Intranasal antihistamines and corticosteroids in allergic rhinitis: A systematic review and meta-analysis.

BACKGROUND: There is insufficient systematized evidence on the effectiveness of individual intranasal medications in allergic rhinitis (AR). OBJECTIVES: We sought to perform a systematic review to compare the efficacy of individual intranasal corticosteroids and antihistamines against placebo in improving the nasal and ocular symptoms and the rhinoconjunctivitis-related quality of life of patients with perennial or seasonal AR. METHODS: The investigators searched 4 electronic bibliographic databases and 3 clinical trials databases for randomized controlled trials (1) assessing adult patients with seasonal or perennial AR and (2) comparing the use of intranasal corticosteroids or antihistamines versus placebo. Assessed outcomes included the Total Nasal Symptom Score, the Total Ocular Symptom Score, and the Rhinoconjunctivitis Quality-of-Life Questionnaire. The investigators performed random-effects meta-analyses of mean differences for each medication and outcome. The investigators assessed evidence certainty using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. RESULTS: This review included 151 primary studies, most of which assessed patients with seasonal AR and displayed unclear or high risk of bias. Both in perennial and seasonal AR, most assessed treatments were more effective than placebo. In seasonal AR, azelastine-fluticasone, fluticasone furoate, and fluticasone propionate were the medications with the highest probability of resulting in moderate or large improvements in the Total Nasal Symptom Score and Rhinoconjunctivitis Quality-of-Life Questionnaire. Azelastine-fluticasone displayed the highest probability of resulting in moderate or large improvements of Total Ocular Symptom Score. Overall, evidence certainty was considered "high" in 6 of 46 analyses, "moderate" in 23 of 46 analyses, and "low"/"very low" in 17 of 46 analyses. CONCLUSIONS: Most intranasal medications are effective in improving rhinitis symptoms and quality of life. However, there are relevant differences in the associated evidence certainty.

Redox imbalance induces remodeling of glucose metabolism in Rhipicephalus microplus embryonic cell line.

Carbohydrate metabolism not only functions in supplying cellular energy but also has an important role in maintaining physiological homeostasis and in preventing oxidative damage caused by reactive oxygen species. Previously, we showed that arthropod embryonic cell lines have high tolerance to H2O2 exposure. Here, we describe that Rhipicephalus microplus tick embryonic cell line (BME26) employs an adaptive glucose metabolism mechanism that confers tolerance to hydrogen peroxide at concentrations too high for other organisms. This adaptive mechanism sustained by glucose metabolism remodeling promotes cell survival and redox balance in BME26 cell line after millimolar H2O2 exposure. The present work shows that this tick cell line could tolerate high H2O2 concentrations by initiating a carbohydrate-related adaptive response. We demonstrate that gluconeogenesis was induced as a compensation strategy that involved, among other molecules, the metabolic enzymes NADP-ICDH, G6PDH, and PEPCK. We also found that this phenomenon was coupled to glycogen accumulation and glucose uptake, supporting the pentose phosphate pathway to sustain NADPH production and leading to cell survival and proliferation. Our findings suggest that the described response is not atypical, being also observed in cancer cells, which highlights the importance of this model to all proliferative cells. We propose that these results will be useful in generating basic biological information to support the development of new strategies for disease treatment and parasite control.

Motivation and Knowledge of Portuguese Community Pharmacists Towards the Reporting of Suspected Adverse Reactions to Medicines: A Cross-Sectional Survey.

