FLOT (a chemotherapy regimen for gastric/esophagogastric junction cancer): to be treated as a highly emetogenic regimen or a moderately emetogenic one? Comparison of the emetogenic potential of FLOT versus FOLFOX and TAC regimens.

PURPOSE: The current study aimed at investigating the efficacy of aprepitant-containing triple antiemetic regimen in FLOT (fluorouracil + leucovorin + oxaliplatin + docetaxel) recipients as well as the emetogenic potential of FLOT regimen, through comparison of nausea and vomiting rates in a moderately emetogenic chemotherapy, FLOT, and a highly emetogenic chemotherapy recipients. STUDY: Patients planned to receive one of FLOT, FOLFOX (fluorouracil + leucovorin + oxaliplatin/moderate-emetic risk), or TAC (docetaxel + doxorubicin + cyclophosphamide/high-emetic risk) regimens were recruited. All patients were treated with the same triple antiemetic regimen containing aprepitant. RESULTS: A total of 165 chemotherapy-naïve patients (52 FLOT recipients) were eligible to enter the study. At the end of day 5, "complete response" (primary efficacy endpoint) was achieved by 84.6%, 63.5%, and 61.5% of the FLOT-receiving patients in acute, delayed, and overall phases, respectively. A significant difference was seen among the odds of FLOT recipients and FOLFOX recipients concerning "complete response" achievement in delayed (p = 0.014) and overall (p = 0.017) phases, "no emesis" in delayed (p = 0.018) and overall (p = 0.010) phases, and also "complete protection" in acute (p = 0.023), delayed (p = 0.009), and overall (p = 0.006) phases; however, the difference between the odds of FLOT recipients and TAC recipients, in relation to achieving these endpoints, was insignificant. FLOT group showed significantly faster time-to-antiemetic regimen failure and time-to-first emetic episode in comparison with the FOLFOX group, which was insignificant in comparison with the TAC group. CONCLUSION: According to the findings, FLOT has to be considered as a high-emetic-risk regimen; provided that, as recommended by the antiemetic guidelines towards better management of delayed nausea and vomiting induced by highly emetogenic regimens, executing clinical trials concerning the efficacy of continuing dexamethasone on days 2-4 in aprepitant-containing triple antiemetic regimen schedule is required.

Effect of Vitamin D Supplementation on the Regulation of Blood Pressure in Iranian Patients with Essential Hypertension: A Clinical Trial.

BACKGROUND: Low serum vitamin D level is associated with both high blood pressure and incidence of primary hypertension. Experimental studies suggest that vitamin D supplements may reduce blood pressure. OBJECTIVE: The aim of this study was to investigate whether vitamin D supplementation reduces systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) in Iranian patients with essential hypertension. METHOD: A total of 173 patients with essential hypertension participated in this open-label clinical trial. SBP, DBP, and serum vitamin D levels were measured at baseline and at the end of the study. Vitamin D was administered at a dose of 50,000 IU/week, and 1000 IU/day in patients with serum vitamin D levels <20 ng/mL and 20-30 ng/mL, respectively, for 8 weeks. RESULTS: Based on serum vitamin D levels, 45.1%, 17.3%, and 29.5% of patients were deficient, insufficient, and sufficient for vitamin D intake, respectively. Baseline serum levels of vitamin D were not correlated with SBP, DBP, and MAP at the beginning of the study (p = ns). Multiple logistic regression analysis revealed that the risk of vitamin D deficiency was 2.5-fold times higher in women than in men (p = 0.03). After 8 weeks of supplementation with vitamin D, mean SBP and MAP were significantly reduced by 5.5 ± 16.16 (p = 0.01) and 3.7 ± 9.24 (p = 0.004) mmHg, respectively. Neither sex nor age could significantly predict BP response to vitamin D supplementation. CONCLUSION: Vitamin D supplementation may significantly reduce SBP and MAP but not DBP in patients with essential hypertension.

Antioxidant effects of curcuminoids in patients with type 2 diabetes mellitus: a randomized controlled trial.

