Imam Hossein Hospital

Selective immunoglobulin A deficiency (SIgAD) is the most common primary antibody deficiency. Although more patients with SIgAD are asymptomatic, selected patients suffer from different clinical complications such as pulmonary infections, allergies, autoimmune diseases, gastrointestinal disorders and malignancy. Pathogenesis of SIgAD is still unknown; however, a defective terminal differentiation of B cells and defect in switching to IgA-producing plasma cells are presumed to be responsible. Furthermore, some cytogenic defects and monogenic mutations are associated with SIgAD. There is no specific treatment for patients with symptomatic IgA deficiency, although prophylactic antibiotic therapy along with circumstantial immunoglobulin replacement with justification and supportive care (using a product that contains minimal IgA) could be helpful for patients with a severe phenotype. The epidemiology, pathogenesis, clinical phenotype, diagnosis, prognosis, management and treatment in patients with SIgAD have been reviewed.

PURPOSE: The aim of the study was to report clinical features, contributing factors and outcome of patients with coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM). METHODS: A cross-sectional descriptive multicentre study was conducted on patients with biopsy-proven mucormycosis with RT-PCR-confirmed COVID-19 from April to September 2020. Demographics, the time interval between COVID-19 and mucormycosis, underlying systemic diseases, clinical features, course of disease and outcomes were collected and analysed. RESULTS: Fifteen patients with COVID-19 and rhino-orbital mucormycosis were observed. The median age of patients was 52 years (range 14-71), and 66% were male. The median interval time between COVID-19 disease and diagnosis of mucormycosis was seven (range: 1-37) days. Among all, 13 patients (86%) had diabetes mellitus, while 7 (46.6%) previously received intravenous corticosteroid therapy. Five patients (33%) underwent orbital exenteration, while seven (47%) patients died from mucormycosis. Six patients (40%) received combined antifungal therapy and none that received combined antifungal therapy died. CONCLUSION: Clinicians should be aware that mucormycosis may be complication of COVID-19 in high-risk patients. Poor control of diabetes mellitus is an important predisposing factor for CAM. Systematic surveillance for control of diabetes mellitus and educating physician about the early diagnosis of CAM are suggested.

This study was conducted to elucidate the effects of decaffeinated green coffee bean extract (GCE) on anthropometric indices, glycaemic control, blood pressure, lipid profile, insulin resistance and appetite in patients with the metabolic syndrome (Mets). Subjects were randomly allocated to consume 400 mg GCE or placebo capsules twice per d for 8 weeks. Both groups were advised to follow an energy balanced diet. After GCE supplementation, systolic blood pressure (SBP) significantly reduced compared with the placebo group (-13·76 (sd 8·48) v. -6·56 (sd 9·58) mmHg, P=0·01). Also, GCE treatment significantly reduced fasting blood glucose (FBS) (-5·15 (sd 60·22) v. 29·42 (sd 40·01) mg/dl (-0·28 (SD 3·34) v. 1·63 (SD 2·22) mmol/l); P=0·03) and homoeostatic model of assessment of insulin resistance in comparison to placebo (-1·41 (sd 3·33) v. 1·23 (sd 3·84), P=0·02). In addition, waist circumference (-2·40 (sd 2·54) v. -0·66 (sd 1·17) cm, P=0·009) and appetite score (-1·44 (sd 1·72) v. -0·2 (sd 1·32), P=0·01) of the individuals supplemented with GCE indicated a significant decline. Besides, weight and BMI reduction in the intervention group was almost twice as much as the placebo group; however, this discrepancy was marginally significant (weight: -2·08 (sd 2·11) v. -0·92 (sd 1·30) kg, P=0·05). No difference was observed in terms of glycated Hb (HbA1c) percentage and lipid profile parameters between the two groups. To sum up, GCE administration had an ameliorating effect on some of the Mets components such as high SBP, high FBS and Mets main aetiological factors including insulin resistance and abdominal obesity. Furthermore, GCE supplementation could reduce appetite level.

