Aptamer Proteomics for Biomarker Discovery in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Proteomic Substudy.

BACKGROUND: Prognostic markers and biological pathways linked to detrimental clinical outcomes in heart failure with preserved ejection fraction (HFpEF) remain incompletely defined. METHODS AND RESULTS: We measured serum levels of 4123 unique proteins in 1117 patients with HFpEF enrolled in the PARAGON-HF (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction) trial using a modified aptamer proteomic assay. Baseline circulating protein concentrations significantly associated with the primary end point and the timing and occurrence of total heart failure hospitalization and cardiovascular death were identified by recurrent events regression, accounting for multiple testing, adjusted for age, sex, treatment, and anticoagulant use, and compared with published analyses in 2515 patients with heart failure with reduced ejection fraction from the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and ATMOSPHERE (Efficacy and Safety of Aliskiren and Aliskiren/Enalapril Combination on Morbidity-Mortality in Patients With Chronic Heart Failure) clinical trials. We identified 288 proteins that were robustly associated with the risk of heart failure hospitalization and cardiovascular death in patients with HFpEF. The baseline proteins most strongly related to outcomes included B2M (ß-2 microglobulin), TIMP1 (tissue inhibitor of matrix metalloproteinase 1), SERPINA4 (serpin family A member 4), and SVEP1 (sushi, von Willebrand factor type A, EGF, and pentraxin domain containing 1). Overall, the protein-outcome associations in patients with HFpEF did not markedly differ as compared with patients with heart failure with reduced ejection fraction. A proteomic risk score derived in patients with HFpEF was not superior to a previous proteomic score derived in heart failure with reduced ejection fraction nor to clinical risk factors, NT-proBNP (N-terminal pro-B-type natriuretic peptide), or high-sensitivity cardiac troponin. CONCLUSIONS: Numerous serum proteins linked to metabolic, coagulation, and extracellular matrix regulatory pathways were associated with worse HFpEF prognosis in the PARAGON-HF proteomic substudy. Our results demonstrate substantial similarities among serum proteomic risk markers for heart failure hospitalization and cardiovascular death when comparing clinical trial participants with heart failure across the ejection fraction spectrum. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifiers: NCT01920711, NCT01035255, NCT00853658.

Effect of Clonal Hematopoiesis Mutations and Canakinumab Treatment on Incidence of Solid Tumors in the CANTOS Randomized Clinical Trial.

Clonal hematopoiesis (CH) is more common in older persons and has been associated with an increased risk of hematological cancers and cardiovascular diseases. The most common CH mutations occur in the DNMT3A and TET2 genes and result in increased pro-inflammatory signaling. The Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS, NCT01327846) evaluated the neutralizing anti-IL-1ß antibody canakinumab in 10,061 randomized patients with a history of myocardial infarction and persistent inflammation; DNA samples were available from 3,923 patients for targeted genomic sequencing. We examined the incidence of non-hematological malignancy by treatment assignment and CH mutations and estimated the cumulative incidence of malignancy events during trial follow-up. Patients with TET2 mutations treated with canakinumab had the lowest incidence of non-hematological malignancy across cancer types. The cumulative incidence of at least one reported malignancy was lower for patients with TET2 mutations treated with canakinumab vs those treated with placebo. These findings support a potential role for canakinumab in cancer prevention and provide evidence of IL-1ß blockade cooperating with CH mutations to modify the disease course.

Effects of IL-1ß inhibition on anemia and clonal hematopoiesis in the randomized CANTOS trial.

Canakinumab, a monoclonal antibody targeting proinflammatory cytokine interleukin-1ß (IL-1ß), improved hemoglobin levels while preventing recurrent cardiovascular events in the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). This cardiovascular (CV) preventive effect was greater in patients with TET2 mutations associated with clonal hematopoiesis (CH). The current proteogenomic analysis aimed to understand the clinical response to canakinumab and underlying proteomic profiles in the context of CH and anemia. The analysis included 4595 patients from the CANTOS study who received either canakinumab or placebo and evaluated multiplexed proteomics (4785 proteins) using SomaScan and targeted deep sequencing for CH mutations. Incident anemia was more common in the presence of CH mutations but reduced by canakinumab treatment. Canakinumab treatment was significantly associated with higher hemoglobin increment in patients with concurrent CH mutations and anemia than patients with CH mutations without anemia or without CH mutations. Compared with those without CH mutations, the presence of CH mutations was associated with proteomic signatures of inflammation and defense response to infection, as well as markers of high-risk CV disease which was further enhanced by the presence of anemia. Canakinumab suppressed hepcidin, proinflammatory cytokines, myeloid activation, and complement pathways, and reversed pathologically deregulated pathways to a greater extent in patients with CH mutations and anemia. These molecular findings provide evidence of the clinical use of IL-1ß blockade and support further study of canakinumab for patients with concurrent anemia and CH mutations. This study was registered at www.clinicaltrials.gov as #NCT01327846.

Glagov revisited: coronary artery disease phenotype on non-invasive imaging provides rationale for implementing preventive pharmacotherapy-a case report.