BACKGROUND: Oxidative stress has a key role in the pathogenesis of type II diabetes mellitus (T2DM) and its vascular complications. Antioxidant therapy has been suggested as a potential approach to blunt T2DM development and progression. The aim of this study was to assess the effects of supplementation with curcuminoids, which are natural polyphenolics from turmeric, on oxidative indices in diabetic individuals. METHODS: In this randomized double-blind placebo-controlled trial, 118 subjects with T2DM were randomized to curcuminoids (1000 mg/day co-administered with piperine 10 mg/day) or matching placebo for a period of 8 weeks. Serum total antioxidant capacity, superoxide dismutase (SOD) activities and malondialdehyde (MDA) concentrations were measured at baseline and after the supplementation period. RESULTS: Curcuminoids supplementation caused a significant elevation in serum total antioxidant capacity (TAC) (p < 0.001) and SOD activities (p < 0.001), while serum MDA levels were significantly reduced compared with the placebo group (p < 0.001). These results remained statistically significant after adjustment for potential confounders (baseline differences in body mass index and fasting serum insulin). CONCLUSION: The present results support an antioxidant effect of curcuminoids supplementation in patients with T2DM, and call for future studies to assess the impact of these antioxidant effects on the occurrence of diabetic complications and cardiovascular endpoints.

Usage Pattern and Serum Level Measurement of Amikacin in the Internal Medicine Ward of the Largest Referral Hospital in the South of Iran: A Pharmacoepidemiological Study.

BACKGROUND: The inappropriate use of aminoglycosides has harmful effects such as the development of resistant pathogens and the incidence of nephrotoxicity and ototoxicity. Therefore, drug utilization evaluation of these drugs may improve their usage remarkably. The aim of this study was to assess the usage pattern of amikacin in an internal medicine ward. METHODS: This cross-sectional study was conducted in the Internal Medicine Ward of Nemazee Teaching Hospital, Shiraz, Iran, in 2011. The guideline for amikacin use was approved by the institutional Pharmacy and Therapeutics Committee, and the study criteria were developed to assess several parameters involved in amikacin therapy such as appropriateness of drug use, dosage, duration of therapy, toxicity monitoring, and serum concentration assay. Serum concentration was assayed using a Cobas Mira AutoAnalyzer. Clinical and paraclinical parameters such as glomerular filtration rate, culture, microbial sensitivity, white blood cell count, and fever were collected. RESULTS: Sixty-three patients were evaluated. Fifty-seven percent of the patients needed dose readjustment; however, it was not performed for 89% of them. Culture between 48 and 72 hours after amikacin administration was not controlled for 79% of the patients. In 19% of the patients, optimum therapeutic effect was not achieved. The mean±SD of the trough and peak concentrations was 7.63±5.4 µg/mL and 15.67±7.79 µg/mL, respectively. Forty-five percent of the trough and 38% of the peak levels were within the therapeutic range. The overall adherence of amikacin usage to the guideline was only 48%. CONCLUSION: To achieve appropriate treatment and prevent toxic effects, we recommend that pharmacokinetic dosing methods, amikacin guideline, and serum monitoring be considered.

Effect of angiotensin receptor blockade on prevention and reversion of tamoxifen-resistant phenotype in MCF-7 cells.

Tamoxifen (TAM) is a standard adjuvant endocrine therapy in postmenopausal breast cancer patients, but innate or acquired TAM resistance has remained to be a therapeutic challenge for clinicians. The aim of this study was to explore the possible participation of renin-angiotensin system (RAS) in the acquisition of TAM resistance and try to prevent and regress the resistance using an angiotensin II receptor type-1 (AGTR1) blocker, losartan. Establishment of TAM-resistant (TAM-R) cells was accomplished by continuous exposure of MCF-7 cells to 1 µmol/L TAM. MTT (3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay was performed to determine cell growth. Moreover, messenger RNA (mRNA) expression levels of AGTR1 and angiotensin II receptor type-2 (AGTR2) were measured by quantitative real-time polymerase chain reaction. A significant increase of AGTR1 and AGTR2 transcripts was observed in TAM-R cells compared to MCF-7 cells. Interestingly, losartan-TAM combination effectively resensitized TAM-R cells to tamoxifen treatment by inducing cell death. Therefore, our findings suggest an important role of RAS in acquired TAM resistance and targeting of RAS by losartan may overcome TAM resistance phenomenon and provide a novel avenue for treatment of resistant breast cancers.

Incidence of Potential Drug-Drug Interaction and Related Factors in Hospitalized Neurological Patients in two Iranian Teaching Hospitals.

