Clinical Research Directory

Diagnosis and Management of Inflammatory and Infectious Diseases

This protocol is being established to cover the evaluation of patients with inflammatory and/or infectious diseases which are not covered under previously existing protocols. The purpose of such a protocol is that frequently patients are referred to us with either diagnosed or undiagnosed illnesses which would be of interest to our teaching program or which would serve as a source of patients to subsequently be entered into established, ongoing protocol studies. Such patients will be admitted to the protocol and handled according to accepted medical practice of diagnosis and treatment....

NADPH Oxidase Correction in mRNA-transfected Granulocyte-enriched Cells in Chronic Granulomatous Disease (CGD)

Background: CGD is caused by a gene mutation. For people with CGD, their cells cannot kill germs well, so they can get frequent or life-threatening infections. Researchers want to see if a new procedure can help a person s cells kill germs for a short time. It uses messenger RNA (mRNA) to deliver correct instructions for the gene mutation to the cells. Objective: To test a procedure in which mRNA is added to a person s blood cells. Eligibility: Males aged 18-75 with CGD with a mutation in the gene that makes the protein gp91phox. Design: Participants will be screened with: Medical history Physical exam Blood and urine tests Swab to test for strep throat Some screening tests will be repeated during the study. Participants will be admitted to the NIH Clinical Center hospital for at least 7 days. They will have apheresis. For this, a medicine is injected under their skin to prepare their white blood cells for collection. An IV line is placed into an arm vein. Blood goes through the IV line into a machine that divides whole blood into red blood cells, plasma, and white blood cells. The white blood cells are removed, and the rest of the blood is returned to the participant through an IV line in their other arm. The next day, they will get their mRNA-corrected cells via IV. They will be monitored for 3 more days. After discharge, participants will keep a symptom diary. They will be contacted weekly for one month, and then once a month. They will have a follow-up visit 3 months after the infusion.

A Study to Compare the Efficacy and Safety of Extended and Intermittent Infusion of Beta-lactams in Critically Ill Paediatric Patients

The goal of this clinical trial is to examine the success and safety of administering certain antibiotics (beta-lactams) given in a longer 3-hour infusion to children (0-17 years) who are critically ill and have severe infection. The main question it aims to answer is: Is the longer infusion more effective than the conventional short-term (0.5-hour-long) infusion? Researchers will compare the 3-hour-long infusion group to the 0.5-hour-long infusion group to determine whether the longer infusion can cure the infection earlier and whether it is equally safe. The doses are the same in the two groups. Only the duration differs until the patient receives the antibiotic. Participants will: * be given the required antibiotic drug in a 3-hour-long or in a 0.5 hour-long infusion. * be examined to make sure their blood drug levels are correct. This will require two blood tests. * be treated according to routine care and have examinations and blood tests performed.

Home Hospital for Suddenly Ill Adults

The investigators propose a home hospital model of care that substitutes for treatment in an acute care hospital. Limited studies of the home hospital model have demonstrated that a sizeable proportion of acute care can be delivered in the home with equal quality and safety, reduced cost, and improved patient experience.

Copper Supplementation in Cirrhosis

End stage liver disease or cirrhosis is a major cause of mortality in the United States and the world. Other than targeting the underlying cause, such as alcohol cessation and antiviral therapy, very few medical treatments can change the natural history of cirrhosis. Malnutrition is one of the few potentially modifiable factors that have been associated with cirrhosis severity and poor prognosis. The transition metal copper (Cu) is an essential trace metal that must be acquired from diet. Its metabolism is primarily regulated by the liver in its role as a master regulator of nutrients. In 2019, the investigators reported that Cu deficiency defined by below normal serum or liver concentrations occurred in a wide range of liver disorders and was associated with a severe disease phenotype. Improvement in liver function was observed in 2 of the 3 patients who received Cu supplementation. In 2023, the investigators conducted a longitudinal cohort study utilizing clinical, serum and liver explant tissue data from 183 cirrhosis patients. The investigators showed that Cu deficiency was associated with 2-fold higher infection rate and a more than 3-fold increase in the risk of death compared to patients with normal Cu status. These preliminary findings and the well-established importance of Cu in human health prompted the investigators to design the current pilot randomized, placebo-controlled, crossover trial to determine the effect of Cu supplementation on Cu dependent biochemical changes, patient safety and patient reported outcomes in cirrhosis.

