A Phase 2 Randomized Trial of a Rifapentine plus Moxifloxacin-Based Regimen for Treatment of Pulmonary Tuberculosis.

BACKGROUND: The combination of rifapentine and moxifloxacin administered daily with other anti-tuberculosis drugs is highly active in mouse models of tuberculosis chemotherapy. The objective of this phase 2 clinical trial was to determine the bactericidal activity, safety, and tolerability of a regimen comprised of rifapentine, moxifloxacin, isoniazid, and pyrazinamide administered daily during the first 8 weeks of pulmonary tuberculosis treatment. METHODS: Adults with sputum smear-positive pulmonary tuberculosis were randomized to receive either rifapentine (approximately 7.5 mg/kg) plus moxifloxacin (investigational arm), or rifampin (approximately 10 mg/kg) plus ethambutol (control) daily for 8 weeks, along with isoniazid and pyrazinamide. The primary endpoint was sputum culture status at completion of 8 weeks of treatment. RESULTS: 121 participants (56% of accrual target) were enrolled. At completion of 8 weeks of treatment, negative cultures using Löwenstein-Jensen (LJ) medium occurred in 47/60 (78%) participants in the investigational arm vs. 43/51 (84%, p = 0.47) in the control arm; negative cultures using liquid medium occurred in 37/47 (79%) in the investigational arm vs. 27/41 (66%, p = 0.23) in the control arm. Time to stable culture conversion was shorter for the investigational arm vs. the control arm using liquid culture medium (p = 0.03), but there was no difference using LJ medium. Median rifapentine area under the concentration-time curve (AUC0-24) was 313 mcg*h/mL, similar to recent studies of rifapentine dosed at 450-600 mg daily. Median moxifloxacin AUC0-24 was 28.0 mcg*h/mL, much lower than in trials where rifapentine was given only intermittently with moxifloxacin. The proportion of participants discontinuing assigned treatment for reasons other than microbiological ineligibility was higher in the investigational arm vs. the control arm (11/62 [18%] vs. 3/59 [5%], p = 0.04) although the proportions of grade 3 or higher adverse events were similar (5/62 [8%] in the investigational arm vs. 6/59 [10%, p = 0.76] in the control arm). CONCLUSION: For intensive phase daily tuberculosis treatment in combination with isoniazid and pyrazinamide, a regimen containing moxifloxacin plus low dose rifapentine was at least as bactericidal as the control regimen containing ethambutol plus standard dose rifampin. TRIAL REGISTRATION: www.ClinicalTrials.gov NCT00728507.

Understanding and retention of trial-related information among participants in a clinical trial after completing the informed consent process.

BACKGROUND METHODS: for assessing the level of understanding of trial-related information during the informed consent (IC) process in developing countries are lacking. PURPOSE: To assess the understanding and retention of trial-related information presented in the IC process by administering an informed consent assessment instrument (ICAI) to participants in a clinical trial for a new tuberculosis (TB) regimen being conducted in Rio de Janeiro (Brazil). Methods The format of the ICAI was based on the language and structure of the United States National Cancer Institute's IC comprehension checklist. The ICAI was designed to assess points of the RioMAR study IC process that addressed the principles of research ethics requested by Brazilian Regulatory Authority: autonomy, beneficence, non-maleficence, and justice. Briefly, (1) Is the respondent participating in a clinical trial? (2) Are two different treatments being evaluated? (3) Is the treatment arm chosen by chance? (4) Is an HIV test required? (5) Are liver function tests required? (6) Can participants leave the study at any time? (7) Are the risks and benefits of taking part in the study clear? (8) May pregnant women participate in the study? (9) Can one of the study drugs reduce the effectiveness of contraceptives? (10) Are patients paid to participate in the study? The ICAI was applied at two time points: immediately after enrollment in the clinical trial and 2 months later. RESULTS: A total of 61 patients who enrolled in the RioMAR study participated in this study. The percentage of correct answers to all questions was 82% at the time of the first ICAI; 31 participants (51%) did not recall that an HIV test was required (question 4) and 43 (70%) did not know that they could leave the study (question 6). Other individual questions were answered correctly by at least 76% of participants. There was no association between incorrect answers and age, gender, monthly family income, neighborhood, or level of education (p > 0.07). When the responses to the first and the second ICAI questions were compared, 15% or more of participants had conflicting answers to 5 of the 10 questions. LIMITATIONS: The ICAI uses dichotomous responses, leading to a 50% chance of guessing the correct answers. Two questions were asked only of women. Finally, only 6 of the 10 questions on the current version of the ICAI apply to most trials; others are trial-specific. CONCLUSIONS: The ICAI may be adapted to an individual trial and may prove to be a useful tool following a consent discussion to identify issues not fully understood by the research participants, thus prompting study staff to re-explain topics, possibly in a more elementary manner.

