Real-world reporting rates of administration-site reactions with on-demand treatment of hereditary angioedema attacks.

Background: Hereditary angioedema (HAE) is characterized by recurrent and unpredictable episodes of subcutaneous and/or submucosal swelling. Objective: To characterize the real-world treatment burden associated with existing on-demand therapies, we analyzed administration-site adverse drug reactions (ADR) associated with approved on-demand HAE therapies reported in the U.S. Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS). Methods: We searched the FAERS database from October 1, 2009, to March 31, 2022, for reports of all FDA-approved on-demand therapies for HAE: plasma-derived C1-inhibitor (pdC1-INH), ecallantide, icatibant, and recombinant C1-inhibitor (rhC1-INH). ADRs in which the drug was listed as the "primary suspect" were recorded for each drug. ADR preferred terms were grouped into 18 ADR domains based on semantic and/or clinical similarity, and the number of reports for each drug was calculated per year from the time of approval through March 2022, and descriptive results were presented. Preferred terms associated with administration-site ADRs identified from clinical trials and denoted on approved HAE drug U.S. package inserts were examined in a complementary analysis. Results: The highest reported rates of administration-site ADRs per year were site pain (17.9 reports per year), site erythema (7.4 per year), and site swelling (6.7 per year). RhC1-INH was the only drug for which access-site complications and/or malfunctions were reported (9.5 per year). PdC1-INH had the highest rate of incorrect route of product administration (3.7 per year). PdC1-INH showed statistically significant elevated reporting rate of injection-site reactions (reporting odds ratio [ROR] 3.59 [2.36-5.46]; empirical Bayesian geometric mean [EBGM] 1.97 [1.39]). Icatibant and rhC1-INH showed a statistical trend toward an increased reporting rate of administration-site reactions. Conclusion: Real-world data from FAERS were generally consistent with adverse events reported in clinical trials and suggest that patients experience substantial treatment burden associated with FDA-approved parenteral on-demand therapies for HAE attacks. It should be noted that ADR rates are not exposure adjusted and are based on spontaneous reporting.

Rehabilitation of a Child with Neonatal Brachial Plexus Palsy: Case Report Described by Parents.

This paper presents a case report of a child with Neonatal Brachial Plexus Palsy on the right arm, with C5, C6, and C7 nerve injuries. The symptoms presented at birth and at the time of diagnosis were absence of movement in the right arm but with mobility of the fingers; internal rotation of the injured limb with elbow extension; active flexion of the wrist and fingers; and ulnar deviation of the hand. The rehabilitation plan followed the conservative approach and included different intervention strategies (passive and active mobilisation, kinesio tape, use of splints, bimanual stimulation, etc.) carried out by the occupational therapist and the physical therapist. The rehabilitation allowed the child to have a functional limb for daily activities, with bimanual motor integration and coordination; passive and active range of motion in the different joints except for pronation, sensibility, and maintained strength. In conclusion, it can be said that this case report describes a set of rehabilitation strategies that were used in the conservative treatment of a child with NBPP and the functional gains they allowed. Early intervention, parental involvement in the rehabilitation process, and continuous follow-up of the child favoured the prognosis and allowed the prevention of functional sequelae of the limb.

Helcococcus kunzii, a skin-colonising microorganism with pathogenic capacity: a case of polymicrobial intracranial empyema.

Helcococcus kunzii is a Gram-positive anaerobic facultative coccus that colonises the skin. Human infection is rare, with very few cases being described in the literature. The authors present the case of a 17-year-old man, with a history of cholesteatoma, diagnosed with mastoiditis complicated by intracranial empyema. After urgent surgical drainage, Gram staining revealed a Gram-negative bacillus and a Gram-positive coccus. The latter exhibited fastidious growth, presented as small grey colonies in blood agar, and was afterwards identified as H. kunzii The patient was started on intravenous antibiotics, switched to oral route after 8 weeks and fully recovered. To the best of our knowledge, this is the third case of an intracranial infection in which H. kunzii is involved, two of them occurring in patients with cholesteatoma.

Impact on the Mental and Physical Health of the Portuguese Population during the COVID-19 Confinement.

