Accuracy of the Simplified HOSPITAL Score to Predict Nonelective Readmission in a Brazilian Tertiary Care Public Teaching Hospital.

BACKGROUND AND OBJECTIVES: Predictive models to identify patients at high risk of readmission have gained the attention of health care teams, which have focused the strategies to reduce unnecessary readmissions on the "at-risk" patients. The HOSPITAL score includes 7 predictor variables with a C-statistic of 0.70 or more when applied to international datasets. Its simplified version retains a C-statistic at around the same level, but only incipient external validation has been attempted to date. The primary objective of this study was to evaluate the prognostic accuracy of the simplified HOSPITAL score to predict nonelective hospital readmissions in a tertiary care public teaching hospital in Brazil. METHODS: We used a retrospective cohort that included all patients discharged from the internal medicine service of a Brazilian tertiary care public teaching hospital in 2018. We excluded patients who died before index discharge, were transferred to another institution, left against medical advice, or were readmitted electively. We calculated the simplified HOSPITAL score for each admission, and admissions were divided into low (0-4 points) or high risk (≥ 5 points) of nonelective 30-day readmission. We estimated accuracy, area under the receiver operating characteristic curve (AUC), and observed/expected (O/E) readmission ratio; the latter using the mid-P exact test with Miettinen's modification at a 95% confidence interval (CI). A P value < .05 was considered significant. RESULTS: A total of 4472 hospital discharges were analyzed during the study period after application of the exclusion criteria. The nonelective 30-day readmission rate was 14.0% (n = 625). Of all patients discharged, 3173 (71.0%) were considered to be at low risk and 1299 (29.0%) at high risk of readmission according to the simplified HOSPITAL score. The AUC was 0.68 (95% CI: 0.66-0.71; P < .001). The nonelective 30-day readmission rate was 9.2% in the low-risk group (expected: 9.2%; O/E: 1.0 [95% CI: 0.89-1.12]) and 25.7% in the high-risk group (expected: 27.2%; O/E: 0.95 [95% CI: 0.85-1.05]) ( P < .001). At a cut-off of 5 points, the score had a sensitivity of 53.4%, specificity of 74.9%, positive predictive value of 25.7%, and negative predictive value (NPV) of 90.8%. CONCLUSIONS: The parameters of the score were almost identical to the original study, with better applicability to exclude low-risk patients given its high NPV. Additional adjustments are still needed for better applicability in daily clinical practice.

Hospital Readmission and Mortality in a Brazilian Tertiary Public Hospital.

BACKGROUND AND OBJECTIVES: Data on mortality associated with hospital readmission are imprecise and highly variable. This study aimed to describe the rate of nonelective 30-day readmission and associated hospital mortality of patients discharged from the Internal Medicine Unit of a Brazilian tertiary public hospital. METHODS: This retrospective cohort study included all patients discharged from the Internal Medicine Unit of our institution between September and November 2017 who were nonelectively readmitted within 30 days. RESULTS: A total of 1047 hospital discharges were analyzed. The rate of nonelective 30-day readmission was 13.7%. Of these, 41 (28.5%) were early readmissions (0-7 days) and 103 (71.5%) were late readmissions (8-30 days). The hospital mortality rate during readmission was 27.8%, being significantly higher during early readmissions (41.5% vs 22.3%; P = .035). Early (as compared with late) readmission was associated with mortality during readmission (relative risk [RR] 1.95; 95% confidence interval, 1.18-3.22; P = .002), regardless of age and Charlson comorbidity index. CONCLUSION: The Readmission rate was 13.7%, with an associated mortality of 27.8%. Early readmission was an independent predictor of mortality (RR 1.95) in relation to late readmission. Larger studies are needed to better identify this group of patients with an aim to adopt preventive measures.

Causes and Predictors of In-Hospital Mortality in Patients Admitted with or for Heart Failure at a Tertiary Hospital in Brazil.

