Rheumatic Fever

Researchers are evaluating whether stopping secondary antibiotic prophylaxis SAP is not worse than continuing SAP in preventing worsening of rheumatic heart disease RHD in children and adolescents. This Phase 3 trial focuses on participants aged 5 to 20 years who have mild RHD and have already received at least two years of SAP. The goal is to see if stopping SAP affects heart disease progression compared to continuing treatment. The study is randomized and controlled with a single masking approach. Participants will be randomly assigned to either stop SAP or continue receiving monthly intramuscular benzathine benzylpenicillin G BPG injections for two years. Dosage is based on weight, with children under 30 kg receiving 600,000 IU and those 30 kg or above receiving 1.2 million IU every 28 days. The control group continues the standard care of monthly BPG injections, while the intervention group receives no prophylaxis for the same period. During the study, participants will be monitored for two years to assess the progression of RHD using echocardiographic evaluations based on the 2023 World Heart Federation criteria. Blinded adjudicators will review heart imaging results to determine disease changes. Researchers will also analyze outcomes for subgroups with either normalized or stable mild RHD and explore differences based on prior prophylaxis routes. The trial spans from enrollment through the end of the 2-year treatment period, with safety and disease progression closely followed.

This research aims to evaluate the feasibility, sustainability, and public health impact of a district-based program for secondary prevention of Rheumatic Heart Disease RHD in Uganda. It is a non-randomized study testing the implementation of decentralized RHD preventive services, overseen by the Uganda Ministry of Health and District Health Offices in partnership with a technical quality assurance team. The study uses the RE-AIM framework to measure program reach, effectiveness, adoption, implementation, and maintenance while also estimating cost-effectiveness and budget impact. The study involves the ADUNU program, which integrates echocardiographic screening for RHD in children and young adults through community and facility-based testing. The program also includes registry-based secondary prophylaxis injections of Benzathine penicillin G BPG administered at local health centers HCIII and HCIV in the participating districts. This approach is designed to improve access to care and maintain patients linked to treatment. Participants and healthcare providers residing or working in the involved districts will engage with the program over several years. Researchers will assess the proportion of persons reached, enrolled, retained, and adherent to treatment at multiple time points up to five years. They will also evaluate program adoption and implementation at organizational, provider, and patient levels through surveys and interviews, alongside a cost analysis of the program at three years. The study ensures ongoing monitoring of adherence and outcomes to understand the programs public health impact.

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 exploring the natural history and genetics of autoinflammatory and autoimmune diseases, including VEXAS syndrome and related disorders. This study aims to discover genetic factors contributing to these inflammatory conditions and to enhance understanding of their immune system mechanisms. It also seeks to describe clinical features of poorly characterized diseases through chart reviews of routine medical care. Participants include individuals with known or suspected autoinflammatory diseases, family members related by blood or marriage, and healthy volunteers. Samples such as blood, saliva, hair, nails, or buccal swabs may be collected for genetic and immunologic studies. Some participants might undergo skin biopsies. The study involves genetic analysis and functional immunologic tests to identify disease-associated variants and features. During the study, participants provide samples for laboratory analysis and may have their medical records reviewed. Researchers measure the number and types of genetic variants linked to inflammatory diseases over up to five years. Study involvement includes mail-in sample collection and possible clinical evaluations. The total participation time can extend up to the study end date in 2032, with ongoing data collection and analysis to improve understanding of these conditions.

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 platforms accuracy and signal calibration in a broad anonymous population.

Researchers are exploring a new way to personalize treatment for autoimmune and autoinflammatory rheumatic diseases. This study aims to develop and use a special cell-based test that helps predict how well patients will respond to disease-modifying antirheumatic drugs DMARDs. By identifying the best treatment for each person, the study hopes to improve treatment success, shorten the time to see benefits, and lower healthcare costs. The approach focuses on analyzing immune cells from patients to better understand their response to different therapies. The study includes several groups newly diagnosed patients without prior treatment, patients already on immunomodulatory therapy, and healthy individuals for comparison. Blood samples are collected at different times depending on the group. Researchers use advanced laboratory methods to test immune cell responses to DMARDs outside the body, measuring specific immune signals and gene activity. Archived tissue samples are also studied to link immune profiles with disease features. This design allows detailed analysis of immune function related to treatment. Participants will provide blood samples and undergo clinical assessments over time, including baseline and follow-up visits at 6 and 12 weeks, with additional optional visits if disease worsens or treatment changes. The study measures changes in immune cell types and activity using the ex vivo assay and other tests. Data are stored securely, and the study will compare predicted responses with actual clinical outcomes to validate the tests usefulness. Participants involvement may last up to a year, with ongoing monitoring and data collection to support personalized therapy development.

