Greg, ML – Machine Learning for Healthcare at a Scale

This paper introduces the Greg, ML platform, a machine-learning engine and toolset conceived to generate automatic diagnostic suggestions based on patient profiles. Greg, ML departs from many other experiences in machine learning for healthcare in the fact that it was designed to handle a large number of different diagnoses, in the order of the hundreds. We discuss the architecture that stands at the core of Greg, ML, designed to handle the complex challenges posed by this ambitious goal, and confirm its effectiveness with experimental results based on the working prototype we have developed. Finally, we discuss challenges and opportunities related to the use of this kind of tools in medicine, and some important lessons learned while developing the tool. In this respect, we underline that Greg, ML should be conceived primarily as a support for expert doctors in their diagnostic decisions, and can hardly replace humans in their judgment

Spleen histology in children with sickle cell disease and hereditary spherocytosis: Hints on the disease pathophysiology

open2Hereditary spherocytosis (HS) and sickle cell disease (SCD) are associated with splenomegaly and spleen dysfunction in pediatric patients. Scant data exist on possible correlations between spleen morphology and function in HS and SCD. This study aimed to assess the histological and morphometric features of HS and SCD spleens, in order to get possible correlations with disease pathophysiology. In a large series of spleens from SCD, HS and control patients the following parameters were considered: (i) macroscopic features; (ii) lymphoid follicle (LF) density; (iii) presence of peri-follicular marginal zones (MZs); (iv) presence of Gamna-Gandy bodies; (v) density of CD8-positive sinusoids; (vi) density of CD34-positive microvessels; (vii) presence/distribution of fibrosis and SMA-positive myoid cells; (viii) density of CD68-positive macrophages. SCD and HS spleens have similar macroscopic features. SCD spleens had lower LF density and fewer MZs than HS spleens and controls. SCD also showed lower CD8-positive sinusoid density, increased CD34-positive microvessel density and SMA-positive myoid cells, and higher prevalence of fibrosis and Gamna-Gandy bodies. HS had lower LF and CD8-positive sinusoid density than controls. No significant differences were noted in red pulp macrophages. By multivariate analysis, the majority of HS spleens clustered with controls, while SCD grouped separately. A multi-parametric score could predict the degree of spleen changes irrespective of the underlying disease. In conclusion, SCD spleens display greater histologic effacement than HS and SCD-related changes suggest impaired function due to vascular damage. These observations may contribute to guide the clinical management of patients.embargoed_20161128Alaggio, RitaAlaggio, Rita; Gamba, Piergiorgi

Reproducibility of the Brazilian Portuguese version of the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire used in conjunction with its lung cancer-specific module

OBJECTIVE: The assessment of the quality of life in patients with lung cancer has become one of the main goals in current clinical trials. To assess the quality of life of these patients, the most widely used instrument is the 30-item European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) in conjunction with its supplemental 13-item lung cancer-specific module (QLQ-LC13). The objective of this study was to assess the reproducibility of the Brazilian Portuguese version of these questionnaires. METHODS: A prospective study involving 30 stable outpatients with lung cancer who completed the instruments on the first day of the study and two weeks later. RESULTS: The test-retest reproducibility using the intraclass correlation coefficient for the EORTC QLQ-C30 and the QLQ-LC13 ranged from 0.64 to 1.00 and from 0.64 to 0.95, respectively. No correlations were found between the domains of the instruments and clinical parameters. CONCLUSIONS: Our findings show that these instruments were reproducible in this sample of patients with lung cancer in Brazil.OBJETIVO: A avaliação da qualidade de vida em pacientes com câncer de pulmão tem se tornado um dos principais objetivos em ensaios clínicos atuais. Para avaliar a qualidade de vida desses pacientes, o instrumento mais utilizado é o 36-item European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) em conjunto com seu módulo específico para câncer de pulmão com 13 itens (QLQ-LC13). O objetivo deste estudo foi avaliar a reprodutibilidade da versão em português do Brasil desses questionários. MÉTODOS: Estudo prospectivo com 30 pacientes ambulatoriais estáveis com câncer de pulmão, os quais completaram os instrumentos no primeiro dia do estudo e duas semanas depois. RESULTADOS: A reprodutibilidade teste-reteste através do coeficiente de correlação intraclasse para o EORTC QLQ-C30 e o QLQ-LC13 variou de 0,64 a 1,00 e de 0,64 a 0,95, respectivamente. Não houve correlações entre os domínios dos instrumentos e os parâmetros clínicos. CONCLUSÕES: Estes achados demonstram a reprodutibilidade dos instrumentos utilizados nesta amostra de pacientes com câncer de pulmão no Brasil.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Ambulatório de OncopneumologiaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MedicinaUNIFESP, EPM, Ambulatório de OncopneumologiaUNIFESP, EPM, Depto. de MedicinaSciEL