Background: Glagov et al. showed that no reduction in vessel lumen occurred until the atherosclerotic plaque burden exceeded 40% of the vessel area. Most major adverse cardiac events occurring in the first 4 years after a myocardial infarction arise from untreated angiographically mild, non-flow-limiting lesions at the time of the index event. We report how computed tomography (CT) coronary angiography (CCTA) can be used to non-invasively risk stratify a patient with non-obstructive coronary artery disease (CAD) and guide further management. Case summary: A 69-year-old non-smoking female with hypertension, dyslipidaemia, and hypothyroidism presented with atypical chest pain. Electrocardiogram and left ventricular ejection fraction were normal. Her lipidic profile was normal. CCTA showed a lipid-rich plaque with very low attenuation (<30 HU) in the left main stem (LMS) extending into the proximal left anterior descending (LAD) and in the mid LAD artery. The maximum plaque burden in the LMS was 67% with a remodelling index of 1.375, and an area stenosis of 22%. Tissue characterization showed a lipid-rich plaque with a thin fibrous cap. The perivascular fat attenuation index (FAI) in the proximal LAD was suggestive of (-69 HU) inflamed perivascular fat. Shear stress analysis of the LMS plaque showed normal wall shear stress (WSS); however, the axial plaque stress was high. Her medications were intensified to rosuvastatin 20 mg once daily (OD) and ezetimibe 10 mg OD. The patient remained asymptomatic at 6 months follow-up. Discussion: Our case exemplifies the value of CCTA as a diagnostic 'one-stop shop' (CCTA, finite element analysis, computed tomographic density [CTD], tissue characterization analysis, FAI analysis, WSS and wall strain, and etc.) when stratifying a patient with non-obstructive CAD. With further development of novel potent anti-lipidaemic and anti-inflammatory drugs, non-obstructive lesions with adverse plaque and haemodynamic parameters will have the opportunity to be treated with additional preventive pharmacological therapy.

Clinical characteristics of heart failure with reduced ejection fraction patients with rare pathogenic variants in dilated cardiomyopathy-associated genes: A subgroup analysis of the PARADIGM-HF trial.

AIMS: To evaluate the prevalence of pathogenic variants in genes associated with dilated cardiomyopathy (DCM) in a clinical trial population with heart failure and reduced ejection fraction (HFrEF) and describe the baseline characteristics by variant carrier status. METHODS AND RESULTS: This was a post hoc analysis of the Phase 3 PARADIGM-HF trial. Forty-four genes, divided into three tiers, based on definitive, moderate or limited evidence of association with DCM, were assessed for rare predicted loss-of-function (pLoF) variants, which were prioritized using ClinVar annotations, measures of gene transcriptional output and evolutionary constraint, and pLoF confidence predictions. Prevalence was reported for pLoF variant carriers based on DCM-associated gene tiers. Clinical features were compared between carriers and non-carriers. Of the 1412 HFrEF participants with whole-exome sequence data, 68 (4.8%) had at least one pLoF variant in the 8 tier-1 genes (definitive/strong association with DCM), with Titin being most commonly affected. The prevalence increased to 7.5% when considering all 44 genes. Among patients with idiopathic aetiology, 10.0% (23/229) had tier-1 variants only and 12.6% (29/229) had tier-1, -2 or -3 variants. Compared to non-carriers, tier-1 carriers were younger (4 years; adjusted p-value [padj ] = 4 × 10-3 ), leaner (27.8 kg/m2 vs. 29.4 kg/m2 ; padj = 3.2 × 10-3 ), had lower ejection fraction (27.3% vs. 29.8%; padj = 5.8 × 10-3 ), and less likely to have ischaemic aetiology (37.3% vs. 67.4%; padj = 4 × 10-4 ). CONCLUSION: Deleterious pLoF variants in genes with definitive/strong association with DCM were identified in ∼5% of HFrEF patients from a PARADIGM-HF trial subset, who were younger, had lower ejection fraction and were less likely to have had an ischaemic aetiology.

Challenges in developmental psychology research during the COVID-19 pandemic / Desafios da pesquisa em psicologia do desenvolvimento durante a pandemia da COVID-19 / Desafíos de la investigación en psicología del desarrollo durante la pandemia de COVID-19

The COVID-19 pandemic brought a series of restructurings necessary for research in Developmental Psychology. The aim of the manuscript is to discuss adaptations we made in our research in this context during the COVID-19 pandemic and to present strategies to adequate research protocols originally designed to occur in person. Although some contexts do not allow the continuity of studies, research at this time can bring essential contributions in this extreme period. This article explores the strategies for adapting recruitment procedures, suggesting dissemination platforms, and using social networks for this purpose. Guidelines are suggested for conducting non-face-to-face interviews with caregivers, ways of assessing the interaction of the mother-child pairs, and problematizing ethical issues. The procedures for returning the results, an ethical researcher commitment, may be improved by resources such as automatic reports. Besides, strategies for better dissemination of the results for the participants are suggested. (AU)