The close contact between patients and community pharmacists, along with the extensive geographical distribution of pharmacies in Portugal, offer exceptional conditions to detect and report adverse drug reactions (ADR). This study aimed to evaluate the motivation and knowledge of spontaneous reporting of ADR by community pharmacists of Porto, Portugal. Secondly, we aimed to generate real-world evidence on the main factors determining ADR report and at raising potential alternatives to the current reporting procedure in community pharmacy. We performed a descriptive, cross-sectional, observational, anonymous web survey-based study. Between April and July 2021, a web survey was implemented, targeting community pharmacists in the Porto district, Portugal. We validated 217 surveys from pharmacists. Regular notifiers seem to be more familiarised than non-regular notifiers with the Portuguese Pharmacovigilance System (PPS), with the Portal RAM for reporting suspected ADR, and with the update of the concept of ADR. Moreover, regular notifiers seem to be more proactive with their care in questioning patients about ADR and have more self-knowledge to identify suspected ADR. Conversely, non-regular notifiers, seem to be more reluctant to be judged by their ADR reporting activities. Respondents suggested to simplify and optimise the reporting process (31% of the suggestions), or to integrate a reporting platform into the pharmacy's software (27%). This study identified opportunities to promote the ADR reporting process by community pharmacists, namely receiving feedback from the PPS on the reported case and its regulatory implications, implementing training programs in pharmacovigilance, and creating solutions to simplify the reporting process.

A comprehensive review of adverse events to drugs used in COVID-19 patients: Recent clinical evidence.

BACKGROUND: Since the breakthrough of the pandemic, several drugs have been used to treat COVID-19 patients. This review aims to gather information on adverse events (AE) related to most drugs used in this context. METHODS: We performed a literature search to find articles that contained information about AE in COVID-19 patients. We analysed and reviewed the most relevant studies in the Medline (via PubMed), Scopus and Web of Science. The most frequent AE identified were grouped in our qualitative analysis by System Organ Class (SOC), the highest level of the MedDRA medical terminology for each of the drugs studied. RESULTS: The most frequent SOCs among the included drugs are investigations (n = 7 drugs); skin and subcutaneous tissue disorders (n = 5 drugs); and nervous system disorders, infections and infestations, gastrointestinal disorders, hepatobiliary disorders, and metabolism and nutrition disorders (n = 4 drugs). Other SOCs also emerged, such as general disorders and administration site conditions, renal and urinary disorders, vascular disorders and cardiac disorders (n = 3 drugs). Less frequent SOC were eye disorders, respiratory, thoracic and mediastinal disorders, musculoskeletal and connective tissue disorders, and immune system disorders (n = 2 drugs). Psychiatric disorders, and injury, poisoning and procedural complications were also reported (n = 1 drug). CONCLUSIONS: Some SOCs seem to be more frequent than others among the COVID-19 drugs included, although neither of the studies included reported causality analysis. For that purpose, further clinical studies with robust methodologies, as randomised controlled trials, should be designed and performed.

Prevalence and factors associated with excessive and severe daytime sleepiness among healthcare university students in the Brazilian Midwest.

The present study aimed to determine the prevalence of, and factors associated with excessive and severe daytime sleepiness in healthcare university students. A cross-sectional university-based study was conducted with 1,779 students from a university located in the Brazilian Midwest State of Goiás, Brazil, in 2018. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS) and classified as excessive daytime sleepiness (EDS; cut-off ESS score ≥10) and severe EDS (S-EDS; cut-off ESS score ≥16). Associated factors included sociodemographic, behavioural, academic, nutritional status, and sleep-related and perceived health characteristics. Poisson regression was used for the data analysis. The mean (SD) age of the sample was 22.5 (3.84) years. The prevalence of EDS was 54.4% (95% confidence interval [CI] 51.9-56.1) and S-EDS was 10.0% (95% CI 9.2-11.7). After adjustment, a higher probability of occurrence of EDS was found among women (prevalence ratio [PR] 1.37, 95% CI 1.24-1.53), younger students (PR 1.23, 95% CI 1.07-1.42), those who were studying medicine (PR 1.14, 95% CI 1.02-1.28), with poor sleep quality (PR 1.29, 95% CI 1.17-1.43), and among those who reported constant loss of sleep due to internet use (PR 1.14, 95% CI 1.02-1.27). After adjustment, the highest probability of occurrence of S-EDS was found among women (PR 1.72, 95% CI 1.22-2.43), among those with poor sleep quality (PR 2.17, 95% CI 1.54-3.08), and medical students (PR 1.39, 95% CI 1.01-1.90). In conclusion, there was a high prevalence of daytime sleepiness among healthcare university students, especially among medical students and women.