Non-small cell lung cancer in never smokers: a clinical entity to be identified

OBJECTIVES: It has been recognized that patients with non-small cell lung cancer who are lifelong never-smokers constitute a distinct clinical entity. The aim of this study was to assess clinical risk factors for survival among neversmokers with non-small cell lung cancer. METHODS: All consecutive non-small cell lung cancer patients diagnosed (n = 285) between May 2005 and May 2009 were included. The clinical characteristics of never-smokers and ever-smokers (former and current) were compared using chi-squared or Student's t tests. Survival curves were calculated using the Kaplan-Meier method, and log-rank tests were used for survival comparisons. A Cox proportional hazards regression analysis was evaluated by adjusting for age (continuous variable), gender (female vs. male), smoking status (never- vs. ever-smoker), the Karnofsky Performance Status Scale (continuous variable), histological type (adenocarcinoma vs. non-adenocarcinoma), AJCC staging (early vs. advanced staging), and treatment (chemotherapy and/or radiotherapy vs. the best treatment support). RESULTS: Of the 285 non-small cell lung cancer patients, 56 patients were never-smokers. Univariate analyses indicated that the never-smoker patients were more likely to be female (68% vs. 32%) and have adenocarcinoma (70% vs. 51%). Overall median survival was 15.7 months (95% CI: 13.2 to 18.2). The never-smoker patients had a better survival rate than their counterpart, the ever-smokers. Never-smoker status, higher Karnofsky Performance Status, early staging, and treatment were independent and favorable prognostic factors for survival after adjusting for age, gender, and adenocarcinoma in multivariate analysis. CONCLUSIONS: Epidemiological differences exist between never- and ever-smokers with lung cancer. Overall survival among never-smokers was found to be higher and independent of gender and histological type

Reliability of the Brazilian version of the Functional Assessment of Cancer Therapy‐Lung (FACT‐L) and the FACT‐Lung Symptom Index (FLSI)

OBJECTIVES: The purpose of this study was to assess the reliability of the Brazilian version of the Functional Assessment of Cancer Therapy-Lung (FACT-L) with the FACT-Lung Symptom Index (FLSI) questionnaire. INTRODUCTION: The assessment of quality of life in patients with lung cancer has become an important evaluative endpoint in current clinical trials. For lung cancer patients, one of the most common quality of life tools available is the FACT-L. Despite the amount of data available regarding this questionnaire, there are no data on its performance in Brazilian lung cancer patients. METHODS: The FACT-L with the FLSI questionnaire was prospectively administered to 30 consecutive, stable, lung cancer outpatients at baseline and at 2 weeks. RESULTS: The intraclass correlation coefficient between test and retest for the FACT-L ranged from 0.79 to 0.96 and for the FLSI was 0.87. There was no correlation between these questionnaire dimensions and clinical or functional parameters. CONCLUSIONS: The Brazilian version of the FACT-L with FLSI questionnaire is reliable and is quick and simple to apply. This instrument can now be used to properly evaluate the quality of life of Brazilian lung cancer patients