BACKGROUND: Although heart failure (HF) has high morbidity and mortality, studies in Latin America on causes and predictors of in-hospital mortality are scarce. We also do not know the evolution of patients with compensated HF hospitalized for other reasons. OBJECTIVE: To identify causes and predictors of in-hospital mortality in patients hospitalized for acute decompensated HF (ADHF), compared to those with HF and admitted to the hospital for non-HF related causes (NDHF). METHODS: Historical cohort of patients hospitalized in a public tertiary hospital in Brazil with a diagnosis of HF identified by the Charlson Comorbidity Index (CCI). RESULTS: A total of 2056 patients hospitalized between January 2009 and December 2010 (51% men, median age of 71 years, length of stay of 15 days) were evaluated. There were 17.6% of deaths during hospitalization, of which 58.4% were non-cardiovascular (63.6% NDHF vs 47.4% ADHF, p = 0.004). Infectious causes were responsible for most of the deaths and only 21.6% of the deaths were attributed to HF. The independent predictors of in-hospital mortality were similar between the groups and included: age, length of stay, elevated potassium, clinical comorbidities, and CCI. Renal insufficiency was the most relevant predictor in both groups. CONCLUSION: Patients hospitalized with HF have high in-hospital mortality, regardless of the primary reason for hospitalization. Few deaths are directly attributed to HF; Age, renal function and levels of serum potassium, length of stay, comorbid burden and CCI were independent predictors of in-hospital death in a Brazilian tertiary hospital.

Causes and Predictors of In-Hospital Mortality in Patients Admitted with or for Heart Failure at a Tertiary Hospital in Brazil / Causas e Preditores de Mortalidade Intra-Hospitalar em Pacientes que Internam com ou por Insuficiência Cardíaca em Hospital Terciário no Brasil

Abstract Background: Although heart failure (HF) has high morbidity and mortality, studies in Latin America on causes and predictors of in-hospital mortality are scarce. We also do not know the evolution of patients with compensated HF hospitalized for other reasons. Objective: To identify causes and predictors of in-hospital mortality in patients hospitalized for acute decompensated HF (ADHF), compared to those with HF and admitted to the hospital for non-HF related causes (NDHF). Methods: Historical cohort of patients hospitalized in a public tertiary hospital in Brazil with a diagnosis of HF identified by the Charlson Comorbidity Index (CCI). Results: A total of 2056 patients hospitalized between January 2009 and December 2010 (51% men, median age of 71 years, length of stay of 15 days) were evaluated. There were 17.6% of deaths during hospitalization, of which 58.4% were non-cardiovascular (63.6% NDHF vs 47.4% ADHF, p = 0.004). Infectious causes were responsible for most of the deaths and only 21.6% of the deaths were attributed to HF. The independent predictors of in-hospital mortality were similar between the groups and included: age, length of stay, elevated potassium, clinical comorbidities, and CCI. Renal insufficiency was the most relevant predictor in both groups. Conclusion: Patients hospitalized with HF have high in-hospital mortality, regardless of the primary reason for hospitalization. Few deaths are directly attributed to HF; Age, renal function and levels of serum potassium, length of stay, comorbid burden and CCI were independent predictors of in-hospital death in a Brazilian tertiary hospital.

Resumo Fundamento: Apesar da insuficiência cardíaca (IC) apresentar elevada morbimortalidade, são escassos os estudos na América Latina sobre causas e preditores de mortalidade intra-hospitalar. Desconhece-se, também, a evolução de pacientes com IC compensada hospitalizados por outros motivos. Objetivo: Identificar causas e preditores de mortalidade intra-hospitalar em pacientes que internam por IC aguda descompensada (ICAD), comparativamente aqueles que possuem IC e internam por outras condições (ICND). Métodos: Coorte histórica de pacientes internados em um hospital público terciário no Brasil com diagnóstico de IC identificados pelo escore de comorbidade de Charlson (ECCharlson). Resultados: Foram avaliados 2056 pacientes que internaram entre janeiro de 2009 e dezembro de 2010 (51% homens; idade mediana de 71 anos; tempo de permanência de 15 dias). Ocorreram 17,6% de óbitos durante a internação, dos quais 58,4% por causa não cardiovascular (63,6% ICND versus 47,4% ICAD, p = 0,004). As causas infecciosas foram responsáveis pela maior parte dos óbitos e apenas 21.6% das mortes foram atribuídas à IC. Os preditores independentes de mortalidade intra-hospitalar foram semelhantes entre os grupos e incluíram: idade, tempo de permanência, potássio elevado, comorbidades clínicas e ECCharlson. A insuficiência renal foi o preditor de maior relevância em ambos grupos. Conclusão: Pacientes internados com IC apresentam elevada mortalidade intra-hospitalar, independentemente do motivo primário de internação. Poucos óbitos são diretamente atribuídos à IC; Idade, alteração na função renal e níveis séricos de potássio, tempo de permanência, comorbidades e ECCharlson foram preditores independentes de morte intra-hospitalar em hospital terciário brasileiro. (Arq Bras Cardiol. 2017; [online].ahead print, PP.0-0)