BACKGROUND: Reciprocal drug interactions are among the most common causes of adverse drug reactions. We investigated the incidence and related risk factors associated with mutual drug interactions in relation to prescriptions written in the neurology wards of two major teaching hospitals in Shiraz, southern Iran. METHODS: Data was collected from hand-written prescriptions on a daily basis. Mutual drug interactions were identified using Lexi-Comp 2012 version 1.9.1. Type D and X drug interactions were considered as potential drug-drug interactions. The potential risk factors associated with drug-drug interactions included the patient's age and gender, number of medications and orders, length of hospitalization and the type of neurological disorder. To determine potential drug-drug interactions, relevant interventions were suggested to the physicians or nurses and the outcome of the interventions were documented. RESULTS: The study comprised 589 patients, of which 53% were males and 47% females, with a mean age of 56.65±18.19 SD years. A total of 4942 drug orders and 3784 medications were prescribed among which 4539 drug-drug interactions were detected, including 4118 type C, 403 type D, and 18 type X. Using a logistic regression model, the number of medications, length of hospitalization and non-vascular type of the neurological disorder were found to be significantly associated with potential drug-drug interactions. From the total interventions, 74.24% were accepted by physicians and nurses. CONCLUSION: Potentially hazardous reciprocal drug interactions are common among patients in neurology wards. Clinical pharmacists can play a critical role in the prevention of drug-drug interactions in hospitalized patients.

Gene polymorphisms of TACR1 serve as the potential pharmacogenetic predictors of response to the neurokinin-1 receptor antagonist-based antiemetic regimens: a candidate-gene association study in breast cancer patients.

PURPOSE: The current candidate gene association study aims to investigate tag SNPs from the TACR1 gene as pharmacogenetic predictors of response to the antiemetic guidelines-recommended, NK-1 receptor antagonist-based, triple antiemetic regimens. METHODS: A set of eighteen tag SNPs of TACR1 were genotyped in breast cancer patients receiving anthracycline and cyclophosphamide (with/without docetaxel) applying real-time PCR-HRMA. Data analysis for 121 ultimately enrolled patients was initiated by defining haplotype blocks using PHASE v.2.1. The association of each tag SNP and haplotype alleles with failure to achieve the defined antiemetic regimen efficacy endpoints was tested using PLINK (v.1.9 and v.1.07, respectively) based on the logistic regression, adjusting for the previously known chemotherapy-induced nausea and vomiting (CINV) prognostic factors. All reported p-values were corrected using the permutation test (n = 100,000). RESULTS: Four variants of rs881, rs17010730, rs727156, and rs3755462, as well as haplotypes containing the mentioned variants, were significantly associated with failure to achieve at least one of the defined efficacy endpoints. Variant annotation via in-silico studies revealed that the non-seed sequence variant, rs881, is located in the miRNA (hsa-miR-613) binding site. The other three variants or a variant in complete linkage disequilibrium with them overlap a region of high H3K9ac-promoter-like signature or regions of high enhancer-like signature in the brain or gastrointestinal tissue. CONCLUSION: Playing an essential role in regulating TACR1 expression, gene polymorphisms of TACR1 serve as the potential pharmacogenetic predictors of response to the NK-1 receptor antagonist-based, triple antiemetic regimens. If clinically approved, modifying the NK-1 receptor antagonist dose leads to better management of CINV in risk-allele carriers.

Using Modern Learning Method to Teach Pharmacy Students Psychopharmacotherapy.

Background: Applying modern educational methods for digital native students seems necessary. Active learning strategies promote students' skills and knowledge. This study was conducted to design and evaluate active learning methods by teaching psychopharmacotherapy to pharmacy students. Methods: This was a quasi-experimental study with three randomized study groups (control, game, and multimedia), using a pre-and post-test design, conducted on 155 students of 5-year pharmacy in 2022 at the Faculty of Pharmacy of Tehran University of Medical Sciences, Iran. Overall, 18 clinical cases were designed for the basic structure of interventions. After teaching psychopharmacotherapy contents through lecturing, the pre-test was held. The next steps were playing the educational game, studying the multimedia case-based learning files, and then completing questionnaires, respectively. Then, a post-test was held. Results: 65.33% of participants were female and 34.66% were male. The pre-test and post-test scores comparison showed no difference in control group (P=0.409). However, in the serious game and multimedia groups, the average score of pre-test and post-test had a statistically significant difference (P<0.001, P=0.002 respectively), this difference was higher in the serious game group. Questionnaire evaluation showed substantial differences between game and multimedia groups. Conclusion: The educational interventions were able to improve student's knowledge and skills so they can better help patients and promote public health. In the sections of Confidence, Social Interactions, Fun, Focused attention, Learnability, Relevance, and Perceived Learning, the serious game far outweighed the multimedia case-based learning.

