RESUMO
BACKGROUND AND AIMS: Smoking is considered the main cause of preventable death world-wide. This study aimed to review the efficacy and safety of cytisine for smoking cessation. METHODS: This review included an exhaustive search of databases to identify randomized controlled trials (RCTs) in health centers of any level with smokers of any age or gender investigating the effects of cytisine at standard dosage versus placebo, varenicline or nicotine replacement therapy (NRT). RESULTS: We identified 12 RCTs. Eight RCTs compared cytisine with placebo at the standard dose covering 5922 patients, 2996 of whom took cytisine, delivering a risk ratio (RR) of 2.25 [95% confidence interval (CI) = 1.42-3.56; I2 = 88%; moderate-quality evidence]. The greater intensity of behavioral therapy was associated directly with the efficacy findings (moderate-quality evidence). The confirmed efficacy of cytisine was not evidenced in trials conducted in low- and middle-income countries. We estimate a number needed to treat (NNT) of 11. Two trials compared the efficacy of cytisine versus NRT, and the combination of both studies yields modest results in favor of cytisine. Three trials compared cytisine with varenicline, without a clear benefit for cytisine. Meta-analyses of all non-serious adverse events in the cytisine group versus placebo groups yielded a RR of 1.24 (95% CI = 1.11-1.39; participants = 5895; studies = 8; I2 = 0%; high-quality evidence). CONCLUSIONS: Cytisine increases the chances of successful smoking cessation by more than twofold compared with placebo and has a benign safety profile, with no evidence of serious safety concerns. Limited evidence suggests that cytisine may be more effective than nicotine replacement therapy, with modest cessation rates.
Assuntos
Alcaloides , Alcaloides Quinolizidínicos , Abandono do Hábito de Fumar , Humanos , Abandono do Hábito de Fumar/métodos , Vareniclina/uso terapêutico , Nicotina/uso terapêutico , Agonistas Nicotínicos/uso terapêutico , Bupropiona/uso terapêutico , Benzazepinas/efeitos adversos , Quinoxalinas/efeitos adversos , Alcaloides/uso terapêutico , Azocinas/uso terapêutico , Quinolizinas/uso terapêuticoRESUMO
INTRODUCTION AND OBJECTIVES: Four regimens are recommended for treating hepatitis C (HCV) genotype 1 infection. Study aims were to (1) compare frequencies of contraindicated drug interactions (XDDIs) when each HCV regimen is added to medication profiles of HCV-monoinfected patients, (2) quantify the proportion of patients with XDDIs to all four regimens and (3) determine covariates independently associated with having a XDDI to all four regimens. MATERIALS AND METHODS: A cross-sectional study was performed within Upstate New York Veterans Healthcare Administration. INCLUSION CRITERIA: (1) age ≥18 years, (2) HCV monoinfection and (3) available medication list. Data extracted were: demographics, comorbidities, and medication list. Primary outcome was XDDIs involving patient's home medications and each HCV regimen. University of Liverpool drug interaction website was used to define XDDIs. Two-way comparisons of regimens were performed using McNemar's test where p<0.0083 was considered statistically significant. Multivariate regression analyses were performed to determine predictors. RESULTS: Of the 4047 subjects, mean±standard deviation age was 59.8±7.6. Median (interquartile range) number of medications used was 7 [4-11]. Frequencies of XDDIs after the addition of each regimen ranged from 2.8% to 17.8% and were mostly statistically different from one another. There were 95 (2.3%) patients with XDDIs to all four regimens. Predictors of having XDDIs to all four regimens were ≥6 medications and HCV infection ≥10 years. CONCLUSION: The frequencies of XDDIs varied between HCV regimens. Number of medications and duration of HCV infection were predictors of having XDDIs to all four regimens.
