Overutilization of head computed tomography in cases of mild traumatic brain injury: a systematic review and meta-analysis.

Head computed tomography (CT) is the preferred imaging modality for mild traumatic brain injury (mTBI). The routine use of head CT in low-risk individuals with mild TBI offers no clinical benefit but also causes notable health and financial burden. Despite the availability of related guidelines, studies have reported considerable rate of non-indicated head CT requests. The objectives were to provide an overall estimate for the head CT overutilization rate and to identify the factors contributing to the overuse. A systematic review of PubMed, Scopus, Web of Science, and Embase databases was conducted up to November 2023, following PRISMA and MOOSE guidelines. Two reviewers independently selected eligible articles and extracted data. Quality assessment was performed using a bias risk tool, and a random-effects model was used for data synthesis. Fourteen studies, encompassing 28,612 patients, were included, with 27,809 undergoing head CT scans. Notably, 75% of the included studies exhibited a moderate to high risk of bias. The overutilization rate for pediatric and adult patients was 27% (95% CI: 5-50%) and 32% (95% CI: 21-44%), respectively. An alternative rate, focusing on low-risk pediatric patients, was 54% (95% CI: 20-89%). Overutilization rates showed no significant difference between teaching and non-teaching hospitals. Patients with mTBI from falls or assaults were less likely to receive non-indicated scans. There was no significant association between physician specialty or seniority and overuse, nor between patients' age or sex and the likelihood of receiving a non-indicated scan. Approximately one-third of head CT scans in mTBI cases are avoidable, underscoring the necessity for quality improvement programs to reduce unnecessary imaging and its associated burdens.

Spectrum of Beta-Thalassemia Mutations in Potential Carriers with Microcytic Hypochromic Anemia from Mazandaran and Golestan, Northern Provinces of Iran.

Introduction: ß-Thalassaemia is the most common genetic disorder and is considered as a major public health concern in Iran. Different countrywide studies have shown a heterogeneous mutational basis of ß-thalassaemia with different frequencies in each area. This study is aimed at investigating the common and rare mutations in Mazandaran and Golestan, northern provinces of Iran. Methods: 5425 microcytic and hypochromic individuals were investigated from Mazandaran and Golestan provinces. From these, 1323 beta carrier or affected individuals were selected where 938 persons were from Mazandaran and 385 people were from Golestan province, respectively. Result: 53 different mutations were identified, IVSII-1 (G>A) was the most common (59.14%) followed by Cd 22/23/24 (-7 bp) (5.34%), Cd 8 (-AA) (4.93%), Cd30 (G>A) (4.00%), and IVSI-5 (G>C) (3.70%) with a total of 77.11% in Mazandaran Province, respectively. In Golestan Province, IVSI-5 (G>C) was the most frequent (44.62%) followed by IVSII-1 (G>A) (27.18%), Cd 15 (TGG>TAG) (4.36%), Fr 8/9(+G) (3.85%), and Cd 8(-AA) (2.05%) with a total of 82.06%, respectively. From the 53 different mutations, 22 numbers have been observed in both provinces. Two deletions of the beta gene named Sicilian and Asian-Indian have been detected in Mazandaran with a frequency of 0.72% each. Conclusion: The 53 different mutations identified in this study were the most ever reported mutations in the country. Due to diversity of different ethnic groups, there are many varieties of mutation in beta globin gene in Iran. It could be assumed that both founder effect and natural selection caused by migration from neighboring areas have complemented each other to produce the high frequency of unique alleles within each region.

Patterns of case fatality and hospitalization duration among nearly 1 million hospitalized COVID-19 patients covered by Iran Health Insurance Organization (IHIO) over two years of pandemic: An analysis of associated factors.

