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.

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.

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.

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.

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.

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.

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.

Moderate to severe liver siderosis and raised AST are independent risk factors for vitamin D insufficiency in ß-thalassemia patients.

Numerous problematic disorders such as vitamin D (Vit-D) deficiency subsequent to large iron loading can be developed in patients with ß-thalassemia. The study aimed to estimate Vit-D insufficiency and its risk factors in patients with ß-thalassemia. In this multicenter and observational study, all ß-thalassemia patients, who referred to 14 hospital-based thalassemia divisions or clinics in Mazandaran province, Iran were included in the study. The data belong to December 2015 until December 2019. The study population was made of transfusion dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) patients. Serum levels of 25-OHD3 have been measured by high performance liquid chromatography (HPLC) method as ng/mL. Demographic and clinical information along with some biological tests, as well as the results of T2*-weighted magnetic resonance imaging were analyzed. Of 1959 registered patients, 487 (24.9%) patients had Vit-D-related data. The prevalence of Vit-D insufficiency (< 30 ng/mL) was 41.9, 95% CI 37.5-46.3. The adjusted risks of moderate to severe liver siderosis and raised AST (aspartate aminotransferase) for Vit-D insufficiency (< 30 ng/mL) were 2.31, 95% CI 1.38-3.89 and 2.62, 95% CI 1.43-4.79, respectively. The receiver operating characteristic (ROC) curve analysis showed that the predictive accuracy of ferritin for Vit-D insufficiency status was 0.61, 95% CI 0.54-0.68 with a cutoff point of 1,078 ng/mL (P = 0.03, sensitivity 67%, specificity 49%, positive predictive value [PPV] 47% and negative predictive value [NPV] 68%). In spite of the national programs for treating Vit-D deficiency and our previous efforts for giving supplements to all patients, Vit-D insufficiency/deficiency is still common in our patients. Also, moderate to severe liver siderosis and raised AST were the independent risk factors for the Vit-D insufficiency.

Pharmacological Methods of Postoperative Pain Management After Laparoscopic Cholecystectomy: A Review of Meta-analyses.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the optimal approach for patients with symptomatic cholecystolithiasis. Although LC has some advantages, many patients experience postoperative pain. METHODS: In this review, we aimed to study the available information and meta-analyses of pharmacological methods of postoperative pain management in patients undergoing LC. Two researchers conducted a literature search in multiple databases (PubMed, Web of Science, Science Direct, Scopus, EMBASE, and Cochrane Library). Papers on pharmacological management of postoperative pain for patients undergoing LC were considered eligible. All meta-analyses, with or without a systematic search, were included in our review. The researchers read the study titles and abstracts to identify relevant articles and appraise the full-text manuscripts. Of 145 papers, the full-text of 11 articles, which met the inclusion criteria, was studied. Information, including the authors' names, publication data, type of review, patients' characteristics, interventions, outcomes, sample size, pooled effect size, publication bias, and statistical and methodological heterogeneity, was extracted. The collected data were presented descriptively, without further statistical analysis. RESULTS AND CONCLUSIONS: Very low to low-quality evidence indicated that pharmacological agents, such as nonsteroidal anti-inflammatory drugs, lidocaine, parecoxib, nefopam, dexamethasone, and magnesium sulfate, could decrease pain intensity in patients undergoing LC. Moreover, moderate to high-quality evidence showed that intravenous infusion of ketamine and opioids, as well as pregabalin, was effective in pain control. Further, robust clinical trials are needed with several arms (eg, pharmacological agents) to compare the efficacy and safety of analgesics under similar clinical conditions and to find optimal regimens for pain management in patients undergoing LC.

The Effect of Ultra-low-dose Intrathecal Naloxone on Pain Intensity After Lumbar Laminectomy With Spinal Fusion: A Randomized Controlled Trial.

BACKGROUND: Despite advances in pain management, several patients continue to experience severe acute pain after lumbar spine surgery. The aim of this study was to assess the safety and effectiveness of single ultra-low-dose intrathecal (IT) naloxone in combination with IT morphine for reducing pain intensity, pruritus, nausea, and vomiting in patients undergoing lumbar laminectomy with spinal fusion. MATERIALS AND METHODS: In this double-blind trial, patients scheduled for lumbar laminectomy with spinal fusion were randomly assigned to receive single ultra-low-dose IT naloxone (20 µg) and IT morphine (0.2 mg) (group M+N) or IT morphine (0.2 mg) alone (group M). The severity of postoperative pain, pruritus and nausea, and frequency of vomiting were assessed at recovery from anesthesia and, subsequently, at 1, 3, 6, 12, and 24 hours postoperatively using an 11-point (0-10) visual analogue scale. RESULTS: A total of 77 patients completed the study, and there were significant differences in postoperative pain, pruritus, and nausea visual analogue scale between the groups (P<0.05). After adjusting for body mass index and surgery duration, IT naloxone administration reduced the pain score (coefficient=1.84; 95% confidence interval [CI], 1.05-2.63; P<0.001), and the scores of pruritus and nausea (coefficient=0.9; 95% CI, 0.44-1.37; P<0.001 and coefficient=0.71; 95% CI, 0.12-1.31; P=0.02, respectively) compared with IT morphine alone. No serious adverse effects were observed. CONCLUSIONS: The addition of ultra-low-dose IT naloxone to IT morphine provides excellent postoperative pain management and effectively controls pruritus and nausea in patients undergoing laminectomy with spinal fusion.