Assuntos
Antivirais/efeitos adversos , Contraindicações de Medicamentos , Interações Medicamentosas , Hepatite C Crônica/tratamento farmacológico , Idoso , Ansiolíticos/efeitos adversos , Antiasmáticos/efeitos adversos , Anticoagulantes/efeitos adversos , Anticonvulsivantes/efeitos adversos , Antidepressivos/efeitos adversos , Antieméticos/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Antipsicóticos/efeitos adversos , Benzimidazóis/efeitos adversos , Benzofuranos/efeitos adversos , Carbamatos/efeitos adversos , Estudos Transversais , Suplementos Nutricionais/efeitos adversos , Combinação de Medicamentos , Feminino , Fluorenos/efeitos adversos , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Humanos , Imidazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/efeitos adversos , Polimedicação , Pirrolidinas/efeitos adversos , Quinoxalinas/efeitos adversos , Sofosbuvir/efeitos adversos , Sulfonamidas/efeitos adversos , Uridina Monofosfato/efeitos adversos , Uridina Monofosfato/análogos & derivados , Veteranos , Vitaminas/efeitos adversosRESUMO
BACKGROUND AND AIM: Grazoprevir is an NS3/4A protease inhibitor (PI), while elbasvir is an NS5A inhibitor. We performed this meta-analysis to directly compare grazoprevir plus elbasvir and ribavirin regimen vs. grazoprevir and elbasvir without ribavirin in the treatment of hepatitis C virus genotype 1 infection and to precisely evaluate the efficacy of the latter regimen in cirrhotic, IL28 CC genotype patients and those coinfected with human immunodeficiency virus. MATERIAL AND METHODS: A computer literature search of PubMed, Scopus, EBSCO, Embase, and Cochrane central was conducted. Studies were screened for eligibility. Sustained virologic response (SVR) rates were pooled using OpenMeta[Analyst] software for windows. A subgroup analysis was performed to stratify the treatment efficacy according to the different baseline characteristics of HCV patients. RESULTS: Eight randomized controlled trials (n = 1,297 patients) were pooled in the final analysis. The overall SVR rate was 96.6% with 95% CI [95.5% to 98%]. For cirrhotic patients, the SVR rate was 95.7% with 95% CI [93.9% to 97.5%] and for non-cirrhotic patients, the SVR rate was 97% with 95% CI [95.9% to 98.4%]. Furthermore, the addition of ribavirin (RBV) to the treatment regimen did not significantly improve the SVR (RR 1.003, 95% CI [0.944 to 1.065]). The dual regimen was effective in patient populations with NS3 resistance-associated (RAS). However, this regimen achieved lower SVR rates (< 90%) in patients with NS5A RAS. CONCLUSIONS: We conclude that the 12-week treatment regimen of the fixed dose combination of grazoprevir plus elbasvir achieved high SVR rates in patients with HCV genotype 1 infection. The addition of ribavirin to this regimen did not add a significant benefit.
