Aspirin versus placebo on estrogen levels in postmenopausal women: a double-blind randomized controlled clinical trial.

BACKGROUND: Estrogen is involved in the pathogenesis of breast and gynecological cancers. Regular use of aspirin reduces estrogen levels. The present study aimed to evaluate the effect of aspirin on estrogen levels in postmenopausal women. METHODS: This double-blind, placebo-controlled parallel-group trial was conducted on postmenopausal women referred to an outpatient clinic at a women's hospital in Tehran. Volunteers were randomly assigned to receive aspirin 100 mg/day or placebo for 6 weeks. Estradiol, sex hormone-binding globulin (SHBG), and testosterone levels at baseline and at the end of the intervention were measured by ELISA. Data were analyzed using SPSS 20, Kolmogorov-Smirnov test, independent samples t-test, and Mann-Whitney U test. RESULTS: Twenty-seven and 28 participants were finally analyzed in the aspirin and placebo groups, respectively. There was no significant difference between the two groups in body mass index (BMI), age, or menopausal years. There was a statistically significant difference (p = 0.002) in the amount of  change in estradiol levels of the intervention group (median=- 3.5 pg/ml) compared to the control group (median=1.5 pg/ml). In contrast, there were no significant differences between the two groups regarding testosterone and SHBG levels (p = 0.58, p = 0.32). CONCLUSIONS: Since low doses of aspirin may decrease estradiol levels, it could be considered a promising adjunctive therapeutic candidate in postmenopausal women to decrease BC incidence. However, further studies with larger sample sizes, measurements of estrogen levels and its related compounds in different time points accompanied by long-term follow-ups are needed to better elucidate the potential mechanisms by which nonsteroidal anti-inflammatory drugs (NSAIDs) negatively affect breast cancer. TRIAL REGISTRATION: IRCT201012195397N1. Date of first registration: 03/01/2011.

Association between MTHFR variant and diabetic neuropathy.

BACKGROUND: Methylene-tetrahydrofolate reductase (MTHFR) gene variant may play an important role in the pathophysiology of diabetes and its complications due to its influence on plasma homocysteine levels and also its effect on scavenging peroxynitrite radicals. Diabetic peripheral neuropathy (DPN) is one of the most common diabetic chronic complications. The aim of this study was to investigate the relationship between diabetic neuropathy and MTHFR gene C677T and 1298A /C polymorphisms. METHOD: Patients with type 2 diabetes N=248 were enrolled in the study, consisting of patients with neuropathy (N=141) and patients without neuropathy (N=107). MTHFR C677T polymorphism was analyzed using polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) of genomic DNA for genotyping of samples. 1298A/C polymorphism was evaluated using ARMS-PCR. RESULT: There was a significant difference in MTHFR polymorphism between the groups with and without neuropathy. CONCLUSION: Our results suggest that MTHFR 677 variant confer risk for diabetic neuropathy among Iranian patients with type 2 diabetes.

Adherence to growth hormone therapy in children and its potential barriers.

BACKGROUND: One of the main concerns in chronic diseases such as growth hormone (GH) deficiency is adherence to the treatment, which significantly affects treatment outcomes. METHODS: This cross-sectional study was conducted among 169 GH recipient children (2-12 years) and teens (13-19 years) referred to a GH distributing teaching pharmacy. The eight-item Morisky Medication Adherence Scale (MMAS) and auto-compliance method were used for the assessment of patients' adherence to GH. The potential barriers to GH therapy adherence and medication persistence were also explored. RESULTS: Based on the MMAS method, 56.7% of the children and 57.9% of the adolescent groups were adherent to GH therapy. Conversely, according to the auto-compliance method almost all the patients were adherent in the children (95.2%) and adolescent (95.5%) groups. Forgetting to take the injection or refill the prescription, being away from home, exhaustion from long-term injection, drug shortage and inaccessibility to the pharmacy were barriers found to be significantly associated with a low adherence in the children group. While in the adolescent group, forgetting to take the injection, painful injection, concern about long-term complications and exhaustion from long-term injection revealed a significant association with low adherence. Persistence with GH therapy was reported in 75.3% and 67% of children and adolescent patients, respectively. CONCLUSIONS: The current study revealed that overall adherence of the study population is low. Considering the barriers with significant association with adherence, different strategies can be incorporated to enhance adherence to GH therapy, i.e. providing early patient and parent education and support, medication reminder systems and longer duration of GH prescriptions.