Confinement of the population has been one of the measures implemented by different governments to address the COVID-19 health crisis, and it has led to social isolation together with a disruption of daily activities. The aim of the study is to analyze psychological distress during the COVID-19 pandemic in Portugal. During the quarantine, a cross-sectional study was carried out on a sample of 2120 subjects over 18 years of age, resident and born in Portugal. Data were collected using a self-developed questionnaire that considered socio-demographic variables, physical symptoms, health conditions, and history of contact with COVID-19, as well as psychological alterations. The General Health Questionnaire (GHQ-12) was also included. Univariate and bivariate statistical analyses were performed. Predictive capacity was studied using logistic regression models. The results showed a higher percentage of individuals presenting psychological distress (57.2.0%), with a higher percentage identified among women (79.0%), and in people with a higher educational level (bachelor's + master's and doctorate) (75.8%). The predictor variables with the greatest weight were sex, educational level (graduation, master's, and doctorate), living with children or under 16 years of age, presence of symptoms, and quarantine in the last 14 days for having symptoms. Good self-assessment of health and working at home appear to be protective against psychological distress. These results highlight the impact of the COVID-19 pandemic on psychological distress and provide an opportunity to consider the need to implement specific multidisciplinary public health and mental health interventions in this pandemic situation.

A integração da família nos cuidados de enfermagem: perspetiva de enfermeiros e estudantes de enfermagem / Integrating the family into nursing care: nurses' and nursing students' perspectives / Integración de la familia en los cuidados de enfermería: perspectiva de los enfermeros y los estudiantes de enfermería

Resumo Enquadramento: A pertinência da integração das famílias nos cuidados de enfermagem permite a promoção, manutenção e recuperação da saúde das famílias. Objetivos: Identificar e descrever a perspetiva dos enfermeiros e estudantes de enfermagem sobre a integração das famílias nos cuidados de enfermagem. Metodologia: Estudo inferencial, transversal, numa população de enfermeiros e estudantes de enfermagem. Foi aplicada a escala Families Importance in Nursing Care - Nurses Attitudes (FINC-NA). Resultados: Amostra constituída por 164 indivíduos, nos quais 71 eram profissionais e 93 estudantes. A média da importância atribuída à família foi maior nos estudantes de enfermagem relativamente aos enfermeiros, sendo a diferença entre os dois grupos significativa. Na análise de regressão linear univariada as variáveis: Idade, Anos de experiência profissional e Formação na área da família parecem estar associadas à importância atribuída à família. Conclusão: Os estudantes atribuem maior importância à integração da família do que os enfermeiros. As variáveis Idade, Anos de exercício profissional e Formação na área da família, nos enfermeiros, associam-se a uma maior importância da integração da família.

Abstract Background: Integrating families into nursing care allows promoting, maintaining, and restoring their health. Objectives: To identify and describe nurses' and nursing students' perspectives of the integration of families into nursing care. Methodology: Inferential, cross-sectional study in a population of nurses and nursing students. The Families' Importance in Nursing Care - Nurses' Attitudes (FINC-NA) scale was applied. Results: Sample consisting of 164 individuals, of whom 71 were nurses and 93 nursing students. On average, the importance attached to the family was higher among nursing students than among nurses, with a significant difference between both groups. In the univariate linear regression analysis, the variables Age, Years of professional experience, and Training in the family nursing seem to be associated with the importance attached to the family. Conclusion: Students attach more importance to family integration than nurses. The variables Age, Years of professional experience, and Training in the family nursing are associated with greater importance attached by nurses to the integration of families into nursing care.

Resumen Marco contextual: La relevancia de la integración de las familias en los cuidados de enfermería permite promover, mantener y recuperar la salud de las familias. Objetivos: Identificar y describir la perspectiva de los enfermeros y los estudiantes de enfermería sobre la integración de las familias en los cuidados de enfermería. Metodología: Estudio inferencial, transversal, en una población de enfermeros y estudiantes de enfermería. Se aplicó la escala Families Importance in Nursing Care - Nurses Attitudes (FINC-NA). Resultados: Muestra compuesta por 164 personas, 71 de las cuales eran profesionales y 93 estudiantes. La media de la importancia concedida a la familia fue mayor entre los estudiantes de enfermería que entre los enfermeros, y la diferencia entre ambos grupos fue significativa. En el análisis de regresión lineal univariante, las variables Edad, Años de experiencia profesional y Formación en el área de la familia parecen estar asociadas a la importancia concedida a la familia. Conclusión: Los estudiantes conceden mayor importancia a la integración de la familia que los enfermeros. Las variables Edad, Años de ejercicio profesional y Formación en el área de la familia, en los enfermeros, se asocian a una mayor importancia de la integración de la familia.

Pharmacogenetics of advanced lung cancer: Predictive value of functional genetic polymorphism AGXT Pro11Leu in clinical outcome?

