Rand Randall Martins

Innate immune receptors are central to host resistance against Trypanosoma cruzi infection, yet how parasite genetic diversity is associated with these responses remains poorly understood. Here, we characterized acute infection outcomes and myocardial innate immune transcriptional profiles in mice subjected to single and mixed infections with genetically distinct T. cruzi parasites (DTUs TcII, TcIII, and TcVI). Swiss mice were infected with RN2, RN23, Y, or CL‐Brener individually or in combination, and parasitemia, survival, and cardiac gene expression were assessed. The Y strain, CL‐Brener clone, and RN2 + RN23 + CL‐Brener condition exhibited a high‐severity profile, with marked parasitemia (8000–28,000 trypomastigotes/5 μL), mortality of 74%–100%, reduced myocardial transcription of Tlr2 , Tlr4 , Tlr9 , Trif , and Myd88 , and increased transcription of Nlrp3 , Casp1 , Il1β , and Tnfα . In contrast, RN2 and RN23 single infections exhibited low‐severity profiles and higher transcription of innate immune mediators associated with parasite control. Mixed‐infection groups displayed transcriptional and infection profiles differing from the corresponding single‐infection groups under a standardized total inoculum. Together, these findings identify distinct myocardial innate immune transcriptional profiles across single and mixed T. cruzi infection conditions and support further investigation of the contributions of parasite population composition and dose to acute infection outcomes.

Background: Hypomagnesemia, characterized by decreased levels of magnesium in the blood, is common among patients with cancer and may be related to the administration of proton pump inhibitors (PPIs) and/or platinum derivatives. Objective: To evaluate the safety and potential impact on serum magnesium levels of concomitant use of the PPI omeprazole in patients receiving a platinum derivative. Methods: This prospective, randomized, double-blind, single-dose, placebo-controlled study involved fixed doses of PPI administered on an outpatient basis. It spanned 4 cycles of platinum-based combination chemotherapy (21 days per cycle), and entailed a screening period (14 days before chemotherapy), 2 PPI treatment periods (total of 60 days), and a follow-up period (1 cycle). Patients recruited between May 2019 and March 2020 at 3 hospitals in Brazil were randomly assigned to receive placebo or PPI in a 1:1 ratio. Data analysis employed a linear mixed-effects model and Kaplan–Meier analysis. Results: A total of 164 patients were included in the study, 83 in the placebo group and 81 in the PPI group. Blood magnesium levels showed a modest decrease over time (by approximately 20%) across all patients. A correlation was observed between treatment duration and decrease in serum magnesium in the total sample (β = –0.035, 95% confidence interval [CI] –0.048 to –0.0021; p < 0.001). Compared with the placebo group, the PPI group showed a slightly greater decline (β = –0.121, 95% CI –0.231 to –0.011; p = 0.031). Additionally, no differences were noted between groups regarding the occurrence of neuropathy (p = 0.77), anorexia (p = 0.77), diarrhea (p = 0.34), or constipation (p = 0.39). Omeprazole use was associated with a lower incidence of nausea and vomiting (p = 0.005). Conclusion: These exploratory findings suggest that the concomitant use of omeprazole with platinum derivatives may be associated with a slightly faster rate of serum magnesium depletion than occurs with chemotherapy alone, but without clinical relevance or occurrence of frank hypomagnesemia. Keywords: magnesium, clinical oncology, platinum compounds, proton pump inhibitors, adverse effects Clinical trial registration: Brazilian Registry of Clinical Trials (ReBEC) RBR-8vsb7k2 RÉSUMÉ Contexte : L’hypomagnésémie se caractérise par une réduction des taux de magnésium dans le sang. Elle est répandue chez les patients atteints d’un cancer et peut être liée à l’administration d’inhibiteurs de la pompe à protons (IPP) et/ou de dérivés du platine. Objectif : Évaluer l’innocuité et l’incidence potentielle sur les taux sériques de magnésium de l’utilisation concomitante de l’IPP oméprazole chez des patients recevant un dérivé du platine. Méthodologie : Cette étude prospective, randomisée, à double insu, à dose unique et contrôlée par placebo portait sur des doses fixes d’IPP administrées en ambulatoire. Elle s’est déroulée pendant 4 cycles de chimiothérapie combinée à base de platine (21 jours par cycle) et comprenait une période de sélection (14 jours avant la chimiothérapie), deux périodes de traitement à l’IPP (comprenant 60 jours au total) et une période de suivi (1 cycle). Des patients recrutés dans 3 hôpitaux du Brésil entre mai 2019 et mars 2020 ont été répartis de manière aléatoire pour recevoir soit un placebo, soit un IPP, selon un ratio de 1:1. Un modèle linéaire à effets mixtes ainsi qu’une analyse de Kaplan-Meier ont été utilisés pour l’analyse des données. Résultats : Au total, 164 patients ont été inclus dans l’étude : 83 dans le groupe placebo et 81 dans le groupe IPP. Une diminution modeste avec le temps (environ 20 %) des taux sanguins de magnésium chez l’ensemble des patients a été constatée. Une corrélation a été observée entre la durée du traitement et la diminution du magnésium sérique chez l’ensemble des patients (β = –0,035; intervalle de confiance [IC] à 95 % : –0,048 à –0,002 1; p < 0,001). Cette diminution était légèrement plus marquée dans le groupe IPP que dans le groupe placebo (β = –0,121; IC à 95 % : –0,231 à –0,011; p = 0,031). De plus, aucune différence n’a été observée entre les groupes concernant la survenuede neuropathie (p = 0,77), d’anorexie (p = 0,77), de diarrhée (p = 0,34) ou de constipation p = 0,39). L’utilisation de l’oméprazole était associée à une incidence plus faible de nausées et de vomissements (p = 0,005). Conclusion : Ces résultats exploratoires indiquent que l’utilisation concomitante de l’oméprazole avec des dérivés du platine pourrait être associée à une diminution légèrement plus rapide des taux sériques de magnésiumque celle observée avec la chimiothérapie seule, sans toutefois présenter de pertinence clinique ni entraîner la survenue d’une hypomagnésémie franche. Mots-clés : magnésium, oncologie clinique, composés du platine, inhibiteurs de la pompe à protons, effets indésirables Inscription à l’essai clinique : Brazilian Registry of Clinical Trials (ReBEC) RBR-8vsb7k2

