Major bleeding in patients with pulmonary embolism presenting with syncope.

INTRODUCTION: Syncope has been shown to be a risk factor of bleeding in patients receiving thrombolytic therapy for acute pulmonary embolism (PE). Whether syncope predicts bleeding in a broader population of patients with PE remains unknown. METHODS: We used the RIETE registry data to assess whether initial presentation with syncope could predict bleeding in PE patients receiving anticoagulant therapy, and to explore the association between presence of syncope and timing and site of major bleeding events. RESULTS: Among 45,765 patients with acute PE from March 2001 to January 2021, 6760 (14.8%) had syncope. Patients with syncope were older and more likely to have hypotension, tachycardia, hypoxaemia or elevated troponin levels than those without syncope. They also were more likely to receive thrombolytics. During the first 90 days, 1097 patients (2.4%) suffered major bleeding (gastrointestinal 335, hematoma 271 and intracranial 163) and 3611 died (158 had fatal bleeding). Patients with syncope had a higher rate of major bleeding (odds ratio [OR]: 1.63; 95% CI: 1.41-1.89) and a nonsignificantly higher rate of fatal bleeding (OR: 1.47; 95% CI: 0.99-2.17) than those without syncope. Multivariable analysis confirmed that patients with syncope were at increased risk for major bleeding (adjusted hazard ratio [aHR]: 1.34; 95% CI: 1.15-1.55). On sensitivity analysis, the increased risk for major bleeding was confirmed in patients initially receiving anticoagulant therapy without thrombolytics at 7 days (aHR: 1.47; 95% CI: 1.13-1.91) and 90 days (aHR: 1.33; 95%CI: 1.13-1.56). DISCUSSION: Syncope is a predictor of major bleeding events in patients with PE, even among those receiving anticoagulation monotherapy.

[Randomized clinical trial investigating three chemoprophylaxis regimens for latent tuberculosis infection in HIV-infected patients]. / Ensayo clínico aleatorizado para evaluar tres pautas cortas de tratamiento de la infección latente tuberculosa en pacientes infectados por el VIH.

OBJECTIVE: To evaluate the adherence to, and safety of three chemoprophylaxis regimens for latent tuberculosis (TB) infection in HIV-infected patients with a positive tuberculin skin test. PATIENTS AND METHODS: A randomized, comparative, open clinical assay was carried out in 316 HIV-infected patients in 12 Spanish hospitals. Patients were randomly assigned to one of three regimens, 108 to isoniazid for six months (6H), 103 to rifampin and isoniazid for three months (3RH), and 105 to rifampin and pyrazinamide for two months (2RZ). After completion of treatment, patients were followed-up for two years. RESULTS: The period of observation following completion of treatment was 115, 108 and 101 person-years for 6H, 3RH and 2RZ, respectively. Twenty-seven percent of patients voluntarily abandoned chemoprophylaxis and 9.7% were withdrawn due to adverse side-effects or interactions. Seven patients were withdrawn due to hepatotoxicity (5 in 6H, 2 in 3RH and 0 in 2RZ). No appreciable differences were found among the three regimens. There were 11 cases of tuberculosis during follow-up. The TB rates (cases per 100 person-years) in the three treatment groups were 3.48 in 6H, 4.63 in 3RH and 1.98 in 2RZ. With respect to 2RZ, the relative risk for TB in the 6H and 3RH regimens was 1.76 and 2.34, respectively. CONCLUSIONS: The safety of the 2RZ regimen for prophylaxis of latent TB infection in HIV patients was similar to that of the 6H and 3RH regimens. The incidence of hepatotoxicity was not higher in patients who received 2RZ.

