Cost-effectiveness Analysis of Triptorelin, Goserelin, and Leuprolide in the Treatment of Patients with Metastatic Prostate Cancer: A Societal Perspective.

OBJECTIVES: Metastatic prostate cancer is the most common malignant cancer and the second leading cause of death due to various types of cancer among men after lung cancer. This study aimed to analyze the cost-effectiveness of triptorelin, goserelin, and leuprolide in the treatment of the patients with metastatic prostate cancer from the societal perspective in Iran in 2020. METHODS: This is a cost-effectiveness study in which a 20-year Markov transition modeling was applied. In this study, local cost and quality-of-life data of each health state were gathered from cohort of patients. The TreeAge pro 2020 and Microsoft Excel 2016 software were used to simulate cost-effectiveness of each treatment in the long term. The one-way and probabilistic sensitivity analyses were also performed to measure robustness of the model outputs. RESULTS: The findings indicated that the mean costs and utility gained over a 20-year horizon for goserelin, triptorelin, and leuprolide treatments were $ 13 539.13 and 6.365 quality-adjusted life-years (QALY), $ 18 124.75 and 6.658 QALY, and $ 26 006.92 and 6.856 QALY, respectively. Goserelin was considered as a superior treatment option, given the estimated incremental cost-effectiveness ratio. The one-way and probabilistic sensitivity analyses confirmed the robustness of the study outcomes. CONCLUSIONS: According to the results of the present study, goserelin was the most effective and cost-effective strategy versus 2 other options. It could be recommended to policy makers of the Iran healthcare system to prioritize it in clinical guidelines and reimbursement policies.

Aminoglycosides: single- or multiple-daily dosing? An updated qualitative systematic review of randomized trials on toxicity and efficacy.

INTRODUCTION: Aminoglycosides are among the first-choice antibiotics for routine clinical use. However, dose-limiting factors such as ototoxicity and nephrotoxicity are considered as serious complications of aminoglycosides. OBJECTIVE: In this systematic review, the main goal was to investigate the efficacy and incidence of nephrotoxicity and ototoxicity of once-daily dosing (ODD) and multiple daily dosing (MDD) regimens of aminoglycosides through available randomized controlled trials (RCTs). METHODS: We performed a literature-based research in relevant databases, including EMBASE, MEDLINE, and SCOPUS published between 1987 and 2023 using the keywords "aminoglycosides", "pharmacokinetics", "ODD", "MDD", "once daily", "multiple daily", "dosing regimen", "nephrotoxicity", "ototoxicity", "efficacy", "safety", and "toxicity". As so told, the results of this article were limited to papers available in English. Our initial search yielded 1124 results. After a review of the titles and abstracts of the articles, 803 articles were excluded from this study because they did not address the toxicity and effectiveness of ODD versus MDD of aminoglycosides. A total number of 21 studies on gentamicin, tobramycin, netilmicin, and amikacin met the inclusion criteria for the efficacy of aminoglycosides and their role in ototoxicity and nephrotoxicity were included in this review. Studies recruited different age classes, and the age of relevant cohorts varied from only a few days to more than 70 years. RESULTS: The most common clinical condition in the included studies was cystic fibrosis. CONCLUSION: In most studies, there were no significant differences between the two regimens regarding ototoxicity. In addition, the ODD regimens were safer than MDD concerning nephrotoxicity.

The ameliorating effect of limosilactobacillus fermentum and its supernatant postbiotic on cisplatin-induced chronic kidney disease in an animal model.

