The efficacy of topical sodium pentaborate formulation on hemorrhoid disease: A randomized, double-blind, placebo-controlled trial.

Background: The topical application of boron has been significantly associated with intensifying wound healing. Using 3% boric acid in deep wounds significantly contributes to wound healing and reduces the duration of hospitalization in the intensive care. The objective of this study was to assess the therapeutic impact of a topical gel containing sodium pentaborate pentahydrate on the management of wounds resulting from grade 1 to 3 hemorrhoids. Methods: In this randomized double-blind placebo-controlled trial, we applied a topical gel consisting of sodium pentaborate pentahydrate 3% on 206 eligible patients with the diagnosis of grade 1, 2, and 3 hemorrhoid diseases. Then patients were randomly allocated to two groups of sodium pentaborate pentahydrate or placebo gel with a ratio of 1:1 and received the allocated gel for four weeks. Patient hemorrhoid symptoms severity, hemorrhoid degree, and anoscopy findings were compared before and after the trial. Results: Before the intervention, symptom severity (p > 0.05) and anoscopy findings (p = 0.815) were similar between the two groups. Subsequent to the intervention, a majority of patients in the intervention group experienced a reduction in anal itching compared to the placebo group [adjusted mean difference (aMD) 95% CI: -1.98 (-2.2 to -1.8), p = 0.007]. Moreover, resting pain [aMD (95% CI): -1.37 (-1.6 to -1.1), p = 0.015], pain during defecation [aMD (95% CI): -2.19 (-2.4 to -2.0), p = 0.005], feeling a lump in the anus (aMD (95% CI): -0.71 (-1.2 to -0.2), p = 0.011), bleeding during defecation (41.7% vs. 66.9%, p = 0.027), and hemorrhoid degree (p < 0.001) in the intervention group was less than the placebo group. Conclusion: Our findings indicate the effectiveness of the study gel on hemorrhoid symptoms and anoscopy findings in patients.

Determination of indoxyl sulfate by spectrofluorimetric method in human plasma through extraction with deep eutectic solvent.

A rapid and efficient analytical method was established to quantify indoxyl sulfate (IS) in plasma through extraction technique with a deep eutectic solvent (DES) and spectrofluorimetric method. DES (choline chloride: urea) was mixed with plasma samples for the extraction of IS, followed by the addition of dipotassium hydrogen phosphate (K2HPO4) solution to form an aqueous two-phase system. The fluorescence intensity of IS which was first extracted to the DES-rich-phase and then back-extracted into the salt-rich-phase, was measured by spectrofluorimetric method. Some key factors such as pH, centrifugation speed and time, the volume ratio of DES/salt, and salt concentration were optimized. Under the optimized conditions, the suggested method had a dynamic range between 20 and 160 µg/mL with a coefficient of determination (R2) of 0.99. Precision (relative standard deviation) was less than 15% and accuracy (% relative recovery) was ± 15% at the nominal concentration level. In addition, results showed that IS levels in real samples were higher than 40 µg/mL which was compatible with reported IS levels in end-stage renal disease (ESRD) patients. Overall, all the results reflect the fact that the presented analytical method can potentially be used for the determination of IS in real plasma samples.

In-situ preparation of norepinephrine-functionalized silver nanoparticles and application for colorimetric detection of tacrolimus in plasma samples.

Tacrolimus (Tac) is a well-documented immunosuppressive agent for the prevention of graft-vs-host diseases in several types of organ transplants. The narrow therapeutic window and the individual-variable pharmacokinetics of Tac demonstrate the importance of regular therapeutic drug monitoring (TDM) as an imperative concept for its oral medication regimens. A simple, one-step, selective, and sensitive colorimetric platform is fabricated for the determination of Tac by surface modification of the silver nanoparticles (AgNPs) via norepinephrine (NE) molecules. The attachment of NE and Tac induces the aggregation of the AgNPs, which is observed by color distinction (yellow to brown) and a noteworthy shifting of the absorption peak in the visible region. The fabricated nanoprobe can detect Tac concentrations in plasma samples in two linear ranges from 2 ng/mL to 70 ng/mL and 70 ng/mL to 1000 ng/mL with R2 > 0.99. The limit of detection (LOD) was calculated as low as 0.1 ng/mL. The developed method was applied for the determination of Tac in patient's plasma samples under Tac medication therapy.