BACKGROUND: Although the Depression Anxiety Stress Scale-21 Items (DASS-21) has been used in different countries and translated into different languages, the Persian version of this scale has not been validated for healthcare professions in Iran. Therefore, the purpose of this study was to examine the psychometric properties of the Persian version of DASS-21 for nurses. METHODS: This cross-sectional study was conducted among 1135 nurses working in public hospitals, who were selected through convenience sampling. DASS-21, which consists of 21 items and three dimensions (depression, anxiety, and stress), has been translated into Persian, and there is an online version available. A confirmatory factor analysis (CFA) was performed to examine the factor structure of this scale. Cronbach's alpha coefficient was also measured to establish internal consistency. Besides, the intraclass correlation coefficient (ICC) was calculated to assess the test-retest reliability. RESULTS: /(df) = 1457/(186), P < 0.001), root mean square error of approximation (RMSEA = 0.078), Tucker-Lewis index (TLI = 0.906), comparative fit index (CFI = 0.917), and standardized root mean square residual (SRMR = 0.047). Fifty-seven nurses were included in the test-retest. The ICCs for all dimensions ranged from 0.75 to 0.86, indicating the acceptable test-retest reliability of the scale. CONCLUSION: The Persian version of DASS-21 showed good psychometric characteristics, and it was confirmed as a valid and reliable tool for evaluating depression, anxiety, and stress among Iranian nurses. However, further validation studies of the Persian DSASS-21 are needed among other healthcare professionals, including physicians, midwives, and allied health professionals.

STUDY DESIGN: Systematic review. OBJECTIVE: Providing a comprehensive review of spinal cord injury cost of illness studies to assist health-service planning. METHODS: We conducted a systematic review of the literature published from Jan. 1990 to Nov. 2020 via Pubmed, EMBASE, and NHS Economic Evaluation Database. Our primary outcomes were overall direct health care costs of SCI during acute care, inpatient rehabilitation, within the first year post-injury, and in the ensuing years. RESULTS: Through a 2-phase screening process by independent reviewers, 30 articles out of 6177 identified citations were included. Cost of care varied widely with the mean cost of acute care ranging from $290 to $612,590; inpatient rehabilitation from $19,360 to $443,040; the first year after injury from $32,240 to $1,156,400; and the ensuing years from $4,490 to $251,450. Variations in reported costs were primarily due to neurological level of injury, study location, methodological heterogeneities, cost definitions, study populations, and timeframes. A cervical level of the injury, ASIA grade A and B, concomitant injuries, and in-hospital complications were associated with the greatest incremental effect in cost burden. CONCLUSION: The economic burden of SCI is generally high and cost figures are broadly higher for developed countries. As studies were only available in few countries, the generalizability of the cost estimates to a regional or global level is only limited to countries with similar economic status and health systems. Further investigations with standardized methodologies are required to fill the knowledge gaps in the healthcare economics of SCI.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the sequestration of various leukocyte subpopulations within both the developing pannus and synovial space. The chronic nature of this disease results in inflammation of multiple joints, with subsequent destruction of the joint cartilage and erosion of bone. Identification of T helper (Th)17 cells led to breaking the dichotomy of the Th1/Th2 axis in immunopathogenesis of autoimmune diseases such as RA, and its experimental model, collagen-induced arthritis (CIA). Th17 cells produce cytokines, including interleukin (IL)-17, IL-6, IL-21, IL-22 and tumor necrosis factor (TNF)-α, with pro-inflammatory effects, which appear to have a role in immunopathogenesis of RA. Regarding the wide ranging production of pro-inflammatory cytokines and chemokines by Th17 cells, it is expected that Th17 cell could be a potent pathogenic factor in disease immunopathophysiology. Thus the identification of effector mechanisms used by Th17 cells in induction of disease lesions may open new prospects for designing a new therapeutic strategy for treatment of RA.

PURPOSE: To evaluate the effect of intraoperative use of mitomycin-C (MMC) on the corneal endothelium during excimer laser photorefractive keratectomy (PRK). SETTING: Vanak Eye Surgery Center, Tehran, Iran. METHODS: This nonrandomized trial comprised 81 patients (162 eyes) with bilateral low to moderate myopia and adequate corneal thickness to allow PRK (estimated postoperative residual stromal thickness >350 microm without considering epithelial thickness). The indication for intraoperative application of MMC 0.02% (0.2 mg/mL) was an ablation depth of 75 microm or more. Patients were divided into 3 groups: bilateral (both eyes treated with MMC), unilateral (only 1 eye treated with MMC), and untreated (no eye treated with MMC). Visual acuity, refraction, endothelial cell density (ECD), and corneal thickness were measured preoperatively as well as 1 week and 1, 3, and 6 months postoperatively. RESULTS: Overall, 76 eyes were treated with MMC. Eyes treated with MMC and untreated eyes were comparable in postoperative visual acuity and refraction. Preoperative to postoperative changes in ECD were statistically significantly greater in the treated eyes (-14.8%) than in untreated eyes (-5.1%) 6 months after PRK (P<.001). Longer MMC contact time (P<.001) and male sex (P= .04) were the only factors independently associated with greater endothelial cell loss. CONCLUSIONS: The prophylactic use of diluted intraoperative MMC 0.02% solution caused corneal endothelial cell loss. The rate of cell loss was correlated with the duration of MMC exposure.