BACKGROUND: Chronic kidney disease (CKD) is a worldwide public health problem affecting millions of people. Probiotics and postbiotics are associated with valuable compounds with antibacterial, anti-inflammatory, and immunomodulatory effects, preserving renal function in CKD patients. The current study is aimed to evaluate the efficacy of Limosilactobacillus fermentum (L. fermentum) and its postbiotic in an animal model of cisplatin-induced CKD. METHODS: The animals were divided into four experimental groups (normal mice, CKD mice with no treatment, CKD mice with probiotic treatment, and CKD mice with postbiotic treatment). CKD mice were induced by a single dose of cisplatin 10 mg/kg, intraperitoneally. For 28 days, the cultured probiotic bacteria and its supernatant (postbiotic) were delivered freshly to the related groups through their daily water. Then, blood urea nitrogen (BUN) and creatinine (Cr) of plasma samples as well as glutathione (GSH), lipid peroxidation, reactive oxygen species, and total antioxidant capacity of kidneys were assessed in the experimental mice groups. In addition, histopathological studies were performed on the kidneys. RESULTS: Application of L. fermentum probiotic, and especially postbiotics, significantly decreased BUN and Cr (P < 0.0001) as well as ROS formation and lipid peroxidation levels (P < 0.0001) along with increased total antioxidant capacity and GSH levels (P < 0.001). The histopathologic images also confirmed their renal protection effect. Interestingly, the postbiotic displayed more effectiveness than the probiotic in some assays. The improvement effect on renal function in the current model is mainly mediated by oxidative stress markers in the renal tissue. CONCLUSIONS: In conclusion, it was found that the administration of L. fermentum probiotic, and particularly its postbiotic in cisplatin-induced CKD mice, showed promising effects and could successfully improve renal function in the animal model of CKD. Therefore, probiotics and postbiotics are considered as probably promising alternative supplements to be used for CKD.

Acute kidney injury in COVID-19 patients receiving remdesivir: A systematic review and meta-analysis of randomized clinical trials

Abstract Objectives: Remdesivir is an antiviral agent with positive effects on the prognosis of Coronavirus Disease (COVID-19). However, there are concerns about the detrimental effects of remdesivir on kidney function which might consequently lead to Acute Kidney Injury (AKI). In this study, we aim to determine whether remdesivir use in COVID-19 patients increases the risk of AKI. Methods: PubMed, Scopus, Web of Science, the Cochrane Central Register of Controlled Trials, medRxiv, and bio-Rxiv were systematically searched until July 2022, to find Randomized Clinical Trials (RCT) that evaluated remdesivir for its effect on COVID-19 and provided information on AKI events. A random-effects model metaanalysis was conducted and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation. The primary outcomes were AKI as a Serious Adverse Event (SAE) and combined serious and non-serious Adverse Events (AE) due to AKI. Results: This study included 5 RCTs involving 3095 patients. Remdesivir treatment was not associated with a significant change in the risk of AKI classified as SAE (Risk Ratio [RR]: 0.71, 95% Confidence Interval [95% CI] 0.43‒1.18, p = 0.19, low-certainty evidence) and AKI classified as any grade AEs (RR = 0.83, 95% CI 0.52‒1.33, p = 0.44, low-certainty evidence), compared to the control group. Conclusion: Our study suggested that remdesivir treatment probably has little or no effect on the risk of AKI in COVID-19 patients.

A randomized double-blinded placebo-controlled clinical trial on protective effects of pentoxifylline on gentamicin nephrotoxicity in infectious patients.

BACKGROUND AND OBJECTIVE: Renal toxicity has limited gentamicin use in clinical practice. The aim of the present clinical trial was to assess the possible nephroprotective effects of pentoxifylline (PTX) against gentamicin nephrotoxicity. MATERIALS AND METHODS: A multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted on patients who had the indication for systemic gentamicin for at least 7 days. Sixty people were selected and randomly assigned. For patients in the intervention and control groups, 400 mg PTX sustained release tablet and placebo were given orally three times daily, respectively. Demographic, clinical, laboratory, and therapeutic information of patients were recorded. malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) levels in serum were measured on days 0 and 7. RESULTS: The incidence of nephrotoxicity in the placebo group was 19.6 times higher than that in the PTX group (OR = 19.6, 95%CI = 3.08-114.32; P value = 0.001). The mean ± SD time onset of ATN was 4.00 ± 2.32 and 5.58 ± 1.59 days in PTX and placebo recipients, respectively (P value < 0.001). No significant differences were observed for hypokalemia, hypomagnesemia, potassium and magnesium wasting between the two groups. The mean ± SD levels of serum MDA and TNF-α at day 7 were significantly lower in the PTX compared to those in the placebo group (P value < 0.001 for both indexes). CONCLUSION: The co-administration of 400 mg PTX orally three times daily along with gentamicin was both well-tolerated and effective in preventing the nephrotoxicity of gentamicin in patients with different infectious diseases.

