Systematic review and meta-analysis of anti-thymocyte globulin dosage as a component of graft-versus-host disease prophylaxis.

Rabbit anti-thymocyte globulin (ATG) has been used in allogeneic hematopoietic stem cell transplantation (Allo-HSCT) for graft-versus-host disease (GvHD) prophylaxis. Since the best dose has not been defined yet, this study aimed to determine the efficacy and safety of different doses of ATG in Allo-HSCT. Data sources were MEDLINE/PUBMED, EMBASE, Cochrane Library, Web of Science, LILACS, and SciELO. Studies were eligible when comparing doses of ATG. The higher dose was in the intervention group. A total of 22 articles (2002-2022) were included. Higher doses (4-12 mg/kg) of ATG-T reduced the incidence of grade III-IV acute GvHD (RR 0.60; 95%CI 0.42-0.84) and limited chronic GvHD (RR 0.64 95%CI 0.45-0.92) compared with lower doses (2-7.5 mg/kg). Higher doses increased the Epstein-Barr virus (RR 1.90 95% CI 1.49-2.42) and Cytomegalovirus reactivation (RR, 1.30; 95% CI 1.03-1.64). Relapse rates were higher in the higher dose group (RR 1.34, 95% CI 1.07-167). The ATG-T dose ≥7mg/kg versus the lower dose showed a number needed to treat 7.4 for acute GvHD III-IV, with a number to harm of 7.7 for relapse at one year in the higher dose group. A dose lower than 7 mg/kg suggests a better risk-benefit ratio than a higher one. Well-designed RCT is needed to define the best risk-benefit doses. Trial registration: Trial registration number: PROSPERO: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020173449.

The pharmaceutical care bundle: development and evaluation of an instrument for inpatient monitoring

Introduction: Care bundles help healthcare professionals provide the best care possible in a structured and reliable way. The purpose of this study was to develop and apply an instrument for inpatient follow-up by clinical pharmacists, and evaluate its results. Methods: The care bundle was based on previously validated instruments. Population consisted of patients monitored by clinical pharmacists at a general hospital. The study was conducted in two phases: the first involved the development and implementation of the bundle, and the evaluation of pharmaceutical interventions; the second involved analyzing data from patients treated with the bundle over one year. Results: The bundle included fourteen pharmaceutical follow-up criteria used in different patterns by each area of care. In the first phase of the study, 3263 patients were monitored and 536 pharmaceutical interventions were performed, with an 85.3% compliance rate. In the second phase of the study, follow-up data was collected from 21,214 patients. The bundle criteria were used in a similar way in clinical, surgical and cancer patients. Pharmacotherapy review was the most prevalent intervention in all cases (60.1%). Hospital discharge planning and medication reconciliation were performed with a similar frequency in clinical, surgical, pediatric and general patients. Conclusions: The development and validation of a bundle aimed at guiding the clinical activities of pharmacists helped standardize procedures and interventions. Pharmacotherapy review was the bundle criterion with the highest rate of application and interventions due to the hospital's complexity and the need to consider individual patient needs and follow institutional policies. (AU)

Comparison of cyclophosphamide-thalidomide-dexamethasone to bortezomib-cyclophosphamide-dexamethasone as induction therapy for multiple myeloma patients in Brazil.

OBJECTIVE/BACKGROUND: Chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) remains the standard treatment for multiple myeloma (MM). Thalidomide or bortezomib may be combined with cyclophosphamide and dexamethasone, in what are known as the CTD and VCD protocols, respectively. The objective of this study was to evaluate the clinical characteristics and response rates obtained with CTD and VCD, observing whether the inclusion of bortezomib to treat MM patients in Brazil increases therapeutic efficiency. METHODS: Forty-three MM patients treated with induction protocols CTD and VCD between January 2010 and March 2015 were included. The parameters analyzed were staging, frequency of comorbidities prior to treatment, response rates obtained at each induction cycle, progression-free survival, and overall survival of patients. RESULTS: Very good partial response and complete response obtained with the VCD protocol were superior, compared with the CTD treatment. The presence of comorbidities was similar in the two groups, except kidney failure, which prevailed in the VCD group. Also, 78.3% and 48.3% of patients treated with the VCD and CTD protocols underwent autologous HSCT, respectively. In patients given the VCD protocol, 45.5% had complete response before autologous HSCT. Among those given CTD, this number was only 7.1% (p=0.023). Disease progression after autologous HSCT did not differ between the two groups. CONCLUSION: VCD afforded better responses than the CTD protocol, and improved patient condition before autologous HSCT. However, more studies are necessary including more patients and addressing various clinical conditions, besides the analysis of cost-effectiveness of these treatments.

