An adapted model of cost-related medication nonadherence among older adult patients with chronic diseases: an Iranian qualitative study.

BACKGROUND: Following the rapid aging of population, some concerns have emerged regarding increasing demand for health care services and the consequent increase in health costs. Besides, older adult patients with chronic disease are more prone to show cost-related medication non-adherence (CRN) to cope with their medication costs. The objective of this qualitative study was to develop an adopted conceptual framework on the contextual determinants that affect the CRN in older adult patients with chronic diseases. METHODS: Problem-centered, semi-structured, in-depth, and face-to-face interviews, were conducted with healthcare informants in Iran, from Sep. 2021 to Feb. 2022. Collected data were analyzed using deductive and inductive analytic approaches and content analysis methodology was used to develop the model. This study applies to the COREQ checklist. RESULTS: Fifteen informants, including 8 (60%) males, with mean ± SD age of 44.4 ± 9.7 years, entered into the study. Based on the data analysis performed on the information obtained from the interview with 3 subgroups of geriatricians, health policymakers, and pharmacists, six major themes identified as determinants: 1) socio-economic factors, 2) health system-related factors, 3) healthcare provider-related factors, 4) medication-related factors, 5) disease-related factors, and 6) patient-related factors. There were also 23 minor themes which were matched with the aforementioned six major themes. CONCLUSION: The final framework obtained in this qualitative study depicts CRN as an issue that is highly likely affected by six main determinants among older patients with chronic disease. Our findings emphasize that policymakers would focus on certain major themes and allocate resources to programs to improve medication therapy management in older adult patients.

Investigation of pharmacokinetic and clinical outcomes of various meropenem regimens in patients with ventilator-associated pneumonia and augmented renal clearance.

INTRODUCTION: Augmented renal clearance (ARC) defined as creatinine clearance (Clcr) above 130 mL/min/1.73m2 may lead to suboptimal antibacterial treatment. The aim of this study was to determine a strategy for meropenem administration to achieve both pharmacodynamic-pharmacokinetic (PK-PD) target (50%fT > MIC) and better clinical outcomes in patients with VAP and ARC. MATERIALS AND METHODS: In this randomized clinical trial, patients with VAP and high risk for ARC were recruited. An 8-h urine collection was performed on the 1st, 3rd, and 5th days of study to measure Clcr. Included patients were divided into three groups: (1) 1 g meropenem, 3-h infusion, (2) 2 g meropenem, 3-h infusion, (3) 1 g meropenem, 6-h infusion. On the 2nd, 3rd, and 5th days of treatment, peak and trough blood samples were collected to undergo HPLC assay. MICs were assessed using microdilution method. Patients were also clinically monitored for 14 days. RESULTS: Forty-five patients were included. Group 3 showed significanty higher rate of patients achieving fT > MIC > 50% (100% for group 3 versus 40% for group 2 and 13% for group 1; p = 0.0001). Mean fT > MIC% was significantly higher in group 3 (78.77 ± 5.87 for group 3 versus 49.6 ± 7.38 for group 2 and 43.2 ± 7.98 for group 1; p = 0.0001). Statistical analysis showed no significant differences among groups regarding clinical improvement. CONCLUSION: According to the findings of this trial, prolonged meropenem infusion is an appropriate strategy compared to dose elevation among ARC patients.

Irrational use of antibiotics in Iran from the perspective of complex adaptive systems: redefining the challenge.

BACKGROUND: Irrational use of antibiotics is proving to be a major concern to the health systems globally. This results in antibiotics resistance and increases health care costs. In Iran, despite many years of research, appreciable efforts, and policymaking to avoid irrational use of antibiotics, yet indicators show suboptimal use of antibiotics, pointing to an urgent need for adopting alternative approaches to further understand the problem and to offer new solutions. Applying the Complex Adaptive Systems (CAS) theory, to explore and research health systems and their challenges has become popular. Therefore, this study aimed to better understand the complexity of the irrational use of antibiotics in Iran and to propose potential solutions. METHOD: This research utilized a CAS observatory tool to qualitatively collect and analyse data. Twenty interviews and two Focus Group discussions were conducted. The data was enriched with policy document reviews to fully understand the system. MAXQDA software was used to organize and analyze the data. RESULT: We could identify several diverse and heterogeneous, yet highly interdependent agents operating at different levels in the antibiotics use system in Iran. The network structure and its adaptive emergent behavior, information flow, governing rules, feedback and values of the system, and the way they interact were identified. The findings described antibiotics use as emergent behavior that is formed by an interplay of many factors and agents over time. According to this study, insufficient and ineffective interaction and information flow regarding antibiotics between agents are among key causes of irrational antibiotics use in Iran. Results showed that effective rules to minimize irrational use of antibiotics are missing or can be easily disobeyed. The gaps and weaknesses of the system which need redesigning or modification were recognized as well. CONCLUSION: The study suggests re-engineering the system by implementing several system-level changes including establishing strong, timely, and effective interactions between identified stakeholders, which facilitate information flow and provision of on-time feedback, and create win-win rules in a participatory manner with stakeholders and the distributed control system.