The Pattern of Cyclosporine Nephrotoxicity and Urinary Kidney Injury Molecule 1 in Allogenic Hematopoietic Stem Cell Transplant Patients.

OBJECTIVES: The typical immunosuppressive regimen of hematopoietic stem cell transplant includes cyclosporine. However, cyclosporine nephrotoxicity is a concern. We studied cyclosporine nephrotoxicity epidemiology in hematopoietic stem cell transplant patients and compared the pattern and urinary levels of the KIM-1 kidney injury molecule versus serum and urine creatinine levels. MATERIALS AND METHODS: The study covered 10 months at Namazi Hospital, Shiraz, Iran. All patients met the following criteria: > 15 years old, received allogenic hematopoietic stem cell transplant without history of acute or chronic kidney disease, and scheduled for at least 1 week of cyclosporine treatment. Urinary and serum levels of creatinine, urea, sodium, potassium, magnesium, and the KIM-1 kidney injury molecule were measured on days 0, 3, 5, 7, 10, and 14 of cyclosporine treatment. RESULTS: Of 42 patients, one-third developed cyclosporine nephrotoxicity (30.95%), and median onset time was 15 days. Hypokalemia and hypomagnesemia were reported in 76.2% and 53.4% of the cohort, respectively. None of the demographic, clinical, and paraclinical parameters was significantly associated with cyclosporine nephrotoxicity. Median duration of hospital stay for patients with cyclosporine nephrotoxicity (41 days) was significantly higher (P < .001) than those without nephrotoxicity (29 days). Area under the curve for receiver operating characteristic showed that accuracy of serum creatinine (0.267; 95% CI, 0.11-0.43) at day 0 of cyclosporine treatment was significantly lower (P = .017) than the accuracy of urine creatinine (0.477; 95% CI, 0.28-0.67) and urine levels of the KIM-1 kidney injury molecule (0.594; 95% CI, 0.41-0.78). CONCLUSIONS: Cyclosporine nephrotoxicity is a common adverse effect in the setting of hematopoietic stem cell transplant and occurs mostly within the first 2 weeks of cyclosporine treatment. Urine KIM-1 kidney injury molecule measurement had no overall superiority and no improved accuracy over serum or urine creatinine measurements for prediction or detection of cyclosporine nephrotoxicity.

Comparison of Ceftizoxime Plus Ampicillin-Sulbactam versus Gentamicin Plus Ampicillin-Sulbactam in the Prevention of Post-Transplant Early Bacterial Infections in Liver Transplant Recipients: A Randomized Controlled Trial.

PURPOSE: In this study, we aimed to compare the efficacy of combined ceftizoxime with ampicillin-sulbactam versus combined gentamicin with ampicillin-sulbactam as prophylactic antibiotic regimen in preventing early bacterial PTIs in liver TX recipients at a referral center. PATIENTS AND METHODS: All patients older than 18 years who had undergone liver TX at Abu-Ali Sina transplantation center in Shiraz, Iran from July 2018 to April 2019 were included in this study. In a single-blinded manner, the participants randomly received either combined intravenous ceftizoxime plus ampicillin-sulbactam (ceftizoxime group) or gentamicin plus ampicillin-sulbactam (gentamicin group) as prophylactic antibiotic regimen before the incision of the surgery, which was continued for 48 hrs after liver Tx. The rate and type of bacterial infections, length of hospital and intensive care unit (ICU) stay, mortality rate, and kidney function were assessed during 1 month following liver TX in the two groups. RESULTS: Two hundred and thirty patients were divided into two groups. One patient in the gentamicin group and five in the ceftizoxime group were excluded due to emergency exploratory laparotomy within the first 3 days after transplantation. The rate of bacterial infections during the first month after transplantation was 25.4%. This rate was significantly lower in the gentamicin group (13.16%) in comparison to the ceftizoxime group (38.18%) (P value<0.01), based on the univariate logistic regression analysis. Length of ICU and hospital stay and also mortality rate were significantly lower in the gentamicin group (P value <0.01). There was no significant difference regarding kidney function between the two groups (P value = 0.16). CONCLUSION: Our results suggested that gentamicin can be considered as a promising agent in prophylactic antibiotic regimen for patients undergoing liver TX. TRIAL REGISTRATION: The study was registered at the Iranian Registry of Clinical Trials (IRCT20120731010453N2; http://www.irct.ir/).