Development of sheep secondary follicles and preservation of aromatase and metalloproteinases 2 and 9 after vitrification and in vitro culture.

The cryopreservation of secondary follicles (SF) is a promising alternative to preserve the reproductive potential both in humans and animals in situations in which the transplantation of ovarian tissue is not possible. The objective of the present study was cryopreserved SF isolated sheep. Beyond follicular morphology, viability and development, we investigated proteins related to steroidogenic function and basement membrane remodeling [metalloproteinases 2 (MMP-2) and 9 (MMP-9)] in fresh SF (FSF) and vitrified SF (VSF) followed by in vitro culture for 6 (D6) or 12 days (D12). The percentage of intact follicles, follicular and oocyte diameter of the VSF were lower than FSF on both days of culture (P < 0.05). The VSF viability was statistically reduced from D6 (95.5%) to D12 (77.3%) but did not differ from the FSF on both days (D6:96.2% to D12:86.5%). Antrum formation in the VSF (D6: 59.13%; D12: 79.56%) was significantly lower than the FSF (D6: 79.61%; D12: 92.23%). However, an increase in this percentage was observed from D6 to D12 in both groups. Aromatase showed stronger labeling on FSF D6 and VSF D12 compared to other treatments (P < 0.05). MMP-2 showed a similar pattern of labeling in FSF D6 and VSF D12, similarly to that observed in FSF D12 and VSF D6. MMP-9 was similar in FSF and VSF cultivated for 6 and 12 days. In conclusion, VSF are able to grow and develop during 12 days of in vitro culture and showed evidence of preservation of steroidogenic function and remodeling of the basement membrane.

Glucose metabolomic profile during embryogenesis in the tick Rhipicephalus microplus.

INTRODUCTION: Metabolomic approaches can assess the actual state of an organism's energy metabolism during a specific morphological event, providing a more accurate insight into the correlations between physiology and metabolic regulation. METHODS: The study of the metabolomic profile aim to identify the largest possible number of biomolecules in a certain organism or specific structures. For this purpose, mass spectrometry (MS) and chromatography have been used in the present study. OBJECTIVES: In this context, the aim of the present work is to evaluate the glucose metabolomic profile during embryogenesis in Rhipicephalus microplus tick, investigating the dynamics of nutrient utilization during tick embryo formation, as well as the control of glucose metabolism. RESULTS: We show that glycogen reserves are preferentially mobilized to sustain the energy-intensive process of embryogenesis. Subsequently, the increase in concentration of specific amino acids indicates that protein degradation would provide carbons to fuel gluconeogenesis, supplying the embryo with sufficient glucose and glycogen during development. CONCLUSION: Altogether, these results demonstrated the presence of a very refined catabolic and anabolic control during embryogenesis in R. microplus tick, suggesting the pronounced gluconeogenesis as a strategy to secure embryo development. Moreover, this research contributes to the understanding of the mechanisms that control glucose metabolism during tick embryogenesis and may aid the identification of putative targets for novel chemical or immunological control methods, which are essential to improve the prevention of tick infestations.

Caffeine Mouth Rinse Does Not Improve Time to Exhaustion in Male Trained Cyclists.

This study investigated the effects of caffeine mouth rinse on cycling time to exhaustion (TTE) and physiological responses in trained cyclists. In a double-blinded randomized counterbalanced cross-over design, 10 recreationally trained male cyclists (mean ± SD: 32 ± 3 years, 72.8 ± 5.3 kg, 1.78 ± 0.06 m, 13.9% ± 3.3% body fat, peak power output = 289.4 ± 24.7 W) completed two TTE tests cycling at 75% of peak aerobic power following 24 hr of dietary and exercise standardization. Cyclists were administered 25-ml mouth rinses for 5 s containing either 85 mg of caffeine or control (water) every 5 min throughout the exercise tests. No significant improvement in TTE was shown with caffeine mouth rinse compared with control (33:24 ± 12:47 vs. 28:08 ± 10:18 min; Cohen's dz effect size: 0.51, p = .14). Caffeine mouth rinse had no significant effect on ratings of perceived exertion (p = .31) or heart rate (p = .35) throughout the cycling TTE protocol. These data indicate that a repeated dose of caffeinated mouth rinse for 5 s does not improve cycling TTE in recreationally trained male cyclists. However, these findings should be taken with caution due to the small sample size and blinding ineffectiveness, while further well-design studies with larger samples are warranted.

