Amlodipine: Can act as an antioxidant in patients with transfusion-dependent ß-thalassemia? A double-blind, controlled, crossover trial.

BACKGROUND AND AIM: This study aimed to assess the antioxidant effects of amlodipine in transfusion-dependent ß-thalassemia (TDT) patients. METHODS: This crossover trial consisted of two sequences (AP and PA). In the AP sequence, nine cases received amlodipine 5 mg daily (phase I) and then were switched to placebo (phase II). In PA sequence, 10 patients took the placebo (phase I) and were shifted to amlodipine (phase II). The washout period was 2 weeks. The length of each phase was 6 months. Serum malondialdehyde (MDA, µmol/L), carbonyl (protein CO, µM/L), glutathione (GSH, nM/L), and total antioxidant capacity (TAC, µmol FeSO4/L) were measured in the beginning and at the end of phases I and II. The clinical significance was viewed as a minimum change difference of 5% for each outcome between amlodipine and placebo. RESULTS: Seventeen cases completed the study. According to the baseline MDA values, the adjusted Hedges's g for MDA was -0.59, 95% confidence interval [CI] -1.26 to 0.08. After controlling the baseline protein CO values, Hedges's g computed for protein CO was -0.11, 95% CI -0.76 to 0.55. The estimated values of the adjusted Hedges's g for GSH and TAC were also 0.26, 95% CI -0.40 to 0.91, and 0.42, 95% CI -0.24 to 1.09, respectively. The change difference for MDA was 8.3% (protein CO 2.2%, GSH 3.1%, and TAC 12.9%). CONCLUSION: Clinically, amlodipine therapy is an efficacious adjuvant treatment with conventional iron chelators for improving the levels of MDA and TAC in patients with TDT.

A double-blind, controlled, crossover trial of amlodipine on iron overload status in transfusion dependent ß-thalassemia patients.

BACKGROUND AND AIM: This study examined whether administration of amlodipine could improve myocardial iron loading status in patients with transfusion dependent ß-thalassemia (TDT), through a placebo-controlled, crossover study. METHODS: Amlodipine (5 mg, daily) or placebo were prescribed to all patients (n = 19) for 6 months, and after a 2-week washout period, patients were crossed over to the other group. The efficacy of amlodipine on iron loading was assessed by measuring myocardial T2*-weighted magnetic resonance imaging (MRI T2*, millisecond [ms]) and serum ferritin (ng/mL). RESULTS: Seventeen patients completed the study. The mean ± standard deviation [SD] of myocardial MRI T2* at baseline was 9.83 ± 2.67 ms Myocardial MRI T2* value rose to 11.44 ± 4.14 ms post amlodipine treatment in all patients. After placebo, myocardial MRI T2* value reached 10.29 ± 4.01 ms After controlling the baseline measures, Hedges's g for ferritin and myocardial MRI T2* outcomes were estimated 3.84 (95% confidence interval [CI] 2.68 to 4.97) and -1.80 (95% CI -2.58 to -0.10), respectively. CONCLUSION: Amlodipine might improve myocardial MRI T2* and serum ferritin level compared to placebo. However, larger clinical studies are needed to confirm the results.

Does co-treatment with ultra-low-dose naloxone and morphine provide better analgesia in renal colic patients?

OBJECTIVE: This study attempted to evaluate the efficacy of ultra-low-dose intravenous (IV) naloxone combined with IV morphine, as compared to IV morphine alone, in terms of reducing pain and morphine-induced side effects in patients with renal colic. METHODS: In this double-blind clinical trial, 150 patients aged 34 to 60 years old who presented to the emergency department (ED) with renal colic were randomly allocated to either an intervention group that received ultra-low-dose IV naloxone combined with IV morphine or to a control group that received morphine plus a placebo. The severity of pain, sedation, and nausea were assessed and recorded for all patients at entrance to the ED (T1), then at 20 (T2), 40 (T3), 60 (T4), 120 (T5), and 180 (T6) minutes after starting treatment. The Numeric Rating Scale (NRS) was used for the assessment of pain and nausea intensities, and the Ramsay Sedation Scale (RSS) was used to assess sedation. RESULTS: A GEE model revealed that patients in the naloxone group had non-significantly reduced pain scores compared to those in the morphine group (coefficient = -0.68; 95% CI: -1.24 to -0.11, Wald X2 (1) = 5.41, p = 0.02). The sedation outcome demonstrated no statistically significant differences at T1 to T4 among patients with renal colic compared to the ones who only received morphine. At T5 and T6, 1.5% vs. 20% and 1.5% vs. 16.9% of subjects from the naloxone group versus the morphine group obtained RSS scores equal to 3, respectively (p = 0.001 and p = 0.004, respectively). CONCLUSIONS: Compared to patients who only received IV morphine, co-treatment of ultra-low-dose naloxone with morphine could not provide better analgesia and sedation/agitation states in renal colic patients.

