Promises and Pitfalls of Calcineurin Inhibitors in COVID-19: A Systematic Review and Meta-analysis of Controlled Trials.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a violent attack on the body that leads to multi-organ failure and death in COVID-19 patients. The aim of this study was to systematically review the existing literature on the potential benefits of calcineurin inhibitors (CIs) as anti-vascular endothelial growth factor (VEGF) agents in improving the clinical outcomes of COVID-19 patients. METHODS: We searched various databases, including PubMed, Scopus, ISI Web of Science, Google Scholar, Cochrane databases, and ClinicalTrials.gov from 31st December, 2019, to 3rd February, 2023, for relevant controlled trials. The quality of the evidence was assessed using the Cochrane Collaboration tool. Comprehensive Meta-Analysis Software was used for the statistical analyses using a random-effects model. RESULTS: Three trials enrolling 293 participants were reviewed in the present systematic review and meta-analysis. The results showed CIs to lead to a significant reduction in mortality rate [risk ratio (RR): 0.598, 95% CI: 0.404-0.885, P-value = 0.010] with a low between-study heterogeneity (Cochrane Q test: I 2 = 0.000%, P-value = 0.371). Pooled analysis of two studies (84 patients) illustrated that CIs could not significantly increase the rate of hospital discharge (RR: 1.161, 95% CI: 0.764-1.764, P-value = 0.485) and heterogeneity was not significant (Cochrane Q test: I 2 = 26.798%, P-value = 0.242). CONCLUSION: CIs are able to inhibit the virus nucleocapsid protein so that they can prevent replication and respiratory tract tissue damage caused by SARS-CoV-2. Based on the characteristics mentioned in detail, CIs can play a potential therapeutic role for COVID-19 patients.

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.

Therapeutic Effect of Curcumin in Women with Polycystic Ovary Syndrome Receiving Metformin: A Randomized Controlled Trial.

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, for which the insulin sensitizer metformin has been used therapeutically. It has been shown that curcumin also exhibits insulin-sensitizing properties. Given that metformin acts as an ovulation inducing agent and both curcumin and metformin can reduce insulin resistance, the aim of the current study was to evaluate the effect of metformin with and without curcumin nanomicelles in the treatment of women with polycystic ovary syndrome. This clinical trial was conducted on 100 women with PCOS, diagnosed according to the Rotterdam criteria, who were sequentially recruited and randomly divided into two groups (n = 50 each). Group 1 received 500 mg metformin three times daily and group 2 received 80 mg/day capsule of curcumin nanomicelle and 500 mg metformin three times a day for 3 months. After collecting fasting blood samples, biochemical parameters including triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, plasma glucose, alanine amino transferase (ALT) and aspartate aminotransferase (AST) were evaluated based on enzymatic methods. Hormonal parameters were assessed using immunoassay kits. Insulin resistance (HOMA-IR) and insulin-sensitivity check index (QUICKI) were also assessed. After treatment, fasting insulin, HOMA-IR, and total testosterone in group 2 were significantly lower than those in group 1 (p < 0.05). Post-treatment LDL-C levels in groups 1 and 2 were 117.9 ± 24 and 91.12 ± 19.46 mg/dL, respectively (p < 0.01). In addition, HDL-C levels were increased with curcumin (group 1: 38.1 ± 4.36 mg/dL; group 2: 44.12 ± 7.3 mg/dL, p < 0.05). Total cholesterol was decreased with curcumin level (group 1: 207.9 ± 39.84 mg/dL; group 2; 159.7 ± 48.43 mg/dL, p < 0.05), with a decrease in triglycerides levels (group 1: 141.6 ± 9.57; group 2: 97.5 ± 8.8 mg/dL, p < 0.01). This study showed that curcumin has a synergistic effect with metformin in the improvement of insulin resistance and lipid profile in patients with PCOS. Therefore, the combined use of metformin and curcumin may have therapeutic utility in patients with PCOS.

Medication Errors in Patients with Enteral Feeding Tubes in the Intensive Care Unit.

