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1.
Pharmacoepidemiol Drug Saf ; 31(2): 225-234, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34757641

RESUMO

BACKGROUND AND PURPOSE: Characterization of emergency department (ED) visits for acute harms related to use of over-the-counter cough and cold medications (CCMs) by patient demographics, intent of CCM use, concurrent substance use, and clinical manifestations can help guide prevention of medication harms. METHODS: Public health surveillance data from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project were used to estimate numbers and population rates of ED visits from 2017 to 2019. RESULTS: Based on 1396 surveillance cases, there were an estimated 26 735 (95% CI, 21 679-31 791) US ED visits for CCM-related harms annually, accounting for 1.3% (95% CI, 1.2-1.5%) of all ED visits for medication adverse events. Three fifths (61.4%, 95% CI, 55.6-67.2%) of these visits were attributed to non-therapeutic CCM use (nonmedical use, self-harm, unsupervised pediatric exposures). Most visits by children aged <4 years (74.0%, 95% CI, 59.7-88.3%) were for unsupervised CCM exposures. Proportion hospitalized was higher for visits for self-harm (76.5%, 95% CI, 68.9-84.2%) than for visits for nonmedical use (30.3%, 95% CI, 21.1-39.6%) and therapeutic use (8.8%, 95% CI, 5.9-11.8%). Overall, estimated population rates of ED visits for CCM-related harms were higher for patients aged 12-34 years (16.5 per 100 000, 95% CI, 13.0-20.0) compared with patients aged <12 years (5.1 per 100 000, 95% CI, 3.6-6.5) and ≥ 35 years (4.3 per 100 000, 95% CI, 3.4-5.1). Concurrent use of other medications, illicit drugs, or alcohol was frequent in ED visits for nonmedical use (61.3%) and self-harm (75.9%). CONCLUSIONS: Continued national surveillance of CCM-related harms can assess progress toward safer use.


Assuntos
Tosse , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Sistemas de Notificação de Reações Adversas a Medicamentos , Criança , Serviço Hospitalar de Emergência , Hospitalização , Humanos , Estados Unidos/epidemiologia
2.
Am J Prev Med ; 58(4): 526-535, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32089287

RESUMO

INTRODUCTION: Characterization of emergency department visits attributed to adverse events involving benzodiazepines can be used to guide preventive interventions. This study describes U.S. emergency department visits attributed to adverse events involving benzodiazepines by intent, patient characteristics, and clinical manifestations. METHODS: Data from the 2016-2017 National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project were analyzed in 2019 to calculate estimated annual numbers and rates of emergency department visits attributed to adverse events involving benzodiazepines, by intent of benzodiazepine use. RESULTS: Based on 6,148 cases, there were an estimated 212,770 (95% CI=167,163, 258,377) emergency department visits annually attributed to adverse events involving benzodiazepines. More than half were visits involving nonmedical use of benzodiazepines (119,008; 55.9%, 95% CI=50.0%, 61.9%), one third were visits involving self-harm with benzodiazepines (64,721; 30.4%, 95% CI=25.6%, 35.2%), and a smaller proportion of visits involved therapeutic use of benzodiazepines (29,041; 13.6%, 95% CI=11.4%, 15.9%). The estimated population rate of visits was highest for nonmedical use of benzodiazepines by patients aged 15-34 years (7.4 visits per 10,000 people). Among visits involving nonmedical use of benzodiazepines, 54.8% (95% CI=49.8%, 59.8%) were made by patients aged 15-34 years, 82.7% (95% CI=80.1%, 85.4%) involved concurrent use of other substances (illicit drugs, alcohol, prescription opioids, and/or other pharmaceuticals), and 24.2% (95% CI=17.7%, 30.6%) involved cardiorespiratory arrest or unresponsiveness. CONCLUSIONS: These findings support recommendations to assess for and address substance use disorder before initiating or continuing benzodiazepines and reinforce the need for validated self-harm risk assessment tools for clinicians.