Comparison of intravenous sodium bicarbonate and sodium chloride combination versus intravenous sodium chloride hydration alone in reducing amphotericin B nephrotoxicity: a randomized clinical trial.

BACKGROUND AND PURPOSE: The most important adverse reaction of amphotericin B (AmB) is nephrotoxicity. The aim of this study was to assess the potential effectiveness of intravenous saline + sodium bicarbonate versus intravenous sodium chloride hydration in preventing or attenuating AmB nephrotoxicity. EXPERIMENTAL APPROACH: A randomized, non-placebo-controlled, single-blinded clinical trial was conducted in two adult hematology-oncology wards of Namazi hospital. Eligible patients were randomly assigned into either the normal saline or normal saline + sodium bicarbonate groups by the ratio of 1:2. In the normal saline group, 1000 mL of sodium chloride 0.9% (154 meq sodium) was given intravenously as two equal 500 mL volumes before and during the infusion of AmB. Patients in the saline + sodium bicarbonate group received 500 mL sodium chloride 0.9% (72 meq sodium) before and 500 mL isotonic sodium bicarbonate (72 meq sodium) intravenously during AmB infusion. FINDINGS/RESULTS: The rate of AmB nephrotoxicity was comparable between normal saline and sodium bicarbonate groups (54.2% and 41.6%, respectively; P = 0.3). This difference did not reach the level of statistical significance after considering AmB dose and duration of the treatment. The frequency of hypokalemia and hypomagnesemia did not differ significantly between the two groups even after adjusting the results according to AmB dose and treatment duration. CONCLUSION AND IMPLICATIONS: The results of the current preliminary clinical trial suggested that the combination of sodium bicarbonate and normal saline compared to normal saline alone appears to have no superiority in preventing or attenuating different studied aspects of AmB nephrotoxicity in patients with hematological malignancies.

Clinical and economical impacts of guideline implementation by the pharmaceutical care unit for high cost medications in a referral teaching hospital.

BACKGROUND: Irrational drug use is a global health challenge in all healthcare settings, such as hospitals. This study evaluated the impact of an intervention by the pharmaceutical care unit on the use pattern of high-value medications and their direct costs in a referral hospital. METHODS: This interventional, prospective study was carried out in clinical wards of Namazi Hospital (Shiraz University of Medical Sciences) during six months from May 2015 to October 2015. Clinical pharmacists completed the checklists for albumin, intravenous (IV) pantoprazole, and IV immune globulin (IVIG), as three high-cost medications. When ordering these medications, the physicians were asked to complete the checklists. Then, trained pharmacists examined the checklists, based on the clinical and paraclinical conditions. RESULTS: The total number of administered medications and their relative cost decreased by 50.76% through guideline implementation; the difference was significant (P <  0.001). In addition, the direct cost of albumin and IV pantoprazole significantly decreased (55.8% and 83.92%, respectively). In contrast, the direct cost of IVIG increased by 40.9%. After guideline implementation, the monthly direct cost of all three medications decreased by $77,720 (55.88%). The all-cause in-hospital mortality rate did not change significantly due to the intervention. The median length of hospital stay was six and seven days, respectively in the pre- and post-intervention periods. CONCLUSION: Based on the findings, implementation of guidelines by the pharmaceutical care unit caused a significant reduction in albumin and IV pantoprazole consumption and reduced their direct costs in a referral center in Iran.

