The effects of different types of smoking on recovery from attack in hospitalized multiple sclerosis patients.

BACKGROUND: Several studies demonstrated the association between tobacco smoking and higher risk and increased progression of multiple sclerosis (MS). Data about the effect of smoking during the recovery from MS attacks is limited. Furthermore, different types of tobacco exposures such as water pipe and passive smoking are not well assessed separately. So this study evaluated the effect of different types of smokes, cigarette and water pipe as well as passive smoking on the function recovery of relapsing-remitting MS (RRMS) attacks METHODS: This cohort study evaluated the adult patients with RRMS and Expanded Disability Status Scale (EDSS) < 5 in the attack phase. Patients were divided into two groups: smokers and non-smokers. The smokers included those who use cigarette, water pipe as well as passive smokers as subgroups for more analyses later. EDSS was monitored after relapse and two months after relapse. Change of EDSS considered as the criteria for functional recovery. The correlation between the amount of consumption and disability level was assessed among smokers by Pearson's correlation test. While, the difference of EDSS between smoker and non-smoker were assessed by Independent samples T-test. RESULTS: 142 patients were evaluated. 79 (55.6%) were smokers (43% male) while 63 (44.4%) were non-smokers (36.5% male). There was a statistically significant difference in change of EDSS between smoker and non-smoker groups, which change of EDSS was higher in non-smoker (-2.62 ± 0.90 non-smoker vs. -1.75 ± 0.76 smoker, P < 0.001). Also, only there was a significantly lesser decline in EDSS after two months in the cigarette smokers in subgroups analyses (P < 0.001). A correlation analysis revealed a significant positive correlation between the number per day of cigarette smoking and EDSS after relapse (r = 0.3, P = 0.03) and a significant positive correlation between minutes per month of smoking of water pipe and EDSS two months after relapse (r =  0.6 , P > 0.001). CONCLUSION: Tobacco smoking especially cigarette smoking is associated with a negative effect on recovery from the attack in patients with RRMS.

Using Two Predictor Scoring Systems Together to Increase the Chance of Identifying the Augmented Renal Clearance Phenomenon: A Cross-sectional Study.

INTRODUCTION: Augmented Renal Clearance (ARC) reflects a measured creatinine clearance (CrCl) of more than 130 ml/min. Also, there are two scoring systems for the prediction of the ARC phenomenon i.e., the ARC score (ARCS) and the Augmented Renal Clearance in Trauma Intensive Care score (ARCTICs). The objectives of the current study were the evaluation the effect of using both scoring systems, on the chance of identifying this phenomenon and evaluating the accuracy of the three commonly used formulas for estimating glomerular filtration rate (eGFR) in ICU patients. METHODS: In this prospective cross-sectional study, the CrCls of all patients admitted to the ICU were evaluated by using ARCS and ARCTICS, and for high-risk subjects based on scoring systems, a 12-hour urine sample was collected to measure CrCl. Besides, daily serum creatinine was recorded to estimate the daily eGFR. RESULTS: During the study period, 810 subjects were evaluated and 145 were categorized as high-risk using scoring systems. The ARC phenomenon was confirmed in 79 patients on the recruitment day and 81.01 and 18.98% of them were recruited by ARCS and ARCTICS, respectively. The ROC curves showed AUCs > 0.5 for CockcroftGault (C-G) and CKD-EPI with the cut-off of 100.48 and 107.05 mL/min/ 1.73m2, respectively; to detect the ARC phenomenon. CONCLUSION: We recommend using ARCS and ARCTICS simultaneously to assess critically ill patients regarding the possibility of the ARC phenomenon which should be confirmed by using urinary CrCl, as none of the formulas could accurately detect the ARC phenomenon, neither the 12-hour CrCl.  DOI: 10.52547/ijkd.6695.

Are Antibiotics Appropriately Dosed in Critically Ill Patients with Augmented Renal Clearance? A Narrative Review.