Assuntos
Benzodiazepinas/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Adolescente , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Vigilância em Saúde Pública , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Estados Unidos/epidemiologia , Adulto Jovem
3.
Pharmacoepidemiol Drug Saf ; 28(7): 951-964, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31144403

RESUMO

PURPOSE: To assess performance of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code assignments for identifying bleeding events resulting in emergency department visits and hospitalizations among outpatient Medicare beneficiaries prescribed anticoagulants. METHODS: Performance of 206 ICD-10-CM code assignments indicative of bleeding, five anticoagulant adverse effect/poisoning codes, and five coagulopathy codes (according to Medicare Parts A and B claims) as assessed among Medicare fee-for-service beneficiaries prescribed anticoagulants between October 1, 2015 and September 30, 2016 (according to Part D claims). Structured medical record review was the gold standard for validating the presence of anticoagulant-related bleeding. Sensitivity was adjusted to correct for partial verification bias due to sampling design. RESULTS: Based on the study sample of 1166 records (583 cases, 583 controls), 57 of 206 codes yielded the optimal performance for anticoagulant-related bleeding (diagnostic odds ratio, 51; positive predictive value (PPV), 75.7% [95% CI, 72.0%-79.1%]; adjusted sensitivity, 70.0% [95% CI, 63.2%-77.7%]). Codes for intracranial bleeding demonstrated the highest PPV (85.0%) and adjusted sensitivity (91.0%). Bleeding codes in the primary position demonstrated high PPV (86.9%), but low adjusted sensitivity (36.0%). The adjusted sensitivity improved to 69.5% when codes in a secondary position were added. Only one adverse effect/poisoning code was used, appearing in 7.8% of cases and controls (PPV, 71.4% and adjusted sensitivity, 6.8%). CONCLUSIONS: Performance of ICD-10-CM code assignments for bleeding among patients prescribed anticoagulants varied by bleed type and code position. Adverse effect/poisoning codes were not commonly used and would have missed over 90% of anticoagulant-related bleeding cases.


Assuntos
Anticoagulantes/efeitos adversos , Grupos Diagnósticos Relacionados/normas , Hemorragia/epidemiologia , Pacientes Ambulatoriais , Adulto , Idoso , Idoso de 80 Anos ou mais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Hemorragia/induzido quimicamente , Hemorragia/diagnóstico , Humanos , Masculino , Medicare , Pessoa de Meia-Idade , Farmacoepidemiologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto Jovem
4.
Am J Prev Med ; 55(2): 244-252, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29910114

RESUMO

CONTEXT: Latent tuberculosis infection diagnosis and treatment is a strategic priority for eliminating tuberculosis in the U.S. The Centers for Disease Control and Prevention has recommended the short-course regimen of 3-month isoniazid-rifapentine administered by directly observed therapy. However, longer-duration regimens remain the most widely prescribed latent tuberculosis infection treatments. Limitation on adoption of 3-month isoniazid-rifapentine in the U.S. might be because of patients' preference for self-administered therapy, providers' lack of familiarity with 3-month isoniazid-rifapentine, or lack of resources to support directly observed therapy. This review examines the most recent evidence regarding 3-month isoniazid-rifapentine's effectiveness, safety, and treatment completion when directly compared with other latent tuberculosis infection regimens primarily comprising 9-month isoniazid treatment. EVIDENCE ACQUISITION: Using Community Guide methodology, reviewers identified, evaluated, and summarized available evidence published during January 2006-June 2017. Analysis of the data was completed in 2017. EVIDENCE SYNTHESIS: The analysis included 15 unique studies. Three-month isoniazid-rifapentine was determined to be equal to other latent tuberculosis infection regimens in effectiveness (OR=0.89, 95% CI=0.46, 1.70), and has higher treatment completion (87.5%, 95% CI=83.2%, 91.3%) compared with other latent tuberculosis infection regimens (65.9%, 95% CI=53.5%, 77.3%). Three-month isoniazid-rifapentine was associated with similar risk to other latent tuberculosis infection regimens for adverse events (relative risk=0.59, 95% CI=0.23, 1.52); discontinuing treatment because of adverse events (relative risk=0.48, 95% CI=0.17, 1.34); and death (relative risk=0.79, 95% CI=0.56, 1.11). CONCLUSIONS: The 3-month isoniazid-rifapentine regimen is as safe and effective as other recommended latent tuberculosis infection regimens and achieves significantly higher treatment completion rates.


