Uma “observação” sobre a utilização de cuidados preventivos pela mulher

As doenças com maior impacto na saúde da mulher devem merecer uma atenção especial e, se a evidência científica assim o indicar, serem objecto de práticas preventivas, nomeadamente, de exames de rastreio, de acordo com protocolos de actuação orientadores de quem deve ser rastreado, da idade de início, do intervalo e descontinuidade do rastreio e da sensibilidade e especificidade que se pode esperar dos respectivos testes, entre outros. Neste contexto, o Departamento de Epidemiologia, do Instituto Nacional de Saúde Doutor Ricardo Jorge e a Divisão de Saúde Reprodutiva, da Direcção-Geral da Saúde consideraram pertinente realizar, colaborativamente, o presente estudo, de modo a contribuir para aumentar a informação e conhecimento sobre a situação dos cuidados preventivos da população feminina de Portugal Continental. Objectivos: Estimar a percentagem de mulheres com determinadas práticas preventivas, na população do Continente. Metodologia: O estudo, descritivo transversal, constou de um inquérito realizado por entrevista telefónica a uma amostra de mulheres das famílias ECOS, em Maio-Junho de 2011. Esta amostra é aleatória e constituída por 1032 Unidades de Alojamento (UAs), contactáveis por telefone fixo e móvel, estratificada por Região de Saúde do Continente, com alocação homogénea. Em cada agregado, foi inquirido apenas um elemento do sexo feminino, com 18 ou mais anos. A recolha de dados foi feita através da aplicação de um questionário de 73 perguntas. As variáveis colhidas contemplaram a caracterização dos inquiridos, nomeadamente, no que diz respeito: tipo de cobertura médica; realização de exame periódico de saúde (EPS); prática de vacinação; práticas preventivas relacionadas com doenças crónicas, nomeadamente, cancro, saúde reprodutiva, saúde oral, da visão e da audição. Resultados: Obtiveram-se 826 questionários válidos, o que corresponde a uma taxa de resposta de 80,0%. As estimativas para os indicadores em estudo foram as seguintes: Ter médico assistente- 85% de mulheres ≥18 anos (n= 824); Exame periódico de saúde, há um ano ou menos- 51% de mulheres ≥50 anos (n=203); Reforço antitetânico há 10 anos ou menos- 86% de mulheres ≥18 anos (n=608);Vacinação para pneumococos- 19% de mulheres ≥65 anos (n=116); Teste para VIH/SIDA- 49% de mulheres 18-64 anos (n=668); Medição da tensão arterial, há 2 anos ou menos- 99% de mulheres ≥18 anos (n=564); Doseamento de colesterolemia, há 5 ou menos anos- 95% de mulheres ≥20 anos (n=454); Terapêutica “preventiva” com Estatinas- 9% de mulheres ≥45 anos (n=209); Doseamento de glicemia, há 3 anos ou menos- 92% de mulheres ≥45 anos (n=380); Realização de uma densitometria- 64% de mulheres ≥65 anos (n=124); Pesquisa de sangue oculto nas fezes, há 2 ou menos anos- 21% de mulheres 50-74 anos (n=314); Realização de uma sigmoidoscopia/colonoscopia, há 10 ou menos anos- 38% de mulheres 50-74 anos (n=329); Exame clínico mamário, no período de tempo adequado à respectiva idade- 52% de mulheres ≥20 anos (n=782); Exame clínico mamário, há 1 ano ou menos- 44% de mulheres ≥40 anos (n=259); Realização de uma mamografia, há 2 ou menos anos- 88% de mulheres 50-69 anos (n=252) ou 87% de mulheres 40-69 anos (n=468); Realização de, pelo menos, um exame pélvico- 71% de mulheres ≥25 anos (n=761); Realização de uma citologia cervical, há 3 ou menos anos- 77% de mulheres dos 25-69 anos (n=679); Planeamento da primeira/única gravidez- 75% de mulheres 18-55 anos (n=437); Realização de consulta preconcepcional relativa à primeira/única gravidez- 71% das gestações planeadas (n=317); Planeamento da última gravidez- 66% de mulheres 18-55 anos multíparas (n=302); Realização de consulta preconcepcional relativa à última gravidez- 74% das gestações planeadas (n=198); Aceitação da primeira/única gravidez, não planeada, por ambos os progenitores- 80% de mulheres 18-55 anos (n=115); Aceitação da última gravidez, não planeada, por ambos os progenitores- 81% de mulheres 18-55 anos (n=104); Terapêutica hormonal na menopausa- 31% de mulheres 45-64 anos em menopausa (n=219); Realização de, pelo menos, um exame clínico dentário- 93% de mulheres ≥18 anos (n=825); Realização de, pelo menos, um exame clínico oftalmológico- 91% de mulheres ≥40 anos (n=567); Realização de, pelo menos, um exame de audição- 40% de mulheres ≥18 anos (n=820). Discussão/Conclusões: Os resultados do estudo, apesar de fragilidades de algumas das estimativas, poderão contribuir para uma reflexão sobre a temática. É nesta, que se deve fundamentar as recomendações para a prestação de cuidados preventivos pela mulher. Afigura-se importante continuar a promover uma maior utilização de cuidados preventivos pela mulhe