Rapid Response Home Care as an Alternative to Acute Admission

This single-center, randomized, unblinded quality-improvement study evaluates whether a structured home-based rapid response team (RRT) intervention can safely reduce total hospital days among adults referred to the emergency department with suspected infection. Patients referred from general practitioners or the regional medical helpline (1813) between 09:00 and 22:00 are randomized 1:1 using Zelen's design to either standard in-hospital evaluation or a home-based assessment pathway delivered by a mobile clinical response team.

Validation of Drug Assays in Various Biological Matrices

This study aims to ensure that assays that measure drug concentrations are accurate and precise in different matrices when quantified using high performance liquid chromatography -tandem mass spectrometry (HPLC-MS/MS). The study involves collecting samples of various bodily fluids to quantify antimicrobials, antivirals, oral contraceptives and erectile dysfunction agents. Samples will also be obtained from individuals not receiving these medications for quality control purposes.

Early Sepsis Recognition Tool

This study seeks to develop early recognition tools specially designed for children meeting the Phoenix definition and explore implementation science aspects by investigating facilitators and barriers to adopting Phoenix sepsis criteria in clinical practice. This addresses the critical need for systemic, evidence-based approaches to paediatric sepsis identification across diverse healthcare settings in Asia.

BLOOM: Pragmatic Feasibility Trial

The goal of this study is to compare two different ways of dosing cefepime, an antibiotic for very sick patients - the usual approach to dosing or a new dosing method. The new dosing method uses only doses that are available in normal care, but choosing between the different doses is based on more information about the patient's body including their kidney function. The primary purpose of this study is to test how easy it is for healthcare professionals to use the new dosing method and how best to conduct the trial. The study will also assess if the new dosing method helps patients recover faster and reduces side effects.

Reducing Blood Culture Contamination With the Use of a Needle-less Blood Draw Device (The PIVO Trial)

Blood cultures (BCs) are a blood test to look for an infection. Two problems with the sample collection are contamination by germs outside of the blood and not collecting enough blood in the tube, resulting in unusable samples. Many patients requiring a BC also have a peripheral intravenous catheter ("catheter") but these are not normally used for blood sampling. This means that patients receive many painful needles for both catheter insertion and blood sampling. There is a needle-free blood collection device (PIVO Pro) which can be used with a catheter to collect a blood sample. The goal of the PIVO Trial is to see if using the PIVO Pro for blood culture sample collection will have a lower amount of contamination than the usual method of blood sample collection. Patients 18 and older at 3 emergency departments will be included. Research nurses will look for patients in emergency who need a blood culture sample taken and they will be asked if they want to be involved in the trial. Half of the participants will use the PIVO Pro to take their blood sample and half will have the usual way of collecting blood. Participants do not have to do anything specifically for the trial. Information about the blood collection and results of the blood culture will be collected from the medical records and recorded for the trial.

Microbial Cell-free Metagenomic Sequencing for Suspected Infections in Adult Immunocompromised Outpatients

This clinical trial is designed to evaluate if adding the Karius Spectrum™ plasma test to usual care diagnostic tests, compared to usual care testing alone, among immunocompromised participants presenting with suspected infection in the outpatient setting leads to faster infection diagnosis and treatment. Participants will give a blood sample one time to be used for the testing. Information about the participant's illness and any treatments within 30 days following enrollment will be recorded.

Study of the Antibiotic-resistance Profile of Enterobacterales Isolated From Rectal Mucosal Buffer of PrEP Subjects

The importance of the study lies mainly in expanding knowledge of the phenomenon of antibiotic resistance in subjects using PrEP, studying for the first time in this population the resistance phenotype in commensal Enterobacterales of the gastrointestinal tract. The data obtained from this study could pave the way for potential surveillance and awareness programs for the critical and conscious use of antimicrobials in PrEP subjects in order to mitigate the problem of antibiotic resistance, which currently represents a real global challenge.