Assuntos
Isoniazida/uso terapêutico , Tuberculose Latente/tratamento farmacológico , Rifampina/análogos & derivados , Terapia Diretamente Observada/métodos , Humanos , Rifampina/uso terapêutico , Fatores de Tempo , Estados Unidos
5.
Ann Am Thorac Soc ; 15(5): 570-580, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29393655

RESUMO

RATIONALE: Data are limited regarding the safety of 12-dose once-weekly isoniazid (H, 900 mg) plus rifapentine (P, 900 mg) (3HP) for latent infection treatment during pregnancy. OBJECTIVES: To assess safety and pregnancy outcomes among pregnant women who were inadvertently exposed to study medications in two latent tuberculosis infection trials (PREVENT TB or iAdhere) evaluating 3HP and 9 months of daily isoniazid (H, 300 mg) (9H). METHODS: Data from reproductive-age (15-51 yr) women who received one or more study dose of 3HP or 9H in either trial were analyzed. Drug exposure during pregnancy occurred if the estimated date of conception was on or before the last dose date. RESULTS: Of 126 pregnancies (125 participants) that occurred during treatment or follow-up, 87 were exposed to study drugs. Among these, fetal loss was reported for 4/31 (13%) and 8/56 (14%), 3HP and 9H, respectively (difference, 13% - 14% = -1%; 95% confidence interval = -17% to +18%) and congenital anomalies in 0/20 and 2/41 (5%) live births, 3HP and 9H, respectively (difference, 0% - 5% = -5%; 95% confidence interval = -18% to +16%). All fetal losses occurred in pregnancies of less than 20 weeks. Of the total 126 pregnancies, fetal loss was reported in 8/54 (15%) and 9/72 (13%), 3HP and 9H, respectively; and congenital anomalies in 1/37 (3%) and 2/56 (4%) live births, 3HP and 9H, respectively. The overall proportion of fetal loss (17/126 [13%]) and anomalies (3/93 [3%]) were similar to those estimated for the United States, 17% and 3%, respectively. CONCLUSIONS: Among reported pregnancies in these two latent tuberculosis infection trials, there was no unexpected fetal loss or congenital anomalies. These data offer some preliminary reassurance to clinicians and patients in circumstances when these drugs and regimens are the best option in pregnancy or in women of child-bearing potential. This work used the identifying trial registration numbers NCT00023452 and NCT01582711, corresponding to the primary clinical trials PREVENT TB and iAdhere (Tuberculosis Trials Consortium Study 26 and 33).


Assuntos
Isoniazida/administração & dosagem , Tuberculose Latente/tratamento farmacológico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Rifampina/análogos & derivados , Adolescente , Adulto , Antituberculosos/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Recém-Nascido , Pessoa de Meia-Idade , Gravidez , Resultado da Gravidez , Rifampina/administração & dosagem , Adulto Jovem
6.
Ann Intern Med ; 167(10): 689-697, 2017 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-29114781

RESUMO

Background: Expanding latent tuberculosis treatment is important to decrease active disease globally. Once-weekly isoniazid and rifapentine for 12 doses is effective but limited by requiring direct observation. Objective: To compare treatment completion and safety of once-weekly isoniazid and rifapentine by self-administration versus direct observation. Design: An open-label, phase 4 randomized clinical trial designed as a noninferiority study with a 15% margin. Seventy-five percent or more of study patients were enrolled from the United States for a prespecified subgroup analysis. (ClinicalTrials.gov: NCT01582711). Setting: Outpatient tuberculosis clinics in the United States, Spain, Hong Kong, and South Africa. Participants: 1002 adults (aged ≥18 years) recommended for treatment of latent tuberculosis infection. Intervention: Participants received once-weekly isoniazid and rifapentine by direct observation, self-administration with monthly monitoring, or self-administration with weekly text message reminders and monthly monitoring. Measurements: The primary outcome was treatment completion, defined as 11 or more doses within 16 weeks and measured using clinical documentation and pill counts for direct observation, and self-reports, pill counts, and medication event-monitoring devices for self-administration. The main secondary outcome was adverse events. Results: Median age was 36 years, 48% of participants were women, and 77% were enrolled at the U.S. sites. Treatment completion was 87.2% (95% CI, 83.1% to 90.5%) in the direct-observation group, 74.0% (CI, 68.9% to 78.6%) in the self-administration group, and 76.4% (CI, 71.3% to 80.8%) in the self-administration-with-reminders group. In the United States, treatment completion was 85.4% (CI, 80.4% to 89.4%), 77.9% (CI, 72.7% to 82.6%), and 76.7% (CI, 70.9% to 81.7%), respectively. Self-administered therapy without reminders was noninferior to direct observation in the United States; no other comparisons met noninferiority criteria. A few drug-related adverse events occurred and were similar across groups. Limitation: Persons with latent tuberculosis infection enrolled in South Africa would not routinely be treated programmatically. Conclusion: These results support using self-administered, once-weekly isoniazid and rifapentine to treat latent tuberculosis infection in the United States, and such treatment could be considered in similar settings when direct observation is not feasible. Primary Funding Source: Centers for Disease Control and Prevention.


