Enabling scalable clinical interpretation of ML-based phenotypes using real world data

The availability of large and deep electronic healthcare records (EHR) datasets has the potential to enable a better understanding of real-world patient journeys, and to identify novel subgroups of patients. ML-based aggregation of EHR data is mostly tool-driven, i.e., building on available or newly developed methods. However, these methods, their input requirements, and, importantly, resulting output are frequently difficult to interpret, especially without in-depth data science or statistical training. This endangers the final step of analysis where an actionable and clinically meaningful interpretation is needed.This study investigates approaches to perform patient stratification analysis at scale using large EHR datasets and multiple clustering methods for clinical research. We have developed several tools to facilitate the clinical evaluation and interpretation of unsupervised patient stratification results, namely pattern screening, meta clustering, surrogate modeling, and curation. These tools can be used at different stages within the analysis. As compared to a standard analysis approach, we demonstrate the ability to condense results and optimize analysis time. In the case of meta clustering, we demonstrate that the number of patient clusters can be reduced from 72 to 3 in one example. In another stratification result, by using surrogate models, we could quickly identify that heart failure patients were stratified if blood sodium measurements were available. As this is a routine measurement performed for all patients with heart failure, this indicated a data bias. By using further cohort and feature curation, these patients and other irrelevant features could be removed to increase the clinical meaningfulness. These examples show the effectiveness of the proposed methods and we hope to encourage further research in this field.Comment: 27 pages, 14 figure

[angioedema Related To The Use Of Streptokinase].

Angioedema is a rare reaction to streptokinase, acute and potentially fatal, which should be quickly diagnosed and treated to guarantee the best prognosis for the patient. We describe here the case of a 65-year-old man, who displayed an anaphylactic reaction after the beginning of thrombolysis with streptokinase, which was quickly treated, and remained hospitalized for one week in the Intensive Care Unit.85131-

Assessment of myocardial infarction by cardiovascular magnetic resonance and computed tomography angiography in patients with cocaine-associated chest pain