Two-photon fluorescence probe for quantification of cyclosporine.

A novel ratiometric fluorescent sensor was fabricated for the fast and facile determination of cyclosporine A (CsA). Due to the narrow therapeutic index of CsA, its desired therapeutic effects are evident within a limited range of blood concentration, indicating the fundamental role of therapeutic drug monitoring in CsA pharmacological response. In this study, a two-photon fluorescence probe based on the zeolitic imidazolate framework (ZIF-8) and norepinephrine-capped silver nanoparticles (AgNPs@NE) was employed for the quantification of the CsA in human plasma samples. In the presence of CsA, the fluorescent emission intensity of ZIF-8-AgNPs@NE was quenched. Under the optimum conditions, the proposed probe determines CsA in plasma samples in two linear ranges of 0.01 to 0.5 µg mL-1 and 0.5 to 10 µg mL-1. The developed probe demonstrates the advantages of a facile and fast platform with limit of detection as low as 0.007 µg mL-1. At last, this method was applied to find CsA concentration in four patients receiving oral CsA regimen which indicates it as a promising method for on-site detection applications.

Dual-emission ratiometric fluorescent probe based on N-doped CQDs@UiO-66/PVA nanocomposite hydrogel for quantification of pethidine in human plasma.

A synchronous fluorescence spectroscopy (SFS) sensor for pethidine detection is described based on UiO-66 metal-organic frameworks (MOFs) modified with N-doped carbon quantum dots (N-CQDs) embedded in hydrogel nanocomposites. Benefitting from the inovative  design of the doping method in the carbonaceous structure, N-CQDs were successfully deposited in the pores of the UiO-66 network. Then, N-CQDs were employed as a sensitive segment toward the target molecules. UiO-66 was used for sensitive and selective sensing of the bonding interactions between N-CQDs and pethidine so that the electron transfer process from UiO-66 to the pethidine-N-CQD complex results in quenching the SFS intensity of UiO-66. To embed the stable and suitable sensing interface for pethidine assessment, the designed nanomaterial was inserted into the hydrogel network. This nanocomposite hydrogel showed two well-resolved emission peaks at 300 nm and 350 nm under ∆λ = 70, which corresponded to N-CQDs and UiO-66, respectively. The SFS sensing platform was employed for ratiometric detection of pethidine with a low limit of detection of 0.002 µg mL-1 over a wide concentration range from 0.005 to 1.0 µg mL-1. The accurate monitoring of pethidine with a good recovery of 90.8-101.5% indicated their independency from matrix effects for pethidine detection in human plasma being a complicated biological matrix. Scheme 1. General procedure for synthesizing N-CQDs@UiO-66/PVA hydrogel-based nanoprobe and its application for pethidine determination.

Comparison of the efficacy of pioglitazone and metformin on ultrasound grade and liver enzymes level in patients with non-alcoholic fatty liver disease: A randomized controlled clinical trial.

BACKGROUND: This study aimed to evaluate the effectiveness of metformin and pioglitazone in combination with vitamin E on sonography grade and liver enzymes level in patients with non-alcoholic fatty liver disease. METHODS: A randomized controlled clinical trial was designed with 68 patients diagnosed with non-alcoholic fatty liver disease by sonography and clinical examinations. Sixty-eight patients were randomly divided into two groups; 34 were assigned to receive 15 mg of pioglitazone per day and 34 were assigned to receive 1000 mg of metformin per day for 6 months. All of the patients received vitamin E at a dose of 800 IU daily for six months. The sonography grade of fatty liver and the levels of alanine aminotransferase and aspartate aminotransferase of patients were evaluated at baseline, and within three and six months after initiation of the intervention. RESULTS: The use of metformin or pioglitazone in combination with vitamin E decreased the sonography grade of non-alcoholic fatty liver disease patients after 6 months of treatment (p-value<0.05); however, patients in metformin group benefit more compared to pioglitazone group. Patients who received metformin and vitamin E had a significant reduction in the levels of alanine aminotransferase and aspartate aminotransferase (p-value<0.05). There were no significant changes in the liver enzymes level of the patients who received pioglitazone and vitamin E (p-value>0.05). MAJOR CONCLUSION: The concomitant use of metformin and vitamin E significantly improves the sonography grade of fatty liver and the level of liver enzymes in patients with non-alcoholic fatty liver disease.