The effects and potential mechanisms of folic acid on cognitive function: a comprehensive review.

Cognitive impairment and dementia are major neurocognitive disorders that cause a noticeable decline in cognitive abilities, including memory and thinking skills. The effectiveness of using folic acid as an adjuvant for management of neurocognitive disorders is not well-known. This paper explains the role of folic acid, including its usefulness, effectiveness, adverse side effects, and active mechanisms on cognitive functions of the elderly. In the current study, we reviewed clinical and experimental studies investigating the use of folic acid prior to November 2017, using PubMed, ISI Web of Knowledge, Science Direct, Scopus, Ovid, and Cochrane Library databases. A total of 142 articles were retrieved by electronic search. Based on the preset inclusion and exclusion criteria, a total of 36 articles were retrieved for full text analysis. According to data obtained from the review, it seems that folic acid supplementation may improve cognitive function by decreasing homocysteine (Hcy), vascular care, attenuating inflammatory status, modification of cerebral folic acid deficiency, and antioxidant responses. Specifically, people with high levels of Hcy have a better response to folic acid supplementation, which may arise from low serum folate concentration.

Iron-chelating effect of silymarin in patients with ß-thalassemia major: A crossover randomised control trial.

This study aimed to determine the potential iron-chelating effects of silymarin in patients with ß-thalassemia major receiving standard iron-chelation therapy. We evaluated whether addition of silymarin to standard iron-chelation therapy could improve iron burden markers and liver and cardiac function in these patients, via a placebo-controlled, crossover clinical study. Silymarin (140 mg) or placebo were administered thrice daily to all patients (n = 82) for 12 weeks, and after a 2-week washout period, patients were crossed over to the other groups. Silymarin efficacy was assessed by measuring serum iron level, ferritin level, total iron-binding capacity and liver and cardiac function on magnetic resonance imaging. Silymarin treatment resulted in a negative change in the serum iron and ferritin levels and a positive change in the total iron-binding capacity levels (treatment effect, p < .001, p = .06, and p = .05, respectively). Silymarin treatment led to positive changes in cardiac and liver function in both treatment sequences of study; however, this was not statistically significant. There was a negative change in liver iron concentration in both treatment sequences (treatment effect, p = .02). In conclusion, combined iron-chelation and silymarin therapy was effective for improving the iron-burden status in patients with ß-thalassemia major.

The Role of Doppler Imaging in the Assessment of Right Ventricular Function: a Case-control Study of Acute Inferior Wall Infarction.

BACKGROUND: Right ventricular infarction (RVI) develops in 30-50% of patients with inferior wall infarction (IWI). The rates of mortality, morbidity, and complications in these patients are greater than in the patients without RVI. We compared the tissue Doppler imaging (TDI) indices between a group of patients with IWI and RVI, with a similar group of patients who had IWI alone to investigate the application of TDI indices in the evaluation and detection of right ventricular function. MATERIAL AND METHODS: We studied 49 patients with first acute IWI in two groups. Group 1 (N=24) were patients with IWI and RVI while group 2 consisted of patients with IWI alone (N=25), based on standard electrocardiogram criteria. The peak systolic (Sm), peak early (Em) and late (Am) diastolic velocities, and Em/Am ratio were obtained from the apical four chamber view, at the lateral side of the tricuspid annulus. We measured trans-tricuspid early (ET) and peak (AT) filling velocity, ET/AT ratio, right ventricular end diastolic diameter (RVEDD), and tricuspid annular plane systolic excursion (TAPSE) by M-mode TDI projected at the long axis of parasternal view. RESULTS: The RVEDD and E/Em ratio were increased, while the TAPSE was significantly decreased in the patients with RVI as compared to those without RVI (4.7± 0.6 vs. 3.1±0.2 cm; p < 0.005, 5.6±2.21 Vs 4.5±1.2; p<0.006 and 1.7±0.4 vs. 2.3±0.5 cm; p <0.0001, respectively). However, the other statistically measured parameters were not significantly different between these groups. CONCLUSION: The measurement of RVEDD, E/Em ratio, and TAPSE, as right ventricular myocardial systolic and diastolic parameters by pulse wave TDI could be used to objectively assess the status of RV condition in patients with first acute IWI.