INTRODUCTION: AGXT gene codes for the enzyme alanine glyoxylate aminotransferase, which is involved in hepatic peroxisomal metabolism of platinum-based chemotherapeutic agents. The association of genetic variant AGXT rs34116584 on the clinical outcome and response to chemotherapy of patients with non-small cell lung cancer (NSCLC) remains to be established. Our aim was to evaluate the association of functional AGXT gene polymorphism in NSCLC progression, considering as primary and secondary endpoint, progression free survival (PFS) and overall survival (OS), respectively. METHODS: Genotyping of theAGXT rs34116584 genetic polymorphism was performed by mass spectrometry on 168 DNA samples from patients with NSCLC (stages IIIA-IVB). Univariate survival analysis included the study of Kaplan-Meier curves with the Log-Rank test, while Cox regression was used as a multivariate analysis. RESULTS: Multivariate analysis showed shorter PFS for T carriers [HR=2.0, 95% CI, 1.4-3.0, p<0.0001] and shorter OS [HR=1.8, 95% CI, 1.1-3.0, p=0.017] globally, as well as in a subgroup of patients (n=144) treated with first line platinum-based chemotherapy [HR=2.0, 95% CI, 1.3-3.1, p=0.001] and [HR=1.8, 95% CI, 1.1-3.1, p=0.026], respectively. CONCLUSION: This polymorphism seems to have an impact on NSCLC progression, opening new perspectives for its inclusion as a pharmacogenetic predictor of response to platinum-based chemotherapy.

Adolescent students attitudes towards sexuality: the construction and validation of a scale / Atitudes dos alunos adolescentes sobre a sexualidade: construção e validação de uma escala

ABSTRACT Objective: To construct a scale of adolescents' attitudes towards sexuality and to determine their psychometric characteristics. Methods: Methodological study conducted with 394 students from the 8th to 12th grades of a school in central Portugal. They answered a questionnaire consisting of the Adolescent Students' Attitude Scale for Sexuality (E3AS) and socio-demographic and academic data. The project received a favorable opinion from the National Data Protection Commission (authorization No. 10421/2017). Construct validity analysis was performed through exploratory factor analysis and internal consistency was performed through Cronbach's alpha. A maximum error probability of 5% was considered. Results: The mean age of the sample was 14.9±1.4 years, with 53.3% being female. The instrument consisted of 34 items distributed into five factors: F1. Family planning and sex education (α=0.826); F2. First sexual relationship (α=0.819); F3. Violation of sexual rights and who to turn to in the event of unplanned pregnancies (α=0.695); F4. Gender expression and identity (α=0.542), and F5. Unplanned pregnancy and parenting (α= 0.761), with a total alpha value of 0.766, accounting for 45.3% of total variance. Conclusions: The psychometric adequacy of the E3AS for the Portuguese population allows us to affirm that it is a valid and reliable instrument that can be used in future studies to assess the attitudes of adolescent students towards sexuality.

RESUMO Objetivo: Construir uma escala de atitudes dos adolescentes em face da sexualidade e determinar as suas caraterísticas psicométricas. Métodos: Estudo metodológico realizado com 394 alunos do 8º ao 12º ano de escolaridade de uma escola da região Centro de Portugal que responderam a um questionário constituído da Escala de Atitudes dos Alunos Adolescentes em face da Sexualidade e de dados sociodemográficos e acadêmicos. O projeto recebeu parecer favorável da Comissão Nacional de Proteção de Dados (autorização nº 10421/2017). Realizou-se a análise de validade do constructo, por análise fatorial exploratória, e de consistência interna, por alfa de Cronbach. Foi considerada probabilidade de erro máximo de 5%. Resultados: A média de idades da amostra foi de 14,9±1,4 anos, e 53,3% dos participantes eram do sexo feminino. O instrumento foi constituído de 34 itens distribuídos por cinco fatores: Fator 1. Planejamento familiar e educação sexual (α=0,826); Fator 2. Primeira relação sexual (α=0,819); Fator 3. Violação dos direitos sexuais e a quem recorrer na gravidez não planejada (α=0,695); Fator 4. Expressão e identidade de gênero (α=0,542); Fator 5. Gravidez não planejada e parentalidade (α=0,761). O valor do alfa total da escala foi 0,766, o que explica 45,3% da variância total. Conclusões: A adequação psicométrica da escala para a população portuguesa permite afirmar que se trata de um instrumento válido e confiável, que poderá ser utilizado em estudos futuros com o intuito de avaliar as atitudes dos alunos adolescentes em face da sexualidade.

Germline Genetic Variants of the Renin-Angiotensin System, Hypoxia and Angiogenesis in Non-Small Cell Lung Cancer Progression: Discovery and Validation Studies.