Anxiety and depression in asthma patients: impact on asthma control

OBJECTIVE: There is evidence that asthma is associated with an increase in psychiatric symptoms and mental disorders. This association can make it difficult to achieve asthma control. The purpose of this study was to determine whether the level of asthma control is associated with anxiety and depression. METHODS: A crosssectional study involving 78 patients with confirmed moderate or severe asthma and under regular treatment at the Asthma Outpatient Clinic of the Federal University of São Paulo Hospital São Paulo, in the city of São Paulo, Brazil. The patients were divided into two groups by asthma control status, as assessed by the asthma control test, and were subsequently compared in terms of demographic, clinical, and spirometric data, as well as scores for asthma quality of life and hospital anxiety/depression. RESULTS: The sample was predominantly female. Of the 78 patients, 49 (63%) were classified as having uncontrolled asthma. The prevalence of anxiety and of anxiety+depression was significantly higher among patients with uncontrolled asthma than among those with controlled asthma (78% and 100%; p = 0.04 and p = 0.02, respectively), whereas there were no differences between the two groups in terms of the prevalence of depression, spirometry results, or quality of life score. CONCLUSIONS: In this sample, the prevalence of anxiety symptoms was higher in the patients with uncontrolled asthma than in those with controlled asthma.In the evaluation of asthma patients, the negative impact of mood states ought to be taken into consideration when asthma control strategies are being outlined.OBJETIVO: Existem evidências da associação entre asma e sintomas psiquiátricos e transtornos mentais. Essa associação pode resultar em dificuldades de se atingir o controle da asma. O objetivo deste estudo foi avaliar a associação de ansiedade e depressão com o controle da asma. MÉTODOS: Estudo transversal com 78 pacientes asmáticos com diagnóstico confirmado de asma moderada a grave e regularmente tratados no Ambulatório de Asma do Hospital São Paulo da Universidade Federal de São Paulo (UNIFESP), São Paulo (SP). Os pacientes foram divididos em dois grupos em relação ao status de controle de asma, determinado através do teste de controle da asma, e, posteriormente, comparados em termos de dados demográficos, clínicos e espirométricos, escore do questionário de qualidade de vida para asma e escore da escala hospitalar de ansiedade e depressão. RESULTADOS: A maioria era do sexo feminino. Dos 78 pacientes, 49 (63%) foram classificados como tendo asma não controlada. A prevalência de ansiedade e do binômio ansiedade/depressão foi significantemente maior entre os pacientes não controlados do que nos controlados (78% e 100%; p = 0,04 e p = 0,02, respectivamente), enquanto nem prevalência de depressão, nem os dados espirométricos ou de qualidade de vida diferiram entre os grupos. CONCLUSÕES: Nesta amostra, os pacientes com asma não controlada apresentaram uma maior prevalência de sintomas de ansiedade que aqueles com asma controlada. Na avaliação de pacientes asmáticos, deve-se considerar o impacto negativo dos distúrbios de humor nas estratégias de controle da asma.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Programa de Pós-Graduação em PneumologiaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PneumologiaUNIFESP, EPM, Programa de Pós-Graduação em PneumologiaUNIFESP, EPM, Depto. de PneumologiaSciEL

Performance of a word labeled visual analog scale in determining the degree of dyspnea during exercise-induced bronchoconstriction in children and adolescents with asthma

OBJECTIVE: There is an indirect relationship between airway obstruction in asthma and the intensity of breathlessness (dyspnea). A word labeled visual analog dyspnea scale with a 0-3 score has been widely used for the assessment of the degree of bronchoconstriction, although the perception of such obstruction varies considerably. The objective of this study was to determine whether children and adolescents are able to perceive acute exercise-induced bronchoconstriction (EIB), as well as to measure the discriminatory power of a word labeled visual analog dyspnea scale in relation to the intensity of the EIB. METHODS: A cross-sectional study involving 134 children and adolescents with asthma and submitted to a six-minute steady-state exercise test on a cycle ergometer. The intensity of dyspnea was determined using a word labeled visual analog dyspnea scale prior to each determination of FEV1. The scale is scored from 0 to 3, with a logical sequence of pictures, ranging from no symptoms to severe dyspnea. Variables were determined at baseline, as well as at 5, 10, and 20 min after the exercise test. The accuracy of the dyspnea scale in identifying the degree of EIB was determined by means of ROC curves for the post-exercise fall in FEV1, using cut-off points of 10%, 20%, 30%, and 40%. RESULTS: Of the patients selected, 111 finished the study, and 52 (46.8%) presented with EIB. The area under the ROC curve increased in direct proportion to increases in the degree of bronchoconstriction. CONCLUSIONS: Among children and adolescents with asthma, the accuracy of this dyspnea scale improves as the post-exercise percentage fall in FEV1 increases. However, the predictive value of the scale is suboptimal when the percentage fall in FEV1 is lower.OBJETIVO: Existe uma relação indireta entre a obstrução das vias aéreas em asma e a intensidade de falta de ar (dispneia). Uma escala visual analógica legendada de dispneia com escore de 0-3 pontos tem sido amplamente utilizada na avaliação da broncoconstrição, embora a percepção de tal obstrução seja muito variável. O objetivo deste estudo foi determinar se crianças e adolescentes são capazes de perceber a broncoconstrição aguda induzida por exercício (BAIE), bem como medir o poder discriminatório de uma escala visual analógica legendada de dispneia em relação à intensidade de BAIE. MÉTODOS: Estudo transversal com 134 crianças e adolescentes asmáticos que foram submetidos a um teste de broncoespasmo induzido por seis minutos de exercício em um cicloergômetro. A intensidade da dispneia foi determinada utilizando-se uma escala visual analógica legendada de dispneia antes de cada determinação de VEF1. A escala tem um escore de 0-3 pontos, com desenhos em uma sequência lógica variando entre sem sintomas e dispneia grave. As variáveis foram determinadas no momento basal, assim como em 5, 10 e 20 minutos após o término do teste de exercício. A acurácia da escala de dispneia em detectar o grau de BAIE foi determinada através de curvas ROC para a queda de VEF1 após o exercício, usando pontos de corte de 10%, 20%, 30% e 40%. RESULTADOS: Dos pacientes selecionados, 111 completaram o estudo, e 52 (46,8%) apresentaram BAIE. A área sob a curva ROC progressivamente aumentou com o aumento do grau de broncoconstrição. CONCLUSÕES: Em crianças e adolescentes asmáticos, a acurácia desta escala de dispneia melhora com o aumento do percentual de queda em VEF1 após o exercício. Entretanto, o valor preditivo da escala é subótimo quando a porcentagem de queda em VEF1é menor.Universidade Federal de São Paulo (UNIFESP) Departamento de MedicinaHospital Darcy VargasUNIFESP, Depto. de MedicinaSciEL

