Repurposed immunomodulatory drugs for Covid-19 in pre-ICu patients - mulTi-Arm Therapeutic study in pre-ICu patients admitted with Covid-19 - Repurposed Drugs (TACTIC-R): A structured summary of a study protocol for a randomised controlled trial.

Project description:Anti-dementia drugs may improve gait performance. No comparison between acetylcholinesterase inhibitors (CEIs) and memantine-related changes in gait variability has been reported. The objectives of this study were to 1) quantify and compare the mean values and coefficients of variation (CoV) of stride time in demented patients with Alzheimer's disease and related disorders (ADRD) before and after the use of CEIs or memantine, and in age- and gender-matched controls patients with ADRD using no anti-dementia drugs; and 2) to determine whether changes in CoV of stride time differed between CEIs or memantine.A total of 120 demented patients with mild-to-moderate ADRD were prospectively included in this pre-post quasi-experimental study with two intervention groups (43 patients taking CEIs, and 41 taking memantine) and a control group (36 age- and gender matched patients without any anti-dementia drugs). CoV of stride time and walking speed were measured with GAITRite® system while usual walking at steady state. Age, gender, number of drugs daily taken, use of psychoactive drugs, body mass index and time between the two visits were also recorded.There was no difference between groups for the time between baseline and follow-up assessments (232.9 ± 103.7 days for patients without anti-dementia drugs, 220.0 ± 67.5 days for patients with CEIs, 186.7 ± 96.2 days for patients with memantine, P?=?0.062). Patients with memantine had a lower (i.e., better) CoV of stride time at follow-up assessment compared to those with CEIs (4.2 ± 2.4% versus 5.8 ± 4.2%, P?=?0.010). Patients with memantine had a greater decrease in CoV of stride time compared to those with CEIs (-1.90% versus 0.93%, P?=?0.010) and mixed-effects linear regressions showed that this decrease was specifically explained by memantine (P?=?0.028).Our results showed that patients with ADRD and treated with memantine, but not those with CEIs, decreased their gait variability, and thus improved their gait safety (Trial registration number: NCT01315704).

Project description:BackgroundCoagulation abnormalities in COVID-19 patients have not been addressed in depth.ObjectiveTo perform a longitudinal evaluation of coagulation profile of patients admitted to the ICU with COVID-19.MethodsConventional coagulation tests, rotational thromboelastometry (ROTEM), platelet function, fibrinolysis, antithrombin, protein C and S were measured at days 0, 1, 3, 7 and 14. Based on median total maximum SOFA score, patients were divided in two groups: SOFA ? 10 and SOFA > 10.ResultsThirty patients were studied. Some conventional coagulation tests, as aPTT, PT and INR remained unchanged during the study period, while alterations on others coagulation laboratory tests were detected. Fibrinogen levels were increased in both groups. ROTEM maximum clot firmness increased in both groups from Day 0 to Day 14. Moreover, ROTEM-FIBTEM maximum clot firmness was high in both groups, with a slight decrease from day 0 to day 14 in group SOFA ? 10 and a slight increase during the same period in group SOFA > 10. Fibrinolysis was low and decreased over time in all groups, with the most pronounced decrease observed in INTEM maximum lysis in group SOFA > 10. Also, D-dimer plasma levels were higher than normal reference range in both groups and free protein S plasma levels were low in both groups at baseline and increased over time, Finally, patients in group SOFA > 10 had lower plasminogen levels and Protein C ??than patients with SOFA <10, which may represent less fibrinolysis activity during a state of hypercoagulability.ConclusionCOVID-19 patients have a pronounced hypercoagulability state, characterized by impaired endogenous anticoagulation and decreased fibrinolysis. The magnitude of coagulation abnormalities seems to correlate with the severity of organ dysfunction. The hypercoagulability state of COVID-19 patients was not only detected by ROTEM but it much more complex, where changes were observed on the fibrinolytic and endogenous anticoagulation system.

Project description:BACKGROUND:Tuberculous meningitis (TBM) is a devastating infection in tuberculosis endemic areas with limited access to intensive care. Functional outcomes of severe adult TBM patients admitted to the ICU in nonendemic areas are not known. METHODS:We conducted a retrospective multicenter cohort study (2004-2016) of consecutive TBM patients admitted to 12 ICUs in the Paris area, France. Clinical, biological, and brain magnetic resonance imaging (MRI) findings at admission associated with a poor functional outcome (i.e., a score of 3-6 on the modified Rankin scale (mRS) at 90 days) were identified by logistic regression. Factors associated with 1-year mortality were investigated by Cox proportional hazards modeling. RESULTS:We studied 90 patients, of whom 61 (68%) had a score on the Glasgow Coma Scale ? 10 at presentation and 63 (70%) required invasive mechanical ventilation. Brain MRI revealed infarction and hydrocephalus in 38/75 (51%) and 25/75 (33%) cases, respectively. A poor functional outcome was observed in 55 (61%) patients and was independently associated with older age (adjusted odds ratio (aOR) 1.03, 95% CI 1.0-1.07), cerebrospinal fluid protein level ? 2 g/L (aOR 5.31, 95% CI 1.67-16.85), and hydrocephalus on brain MRI (aOR 17.2, 95% CI 2.57-115.14). By contrast, adjunctive steroids were protective (aOR 0.13, 95% CI 0.03-0.56). The multivariable adjusted hazard ratio of adjunctive steroids for 1-year mortality (47%, 95% CI 37%-59%) was 0.23 (95% CI 0.11-0.44). Among survivors at 1 year, functional independence (mRS of 0-2) was observed in 27/37 (73%, 95% CI 59%-87%) cases. CONCLUSIONS:A poor functional outcome in adult TBM patients admitted to the ICU in a nonendemic area is observed in 60% of cases and is independently associated with elevated cerebrospinal fluid protein level and hydrocephalus. Our data also suggest a protective effect of adjunctive steroids, with reduced disability and mortality, irrespective of immune status and severity of disease at presentation. One-year follow-up revealed functional independence in most survivors.

