Strategies for optimising early detection and obstetric first response management of postpartum haemorrhage at caesarean birth: a modified Delphi-based international expert consensus.

OBJECTIVE: There are no globally agreed on strategies on early detection and first response management of postpartum haemorrhage (PPH) during and after caesarean birth. Our study aimed to develop an international expert's consensus on evidence-based approaches for early detection and obstetric first response management of PPH intraoperatively and postoperatively in caesarean birth. DESIGN: Systematic review and three-stage modified Delphi expert consensus. SETTING: International. POPULATION: Panel of 22 global experts in PPH with diverse backgrounds, and gender, professional and geographic balance. OUTCOME MEASURES: Agreement or disagreement on strategies for early detection and first response management of PPH at caesarean birth. RESULTS: Experts agreed that the same PPH definition should apply to both vaginal and caesarean birth. For the intraoperative phase, the experts agreed that early detection should be accomplished via quantitative blood loss measurement, complemented by monitoring the woman's haemodynamic status; and that first response should be triggered once the woman loses at least 500 mL of blood with continued bleeding or when she exhibits clinical signs of haemodynamic instability, whichever occurs first. For the first response, experts agreed on immediate administration of uterotonics and tranexamic acid, examination to determine aetiology and rapid initiation of cause-specific responses. In the postoperative phase, the experts agreed that caesarean birth-related PPH should be detected primarily via frequently monitoring the woman's haemodynamic status and clinical signs and symptoms of internal bleeding, supplemented by cumulative blood loss assessment performed quantitatively or by visual estimation. Postoperative first response was determined to require an individualised approach. CONCLUSION: These agreed on proposed approaches could help improve the detection of PPH in the intraoperative and postoperative phases of caesarean birth and the first response management of intraoperative PPH. Determining how best to implement these strategies is a critical next step.

European Association of Perinatal Medicine (EAPM), European Board and College of Obstetricians and Gynaecologists (EBCOG), European Midwives Association (EMA). Joint position statement: Substandard and disrespectful care in labour - because words matter.

Substandard or disrespectful care during labour should be of serious concern for healthcare professionals, as it can affect one of the most important events in a woman's life. Substandard care refers to the use of interventions that are not considered best-practice, to the inadequate execution of interventions, to situations where best-practice interventions are withheld from patients, or there is lack of adequate informed consent. Disrespectful care refers to forms of verbal and non-verbal communication that affect patients' dignity, individuality, privacy, intimacy, or personal beliefs. There are many possible underlying causes for substandard and disrespectful care in labour, including difficulties in modifying behaviours, judgmental or paternalistic attitudes, personal interests and individualism, and a human tendency to make less arduous, less difficult, or less stressful clinical decisions. The term "obstetric violence" is used in some parts of the world to describe various forms of substandard and disrespectful care in labour, but suggests that it is mainly carried out by obstetricians and is a serious form of aggression, carried out with the intent to cause harm. We believe that this term should not be used, as it does not help to identify the underlying problem, its causes, or its correction. In addition, it is generally seen by obstetricians and other healthcare professionals as an unjust and offensive term, generating a defensive and less collaborative mindset. We reach out to all individuals and institutions sharing the common goal of improving women's experience during labour, to work together to address the underlying causes of substandard and disrespectful care, and to develop common strategies to deal with this problem, based on mutual comprehension, trust and respect.

Influence of preconception body mass index on perinatal outcomes after metabolic and bariatric surgery.