BACKGROUND: Different populations and areas of the world experienced diverse COVID-19 hospitalization and mortality rates. Claims data is a systematically recorded source of hospitalized patients' information that could be used to evaluate the disease management course and outcomes. We aimed to investigate the hospitalization and mortality patterns and associated factors in a huge sample of hospitalized patients. METHODS: In this retrospective registry-based study, we utilized claim data from the Iran Health Insurance Organization (IHIO) consisting of approximately one million hospitalized patients across various hospitals in Iran over a 26-month period. All records in the hospitalization dataset with ICD-10 codes U07.1/U07.2 for clinically/laboratory confirmed COVID-19 were included. In this study, a case referred to one instance of a patient being hospitalized. If a patient experienced multiple hospitalizations within 30 days, those were aggregated into a single case. However, if hospitalizations had longer intervals, they were considered independent cases. The primary outcomes of study were general and intensive care unit (ICU) hospitalization periods and case fatality rate (CFR) at the hospital. Besides, various demographic and hospitalization-associated factors were analyzed to derive the associations with study outcomes using accelerated failure time (AFT) and logistic regression models. RESULTS: A total number of 1 113 678 admissions with COVID-19 diagnosis were recorded by IHIO during the study period, defined as 917 198 cases, including 51.9% females and 48.1% males. The 61-70 age group had the highest number of cases for both sexes. Among defined cases, CFR was 10.36% (95% CI: 10.29-10.42). The >80 age group had the highest CFR (26.01% [95% CI: 25.75-26.27]). The median of overall hospitalization and ICU days were 4 (IQR: 3-7) and 5 (IQR: 2-8), respectively. Male patients had a significantly higher risk for mortality both generally (odds ratio (OR) = 1.36 [1.34-1.37]) and among ICU admitted patients (1.12 [1.09-1.12]). Among various insurance funds, Foreign Citizens had the highest risk of death both generally (adjusted OR = 2.06 [1.91-2.22]) and in ICU (aOR = 1.71 [1.51-1.92]). Increasing age groups was a risk of longer hospitalization, and the >80 age group had the highest risk for overall hospitalization period (median ratio = 1.52 [1.51-1.54]) and at ICU (median ratio = 1.17 [1.16-1.18]). Considering Tehran as the reference province, Sistan and Balcuchestan (aOR = 1.4 [1.32-1.48]), Alborz (aOR = 1.28 [1.22-1.35]), and Khorasan Razavi (aOR = 1.24 [1.20-1.28]) were the provinces with the highest risk of mortality in hospitalized patients. CONCLUSION: Hospitalization data unveiled mortality and duration associations with variables, highlighting provincial outcome disparities in Iran. Using enhanced registry systems in conjunction with other studies, empowers policymakers with evidence for optimizing resource allocation and fortifying healthcare system resilience against future health challenges.

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.

Severity of oxidative stress as a hallmark in COVID-19 patients.

INTRODUCTION: Understanding the mechanisms and identifying effective treatments for the COVID-19 outbreak are imperative. Therefore, this study aimed to assess the antioxidant status and oxidative stress parameters as potential pivotal mechanisms in asymptomatic, non-severe, and severe COVID-19 patients. METHODS: This study is a case-control study that was performed on patients referred to the Persian Gulf Martyrs Hospital of Bushehr University of Medical Sciences, Bushehr, Iran, from May 2021 to September 2021. A total of 600 COVID-19 patients (non-severe and severe group) and 150 healthy volunteers of the same age and sex were selected during the same period. On the first day of hospitalization, 10 ml of venous blood was taken from subjects. Then, hematological, biochemical, serological, antioxidant and oxidative stress parameters were determined. RESULTS: Our results indicated that ESR, CRP, AST, ALT, and LDH significantly augmented in the severe group as compared to the non-severe and normal groups (P ≤ 0.05). It was observed that the levels of FRAP, G6PD activity, and SOD activity significantly reduced in the non-severe patients in comparison with the severe and normal groups (P ≤ 0.05). We found that MDA content and NO metabolite markedly increased in severe patients as compared to the non-severe group. CONCLUSIONS: Taken together, it seems that the balance between antioxidants and oxidants was disturbed in COVID-19 patients in favor of oxidant markers. In addition, this situation caused more aggravation in severe patients as compared to the non-severe group.

Expression of Galectin-9-related immune checkpoint receptors in B-cell acute lymphoblastic leukemia.