Trichoepithelioma: A Comprehensive Review.

Trichoepithelioma is an uncommon benign adnexal neoplasm. It can present as a solitary non-familial or multiple familial form. Trichoepithelioma usually develops in early childhood or puberty. Females are more affected. It is attributed to two genetic mutations on chromosomes 9p21 and 16q12-q13. Multiple familial trichoepithelioma is an autosomal-dominant disorder, characterized by numerous nodules and papules, predominantly on the face and occasionally on the scalp, neck, or upper trunk, positive family history, and histopathological findings. The lesions gradually increase in both size and number over time; however, they remain mostly asymptomatic. Although it is rare, trichoepithelioma lesions can undergo malignant transformation to trichoblastic carcinoma or basal cell carcinoma. Patients mainly seek treatment because the lesions are usually disfiguring and can lead to psycho-social issues. Non-pharmacologic approaches (e.g., excisional surgery, laser resurfacing), as the current mainstay of management, suffer from several drawbacks. New treatment techniques such as pharmacotherapy with potentially effective agents deserve more attention and investigation.

Urinary Neutrophil Gelatinase-associated Lipocalin as a Biomarker of Kidney Injury in Hematologic-Oncologic Patients Receiving Amphotericin B.

INTRODUCTION: The aim of the present study was to compare the changing pattern of urine neutrophil gelatinase-associated lipocalin (NGAL) with serum as well as urine creatinine during amphotericin B treatment and determine its accuracy in the early detection of amphotericin B nephrotoxicity. MATERIALS AND METHODS: A cohort study was performed during 9 months at 3 hematology-oncology services. Patients aged 15 years and greater with no documented history of acute kidney injury or chronic kidney disease, planned to receive any formulation of amphotericin B for at least 1 week, were included. Serum as well as urine creatinine and urine NGAL were determined on days zero, 3, 5, 7, 10, and 14 of amphotericin B treatment. RESULTS: Forty patients with the mean age of 38.0 ± 14.1 years were recruited. Eleven of 40 patients (27.5%) developed amphotericin B nephrotoxicity. The overall changes in the mean values of urine NGAL were not significant during amphotericin B treatment, neither within nor between the two groups. The area under the curve of urine NGAL (0.765; 95% confidence interval, 0.588 to 0.962) on day zero was significantly higher than that of serum creatinine (0.464; 95% confidence interval, 0.268 to 0.660; P = .01) for predicting amphotericin nephrotoxicity. CONCLUSIONS: The incremental pattern of urine NGAL during amphotericin B treatment was not significant compared to baseline values. The urine level of NGAL on the first day of amphotericin B administration was more accurate than serum creatinine in predicting acute kidney injury caused by this agent.

Infective endocarditis; report from a main referral teaching hospital in Iran.

BACKGROUND/OBJECTIVE: The aim of the present preliminary study was to assess the demographic, clinical, paraclinical, microbiological, echocardiographic, and therapeutic profile as well as in-hospital outcome of patients with infective endocarditis at a referral center for various infectious diseases in Iran. METHODS: Required demographic, clinical, plausible complications and paraclinical data were collected from patients' medical charts. Echocardiographic findings were obtained by performing transthoracic and/or transesophageal echocardiography as clinically indicated. In addition, details of management modalities and in-hospital outcome of patients were recorded. RESULTS: During a 3-year period, 55 patients with definite or possible diagnosis of Infective endocarditis were admitted to the ward. Twenty one (38.2%) patients were injection drug users. Staphylococcus aureus and S.epidermidis were the most commonly isolated microorganisms. Management modalities of Infective endocarditis included antimicrobial therapy alone (48 cases) and the combination of antimicrobial therapy and surgery (7 cases). CONCLUSION: The rate of negative blood culture in our cohort is high. S. aureus and S.epidermidis were the most commonly isolated microorganisms from positive blood cultures. Congestive heart failure was the most frequent infective endocarditis complication as well as indication for surgery. In-hospital mortality rate of patients was unexpectedly low.