Inter- and intra-genotype differences in induced cystogenesis of recombinant strains of Toxoplasma gondii isolated from chicken and pigs.

The ability to differentiate from the proliferative (tachyzoite) to the latent (bradyzoite) stage of isolates of Toxoplasma gondii recombinant genotypes (I/II/III and I/III) and reference strains from a clonal line (RH and ME49) was investigated in this study. Two isolates from chicken (#114 and #277; ToxoDB) and 3 from pigs (#114; ToxoDB) were the subjects for evaluation. The isolates were grown in cell culture under 2 different conditions: culture medium at pH 7.0 (neutral, without stress induction) or pH 8.0 (alkaline, stress inducing). After 4 days, the cultures were fixed and the events resulting from infection and induction were labeled. T. gondii cysts were labeled using Dolichos biflorus-FITC lectin (DBL-cysts) and free tachyzoites or vacuolar were labeled using an anti-T. gondii polyclonal antibody followed by an Alexa 594-conjugated secondary antibody (DBL-negative structures compatible with parasite structures - lysis plaques or vacuole). Differences in DBL-cysts formation in vitro in response to exogenous stress were observed between recombinant genotype isolates and the typical genotypes. The differences in conversion rates and the patterns of lysis plate production between genotype I/III isolates (#114) indicate that care should be taken when extrapolating the in vitro phenotypic characteristics of parasites from the same genotype.

Non-classical gluconeogenesis-dependent glucose metabolism in Rhipicephalus microplus embryonic cell line BME26.

In this work we evaluated several genes involved in gluconeogenesis, glycolysis and glycogen metabolism, the major pathways for carbohydrate catabolism and anabolism, in the BME26 Rhipicephalus microplus embryonic cell line. Genetic and catalytic control of the genes and enzymes associated with these pathways are modulated by alterations in energy resource availability (primarily glucose). BME26 cells in media were investigated using three different glucose concentrations, and changes in the transcription levels of target genes in response to carbohydrate utilization were assessed. The results indicate that several genes, such as glycogen synthase (GS), glycogen synthase kinase 3 (GSK3), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6 phosphatase (GP) displayed mutual regulation in response to glucose treatment. Surprisingly, the transcription of gluconeogenic enzymes was found to increase alongside that of glycolytic enzymes, especially pyruvate kinase, with high glucose treatment. In addition, RNAi data from this study revealed that the transcription of gluconeogenic genes in BME26 cells is controlled by GSK-3. Collectively, these results improve our understanding of how glucose metabolism is regulated at the genetic level in tick cells.

Unveiling the future: precision pharmacovigilance in the era of personalized medicine.

In the era of personalized medicine, pharmacovigilance faces new challenges and opportunities, demanding a shift from traditional approaches. This article delves into the evolving landscape of drug safety monitoring in the context of personalized treatments. We aim to provide a succinct reflection on the intersection of tailored therapeutic strategies and vigilant pharmacovigilance practices. We discuss the integration of pharmacogenetics in enhancing drug safety, illustrating how genetic profiling aids in predicting drug responses and adverse reactions. Emphasizing the importance of phase IV-post-marketing surveillance, we explore the limitations of pre-marketing trials and the necessity for a comprehensive approach to drug safety. The article discusses the pivotal role of pharmacogenetics in pre-exposure risk management and the redefinition of pharmacoepidemiological methods for post-exposure surveillance. We highlight the significance of integrating patient-specific genetic profiles in creating personalized medication leaflets and the use of advanced computational methods in data analysis. Additionally, we examine the ethical, privacy, and data security challenges inherent in precision medicine, emphasizing their implications for patient consent and data management.