A pandemia COVID-19 trouxe uma série de reestruturações necessárias à pesquisa em Psicologia do Desenvolvimento. O objetivo deste artigo é discutir as adaptações que realizamos em pesquisas neste contexto durante a pandemia de COVID-19 e apresentar estratégias para adequação de protocolos de pesquisa originalmente planejados para ocorrer de forma presencial. Embora alguns contextos não permitam a continuidade dos estudos, pesquisas nesse momento podem trazer importantes contribuições sobre este período ímpar. No presente artigo são exploradas estratégias de adaptação dos procedimentos de recrutamento, sugeridas plataformas de divulgação e como melhor usar as redes sociais para esse fim. Também são descritos procedimentos para realização de entrevistas não presenciais com responsáveis, formas de avaliação da interação das duplas mãe-criança e problematizadas questões éticas. Os procedimentos de devolução dos resultados, um compromisso ético dos pesquisadores, podem ser facilitados por recursos como relatórios automáticos. Além disso, sugerimos estratégias para melhor divulgação dos resultados ao público participante. (AU)

La pandemia del COVID-19 trajo una serie de reestructuraciones necesarias para la investigación en Psicología del Desarrollo. El objetivo de este artículo es discutir las adaptaciones realizadas en las investigaciones en este contexto durante la pandemia de COVID-19 y presentar algunas estrategias para la adaptación de los protocolos de investigación originalmente planeados para ser presenciales. Si bien algunos contextos no permitan la continuidad de los estudios, la investigación en este momento puede aportar importantes avances sobre estos tiempos de crisis. Este artículo explora las estrategias para adaptar los procedimientos de contratación, sugiriendo algunas plataformas de difusión y la mejor manera de utilizar las redes sociales para este fin. También se describen los procedimientos para la realización de entrevistas no presenciales con padres o tutores legales, las formas de evaluar la interacción madre-hijo y las cuestiones éticas. Los procedimientos para la devolución de los resultados, un compromiso ético de los investigadores, pueden verse facilitados por funciones como informes automáticos. Además, se recomienda estrategias para una mejor difusión de los resultados al público participante. (AU)

Follow-up em avaliação psicológica em uma amostra de serviço-escola / Follow-up on psychological assessment with a clinical school sample

A Avaliação Psicológica (AP) no contexto clínico, chamada psicodiagnóstico, possui a finalidade de auxiliar na tomada de decisão clínica do avaliado. A entrevista de devolução compõe o seu momento final, quando são dadas as indicações terapêuticas específicas do caso. Apesar da procura e do início dessas indicações constituírem o objetivo da AP, até o momento, nenhum estudo nacional abordou diretamente o que acontece após o psicodiagnóstico. Este é um estudo longitudinal quantitativo que buscou delinear os seguimentos das indicações e identificar possíveis associações entre a taxa de procura das indicações com dados clínicos e sociodemográficos. Setenta e cinco famílias provenientes de um serviço-escola em AP passaram por uma entrevista de follow-up conduzida a partir de três meses da entrevista de devolução. Análises de frequência, correlação e comparação entre grupos foram realizadas. Taxa de procura correlacionou-se negativa e moderadamente com quantidade de indicações (rs = -0,282, p < 0,02), sendo maior no grupo de pacientes que faziam uso contínuo de medicação psiquiátrica do que os que não faziam (U = 904,50, z = 2,51, p = 0,01). Discute-se a variabilidade da taxa de procura/início de acordo com as indicações terapêuticas. O modelo Barreiras ao Tratamento é abordado e foram feitas sugestões práticas que podem ser implementadas durante o processo psicodiagnóstico ou durante a entrevista de devolução.

Psychological Assessment (PA) in the clinical context, called psychodiagnosis, has the purpose of assisting in the clinical decision making of the evaluated person. The return interview is its final moment, when the specific therapeutic recommendations of the case are given. Despite the search for and the beginning of these indications constituting the main goal of PA, so far, no national study has directly addressed what happens after the psychodiagnosis. This is a quantitative longitudinal study that sought to outline referral follow-up and identify possible associations between the rate of search for referral with clinical and sociodemographic data. Seventy-five families from a school service dedicated to PA underwent a follow-up interview conducted three months from the return interview. Frequency, correlation and between groups comparison analyzes were performed. Rate of search correlated negatively and moderately with quantity of indications (rs = -.282, p < .02), being higher in the group of patients who were on continuous psychiatric medication use than those who were not (U = 904.50, z = 2.51, p = .01). The variability in the rate of search/initiation according to therapeutic indications is discussed. The Barriers to Treatment model is addressed and practical suggestions were made that can be implemented during the psychodiagnostic process or during the return interview.

Effect of indacaterol/glycopyrronium on ventilation and perfusion in COPD: a randomized trial.