Frequency and Associated Factors of Amphotericin B Nephrotoxicity in Hospitalized Patients in Hematology-Oncology Wards in the Southwest of Iran.

BACKGROUND: Nephrotoxicity is the most clinically significant adverse reaction of amphotericin B. Different aspects of amphotericin B (AmB) nephrotoxicity have not been studied well in our population. OBJECTIVES: The purpose of this study was to assess the frequency, time onset, and possible associated factors of AmB nephrotoxicity in hospitalized patients in hematology-oncology wards in the southwest of Iran. PATIENTS AND METHODS: A cross-sectional, observational study was performed over a period of 9 months at 2 hematology-oncology and 1 hematopoietic stem cell transplantation wards at Namazi Hospital. Patients aged 15 years or older with no documented history of acute kidney injury or chronic kidney disease who were scheduled to receive formulations of AmB intravenously for at least 1 week were included. The required demographic and clinical data of the patients were recorded. Urine urea, creatinine, sodium, potassium, and magnesium levels were measured at days 0, 3, 5, 7, 10, and 14 of the AmB treatment. AmB nephrotoxicity based on serum creatinine increase, renal potassium wasting, hypokalemia, and hypomagnesemia were determined. RESULTS: Among the 40 patients recruited for the study, 11 (27.5%) patients developed AmB nephrotoxicity with a mean ± standard deviation onset of 6.73 ± 2.36 days. In 5 patients, AmB nephrotoxicity resolved spontaneously without any intervention. According to the multivariate logistic regression model, none of the studied demographic, clinical, and paraclinical variables were significantly associated with AmB nephrotoxicity. The duration of hospitalization (P = 0.541) and the mortality rate (P = 0.723) were comparable between the patients with and without AmB nephrotoxicity. Hypokalemia and renal potassium wasting were identified in 45% and 27.5% of the patients during AmB treatment, respectively. CONCLUSIONS: Nearly one-third (27.5%) of our cohort developed nephrotoxicity within the first week of AmB treatment. Hypokalemia and renal potassium wasting were more notable, affecting about one-half and one-third of the AmB recipients, respectively.

Comparison between a serum creatinine-and a cystatin C-based glomerular filtration rate equation in patients receiving amphotericin B.

Serum cystatin C (Cys C) has a number of advantages over serum creatinine in the evaluation of kidney function. Apart from Cys C level itself, several formulas have also been introduced in different clinical settings for the estimation of glomerular filtration rate (GFR) based upon serum Cys C level. The aim of the present study was to compare a serum Cys C-based equation with Cockcroft-Gault serum creatinine-based formula, both used in the calculation of GFR, in patients receiving amphotericin B. Fifty four adult patients with no history of acute or chronic kidney injury having been planned to receive conventional amphotericin B for an anticipated duration of at least 1 week for any indication were recruited. At three time points during amphotericin B treatment, including days 0, 7, and 14, serum cystatin C as well as creatinine levels were measured. GFR at the above time points was estimated by both creatinine (Cockcroft-Gault) and serum Cys C based equations. There was significant correlation between creatinine-based and Cys C-based GFR values at days 0 (R = 0.606, P = 0.001) and 7 (R = 0.714, P < 0.001). In contrast to GFR estimated by the Cockcroft-Gault equation, the mean (95 % confidence interval) Cys C-based GFR values at different studied time points were comparable within as well as between patients with and without amphotericin B nephrotoxicity. Our results suggested that the Gentian Cys C-based GFR equation correlated significantly with the Cockcroft-Gault formula at least at the early time period of treatment with amphotericin B. Graphical abstract Comparison between a serum creatinine-and a cystatin C-based glomerular filtration rate equation in patients receiving amphotericin B.

A double-blinded, placebo-controlled, multicenter clinical trial of N-acetylcysteine for preventing amphotericin B-induced nephrotoxicity.