Developing Clinical and Research Priorities for Pain and Psychological Features in People With Patellofemoral Pain:An International Consensus Process With Health Care Professionals

OBJECTIVE: To decide clinical and research priorities on pain features and psychological factors in persons with patellofemoral pain. DESIGN: Consensus development process. METHODS: We undertook a 3-stage process consisting of (1) updating 2 systematic reviews on quantitative sensory testing of pain features and psychological factors in patellofemoral pain, (2) an online survey of health care professionals and persons with patellofemoral pain, and (3) a consensus meeting with expert health care professionals. Participants responded that they agreed, disagreed, or were unsure that a pain feature or psychological factor was important in clinical practice or as a research priority. Greater than 70% participant agreement was required for an item to be considered important in clinical practice or a research priority. RESULTS: Thirty-five health care professionals completed the survey, 20 of whom attended the consensus meeting. Thirty persons with patellofemoral pain also completed the survey. The review identified 5 pain features and 9 psychological factors—none reached 70% agreement in the patient survey, so all were considered at the meeting. Afte the meeting, pain catastrophizing, fear-avoidance beliefs, and pain self-efficacy were the only factors considered clinically important. All but the therma pain tests and 3 psychological factors were consid ered research priorities. CONCLUSION: Pain catastrophizing, pain self-efficacy, and fear-avoidance beliefs were factors considered important in treatment planning, clinical examination, and prognostication. Quantitative sensory tests for pain were not regarded as clinically important but were deemed to be research priorities, as were most psychological factors.</p

Gene-based analysis of regulatory variants identifies 4 putative novel asthma risk genes related to nucleotide synthesis and signaling

Background Hundreds of genetic variants are thought to contribute to variation in asthma risk by modulating gene expression. Methods that increase the power of genome-wide association studies (GWASs) to identify risk-associated variants are needed. Objective We sought to develop a method that aggregates the evidence for association with disease risk across expression quantitative trait loci (eQTLs) of a gene and use this approach to identify asthma risk genes. Methods We developed a gene-based test and software package called EUGENE that (1) is applicable to GWAS summary statistics; (2) considers both cis- and trans-eQTLs; (3) incorporates eQTLs identified in different tissues; and (4) uses simulations to account for multiple testing. We applied this approach to 2 published asthma GWASs (combined n\ua0=\ua046,044) and used mouse studies to provide initial functional insights into 2 genes with novel genetic associations. Results We tested the association between asthma and 17,190 genes that were found to have cis- and/or trans-eQTLs across 16 published eQTL studies. At an empirical FDR of 5%, 48 genes were associated with asthma risk. Of these, for 37, the association was driven by eQTLs located in established risk loci for allergic disease, including 6 genes not previously implicated in disease cause (eg, LIMS1, TINF2, and SAFB). The remaining 11 significant genes represent potential novel genetic associations with asthma. The association with 4 of these replicated in an independent GWAS: B4GALT3, USMG5, P2RY13, and P2RY14, which are genes involved in nucleotide synthesis or nucleotide-dependent cell activation. In mouse studies, P2ry13 and P2ry14—purinergic receptors activated by adenosine 5-diphosphate and UDP-sugars, respectively—were upregulated after allergen challenge, notably in airway epithelial cells, eosinophils, and neutrophils. Intranasal exposure with receptor agonists induced the release of IL-33 and subsequent eosinophil infiltration into the lungs. Conclusion We identified novel associations between asthma and eQTLs for 4 genes related to nucleotide synthesis/signaling and demonstrated the power of gene-based analyses of GWASs

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Long-range modulation of PAG1 expression by 8q21 allergy risk variants

The gene(s) whose expression is regulated by allergy risk variants is unknown for many loci identified through genome-wide association studies. Addressing this knowledge gap might point to new therapeutic targets for allergic disease. The aim of this study was to identify the target gene(s) and the functional variant(s) underlying the association between rs7009110 on chromosome 8q21 and allergies. Eight genes are located within 1 Mb of rs7009110. Multivariate association analysis of publicly available exon expression levels from lymphoblastoid cell lines (LCLs) identified a significant association between rs7009110 and the expression of a single gene, PAG1 (p = 0.0017), 732 kb away. Analysis of histone modifications and DNase I hypersensitive sites in LCLs identified four putative regulatory elements (PREs) in the region. Chromosome conformation capture confirmed that two PREs interacted with the PAG1 promoter, one in allele-specific fashion. To determine whether these PREs were functional, LCLs were transfected with PAG1 promoter-driven luciferase reporter constructs. PRE3 acted as a transcriptional enhancer for PAG1 exclusively when it carried the rs2370615:C allergy predisposing allele, a variant in complete linkage disequilibrium with rs7009110. As such, rs2370615, which overlaps RelA transcription factor (TF) binding in LCLs and was found to disrupt Foxo3a binding to PRE3, represents the putative functional variant in this locus. Our studies suggest that the risk-associated allele of rs2370615 predisposes to allergic disease by increasing PAG1 expression, which might promote B cell activation and have a pro-inflammatory effect. Inhibition of PAG1 expression or function might have therapeutic potential for allergic diseases