Medication adherence and its possible associated factors in patients with acne vulgaris: A cross-sectional study of 200 patients in Iran.

There are several etiologic factors involved in the pathogenesis of acne vulgaris. Therefore, current treatment guidelines recommend applying different classes of medications for it. This makes medication adherence a challenging issue in acne patients. The current study was designed to assess medication adherence and its possible associated factors in patients with acne vulgaris. This study was performed on patients with acne vulgaris in two dermatology clinics of Imam Khomeini Hospital and Razi Hospital. A validated questionnaire (ECOB, Elaboration d'un outil d'evaluation de l'observance des traitements medicamenteux) was applied to evaluate adherence to topical and oral therapies. We assessed relationship between patients' medication adherence and their sociodemographic, medication, and medical histories. A total of 200 patients, 136 females (68%), and 64 males (32%), with a mean age of 22 years were entered into the study. Overall, only 30 out of 200 patients (15%) were adherent to their treatments. Based on the bivariate analyses, food exacerbations, and severity of the disease by the patient's opinion was significantly associated with overall medication adherence (P = .03). Moreover, patients who were more adherent to topical treatment were more adherent to systemic treatment, as well (P = .007). The current study showed that treatment adherence was very low among patients with acne vulgaris. It is recommended to educate patients on the proper use of anti-acne medications. Besides, it is highly recommended that physicians and pharmacists use ECOB questionnaire regularly to guide patients accurately with the use of their drug regimens.

Effects of High-Dose Vitamin D Replacement on the Serum Levels of Systemic Inflammatory Biomarkers in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Chronic Obstructive Pulmonary Disease (COPD) is associated with increased inflammatory responses to noxious particles, which can be further enhanced during Acute Exacerbation of COPD (AECOPD). Considering the important immunoregulatory function of vitamin D, high prevalence of Vitamin D Deficiency (VDD) in COPD patients and a negative link between vitamin D levels and inflammatory biomarkers, suggests the seemingly interesting mechanism of vitamin D effects on inflammation resolution during the conventional treatment of AECOPD. The admitted AECOPD patients with VDD were recruited and randomly allocated to receive either 300,000 IU of intramuscular vitamin D (n = 35) or placebo (n = 35). Primary outcomes included inflammation resolution dynamics, which were assessed by monitoring the serum levels of IL-6, IL-8, and hs-CRP. Symptom recovery was evaluated based on the modified Medical Research Council (mMRC) dyspnea scale on the 1st and 6th days of admission. Secondary outcomes included the length of hospital stay (LOS) and 30-day mortality rates. Inflammatory biomarkers were highest at Day 1. Baseline vitamin D levels were 11.25 ± 3.09 and 10.59 ± 3.90 ng/ml (P = 0.45), which reached 11.35 ± 3.16 and 18.17 ± 4.24 by Day 6 (P < 0.001) in the placebo and, vitamin-D groups, respectively. IL-6 levels significantly decreased in the vitamin-D vs. placebo group on the 6th day (P = 0.02); however, no significant differences were observed in IL-8 (P = 0.15) and hs-CRP (P = 0.24) levels, mMRC scale (P = 0.45), LOS (P = 0.20), and mortality rates (P = 0.61). Vitamin D replacement as adjunctive therapy may accelerate inflammation resolution in hospitalized AECOPD patients. Further studies were needed to establish vitamin D exact role on inflammation resolution in AECOPD.