Assuntos
Antituberculosos/administração & dosagem , Terapia Diretamente Observada , Isoniazida/administração & dosagem , Adesão à Medicação , Rifampina/análogos & derivados , Autoadministração , Adulto , Antibióticos Antituberculose/administração & dosagem , Antibióticos Antituberculose/efeitos adversos , Antituberculosos/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Isoniazida/efeitos adversos , Tuberculose Latente/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Sistemas de Alerta , Rifampina/administração & dosagem , Rifampina/efeitos adversos , Envio de Mensagens de Texto
7.
Clin Infect Dis ; 65(7): 1085-1093, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28575208

RESUMO

Background: Randomized controlled trials have demonstrated that the newest latent tuberculosis (LTBI) regimen, 12 weekly doses of directly observed isoniazid and rifapentine (3HP), is as efficacious as 9 months of isoniazid, with a greater completion rate (82% vs 69%); however, 3HP has not been assessed in routine healthcare settings. Methods: Observational cohort of LTBI patients receiving 3HP through 16 US programs was used to assess treatment completion, adverse drug reactions, and factors associated with treatment discontinuation. Results: Of 3288 patients eligible to complete 3HP, 2867 (87.2%) completed treatment. Children aged 2-17 years had the highest completion rate (94.5% [155/164]). Patients reporting homelessness had a completion rate of 81.2% (147/181). In univariable analyses, discontinuation was lowest among children (relative risk [RR], 0.44 [95% confidence interval {CI}, .23-.85]; P = .014), and highest in persons aged ≥65 years (RR, 1.72 [95% CI, 1.25-2.35]; P < .001). In multivariable analyses, discontinuation was lowest among contacts of patients with tuberculosis (TB) disease (adjusted RR [ARR], 0.68 [95% CI, .52-.89]; P = .005) and students (ARR, 0.45 [95% CI, .21-.98]; P = .044), and highest with incarceration (ARR, 1.43 [95% CI, 1.08-1.89]; P = .013) and homelessness (ARR, 1.72 [95% CI, 1.25-2.39]; P = .001). Adverse drug reactions were reported by 1174 (35.7%) patients, of whom 891 (76.0%) completed treatment. Conclusions: Completion of 3HP in routine healthcare settings was greater overall than rates reported from clinical trials, and greater than historically observed using other regimens among reportedly nonadherent populations. Widespread use of 3HP for LTBI treatment could accelerate elimination of TB disease in the United States.


Assuntos
Antibióticos Antituberculose/uso terapêutico , Antituberculosos/uso terapêutico , Isoniazida/uso terapêutico , Tuberculose Latente/tratamento farmacológico , Mycobacterium tuberculosis/efeitos dos fármacos , Rifampina/análogos & derivados , Adolescente , Adulto , Idoso , Antibióticos Antituberculose/efeitos adversos , Antituberculosos/efeitos adversos , Criança , Pré-Escolar , Esquema de Medicação , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Pessoas em Situação de Rua , Humanos , Isoniazida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Rifampina/efeitos adversos , Rifampina/uso terapêutico , Estudantes , Estados Unidos , Adulto Jovem
8.
Clin Infect Dis ; 62(11): 1390-1400, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-26951571