Assuntos
Antivirais/uso terapêutico , Benzofuranos/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Imidazóis/uso terapêutico , Quinoxalinas/uso terapêutico , Adulto , Idoso , Antivirais/efeitos adversos , Benzofuranos/efeitos adversos , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Combinação de Medicamentos , Farmacorresistência Viral , Inibidores Enzimáticos/efeitos adversos , Feminino , Genótipo , Hepacivirus/enzimologia , Hepacivirus/genética , Hepatite C/diagnóstico , Hepatite C/virologia , Humanos , Imidazóis/efeitos adversos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Pessoa de Meia-Idade , Quinoxalinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ribavirina/uso terapêutico , Resposta Viral Sustentada , Resultado do Tratamento , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Adulto JovemRESUMO
This study assessed the efficacy and safety of ribavirin-free coformulated glecaprevir/pibrentasvir (G/P) in patients with hepatitis C virus genotype 3 infection with prior treatment experience and/or compensated cirrhosis, a patient population with limited treatment options. SURVEYOR-II, Part 3 was a partially randomized, open-label, multicenter, phase 3 study. Treatment-experienced (prior interferon or pegylated interferon ± ribavirin or sofosbuvir plus ribavirin ± pegylated interferon therapy) patients without cirrhosis were randomized 1:1 to receive 12 or 16 weeks of G/P (300 mg/120 mg) once daily. Treatment-naive or treatment-experienced patients with compensated cirrhosis were treated with G/P for 12 or 16 weeks, respectively. The primary efficacy endpoint was the percentage of patients with sustained virologic response at posttreatment week 12 (SVR12). Safety was evaluated throughout the study. There were 131 patients enrolled and treated. Among treatment-experienced patients without cirrhosis, SVR12 was achieved by 91% (20/22; 95% confidence interval [CI], 72-97) and 95% (21/22; 95% CI, 78-99) of patients treated with G/P for 12 or 16 weeks, respectively. Among those with cirrhosis, SVR12 was achieved by 98% (39/40; 95% CI, 87-99) of treatment-naive patients treated for 12 weeks and 96% (45/47; 95% CI, 86-99) of patients with prior treatment experience treated for 16 weeks. No adverse events led to discontinuation of study drug, and no serious adverse events were related to study drug. Conclusion: Patients with hepatitis C virus genotype 3 infection with prior treatment experience and/or compensated cirrhosis achieved high SVR12 rates following 12 or 16 weeks of treatment with G/P. The regimen was well tolerated. (Hepatology 2018;67:514-523).
Assuntos
Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/etiologia , Quinoxalinas/administração & dosagem , Sulfonamidas/administração & dosagem , Adulto , Idoso , Alanina Transaminase/sangue , Ácidos Aminoisobutíricos , Benzimidazóis/efeitos adversos , Ciclopropanos , Quimioterapia Combinada , Feminino , Genótipo , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Masculino , Pessoa de Meia-Idade , Prolina/análogos & derivados , Pirrolidinas , Quinoxalinas/efeitos adversos , Sulfonamidas/efeitos adversos , Resposta Viral SustentadaRESUMO
BACKGROUND: Therapies to quit smoking are based on counseling, psychological therapy (PT), nicotine replacement therapy, bupropion or varenidine. AIM: To report the results of a multidisciplinary program to quit smoking. MATERIAL AND METHODS: Patients aged l8 years or more, motivated to quit smoking were admitted in a program based in counseling and PT, with or without pharmacological therapy. They were assessed by telephone during one year of follow up. Patients with unstable psychiatric diseases were excluded. Results were considered as "successful" when patients maintained abstinence during the year of follow up. A logistic regression analysis was done to identify factors associated with treatment success. RESULTS: Between 2005 and 2011, 198 patients aged 45 ± 11 years (56% males), who smoked 31.5 ± 20.6 packages/year, were treated. Of these, 155 (78%) were treated with varenidine, 26 (13%) with bupropion and 17 (9%>) did not receive pharmacological therapy. One hundred sixty eight patients completed the year of follow up. In 82 (49%>), treatment was successful and was negatively associated with a history of depression (odds ratio = 4 (95% confidence intervals 1.23-38.33). The main side effeets associated to varenidine and bupropion were nausea in 37 and 23%o, sleep disorders in 20 and 19%o and headache in 12 and 0%>, respectively. CONCLUSIONS: A multidisciplinary program to quit smoking achieved a 49%> of abstinence during a year of follow up.
