Central auditory system assessment in children and adolescents with cystic fibrosis: electrophysiology and central auditory processing.

OBJECTIVE: This study aims to evaluate the central auditory system of children and adolescents with cystic fibrosis through behavioral assessment of central auditory processing and electrophysiological tests to investigate short and long-latency auditory potentials, comparing them with the results obtained in the control group. METHODS: 117 from 7 to 21 years old patients were evaluated, 57 of them with cystic fibrosis and 60 of the control group, using behavioral evaluation of central auditory processing, auditory brainstem response and long latency auditory evoked potential. The comparison of the research groups was performed using ANOVA for Auditory Brain Response and P300 responses and Wilcoxon and Mann-Whitney tests for Central Auditory Processing responses. RESULTS: A statistically significant difference was found in the results of the GIN test between the groups and in the auditory brainstem response latency responses in waves I and V in the comparison between the groups with higher latencies in the study group. A difference was also found between latencies in the interpeak intervals I-III and III-V. The long latency auditory evoked potential analysis shows a statistically significant difference in the latency of the P300 potential, with higher latencies in the study group. CONCLUSION: Cystic fibrosis participants presented worse performance in the gaps-in-noise test compared to the control group in the evaluation of central auditory processing, which indicates impairment of temporal resolution auditory ability. They also showed increased latency in I and V waves of auditory brainstem response, as well as an increase P300 latency in long latency auditory evoked potential.

Identification of Chagas disease biomarkers using untargeted metabolomics.

Untargeted metabolomic analysis is a powerful tool used for the discovery of novel biomarkers. Chagas disease (CD), caused by Trypanosoma cruzi, is a neglected tropical disease that affects 6-7 million people with approximately 30% developing cardiac manifestations. The most significant clinical challenge lies in its long latency period after acute infection, and the lack of surrogate markers to predict disease progression or cure. In this cross-sectional study, we analyzed sera from 120 individuals divided into four groups: 31 indeterminate CD, 41 chronic chagasic cardiomyopathy (CCC), 18 Latin Americans with other cardiomyopathies and 30 healthy volunteers. Using a high-throughput panel of 986 metabolites, we identified three distinct profiles among individuals with cardiomyopathy, indeterminate CD and healthy volunteers. After a more stringent analysis, we identified some potential biomarkers. Among peptides, phenylacetylglutamine and fibrinopeptide B (1-13) exhibited an increasing trend from controls to ICD and CCC. Conversely, reduced levels of bilirubin and biliverdin alongside elevated urobilin correlated with disease progression. Finally, elevated levels of cystathionine, phenol glucuronide and vanillactate among amino acids distinguished CCC individuals from ICD and controls. Our novel exploratory study using metabolomics identified potential biomarker candidates, either alone or in combination that if confirmed, can be translated into clinical practice.

Cross-cultural adaptation and validation of the CFAbd-Score for gastrointestinal symptoms in patients with cystic fibrosis.

OBJECTIVE: Translating and cross-culturally adapting the CFAbd-Score, Cystic Fibrosis (CF) Abdominal Score, to use in Brazilian spoken Portuguese. The CFAbd-Score is a questionnaire for assessing CF-related abdominal symptoms and their influence on the quality of life (QoL). It comprises 28 questions on five domains: abdominal pain, bowel movements, eating and appetite, gastroesophageal reflux symptoms, and the impact of gastrointestinal (GI) symptoms on QoL. METHOD: Cross-cultural adaptation included assessment of conceptual and item equivalence, semantic, operational, and measurement equivalence. Content validity was assessed. The validation and psychometric analysis phase included 97 people with CF (pwCF), median age:14.58y (IQR 9/19), and 105 healthy individuals, 15.10y (IQR 9/20). Exploratory factor analysis (FA) identified retained factors. Internal consistency of the extracted domains was evaluated using Cronbach's α, and the Kaiser-Meyer-Olkin test (KMO) was used to check the sample adequacy. Bartlett's test tested the null hypothesis that the correlation matrix is an identity matrix. RESULTS: All items were considered relevant to the construct and good semantic equivalence of the version was recognized. FA showed the appropriate weight of all items and good internal consistency, with Cronbach's alpha 0.89. Bartlett's test significance level (p < 0.001) and KMO coefficient of 0.72 indicated good adequacy for structure. Internal consistency coefficients (Cronbach's alpha) were good for abdominal pain: 0.84; abdominal bloating: 0.73; flatulence: 0.76; heartburn: 0.81, and low for reflux: 0.54. CONCLUSION: The CFAbd-Score was adapted to the Brazilian spoken Portuguese and demonstrated content and semantic equivalence. The final version showed appropriate validity, and internal consistency, preserving the psychometric properties of the original version.