Vital capacity and inspiratory capacity as additional parameters to evaluate bronchodilator response in asthmatic patients: a cross sectional study.

BACKGROUND: Bronchodilator response in patients with asthma is evaluated based on post-bronchodilator increase in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). However, the need for additional parameters, mainly among patients with severe asthma, has already been demonstrated. METHODS: The aim of this study was to evaluate the usefulness of vital capacity (VC) and inspiratory capacity (IC) to evaluate bronchodilator response in asthma patients with persistent airflow obstruction. The 43 asthma patients enrolled in the study were stratified into moderate or severe airflow obstruction groups based on baseline FEV1. All patients performed a 6-minute walk test before and after the bronchodilator (BD). A bipolar visual analogue scale post-BD was performed to assess clinical effect. The correlation between VC and IC and clinical response, determined by visual analogue scale (VAS) and 6-minute walk test (6MWT), was investigated. RESULTS: Patients in the severe group presented: 1) greater bronchodilator response in VC (48% vs 15%, p = 0.02), 2) a significant correlation between VC variation and the reduction in air trapping (Rs = 0.70; p < 0.01), 3) a significant agreement between VC and VAS score (kappa = 0.57; p < 0.01). There was no correlation between IC and the reduction in air trapping or clinical data. CONCLUSIONS: VC may be a useful additional parameter to evaluate bronchodilator response in asthma patients with severe airflow obstruction.

Evaluation of real-time PCR of patient pleural effusion for diagnosis of tuberculosis.

BACKGROUND: Pleural tuberculosis (TB) diagnosis often requires invasive procedures such as pleural biopsy. The aim of this study was to evaluate the role of real-time polymerase chain reaction (PCR) for the IS6110 sequence of M. tuberculosis in pleural fluid specimens as a rapid and non-invasive test for pleural TB diagnosis. FINDINGS: For this cross-sectional study, 150 consecutive patients with pleural effusion diagnosed by chest radiography, who were referred for diagnostic thoracocentesis and pleural biopsy and met eligibility criteria, had a pleural fluid specimen submitted for real-time PCR testing. Overall, 98 patients had pleural TB and 52 had pleural effusion secondary to other disease. TB diagnosis was obtained using acid-fast bacilli (AFB) smear or culture for mycobacteria and/or histopathologic examination in 94 cases and by clinical findings in 4 cases. Sensitivity, specificity, positive and negative predictive values of PCR testing for pleural TB diagnosis were 42.8% (95% CI 38.4 - 44.8), 94.2% (95% CI 85.8 - 98.0), 93.3% (95% CI 83.6 - 97.7), and 48.5% (95% CI 44.2 - 50.4), respectively. The real-time PCR test improved TB detection from 30.6% to 42.9% when compared to AFB smear and culture methods performed on pleural fluid specimens, although the best sensitivity was achieved by combining the results of culture and histopathology of pleural tissue specimens. CONCLUSION: The real-time PCR test of pleural fluid specimens is a useful and non-invasive additional assay for fast diagnosis of pleural TB.

New regimens for reducing the duration of the treatment of drug-susceptible pulmonary tuberculosis.