Treatment Status of Patients with B-Thalassemia Major in Northern Iran: Thalassemia Registry System.

BACKGROUND: Electronic registry system of beta-thalassemia patients was run by Thalassemia Research Center (TRC) in 2017. The aim of the current study was presentation of therapeutic status in these patients at Mazandaran Province, Iran. METHODS: Therapeutic status variables including: Name of cities and hospitals, age and sex of patients, dependent and non-transfusion-dependent, starting age of the blood transfusion and iron-chelating agents, blood group and Rh, washed blood transfusion, abnormal antibody, transfusion reactions, mean hemoglobin during the last 3 months, type of iron chelators, iron chelators dosage, serum ferritin, and the use of hydroxyurea. RESULTS: Overall, 1831 patients were registered [891 male (48.7%)]. Mean age of patients was 30±9.7 yr. Average of hemoglobin levels for female and male were 9.1±5.1 and 9.4±6.3 gr/dl, respectively. Seventy-six percent of transfusion-dependent patients (1385) have received iso-group PRBC (packed red blood cells), after crossmatch. The most common blood group among patient was type O-positive (35.7%). Monotherapy with desferrioxamine was most type of used iron-chelating agent in these patients (47.2%). Mean of ferritin was 3300±7800 (ng/ml). Twenty-eight percent of patients (484) have received hydroxyurea; proportion of male and female was approximately equal. T2 weighted magnetic resonance imaging (MRIT2*) was measured in 62.2% of patients. Moderate and severe hepatosiderosis was 10.1% and 2.9%, respectively. Patients with moderate and severe cardiac siderosis were 11% and 5%, respectively. CONCLUSION: Registry findings are valuable for treatment management and ensuring patients medications. It will also provide accessibility to various levels of patients' information for health care managers and experts to help them make appropriate decisions.

The improvement of pulmonary artery pressure after bosentan therapy in patients with ß-thalassemia and Doppler-defined pulmonary arterial hypertension.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is relatively prevalent in patients with thalassemia. PAH treatment is necessary as the prevalence of Doppler-estimated PAH and the resultant mortality is high in such patients. MATERIALS AND METHODS: This study aimed at evaluating the effect of bosentan therapy on patients with thalassemia suspected of PAH. Based on pulsed Doppler echocardiography, all the cases were suspected of severe PAH. Consequently, bosentan was initiated at a dose of 62.5 mg twice a day for 4 weeks, which was increased to 62.5-125 mg twice a day, if no adverse side effects were observed. RESULTS: The results of this study showed that pulmonary artery pressure (PAP) decreased after the administration of bosentan in three cases, from 160 to 120, 110 to 65, and 60 to 25 mmHg; in other words, the PAP reduced in the mentioned cases by 25%, 36.4%, and 58.4%, respectively. CONCLUSION: In this study, PAP improved after bosentan therapy in patients with ß-thalassemia suspected of PAH; however, further studies are required to confirm the findings.

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.

Administration of Intravenous Zoledronic Acid Every 3 Months vs. Annually in ß-thalassemia Patients with Low Bone Mineral Density: a Retrospective Comparison of Efficacy.

INTRODUCTION: The benefit of annual administration of zoledronic acid in the management of thalassemia-associated osteoporosis is unknown. AIM: The aims of this study were to evaluate the efficacy of treatment with two different dosing regimens of IV zoledronic acid (annually versus every 3 months) for increasing low bone mineral density (BMD) in patients with osteoporosis associated with ß-thalassemia as annually and 3-monthly on bone density in patients. MATERIALS AND METHODS: This retrospective, single-center study analyzed patients' clinical records and bone density measurements. Those enrolled in the study were 14 to 53 years of age, had documented ß-thalassemia, and were treated with IV zoledronic acid on either an annual or every 3 months dosing regimen. Dual-energy X-ray absorptiometry was used to obtain the z-score for BMD in the lumbar spine and femoral neck. RESULTS: Thirty-four patients were enrolled in the study; 15 (44.1%) had been treated annually, and 19 (55.9%) had been treated every month. In patients receiving treatment with the once-yearly dose of zoledronic acid, significant increases were observed in the lumbar spine BMD z-score, from -2.45 ± 0.69 to -1.97 ± 0.82 (P=0.02). When comparing BMD across the two treatment regimens, the mean lumbar spine BMD was 0.82 greater (95% CI 0.31, 1.33, P=0.003) and the mean femoral neck BMD 0.37 greater (95% CI -0.15, 0.87, P=0.1) in the group receiving annual zoledronic acid treatment. CONCLUSIONS: In patients with thalassemia-associated osteopenia, annual treatment with zoledronic acid increases lumbar spine bone density while being more effective, less expensive, and associated with fewer adverse events than dosing every 3 months.

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.