N-acetylcysteine decreases urinary level of neutrophil gelatinase-associated lipocalin in deceased-donor renal transplant recipients: a randomized clinical trial.

CONTEXT: Acute kidney injury (AKI) is a common complication after kidney transplantation (KT), especially in recipients from deceased donors. Urinary neutrophil gelatinase-associated lipocalin (u-NGAL) is an early and sensitive marker of AKI after transplantation. OBJECTIVES: We assessed the renoprotective effect of N-acetylcysteine (NAC) on u-NGAL levels as an early prognostic marker of graft function immediately after transplantation. MATERIALS AND METHODS: A double-blind, randomized, placebo-controlled trial was conducted on 70 deceased-donor KT recipients ( www.irct.ir , trial registration number: IRCT2014090214693N4). Patients received 600 mg oral NAC or placebo twice daily from day 0 to 5 and urine samples were taken before, and on the first and fifth days after transplantation. U-NGAL and early graft function were compared between the two groups. RESULTS: NAC significantly reduced u-NGAL levels compared to placebo (p value = 0.02), while improvement in early graft function with NAC did not reach statistical significance. CONCLUSIONS: This study showed that NAC administration in deceased-donor KT recipients can reduce tubular kidney injury, evidenced by u-NGAL measurements. Improvement in early graft function needs a larger sample size to reach a statistical conclusion.

Evaluating the Effect of Intracoronary N-Acetylcysteine on Platelet Activation Markers After Primary Percutaneous Coronary Intervention in Patients With ST-Elevation Myocardial Infarction.

During percutaneous coronary intervention (PCI), trauma occurs in the arterial endothelium, resulting in platelet activation and aggregation. As platelet aggregation may lead to coronary thrombosis, antiplatelet agents are essential adjunctive therapies in patients undergoing PCI. The aim of this study was to determine the effect of the intracoronary administration of high-dose N-acetylcysteine (NAC) for the evaluation of its antiplatelet effects in human subjects. In this triple-blind trial, 147 patients undergoing primary PCI were enrolled. Finally, 100 patients were randomized to receive high-dose intracoronary NAC (100 mg/kg bolus, followed by 10 mg·kg⁻¹·h⁻¹ intracoronary continued intravenously for 12 hours) (n = 50) or dextrose solution (n = 50). Platelet activation biomarkers were measured before and 24 hours after the procedure. Secondary end points, comprising all-cause death, reinfarction, and target-vessel revascularization, were assessed at 30 days and 2 years. In comparison with the placebo, NAC could not reduce the level of platelet activation biomarkers within a 24-hour period after its prescription. Major adverse clinical events at 30 days and 2 years were infrequent and not statistically different between the 2 groups. Our results revealed that NAC, compared with the placebo, did not provide an additional clinical benefit as an effective antiplatelet agent after PCI.

Effects of atorvastatin on plasma matrix metalloproteinase-9 concentration after glial tumor resection; a randomized, double blind, placebo controlled trial.

BACKGROUND: Neurosurgical procedures such as craniotomy and brain tumor resection could potentially lead to unavoidable cerebral injuries. Matrix metalloproteinase-9 (MMP-9) is up-regulated in neurological injuries. Statins have been suggested to reduce MMP- 9 level and lead to neuroprotection. Atorvastatin preoperatively administered to evaluate its neuroprotective effects and outcome assessment in neurosurgical-induced brain injuries after glial tumor resection. In this prospective, randomized, double-blind, placebo-controlled trial, 42 patients undergoing glial tumor surgery randomly received 40 mg atorvastatin or placebo twice daily from seven days prior to operation and continued for a 3 weeks period. Plasma MMP-9 concentration measured 4 times, immediately before starting atorvastatin or placebo, immediately before surgery, 24 hours and two weeks after the surgery. Karnofsky performance score was assessed before first dose of atorvastatin as a baseline and 2 months after the surgery. RESULTS: Karnofsky performance scale after surgery raised significantly more in Atorvastatin group (11.43 +/- 10.62 vs. 4.00 +/- 8.21) (p = 0.03). Atorvastatin did not significantly reduce MMP-9 plasma concentration 24 hours after surgery in comparison to placebo. No statistical significance detected regarding length of hospital stay among the groups. Significant reduction in MMP-9 plasma concentration was recorded in atorvastatin group two weeks after surgery (p = 0.048). CONCLUSIONS: Significant statistical differences detected with atorvastatin group regarding MMP-9 plasma concentration, clinical outcome and Karnofsky performance score. Consequently, atorvastatin use may lead to better outcome after neurosurgical procedures.