Association Between the Polymorphism of Glu298Asp in Exon 7 of the eNOS Gene With Foot Ulcer and Oxidative Stress in Adult Patients With Type 2 Diabetes.

OBJECTIVES: Diabetic foot ulcer (DFU) is a common and major manifestation in patients with diabetes. Oxidative stress (OS) plays an important role in diabetic complications, such as DFU. Nitric oxide deficiency contributes to the impairment of diabetic wound healing. The aim of this study was to examine the association between the eNOS Glu298Asp polymorphism and DFU and oxidative stress in patients with type 2 diabetes mellitus in an Iranian population. METHODS: In this case-control study, 123 patients with type 2 diabetes and DFU and 134 patients without DFU were recruited. The genotypes of eNOS Glu298Asp polymorphism in exon 7 were determined by the polymerase chain reaction-restriction fragment length polymorphism analysis. We measured the levels of thiobarbituric reactive substances and ferric-reducing ability of plasma as the potential markers of OS. RESULTS: There were significant differences in genotype frequencies of eNOS Glu298Asp polymorphism between case and control groups (GG+TG vs. TT; p=0.002; OR=0.22, 95% CI 0.83 to 0.62). Also, the frequency of the T allele in cases was less common than in controls (p=0.004). There was no significant difference in levels of OS parameters and various genotypes (p>0.05). CONCLUSIONS: These results imply that the T allele might be protective against DFU.

Growth Hormone Utilization Review in a Pediatric Primary Care Setting.

OBJECTIVE: One of the main problems facing public health providers and administrators in many countries is ensuring the rational use of high-cost drugs. In this regard, on-going process of medication use evaluation can be considered as a useful tool. In this study, we evaluated certain usage aspects of a highly-cost medication, that is, recombinant growth hormone (GH). METHODS: This cross-sectional study conducted from August 2012 to August 2014. Children receiving GH ± gonadotropin releasing hormone (GnRH) analogs were included in the study. A researcher-designed checklist was developed to evaluate the GH utilization in these patients. Baseline demographic characteristics and background clinical and growth data, as well as any aspects of drug therapy including indications, dosing, monitoring, and discontinuation were collected from the patients' medical records. FINDINGS: Seventy children receiving GH entered the study, of which 23 patients (32.85%) received GH and GnRH analogs simultaneously. At the baseline, 67 children (95.7%) had GH stimulation test, whereas serum insulin-like growth factor-1 (IGF-1) levels were measured in 63 (90%) patients. Sixty-seven patients (95.71%) had thyroid function test, whereas bone age was determined in 68 children (97.14%). The mean ± standard deviation of GH dose for idiopathic short stature, GH deficiency, Turner's syndrome and born small for gestational age in our study was 0.22 ± 0.025 mg/kg/week, 0.23 ± 0.04 mg/kg/week, 0.22 ± 0.015 mg/kg/week, and 0.23 ± 0.02 mg/kg/week, respectively. Height and weight of all patients were followed every 3-6 months, regularly. Thirty patients were treated with GH for at least 1 year, of which thyroid hormones and IGF-1 levels were measured annually in 25 (83.33%) and 26 (86.66%) patients, respectively; while bone age was evaluated in 13 (43.33%) children, annually. GH treatment was discontinued in 15 patients (21.42%), while financial problem was the major reason. CONCLUSION: Diagnostic tests and monitoring of height, weight, IGF-1 level and thyroid function was properly performed in this setting. However, a number of patients with ISS and Turner's syndrome were under-dosed.

The efficacy of erythropoietin mouthwash in prevention of oral mucositis in patients undergoing autologous hematopoietic SCT: a double-blind, randomized, placebo-controlled trial.