Rheumatoid arthritis (RA) is a common autoimmune disease and a systemic inflammatory disease which is characterized by chronic joint inflammation and variable degrees of bone and cartilage erosion and hyperplasia of synovial tissues. Considering the role of autoreactive T cells (particularly Th1 and Th17 cells) in pathophysiology of RA, it might be assumed that the regulatory T cells (Tregs) will be able to control the initiation and progression of disease. The frequency, function, and properties of various subsets of Tregs including natural Tregs (nTregs), IL-10-producing type 1 Tregs (Tr1 cells), TGF-β-producing Th3 cells, CD8(+) Tregs, and NKT regulatory cells have been investigated in various studies associated with RA and collagen-induced arthritis (CIA) as experimental model of this disease. In this paper, we intend to submit the comprehensive information about the immunobiology of various subsets of Tregs and their roles and function in immunopathophysiology of RA and its animal model, CIA.

PURPOSE: The purpose of this study was to report the 24-month findings of a randomized clinical trial comparing intravitreal bevacizumab (IVB) injection alone or in combination with intravitreal triamcinolone acetonide (IVT) versus macular laser photocoagulation (MPC) as a primary treatment for diabetic macular edema. METHODS: The eyes were randomly assigned to 1 of the 3 study arms: the IVB group, patients who received 1.25 mg IVB; the IVB/IVT group, patients who received 1.25 mg of IVB and 2 mg of IVT; and the MPC group, patients who underwent focal or modified grid laser. Of 150 eyes (50 in each group) in the primary trial, 123, 119, and 113 eyes completed follow-ups at 12, 18, and 24 months, respectively. A total of 39 (78%), 36 (72%), and 38 (76%) eyes in the IVB, IVB/IVT, and MPC groups remained in the study within 24 months, respectively. Retreatment was performed at 3-month intervals whenever indicated. Data from a 24-month follow-up are presented. Changes in best-corrected visual acuity and central macular thickness up to 24 months were the main outcome measures in this study. RESULTS: Retreatment was required in 37 (94.9%), 27 (75.0%), and 31 (81.6%) eyes, respectively, in the IVB, IVB/IVT, and MPC groups up to 24 months. The significant superiority of visual acuity improvement in the IVB group, which had been noted at Month 6, did not sustain thereafter up to 24 months, and the difference among the groups was not significant at all visits. However, the mean visual acuity improvement was greater in the IVB group than the other groups and in the IVB/IVT group compared with the MPC group. The reduction of central macular thickness was more in the IVB group in relation to the other two treatment groups; however, the difference among the groups was not statistically significant at any of the follow-up visits. CONCLUSION: In terms of vision improvement, the significant superiority of the IVB over the combined IVB/IVT and MPC treatment that had been observed at Month 6 did not sustain up to 24 months. This means that although IVB treatment may be a better choice than two other options in short term, the magnitude of this beneficial effect diminishes over time.

Our objective was to study skin disorders in neonates within the first 48 hours of life in Ahvaz, Iran. One thousand consecutive neonates were examined in a descriptional prospective cohort study for 1 year (2002-03). The rate of skin disorders and their relationship to age of gestation and sex were calculated and analyzed using the computerized program SPSS version 10 and chi-squared test (chi2). Our findings were Mongolian spots (71.3%), Epstein pearls (70.2%), sebaceous hyperplasia (43.7%), salmon patch (26.2%), hypertrichosis (25.7%), erythema toxicum (11.1%), milia (7.5%), desquamation (1.9%), hemangioma (1.3%), and miliaria (1.3%). The most frequent skin disorders were Mongolian spots, Epstein pearls, and sebaceous hyperplasia. Differences between our study findings and those of others may be based on racial differences and study method.

