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

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

Catastrophic pharmaceutical expenditure in patients with type 2 diabetes in Iran.

OBJECTIVES: This study aimed to assess the financial burden of out-of-pocket (OOP) payments to purchase antidiabetic medicines for type 2 patients in Iran. METHOD: The "budget share" and "capacity to pay" approaches were employed to assess the catastrophic pharmaceutical expenditures of antidiabetic medication therapies. The catastrophic thresholds were adjusted for pharmaceutical sectors. The data was 2019 monthly household expenditures in rural and urban areas, insurance coverages of antidiabetic medicines and patients' out-of-pocket (OOP) payments in 30-day treatment schedules. RESULTS: The results show that expenditure on diabetes medication therapies in the form of mono-dual therapy and some cases triple oral therapies were not catastrophic even for rural households. Insulin puts patients at risk of catastrophic pharmaceutical expenditures when added to the treatment schedules, and lack of financial protection intensifies it. In general, the poorer households and those resistant to first-line treatments were at increased risk of catastrophic pharmaceutical expenditures. The number of treatments that put patients at risk of catastrophic pharmaceutical expenditure in "budget share" was higher than the "capacity to pay" approach. CONCLUSIONS: Assessing medication treatment affordability instead of a single medicine assessment is needed. Assessment could be done by utilizing a macro-level data approach and applying adjusted pharmaceutical sector threshold values. Considering the variation between treatment schedules that put patients at risk of catastrophic pharmaceutical expenditures, targeted pharmaceutical policies and reimbursement decisions are recommended to promote Universal Health Coverage (UHC) and to protect vulnerable populations from hardship.

Compliance with Antibiotics Prophylaxis Guideline in Surgical Patients in ICUs of a Teaching Referral Hospital.

Antimicrobial prophylaxis used for surgical procedures remains one of the measures for the prevention of surgical site infections (SSIs). The present study was designed to assess the compliance with clinical practice guideline for antimicrobial prophylaxis in variable surgeries conducted in the intensive care units (ICUs) of a major referral hospital. This cross-sectional investigation was carried out by prospective data collected from October 2017 to March 2018 in the intensive care unit (ICU) of Nemazi hospital in Shiraz. Demographic characteristics, surgery type as well as antibiotic treatment were gathered from medical records and entered in data collection forms. We reviewed compliance and adherence of prophylactic antibiotic administration to the Infectious Diseases Society of America (IDSA) guideline and evaluated the courses of antimicrobial drugs. If an antibiotic administrated for surgical prophylaxis was different from the guideline, the antibiotic was classified as non-guideline-based antibiotics. Most patients participated in this study were male (64.5%). Only 8.75% of the administrated antibiotics chosen for surgical prophylaxis were found to be appropriate antibiotic prescriptions; however, those patients receiving appropriate antibiotics prescribed an inappropriate dosage. In addition, the antibiotics were administrated with inappropriate durations in all cases. Our findings indicated that adherence to the IDSA international guideline seems to be far from ideal in Namazi hospital for antimicrobial prophylaxis, resulting in the unsuitable administration of a wide variety of antibiotics.

Assessing the Performance of Community Pharmacies in Iran by Measuring Responsiveness to Non-Medical Needs: An Application of WHO Responsiveness Framework.

OBJECTIVE: Despite growing debates about the health systems' nonmedical performance, there has not been any empirical research on nonmedical performance and patients' rights consideration as a driver of human rights in the pharmaceutical sector. This study's main objective was to assess the nonmedical performance of community pharmacies of Shiraz, Iran. METHODS: A cross-sectional study was conducted using two self-administrated Likert-based questionnaires based on the World Health Organization (WHO) responsiveness framework and the legal charter communicated by the Ministry of Health and Medical Education of Iran. The population was patients older than 18 years who took a prescription from community pharmacies located in Shiraz and willing to answer the questions voluntarily, from 2018 to 2019. Considering the weights of subdimensions of responsiveness provided by the WHO framework, the total score of responsiveness was calculated ranging from 0 to 100. FINDINGS: The response rate was 80.5%. The mean (standard deviation) overall score of responsiveness was 57.18 (21.61), with a median of 56.71. The mean score of client orientation was lower in respondents with a high education level than those with a diploma and under diploma (P = 0.028). CONCLUSION: Nonmedical pharmacy performance was considered either medium or high in more than half of the cases based on the participants' views. Regarding client, orientation was seen less often in patients with high education level compared to those with a lower education level.