Oral mucositis (OM) as a complication of high-dose chemotherapy is frequently occurred in hematopoietic stem cell transplantation (HSCT) settings. Erythropoietin (EPO) has anti-inflammatory, antioxidant and wound-healing properties and therefore could have an important role in the prevention of OM. We conducted a double-blind, randomized, placebo-controlled trial to evaluate the EPO mouthwash effect on OM incidence and severity in 80 patients with non-Hodgkin's lymphoma, Hodgkin disease (HD) or multiple myeloma, undergoing autologous hematopoietic stem cell transplantation. Patients received either EPO mouthwash (50 IU/ml, 15 ml four times a day) (n = 40) or placebo (n = 40) from the starting day of high-dose chemotherapy until day +14 after transplantation or until the day of discharge from the hospital, whichever occurred first. OM was evaluated daily for 21 days after transplantation or until resolution of OM according to World Health Organization oral toxicity scale. The incidence of OM (grades 1-4) in the EPO mouthwash group and control group was significantly different (27.5% vs 77.5%, p < 0.001). The mean ± SD of two other parameters of OM including maximum intensity OM score (0.60 ± 1.06 vs 1.67 ± 1.27) and average intensity OM score (0.47 ± 0.80 vs 1.28 ± 0.86) was significantly lower in the intervention group (p < 0.001). Moreover, the mean ± SD duration of OM was also significantly shorter among the EPO mouthwash recipients (1.92 ± 3.42 days vs 5.42 ± 3.86 days, P < 0.001). Also, the duration of neutropenic fever was significantly shorter in the intervention group (2.12 ± 2.42 days vs 3.95 ± 4.01 days, p = 0.016). It is concluded that EPO mouthwash can reduce the incidence and duration of OM. Copyright © 2015 John Wiley & Sons, Ltd.

Ciprofloxacin Use in Hospitalized Children: Approved or Off-label?

OBJECTIVE: Fluoroquinolones are not routinely used as the first-line antimicrobial therapy in pediatrics. The American Academy of Pediatrics (AAP) and the United States Food and Drug Administration (FDA) approved fluoroquinolones on certain indications in children. The aim of this study was to evaluate to what extent and how ciprofloxacin is used on approved indication or as off-label. Besides, dose adequacy and treatment duration were assessed. METHODS: In a 10-month observational study, all children receiving systemic ciprofloxacin were assessed. We classified ciprofloxacin prescription to an AAP/FDA or off-label indication. The off-label prescriptions were further categorized to justified and unjustified therapy subgroups. The AAP/FDA category and the justified subgroup constituted the appropriate prescriptions. FINDINGS: During the study period, 32 patients were prescribed ciprofloxacin. In general, 37% (12) of prescriptions determined to be appropriate. Of the appropriate prescriptions, 7 were AAP/FDA-approved indications. Children with Crohn's disease with abdominal abscess and children with infectious bloody diarrhea constituted the off-label; justified therapy subgroup. Unjustified prescriptions mainly occurred in the presence of a suitable alternative antibiotic for ciprofloxacin. Mean ± SD of ciprofloxacin dose (mg/kg/day) and duration (days) were 21.25 ± 6.35 and 13.56 ± 8.48, respectively. Of the appropriate prescriptions, 41% were underdosed. Underdosing was more encountered in patients with cystic fibrosis. Duration of treatment of the appropriate prescriptions was determined to be appropriate. CONCLUSION: The majority of children were receiving ciprofloxacin off-label and in an inappropriate manner. This issue emphasizes that antimicrobial stewardship program on ciprofloxacin use in pediatric hospitals should be implemented. Further studies evaluating clinical and microbiological outcomes of these programs in children are needed.

Vitamin D receptor gene FokI variant in diabetic foot ulcer and its relation with oxidative stress.

PURPOSE: The patient's suffering and financial costs affiliated with Diabetic Foot Ulcer (DFU), as one of the most important complications of diabetes, are highly undesirable and this highlights the importance of preventive medicine about this disorder. Furthermore hyperglycemia causes generation of free radicals which leads to oxidative stress (OS). Hence, this study aims to examine the association between vitamin D receptor (VDR) gene FokI polymorphism and DFU in Iranian population and also its correlation with OS biomarkers. MATERIALS AND METHODS: In a case-control study, a total of 212 patients with type 2 diabetes with and without diabetic foot ulcer were included. Genotyping was conducted by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. Samples were analyzed for thiobarbituric reactive substances (TBARS) and ferric reducing ability of plasma (FRAP) as markers of OS. RESULTS: The results indicated a significant difference in genotype frequencies of VDR gene FokI polymorphism in patients with diabetic foot ulcer in comparison to those without diabetic foot ulcer (TT+TC vs. CC p=0.04; OR=1.76; 95% CI=1.02-3.05). Moreover, the patients carrying the T allele had a significantly higher level of TBARS (p=0.01). CONCLUSIONS: We found a significant association between FokI functional variant of VDR gene and diabetic foot ulcer in an Iranian population. Increased levels of TBARS in patients carrying the T allele of FokI polymorphism indicate an association between this variant and OS in patients with diabetes.