Aims: Augmented renal clearance (ARC), which is commonly defined as increased renal clearance above 130 ml/min/1.73 m2, is a common phenomenon among critically ill patients. The increased elimination rate of drugs through the kidneys in patients with ARC can increase the risk of treatment failure due to the exposure to subtherapeutic serum concentrations of medications and affect the optimal management of infections, length of hospital stay, and outcomes. The main goal of this review article is to summarize the recommendations for appropriate dosing of antibiotics in patients with ARC. Methods: This article is a narrative review of the articles that evaluated different dosing regimens of antibiotics in patients with ARC. The keywords "Augmented Renal Clearance," "Critically ill patients," "Drug dosing," "Serum concentration," "Beta-lactams," "Meropenem," "Imipenem," "Glycopeptide," "Vancomycin," "Teicoplanin," "Linezolid," "Colistin," "Aminoglycosides," "Amikacin," "Gentamycin," "Fluoroquinolones," "Ciprofloxacin," and "Levofloxacin" were searched in Scopus, Medline, PubMed, and Google Scholar databases, and pediatric, nonhuman, and non-English studies were excluded. Results: PK properties of antibiotics including lipophilicity or hydrophilicity, protein binding, the volume of distribution, and elimination rate that affect drug concentration should be considered along with PD parameters for drug dosing in critically ill patients with ARC. Conclusion: This review recommends a dosing protocol for some antibiotics to help the appropriate dosing of antibiotics in ARC and decrease the risk of subtherapeutic exposure that may be observed while receiving conventional dosing regimens in critically ill patients with ARC.

Compensatory Role of Insulin in the Extinction but Not Reinstatement of Morphine-Induced Conditioned Place Preference in the Streptozotocin-Induced Diabetic Rats.

Insulin receptors are distributed in the whole brain, including different parts of the reward circuit that modulate dopamine as the primary neurotransmitter implicated in addiction. The goal of the current study was to illuminate the role of insulin in the extinction period and reinstatement of morphine-induced conditioned place preference (CPP) in the naïve and diabetic rats. One hundred and twelve male rats were randomly divided into two naïve and diabetic groups. Diabetes was induced by one dose administration of streptozotocin (STZ; 60 mg/kg; IP) ten days before the conditioning procedure. To evaluate the insulin's role in the duration of extinction period of morphine-CPP, naïve and diabetic rats received insulin (10 U/kg; IP) before each morphine injection (5 mg/kg; sc) during the 3-day conditioning phase. All rats that passed the conditioning phase and then underwent the extinction period. Morphine priming-induced reinstatement was determined in both naïve and diabetic rats by injection of different ineffective doses of morphine (0.5 and 1 mg/kg; sc) in extinguished rats. In the following experiments, three groups of diabetic rats received insulin during the conditioning, expression, or reinstatement phase to illustrate insulin's effect on the morphine-induced reinstatement and the duration of the extinction period (insulin was only treated during the acquisition phase). The results showed that the extinction period and reinstatement of morphine were potentiated in the STZ-induced diabetic rats. The obtained findings also revealed that insulin replacement shortened the extinction period of morphine-induced CPP in STZ-diabetic rats. However, insulin replacements in conditioning, expression, and reinstatement phases did not affect morphine priming-induced reinstatement in diabetic animals.

The Evaluation of the Neuroprotective Effect of a Single High-Dose Vitamin D3 in Patients with Moderate Ischemic Stroke.