Assuntos
Benzazepinas/uso terapêutico , Bupropiona/uso terapêutico , Terapia Cognitivo-Comportamental , Agonistas Nicotínicos/uso terapêutico , Equipe de Assistência ao Paciente , Quinoxalinas/uso terapêutico , Abandono do Hábito de Fumar/métodos , Fumar/terapia , Adolescente , Adulto , Idoso , Benzazepinas/efeitos adversos , Bupropiona/efeitos adversos , Terapia Combinada/métodos , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agonistas Nicotínicos/efeitos adversos , Avaliação de Programas e Projetos de Saúde , Quinoxalinas/efeitos adversos , Fatores Socioeconômicos , Resultado do Tratamento , Vareniclina , Adulto JovemRESUMO
PURPOSE: To compare the hypotensive effect in normal eyes of three formulations with different concentrations of brimonidine tartrate: 0.2%; 0.15% and 0.1%. METHODS: Prospective, randomized, double-blind study included 60 volunteers, who underwent initial ophthalmologic examination and measurement of intraocular pressure (IOP). Individuals were divided into three groups: (1) brimonidine tartrate 0.15%, (2) brimonidine tartrate 0.2% and (3) brimonidine tartrate 0.1% and randomly received one drop each of drops in each eye. The IOP was measured after 30 minutes, 1 hour and 2 hours. RESULTS: We found that all concentrations of brimonidine tartrate significantly reduced intraocular pressure during the study period, with p<0.05. When analyzing the percentage difference of the hypotensive effect of each group, we found no significant difference between the studied groups: (1) -13.50%, (2) -11.50%, (3) -11.90% after 30 minutes (p=0.650); (1) -24.30%, (2) -18.60%, (3) -18.30% after 1 hour (p=0.324); (1) -29.14%, (2) -21.20%, (3) -25.60% after 2 hours (p=0.068). CONCLUSION: There is no statistically significant difference in intraocular pressure reduction (peak period) between the three formulations of brimonidine.
Assuntos
Anti-Hipertensivos/administração & dosagem , Pressão Intraocular/efeitos dos fármacos , Hipertensão Ocular/prevenção & controle , Quinoxalinas/administração & dosagem , Adolescente , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Agonistas de Receptores Adrenérgicos alfa 2/efeitos adversos , Adulto , Anti-Hipertensivos/efeitos adversos , Tartarato de Brimonidina , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Quinoxalinas/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: To assess the efficacy and safety of varenicline (Chantix) for the treatment of alcohol dependence. Varenicline is a partial α4ß2 nicotinic acetylcholine agonist approved by the Food and Drug Administration for smoking cessation. It has reduced drinking in animal studies and in small studies of humans who were both heavy drinkers and smokers. This is the first multisite clinical trial of varenicline in a population of smokers and nonsmokers with alcohol dependence. METHODS: Men and women (n = 200) meeting the criteria for alcohol dependence were recruited across 5 clinical sites. Patients received double-blind varenicline or placebo and a computerized behavioral intervention. Varenicline was titrated during the first week to 2 mg/d, which was maintained during weeks 2 to 13. RESULTS: The varenicline group had significantly lower weekly percent heavy drinking days (primary outcome) (adjusted mean difference = 10.4), drinks per day, drinks per drinking day, and alcohol craving compared with the placebo group (P < 0.05). The average treatment effect on alcohol use was similar for smokers and nonsmokers. Varenicline was well-tolerated; adverse events were expected and mild. CONCLUSIONS: Varenicline significantly reduced alcohol consumption and craving, making it a potentially viable option for the treatment of alcohol dependence.