Influence of oscillating positive expiratory pressure and the forced expiratory technique on sputum cell counts and quantity of induced sputum in patients with asthma or chronic obstructive pulmonary disease

OBJECTIVE: To evaluate whether respiratory therapy techniques influence the number of cells within and quantity of induced sputum in patients with asthma or chronic obstructive pulmonary disease (COPD). METHODS: Randomized clinical trial, in which patients with asthma or COPD under intervention (n = 16 and 10, respectively) were compared with control groups (n = 16 and 10). Patients in the asthma/intervention (A/I) and COPD/intervention (C/I) groups were submitted to oscillating positive expiratory pressure maneuvers for 5 min, followed by 10 forced expiratory technique sequences. These patients were also submitted to an induced sputum protocol with inhaled hypertonic saline (3%, 4% or 5%; A/I group) or inhaled isotonic saline (C/I group). The asthma/control (A/C) and COPD/control (C/C) groups were submitted only to the standard induced sputum protocol. RESULTS: The final mean weight of the sputum samples was significantly greater in the A/I group than in the A/C group (2,767.25 ± 998.08 mg vs. 1,689.17 ± 1,189.96 mg; p = 0.03). The mean/median total cell counts (×10(6)/mL) were higher in the A/I and C/I groups than in the A/C and C/C groups (4.06/0.95 and 0.63/0.39, p = 0.05, vs. 5.08/1.77 and 0.64/0.40, p = 0.02). There were no statistically significant differences among the groups in terms of cell viability. CONCLUSIONS: The use of respiratory therapy techniques can increase sputum sample weight in asthma patients, as well as increasing total cell counts in patients with asthma or COPD.OBJETIVO: Avaliar se técnicas fisioterápicas interferem no número de células e na quantidade do escarro obtido por coleta induzida, em pacientes com asma e doença pulmonar obstrutiva crônica (DPOC). MÉTODOS: Ensaio clínico prospectivo e randomizado, no qual os pacientes com asma ou DPOC sob intervenção (n = 16 e 10, respectivamente) foram comparados com grupos controle (n = 16 e 10). Pacientes dos grupos asma/intervenção (A/I) e DPOC/intervenção (D/I) foram submetidos a manobras de pressão expiratória positiva oscilante por 5 min, seguidas de 10 repetições da técnica de expiração forçada. Além disso, esses pacientes foram submetidos a um protocolo de indução de escarro com a inalação de solução salina hipertônica (3%, 4% e 5%), no caso dos A/I, e de solução salina isotônica, no caso dos D/I. Os grupos asma/controle(A/C) e DPOC/controle (D/C) foram somente submetidos ao protocolo padrão de indução de escarro. RESULTADOS: Houve aumento significante do peso média final de escarro no grupo A/I vs. grupo A/C (2.767,25 ± 998,08 mg e 1.689,17 ± 1.189,96 mg, respectivamente; p = 0,03). O número absoluto de células (×10(6)/mL) foi maior nos grupos A/I e D/I do que nos grupos A/C e D/C (média/mediana, 4,06/0,95 e 0,63/0,39, respectivamente; p = 0,05; e 5,08/1,77 e 0,64/0,40; p = 0,02). A viabilidade celular não apresentou diferença estatisticamente significante entre os grupos. CONCLUSÕES: O uso de técnicas respiratórias pode aumentar o peso do escarro em pacientes com asma, assim como aumentar o número absoluto de células em pacientes com asma ou DOPC.Universidade Regional IntegradaUniversidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Assessment of the quality of life of patients with lung cancer using the Medical Outcomes Study 36-item Short-Form Health Survey