Tuberculosis (TB) remains an important health problem worlwide. The structure necessary for delivering TB treatment and implementing the directly observed treatment accounts for more than two-thirds of its final cost. Furthemore, although with efficacy greater than 90%, the effectiveness of present treatment regimens ranges from 55-85%, depending on the setting, mainly due to poor adherence. Duration of treatment with the current first-line anti-TB drugs is a minimum of 6 months. Reducing the duration of the treatment from six to two months or less could result in significant increase of adherence to treatment and cost reduction. The aim of this review is to highlight potential new agents or new drug combinations that could reduce the time of treatment of drug-susceptible TB, currently under study or recently evaluated through clinical trials. We conducted a literature search in the English language for clinical studies as well as an electronic computer-assisted and manual search. The literature search was conducted on November 2010, using MEDLINE (2000-2010), EMBASE (2000-2010) and the National Institute of Health (NIH) Clinical Trials Register database (2000-2010). Most of the new agents identified as anti-TB drug candidates are still in the preclinical phases. Nitroimidazole-PA-824 and fluoroquinolones are evaluated while two first line drugs - rifampicin and rifapentine -are re-evaluated to optimize their efficacy in new ultra-short anti-TB regimens through phases II/III clinical studies. A summary of the studies are presented, with their potential to change recommendations for TB treatment in the near future.

Effect of continuous positive airway pressure on fluid absorption among patients with pleural effusion due to tuberculosis.

BACKGROUND: Tuberculosis (TB) remains as an important public health problem worldwide. The most common type is pulmonary TB, and the most prevalent form of extra-pulmonary disease among HIV-negative patients is pleural disease. OBJECTIVE: The objective of the present study was to determine the effect of continuous positive airway pressure (CPAP) on fluid absorption among patients with pleural effusion due to TB. METHODS: Twenty patients were randomized into two groups. The interventional group (n=10) received CPAP three times a week during the initial four weeks of anti-TB treatment, and the control group (n=10) received anti-TB drugs only. The primary endpoint was the volume of pleural fluid after four weeks of treatment. Both groups were submitted to thoracic computed tomography using three-dimensional image reconstruction. The Mann-Whitney test for independent samples and the Wilcoxon paired samples test were used for statistical analysis. The normal distribution samples were analyzed using the unpaired t test. RESULTS: The reduction of pleural effusion volume was significantly greater in the intervention group (83.5%+/-SD 3.6) than in the control group (36.9%+/-SD 2.9; p<0.001), and the final dyspnea index was lower in the Intervention group than in the control group (p=0.002). CONCLUSION: Our findings indicate that CPAP during the first month of TB treatment accelerates the absorption of pleural effusion, however, additional studies are needed to confirm these findings and evaluate the impact of CPAP on pleural sequelae after the end of anti-TB treatment. Article registered in the Clinical Trials under the number NCT00560521.

Effect of continuous positive airway pressure on fluid absorption among patients with pleural effusion due to tuberculosis / Efeito da pressão positiva nas vias aéreas sobre a absorção do derrame pleural em pacientes devido à tuberculose

BACKGROUND: Tuberculosis (TB) remains as an important public health problem worldwide. The most common type is pulmonary TB, and the most prevalent form of extra-pulmonary disease among HIV-negative patients is pleural disease. OBJECTIVE: The objective of the present study was to determine the effect of continuous positive airway pressure (CPAP) on fluid absorption among patients with pleural effusion due to TB. METHODS: Twenty patients were randomized into two groups. The interventional group (n=10) received CPAP three times a week during the initial four weeks of anti-TB treatment, and the control group (n=10) received anti-TB drugs only. The primary endpoint was the volume of pleural fluid after four weeks of treatment. Both groups were submitted to thoracic computed tomography using three-dimensional image reconstruction. The Mann-Whitney test for independent samples and the Wilcoxon paired samples test were used for statistical analysis. The normal distribution samples were analyzed using the unpaired t test. RESULTS: The reduction of pleural effusion volume was significantly greater in the intervention group (83.5 percent±SD 3.6) than in the control group (36.9 percent±SD 2.9; p<0.001), and the final dyspnea index was lower in the Intervention group than in the control group (p=0.002). CONCLUSION: Our findings indicate that CPAP during the first month of TB treatment accelerates the absorption of pleural effusion, however, additional studies are needed to confirm these findings and evaluate the impact of CPAP on pleural sequelae after the end of anti-TB treatment.