Epidemic Intelligence Threat Reporting Profile in Portugal during the COVID-19: 2 Years of Decrease in Reporting on Non-COVID-19 Threats.

Background: Epidemic intelligence (EI) ensures early detection, assessment, and communication of public health threats. Threat reporting defines priorities and mobilize resources for surveillance, prevention, and control. In Portugal, the Directorate-General of Health (DGS) is responsible for EI and publishes a weekly public health threat report (RONDA). Changes in threats in regular threat reports since COVID-19 have not been previously described. We analysed changes in non-COVID threat reporting in the weekly threat report. Methods: Using the DGS Emergency Operations Centre's threat reporting database, we compared threats reported in RONDAs from 2016 to 2022 in three sequential periods: P1 before COVID-19 (January 2016-March 2020), P2 during acute COVID-19 restrictions (April 2020-February 2022), and P3 in post-acute COVID-19 phase (February 2022-September 2022). We described the monthly average frequency of reports on non-COVID-19 threats in those periods considering different disease groups, geographical focus, and information sources. We estimated expected non-COVID-19 reports on threats using a forecast model fitted to the time series until March 2020 and compared observed and expected values. Results: Non-COVID-19 threats had a decrease in the monthly average frequency of reporting in period 2 ( x ¯ 1 : 4.7 vs. x ¯ : 2.3, p < 0.001) compared to period 1. Using the forecast methods, there were 114 fewer non-COVID threats than the 162 expected (-70%) in period 2. In period 3, there were 105 more threats than expected (+256%). The ECDC and the WHO were the most frequent sources of information followed by national Public Health sources. Conclusions: During COVID-19, there was a decrease in reports on non-COVID threats in Portugal. COVID-19 possibly affected global EI, by shifting attention and resources from other threats to the pandemic. However, the number of threats that warrant follow-up and communication is increasing. Further research is necessary to inform the EI research and development agenda, to ensure that all relevant threats are detected, accessed, and communicated according to evolving EI objectives and priorities while resources and preparedness are guaranteed.

Introdução: A epidemic intelligence (EI) assegura a deteção precoce, a avaliação e a comunicação das ameaças para a saúde pública para definir prioridades e mobilizar recursos para a investigação, vigilância, prevenção e controlo. Em Portugal, a Direção-Geral da Saúde (DGS) é responsável pela EI e publica semanalmente um relatório de ameaças para a saúde pública (RONDA) que é partilhado com a rede de autoridades de saúde, instituições e profissionais de saúde pública. As alterações nas ameaças comunicadas em relatórios periódicos de ameaças desde a COVID-19 não foram descritas anteriormente. Métodos: Comparámos as ameaças reportadas na RONDA entre 2016 a 2022 em três períodos sequenciais: antes da COVID-19 (janeiro de 2016 - março de 2020), P2 durante as restrições (abril de 2020 - fevereiro de 2022) e P3 na fase pós-aguda da COVID-19 (fevereiro de 2022 - setembro de 2022). Comparamos a frequência média mensal de ameaças não COVID-19 relatadas entre todas as ameaças relatadas nesses períodos, considerando diferentes categorias dentro do grupo de doenças, foco geográfico e fontes de informação. Resultados: As ameaças não-COVID-19 tiveram uma diminuição na frequência média mensal de reporte no Período2 (14,7 vs. 2,3 p < 0.001) em comparação com o Período1, antes da COVID-19. Houve um retorno ao padrão pré-pandêmico de notificação no Período 3 (14,67 vs. 17,63 p < 0.208) para ameaças não COVID-19 com um aumento nas doenças virais emergentes (2,20 vs. 7,62 p < 0.001). O ECDC e a OMS são as fontes de informação mais frequentes, seguidas das fontes nacionais de saúde pública. Conclusões: Durante a COVID-19, houve alterações no reporte de ameaças em Portugal. A COVID-19 possivelmente afetou a EI e os relatórios de ameaças epidémicas globais, possivelmente desviando a atenção e os recursos de outras ameaças para a pandemia. No entanto, a quantidade de ameaças que justificam o acompanhamento e a comunicação pode estar a aumentar. É necessária investigação em comunicação de ameaças detetadas no âmbito da EI a fim de assegurar que todas as ameaças relevantes são avaliadas e comunicadas de acordo com os objetivos da EI, garantindo simultaneamente o investimento em recursos e a preparação para a prevenção e resposta.

