Background: Acute respiratory infections (ARIs) are a leading cause of morbidity and mortality worldwide with sub-Saharan Africa accounting for approximately 50% of the 5.8 million ARI-related deaths globally. Despite this substantial burden, pathogen-based surveillance remains limited in these regions. The post-pandemic phase presents a unique epidemiological landscape, with SARS-CoV-2 transitioning towards endemicity and potentially interacting with other circulating respiratory pathogens. This study aimed to characterize viral ARI etiology and the influence of SARS-CoV-2 serostatus and malaria co-infection on clinical outcomes during the immediate post-pandemic period in a rural Ghanaian setting. Methods: We conducted a prospective-observational study at a district hospital in Ghana between May 2022 and September 2023. Adults with acute respiratory infection were enrolled, and nasopharyngeal swabs were tested using a multiplex PCR panel detecting 22 respiratory, mainly viral, pathogens. SARS-CoV-2 serostatus and malaria infection status were determined, and broader clinical parameters were examined. Clinical severity was assessed using the PRIEST score, and participants were followed up for 28 days to evaluate symptom resolution. Multivariable logistic regression identified potential predictors of hospitalization. Results: Among 347 participants, the most frequently detected respiratory pathogens were rhinovirus/enterovirus (12.4%, n=43), acute SARS-CoV-2 (11.0%, n=38), and influenza A (6.3%, n=22). Among all participants, 79.8% (n=277) were seropositive for SARS-CoV-2 and 28.5% (n=99) were carrying malaria parasites. Hospitalization rates were comparable across SARS-CoV-2 serostatus, acute infection, and malaria status groups (25-30%). Higher PRIEST scores were associated with higher odds of hospitalization (OR: 1.50, 95% CI: 1.32-1.74), while COVID-19 vaccination was associated with lower odds (OR: 0.41, 95% CI: 0.18-0.93). Participants with acute SARS-CoV-2 infection experienced delayed symptom resolution. Conclusion: Post-pandemic ARI etiology in rural Ghana exhibits a diverse viral profile, with rhinovirus/enterovirus, SARS-CoV-2 and influenza A predominating. Clinical outcomes were more strongly associated with high PRIEST scores than with specific pathogens, with vaccination decreasing the odds for hospitalization. While this study did not identify pathogen-specific associations with clinical severity, sustained surveillance remains important for detecting shifts in viral circulation and informing tailored public health responses.
ImportanceSex is associated with the clinical presentation, outcomes, and response to treatment in patients with heart failure (HF). However, little is known about the safety and efficacy of treatment with finerenone according to sex. ObjectiveTo estimate the efficacy and safety of finerenone compared with placebo in both women and men. Design, Setting, and ParticipantsPrespecified analyses were conducted in the phase 3 randomized clinical trial Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure (FINEARTS-HF). The trial was conducted across 653 sites in 37 countries. Participants were adults aged 40 years and older with symptomatic HF and left ventricular ejection fraction (LVEF) of 40% or greater randomized between September 2020 and January 2023. InterventionFinerenone (titrated to 20 mg or 40 mg) or placebo. Main Outcomes and MeasuresThe primary outcome was a composite of cardiovascular death and total (first and recurrent) HF events (unplanned HF hospitalizations or urgent HF visits). ResultsA total of 6001 patients were randomized in FINEARTS-HF, of whom 2732 were women (45.5%), with a mean (SD) age of 73.6 (9.1) years. Women had higher rates of any obesity, higher LVEF (54.6 [7.6%] vs 50.9 [7.6] for men), lower mean (SD) estimated glomerular filtration rate than men (59.7 [19.1] vs 64.1 [20.0] for men; P<.001) , worse New York Heart Association functional class, and lower Kansas City Cardiomyopathy Questionnaire-Total Symptom Scores (KCCQ-TSS) (mean [SD] 62.3 [24.0] vs 71.0 [23.1]). The incident rate of the primary outcome was slightly lower in women (15.7; 95% CI, 14.3-17.3) than in men (16.8; 95% CI, 15.4-18.3) per 100 person-years. Compared with placebo, finerenone reduced the risk of the primary end point similarly in women and men: rate ratio 0.78 (95% CI, 0.65-0.95) in women and 0.88 (95% CI, 0.74-1.04) in men (P = .41 for interaction). Consistent effects were observed for the components of the primary outcome and all-cause mortality. The mean increase (improvement) in KCCQ-TSS from baseline to 12 months was greater with finerenone, regardless of sex (P = .73 for interaction). Finerenone had similar tolerability in women and men. Conclusions and RelevanceIn FINEARTS-HF, finerenone reduced the risk of the primary end point similarly in women and men with heart failure with mildly reduced or preserved ejection fraction. Finerenone had similar tolerability in women and men. Trial RegistrationClinicalTrials.gov Identifier: NCT04435626
