Fever

Researchers are investigating whether adding a rapid biomarker test to current clinical guidelines can better identify young children with fever who are at risk of serious infections in sub-Saharan Africa. This study compares standard care based on integrated management of childhood illness (IMCI) guidelines alone to an approach enhanced by measuring suPAR levels, a biomarker, during the first clinical assessment. The goal is to see if this combined strategy improves decisions about hospital admission or discharge and leads to better health outcomes for children aged 2 to under 60 months. The trial is a multi-country, open-label, randomized study with two groups: one receiving the standard IMCI-based care and the other receiving IMCI care plus a point-of-care suPAR test. Blood samples will be taken from all children, but only the intervention group will have their suPAR levels measured immediately. Clinicians will use these results along with IMCI guidelines to decide whether to admit or discharge each child during the first clinical visit. A second, more detailed clinical assessment will also be performed on all participants to confirm or adjust decisions and ensure safety. Children will be followed up on days 3 and 7 after enrollment with additional visits if clinical worsening occurs. A day 28 follow-up will collect information on serious events, hospitalizations, or deaths, with an optional extra interview at three months. Participants with respiratory symptoms may join a substudy involving lung exams and sample collections. The study team will measure outcomes like the appropriateness of discharge decisions, hospital admissions, severity of illness, and mortality to evaluate the new triage approach's effectiveness and safety over these timeframes.

This research aims to improve antibiotic treatment for children with cancer who develop febrile neutropenia, a condition where fever occurs alongside a low white blood cell count due to chemotherapy. This condition often requires broad-spectrum antibiotics to fight bacterial infections. However, some children experience faster kidney clearance of antibiotics (augmented renal clearance), which may reduce antibiotic levels and affect treatment effectiveness. The study focuses on two antibiotics, piperacillin-tazobactam and meropenem, to see if adjusting doses based on kidney function can improve outcomes. Participants will be divided into three groups based on kidney function and treatment: children with normal or low kidney function receiving standard antibiotic doses, children with increased kidney function randomly assigned to either standard doses or higher adjusted doses. Blood tests will be done to estimate kidney function and therapeutic drug monitoring will be performed regularly to measure antibiotic levels and adjust doses as needed. The study uses a randomized design and includes monitoring drug concentrations and adjusting doses to reach target levels safely. Children involved will undergo regular assessments including blood tests to monitor kidney function and antibiotic levels, clinical evaluations of fever duration, and tracking of any side effects related to antibiotics. Monitoring will continue throughout antibiotic treatment and up to two weeks after. The main outcome is the early achievement of target antibiotic levels, with secondary measures including fever duration, side effects, and the accuracy of different kidney function formulas. Participation involves close clinical and laboratory follow-up during febrile neutropenia episodes, with treatment adjustments guided by blood results.

Researchers are studying preterm infants born between 25 and 32 weeks of gestation to compare two methods of incubator temperature control and their effects on infant weight growth and health. The study is based on earlier findings that lower body temperature on admission relates to higher illness and death rates in preterm infants. It aims to see if using a new software to calculate personalized air temperature in incubators can improve growth and reduce side effects compared to the traditional skin temperature control method. The study compares two incubator control methods: air temperature control (ATC), which uses software to set air temperature to reduce body heat loss to zero, and skin servocontrol (SSC), which adjusts incubator temperature based on the infant's skin temperature. Both methods are evaluated in closed incubators for preterm infants. The trial randomly assigns infants to one of these two methods to study their effects during the first 10 days of life. Participants will be monitored for changes in body weight until day 10, along with comfort, thermal stress, and humidity challenges. The study also tracks neonatal illness occurrences up to 40 weeks of amenorrhea and length of hospital stay until discharge or 40 weeks of amenorrhea. Parents provide written consent, and infants are included within the first day of life. The study continues through hospitalization, assessing health outcomes and safety related to the incubator settings.

