of FcεRI in human primary basophils. Our data suggest that IL-3 but not monomeric IgE regulates FcεRI expression and cell survival in primary human basophils. Thus, blocking of IL-3 signaling in allergic effector cells might represent an interesting approach to diminish surface FcεRI levels and to prevent prolonged cell survival in allergic inflammation.

6.
Int J Chron Obstruct Pulmon Dis ; 13: 1229-1237, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29713156

RESUMO

Purpose: COPD is a progressive disease characterized by exacerbations and a decline in health status and lung function. Clinically important deterioration (CID) is a composite endpoint used to evaluate treatment efficacy. This analysis evaluated the impact of a direct switch to once-daily indacaterol/glycopyrronium 110/50 µg (IND/GLY) from previous monotherapy with a long-acting ß2-agonist (LABA) or long-acting muscarinic antagonist (LAMA) or with an LABA and an inhaled corticosteroid (LABA + ICS) on reducing CID. Methods: CRYSTAL was a 12-week, prospective, multicenter, randomized, open-label study conducted in clinical practice settings. Three definitions of CID (D1-D3) were used, including: 1) ≥100 mL decrease in trough forced expiratory volume in 1 second (FEV1), 2) ≥1 point decrease in transition dyspnea index (TDI) and/or ≥0.4 points increase in clinical COPD questionnaire score (CCQ), or 3) an acute moderate/severe exacerbation (AECOPD). In D1 and D2, either TDI or CCQ was evaluated along with FEV1 and AECOPD, whereas in D3, all 4 parameters were included. ClinicalTrials.gov number: NCT01985334. Results: Of the 2,159 patients analyzed, 1,622 switched to IND/GLY and 537 continued their baseline treatments. The percentage of patients with a CID was significantly lower after a direct switch to IND/GLY versus LABA or LAMA using all 3 CID definitions (D1: odds ratio [OR] 0.41 [95% CI: 0.30-0.55]; D2: OR 0.41 [95% CI: 0.31-0.55]; D3: OR 0.39 [95% CI: 0.29-0.52]). Compared with LABA + ICS, IND/GLY also reduced the risk of CID (D1: OR 0.76 [95% CI: 0.56-1.02]; D2: OR 0.75 [95% CI: 0.56-1.00]; D3: OR 0.67 [95% CI: 0.51-0.89]). Conclusion: In this analysis, IND/GLY reduced the risk of a CID in moderate COPD patients after direct switch from LABA + ICS or LABA or LAMA in real-life clinical practice.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Broncodilatadores/administração & dosagem , Substituição de Medicamentos , Glicopirrolato/administração & dosagem , Indanos/administração & dosagem , Pulmão/efeitos dos fármacos , Antagonistas Muscarínicos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinolonas/administração & dosagem , Administração por Inalação , Corticosteroides/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Idoso , Broncodilatadores/efeitos adversos , Progressão da Doença , Europa (Continente) , Feminino , Volume Expiratório Forçado , Glicopirrolato/efeitos adversos , Nível de Saúde , Humanos , Indanos/efeitos adversos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/efeitos adversos , Estudos Prospectivos , 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
7.
COPD ; 15(2): 185-191, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29658810

RESUMO

Early detection of treatment response is important in the long-term treatment and management of patients with chronic obstructive pulmonary disease (COPD). This analysis evaluated whether early improvement in symptoms, recorded in the first 7 or 14 days via an electronic diary (eDiary) compared with baseline, can predict clinically meaningful treatment responders at 12 weeks. CRYSTAL was a 12-week, randomized, open-label study that demonstrated the increased effectiveness of indacaterol/glycopyrronium (IND/GLY) or glycopyrronium (GLY), after a direct switch from on-going baseline therapies, in patients with symptomatic COPD and moderate airflow obstruction. The co-primary endpoints were trough forced expiratory volume in 1 second (FEV1) and transition dyspnea index (TDI) at Week 12. Patients' symptom status was recorded daily in an eDiary. Of 4,389 patients randomized, 3,936 and 3,855 reported symptoms on Days 7 and 14, respectively. Patients who reported an early decrease in symptoms on Day 7 or 14 were more likely to achieve the minimal clinically important difference of ≥100 mL in trough FEV1 or ≥ 1 point in TDI at Week 12. Using stepwise multivariate regression models we identified as best predictors of FEV1 responders the decrease in wheeze on Day 7, and nighttime symptoms and wheeze on Day 14; best predictors of TDI responders were decrease in nighttime symptoms and wheeze on Day 7, and nighttime symptoms, sputum and wheeze on Day 14. Early symptom improvement at Day 7 or 14, especially wheeze and nighttime symptoms, may identify patients with clinically important improvement in lung function and dyspnea at Week 12.

