Fever

This is a multi-country, open label, two-arm, parallel-group, superiority, individually randomised clinical trial involving 2,606 febrile children per country (two countries, total n=5212). The trial will compare the performance of a point-of-care rapid triage test (POC-RTT) based on suPAR levels (i.e.suPARnostic®) (in combination with IMCI-based strategies, which are the SoC) to appropriately support admission/referral vs discharge decisions during the first clinical assessment of febrile children aged 2-\<60 months compared to the standard of care based on IMCI guidelines. Febrile children meeting the study eligibility criteria will be randomly allocated (1:1) to one of the two triaging approaches (arms): 1) IMCI-based standard of care (SoC); or 2) IMCI-enhanced by suPAR levels (SoC + suPAR POC). Blood will be collected from all participants and only those randomised to the intervention arm (arm 2) will have suPAR levels determined at the POC using suPARnostic® device. At baseline, all children will undergo two clinical assessments. Primary composite endpoint of "appropriateness of discharge" will be based on the first clinical assessment, which is more representative of real-world clinical practice. However, the ultimate decision on admission/referral vs discharge will be based on the second clinical assessment, which will ensure the safest possible clinical practice in the context of a clinical trial. 1. At baseline, during the first clinical assessment, all participants will be evaluated following the SoC based on IMCI guidelines, which will guide management decisions, including clinical diagnosis and treatment. This IMCI-guideline based evaluation during this first clinical assessment will be conducted by a health worker as per routine clinical practice in the outpatient departments of each study site. 1. In the participants randomised to the control arm, decision of admission/referral vs discharge home will be informed by IMCI-based evaluation alone (SoC). 2. In the participants randomised to the intervention arm, decision of admission/referral vs discharge home will be informed by IMCI-based evaluation enhanced by suPAR levels (SoC + suPAR POC). Clinicians will be instructed to admit for further observation any child with suPAR levels equal or superior to 4 ng/mL (except for confirmed malaria, that it will be equal or superior to 6 ng/mL), as these patients are at moderate or high risk of adverse outcomes and death. On the other hand, children with suPAR levels below 4 ng/mL (or below 6 ng/mL in case of confirmed malaria) will be eligible for discharge home at the criteria of the clinician, considering the signs and symptoms found, and based on IMCI guidelines. Hence, should clinicians in charge deem that any of these children still require admission, they will be instructed to continue with the admission regardless of suPAR levels. The study intervention will be implemented during the first clinical assessment, and consequently, primary composite endpoint of "appropriateness of discharge" will be based on the decision of admission/referral vs discharge home during this first clinical assessment, which is more representative of routine clinical practice in each study site. 2. All randomised participants will be also evaluated by an independent study physician in a second clinical assessment, for the implementation of a systematised clinical evaluation (IMCI-based) to uncover any danger signs or severity criteria potentially missed or misinterpreted during the first assessment. This second assessment will also include clinical variables of the clinical scores ED-PEWS, LqSOFA and LODS, as well as temperature and oxygen saturation measures. Hence, study clinicians during this second clinical assessment might be able to uncover more symptoms and signs that are admission criteria due to the tools available in the context of this clinical trial. Initially discharged patients from both arms showing a danger sign during this second assessment will be admitted, as well as those from the intervention arm with suPAR high-risk (red light) and moderate-risk (yellow light) levels, in case that the first clinician might not have adhered to the protocol during the first assessment. On the other hand, this second assessment will not overturn the decision of the first clinician if admission has been decided in case of low-risk (suPAR levels below 4 ng/mL; or below 6 ng/mL in case of confirmed malaria). This second clinical assessment will guide the ultimate decision on admission/referral vs discharge in order to ensure the safest possible clinical practice in the context of a clinical trial. Moreover, those participants with respiratory symptoms will be eligible for the respiratory tract infection (RTI) sub-study, where digital lung auscultations, a mid-turbinate nasal swab and a saliva sample will be collected. Throughout the study, all participants will receive treatment as per the routine clinical practice and SoC for each diagnosis at each study site, administered by clinical staff routinely working in the participating facilities. All participants will have follow-up evaluations by study clinicians on days 3 and 7 post-enrolment, or at any time in-between in case of clinical deterioration according to caregivers' evaluation. All participants will be also followed-up on day 28 for an interview to follow-up on serious adverse events (SAEs), as well as to collect information on secondary consultations and hospitalisation, or death. A follow-up extra visit at day 91 (month 3) can be conducted for an interview to ask for hospitalisation or death.