Characterization of Patients with Chronic Myeloid Leukemia Unresponsive to Tyrosine Kinase Inhibitors Who Underwent Allogeneic Hematopoietic Stem Cell Transplantation.

Background: Tyrosine kinase inhibitors (TKIs) were the first drugs to use an intracellular signaling molecule as a therapeutic target. Unresponsiveness to TKIs limits therapeutic options, making allogeneic hematopoietic stem cell transplantation (HSCT) the only option leading to molecular remission. The aim of this study is to characterize CML patients unresponsive to first- and/or second-generation TKI therapy who underwent HSCT and to describe the main factors associated with treatment failure. Subjects and Methods: Twenty one CML patients who underwent allogeneic HSCT and had previously used first- and/or second-generation TKIs from January 2005 to May 2014. Results: Of the 21 patients, 52.4% were male, with a median age of 49 years (23-65 years) and 85.7% had chronic phase CML at the time of diagnosis; 28.6% showed inadequate treatment adherence to TKI therapy. Thirteen patients were resistant and eight were intolerant to TKIs; additionally, nine did not have T315I mutation. Ten transplantations involved related donors, and more than a half of patients (11) died, three of which due to graft failure. Most patients who survived transplantation were in the chronic phase of disease at the time of HSCT. Conclusion: The population was composed mainly of young age patients at diagnosis, male, white, and coming from areas in the state of Rio Grande do Sul other than Porto Alegre and metropolitan region. Low adherence to TKI therapy may be related to unresponsiveness to treatment, especially in patients with acquired resistance, or this low adherence, together with the presence of molecular changes, may have led to the need for HSCT.

Immunosuppressive serum levels in allogeneic hematopoietic stem cell transplantation: pharmaceutical care contribution.

BACKGROUND: Cyclosporine and tacrolimus are limited by a narrow therapeutic window. Maintaining immunosuppressive drugs at desired levels may be difficult. Pharmaceutical care emerges as a philosophy of practice that enhances medication use and leads to a better control of serum concentration. OBJECTIVE: This study aims to evaluate the impact of pharmaceutical care in the maintaining of proper serum levels of immunosuppressive medications in patients who have undergone allo-HSCT. METHODS: The study had a quasi-experimental design that included a comparison group. The service model used was pharmacotherapy follow-up, according to an adaptation of the Dader method. The pharmacist consultation was carried out at a day-hospital or at the outpatient hematology clinic as needed. The intervention group consisted of 22 patients seen by a clinical pharmacist. The control group consisted of 44 patients that received standard care. This study aims to evaluate the impact of pharmaceutical care on keeping patient serum levels of cyclosporine and tacrolimus within the desired range. RESULTS: Control group displayed 65% of the proper serum levels of immunosuppressive agents. While In intervention group, the figure was 82% (p = 0.004). CONCLUSION: The role of the pharmacist in the multidisciplinary team may contribute to a greater success in attaining the patients' therapeutic targets with regard to the use of immunosuppressant.

Immunosuppressive serum levels in allogeneic hematopoietic stem cell transplantation: pharmaceutical care contribution

Background: Cyclosporine and tacrolimus are limited by a narrow therapeutic window. Maintaining immunosuppressive drugs at desired levels may be difficult. Pharmaceutical care emerges as a philosophy of practice that enhances medication use and leads to a better control of serum concentration. Objective: This study aims to evaluate the impact of pharmaceutical care in the maintaining of proper serum levels of immunosuppressive medications in patients who have undergone allo-HSCT. Methods: The study had a quasi-experimental design that included a comparison group. The service model used was pharmacotherapy follow-up, according to an adaptation of the Dader method. The pharmacist consultation was carried out at a day-hospital or at the outpatient hematology clinic as needed. The intervention group consisted of 22 patients seen by a clinical pharmacist. The control group consisted of 44 patients that received standard care. This study aims to evaluate the impact of pharmaceutical care on keeping patient serum levels of cyclosporine and tacrolimus within the desired range. Results: Control group displayed 65% of the proper serum levels of immunosuppressive agents. While In intervention group, the figure was 82% (p = 0.004). Conclusion: The role of the pharmacist in the multidisciplinary team may contribute to a greater success in attaining the patients’ therapeutic targets with regard to the use of immunosuppressant (AU)