Viral Infections of the Central Nervous System: Diagnosis and Clinical Outcome

Central Nervous System (CNS) infections are caused by bacteria, viruses, fungi, helminths, with several clinical aspects. Studies in the literature generally focus on a single patient type, and no experiences have been reported in which immunosuppressed and immunocompetent adult and pediatric patients were simultaneously examined. Our study will include all possible patient types (immunocompetent adults, immunocompetent pediatric patients, and subjects immunosuppressed by co-softness), to try to more precisely define the clinical and population characteristics of patients who have had an episode of CNS viral infection. These indications may be useful in the future to more specifically guide diagnostic investigations on patients considered at risk.

KInetics of Procalcitonin to Reduce Unnecessary aNtibiotic Use - Comparing Procalcitonin Kinetics-guided and Absolute Procalcitonin Value-guided Antibiotic Initiation in Reducing Unnecessary Antibiotic Use in Critically Ill Patients

The study aims to compare the efficacy and safety of an absolute procalcitonin (PCT) value-guided antibiotic initiation protocol and a protocol using the kinetics of PCT (the difference between the actual and the previous day value) in hemodynamically stable critically ill patients with suspected new-onset infection on admission or during ICU stay. The main question it aims to answer: * Can the investigators decrease the number of unnecessary AB therapies using the kinetics of PCT insted of using absolute PCT values? * Is it safe to use PCT kinetics together with the clinical picture to guide AB initiation? AB therapy will be initiated according to predefined PCT protocols (Kinetics and Absolute Group). After 72 hours of treatment, an independent multidisciplinary team (infectologist, microbiologist and intensivist) will decide about the necessity of the treatment with all the relevant results in hand.

Diagnostic and Prognostic Evaluation of Vasorin During Septic Shock

Septic shock is the most severe form of infection. Currently, an early specific biomarker for septic shock is needed. Remember that shock situations are numerous, not only septic (eg hemorrhagic, cardiogenic...), and also accompanied by a severe pro-inflammatory state that it is sometimes difficult to distinguish from a septic state. Procalcitonin (PCT) is the most studied biomarker but still lacks sensitivity (77%) and specificity (79%). The investigators hypothesize that the Vasn could become this potential new biomarker and would allow a better diagnosis and thus the need or not to treat patients with antibiotics. The laboratory studies suggest a link between Vasn and septic shock. The goal of this project is to measure and compare plasma Vasn concentrations in 2 groups of patients = group 1: septic shock versus group 2: non-septic shock. Briefly, shock is defined as low blood pressure requiring vasopressor agents with confirmed infection (group 1) or without suspected infection such as patients admitted in intensive care unit post cardiac surgery with CBP (group 2). The investigators will also assess patient 28-day mortality to identify Vasn as a potential prognostic biomarker.

The Extended Study of Prevalence of Infection in Intensive Care IV

The goal of this observational study is to learn how common infections are in intensive care units (ICUs) around the world and how they are treated. The study will look at all adults in the ICU during a single 24-hour period. The main questions it aims to answer are: * What types of infections and antibiotic-resistant bacteria are most common in ICUs worldwide? * How do resistance patterns affect how participants are treated and how they recover? How are antibiotics used in ICUs, and how do hospitals practice antibiotic stewardship? * What organ support treatments do participants with infections receive? * What are the outcomes of participants with severe infections, including survival at hospital discharge (up to 60 days)? Researchers will compare ICUs across regions and income levels to see how infection patterns, treatments, and outcomes differ around the world. Participants will: * Be counted if they are present in the ICU at any time during the study day. * Have information collected from their medical record about their health, the infection they may have, treatments they receive, and their outcome at ICU and hospital discharge (up to 60 days). Because this is an observational study, participants will not receive any new treatments as part of the study.