Assessing medication use patterns by clinical outcomes severity among inpatients with COVID-19: A retrospective drug utilization study.

PURPOSE: This study assessed medication patterns for inpatients at a central hospital in Portugal and explored their relationships with clinical outcomes in COVID-19 cases. METHODS: A retrospective study analyzed inpatient medication data, coded using the Anatomical Therapeutic Chemical classification system, from electronic patient records. It investigated the association between medications and clinical severity outcomes such as ICU admissions, respiratory/circulatory support needs, and hospital discharge status, including mortality (identified by ICD-10-CM/PCS codes). Multivariate analyses incorporating demographic data and comorbidities were used to adjust for potential confounders and understand the impact of medication patterns on disease progression and outcomes. RESULTS: The analysis of 2688 hospitalized COVID-19 patients (55.3% male, average age 62.8 years) revealed a significant correlation between medication types and intensity and disease severity. Cases requiring ICU admission or ECMO support often involved blood and blood-forming organ drugs. Increased use of nervous system and genitourinary hormones was observed in nonsurvivors. Corticosteroids, like dexamethasone, were common in critically ill patients, while tocilizumab was used in ECMO cases. Medications for the alimentary tract, metabolism, and cardiovascular system, although widely prescribed, were linked to more severe cases. Invasive mechanical ventilation correlated with higher usage of systemic anti-infectives and musculoskeletal medications. Trends in co-prescribing blood-forming drugs with those for acid-related disorders, analgesics, and antibacterials were associated with intensive interventions and worse outcomes. CONCLUSIONS: The study highlights complex medication regimens in managing severe COVID-19, underscoring specific drug patterns associated with critical health outcomes. Further research is needed to explore these patterns.

A Comparison of Active Pharmacovigilance Strategies Used to Monitor Adverse Events to Antiviral Agents: A Systematic Review.

INTRODUCTION: The safety of antiviral agents in real-world clinical settings is crucial, as pre-marketing studies often do not capture all adverse events (AE). Active pharmacovigilance strategies are essential for detecting and characterising these AE comprehensively. OBJECTIVE: The aim of this study was to identify and characterise active pharmacovigilance strategies used in real-world clinical settings for patients under systemic antiviral agents, focusing on the frequency of AE and the clinical data sources used. METHODS: We conducted a systematic review by searching three electronic bibliographic databases targeting observational prospective active pharmacovigilance studies, phase IV clinical trials for post-marketing safety surveillance, and interventional studies assessing active pharmacovigilance strategies, focusing on individuals exposed to systemic antiviral agents. RESULTS: We included 36 primary studies, predominantly using Drug Event Monitoring (DEM), with a minority employing sentinel sites and registries. Human immunodeficiency virus (HIV) was the most common condition, with the majority using DEM. Within the DEM, there was a wide range of incidences of patients experiencing at least one AE, and most of these studies used one or two data sources. Sentinel site studies were less common, with two on hepatitis C virus (HCV) and one on HIV, each relying on one or two data sources. The single study using a registry focusing on HIV therapy reported using just one data source. Patient interviews were the most common data source, followed by medical records and laboratory tests. The quality of the studies was considered 'good' in 18/36, 'fair' in 1/36, and 'poor' in 17/36 studies. CONCLUSION: DEM was the predominant pharmacovigilance strategy, employing multiple data sources, and appears to increase the likelihood of detecting higher AE incidence. Establishing such a framework would facilitate a more detailed and consistent approach across different studies and settings.

Reaction Risk to Direct Penicillin Challenges: A Systematic Review and Meta-Analysis.