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Microbiological findings in febrile neutropenic patients in a tertiary hospital of Southern Brazil / Achados microbiológicos em pacientes neutropênicos febris em um hospital terciário do sul do Brasil

Introdução: Neutropenia é um forte fator de risco para infecção. A prevalência de bactérias Gramnegativas diminuiu no início da década de 90 e a frequência de bactérias Gram-positivas aumentou em 55 a 70% em todos os episódios de bacteremia. Porém, mais recentemente, infecções por bactéria Gram-negativas ressurgiram. O objetivo deste estudo é descrever os achados microbiológicos em uma coorte de pacientes neutropênicos febris em um hospital terciário de ensino do sul do Brasil.Metodologia: Estudo coorte para avaliação da implementação de um protocolo clínico para o tratamento de pacientes neutropênicos febris. Foram incluídos prospectivamente pacientes com neutropenia febril (NF) admitidos entre janeiro de 2004 e dezembro de 2005 no Hospital de Clínicas de Porto Alegre. Controles históricos foram selecionados de visitas de pacientes entre março de 2001 e abril de 2003 ou antes do protocolo clínico ter sido implementado.Resultados: Nos períodos do estudo de 2004-2005 e 2001-2003, foram documentados 164 e 159 patógenos, respectivamente. Em 93 de 190 episódios (48,9%) e 84 de 193 episódios (43,5%) foram documentadas infecções microbiológicas.

Infecções fúngicas foram documentadas em poucos episódios (6,1 e 5,7%). Observou-se uma prevalência de 52,8% de bactérias Gram-positivas e 47,2% de bactérias Gram-negativas no período de 2001-2003. No período de 2004-2005, foram observadas 38,1% de bactérias Gram-positivas e 61,9% de bactérias Gram-negativas (P=0,012).Também houve um aumento significativo da prevalência de Pseudomonas aeruginosa no segundo período de estudo (1,9 para 11,6%; P<0,001). Em 2004-2005, seis isolados eram multirresistentes(31,6%). A prevalência de Staphylococcus resistente à oxacilina foi de 53,5 e 65,8% nos primeiros e segundos períodos, respectivamente (P=0,23).Conclusão: Os patógenos documentados neste estudo são os mais comuns em pacientes neutropênicos febris, mas a emergência de Pseudomonas aeruginosa resistente a multidrogas é uma preocupação.

Background: Neutropenia is a major risk factor for infection. The prevalence of Gram-negative bacteria decreased in the early nineties, while the frequency of Gram-positive bacteria increased from between 55 to 70% of all bacteremia episodes. Even more recently there has been a resurgence of Gram-negative infections. The aim of this report is to describe the microbiological findings in a cohort of febrile neutropenic patients in a tertiary teaching hospital of Southern Brazil.Methods: This was a cohort study designed to evaluate the implementation ofa clinical protocol for treatment of febrile neutropenic patients. Prospectively included in our study were patients with febrile neutropenia (FN) admitted between January 2004 and December 2005 at the Hospital de Clínicas of Porto Alegre.Historical controls were selected from patient visits recorded between March 2001 and April 2003 - or recorded before the clinical protocol was introduced.Results: During the 2004-2005 and 2001-2003 study periods, 164 and 159 pathogens were documented, respectively. In 93 of 190 episodes (48.9%), and 84 of 193 episodes (43.5%) there were documented microbiological infections. Fungal infection was documented in very few episodes (6.1 vs. 5.7%).