The effect of vitamin D on primary dysmenorrhea with vitamin D deficiency: a randomized double-blind controlled clinical trial.

Dysmenorrhea is common among women of reproductive age. This study aim was to investigate the effect of vitamin D (vit D) supplementation in treatment of primary dysmenorrhea with vit D deficiency. A randomized double-blind placebo-controlled clinical trial was conducted on 60 women with primary dysmenorrhea and vit D deficiency referred to our clinic at Arash Women's Hospital from September 2013 to December 2014. Eligible women were randomly assigned into treatment and control groups (30 in each group). Individuals in the treatment group received 50 000 IU oral vit D and the control group received placebo weekly for eight weeks. After two months of treatment, there was a significant difference in serum vit D concentration between the two groups (p < 0.001). Pain severity decreased significantly in treatment group after eight weeks of treatment. There was a significant difference in pain intensity between the two groups after eight weeks of treatment and one month after the end of treatment (p < 0.001 for both). A weekly high dose (50 000 IU) oral vit D supplementation for eight weeks in patients with primary dysmenorrhea and vit D deficiency could improve pain intensity.

Calcitriol for Oral Mucositis Prevention in Patients With Fanconi Anemia Undergoing Hematopoietic SCT: A Double-Blind, Randomized, Placebo-Controlled Trial.

Fanconi anemia is a rare inherited aplastic anemia, which is cured only by hematopoietic stem-cell transplantation (HSCT). One of the most debilitating complications of high-dose chemotherapy regimen before HSCT is oral mucositis (OM), which occurs frequently in this population. Vitamin D has identified immunoregulatory, anti-inflammatory, and antioxidant role. This study was designed to examine the efficacy of vitamin D in the prevention of OM in patients with Fanconi anemia undergoing allogenic HSCT. Twenty-eight patients were enrolled in the study. They received either calcitriol (0.025 µg) or placebo capsule once daily, from the first day of chemotherapy schedule for 14 consecutive days. Incidence of OM was assessed as the primary outcome. Moreover, the association of baseline vitamin D level with OM was evaluated. In this study, calcitriol did not change OM incidence (P = 1) and severity (P = 0.54) significantly; however, a significant association of baseline vitamin D level with OM complete resolution was found (P = 0.03; hazard ratio, 1.01; 95% confidence interval, 1.00-1.01). In conclusion, we did not find considerable benefits of calcitriol in the prevention of OM. However, further studies with bigger sample size and different calcitriol supplementation schedules are needed to confirm these findings.

Effectiveness of regular versus glargine insulin in stable critical care patients receiving parenteral nutrition: a randomized controlled trial.

STUDY OBJECTIVE: To compare the effectiveness and safety of two glycemic control regimens in stable critical care patients receiving parenteral nutrition (PN). DESIGN: Prospective, randomized open-label clinical trial. METHODS: Eligible postoperative critical care patients in the ICU began PN on the first to the seventh day of ICU admission. The PN admixture included regular insulin, in doses sufficient to maintain 3 or more goal blood glucose (BG) levels between 110 and 180 mg/dl. After 3 to 5 days of PN containing regular insulin, patients were randomized to 3 more days of regular insulin at the same dose or 80% of their total daily regular insulin dose provided in PN solution as glargine insulin. Capillary BG monitoring was performed every 6 hours. RESULTS: Twenty one patients were randomized to each treatment group. Median APACHE II scores were not significantly different between the two groups within the first 24-hour of ICU admission. There were no significant differences between the two groups at day 3 for mean daily dextrose (306.9 ± 46.2 vs. 305.2 ± 52.2 g; p=0.913) or insulin (18.3 ± 8.8 vs. 19.5 ± 10.0 units; p=0.696) doses. The percentage of BG values in the goal (110-180 mg/dl), hyperglycemic (> 180 mg/dl), and hypoglycemic (< 70 mg/dl) BG levels were similar between the two groups (69.0% vs. 66.7%, p=0.567; 11.9% vs. 11.1%, p=0.780; 0% vs. 1.6%, p=0.124, respectively). Mean daily BG levels were not significantly different between the two groups on each of the 3 study days (day 1: 140 ± 20 vs. 131 ± 25 mg/dl, p=0.194; day 2: 136 ± 20 vs. 140 ± 18 mg/dl, p=0.498; day 3: 142 ± 15 vs. 140 ± 19 mg/dl; p=0.741). CONCLUSION: These data suggest that, compared with regular insulin added to PN, glargine insulin results in similar glycemic control and rates of hyperglycemia and hypoglycemia in stable critical care patients.