Short-term consumption of oral omega-3 and dry eye syndrome.

PURPOSE: To assess the effect of oral omega-3 fatty acids on tear break-up time (TBUT), Schirmer's score, and Ocular Surface Disease Index (OSDI) through a double-blind clinical trial. DESIGN: Randomized, double-blind clinical trial. PARTICIPANTS: Sixty-four patients with dry eye symptoms between the ages of 45 and 90 years were randomized into 2 groups: 33 persons in the treatment group and 31 persons in the placebo group. METHODS: The treatment group received 2 capsules of omega-3 (each containing 180 mg eicosapentaenoic acid [EPA] and 120 mg docosahexaenoic acid [DHA]) daily for 30 days, and the placebo group received 2 medium-chain triglyceride oil capsules daily for 1 month. The outcomes were measured 1 month after the intervention. MAIN OUTCOME MEASURES: The primary outcome measure was an increase from baseline in TBUT at day 30. Secondary outcome measures were a decrease from baseline in the OSDI score and an increase in the Schirmer's score at day 30. RESULTS: In the placebo group, before the intervention, the mean TBUT, OSDI, and Schirmer's scores were 4.5 ± 2.1 seconds, 36.4 ± 13.8, and 6.0 ± 2.6 mm, respectively, and 1 month later were 4.7 ± 2.6 seconds, 37.6 ± 13.5, and 6.2 ± 2.5 mm, respectively. In the treatment group, these values were 3.9 ± 1.7 seconds, 38.7 ± 16.5, and 5.8 ± 2.5 mm before the intervention and 5.67 ± 2.6 seconds, 29.3 ± 15.9, and 6.8 ± 2.8 mm after the intervention, respectively. Repeated-measures analysis of variance showed that improvements in TBUT, OSDI, and Schirmer's scores were significantly better in the treatment group than in the placebo group. The changes in the treatment and placebo groups were 71% and 3.3% for TBUT (P < 0.001), 26% and 4% (P=0.004) for dry eye symptoms, and 22.3% and 5.1% for Schirmer's score (P=0.033), respectively. CONCLUSIONS: This study demonstrated that oral consumption of omega-3 fatty acids (180 mg EPA and 120 mg DHA twice daily for 30 days) is associated with a decrease in the rate of tear evaporation, an improvement in dry eye symptoms, and an increase in tear secretion.

Organizational performance, Marketing strategy, and Financial strategic alignment: an empirical study on Iranian pharmaceutical firms.

BACKGROUND: Strategic Functional-level planning should be aligned with business level and other functional strategies of a company. It is presumed that assimilating the strategies could have positive contribution to business performance, in this regard alignment between marketing strategy and financial strategy seems to be the most important strategies being studied. An empirical work in generic pharmaceutical manufacturing companies for evaluating effect of alignment between these two functions on organizational performance was developed in this paper. METHODS: All Iranian pharmaceutical generic manufactures listed in Tehran stock market have been tested for period of five years between 2006-2010 and their marketing strategies were determined by using Slater and Olson taxonomy and their financial strategies have been developed by calculating total risk and total return of sample companies for five years based on rate of risk and return in the frame of a 2 × 2 matrix. For the business performance three profitability indices including Q-Tubin (Rate of market value to net asset value), ROA (Return on Asset), ROE (Return on Equity) have been tested. For analysis, a series of one-way ANOVAs as a collection of statistical models within marketing strategies considering financial strategy as independent variable and the three performance measures as dependent variables was used. RESULTS: Results show strategic alignment between financial and marketing has significant impact on profitability of company resulting in arise of all three profitability indices. Q tubing's rate were 2.33,2.09,2.29,2.58 and rate of ROA were 0.21,0.194,0.25,0.22 and rate of ROE were 0.44,0.46,0.45,0.42 for matched strategy types, respectively the rates shown here are more than average meaning that specific type of marketing strategy is fitted with specific type of financial strategy. CONCLUSION: Managers should not consider decisions regarding marketing strategy independently of their financial strategy.

