Fidaxomicin monotherapy versus standard therapy combined with bezlotoxumab for treating patients with Clostridioides difficile infection at high risk of recurrence: a matched cohort study.

BACKGROUND: Both fidaxomicin and bezlotoxumab (used in combination with an antibiotic against Clostridioides difficile) achieve reductions in recurrence rates of C. difficile infection (CDI). However, the two strategies have never been compared. METHODS: Data from two retrospective cohorts of 'real-life' use of fidaxomicin and bezlotoxumab in combination with a standard anti-C. difficile antibiotic were used to compare the rates of recurrence of both strategies. Since the two cohorts were not identical, we used a propensity score analysis. RESULTS: Three hundred and two patients were included: 244 in the fidaxomicin cohort and 78 in the bezlotoxumab cohort. A history of renal failure or immunosuppression was more frequent in patients receiving bezlotoxumab (39.7% and 66.7% versus 26.6% and 38.9%; P = 0.03 and P < 0.001, respectively), but the severity and number of previous CDI episodes were similar in both cohorts. We observed that 19.3% of the patients in the fidaxomicin cohort experienced recurrence, compared with 14.1% in the bezlotoxumab cohort (OR 1.45; 95% CI 0.71-2.96; P = 0.29) but the difference remained non-significant after propensity score matching using previously defined variables (OR 1.24; 95% CI 0.50-3.07; P = 0.64). Moreover, the multivariate analysis did not show differences depending on the drug used. CONCLUSIONS: We observed that fidaxomicin and bezlotoxumab are prescribed in similar clinical scenarios, although those treated with bezlotoxumab have greater comorbidity. The proportion of recurrences was numerically lower in those treated with bezlotoxumab, although the propensity analysis did not find significant differences between the two drugs.

Evaluación de la adherencia y de los resultados en salud en trasplante alogénico de progenitores hematopoyéticos / Evaluation of adherence and clinical outcomes in patients undergoing allogeneic haematopoietic stem cell transplantation

OBJETIVO: Medir la adherencia a la profilaxis del fallo secundario del implante (ciclosporina, tacrolimus, sirolimus), de la enfermedad injerto contra receptor (ciclosporina, tacrolimus, sirolimus, micofenolato) y de las infecciones (posaconazol, voriconazol, valganciclovir) en el paciente sometido a trasplante alogénico de progenitores hematopoyéticos. Compa-rar la incidencia de complicaciones agudas en función de la adherencia.MÉTODO: Estudio observacional retrospectivo en pacientes sometidos a trasplante alogénico de progenitores hematopoyéticos desde mayo de 2017 hasta mayo de 2018, entre el día 0 y +100 postrasplante. La adherencia a micofenolato, tacrolimus, sirolimus, posaconazol, voriconazol y valganciclovir se evaluó mediante los registros de dispensación del servicio de farmacia, siempre que fuera posible. Se definió como paciente adherente aquel con un porcentaje de adherencia igual o superior al 95%. La evaluación de la adherencia a ciclosporina se realizó mediante medida de los niveles plasmáticos. Se definió como paciente no adherente aquel cuyos niveles plasmáticos de ciclosporina fueran inferiores a 100 ng/ml en alguna medida entre los días 0 y +100, en ausencia de factores asociados que lo justificaran. La asociación entre adherencia e incidencia de complicaciones agudas (fallo secundario del implante, enfermedad injerto contra receptor aguda e infección) se estimó mediante la odds ratio y su intervalo de confianza del 95%. RESULTADOS: Se incluyó a 46 pacientes. Todos comenzaron profilaxis inmunosupresora con ciclosporina; en el 8,7% se cambió a tacrolimus o sirolimus por toxicidad. Todos los pacientes recibieron ciclosporina para la profilaxis de la enfermedad injerto contra receptor. En el 41,3% de los casos también se administró micofenolato. El 82,6% fueron adherentes a la profilaxis del fallo de injerto. En cuanto a la profilaxis de enfermedad injerto contra receptor, resultó adherente el 80,4%. Todos los pacientes resultaron adherentes a la profilaxis infecciosa. La incidencia de enfermedad injerto contra receptor aguda de los pacientes adherentes a la profilaxis fue del 45,9% frente al 55,6% en los no adherentes (odds ratio 0,68; intervalo de confianza del 95% 0,157-2,943; p = 0,718). CONCLUSIONES: Los pacientes sometidos a trasplante alogénico de progenitores hematopoyéticos presentan una aceptable adherencia a la profilaxis de complicaciones agudas, pero existe un considerable porcentaje de pacientes que no toman su tratamiento adecuadamente. La correcta adherencia a los inmunosupresores parece disminuir el riesgo de sufrir enfermedad injerto contra receptor aguda