We also observed a 52.8% prevalence of Gram-positive and a 47.2% prevalence of Gram-negative bacteria in the 2001-2003 period. Observed in the 2004-2005 period were 38.1%Gram-positive and 61.9% Gram-negative bacteria (P=0.012). There was also a significant increase in Pseudomonas aeruginosa prevalence in the second study period (1.9 to 11.6%; P<0.001). Six isolates (31.6%) were discovered to be multiresistant in the 2004-2005 period versus none in the first period. The prevalence of Oxacillin-resistant Staphylococcus was 53.5 and 65.8% in the first and secondperiods, respectively (P=0.23).Conclusion: These documented pathogens are the most commonly observed in febrile neutropenic patients, but the emergence of multidrug-resistantPseudomonas aeruginosa is of some concern.

Implementação de um programa para evitar possíveis interações fármaco-alimento em pacientes adultos internados em unidades clínicas e cirúrgicas de um hospital universitário / Implementation of a program to prevent possible drug-food interactions in adult patients hospitalized in the clinical and surgical units of a university hospital

Introdução: As interações fármaco-alimento (IFA) são definidas como alterações produzidas nos efeitos terapêuticos de um medicamento em razão da ingestão concomitante de alimento. Objetivo: Identificar prescrições médicas com possíveis IFA dos pacientes internados no Hospital de Clínicas de Porto Alegre (HCPA) e orientar o corpo clínico quanto aos horários adequados de administração dos medicamentos. Métodos: O estudo analisou, entre fevereiro e julho de 2006, 2.645 prescrições de pacientes adultos internados nas unidades clínicas e cirúrgicas do HCPA e que recebiam dieta oral. Resultados: Observou-se que 54,5% (1.442) das prescrições apresentavam potenciais IFA. Nesses casos, as equipes assistenciais recebiam, através de notificação em prontuário médico, informações sobre os medicamentos que necessitavam de intervalo de jejum para garantir sua máxima biodisponibilidade. Conclusão: A alta incidência de prescrições contendo medicamentos possíveis de interagir com os alimentos demonstra a necessidade de um sistema que disponibilize, sistematicamente, as orientações relacionadas à correta administração dos medicamentos.

Background: Drug-food interactions (DFI) are defined as alterations produced in the therapeutic effects of a drug due to concomitant food ingestion. Objective: To identify medical prescriptions with possible DFI in patients hospitalized at Hospital de Clínicas de Porto Alegre (HCPA) and to provide guidance to the clinical staff about the appropriate time for drug administration. Methods: Between February and July 2006, we analyzed 2,645 prescriptions of adult inpatients receiving oral diet. Results: We found that 54.5% (1,442) of the prescriptions had potential DFI. In such cases, the medical staff was receiving information about the drugs that needed a fasting interval to ensure maximum bioavailability by means of notifications in medical records. Conclusions: The high incidence of prescriptions with possible DFI shows the need for a system that provides systematic guidance regarding the adequate administration of drugs.

Centro de informações sobre medicamentos: avaliação das informações passivas em hospital universitário no sul do Brasil / Drug information center: survey of passive information in university hospital in southern Brazil

Objetivo: O objetivo deste trabalho foi descrever as atividades passivas realizadas por um Centro de Informações sobre Medicamentos (CIM) de hospital universitário no sul do Brasil. Resultados: de 2002 a 2008, o total de solicitações recebidas foi de 8035, das quais 30,3% foram realizadas por enfermeiros, 24,3% por farmacêuticos e 15% por técnicos de enfermagem. O tempo gasto para a resposta foi em 56,8% das vezes de até 10 minutos. Os temas mais solicitados foram administração de medicamentos (25,6%), identificação do produto (16,4%), posologia (10,6%) e estabilidade (9,6%). Conclusão: O CIM é uma estratégia na busca pelo uso seguro e racional de medicamentos nos hospitais.

Aim: The aim of this study was to describe the passive activities of Drug Information Center (DIC) of a university hospital in southern Brazil. Results: From 2002 to 2008, the total of requests was 8035, of which 30.3% were answered by nurses, 24.3% pharmacists and 15% technical nursing. The time spent to response was less than 10 minutes in 56.8%. The principal requests were about drug administration (25.6%), identification of the product (16.4%), dosage (10.6%) and stability (9.6%). Conclusion: The DIC is a strategy in the search for safe and rational use of drugs in hospitals.