OBJECTIVE: Most patients admitted to Intensive Care Units (ICU) have problems in using oral medication or ingesting solid forms of drugs. Selecting the most suitable dosage form in such patients is a challenge. The current study was conducted to assess the frequency and types of errors of oral medication administration in patients with enteral feeding tubes or suffering swallowing problems. METHODS: A cross-sectional study was performed in the ICU of Shahid Sadoughi Hospital, Yazd, Iran. Patients were assessed for the incidence and types of medication errors occurring in the process of preparation and administration of oral medicines. FINDINGS: Ninety-four patients were involved in this study and 10,250 administrations were observed. Totally, 4753 errors occurred among the studied patients. The most commonly used drugs were pantoprazole tablet, piracetam syrup, and losartan tablet. A total of 128 different types of drugs and nine different oral pharmaceutical preparations were prescribed for the patients. Forty-one (35.34%) out of 116 different solid drugs (except effervescent tablets and powders) could be substituted by liquid or injectable forms. The most common error was the wrong time of administration. Errors of wrong dose preparation and administration accounted for 24.04% and 25.31% of all errors, respectively. CONCLUSION: In this study, at least three-fourth of the patients experienced medication errors. The occurrence of these errors can greatly impair the quality of the patients' pharmacotherapy, and more attention should be paid to this issue.

Effects of atorvastatin on biomarkers of acute kidney injury in amikacin recipients: A pilot, randomized, placebo-controlled, clinical trial.

BACKGROUND: The most common clinical indication of aminoglycosides (AG) is the treatment of serious Gram-negative infections. The aim of this study was to evaluate plausible effects of atorvastatin on the biomarkers of acute kidney injury (AKI) in patients receiving amikacin. MATERIALS AND METHODS: In this double-blinded randomized clinical trial, fifty patients (25 in each group) receiving amikacin (15 mg/kg/day) were randomly assigned to either atorvastatin (40 mg/day) or placebo (40 mg/day) groups for 7 days. Blood urea nitrogen (BUN), serum creatinine (SCr), and urinary neutrophil gelatinase-associated lipocalin (NGAL) levels were measured at days 0, 1, and 7 of amikacin treatment. RESULTS: During the study period, 4 (8%) patients including two patients in each atorvastatin and placebo group experienced AKI. Urine NGAL/urine Cr did not change significantly between and within placebo and atorvastatin groups during the study period. Similarly, the mean changes in SCr, BUN, and urine NGAL/urine Cr values did not differ significantly between and within patients with and without AKI. CONCLUSION: Our data suggested that the changing pattern of urine NGAL/urine Cr ratio did not differ significantly between the atorvastatin and placebo groups during the early phase of amikacin treatment.

Infective endocarditis; report from a main referral teaching hospital in Iran.

BACKGROUND/OBJECTIVE: The aim of the present preliminary study was to assess the demographic, clinical, paraclinical, microbiological, echocardiographic, and therapeutic profile as well as in-hospital outcome of patients with infective endocarditis at a referral center for various infectious diseases in Iran. METHODS: Required demographic, clinical, plausible complications and paraclinical data were collected from patients' medical charts. Echocardiographic findings were obtained by performing transthoracic and/or transesophageal echocardiography as clinically indicated. In addition, details of management modalities and in-hospital outcome of patients were recorded. RESULTS: During a 3-year period, 55 patients with definite or possible diagnosis of Infective endocarditis were admitted to the ward. Twenty one (38.2%) patients were injection drug users. Staphylococcus aureus and S.epidermidis were the most commonly isolated microorganisms. Management modalities of Infective endocarditis included antimicrobial therapy alone (48 cases) and the combination of antimicrobial therapy and surgery (7 cases). CONCLUSION: The rate of negative blood culture in our cohort is high. S. aureus and S.epidermidis were the most commonly isolated microorganisms from positive blood cultures. Congestive heart failure was the most frequent infective endocarditis complication as well as indication for surgery. In-hospital mortality rate of patients was unexpectedly low.

Clinical, Paraclinical, and Antimicrobial Resistance Features of Community-Acquired Acute Bacterial Meningitis at a Large Infectious Diseases Ward in Tehran, Iran.