INTRODUCTION: The renin-angiotensin system (RAS) is involved in cell proliferation, immunoinflammatory response, hypoxia and angiogenesis, which are critical biological processes in lung cancer. Our aim was to study the association of putatively functional genetic polymorphisms in genes coding for proteins involved in RAS, hypoxia and angiogenesis with non-small cell lung cancer (NSCLC) prognosis. METHODS: Genotyping of 52 germline variants from genes of the RAS and hypoxic/angiogenic factors/receptors was performed using MassARRAY iPLEX Gold in a retrospective cohort (n = 167) of advanced NSCLC patients. Validation of the resulting genetic markers was conducted in an independent group (n = 190), matched by clinicopathological characteristics. RESULTS: Multivariate analysis on the discovery set revealed that MME rs701109 C carriers were protected from disease progression in comparison with homozygous T (hazard ratio (HR) = 0.5, 95% confidence interval (CI) = 0.2-0.8, p = 0.010). Homozygous A and T genotypes for KDR rs1870377 were at increased risk for disease progression and death compared to heterozygous (HR = 1.7, 95% CI = 1.2-2.5, p = 0.005 and HR = 2.1, 95% CI = 1.2-3.4, p = 0.006, respectively). Carriers of homozygous genotypes for ACE2 rs908004 presented increased risk for disease progression, only in the subgroup of patients without tumour actionable driver mutations (HR = 2.9, 95% CI = 1.3-6.3, p = 0.010). Importantly, the association of homozygous genotypes in MME rs701109 with risk for disease progression was confirmed after multivariate analysis in the validation set. CONCLUSION: This study provides evidence that MME polymorphism, which encodes neprilysin, may modulate progression-free survival in advanced NSCLC. Present genetic variation findings will foster basic, translational, and clinical research on their role in NSCLC.

Adult-onset autoimmune diabetes: comparative analysis of classical and latent presentation.

INTRODUCTION: Adult-onset autoimmune diabetes (AID) has two different phenotypes: classic type 1 diabetes mellitus (T1DM), with insulin requirement just after diagnosis, and latent autoimmune diabetes in adults (LADA). The purpose of this study is to characterize patients with AID followed on a tertiary centre, comparing classic T1DM and LADA. METHODS: We collected data from patients with diabetes and positive islet autoantibodies, aged 30 years old and over at diagnosis. Patients who started insulin in the first 6 months were classified as T1DM and patients with no insulin requirements in the first 6 months were classified as LADA. Data regarding clinical presentation, autoantibodies, A1C and C-peptide at diagnosis, pharmacologic treatment and complications were analysed. RESULTS: We included 92 patients, 46 with classic T1DM and 46 with LADA. The percentage of females was 50% in T1DM group and 52.1% in LADA group. The median age at diagnosis was 38 years (IQR-15) for T1DM and 42 years (IQR-15) for LADA (p = 0.057). The median time between diagnosis of diabetes and diagnosis of autoimmune aetiology was 0 months in T1DM group and 60 months in LADA group (p < 0.001). The mean BMI at diagnosis was 24.1 kg/m2 in T1DM group and 26.1 kg/m2 in LADA group (p = 0.042). In T1DM group, 67.4% of the patients had more than one positive autoantibody, comparing to 41.3% of LADA patients (p = 0.012). There was no statistical difference in what concerns to title of GAD autoantibodies, A1C and C-peptide at diagnosis of autoimmune aetiology. The presence of symptoms at diagnosis was associated with T1DM group (p < 0.001). The median daily insulin dose was 40 IU for T1DM (0.58 IU/kg) and 33.5 IU for LADA (0.57 IU/kg), with no statistical difference. LADA patients were more often under non-insulin antidiabetic drugs (p = 0.001). At 10 years follow up, 21.1% of T1DM patients and 63.3% of LADA patients had microvascular complications (p = 0.004). Diabetic nephropathy was present in 23.5% of T1DM patients and 53.3% of LADA patients (p = 0.047). At the last evaluation, 55.6% of T1DM and 82.6% of LADA patients had metabolic syndrome and this difference was independent of diabetes duration. CONCLUSION: Patients with classic T1DM presented more often with symptoms, lower BMI and higher number of autoantibodies, which may be related to a more aggressive autoimmune process. Patients with LADA developed more frequently microvascular complications for the same disease duration, namely diabetic nephropathy, and had more often metabolic syndrome.

ADOLESCENT STUDENTS' ATTITUDES TOWARDS SEXUALITY: THE CONSTRUCTION AND VALIDATION OF A SCALE.