CONTEXTUALIZAÇÃO: A tuberculose (TB) permanece como um importante problema de saúde pública no mundo. A forma mais comum de apresentação é a pulmonar e, em pacientes soronegativos, a forma de doença extrapulmonar mais prevalente é a pleural. OBJETIVO: O objetivo deste estudo foi determinar o efeito da pressão positiva contínua em vias aéreas (CPAP) na absorção do derrame pleural em pacientes com tuberculose. MÉTODOS: Vinte pacientes foram randomizados em dois grupos. O grupo intervenção (n=10) recebeu CPAP três vezes por semana durante as quatro primeiras semanas do tratamento anti-TB, e o grupo controle (n=10) recebeu somente droga anti-TB. O ponto final de avaliação foi o volume de líquido pleural após quatro semanas de tratamento. Ambos os grupos foram submetidos à tomografia computadorizada, usando a reconstrução tridimensional (3D) da imagem. A análise estatística foi realizada por meio do teste de Mann-Whitney para amostras independentes e Wilcoxon para amostras pareadas, e as que apresentaram distribuição normal foram analisadas por meio do teste t de Student não pareado. RESULTADOS: A redução do volume de derrame pleural foi significativamente maior no grupo intervenção (83,5 por cento±DP 3,6) que no grupo controle (36,9 por cento±DP 2,9) (p<0,001), e o índice de dispnéia final foi menor no grupo CPAP que no grupo controle (p=0,002). CONCLUSÃO: Tais achados indicam que a CPAP, durante o primeiro mês de tratamento anti-TB, acelera a absorção do derrame pleural, no entanto estudos adicionais são necessários para confirmar estes achados e avaliar o impacto da CPAP na sequela pleural após o término do tratamento anti-TB.

Point-of-care Arkansas method for measuring adherence to treatment with isoniazid.

We evaluated the accuracy of a point-of-care test designed to measure adherence to isoniazid (INH) preventive therapy in a hospital setting in Rio de Janeiro, Brazil. Patients on treatment with daily INH and patients not receiving INH were included. Sensitivity and specificity of the test were 84%/98% at the first minute, and 95%/98% at the fifth minute, respectively. Among smokers, sensitivity and specificity was reduced (80%/89% at the fifth minute, respectively), but only 17% smoked. This test accurately detected INH metabolites 24h following directly observed INH intake, though sensitivity and specificity may be compromised by tobacco smoke exposure.

Prolonged recruitment manoeuvre improves lung function with less ultrastructural damage in experimental mild acute lung injury.

The effects of prolonged recruitment manoeuvre (PRM) were compared with sustained inflation (SI) in paraquat-induced mild acute lung injury (ALI) in rats. Twenty-four hours after ALI induction, rats were anesthetized and mechanically ventilated with VT=6 ml/kg and positive end-expiratory pressure (PEEP)=5 cmH(2)O for 1h. SI was performed with an instantaneous pressure increase of 40 cmH(2)O that was sustained for 40s, while PRM was done by a step-wise increase in positive inspiratory pressure (PIP) of 15-20-25 cmH(2)O above a PEEP of 15 cm H(2)O (maximal PIP=40 cmH(2)O), with interposed periods of PIP=10 cmH(2)O above a PEEP=15 cmH(2)O. Lung static elastance and the amount of alveolar collapse were more reduced with PRM than SI, yielding improved oxygenation. Additionally, tumour necrosis factor-alpha, interleukin-6, interferon-gamma, and type III procollagen mRNA expressions in lung tissue and lung epithelial cell apoptosis decreased more in PRM. In conclusion, PRM improved lung function, with less damage to alveolar epithelium, resulting in reduced pulmonary injury.

Moxifloxacin versus ethambutol in the initial treatment of tuberculosis: a double-blind, randomised, controlled phase II trial.

BACKGROUND: New treatments are needed to shorten the time required to cure tuberculosis and to treat drug-resistant strains. The fluoroquinolone moxifloxacin is a promising new agent that might have additive activity to existing antituberculosis agents. We assessed the activity and safety of moxifloxacin in the initial stage of tuberculosis treatment. METHODS: We undertook a phase II, double-blind, randomised controlled trial of a regimen that included moxifloxacin in adults with sputum smear-positive tuberculosis at one hospital in Rio de Janeiro, Brazil. 170 participants received isoniazid, rifampicin, and pyrazinamide at standard doses and were assigned by permuted block randomisation to receive either moxifloxacin (400 mg) with an ethambutol placebo (n=85) or ethambutol (15-20 mg/kg) plus moxifloxacin placebo (n=85) 5 days per week for 8 weeks. The primary endpoint was the proportion of patients whose sputum culture had converted to negative by week 8. Analysis was by modified intention to treat (ITT); patients whose baseline cultures were negative, contaminated, or contained drug-resistant Mycobacterium tuberculosis were excluded from the analysis. Additionally, all missing 8-week results were deemed treatment failures. This study is registered with ClinicalTrials.gov, number NCT00082173. FINDINGS: 74 patients assigned to the moxifloxacin group and 72 in the ethambutol group were included in the modified ITT population. 125 patients had 8-week data (moxifloxacin n=64, ethambutol n=61); the main reason for absence of data was culture contamination. At 8 weeks, culture conversion to negative had occurred in 59 (80%) of 74 patients in the moxifloxacin group compared with 45 (63%) of 72 in the ethambutol group (difference 17.2%, 95% CI 2.8-31.7; p=0.03). There were 16 adverse events (eight in each group) in 12 patients. Only one event was judged related to study drug (grade 3 cutaneous reaction in the ethambutol group). INTERPRETATION: Moxifloxacin improved culture conversion in the initial phase of tuberculosis treatment. Trials to assess whether moxifloxacin can be used to shorten the duration of tuberculosis treatment are justified.