Background and Rationale In pediatric cancer patients, Augmented Renal Clearance (ARC) is a common factor that affects outcomes. Febrile neutropenia, a frequent occurrence during cancer treatment, requires anti-infective drugs for treatment. However, ARC increases the elimination of these drugs through glomerular filtration, posing a risk of antibiotics insufficient blood levels. This may lead to difficulties in managing infections and the risk of antibiotic-resistant bacterial strains emerging. Febrile neutropenia is often associated with ARC, and in these patients standard antibiotic dosages frequently miss target concentrations. We propose defining categories of renal hyperfiltration to adjust antibiotic dosages upward in pediatric patients with ARC. To estimate renal function, molecules such as creatinine or cystatin C are routinely measured in the blood. Clinicians commonly rely on the Schwartz formula for determining the patients glomerular filtration rate (GFR) when adjusting antibiotic treatment. Although other formulas based on creatinine and/or cystatin C have been developed, their effectiveness in oncological patients with ARC remains unexplored. If these alternative formulas prove more effective in ARC situations, it may prompt a reconsideration of how we determine GFR in hyperfiltrating children. Measurement and procedures Clinicians will decide if prescribe piperacillin-tazobactam or meropenem, according to the clinical situation. The trial will have 3 arms, the two control arms will receive standard dosages of antibiotics (non-hyperfiltrating patients, control group 2, and hyperfiltrating patients randomized to control group 1c). The third group, hyperfiltrating patients randomized to intervention group 1i, will receive experimental doses. The randomization will be made using REDCap®. A TDM at trough level (Ctrough) of meropenem (MER) or piperacillin-tazobactam (PIP) will be systematically performed just before the fourth dose, and again before the fourth dose after each further dosage adaptation. The dosage will be adjusted if blood levels are outside the target therapeutic ranges. TDM will be monitored at least twice a week and more frequently in case of unfavorable clinical outcome or significant change in serum creatinine. Objectives Primary objective: To compare the proportion of early achievement of antibiotic concentration targets in hyperfiltrating patients, using either standard dosage recommendations (control group, 1C) or a new set of Dosage Adjustment Rules for Augmented Renal Clearance (DAR-ARC) (intervention group, 1i). Secondary objectives: 1. To compare the proportion of early achievement of antibiotic concentration targets (for MER or PIP) between non hyperfiltrating patients (control group 2) and the intervention group (1i). 2. To compare the mean/median duration of fever episodes between control groups and intervention group (1i) 3. To compare the incidence of intervention-drug adverse effects (CTCAE v5, grade 3 or higher, grade 2 judged to be probably/definitely related to study intervention and SAE) between the control groups (group 1c and 2) and the intervention group (1i) 4. To compare the proportion of patients requiring TDM-based readjustment of antibiotic dosages due to blood level below or above the target ranges between the control group 1c and the intervention group 1i, at any time during the antibiotic treatment. 5. To compare the eGFR estimated by creatinine-based Schwartz formula in comparison to creatinine and cystatin C based Schwartz formula, creatinine-based quadratic formula, combined creatinine and cystatin C Quadratic formulas, Zappitelli formula, and Schwartz-Lyon formula. Statistical Considerations The proportion of achievement of the target ranges before the fourth antibiotic dose will be compared between the two randomized groups with a mixed effects logistic regression. Duration of fever will be analyzed by the Kaplan-Meier method. Cox regression analysis will be used to evaluate if the intervention decreases duration of fever. The occurrence of adverse events and the outcome of the febrile neutropenia episode will be compared between groups using a Chi-square test. The use of TDM for further adjustment of MER and PIP dosage will be explored with descriptive statistics. A population pharmacokinetic description of MER and PIP concentration will be attempted. To evaluate different eGFR formulas, we will calculate the mean difference in eGFR estimation for each formula compared to the creatinine-based Schwartz formula and determine a 95% confidence interval for each formula. Comparison between hyperfiltrating non hyperfiltrating will be made using student T-test or Kruskal-Wallis tests. Unless otherwise stated, the α risk p -values reported will be two-sided and the nominal limit will be set to 0.05. Risk / Benefit Assessment The risk of this study is over exposure to wide-spectrum antibiotics. This implies drugs dose-dependent adverse events. High blood trough concentrations (Ctrough) of broad-spectrum antibiotics have been associated with reversible neurological and nephrological side effects in adults. The threshold level chosen in this protocol is well below the values for which there is a risk of a 50% increase in side effects for both antibiotics. Doses of MER and PIP excess of authorized doses, guided by therapeutic drug monitoring, have not been associated with additional toxicities in adults. The evaluation of renal clearance before the choice of dosage, daily clinical and biological monitoring and regular monitoring of Ctrough will limit risks. The expected benefit will be improved circulating exposure to broad-spectrum antibiotics. This could allow better control of the infection with a more rapid and favorable clinical course.