Project description:ObjectivesWe investigate the effects of melatonin, compared to the usual therapeutic regimen on clinical symptoms and laboratory signs in severely ill patients with confirmed COVID-19 who are admitted to the Intensive Care Unit (ICU).Trial designThis is a single-center, open-label, randomized, clinical trial with a parallel-group design. This study is being conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran.ParticipantsAll patients admitted to the ICU of Shahid Mohammadi Hospital, Bandar Abbas, Iran, will be screened for the following criteria. Inclusion criteria 1. Age >20 years 2. Definitive diagnosis of COVID-19 based on RT-PCR or/and serological testing 3. Severe pneumonia and lung involvement in imaging 4. Signing informed consent Exclusion criteria 1. Underlying diseases, including convulsive disorders, chronic hepatic and renal diseases 2. Use of mechanical ventilation 3. History of known allergy to Melatonin 4. Pregnancy and breastfeeding INTERVENTION AND COMPARATOR: Intervention group: The standard treatment regimen for COVID-19, according to the Iranian Ministry of Health and Medical Education's protocol, along with Melatonin soft gelatin capsule (Danna Pharmaceutical Company) at a dose of 5 mg twice a day for a period of seven days.Control groupThe standard treatment for COVID-19 based on the Iranian Ministry of Health and Medical Education's protocol for a period of seven days.Main outcomesThe primary outcomes are the recovery rate of clinical symptoms and checking arterial blood gas (ABG), C-reactive protein (C-RP), Ferritin, Lactate dehydrogenase (LDH) within seven days of randomization. The secondary outcomes are time to improvement of clinical and paraclinical features and length of stay in the ICU, need for mechanical ventilation, and mortality rate within seven days of randomization.RandomizationIncluded patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 6 patients). This randomization method ensures a balanced allocation between the arms during the study. A web-based system will generate random numbers for the allocation sequence and concealment of participants. Each number relates to one of the study arms.Blinding (masking)This is an open-label trial without blinding and placebo control.Numbers to be randomized (sample size)A total of 60 participants randomizes (30 patients allocated to the intervention group and 30 patients allocated to the control group).Trial statusThe protocol is Version 1.0, February 16, 2021. Recruitment began February 28, 2021, and is anticipated to be completed by July 31, 2021.Trial registrationThe trial protocol has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is " IRCT20200506047323N7 ". The registration date was February 16, 2021.Full protocolThe full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Project description:ImportancePrognostication following ICU admission can often be determined based on known risk factors, including demographics and illness severity; however, little is known about outcomes of patients deemed to be "low-risk" at the time of hospital admission who subsequently are admitted to the ICU.ObjectivesThe objectives of this study were to determine the characteristics, outcomes, and costs for patients requiring ICU admission despite having lower predicted mortality when they were admitted to the hospital.Design setting and participantsIn this historical cohort study, we used a prospectively maintained ICU registry that included all ICU admissions to The Ottawa Hospital for patients 18 years or older from January 2011 to December 2016. We classified patients as low-risk using the Hospital-patient 1-year Mortality Risk at admission score, a hospital admission score validated to predict 1-year mortality.Main outcomes and measuresThe primary outcome was inhospital mortality. Secondary outcomes included adverse events, resource utilization, and costs.ResultsOf the 17,173 total ICU patients, 3,445 (20.1%) were classified as low-risk at hospital admission. Low-risk patients were younger (48.7 vs 67.5 yr; p < 0.001) and had a lower Multiple Organ Dysfunction Score (2.37 vs 4.14; p < 0.001). Mortality for low-risk patients was significantly lower than for non-low-risk patients (4.1% vs 25.4%; p < 0.001). For low-risk patients, multivariable logistic regression showed mortality was independently associated with older age (odds ratio, 1.02 per 1 yr; 95% CI, 1.00-1.03 per 1 yr), Multiple Organ Dysfunction Score (odds ratio, 1.42 per 1 point; 95% CI, 1.31-1.54 per 1 point), fluid management adverse events (odds ratio, 2.84; 95% CI, 1.29-6.25), hospital-acquired infections (odds ratio, 1.60; 95% CI, 1.02-2.51), and mechanical ventilation (odds ratio, 1.98; 95% CI, 1.20-3.26).Conclusions and relevanceDespite their robust premorbid status, low-risk patients admitted to the ICU had significant inhospital mortality. Fluid management adverse events, hospital-associated infections, multiple organ dysfunction, and mechanical ventilation are important prognostic factors for low-risk patients.

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MuLTi-Arm Therapeutic study in pre-ICu patients admitted with Covid-19-Experimental drugs and mechanisms (TACTIC-E): A structured summary of a study protocol for a randomized controlled trial.

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