Prevalence and Predicting Risk Factors of Polypharmacy in Azar Cohort Population.

Background: As polypharmacy has some medically negative impacts, it has become a challenging issue for public health and affected people. Therefore, we decided to investigate the prevalence of polypharmacy and its predicting risk factors in the Azar cohort population. Methods: In this cross-sectional population-based cohort study, the prevalence of polypharmacy was evaluated in 15,001 subjects who participated in the Azar cohort study. We measured demographic characteristics (age, gender, socioeconomic status, smoking status, marital status, and education level), physical activity level, body mass index (BMI), blood pressure, multimorbidity (coexistence of two or more chronic diseases (CDs)), and polypharmacy status (a daily intake of five or more medicines for a minimum of 90 days). Results: Based on our results, 9.51% of the population had polypharmacy. The five most prescribed medications were drugs acting on the cardiovascular system (19.9%), central nervous system (16.7%), endocrine system (13.3%), NSAIDs (11.5%), and drugs used for musculoskeletal and joint diseases (11.4%). Being female, illiterate, and having the lowest tertile of physical activity level significantly increased the risk of polypharmacy. The risk of polypharmacy was 49.36 times higher in patients with four or more CDs than in those without. Conclusions: Our study emphasized the importance of routine monitoring to evaluate polypharmacy among those aged 35 to 59 and the elderly. Physicians should carefully assess drug suitability, especially in multimorbid and obese patients, to prevent excessive polypharmacy and its potentially negative impacts.

Value of Canadian C-spine rule versus the NEXUS criteria in ruling out clinically important cervical spine injuries: derivation of modified Canadian C-spine rule.

PURPOSE: Although, Canadian C-spine rule and the National Emergency X-Radiography Utilization Study (NEXUS) criteria in ruling out clinically important cervical spine injuries have been validated using large prospective studies, no consensus exist as to which rule should be endorsed. Therefore, the aim of the present study was to compare the accuracy of the Canadian C-spine and NEXUS criteria in ruling out clinically important cervical spine injuries in trauma patients. Finally, we introduced the modified Canadian C-spine rule. METHODS: A prospective diagnostic accuracy study was conducted on trauma patients referred to four emergency departments of Iran in 2018. Emergency physicians evaluated the patients based on the Canadian C-spine rule and NEXUS criteria in two groups of low risk and high risk for clinically important cervical spine injury. Afterward, all patients underwent cervical imaging. In addition, modified Canadian C-spine rule was derived by removing dangerous mechanism and simple rear-end motor vehicle collision from the model. RESULTS: Data from 673 patients were included. The area under the curve of the NEXUS criteria, Canadian C-spine, and modified Canadian C-spine rule were 0.76 [95% confidence interval (CI) 0.71-0.81)], 0.78 (95% CI 0.74-0.83), and 0.79 (95% CI 0.74-0.83), respectively. The sensitivities of NEXUS criteria, Canadian C-spine, and modified Canadian C-spine rule were 93.4%, 100.0% and 100.0%, respectively. CONCLUSIONS: The modified Canadian C-spine rule has fewer variables than the original Canadian C-spine rule and is entirely based on physical examination, which seems easier to use in emergency departments.

The Effect of Treating Vitamin D Deficiency or Insufficiency on Serum Adiponectin, Leptin and Insulin Resistance of Type 2 Diabetes Mellitus Patients: A Pilot Study.

Vitamin D deficiency is considered as one of the most prevalent healthcare problems in the world. Vitamin D contributes to insulin synthesis and secretion. Deficiency of vitamin D leads to insulin resistance which is the major cause of type 2 diabetes mellitus. We aim to evaluate the effect of treating vitamin D deficiency or insufficiency on serum adiponectin, leptin, and leptin to adiponectin ratio (LAR) of type 2 diabetes mellitus patients. Forty patients with type 2 diabetes mellitus were included according to the inclusion criteria of the study. Fasting venous blood samples were obtained and evaluated before and after the treatment of vitamin D deficiency or insufficiency. Then, blood levels of leptin, adiponectin, and LAR (an indicator of insulin resistance) were measured. The results of study indicate a significant decline in circulating leptin and adiponectin after vitamin D treatment, but it doesn't cause a noteworthy change in LAR. Furthermore, the study demonstrates that female gender, higher body mass index, and triglyceride levels increase LAR significantly. It was concluded that the treatment of vitamin D deficiency or insufficiency doesn't change insulin resistance in diabetic patients. Moreover, we concluded that LAR is not a reliable method to compare insulin resistance between men and women due to sex-related differences in adipose tissue.

