Optimal dosing interval of intravenous Colistin monotherapy versus combination therapy: A systematic review and meta-analysis.

We aimed to maximize the clinical response and effectiveness of colistin antibiotics in patients with multi-drug (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria, there is an increasing interest in colistin combination therapy with other antibiotics and extended interval dosing regimens. This systematic review and meta-analysis aim is to evaluate if the combination therapy is superior to monotherapy with colistin regarding increased survival and also which dose interval is the most effective to utilize. English language, peer-reviewed journal publications from the first date available to 25 January 2022 were identified by searching the PubMed and Web of Science databases. Forest plots for overall and subgroups and funnel plots were graphed. 42 studies were included in the study. Among them, 38 studies were on combination therapy, and four on dose interval. The overall pooled odds ratio is 0.77 (CI: 0.62; 0.95) (p value < 0.017). The I^2 value was 43% (p value < 0.01). The Begg correlation test of funnel plot asymmetry showed no significant publication bias (0.064). The overall pooled odds ratio for Carbapenem is 0.74 (CI: 0.48; 1.13). A prospective randomized controlled trials (RCT) on 40 adults intensive care unit (ICU) patients with ventilator-associated pneumonia (VAP), comparing the mortality and ICU length of stay of 8- or 24- hour intervals regimens, showed that the ICU length of stay and ICU mortality were; 31.31, 35.3 days, and 32.06, 22.2% in groups 24-h interval and 8- hour interval (p value: 0.39, 0.87), respectively. It seems that combination therapy is associated with drug synergism and increased survival. The extended interval colistin administration may result in higher peak concentration and bacterial eradication. In both cases, we face a dearth of literature.

The effects of memantine on the serum concentrations of matrix metalloproteinases and neurologic function of patients with ischemic stroke.

Memantine was suggested as a promising treatment for stroke due to its neuroprotective property and efficacy in reducing ischemic brain injury and improving post-ischemic neurological recovery. This pilot, open-label, randomized clinical trial was conducted to investigate the impact of memantine on serum concentrations of matrix metalloproteinases (MMP)-2 and MMP-9, as neuronal damage biomarkers, and neurologic function evaluated by the National Institute of Health Stroke Scale(NIHSS) and Barthelindex(BI) in patients with ischemic stroke. Admitted patients with mild to moderate ischemic stroke were assessed for eligibility, and eligible patients were randomized to the intervention or control group. Enrolled patients in the intervention group received 20 mg memantine every 8 h for five days and then 20 mg daily for three months. Both groups managed with the standard treatments. From 77 randomized patients, 29 participants in the control group and 24 patients in the intervention group completed the study. Data showed that the increase in the serum concentrations of MMP-9 within the first 5 days of the study was significantly lower in the intervention group (P = 0.005). This effect of memantine on the MMP-2 was not significant (P = 0.448). memantine also could significantly improve the neurologic function of the patients according to NIHSS (P < 0.0001) and BI (P = 0.002) during hospitalization and after that. In conclusion, memantine could be considered as a neuroprotective agent in patients with mild to moderate ischemic stroke, based on its significant effects on reducing brain damage and improving neurologic function of the patients.

Impact of a High-protein Nutritional Intake on the Clinical Outcome of the Neurocritical Patients.

Disease-related malnutrition of neurocritical illness harms its treatment, which increases the mortality rate. The aim of this study was evaluating the effect of a high protein diet on the dietary factors, clinical outcome, and mortality rate of neurocritical patients. In a randomized controlled trial, 15 neurocritical patients were recruited in each group. The patients in the intervention and control groups received high protein and conventional protein regimens, respectively. The Clinical Extended Glasgow Outcome Scale (GOSE) measured at one, two, and three months later. Acute Physiology and Chronic Health Evaluation II (APACHE-II) score, Glasgow Coma Scale, the serum level of transthyretin (TTR) on the first, 3rd and fifth days of admission, and nitrogen balance (NB) at the baseline and fifth day of the study were recorded. Thirty patients, 15 in each group, entered into the study. There was no statistically significant difference in the baseline characteristics of the patients between the two groups of the study. The 28-days-mortality rate in the intervention and control group were 33.3% (n = 5) and 73.3% (n = 11), P-value = 0.034, respectively. The GOSE scores were higher in the patients who received a high protein diet, and lower in the patients with lower baseline TTR, higher APACHE-II score, older age, and a baseline negative nitrogen balance. The high protein diet may decrease the mortality rate, and improve the clinical outcome of neurocritical patients. The baseline TTR level, APACHE II score, and NB are prognostic factors for the prediction of the GOSE in neurocritical patients.

The Antioxidant Capacity and Anti-diabetic Effect of Boswellia serrata Triana and Planch Aqueous Extract in Fertile Female Diabetic Rats and the Possible Effects on Reproduction and Histological Changes in the Liver and Kidneys.

BACKGROUND: Boswellia serrata has been used in a wide variety of diseases, including diabetes mellitus and inflammatory diseases. OBJECTIVES: This study focused on the effects of Boswellia serrata aqueous extract on blood glucose and the complications of diabetes in the liver and kidneys and examined the impact of plant on reproduction in diabetic rats. MATERIALS AND METHODS: The antioxidant capacity of plant extract was performed using FRAP assay. Diabetic and control rats were administered 200, 400, and 600 mg/kg Boswellia serrata extract. Vaginal plaque was mentioned as a positive sign of pregnancy ;and treatment started with extract or vehicle from 1th to 17th day of gestation by gastric gavage. Blood glucose was measured during 17 days. RESULTS: The Administration of Boswellia serrata in diabetic rats significantly decreased the level of blood glucose and HbA1c after 17th days (P ≤ 0.01). In diabetic group that received no treatment, the abortion of fetus spontaneous was 19.14%. The percentage of absorptions significantly was elevated in vehicle-treated diabetic rats, in comparison with vehicle- treated healthy rats. In the diabetic group, separated necrosis of hepatocytes, anarchism of liver plates, and lymphocytic inflammation were improved. Diabetic complications were not seen and the severity of damage was reduced. These damages include: lymphocytic inflammation in the port areas, irregularities, apoptosis of liver cells, and dilatation of the sinusoids. CONCLUSIONS: The results suggest that Boswellia serrata extract has the antidiabetic effects and can prevent the complications of diabetes in the kidneys and liver.