Lack of association of genetic polymorphisms of angiotensin converting enzyme 1 and angiotensin II type 1 receptor with breast cancer risk in Iranian population.

We aimed to investigate the association of insertion/deletion (I/D) and A1166C polymorphisms of angiotensin I converting enzyme 1 and angiotensin II type 1 receptor genes, respectively and their combination on breast cancer risk in an Iranian population. A case-control study (70 cases, 70 controls) was performed on an Iranian population. The I/D and A1166C polymorphisms were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism PCR, respectively. The results revealed no significant difference between cases and controls in I/D (p = 0.14) and A1166C (p = 0.94) polymorphisms after adjustment for breast cancer known risk factors. In combined genotype analysis, considering DD and AA genotypes as low-risk genotypes, women with one and two high-risk genotypes (one high-risk genotype: adjusted odds ratio (OR), 1.24; two high-risk genotypes: adjusted OR, 1.97) were at higher risk for breast cancer. Also, the highest risk for breast cancer was seen in a subgroup of postmenopausal women carriers of two high-risk genotypes (adjusted OR, 2.41). In conclusion, I/D and A1166C polymorphisms are not significantly associated with breast cancer risk in the Iranian population; however, the combination of these two polymorphisms seems to have a synergic effect on the risk of breast cancer particularly in postmenopausal women, which may deserve consideration in large-scale case-control studies.

Trimethoprim/sulfamethoxazole desensitization in an HIV-positive patient with previous Stevens-Johnson syndrome; a failed study.

Drug-induced Stevens-Johnson syndrome (SJS) is a rare but life-threatening hypersensitivity reaction. Drug desensitization might be considered in drug-allergic patients with no therapeutic alternative. A 29-year-old man with a recent diagnosis of HIV and HBV (CD4 count: 4 cells/mm3) who has been receiving Trimethoprim/sulfamethoxazole (TMP/SMX) for Pneumocystis pneumonia (PCP) prophylaxis was admitted at Imam Khomeini hospital complex affiliated to Tehran University of Medical Sciences, with the diagnosis of SJS due to TMP/SMX. After 45 days of supportive care, the patient was a candidate for TMP/SMX desensitization due to our region's unavailability of alternative agents. A 9-day desensitization protocol was used, but the patient complained about diarrhea with severe pain in the rectal mucosa, and macules developed over his lips again on the third day. As a result, the desensitization process immediately stopped, and after the signs and symptoms were resolved, the patient was discharged with Clindamycin tablet 600 mg TDS. Unfortunately, two weeks after discharge, the patient experienced acute kidney injury (AKI) and expired after two dialysis sessions.

Immediate hypersensitivity reaction to levetiracetam: a case report study.

BACKGROUND: Anticonvulsant drugs are one of the most common causes of delayed hypersensitivity reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). These reactions are more prevalent with aromatic anticonvulsant drugs such as phenytoin and carbamazepine. However, immediate hypersensitivity reactions such as urticaria, angioedema, and anaphylaxis with anticonvulsant drugs are rare. We describe a 51-year-old woman who developed spreading skin rashes on her wrists with urticaria and pruritus 24 h after receiving intravenous levetiracetam. CONCLUSION: Clinicians should be aware of immediate hypersensitivity reactions with intravenous levetiracetam.

The approach of Iranian clinical pharmacists in the treatment of dyslipidemia based on international guidelines.