Epidemiology of cardiometabolic health in Latin America and strategies to address disparities.

In Latin America and the Caribbean (LAC), sociodemographic context, socioeconomic disparities and the high level of urbanization provide a unique entry point to reflect on the burden of cardiometabolic disease in the region. Cardiovascular diseases are the main cause of death in LAC, precipitated by population growth and ageing together with a rapid increase in the prevalence of cardiometabolic risk factors, predominantly obesity and diabetes mellitus, over the past four decades. Strategies to address this growing cardiometabolic burden include both population-wide and individual-based initiatives tailored to the specific challenges faced by different LAC countries, which are heterogeneous. The implementation of public policies to reduce smoking and health system approaches to control hypertension are examples of scalable strategies. The challenges faced by LAC are also opportunities to foster innovative approaches to combat the high burden of cardiometabolic diseases such as implementing digital health interventions and team-based initiatives. This Review provides a summary of trends in the epidemiology of cardiometabolic diseases and their risk factors in LAC as well as context-specific disease determinants and potential solutions to improve cardiometabolic health in the region.

Evaluation of Silybin Nanoparticles against Liver Damage in Murine Schistosomiasis mansoni Infection.

Silybin (SIB) is a hepatoprotective drug known for its poor oral bioavailability, attributed to its classification as a class IV drug with significant metabolism during the first-pass effect. This study explored the potential of solid lipid nanoparticles with (SLN-SIB-U) or without (SLN-SIB) ursodeoxycholic acid and polymeric nanoparticles (PN-SIB) as delivery systems for SIB. The efficacy of these nanosystems was assessed through in vitro studies using the GRX and Caco-2 cell lines for permeability and proliferation assays, respectively, as well as in vivo experiments employing a murine model of Schistosomiasis mansoni infection in BALB/c mice. The mean diameter and encapsulation efficiency of the nanosystems were as follows: SLN-SIB (252.8 ± 4.4 nm, 90.28 ± 2.2%), SLN-SIB-U (252.9 ± 14.4 nm, 77.05 ± 2.8%), and PN-SIB (241.8 ± 4.1 nm, 98.0 ± 0.2%). In the proliferation assay with the GRX cell line, SLN-SIB and SLN-SIB-U exhibited inhibitory effects of 43.09 ± 5.74% and 38.78 ± 3.78%, respectively, compared to PN-SIB, which showed no inhibitory effect. Moreover, SLN-SIB-U demonstrated a greater apparent permeability coefficient (25.82 ± 2.2) than PN-SIB (20.76 ± 0.1), which was twice as high as that of SLN-SIB (11.32 ± 4.6) and pure SIB (11.28 ± 0.2). These findings suggest that solid lipid nanosystems hold promise for further in vivo investigations. In the murine model of acute-phase Schistosomiasis mansoni infection, both SLN-SIB and SLN-SIB-U displayed hepatoprotective effects, as evidenced by lower alanine amino transferase values (22.89 ± 1.6 and 23.93 ± 2.4 U/L, respectively) than those in control groups I (29.55 ± 0.7 U/L) and I+SIB (34.29 ± 0.3 U/L). Among the prepared nanosystems, SLN-SIB-U emerges as a promising candidate for enhancing the pharmacokinetic properties of SIB.

Venomous gland transcriptome and venom proteomic analysis of the scorpion Androctonus amoreuxi reveal new peptides with anti-SARS-CoV-2 activity.

The recent COVID-19 pandemic shows the critical need for novel broad spectrum antiviral agents. Scorpion venoms are known to contain highly bioactive peptides, several of which have demonstrated strong antiviral activity against a range of viruses. We have generated the first annotated reference transcriptome for the Androctonus amoreuxi venom gland and used high performance liquid chromatography, transcriptome mining, circular dichroism and mass spectrometric analysis to purify and characterize twelve previously undescribed venom peptides. Selected peptides were tested for binding to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and inhibition of the spike RBD - human angiotensin-converting enzyme 2 (hACE2) interaction using surface plasmon resonance-based assays. Seven peptides showed dose-dependent inhibitory effects, albeit with IC50 in the high micromolar range (117-1202 µM). The most active peptide was synthesized using solid phase peptide synthesis and tested for its antiviral activity against SARS-CoV-2 (Lineage B.1.1.7). On exposure to the synthetic peptide of a human lung cell line infected with replication-competent SARS-CoV-2, we observed an IC50 of 200 nM, which was nearly 600-fold lower than that observed in the RBD - hACE2 binding inhibition assay. Our results show that scorpion venom peptides can inhibit the SARS-CoV-2 replication although unlikely through inhibition of spike RBD - hACE2 interaction as the primary mode of action. Scorpion venom peptides represent excellent scaffolds for design of novel anti-SARS-CoV-2 constrained peptides. Future studies should fully explore their antiviral mode of action as well as the structural dynamics of inhibition of target virus-host interactions.