INTRODUCTION: Metabolic and bariatric surgery (MBS) is a very effective weight loss intervention, although does not invariably reverses the obesity status. Our aim was to evaluate whether despite successful weight loss after MBS, persistence of obesity at time of conception still carries additional risks of adverse perinatal pregnancy outcomes. METHODS: Retrospective study comparing pregnancy outcomes of women previously submitted to MBS with a preconception (PC) body mass index BMI < 30 kg/m2 or PC BMI ≥ 30 kg/m2. RESULTS: Eighty pregnancies (n = 80) were included, 49 from women with a PC BMI < 30 kg/m2 and 31 with a PC BMI ≥ 30 kg/m2. Gestational weight gain was significantly lower (9.72 ± 7.10 vs. 13.81 ± 7.16 respectively; p = 0.01) and neonatal intensive care unit admissions were significantly higher (5% vs. 0% respectively; p = 0.02) in women with PC BMI ≥ 30 kg/m2 as compared to those with PC BMI < 30 kg/m2. There were no statistically significant differences in gestational diabetes, anemia, fetal growth restriction, prematurity rate, mode of delivery or birth weight between groups. CONCLUSION: Perinatal outcomes of pregnancies after MBS may be significantly influenced by PC BMI. The benefits of MBS induced weight loss on obesity-associated adverse pregnancy outcomes can be maximized if the obesity status can be reverted before pregnancy.

EUROPEAN ASSOCIATION OF PERINATAL MEDICINE (EAPM) Position statement: Use of appropriate terminology for situations related to inadequate fetal oxygenation in labor.

In high-resource countries, adverse perinatal outcomes are currently rare in term, non-malformed fetuses, undergoing labor, but they remain a leading cause of medico-legal dispute. Precise terminology is important to describe situations related to inadequate fetal oxygenation in labor, to ensure appropriate communication between healthcare professionals and adequate transmission of information to parents. This position statement provides consensus definitions from European perinatologists and midwives regarding the most appropriate terminology to describe situations related to inadequate fetal oxygenation in labor: suspected fetal hypoxia, severe newborn acidemia, newborn metabolic acidosis, and hypoxic-ischemic encephalopathy. It also identifies terms that are imprecise or nonspecific to this situation, and should therefore be avoided by healthcare professionals: fetal well-being, fetal stress, fetal distress, non-reassuring fetal state, and birth asphyxia.

FIGO good practice recommendations on surgical techniques to improve safety and reduce complications during cesarean delivery.

FIGO is actively contributing to the global effort to reduce maternal morbidity, mortality, and disability worldwide. Cesarean delivery rates are increasing globally, without signs of slowing down. Bleeding associated with cesarean delivery has become an important cause of hemorrhage-related maternal deaths in many low- and middle-income countries. Correct surgical techniques to improve safety and reduce complications of cesarean delivery is of the utmost importance. This article presents FIGO's good practice recommendations for effective surgical techniques to reduce cesarean complications. Evidence-based information is included where data are available. An expanded WHO Surgical Safety Checklist for maternity cases is suggested. Different incision techniques through the layers of the abdominal wall with appropriate indications are discussed. Hysterotomy through a transverse incision is described, as are indications for low vertical and classical incisions. Important precautions when extracting the fetus are explained. Uterine closure includes a safe method ensuring adequate reapproximation of the upper segment if a vertical incision is made. The paper concludes with the management of two common bleeding problems following delivery of the placenta.

Machine learning models based on clinical indices and cardiotocographic features for discriminating asphyxia fetuses-Porto retrospective intrapartum study.