Investigating the sequential patterns of methamphetamine use initiation in Iran.

BACKGROUND: Methamphetamine (MA) remains one of the most commonly used amphetamine-type stimulants, accounting for the second most widely-used substance after marijuana. Due to increased use of MA, a wide variety of research has focused on the patterns of MA use initiation among adolescents. Nevertheless, there are few data available for people who use MA. The present study set out to assess the sequential patterns of substance use initiation in patients with MA use disorders in Iran. MATERIALS AND METHODS: This cross-sectional study described substance initiation patterns for 302 patients who used MA admitted to hospitals and psychiatric centers of Shiraz University of Medical Sciences. The study was conducted between April 2015 and June 2016. After obtaining informed consents, participants were interviewed by trained interviewers using face-to-face, semi-structured interviews. The collecting data were analyzed using the chi square tests and one-way analysis of variance (ANOVA) tests to compare the relationship between qualitative and quantitative variables, respectively. RESULTS: Out of 302 participants enrolled in the study, 16 (5.3%) and 286 (94.7%) were female and male, respectively. The mean age of participants in the study was 37.29 years. The mean age of onset of MA use was found to be 15.9 years. 46.1% of the patients started MA use before 15 years. 77.2% of the patients who used MA had family members with a history of substance use. 93.71% of the patients who used MA started substance use with tobacco, alcohol, or opium, as the most frequent substances. Tobacco, as the first substance or starting substance, exhibited the most widely-used substance (69.53% of the cases). Tobacco-alcohol-cannabis-opium-heroin-MA sequencing was significantly related to the early onset of the substance use. Early-onset substance use was significantly higher in those with lower income, primary education, and family history of substance use. No significant relationship was found between employment status with the age of onset of substance use, and different substance use with marital status. CONCLUSION: Tobacco, alcohol and opium can be considered as the main sequencing substances for initiation to MA use. Standardized measures to decrease and control access to main starting and sequencing substances, including tobacco, alcohol, and opium, can greatly help decrease the early onset of the MA use, develop suitable prevention, and establish early intervention strategies.

Key Regulatory miRNAs and their Interplay with Mechanosensing and Mechanotransduction Signaling Pathways in Breast Cancer Progression.

According to the WHO, breast cancer is the most common cancer in women worldwide. Identification of underlying mechanisms in breast cancer progression is the main concerns of researches. The mechanical forces within the tumor microenvironment, in addition to biochemical stimuli such as different growth factors and cytokines, activate signaling cascades, resulting in various changes in cancer cell physiology. Cancer cell proliferation, invasiveness, migration, and, even, resistance to cancer therapeutic agents are changed due to activation of mechanotransduction signaling. The mechanotransduction signaling is frequently dysregulated in breast cancer, indicating its important role in cancer cell features. So far, a variety of experimental investigations have been conducted to determine the main regulators of the mechanotransduction signaling. Currently, the role of miRNAs has been well-defined in the cancer process through advances in molecular-based approaches. miRNAs are small groups of RNAs (∼22 nucleotides) that contribute to various biological events in cells. The central role of miRNAs in the regulation of various mediators involved in the mechanotransduction signaling has been well clarified over the last decade. Unbalanced expression of miRNAs is associated with different pathologic conditions. Overexpression and downregulation of certain miRNAs were found to be along with dysregulation of mechanotransduction signaling effectors. This study aimed to critically review the role of miRNAs in the regulation of mediators involved in the mechanosensing pathways and clarify how the cross-talk between miRNAs and their targets affect the cell behavior and physiology of breast cancer cells.