INTRODUÇÃO: A cocaína é a terceira droga ilícita mais comumente utilizada nos Estados Unidos e a principal responsável pelo atendimento de pacientes usuários de drogas em serviços de emergência médica. A queixa mais comum na entrada da emergência é a dor torácica, referida em 40% dos casos. Além disso, o uso crônico leva a piora da hipertensão, hipertrofia ventricular esquerda e acelera a aterosclerose. A ressonância magnética cardiovascular é um excelente método para avaliação da morfologia e função ventricular, com excelente reprodutibilidade, e atualmente considerada padrão ouro. A angiotomografia coronária é um método diagnóstico em ascensão, permitindo a detecção de DAC obstrutiva e não obstrutiva, acrescentando informação para a estratificação de risco cardiovascular. O objetivo desse estudo foi avaliar a eventual presença de infarto prévio em pacientes jovens (18 a 40 anos) usuários de cocaína, que apresentavam dor torácica, através da detecção de fibrose miocárdica por exame de ressonância magnética cardiovascular. O objetivo secundário foi avaliar alterações parietais e obstruções das coronárias desses pacientes por angiotomografia coronária. MÉTODOS: Avaliamos 24 pacientes usuários de cocaína (nas formas inalatória, injetável ou crack) que apresentavam dor torácica freqüente e de longa duração relacionada ao seu uso. Esses pacientes realizaram a angiotomografia coronária e a ressonância magnética cardiovascular. A angiotomografia coronária avaliou o escore de cálcio e árvore coronária por segmentos, e a ressonância magnética cardiovascular avaliou dimensões, volumes e função ventricular, bem como a eventual presença de realce tardio miocárdico. RESULTADOS: Foram estudados 24 pacientes, 22 homens, com idade média de 29,7 anos (18 a 40 anos). A grande maioria dos pacientes (79%) fazia uso de cocaína inalatória de forma freqüente e 71% dos pacientes já haviam usado crack. O escore de cálcio foi positivo em apenas um paciente [54 (Agatston) e 56 (volume)]. Nenhum dos pacientes apresentou redução luminal significativa. Dos segmentos coronários avaliados, apenas um paciente apresentou placas calcificadas na artéria descendente anterior, nos segmentos proximal e médio. A análise da função ventricular global através da fração de ejeção (FE), volume diastólico final (VDF), volume sistólico final (VSF), e massa ventricular foi considerada normal em 100% da amostra. As médias da FE, VDF e VSF foram 60,7%, 147,7 ml e 59,1 ml, respectivamente. O índice cardíaco foi considerado normal em todos os pacientes, com média de 2,9. Nenhum paciente apresentou hipertrofia miocárdica. A análise da função ventricular segmentar através da análise dos 17 segmentos foi normal em todos os pacientes. Nenhum paciente apresentou realce tardio indicativo de fibrose miocárdica. CONCLUSÃO: A ressonância magnética cardiovascular não demonstrou, na população estudada, a presença de realce tardio miocárdico indicativo de fibrose, em indivíduos jovens e de baixo risco para doença arterial coronária, e com episódios de dor precordial prolongada durante ou após o uso de cocaína. A tomografia computadorizada corroborou o perfil de baixo risco clínico, demonstrando a ausência de ateromatose coronária na grande maioria (96%) dos indivíduos estudados. Apenas uma pequena porcentagem (4%) dos indivíduos apresentou ateromatose coronária discreta, sem obstruções significativasINTRODUCTION: Cocaine is the third most commonly used illicit drug in the United States and the leading cause of emergency department visits among drug users. Chest pain is the most common cocaine-related presentation, being reported in 40% of patients. Its chronic use causes hypertensive crises, myocardium hypertrophy and accelerates the process of atherosclerosis. Cardiovascular magnetic resonance provides an accurate assessment of cardiac morphology and ventricular function with excellent reproductibility, and it is considered the gold standard method. Computed tomography angiography has emerged as a powerful tool to evaluate patients with suspected coronary artery disease at the same time that it helps in the prognostic assessment of the patient. The purpose of this study was to evaluate the incidence of previous myocardial infarction among young cocaine users (18 to 40 years) with chest pain related with the use of the drug by the assessment of myocardial fibrosis through cardiovascular magnetic resonance. Secondarily, was also meant the evaluation of the coronary tree by the computed tomography angiography. METHODS: We studied 24 cocaine users (crystalline, powder or granular forms) that frequently complained about chest pain related to the use of the cocaine. These patients underwent computed tomography angiography with assessment of calcium score and the evaluation of the segmented coronary arteries, and cardiovascular magnetic resonance to assess dimensions, volumes and ventricular function of the heart, and the presence of myocardial fibrosis. RESULTS: We studied 24 patients (22 male), mean age of 29.7 years. Most of the patients (79%) had frequently used inhalatory cocaine, 71% of them had also used the crack cocaine form. The calcium score turned out to be positive in only one patient [54 (Agatston) and 56 (volume)]. None of them showed significant coronary stenosis. Among the coronary segments evaluated, only one patient had calcified plaques at the anterior descending coronary artery (proximal and medium segments). The global analysis of the left ventricular function assessed by the ejection fraction (EF), end diastolic volume (EDV), end sistolic volume (ESV) and ventricular mass were considered normal in 100% of the patients. Mean EF, EDV and ESV were 60.7%, 147.7mL and 59.1mL respectivelly. Cardiac index was normal in all patients. None of the patients showed myocardial hypertrophy. Assessment of regional ventricular function by the evaluation of 17 segments was normal in all patients. None of the patients showed myocardial delayed-enhancement, indicative of myocardial fibrosis. CONCLUSION: Cardiovascular magnetic resonance did not detect the presence of delayed enhancement indicative of myocardial fibrosis among young cocaine users with low cardiovascular risk with complaints of chest pain during or after cocaine abuse. Computed tomography angiography confirmed low cardiovascular risk of these patients, since most of them (96%) had no atherosclerosis detected by this exam. Only one patient (4%) had coronary atherosclerosis detected, without significant coronary stenosi