RATIONALE: The long-acting ß2-agonist/long-acting muscarinic antagonist combination indacaterol/glycopyrronium (IND/GLY) elicits bronchodilation, improves symptoms, and reduces exacerbations in COPD. Magnetic resonance imaging (MRI) of the lung with hyperpolarized gas and gadolinium contrast enhancement enables assessment of whole lung functional responses to IND/GLY. OBJECTIVES: The primary objective was assessment of effect of IND/GLY on global ventilated lung volume (%VV) versus placebo in COPD. Lung function, regional ventilation and perfusion in response to IND/GLY were also measured. METHODS: This double-blind, randomized, placebo-controlled, crossover study assessed %VV and pulmonary perfusion in patients with moderate-to-severe COPD after 8 days of once-daily IND/GLY treatment (110/50 µg) followed by 8 days of placebo, or vice versa, using inhaled hyperpolarized 3He gas and gadolinium contrast-enhanced MRI, respectively. Lung function measures including spirometry were performed for each treatment after 8 days. MEASUREMENTS AND MAIN RESULTS: Of 31 patients randomized, 29 completed both treatment periods. IND/GLY increased global %VV versus placebo (61.73% vs. 56.73%, respectively, least squares means treatment difference: 5.00% [90% CI 1.40 to 8.60]; P = 0.025). IND/GLY improved whole lung index of ventilation volume to perfusion volume (V/Q) ratio versus placebo; 94% (90% CI 83 to 105) versus 86% (90% CI 75 to 97; P = 0.047), respectively. IND/GLY showed a trend to improve diffusing capacity for carbon monoxide (DLCO) (+ 0.66 mL/min/mmHg; P = 0.082). By Day 8, forced expiratory volume in 1 s (FEV1) was increased by 0.32 L versus placebo (90% CI 0.26 to 0.38; P < 0.0001), substantiating earlier findings and providing evidence of assay sensitivity for this trial. CONCLUSIONS: IND/GLY improved lung ventilation assessed by 3He MRI after 1 week of treatment. This observation may provide mechanistic support for the symptomatic clinical benefit shown with IND/GLY in COPD. Clinical trial registered with www.clinicaltrials.gov (NCT02634983).

CBCL/6-18 e TRF/6-18: contribuições para o processo psicodiagnóstico / CBCL/6-18 and TRF/6-18: contributions to psychological assessment / CBCL/6-18 y TRF/6-18: contribuciones al proceso psicodiagnóstico

Alguns dos instrumentos mais utilizados em psicodiagnóstico de crianças/adolescentes são os questionários ASEBA. Os objetivos dessa pesquisa foram: verificar quais escalas discriminariam melhor três grupos (controle, diagnóstico neurodesenvolvimental e diagnóstico neurodesenvolvimental-emocional) e avaliar a predição diagnóstica das escalas a partir da análise discriminante. Participaram 58 crianças/adolescentes, com CBCL e TRF respondidos. As escalas que discriminaram controle e neurodesenvolvimental foram Escola e Retraimento/Depressão (CBCL) e as que discriminaram neurodesenvolvimental e neurodesenvolvimental-emocional foram Problemas Sociais (CBCL) e Tempo Cognitivo Lento (TRF). Os resultados apontaram bons valores de predição dos grupos a partir das escalas mencionadas, indicando ser uma ferramenta importante na formulação de hipóteses no psicodiagnóstico.

Some of the most used instruments for children/adolescents' psychological assessment are the ASEBA forms. The objectives of this study were: to verify which scales would best discriminate three groups (control, neurodevelopmental diagnosis, and neurodevelopmental-emotional diagnosis) and to evaluate the diagnostic prediction of the subscales through discriminant analysis. Fifty-eight children/adolescents who answered the CBCL and TRF participated in the study. The subscales that discriminated better the control group from the neurodevelopmental group were School and Withdrawn/Depressed (CBCL) and the neurodevelopmental group from the neurodevelopmental and emotional group were Social Problems (CBCL) and Sluggish Cognitive Tempo (TRF). The results indicated good values ​​of diagnostic prediction from the subscales mentioned, indicating that these might be helpful for hypotheses formulation in psychological assessment.

Algunos de los instrumentos más utilizados para la evaluación psicológica de niños/adolescentes son los cuestionarios ASEBA. Los objetivos de esta investigación fueron: verificar cuáles escalas discriminarían mejor a los tres grupos de diagnóstico (control, diagnóstico de neurodesarrollo y diagnóstico concomitante emocional y de neurodesarrollo) y evaluar la predicción diagnóstica de las escalas a partir del análisis discriminante. Participaron 58 niños/adolescentes que respondieron al CBCL y TRF. Las escalas que mejor discriminaron el control y el neurodesarrollo fueron Escuela y Retraimiento/Depresión (CBCL) y las que mejor discriminaron el neurodesarrollo y diagnóstico concomitante emocional y de neurodesarrollo fueron Problemas sociales (CBCL) y Tiempo cognitivo lento (TRF). Los resultados mostraron buenos valores de predicción diagnóstica de las escalas mencionadas, lo que indica que estos pueden ayudar en la formulación de hipótesis en el psicodiagnóstico.