Outcomes of latent rheumatic heart disease: External validation of a simplified score in patients with and without secondary prophylaxis.

BACKGROUND: Secondary antibiotic prophylaxis reduces progression of latent rheumatic heart disease (RHD) but not all children benefit. Improved risk stratification could refine recommendations following positive screening. We aimed to evaluate the performance of a previously developed echocardiographic risk score to predict mid-term outcomes among children with latent RHD. METHODS: We included children who completed the GOAL, a randomized trial of secondary antibiotic prophylaxis among children with latent RHD in Uganda. Outcomes were determined by a 4-member adjudication panel. We applied the point-based score, consisting of 5 variables (mitral valve (MV) anterior leaflet thickening (3 points), MV excessive leaflet tip motion (3 points), MV regurgitation jet length ≥ 2 cm (6 points), aortic valve focal thickening (4 points) and any aortic regurgitation (5 points)), to panel results. Unfavorable outcome was defined as progression of diagnostic category (borderline to definite, mild definite to moderate/severe definite), worsening valve involvement or remaining with mild definite RHD. RESULTS: 799 patients (625 borderline and 174 definite RHD) were included, with median follow-up of 24 months. At total 116 patients (14.5%) had unfavorable outcome per study criteria, 57.8% not under prophylaxis. The score was strongly associated with unfavorable outcome (HR = 1.26, 95% CI 1.16-1.37, p < 0.001). Unfavorable outcome rates in low (≤6 points), intermediate (7-9 points) and high-risk (≥10 points) children at follow-up were 11.8%, 30.4%, and 42.2%, (p < 0.001) respectively (C-statistic = 0.64 (95% CI 0.59-0.69)). CONCLUSIONS: The simple risk score provided an accurate prediction of RHD status at 2-years, showing a good performance in a population with milder RHD phenotypes.

Associação entre o Perfil Hemodinâmico da Insuficiência Cardíaca à Admissão Hospitalar e Mortalidade - Programa Boas Práticas Clínicas em Cardiologia / Association between Hemodynamic Profile at Hospital Admission and Mortality in Acute Heart Failure Patients Included in the Best Practice in Cardiology Program in Brazil

Resumo Fundamento: A insuficiência cardíaca (IC) é responsável por alta carga de internações hospitalares. A sua forma de apresentação está relacionada ao prognóstico da doença. Objetivos: Descrever a associação entre o perfil hemodinâmico de admissão hospitalar na IC aguda, baseado em congestão (úmido ou seco) e perfusão (frio ou quente), e desfechos de mortalidade, tempo de internação e chance de reinternação. Métodos: Estudo de coorte, envolvendo pacientes do projeto "Boas Práticas Clínicas em Cardiologia", internados por IC aguda em hospitais públicos brasileiros, entre março de 2016 a dezembro de 2019, com seguimento de seis meses. Foram realizadas análises das características populacionais e do perfil hemodinâmico de admissão, além de análises de sobrevivência pelos modelos de Cox para associação entre o perfil de admissão e mortalidade, e regressão logística para chance de reinternação, considerando nível de significância estatística de 5%. Resultados: Foram avaliados 1978 pacientes, com idade média foi 60,2 (±14,8) anos e fração de ejeção média do ventrículo esquerdo de 39,8% (±17,3%). Houve altas taxas de mortalidade no seguimento de seis meses (22%), com associação entre os perfis hemodinâmicos frios e a mortalidade hospitalar (HR=1,72; IC95% 1,27-2,31; p < 0,001) e em 6 meses (HR= 1,61, IC 95% 1,29-2,02). A taxa de reinternação em 6 meses foi de 22%, sendo maior para os pacientes admitidos em perfis úmidos (OR 2,30; IC95% 1,45-3,65; p < 0,001). Conclusões: A IC aguda no Brasil apresenta altas taxas de mortalidade e reinternações e os perfis hemodinâmicos de admissão hospitalar são bons marcadores prognósticos dessa evolução.