Researchers are evaluating a telemedicine system designed for continuous monitoring of body temperature in adults who have fever. This pilot study is nonrandomized and conducted at a single center, aiming to assess both the effectiveness and safety of the device. Up to 40 adults hospitalized for infections or other conditions causing temperature changes will participate, with no randomization or stratification of participants. The investigational device will be placed in the armpit area and connected to a mobile phone to continuously record temperature readings. Study staff will also manually measure skin temperature in the opposite armpit using a gallium thermometer every 30 to 60 minutes, increasing frequency if the temperature rises or if temperature-lowering drugs are administered. The device will stay in place for up to 72 hours, followed by an additional 72-hour monitoring period after removal to observe for any side effects. Participants will be monitored closely by research staff during device placement and after removal, with temperature checks and safety evaluations continuing throughout the six-day period. The main measurement is the correlation between the telemedicine device readings and standard thermometer measurements over 72 hours. Researchers will also track any adverse events related to the device or procedures during the entire monitoring period.

Researchers are working to adapt and pilot the WHO Package of Essential Non-communicable Diseases PEN Plus intervention in Zambia to address the growing burden of complex chronic diseases such as diabetes, hypertension, and cancer. The study focuses on improving management of these diseases at first-level hospitals using an implementation framework designed to tailor interventions locally and prepare for national scale-up. This effort responds to increasing cases and insufficient primary care capacity in Zambia. The study involves adapting the PEN-Plus model through stakeholder engagement, training of frontline health workers, and establishing PEN-Plus clinics at selected peri-urban and rural hospitals. These clinics will provide care led by mid-level providers supported by specialists. The intervention includes supportive treatment, provision of necessary drugs and equipment, and integration with existing health information systems. The project will also develop national policies and operational plans to enable wider implementation. Participants are patients with chronic non-communicable diseases receiving care at first-level hospitals. Researchers will monitor implementation outcomes such as patient enrollment, care quality, and cost, as well as training outcomes for healthcare providers. Data collection includes routine visits and patient records integrated with national systems. The primary outcome measures the increase in patients diagnosed and managed according to WHO PEN-Plus guidelines over six years, with ongoing monitoring and evaluation of the program impact.

Juvenile idiopathic arthritis JIA is a common chronic rheumatic disease in children that causes pain, joint swelling, and loss of function, which can reduce quality of life and lead to muscle weakness, limited motion, and walking difficulties. Researchers are evaluating the Dynamic Gait Index DGI as a new tool to assess walking ability in children with JIA, since current methods lack a functional walking test for this group. The study aims to determine whether the DGI is a reliable and valid measure for evaluating walking challenges in these children. The study includes two groups children diagnosed with JIA and age-matched healthy volunteers. The DGI test measures walking on level ground, changing speed, head turns, pivot turns, jumping over obstacles, walking around obstacles, and climbing stairs. Each activity is scored to assess walking ability. Additional physical tests include the Timed Up and Go Test, walking speed measurement, Wong-Baker FACES Pain Scale for pain assessment, Pediatric Balance Scale, and Childhood Health Assessment Questionnaire. These tests will be conducted at the start and again two weeks later. Participants will undergo physical examinations involving several walking and balance tests. Researchers will measure outcomes such as the DGI score, walking speed, timed up and go performance, pain levels, and balance ability. These measurements will help evaluate the walking function and risks related to falls in children with JIA compared to healthy peers. The study will monitor participants over a two-week period after baseline testing to assess the consistency and reliability of the DGI for this purpose.

This research aims to evaluate how effective a school-centered program is at preventing latent rheumatic heart disease among schoolchildren in Nepal. It also investigates how socioeconomic and environmental factors influence the development and progression of this disease. Rheumatic heart disease is a serious condition affecting many children worldwide, especially in regions where group A beta-hemolytic streptococcal GAHBS infections are common, which can lead to acute rheumatic fever and heart damage. The study involves implementing a dedicated school nurse program at Tulsi Secondary Boarding School, focusing on assessing, intervening, and following up on cases of GAHBS pharyngitis. This program also facilitates secondary antibiotic prevention for children identified with latent rheumatic heart disease through echocardiography screening. The program is designed to provide timely detection and treatment to reduce the disease burden through primary and secondary prevention efforts. Participants, children aged 5 to 16 years attending the school, will undergo echocardiography before the program starts and again two and four years after implementation to measure the prevalence of latent rheumatic heart disease. Researchers will collect sociodemographic information through interviews and monitor outcomes such as GAHBS pharyngitis, acute rheumatic fever, and adverse reactions to penicillin. This longitudinal approach aims to assess the programs impact on disease prevalence and identify factors related to disease progression over a four-year period.