T-SPOT.TB responses during treatment of pulmonary tuberculosis.

BACKGROUND: Immune responses to Mycobacterium tuberculosis antigens could serve as surrogate markers of treatment response. METHODS: Using the T-SPOT.TB assay and frozen peripheral blood mononuclear cells, we enumerated ESAT-6- and CFP-10-specific IFN-gamma-producing T cells over time in pulmonary TB patients receiving directly observed treatment. T cell responses (measured as "spot forming cells" or "SFCs") were assessed prior to treatment and at 16 and 24 weeks of treatment. RESULTS: 58 patients were evaluated, of whom 57 were HIV seronegative. Mean (SD) ESAT-6, CFP-10, and summed RD1 specific SFCs declined from 42.7 (72.7), 41.2 (66.4), and 83.8 (105.7) at baseline to 23.3 (39.4, p = 0.01), 23.2 (29.4, p = 0.18), and 46.5 (59.5, p = 0.02) at completion of 24 weeks of treatment, respectively. Only 10% of individuals with a baseline reactive test reverted to negative at treatment week 24. For the group that was culture positive at completion of 8 weeks of treatment compared to the culture negative group, the incidence rate ratio (IRR) of ESAT-6, CFP-10, and summed RD1 specific SFC counts were, respectively, 2.23 (p = 0.048), 1.51 (p = 0.20), and 1.83 (p = 0.047). Patients with cavitary disease had mean ESAT-6 specific SFC counts that were higher than those without cavitary disease (IRR 2.08, p = 0.034). CONCLUSION: IFN-gamma-producing RD1-specific T cells, as measured in the T-SPOT.TB assay, may be directly related to bacterial load in patients undergoing treatment for pulmonary TB. However, high inter-subject variability in quantitative results coupled with failure of reversion to negative of qualitative results in most subjects at treatment completion may limit the utility of this assay as a surrogate marker for treatment efficacy.

The presence of a booster phenomenon among contacts of active pulmonary tuberculosis cases: a retrospective cohort.

BACKGROUND: Assuming a higher risk of latent tuberculosis (TB) infection in the population of Rio de Janeiro, Brazil, in October of 1998 the TB Control Program of Clementino Fraga Filho Hospital (CFFH) routinely started to recommend a two-step tuberculin skin test (TST) in contacts of pulmonary TB cases in order to distinguish a boosting reaction due to a recall of delayed hypersensitivity previously established by infection with Mycobacterium tuberculosis (M.tb) or BCG vaccination from a tuberculin conversion. The aim of this study was to assess the prevalence of boosted tuberculin skin tests among contacts of individuals with active pulmonary tuberculosis (TB). METHODS: Retrospective cohort of TB contacts > or = 12 years old who were evaluated between October 1st, 1998 and October 31st 2001. Contacts with an initial TST < or = 4 mm were considered negative and had a second TST applied after 7-14 days. Boosting reaction was defined as a second TST > or = 10 mm with an increase in induration > or = 6 mm related to the first TST. All contacts with either a positive initial or repeat TST had a chest x-ray to rule out active TB disease, and initially positive contacts were offered isoniazid preventive therapy. Contacts that boosted did not receive treatment for latent TB infection and were followed for 24 months to monitor the development of TB. Statistical analysis of dichotomous variables was performed using Chi-square test. Differences were considered significant at a p < 0.05. RESULTS: Fifty four percent (572/1060) of contacts had an initial negative TST and 79% of them (455/572) had a second TST. Boosting was identified in 6% (28/455). The mean age of contacts with a boosting reaction was 42.3 +/- 21.1 and with no boosting was 28.7 +/- 21.7 (p = 0.01). Fifty percent (14/28) of individuals whose test boosted met criteria for TST conversion on the second TST (increase in induration > or = 10 mm). None of the 28 contacts whose reaction boosted developed TB disease within two years following the TST. CONCLUSION: The low number of contacts with boosting and the difficulty in distinguishing boosting from TST conversion in the second TST suggests that the strategy of two-step TST testing among contacts of active TB cases may not be useful. However, this conclusion must be taken with caution because of the small number of subjects followed.