Introduction: Optimal treatment of dyslipidemia is a top priority in the prevention of cardiovascular diseases. For this purpose, clinicians in Iran usually refer to four current international guidelines. The aim of this study was to assess the approach of Iranian clinical pharmacists in the treatment of dyslipidemia based on international guidelines. Methods: A structured questionnaire was prepared. Questions (n=24) included the demographics (n=7), dyslipidemia references (n=3), dyslipidemia general knowledge of respondents (n=10), and questions (n=4) designed based on the difference among the latest version of guidelines participants stated they use in their practice. After validity conformation, the questionnaire was distributed to 120 clinical pharmacists, electronically from May to August 2021. Results: Response rate was 77.5% (n=93). The majority of participants (80.6%, n=75) claimed to have used the 2018 ACC/AHA guideline. The Median (interquartile range [IQR]) score of the general knowledge questions was 5.0 (2.0) out of 10. The Median (IQR) score of questions designed based on the difference among guidelines was calculated 3(1) out of 4. There was no significant (P=0.25) difference in score among participants according to their guideline selection. Moreover, the gender and length of experience as a clinical pharmacist had no significant (P>0.05) effect on the score of participants. Conclusion: In this study, Iranian clinical pharmacists answered half of the dyslipidemia general knowledge questions correctly. Also, Participants were up-to-date on 75% of the questions designed based on the latest version of the guideline they had been using in their practice.

Design, Development and Evaluation of an Application based on Clinical Decision Support Systems (CDSS) for Over-The-Counter (OTC) Therapy: An Educational Interventions in Community Pharmacists.

Introduction: Mobile health (mHealth) technology-based applications provide strong medical health-care support. Applications have an important impact as tools to improve the knowledge and support the health-care team practice. In this study, an over-the-counter (OTC) therapy application was developed based on Clinical Decision Support Systems (CDSS). CDSS is a key to improve health-related decisions and healthcare delivery. Furthermore, the quality and effectiveness of this application were evaluated among community pharmacists. Methods: The application was designed and developed for 10 topics of OTC therapy. After the approval of the expert panel, 40 pharmacists affiliated with Tehran University of Medical Science (TUMS) participated in this before and after quasi-experimental study. The related scenarios and checklists were designed for the ten topics. The participants had to manage the scenarios first by their knowledge and then with the application. The knowledge and pharmaceutical skills in OTC therapy were evaluated based on the obtained scores and the time recorded. The quality of the application was evaluated by pharmacists using user version of mobile application rating scale (uMARS) questionnaire. To compare before/after measurements of parametric and non-parametric data, we used the paired t-test and Wilcoxon matched-pairs test, respectively. Besides, the variables was compared using Mann-Whitney test. The statistical significance was considered at P<0.05. The analyses were performed using the statistical software Stata (ver. 13). Results: All scores after using the application increased, and the P-value was not significant. Also, the recorded time was increased after the use of the application, and the P-value was not significant. The minimum mean scores of the six uMARS questionnaire sections were 3. It means that acceptable scores were obtained in all sections of the questionnaire. The "App quality score" section of the application was reported 3.45±0.94. No relationship was found between gender and the median score of each section of the uMARS questionnaire. Conclusion: The OTC therapy application developed in this study will help Persian-speaking pharmacists to increase their knowledge and pharmaceutical skills.

Evaluation of important human CYP450 isoforms and P-glycoprotein phenotype changes and genotype in type 2 diabetic patients, before and after intensifying treatment regimen using Geneva cocktail.

The present study evaluates the influence of type 2 diabetes (T2D) on important CYP450 (CYP) isoforms and P-glycoprotein (Pgp) transporter activities before and 3 months after an intensifying treatment regimen involving 40 patients. Results have been compared with 21 non-T2D healthy participants (the control group). CYPs and Pgp activities were assessed after administering the Geneva cocktail. The mean metabolic ratios (MR) for CYP2B6 (1.81 ± 0.93 versus 2.68 ± 0.87), CYP2C19 (0.420 ± 0.360 versus 0.687 ± 0.558) and CYP3A4/5 (0.487 ± 0.226 versus 0.633 ± 0.254) significantly decreased in T2D patients compared to the control group (p < 0.05). CYP2C9 (0.089 ± 0.037 versus 0.069 ± 0.017) activities slightly increased in diabetic patients, and no difference was observed regarding CYP1A2 (0.154 ± 0.085 versus 0.136 ± 0.065), CYP2D6 (1.17 ± 0.56 versus 1.24 ± 0.83), and Pgp activities in comparison to the control group. Three months after the intensifying treatment regimen, MRs of CYP2C9 (0.080 ± 0.030) and CYP3A4/5 (0.592 ± 0.268) improved significantly and were not statistically different compared to the control group (P > 0.05). Several covariables, such as inflammatory markers (IL-1ß and IL-6), genotypes, diabetes and demographic-related factors, were considered in the analyses. The results indicate that chronic inflammatory status associated with T2D modulates CYP450 activities in an isoform-specific manner.