Introduction: Perinatal asphyxia is one of the most frequent causes of neonatal mortality, affecting approximately four million newborns worldwide each year and causing the death of one million individuals. One of the main reasons for these high incidences is the lack of consensual methods of early diagnosis for this pathology. Estimating risk-appropriate health care for mother and baby is essential for increasing the quality of the health care system. Thus, it is necessary to investigate models that improve the prediction of perinatal asphyxia. Access to the cardiotocographic signals (CTGs) in conjunction with various clinical parameters can be crucial for the development of a successful model. Objectives: This exploratory work aims to develop predictive models of perinatal asphyxia based on clinical parameters and fetal heart rate (fHR) indices. Methods: Single gestations data from a retrospective unicentric study from Centro Hospitalar e Universitário do Porto de São João (CHUSJ) between 2010 and 2018 was probed. The CTGs were acquired and analyzed by Omniview-SisPorto, estimating several fHR features. The clinical variables were obtained from the electronic clinical records stored by ObsCare. Entropy and compression characterized the complexity of the fHR time series. These variables' contribution to the prediction of asphyxia perinatal was probed by binary logistic regression (BLR) and Naive-Bayes (NB) models. Results: The data consisted of 517 cases, with 15 pathological cases. The asphyxia prediction models showed promising results, with an area under the receiver operator characteristic curve (AUC) >70%. In NB approaches, the best models combined clinical and SisPorto features. The best model was the univariate BLR with the variable compression ratio scale 2 (CR2) and an AUC of 94.93% [94.55; 95.31%]. Conclusion: Both BLR and Bayesian models have advantages and disadvantages. The model with the best performance predicting perinatal asphyxia was the univariate BLR with the CR2 variable, demonstrating the importance of non-linear indices in perinatal asphyxia detection. Future studies should explore decision support systems to detect sepsis, including clinical and CTGs features (linear and non-linear).

Acceptability and applicability of an intervention programme with substance addicts. / Aceitabilidade e aplicabilidade de um programa de intervenção com usuários dependentes de substâncias.

The complexity of the problems related to the harmful use of substances requires regular questioning of practices. This article aims to explore the acceptability and applicability of an intervention programme for patients with problematic substance use. Qualitative study. Data collection, through a focus group with 6 nurses and 6 semi-structured interviews with patients under treatment. We have used lexicographic textual analysis. From the focus group, 151 text segments were analysed, retaining 85.8% of the total for the creation of five classes. An analysis of similarity led to the formation of two central nuclei, represented by the words "Nursing" and "Intervention". From interviews, 252 text segments were analysed, retaining 71.83% for the creation of 5 classes. An analysis of similarity led to the formation of three central nuclei, represented by the words "want", "programme" and "see". Nurses recognise the need for a more structured and flexible approach focused on people's needs. Users also affirm the need for flexible interventions, without a pre-established time frame, that promote labour integration, therapeutic support for abstinence and management of comorbidities.

A complexidade dos problemas relacionados com o uso problemático de substâncias requer questionamento regular das práticas. O objetivo deste artigo é explorar a aceitabilidade e a aplicabilidade de um programa de intervenção com pessoas dependentes de substâncias. Estudo qualitativo. Recolha de dados, realizada através de 1 grupo focal com 6 enfermeiros e 6 entrevistas semiestruturadas a usuários em tratamento. Utilizou-se à análise textual lexicográfica. No grupo focal, foram analisados 151 segmentos de texto, retendo 85,8% do total para a criação de cinco classes. A análise de similitude conduziu à formação de dois núcleos centrais, representados pelas palavras: Enfermeiro e Intervenção. Das entrevistas, foram analisados 252 segmentos de texto, retendo 71,83% para a criação de 5 classes. A análise de similitude conduziu à formação de três núcleos centrais, representados pelas palavras: querer, programa e ver. Os enfermeiros reconhecem a necessidade de uma abordagem mais estruturada, centrada nas necessidades das pessoas e flexível. Os usuários, acrescentam a necessidade de ser flexível, sem tempo definido à partida, promovendo trabalho, suporte terapêutico para abstinência e gestão das comorbilidades.

Aceitabilidade e aplicabilidade de um programa de intervenção com usuários dependentes de substâncias / Acceptability and applicability of an intervention programme with substance addicts