Objective To identify medications associated with changes in serum potassium concentrations in critically ill neonates. Methods A prospective cohort study was conducted between March 2023 and March 2024 in the neonatal intensive care units of a public maternity hospital in Brazil. Neonates admitted for over 24 hours and receiving at least one medication were […] ABSTRACT Objective To identify medications associated with changes in serum potassium concentrations in critically ill neonates. Methods A prospective cohort study was conducted between March 2023 and March 2024 in the neonatal intensive care units of a public maternity hospital in Brazil. Neonates admitted for over 24 hours and receiving at least one medication were […]

Introduction: Proton pump inhibitors (PPIs) are widely used medications for the treatment of gastrointestinal diseases and generally exhibit therapeutic equivalence. However, the acquisition of these medications can be hindered by socioeconomic disparities across different regions within the same city. Objective: To characterize the consumption profile of PPIs and its relationship with the socio-economic characteristics of the place of residence in a capital city in Northeastern Brazil. Methods: A cross-sectional study was conducted with 295 patients who acquired PPIs from a private network of community pharmacies comprising twenty-two units. Data were obtained through structured interviews, statistically analyzed, and combined with geospatial analyses to correlate the place of residence, income, and PPI acquisition. Results: 86.8% of acquisitions were made with medical prescription issued by gastroenterologists (50.7%), mainly for dyspepsia and gastroesophageal reflux (78.5%). Socioeconomic data revealed a predominance of patients with incomes below five minimum wages (70.1%). However, no spatial autocorrelation was identified between PPI prescriptions and the analyzed socioeconomic variables. Conclusions: The study identified no spatial autocorrelation between socioeconomic variables and PPI use. Areas with a higher HDI exhibit a favorable profile for acquiring these medications, while those with a lower HDI face challenges in doing so. However, this discrepancy has not been considered in prescribing practices, particularly in economically disadvantaged areas, potentially limiting access to appropriate pharmacotherapy.

Objectives: To evaluate the impact on clinical parameters and maternal-foetal outcomes of serious drug interactions in high-risk hospitalized pregnant women. Methods: A prospective cohort study including 571 pregnant women hospitalized between September 2019 and June 2022, with an average age of 30.6 years, mostly diagnosed with hypertensive syndromes (69.7%) and gestational diabetes (57.1%). Drug interactions were characterized daily through Lexicomp®, with monitoring of clinical parameters linked to their mechanisms of action. We used a multivariable logistic regression model with demographic and treatment variables to identify factors associated with drug interactions. In a second model, we analysed the impact of serious drug interactions on clinical outcomes, including maternal-foetal outcomes such as macrosomia, foetal tachycardia, amniotic fluid abnormalities, and prematurity. Key findings: We identified 203 pregnant women with one or more serious drug interactions (35.6%), and the risk factors were gestational age (adjusted odds ratio [AOR]: 0.96; 95% CI: 0.93–0.98), diagnosis of hypertension (AOR: 3.00; 95% CI: 2.49–6.41), number of medications (AOR: 1.09; 95% CI: 1.03–1.15), and length of hospitalization (AOR: 1.18; 95% CI: 1.12–1.26). Dipyrone and acetylsalicylic acid co-administration increased systolic blood pressure (AOR: 2.12; 95% CI: 1.01–4.47), while scopolamine and levomepromazine resulted in greater drowsiness (AOR: 5.38; 95% CI: 1.66–17.40) and a temperature increase (AOR: 5.96; 95% CI: 1.23–28.98). Conclusion: High-risk pregnant women of lower gestational age or with hypertensive syndromes are exposed to severe drug interactions, yet these interactions show limited clinical impact and do not significantly affect maternal-foetal outcomes.