OBJECTIVE: To evaluate the effectiveness of oral N-acetylcysteine (NAC) co-treatment in preventing amphotericin B (AmB)-induced nephrotoxicity (AIN), including creatinine clearance and biomarkers of renal function (cystatin C [Cys C] and kidney injury molecule-1 [KIM-1]). METHODS: Either placebo or 600 mg oral NAC was given twice daily during the treatment course of AmB. Renal function test, serum as well as urinary level of Cys C and urinary KIM-1 were determined. RESULTS: Among the study population (n = 54), 23 (42.59%) patients developed AmB nephrotoxicity during their treatment course. NAC co-treatment was significantly associated with mitigating AmB nephrotoxicity (OR = 0.286, 95% CI: 0.082 - 0.993; p = 0.049). No statistically significant difference regarding accuracy of measured biomarkers including serum creatinine, serum and urine Cys C and urine KIM-1 at days 0 and 7 of treatment in predicting and detecting AmB nephrotoxicity was identified. The changes in mean serum and urine Cys C and urine KIM during AmB treatment within and between treatment groups were not statistically significant. CONCLUSIONS: Co-treatment with 600 mg oral NAC twice a day during AmB treatment, after adjusting for multiple variables, was associated with prevention of AIN. However, significantly higher adverse reactions developed in the patients who were treated with NAC.

The role of N-acetylcysteine in the management of acute and chronic pulmonary complications of sulfur mustard: a literature review.

CONTEXT: Sulfur mustard exposure, as the most widely used chemical weapon, can lead to acute and long-term pulmonary complications via various pathways, such as triggering an imbalance between the oxidant and antioxidant system. Currently, there is no validated antidote, chemoprophylaxis and curative modality for pulmonary toxicities secondary to sulfur mustard exposure. OBJECTIVE: The aim of this literature review is to collect available experimental and clinical data on the efficacy of N-acetylcysteine (NAC), as a prominent antioxidant agent, in the prevention and/or treatment of sulfur mustard-induced acute and chronic pulmonary toxicities. METHODS: A literature search was performed by the relevant keywords like "N-acetyl cysteine", "Sulfur mustard" and "Lung injury" in databases such as Scopus, Medline, Embase and ISI Web of Knowledge. No time limitation was considered. Nineteen articles were selected for review. RESULTS: A number of in vitro and experimental studies concluded that oral, intravenous, intraperitoneal and intra-tracheal administration of NAC is effective in the management of sulfur mustard-induced acute lung injury, in a time-dependent manner, via direct scavenging, inhibition of oxidative stress, inflammatory responses and apoptosis. In addition, oral NAC alone (1200 or 1800 mg/day for 4 months) or at a dose 600 mg/day for 6 months in combination with clarithromycin (500 mg/day) have led to improvements of clinical and paraclinical pulmonary parameters of patients with bronchiolitis obliterans due to sulfur mustard, through undetermined mechanisms. CONCLUSION: Despite limitations of relevant experimental and clinical studies, NAC can be considered as a candidate agent for prevention and/or treatment of sulfur mustard-induced acute lung injuries, as well as its long-term pulmonary toxicities, especially bronchiolitis obliterans.

Pattern and associated factors of potential drug-drug interactions in both pre- and early post-hematopoietic stem cell transplantation stages at a referral center in the Middle East.