Correlation of Pancreatic Iron Overload Measured by T2*-Weighted Magnetic Resonance Imaging in Diabetic Patients with ß-Thalassemia Major.

Diabetes mellitus (DM) is one of the potential complications in patients with transfusion-dependent ß-thalassemia major (ß-TM). In this case-controlled study, we examined the pancreatic iron levels in outpatients with ß-TM. In this study, cases of patients with ß-TM and DM were gender- and age-matched with control subjects, who were non-diabetic and had normal blood glucose on standard oral glucose tolerance (OGTT) tests. One of four diagnoses [normal, pre-diabetes, impaired glucose tolerance (IGT), DM] was made according to the American Diabetes Association (ADA) criteria. The T2*-weighted magnetic resonance imaging (T2*-weighted MRI) of the heart, liver, and pancreas was performed using a 1.5 Tesla scanner. The study enrolled 26 diabetic cases, 17 non-diabetic cases, and eight cases of IGT or pre-diabetes cases. The severity of pancreatic and cardiac iron siderosis was significantly different between the groups. We found a statistically significant difference at 5.6 ms in the T2*-weighted MRI values for the pancreas between patients with normal vs. abnormal glucose metabolism [p < 0.009; odds ratio (OR): 11.2; 95% confidence interval (95% CI): 1.32-94.4)]. The receiver operating characteristic (ROC) curve for the 5.6 ms cutoff led to an area under the curve (AUC) of 0.69 (95% CI: 55.0-84.0; p < 0.02), with sensitivity and specificity of 94.0 and 42.0%, respectively. There was a moderate positive correlation between pancreatic and cardiac T2*-weighted MRI (r = 0.4; p < 0.001), and a weak correlation between the pancreas and the liver (r = 0.38; p < 0.005). To conclude, we have introduced a cutoff of 5.6 ms on T2*-weighted MRI of the pancreas for prediction of abnormal glucose metabolism in ß-TM patients.

Zinc Supplementation in Adult Mechanically Ventilated Trauma Patients is Associated with Decreased Occurrence of Ventilator-associated Pneumonia: A Secondary Analysis of a Prospective, Observational Study.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a type of lung infection that typically affects critically ill patients undergoing mechanical ventilation (MV) in the Intensive Care Unit (ICU). The aim of this analysis is to determine potential association between zinc supplementation with the occurrence of VAP in adult mechanically ventilated trauma patients. SUBJECTS AND METHODS: This secondary analysis of a prospective observational study was carried out over a period of 1 year in ICUs of one teaching hospital in Iran. A total of 186 adults mechanically ventilated trauma patients, who required at least 48 h of MV and received zinc sulfate supplement (n = 82) or not (n = 104) during their ICU stay, were monitored for the occurrence of VAP until their discharge from the ICU or death. RESULTS: Forty-one of 186 patients developed VAP, 29.09 days after admission (95% confidence interval [CI]: 26.27-31.9). The overall incidence of VAP was 18.82 cases per 1000 days of intubation (95% CI: 13.86-25.57). Patients who received zinc sulfate supplement have smaller hazard of progression to VAP than others (hazard ratio: 0.318 [95% CI: 0.138-0.732]; P < 0.0001). CONCLUSION: The findings show that zinc supplementation may be associated with a significant reduction in the occurrence of VAP in adult mechanically ventilated trauma patients. Further well-designed randomized clinical trials to confirm the efficacy of this potential preventive modality are warranted.

Is Vitamin C Supplementation in Patients with ß-Thalassemia Major Beneficial or Detrimental?

Globally, ß-thalassemia major (ß-TM) is one of the most common hereditary disorders. Multiple blood transfusions, that are a life-saving therapy in patients with ß-TM, is a major source of iron overload. Iron overload can lead to significant morbidity and mortality. Research evidence indicates that oxidative stress induced by iron overload, is one of the major precipitating causes of vitamin C deficiency in ß-TM patients. It has previously been shown that patients with ß-TM have significantly lower levels of vitamin C as compared to healthy individuals. It is believed that vitamin C can reduce both ferric (Fe(3+)) and ferrous (Fe(2+)) ions, and also facilitate the accessibility of iron to chelators through increase of iron release from the reticuloendothelial system. Despite the potential benefits of vitamin C in patients with ß-TM, several areas of concern exist that should be addressed by high quality research designs. Some recommendations have been provided through this study.