Causas e preditores de mortalidade em pacientes que internam com ou por insuficiência cardíaca em hospital terciário no Brasil

Comparar, em hospital brasileiro, preditores e causas de morte em pacientes que internam por insuficiência cardíaca aguda descompensada (ICAD) versus pacientes com insuficiência cardíaca (IC) que internam por outros motivos (ICND): Coorte prospectiva de pacientes internados com diagnóstico de IC identificado pelo escore de Charlson, com acompanhamento mediano de 46 meses. Avaliamos 2.056 pacientes (17,6% óbitos no hospital e 38,7% óbitos após alta). Houve mais óbitos por causa cardiovascular no grupo ICAD (principalmente IC) e por doença não cardiovascular no grupo ICND. Não houve diferença de sobrevida pós-alta entre os grupos. O escore de Charlson e a idade foram preditores independentes de morte comum tanto no ambiente hospitalar como extra-hospitalar. A identificação de paciente de alto risco, independente do motivo de internação, é fundamental para se criar modelos prognósticos e assistenciais. Sugere-se pesquisar causas de óbito e populações variadas para diminuir sua morbimortalidade.

Decreased mortality in patients hospitalized due to respiratory diseases after installation of an intensive care unit in a secondary hospital in the interior of Brazil.

OBJECTIVE: To evaluate the association between the in-hospital mortality of patients hospitalized due to respiratory diseases and the availability of intensive care units. METHODS: This retrospective cohort study evaluated a database from a hospital medicine service involving patients hospitalized due to respiratory non-terminal diseases. Data on clinical characteristics and risk factors associated with mortality, such as Charlson score and length of hospital stay, were collected. The following analyses were performed: univariate analysis with simple stratification using the Mantel Haenszel test, chi squared test, Student's t test, Mann-Whitney test, and logistic regression. RESULTS: Three hundred thirteen patients were selected, including 98 (31.3%) before installation of the intensive care unit and 215 (68.7%) after installation of the intensive care unit. No significant differences in the clinical and anthropometric characteristics or risk factors were observed between the groups. The mortality rate was 18/95 (18.9%) before the installation of the intensive care unit and 21/206 (10.2%) after the installation of the intensive care unit. Logistic regression analysis indicated that the probability of death after the installation of the intensive care unit decreased by 58% (OR: 0.42; 95%CI 0.205 -0.879; p = 0.021). CONCLUSION: Considering the limitations of the study, the results suggest a benefit, with a decrease of one death per every 11 patients treated for respiratory diseases after the installation of an intensive care unit in our hospital. The results corroborate the benefits of the implementation of intensive care units in secondary hospitals.

Redução de mortalidade em pacientes internados por doenças respiratórias após a implementação de unidade de cuidados intensivos em hospital secundário do interior do Brasil / Decreased mortality in patients hospitalized due to respiratory diseases after installation of an intensive care unit in a secondary hospital in the interior of Brazil

RESUMOObjetivo:Avaliar relação entre a mortalidade intra-hospitalar de pacientes internados por doenças respiratórias e a disponibilidade de unidades de terapia intensiva.Métodos:Foi realizada coorte retrospectiva do banco de dados em um serviço de medicina hospitalar. Selecionaram- se pacientes internados por doenças respiratórias não terminais. Características clínicas, fatores de risco associado à mortalidade, como o escore de Charlson, e tempo de internação foram coletados. Foram realizados: análise univariada com estratificação simples por Mantel Haenszel, e testes qui quadrado, t de Student e Mann-Whitney, além de regressão logística.Resultados:Foram selecionados 313 pacientes, 98 (31,3%) antes da instalação da unidade de terapia intensiva e 215 (68,7%) após a disponibilização de unidade de terapia intensiva. Quando comparados quanto a características clínicas, antropométricas e fatores de risco, não houve diferença significativa. A mortalidade antes da disponibilidade da unidade de terapia intensiva foi de 18/95 (18,9%) e, após, de 21/206 (10,2%). Na regressão logística, a chance de morte após implantação da unidade de terapia intensiva diminuiu em 58% (OR: 0,42; IC95% 0,205 - 0,879; p = 0,021).Conclusão:Respeitando as limitações do estudo, conjetura-se benefício na redução de uma morte a cada 11 pacientes tratados por doenças respiratórias após a implantação da unidade de terapia intensiva no hospital. Estes resultados corroboram a impressão do benefício da implantação de unidades de terapia intensiva em hospitais de nível secundário.