Ensayo clínico aleatorizado para evaluar tres pautas cortas de tratamiento de la infección latente tuberculosa en pacientes infectados por el VIH / Randomized clinical trial investigating three chemoprophylaxis regimens for latent tuberculosis infection in HIV-infected patients

Objetivo. Evaluar la adherencia y seguridad de 3 pautas cortas de tratamiento de la infección latente tuberculosa (ILT) en pacientes infectados por el virus de la inmunodeficiencia humana (VIH). Pacientes y métodos. Ensayo clínico, aleatorizado, multicéntrico, comparativo y abierto, realizado en 12 hospitales españoles. Los pacientes se distribuyeron de forma aleatoria a una de las siguientes 3 pautas de tratamiento, isoniazida durante 6 meses (6H) y rifampicina más isoniazida durante 3 meses (3RH) y rifampicina más pirazinamida durante 2 meses (2RZ). Tras finalizar el tratamiento los pacientes fueron seguidos durante un período de 2 años. Resultados. Se incluyeron en el estudio 316 pacientes, 105 en la pauta 2RZ, 103 en la pauta 3RH y 108 en la pauta 6H. El período de observación tras la finalización del tratamiento fue de 115, 108 y 101 personas/año, respectivamente, para 6H, 3RH y 2RZ. El 27% de los pacientes abandonaron voluntariamente el estudio antes de finalizar el tratamiento al que fueron asignados y el 9,7% abandonaron el mismo por reacciones adversas o interacciones. Se produjeron 7 retiradas del estudio por hepatotoxicidad, cinco en el grupo 6H y dos en 3RH. No se observaron retiradas por hepatotoxicidad en el brazo 2RZ. Se produjeron 11 casos de tuberculosis durante el seguimiento. Las tasas de tuberculosis (casos por 100 personas/año) en los distintos grupos de tratamiento fueron de 3,48 en 6H, 4,63 en 3RH y 1,98 en 2RZ, con un riesgo relativo para tuberculosis en las pautas 6H y 3RH de 1,76 y 2,34, respectivamente, respecto a 2RZ. Conclusiones. En nuestro estudio la seguridad de la pauta 2RZ en el tratamiento de la ILT de la pauta 2RZ fue similar a la observada con las pautas 6H y 3RH, no observándose una mayor incidencia de hepatotoxicidad en pacientes que recibieron 2RZ (AU)

Objective. To evaluate the adherence to, and safety of three chemoprophylaxis regimens for latent tuberculosis (TB) infection in HIV-infected patients with a positive tuberculin skin test. Patients and methods. A randomized, comparative, open clinical assay was carried out in 316 HIV-infected patients in 12 Spanish hospitals. Patients were randomly assigned to one of three regimens, 108 to isoniazid for six months (6H), 103 to rifampin and isoniazid for three months (3RH), and 105 to rifampin and pyrazinamide for two months (2RZ). After completion of treatment, patients were followed-up for two years. Results. The period of observation following completion of treatment was 115, 108 and 101 person-years for 6H, 3RH and 2RZ, respectively. Twenty-seven percent of patients voluntarily abandoned chemoprophylaxis and 9.7% were withdrawn due to adverse side-effects or interactions. Seven patients were withdrawn due to hepatotoxicity (5 in 6H, 2 in 3RH and 0 in 2RZ). No appreciable differences were found among the three regimens. There were 11 cases of tuberculosis during follow-up. The TB rates (cases per 100 person-years) in the three treatment groups were 3.48 in 6H, 4.63 in 3RH and 1.98 in 2RZ. With respect to 2RZ, the relative risk for TB in the 6H and 3RH regimens was 1.76 and 2.34, respectively. Conclusions. The safety of the 2RZ regimen for prophylaxis of latent TB infection in HIV patients was similar to that of the 6H and 3RH regimens. The incidence of hepatotoxicity was not higher in patients who received 2RZ (AU)

[Randomized trial of three regimens to prevent tuberculosis in HIV-infected patients with anergy]. / Ensayo clínico aleatorizado de tres aputas de quimioprofilaxis para prevenir la tuberculosis en pacientes infectados por el VIH con anergia cutánea.