8.
Respir Res ; 18(1): 140, 2017 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-28720132

RESUMO

BACKGROUND: Dual bronchodilation combining a long-acting ß2-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) is the preferred choice of treatment recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 guidelines for the management of patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). The once-daily (q.d.) fixed-dose combination (FDC) of LABA, indacaterol 110 µg and LAMA, glycopyrronium 50 µg (IND/GLY 110/50 µg q.d.) demonstrated superior improvements in lung function, dyspnoea and overall health status and better tolerability against LABA or LAMA monotherapies and combination of LABA and inhaled corticosteroid (ICS) in more than 11,000 patients with moderate-to-severe COPD in several randomised controlled clinical trials. METHODS: The CRYSTAL study was the first, 12-week, randomised, open-label trial that evaluated the efficacy and safety of a direct switch from previous treatments to IND/GLY 110/50 µg q.d. on lung function and dyspnoea in patients with moderate COPD and a history of up to one exacerbation in the previous year. Patients were divided into 2 groups according to their background therapy and symptom scores and were randomised (3:1) to IND/GLY or to continue with their previous treatments. RESULTS: The study included 4389 randomised patients, of whom 2160 were in groups switched to IND/GLY (intention-to-treat population). The effect of IND/GLY was superior to LABA + ICS on trough forced expiratory volume in 1 s (FEV1; treatment difference, Δ = +71 mL) and transition dyspnoea index (TDI; [Δ = 1.09 units]), and to LABA or LAMA on trough FEV1 (Δ = +101 mL) and a TDI (Δ = 1.26 units). Improvements in health status and lower rescue medication use were also observed with IND/GLY. The safety profile of the study medication was similar to that observed in previous studies. CONCLUSIONS: IND/GLY demonstrated superior improvements in lung function and dyspnoea after direct switch from previous treatments. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01985334 .


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Broncodilatadores/administração & dosagem , Substituição de Medicamentos , Glicopirrolato/administração & dosagem , Indanos/administração & dosagem , Pulmão/efeitos dos fármacos , Antagonistas Muscarínicos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinolonas/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Adulto , Idoso , Broncodilatadores/efeitos adversos , Progressão da Doença , Dispneia/diagnóstico , Dispneia/tratamento farmacológico , Dispneia/fisiopatologia , Europa (Continente) , Feminino , Volume Expiratório Forçado , Glicopirrolato/efeitos adversos , Nível de Saúde , Humanos , Indanos/efeitos adversos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/efeitos adversos , Segurança do Paciente , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Qualidade de Vida , Quinolonas/efeitos adversos , Recuperação de Função Fisiológica , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
9.
Respir Res ; 18(1): 13, 2017 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-28077140

RESUMO

BACKGROUND: Dual bronchodilator therapy is recommended for symptomatic patients with chronic obstructive pulmonary disease (COPD). There are limited data on effects of a combination of two long-acting bronchodilators on lung function including body plethysmography. METHODS: This multicentre, randomised, double-blind, single-dose, cross-over, placebo-controlled study evaluated efficacy and safety of the free combination of indacaterol maleate (IND) and glycopyrronium bromide (GLY) versus IND alone on spirometric and body plethysmography parameters, including inspiratory capacity (IC), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), total lung capacity (TLC) and airway resistance (Raw) in moderate-to-severe COPD patients. RESULTS: Seventy-eight patients with FEV1 % pred. (mean ± SD) 56 ± 13% were randomised. The combination of IND + GLY versus IND presented a numerically higher peak-IC (Δ = 0.076 L, 95% confidence interval [CI]: -0.010 - 0.161 L; p = 0.083), with a statistically significant difference in mean IC over 4 h (Δ = 0.054 L, 95%CI 0.022 - 0.086 L; p = 0.001). FEV1, FVC and Raw, but not TLC, were consistently significantly improved by IND + GLY compared to IND alone. Safety profiles of both treatments were comparable. CONCLUSION: The free combination of IND + GLY improved lung function parameters as evaluated by spirometry and body plethysmography, with a similar safety profile compared to IND alone. TRIAL REGISTRATION: NCT01699685.