ABSTRACTObjective:To evaluate the association between the in-hospital mortality of patients hospitalized due to respiratory diseases and the availability of intensive care units.Methods:This retrospective cohort study evaluated a database from a hospital medicine service involving patients hospitalized due to respiratory non-terminal diseases. Data on clinical characteristics and risk factors associated with mortality, such as Charlson score and length of hospital stay, were collected. The following analyses were performed: univariate analysis with simple stratification using the Mantel Haenszel test, chi squared test, Student’s t test, Mann-Whitney test, and logistic regression.Results:Three hundred thirteen patients were selected, including 98 (31.3%) before installation of the intensive care unit and 215 (68.7%) after installation of the intensive care unit. No significant differences in the clinical and anthropometric characteristics or risk factors were observed between the groups. The mortality rate was 18/95 (18.9%) before the installation of the intensive care unit and 21/206 (10.2%) after the installation of the intensive care unit. Logistic regression analysis indicated that the probability of death after the installation of the intensive care unit decreased by 58% (OR: 0.42; 95%CI 0.205 -0.879; p = 0.021).Conclusion:Considering the limitations of the study, the results suggest a benefit, with a decrease of one death per every 11 patients treated for respiratory diseases after the installation of an intensive care unit in our hospital. The results corroborate the benefits of the implementation of intensive care units in secondary hospitals.

A clinical decision support system for venous thromboembolism prophylaxis at a general hospital in a middle-income country.

OBJECTIVE: To determine the impact that implementing a combination of a computer-based clinical decision support system and a program of training seminars has on the use of appropriate prophylaxis for venous thromboembolism (VTE). METHODS: We conducted a cross-sectional study in two phases (prior to and after the implementation of the new VTE prophylaxis protocol) in order to evaluate the impact that the combined strategy had on the use of appropriate VTE prophylaxis. The study was conducted at Nossa Senhora da Conceição Hospital, a general hospital in the city of Porto Alegre, Brazil. We included clinical and surgical patients over 18 years of age who were hospitalized for > 48 h. The pre-implementation and post-implementation phase samples comprised 262 and 261 patients, respectively. RESULTS: The baseline characteristics of the two samples were similar, including the distribution of patients by risk level. Comparing the pre-implementation and post-implementation periods, we found that the overall use of appropriate VTE prophylaxis increased from 46.2% to 57.9% (p = 0.01). Looking at specific patient populations, we observed that the use of appropriate VTE prophylaxis increased more dramatically among cancer patients (from 18.1% to 44.1%; p = 0.002) and among patients with three or more risk factors (from 25.0% to 42.9%; p = 0.008), two populations that benefit most from prophylaxis. CONCLUSIONS: It is possible to increase the use of appropriate VTE prophylaxis in economically constrained settings through the use of a computerized protocol adhered to by trained professionals. The underutilization of prophylaxis continues to be a major problem, indicative of the need for ongoing improvement in the quality of inpatient care.

Sistema de suporte à decisão clínica para um programa para profilaxia de tromboembolia venosa em um hospital geral de um país de renda média / A clinical decision support system for venous thromboembolism prophylaxis at a general hospital in a middle-income country

OBJETIVO: Determinar o impacto da implantação de um sistema informatizado de suporte à decisão clínica combinado com seminários instrucionais na utilização de profilaxia para tromboembolia venosa (TEV) de forma adequada. MÉTODOS: Estudo transversal em duas fases (antes e depois da implantação de um novo protocolo de profilaxia para TEV) para avaliar o impacto que a estratégia combinada teve na utilização adequada da profilaxia para TEV. O estudo foi conduzido no Hospital Nossa Senhora da Conceição, um hospital geral localizado em Porto Alegre (RS). Foram incluídos pacientes clínicos e cirúrgicos com mais de 18 anos com tempo de hospitalização > 48 h. Nas fases pré e pós-implantação, foram incluídos 262 e 261 pacientes, respectivamente. RESULTADOS: As características de base das duas amostras foram semelhantes, inclusive em relação à distribuição dos pacientes por nível de risco. Comparando-se os períodos pré e pós-implantação, verificou-se que a adequação da profilaxia para TEV aumentou de 46,2% para 57,9% (p = 0,01). Ao se observar populações específicas de pacientes, o uso adequado da profilaxia para TVE aumentou dramaticamente em pacientes com câncer (de 18,1% para 44,1%; p = 0,002) e em pacientes com três ou mais fatores de risco (de 25,0% para 42,9%; p = 0,008), populações essas que mais se beneficiam da profilaxia. CONCLUSÕES: É possível aumentar o uso de profilaxia adequada para TEV em cenários economicamente desfavoráveis através do uso de protocolos informatizados e de profissionais treinados. A subutilização da profilaxia permanece como um problema importante, destacando a necessidade da melhora continuada na qualidade da assistência hospitalar.