Resumo A complexidade dos problemas relacionados com o uso problemático de substâncias requer questionamento regular das práticas. O objetivo deste artigo é explorar a aceitabilidade e a aplicabilidade de um programa de intervenção com pessoas dependentes de substâncias. Estudo qualitativo. Recolha de dados, realizada através de 1 grupo focal com 6 enfermeiros e 6 entrevistas semiestruturadas a usuários em tratamento. Utilizou-se à análise textual lexicográfica. No grupo focal, foram analisados 151 segmentos de texto, retendo 85,8% do total para a criação de cinco classes. A análise de similitude conduziu à formação de dois núcleos centrais, representados pelas palavras: Enfermeiro e Intervenção. Das entrevistas, foram analisados 252 segmentos de texto, retendo 71,83% para a criação de 5 classes. A análise de similitude conduziu à formação de três núcleos centrais, representados pelas palavras: querer, programa e ver. Os enfermeiros reconhecem a necessidade de uma abordagem mais estruturada, centrada nas necessidades das pessoas e flexível. Os usuários, acrescentam a necessidade de ser flexível, sem tempo definido à partida, promovendo trabalho, suporte terapêutico para abstinência e gestão das comorbilidades.

Abstract The complexity of the problems related to the harmful use of substances requires regular questioning of practices. This article aims to explore the acceptability and applicability of an intervention programme for patients with problematic substance use. Qualitative study. Data collection, through a focus group with 6 nurses and 6 semi-structured interviews with patients under treatment. We have used lexicographic textual analysis. From the focus group, 151 text segments were analysed, retaining 85.8% of the total for the creation of five classes. An analysis of similarity led to the formation of two central nuclei, represented by the words "Nursing" and "Intervention". From interviews, 252 text segments were analysed, retaining 71.83% for the creation of 5 classes. An analysis of similarity led to the formation of three central nuclei, represented by the words "want", "programme" and "see". Nurses recognise the need for a more structured and flexible approach focused on people's needs. Users also affirm the need for flexible interventions, without a pre-established time frame, that promote labour integration, therapeutic support for abstinence and management of comorbidities.

Tradução e validação do Questionário de Qualidade de Vida em Hipersensibilidade a Drogas (DrHy-Q) para a língua portuguesa (cultura brasileira, DrHy-Qb) / Translation and validation of the Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q) to Brazilian Portuguese

Introdução: A hipersensibilidade a fármacos é uma condição clínica debilitante, acompanhada de experiência emocional intensa e pode afetar a qualidade de vida relacionada à saúde (QVRS). A repercussão das reações de hipersensibilidade a drogas (RHD) na qualidade vida (QV) pode ser verificada pela utilização de questionário específico, o Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q), desenvolvido originalmente na língua italiana. O objetivo foi traduzir, adaptar transculturalmente e validar a versão do DrHy-Q para a língua portuguesa (cultura brasileira, DrHy-Qb), verificando a consistência interna, validação de constructo e reprodutibilidade do DrHy-Qb, como instrumento específico de avaliação da QV nos pacientes brasileiros com hipersensibilidade a fármacos. Métodos: A adaptação do questionário consistiu na tradução e retrotradução realizadas de forma independente por três tradutores bilíngues, seguidas por pré-teste. A versão final, DrHy-Qb juntamente com o questionário de qualidade de vida resumido (SF-36), foi respondido por 84 pacientes (69% feminino, 40,3±15,2 anos) acompanhados em ambulatório especializado. Na análise fatorial, a validação de constructo foi realizada pelo cálculo do coeficiente de correlação de Pearson, de consistência interna pelo coeficiente alfa de Cronbach, e da reprodutibilidade pelo coeficiente de correlação intraclasse. Resultados: A análise estatística evidenciou consistência interna (α = 0,936) e reprodutibilidade (r: 0,984; IC95% = 0,963-0,993; p < 0,001) excelentes. A correlação entre o DrHy-Qb e o SF-36 total foi negativa e moderada (r = -0,394; p < 0,01). Conclusões: O DrHy-Qb foi adequadamente traduzido, adaptado e validado para a cultura brasileira, podendo ser útil na avaliação da qualidade de vida dos pacientes com hipersensibilidade a fármacos.