RESUMO

BACKGROUND: Overall rates of noncompletion of treatment (NCT) for latent tuberculosis infection (LTBI) in the PREVENT TB trial were 18% for 3 months of directly observed once-weekly rifapentine (maximum dose, 900 mg) plus isoniazid (maximum dose, 900 mg) (3HP-DOT) and 31% for 9 months of daily self-administered isoniazid (maximum dose, 300 mg; 9H-SAT). NCT for LTBI reduces its effectiveness. The study objective was to assess factors associated with NCT for LTBI among adult participants enrolled at US and Canadian sites of the PREVENT TB trial. METHODS: This was a post hoc exploratory analysis of the randomized, open-label PREVENT TB trial. Factors were analyzed by univariate and multivariate logistic regression (with enrollment site as a random effect). RESULTS: From 6232 participants analyzed, 1406 (22.6%) did not complete LTBI treatment (317 NCT attributed to an adverse event [NCT-AE] and 1089 NCT attributed to reasons other than an adverse event [NCT-O]). The proportion of NCT-AE was similar with both regimens (3HP-DOT = 6.4% vs 9H-SAT = 5.9%; P = .23); NCT-O was higher among participants enrolled in 9H-SAT (9H-SAT = 24.5% vs 3HP-DOT = 12.7%; P = .02). Among those in the NCT-AE group, being non-Hispanic and receiving 3HP-DOT, having cirrhosis and receiving 9H-SAT, alcohol consumption among men, and use of concomitant medication were associated with NCT-AE. Among those in the NCT-O group, receiving 9H-SAT, missing ≥1 early visit, men receiving 9H-SAT, men with a history of incarceration, alcohol abuse, use ever of intravenous drugs, younger age receiving 9H-SAT, and smoking were associated with NCT-O. CONCLUSIONS: Factors associated with NCT, such as missing a clinic visit early during treatment, might help identify persons for whom tailored interventions could improve completion of LTBI treatment. CLINICAL TRIALS REGISTRATION: NCT00023452.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/epidemiologia , Adesão à Medicação/estatística & dados numéricos , Adulto , Canadá/epidemiologia , Feminino , Humanos , Masculino , Estados Unidos/epidemiologia
9.
Clin Infect Dis ; 61(4): 527-35, 2015 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-25904367

RESUMO

BACKGROUND: Weekly rifapentine plus isoniazid for 3 months (3HP) is as effective as daily isoniazid for 9 months (9H) for latent tuberculosis infection in high-risk persons, but there have been reports of possible flu-like syndrome. METHODS: We identified clinically significant systemic drug reactions (SDR) and evaluated risk factors in patients who did not complete treatment in the PREVENT Tuberculosis study. RESULTS: Among 7552 persons who received ≥ 1 dose of study drug, 153 had a SDR: 138/3893 (3.5%) with 3HP vs 15/3659 (0.4%) with 9H (P < .001). In the 3HP arm, 87 (63%) had flu-like syndrome and 23 (17%) had cutaneous reactions; 13/3893 (0.3%) had severe reactions (6 were hypotensive) and 6 reported syncope. Symptoms occurred after a median of 3 doses, and 4 hours after the dose; median time to resolution was 24 hours. There were no deaths. In multivariate logistic regression analysis, factors independently associated with SDR included receipt of 3HP (adjusted odds ratio [aOR] 9.4; 95% confidence interval [CI], 5.5, 16.2), white non-Hispanic race/ethnicity (aOR 3.3; 95% CI, 2.3, 4.7), female sex (aOR 2.0; 95% CI, 1.4, 2.9), age ≥ 35 years (aOR 2.0; 95% CI, 1.4, 2.9), and lower body mass index (body mass index [BMI]; P = .009). In a separate multivariate analysis among persons who received 3HP, severe SDR were associated with white non-Hispanic race/ethnicity (aOR 5.4; 95% CI, 1.8, 16.3), and receipt of concomitant non-study medications (aOR 5.9; 95% CI, 1.3, 27.1). CONCLUSIONS: SDR were more common with 3HP, and mostly flu-like. Persons of white race, female sex, older age, and lower BMI were at increased risk. Severe reactions were rare and associated with 3HP, concomitant medication, and white race. The underlying mechanism is unclear. CLINICAL TRIALS REGISTRATION: NCT00023452.