Implementation of an RT-PCR Assay for the Diagnosis of Rickettsia Spp. Infection

Rickettsia2024 is a multicenter, tissue observational, retrospective and prospective cohort study. Enrollment will take place within the outpatient clinics of the Infectious Diseases and Dermatology Unit of the IRCCS AOUBO and, following an infectious disease consultation in the Bologna Metropolitan area, at the Hospitals and CAUs of the Bologna Local Health Authority. Within these UUOOs, biopsy samples from normal clinical practice are performed on patients with strong clinical suspicion of Rickettsia infection: therefore, it will not be necessary to perform any additional samples for the conduct of this study. Samples from the normal diagnostic process are sent to the Microbiology UOC, where they are subjected to various analyses. RT-PCR analyses (commercial or in-house kit) and assay of species-specific IgG antibodies will be performed according to clinical practice. Additional tests will be performed with a commercial kit for retrospective samples and with a home-made method for prospective samples.

Metagenomic Next-Generation Sequencing for the Diagnosis of Fracture-related Infection

The value of next-generation sequencing (NGS) using Nanopore technology has been demonstrated in the case of diabetic patients' wounds or in prosthetic joint infections. The aim of this study is to demonstrate its relevance as a new diagnostic approach for fracture-related infections (FRI). Bone samples from patient with FRI will be submitted to shotgun metagenomic Next-generation sequencing using Oxford Nanopore Technology (ONT) in order to establish its diagnostic value in this context in comparison with the reference method.

Improving Implementation of Evidence-based Approaches and Surveillance to Prevent Bacterial Transmission and Infection

Surgical site infections (SSIs) are associated with increased patient morbidity, mortality, and healthcare costs. ESKAPE (Enterococcus, S. aureus, Klebsiella, Acinetobacter, Pseudomonas, and Enterobacter spp.) pathogens are particularly pathogenic because they have increased capacity to acquire resistance and virulence traits. The investigators have proven that a multifaceted program involving improved basic perioperative preventive measures can generate substantial reductions in S. aureus transmission and significant reductions in SSIs (88% reduction as compared to usual care). In this study, the investigators aim to examine the relative effectiveness of each component of this program in controlling ESKAPE transmission and reducing SSIs and to identify an optimal implementation strategy for national dissemination. Randomization occurs at the site level, and sites adopt preventative programs. This work will improve perioperative patient safety for the 51 million patients who undergo surgery each year.

Single Dose Intravenous Antibiotics for Complicated Urinary Tract Infections in Children

Urinary tract infections (UTI) are commonly encountered in children, with 7% diagnosed with at least one UTI by the age of 19 years. The evidence for treatment of uncomplicated UTI is clear; oral antibiotics are as good as intravenous (IV) antibiotics, usually for a total of 7 days. Complicated UTIs (cUTIs) on the other hand, are common reasons for hospital admissions for IV antibiotics and constitute a major burden for healthcare systems. There is considerable variation in care for children who present with UTI and have complicating features such as vomiting, dehydration, urological abnormalities or have a previous history of UTI. Australian and international guidelines lack clear, evidence-based recommendations to guide treatment in this group. Without gold standard evidence, these children will continue to receive unnecessary IV antibiotics, longer hospital stays and poorer health outcomes. This multicentre, non-inferiority randomised trial will investigate if One dose - single dose of IV followed by 2 days oral antibiotics is as non-inferior to Three doses for children with UTI and co-existing complicating factors presenting to the Emergency Department (ED). In other words, this study will compare if a single dose of IV antibiotics plus two days oral antibiotics is as clinically effective as 3 doses antibiotics in resolving UTI symptoms at 72 hours after the first dose of IV antibiotics, for complicated UTIs in children presenting to the ED. All participants will receive a total of 7 days of antibiotics for the complicated urinary tract infection. If 1 dose IV and 2 days oral antibiotics is found to be as good as 3 days, the duration of IV antibiotics for complicated UTI can be reduced along with avoidance of the inherent risks of unnecessary hospital admission by administering a single IV dose in an outpatient/ED setting. On the other hand if a single IV dose results in prolonged symptoms or treatment failure, this will inform practice for the proportion of children who have a single dose of IV antibiotics in the ED and are sent home on oral antibiotics. Regardless of the outcome, this trial will inform clinical practice for complicated UTI to improve health outcomes for this group.