INTRODUCTION: To evaluate the efficacy of three regimens of prophylactic therapy for tuberculosis in HIV-infected patients with anergy. METHODS: Prospective, multi-center, randomized, comparative, and open clinical trial. Anergy was defined as absence of induration in response to three antigens (PPD, Candida albicans and parotiditis antigen) applied by the Mantoux method. Patients were randomized into one of the following prophylactic treatment groups: isoniazid for six months (6H), rifampin plus isoniazid for three months (3RH), rifampin plus pyrazinamide for two months (2RZ) or no treatment (NT). After completion of treatment, patients were followed up for two years. RESULT: A total of 319 patients were included in the study, 83 in the 6H regimen, 82 in 3RH, 77 in 2RZ and 77 in NT. The observation period following treatment was 88, 96, 81 and 126 person-years, respectively, for 6H, 3RH, 2RZ and NT. There were 11 cases of tuberculosis during the follow-up period. The tuberculosis rates (cases per 100 person-years) were 3.4, 3.1, 1.2 and 3.1 for 6H, 3RH, 2RZ and NT respectively, with relative risks in regimens 6H, 3RH and 2RZ with respect to NT of 1.07 (0.24-4.80), 0.98 (0.22-4.4) and 0.39 (0.04-3.48), all statistically non-significant. Twenty-nine patients died during the follow-up period, none due to tuberculosis, and no appreciable differences were found among the groups. CONCLUSIONS: The results showed no significant decrease in the risk of developing tuberculosis with any of the evaluated regimens and, therefore, do not support the use of antituberculosis chemoprophylaxis in anergic HIV-infected patients.

Ensayo clínico aleatorizado de tres pautas de quimioprofilaxis para prevenir la tuberculosis en pacientes infectados por el VIH con anergia cutánea / Randomized trial of three regimens to prevent tuberculosis in HIV-infected patients with anergy

INTRODUCCIÓN. Evaluar la eficacia de tres pautas de quimioprofilaxis antituberculosa en pacientes infectados por el virus de la inmunodeficiencia humana (VIH) con anergia cutánea. MÉTODOS. Ensayo clínico prospectivo, multicéntrico, aleatorizado, comparativo y abierto. La anergia cutánea se definió por la ausencia de reactividad a 3 antígenos aplicados por la técnica de Mantoux (PPD, candidina y parotiditis). Los pacientes se distribuyeron de forma aleatoria a uno de los siguientes grupos de tratamiento: isoniacida durante 6 meses (6H), rifampicina más isoniacida, 3 meses (3RH), rifampicina más piracinamida, 2 meses (2RZ) o sin tratamiento (NT). Tras finalizar la quimioprofilaxis los pacientes fueron seguidos 2 años. ESULTADOS. Se incluyeron en el estudio 319 pacientes, 83 en la pauta 6H, 82 en 3RH, 77 en 2RZ y 77 en NT. El período de observación tras el tratamiento fue de 88, 96, 81 y 126 personas años, respectivamente para 6H, 3RH, 2RZ y NT. Se produjeron 11 casos de tuberculosis durante el seguimiento. Las tasas de tuberculosis (casos por 100 personas/año) fueron respectivamente de 3,4, 3,1, 1,2 y 3,1 para 6H, 3RH, 2RZ y NT, con un riesgo relativo en las pautas 6H, 3RH y 2RZ respecto a NT de 1,07 (0,24-4,80), 0,98 (0,22-4,4) y 0,39 (0,04-3,48), estadísticamente no significativo. Durante el seguimiento fallecieron 29 pacientes, ninguno de ellos por tuberculosis, sin que se apreciaran diferencias entre grupos. CONCLUSIONES. Nuestro estudio no demuestra una reducción significativa del riesgo de tuberculosis en ninguna de las 3 pautas evaluadas y, por tanto, no apoya el empleo de quimioprofilaxis antituberculosa en pacientes con anergia cutánea (AU)