Is type 2 diabetes mellitus in mechanically ventilated adult trauma patients potentially related to the occurrence of ventilator-associated pneumonia?

BACKGROUND: Ventilator-associated pneumonia (VAP) is a type of lung infection that typically affects critically ill patients undergoing mechanical ventilation (MV) in the intensive care unit (ICU). Patients with type 2 diabetes mellitus (T2DM) are considered to be more susceptible to several types of infections including community-acquired pneumonia. However, it is not clear whether T2DM is a risk factor for the development of VAP. The purpose of this study was to determine the risk of VAP for diabetic and nondiabetic mechanically ventilated trauma patients. MATERIALS AND METHODS: This study is a secondary analysis of a prospective observational study of the history of T2DM in the ICU over a period of 1 year at Imam Khomeini Hospital in Iran. A total of 186 critically ill trauma patients who required at least 48 h of MV were monitored for the occurrence of VAP by their clinical pulmonary infection score (CPIS) until ICU discharge, VAP diagnosis, or death. RESULTS: Forty-one of the 186 patients developed VAP. The median time from hospitalization to VAP was 29.09 days (95% CI: 26.27-31.9). The overall incidence of VAP was 18.82 cases per 1,000 days of intubation (95% CI: 13.86-25.57). Risk of VAP in diabetic patients was greater than nondiabetic patients after adjustments for other potential factors [hazard ratio (HR): 10.12 [95% confidence interval (CI): 5.1-20.2); P < 0.0001)]. CONCLUSION: The findings show that T2DM is associated with a significant increase in the occurrence of VAP in mechanically ventilated adult trauma patients.

Two risk factors for hypozincemia in diabetic ß-thalassemia patients: Hepatitis C and deferasirox.

BACKGROUND AND AIM: Hypozincemia is a prevalent adverse consequence in diabetes mellitus (DM) and ß-Thalassemia patients. We aimed to evaluate the level of serum zinc in ß-thalassemia patients with DM and a risk assessment for hypozincemia. METHODS: The study population included transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) with overt DM (fasting plasma glucose (FPG) ≥126 mg/dL, and/or 2-h plasma glucose≥200 mg/dL). Serum zinc concentration was measured by the colorimetric method, and the values below 70 µg/dL were defined as hypozincemia. Myocardial and liver T2*-weighted magnetic resonance imaging (MRI T2*, millisecond [ms]) were valued by a free contrast MRI. The demographic, clinical, paraclinical, and laboratory data were also recorded. The data belonged to the period from December 2018 until December 2020. RESULTS: Of 64 diabetic ß-thalassemia patients, 41 cases had zinc data in their medical files (aged 38 ± 9 years, 48.8% female). 78.05% of patients (n = 32) were TDT, and 21.95% were NTDT (n = 9). The mean ± standard deviation of zinc level was 110.2 ± 127.6 µg/dL. The prevalence of hypozincemia was 9.76%, 95% confidence interval [CI] 0.27 to 19.24 (four cases). After controlling age, the odds of hypozincemia for using deferasirox (DFX) was 8.77, 95% CI 0.60 to 127.1. In ß-thalassemia patients, the age-adjusted risk of hypozincemia was calculated at 15.85, 95% CI 0.47 to 529.3 for hepatitis C. The adjusted risk of hypozincemia based on age for antacid use was 6.34, 95% CI 0.39 to 102.7. CONCLUSION: In light of this study, as well as hepatitis C, using DFX and antacids is associated with a high risk of hypozincemia amid diabetic ß-thalassemia cases. However, upward bias should be taken into consideration.

Comparison of the antibacterial effects of matrica & Persica™ and chlorhexidine gluconate mouthwashes in mechanically ventilated ICU patients: a double blind randomized clinical trial.