Abstract Background: Heart failure (HF) contributes to a high burden of hospitalization, and its form of presentation is associated with disease prognosis. Objectives: To describe the association of hemodynamic profile of acute HF patients at hospital admission, based on congestion (wet/dry) and perfusion (cold/warm), with mortality, hospital length of stay and risk of readmission. Methods: Cohort study, with patients participating in the "Best Practice in Cardiology" program, admitted for acute HF in Brazilian public hospitals between March 2016 and December 2019, with a six-month follow-up. Characteristics of the population and hemodynamic profile at admission were analyzed, in addition to survival analysis using Cox proportional hazard model for associations between hemodynamic profile at admission and mortality, and logistic regression for the risk of rehospitalization, using a statistical significance level of 5%. Results: A total of 1,978 patients were assessed, with mean age of 60.2 (±14.8) years and mean left ventricular ejection fraction of 39.8% (±17.3%). A high six-month mortality rate (22%) was observed, with an association of cold hemodynamic profiles with in-hospital mortality (HR=1.72, 95%CI 1.27-2.31; p < 0.001) and six-month mortality (HR= 1.61, 95%CI 1.29-2.02). Six-month rehospitalization rate was 22%, and higher among patients with wet profiles (OR 2.30; 95%CI 1.45-3.65; p < 0.001). Conclusions: Acute HF is associated with high mortality and rehospitalization rates. Patient hemodynamic profile at admission is a good prognostic marker of this condition.

Combinação de Ferramentas de Telecardiologia para Estratificação de Risco Cardiovascular na Atenção Primária: Dados do Estudo PROVAR+ / Combination of Tele-Cardiology Tools for Cardiovascular Risk Stratification in Primary Care: Data from the PROVAR+ Study

Resumo Fundamento: As ferramentas de telecardiologia são estratégias valiosas para melhorar a estratificação de risco. Objetivo: Objetivamos avaliar a acurácia da tele-eletrocardiografia (ECG) para predizer anormalidades no ecocardiograma de rastreamento na atenção primária. Métodos: Em 17 meses, 6 profissionais de saúde em 16 unidades de atenção primária foram treinados em protocolos simplificados de ecocardiografia portátil. Tele-ECGs foram registrados para diagnóstico final por um cardiologista. Pacientes consentidos com anormalidades maiores no ECG pelo código de Minnesota e uma amostra 1:5 de indivíduos normais foram submetidos a um questionário clínico e ecocardiograma de rastreamento interpretado remotamente. A doença cardíaca grave foi definida como doença valvular moderada/grave, disfunção/hipertrofia ventricular, derrame pericárdico ou anormalidade da motilidade. A associação entre alterações maiores do ECG e anormalidades ecocardiográficas foi avaliada por regressão logística da seguinte forma: 1) modelo não ajustado; 2) modelo 1 ajustado por idade/sexo; 3) modelo 2 mais fatores de risco (hipertensão/diabetes); 4) modelo 3 mais história de doença cardiovascular (Chagas/cardiopatia reumática/cardiopatia isquêmica/AVC/insuficiência cardíaca). Foram considerados significativos valores de p < 0,05. Resultados: No total, 1.411 pacientes realizaram ecocardiograma, sendo 1.149 (81%) com anormalidades maiores no ECG. A idade mediana foi de 67 anos (intervalo interquartil de 60 a 74) e 51,4% eram do sexo masculino. As anormalidades maiores no ECG se associaram a uma chance 2,4 vezes maior de doença cardíaca grave no ecocardiograma de rastreamento na análise bivariada (OR = 2,42 [IC 95% 1,76 a 3,39]) e permaneceram significativas (p < 0,001) após ajustes no modelo 2 (OR = 2,57 [IC 95% 1,84 a 3,65]), modelo 3 (OR = 2,52 [IC 95% 1,80 a 3,58]) e modelo 4 (OR = 2,23 [IC 95% 1,59 a 3,19]). Idade, sexo masculino, insuficiência cardíaca e doença cardíaca isquêmica também foram preditores independentes de doença cardíaca grave no ecocardiograma. Conclusões: As anormalidades do tele-ECG aumentaram a probabilidade de doença cardíaca grave no ecocardiograma de rastreamento, mesmo após ajustes para variáveis demográficas e clínicas.

