Intensified Short Course Regimen for TBM in Adults
Tuberculous MeningitisTuberculous meningitis (TBM) is the most lethal form of extra pulmonary tuberculosis. This devastating disease kills almost a third of its sufferers and disables a significant proportion of the survivors. TBM poses one of the most difficult diagnostic and therapeutic challenges in modern clinical practice. High-quality robust clinical trials have made a considerable contribution to the treatment of pulmonary tuberculosis in the last four decades. However, evidence from such clinical trials is lacking in TBM and the treatment remains uncertain. There is a significant variation in the choice, dose and duration of drugs between countries, institutions and clinicians. Investigators propose a multi-centric open-label clinical trial to assess the efficacy of short-course anti-TB drugs with high dose rifampicin, and moxifloxacin along with conventional anti-TB drugs and adjuvant therapy with aspirin and corticosteroids. Controls will receive standard treatment as per national guidelines for TBM. The investigators also aim to assess the safety and tolerability of high-dose Rifampicin and Moxifloxacin and the Pharmacodynamics and Pharmacokinetics parameters of ATT (Rifampicin, INH, Moxifloxacin and Pyrazinamide) in CSF between the two groups
Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial 3
Cryptococcal MeningitisThis pivotal, confirmatory trial seeks to independently verify the results observed in the EnACT Phase II Stage 2 trial (MB-70007).
Meningococcal Serogroup ACYWX Conjugate Vaccine in Comparison With MenACWY-TT Conjugate Vaccine...
MeningitisInfants aged 9 months will be randomized to receive a meningococcal vaccine at 9 months or 15 months. Infants randomized to the 9-month age group will be further randomized in a 2:1 ratio to receive a single dose of the experimental meningococcal vaccine (NmCV-5) or a single dose of the comparator meningococcal vaccine (MenACWY-TT). Prospectively identified and consented infants randomized to the 15-month age group will return when aged 15 months and will be randomized in a 2:1 ratio to receive a single dose of NmCV-5 or a single dose of MenACWY-TT.
Fosfomycin i.v. for Treatment of Severely Infected Patients
Bacterial InfectionsBone Diseases19 moreThe purpose of this European, multicentric, prospective, non-interventional study is to document and evaluate the efficacy and safety of the treatment of severely infected patients with intravenously administered fosfomycin, including patients with osteomyelitis, complicated urinary tract infection, nosocomial lower respiratory tract infection, bacterial meningitis/central nervous system infection, bacteraemia/sepsis, skin and soft tissue infection, endocarditis or other infections, each as far as covered by the respective nationally relevant SmPC.
Central Nervous System Infections in Denmark
Central Nervous System InfectionsBacterial Meningitis10 moreThe Danish Study Group of Infections of the Brain is a collaboration between all departments of infectious diseases in Denmark. The investigators aim to monitor epidemiological trends in central nervous system (CNS) infections by a prospective registration of clinical characteristics and outcome of all adult (>17 years of age) patients with community-acquired CNS infections diagnosed and/or treated at departments of infectious diseases in Denmark since 1st of January 2015.
Etiology, Pathogenesis, and Natural History of Idiopathic CD4+ Lymphocytopenia
Idiopathic CD4+ LymphocytopeniaCryptococcal Meningitis1 moreBackground: Idiopathic CD4+ lymphocytopenia (ICL) is a condition in which there is a decreased level of CD4+ lymphocytes (a type of white blood cell), which can lead to opportunistic infections or autoimmune disorders and diseases. Objectives: To characterize the natural history with regard to CD4+ T cell count and onset of infection, malignancy, and autoimmunity. To describe the immunological status of patients affected by ICL while providing the best possible standard therapy to eradicate opportunistic infections. To establish the timeline of CD4 lymphocytopenia, with particular focus on defining subgroups of patients according to the decline, stabilization, or rise of CD4+ T cell counts over time. To characterize the opportunistic infections that occur in ICL patients at microbiologic and molecular levels. To characterize the immunophenotype and possible genetic immunodeficiency causes of ICL. To determine whether measurable immunologic parameters correlate with the development of opportunistic infections or other comorbidities such as lymphoma in patients with ICL. To determine whether there is any association between ICL and autoimmunity. To determine CD4+ T cell turnover, survival, functionality, and cytokine responsiveness in ICL patients. Eligibility: Patients 2 years of age and older with an absolute CD4 count less than 300 in children 6 years or older and adults or less than 20% of T cells in children younger than 6 on two occasions at least 6 weeks apart. Patients with negative results of HIV testing by ELISA, Western Blot, and viral load. Patients must not have underlying immunodeficiency conditions, be receiving cytotoxic chemotherapy (anti-cancer drugs that kill cells), or have cancer. Design: At the initial visit to the National Institutes of Health, the following evaluations will be conducted: Personal and family medical histories. Physical examination, including rheumatology evaluation and other consultations as medically indicated (e.g., dermatology, pulmonology, ophthalmology, imaging studies). Blood samples for analysis of red and white blood cell counts, liver function, immune hormones, and antibody and autoantibody levels, white blood cell growth and function, and DNA. Urinalysis and urine pregnancy testing for female patients of childbearing age. Evaluation and treatment of active infections as medically indicated, including biopsies, buccal swabs, pulmonary function tests, and imaging studies. Follow-up visits will take place approximately every 12 months or more frequently if indicated, and will continue for a minimum of 4 years and a maximum of 10 years. Evaluations at follow-up will include blood samples (i.e., CBC with differential, biochemical profile, HIV testing, etc.) and urinalysis and rheumatology consults.