The hypoglycemic effects of Juglans regia L. internal septum in type 2 diabetic patients: A double-blind, randomized, placebo-controlled clinical trial.

Introduction: The internal septum of J.regia is traditionally used to control diabetes, and its effectiveness has been shown in animal studies. Accordingly, human clinical trials are needed to confirm its effectiveness on hemoglobin A1c (HbA1c), fasting blood sugar (FBS), blood insulin level, and insulin resistance as a complementary for better control of type 2 diabetes. Methods: This study was a randomized, double-blinded, controlled trial. The lyophilized powder of extract of the internal septum of J.regia was used to fill the capsules. Sixty type 2 diabetic patients were randomly divided into two groups. 500 mg capsules three times daily before meal was added to their routine drug regimen, and HbA1c, FBS, and blood insulin level were checked at the baseline and after three months. Results: Sixty patients completed the study. The mean(±SD) age of patients was 49.1(10.2) and 50.9(12.7) years in the placebo and J.regia groups, respectively. We observed that J.regia internal septum increases the level of HbA1c by about 0.02 units, but this effect was not significant (MD=0.02,95%CI=-0.36 to 0.40, P=0.93). Regarding the impact of capsules on insulin level, it seems that J.regia-containing capsules can raise insulin level by one unit. However, it was not significant (MD=1.01,95%CI=-0.86 to 2.88, P=0.28). As for FBS, it can cause a decrease of four units, but this effect is also not significant (MD=-3.98,95%CI=-18.33 to 10.37, P=0.58). Conclusion: Based on our study, the internal septum of J.regia has no significant effect on HbA1c, FBS, and insulin resistance. Moreover, no specific adverse reaction was observed in any of the patients.

Iranian Consensus Guideline for Pharmacotherapy with Biologics and Small Molecules Drugs in Adults with Inflammatory Bowel Diseases.

Background: Pharmacotherapy with biologics and small molecules, as the more effective therapies for moderate to severe ulcerative colitis (UC) and Crohn's disease (CD), is complex. Choosing the best methods for their utilization in order to induce and maintain remission are critical for practicing gastroenterologists. We aimed to develop an Iranian consensus on the management of inflammatory bowel disease (IBD) patients with biologics and small molecules. Methods: A Delphi consensus was undertaken by experts who performed a literature summary and voting process. Quality of evidence was assessed using the Grading and Recommendations Assessment, Development, and Evaluation; and an additional risk of bias-protocol. Results: Following an extensive search of the literature, 219 studies were used to determine the quality of the evidence. After three rounds of voting, consensus (defined as≥80% agreement) was reached for 87 statements. Conclusion: We considered different aspects of pharmacotherapy in this consensus. This guideline, along with clinical judgment, can be used to optimize management of IBD patients.

Bosentan-induced immune hemolytic anemia in 17 years old man. A case report.

Hemolytic anemia is a very important immune-mediated reaction, which its late diagnosis can be fatal. Medications along with other causes can induce hemolytic anemia. Drug induced immune hemolytic anemia (DIIHA) is caused by the development of autoantibodies. Accordingly, DIIHA is rare and there is not enough data for its prevalence. Number of drugs that can cause DIIHA have increased in recent decades. A 17-year-old man who had congenital single ventricle heart (CHB) and pulmonary artery hypertension (PAH) was admitted at Imam Khomeini hospital complex affiliated to Tehran University of Medical Sciences, with chief complaint of jaundice and icter. Bosentan and Tadalafil were in the list of the drugs used by this patient. Although both drugs were recommended to be discontinued in the patient, in the course of hospitalization, the patient accidentally continued to take his Tadalafil. However, the patient's recovery continued. Given that the patient's Coombs test was positive, his hemolytic anemia mechanism was drug-induced immune-mediated hemolytic anemia. As a result, according to Naranjo score = 6, Bosentan was considered as the main possible culprit to induce DIIHA in this patient. Following the discontinuation of Bosentan and receiving Prednisolone, the patient's clinical symptoms and laboratory parameters resolved and the patient was then discharged.

Melatonin effect on platelet count in patients with liver disease.