Due to the high atomic number of gold nanoparticles (GNPs), they are known as new radiosensitizer agents for enhancing the efficiency of superficial radiotherapy techniques by increasing the dose absorbed in tumor cells wherein they can be accumulated selectively. The aim of this study was to compare the effect of various common low energy levels of orthovoltage x-rays and megavoltage γ-rays (Co-60) on enhancing the therapeutic efficiency of HeLa cancer cells in the presence of conjugated folate and non-conjugated (pegylated) GNPs. To achieve this, GNPs with an average diameter of 52 nm were synthesized and conjugated to folic acid molecules. Pegylated GNPs with an average diameter of 47 nm were also synthesized and used as non-conjugated folate GNPs. Cytotoxicity assay of the synthesized folate-conjugated and pegylated GNPs was performed using different levels of nanoparticle concentration incubated with HeLa cells for 24 h. The radiosensitizing effect of both the conjugated and pegylated GNPs on the cells at a concentration of 50 µM was compared using MTT as well as clonogenic assays after exposing them to 2 Gy ionizing radiation produced by an orthovoltage x-ray machine at four different kVps and γ-rays of a Co-60 unit. Significant differences were noted among various irradiated groups with and without the folate conjugation, with an average dose enhancement factor (DEF) of 1.64 ± 0.05 and 1.35 ± 0.05 for the folate-conjugated and pegylated GNPs, respectively. The maximum DEF was obtained with the 180 kVp x-ray beam for both of the GNPs. Folate-conjugated GNPs can significantly enhance the cell killing potential of orthovoltage x-ray energies (especially at 180 kVp) in folate receptor-expressing cancer cells, such as HeLa, in superficial radiotherapy techniques.

Introduction: Acute kidney injury (AKI) has been associated with an increased mortality rate among hospitalized patients with Coronavirus disease 2019 (COVID-19). The current review aimed to evaluate the symptoms, complications, and treatments performed to manage AKI in patients with COVID-19. Methods: We searched PubMed/Medline, Web of Science, and Embase for the relevant scientific literature published up to February 1, 2022. The following keywords were used: "COVID-19", "SARS-CoV-2", and "Acute kidney injury". Results: Forty-four studies with a total number of 114 COVID-19 patients with AKI (Mean age: 53.6 years) were included in our systematic review. The most common comorbidities in patients with COVID-19 suffering from AKI were the history of diabetes, hypertension, and hyperlipidemia. Twelve out of the 44 included studies reported a history of chronic kidney disease (CKD) in this group of patients. Focal segmental glomerulosclerosis (FSGS) and acute tubular necrosis (ATN) were the most common pathological evidence. The average length of hospital stay was 19 days, and the average duration of need for mechanical ventilation was 3 days. Conclusions: The current systematic review shows that AKI frequently complicates the course of COVID-19 hospitalizations and is associated with increased severity of illness, prolonged duration of hospitalization, and poor prognosis. Given the extent of the adverse impact of AKI, early detection of comorbidities and renal complications is essential to improve the outcomes of COVID-19 patients.

BACKGROUND: Evidence recommends that vitamin D might be a crucial supportive agent for the immune system, mainly in cytokine response regulation against COVID-19. Hence, we carried out a systematic review and meta-analysis in order to maximise the use of everything that exists about the role of vitamin D in the COVID-19. METHODS: A systematic search was performed in PubMed, Scopus, Embase and Web of Science up to December 18, 2020. Studies focused on the role of vitamin D in confirmed COVID-19 patients were entered into the systematic review. RESULTS: Twenty-three studies containing 11 901 participants entered into the meta-analysis. The meta-analysis indicated that 41% of COVID-19 patients were suffering from vitamin D deficiency (95% CI, 29%-55%), and in 42% of patients, levels of vitamin D were insufficient (95% CI, 24%-63%). The serum 25-hydroxyvitamin D concentration was 20.3 ng/mL among all COVID-19 patients (95% CI, 12.1-19.8). The odds of getting infected with SARS-CoV-2 are 3.3 times higher among individuals with vitamin D deficiency (95% CI, 2.5-4.3). The chance of developing severe COVID-19 is about five times higher in patients with vitamin D deficiency (OR: 5.1, 95% CI, 2.6-10.3). There is no significant association between vitamin D status and higher mortality rates (OR: 1.6, 95% CI, 0.5-4.4). CONCLUSION: This study found that most of the COVID-19 patients were suffering from vitamin D deficiency/insufficiency. Also, there is about three times higher chance of getting infected with SARS-CoV-2 among vitamin-D-deficient individuals and about five times higher probability of developing the severe disease in vitamin-D-deficient patients. Vitamin D deficiency showed no significant association with mortality rates in this population.