Assuntos
Glicopirrolato/administração & dosagem , Indanos/administração & dosagem , Pletismografia Total/métodos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinolonas/administração & dosagem , Espirometria/métodos , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Cross-Over , Diagnóstico por Computador/métodos , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/administração & dosagem , Efeito Placebo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Reprodutibilidade dos Testes , Testes de Função Respiratória/métodos , Sensibilidade e Especificidade , Suíça , Resultado do Tratamento
10.
Asian J Surg ; 40(2): 145-151, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27143213

RESUMO

OBJECTIVE: In the Re-NOVATE II study, oral dabigatran provided thromboprophylaxis after total hip arthroplasty and improved compliance postdischarge in a global population. This article aims to identify trends (if any) in the Indian population. METHODS: In this prospective, double-blind, double-dummy study, patients scheduled for primary, unilateral, elective total hip arthroplasty were randomized to 220 mg oral dabigatran once daily, starting with a 110 mg half-dose, 1-4 hours after surgery, or subcutaneous enoxaparin 40 mg once daily, starting the evening before surgery. Each group received a placebo of the other study drug. The primary efficacy outcome was the composite of total venous thromboembolism (VTE) and all-cause mortality. Secondary outcome measures were composite of major VTE and VTE-related mortality during the treatment period. The major safety outcome was incidence of bleeding events. RESULTS: Of the 179 Indian patients randomized, 91 received oral dabigatran and 88 received subcutaneous enoxaparin for 28-35 days. Total VTE and all-cause mortality occurred in 18.7% of patients in the dabigatran group and 13.7% in the enoxaparin group [odds ratio = 1.4 (95% confidence interval 0.6, 3.5)]. Major VTE and VTE-related mortality was numerically lower in the dabigatran group (7.9%) compared with the enoxaparin group (9.9%). Safety outcomes were comparable between both groups. CONCLUSION: Dabigatran is an effective oral alternative to enoxaparin for thromboprophylaxis as demonstrated by the RE-NOVATE II study global results. Data analyzed in Indian patients indicate comparable effects of dabigatran etexilate for major efficacy and safety outcomes.


Assuntos
Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos , Dabigatrana/administração & dosagem , Enoxaparina/administração & dosagem , Tromboembolia Venosa/prevenção & controle , Administração Oral , Idoso , Intervalos de Confiança , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Incidência , Índia , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Razão de Chances , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/prevenção & controle , Prevenção Primária/métodos , Estudos Prospectivos , Medição de Risco , Resultado do Tratamento , Tromboembolia Venosa/epidemiologia
11.
Circulation ; 134(8): 589-98, 2016 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-27496855

RESUMO

BACKGROUND: The RE-LY trial (Randomized Evaluation of Long-Term Anticoagulant Therapy) compared dabigatran 150 and 110 mg twice daily with warfarin in 18 113 patients with atrial fibrillation. Those with prosthetic heart valves, significant mitral stenosis, and valvular heart disease (VHD) requiring intervention were excluded. Others with VHD were included. METHODS: This is a post hoc analysis of the RE-LY trial. RESULTS: There were 3950 patients with any VHD: 3101 had mitral regurgitation, 1179 with tricuspid regurgitation, 817 had aortic regurgitation, 471 with aortic stenosis, and 193 with mild mitral stenosis. At baseline, patients with any VHD had more heart failure, coronary disease, renal impairment, and persistent atrial fibrillation. Patients with any VHD had higher rates of major bleeds (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.16-1.5) but similar stroke or systemic embolism event rates (HR, 1.09; 95% CI, 0.88-1.33). For patients receiving dabigatran 110 mg, major bleed rates were lower than for patients taking warfarin (HR, 0.73; 95% CI, 0.56-0.95 with VHD; HR, 0.84; 95% CI, 0.71-0.99 without VHD), and major bleed rates for dabigatran 150 mg were similar to those for warfarin in patients with VHD (HR, 0.82; 95% CI, 0.64-1.06) or without VHD (HR, 0.98; 95% CI, 0.83-1.15). For dabigatran 150 mg, stroke/systemic embolic event rates were lower compared with warfarin in those with VHD (HR, 0.59; 95% CI, 0.37-0.93) and those without VHD (HR, 0.67; 95% CI, 0.52-0.86), and stroke/systemic embolic event rates were similar for warfarin and dabigatran 110 mg regardless of the presence of VHD (HR, 0.97; 95% CI, 0.65-1.45; and HR, 0.88; 95% CI, 0.70-1.10). Intracranial bleeds and death rates for dabigatran 150 and 110 mg were lower compared with warfarin independently of the presence of VHD. CONCLUSIONS: The presence of any VHD did not influence the comparison of dabigatran with warfarin. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/uso terapêutico , Doenças das Valvas Cardíacas/tratamento farmacológico , Varfarina/uso terapêutico , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Estudos de Coortes , Esquema de Medicação , Feminino , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/epidemiologia , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Tempo
12.
Prim Care Diabetes ; 10(6): 425-433, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27388795