Importance: While direct penicillin challenges might support the expansion of penicillin allergy delabeling efforts, the perceived risk of reactions remains a key barrier. Objective: To evaluate the frequency of reactions to direct penicillin challenges in individuals with penicillin allergy labels and to identify factors associated with such reactions. Data Sources: Three electronic databases were searched (MEDLINE, Web of Science, and Scopus) from inception to July 19, 2023, for primary studies assessing patients undergoing direct penicillin challenges. Articles were included regardless of publication year, language, status, or definition of allergy risk. Study Selection: Two reviewers independently selected original studies reporting the frequency of immunologically mediated reactions following a direct penicillin challenge in patients reporting a penicillin allergy. Data Extraction and Synthesis: Two reviewers independently extracted data and independently assessed the quality of each primary study using a risk-of-bias tool for prevalence studies. Main Outcomes and Measures: The primary outcome was the frequency of reactions to direct penicillin challenges as calculated using random-effects bayesian meta-analysis of proportions. Secondary outcomes included risk factors for reactions and the frequency of severe reactions. Results: A total of 56 primary studies involving 9225 participants were included. Among participants, 438 experienced reactions to direct penicillin challenges without prior testing, corresponding to an overall meta-analytic frequency of 3.5% (95% credible interval [CrI], 2.5%-4.6%). Meta-regression analyses revealed that studies performed in North America had lower rates of reaction to direct challenges (odds ratio [OR], 0.36; 95% CrI, 0.20-0.61), while studies performed in children (OR, 3.37; 95% CrI, 1.98-5.98), in outpatients (OR, 2.19; 95% CrI, 1.08-4.75), and with a graded (OR, 3.24; 95% CrI, 1.50-7.06) or prolonged (OR, 5.45; 95% CrI, 2.38-13.28) challenge had higher rates of reaction. Only 5 severe reactions (3 anaphylaxis, 1 fever with rash, and 1 acute kidney injury) were reported, none of which were fatal. Conclusions and Relevance: This systematic review and meta-analysis found that reactions to direct penicillin challenges are infrequent, with rates comparable to indirect challenges after allergy testing. These findings suggest that direct challenges are safe for incorporation into penicillin allergy evaluation efforts across age groups and clinical settings.

Isolation and genetic characterization of Toxoplasma gondii from chickens from public markets in Pernambuco State, Brazil.

This study aimed to evaluate the presence and viability of Toxoplasma gondii in chickens intended for human consumption in the Pernambuco State, Brazil. Blood and tissue samples were collected from 25 chickens sold in markets in Recife, Pernambuco. Samples were evaluated by indirect immunofluorescence assay (IFA) to detect antibodies to T. gondii. Pools of brain and heart of seropositive chickens were subjected to bioassay in two Swiss Webster mice, which were evaluated for 45 days then tested by IFA to detect seroconversion. The mice were euthanized, and their brains were evaluated for cysts. Peritoneal lavage was also conducted in mice that exhibited clinical signs. Brains containing cysts or peritoneal lavage with tachyzoites were inoculated into MA-104 cells. Brains of mice inoculated with the same tissue were pooled and analysed by ITS1-PCR. We obtained a frequency of antibodies to T. gondii of 68.00% (17/25) in chickens, and a seroconversion rate of 70.58% (24/34) in mice. Detection of Toxoplasma ITS1 DNA confirmed an isolation rate of 41.1% (7/17). Three isolates were characterized by mnPCR-RFLP as genotypes ToxoDB#36 and ToxoDB#114. We highlight the occurrence of ToxoDB#36 in chickens in Pernambuco State and the parasites' viability in chickens intended for human consumption.

Protocol for the systematic reviews on the desirable and undesirable effects of pharmacological treatments of allergic rhinitis informing the ARIA 2024 guidelines.

