Effect of adjunctive tobramycin inhalation versus placebo on early clinical response in the treatment of ventilator-associated pneumonia: the VAPORISE randomized-controlled trial.
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ABSTRACT:
SUBMITTER: Stokker J
PROVIDER: S-EPMC7222068 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
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Effect of adjunctive tobramycin inhalation versus placebo on early clinical response in the treatment of ventilator-associated pneumonia: the VAPORISE randomized-controlled trial.
Stokker Jason J Karami Mina M Hoek Rogier R Gommers Diederik D van der Eerden Menno M
Intensive care medicine 20200123 3
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Project description:BackgroundPsychotic disorders are a leading cause of disability in young adults. Antipsychotics have been the primary intervention for psychosis for over 60 years, and yet, we have made little progress in treating negative symptoms, neurocognition, and functional disability. There is growing evidence that cannabidiol (CBD) is effective in treating positive psychotic symptoms, possibly also negative and neurocognitive symptoms, and moreover is well tolerated compared to other psychotropic medications. Anecdotally, patients participating in the Cognitive Assessment and Risk Evaluation (CARE) Early Psychosis Treatment Program at the University of California, San Diego, are self-administering CBD and report subjective improvement in stress, anxiety, and ability to cope with symptoms. The overarching aim of the trial is to explore the effectiveness of CBD augmentation on symptoms and neurocognition in early psychosis while also exploring the mechanism of action of CBD and predictors of response to treatment. The mechanism by which cannabidiol has a therapeutic effect on psychosis is poorly understood. Recent evidence has suggested that CBD may reduce stress and pro-inflammatory biomarker levels. Endocannabinoids also have powerful roles in eating behavior, reward, and mood, indicating these neurotransmitters may play a role in reducing hyperphagia and metabolic abnormalities that are present early in the course of psychotic illness and exacerbated by antipsychotic medication. The neurophysiological effects of CBD have been studied in animal models of psychosis that show improvements in information processing in response to CBD, but there are no studies in individuals with early psychosis.MethodA total of 120 individuals in the early stages of psychosis will be randomized to 1000 mg of CBD versus placebo as an adjunct to existing treatment in a 8-week, double-blind superiority randomized control trial. The primary outcome measures are symptoms and neurocognition.DiscussionWe hypothesized that CBD will improve symptoms and neurocognition as well as secondary outcome measures of neurohormones, inflammation, eating behaviors, and information processing. Importantly, predictors, moderators, and mediators of the CBD effects will be examined. A better understanding of which individuals are likely to respond to CBD can inform treatment planning and personalize treatment.Trial registrationClinicalTrials.gov NCT04411225. Registered on June 2, 2020.
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Project description:The effect of routine inhalation therapy on ventilator-associated pneumonia (VAP) in mechanically ventilated patients with the coronavirus disease (COVID-19) has not been well-defined. This randomized controlled trial included 175 eligible adult patients with COVID-19 who were treated with mechanical ventilation at the University Hospital of Split between October 2020 and June 2021. Patients were randomized and allocated to a control group (no routine inhalation) or one of the treatment arms (inhalation of N-acetylcysteine; 5% saline solution; or 8.4% sodium bicarbonate). The primary outcome was the incidence of VAP, while secondary outcomes included all-cause mortality. Routine inhalation therapy had no effect on the incidence of bacterial or fungal VAP nor on all-cause mortality (p > 0.05). Secondary analyses revealed a significant reduction of Gram-positive and methicillin-resistant Staphylococcus aureus (MRSA) VAP in the treatment groups. Specifically, the bicarbonate group had a statistically significantly lower incidence of Gram-positive bacterial VAP (4.8%), followed by the N-acetylcysteine group (10.3%), 5% saline group (19.0%), and control group (34.6%; p = 0.001). This difference was driven by a lower incidence of MRSA VAP in the bicarbonate group (2.4%), followed by the N-acetylcysteine group (7.7%), 5% saline group (14.3%), and control group (34.6%; p < 0.001). Longer duration of ventilator therapy was the only significant, independent predictor of any bacterial or fungal VAP in the multivariate analysis (aOR 1.14, 95% CI 1.01-1.29, p = 0.038 and aOR 1.05, 95% CI 1.01-1.10, p = 0.028, respectively). In conclusion, inhalation therapy had no effect on the overall VAP incidence or all-cause mortality. Further studies should explore the secondary findings of this study such as the reduction of Gram-positive or MRSA-caused VAP in treated patients.