RESUMO

AIMS: To evaluate the real-world effectiveness of vildagliptin and vildagliptin/metformin, combined with patient engagement, on glycemic outcomes. Patient engagement included both clinicians' engaging patients through education and counseling; and patients' self-engagement through disease awareness, lifestyle changes, and medication adherence. METHODS: Prospective, observational, open-label, multi-center, pharmacoepidemiologic study of type 2 diabetes mellitus (T2DM) patients treated de novo with vildagliptin or vildagliptin/metformin. Data were collected at baseline (treatment initiation), 105±15d, and ≥145d. RESULTS: The evaluable sample included 896 mainly male (58%), overweight (mean±SD BMI=30.3±5.4kg/m2), in later middle age (mean±SD age=64±11years) patients. Over the three visits, mean(±SD) HbA1c levels declined from 8.1%(±1.0) to 7.3%(±1.0) to 7.2%(±0.9); HbA1c control rates rose from 7% to 36% to 43%. Mean±SD FPG levels decreased from 170(±49) to 141(±41) to 139(±42)mg/dL; control rates increased from 12% to 39% to 43% (all p<0.0001). Weight decreased nominally by 2kg (p=0.0290) and BMI by 0.8kg/m2 (p<0.0001). Modeling showed patient engagement activities by clinicians and by patients to be major determinants of glycemic outcomes. No unknown safety signals were detected. CONCLUSIONS: Vildagliptin and vildagliptin/metformin are effective and safe oral agents in the management of T2DM, especially if part of a treatment program with active patient engagement by clinicians and empowered patients.


Assuntos
Adamantano/análogos & derivados , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Nitrilos/administração & dosagem , Participação do Paciente , Pirrolidinas/administração & dosagem , Adamantano/administração & dosagem , Adamantano/efeitos adversos , Administração Oral , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Aconselhamento , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/psicologia , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Combinação de Medicamentos , Feminino , Hemoglobina A Glicada/metabolismo , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Hipoglicemiantes/efeitos adversos , Masculino , Adesão à Medicação , Metformina/efeitos adversos , Pessoa de Meia-Idade , Nitrilos/efeitos adversos , Educação de Pacientes como Assunto , Estudos Prospectivos , Pirrolidinas/efeitos adversos , Comportamento de Redução do Risco , Autocuidado , Comprimidos , Resultado do Tratamento , Vildagliptina
13.
Int J Chron Obstruct Pulmon Dis ; 11: 1297-306, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27366057