Abstract Background: Tele-cardiology tools are valuable strategies to improve risk stratification. Objective: We aimed to evaluate the accuracy of tele-electrocardiography (ECG) to predict abnormalities in screening echocardiography (echo) in primary care (PC). Methods: In 17 months, 6 health providers at 16 PC units were trained on simplified handheld echo protocols. Tele-ECGs were recorded for final diagnosis by a cardiologist. Consented patients with major ECG abnormalities by the Minnesota code, and a 1:5 sample of normal individuals underwent clinical questionnaire and screening echo interpreted remotely. Major heart disease was defined as moderate/severe valve disease, ventricular dysfunction/hypertrophy, pericardial effusion, or wall-motion abnormalities. Association between major ECG and echo abnormalities was assessed by logistic regression as follows: 1) unadjusted model; 2) model 1 adjusted for age/sex; 3) model 2 plus risk factors (hypertension/diabetes); 4) model 3 plus history of cardiovascular disease (Chagas/rheumatic heart disease/ischemic heart disease/stroke/heart failure). P-values < 0.05 were considered significant. Results: A total 1,411 patients underwent echo; 1,149 (81%) had major ECG abnormalities. Median age was 67 (IQR 60 to 74) years, and 51.4% were male. Major ECG abnormalities were associated with a 2.4-fold chance of major heart disease on echo in bivariate analysis (OR = 2.42 [95% CI 1.76 to 3.39]), and remained significant after adjustments in models (p < 0.001) 2 (OR = 2.57 [95% CI 1.84 to 3.65]), model 3 (OR = 2.52 [95% CI 1.80 to3.58]), and model 4 (OR = 2.23 [95%CI 1.59 to 3.19]). Age, male sex, heart failure, and ischemic heart disease were also independent predictors of major heart disease on echo. Conclusions: Tele-ECG abnormalities increased the likelihood of major heart disease on screening echo, even after adjustments for demographic and clinical variables.

Manejo clínico da doença de Chagas na atenção primária à saúde em área endêmica do estado de Minas Gerais, Brasil / Clinical management of Chagas disease in primary health care in an endemic area in the state of Minas Gerais, Brazil

Objetivo: Descrever o manejo clínico da Doença de Chagas (DC) por profissionais médicos da Atenção Primária à Saúde (APS) de região endêmica. Metodologia: Estudo transversal entre médicos da APS de 23 municípios. A coleta contemplou questões Demográficas, Formação Acadêmica, Características da APS de Atuação, Práticas e Conhecimento Relativos à DC. Conduziram-se análises descritivas de todas as variáveis e bivariadas para os blocos de práticas e conhecimento relativos à DC considerando o tempo de conclusão da graduação. Resultados: Foram incluídos 136 médicos. A maioria mencionou conhecer o Protocolo Clínico e Diretriz Terapêutica da DC, mas não prescreveu o benzonidazol e se sente insegura no manejo do paciente. Na análise bivariada, a variável conhecimento sobre a DC adquirido na graduação mostrou-se associada estatisticamente ao tempo de graduação. Conclusão: Importantes obstáculos ainda persistem no manejo médico ao paciente com DC na APS. A partir desse achado espera-se incentivar a qualificação.

Objective: To describe the clinical management of Chagas Disease (CD) by Primary Health Care (PHC) physicians in an endemic region. Methodology: Cross-sectional study with PHC physicians from 23 municipalities. The collection included questions on Demographics, Academic Background, Characteristics of the APS in Action, Practices and Knowledge Relating to CD. Descriptive analyzes of all variables and bivariates were carried out for the blocks of practices and knowledge related to CD, considering the time of completion of graduation. Results: 136 physicians were included. Most mentioned knowing the CD Clinical Protocol and Therapeutic Guideline, but did not prescribe benznidazole and feel insecure in-patient management. In the bivariate analysis, the variable knowledge about CD acquired during graduation was statistically associated with graduation time. Conclusion: Important obstacles still persist in the medical management of patients with CD in PHC. Based on this finding, it is expected to encourage qualification.

Vidjil add-on for MRD quantification of samples processed using the EuroClonality-NGS protocol.

Assessment of minimal residual disease in acute lymphoblastic leukemia by immune repertoire NGS requires spiking CDR3 sequences at known quantities into the patient's sample. Recently, the EuroClonality-NGS group released one of the most comprehensive protocols for this purpose. ARResT/Interrogate is a closed-source software for processing these NGS libraries, developed by this same group. Vidjil, an open-source alternative, currently cannot handle libraries prepared using this protocol. Here, we present a Vidjil add-on to solve this issue. EuroClonality-NGS prepared samples analyzed with Vidjil and ARResT/Interrogate were highly concordant (r = 0.998) and presented low error (root-mean-square error, RMSE = 0.112).