How hypoxia regulate exosomes in ischemic diseases and cancer microenvironment?

Exosomes, as natural occurring vesicles, play highly important roles in the behavior and fate of ischemic diseases and different tumors. Secretion, composition, and function of exosomes are remarkably influenced by hypoxia in ischemic diseases and tumor microenvironment. Exosomes secreted from hypoxic cells affect development, growth, angiogenesis, and progression in ischemic diseases and tumors through a variety of signaling pathways. In this review article, we discuss how hypoxia affects the quantity and quality of exosomes, and review the mechanisms by which hypoxic cell-derived exosomes regulate ischemic cell behaviors in both cancerous and noncancerous cells.

Protective effects of pharmacological agents against aminoglycoside-induced nephrotoxicity: A systematic review.

Introduction: Aminoglycosides have been long used for antibacterial treatment and are still commonly used in clinical practice. Despite their extensive application and positive effects, drug-related toxicity is considered as the main obstacle for aminoglycosides. Aminoglycosides induce nephrotoxicity through the endocytosis and accumulation of the antibiotics in the epithelial cells of proximal tubule. Most importantly, however, a number of pharmacological agents were demonstrated to have protective activities against nephrotoxicity in experimental animals.Areas covered: In the present systematic review, the authors provide and discuss the mechanisms and epidemiological features of aminoglycoside-induced nephrotoxicity, and focus mainly on recent discoveries and key features of pharmacological interventions. In total, 39 articles were included in this review.Expert opinion: The majority of studies investigated gentamicin-induced nephrotoxicity in animal models. Antioxidants, chemicals, synthetic drugs, hormones, vitamins, and minerals showed potential values to prevent gentamicin-induced nephrotoxicity. Indicators used to evaluate the effectiveness of nephroprotection included antioxidative indexes, inflammatory responses, and apoptotic markers. Among the nephroprotective agents studied, herbs and natural antioxidant agents showed excellent potential to provide a protective strategy against gentamicin-induced nephrotoxicity.

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

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

Optimizing compliance with surgical antimicrobial prophylaxis guidelines in patients undergoing gastrointestinal surgery at a referral teaching hospital in southern Iran: clinical and economic impact.

BACKGROUND: Antibiotic prophylaxis is one of the major approaches to prevent surgical site infection. Despite the availability of international guidelines on it, the practice of antibiotic prophylaxis is still far from optimal. This study aimed to assess the impact of guideline implementation on the rational use of prophylactic antibiotics and its cost-saving effect in gastrointestinal surgery by clinical pharmacist intervention. METHODS: A pre and post intervention study was carried out between October 2017 and June 2018 on patients who underwent gastrointestinal surgery in a major referral teaching hospital in Shiraz, southern Iran. The intervention phase consisted of revising the institutional guidelines for surgical antimicrobial prophylaxis, assigning a clinical pharmacist to the surgical department, and arranging several meetings with the surgical department regarding the appropriate utilization of antibiotics. Differences in antibiotic utilization in patients before and after the intervention phase were compared. Exposures were surgical antimicrobial prophylaxis timing and agents, and main outcomes were incidence of surgical site infection and length of hospital stay. RESULTS: A total of 430 patients were included in the post intervention phase, while 445 patients were included in the baseline evaluation. Promoting appropriate antibiotic use in the post intervention group had the potential to decrease medication costs by reducing unnecessary prescriptions and duration of antibiotic usage (P<0.001). In the pre intervention group, the mean cost of antibiotic prescriptions was 11.5 times that of the post intervention group. Mean hospitalization in the pre intervention group was greater than the post intervention group (P<0.001). Furthermore, our data revealed that the rate of postsurgery infection in the post intervention group was 3.03%, while this rate was 6.76% in the preintervention group (P=0.01). CONCLUSION: This study provides evidence that adherence to surgical antimicrobial prophylaxis guidelines increased the rational use of prophylactic antibiotics, with substantial cost savings in patients who underwent surgery.