OBJECTIVE: To construct a scale of adolescents' attitudes towards sexuality and to determine their psychometric characteristics. METHODS: Methodological study conducted with 394 students from the 8th to 12th grades of a school in central Portugal. They answered a questionnaire consisting of the Adolescent Students' Attitude Scale for Sexuality (E3AS) and socio-demographic and academic data. The project received a favorable opinion from the National Data Protection Commission (authorization No. 10421/2017). Construct validity analysis was performed through exploratory factor analysis and internal consistency was performed through Cronbach's alpha. A maximum error probability of 5% was considered. RESULTS: The mean age of the sample was 14.9±1.4 years, with 53.3% being female. The instrument consisted of 34 items distributed into five factors: F1. Family planning and sex education (α=0.826); F2. First sexual relationship (α=0.819); F3. Violation of sexual rights and who to turn to in the event of unplanned pregnancies (α=0.695); F4. Gender expression and identity (α=0.542), and F5. Unplanned pregnancy and parenting (α= 0.761), with a total alpha value of 0.766, accounting for 45.3% of total variance. CONCLUSIONS: The psychometric adequacy of the E3AS for the Portuguese population allows us to affirm that it is a valid and reliable instrument that can be used in future studies to assess the attitudes of adolescent students towards sexuality.

Nuclear gene proximity and protein interactions shape transcript covariations in mammalian single cells.

Single-cell RNA sequencing studies on gene co-expression patterns could yield important regulatory and functional insights, but have so far been limited by the confounding effects of differentiation and cell cycle. We apply a tailored experimental design that eliminates these confounders, and report thousands of intrinsically covarying gene pairs in mouse embryonic stem cells. These covariations form a network with biological properties, outlining known and novel gene interactions. We provide the first evidence that miRNAs naturally induce transcriptome-wide covariations and compare the relative importance of nuclear organization, transcriptional and post-transcriptional regulation in defining covariations. We find that nuclear organization has the greatest impact, and that genes encoding for physically interacting proteins specifically tend to covary, suggesting importance for protein complex formation. Our results lend support to the concept of post-transcriptional RNA operons, but we further present evidence that nuclear proximity of genes may provide substantial functional regulation in mammalian single cells.

Mumps antibodies in the cord blood: Association with maternal recall of mumps. Possible consequences for vaccination strategies.

The present study aims to contribute to the evaluation of the serological impact of vaccination against mumps in Portugal, measuring anti-mumps IgG (MuIgG) levels in cord sera and the corresponding proportions of seropositive newborns, and their association with potential predictive variables. The data from this study came from 198 umbilical cord sera. Detailed vaccination records were available for all mothers. MuIgG were measured in the sera, using a commercial immunoassay. The geometric mean concentration (GMC) of MuIgG was 31.7 RU/ml. Seropositive/immune sera (concentration ≥16 RU/ml) were 75.3%. While 49 mothers were "unsure" about ever having had mumps, 46 said they had had the disease and 103 said they had not had it. Eighty eight women did not receive a single dose of MMR while the other received 1 or 2 doses, with different combinations of vaccine strains. This study found that recalling mumps was predictive of higher MuIgG GMC and seropositivity. Maternal age and vaccination status were not associated with GMC or seropositivity. Nevertheless, in the small subset of newborns from vaccinated mothers not recalling mumps, receiving two doses was predictive of higher GMC than just receiving one. Maternal recall of mumps is highly predictive of seropositivity while not recalling the disease results in numerous false-negatives. This is consistent with other studies and with the fact that infection with mumps virus can result in a wide range of clinical manifestations. We agree on the need for further research to support a recommendation of a three (or more)-dose MMR strategy but we also believe that evidence is fast accumulating in favour of a higher dose strategy. The issue of waning immunity due to vaccines when vaccination succeeds in controlling (and nationally eliminating) target diseases like measles and mumps must be urgently taken into account.

Controlled ploidy reduction of pluripotent 4n cells generates 2n cells during mouse embryo development.

Cells with high ploidy content are common in mammalian extraembryonic and adult tissues. Cell-to-cell fusion generates polyploid cells during mammalian development and tissue regeneration. However, whether increased ploidy can be occasionally tolerated in embryonic lineages still remains largely unknown. Here, we show that pluripotent, fusion-derived tetraploid cells, when injected in a recipient mouse blastocyst, can generate diploid cells upon ploidy reduction. The generated diploid cells form part of the adult tissues in mouse chimeras. Parental chromosomes in pluripotent tetraploid cells are segregated through tripolar mitosis both randomly and nonrandomly and without aneuploidy. Tetraploid-derived diploid cells show a differentiated phenotype. Overall, we discovered an unexpected process of controlled genome reduction in pluripotent tetraploid cells. This mechanism can ultimately generate diploid cells during mouse embryo development and should also be considered for cell fusion-mediated tissue regeneration approaches.