OBJECTIVE: To assess the quality of life of patients with lung cancer and to compare it with that of individuals without cancer. METHODS: The Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) was administered to 57 patients diagnosed with lung cancer, treated at the Lung Cancer Outpatient Clinic of the Hospital São Paulo, and to a control group of 57 individuals recruited from the Extra Penha workout group. The Mann-Whitney test was used to compare the groups, domain by domain. The first model of logistic regression was adjusted for male gender, nonsurgical treatment, Karnofsky performance status and smoking, which were included as predictors. The second model was adjusted for each SF-36 domain in order to identify increases in the proportions of patients in stage IIIB or IV. RESULTS: The lung cancer group and the control group presented the following mean scores, respectively, for the SF-36 domains: role limitations due to physical health problems, 29.39 ± 36.94 and 82.89 ± 28.80; role limitations due to emotional problems, 42.78 ± 44.78 and 86.55 ± 28.77; physical function, 56.49 ± 28.39 and 89.00 ± 13.80; vitality, 61.61 ± 23.82 and 79.12 ± 17.68; bodily pain, 62.72 ± 28.72 and 81.54 ± 19.07; general health, 62.51 ± 25.57 and 84.47 ± 13.47; emotional well-being, 68.28 ± 23.46 and 82.63 ± 17.44; and social functioning, 72.87 ± 29.20 and 91.67 ± 17.44. The logistic regression model showed that role limitations due to physical health problems, physical function and emotional well-being were predictors of stages IIIB and IV. CONCLUSIONS: The patients with lung cancer had a poorer quality of life, especially regarding physical aspects, than did the control subjects.OBJETIVO: Avaliar a qualidade de vida de pacientes com câncer de pulmão e compará-la com a qualidade de vida de indivíduos sem câncer. MÉTODOS: O questionário Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) foi aplicado em 57 pacientes com diagnóstico de câncer de pulmão provenientes do Ambulatório de Oncopneumologia do Hospital São Paulo e em um grupo controle de 57 indivíduos participantes do Grupo de Ginástica Extra Penha. O teste de Mann-Whitney foi utilizado para comparar cada domínio entre os grupos. O primeiro modelo de regressão logística foi ajustado para sexo masculino, tratamento não cirúrgico, índice de Karnofsky e tabagismo, que foram incluídos como preditores. O segundo modelo foi ajustado para cada domínio do SF-36 para identificar aumento na proporção de estádios IIIB e IV. RESULTADOS: O grupo com câncer de pulmão e o grupo controle apresentaram, respectivamente, as seguintes pontuações médias para os domínios do SF-36: aspectos físicos, 29,39 ± 36,94 e 82,89 ± 28,80; aspectos emocionais, 42,78 ± 44,78 e 86,55 ± 28,77; capacidade funcional, 56,49 ± 28,39 e 89,00 ± 13,80; vitalidade, 61,61 ± 23,82 e 79,12 ± 17,68; dor, 62,72 ± 28,72 e 81,54 ± 19,07; estado geral de saúde, 62,51 ± 25,57 e 84,47 ± 13,47; saúde mental, 68,28 ± 23,46 e 82,63 ± 17,44; e aspectos sociais, 72,87 ± 29,20 e 91,67 ± 17,44. O modelo de regressão logística demonstrou que aspectos físicos, capacidade funcional e saúde mental foram preditores de estádios IIIB e IV. CONCLUSÕES: Os pacientes com câncer de pulmão apresentaram pior qualidade de vida em relação ao grupo controle, principalmente em relação aos aspectos físicos.Universidade Federal de São Paulo (UNIFESP)Centro Universitário São CamiloUNIFESPSciEL