Introduction: Drug hypersensitivity is a clinical condition that can impair health-related quality of life. Originally developed in Italian, the Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q) measures the impact of drug hypersensitivity on quality of life. The objective of this study was to translate, crossculturally adapt, and validate the DrHy-Q to Brazilian Portuguese (DrHy-Qb). To be successful, the DrHy-Qb must be internally consistent, maintain construct validity, and be reproducible as an assessment tool for quality of life in Brazilian patients with drug hypersensitivity. Methods: Translation and back-translation were performed by 3 bilingual translators, followed by a pretest and a final version. The final version, the DrHy-Qb, and the 36-Item Medical Outcomes Study Short-Form General Health Survey (SF-36) were administered to 84 patients (69% female, 40.3±15.2 years) from a specialized outpatient clinic. Factorial analysis included Pearson's correlation coefficient to validate the construct, Cronbach's alpha to assess the internal consistency, and intraclass correlation coefficient to determine reproducibility. Results: Statistical analysis showed excellent internal consistency (α = 0.936) and reproducibility (r: 0.984; 95% CI: 0.963-0.993; p < 0.001). The correlation between the DrHy-Qb and the SF-36 was moderate and negative (r: -0.394; p < 0.01). Conclusions: This study showed that the DrHy-Qb was successfully translated, adapted, and validated into Brazilian Portuguese, and can be used to assess quality of life in patients with drug hypersensitivity.

Designing a Nurse-Led Program for Self-Management of Substance Addiction Consequences: A Modified e-Delphi Study.

Therapeutic interventions for people with problematic use of psychoactive substances can help tackle specific needs related to substance addiction consequences. This modified e-Delphi study aimed to establish consensus on a training program for self-management of substance addiction consequences. The study was conducted between February and April 2022, with an experts' sample of 28 participants in the first round and 24 in the second. A priori consensus criteria were defined for each round. The results revealed a very strong consensus was achieved on the structure of the program and on clinical areas, such as the problematic use of substances, general health knowledge, health-seeking behavior and adherence, self-knowledge and well-being, social role and personal dignity, and family process. Additionally, over 80% participant consensus was achieved on an extensive number of interventions categorized as psychoeducational, psychotherapeutic, socio therapeutic, brief interventions, social skills training, problem solving techniques, relaxation techniques, and counseling. These findings may be able to fulfill a gap concerning structured treatment approaches for people with problematic use of psychoactive substances. Supporting self-management of the consequences of substance addiction and its application can change nurses' interventions.

Exploring new antiviral targets for influenza and COVID-19: Mapping promising hot spots in viral RNA polymerases.

Influenza and COVID-19 are infectious respiratory diseases that represent a major concern to public health with social and economic impact worldwide, for which the available therapeutic options are not satisfactory. The RdRp has a central role in viral replication and thus represents a major target for the development of antiviral approaches. In this study, we focused on Influenza A virus PB1 polymerase protein and the betacoronaviruses nsp12 polymerase protein, considering their functional and structural similarities. We have performed conservation and druggability analysis to map conserved druggable regions, that may have functional or structural importance in these proteins. We disclosed the most promising and new targeting regions for the discovery of new potential polymerase inhibitors. Conserved druggable regions of putative interaction with favipiravir and molnupiravir were also mapped. We have also compared and integrated the current findings with previous research.

Atualização em reações de hipersensibilidade aos anti-inflamatórios não esteroidais ­ Parte 2: manifestações clínicas, fenótipos, diagnóstico e manejo / Update on hypersensitivity reactions to nonsteroidal anti-inflammatory drugs ­ Part 2: clinical features, phenotypes, diagnosis, and management

Os anti-inflamatórios não esteroidais (AINE) são os fármacos mais frequentemente associados a reações de hipersensibilidade (RH) na prática clínica. Na parte 2 dessa atualização sobre as RH aos AINE, discutiremos os aspectos clínicos dessas reações, com foco nos sinais e sintomas, como diferenciar os fenótipos clínicos, fazer a orientação desses pacientes e quando indicar procedimentos complementares, como testes cutâneos, de provocação e dessensibilização.