Introduction The escalating resistance of microorganisms to antimicrobials poses a significant public health threat. Strategies that use biomarkers to guide antimicrobial therapy—most notably Procalcitonin (PCT) and C-reactive protein (CRP)—show promise in safely reducing patient antibiotic exposure. While CRP is less studied, it offers advantages such as lower cost and broader availability compared with PCT.Methods and analysis This randomised clinical trial aims to evaluate a novel algorithm for non-critically ill adult patients. The algorithm incorporates key clinical variables and CRP behaviour. It will be applied through a mobile application as a digital clinical decision support system. The primary goal will be to assess the algorithm’s effectiveness in reducing treatment duration compared with standard care based on current guidelines, while ensuring patient safety by monitoring the occurrence of adverse events.Ethics and dissemination Only patients who agree to participate in the study after reading the informed consent form will be included. This project was submitted for consideration to the Research Ethics Committee of the Federal University of Minas Gerais (COEP-UFMG) and received approval (Approval Number: 5.905.290). Collection of clinical and laboratory data from 200 patients is expected, extracted from electronic medical records and laboratory systems, along with serum samples stored for potential future analyses. Data will be preserved using the Research Electronic Data Capture platform, and serum samples will be stored in a regulated biorepository at UFMG. Access will be controlled via credentials, with privacy protections and anonymisation prior to sharing, which will occur during scientific publications.Trial registration number This trial was registered on ClinicalTrials.gov (NCT05841875) and was last updated on 5 December 2024 at 12:49.
RATIONALE Mechanical ventilation strategies for acute respiratory distress syndrome (ARDS) are mostly driven by severity of hypoxemia based on PaO2/FiO2 ratios and do not routinely rely on ARDS subphenotypes. Identifying ARDS subphenotypes based on lung morphology (“focal” or “non focal”) could optimize ventilation strategies and improve patient outcomes, although misclassification seems harmful. The PEGASUS study aims to evaluate personalized mechanical ventilation guided by lung ultrasound (LUS) compared to the standard of care. This pilot phase will assess inter-observer agreement of LUS between the local investigator and an expert panel in classifying ARDS subphenotypes, alongside protocol adherence and patient safety endpoints. METHODS The first 80 patients were enrolled in the pilot phase of the PEGASUS study. Participants were eligible if they were mechanically ventilated and diagnosed with moderate to severe ARDS, as defined by the Berlin criteria, and did not meet any exclusion criteria. Patient phenotypes were determined using a 12-region lung ultrasound (LUS) exam, in which each region was scored from A-pattern to C-pattern (scored from 0 to 3). The interobserver agreement was evaluated using the Cohen Kappa coefficient. Patients were ventilated according to the PEGASUS study protocol, based on randomization and lung morphology. Protocol adherence along with study safety and missing values were described using descriptive analysis. RESULTS For this analysis, 68 of the available exams (91%) were of sufficient quality to assess the lung morphology. The time needed to complete the LUS exam was 14.5 (9, 19) minutes. Interobserver agreement for the LUS was 0.717 (0.53 – 0.9) between local investigator and consensus of the expert panel with misclassification in 8/68 exams (11.8% ). Median tidal volumes and positive end-expiratory pressures were generally set according to the protocol. An exception was the tidal volume in the non-focal ARDS patients randomized for the personalized ventilation with a median of 6.3 (IQR: 5.7-6.7) mL/ kg predicted body weight (PBW), while 4-6 mL/kg was targeted. Missing values were all under 5% for the preset endpoints. Out of the 189 tidal volume measurements, 1 (0.5%) exceeded 10 mL/kg PBW, which was set as safety limit. CONCLUSIONS In the PEGASUS pilot phase there is a substantial agreement in lung morphology between the local research team and the expert panel. Protocol adherence is sufficient, however the tidal volume in the non-focal group is a point of attention. Safety endpoints were shared with the data and safety monitoring board and the study continues to recruit.