Objectives: Exhausted CD8+ T-cells over-express immune checkpoint receptors (ICRs), which interact with their ligands on malignant cells. However, some ICRs have been reported to be expressed on both T-cells and tumor cells, including V-domain immunoglobulin suppressor of T cell activation (VISTA), Galectin-9, and T-cell immunoglobulin mucin-3 (TIM-3). We aimed to evaluate the mRNA expression of VISTA, Galectin-9, and TIM-3 on CD8+ T-cells and leukemic cells in B-cell acute lymphoblastic leukemia (B-ALL). Materials and Methods: Samples were obtained from 26 untreated B-ALL patients and 25 control subjects. CD8+ T-cells were isolated using Magnetic Activated Cell Sorting (MACS). Relative gene expression was then evaluated by qRT-PCR with specific primers for VISTA, Galectin-9, and TIM-3. Also, the mRNA expression profile and clinical data of 154 B-ALL patients were obtained from the TARGET. Results: mRNA expression of Galectin-9 on CD8+ T-cells in B-ALL patients was significantly lower than those in the control group (P=0.043), while VISTA expression was not significantly different between the two study groups (P=0.259). Besides, TIM-3 expression was significantly higher in B-ALL patients than in the control group (P<0.001). Also, data obtained from TARGET showed that the relapse incidence was not significantly different between patients with high and low expression of Galectin-9 and TIM-3 in leukemic cells (P=0.360 and P=0.655, respectively). Conclusion: Collectively, gene expression results suggest an important role for TIM-3, but not VISTA and Galectin-9, in B-ALL and it seems that TIM-3 could be a candidate for immune checkpoint therapy.

Evaluation of mRNA Expressions of TOX and NR4As in CD8+ T cells in Acute Leukemia.

Background: Thymocyte selection-associated high mobility group box protein (TOX) and members of the nuclear receptor 4A (NR4A) are known as transcription factors involved in T cell exhaustion. Objective: To evaluate the mRNA expression of TOX and NR4A1-3 in CD8+ T cells in acute leukemia. Methods: Blood samples were obtained from 21 ALL and 6 AML patients as well as 20 control subjects. CD8+ T cells were isolated using MACS. Relative gene expression of TOX and NR4A1-3 was then evaluated using qRT-PCR. Results: Comparison of mRNA expression of TOX in CD8+ T cells showed no significant difference among the study groups (p>0.05), while the expression of NR4A1 was significantly lower in AML patients than in the control group (p=0.0006). Also, the expression of NR4A2 and NR4A3 was significantly lower in both ALL (p=0.0049 and p=0.0005, respectively) and AML (p=0.0019 and p=0.0055, respectively) patients. Conclusion: NR4As expressions were found to be lower in CD8+ T cells from patients with AML and ALL compared to controls, whereas the mRNA expression of TOX showed no significant difference. Although TOX and NR4As are associated with CD8+ T cell exhaustion in solid tumors, they might play different roles in acute leukemia, which requires further investigation.

Exploiting Natural Locomotion Synergies to Incorporate Motion of Crutches for Adaptive Gait Pattern Shaping.

This paper addresses the problem of online and adaptive gait pattern generation for powered lower-limb exoskeletons (PLLEs), exploiting the motion of sensorized crutches. We conduct a series of experiments with subjects walking with and without crutches to investigate the synergies of walking between upper and lower body segments, by adopting principal component analysis (PCA), We also evaluate the effect of using crutches on the walking synergies, and we demonstrate that upper and lower limb walking synergies undergo slight changes in that case. However, the upper and lower limb synergies remain evident and can be exploited in order to use the motion of crutches as an input to PLLEs to identify a desired motion of the lower limb. We propose a method to use the results of synergy analysis to shape gait parameters in the real-time control of PLLEs. To evaluate the scalability of our approach for real-world applications, we conduct a number of experiments with subjects wearing a PLLE and using sensorized crutches to adaptively change the gait parameters of walking steps, depending on upper body actions.

Integrating climate change adaptation policies in spatial development planning in hyperarid regions of Kerman province, Iran.