Nonsteroidal anti-inflammatory drugs are a major cause of drug hypersensitivity reactions in clinical practice. In this "Update Part 2", we discuss the clinical picture, including the main signs and symptoms, how to distinguish clinical phenotypes, how to manage affected patients, and when to indicate additional procedures, such as skin testing, challenge, and desensitization.

Mastocytosis: the safety of different COVID-19 vaccines / Mastocitose: segurança de diferentes vacinas contra a COVID-19

The COVID-19 pandemic has forced the development of vaccines to fight SARS-CoV-2. After vaccination began, reports of adverse reactions, including anaphylaxis, emerged. This raised concerns about the safety of COVID-19 vaccines in patients diagnosed with mastocytosis. The authors share their experience in administering different COVID-19 vaccines to patients diagnosed with mastocytosis.

A pandemia por COVID-19 obrigou ao rápido desenvolvimento de vacinas para combate ao SARS-CoV-2. Após o início da vacinação começaram a surgir relatos de reações adversas às vacinas, incluindo reações anafiláticas, surgindo dúvidas sobre a segurança das vacinas em doentes com mastocitose. Os autores apresentam a sua experiência em relação à administração de diferentes vacinas contra a COVID-19 em doentes com diagnóstico de mastocitose.

Preparação do enfermeiro para intervir em situação de catástrofe / Preparing nurses to intervene in a disaster situation

Introdução: Os enfermeiros sempre foram elementos fundamentais no planeamento e gestão de uma catástrofe. Assim, foi desenvolvido um estudo com os objetivos principais de avaliar a perceção dos enfermeiros sobre a sua preparação perante uma situação de catástrofe, determinar as necessidades de formação dos enfermeiros para intervir em situações de catástrofe e avaliar se a experiência da prática durante a fase crítica da pandemia COVID-19 contribuiu para preparar os enfermeiros para intervir em catástrofe. Metodologia: A população alvo este estudo descritivo simples e quantitativo ficou constituída por um total de 155 enfermeiros a exercer funções em Portugal. Para a recolha de dados foi elaborado um e-questionário estruturado em três partes: caraterização sociodemográfica e profissional; escala "Disaster Preparedness Evaluation Tool (DPET®)", qual a formação em catástrofe e experiência profissional durante o contexto de pandemia. O projeto teve o parecer positivo da Comissão de Ética. Resultados: Da amostra obtida, 60,0% respondeu que seria parcialmente capaz de responder a uma situação de catástrofe e no global, a perceção dos enfermeiros sobre a capacidade de intervenção em catástrofes encontra-se em média abaixo do valor da mediana da escala, refletindo a falta de preparação. Apenas 15,5% dos enfermeiros dizem ter tido formação em catástrofe durante a licenciatura, indicando que têm falta de formação, sendo que, apenas 30% referiram algum tipo de participação em situações de catástrofe. Da amostra, 74,8% responderam que o serviço tem um plano de emergência. No entanto, 18,2% avaliam-no como desadequado. Constatou-se ainda que 84.45% dos enfermeiros questionados gostariam de aprofundar conhecimentos acerca do seu papel (competências) como enfermeiro numa situação de desastre. Apenas 8% dos enfermeiros não tiveram qualquer tipo de contato com a COVID-19 sendo que 20,6% tiveram de mudar de serviço durante a pandemia. 90,3% dos enfermeiros não realizaram formação nos 6 meses que antecederam a pandemia. No entanto, são da opinião que uma formação adequada teria sido uma mais-valia na sua preparação para esta situação. Conclusão: Os enfermeiros não se consideram preparados e referem a necessidade de formação e adequação do plano de intervenção.

