Liposomal amphotericin for secondary prophylaxis: A systematic review and meta-analysis.

INTRODUCTION: This systematic review and meta-analysis aimed to determine the safety of liposomal amphotericin B (L-AMB) compared to other antifungal agents for secondary prophylaxis. METHOD: We conducted a comprehensive search across international databases and reference lists of articles to compile all relevant published evidence evaluating the efficacy and safety of L-AMB versus other antifungals (NLAMB) for secondary prophylaxis against invasive fungal infections. Pooled estimates were calculated after data transformation to evaluate mortality, breakthrough infections, and the frequency of adverse effects, including hypokalemia and nephrotoxicity. Comparisons of breakthrough fungal infection and mortality between the L-AMB and NLAMB groups were performed. RESULT: We identified 10 studies. The cumulative frequency of patients using L-AMB was 148, compared to 341 patients in the NLAMB group. The mortality rates in the L-AMB and NLAMB groups were 10% and 0%, respectively. However, based on the odds ratio, the mortality in the L-AMB group was lower than that in the NLAMB group. No significant difference was observed in breakthrough invasive fungal infections between the L-AMB and NLAMB groups. The frequencies of nephropathy and hypokalemia in the L-AMB group were 36% and 18%, respectively. CONCLUSION: Our findings indicate a lower incidence of mortality in the L-AMB group compared to the NLAMB group. No statistically significant difference was observed in the incidence of breakthrough infection between the two groups. L-AMB administration is associated with nephropathy and hypokalemia. However, the refusal to continue treatment due to adverse effects is not significantly high.

A rare case report of lead encephalopathy due to high blood lead level.

Here we report a case of lead poisoning having a serum lead level of 412 mcg dL-1 who presented with decreasing level of consciousness and recurrent seizures. He responded well to treatment with chelation therapy.

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.

Serotonin syndrome due to concomitant use of linezolid and methadone.

Serotonin syndrome is a potentially life-threatening adverse drug reaction typically caused by a single or combination of two or more medications with serotonergic properties due to increased serotonin release. Our case is a 60-year-old drug-addict man who was admitted to the poisoning department of Loghman hospital with methadone poisoning. On the fifth day of hospitalization and after initiating the linezolid treatment for VAP, the patient began to run a fever with agitation, tremor, spontaneous clonus movement in the hands, and tachycardia. Due to patients' manifestations and after ruling out other diagnoses, serotonin syndrome was confirmed with the possibility of concomitant use of linezolid and methadone. Linezolid administration was promptly discontinued, and vancomycin therapy was initiated (1000 mg twice a day intravenously). Supportive therapies were performed. Finally, tremor, rigidity, and clonus movement disappeared within 48 h.

Antibiotic use during the first 6 months of COVID-19 pandemic in Iran: A large-scale multi-centre study.

WHAT IS KNOWN AND OBJECTIVE: Although antibiotics are ineffective against viral infections, epidemiological studies have revealed that the COVID-19 pandemic resulted in the overuse of antibiotics and disruption of antimicrobial stewardship programmes. We investigated the pattern of antibiotic use during the first 6 months of the COVID-19 pandemic in Iran. METHODS: A multi-centre retrospective study was designed to investigate the use of 16 broad-spectrum antibiotics in 12 medical centres. The rate of antibiotic use was calculated and reported based on the Defined Daily Dose (DDD) per 100 hospital bed-days. The bacterial co-infection rate was also reported. RESULTS AND DISCUSSION: Totally, 43,791 hospitalized COVID-19 patients were recruited in this study. It was found that 121.6 DDD of antibiotics were used per 100 hospital bed-days, which estimated that each patient received approximately 1.21 DDDs of antibiotics every day. However, the bacterial co-infections were detected only in 14.4% of the cases. A direct correlation was observed between the rate of antibiotic use and mortality (r[142] = 0.237, p = 0.004). The rate of antibiotic consumption was not significantly different between the ICU and non-ICU settings (p = 0.15). WHAT IS NEW AND CONCLUSION: In this study, widespread antibiotic use was detected in the absence of the confirmed bacterial coinfection in COVID-19 patients. This over-consumption of broad-spectrum antibiotics may be associated with increased mortality in hospitalized COVID-19 patients, which can be an alarming finding.

Nonviral siRNA delivery systems for pancreatic cancer therapy.