Alzheimer's disease (AD) is a neurodegenerative disorder and leading cause of dementia, which begins with impaired memory. The neuropathological hallmarks of AD include destructive alterations of neurons by neurofibrillary tangles, neuritic amyloid plaques, and neuroinflammatory process in the brain. Chemokines have a major role in inflammatory cell attraction and glial cell activation and/or modulation in the central nervous system. Moreover, the clinical and immunopathological evidence could show dual key role of chemokines in their pro- and anti-inflammatory properties in AD. However, their effects in neurodegeneration and/or neuroprotection remain an area of investigation. This review article provides an overview of characteristic, cellular source and activity of chemokines, and their roles in neuronal glial cell interaction in AD.

Common variable immunodeficiency (CVID) is the most common clinical primary immunodeficiency. It is characterized by a defect in B-cell differentiation to plasma and memory B cells. Moreover, numerous T-cell abnormalities have been reported and include decreased T-cell count and proliferative response, increased T-cell activation and apoptosis, and abnormalities in cytokine production. The aims of this review are to describe phenotypic and functional defects in T cells in CVID patients and to review the literature with respect to the effects of immunoglobulin replacement on the T-cell component in CVID patients.

BACKGROUND: Carpal tunnel syndrome is the most common peripheral entrapment neuropathy, for which conservative treatments are the first measures taken. However, these measures are not usually sufficient. Recently major attention has been drawn to platelet-rich plasma for its possible effects on axon regeneration and neurological recovery. Although few studies have evaluated the effects of this treatment in carpal tunnel syndrome, further investigation is required to reach concrete conclusion. METHODS: In this randomized controlled trial, women referring to the physical medicine and rehabilitation clinic at Shahid Modarres Hospital during 2016 with a diagnosis of mild and moderate idiopathic carpal tunnel syndrome were chosen. They were randomly assigned to two groups: (i) a control group using only a wrist splint, and (ii) a platelet-rich plasma group that received wrist splints along with a single local injection of platelet-rich plasma. The outcome measures were assessed via Visual Analogue Scale, the Boston Carpal Tunnel Syndrome Questionnaire and electrophysiological findings including the peak latency of sensory nerve action potential and the onset latency of the compound muscle action potential. RESULTS: A total of 41 women were included (20 wrists as control group) and (21 wrists as platelet-rich plasma group). Before treatment there were no significant differences between the two groups except for the median peak latency of sensory nerve action potential which was significantly higher among the patients in the platelet-rich plasma group (p = 0.03). All the measured variables significantly decreased in both groups after 10 weeks of treatment except for the median onset latency of the compound muscle action potential (p = 0.472). Finally, the changes in neither of the evaluated outcome measures were found to significantly differ between the two groups, even when the analyses were adjusted for age of the patients. CONCLUSION: The findings of this study showed that in a relatively short period of time after treatment, a single injection of platelet-rich plasma in the wrist does not significantly add to the effects of conservative treatment with wrist splints, in regards to the women pain and symptom severity, functional status and electrophysiological parameters. TRIAL REGISTRATION: The trial has been retrospectively registered with an ID: IRCT2017041513442N13 (Date of registration: 2017-06-19).

OBJECTIVES: Previous studies have shown that serum levels of vitamin D were lower in attention deficit hyperactivity disorder (ADHD) children compared to healthy controls. The aim of the study was to determine the effect of vitamin D supplementation as adjunctive therapy to methylphenidate on symptoms of children with ADHD. METHODS: Sixty-two children aged 5-12 years with a diagnosis of ADHD based on DSM-IV criteria were randomly assigned into two groups to receive either 2000IU vitamin D or placebo in addition to methylphenidate for 8 weeks. Symptoms severity was assessed by Conner's Parent Rating Scale-Revised[S] (CPRS), ADHD rating scale-IV (ADHD-RS), and Weekly Parent Ratings of Evening and Morning Behavior (WPREMB) at weeks 0, 4, and 8. Serum levels of 25(OH)D were measured at baseline and after 8 weeks. Anthropometric variables, dietary intake, physical activity, sun exposure, and side effects were assessed. RESULTS: Fifty-four participants completed the trial. After 8 weeks of supplementation, serum levels of 25(OH)D significantly increased in the vitamin D group. ADHD symptoms decreased significantly in both groups (P < 0.05). Evening symptoms and total score of WPREMB scale were significantly different at weeks 4 and 8 between the two groups (P = 0.013, 0.016, respectively), but no differences were found in symptoms by CPRS and ADHD-RS scales. DISCUSSION: Vitamin D supplementation as adjunctive therapy to methylphenidate improved ADHD evening symptoms. Future research is needed to clarify vitamin D effects as monotherapy in ADHD and its mechanism. The trial was registered in www.irct.ir is (IRCT201404222394N10).