Performance Evaluation of Biochip Chemiluminescent Immunoassay for Screening Seven Mycotoxins in Wheat Flour Simultaneously.

Background: Wheat grains are susceptible to mycotoxins, toxic natural secondary metabolites generated by certain fungi on agricultural produce in the field during growth, harvest, transportation, or storage. Therefore, wheat flour can be contaminated with mycotoxins, which seriously threaten human health. Methods: A rapid method for screening seven mycotoxins in wheat flour was validated in accordance with Commission Decision 2002/657/EC. With this multi-analytical screening method, 7 prevalent mycotoxins (fumonisin B1, ochratoxin A, aflatoxin G1, deoxynivalenol, T-2 toxin, aflatoxin B1, and zearalenone) can be determined simultaneously. The method's applicability was demonstrated by screening 7 mycotoxins in 39 wheat flour samples collected from different bakeries in Tehran province, Iran. Results: The validation results indicated that for all 7 mycotoxins, the positivity threshold (T) was above the cut-off value (Fm), and no false positive results were obtained for any of the mycotoxins. The screening results of 12 packaged and 27 bulk wheat flour samples indicated that the concentrations of all mentioned mycotoxins were higher than the cut-off (in the relative light unit [RLU]), and all the samples were compliant. Conclusions: The present study revealed that the biochip-based technique is valid for identifying and assessing the levels of 7 mycotoxins in grain samples, such as wheat flour, at the measured validation concentrations. The method was simple, fast, and able to screen 7 mycotoxins simultaneously. The test process of the kit is easy to conduct, and the results are straightforward to interpret.

Simultaneous Screening of Six Families of Antibiotic Residues in Milk Samples by Biochip Multi-array Technology.

Background: Antimicrobial compounds are used in animal husbandry to prevent and treat bacterial diseases and as illegal growth-promoting agents. Due to the excessive and inappropriate use of antibiotics, the antibiotic residues in milk can cause allergic reactions and antibiotic resistance. A rapid biochip-based method for the multi-analyte screening of 6 families of antibiotic residues (quinolones, ceftiofur, florfenicol, streptomycin, tylosin, and tetracyclines) in milk was validated based on Commission Decision 2002/657 and the European guidance for screening methods for veterinary medicinal products. Methods: This methodology allows the 6 antibiotic families to be detected simultaneously, increasing the screening capacity and reducing costs in test settings. The method's applicability was shown by screening 38 UHT cow milk samples taken from Tehran province, IR Iran. Results: The results showed that the positive threshold T was above Fm, and the CCß was below the European Commission's Maximum Residue Limit (MRL) (100 ppb for ceftiofur and tetracycline and 50 ppb for tylosin in milk). Norfloxacin was detected in about 8% of the samples and tylosin in 2.63%. The total antibiotic concentration in UHT cow milk samples was lower than the European Commission's MRL. Conclusions: This study showed that the biochip technique is valid for screening tylosin, ceftiofur, streptomycin, tetracycline, norfloxacin, and florfenicol in milk. It was found that the method was easy, quick, and capable of detecting 6 families of antibiotic residues simultaneously from a single milk sample without sample preparation.

The Efficacy of High-Dose Pulse Therapy vs. Low-Dose Intravenous Methylprednisolone on Severe to Critical COVID-19 Clinical Outcomes: A Randomized Clinical Trial.