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Project description:ObjectiveTo compare the safety and efficacy of adjunctive aripiprazole versus placebo for antipsychotic-induced hyperprolactinemia.MethodsPopulationadult patients presenting with antipsychotic-induced hyperprolactinemia diagnosed by prolactin level with or without prolactin-related symptoms.Interventionsadjunctive aripiprazole vs. adjunctive placebo.Outcome measuresadverse events and efficacy of treatment.Studiesrandomized controlled trials.ResultsFive randomized controlled trials with a total of 639 patients (326 adjunctive aripiprazole, 313 adjunctive placebo) met the inclusion criteria. Adjunctive aripiprazole was associated with a 79.11% (125/158) prolactin level normalization rate. Meta-analysis of insomnia, headache, sedation, psychiatric disorder, extrapyramidal symptom, dry mouth, and fatigue showed no significant differences in the adjunctive aripiprazole treatment group compared with the placebo group (risk difference (Mantel-Haenszel, random or fixed) -0.05 to 0.04 (95% confidence interval -0.13 to 0.16); I(2) =0% to 68%, P=0.20 to 0.70). However, sedation, insomnia, and headache were more frequent when the adjunctive aripiprazole dose was higher than 15 mg/day. Meta-analysis of the prolactin level normalization indicated adjunctive aripiprazole was superior to placebo (risk difference (Mantel-Haenszel, random) 0.76 (95% confidence interval 0.67 to 0.85); I(2) =43%, P<0.00001). The subgroup analysis confirmed that the subjects who received adjunctive aripiprazole 5 mg/day showed a degree of prolactin normalization similar to that of all participants. No significant differences between groups in discontinuation and improvements of psychiatric symptoms.ConclusionAdjunctive aripiprazole is both safe and effective as a reasonable choice treatment for patients with antipsychotic-induced hyperprolactinemia. The appropriate dose of adjunctive aripiprazole may be 5 mg/day.
| S-EPMC3731351 | biostudies-literature
Project description:IntroductionPre-emptive inhaled antibiotics may be effective to reduce the occurrence of ventilator-associated pneumonia among critically ill patients. Meta-analysis of small sample size trials showed a favourable signal. Inhaled antibiotics are associated with a reduced emergence of antibiotic resistant bacteria. The aim of this trial is to evaluate the benefit of a 3-day course of inhaled antibiotics among patients undergoing invasive mechanical ventilation for more than 3 days on the occurrence of ventilator-associated pneumonia.Methods and analysisAcademic, investigator-initiated, parallel two group arms, double-blind, multicentre superiority randomised controlled trial. Patients invasively ventilated more than 3 days will be randomised to receive 20 mg/kg inhaled amikacin daily for 3 days or inhaled placebo (0.9% Sodium Chloride). Occurrence of ventilator-associated pneumonia will be recorded based on a standardised diagnostic framework from randomisation to day 28 and adjudicated by a centralised blinded committee.Ethics and disseminationThe protocol and amendments have been approved by the regional ethics review board and French competent authorities (Comité de protection des personnes Ouest I, No.2016-R29). All patients will be included after informed consent according to French law. Results will be disseminated in international scientific journals.Trial registration numbersEudraCT 2016-001054-17 and NCT03149640.
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Project description:RationaleEnteral administration of probiotics may modify the gastrointestinal environment in a manner that preferentially favors the growth of minimally virulent species. It is unknown whether probiotic modification of the upper aerodigestive flora can reduce nosocomial infections.ObjectivesTo determine whether oropharyngeal and gastric administration of Lactobacillus rhamnosus GG can reduce the incidence of ventilator-associated pneumonia (VAP).MethodsWe performed a prospective, randomized, double-blind, placebo-controlled trial of 146 mechanically ventilated patients at high risk of developing VAP. Patients were randomly assigned to receive enteral probiotics (n = 68) or an inert inulin-based placebo (n = 70) twice a day in addition to routine care.Measurements and main resultsPatients treated with Lactobacillus were significantly less likely to develop microbiologically confirmed VAP compared with patients treated with placebo (40.0 vs. 19.1%; P = 0.007). Although patients treated with probiotics had significantly less Clostridium difficile-associated diarrhea than patients treated with placebo (18.6 vs. 5.8%; P = 0.02), the duration of diarrhea per episode was not different between groups (13.2 ± 7.4 vs. 9.8 ± 4.9 d; P = 0.39). Patients treated with probiotics had fewer days of antibiotics prescribed for VAP (8.6 ± 10.3 vs. 5.6 ± 7.8 d; P = 0.05) and for C. difficile-associated diarrhea (2.1 ± 4.8 SD d vs. 0.5 ± 2.3 d; P = 0.02). No adverse events related to probiotic administration were identified.ConclusionsThese pilot data suggest that L. rhamnosus GG is safe and efficacious in preventing VAP in a select, high-risk ICU population. Clinical trial registered with www.clinicaltrials.gov (NCT00613795).