Angioedema relacionado ao uso de estreptoquinase

O angioedema é uma reação rara, aguda e potencialmente fatal, à estreptoquinase, devendo ser diagnosticada prontamente e tratada para garantir melhor prognóstico ao paciente. Descrevemos aqui o caso de um homem de 65 anos, que apresentou reação anafilática após o início de trombólise com estreptoquinase, sendo rapidamente tratado, permaneceu uma semana internado em Unidade de Terapia Intensiva

Switching to riociguat versus maintenance therapy with phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension (REPLACE): a multicentre, open-label, randomised controlled trial

Background Riociguat and phosphodiesterase-5 inhibitors (PDE5i), approved for the treatment of pulmonary arterial hypertension (PAH), act on the same pathway via different mechanisms. Riociguat might be an alternative option for patients with PAH who do not respond sufficiently to treatment with PDE5i, but comparisons of the potential benefits of riociguat and PDE5i in these patients are needed. The aim of this trial was to assess the effects of switching to riociguat from PDE5i therapy versus continued PDE5i therapy in patients with PAH at intermediate risk of 1-year mortality. Methods Riociguat rEplacing PDE5i therapy evaLuated Against Continued PDE5i thErapy (REPLACE) was an openlabel, randomised controlled trial in 81 hospital-based pulmonary hypertension centres in 22 countries. The study enrolled patients aged 18-75 years with symptomatic PAH at intermediate risk of 1-year mortality (based on the European Society for Cardiology-European Respiratory Society guideline thresholds for WHO functional class and 6-min walk distance [6MWD]) who were receiving treatment with a PDE5i with or without an endothelin receptor antagonist for at least 6 weeks before randomisation. Patients were excluded if they had been previously treated with riociguat, had used prostacyclin analogues or prostacyclin receptor agonists within 30 days before randomisation, had clinically significant restrictive or obstructive parenchymal lung disease, or had left heart disease. Patients were randomly assigned (1:1) to remain on PDE5i treatment (oral sildenafil [>= 60 mg per day] or oral tadalafil [20-40 mg per day]; the PDE5i group) or to switch to oral riociguat (up to 2.5 mg three times per day; the riociguat group), using an interactive voice and web response system, stratified by cause of PAH. The primary endpoint was clinical improvement by week 24, defined as an absence of clinical worsening and prespecified improvements in at least two of three variables (6MWD, WHO functional class, and N-terminal prohormone of brain natriuretic peptide), analysed using last observation carried forward in all randomly assigned patients with observed values at baseline and week 24 who received at least one dose of study medication (the full analysis set). Secondary endpoints included clinical worsening events. The trial has been completed and is registered with ClinicalTrials.gov, NCT02891850. Findings Between Jan 11, 2017, and July 31, 2019, 293 patients were screened, of which 226 patients were randomly assigned to the riociguat group (n=111) or to the PDE5i group (n=115). 211 patients completed the study and 14 patients discontinued (seven in each group). One patient assigned to the PDE5i group did not receive treatment, so 225 patients were included in the safety analysis, and one further patient in the PDE5i group had missing components of the composite primary endpoint at baseline, so 224 patients were included in the full analysis set. The primary endpoint was met by 45 (41%) of 111 patients in the riociguat group and 23 (20%) of 113 patients in the PDE5i group; odds ratio [OR] 2.78 (95% CI 1.53-506; p=0.0007). Clinical worsening events occurred in one (1%) of 111 patients in the riociguat group (hospitalisation due to worsening PAH) and 10 (9%) of 114 patients in the PDE5i group (hospitalisation due to worsening PAH [n=9]; disease progression [n=1]; OR 0.10 [0.01-0.73]; p=0.0047). The most frequently occurring adverse events were hypotension (15 [14%]), headache (14 [13%]), and dyspepsia (10 [9%]) in the riociguat group, and headache (eight [7%]), cough (seven [6%]), and upper respiratory tract infection (seven [6%]) in the PDE5i group. Serious adverse events were reported in eight (7%) of 111 patients in the riociguat group and 19 (17%) of 114 patients in the PDE5i group. During the study, four patients died in the PDE5i group, one of them during the safety follow-up period. Interpretation Switching to riociguat from PDE5i treatment, both of which act via the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate pathway, could be a strategic option for treatment escalation in patients with PAH at intermediate risk of 1-year mortality