Assuntos
Antituberculosos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Isoniazida/efeitos adversos , Tuberculose Latente/tratamento farmacológico , Doenças Respiratórias/induzido quimicamente , Doenças Respiratórias/patologia , Rifampina/análogos & derivados , Adolescente , Adulto , Antituberculosos/administração & dosagem , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Isoniazida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doenças Respiratórias/epidemiologia , Rifampina/administração & dosagem , Rifampina/efeitos adversos
10.
JAMA Pediatr ; 169(3): 247-55, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25580725

RESUMO

IMPORTANCE: Three months of a once-weekly combination of rifapentine and isoniazid for treatment of latent tuberculosis infection is safe and effective for persons 12 years or older. Published data for children are limited. OBJECTIVES: To compare treatment safety and assess noninferiority treatment effectiveness of combination therapy with rifapentine and isoniazid vs 9 months of isoniazid treatment for latent tuberculosis infection in children. DESIGN, SETTING, AND PARTICIPANTS: A pediatric cohort nested within a randomized, open-label clinical trial conducted from June 11, 2001, through December 17, 2010, with follow-up through September 5, 2013, in 29 study sites in the United States, Canada, Brazil, Hong Kong (China), and Spain. Participants were children (aged 2-17 years) who were eligible for treatment of latent tuberculosis infection. INTERVENTIONS: Twelve once-weekly doses of the combination drugs, given with supervision by a health care professional, for 3 months vs 270 daily doses of isoniazid, without supervision by a health care professional, for 9 months. MAIN OUTCOMES AND MEASURES: We compared rates of treatment discontinuation because of adverse events (AEs), toxicity grades 1 to 4, and deaths from any cause. The equivalence margin for the comparison of AE-related discontinuation rates was 5%. Tuberculosis disease diagnosed within 33 months of enrollment was the main end point for testing effectiveness. The noninferiority margin was 0.75%. RESULTS: Of 1058 children enrolled, 905 were eligible for evaluation of effectiveness. Of 471 in the combination-therapy group, 415 (88.1%) completed treatment vs 351 of 434 (80.9%) in the isoniazid-only group (P = .003). The 95% CI for the difference in rates of discontinuation attributed to an AE was -2.6 to 0.1, which was within the equivalence range. In the safety population, 3 of 539 participants (0.6%) who took the combination drugs had a grade 3 AE vs 1 of 493 (0.2%) who received isoniazid only. Neither arm had any hepatotoxicity, grade 4 AEs, or treatment-attributed death. None of the 471 in the combination-therapy group developed tuberculosis vs 3 of 434 (cumulative rate, 0.74%) in the isoniazid-only group, for a difference of -0.74% and an upper bound of the 95% CI of the difference of +0.32%, which met the noninferiority criterion. CONCLUSIONS AND RELEVANCE: Treatment with the combination of rifapentine and isoniazid was as effective as isoniazid-only treatment for the prevention of tuberculosis in children aged 2 to 17 years. The combination-therapy group had a higher treatment completion rate than did the isoniazid-only group and was safe. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00023452.


Assuntos
Antituberculosos/uso terapêutico , Isoniazida/uso terapêutico , Tuberculose Latente/prevenção & controle , Rifampina/análogos & derivados , Adolescente , Antituberculosos/administração & dosagem , Antituberculosos/efeitos adversos , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Humanos , Isoniazida/administração & dosagem , Isoniazida/efeitos adversos , Masculino , Rifampina/administração & dosagem , Rifampina/efeitos adversos , Rifampina/uso terapêutico , Resultado do Tratamento
11.
Am J Respir Crit Care Med ; 191(3): 333-43, 2015 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-25489785