In this study demographic, clinical, paraclinical, microbiological, and therapeutic features of patients with community-acquired acute bacterial meningitis admitted to a referral center for infectious diseases in Iran, have been evaluated. Medical records of adult (> 18 years) individuals with confirmed diagnosis of community-acquired bacterial meningitis during a 4-year period were retrospectively reviewed. All required data were obtained from patients' medical charts. Available findings about antimicrobial susceptibility of isolated bacteria from CSF and/or blood were also collected. Kirby-Bauer disc diffusion method was used to determine their antimicrobial susceptibility profile. Details of medical management including antibiotic regimen, duration, patients' outcome, and possible sequelae of meningitis were recorded. The most commonly isolated microorganism from CSF or blood of patients was Streptococcus pneumonia (33.33%) followed by Neisseria meningitidis (27.78%) and Haemophilus influenza (16.67%). The most common antimicrobial regimen was ceftriaxone plus vancomycin (69.44%) followed by ceftriaxone plus vancomycin plus ampicillin (11.11%). Neurological sequelae of meningitis including cranial nerve palsy, deafness, and hemiparesis were identified in 4 (11.11%), 2 (5.56%), and 1 (2.78%) subjects, respectively. Regarding mortality, only 3 (8.33%) patients died from bacterial meningitis and the remaining 33 individuals discharged from the hospital. In conclusion, findings of the current study demonstrated that the mean incidence of acute bacterial meningitis in a referral infectious diseases ward in Iran was 9 episodes per year. The majority cases of community-acquired acute bacterial meningitis admitted to our center had negative CSF culture and classic triad of meningitis was absent in them.

Atorvastatin for Prevention of Amikacin-induced Electrolytes Imbalances; a Randomized Clinical Trial.

Aminoglycosides are still widely used for treatment of gram-negative sepsis in critically ill patients. The most reported electrolyte abnormalities related to these drugs are hypokalemia, hypomagnesemia, and hypocalcemia.In this study potential benefit of atorvastatin in prevention of amikacin-induced electrolytes imbalances has been evaluated. In this trial 44 patients were assigned to the atorvastatin or placebo group based on the simple randomization method. Atorvastatin group received amikacinwith dose of 15 mg/kg/day in two equal divided doses every 12 h as intravenous infusion during 30 min and atorvastatin 40 mg tablet as daily oral dose for 7 days. Patients in the placebo group received same dose of amikacinand placebo tablet (Placebo group) for at least 7 days. Serum electrolytes (sodium, potassium, calcium, phosphor and magnesium) concentrations, blood urea nitrogen and serum creatinine levels were measured at day 0 and end of the study. Baseline mean ± SDof serum potassium concentration in the atorvastatin and placebo group was 4.07± 0.37 and 4.15 ± 0.53 meq/l respectively (p=0.88). Serum potassium concentration remained unchanged at the end of the study in the atorvastatin group (P=0.61) but significantly decreased from 4.15 ± 0.53 to 3.80 ± 0.55meq/l in the placebo group at day 7(P = 0.02).In this pilot study, atorvastatin as 40 mg daily oral dose prevented renal potassium loss during course of amikacin therapy in the critically ill patients. In the future well designed randomized clinical trials with adequate sample size,renoprotective effects of statins should be examined.

Statins against drug-induced nephrotoxicity.

Drug-induced nephrotoxicity (DIN) accounts for up to 60% of hospital acquired acute kidney injury with considerable morbidity and mortality. Several efforts have been made to reduce drug-induced nephrotoxicity; however, DIN remains a matter of concern. Statins with their antioxidant, anti-inflammatory and anti-apoptotic effects may have the potential to protect kidney against DIN. The present review evaluated all of the available in vitro and in vivo studies that examined the use of statins as renoprotective agents against nephrotoxic drugs. Materials for this review were obtained by searching Medline, PubMed, Scopus, Cochrane central register of controlled trials, and Cochrane database of systematic reviews. Key words used as search terms included "statin", "3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, "HMG-CoA reductase inhibitors", "nephroprotective", "renoprotective", "drug-induced renal diseases", "drug-induced nephrotoxicity", "drug-induced renal toxicity", "drug-induced nephropathy", "drug-induced renal side effects", and "contrast-induced nephropathy". This search was performed without time limitation. Only English language articles were included in this review. This review concluded that chronic statin user may be less prone to contrast-induced nephropathy (CIN) compared with statin non-users. Short-term high dose statin administration may also reduce the incidence of CIN in statin naïve patients. This renoprotective effect of statins against CIN is seen in low risk patients with normal kidney function or mild kidney dysfunction, but probably not in patients with moderate to severe renal dysfunction. Based on available animal data, statins may protect kidney against gentamicin-, cisplatin- and cyclosporine-induced nephrotoxicity, however, theses animal results have not yet been confirmed by human data. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.