Background and Aims: Neonates admitted to neonatal intensive care units (NICUs) are frequently exposed to multiple medications, increasing the risk of potential drug–drug interactions (pDDIs). However, the clinical impact of these interactions remains poorly understood in this population. This study aimed to evaluate the occurrence of pDDIs in critically ill neonates and their association with clinical outcomes and laboratory parameters. Methods: This prospective cohort study included 365 neonates admitted to a NICU in Brazil between March 2023 and March 2024. Pharmacotherapy was monitored daily for the identification of pDDIs using the UpToDate database. Interactions were grouped according to their potential clinical outcomes and analyzed for their association with clinical and laboratory parameters. The evaluated parameters included heart rate, respiratory rate, blood pressure, creatinine clearance, urine output, and blood urea nitrogen. Results: A total of 255 neonates (69.9%) experienced at least one pDDI, most of which were classified as risk category C (88.0%). The most frequent mechanisms of pDDIs were associated with heart rate changes (27.4%), nephrotoxicity (18.3%), central nervous system (CNS) depression (14.8%), and hypotension (14.8%). Neonates with pDDIs associated with heart rate changes had higher heart rates (158.1 ± 16.7 vs. 148.7 ± 17.0 bpm; p < 0.001). Nephrotoxic pDDIs were associated with reduced creatinine clearance (14.4 ± 13.5 vs. 25.8 ± 18.2 mL/min/1.73 m ² ; p < 0.001) and higher blood urea nitrogen levels (52.9 ± 36.2 vs. 27.6 ± 24.4 mg/dL; p < 0.001). pDDIs associated with hypotension significantly reduced mean arterial pressure (51.1 ± 11.5 vs. 58.3 ± 11.8 mmHg; p < 0.001). Conclusion: pDDIs are frequent in NICUs and are associated with clinically relevant changes, particularly those involving an increased risk of higher heart rates, renal impairment, and hypotension.

Background: The correct use of inhalation devices is essential for achieving adequate control of asthma and COPD; however, critical errors in inhalation technique are frequent and substantially reduce treatment effectiveness. This study’s objective was to evaluate the prevalence of inadequate inhalation technique among patients with asthma and COPD and to identify the most common critical errors and the factors associated with incorrect use. Methods: This cross‐sectional observational study included 575 patients (aged ≥ 18 years) with asthma and/or COPD, recruited from a university hospital outpatient pulmonology clinic and a public specialized pharmacy (Natal, Brazil). Participants completed sociodemographic questionnaires and demonstrated their inhaler technique, which was assessed using device‐specific checklists to identify critical errors. Factors associated with critical errors were analyzed using multivariable logistic regression. Results: Only 8.2% of participants correctly performed all steps of the inhalation technique. At least one critical error was observed in 73.4% of the cohort. In multivariable analysis, advanced age (OR: 1.029; 95% CI: 1.016–1.044), use of multiple devices (OR: 2.500; 95% CI: 1.754–3.562), and type of mechanism independent of inspiration (OR: 0.262; 95% CI: 0.160–0.430; protective factor) were significantly associated with critical errors ( p < 0.001). Conclusions: Inadequate inhalation technique, particularly the occurrence of critical errors, was highly prevalent, especially among older patients and those using multiple devices. Inhalers dependent on inspiratory effort demonstrated greater vulnerability to incorrect use.

Background: The genetic diversity of Trypanosoma cruzi and the epidemiological characteristics of the environments in which the parasite occurs are essential for understanding infection dynamics and controlling Chagas disease. This systematic review aimed to: (i) identify and analyze studies that evaluated the genetic variability and epidemiological aspects of T. cruzi infection in the state of Rio Grande do Norte, Brazil; (ii) summarize the information reported in the literature; and (iii) suggest new control strategies tailored to the region’s epidemiological profile.

Preterm labor, defined as contractions occurring every 5-10 minutes with cervical changes before the 37th week of estimated gestation, is a significant cause of perinatal mortality. This meta-analysis aims to evaluate the effectiveness and safety of magnesium sulfate compared to nifedipine in managing preterm labor. The systematic review protocol was registered with PROSPERO (CRD42023422419). Manuscripts published up to September 2024 were systematically searched in databases. Dichotomous data were pooled as odds ratios using a random-effects model with the Mantel-Haenszel method, while continuous data were analyzed as mean +/- standard deviation values, mean differences, and standardized mean differences using inverse-variance fixed-effects analysis. Fifteen randomized clinical trials (RCTs) were included, enrolling a total of 2,186 pregnant women. Nifedipine showed a greater effect compared to a 4-gram IV dose of magnesium sulfate. However, the efficacy of these tocolytics in prolonging pregnancy by 48 hours did not significantly differ between nifedipine and a 6-gram IV dose of magnesium sulfate. Additionally, magnesium sulfate was associated with more adverse drug reactions. The moderate certainty of evidence found here requires confirmation in large, adequately powered RCTs.