Treatments of nonalcoholic fatty liver disease in adults who have no other illness: A Review article.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. In the absence of treatment, NAFLD can damage the liver tissue and even have extra-hepatic complications. No therapeutic regimen has ever been approved for the treatment of this disease. A variety of clinical trials have been conducted in the field of NAFLD. Reviewing these trials is necessary to provide the most effective treatments. In this article, we aimed to review randomized controlled trials that evaluate the effects of pharmacological agents on NAFLD adults without other illness.

Stomach-Specific Drug Delivery of Clarithromycin Using a Semi Interpenetrating Polymeric Network Hydrogel Made of Montmorillonite and Chitosan: Synthesis, Characterization and In Vitro Drug Release Study.

Purpose: In this study, we aimed to prepare an extended drug delivery formulation of clarithromycin (CAM) based on a semi-interpenetrating polymer network (semi-IPN) hydrogel. Methods: Synthesis of semi-IPN hydrogel nanocomposite made of chitosan (CS), acrylic acid (AA), acrylamide (AAm), polyvinylpyrrolidone (PVP), and montmorillonite (MMT) was performed by free radical graft copolymerization method. Swelling kinetic studies were done in acidic buffer solutions of hydrochloric acid (pH = 1.2), acetate (pH = 4), and also distilled water. Also, the effects of MMT on the swelling kinetic, thermal stability, and mechanical strength of the hydrogels were evaluated. Moreover, in vitro release behavior of CAM and its release kinetics from hydrogels were studied in a hydrochloric acid buffer solution. Results: Fourier transform infrared spectroscopy (FTIR) results revealed that synthesis of semi- IPN superabsorbent nanocomposite and CAM incorporation into hydrogel was performed, successfully. Introducing MMT into hydrogel network not only improved its thermal stability but also increased mechanical strength of the final hydrogel product. Also, in comparison with neat hydrogel (1270 g/g), hydrogel nanocomposite containing 13 wt% MMT exhibited greater equilibrium swelling capacity (1568 g/g) with lower swelling rate. In vitro drug release experiments showed that CS-g-poly(AA-co-AAm)/PVP/MMT/CAM formulation possesses a sustained release character over extended period of time compared with CS-g-poly(AA-co- AAm)/PVP/CAM formulation. Conclusion: In the presence of MMT, the effective life time of drug is prolonged, demonstrating a sustained release property. The reason is that interlinked porous channels within superabsorbent nanocomposite network hinder penetration of aqueous solutions into hydrogel and subsequently cause a slower drug release.

Detection and Management of Common Medication Errors in Internal Medicine Wards: Impact on Medication Costs and Patient Care.

Purpose: Medication errors (MEs) are a leading cause of morbidity and mortality, yet they have remained as confusing and underappreciated concept. The complex pharmacotherapy in hospitalized patients necessitates continued report and surveillance of MEs as well as persistent pharmaceutical care. This study evaluated the frequency, types, clinical significance, and costs of MEs in internal medicine wards. Methods: In this 8-month prospective and cross-sectional study, an attending clinical pharmacist visited the patients during each physician's ward round at the morning. All MEs including prescription, transcription, and administration errors were detected, recorded, and subsequently appropriate corrective interventions were proposed during these rounds. The changes in the medications' cost after implementing clinical pharmacist's interventions were compared to the calculated medications' cost, assuming that the MEs would not have been detected by clinical pharmacist and continued up to discharge time of the patients. Results: 89% of the patients experienced at least one ME during their hospitalization. A mean of 2.6 errors per patient or 0.2 errors per ordered medication occurred in this study. More than 70% of MEs happened at the prescription stage by treating physicians. The most prevalent prescription errors were inappropriate drug selection, unauthorized drugs and untreated indication. The highest MEs occurred on cardiovascular agents followed by antibiotics, and vitamins, minerals, and electrolytes. The net effect of clinical pharmacist's contributions in medication therapy management was to decline medications' costs by 33.9%. Conclusion: The role of clinical pharmacy services in detection, prevention and reducing the cost of MEs is of paramount importance to internal medicine wards.