Background: It remains unclear which formulation of the corticosteroid regimen has the optimum efficacies on COVID-19 pneumonia. Objectives: The aim of this study was to compare the clinical outcomes of 2 different regimens in the treatment of acute respiratory distress syndrome (ARDS) caused by COVID-19: Methylprednisolone at a dose of 1 mg/kg every 12 hours (low-dose group) and 1000 mg/day pulse therapy for 3 days following 1 mg/kg methylprednisolone every 12 hours (high-dose group). Methods: In this randomized clinical trial, patients with mild to moderate ARDS due to COVID-19 were randomly assigned to receive either low-dose (n = 47) or high-dose (n = 48) intravenous methylprednisolone regimens. Two groups were matched for age, gender, body mass index (BMI), comorbidities, leukocytes, lymphocytes, neutrophil/lymphocyte, platelet, hemoglobin, and inflammatory markers (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], and ferritin). Both regimens were initiated upon admission and continued for 10 days. The clinical outcome and secondary complications were evaluated. Results: Evaluating in-hospital outcomes, no difference was revealed in the duration of intensive care unit (ICU) stays (5.4 ± 4.6 vs. 4.5 ± 4.9; P = 0.35), total hospital stays (8 ± 3.1 vs. 6.9 ± 3.4; P = 0.1), requirement rate for invasive ventilation (29.2% vs. 36.2%; P = 0.4) or non-invasive ventilation (16.6% vs 23.4%; P = 0.4), and hemoperfusion (16.6% vs 11.3%; P = 0.3) between the low- and high-dose groups. There was no significant difference in fatality due to ARDS (29.2% vs. 38.3%; P = 0.3) and septic shock (4.2% vs. 6.4%; P = 0.3) between the low- and high-dose groups. Patients in the high-dose group had significantly higher bacterial pneumonia co-infection events compared with those in the low-dose group (18.7% vs 10.6%; P = 0.01). Conclusions: The use of adjuvant pulse therapy with intravenous methylprednisolone did not result in improved in-hospital clinical outcomes among patients with mild to moderate ARDS due to COVID-19. A higher risk of bacterial pneumonia should be considered in such cases as receiving a higher dose of steroids.

A ten-year study of anti-diabetic drugs utilization in Iran.

Objectives: According to the world health organization (WHO), by the year 2030 diabetes will become the world's seventh leading cause of death. This study aimed to design and conduct a descriptive pharmacoepidemiological investigation of anti-diabetic drugs utilization during a ten-year period using the anatomical therapeutic classification/defined daily dose (ATC / DDD) system in Iran. Methods: Based on pharmaceutical wholesalers' sale reports, sale data, including value and volume, were retrieved from the Iranian Annual Pharma Statistics for 2009-2018. The ATC/DDD system was used to standardize the raw sales data. Anti-diabetic drug utilization was reported as DDD per 1000 person in the population per day. Expenditure was calculated as USD per DDD. Results were then analyzed descriptively. Results: During the ten-year study period, total anti-diabetic drug consumption increased by 235.53%. Insulin utilization grew by 148.65%, whereas non-insulin agents' use showed a 132.68% increase. Anti-diabetic drugs' expenditure increased by almost 9-fold, but changes were accompanied with many fluctuations. Although the absolute expenditure of almost all classes of anti-diabetic drugs were increasing, this growth was greater in biguanides, which only includes metformin in Iran. Approximately one-third of anti-diabetic drugs expenditures were related to fast-acting insulins. Imported drugs share in cost was significant, but not in consumption. The overall share of insulin consumption was less than 19%, but their share of total value reached 60% of the anti-diabetic market. Conclusions: The growing trend in both insulin and non-insulin anti-diabetic drugs utilization is a substantial issue for health authorities' policy making for sustainable access to medicine.

Study of the Effects of Melatonin on Sleep Disorders in Pulmonary Sarcoidosis Patients.

Background: The symptoms of pulmonary sarcoidosis may lead to fatigue, excessive daytime sleepiness, poor sleep quality, and a decrease in quality of life in these patients. Objectives: This study was designed to evaluate the effects of oral melatonin on sleep disorders of patients with pulmonary sarcoidosis. Methods: A randomized, single-blinded clinical trial was conducted on patients with pulmonary sarcoidosis. Eligible patients were randomly allocated into melatonin and control groups. Patients in the melatonin group were given 3 mg melatonin one hour before bedtime for three months. Sleep quality, daytime sleepiness, fatigue status, and quality of life were assessed applying General Sleep Disturbance Scale (GSDS), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Fatigue Assessment Scale (FAS), and the Patient-Reported Outcomes Measurement Information System (PROMIS), respectively, as well as the 12-item Short Form Survey (SF-12) scores at the baseline and three months after treatment. Results: There was a significant change in the GSDS (P < 0.001), PSQI (P < 0.001), ESS (P = 0.002), and FAS (P < 0.001) scores, which were decreased, compared to those of the control group. After intervention¸ global physical health and global mental health raw scores were improved comparing to the control group (P = 0.006, P = 0.02, respectively). The 12-item Short Form Survey evaluation showed that there was a significant difference between the melatonin (3.38 ± 4.61) and control (0.55 ± 7.25) groups in PCS-12 score after three months of therapy (P = 0.02). Conclusions: Our findings showed that supplemental melatonin could significantly improve sleep problems, quality of life, and excessive daytime sleepiness in sarcoidosis patients.