AIM: A positive effect of melatonin on platelet count in patients with chronic liver disease is reported in the current study. BACKGROUND: Thrombocytopenia occurs when the severity of liver disease is exacerbated. Reduction in the secretion of thrombopoetin, as an intrinsic hormone produced mainly by the liver, plays an important role in this complication induced by liver disease. METHODS: This research was a double-blind, cross-over, placebo-controlled pilot study. Patients with liver disease were given two 5-mg pearls of melatonin or a placebo for two weeks, and after a 2-week washout period, their groups were switched. Liver function tests and platelet counts were assessed once at the beginning and once at the end of each phase of the study. RESULTS: In the current study, 40 patients meeting the eligibility criteria were included. The average platelet count was significantly increased by melatonin in comparison with the placebo (from 175.67±92.84 to 191.10±98.82 vs. from 185.22±98.39 to 176.45±91.45) (p-value <0.001). Melatonin also significantly reduced ALT, AST, total bilirubin, and direct and MELD scores in patients with liver disease (p-value <0.05). CONCLUSION: Melatonin may increase platelet count and inhibit thrombocytopenia in patients with liver disease; however, more investigations are needed to confirm the current results.

Evaluation of Antipruritic Effect of Melatonin on Hemodialysis Patients with Uremic Pruritus, A Double-Blind, Randomized, Crossover Trial.

INTRODUCTION: Uremic pruritus (UP) is one of the major complaints in hemodialysis patients without specific treatment. Considering the antipruritic effect of melatonin in atopic dermatitis (AD) and similarities in mechanism between pruritus in AD and UP, this randomized clinical trial designed to evaluate the antipruritic effect of melatonin on hemodialysis patients with UP. METHODS: This multicenter double-blind randomized clinical trial was conducted among the hemodialysis patients with UP. Adult patients were randomly assigned to receive two capsules of melatonin 5 mg /d for a 2 weeks period, undergoing a 1 week washout period, and then two capsules of placebo for another 2 weeks period, or the reverse sequence. Visual Analogue Scale (VAS), % affected Body Surface Area (%BSA) and 12-Pruritus Severity Scale questionnaire (12-PSS) were measured before and after each of the three periods. A crossover analysis of variance adjusted by treatment, period and carryover effect was performed by STATA 14. RESULTS: Thirty-nine patients under hemodialysis (mean age of 55.08 ± 12.34 years) completed the study. Mean changes in VAS, 12-PSS, and %BSA after the interventions (melatonin vs. placebo, mean ± SD) were as follows, respectively: -3.21 ± 3.33 vs. -1.38 ± 2.23, -4.59 ± 5.22 vs. -2.08 ± 4.35, and -19.10 ± 30.31 vs. 4.64 ± 29.11 (P < .05). However, the statistical significance of the treatment effect from melatonin was observed, carryover and period effects were not significant (P > .05) for any of the main variables. CONCLUSION: Based on to the preliminary results of this study, melatonin can be introduced as an effective drug for management of pruritus in uremic patients.

A Pilot Randomized, Clinical Trial of the Anti-pruritus Effect of Melatonin in Patients with Chronic Liver Disease.

Pruritus is one of the disturbing complications induced by chronic liver disease (CLD), bearing a negative impact on patient quality of life and potentially resulting in early liver transplants. Given the main role of the autotaxin enzyme in pruritus induced by CLD and the suppressive effects of melatonin on the expression of the autotaxin gene, this study was designed to evaluate the antipruritic effect of melatonin in patients with CLD. A double-blind, cross-over, randomized, placebo-controlled pilot trial was conducted on patients with CLD -induced pruritis. Patients were randomly assigned to two groups where they received melatonin 10-mg at night or placebo for 2 weeks. After a 2-week washout period, patients were then crossed over to the other group. The Visual Analog Scale (VAS) and the 12-Item Pruritus Severity Score (12-PSS) were used to assess patient response to therapy as the co-primary outcomes, while liver function tests were assayed too. Forty patients completed the study. The VAS score showed alleviation of 3.21 ± 2.24 (in pruritus) with melatonin (p-value <0.05). The study goal (a reduction of at least 20% in VAS) was achieved in 33 (82%) of study participants. In patients who received melatonin, the 12-PSS and Body Surface Area (BSA) affected by pruritus decreased on average 46.57% and 51.71%, respectively, with mood, sleep pattern and daily activity levels also demonstrating significant improvement (p-value < 0.05). Melatonin was found to be effective for managing pruritus in patients with CLD.