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Project description:BACKGROUND:Vitamin D status may influence heart failure (HF) patient outcomes by affecting b-type natriuretic peptide (BNP), parathyroid hormone (PTH), and enhancing cardiac contractility. Vitamin D deficiency is associated with morbidity and mortality in HF patients. The objective of this study was to determine if vitamin D3 at a comparatively high dose would replete 25-hydroxyvitamin D (25(OH)D) stores, improve BNP, PTH, cardiopulmonary function, reduce inflammatory markers, and improve quality of life (QOL) in HF patients. METHODS:This was a 6 month, parallel group, double-blind, placebo-controlled, single clinic center, randomized trial of supplemental vitamin D3 using a dose of 10,000 IU daily or placebo in 40 vitamin D deficient or insufficient (25(OH)D level ≤ 32 ng/ml) patients with stable New York Heart Association Class II-III HF in a specialty cardiology clinic. All variables were measured at baseline and 6 months. Values between the two treatment groups were assessed using Student's t-test or Mann-Whitney Test. Univariate analysis of covariance was conducted to adjust for variance in baseline 25(OH)D. RESULTS:All results were adjusted for baseline 25(OH)D. The change in BNP from baseline was ∆ +30 ± 950 pg/ml for treatment vs. placebo ∆ +400 ± 1900 pg/ml, p = 0.003. 25(OH)D serum levels rose by 49 ± 32 ng/ml in the treatment group vs 4 ± 10 ng/ml in the placebo group, p < 0.001. PTH and exercise chronotropic response index improved in the treatment group vs placebo group, respectively, but both were attenuated by adjustment ((∆-20 ± 20 pg/ml vs ∆ + 7 ± 53 pg/ml respectively (p = 0.01, adjusted p = 0.07)) and (∆ + 0.13 ± 0.26 vs. ∆-0.03 ± 02.9 respectively, p < 0.01, adjusted p = 0.17)). Other measured cardiopulmonary parameters remained unchanged. High sensitivity C-reactive protein (hsCRP) remained unchanged for women, but improved for men (∆-2 ± 4 treatment versus ∆2 ± 5 mg/L placebo, p = 0.05). QOL scores, including composite overall and clinical summary scores significantly improved in treatment compared to placebo (∆ + 10 ± 15 versus -6 ± 15, p < 0.01 and ∆ + 8 ± 14 versus -8 ± 18, p = 0.01, respectively). CONCLUSIONS:Repletion of 25(OH)D may improve QOL in HF patients and may help to normalize BNP, PTH, and hsCRP. TRIAL REGISTRATION:Clinicaltrials.gov, Trial Registration Number: NCT01636570 , First registered 3 July 2012.
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2018-03-01 | GSE97248 | GEO
Project description:Two previous randomized controlled trials (RCTs) suggested that adjunctive aspirin is efficacious in treating schizophrenia. We conducted two 16-week double-blind randomized placebo-controlled RCTs of adjunctive 1000 mg aspirin vs placebo in schizophrenia. Study 1 included 200 patients, with Positive and Negative Syndrome Scale (PANSS) total score as the primary outcome. Study 2 included 160 patients with C-reactive protein (CRP) >1 mg/L at baseline; the primary outcome was PANSS-positive score. Dropout rates for aspirin/placebo were 12% in study 1 and 20% in study 2. Differences in outcome between aspirin and placebo were calculated with linear regression, adjusting for the baseline value of the outcome. No statistically significant between-group differences were found in primary or secondary outcomes in either study. Study 1: mean difference in PANSS at 16 weeks was -3.9 (95% CI: -8.4 to 0.5, P = .10, effect size (ES) = -0.25) and at 8 weeks was -3.5 (95% CI: -7.5 to 0.5, P = .11, ES = -0.22). Study 2: mean difference in PANSS at 16 weeks was 0.3 (95% CI: -4.1 to 4.7, P = .90, ES = 0.02) and in positive PANSS was 0.5 (95% CI: -1.0 to 2.1, P = .50, ES = 0.11). A meta-analysis of these data with the existing studies, excluding one with large baseline differences in total PANSS, found that the overall estimate of the effect of adjunctive aspirin on the PANSS total score comparing group means at the end of the study was -2.9 (95% CI: -6.6 to 0.7; P = .21), favoring aspirin. Our studies and meta-analysis failed to find a statistically significant improvement in the symptoms of schizophrenia from adjunctive aspirin therapy in comparison to placebo in schizophrenia. Trial registration: study 1: Clinicaltrials.gov: NCT01320982; study 2 (high CRP): EudraCT Number: 2014-000757-36.
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