In recent years, lifestyle changes and urbanization of societies, as well as macro-environmental changes, i.e. climate changes (CCs), have caused changes in the land spatial structure and the transfer of resources between different economic sectors of the land. The development of long-term spatial development plans (SDPs) needs to be compatible with CCs, especially in hyperarid areas with low supplies and high demands. In this research, machine learning methods; including Cellular Automata (CA), Random Forest (RF) and regression models through PLUS model were used to simulate the amount of supplies and demands based on land cover (LC) maps during the years 2000, 2010 and 2020 in the hyperarid areas of Kerman, Iran. Then, the best predicted model (Kappa = 0.94, overall accuracy = 0.98) was used to simulate changes in LC classes under climate change scenarios (CCSs) for 2050. The results showed the efficiency of machine learning in simulating land cover changes (LCCs) under CCSs. Findings revealed that SDPs of these areas are not compatible under any possible consideration of CCSs. The modeling results showed that spatial development plans under CCSs is not environmentally efficient and there is no compatibility between supplies, based on agricultural lands, and demands, based on increased population, by 2050. Overall, under the scenario of RCP 8.5, man-made, agriculture and natural LC classes with 106.9, 2.9, and 18.6% changes, respectively, showed the greatest changes compared to 2020. Population control, adjustment of infrastructures, and changes in LC plans can reduce socio-economical and socio-environmental problems in the future of hyperarid areas to some extent.

Evaluation of mRNA Expression of CD244 and Its Adapter Molecules in CD8+ T Cells in Acute Leukemia.

Background: This study investigated the role of the immune-checkpoint receptor (ICR), CD244, and its adapter molecules, in CD8+ T cells in acute leukemia. Methods: Blood samples were obtained from 21 acute lymphoblastic leukemia (ALL) and 6 acute myeloid leukemia (AML) patients and 20 control subjects. Relative gene expression of CD244, immune receptor tyrosine-based switch motif-associated protein (SA), EWS/FLI1-activated transcript 2 (EAT-2), and LncRNA-GSTT1-AS1 were evaluated using quantitative reverse transcription polymerase chain reaction. Results: Expression of CD244, SAP, and EAT-2 were significantly lower in CD8+ T cells from ALL patients than those from control subjects. Interestingly, the expression of SAP was much lower than that of CD244, indicating a lower ratio of SAP to CD244. Also, SAP expression was significantly lower in AML patients compared to the control group. Expression of LncRNA-GSTT1-AS1 showed no significant difference in ALL and AML patients compared to control subjects. Conclusion: The low SAP/CD244 expression ratio in CD8+ T cells in ALL suggests an inhibitory role for CD244 in ALL.

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.

Drug prescription patterns and their association with mortality and hospitalization duration in COVID-19 patients: insights from big data.

Background: Different medication prescription patterns have been associated with varying course of disease and outcomes in COVID-19. Health claims data is a rich source of information on disease treatment and outcomes. We aimed to investigate drug prescription patterns and their association with mortality and hospitalization via insurance data for a relatively long period of the pandemic in Iran. Methods: We retrieved hospitalized patients' data from Iran Health Insurance Organization (IHIO) spanning 26 months (2020-2022) nationwide. Included were patients with ICD-10 codes U07.1/U07.2 for confirmed/suspected COVID-19. A case was defined as a single hospitalization event for an individual patient. Multiple hospitalizations of a patient within a 30-day interval were aggregated into a single case, while hospitalizations with intervals exceeding 30 days were treated as independent cases. The Anatomical Therapeutic Chemical (ATC) was used for medications classification. The two main study outcomes were general and intensive care unit (ICU) hospitalization periods and mortality. Besides, various demographic and clinical associate factors were analyzed to derive the associations with medication prescription patterns and study outcomes using accelerated failure time (AFT) and logistic regression models. Results: During the 26 months of the study period, 1,113,678 admissions with COVID-19 diagnosis at hospitals working in company with IHIO were recorded. 917,198 cases were detected from the database, among which 51.91% were females and 48.09% were males. Among the main groups of medications, antithrombotics (55.84% [95% CI: 55.74-55.94]), corticosteroids (54.14% [54.04-54.24]), and antibiotics (42.22% [42.12-42.32]) were the top used medications among cases with COVID-19. Investigation of the duration of hospitalization based on main medication groups showed antithrombotics (adjusted median ratio = 0.94 [0.94-0.95]) were significantly associated with shorter periods of overall hospitalization. Also, antithrombotics (adjusted odds ratio = 0.74 [95%CI, 0.73-0.76]), corticosteroids (0.97 [0.95-0.99]), antivirals (0.82 [0.80-0.83]), and ACE inhibitor/ARB (0.79 [0.77-0.80]) were significantly associated with lower mortality. Conclusion: Over 2 years of investigation, antithrombotics, corticosteroids, and antibiotics were the top medications for hospitalized patients with COVID-19. Trends in medication prescription varied based on various factors across the country. Medication prescriptions could potentially significantly impact the trends of mortality and hospitalization during epidemics, thereby affecting both health and economic burdens.