OBJECTIVE: To determine the impact that implementing a combination of a computer-based clinical decision support system and a program of training seminars has on the use of appropriate prophylaxis for venous thromboembolism (VTE). METHODS: We conducted a cross-sectional study in two phases (prior to and after the implementation of the new VTE prophylaxis protocol) in order to evaluate the impact that the combined strategy had on the use of appropriate VTE prophylaxis. The study was conducted at Nossa Senhora da Conceição Hospital, a general hospital in the city of Porto Alegre, Brazil. We included clinical and surgical patients over 18 years of age who were hospitalized for > 48 h. The pre-implementation and post-implementation phase samples comprised 262 and 261 patients, respectively. RESULTS: The baseline characteristics of the two samples were similar, including the distribution of patients by risk level. Comparing the pre-implementation and post-implementation periods, we found that the overall use of appropriate VTE prophylaxis increased from 46.2% to 57.9% (p = 0.01). Looking at specific patient populations, we observed that the use of appropriate VTE prophylaxis increased more dramatically among cancer patients (from 18.1% to 44.1%; p = 0.002) and among patients with three or more risk factors (from 25.0% to 42.9%; p = 0.008), two populations that benefit most from prophylaxis. CONCLUSIONS: It is possible to increase the use of appropriate VTE prophylaxis in economically constrained settings through the use of a computerized protocol adhered to by trained professionals. The underutilization of prophylaxis continues to be a major problem, indicative of the need for ongoing improvement in the quality of inpatient care.

Venous thromboembolism prophylaxis in a general hospital.

OBJECTIVE: To evaluate the use of venous thromboembolism (VTE) prophylaxis in a general hospital. METHODS: A cross-sectional cohort study at the Hospital Nossa Senhora da Conceição, located in the city of Porto Alegre, Brazil, involving a random sample of patients admitted between October of 2008 and February of 2009. We included patients over 18 years of age and hospitalized for more than 48 h. The exclusion criteria were anticoagulant use, pregnancy, puerperium, and a history of thromboembolic disease. The adequacy of prophylaxis was evaluated in accordance with a protocol created by the Hospital and principally based on the American College of Chest Physicians guidelines, eighth edition. RESULTS: We included 262 patients. The mean age was 59.1 ± 16.6 years. The most common risk factors were immobilization (in 70.6%), infection (in 44.3%), cancer (in 27.5%), obesity (in 23.3%), and major surgery (in 14.1%). The risk of VTE was classified as high and moderate in 143 (54.6%) and 117 (44.7%) of the patients, respectively. Overall, 46.2% of the patients received adequate prophylaxis, 25% of those with > three risk factors for VTE and 18% of those with cancer, the differences between these last two groups and their counterparts (patients with < three risk factors and those without cancer) being statistically significant (p < 0.001 for both). CONCLUSIONS: Our data reveal that nearly all patients at our hospital were at risk for VTE, and that less than half received adequate VTE prophylaxis, which is in agreement with the literature. It is surprising that inadequate prophylaxis is more common in high-risk patients.