Effect of a community pharmacist-delivered diabetes support program for patients receiving specialty medical care: a randomized controlled trial.

PURPOSE: The purpose of the study was to investigate the efficacy of a community pharmacist-delivered diabetes support program for patients receiving specialty medical care in a middle-income country (Iran). METHODS: A randomized controlled trial was conducted on 101 patients who received diabetes care from an endocrinologist. A qualified community pharmacist educated patients about medications, clinical goals, self-care activities, and self-monitoring of blood glucose. The pharmacist trained patients in the intervention group for 5 months (5 follow-up visits and 5 phone calls) and recommended physician visits when necessary. The primary outcome was A1C, and the secondary outcomes included self-care activities, medication adherence, blood pressure, and body mass index. Satisfaction and willingness to pay was assessed in the intervention group. RESULTS: Eighty-five patients completed the study, and baseline A1C was similar between groups (intervention: 7.6 ± 1.6 [59 mmol/mol] vs control: 7.5 ± 1.9 [58 mmol/mol]). No significant difference was observed between study groups at the end of the trial period; however, the amount of A1C reduction was higher in the intervention group (1.0% ± 1.5% vs 0.5% ± 1.5%). Self-care activity was improved in general diet, blood glucose monitoring, and foot care subcategories in the intervention group. Medication adherence and body mass index were significantly improved in the intervention group at the end of study. CONCLUSIONS: A community pharmacist intervention improved self-care activity, medication adherence, and body mass index in patients receiving specialty medical care. Baseline A1C values and the presence of specialty medical care should be considered in the interpretation of clinical findings.

Impact of preexisting diabetes mellitus on transplantation outcomes in hematopoietic stem cell transplantation.

New onset diabetes mellitus is frequently observed following hematopoietic stem cell transplantation (HSCT) and is associated with adverse transplantation outcomes. However, the outcomes of patients with preexisting diabetes mellitus undergoing HSCT are largely unknown. We aimed to explore the impact of preexisting diabetes on transplantation outcomes in HSCT. In a retrospective study, medical charts of 34 HSCT recipients with diabetes mellitus undergoing allogeneic or autologous transplantation were reviewed and compared with 71 HSCT recipients without diabetes. Primary outcome was overall survival. Secondary outcomes included hematopoietic recovery, length of hospital stay, febrile neutropenia, acute and chronic graft-versus-host disease (GVHD), primary disease recurrence, and non-relapse mortality (NRM). On univariate analysis, there was no difference in transplantation outcomes in recipients with diabetes compared with recipients without diabetes. However, after adjusting for potential covariates, multivariate analysis demonstrated that having diabetes before HSCT significantly predicted outcome and decreased overall survival (hazard ratio 0.51, 95% confidence interval: 0.27-0.97, p value: 0.04). This study suggests that patients with diabetes mellitus undergoing allogeneic or autologous HSCT may have inferior survival rates and warrant further attention.

Comparison of the Effects of Enoxaparin and Heparin on Inflammatory Biomarkers in Patients with ST-segment Elevated Myocardial Infarction: A prospective Open Label Pilot Clinical Trial.

Heparin and enoxaparin possess anti-inflammatory properties. We compared the effects of these drugs on inflammatory biomarkers in patients with ST-segment Elevated Myocardial Infarction (STEMI). Thirty four patients with STEMI randomly separated in two groups and received standard doses of heparin and enoxaparin. The serum concentration of Serum Amyloid A (SAA), C-Reactive Protein (CRP), Interleukin (IL)-6, ferritin and Myeloperoxidase (MPO) were measured at baseline, 12 ,24 and 48 hours after drug administration. SERUM CONCENTRATIONS OF SAA (P: 0.02), CRP (P: 0.02) and ferritin (P: 0.01) significantly reduced in heparin group during measurements compared to baseline, circulating levels of IL-6 (P: 0.002), SAA (P: 0.009), CRP (P: 0.01) were significantly decreased in enoxaparin group. The overall difference in inflammatory biomarkers between heparin and enoxaparin group was not significant. Both heparin and enoxaparine reduced serum levels of inflammatory biomarkers in patients with STEMI. This effect may provide additional clinical benefit of these drugs in the treatment of STEMI patients.