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.

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.

Two trade names of deferasirox (Osveral® and Exjade®) in reduction of iron overload parameters in major beta-thalassemia patients: A randomized open labeled clinical trial.

BACKGROUND: Beta-thalassemia major patients typically require chronic transfusion and iron-chelating agents to reduce serum iron overload. Osveral® is an available Iranian brand name of deferasirox used by majority of thalassemic patients. The aim of this study was to compare the efficacy of Osveral® vs. Exjade® in major beta- thalassemia patients. METHODS: In this randomized clinical trial, all patients received a single daily dose of 30 mg/kg either of Osveral® or Exjade® for 6 months. Primary outcome was the mean of bimonthly changes in serum ferritin concentration and secondary outcomes included mean changes of heart and liver MRI T2* after a year. RESULTS: Finally, 80 patients completed the study. The mean serum ferritin level at the end of sixth month significantly decreased in Osveral® and Exjade® groups (p<0.01). After a year, means cardiac MRI T2* in Osveral® group were changed from 25.9±9.6 ms to 25.4±9.7 ms and in Exjade® group from 24.8±9.2 ms to 26.9±5.9 ms, with no significant difference (P=0.43). Mean liver MRI T2* for Osveral® and Exjade® groups were 8.6±6.4 ms (baseline 6.3±4.7) and 6.3±4 ms (baseline 4.9±3.5), respectively and there was no significant difference between two study arms (P=0.1). CONCLUSION: Osveral® decreased significantly the serum ferritin level and improved heart and liver iron overload as efficient as Exjade®. It can be a suitable cost-effective alternative agent in beta-thalassemia major patients.

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.

Efficacy and Safety of Adding Olanzapine to the Standard Preventive Regimen for Chemotherapy-induced Nausea and Vomiting in Children: A Randomized Double-blind Controlled Trial.

This study aimed to assess the additive value of olanzapine to a combination of ondansetron and dexamethasone to prevent chemotherapy-induced nausea and vomiting (CINV) in pediatric patients. A total of 40 patients between 4 to 18 years of age were enrolled in this randomized clinical trial. Both groups received a combination of ondansetron and dexamethasone, and 0.14 mg/kg olanzapine or matched placebo were administered for olanzapine and control groups, respectively. The primary end points were complete response and lack of nausea as far as three days after chemotherapy evaluated by the Common Terminology Criteria for Adverse Effects (CTCAE) v5.0 and the Multinational Association of Supportive Care in Cancer (MASCC) Anti-emesis Tool (MAT). Side effects of olanzapine were also analyzed. In patients receiving the standard regimen of ondansetron and dexamethasone, nausea was observed in 10.5% and 21% of patients according to MAT and CTCAE scales, respectively. In the olanzapine group, 37.5% (MAT scale) and 31.3% (CTCAE scale) of patients developed nausea. Complete response was observed in 84% (MAT scale) and 94.7% (CTCAE scale) of patients in the placebo group receiving ondansetron and dexamethasone. In comparison, it was observed in 87.5% (MAT scale) and 81.25% (CTCAE scale) for patients allocated to the olanzapine group. Neither acute nor delayed CINV was statistically different between placebo and olanzapine groups. The frequency of adverse effects was higher in the olanzapine group. Adding olanzapine to the standard regimen of CINV prophylaxis was only unhelpful in pediatric patients receiving moderately emetogenic chemotherapy but also associated with a higher rate of minor side effects.

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.

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.