Cyclophosphamide in the Treatment of Refractory Proliferative Arachnoiditis in CNS Tuberculosis...
TuberculosisTubercular Meningitis1 moreTubercular meningitis occurs in around 10% of those with extrapulmonary tuberculosis and is a major cause of mortality and morbidity. Inspite of effective Anti-tubercular drugs, still around 30% of patients develop complications due to arachnoiditis such as spinal tubercular radiculomyelitis, optico-chiasmatic arachnoiditis, development of new tuberculomas after starting therapy etc. which are probably immune mediated inflammatory responses due to paradoxical reaction to ATT. The management of arachnoiditis is far from satisfactory. High dose methylprednisolone, intrathecal hyaluronic acid, thalidomide have been tried in small case series and case reports. However, the results have not been satisfactory. There are two published reports of cyclophosphamide usage in TBM related vasculitis and stroke The investigators tried cyclophosphamide in four patients after consent, and found remarkable improvement in all of them. (Under peer review) In order to test this hypothesis, a randomized controlled trial is needed.
MUSic Therapy In Complex Specialist Neurorehabilitation
StrokeSubarachnoid Hemorrhage8 moreAim: Investigate whether patients undergoing specialist rehabilitation after complex neurological injury show different functional outcomes if music therapy is included in their rehabilitation program compared to usual care. Background: Patients with complex needs following a brain, spinal cord, and/or peripheral nerve injury often require a period of specialist neurorehabilitation. This involves multiple therapy disciplines, led by a Consultant in Rehabilitation Medicine, Neurology, or Neuropsychiatry. Although music therapy is suggested to enhance neuroplasticity and recovery in patients with brain injury, it is not routinely commissioned in clinical care due to a lack of supportive evidence. Hypothesis: Patients undergoing music therapy in addition to complex specialist rehabilitation show better functional outcomes compared to usual care. Number of participants: 75, aged 16-80 years. Methods: Patients undergo baseline assessments and are randomised to MUSIC or CONTROL Therapy. Both arms receive 1-3 additional therapy sessions per week, matched for duration and number, total 15 hours. After approximately 10-weeks intervention, assessments are repeated. All participants then have access to music therapy until they are discharged from Neurorehabilitation Unit (NRU), with additional qualitative data collection using semi-structured interviews, field notes, staff reports, staff stress surveys, and broader ecological observations. Duration for Participants: From consent to discharge from NRU. Primary Outcome: Change in Functional Independence Measure+Functional Assessment Measure (FIM+FAM), Northwick Park Dependency Scale (NWPDS), and Barthel Activities of Daily Living pre and post 15 hours intervention. Secondary Outcome: Change in quality of life (Flourishing Scale), psychological distress (Hospital Anxiety and Depression Scale, Depression Intensity Scale Circles), social interaction (Sickness Impact Profile Social Interaction Subscale), well-being (WHO Well-Being Index), and communication (Communication Outcomes After Stroke Scale), pre and post 15 hours intervention. Mean difference in well-being (WHO Well-Being Index) throughout the intervention period between music therapy and control therapy groups. Mean difference in post-intervention pain and mood visual analogue scores between music therapy and control therapy groups.
Clinical Study of ABCD in the Treatment of Cryptococcal Meningitis
Cryptococcal MeningitisTo evaluate the efficacy and safety of ABCD in the treatment of cryptococcal meningitis in non-HIV patients at week 4, the end of induction therapy, week 10 and the end of consolidation therapy.
Neonatal Bacterial Meningitis Cohort
Bacterial MeningitisNeonatal InfectionNeonatal bacterial meningitis (BM) is a devastating infection that occurs more commonly in neonates than in any other age group, and is associated with significant morbidity and mortality, especially in developing countries. In this study, we aimed to develop a clinical risk score model, according to the available clinical syndromes and commonly laboratory tests, for screening BM among full-term neonates in a large-scale retrospective cohort, and prospectively validated the risk score in multicenter cohort.