BACKGROUND: Accumulation of bacteria in the pharynx is one of the risk factors of pneumonia due to ventilation. One of the methods of prevention from accumulation of bacteria in the pharynx is the use of oral solutions. Chlorhexidine is considered as the gold standard, but it has various side effects. AIM: Present study was aimed to determine and compare anti-bacterial effects of the chlorhexidine gluconate 0.2%, herbal mouthwash of Matrica® (chamomile extracts) 10%, PersicaTM 10% and normal saline in intensive care unit patients. METHODS: In this double blind randomized clinical trial, 80 patients who were admitted in ICU divided into four groups of 20 patients each one. Researchers applied PersicaTM to group one, chlorhexidine gluconate mouth wash 0.2% to group two and third group received Matrica, finally in the control group, normal saline were used. In order to culturing of Staphylococcus aureus and S. pneumoniae,salivary samples were obtained without any stimulation after six minimums oral rinsing. The data were processed in SPSS17 software and analyzed by appropriate statistical tests. RESULTS: Decreased rate of bacterial colonies after intervention in the whole four groups was significant (p < 0.001). The mouth wash of chlorhexidine (p < 0.001), PersicaTM (p: 0.008) and Matrica (p: 0.01) had a significant antibacterial effect on S. aureus and S. pneumoniae(p < 0.001). CONCLUSION: Herbal oral mouthwash of persica and matrica has the effect on S. pneumoniae and S. aureus of oropharynx area in mechanically ventilated patients. However, there is a need for further research to be considered as an alternative to chlorhexidine for prevention of VALP in ICU patients.

Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients.

Iron-overload-associated cardiomyopathy has been one of the primary causes of mortality in thalassemia patients with iron burden. There is growing evidence citing the beneficial effects of ebselen as an antioxidant selectively blocking the divalent metal transporter 1 (DMT-1) to deter iron ingress into cardiomyocytes, raising internets in viewing this component in this population in order to treat and even prevent cardiomyopathy occurring from iron surplus. In this article, we reviewed the potential advantageous effects of ebselen in thalassemia patients who suffer from iron excess, susceptible to cardiomyopathy induced by iron overload. A systematic search in several databases, including PubMed, Scopus, and Web of Science, was conducted to explore the role of ebselen in controlling iron-overload-related cardiomyopathy in thalassemia patients by the keywords of Ebselen AND iron. The inclusion criteria were English-written preclinical and clinical studies investigating the efficacy and side effects of ebselen in an iron-overload context. After searching the databases, 44 articles were found. Next, of 19 published articles, 3 were included in this article. After reviewing the references of the included studies, no articles were added. In conclusion ebselen can be a promising adjuvant therapy in patients with thalassemia alongside the standard treatment with iron chelators, particularly in severe cases with cardiomyopathy, due to falling iron inflow by inhibiting DMT-1 and increasing ferroportin-1 expression and antioxidant properties. However, clinical studies need to be carried out to reach a definite conclusion.

Relationship between medical history and multiple sclerosis: A-case-control study.

This project sought to explore the potential association between medical history and the development of multiple sclerosis (MS) by conducting a retrospective study. This population-based case-control study included 200 MS cases and 2 control groups of 200 patients and healthy individuals each. Data was collected through face-to-face interviews, medical file reviews, and an electronic checklist. Multivariable analysis was used to calculate odds ratios and 95% confidence intervals to estimate the risk of each medical history on MS occurrences. Of 600 participants, 381 (63.5%) individuals were female. The mean age of the participants was 36.5 ±â€…11.9 years. The adjusted risks of MS were 4.40; 95% CI: 1.73 to 11.1 for measles and 4.75; 95% CI: 2.05 to 11 for amoxicillin consumption. The adjusted MS odds for autoimmune disease including 4.63; 95% CI: 0.35 to 60.6 for psoriasis and 7.15; 95% CI: 1.87 to 27.2 for myasthenia gravis. On the other hand, the calculated adjusted odds of MS occurrence were 0.14; 95% CI: 0.03 to 0.69 for seizure and 0.17; 95% CI: 0.02 to 1.49 for epilepsy. This study suggested that individuals with autoimmune diseases should be monitored more closely, as they may be at an increased risk of developing other autoimmune conditions, particularly MS.

Clinical competence of Iranian nurses: A systematic review and meta-analysis.