RESUMO

The term asthma-COPD overlap syndrome (ACOS) is one of multiple terms used to describe patients with characteristics of both COPD and asthma, representing ~20% of patients with obstructive airway diseases. The recognition of both sets of morbidities in patients is important to guide practical treatment decisions. It is widely recognized that patients with COPD and coexisting asthma present with a higher disease burden, despite the conceptual expectation that the "reversible" or "treatable" component of asthma would allow for more effective management and better outcomes. However, subcategorization into terms such as ACOS is complicated by the vast spectrum of heterogeneity that is encapsulated by asthma and COPD, resulting in different clinical clusters. In this review, we discuss the possibility that these different clusters are suboptimally described by the umbrella term "ACOS", as this additional categorization may lead to clinical confusion and potential inappropriate use of resources. We suggest that a more clinically relevant approach would be to recognize the extreme variability and the numerous phenotypes encompassed within obstructive airway diseases, with various degrees of overlapping in individual patients. In addition, we discuss some of the evidence to be considered when making practical decisions on the treatment of patients with overlapping characteristics between COPD and asthma, as well as the potential options for phenotype and biomarker-driven management of airway disease with the aim of providing more personalized treatment for patients. Finally, we highlight the need for more evidence in patients with overlapping disease characteristics and to facilitate better characterization of potential treatment responders.


Assuntos
Obstrução das Vias Respiratórias/classificação , Asma/classificação , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/classificação , Terminologia como Assunto , Obstrução das Vias Respiratórias/diagnóstico , Obstrução das Vias Respiratórias/epidemiologia , Obstrução das Vias Respiratórias/fisiopatologia , Asma/diagnóstico , Asma/epidemiologia , Asma/fisiopatologia , Humanos , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Síndrome
14.
Artigo em Inglês | MEDLINE | ID: mdl-27418815

RESUMO

BACKGROUND: Morning symptoms associated with COPD have a negative impact on patients' quality of life. Long-acting bronchodilators with rapid onset may relieve patients' symptoms. In the Symptoms and Pulmonary function in the moRnING study, we prospectively compared the rapid onset bronchodilator profile of glycopyrronium (GLY) and tiotropium (TIO) during the first few hours after dosing in patients with moderate-to-severe COPD. METHODS: Patients were randomized (1:1) to receive either once-daily GLY (50 µg) or TIO (18 µg) and corresponding placebos in a cross-over design for 28 days. The primary objective was to demonstrate the superiority of GLY versus TIO in area under the curve from 0 to 4 hours (AUC0-4h) forced expiratory volume in 1 second (FEV1) after the first dose. The secondary objective was to compare GLY versus TIO using the patient reported outcomes Morning COPD Symptoms Questionnaire 3 hours post-inhalation. RESULTS: One-hundred and twenty-six patients were randomized (male 70.2%; mean age 65.7 years) and 108 patients completed the study. On Day 1, GLY resulted in significantly higher FEV1 AUC0-4h after the first dose versus TIO (treatment difference [Δ], 0.030 L, 95% confidence interval 0.004-0.056, P=0.025). Improvements in morning COPD symptoms from baseline at Days 1 and 28 were similar between GLY and TIO. Post hoc analysis of the FEV1 AUC0-4h by time point on Day 1 showed significant improvements in patients receiving GLY versus TIO at 5 minutes (Δ=0.029 L, P=0.015), 15 minutes (Δ=0.033 L, P=0.026), and 1 hour (Δ=0.044 L, P=0.014). Safety results were comparable between both treatments. CONCLUSION: The SPRING study demonstrates the superiority of GLY versus TIO in terms of superior bronchodilation in the first 4 hours after administration, thus extending the clinical data that support a faster onset of action of GLY versus TIO.


Assuntos
Broncodilatadores/administração & dosagem , Glicopirrolato/administração & dosagem , Pulmão/efeitos dos fármacos , Antagonistas Muscarínicos/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Brometo de Tiotrópio/administração & dosagem , Administração por Inalação , Idoso , Broncodilatadores/efeitos adversos , Ritmo Circadiano , Estudos Cross-Over , Esquema de Medicação , Europa (Continente) , Feminino , Volume Expiratório Forçado , Glicopirrolato/efeitos adversos , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/efeitos adversos , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Qualidade de Vida , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Fatores de Tempo , Brometo de Tiotrópio/efeitos adversos , Resultado do Tratamento , Capacidade Vital
15.
Eur Respir J ; 48(5): 1369-1376, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27471209