Avaliação de aspectos emocionais e comportamentais de crianças com Transtorno do Espectro Autista / Evaluation of emotional and behavioral aspects in children with Autism Spectrum Disorder (ASD)

RESUMO O Transtorno do Espectro Autista (TEA) tem início precoce e é caracterizado predominantemente por prejuízos persistentes na comunicação social recíproca/interação social e por padrões restritos e repetitivos de comportamento, interesses ou atividades. Pesquisas apontam que indivíduos com TEA apresentam altas taxas de problemas emocionais e de comportamento. O objetivo do presente estudo é avaliar os aspectos emocionais e comportamentais através do Child Behavior Checklist (CBCL) em crianças que preencheram critérios para o diagnóstico de TEA. Trata-se de um estudo descritivo, quantitativo e retrospectivo. No CBCL/1½-5, contatou-se que a escala Problemas do Espectro Autista apresentou escore clínico. Quanto ao CBCL/6-18, as escalas Retraimento, Problemas de Pensamento, Problemas de Atenção e Problemas de Estresse (DSM) apresentaram sintomatologia clínica. Os achados desse estudo estão de acordo com outras pesquisas da área. Os resultados do presente estudo sugerem que o CBCL é útil para a identificação de sinais de alerta de TEA.

ABSTRACT Autism Spectrum Disorder (ASD) is a neurodevelopment disorder characterized by impairments in social interaction/communication and stereotyped behavior. The literature suggests that individuals with ASD often presents emotional and behavioral problems. The aim of this study was to examine emotional and behavioral aspects in patients who have been diagnosed with ASD after a psychological evaluation. The tool used for investigation was the Child Behavior Checklist (CBCL), in both versions (1½-5 and 6-18). This is a quantitative, descriptive and retrospective study. The CBCL/1½-5 profiles showed elevated scores in Withdrawn, Internalizing Problems and Autism Spectrum Problems scales. The CBCL/6-18 showed clinical scores for Withdrawn/Depressed, Thougt Problems, Attention Problems And Stress Problems. The pattern of elevations found in this study is consistent with prior studies. Although CBCL is not a diagnostic tool, it can be considered an useful instrument for detecting alarm signs of ASD.

Vascular effects of serelaxin in patients with stable coronary artery disease: a randomized placebo-controlled trial.

AIMS: The effects of serelaxin, a recombinant form of human relaxin-2 peptide, on vascular function in the coronary microvascular and systemic macrovascular circulation remain largely unknown. This mechanistic, clinical study assessed the effects of serelaxin on myocardial perfusion, aortic stiffness, and safety in patients with stable coronary artery disease (CAD). METHODS AND RESULTS: In this multicentre, double-blind, parallel-group, placebo-controlled study, 58 patients were randomized 1:1 to 48 h intravenous infusion of serelaxin (30 µg/kg/day) or matching placebo. The primary endpoints were change from baseline to 47 h post-initiation of the infusion in global myocardial perfusion reserve (MPR) assessed using adenosine stress perfusion cardiac magnetic resonance imaging, and applanation tonometry-derived augmentation index (AIx). Secondary endpoints were: change from baseline in AIx and pulse wave velocity, assessed at 47 h, Day 30, and Day 180; aortic distensibility at 47 h; pharmacokinetics and safety. Exploratory endpoints were the effect on cardiorenal biomarkers [N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), endothelin-1, and cystatin C]. Of 58 patients, 51 were included in the primary analysis (serelaxin, n = 25; placebo, n = 26). After 2 and 6 h of serelaxin infusion, mean placebo-corrected blood pressure reductions of -9.6 mmHg (P = 0.01) and -13.5 mmHg (P = 0.0003) for systolic blood pressure and -5.2 mmHg (P = 0.02) and -8.4 mmHg (P = 0.001) for diastolic blood pressure occurred. There were no between-group differences from baseline to 47 h in global MPR (-0.24 vs. -0.13, P = 0.44) or AIx (3.49% vs. 0.04%, P = 0.21) with serelaxin compared with placebo. Endothelin-1 and cystatin C levels decreased from baseline in the serelaxin group, and there were no clinically relevant changes observed with serelaxin for NT-proBNP or hsTnT. Similar numbers of serious adverse events were observed in both groups (serelaxin, n = 5; placebo, n = 7) to 180-day follow-up. CONCLUSION: In patients with stable CAD, 48 h intravenous serelaxin reduced blood pressure but did not alter myocardial perfusion.

Orientação a práticas parentais: descrição de um programa de intervenção individual breve / Parenting practices orientation: description of a brief individual intervention program / Orientación a prácticas parentales: descripción de un breve programa de intervención individual

A orientação a práticas parentais visa modificar o contexto no qual as crianças estão inseridas como forma de potencializar mudanças em seu comportamento. Esse artigo descreve uma intervenção breve de sete encontros em modalidade individual. O programa teve como finalidades principais auxiliar os cuidadores a identificar e estimular comportamentos adequados em seus filhos; ensinar novos comportamentos; incentivar a autonomia das crianças; encontrar abordagens não-agressivas para lidar com maus comportamentos; e auxiliar na organização da rotina. Como metodologia, realizou-se a descrição de três casos, exemplificando as estratégias adotadas em cada um. A análise dos casos permitiu o delineamento de características comuns entre as práticas parentais dos pais ou cuidadores. Os casos relatados neste estudo evidenciam que as famílias utilizam punição corporal, apresentam dificuldade de empatizar com a criança, possuem um estilo parental autoritário e expectativas incompatíveis com a idade das crianças. Além disso, a infância dos pais ou cuidadores apresentou forte influência no desenvolvimento de suas práticas parentais. A sobrecarga na figura materna também ficou evidente nos casos de famílias intactas. Por fim, a intervenção pode estabelecer um contato inicial da família com um serviço de psicologia, incentivando contato posterior com serviços que possam atender às demais dificuldades. A partir dos resultados examinados, conclui-se que a intervenção breve apresentou resultados positivos na mudança das relações familiares. Porém, o estudo precisa estabelecer uma medição quantitativa antes e depois da intervenção, além de uma sessão de seguimento para verificar se as mudanças são de longo prazo.(AU)