Associations Between Coronary Artery Calcification and Left Ventricular Global Longitudinal Strain and Diastolic Parameters: the ELSA-Brasil Study.

Atherosclerosis burden can be evaluated in asymptomatic patients by measuring coronary artery calcification (CAC), whereas the global longitudinal strain (GLS) and diastolic function parameters (mitral E/e' ratio, septal e', and lateral e') are used to evaluate subclinical left ventricular (LV) dysfunction. We investigated whether subjects with CAC (CAC >0 Agatston units) would present with an impairment in LV functional parameters. Among the participants of the ELSA-Brasil cohort free of clinically prevalent cardiovascular disease who performed cardiac computed tomography and echocardiography within the study protocol, we tested whether those with CAC >0 presented with worse GLS and diastolic function parameters. CAC >0 was present in 203 of the 612 included participants (33.17%; age 51.4 ± 8.6 years, 52.1% women). Absolute CAC values did not correlate with GLS (ro = 0.07, p = 0.105) but did so with E/e' (ro = 0.19, p <0.001), septal e' (ro = 0.28, p <0.001), and lateral e' (ro = 0.30, p <0.001), with stronger correlations in men. Those with CAC >0 had worse mitral E/e' ratios (7.75 ± 0.13 vs 7.01 ± 0.09; p ≤0.001), septal e' (8.25 ± 0.15 vs 9.59 ± 0.11 cm/s; p <0.001), and lateral e' (10.13 ± 0.20 vs 11.99 ± 0.14 cm/s; p ≤0.001), respectively. However, these associations were not independent of diabetes, obesity, hypertension, smoking, and low-density lipoprotein cholesterol, persisting only as significant associations of CAC >0 with mitral E/e' ratio and septal e' in men. There is an association between subclinical coronary atherosclerosis and impaired LV functional parameters. These associations are more likely attributed to the presence of common cardiovascular risk factors in the general population. However, in men, it seems to exist as an independent association.

Combined multi-channel intraluminal impedance measurement and pHmetry in the detection of gastroesophageal reflux disease in children with cystic fibrosis

Abstract Objective To assess the prevalence of GERD exclusively by means of multichannel intraluminal impedanciometry associated with pH monitoring (MIIpH) and compare it with respiratory symptoms in children with CF. To compare MIIpH with pHmetry alone to perform GERD diagnosis. Methods An analytical cross-sectional study was conducted with children diagnosed with CF who underwent MIIpH. Clinical and laboratory markers, including respiratory and digestive symptoms, were used for comparative analyses. High-resolution chest computed tomography was performed on patients with symptoms of chronic lung disease. Severity was classified according to the Bhalla score. Results A total of 29 children < 10 yo (18 girls) were evaluated; 19 of whom with physiological GER and 10 with GERD. Of the children with GERD, seven had predominantly acid GER, two acid+non-acid GER, and one non-acid GER. Three patients had GERD diagnosed only by MIIpH. Bhalla scores ranged from seven to 17.75 with no significant relationship with GERD. The number of pulmonary exacerbations was associated with a decrease in esophageal clearance regardless of the position in pHmetry and MIIpH. Conclusions The prevalence of GERD was 34% in children with CF. There was no association between respiratory disease severity and GER types. MIIpH detected 30% more patients with GERD than pHmetry.

Health Literacy, Patient Knowledge and Adherence to Oral Anticoagulation in Primary Care

Abstract Background Warfarin is the only oral anticoagulant available in the Brazilian public health system. Health knowledge and treatment are essential to achieving the desirable therapeutic effect. However, data on these aspects among primary care patients are still lacking. Objective To assess health literacy, patient knowledge, and adherence to oral anticoagulation with warfarin, as well as the medication regimen complexity in primary health units in the municipality of Divinópolis, Minas Gerais, Brazil. Methods This cross-sectional study included patients using warfarin from primary care settings. Sociodemographic and clinical data were collected from medical records. Short Assessment of Health Literacy for Portuguese-Speaking Adults (SAHLPA-18), Oral Anticoagulation Knowledge (OAK), adaptation of the Measure of Adherence to Treatment (MAT-adapted) to oral anticoagulation, and Medication Regimen Complexity Index (MRCI) were applied, and the time in therapeutic range (TTR) was calculated. Patients were stratified in two groups (TTR < 60% and TTR ≥ 60%) and compared using Fisher's exact test at a significance level of p < 0.050. Results Analysis included 162 patients (64.8 ± 12.7 years old, 55.6% women). Nonvalvular atrial fibrillation (26.5%) and venous thromboembolism (24.1%) were the main indications for warfarin, and 67.9%, 88.3%, and 16.7% of the patients had inadequate health literacy, insufficient knowledge regarding anticoagulant therapy, and non-adherence to warfarin therapy, respectively. There was no significant association of these parameters in relation to TTR. MRCI showed high pharmacotherapy complexity between the drug prescriptions. Conclusion This study showed alarming insufficient knowledge about warfarin therapy and low health literacy in primary care patients.