RESUMO

RATIONALE: Rifapentine has potent activity in mouse models of tuberculosis chemotherapy but its optimal dose and exposure in humans are unknown. OBJECTIVES: We conducted a randomized, partially blinded dose-ranging study to determine tolerability, safety, and antimicrobial activity of daily rifapentine for pulmonary tuberculosis treatment. METHODS: Adults with sputum smear-positive pulmonary tuberculosis were assigned rifapentine 10, 15, or 20 mg/kg or rifampin 10 mg/kg daily for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. The primary tolerability end point was treatment discontinuation. The primary efficacy end point was negative sputum cultures at completion of intensive phase. MEASUREMENTS AND MAIN RESULTS: A total of 334 participants were enrolled. At completion of intensive phase, cultures on solid media were negative in 81.3% of participants in the rifampin group versus 92.5% (P = 0.097), 89.4% (P = 0.29), and 94.7% (P = 0.049) in the rifapentine 10, 15, and 20 mg/kg groups. Liquid cultures were negative in 56.3% (rifampin group) versus 74.6% (P = 0.042), 69.7% (P = 0.16), and 82.5% (P = 0.004), respectively. Compared with the rifampin group, the proportion negative at the end of intensive phase was higher among rifapentine recipients who had high rifapentine areas under the concentration-time curve. Percentages of participants discontinuing assigned treatment for reasons other than microbiologic ineligibility were similar across groups (rifampin, 8.2%; rifapentine 10, 15, or 20 mg/kg, 3.4, 2.5, and 7.4%, respectively). CONCLUSIONS: Daily rifapentine was well-tolerated and safe. High rifapentine exposures were associated with high levels of sputum sterilization at completion of intensive phase. Further studies are warranted to determine if regimens that deliver high rifapentine exposures can shorten treatment duration to less than 6 months. Clinical trial registered with www.clinicaltrials.gov (NCT 00694629).


Assuntos
Antibióticos Antituberculose/administração & dosagem , Rifampina/análogos & derivados , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , África , Idoso , Antituberculosos/administração & dosagem , Ásia , Esquema de Medicação , Quimioterapia Combinada , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , América do Norte , Rifampina/administração & dosagem , Método Simples-Cego , América do Sul , Resultado do Tratamento
12.
PLoS Negl Trop Dis ; 5(4): e1034, 2011 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-21532747

RESUMO

BACKGROUND: Foreign-born, HIV-infected persons are at risk for sub-clinical parasitic infections acquired in their countries of origin. The long-term consequences of co-infections can be severe, yet few data exist on parasitic infection prevalence in this population. METHODOLOGY/PRINCIPAL FINDINGS: This cross-sectional study evaluated 128 foreign-born persons at one HIV clinic. We performed stool studies and serologic testing for strongyloidiasis, schistosomiasis, filarial infection, and Chagas disease based on the patient's country of birth. Eosinophilia and symptoms were examined as predictors of helminthic infection. Of the 128 participants, 86 (67%) were male, and the median age was 40 years; 70 were Mexican/Latin American, 40 African, and 18 from other countries or regions. Strongyloides stercoralis antibodies were detected in 33/128 (26%) individuals. Of the 52 persons from schistosomiasis-endemic countries, 15 (29%) had antibodies to schistosome antigens; 7 (47%) had antibodies to S. haematobium, 5 (33%) to S. mansoni, and 3 (20%) to both species. Stool ova and parasite studies detected helminths in 5/85 (6%) persons. None of the patients tested had evidence of Chagas disease (n = 77) or filarial infection (n = 52). Eosinophilia >400 cells/mm(3) was associated with a positive schistosome antibody test (OR 4.5, 95% CI 1.1-19.0). The only symptom significantly associated with strongyloidiasis was weight loss (OR 3.1, 95% CI 1.4-7.2). CONCLUSIONS/SIGNIFICANCE: Given the high prevalence of certain helminths and the potential lack of suggestive symptoms and signs, selected screening for strongyloidiasis and schistosomiasis or use of empiric antiparasitic therapy may be appropriate among foreign-born, HIV-infected patients. Identifying and treating helminth infections could prevent long-term complications.


Assuntos
Emigrantes e Imigrantes , Infecções por HIV/complicações , Doenças Parasitárias/epidemiologia , Adulto , Animais , Sangue/imunologia , Estudos Transversais , Fezes/parasitologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estados Unidos/epidemiologia
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