Previous studies have shown that mortality and morbidity in preterm neonates are correlated with the fall in body temperature on admission. Hypothermia can be decreased by reducing body heat losses to the environment. The investigator research hypothesis is that a new calculation of the air temperature in the incubator would promote the newborn infant weight growth from the period between birth and day 10 of life compared to cutaneous mode. The secondary hypotheses assumes a decrease in the side effects usually observed in both morbidity and mortality. A software is used to calculate the body heat loss (BHL) of each individual preterm infant, and to propose a specific air temperature setting inside the incubator to reduce BHL to zero. This software has been validated in a previous pilot study (Degorre et al. 2015). This study aims to compare the energy costs of providing incubated preterm infants born between 25 and 32 weeks of gestation with homeothermia using either specific individualized air temperature control (ATC) or skin servocontrol (SSC).

Gastric varices is not uncommon is patients with chronic liver diseases including liver cirrhosis and hepatocellular carcinoma. Occurrence of gastric varices (GV) rupture is less often than esophageal varices (EV) but it is characteristic of higher rebleeding rate and mortality and represents an even tougher problem than EV hemorrhage. Endoscopic treatment is an alternative in the management of GV bleeding. Injection sclerotherapy has been applied to arrest GV hemorrhage but it is associated with a high rebleeding rate (50\~90%) and thus is regarded as only a temporary hemostatic measure. The advantage of endoscopic variceal ligation is not suggested due to its high rebleeding rate more than 50%. Endoscopic injection of N-butyl-2-cyanoacrylate, a so-called "tissue glue",is more effective to treat GV bleeding because of more than 90% successful rate to arrest acute bleeding. The theoretical advantages of tissue glue derives from its unique ability to plug the varix lumen immediately after injection into varices. However, its rebleeding rate is still high around 30\~40% and has potential treatment-related morbidity such as embolic and septic complications. Regardless of these disadvantage, the guideline form major international society and Bavenoconsensus recommend GVO as the first treatment of choice for GV bleeding. Therefore how to prevent the potential complications and reduce rebleedingremains an important and practical issue. With regarding to potential septic infections and rebleeding, the effects of impaired leukocyte function in cirrhotic patients and reduced immunity and increased gut permeability of severe hemorrhagic patients were contributory. In these immunocompromised hosts, when invasive procedure such as GVO is deployed for these patients, the septic complication become un-neglectable, We found (Gastrointest Endosc 2001) more than 1/3 patients undergoing GVO may complicated with bacteremia. Although most of these bacteremia were self-limited, 2% died of sepsis. Moreover, lots of cases were reported due to persistent and recurrent bacterial infections caused by GVO. Antibiotic prophylaxis has been suggested as an integral part for the management of cirrhotic patients with acute varicealbleeding by major international society and Baveno consensus. However, there is no evidence to suggest antibiotic prophylaxis for the patients treated by elective GVO. Therefore we design a randomized trial to clarify the necessity of antibiotic prophylaxis for the patients chronic liver disease with gastric varices treated by elective GVO.

The goal of this clinical trial is to learn whether AI-enabled, nurse-led treatment planning can improve the quality of clinical reasoning and management compared with standard physician-led care in adult primary care patients (≥18 years) presenting with hypertension, diabetes mellitus, fever, breathlessness, or musculoskeletal pain in rural and semi-urban India. The main questions it aims to answer are: * Does a nurse + large language model (LLM) consultation achieve non-inferior clinical quality scores compared with a standard doctor consultation? * Is AI-assisted nurse-led care acceptable and satisfactory to patients in primary healthcare settings? Researchers will compare nurse + LLM-led consultations with physician-led standard-of-care consultations within the same participant to see if the AI-enabled nurse model delivers comparable or improved clinical reasoning and treatment planning. Participants will: * Receive two sequential consultations for the same visit (one with a nurse using an AI tool and one with a physician, order randomized). * Have both consultations audio recorded for blinded clinical quality assessment. * Complete a brief exit survey on communication, trust, and satisfaction after the AI-assisted nurse consultation.