Assuntos
Alcoolismo/tratamento farmacológico , Benzazepinas/uso terapêutico , Quinoxalinas/uso terapêutico , Adulto , Benzazepinas/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Quinoxalinas/efeitos adversos , Resultado do Tratamento , VareniclinaRESUMO
OBJETIVO: Comparar o efeito hipotensor a curto prazo das três formulações de colírio de tartarato de brimonidina, Alphagan®, Alphagan® P e Alphagan® Z em olhos normais. MÉTODO: Estudo prospectivo, randomizado, duplo-cego que contou com 60 voluntários, os quais foram submetidos a exame oftalmológico inicial e aferição da pressão intraocular (PIO). Os participantes foram distribuídos em três grupos: 1 tartarato de brimonidina 0,15%, 2 tartarato de brimonidina 0,2% e 3 tartarato de brimonidina 0,1%, aleatoriamente, cada um recebeu uma gota de colírio em cada olho e a pressão intraocular foi aferida após 30 minutos, 1 hora e 2 horas. RESULTADOS: Observou-se que todas as concentrações de tartarato de reduziram significativamente a pressão intraocular durante o tempo estudado, com p<0,05. Ao ser analisada a diferença percentual do efeito hipotensor de cada grupo, verificou-se que não há diferença significativa entre os colírios estudados: (1) -13,50%, (2) -11,50%, (3) -11,90% após 30 minutos (p=0,650); (1) -24,30%, (2) -18,60%, (3) -18,30% após 1 hora (p=0,324); (1) -29,14% (2) -21,20%, (3) -25,60% após 2 horas (p=0,068). CONCLUSÃO: Não há diferença estatisticamente significativa para redução da pressão intraocular (no período de pico) entre as três formulações de brimonidina.
PURPOSE: To compare the hypotensive effect in normal eyes of three formulations with different concentrations of brimonidine tartrate: 0.2%; 0.15% and 0.1%. METHODS: Prospective, randomized, double-blind study included 60 volunteers, who underwent initial ophthalmologic examination and measurement of intraocular pressure (IOP). Individuals were divided into three groups: (1) brimonidine tartrate 0.15%, (2) brimonidine tartrate 0.2% and (3) brimonidine tartrate 0.1% and randomly received one drop each of drops in each eye. The IOP was measured after 30 minutes, 1 hour and 2 hours. RESULTS: We found that all concentrations of brimonidine tartrate significantly reduced intraocular pressure during the study period, with p<0.05. When analyzing the percentage difference of the hypotensive effect of each group, we found no significant difference between the studied groups: (1) -13.50%, (2) -11.50%, (3) -11.90% after 30 minutes (p=0.650); (1) -24.30%, (2) -18.60%, (3) -18.30% after 1 hour (p=0.324); (1) -29.14%, (2) -21.20%, (3) -25.60% after 2 hours (p=0.068). CONCLUSION: There is no statistically significant difference in intraocular pressure reduction (peak period) between the three formulations of brimonidine.
Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Anti-Hipertensivos/administração & dosagem , Pressão Intraocular/efeitos dos fármacos , Hipertensão Ocular/prevenção & controle , Quinoxalinas/administração & dosagem , /administração & dosagem , /efeitos adversos , Anti-Hipertensivos/efeitos adversos , Método Duplo-Cego , Estudos Prospectivos , Quinoxalinas/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
Background: Therapies to quit smoking are based on counseling, psychological therapy (PT), nicotine replacement therapy, bupropion or varenidine. Aim: To report the results of a multidisciplinary program to quit smoking Material and Methods: Patients agedl8years or more, motivated to quit smoking were admitted in a program based in counseling and PT, with or without pharmacological therapy. They were assessed by telephone during one year offollow up. Patients with unstable psychiatric diseases were excluded. Results were considered as "successful" when patients maintained abstinence during the year offollow up. A logistic regression analysis was done to identify factors associated with treatment success. Results: Between 2005 and 2011, 198 patients aged 45 ± 11 years (56% males), who smoked 31.5 ± 20.6 packages/year, were treated. Ofthese, 155 (78%) were treated with varenidine, 26 (13%) with bupropion and 17 (9%>) did not receive pharmacological therapy. One hundred sixty eightpatients completed the year offollow up. In 82 (49%>), treatment was successful and was negatively associated with a history of depression (odds ratio = 4 (95% confidence intervals 1.23-38.33). The main side effeets associated to varenidine and bupropion were nausea in 37 and 23%o, sleep disorders in 20 and 19%o and headache in 12 and 0%>, respectively Conclusions: A multidisciplinary program to quit smoking achieved a 49%> of abstinence during a year offollow up.