INTRODUCTION: Vitamin D insufficiency is highly prevalent and is a negative predictor for survival in ischemic stroke patients. We evaluated the effect of a high dose of vitamin D3 on the Neuron-Specific Enolase (NSE) level, National Institute of Health Stroke Scale (NIHSS), and Barthel Index (BI) scoring system in moderate ischemic stroke patients. METHODS: This prospective, double-blind, randomized clinical trial (RCT) study was conducted from April 2020 to March 2021. Patients with moderate ischemic stroke (NIHSS 5 to 15) who had vitamin D deficiency (serum 25-OH vitamin D ≤30 ng/mL) were recruited and randomized into intervention and control groups. Subjects in the intervention group received a single dose, intramuscular (IM) injection of 600000 international unit (IU) vitamin D3, in addition to the standard treatment. NSE level and NIHSS were evaluated at baseline and 48 hours after the intervention. The BI was monitored three months after discharge. RESULTS: During the study period, 570 patients were assessed; finally, forty-one patients completed the study. Except for the age which was higher in the control group (p = 0.04), there were no statistically significant differences in other baseline characteristics between the two groups. After 48 hours, the NIHSS score was significantly lower in the intervention group (median 8 vs. 6.5, p = 0.008 in the control and intervention groups, respectively), but there was no significant difference in the NSE level (p = 0.80). Three months after discharge, the BI was significantly higher in the intervention group (median 8 vs. 9, p = 0.03 in the control and intervention groups, respectively). CONCLUSIONS: Administration of a single 600000 IU of vitamin D3 could have neuroprotective effects in patients with moderate ischemic stroke, according to its significantly positive effects on functional clinical outcomes (NIHSS and BI), but this effect on the biomarker related to neural damage (NSE) was not significant.

Insulin replacement prevents the acquisition but not the expression of morphine-induced conditioned place preference in streptozotocin-induced diabetic rats

Abstract Insulin receptors have distributed in all brain regions, including the nucleus Accumbens (NAc), and where is implicated in the reward properties of drugs. It is well known that insulin signaling can regulate dopamine release. Therefore, in the present study, we tried to examine the effect of insulin replacement on the acquisition and expression of morphine-induced conditioned place preference (CPP) in diabetic rats. Forty-eight male Wistar rats were divided into two non-diabetic (Naïve) and diabetic groups rendered by a single injection of streptozotocin (STZ). These groups separately received insulin (10U/kg) or saline (1 ml/kg) one hour prior to morphine administration (5mg/kg;s.c.) during conditioning days (acquisition phase) or post-conditioning day (expression phase) in the CPP paradigm. In this paradigm, conditioning score (CS) and locomotion activity were recorded by Ethovision. The STZ-induced diabetic rats displayed higher CS compared to naïve rats (P<0.05). This effect was abolished in all diabetic rats that received insulin during conditioning days but not the expression phase. This study has provided evidence that insulin plays a modulatory role in morphine-induced CPP, and insulin replacement during the acquisition phase could reduce the rewarding properties of morphine in diabetes conditions through a possible modulating effect on dopamine release in the NAc region

Evaluation of pharmacokinetic and pharmacodynamic parameters of meropenem in critically ill patients with acute kidney disease.

PURPOSE: No study has been evaluated pharmacokinetic (PK) and pharmacodynamic (PD) properties of ß-lactam antibiotics in patients with acute kidney injury (AKI), not requiring renal replacement therapy (RRT). We evaluated the time that plasma concentrations remain above four times the MIC (ft > 4MIC) and PK parameters of meropenem in this population. METHODS: In this prospective, randomized clinical trial (RCT), all patients received standard dose (3 g daily) of meropenem for 48 h, then randomly allocated in standard or adjusted groups. The standard group received meropenem without dose adjustment. In the adjusted group, the meropenem dose was adjusted based on the Cockcroft-Gault(C-G) equation. Meropenem concentrations were measured at the peak and trough times on the 2nd and 5th days of the study. RESULTS: On the 2nd day of the study, 3 out of 10 (30%) of patients attained the PD target (≥ 80%ft > 4MIC). In the 5th day of the study, the PD target was attained in 2 out of 10 (20%) and 1 out of 5 (20%) of patients who received standard and adjusted doses of meropenem, respectively (p = 1). In all samples, increased volume of distribution (Vd) (median; IQR) (46.04; 23.06-103.18 L), terminal half-life (T1/2) (4.51; 2.67-8.88 h) and decreased clearance (6.52; 4.43-10.16 L/h) have been shown. CONCLUSION: In critically ill patients with AKI, who not receive RRT, standard doses, and adjusted according to renal function of meropenem failed to achieve PD target of ≥ 80%ft > 4MIC. Higher doses are required for this target. RETROSPECTIVELY REGISTERED: The study protocol with registered retrospectively and approved on January 19, 2019, with the number of IRCT20160412027346N5.