Late-Night Salivary Cortisol: Cut-Off Definition and Diagnostic Accuracy for Cushing's Syndrome in a Portuguese Population.

INTRODUCTION: Diagnosis of Cushing's syndrome remains a challenge in clinical endocrinology. Even though late-night salivary cortisol is used as screening tool, individualized cut-off levels for each population must be defined. MATERIAL AND METHODS: Three groups of subjects were studied: normal subjects, suspected and proven Cushing's syndrome. Salivary cortisol was measured using an automated electrochemiluminescence assay. The functional sensitivity of the assay is 0.018 µg/dL. The diagnostic cut-off level was defined by Receiver Operating Characteristic curve and Youden's J index. RESULTS: We studied 127 subjects: 57 healthy volunteers, 39 patients with suspected and 31 with proven Cushing's syndrome. 2.5th - 97.5th percentile of the late-night salivary cortisol concentrations in normal subjects was 0.054 to 0.1827 µg/dL. Receiver Operating Characteristic curve analysis showed an area under the curve of 0.9881 (p < 0.0001). A cut-off point of 0.1 µg/dL provided a sensitivity of 96.77% (95% CI 83.3 - 99.92%) and specificity of 91.23% (95% CI 80.7 - 97.09%). There was a significant correlation between latenight salivary cortisol and late-night serum cortisol (R = 0.6977; p < 0.0001) and urinary free cortisol (R = 0.5404; p = 0.0025) in proven Cushing's syndrome group. DISCUSSION: The mean ± SD late-night salivary cortisol concentration in patients with proven Cushing's syndrome (0.6798 ± 0.52 µg/ dL) was significantly higher (p < 0.0001). In our population, the late-night salivary cortisol cut-off was 0.1 µg/dL with high sensitivity and specificity. CONCLUSION: Late-night salivary cortisol has excellent diagnostic accuracy, making it a highly reliable, noninvasive, screening tool for outpatient assessment. Given its convenience and diagnostic accuracy, late-night salivary cortisol may be added to other traditional screening tests on hypercortisolism.

Introdução: O diagnóstico de síndrome de Cushing continua a ser um desafio complexo. Apesar do cortisol salivar noturno ser utilizado como teste de rastreio, a definição de um valor diagnóstico deverá ser individualizada. Material e Métodos: Foram estudados 3 grupos: voluntários saudáveis, com suspeita clínica e com diagnóstico estabelecido de Síndrome de Cushing. O doseamento de cortisol salivar foi realizado por eletroquimioluminescência automatizado. A definição do ponto-de-corte foi obtida pela curva Receiver Operating Characteristic e índice J de Youden. Resultados: Entre os 127 indivíduos, 57 pertenciam ao grupo de voluntários saudáveis, 39 com suspeita clínica e 31 com diagnóstico estabelecido. O percentil 2,5 ­ 97,5 de cortisol salivar noturno no grupo de voluntários saudáveis foi 0,054 ­ 0,1827 µg/dL. A análise da curva Receiver Operating Characteristic revelou uma área abaixo da curva de 0,9881 (p < 0,0001) e o ponto-de-corte de 0,1 µg/dL com sensibilidade de 96,77% e especificidade de 91,23%. Verificou-se uma correlação significativa entre cortisol salivar noturno e o cortisol sérico noturno (R = 0,6977; p < 0,0001), bem como, com cortisol livre urinário (R = 0,5404; p = 0,0025) no grupo com diagnóstico estabelecido. Discussão: A concentração média ± DP cortisol salivar noturno no grupo com diagnóstico estabelecido (0,6798 ± 0,52 µg/dL) foi significativamente superior aos restantes grupos. Na nossa população, o valor de ponto-de-corte foi de 0,1 µg/dL com elevada sensibilidade e especificidade. Conclusão: Os resultados demonstram uma excelente acurácia do cortisol salivar noturno. Dada a sua conveniência e elevada exatidão, o doseamento de cortisol salivar noturno poderá ser adicionado aos testes de rastreio tradicionais para estudo de hipercortisolismo.