Simultaneous Screening of Nitrofuran Metabolites in Honey Using Biochip Array Technology: Validation Study According to the Decision 2002/657/EC of the European Union.

Background: Although no authorization is available for antibiotics to treat bee diseases, some veterinary compounds are used by beekeepers, and each country sets its own thresholds. Inappropriate and excessive use of these drugs can cause allergic reactions and antibiotic resistance in humans who consume the remaining antibiotic residues in honey and its products. It is, therefore, relevant to monitor the presence of antibiotic residues in this matrix. Objectives: A rapid method for the simultaneous screening of nitrofuran metabolite residues in honey was validated according to Commission Decision 2002/657/EC (C.D 657) and the European guideline for the validation of screening methods for veterinary medicines. Methods: This multi-analytical screening method enables the simultaneous determination of four nitrofuran metabolites [3-amino-2-oxazolidone (AOZ), 3-amino-5-morpholinomethyl-2-oxazolidinone (AMOZ), 1-Aminohydantoin HCl (ADH), and semicarbazide (SEC)] from a single honey sample. Thirty-five honey samples were collected randomly as real samples for screening from Tehran, IR Iran, Germany, and the Netherlands in 2018. Results: For all four antibiotic residues, the positivity threshold T was higher than the cut-off value Fm, and no false-positive results were obtained for three antibiotics (AOZ, AMOZ, and SEC). Detection capabilities (CCß) of all compounds were under the minimum required performance limit (MRPL) authorized by the European Commission (currently 1 µg/kg). The screening results of 15 domestic and 20 imported honey samples showed that the levels of AOZ in 6.66% and 10% of the samples, the level of AMOZ in 13.33% and 0% of the samples, and the level of SEC in 33.33% and 40% of the samples were less than the cut-off ([in relative light units (RLUs)], respectively. Conclusions: This study found that this technique is valid for detecting and quantifying three antibiotic residues in honey samples at the measured validation levels. This method was simple, rapid, and capable of simultaneously screening three nitrofuran metabolites from a single honey sample.

Probiotic prophylaxis to prevent ventilator-associated pneumonia in children on mechanical ventilation: A randomized double-blind clinical trial.

Purpose: Ventilator-Associated Pneumonia (VAP) is one of the most common nosocomial infections in the Pediatric Intensive Care Unit (PICU). Using new strategies to prevent nosocomial infections is crucial to avoid antibiotic resistance. One of these strategies is the utilization of probiotics. This study aims to investigate the efficacy of probiotic prophylaxis in preventing VAP in mechanically ventilated children. Method: This study was a randomized, double-blind clinical trial. The study included 72 children under 12 years of age under mechanical ventilation for more than 48 h in the Mofid Children's Hospital. Patients were randomly divided into Limosilactobacillus reuteri DSM 17938 probiotic recipients (n = 38) and placebo groups (n = 34). In addition to the standard treatment, both groups received a sachet containing probiotics or a placebo twice a day. Children were screened for VAP based on clinical and laboratory evidence. Results: The mean age of children in the intervention and placebo groups was 4.60 ± 4.84 and 3.38 ± 3.49 years, respectively. After adjusting the other variables, it was observed that chance of VAP among probiotics compared to the placebo group was significantly decreased (OR adjusted = 0.29; 95% CI: 0.09-0.95). Also, probiotic was associated with a significantly lower chance of diarrhea than the placebo group (OR adjusted = 0.09; 95% CI: 0.01-0.96). Conclusion: Probiotic utilization is effective in preventing the incidence of VAP and diarrhea in children under mechanical ventilation in the PICU.

Evaluation of vancomycin pharmacokinetics in patients with augmented renal clearances: A randomized clinical trial.