Cytarabine and Doxorubicin-Induced Palmoplantar Erythrodysesthesia Syndrome: The Possible Role of Voriconazole Interaction.

Palmoplantar Erythrodysesthesia Syndrome (PPES) caused by chemotherapeutic agents is rarely life threatening and requires a reduction in dose or discontinuation of chemotherapy. The use of cytarabine and doxorubicin in the treatment of acute myeloid leukemia (AML) along with voriconazole can potentially alter the metabolism of the drugs and cause some interactions. In this study, we presented a case of AML who received cytarabine and doxorubicin as a chemotherapy regimen and voriconazole as a prophylactic anti-fungal. In this combination, voriconazole probably inhibits the P-glycoprotein pump, which leads to an increase in the cytarabine concentration. The emphasis of this report is the awareness of clinicians and pharmacotherapists about these interactions.

Comparison of Intravenous Ampicillin-sulbactam Plus Nebulized Colistin with Intravenous Colistin Plus Nebulized Colistin in Treatment of Ventilator Associated Pneumonia Caused by Multi Drug Resistant Acinetobacter Baumannii: Randomized Open Label Trial.

The purpose of this study was evaluating the efficacy and safety of intravenous (IV) ampicillin-sulbactam plus nebulized colistin in the treatment of Ventilator-Associated Pneumonia (VAP) caused by MDR Acinetobacter (MDRA) in ICU patients as an alternative to IV plus nebulized colistin. In this single-blinded RCT, one group received IV colistin and another group IV ampicillin-sulbactam (16 and 12 patients from total 28 patients, respectively) for 14 days or since clinical response. Both groups received nebulized colistin by mesh nebulizer. There were no statistically significant differences between the 2 groups in baseline characteristics and previous antibiotic therapy. In follow up period, no significant difference was observed between 2 groups in rate of microbiological eradication, clinical signs of VAP improvement, survival rate and length of hospital as well as ICU stays. Although we have found no significant differences in Acute Kidney Injury (AKI) incidence between two groups, comparison of cumulative patient-days with stages 2 and 3 AKI with days with no or stage 1 AKI, according to AKIN criteria, revealed significant difference in IV colistin versus IV ampicillin-sulbactam group (p = 0.013). The results demonstrated that the high dose IV ampicillin-sulbactam plus nebulized colistin regimen has comparable efficacy with IV plus nebulized colistin in the treatment of VAP caused by MDRA, with sensitivity to colistin only, with probably lower incidence of kidney injury.

Streptozotocin-induced diabetes affects the development and maintenance of morphine reward in rats.

Diabetes mellitus is a chronic illness that has been associated with the decrease of insulin in type I diabetes. Insulin has an impact not only on the direct control of food intake and plasma glucose levels, but also on brain pathways associated with reward. It affects brain reward pathways through regulation of the dopamine (DA) transporter (DAT). Moreover, it has been found to affect the ability of drugs that target the DA system. In the present study, the effects of streptozotocin (STZ)-induced diabetes on the acquisition (development) and maintenance of morphine-induced conditioned place preference (CPP) were investigated in rats. Forty adult male Albino Wistar rats were used in these experiments. For induction of diabetes, STZ was administered at a dose of 60 mg/kg. After seven days, the CPP paradigm was done; conditioning score and locomotor activity were recorded by Ethovision software. The results showed that diabetes significantly increased the magnitude of conditioning scores, acquisition of morphine-induced CPP in compared to naive animals (P<0.05). Moreover, in the diabetic group, there were significant differences among conditioning scores in the post-conditioning phase and the last four days (7th-10th), but these differences elongated up to 10 days after the CPP protocol while the extinction period was eight days in the naive group. Our findings indicated that the magnitude and maintenance of morphine rewarding properties have been changed in STZ-induced diabetic animals. It seems that a level of insulin and their receptors are involved in the development and maintenance of morphine-induced CPP in the rats.