Isotretinoin; A review on the Utilization Pattern in Pregnancy.

Purpose: Isotretinoin is the most effective anti-acne drug with a long-term remission. However; it contains severe teratogenic effects with serious adverse drug reactions, which limits the use of medication. Methods: To review the use of isotretinoin during pregnancy, we carried out a comprehensive search of literature in Google Scholar, Scopus and PubMed/Medline from their inception until April 2015. Results: Database searching identified 277 records, of which, 38 articles were retrieved according to abstract and title assessment. After full-text review, 17 articles were excluded and finally, a total of 21 studies met the inclusion criteria. Data showed an increased pattern in the use of isotretinoin. In some studies, health care providers were not fully adhered to the risk reduction programs in pregnancy. Exposing to isotretinoin among pregnant women has still occurred due to detrimental adherence to risk reduction programs which resulted in live-born infants with different kinds of abnormalities. Conclusion: Despite the known serious adverse effect of isotretinoin, the use of drug was not based on the guidelines in some cases, which needs more attentions to prevent the severe drug related problems.

Potential Effects of Omega-3 Fatty Acids on Insulin Resistance and Lipid Profile in Maintenance Hemodialysis Patients: a Randomized Placebo-Controlled Trial.

INTRODUCTION: Insulin resistance (IR), a risk factor for cardiovascular disease and all-cause mortality, is prevalent among maintenance hemodialysis patients. Effects of omega-3 fatty acids on IR in hemodialysis patients have not been well understood. This study aimed to determine the effects of omega-3 fatty acids on IR and serum lipids of hemodialysis patients. MATERIALS AND METHODS: Fifty-four adult patients on hemodialysis were randomly assigned to receive either 1800 mg of omega-3 fatty acids or placebo daily for 4 months. Serum concentrations of glucose, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, C-reactive protein, insulin, leptin, and adiponectin were measured at baseline and after 4 months of the intervention. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance and 2 adipokine-based measures of IR, including the leptin-adiponectin ratio and homeostasis model assessment corrected by adiponectin. RESULTS: Mean differences of serum C-reactive protein, insulin, leptin, and adiponectin concentrations did not show significant difference between the two groups following 4 months of intervention. Fasting serum glucose and low-density lipoprotein cholesterol were not significantly influenced by omega-3 supplementation, either. Serum triglyceride, total cholesterol, and high-density lipoprotein cholesterol levels significantly decreased in the omega-3 group (P = .02, P = .03, and P < .001, respectively). None of the indirect indexes of IR showed significant changes at the end of the study in either the omega-3 or placebo group. CONCLUSIONS: Supplemental use of omega-3 fatty acids showed some beneficial effects on lipid profile of hemodialysis patients without any improvement in IR.

Role of Vitamin D in Cardiovascular Disease.

BACKGROUND: According to many studies, vitamin D deficiency has been linked to cardiovascular diseases (CV). Other than maintaining skeletal health, vitamin D has been shown to decrease the risk of developing CV disease such as hypertension, coronary artery disease (CAD) and thromboembolism. MATERIALS AND METHODS: To perform a comprehensive review of the current literature on vitamin D and CV disease, we searched the online database, including PUBMED, Scopus, and Google Scholar until data inception January 2016. The search term included "vitamin D", "blood pressure", "hypertension", "coronary artery disease "and "thrombosis". We only included human studies that were published in English. RESULTS: A majority of data indicate that there is no relationship between vitamin D and hypertension, but the association of vitamin D with thrombosis is yet to be determined. Vitamin D is a fair predictor of adverse outcomes in coronary artery disease (CAD), which highlights it for future studies. CONCLUSION: According to research, there is a high prevalence of vitamin D deficiency among patients with CV diseases, which needs to be diagnosed and treated.

Therapeutic Effects of Omega-3 Fatty Acids on Chronic Kidney Disease-Associated Pruritus: a Literature Review.