Pattern and associated factors of potential drug-drug interactions in both pre- and early post-hematopoietic stem cell transplantation stages at a referral center in the Middle East.

The aim of this study was to determine the pattern as well as associated factors of moderate and major potential drug-drug interactions (PDDIs) in both the pre- and early post-transplantation stages at a referral hematopoietic stem cell transplantation (HSCT) center. All adolescents and adults undergone HSCT within a 3-year period were screened retrospectively for potential moderate or severe PDDIs by the Lexi-Interact On-Desktop software. Among 384 patients, a total of 13,600 PDDIs were detected. The median (interquartile range) cumulative PDDIs burden was 41 (28). All (100 %) individuals experienced at least one PDDI. More than four fifths (81.8 %) of detected PDDIs were moderate. The predominant mechanism of PDDIs was pharmacokinetics (54.3 %). Interaction between sulfamethoxazole-trimethoprim and fluconazole was the most common PDDIs involving 95.3 % of the study population. More than three fifths (61.5 %) of detected PDDIs were caused by HSCT-related medications. No interaction was identified between two anticancer agents. Interactions of cyclophosphamide with phenytoin, busulfan with metronidazole, dexamethasone, or clarithromycin were the only detected PDDI between anticancer and non-anticancer medications. Type of HSCT and the numbers of administered medications were significantly associated with major PDDIs. The epidemiology, real clinical consequence, and economic burden of DDIs on patients undergone HSCT particularly around the transplantation period should be assessed further by prospective, multicenter studies.

Anti-tuberculosis drugs adverse reactions: a review of the Iranian literature.

INTRODUCTION: Tuberculosis (TB) treatment, in particular therapy for multidrug-resistant TB (MDR-TB), is associated with toxicities and adverse drug reactions (ADRs). AREAS COVERED: This paper reviews Iranian literature reporting ADRs which occurred during tuberculosis treatment. English language papers were sourced from PubMed, ScienceDirect, Wiley, Ovid and Proquest, with Google Scholar searched for Persian language articles. Reported ADRs, proportion of patients with ADRs, risk factors and determinants, as well as the characteristics of the studies were reviewed. 21 articles were included; about 60% of them were in English and three included patients with MDR-TB. The ratio of ADR per capita was 1.9 (in 6 studies) and 33.63% of patients developed an ADR (in 7 studies). Hepatitis (2.5 - 45.3%) was reported in nearly all of the studies. The mean time from initiation of medication to development of hepatitis ranged from 4.67 to 25.25 days (in 6 studies). Most cases of mortality were due to hepatotoxicity. Except for comorbidities and female gender, other risk factors such as HIV and length of hospitalization were only reported in one article. EXPERT OPINION: The pattern of ADRs in Iranian articles was found to be similar to many other studies in the present review. We suggest that future studies resolve the confounding factors in this area that are mentioned in this review.

Selenium supplementation in patients undergoing hematopoietic stem cell transplantation: effects on pro-inflammatory cytokines levels.

BACKGROUND: Pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) play an important role in the development of hematopoietic stem cell transplantation (HSCT) complications. We explored the effect of Selenium as an antioxidant and anti-inflammatory agent on pro-inflammatory cytokines levels in HSCT candidates. FINDINGS: Plasma concentrations of TNF-α, IL-1ß and IL-6 were measured in 74 patients from a double-blind, randomized, placebo-controlled study. In both groups, there were 37 patients with median age of 32 years. Patients received oral Se tablets (200 mcg) or placebo twice daily beginning from the first day of high dose chemotherapy (HDC) through 14 days after HSCT. Cytokine levels were determined before starting HDC (prior to first dose of Se), 7 and 14 days after HSCT. Plasma levels of TNF-α were not significantly different between Se and control group (P = 0.13). IL-1 levels were similar between two groups (P = 0.88). No significant differences were detected in IL-6 levels between Se and control group (P = 0.96). CONCLUSION: Selenium had no effect on pro-inflammatory cytokines levels in patients undergoing HSCT. It is likely that earlier initiation and/or larger doses of Se are required to affect inflammatory cytokines significantly.