BACKGROUND: One of the most important steps in increasing the nurses' professional competence and consequently improving the quality of nursing care is to evaluate nurses' clinical competency and then take effective actions to enhance it. This study aimed at exploring the clinical competence of Iranian nurses and factors related to it. MATERIALS AND METHODS: In this systematic review and meta-analysis, PubMed, Scopus, Web of Science, Scientific Information Database, and Iranmedex databases and Google Scholar search engine were searched to February 14, 2020. RESULTS: After screening, a total of 25 articles were included. In general, the level of clinical competence of Iranian nurses was at a desirable level. After meta-analysis of the mean score of nurses' clinical competence, the combined mean was 161.13 (95% confidence interval [CI]: 137.78-184.48; P < 0.001; I 2 = 99.8%; P value for heterogeneity = P < 0.001) by the Competency Inventory for Registered Nurses (CIRN) questionnaire. The summarized mean of clinical competency measured by the Nurse Competence Scale (NCS) questionnaire was 70.75 (95% CI: 60.80-80.70; P < 0.001; I 2 = 99.9%; P value for heterogeneity = P < 0.001). Factors affecting nurses' clinical competence were age ≥33 years, nursing work experience ≥9 years, and a master's degree in nursing. However, the clinical competence of nurses had a significant negative relationship with job stress. CONCLUSION: The level of clinical competence of Iranian nurses was desirable. Studies that used the CIRN, reported the highest and lowest clinical competence in clinical care and professional development dimensions, respectively. Studies that used the NCS, reported the highest and lowest clinical competence in dimensions of work role and ensuring quality, respectively.

Ferritin thresholds for cardiac and liver hemosiderosis in ß-thalassemia patients: a diagnostic accuracy study.

Ferritin is frequently used to screen some dire consequences of iron overload in ß-thalassemia patients. The study aimed to define the best cutoff point of ferritin to screen for cardiac and liver hemosiderosis in these cases. This was a registry-based study on ß-thalassemia patients living throughout Mazandaran province, Iran (n = 1959). In this diagnostic research, the index test was ferritin levels measured by a chemiluminescent immunoassay. As a reference test, T2*-weighted magnetic resonance imaging (T2*-weighted MRI) was applied to determine cardiac and liver hemosiderosis. A cutoff point of 2027 ng/mL for ferritin showed a sensitivity of 50%, specificity 77.4%, PPV 42.1%, and NPV 82.5% for cardiac hemosiderosis (area under curve [AUC] 0.66, 95% CI 0.60-0.71, adjusted odds ratio [OR] 2.05, 95% CI 1.05-4.01). At an optimum cutoff point of 1090 ng/mL, sensitivity 66.7%, specificity 68%, PPV 82.9%, and NPV 46.8% for liver hemosiderosis were estimated (AUC 0.68, 95% CI 0.63-0.73, adjusted OR 3.93, 95% CI 2.02-7.64. The likelihood of cardiac hemosiderosis serum ferritin levels below 2027 ng/mL is 17.5%. Moreover, 82.9% of ß-thalassemia patients with serum ferritin levels above 1090 ng/mL may suffer from liver hemosiderosis, regardless of the grades.

Luspatercept: A Gigantic Step in the Treatment of Transfusion-Dependent ß-Thalassemia Patients-a Quick Review.

INTRODUCTION: Some studies have indicated that the use of luspatercept may be a novel and efficient treatment for ß-thalassemia patients. In this article, we aimed to review the current evidence related to luspatercept prescription and its clinical effectiveness in patients with ß-thalassemia. METHODS: PubMed, Web of Science, Scopus, Trip and CENTRAL were searched up to June 2020. The inclusion criteria were English-language articles that studied the effects of luspatercept on improving anemia severity in patients with ß-thalassemia in a clinical setting. RESULTS: The search strategy yielded 273 potentially relevant articles. After searching the databases, scanning of titles, abstracts and full texts for relevancy was performed to identify suitable articles. A total of 77 articles were confirmed for full text analysis. The estimated number of patients needed to treat (NNT) for luspatercept treatment, using data derived from conducted clinical trials, according to a reduction in transfusion need of ≥ 33% or ≥ 50 from baseline, during week 13-24/week 37-48/any 12- and 24-week intervals as outcomes, was 3-5 in patients with ß-thalassemia. CONCLUSION: Based on the conducted studies, the effectiveness of luspatercept on transfusion burden and hemoglobin levels was outstanding in ß-thalassemia patients. Further large and well-designed clinical studies are needed to identify any unforeseen complications subsequent to use of luspatercept, particularly when used with other treatments with potentially serious adverse effects such as anti-osteoporotic and iron chelator agents.

Can Use of Silymarin Improve Inflammatory Status in Patients with ß-Thalassemia Major? A Crossover, Randomized Controlled Trial.