Association of lifestyle with deep learning predicted electrocardiographic age.

Background: People age at different rates. Biological age is a risk factor for many chronic diseases independent of chronological age. A good lifestyle is known to improve overall health, but its association with biological age is unclear. Methods: This study included participants from the UK Biobank who had undergone 12-lead resting electrocardiography (ECG). Biological age was estimated by a deep learning model (defined as ECG-age), and the difference between ECG-age and chronological age was defined as Δage. Participants were further categorized into an ideal (score 4), intermediate (scores 2 and 3) or unfavorable lifestyle (score 0 or 1). Four lifestyle factors were investigated, including diet, alcohol consumption, physical activity, and smoking. Linear regression models were used to examine the association between lifestyle factors and Δage, and the models were adjusted for sex and chronological age. Results: This study included 44,094 individuals (mean age 64 ± 8, 51.4% females). A significant correlation was observed between predicted biological age and chronological age (correlation coefficient = 0.54, P < 0.001) and the mean Δage (absolute error of biological age and chronological age) was 9.8 ± 7.4 years. Δage was significantly associated with all of the four lifestyle factors, with the effect size ranging from 0.41 ± 0.11 for the healthy diet to 2.37 ± 0.30 for non-smoking. Compared with an ideal lifestyle, an unfavorable lifestyle was associated with an average of 2.50 ± 0.29 years of older predicted ECG-age. Conclusion: In this large contemporary population, a strong association was observed between all four studied healthy lifestyle factors and deaccelerated aging. Our study underscores the importance of a healthy lifestyle to reduce the burden of aging-related diseases.

The burden of Noncommunicable Diseases in Portuguese Language Countries. / Carga das Doenças Crônicas Não Transmissíveis nos Países de Língua Portuguesa.

The present study analyzed trends in premature mortality from Noncommunicable diseases (NCDs) between 1990 and 2019, the projections up to 2030, and the risk factors (RFs) attributable to these diseases in the Community of Portuguese Language Countries (CPLP). Estimates from the Global Burden of Disease (GBD) study and the analysis of the burden of premature mortality due to NCDs were used for nine CPLP countries, applying age-standardized rates, using RStudio. Portugal, Brazil, Equatorial Guinea, Angola, and Guinea Bissau showed declining premature mortality rates caused by NCDs, while East Timor, Cape Verde, São Tomé and Príncipe, and Mozambique showed an increase in rates. Projections indicate that none of the countries is expected to achieve the goals of reducing premature mortality due to NCDs by one third by 2030. The attributable burden of disease showed that the most important RFs in 2019 were: high systolic blood pressure (SBP), tobacco, dietary risks, high body mass index (BMI), and air pollution. It can therefore be concluded that there are profound differences in the burden of NCDs among the countries, with better results in Portugal and Brazil, and that no CPLP country is likely to reach the NCD reduction target by 2030.

Foram analisadas tendências da mortalidade prematura por doenças crônicas não transmissíveis (DCNT) entre 1990 e 2019, as projeções até 2030 e os fatores de risco atribuíveis a estas doenças na Comunidade dos Países de Língua Portuguesa (CPLP). Utilizou-se estimativas do estudo Carga Global de Doenças e análise da carga de mortalidade prematura por DCNT para nove países da CPLP, utilizando taxas padronizadas por idade, usando-se RStudio. Portugal, Brasil, Guiné Equatorial, Angola e Guiné Bissau apresentam taxas de mortalidade prematura por DCNT em declínio e; Timor Leste, Cabo Verde, São Tomé e Príncipe e Moçambique apresentaram aumento das taxas. As projeções indicam que nenhum dos países deverá atingir as metas de redução em um terço da mortalidade prematura por DCNT até 2030. A carga de doença atribuível mostrou que os fatores de riscos mais importantes em 2019 foram: pressão arterial sistólica elevada, tabaco, riscos dietéticos, índice de massa corporal elevado e poluição do ar. Conclui-se pelas profundas diferenças na carga de DCNT entre os países, com melhores resultados em Portugal e Brasil e que nenhum país do CPLP deverá atingir a meta de redução das DCNT até 2030.