Purpose: Vancomycin is a narrow therapeutic window glycopeptide antibiotic that acts against Gram-positive bacteria. As it is renally eliminated, therapeutic drug monitoring is recommended for vancomycin, especially in case of kidney function alteration. Augmented renal clearance (ARC), defined as a creatinine clearance of more than 130 ml/min, is a risk factor for sub-therapeutic concentrations of vancomycin. This study aimed to evaluate the vancomycin pharmacokinetics following the administration of two different regimens in ARC patients. Methods: A randomized clinical trial (IRCT20180802040665N1) was conducted on patients in need of vancomycin therapy. Eight hours of urine was collected and 56 patients divided into two groups with creatinine clearance of more than 130 ml/min were included in the study. The first group received 15 mg/kg of vancomycin every 12 h and the second group 15 mg/kg every 8 h. After four doses, the peak and trough concentrations were measured from two blood samples. The primary outcome was the percentage of patients who attainted AUC more than 400. The occurrence of acute kidney injury also was evaluated after seven days. Results: The mean age of patients in the every 12 h and every 8 h groups was 44.04 ± 16.55 and 42.86 ± 11.83 years, respectively. While neurosurgical issues were the most common causes of hospitalization, central nervous infections were the most common indications for vancomycin initiation. Urinary creatinine clearance was 166.94 ± 41.32 ml/min in the every 12 h group and 171.78 ± 48.56 ml/min in the every 8 h group. 46.42% of patients in the every 12 h group and 82.14% of patients in the every 8 h group attained AUC/MIC of more than 400 mg × hr/L. None of the patients in the every 12 h group reached more than 15 mcg/ml concentration. At the 7-day follow-up, 10.7% patients in the BD group and 28.6% patients in the TDS group developed acute kidney injury (p = 0.089). Conclusion: Administration of vancomycin at a dose of 15 mg/kg every 8 h is associated with higher pharmacokinetic attainment in ARC patients. The occurrence of acute kidney injury also was not significantly higher in this therapeutic regimen. AUC/MIC monitoring is necessary in this population.

Isoniazid blood levels in patients with pulmonary tuberculosis at a tuberculosis referral center.

BACKGROUND: Serum concentrations of isoniazid (INH) were evaluated in Iranian patients admitted to the Tuberculosis Ward of Masih Daneshvari Hospital, Tehran, Iran. Factors correlated to plasma INH levels were determined. METHODS: Blood samples were obtained 2 h after ingestion of 5 mg/kg INH in 82 patients (1 sample/patient) on days 3-15 of treatment. The following variables were investigated: INH plasma level, duration of therapy, age, sex, weight, dose of INH administered and smoking status. RESULTS: The average (±SD) age and weight of patients were 60.68 ± 18.53 years and 74.96 ± 7.15 kg, respectively. INH concentrations were low in 14.63% and high in 23.17% of the patients (INH reference range: 3-5 µg/ml). Plasma INH was statistically correlated with duration of INH administration (Kendall's rank correlation, r = 0.66, p < 0.001) but not with other variables. CONCLUSION: Based on the result of this study, plasma INH concentrations were not within the therapeutic range for 37.80% of the patients on conventional therapy. Therefore therapeutic drug monitoring may be needed to optimize INH dosage, especially in patients with inadequate clinical response or toxicity to INH.

Study of the Effects of N-acetylcysteine on Inflammatory Biomarkers and Disease Activity Score in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is considered as an autoimmune-related condition in which the overproduction of pro-inflammatory cytokines leads to an inflammatory cascade. N-acetylcysteine (NAC) is a potent anti-inflammatory and anti-oxidant agent. We aimed to explore the impact of oral NAC on cytokines activities and clinical indicators in RA patients. In this placebo-controlled randomized double-blind clinical trial, 41 active RA patients were allocated in either NAC (600 mg, twice a day) or placebo group, as add-on therapy to the routine regimen, for 8 weeks. Disease activity score with an erythrocyte sedimentation rate (DAS28-ESR), and serum concentrations of interleukin (IL)-1ß and IL-17 were assessed at baseline and end of the trial for all participants in the test and control groups. The reduction of the DAS28-ESR was higher considerably in the NAC group compared to that of the control group. No statistically significant differences were seen in the reduction of IL-1ß and IL-17 cytokines between the NAC and control groups. In addition, improvements in the patient global assessment, number of tender joints, number of swollen joints, and the ESR rates were in favor of the NAC group. Our findings reveal that NAC may have a beneficial effect on all of the clinical features of RA. However, non-significant variations in the IL-1ß and IL-17 levels suggest an alternative way of NAC effectiveness without influencing the measured cytokines. Nevertheless, these results need to be confirmed by further investigations.