There is insufficient evidence regarding the comparative efficacy and safety of pharmacological treatments of allergic rhinitis (AR). In the context of informing the 2024 revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines, we plan to perform three systematic reviews of randomized controlled trials (RCTs) comparing the desirable and undesirable effects (i) between intranasal and oral medications for AR; (ii) between combinations of intranasal and oral medications versus nasal or oral medications alone; and (iii) among different intranasal specific medications. We will search four electronic bibliographic databases and three clinical trials databases for RCTs examining patients ≥ 12 years old with seasonal or perennial AR. Assessed outcomes will include the Total Nasal Symptom Score, the Total Ocular Symptom Score, and the Rhinoconjunctivitis Quality-of-Life Questionnaire. We will assess the methodological quality of included primary studies by using the Cochrane risk-of-bias tool. If appropriate, we will perform a pairwise random-effects meta-analysis for each pair of assessed medication classes and outcomes, as well as a network meta-analysis to assess the comparative efficacy of intranasal medications among each other. Heterogeneity will be explored by sensitivity and subgroup analyses. This set of systematic reviews will allow for a comprehensive assessment of the effectiveness and safety of pharmacological interventions for AR and inform recommendations in the context of the ARIA guidelines.

Intranasal Versus Oral Treatments for Allergic Rhinitis: A Systematic Review With Meta-Analysis.

BACKGROUND: Treatments for allergic rhinitis include intranasal or oral medications. OBJECTIVE: To perform a systematic review with meta-analysis comparing the effectiveness of intranasal corticosteroids or antihistamines versus oral antihistamines or leukotriene receptor antagonists in improving allergic rhinitis symptoms and quality of life. METHODS: We searched four bibliographic databases and three clinical trial datasets for randomized controlled trials (1) assessing patients aged 12 years and older with seasonal or perennial allergic rhinitis, and (2) comparing intranasal corticosteroids or antihistamines versus oral antihistamines or leukotriene receptor antagonists. We performed a meta-analysis of the Total Nasal Symptom Score (TNSS), Total Ocular Symptom Score, Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), development of adverse events, and withdrawals owing to adverse events. Certainty of evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. RESULTS: We included 35 studies, most of which assessed patients with seasonal allergic rhinitis and displayed an unclear risk of bias. Superiority of intranasal treatments was found for all assessed outcomes. Intranasal corticosteroids were more effective than oral antihistamines at improving the TNSS (mean difference [MD], -0.86; 95% CI, -1.21 to -0.51; I2 = 70%), Total Ocular Symptom Score (MD, -0.36; 95% CI, -0.56 to -0.17; I2 = 0%), and RQLQ (MD, -0.88; 95% CI, -1.15 to -0.61; I2 = 0%), which were mostly associated with clinically meaningful improvements. Superiority of intranasal corticosteroids at improving the TNSS was also found against oral leukotriene receptor antagonists (MD, -1.05; 95% CI, -1.33 to -0.77). Intranasal antihistamines were more effective than oral antihistamines at improving the TNSS (MD, -0.47; 95% CI, -0.81 to -0.14; I2 = 0%) and RQLQ (MD, -0.31; 95% CI, -0.56 to -0.06; I2 = 0%). CONCLUSIONS: Randomized controlled trials suggest that intranasal treatments are more effective than oral treatments at improving symptoms and quality of life in seasonal allergic rhinitis.

PEPCK and glucose metabolism homeostasis in arthropods.

The fat body is responsible for a variety of functions related to energy metabolism in arthropods, by controlling the processes of de novo glucose production (gluconeogenesis) and glycogen metabolism. The rate-limiting factor of gluconeogenesis is the enzyme phosphoenolpyruvate carboxykinase (PEPCK), generally considered to be the first committed step in this pathway. Although the study of PEPCK and gluconeogenesis has been for decades restricted to mammalian models, especially focusing on muscle and liver tissue, current research has demonstrated particularities about the regulation of this enzyme in arthropods, and described new functions. This review will focus on arthropod PEPCK, discuss different aspects to PEPCK regulation and function, its general role in the regulation of gluconeogenesis and other pathways. The text also presents our views on potentially important new directions for research involving this enzyme in a variety of metabolic adaptations (e.g. diapause), discussing enzyme isoforms, roles during arthropod embryogenesis, as well as involvement in vector-pathogen interactions, contributing to a better understanding of insect vectors of diseases and their control.