Assessment of cyclosporine serum concentrations on the incidence of acute graft versus host disease post hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment option for hematological disorders. Cyclosporine (CsA) is one of the major immunosuppressive agents for the prophylaxis against graft versus host disease (GvHD). In this retrospective study, we evaluated the effects of CsA serum levels on the incidence of acute GvHD and transplant outcomes. Retrospective study in 103 adult patients received Hematopoitic Stem Cell Transplantation (HSCT) in the Hematology-Oncology, Bone Marrow Transplantation center at Shariati Hospital in Tehran, Iran. All participants received prophylactic regimen of cyclosporine plus methotrexate. CsA dose titration was done according to patientsá¾½ serum levels and drug toxicity. Serum levels tested on the twice weekly basis in first 4 weeks after transplantation. Acute GvHD (grades II-IV) developed in 44 patients (43%, 95%CI: 33%-52%). The median time to ANC and PLT recovery was 13 days (range: 9-31 days) and 16 days (range: 0-38 days), respectively. Univariate analysis of risk factors related to aGvHD (grade II-IV) development showed a higher risk of incidence of aGvHD (grades II-IV) for patients having the lowest blood CSA concentration (<200 ng/mL) in the third weeks after transplantation (36% vs. 12%, P = 0.035). The only risk factors related to incidence of aGvHD grades III-IV was also blood CsA concentration at 3(rd) week post-transplant (15% vs. 3%, P = 0.047). The CsA concentration at 3(rd) week was not related to disease free survival and overall survival (P = 0.913 vs. P = 0.81) respectively. Higher CsA serum levels in the third week post HSCT significantly decreased incidence of acute GvHD.

Insulin adherence in patients with diabetes: risk factors for injection omission.

AIMS: The purpose of this study was to evaluate adherence to insulin therapy in patients with diabetes. The underlying factors affecting insulin injection omission among patients with type 1 or 2 diabetes were also investigated. METHODS: This cross-sectional study has been conducted on 507 patients with diabetes. Adherence to insulin therapy was measured by the 8-Item Moriskey Medication Adherence Scale (MMS) and the autocompliance method. Furthermore, socio-demographic, disease and injection-related barriers to insulin injection were assessed. RESULTS: Based on the Morisky Green test, 14.3% and 28.8% of patients with type 1 and 2 diabetes respectively had low adherence to insulin therapy. However, almost all patients were adherent according to the autocompliance method. Different factors showed a significant association with insulin compliance in both groups. CONCLUSIONS: The current study suggests acceptable adherence to insulin therapy among patients with type 1, and poor adherence in patients with type 2, diabetes. Our findings regarding barriers with significant effect on insulin adherence may be useful to identify patients at risk for low compliance, and to guide the design of proper strategies to improve adherence and the consequential clinical outcomes.

A randomized, placebo-controlled trial of selenium supplementation in patients with type 2 diabetes: effects on glucose homeostasis, oxidative stress, and lipid profile.

Selenium is an antioxidant trace element. Patients with diabetes are shown to have increased oxidative stress together with decreased selenium concentrations. Whether raising serum selenium will improve blood glucose management in diabetes is largely unknown. In this randomized, double-blind placebo-controlled trial, we assessed the effects of selenium on blood glucose, lipid profile, and oxidative stress in 60 patients with type 2 diabetes. Selenium 200 µg/d or placebo was administered orally for 3 months. Serum concentrations of fasting plasma glucose, glycosylated hemoglobin A1c (HbA1c), insulin, and lipid profile, as well as ferric-reducing ability of plasma and thiobarbituric acid-reactive substances were determined in the fasting state at baseline and after 3 months. Mean (SD) serum selenium at baseline was 42.69 (29.47) µg/L and 47.11 (42.86) µg/L in selenium and placebo groups, respectively. At endpoint, selenium concentration reached to 71.98 (45.08) µg/L in selenium recipients compared with 45.38 (46.45) µg/L in placebo recipients (P<0.01). Between-group comparison showed that fasting plasma glucose, glycosylated hemoglobin A1c, and high-density lipoprotein cholesterol were statistically significantly higher in the selenium recipient arm. Other endpoints changes during the course of trial were not statistically different across the 2 treatment arms. This study suggests that selenium supplementation in patients with type 2 diabetes may be associated with adverse effects on blood glucose homeostasis, even when plasma selenium concentration is raised from deficient status to the optimal concentration of antioxidant activity. Until results of further studies become available, indiscriminate use of selenium supplements in patients with type 2 diabetes warrants caution.