Immunoglobulin A (IgA) and IgG immune responses against P-90 antigen for diagnosis of pulmonary tuberculosis and screening for Mycobacterium tuberculosis infection.

The purpose of the present study was to evaluate the usefulness of detection of serum immunoglobulin A (IgA) and IgG antibodies directed against the mycobacterial P-90 antigen for the diagnosis of active pulmonary tuberculosis (PTB) among symptomatic individuals and for the detection of Mycobacterium tuberculosis infections among close contacts of PTB patients. Two commercially available enzyme immunoassay (EIA) kits (IgA EIA-TB [EIA-IgA] and IgG EIA-TB [EIA-IgG]; Kreatech Diagnostics) were evaluated in a blinded fashion by using stored serum samples from 268 individuals, including 69 patients with PTB, 41 patients with diseases other than tuberculosis (TB), 12 subjects with healed PTB, 39 close contacts of PTB patients, and 107 healthy volunteers. For the EIA-IgA, the sensitivity was 74% and the specificity was 68% when a cutoff determined by a receiver operator characteristic curve was used. For the EIA-IgG, the sensitivity was 69% and the specificity was 64%. The EIA-IgA was positive for 54% of healthy close contacts of PTB patients but only 8% of healthy controls without contact with a PTB patient or a prior personal history of TB (P < 0.001). The relatively low sensitivities and specificities of these serologic tests make them poor tools for the diagnosis of PTB among patients with suspected PTB. However, the relatively high prevalence of positive EIA-IgA results among healthy close contacts of PTB patients warrants further evaluation of this test with close contacts and other populations at risk for recent M. tuberculosis exposure and development of disease.

Yield of sputum induction in the diagnosis of pleural tuberculosis.

We prospectively evaluated the diagnostic yield of acid-fast bacilli smear and culture for Mycobacterium tuberculosis using sputum induction (SI) in the workup of patients with suspected pleural tuberculosis (TB) who were unable to produce sputum spontaneously. Of the 113 patients studied, a final diagnosis of pleural TB was made in 84 patients (71 HIV seronegative) and a final diagnosis of another disease in 29 patients. Histopathologic examination of the pleural biopsy tissue had the highest diagnostic yield (78%; 66/84). The bacteriologic yield was 62% (52/84) for the pleural tissue, 12% (10/84) for pleural fluid, and 52% (44/84) for sputum cultures obtained by SI. The yield of SI culture for M. tuberculosis was 55% (35/64) in patients with a normal radiograph (except for the pleural effusion) and 45% (9/20) in those with evidence of parenchymal disease suggestive of pulmonary TB (p = 0.6). The yield of sputum cultures obtained by SI is high in patients suspected of having pleural TB even in those cases with no pulmonary parenchymal abnormalities on the chest radiograph.

Taxa de abandono do tratamento antituberculose / Non-adherence rate of anti-tuberculosis treatment