BACKGROUND: In ß-thalassemia major (ß-TM) patients, iron overload is one of the main causes of inflammation. This study investigated whether use of silymarin could improve inflammatory status in patients with ß-TM and iron overload, through a placebo-controlled, crossover study. METHODS: Silymarin (140 mg, 3 times a day) or placebo were prescribed to all patients (n = 82) for 12 weeks, and after a 2-week washout period, patients were crossed over to the other group. The efficacy of silymarin was assessed by measuring serum C-reactive protein (CRP) (mg/dL), interleukin (IL)-6 (pg/mL), and IL-10 (pg/mL). RESULTS: Sixty-nine patients completed the study. Data analysis showed that compared to the placebo, silymarin could decrease CRP, IL-6, and raise IL-10 significantly (the p values for all variables were <0.001). Cohen's d for CRP adjusted according to the baseline CRP value was -1.72, the 95% confidence interval (CI) -2.12 to -1.33. The adjusted Cohen's d equal to -1.12, 95% CI -1.48 to -0.76, and 0.78, 95% CI 0.43-1.12, were also estimated for IL-6 and IL-10, respectively. CONCLUSION: The results of the current study demonstrate that the combination of iron chelation therapy with silymarin can improve inflammatory status in patients with ß-TM in the clinical setting.

Coadministration of silymarin with iron chelators in transfusion-dependent ß-thalassemia patients: a systematic review and meta-analysis for effect on iron overload.

Background and aim: We conducted a systematic review to apprise the efficacy of silymarin in conjunction with standard iron chelators on iron overload for transfusion-dependent ß-thalassemia (TDT) patients.Methods: We searched PubMed, Web of Science, Scopus, Sciencedirect, the Cochrane Library (the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials (CENTRAL) to 1 May 2020. All randomized controlled trials (RCTs) studies comparing the effect of iron chelators alone versus silymarin plus standard routine treatment on iron burden amid TDT were included in this review. Primary outcomes comprised serum ferritin level (ng/mL), liver iron concentration (LIC Fe/kg dry weight), and total iron binding capacity (TIBC mcg/dL)Results: Combination therapy of silymarin and iron chelators showed a significant improvement in serum ferritin level in TDT patients, compared to nonsilymarin users [eight studies, n = 477]; weighted mean difference (WMD) -1.79, 95% confidence interval [CI] -2.86 to -0.72, I2 96.1%; P = 0.001. Concurrent treatment with silymarin failed to significantly decrease LIC in TDT patients [two studies, n = 106]; WMD 0.74, 95% CI -1.62 to 3.10, I2 96.6%; P = 0.54.Conclusion: There is no evidence of the effectiveness of adding silymarin to standard iron chelators to reduce iron load in TDT.

The Effect of Oral Simvastatin on the Clinical Outcome of Patients with Severe Traumatic Brain Injury: A Randomized Clinical Trial.

Background: Despite recent promising pharmacological and technological advances in neurosurgical intensive care, the overall TBI-related mortality and morbidity remain high and still pose a major clinical problem. The aim of this study was to evaluate the effect of oral simvastatin on the clinical outcome of patients with severe TBI. Methods: In a double-blind placebo-controlled randomized clinical trial a total of 98 patients with severe TBI in Imam Khomeini Hospital in Sari, Iran, were evaluated. Patients who meet the inclusion criteria were randomly allocated into two groups (n=49). In addition to supportive therapies, the intervention group received oral simvastatin (40 mg, daily) for 10 days, and the control group received the placebo (10 days). Patients' Glasgow coma scale (GCS) score, in hospital mortality, duration of mechanical ventilation and length of ICU and neurosurgery ward stay were evaluated during three-time intervals (T1: admission, T2: discharge and T3: one month after discharge). Results: The percentage of conscious patients was 18.9% (7 cases) in the simvastatin group and 3.1% (1 case) in controls (P=0.06) at T2. One month after discharge (T3) the proportion of conscious patients significantly increased in the simvastatin group compared to control group (64.9 % versus 28.1 %; P=0.002). There was no significant difference for the mean of GCS score between the simvastatin group and control group at T1 (6.41 ± 1.30 versus 6.41 ± 1.28, respectively; P = 0.98). However, the mean score of GCS in patients who received simvastatin was significantly greater than controls at T2 and T3 (p<0.05). There was no significant differences between two group in-terms of length of mechanical ventilation, ICU and neurosurgery ward stay. Conclusion: According to the results of this study it seems that using simvastatin may be an effective and promising therapeutic modality for improving GCS score during TBI recovery.