Registos vacinais de enfermagem: importância para vigilância da saúde das populações / Vaccination nursing records: importance for monitoring the health of populations / Registros de vacunación de enfermería: importancia para el control de la salud de la población

Enquadramento: Os registos vacinais de enfermagem são uma fonte de informação relevante para uma adequada vigilância epidemiológica da aplicação do Programa Nacional de Vacinação. Objetivos: Avaliar a fiabilidade e precisão dos registos vacinais de enfermagem relativos à estratégia vacina antissarampo, parotidite e rubéola (VASPR). Metodologia: Foram consultados os registos oficiais de vacinação de 411 indivíduos, nascidos entre 1970 e 2004. Através destes registos estudou-se a história vacinal, de doença e de reações adversas à vacinação. Resultados: Existe informação vacinal coincidente registada na ficha individual de vacinação e no boletim individual de saúde em 96,22%. Os esquemas vacinais seguidos estiveram associados a gerações de nascimento às quais os indivíduos pertencem (r = 0,720; p = 0,020). O estado vacinal não esteve associado nem à história de doença nem à história de reações adversas à vacinação (p > 0,05). Conclusão: Os registos vacinais de enfermagem são fiáveis e precisos, permitem a monitorização e vigilância da saúde das populações e garantem o sucesso da aplicação do Programa Nacional de Vacinação em Portugal.

Background: Vaccination nursing records are a source of relevant information for adequate epidemiological surveillance of the implementation of the National Vaccination Program. Objectives: To evaluate the reliability and accuracy of vaccination nursing records related to the measles-mumps-rubella vaccination strategy (MMR). Methodology: The official vaccination records of 411 individuals, born between 1970 and 2004, were examined. We studied their vaccination, disease, and vaccination adverse reactions history. Results: There is a coincidence of vaccination information recorded in the Individual Vaccination Record and the Individual Health card in 96.22%. The followed vaccination schedules were associated with the birth generations to which individuals belong (r = 0.720; p = 0.020). Vaccination status was not associated with either the history of disease or the history of adverse reactions to vaccination (p > 0.05). Conclusion: Vaccination nursing records are reliable and accurate, allow the monitoring and surveillance of the health of populations, and ensure the success of the implementation of the National Vaccination Program in Portugal.

Marco contextual: Los registros de vacunación de enfermería son una fuente de información pertinente para realizar un control epidemiológico adecuado de la aplicación del Programa Nacional de Vacunación. Objetivos: Evaluar la fiabilidad y la precisión de los registros de vacunación de enfermería relativos a la estrategia de vacunación contra el sarampión, la parotiditis y la rubeola (VASPR). Metodología: Se consultaron los registros oficiales de vacunación de 411 individuos nacidos entre 1970 y 2004. A través de estos registros, se estudió el historial de vacunación, de enfermedad y de reacciones adversas a la vacunación. Resultados: Existe información de vacunación coincidente registrada en la cartilla de vacunación individual y en el boletín individual de salud al 96,22%. Los esquemas de vacunación seguidos se asociaron con generaciones de nacimiento a las cuales pertenecen los individuos (r = 0,720; p = 0,020). El estado de vacunación no se asoció ni con el historial de enfermedad ni con el historial de reacciones adversas a la vacunación (p > 0,05). Conclusión: Los registros de vacunación de enfermería son fiables y precisos, permiten el seguimiento y el control de la salud de las poblaciones y garantizan el éxito de la aplicación del Programa Nacional de Vacunación en Portugal.

Evaluation of Procalcitonin Accuracy for the Distinction Between Gram-Negative and Gram-Positive Bacterial Sepsis in Burn Patients.

Sepsis is the main cause of death in burns. Early institution of antimicrobial therapy is crucial to optimize outcomes but superfluous therapy increases adverse events, microbial resistance, and costs. Blood cultures are the gold standard for diagnosis but can take 48 to 72 hours. Biomarkers are used to help sepsis diagnosis and distinction between Gram-negative and Gram-positive bacterial cause. The aim of this work is to evaluate procalcitonin (PCT) accuracy for this distinction in burn patients. Retrospective observational study of adult septic burn patients with ≥15% total burn surface area admitted from January 2011 to December 2014 at a Burn Unit in Portugal. A statistical analysis was done, evaluating the correlation between PCT levels on the day of the first positive blood culture and microbiological data for Gram-negative and Grand-positive bacteria. Patients with mixed bacterial and/or fungal blood cultures were excluded. Data were summarized by quartiles statistics. Blood cultures were positive in 189 patients: 75 (39.7%) showed growth for Gram-negative and 114 (60.3%) for Gram-positive bacteria. Patients with Gram-negative bacteria have significantly higher PCT levels. Receiver operating characteristic curve analysis showed accuracy for Gram-negative discrimination with area under the curve = 0.687. Most elevated levels were related to nonfermentative Gram-negative bacteria and by Klebsiella pneumoniae and other Enterobacteriaceae. PCT levels were significantly higher in burn patients with Gram-negative sepsis comparing to patients with Gram-positive sepsis and controls. The determination of PCT levels may help the choice of empirical antimicrobial therapy while microbiological culture results are not available, despite not fully ensuring the desirable degree of precision.