Carga das Doenças Crônicas Não Transmissíveis nos Países de Língua Portuguesa / The burden of Noncommunicable Diseases in Portuguese Language Countries

Resumo Foram analisadas tendências da mortalidade prematura por doenças crônicas não transmissíveis (DCNT) entre 1990 e 2019, as projeções até 2030 e os fatores de risco atribuíveis a estas doenças na Comunidade dos Países de Língua Portuguesa (CPLP). Utilizou-se estimativas do estudo Carga Global de Doenças e análise da carga de mortalidade prematura por DCNT para nove países da CPLP, utilizando taxas padronizadas por idade, usando-se RStudio. Portugal, Brasil, Guiné Equatorial, Angola e Guiné Bissau apresentam taxas de mortalidade prematura por DCNT em declínio e; Timor Leste, Cabo Verde, São Tomé e Príncipe e Moçambique apresentaram aumento das taxas. As projeções indicam que nenhum dos países deverá atingir as metas de redução em um terço da mortalidade prematura por DCNT até 2030. A carga de doença atribuível mostrou que os fatores de riscos mais importantes em 2019 foram: pressão arterial sistólica elevada, tabaco, riscos dietéticos, índice de massa corporal elevado e poluição do ar. Conclui-se pelas profundas diferenças na carga de DCNT entre os países, com melhores resultados em Portugal e Brasil e que nenhum país do CPLP deverá atingir a meta de redução das DCNT até 2030.

Abstract The present study analyzed trends in premature mortality from Noncommunicable diseases (NCDs) between 1990 and 2019, the projections up to 2030, and the risk factors (RFs) attributable to these diseases in the Community of Portuguese Language Countries (CPLP). Estimates from the Global Burden of Disease (GBD) study and the analysis of the burden of premature mortality due to NCDs were used for nine CPLP countries, applying age-standardized rates, using RStudio. Portugal, Brazil, Equatorial Guinea, Angola, and Guinea Bissau showed declining premature mortality rates caused by NCDs, while East Timor, Cape Verde, São Tomé and Príncipe, and Mozambique showed an increase in rates. Projections indicate that none of the countries is expected to achieve the goals of reducing premature mortality due to NCDs by one third by 2030. The attributable burden of disease showed that the most important RFs in 2019 were: high systolic blood pressure (SBP), tobacco, dietary risks, high body mass index (BMI), and air pollution. It can therefore be concluded that there are profound differences in the burden of NCDs among the countries, with better results in Portugal and Brazil, and that no CPLP country is likely to reach the NCD reduction target by 2030.

Primary Lateral Sclerosis: Can Rocuronium Be an Option?

Primary lateral sclerosis (PLS) is a neurodegenerative motor neuron disorder that is characterized by corticospinal and corticobulbar dysfunction. In this disease, muscle relaxants in general anesthesia should be used with extreme caution. A 67-year-old woman with a history of PLS was scheduled for laparoscopic gastrostomy due to long-term dysphagia. In the preoperative assessment, she presented a tetrapyramidal syndrome with generalized muscle weakness. A priming dose of 5 mg of rocuronium was administered and the train-of-four (TOF) ratio (T4/T1) after 60 seconds was 70% so induction was followed with fentanyl, propofol, and additional 40 mg of rocuronium. After 90 seconds when T1 was lost, the patient was intubated. During surgery, the TOF ratio increased progressively until 65%, 22 minutes after a final bolus of 10 mg of rocuronium. Prior to emergence, 150 mg of sugammadex was given and neuromuscular block reversal was evidenced with a TOF ratio > 90%. As it was decided to perform the surgery laparoscopically, general anesthesia with a neuromuscular blockade was necessary. Since it is reported that patients with motor neuron diseases show an increased sensibility to non-depolarizing muscle relaxants (NDMR), these agents should be used cautiously. Adversely to what studies document, no augmented responsiveness was shown in TOF monitoring, so the standard dose of 0.6 mg/kg of rocuronium was safely given. A final bolus of NDMR was administered after 54 minutes, demonstrating a similar pharmacokinetics profile in terms of duration of action as reported in several studies (45-70 minutes). In addition, a full and rapid neuromuscular blockade recovery with 2 mg/kg of sugammadex was seen, as previously demonstrated in a case series.