The AIDA registry service is based on REDCap (Research Electronic Data Capture, project-redcap.org), a secure web application for building and managing online surveys and databases, designed to support data capture for research studies. The platform is directly accessible through the AIDA website, after inserting a personal username and password. Currently, 11 registries are available, each one dedicated to the collection of data about: * monogenic AID * PFAPA syndrome * undifferentiated systemic AID (USAID) * Behçet's disease * Schnitzler's disease * VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome * Still disease * noninfectious uveitis * noninfectious scleritis * spondyloarthritis * Castleman disease The registry will pursue the following aims within the first 36 months from the start of the enrollment: 1. to identify any association between clinical manifestations and gender, disease duration, body mass index and tabagism; 2. to detect differences in the clinical phenotype between pediatric-onset and adult-onset patients; 3. to identify the impact of different treatment approaches on clinical and laboratory disease manifestations. Additional aims of the AIDA project, to be reached over the next 10 years, are the following: 1. to overcome fragmentation in the clinical experience on these rare conditions by sharing the knowledge at the international level; 2. to improve knowledge about the clinical presentation, genotype-phenotype correlations, response to treatment, long-term complications and social impact when monogenic and polygenic AID manifest during either childhood or adulthood; 3. to identify the long-term clinical course of patients diagnosed with monogenic or polygenic AID; 4. to promote awareness among physicians and enhance early recognition of these diseases; 5. to describe the impact of AID on quality of life; 6. to identify any impact of monogenic and polygenic AID on fertility; 7. to study the course of AID during pregnancy; 8. to assess the socioeconomic impact of AID; 9. to promote future multicentric studies. Data collection is both retrospective and prospective. It includes demographic, clinical, diagnostic, genetic, clinimetric, laboratory, radiologic, therapeutic and socio-economic data. Instruments are designed to be filled out during routine clinical visits, usually scheduled every 3-6 months. Separation of personally identifiable information and medical data by using only pseudonyms for storing medical data ensures compliance with data protection regulations. The description of symptoms, diseases, procedures and injuries is based on the International Statistical Classification of Diseases and Related Health Problems (ICD)-10 coding system. Data management is both central and decentral. Data are extracted and statistically analyzed on a regular basis according to individual study protocols. A policy for authorship and dissemination of research findings is in place among the AIDA partners contributing to the registry. The AIDA registry will support data collection for the conduction of clinical trials, observational studies, comparative effectiveness research, and other research on patients with monogenic and polygenic AID. Several healthcare providers contributing to the AIDA Network are members of the European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA).

The majority of people in low- and middle-income countries (LMICs) in South and Southeast Asia live in rural areas. These people are some of the poorest in the region and the exact health issues which concern them have not been well defined, in that they have not been fully studied. Despite this lack of data, there are indications that disease of an infectious aetiology, 'febrile illness,' in particular in the tropics, still accounts for significant morbidity and mortality. This is in contrast to higher-income countries. The South and Southeast Asian Community-based Trials Network in Rural Febrile Illness project (SEACTN RFI) aims to better understand and quantify the burden of febrile illness, the aetiological causes and the manner in which it affects the people of the area, all on a scale which has not been attempted before. It will collect information to help better understand and predict these outcomes based on a multitude of factors, which will form the basis for interventions within the network in the future. The initial study will be observational, as the current understanding of the local health issues and the health systems in these areas is insufficient to know how best to intervene. In a separate work package, Work Package A (WP-A), the investigators will be collecting data from within the participating SEACTN communities through village health workers (VHWs) and local health facilities on the incidence, causes and outcomes of febrile illness in these areas. In Work Package B (WP-B) will recruit patients seeking care at higher level facilities than the WP-A VHWs and health centres. These patients are likely to be more severely ill, in order to obtain a more thorough understanding of the causes and burden of febrile illness in these areas. A broader range of specimens, including venous blood samples and respiratory specimens will be collected. In-depth diagnostic testing including blood cultures, serological assays, pathogen molecular diagnostics, host biomarker assays, and validation of pathogen-blind next generation sequencing approaches will be conducted. The data from WP-A gathered in the community complemented by the WP-B data from higher level health facilities in the same regions will provide a rich understanding of the causes, incidence and outcomes of febrile illness in these areas. These data will be analysed using advanced statistical methodology to create electronic decision-support tools (eDSTs) to aid VHWs in their assessment, triage and treatment of patients. These and other relevant interventions will later be trialled across the SEACTN villages.