Uremic pruritus remains one of the most tormenting, frequent and potentially disabling problem in chronic kidney disease (CKD) patients. However, an area of substantial etiological interest with relation to uremic pruritus is the essential fatty acids deficiency. So we performed a literature review to elucidate the efficacy of omega-3 fatty acids on uremic pruritus. This review evaluated all of the studies published in English language, focusing on the clinical effects of omega-3 fatty acids on uremic pruritus. The literature review was conducted in December 2015 and carried out by searching Scopus, Medline, Cochrane central register of controlled trials, and Cochrane database of systematic reviews. The search terms were "kidney injury", "kidney failure", "chronic kidney disease", "end-stage renal disease", "dialysis", "hemodialysis", "peritoneal dialysis", "pruritus", "itch", "skin problems", "fish oil", "omega 3", "n-3 fatty acids", "polyunsaturated fatty acids", "docosahexaenoic acid", and "eicosapentaenoic acid". Four small studies investigating potential benefits of omega-3 fatty acids on symptoms of uremic pruritus were found. Among them, three small randomized controlled trials have shown a significant improvement in pruritus symptoms (evaluated by a standard questionnaire) in CKD patients who took omega-3 supplement compared to omega-6, omega-9, and placebo supplementation. Despite numerous limitations of the studies, it is worth noting that even minor reduction in itching symptoms may be clinically significant for CKD patients. Therefore, and considering multiple health benefits of omega-3 fatty acids in advanced CKD and negligible risk profile, omega-3 intake can wisely be applied to CKD patients with uremic pruritus.

Prevention of hemodialysis catheter-related blood stream infections using a cotrimoxazole-lock technique.

BACKGROUND & AIM: This trial assessed the efficacy of cotrimoxazole lock solution in reducing catheter-related blood stream infections (CRBSIs) among hemodialysis (HD) patients who were dialyzed using tunneled catheters. METHOD: Patients randomly received either heparin (2500 U/ml) (control group) or a mixture of 10 mg/ml cotrimoxazole (based on trimethoprim) and 2500 U/ml heparin (antibiotic group) as catheters lock solution. RESULTS: Compared with the control group, CRBSIs rates per 1000 catheter-days was significantly lower (0.58 vs 4.4 events; p = 0.002) and cumulative infection-free catheter survival was significantly higher (log rank statistic 5.88; p = 0.015) in the antibiotic group. There were no statistical differences regarding incidences of catheter removal (8.7% in the antibiotic group vs 22% in the control group; p = 0.116) or thrombosis (2.2% in the antibiotic group vs 9.8% in the control group; p = 0.129) between the two groups. CONCLUSION: cotrimoxazole containing catheter lock solution is effective in reducing CRBSIs incidence and prolonging dialysis catheter survival in HD patients.

Frequency, types, and direct related costs of medication errors in an academic nephrology ward in Iran.

Medication errors are ongoing problems among hospitalized patients especially those with multiple co-morbidities and polypharmacy such as patients with renal diseases. This study evaluated the frequency, types and direct related cost of medication errors in nephrology ward and the role played by clinical pharmacists. During this study, clinical pharmacists detected, managed, and recorded the medication errors. Prescribing errors including inappropriate drug, dose, or treatment durations were gathered. To assess transcription errors, the equivalence of nursery charts and physician's orders were evaluated. Administration errors were assessed by observing drugs' preparation, storage, and administration by nurses. The changes in medications costs after implementing clinical pharmacists' interventions were compared with the calculated medications costs if the medication errors were continued up to patients' discharge time. More than 85% of patients experienced medication error. The rate of medication errors was 3.5 errors per patient and 0.18 errors per ordered medication. More than 95% of medication errors occurred at prescription nodes. Most common prescribing errors were omission (26.9%) or unauthorized drugs (18.3%) and low drug dosage or frequency (17.3%). Most of the medication errors happened on cardiovascular drugs (24%) followed by vitamins and electrolytes (22.1%) and antimicrobials (18.5%). The number of medication errors was correlated with the number of ordered medications and length of hospital stay. Clinical pharmacists' interventions decreased patients' direct medication costs by 4.3%. About 22% of medication errors led to patients' harm. In conclusion, clinical pharmacists' contributions in nephrology wards were of value to prevent medication errors and to reduce medications cost.