Orientation to parenting practices aims to modify the context in which children are inserted as a means to induce changes in their behavior. This article describes a brief seven-session individual intervention program aimed to help guardians identifying and encouraging appropriate behavior in their children, teaching new behaviors, encouraging autonomy, finding non-aggressive approaches to dealing with bad behavior, and assisting in the routine organization. The study describes three cases, exemplifying the strategies adopted in each of them. The analysis allowed the delineation of common characteristics among parental practices, indicating that families use corporal punishment, struggle in empathizing with the child, and have an authoritarian parental style and expectations that are incompatible with children's age. The results indicate that the childhood of parents and guardians had a strong influence on the development of their parental practices. Moreover, intact families presented an overload in the maternal figure. In this scenario, the intervention can bridge an initial contact between the family and a psychology service, encouraging later contact that can attend to other family difficulties. Despite the positive changes in family relationships enabled by this brief intervention, the study requires a pre- and post-intervention quantitative measurement and a follow-up session to verify whether these changes are long-term.(AU)

La orientación a prácticas parentales tiene por objetivo modificar el contexto en el que viven los niños como forma de potenciar cambios en su comportamiento. Este artículo describe una intervención breve de siete encuentros individuales. El programa tuvo como finalidades principales: auxiliar a los cuidadores en la identificación y estimulación de comportamientos adecuados en sus hijos; enseñar nuevos comportamientos; fomentar la autonomía de los niños; encontrar enfoques no agresivos para manejar malos comportamientos; y ayudar en la organización de la rutina. Para ello, se describió tres casos, ejemplificando las estrategias adoptadas en cada uno. El análisis de los casos permitió el delineamiento de características comunes entre las prácticas parentales de los padres/cuidadores. Los casos reportados en este estudio evidencian que las familias utilizan castigo corporal, presentan dificultad para tener empatía con el niño, poseen un estilo parental autoritario y expectativas incompatibles con la edad de los niños. Además, la infancia de los padres/cuidadores presentó una fuerte influencia en el desarrollo de sus prácticas parentales. La sobrecarga en la figura materna también estuvo evidente en los casos de familias intactas. Por último, la intervención puede establecer un contacto inicial de la familia con un servicio de psicología, incentivando un contacto posterior con servicios que puedan atender las demás dificultades de la familia. La intervención breve presentó resultados positivos en el cambio de las relaciones familiares, pero el estudio necesita establecer una medición cuantitativa pre- y posintervención y una sesión de seguimiento para verificar si los cambios son a largo plazo.(AU)

Efficacy and Safety of the CFTR Potentiator Icenticaftor (QBW251) in COPD: Results from a Phase 2 Randomized Trial.

Rationale: Excess mucus plays a key role in COPD pathogenesis. Cigarette smoke-induced cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction may contribute to disease pathogenesis by depleting airway surface liquid and reducing mucociliary transport; these defects can be corrected in vitro by potentiating CFTR. Objective: To assess the efficacy of the CFTR potentiator icenticaftor in improving airflow obstruction in COPD patients with symptoms of chronic bronchitis. Methods: In this double-blind, placebo-controlled study, COPD patients were randomized (2:1) to either icenticaftor 300 mg or placebo b.i.d. This non-confirmatory proof of concept study was powered for lung clearance index (LCI) and pre-bronchodilator FEV1, with an estimated sample size of 90 patients. The primary endpoint was change from baseline in LCI for icenticaftor versus placebo at Day 29; key secondary endpoints included change from baseline in pre- and post-bronchodilator FEV1 on Day 29. Key exploratory endpoints included change from baseline in sweat chloride, plasma fibrinogen levels, and sputum colonization. Results: Ninety-two patients were randomized (icenticaftor, n=64; placebo, n=28). At Day 29, icenticaftor showed no improvement in change in LCI (treatment difference: 0.28 [19% probability of being better than placebo]), an improvement in pre-bronchodilator FEV1 (mean: 50 mL [84% probability]) and an improvement in post-bronchodilator FEV1 (mean: 63 mL [91% probability]) over placebo. Improvements in sweat chloride, fibrinogen and sputum bacterial colonization were also observed. Icenticaftor was safe and well tolerated. Conclusion: The CFTR potentiator icenticaftor increased FEV1 versus placebo after 28 days and was associated with improvements in systemic inflammation and sputum bacterial colonization in COPD patients; no improvements in LCI with icenticaftor were observed.

On the optimal temporal resolution for phase contrast cardiovascular magnetic resonance imaging: establishment of baseline values.