RESUMO

Attempts at identifying patients with an elevated risk of bleeding while on anticoagulation following acute venous thromboembolism (VTE) have largely been unsuccessful thus far. We sought to develop a clinical prediction score for bleeding during stable anticoagulation treatment after acute VTE.We performed a post hoc analysis of the pooled RE-COVER studies, two double-blind randomised "sister" trials evaluating dabigatran versus standard treatment in 5107 VTE patients.A score was derived from patients randomised to dabigatran using logistic regression analysis covering the complete follow-up period. The final model, named VTE-BLEED, included six variables and yielded a c-statistic of 0.72 (95% CI 0.67-0.76). Patients from the derivation cohort in the low-risk group (<2 points; 74% of the derivation population) had a bleeding incidence of 2.8% compared to 12.6% in the elevated-risk group (OR 5.0; 95% CI 3.5-7.1). The score proved accurate for our primary end-point, i.e. prediction of major bleeding after day 30 ("stable" anticoagulation), both in patients on dabigatran (c-statistic 0.75, 95% CI 0.61-0.89) and those on warfarin (0.78, 95% CI 0.68-0.86; p=0.77 for difference).The new VTE-BLEED score accurately predicted major bleeding events in VTE patients on stable anticoagulation with both dabigatran and warfarin.


Assuntos
Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Dabigatrana/administração & dosagem , Hemorragia/prevenção & controle , Tromboembolia Venosa/tratamento farmacológico , Varfarina/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Estudos de Coortes , Interpretação Estatística de Dados , Tomada de Decisões , Feminino , Humanos , Masculino , Modelos Estatísticos , Curva ROC , Análise de Regressão , Fatores de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Adulto Jovem
16.
Diabetes Ther ; 7(3): 483-96, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27262995

RESUMO

INTRODUCTION: Preliminary data suggest that dipeptidyl peptidase-4 (DPP-4) inhibitors may reduce microvascular events, but there is a little evidence to support this from adequate real-world studies. This study aimed to compare microvascular outcomes between patients-prescribed vildagliptin and those prescribed sulfonylurea (SU). METHODS: This retrospective cohort study was conducted on a large sample from the German electronic medical records database IMS Lifelink Disease Analyzer. We used propensity score-matched samples of patients prescribed either vildagliptin or SU. Exposure was defined as therapy (SU or vildagliptin); primary outcomes were a diagnosis of retinopathy, nephropathy, neuropathy, or diabetic foot ulcer over the observation period in patients with no previous record of these outcomes. Secondary outcome was a composite of any primary outcome occurring in the observation period. RESULTS: In total, 16,321 patients prescribed SU and 4481 prescribed vildagliptin met the inclusion criteria. After propensity score matching, each sample comprised 3015 patients. Mean age was 63.7/64.6 years for SU/vildagliptin, respectively, with mean disease duration of 3.2/3.1 years, and mean treatment duration of 2.5/2.3 years. Treatment with vildagliptin was associated with a significant lower incidence of retinopathy [odds ratio (OR) = 0.55, P = 0.0004], neuropathy (OR 0.71, P = 0.0001), and composite outcome (OR 0.70, P < 0.0001). Incidences of nephropathy and diabetic foot ulcer were lower for vildagliptin, but not significantly so (OR 0.90, P = 0.3920; OR 0.76, P = 0.0742, respectively). There were no significant differences in incident rate ratios (all P > 0.05). CONCLUSION: Treatment with vildagliptin was associated with a reduced incidence of microvascular complications, especially neuropathy and retinopathy, compared to treatment with SU in this clinical practice setting. FUNDING: Novartis Pharma AG.

18.
Thromb Res ; 143: 103-10, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27208980

RESUMO

INTRODUCTION: The standard dabigatran etexilate dosage for prevention of venous thromboembolism (VTE) after elective total hip or knee replacement (THR/TKR) is 220mg once daily (qd), with 150mg qd for patients with moderate renal impairment. As clinical trial experience in patients with moderate renal impairment was limited at the time of approval, we conducted an observational study to evaluate the 150mg qd dose. MATERIALS AND METHODS: This open-label, prospective, uncontrolled, observational study in patients with creatinine clearance (CrCl) 30-50mL/min was conducted in seven European countries. Patients received 75mg dabigatran etexilate 1-4h after surgery and 150mg qd on days 2-10 (TKR) or 2-35 (THR), per the European Summary of Product Characteristics. Coprimary outcomes were major bleeding events (MBEs) and a composite of symptomatic VTE and all-cause mortality. RESULTS: 428 renally impaired patients with median CrCl 43.4mL/min (range 30.0-49.9), and median age 80years (range 32-96) received dabigatran etexilate: median treatment duration THR 31days, TKR 28days. Ten MBEs occurred in nine patients (2.1%; 95% confidence interval [CI]: 1.0-4.0; THR 1.8%; TKR 2.4%); none were fatal or involved a critical organ. Symptomatic VTE and all-cause mortality occurred in three patients (0.7%; 95% CI: 0.1-2.0; THR 0.9%; TKR 0.5%). Overall, 54 patients discontinued treatment prematurely, including 35 due to an adverse event (nine bleeding-related) and 16 switching to another anticoagulant. CONCLUSIONS: Dabigatran etexilate 150mg qd had a good safety profile and was efficacious in fragile, elderly, renally impaired patients undergoing THR or TKR. These findings from the clinical practice setting add to the existing clinical trial data.


