Patients presenting to the ED with suspected sepsis who develop altered mental status

Patients presenting to the ED with suspected sepsis without change in mental status

Patients presenting to the ED with no suspicion of systemic inflammation that need hospitalization (control category)

Sepsis

Altered Mental Status

Sepsis-Associated Delirium

Sepsis Associated Encephalopathy

Delirium, Sepsis Associated

Blood draws will be collected via venipuncture or IV at hours 0, 6, 12, 18, 24, 48, 72 (7 draws total). Each draw would be up to 20 mL of blood (but no less than 10 mL).

Blood draws

University of Florida

Sepsis Associated Encephalopathy (SAE) Biomarkers

Serum Biomarkers in Sepsis Associated Encephalopathy (SAE)

Acute encephalopathy will be measured using the mental status assessment including the Delirium Triage Screen (DTS) Brief Confusion Assessment Method (bCAM). DTS-bCAM assessment is a flowchart that helps diagnose a patient who is altered.

Acute encephalopathy will be measured using the mental status assessment short blessed test (SBT). Sum Total (range 0-28) [0-4 = normal cognition, 5-9 = questionable impairment, ≥ 10 = Impairment consistent with dementia]

Organ dysfunction will be assessed using Sequential Organ Failure Assessment (SOFA) methodology, a mortality assessment tool that monitors the dynamics of cardiovascular, respiratory, neurological, renal, hepatic, and hematological organ function.

Date of death will be recorded for all patients who died during the study period. Rate of survival will be assessed.

assessed using the Cerebral Performance Category (CPC) scoring [CPC 1: A return to normal cerebral function and normal living, CPC 2: Cerebral disability but sufficient function for independent activities of daily living, CPC 3: Severe disability, limited cognition, inability to carry out independent existence, CPC 4: Coma, CPC 5: Brain death

Cognitive Failure Questionnaire (CFQ) sum of 25 questions, range 0-100 assessing Forgetfulness, Distractibility, and False Triggering

standard anti-tuberculosis drugs plus dexamethasone for 6-8 weeks

standard anti-tuberculosis drugs plus placebo for 6-8 weeks

Tuberculosis

Tuberculous Meningitis

Drug-Induced Liver Injury

Active treatment with dexamethasone from randomisation (IV followed by oral according to disease severity at the start of treatment): Dexamethasone for intravenous injection and dexamethasone for oral ingestion

Dexamethasone

Treatment with matched placebo: Standard saline for intravenous injection and placebo oral tablets containing cellulose

Placebo

Hospital for Tropical Diseases

Oxford University Clinical Research Unit

Pham Ngoc Thach Hospital

Leukotriene A4 Hydrolase Stratified Trial of Adjunctive Corticosteroids for HIV-uninfected Adults With Tuberculous Meningitis

A Randomized Double Blind Placebo Controlled Non-inferiority Trial of Adjunctive Dexamethasone for the Treatment of HIV-uninfected Adults With Tuberculous Meningitis Stratified by Leukotriene A4 Hydrolase Genotype

The primary endpoint is all cause mortality or new neurological event (defined as a fall in Glasgow coma score by ≥2 points for ≥2 days from the highest previously recorded Glasgow coma score (including baseline) or the onset of any of the following clinical adverse events: cerebellar symptoms, focal neurological signs, or new onset of seizures) during 12 months from randomisation. Survivors without a new neurological event known to be alive at 12 months will be censored at that time-point and subjects who withdrew or were lost to follow-up before 12 months will be censored at the date they were last known to be alive.

Overall survival is defined as the time from randomization to death, during a follow-up period of 12 months. Survivors known to be alive at 12 months will be censored at that time-point and subjects who withdrew or were lost to follow-up before 12 months will be censored at the date they were last known to be alive.

Neurological disability will be assessed by the modified Rankin score on months 3, 6, 9, and 12 from randomisation. The main endpoint is the 12 month assessment and subjects who died before 12 months will be treated as having a score of 6 ('Dead')

Comparison of the frequency of severe (grade 3&4) and serious adverse events, respectively, between treatment groups will form an important part of the study analysis.

Neurological complications occurring after the start of anti-tuberculosis chemotherapy for TBM are common. The cause varies, but includes hydrocephalus, infarcts, tuberculoma formation and hyponatraemia. If the symptoms are thought to be caused by tuberculomas, many doctors will re-start or increase the dose of corticosteroids. In this trial, any re-start or dose increase of corticosteroids during the 12 month follow-up will be defined as 'rescue' corticosteroids.

The Oxford University Clinical Research Unit recognizes the ethical obligation to ensure that optimal use is made of the data and specimens that the investigators collect for the research and the value of sharing individual level data. The investigators aim to ensure that data generated from all the research are collected, curated, managed and shared in a way that maximizes their benefit. When sharing data the investigators have an obligation to ensure that the interests of research participants, researchers and other stakeholders are appropriately protected. The Oxford University Clinical Research Unit data sharing policy and the data request form outline the default procedures for data sharing.

Oxford University Clinical Research Unit, Vietnam

Pham Ngoc Thach Hospital, Ho Chi Minh City, Vietnam

Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

Patients with GM1/GM2-Gangliosidosis or high-grade suspicion for GM1/GM2-Gangliosidosis

For the development of the new biomarkers using the technique of Mass-spectometry, maximal 10 ml blood will be taken via using a dry blood spot filter card. To proof the cor-rect GM1/GM2 diagnosis in those patients where up to the enrollment into the study no genetic testing has been done, sequencing of GM1/GM2 will be done. The analyses will be done at the Centogene AG Am Strande 7 18055 Rostock Germany

Hepato-splenomegaly

Dysostosis Multiplex

Seizures

Mental Retardation

Centogene is one of the leading laboratories focusing on genetic testing for rare hereditary disorders. We now offer more than 2200 routine genetic and biochemical tests.

Children's Hospital, Faculty of Medicine, Ain Shams University

Centogene AG

Amrita Institute of Medical Sciences & Research Centre

Navi Mumbai Institute of Research In Mental And Neurological Handicap (NIRMAN)

Lady Ridgeway Hospital for Children

Biomarker for Gangliosidosis: BioGM1/BioGM2 (BioGM1/GM2)

Biomarker for Gangliosidosis: BioGM1 / BioGM2 AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGICAL PROTOCOL

New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood of affected patients that allow diagnosing in the future the disease earlier, with a higher sensitivity and specificity.

the goal of the study to identify and validate a new biochemical marker from the blood of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment.

hydrolase/seizures

Sepsis Associated Encephalopathy (SAE) Biomarkers

Leukotriene A4 Hydrolase Stratified Trial of Adjunctive Corticosteroids for HIV-uninfected Adults With Tuberculous Meningitis

Biomarker for Gangliosidosis: BioGM1/BioGM2 (BioGM1/GM2)

Drug Interaction Study of Tegretol (Carbamazepine) and St. John's Wort in Normal Volunteers

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