The study proposes a planned, double-blind, non-inferiority clinical trial involving patients with febrile neutropenia and risk of extended-spectrum beta-lactamase (ESBL) infection. The goal is: \- Analyze the efficacy and tolerability of Ceftolozane/tazobactam (CEF/TAZ) compared to the current standard of care (meropenem) in patients with febrile neutropenia and risk of ESBL infection. Patients will be randomly assigned to receive CEF/TAZ or meropenem, with assessment of clinical response, toxicity and microbiological evolution. Stool samples will be collected before, during and after treatment for intestinal microbiota analysis and intestinal microbiome analysis to evaluate possible effects on GVHD. Analysis of the results will include the taxonomic classification of the organisms present. Data will be analyzed to assess non-inferiority in clinical response, incidence of GVHD, antimicrobial resistance and other outcomes.

Furthermore, this clinical trial aims to: 1. Compare the efficacy of empirical antibiotic administration of Ciprofloxacin and Ceftazidime in pediatric malignancy patients with high-risk neutropenic fever. 2. Analyze the differences in clinical effectiveness between ceftazidime and ciprofloxacin antibiotics based on the duration of fever, duration of neutropenia, duration of hospitalization in high-risk neutropenic fever in children with hematological malignancies. 3. Compare the mortality of pediatric patients with high-risk neutropenic fever due to hematological malignancies who received empirical antibiotic therapy of ceftazidime and ciprofloxacin. 4. Compare antibiotic escalation decisions in pediatric patients with high-risk neutropenic fever due to hematological malignancies who received empirical antibiotic therapy of ceftazidime and ciprofloxacin.

* . Type of Study: Randomized controlled clinical trial. * Study Settings: Ain Shams University hospitals, Cairo, Egypt. * Study Population: patients undergoing abdominal open surgeries with general anesthesia. * Inclusion Criteria: * ASA I or ASA II patients Scheduled for abdominal surgery under general anaesthesia. * Age between18-65 years. * Procedure duration ≤ 120 minutes. * Exclusion Criteria: * Patients with known neurologic and psychiatric illness. * Uncontrolled diabetic patients. * Patients on long term steroid therapy. * Allergy to any of the drugs used in the study. * Pregnancy and lactation. * Hypo or hyperthyroidism. * Sampling Method: Simple randomization * Standard care Standard care for all patients undergoing this study will be done by senior staff expert members of Ain-Shams University Anesthesia department and will be monitored by supervisors. * Study Procedures: * Preoperative settings: All patients will be assessed preoperatively by careful history taking, full physical examination, and laboratory evaluation. An informed written consent will be taken from every patient just before the surgery. • Intraoperative and postoperative settings: Patients will be divided into two groups: * Group A: (HYDROCORTISONE group): will receive 2mg/kg . * Group B: (Dexmedetomidine group): will receive 1 µg/kg . On arrival to the operating room, routine monitors will be applied, including a blood pressure cuff, electrocardiogram, pulse oximeter, and capnogram. core temperature will be measured using temperature probe to determine baseline values. An intravenous ringer infusion will be started. Pre oxygenation will be done with 100% oxygen on 6L\\m for 3 minutes. Anesthesia will be induced with propofol 2 mg/kg, fentanyl 2 mic\\kg and atracurium 0.5 mg/kg. After endotracheal intubation, anesthesia will be maintained with 1.2-1.5% isoflurane. Mechanical ventilation will be adjusted to maintain end-tidal carbon dioxide tension at 30-35 mmHg Patients will be covered with surgical drapes. Supplemental doses of atracurium will be given every 20 minutes to maintain muscle relaxation during surgery. Approximately 30 minutes before the anticipated completion of surgery, the study drugs will be given to the two groups. Ephedrine (10 mg IV bolus) will be given for hypotension (systolic blood pressure \< 80 mmHg) and atropine (0.5 mg IV bolus) will be given for bradycardia (HR \< 50 BPM). At the end of surgery, extubation will be done and patients will be transferred to the post-anaesthesia care unit (PACU), for further monitoring. • Postoperative settings: Patients will be transferred to the post-anaesthesia care unit (PACU) and will be put under observation for 30 minutes. • Measurements: Baseline core temperature (pre-induction) will be taken as the first measurement in the operating room. Heart rate and non-invasive blood pressure readings will be recorded. Core temperature will be measured directly after endotracheal intubation and every 15 minutes during the operation. Upon transferal of the patient to the post-anesthesia care unit (PACU), core temperature will be measured and shivering will be graded from (0-3) according to the shivering scale validated by Crossley and Mahajan as follows: 0 = no shivering, 1 = mild fasciculation of the face or neck, 2 = visible tremor involving more than one muscle group, 3 = gross muscular activity involving the entire body. • Primary outcome: To compare the efficacy of hydrocortisone and dexmedetomidine in reducing shivering post operatively. • Secondary outcomes: Measurement of the hemodynamic changes if present.