Mobile App-Based Infection Monitoring in Familial Mediterranean Fever

Familial Mediterranean Fever (FMF) is an autoinflammatory disease characterized by recurrent episodes of fever, abdominal pain, and serositis. FMF attacks often present with fever and systemic symptoms resembling infectious diseases, making it challenging in clinical practice to distinguish between an attack and an infection. Moreover, infections are known to trigger FMF attacks; however, the number of prospective studies evaluating this association remains limited. In the current literature, the frequency of attacks and triggering factors in FMF patients have mostly been assessed through retrospective chart reviews. Such methods are prone to incomplete or recall-based data regarding the onset of attacks and infection-related symptoms. With the growing availability of digital health applications, it has become possible to record disease symptoms in real time and on a regular basis, providing more reliable data for both clinicians and researchers. The present study aims to prospectively evaluate the relationship between infections and disease flares in FMF patients by systematically recording infection symptoms and attack characteristics through a mobile application. This approach is intended to achieve a better understanding of the infection-flare association, improve patient management, and prevent unnecessary treatments. In addition, the feasibility of mobile application-based patient monitoring will be assessed, and its potential contribution to routine clinical practice will be explored.

Quality Improvement Intervention for a Safe Antimicrobial Use Reduction in Critically Ill Patients

The goal of this clinical trial is to learn if an educational intervention with audit and feedback on physicians and health care professionals who participate in antimicrobial treatment decisions can reduce the use of antimicrobials in adult patients admitted to a sample of Brazilian intensive care units (ICUs). The educational intervention is based on a literature review of current recommendations for a more rational use of antimicrobials and microbiological tests in daily ICU practice. The main questions it aims to answer are: * Does the educational intervention reduce the antimicrobial consumption in the intensive care units? * Does this educational intervention aiming to reduce antimicrobial utilization in accordance with the latest guidelines have any safety signals regarding ICU mortality rates or ICU length-of-stay? Researchers will compare (1) ICUs sequentially randomized to this quality improvement educational intervention aimed at improving antimicrobial utilization to (2) the same ICUs at months where the educational intervention has not been delivered yet. Each participant ICU will transition to the quality improvement intervention approximately each month, starting at July, 2025. This quality improvement intervention is based on current recommendations for antimicrobial stewardship from regulatory agencies and medical societies, including cognitive aids for physicians to improve decision-making regarding the commencement of antimicrobials, their duration and antimicrobial time-outs. The investigators hypothesize that intensivists (ICU doctors) need to embrace antimicrobial stewardship as a core competence of their daily activities.

Postoperative Infections and Immune Profiles in Patients Undergoing LVAD Implantation

The objective of this study is to investigate the incidence of infection and changes in the immune profile following left ventricular assist device implantation. The primary aim is to elucidate the relationship between postoperative infection and immune alterations and to identify risk factors predictive of postoperative infection.

Metagenomics for Ocular Inflammation

The aim of this study is to apply a diagnostic test called 'metagenomic sequencing' to identify the involvement of potential infections in patients with ocular inflammation, where this hasn't been detected by currently available standard testing. For many people with ocular inflammation, no cause is ever found for their disease. In some cases, an infection or infectious trigger is suspected, but currently available tests are inadequate. Metagenomic sequencing can identify almost every globally known infection (bacteria, virus, fungi, parasites) in a sample. Therefore, it has the potential to identify an infection that has caused or triggered ocular inflammation, and as a consequence may help to identify specific treatments. It has the potential to improve our understanding of how to diagnose and treat people with this problem. This study will allow us to test the technique that has been previously optimised for brain infections, on ocular fluids. Participants will be 18 years of age or over and have active ocular inflammation which is suspected to be due to an infection, or an autoimmune process which has been triggered by an infection, but identification of this infection has not been possible using the investigations available as part of standard NHS care. Participants will be identified by the treating clinical team as requiring a sample of fluid from inside of the eye, and some of this fluid will be sent for metagenomic sequencing alongside standard testing. This study will be conducted at Moorfields Eye Hospital, London and will last for approximately a year. Participants will undergo additional non-invasive ocular imaging on the day of their clinic visit, but will not have to attend any additional research visits.