OBJECTIVE: To measure adherence to cyclosporine, tacrolimus and siroli-mus prophylaxis against secondary graft failure; cyclosporine, tacrolimus, sirolimus and mycophenolate prophylaxis against graft-versus-host disease; and posaconazole, voriconazole, valganciclovir prophylaxis against infec-tion in patients undergo to transplantation of haematopoietic stem cells; and to analise the incidence of acute complications based on adherence.METHOD: Retrospective observational study of patients who underwent allo-geneic haematopoietic stem cell transplantation between May 2017 and May 2018. Analyses were carried out between 0 and +100 days post-engraftment.Whenever possible, adherence to mycophenolate, tacrolimus, sirolimus, posaconazole, voriconazole and valganciclovir was evaluated by means of the dispensation records of the Pharmacy Department of our hospital. To be considered adherent, patients should have proved an adherence rate equal to or higher than 95%. Adherence to cyclosporine was determi-ned based on serum levels. Patients were considered to be non-adherent if their cyclosporine serum concentrations dropped below 100 ng/mL at any time between days 0 and +100, in the absence of any specific justifying circumstances. The association between adherence and the incidence of acute complications (secondary graft failure, acute graft-versus-host disease and infection) was determined by means of the odds ratio (confidence interval: 95%). RESULTS: The study sample was made up by 46 patients, all of whom were started on immunosuppressive cyclosporine prophylaxis; 8.7% needed to be switched to tacrolimus or sirolimus due to toxicity issues. All the pa-tients received cyclosporine as prophylaxis against graft-versus-host disea-se. Mycophenolate was also administered in 41.3% of cases. A total of 82.6% patients were found to be adherent to their prophylaxis treatment against graft failure and 80.4% were found to be adherent to prophylaxis against graft-versus-host disease. All patients were adherent to anti-infection prophylaxis. The incidence of acute graft-versus-host disease in prophylaxis-adherent patients was 45.9%, compared with 55.6% for non-adherent pa-tients (odds ratio 0.68; confidence interval: 95% 0.157-2.943; p = 0.718). CONCLUSIONS: Patients undergoing allogeneic haematopoietic stem cell transplantation demonstrated acceptable adherence to prophylaxis aga-inst acute complications, although a considerable percentage of patients was found not to take their medication as prescribed. Correct adherence to immunosuppressants seems to reduce the risk of developing acute graft-versus-host disease

Evaluation of adherence and clinical outcomes in patients undergoing allogeneic haematopoietic stem cell transplantation.

OBJECTIVE: To measure adherence to cyclosporine, tacrolimus and  sirolimus prophylaxis against secondary graft failure; cyclosporine,  tacrolimus, sirolimus and mycophenolate prophylaxis against graft- versus-host disease; and posaconazole, voriconazole, valganciclovir  prophylaxis against infection in patients undergo to transplantation of  haematopoietic stem cells; and to analise the incidence of acute  complications based on adherence. METHOD: Retrospective observational study of patients who underwent  allogeneic haematopoietic stem cell transplantation between May 2017  and May 2018. Analyses were carried out between 0 and +100 days  post-engraftment. Whenever possible, adherence to mycophenolate,  tacrolimus, sirolimus, posaconazole, voriconazole and valganciclovir was  evaluated by means of the dispensation records of the Pharmacy  Department of our hospital. To be considered adherent, patients should  have proved an adherence rate equal to or higher than 95%. Adherence  to cyclosporine was determined based on serum levels.  Patients were considered to be non-adherent if their cyclosporine serum  concentrations dropped below 100 ng/mL at any time between days 0  and +100, in the absence of any specific justifying circumstances. The  association between adherence and the inci dence of acute  complications (secondary graft failure, acute graft-versushost disease  and infection) was determined by means of the odds ratio (confidence  interval: 95%). RESULTS: The study sample was made up by 46 patients, all of whom were started on immunosuppressive cyclosporine prophylaxis; 8.7%   needed to be switched to tacrolimus or sirolimus due to toxicity issues.   All the patients received cyclosporine as prophylaxis against graft-  versus-host disease. Mycophenolate was also administered in 41.3% of  cases. A total of 82.6% patients were found to be adherent to their  prophylaxis treatment against graft failure and 80.4% were found to be  adherent to prophylaxis against graft-versus-host disease. All patients  were adherent to anti-infection prophylaxis. The incidence of acute  graft-versus-host disease in prophylaxisadherent patients was 45.9%,  compared with 55.6% for non-adherent patients (odds ratio 0.68;  confidence interval: 95% 0.157-2.943; p = 0.718). CONCLUSIONS: Patients undergoing allogeneic haematopoietic stem cell transplantation demonstrated acceptable adherence to prophylaxis  against acute complications, although a considerable percentage of  patients was found not to take their medication as prescribed. Correct  adherence to immunosuppressants seems to reduce the risk of  developing acute graftversus- host disease.