Measles antibodies in cord blood in Portugal: Possible consequences for the recommended age of vaccination.

The optimum age to give the first dose of measles vaccine must balance the risks of disease and vaccine failure. Both are influenced by the levels of transplacentally acquired maternal antibodies. This study was conducted in the Obstetric service of Portuguese hospital, in 2012-2013. Mothers were recruited after informed consent. Measles IgG was measured in 206 cord sera, using a commercial immunoassay. Geometric mean concentrations (and 95% CI) were 1849mIU/ml (1196-2857) and 790mIU/ml (618-1008) in cord sera of newborns from unvaccinated and vaccinated mothers respectively. Maternal age and vaccination status were both associated with the concentration in cord sera, but maternal age was the major predictor. The likely explanation is the same already mentioned in other studies: as a vaccination program progresses, vaccination coverage increases as measles incidence decreases. That results newborns from younger vaccinated mothers having less measles antibodies while the older mothers are more likely to have been infected with the wild virus. As the proportion of vaccinated mothers increase, developed countries tend to anticipate the recommended age of the first dose to 12 months of age. Models using hypothetical measles antibody decay rates in infancy were explored. Anticipating the first dose of MMR1 in Portugal to the age of 12 months might have not been the best decision but results were not conclusive, and arguments supporting or not the anticipation were discussed.

Persistence of measles antibodies, following changes in the recommended age for the second dose of MMR-vaccine in Portugal.

In populations vaccinated with two doses of combined measles-mumps-rubella vaccine (MMR), the serum levels of antibodies against measles depend on the vaccination schedule, time elapsed from the last dose and the area-specific epidemiological situation. Variables measuring "schedule" are age at first and second doses of MMR and intervals derived from that. Changes in vaccination schedules have been made in Portugal. The specific objectives of this study were to measure the association between those potential determinants and the concentration of measles-specific IgG antibodies, after the second dose of MMR. Convenience samples of three Portuguese birth cohorts were selected for this study (41, 66 and 60 born, respectively, in 2001-2003, 1990-1993 and 1994-1995). Geometric mean concentrations (GMC) for measles IgG were, respectively, 934, 251 and 144mIU/ml; p<0.001). Anti-measles-IgG serum concentration decreased with time since last vaccination (waning immunity) and was not influenced by any other component of vaccination schedule, namely age at vaccination with the second dose of MMR. Waning levels of measles antibodies have been observed elsewhere but not as fast as it was observed in Portuguese birth cohorts in this study. Changes in the vaccination schedules might have to be considered in the future.

Bloodstream and non-invasive isolates of Candida glabrata have similar population structures and fluconazole susceptibilities.

We have compared multilocus sequence typing (MLST) and fluconazole susceptibility profiles of Candida glabrata bloodstream isolates obtained during active, population-based surveillance to those obtained from non-sterile sites of individuals with no evidence of fungal disease (i.e., non-invasive isolates) in the same US city during an overlapping time period. In each of the two populations, different proportions of the same six major sequence types (STs) encompassed 82% of the isolates. One ST was more prevalent in the candidemia population and two other STs were more prevalent in the non-invasive population, but the overall allelic frequencies within the groups suggested little, if any, genotypic diversity between them. Fluconazole susceptibility profiles of isolates from the patients in the two groups were not significantly different and were not associated with a particular sequence type. Our results support the hypothesis that C. glabrata strains causing bloodstream infections are genetically indistinguishable from those normally residing in/on the host, suggesting that relative pathogenicity may be closely tied to commensalism.

Azole resistance in Aspergillus fumigatus isolates from the ARTEMIS global surveillance study is primarily due to the TR/L98H mutation in the cyp51A gene.

We surveyed 497 isolates of Aspergillus fumigatus collected from 2008 to 2009 as part of the ARTEMIS global surveillance study for elevated MIC values to itraconazole, voriconazole, and posaconazole. Sequencing of the cyp51A gene revealed that 8/29 isolates with elevated MIC values to one or more triazoles, all originating in China, contained the TR/L98H mutation associated with resistant European isolates of A. fumigatus. This is the first time the TR/L98H mutation has been identified outside Europe.