Profile of drug interactions in hospitalized children

Introduction: The expected therapeutic response may be affected by the presence of drug interactions. With the high number of reports on new drug interactions, it has been difficult for health professionals to keep constantly updated. For this reason, computer systems have helped identify such interactions. Objectives: To verify the rate and profile of drug interactions in medical prescriptions to hospitalized pediatric patients. Methods: A descriptive study investigated prescriptions to hospitalized pediatric patients. The study included patients between 0 and 12 years old, containing 4 or more drugs in their prescriptions. The analysis of interaction and incompatibility possibilities in prescribed drugs used Micromedex / Drug-Reax® program. Results: From 2005 to 2006, 3,170 patients were investigated, and 11,181 prescriptions were analyzed, a mean value of 3.5 prescriptions/patient. In total, 6,857 drug interactions were found, which corresponds to 1.9 interaction/prescription. Among them, relevance to ampicillin and gentamicin, found in 220 (3.2%) prescriptions. In total, 2,411 drug incompatibilities in via y were found, a mean value of 0.5/prescription, with emphasis on vancomycin and cefepime, found in 243 (10.0%) prescriptions. Conclusion: The presence of drug interactions is a permanent risk in hospitals. This way, the utilization of computer programs, pharmacotherapy monitoring of patients and the pharmacist presence in the multidisciplinary team are some manners of contributing to hospitalized patients' treatment (AU)

Introducción: La respuesta terapéutica esperada puede modificarse por la presencia de interacciones medicamentosas. Con el elevado número de comunicaciones de nuevas interacciones medicamentosas, ha sido difícil para los profesionales de la salud mantenerse constantemente actualizados. Por este motivo, los ordenadores han ayudado a identificar estas interacciones. Objetivos: Verificar la tasa y el perfil de las interacciones medicamentosas en las prescripciones médicas a pacientes pediátricos hospitalizados. Métodos: Un estudio descriptivo investigó las prescripciones a pacientes pediátricos hospitalizados. El estudio incluyó pacientes entre 0 y 12 años, que tenían 4 o más medicamentos en sus prescripciones. El análisis de las interacciones y las incompatibilidades posibles en los medicamentos prescritos utilizó el programa Micromedex / Drug-Reax®. Resultados: De 2005 a 2006, se investigó a 3.170 pacientes y se analizaron 11.181 prescripciones con una media de 3,5 recetas/paciente. En total se encontraron 6.857 interacciones medicamentosas, que corresponden a 1,9 interacciones/prescripción. Entre ellas, se encontró relación a ampicilina y gentamicina en 220 (3,2%). En total, se encontraron 2.411 incompatibilidades de vía, con una media de 0,5 por prescripción, con énfasis en vancomicina y cefepime, encontradas en 243 (10,0%). Conclusión: La presencia de interacciones medicamentosas es un riesgo permanente en hospitales. Así que, la utilización de un programa informático, el seguimiento farmacoterapéutico de los pacientes y la presencia de un farmacéutico en el equipo multidisciplinario son algunas de las maneras de mejorar el tratamiento de los pacientes hospitalizados (AU)

Profile of drug interactions in hospitalized children.

INTRODUCTION: The expected therapeutic response may be affected by the presence of drug interactions. With the high number of reports on new drug interactions, it has been difficult for health professionals to keep constantly updated. For this reason, computer systems have helped identify such interactions. OBJECTIVES: To verify the rate and profile of drug interactions in medical prescriptions to hospitalized pediatric patients. METHODS: A descriptive study investigated prescriptions to hospitalized pediatric patients. The study included patients between 0 and 12 years old, containing 4 or more drugs in their prescriptions. The analysis of interaction and incompatibility possibilities in prescribed drugs used Micromedex / Drug-Reax® program. RESULTS: From 2005 to 2006, 3,170 patients were investigated, and 11,181 prescriptions were analyzed, a mean value of 3.5 prescriptions/patient. In total, 6,857 drug interactions were found, which corresponds to 1.9 interaction/prescription. Among them, relevance to ampicillin and gentamicin, found in 220 (3.2%) prescriptions. In total, 2,411 drug incompatibilities in via y were found, a mean value of 0.5/prescription, with emphasis on vancomycin and cefepime, found in 243 (10.0%) prescriptions. CONCLUSION: The presence of drug interactions is a permanent risk in hospitals. This way, the utilization of computer programs, pharmacotherapy monitoring of patients and the pharmacist presence in the multidisciplinary team are some manners of contributing to hospitalized patients' treatment.