Profilaxia para tromboembolia venosa em um hospital geral / Venous thromboembolism prophylaxis in a general hospital

OBJETIVO: Avaliar a prática de profilaxia para tromboembolia venosa (TEV) em pacientes em um hospital geral. MÉTODOS: Estudo de coorte transversal conduzido no Hospital Nossa Senhora da Conceição, localizado na cidade de Porto Alegre (RS), com uma amostra constituída de pacientes internados selecionados randomicamente entre outubro de 2008 e fevereiro de 2009. Foram incluídos pacientes maiores de 18 anos e internados por mais de 48 h. Os critérios de exclusão foram pacientes em uso de anticoagulantes, história de doença tromboembólica, gestação e puerpério. A adequação da profilaxia foi avaliada seguindo as recomendações de um protocolo criado pela instituição e tendo como base principal a diretriz da American College of Chest Physician, oitava edição. RESULTADOS: Foram incluídos 262 pacientes com média de idade de 59,1 ± 16,6 anos. Os fatores de risco mais comuns foram imobilização (70,6 por cento), infecção (44,3 por cento), câncer (27,5 por cento), obesidade (23,3 por cento) e cirurgia maior (14,1 por cento). Na avaliação do nível de risco para TEV, 143 (54,6 por cento) e 117 pacientes (44,7 por cento), respectivamente, foram classificados como de risco alto e moderado. No geral, 46,2 por cento dos pacientes tiveram profilaxia adequada, assim como 25 por cento dos pacientes com três ou mais fatores de risco e 18 por cento dos pacientes com câncer, e houve diferenças estatisticamente significativas entre esses grupos quando comparados àqueles com menos de três fatores de risco e sem câncer (p < 0,001 para ambos). CONCLUSÕES: Os dados demonstram que quase a totalidade dos pacientes do hospital estava em risco para TEV e que menos da metade deles recebeu profilaxia adequada, dados esses semelhantes aos da literatura. A inadequação da profilaxia é surpreendentemente maior em pacientes de alto risco.

OBJECTIVE: To evaluate the use of venous thromboembolism (VTE) prophylaxis in a general hospital. METHODS: A cross-sectional cohort study at the Hospital Nossa Senhora da Conceição, located in the city of Porto Alegre, Brazil, involving a random sample of patients admitted between October of 2008 and February of 2009. We included patients over 18 years of age and hospitalized for more than 48 h. The exclusion criteria were anticoagulant use, pregnancy, puerperium, and a history of thromboembolic disease. The adequacy of prophylaxis was evaluated in accordance with a protocol created by the Hospital and principally based on the American College of Chest Physicians guidelines, eighth edition. RESULTS: We included 262 patients. The mean age was 59.1 ± 16.6 years. The most common risk factors were immobilization (in 70.6 percent), infection (in 44.3 percent), cancer (in 27.5 percent), obesity (in 23.3 percent), and major surgery (in 14.1 percent). The risk of VTE was classified as high and moderate in 143 (54.6 percent) and 117 (44.7 percent) of the patients, respectively. Overall, 46.2 percent of the patients received adequate prophylaxis, 25 percent of those with > three risk factors for VTE and 18 percent of those with cancer, the differences between these last two groups and their counterparts (patients with < three risk factors and those without cancer) being statistically significant (p < 0.001 for both). CONCLUSIONS: Our data reveal that nearly all patients at our hospital were at risk for VTE, and that less than half received adequate VTE prophylaxis, which is in agreement with the literature. It is surprising that inadequate prophylaxis is more common in high-risk patients.

Synaptic plasma membrane Na(+), K (+)-ATPase activity is significantly reduced by the alpha-keto acids accumulating in maple syrup urine disease in rat cerebral cortex.

The objective of the present study was to investigate the in vitro effects of the branched-chain alpha-keto acids accumulating in maple syrup urine disease, namely L-2-ketoisocaproic acid, L-2-keto-3-methylvaleric acid and L-2-ketoisovaleric acid on Na(+), K(+)-ATPase activity in synaptic plasma membranes from cerebral cortex of 35-day-old rats. All keto acids significantly inhibited Na(+), K(+)-ATPase activity at concentrations similar (1 mM) or even lower (0.5 mM) than those found in blood and cerebrospinal fluid of maple syrup urine disease patients. We also tested the effects of alanine on this enzyme activity. Alanine per se did not alter Na(+), K(+)-ATPase activity, but totally prevented the branched-chain alpha-keto acids-induced Na(+), K(+)-ATPase inhibition, indicating that alanine and the keto acids may possibly bind to the same site on the enzyme. We also observed that the branched-chain amino acids leucine, isoleucine and valine also inhibited Na(+) K(+)-ATPase activity to a similar degree as that of the branched-chain alpha-keto acids and that alanine was able to fully prevent these effects. Considering that Na(+), K(+)-ATPase is a critical enzyme for normal brain development and functioning, it is presumed that these findings may be involved in the pathophysiology of the neurological dysfunction of maple syrup urine disease.