Introdução: São raros os estudos sobre os fatores associados à ocorrência do abandono do tratamento antituberculose (TB) em pacientes atendidos em hospitais nos países em desenvolvimento, aonde, usualmente, inexistem atividades de controle de TB. Objetivos: Identificar fatores associados à ocorrência de abandono do tratamento anti-TB em pacientes atendidos num hospital geral, referência para AIDS. Desenho: estudo caso-controle. Métodos: os pacientes que iniciaram tratamento anti-TB, no período de 01 de janeiro a 31 de dezembro de 1997, foram considerados ilegíveis. Paciente caso foi definido como o indivíduo que não retornou para receber medicação decorridos 60 dias depois de sua última consulta médica. Análise logística condicional foi utilizada para identificar as características que, independentemente, estavam associadas à ocorrência de abandono do tratamento. Resultados: 228 pacientes foram registrados como TB no período. Após a revisão dos prontuários médicos e visita em 189 domicílios, o abandono do tratamento, de 28,9%, baixou para 20,2%. Na análise multivariada, os fatores associados ao abandono foram: a) não fornecimento de cartão retorno (OR =0.099; IC 0.008-1.2; p = 0.07), b) não sentir-se a vontade na consulta médica (OR = 0,16; IC 0.33 - 0.015; p = 0.001) e, c) pressão arterial não foi medida (OR = 0.072; IC 0.036-0,79; p= 0.024). Comentários: Provavelmente, em hospitais gerais na cidade do Rio de Janeiro, torna-se necessária a implementação de programas de controle de TB. Tais programas devem utilizar estratégias específicas para o tipo de paciente atendido visando menores taxas de abandono e de morbi/mortalidade.

Efeitos adversos hepáticos durante o tratamento para tuberculose em hospital geral referência para Aids, Rj, Brasil / Hepatic adverse efects anti-tuberculosis tratment in a geral hospital, Rio de Janeiro, Brasil

Introdução: a frequência de efeitos adversos hepáticos e os fatores associados com a sua ocorrência em um hospital universitário referência para Aids e tuberculose não é completamente conhecida. Métodos: foi realizado um estudo tipo caso-controle com o objetivo de medir prevalência de efeitos hepáticos adversos (EAH) em pacientes sob tratamento medicamentoso anti-tuberculose (TB) e de fatores associados à sua ocorrência. Resultados: foram analisados 588 prontuários médicos de pacientes que fizeram uso de esquema anti-TB com isoniazida, rifampicina e pirazinamida, acrescido ou não de etambutol, atendidos no período de Janeiro de 1994 a dezembro de 1995. EAH foi observado em 40 (6,8%) casos. Foram pareados 200 casos para o grupo controle. Na análise univariada dos grupos caso e controle não houve diferença estatisticamente significativa entre a ocorrência de EAH e os seguintes parâmetros: a idade, gênero esquema inicial de tratamento anti-TB, a história prévia de hepatopatia e/ou presença de alcoolismo. Entretanto, a ocorrência de EAH esteve significamente associada a hospitalização no momento do diagnóstico da TB, a presença de síndrome de imunodeficiência adquirida (SIDA/AIDS), a forma disseminada da TB, a apresentação radiográfica atípica da TB pulmonar, a sorologia positiva para hepatite a vírus B e/ou C, e a evolução clínica desfavorável ou tratamento. Na análise multivariada, somente a hospitalização e o diagnóstico de SIDA permaneceram associados significantemente a EAH. Conclusões: em um hospital Universitário, referência para AIDS e TB, a presença de Aids, de imagem radiológica de TB pulmonar atípica e a TB disseminada estão associados a uma maior taxa de EAH.

Introduction: the frequency of hepatic adverse effects and factors associated with its occurrence in an Universitary Hospital, reference for AIDS and tuberculosis (TB) is not completely known. Methods: a case-control study was conducted to assess the prevalence of hepatic adverse effects of patients using anti-TB treatment and the factors associated with its occurrence. Results: 588 medical charts of TB patients receiving anti-TB treatment with isoniazid, ripampin, pirazinamide, with or without ethambutol attendent betwee January, 1994 and December, 1995 were analyzed. HAE was observed in 40 (6.8%) patients. Two-hundred patients were included as control group. Using univariate analysis to evaluate case and control groups no statistically difference was found between HAE and the following variables: age, gender, anti-TB treatment, liver disease in the past and/or alcohol abuse. However, HAE was significantly associated with hospitalization at the time that TB diagnosis was made, immunosupression, disseminated TB, radiographic atypical presentation of pulmonary TB, seropositivy for B and C hepatitis and clinical unfavorable evolution. In multivariate analysis only hospitalization and Aids were associated to HAE. Conclusion: in a University Hospital, reference for TB and AIDS, the presence of Aids, radiographic atypical presentation of pulmonary TB and disseminated form of TB were associated with higher prevalence of HAE.