Introduction: Nurses have always been key elements in planning and managing a disaster. Thus, a study was developed with the main objectives of assessing nurses' perceptions of their preparation in a disaster situation, determining the nurses' training needs to intervene in disaster situations, and assessing whether the experience of practice during the critical phase of the pandemic COVID-19 contributed to preparing nurses to intervene in a disaster situation. Methodology: The target population of this simple descriptive and quantitative study was a total of 155 nurses working in Portugal. For data collection, an e-questionnaire structured in three parts was designed: sociodemographic and professional characterization; "Disaster Preparedness Evaluation Tool (DPET®)" scale; disaster training; and professional experience during the pandemic context. The project had the positive opinion of the Ethics Committee. Results: Of the sample obtained, 60.0% responded that they would be partially able to respond to a disaster situation and overall, the nurses' perception of their ability to intervene in disasters is on average below the median value of the scale, reflecting the lack of preparedness. Only 15.5% of the nurses reported having had training on disasters during their degree, indicating a lack of training, and only 30% reported some type of participation in disaster situations. Of the sample, 74.8% responded that the service has an emergency plan. However, 18.2% evaluated it as inadequate. It was also found that 84.45% of the nurses questioned would like to deepen their knowledge about their role (skills) as nurses in a disaster situation. Only 8% of the nurses had no contact with COVID-19 and 20.6% had to change service during the pandemic. 90.3% of the nurses had no training in the 6 months preceding the pandemic. However, they are of the opinion that adequate training would have been an added value in their preparation for this situation. Conclusion: Nurses consider themselves unprepared and refer the need for training and adaptation of the intervention plan.

Atualização em reações de hipersensibilidade aos anti-inflamatórios não esteroidais ­ Parte 1: definições, farmacologia, epidemiologia, fisiopatologia e fatores genéticos / Update on hypersensitivity reactions to nonsteroidal anti-inflammatory drugs ­ Part 1: definitions, pharmacology, epidemiology, pathophysiology, and genetics

Os anti-inflamatórios não esteroidais (AINE) estão entre os medicamentos mais utilizados no mundo e são os fármacos mais frequentemente associados à ocorrência de reações de hipersensibilidade na América Latina. As reações têm grande variabilidade de apresentações clínicas e, consequentemente, com abordagem terapêutica difícil. Nesta revisão, abordamos aspectos farmacológicos dos AINE, bem como as definições, epidemiologia e fisiopatologia das reações de hipersensibilidade aos AINE. Por fim, discutimos aspectos genéticos associados à intolerância e alergia a esses fármacos.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used medications worldwide and the drugs most frequently associated with the occurrence of hypersensitivity reactions in Latin America. The clinical presentation of the reactions varies widely, which makes them difficult to treat. In this review, we address pharmacological aspects of NSAIDs, as well as the definitions, epidemiology, and pathophysiology of hypersensitivity reactions to NSAIDs. Finally, we discuss genetic factors associated with intolerance and allergy to these drugs.

Succession of the wheat seed-associated microbiome as affected by soil fertility level and introduction of Penicillium and Bacillus inoculants in the field.

During germination, the seed releases nutrient-rich exudates into the spermosphere, thereby fostering competition between resident microorganisms. However, insight into the composition and temporal dynamics of seed-associated bacterial communities under field conditions is currently lacking. This field study determined the temporal changes from 11 to 31 days after sowing in the composition of seed-associated bacterial communities of winter wheat as affected by long-term soil fertilization history, and by introduction of the plant growth-promoting microbial inoculants Penicillium bilaiae and Bacillus simplex. The temporal dynamics were the most important factor affecting the composition of the seed-associated communities. An increase in the relative abundance of genes involved in organic nitrogen metabolism (ureC and gdhA), and in ammonium oxidation (amoA), suggested increased mineralization of plant-derived nitrogen compounds over time. Dynamics of the phosphorus cycling genes ppt, ppx and cphy indicated inorganic phosphorus and polyphosphate cycling, as well as phytate hydrolysis by the seed-associated bacteria early after germination. Later, an increase in genes for utilization of organic phosphorus sources (phoD, phoX and phnK) indicated phosphorus limitation. The results indicate that community temporal dynamics are partly driven by changed availability of major nutrients, and reveal no functional consequences of the added inoculants during seed germination.