BACKGROUND: The aim of this study is to quantify the frequency content of the blood velocity waveform in different body regions by means of phase contrast (PC) cardiovascular magnetic resonance (CMR) and Doppler ultrasound. The highest frequency component of the spectrum is inversely proportional to the ideal temporal resolution to be used for the acquisition of flow-sensitive imaging (Shannon-Nyquist theorem). METHODS: Ten healthy subjects (median age 33y, range 24-40) were scanned with a high-temporal-resolution PC-CMR and with Doppler ultrasound on three body regions (carotid arteries, aorta and femoral arteries). Furthermore, 111 patients (median age 61y) with mild to moderate arterial hypertension and 58 patients with aortic aregurgitation, atrial septal defect, or repaired tetralogy of Fallot underwent aortic CMR scanning. The frequency power distribution was calculated for each location and the maximum frequency component, fmax, was extracted and expected limits for the general population were inferred. RESULTS: In the healthy subject cohort, significantly different fmax values were found across the different body locations, but they were nonsignificant across modalities. No significant correlation was found with heart rate. The measured fmax ranged from 7.7 ± 1.1 Hz in the ascending aorta, up to 12.3 ± 5.1 Hz in the femoral artery (considering PC-CMR data). The calculated upper boundary for the general population ranged from 11.0 Hz to 27.5 Hz, corresponding to optimal temporal resolutions of 45 ms and 18 ms, respectively. The patient cohort exhibited similar values for the frequencies in the aorta, with no correlation between blood pressure and frequency content. CONCLUSIONS: The temporal resolution of PC-CMR acquisitions can be adapted based on the scanned body region and in the adult population, should approach approximately 20 ms in the peripheral arteries and 40 ms in the aorta. TRIAL REGISTRATION: This study presents results from a restrospective analysis of the clinical study NCT01870739 (ClinicalTrials.gov).

Mucus plugging, air trapping, and bronchiectasis are important outcome measures in assessing progressive childhood cystic fibrosis lung disease.

OBJECTIVE: To determine which outcome measures could detect early progression of disease in school-age children with mild cystic fibrosis (CF) lung disease over a two-year time interval utilizing chest computed tomography (CT) scores, quantitative CT air trapping (QAT), and spirometric measurements. METHODS: Thirty-six school-age children with mild CF lung disease (median [interquartile range] age 12 [3.7] years; percent predicted forced expiratory volume in 1 second (ppFEV1 ) 99 [12.5]) were evaluated by serial spirometer-controlled chest CT scans and spirometry at baseline, 3-month, 1- and 2-years. RESULTS: No significant changes were noted at 3-month for any variable except for decreased ppFEV1 . Mucus plugging score (MPS) and QATA1andA2 increased at 1- and 2-years. The bronchiectasis score (BS), and total score (TS) were increased at 2-year. All variables tested with the exception of bronchial wall thickness score, parenchymal score (PS), and ppFEV1 , were consistent with longitudinal worsening of lung disease. Multivariate analysis revealed baseline PS, baseline TS, and 1-year changes in BS and air trapping score were predictive of 2-year changes in BS. CONCLUSIONS: MPS and QATA1-A2 were the most sensitive indicators of progressive childhood CF lung disease. The 1-year change in the bronchiectasis score had the most positive predictive power for 2-year change in bronchiectasis.

Variability of MRI Aortic Stiffness Measurements in a Multicenter Clinical Trial Setting: Intraobserver, Interobserver, and Intracenter Variability of Pulse Wave Velocity and Aortic Strain Measurement.

PURPOSE: To assess intraobserver, interobserver, and scan-rescan variability of MRI aortic stiffness measurements in a multicenter trial setting. MATERIALS AND METHODS: This study was a retrospective analysis of prospectively collected data in a multicenter prospective clinical trial (clinicaltrials.gov ID NCT01870739). Forty-five adult patients (31 men; mean age, 58 years ± 12 [standard deviation]; 15 patients per center; three centers) with arterial hypertension underwent standardized 3-T baseline MRI assessments between June and September 2014. Aortic strain was calculated from maximum and minimum aortic area measurements repeated three times by three readers at three aortic levels on three retrospectively gated axial gradient-echo (GRE) data sets. Pulse wave velocity (PWV) was assessed three times by five readers as Δx/Δt: Δx was measured on a parasagittal GRE image of the aortic arch, and Δt was extracted from ascending and descending aortic velocity curves created on three axial phase-contrast acquisitions. Intraobserver, interobserver, and scan-rescan variability was calculated using percentage coefficient of variation (COV). RESULTS: Aortic strain variability was lowest at the level of the distal descending aorta (DDA) with median COVs of 1.6% for intraobserver variability, 4.0% for interobserver variability, and 10.3% for scan-rescan variability. It was highest at the ascending aorta (AA) with COVs of 3.6% for intraobserver variability, 10.7% for interobserver variability, and 19.8% for scan-rescan variability. Variability of PWV was low: 0.7% for intraobserver variability, 1.5% for interobserver variability, and 8.1% for scan-rescan variability. CONCLUSION: Low variability can be achieved for aortic strain and PWV measurements in a multicenter trial setting using standardized MRI protocols. Although COV was lower when measuring aortic strain at DDA compared with AA, variability was acceptable at both anatomic locations.Supplemental material is available for this article.© RSNA, 2020.