Researchers are evaluating the need for antibiotic prevention in patients with chronic liver disease who have gastric varices and are treated with elective endoscopic injection of cyanoacrylate (GVO). Gastric varices can cause serious bleeding with a high chance of rebleeding and mortality. While endoscopic injection of tissue glue is effective in stopping acute bleeding, it still carries risks of rebleeding and infection, which are important concerns for patients with weakened immune systems due to liver conditions. The study compares two groups: one receiving an antibiotic called ertapenem injected intravenously before the endoscopic cyanoacrylate injection, and the other not receiving this antibiotic before the procedure. The trial is randomized and aims to clarify whether giving this antibiotic can help prevent infections and complications after GVO treatment. The treatment is delivered during an elective endoscopic procedure to manage gastric varices. Participants will be monitored for three years to evaluate key outcomes such as the prevention of sepsis, rebleeding rates, refractory bacterial infections, and mortality. Assessments will include tracking infections and bleeding events over time. The study is designed to provide long-term data on the benefits and risks of using antibiotic prophylaxis in this patient group, with ongoing safety monitoring throughout the follow-up period.

Researchers are evaluating whether AI-enabled, nurse-led treatment planning can match or improve the quality of clinical reasoning and management compared to standard physician-led care in adults aged 18 years and older. The study focuses on patients in rural and semi-urban India presenting with hypertension, diabetes mellitus, fever, breathlessness, or musculoskeletal pain. It aims to determine if nurse consultations supported by a large language model (LLM) achieve clinical quality scores that are not worse than those of physician consultations and to assess patient acceptance and satisfaction with AI-assisted nurse care. Participants receive two consultations during the same visit: one led by a nurse using an AI-based clinical decision support tool and one by a physician providing standard care. The nurse-led consultation involves routine history taking and clinical assessment, with interaction through a digital interface to the LLM for assistance in diagnosis, reasoning, and treatment planning. The physician consultation follows usual clinical practice without AI support. The study compares these two approaches in a randomized order within each participant. Throughout the study visit, both consultations are audio recorded for blinded clinical quality evaluation. After the nurse + LLM consultation, participants complete an exit survey measuring communication, trust, and satisfaction. Researchers also gather nurse-reported feedback on acceptability and feasibility through interviews after nurses complete at least 10 AI-assisted consultations. The main outcome measured is the clinical quality of the consultations immediately after both visits, with additional assessments of patient experience and nurse perspectives over up to nine months.

Researchers are investigating autoinflammatory diseases (AID), which involve recurring inflammatory episodes without infection, cancer, or adaptive immune system problems. This study focuses on both monogenic hereditary periodic syndromes and polygenic or multifactorial AID, including rare conditions like Behçet's disease, Still disease, Schnitzler's disease, PFAPA syndrome, chronic recurrent multifocal osteomyelitis, non-infectious uveitis and scleritis, among others. The goal is to gather detailed data to improve understanding and management of these rare diseases through an international collaboration. The study uses the AIDA registry, a secure online platform for collecting demographic, genetic, clinical, laboratory, radiologic, and therapeutic information. Data are gathered retrospectively and prospectively during routine clinical visits scheduled every 3-6 months. Eleven registries focus on different AID conditions, enabling comprehensive data collection to identify clinical patterns, treatment impacts, and long-term outcomes over a period of at least 10 years. Participants provide information during their usual care visits, allowing researchers to track changes in disease activity, organ involvement, inflammatory markers, visual function, pain levels, fatigue, fertility, and socioeconomic factors. The study monitors these outcomes over multiple timepoints up to 120 months. Data privacy is ensured by pseudonymizing patient information. This registry supports multiple clinical studies and aims to enhance knowledge, awareness, and future research on autoinflammatory diseases worldwide.

This research evaluates the accuracy and consistency of an AI platform called OpenGenome that analyzes free-text symptom descriptions submitted voluntarily by adults. The study collects anonymous symptom data and matches it with real biomedical literature from PubMed and ClinicalTrials.gov to generate structured biological signal reports. It aims to assess how well the extracted signals align with sources, how confidence scores correlate with dataset size and symptom specificity, and the distribution of biological signals across a large population. Adults aged 18 or older can submit free-text symptom descriptions via the OpenGenome platform, which then uses an AI-assisted method to extract primary and secondary biological signals grounded in biomedical evidence. For each submission, the system retrieves up to 16 relevant sources and provides a confidence score and signal strength. No treatment or intervention is given, and no participant contact occurs during the observational registry. Participants are involved by voluntarily submitting symptom descriptions online through the platform, with all data anonymized at collection. The study continuously monitors the internal signal-source concordance rate over 12 months. There are no in-person visits or direct assessments, ensuring privacy and minimal burden. This ongoing data collection helps researchers understand the platform's accuracy and signal calibration in a broad anonymous population.