Primary immunodeficiency disorders (PIDs) are caused by 1 or more defects of the immune system. Patients are more likely to experience recurrent and/or severe infections and tend to develop a wide range of complications. Respiratory diseases are the main and initial manifestation in most cases and the most common complication. Pulmonary complications cause significant morbidity and mortality in patients with PIDs. Early diagnosis and appropriate treatment can prevent or at least slow the development of respiratory complications. Since the spectrum of pulmonary complications in PIDs is broad, we divided pulmonary complications into upper respiratory complications (eg, sinusitis, otitis media, and laryngeal angioedema) and lower respiratory complications (eg, pneumonia, bronchitis, bronchiectasis, interstitial lung diseases, organizing pneumonia, pulmonary adenopathies and malignancies, hyperreactive airway diseases, pulmonary dysgenesis, and adverse reactions to treatment). This review covers the main respiratory manifestations in patients with PIDs.

INTRODUCTION: Common variable immunodeficiency (CVID) comprises a large heterogeneous group of patients with primary antibody deficiency. Areas covered: The affected patients are characterized by increased susceptibility to infections and low levels of serum immunoglobulin. However, enteropathy, granulomatous organ infiltrates, malignancy, inflammatory and autoimmune conditions are also prevalent. The concomitance of immunodeficiency and autoimmunity appears to be paradoxical and creates difficulties in the management of autoimmune complications affecting these patients. Expert commentary: The management of autoimmunity in patients with CVID requires special considerations because dysregulation and dysfunctions of the immune system along with persistent inflammation impair the process of diagnosis and treatment.

OBJECTIVES: This study was conducted to evaluate the effect of simvastatin (40 mg/day) as an adjuvant therapy to interferon beta (IFNb 1a, 30 microg once weekly) in relapsing-remitting multiple sclerosis patients, compared with placebo. METHODS: We enrolled 85 patients with relapsing-remitting multiple sclerosis (71% female) who were already receiving IFNb 1a (Avonex), with Expanded Disability Status Scale score of less than 5.0. The patients were assigned (in random and double-blinded fashion) into the two groups of simvastatin and placebo. All patients continued to receive their current IFNb treatment. The outcome measures were total relapse rate, Expanded Disability Status Scale score, and the number of gadolinium-enhanced (Gd+) and new T2 lesions in magnetic resonance imaging after a 1-year follow-up. We used Mann-Whitney and one-way multivariate analysis of variances to analyze the data. RESULTS: Four patients in the placebo and two in the simvastatin group prematurely withdrew from the study due to experiencing two attacks. The total attack number in the simvastatin group was significantly lower than placebo group (moderate effect size r = 0.29) (p = 0.01). The final Expanded Disability Status Scale scores were lower in the simvastatin group (1.01 +/- 1.40, mean +/- SD) than in the placebo group (1.73 +/- 1.49, mean +/- SD), but this difference was not significant after controlling the baseline Expanded Disability Status Scale score (p = 0.07). In the simvastatin group, the mean +/- SD of gadolinium-enhanced and new T2 lesions were 0.66 +/- 1.18 and 3.39 +/- 3.55, respectively, (compared with 0.74 +/- 1.21 and 3.39 +/- 3.55 in the placebo group). Although there was a decreasing trend in lesions on magnetic resonance imaging, this difference was not statistically significant (p = 0.62). The combination therapy was safe and well tolerated, and no serious adverse effect was noted. CONCLUSION: Our study supports the safety and efficacy of simvastatin as an add-on therapy to INFb 1a in patients with relapsing-remitting multiple sclerosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00668343. This interventional study provides Class I evidence stating that adding simvastatin 40 mg/day to IFNb 1a 30 microg a week in patients with relapsing-remitting multiple sclerosis may reduce the relapse rate (moderate effect size r = 0.29) (p = 0.01) compared with treatment with IFNb 1a alone.