Intelligence and Socioeconomic Context on Childhood: Comparisons by Place of Residence and School Type / Inteligência e Contexto Socioeconômico na Infância: Comparação por Região de Moradia e Tipo de Escola / Inteligencia y Contexto Socioeconómico en la Infancia: Comparación por Región de Vivienda y Tipo de Escuela

Abstract Different aspects of the socioeconomic context can affect intelligence. This study investigated the intellectual performance of children from different places of residence and school types. The analyses compared children from the outskirts (n = 169) and the central region (n = 110) from Porto Alegre; and children from private (n = 49) and public (n = 61) schools. Data collection included the Wechsler Abbreviated Scale of Intelligence (WASI) and sociodemographic record. Analysis of covariance (between groups) and Analysis of Variance for repeated measures (within-group) were used. Children from the outskirts region showed poorer performance on all WASI scores and, in the within-group comparison, lower results on verbal tasks - which did not occur in the central region group. Children from public and private schools differed in all WASI scores but had a similar within-group performance.

Resumo Diferentes aspectos do contexto socioeconômico podem afetar a inteligência. Este estudo investigou o desempenho intelectual de crianças de diferentes regiões de moradia e tipos de escola. As análises compararam crianças da periferia (n = 169) e da região central (n = 110) de Porto Alegre; e crianças de escola privada (n = 49) e pública (n = 61). A coleta de dados incluiu a Escala Wechsler Abreviada de Inteligência (WASI) e ficha sociodemográfica. Utilizou-se Análise de Covariância (entre grupos) e Análise de Variância para medidas repetidas (intragrupo). O grupo de periferia apresentou menor desempenho em todos os escores da WASI e, na comparação intragrupo, resultados mais baixos nas tarefas verbais - o que não ocorreu no grupo da região central. Crianças de escolas públicas e privadas diferiram em todos os escores da WASI, mas apresentaram desempenho intragrupo semelhante.

Resumen Los diferentes aspectos del contexto socioeconómico pueden afectar la inteligencia. Este estudio investigó el desempeño intelectual de niños de diferentes regiones de vivienda y tipos de escuela. Se llevó a cabo una comparación de niños de la periferia (n = 169) y de la región central (n = 110) de Porto Alegre con niños de escuelas privadas (n = 49) y públicas (n = 61). Para recopilar los datos se utilizó la Escala de Inteligencia Abreviada de Wechsler (WASI) y la ficha sociodemográfica. Se aplicó el análisis de covarianza (entre grupos) y el análisis de varianza para medidas repetidas (intragrupo). El grupo de la periferia tuvo un desempeño más bajo en todos los puntajes de la WASI y presentó los resultados más bajos en las tareas verbales en la comparación intragrupo, lo que no ocurrió con el grupo de la región central. Los puntajes de los niños de las escuelas públicas y privadas fueron distintos en todos los puntajes de la WASI, pero en la comparación intragrupo tuvieron un rendimiento similar.

Avaliação psicológica online: considerações a partir da pandemia do novo coronavírus (COVID-19) para a prática e o ensino no contexto a distância / Psychological assessment online: repercussions of the new coronavirus (COVID-19) pandemic on remote practice and distance teaching

As restrições impostas pelo distanciamento social decorrente da pandemia do novo coronavírus exigiram adaptações dos psicólogos a uma nova realidade de trabalho que privilegia atividades remotas. O ensino e a prática em Avaliação Psicológica foram algumas das áreas afetadas, demandando que psicólogos, conselho profissional e sociedades científicas discutam diretrizes para o contexto da pandemia. Também, ainda que exista um aumento de cursos a distância, são apontadas restrições para o ensino de técnicas psicológicas em ambiente online. Visto as mudanças no cenário de trabalho e a necessidade de adaptação à situação atual, este estudo busca discutir a viabilidade de processos de Avaliação Psicológica online e apontar direções para seu aperfeiçoamento. Procura-se também apresentar possibilidades para ensino e supervisão a distância. Discutem-se evidências científicas e regulamentações nacionais e internacionais que embasam essas práticas. Por fim, reforça-se a necessidade do desenvolvimento de tecnologias que permitam conduzir o processo de maneira ética e segura.

Given the restrictions imposed by social distancing as a result of the new coronavirus pandemic, psychologists are dealing with a new working reality that is shifting the focus towards remote activities. Teaching and practice in psychological assessment are just two of the areas that have been affected, requiring psychologists, professional bodies and scientific societies to discuss guidelines relating to pandemic scenarios. Although there has been an increase in distance learning courses, restrictions have been recommended for the teaching of psychological assessment techniques in the online environment. Given the changes in the work scenario and the need to adapt to the current situation, the aim of this study is to discuss the viability of online psychological assessment processes and to devise guidelines for their improvement. It also seeks to propose options for distance education and supervision. Scientific tests and national and international regulations that support these practices are discussed. Lastly, the need to develop technologies that will allow the process to be ethically and safely conducted is emphasized.