The aim of this study was to determine the pattern as well as associated factors of moderate and major potential drug-drug interactions (PDDIs) in both the pre- and early post-transplantation stages at a referral hematopoietic stem cell transplantation (HSCT) center. All adolescents and adults undergone HSCT within a 3-year period were screened retrospectively for potential moderate or severe PDDIs by the Lexi-Interact On-Desktop software. Among 384 patients, a total of 13,600 PDDIs were detected. The median (interquartile range) cumulative PDDIs burden was 41 (28). All (100 %) individuals experienced at least one PDDI. More than four fifths (81.8 %) of detected PDDIs were moderate. The predominant mechanism of PDDIs was pharmacokinetics (54.3 %). Interaction between sulfamethoxazole-trimethoprim and fluconazole was the most common PDDIs involving 95.3 % of the study population. More than three fifths (61.5 %) of detected PDDIs were caused by HSCT-related medications. No interaction was identified between two anticancer agents. Interactions of cyclophosphamide with phenytoin, busulfan with metronidazole, dexamethasone, or clarithromycin were the only detected PDDI between anticancer and non-anticancer medications. Type of HSCT and the numbers of administered medications were significantly associated with major PDDIs. The epidemiology, real clinical consequence, and economic burden of DDIs on patients undergone HSCT particularly around the transplantation period should be assessed further by prospective, multicenter studies.

Serum cystatin C as a marker of renal function in critically ill patients with normal serum creatinine.

BACKGROUND: Serum creatinine as a classic marker of renal function has several limitations in the detection of renal dysfunction. OBJECTIVES: This study assessed the validity of serum cystatin C as a marker of renal function in critically ill patients with normal serum creatinine. PATIENTS AND METHODS: Eighty adult patients referred to intensive care units with serum creatinine levels < 1.5 mg/dL and without hemodynamic instability were chosen and their serum creatinine and cystatin C levels were measured. A 24-hour urine sample was collected to calculate creatinine clearance (Ccr). Renal dysfunction was defined as Ccr < 80 mL/min/1.73 m(2). RESULTS: There were significant correlations between measured Ccr and 1/serum creatinine (R = 0.51, P < 0.001) and 1/serum cystatin C (R = 0.25, P = 0.028). The difference between false negative rates of serum creatinine (93.33%) and cystatin C (80%) in the detection of renal dysfunction was significant (P = 0.032). Receiver operating characteristic curve analysis illustrated that area under the curve of serum creatinine and cystatin C for detecting renal dysfunction were 0.711 and 0.607, respectively; however, this difference was not significant (P = 0.222). CONCLUSIONS: Our data demonstrated that serum cystatin C is not superior to serum creatinine in the early detection of renal dysfunction in critically ill patients.

N-acetyl cysteine in prevention of amphotericin- induced electrolytes imbalances: a randomized, double-blinded, placebo-controlled, clinical trial.

PURPOSE: The aim of this study was to evaluate the effectiveness of oral n-acetyl cysteine, as a potential nephroprotective agent, in preventing and/or attenuating amphotericin B-induced electrolytes imbalances. METHODS: During a one year period, patients were to receive conventional amphotericin b for any indication for at least one week and were randomly allocated to receive either placebo or 600 mg oral n-acetyl cysteine twice daily during the treatment course of amphotericin b. Demographic and clinical data of the study population were gathered. Different aspects of amphotericin b nephrotoxicity including decrease of glomerular filtration rate, hypokalemia, hypomagnesemia, renal magnesium and potassium wasting were assessed. Each patient was monitored for any adverse reaction to n-acetyl cysteine. Sixteen and 14 patients in the n-acetyl cysteine and placebo groups completed the study, 3incidences of hypokalemia (75 % versus 70 %; P = 0.724) and hypomagnesemia (30 % versus 20 %; P = 0.468) did not differ significantly between placebo and NAC groups, respectively. Although the rate of AmB nephrotoxicity was higher in the placebo than in the NAC group (60 % versus 40 %), this difference was not statistically significant (P = 0.209) even after adjusting for probable associated factors of amphotericin b nephrotoxicity (P = 0.206). The incidence as well as time of onset of electrolyte abnormalities also did not differ significantly between placebo and n-acetyl cysteine groups. About 44 % of n-acetyl cysteine recipients experienced new onset nausea and a mild unpleasant taste during the study. CONCLUSION: Oral n-acetyl cysteine during the amphotericin B treatment course was not significantly effective in preventing or mitigating different features of its nephrotoxicity including decrease of glomerular filtration rate, hypokalemia, hypomagnesemia, and renal potassium as well as magnesium wasting.