Researchers are studying acute febrile illness in patients older than 28 days who live in rural areas of Laos, Myanmar, Thailand (including the Thai-Myanmar border region), and Bangladesh. This observational study aims to describe the causes, clinical outcomes, and host biomarkers associated with these illnesses, which last 14 days or less. The study is part of a larger community-based network seeking to improve understanding and future interventions for febrile illness in low- and middle-income countries in South and Southeast Asia. The study involves two main parts: Work Package A collects data from village health workers and local health facilities to understand the incidence and outcomes of febrile illness at the community level. Work Package B recruits patients seeking care at higher-level health facilities who may be more severely ill. In Work Package B, researchers collect various samples including venous blood and respiratory specimens for detailed diagnostic testing such as blood cultures, serological assays, molecular diagnostics, and host biomarker assays. Participants will be monitored for about one month to measure the prevalence of pathogens and recovery status. The study will analyze the association between host biomarkers and clinical outcomes to help create electronic decision-support tools for village health workers. These tools and other interventions will be tested later to improve assessment, triage, and treatment of patients with febrile illness. The total duration of participation and follow-up is approximately one month.

Researchers are evaluating the effectiveness and tolerability of Ceftolozane/tazobactam compared to the standard treatment, Meropenem, in patients with febrile neutropenia who are colonized with or at risk for infections caused by extended-spectrum beta-lactamase (ESBL)-producing pathogens. This is a planned, double-blind, randomized, non-inferiority clinical trial aiming to assess clinical response, toxicity, and microbiological changes in this patient population. Participants will be randomly assigned to receive either 3g of Ceftolozane/tazobactam or 2g of Meropenem intravenously every 8 hours. The treatment duration will follow local guidelines, allowing adjustment after identifying the causative pathogens. The study includes stool sample collections before, during, and after treatment to analyze intestinal microbiota and microbiome effects, particularly regarding graft versus host disease (GVHD). During the trial, researchers will monitor clinical cure rates at the end of therapy and test-of-cure visits, microbiologically documented infections, mortality, incidence of GVHD, and multidrug-resistant infections for up to 100 days post-treatment. Safety is tracked through adverse events and serious adverse events up to 35 days after the last dose. The trial's total participation timeline includes therapy duration and follow-up assessments, ensuring thorough evaluation of treatment impact and safety.

This research aims to compare the use of ciprofloxacin and ceftazidime in treating high-risk fever caused by low neutrophil count in children with hematological malignancies. It focuses on children aged 0 to 18 years diagnosed with blood cancers such as acute lymphoblastic leukemia, acute myeloblastic leukemia, and non-Hodgkin lymphoma. The study evaluates which antibiotic works better as a first-choice treatment and investigates factors influencing response to these drugs. Participants will be randomly assigned to receive either intravenous ciprofloxacin at 10 mg/kg every 12 hours or intravenous ceftazidime at 150 mg/kg per day divided into three doses. The treatments are given during hospitalization between June and December 2025. Both groups will be monitored for outcomes like the length of fever, duration of low white blood cell count, hospital stay length, antibiotic use duration, any changes in antibiotic treatment, and death rates. Throughout the trial, participants will undergo medical history collection, physical exams, and supportive tests. Researchers will track key measures including duration of fever and neutropenia from the start of antibiotic treatment, hospitalization duration, and antibiotic escalation decisions. Safety and mortality will also be assessed up to 30 days after enrollment. This comprehensive monitoring aims to understand the effectiveness and clinical impact of these antibiotics in managing high-risk neutropenic fever in children with blood cancers.