The serious drawbacks of the conventional treatment of pancreatic ductal adenocarcinoma (PDAC) such as nonspecific toxicity and high resistance to chemo and radiation therapy, have prompted the development and application of countless small interfering RNA (siRNA)-based therapeutics. Recent advances in drug delivery systems hold great promise for improving siRNA-based therapeutics and developing a new class of drugs, known as nano-siRNA drugs. However, many fundamental questions, regarding toxicity, immunostimulation, and poor knowledge of nano-bio interactions, need to be addressed before clinical translation. In this review, we provide recent achievements in the design and development of various nonviral delivery vehicles for pancreatic cancer therapy. More importantly, codelivery of conventional anticancer drugs with siRNA as a new revolutionary pancreatic cancer combinational therapy is completely discussed.

Antimicrobial peptides: a promising strategy for lung cancer drug discovery?

INTRODUCTION: Antimicrobial peptides (AMPs), also called host defense peptides (HDPs), are identified in almost any form of life, which play an important role in innate immune systems. They have a broad spectrum of antifungal, antiviral, antibacterial, and anticancer activities. Lung cancer remains the leading cause of global cancer-related death. Unfortunately, lung cancer chemotherapy is accompanied by serious side effects, nonspecific toxicity, and multidrug resistance. Hence, to overcome these drawbacks, anticancer peptides (ACPs) derived from AMPs may represent a potential promising synergistic treatment strategy for lung cancer. AREAS COVERED: In this review, the authors provide the recent advancements in the use of AMPs for the treatment of lung cancer. Furthermore, the anti-lung cancer modes of action of these peptides have been fully reviewed. Importantly, various strategies for increasing the efficiency and safety of AMPs have been discussed. EXPERT OPINION: The combination of AMPs and other cancer treatment approaches such as chemotherapy, nanoparticle-based delivery systems, and photodynamic therapy can be used as a promising revolutionary strategy for the treatment of lung cancer. The most significant limitations of this strategy that need to be focused on are low efficiency and off-target events.

Delivery of genome editing tools: A promising strategy for HPV-related cervical malignancy therapy.

INTRODUCTION: Persistent high-risk human papillomavirus infection is the main cause of various types of cancer especially cervical cancer. The E6 and E7 oncoproteins of HPV play critical roles in promoting carcinogenesis and cancer cell growth. As a result, E6 and E7 oncogenes are considered as promising therapeutic targets for cervical cancer. Recently, the development of genome-editing technologies including transcription activator-like effector nucleases (TALEN), meganucleases (MNs), zinc finger nucleases (ZFN), and more importantly clustered regularly interspaced short palindromic repeat-CRISPR-associated protein (CRISPR-Cas) has sparked a revolution in the cervical cancer-targeted therapy. However, due to immunogenicity, off-target effect, renal clearance, guide RNA (gRNA) nuclease degradation, and difficult direct transportation into the cytoplasm and nucleus, the safe and effective delivery is considered as the Achilles' heel of this robust strategy. AREAS COVERED: In this review, we discuss cutting-edge available strategies for in vivo delivery of genome-editing technologies for HPV-induced cervical cancer therapy. Moreover, the combination of genome-editing tools and other therapies has been fully discussed. EXPERT OPINION: The combination of nanoparticle-based delivery systems and genome-editing tools is a promising powerful strategy for cervical cancer therapy. The most significant limitations of this strategy that need to be focused on are low efficiency and off-target events.

Validating a Drug-Related Problems Classification System in Outpatient Setting in Iran.

OBJECTIVE: Medication Therapy Management service (MTMs) has been introduced to improve cooperation among pharmacists and other healthcare professionals in the management of chronic diseases, drug therapy, and patients on polypharmacy. One part of MTMs is detection and resolution of possible drug-related problems (DRPs). Nowadays, numerous DRPs classification systems are available, but due to some defects none of them are currently accepted and implemented universally. The purpose of this study is to design and validate a comprehensive system for classification and documentation of possible DRPs for the Iranian patients. METHODS: In this methodological study, four classification systems were studied, and their differences were reviewed, compared. Ultimately, a comprehensive documentation system was developed and tested for validity using experts' opinions. FINDINGS: A comprehensive list of 53 DRPs under eight categories was developed and examined for validity. After collecting the data and validity assessment, questions with content validity ratio of <0.4 and content validity index of <70% were excluded and modified. Finally, with the exclusion and modification of eight DRPs, a modified DRPs list was created. CONCLUSION: According to the universality and validity assessment and based on consensus of 20 experts, this DRPs list can be used to regulate the standard operation procedure of outpatient clinics in Iran, and could act toward standardization of this service.