Objetivo: Medir la adherencia a la profilaxis del fallo secundario del implante (ciclosporina, tacrolimus, sirolimus), de la enfermedad  injerto contra receptor (ciclosporina, tacrolimus, sirolimus,  micofenolato) y de las infecciones (posaconazol, voriconazol,  valganciclovir) en el paciente sometido a trasplante alogénico de  progenitores hematopoyéticos. Comparar la incidencia de  complicaciones agudas en función de la adherencia.Método: Estudio observacional retrospectivo en pacientes sometidos a trasplante alogénico de progenitores hematopoyéticos desde mayo de 2017 hasta mayo de 2018, entre el día 0 y +100 postrasplante. La adherencia a micofenolato, tacrolimus, sirolimus, posaconazol,  voriconazol y valganciclovir se evaluó mediante los registros de  dispensación del servicio de farmacia, siempre que fuera posible. Se  definió como paciente adherente aquel con un porcentaje de adherencia  igual o superior al 95%. La evaluación de la adherencia a ciclosporina se  realizó mediante medida de los niveles plasmáticos. Se definió como  paciente no adherente aquel cuyos niveles plasmáticos de ciclosporina  fueran inferiores a 100 ng/ml en alguna medida entre los días 0 y +100,  en ausencia de factores asociados que lo justificaran. La  asociación entre adherencia e incidencia de complicaciones agudas (fallo  secundario del implante, enfermedad injerto contra receptor  aguda e infección) se estimó mediante la odds ratio y su intervalo de  confianza del 95%.Resultados: Se incluyó a 46 pacientes. Todos comenzaron rofilaxis inmunosupresora con ciclosporina; en el 8,7% se cambió a  tacrolimus o sirolimus por toxicidad. Todos los pacientes recibieron  ciclosporina para la profilaxis de la enfermedad injerto contra receptor.  En el 41,3% de los casos también se administró micofenolato. El 82,6%  fueron adherentes a la profilaxis del fallo de injerto. En cuanto a la  profilaxis de enfermedad injerto contra receptor, resultó adherente el  80,4%. Todos los pacientes resultaron adherentes a la profilaxis  infecciosa. La incidencia de enfermedad injerto contra receptor aguda de  los pacientes adherentes a la profilaxis fue del 45,9% frente al  55,6% en los no adherentes (odds ratio 0,68; intervalo de confianza del  95% 0,157-2,943; p = 0,718). Conclusiones: Los pacientes sometidos a trasplante alogénico de  progenitores hematopoyéticos presentan una aceptable adherencia a la  profilaxis de complicaciones agudas, pero existe un considerable  porcentaje de pacientes que no toman su tratamiento adecuadamente.  La correcta adherencia a los inmunosupresores parece disminuir el  riesgo de sufrir enfermedad injerto contra receptor aguda.

Chemotherapy Near the End of Life in Onco-Hematological Adult Patients.

OBJECTIVE: The use of chemotherapy near the end of life is not advisable. There are scarce data in Europe but shows signs of aggressiveness. We designed this study to analyze the proportion of onco-hematological patients receiving chemotherapy within their last 2 weeks of life as well as starting a new chemotherapy regimen in the 30 days prior to death. METHODS: A retrospective observational study was conducted in a tertiary hospital. Adults who died of an onco-hematological neoplasia while hospitalized between April 2017 and March 2018 were included. We assessed the use of chemotherapy over the course of the last 14 days of life, defined as the administration of at least one dose of chemotherapy. We also examined the proportion of patients starting a new chemotherapy regimen in the last 30 days of life. RESULTS: A total of 298 inpatients died in the Hematology and Oncology units. During the last 14 days, 28.2% (n = 11) of hematological and 26.3% (n = 68) of oncological patients received chemotherapy; the overall rate was 26.5% (n = 79). Furthermore, the proportion of patients starting a new chemotherapy regimen in the last 30 days of life was high (20.5% and 20.8%, respectively). Female gender (odds ratio [OR] = 1.99, 95% confidence interval [CI] = 1.18-3.35) and age <45 (OR = 2.68, 95% CI = 1.05-6.88) were associated with higher rates of chemotherapy. CONCLUSION: The proportion of patients receiving chemotherapy in the last 14 days of life was high, as well as the proportion of patients starting a new regimen in their last 30 days. This was indicative of excessive aggressiveness at the end-of-life care.