Assuntos
Antitrombinas/uso terapêutico , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Dabigatrana/uso terapêutico , Insuficiência Renal/complicações , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Antitrombinas/administração & dosagem , Antitrombinas/efeitos adversos , Dabigatrana/administração & dosagem , Dabigatrana/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Tromboembolia Venosa/complicações
19.
Expert Rev Respir Med ; 10(7): 739-53, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27135786

RESUMO

INTRODUCTION: Exacerbations of chronic obstructive pulmonary disease (COPD) are important events in the natural history of the disease that have significant impact on important outcomes for patients with COPD, including disease progression and mortality. AREAS COVERED: In the present review, we summarize the risk factors and characteristics of patients with COPD who are at an increased risk for exacerbations and mortality. We will also examine currently available interventions that may lead to the effective prevention of future events. Several pharmacotherapy options have been shown to be effective in preventing exacerbations, including long-acting bronchodilators, inhaled corticosteroids and phosphodiesterase-4 inhibitors, as well as macrolides and mucolytics/antioxidants. Improvement in mortality would result from a holistic approach, combining pharmacotherapy and nonpharmacological options, as well as the appropriate management of comorbidities, which are frequent in this population. Expert Commentary: Prevention of COPD exacerbations should follow a holistic approach, including improvement in physical activity, nonpharmacological and pharmacotherapy options, and management of comorbidities. Such a comprehensive approach may result in an improvement in the overall mortality of COPD patients.


Assuntos
Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Corticosteroides/uso terapêutico , Broncodilatadores/uso terapêutico , Progressão da Doença , Expectorantes/uso terapêutico , Humanos , Doença Pulmonar Obstrutiva Crônica/mortalidade
20.
Thromb J ; 14: 8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27042163

RESUMO

BACKGROUND: Thromboprophylaxis is recommended for patients undergoing total hip or total knee replacement (THR, TKR). An international, open-label, prospective, observational, single-arm study in a routine clinical setting was performed to assess the safety and efficacy of dabigatran etexilate 220 mg once daily in patients undergoing THR or TKR, and in subgroups of patients with potentially increased risk of bleeding or venous thromboembolism (VTE). MATERIALS AND METHODS: Patients were ≥18 years and required to be eligible to receive dabigatran 220 mg once daily (first dose 110 mg 1-4 h after THR/TKR surgery) according to the European Summary of Product Characteristics. The primary safety and efficacy outcomes were incidence of major bleeding events (MBEs), and the composite incidence of symptomatic VTE events and all-cause mortality, respectively. RESULTS: In total, 5292 patients (median age 64 years) were enrolled and received dabigatran (2734 THR and 2558 TKR). Median drug exposure was 31 days (THR 34 days; TKR 27 days). Overall incidence of MBEs was 0.72 % (95 % confidence interval [CI] 0.51, 0.98), and this rate was comparable between types of surgery and was not significantly affected by protocol-defined risk factors. The overall incidence of symptomatic VTE and all-cause mortality was 1.04 % (95 % CI 0.78, 1.35); the only significant risk factor was history of VTE events (odds ratio 5.59; 95 % CI 2.53, 11.08). A post-hoc analysis showed that the incidence of MBEs in this observational study was similar to or lower than those reported in previous phase 3 trials. CONCLUSIONS: Results from this observational study of dabigatran etexilate administered to patients undergoing THR or TKR surgery are reassuring and supportive of those obtained in dabigatran phase 3 trials. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00846807.

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