The role of TNF-α and anti-TNF-α agents in the immunopathogenesis and management of immune dysregulation in primary immunodeficiency diseases.

Primary immunodeficiency diseases (PIDs) consist of a heterogeneous group of genetically disorders that affect distinct components of the immune system. They manifest as increased susceptibility to life-threatening infections, as well as autoimmunity and inflammatory disease. Among them, patients with diseases of immune dysregulation and autoinflammatory disorders are more complicated with autoimmunity. On the other hand, tumor necrosis factor alpha (TNF-α) is one of the major players in the pathogenesis of autoimmunity and inflammation in PID patients. Monoclonal antibodies (mAbs) targeting TNF-α would be a potential approach as a therapeutic tool for these diseases. In the current review, we aimed to highlight the characteristics of TNF-α and its important role in the pathogenesis of related complication in PID diseases. Critical evaluation of the mAbs targeting TNF-α (e.g. infliximab, etanercept, and adalimumab) in various immune-mediated complications in PID diseases will be provided, and finally, their clinical efficacy and safety will be reported.

Type 2 diabetes: patient assessment of chronic illness care.

OBJECTIVE: We tried to assess perception of chronic illness care in people with type 2 diabetes and to determine whether demographic variables, self-care behavior, as well as affective variables were related with perception of chronic illness care. METHODS: We conducted a secondary analysis of the previously published cross-sectional study in 441 Iranian people with type 2 diabetes. Chronic illness care was assessed with the validated tool of patient assessment of chronic illness care (PACIC). Different aspects of care according to the chronic care model are measured on a scale of 1-5, with 5 being highest perception of care. The association between perception of chronic illness care and measured variables were tested using spearman correlation test as well as univariate and multiple linear regression analysis. RESULTS: Finally, 380 filled out the PACIC questionnaire, completely (53.4% female, mean age: 54.73 ± 8.0 years, mean PACIC score: 2.52 ± 0.87). In spearman correlation test, considering PACIC score as the dependent variable, chronic illness care was inversely associated with level of education and distress, whereas, insulin treatment, wellbeing, family-social support and self-management were positively associated with chronic care (All p value<0.05). In the multiple linear regression analysis, family-social support was positively related to chronic care while level of education, marital status, diabetes-related distress, and high density lipoprotein had significant negative relationship with PACIC score (All p value<0.05). CONCLUSIONS: Family-social support, level of education, marital status, and diabetes-related distress are the major determinants of patient experience of chronic illness care in people with type 2 diabetes.

Correction to: The efficacy of etanercept as anti-breast cancer treatment is attenuated by residing macrophages.

An amendment to this paper has been published and can be accessed via the original article.

The efficacy of etanercept as anti-breast cancer treatment is attenuated by residing macrophages.

BACKGROUND: Interaction between microenvironment and breast cancer cells often is not considered at the early stages of drug development leading to failure of many drugs at later clinical stages. Etanercept is a TNF-alpha inhibitor that has been investigated for potential antitumor effect in breast cancer with conflicting results. METHODS: Secretome data on MDA-MB-231 cancer cell-line were from public repositories and subjected to gene enrichment analyses. Since MDA-MB-231 cells secrete high levels of Granulocyte-Monocyte Colony Stimulating Factor, which activates macrophages to promote tumor growth, the effect of macrophage co-culturing on anticancer efficacy of Etanercept in breast cancer was evaluated using the Boolean network modeling and in vitro experiments including invasion, cell cycle, Annexin PI, and tetrazolium based viability assays and NFKB activity. RESULTS: The secretome profile of MDA-MB-231 cells was similar to the expression of genes following treatment of breast cancer cells with TNF-α. Accordingly, inhibition of TNF-α by Etanercept decreased MDA-MB-231 cell survival, induced apoptosis and cell cycle arrest in vitro and inhibited NFKB activation. The inhibitory effect of Etanercept on cell viability, cell cycle progression, invasion and induction of apoptosis decreased following co-culturing of the cancer cells with macrophages. The Boolean network modeling of the changes in the dynamics of intracellular signaling pathways revealed NFKB activation by secretome of macrophages, leading to a decreased efficacy of Etanercept, suggesting NFKB inhibition as an alternative approach to inhibit cancer cell growth in the presence of macrophage crosstalk. CONCLUSION: This study indicates that the effect of Etanercept may be influenced by residing macrophages in tumor microenvironment, and suggests a method to predict the effect of drugs in the presence of stromal cells to guide experimental designs in drug development.

Aloe Vera-Derived Gel-Blended PHBV Nanofibrous Scaffold for Bone Tissue Engineering.

Today, composite scaffolds fabricated by natural and synthetic polymers have attracted a lot of attention among researchers in the field of tissue engineering, and given their combined properties that can play a very useful role in repairing damaged tissues. In the current study, aloe vera-derived gel-blended poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofibrous scaffold was fabricated by electrospinning, and then, PHBV and PHBV gel fabricated scaffolds characterized by scanning electron microscope, protein adsorption, cell attachment, tensile and cell's viability tests. After that, osteogenic supportive property of the scaffolds was studied by culturing of human-induced pluripotent stem cells on the scaffolds under osteogenic medium and evaluating of the common bone-related markers. The results showed that biocompatibility of the PHBV nanofibrous scaffold significantly improved when combined with the aloe vera gel. In addition, higher amounts of alkaline phosphatase activity, mineralization, and bone-related gene and protein expression were detected in stem cells when grown on PHBV-gel scaffold in comparison with those stem cells grown on the PHBV and culture plate. Taken together, it can be concluded that aloe vera gel-blended PHBV scaffold has a great promising osteoinductive potential that can be used as a suitable bioimplant for bone tissue engineering applications to accelerate bone regeneration and also degraded completely along with tissue regeneration.

The challenge of living with diabetes in women and younger adults: A structural equation model.

BACKGROUND: Attitudes toward diabetes care are different between genders and age-groups. Furthermore, diabetes related challenges may cause psychosocial problems. Therefore, we were to compare the psychosocial status and glycemic control in women and men with type 2 diabetes (T2D) in different age-groups. METHODS: 441 adults with T2D were recruited. Demographic, self-care behavior, resources and affective variables as well as the health related quality of life (HRQoL) were measured. The median age of 55 was used as the cut-off for the age comparison. Structured equation modeling (SEM) investigated the relationship between age, gender, psychosocial factors and glycemic control. RESULTS: Finally, 203 women and 177 men completed the study (86.1%). There was no significant difference in mean duration of T2D, or glycemic control between genders or age-groups. Women, especially those below the median age of 55, had significantly higher level of diabetes-related distress (2.16±0.94 vs. 1.92±0.81), depression (9.67±5.37 vs. 7.54±5.06), and anxiety (19.81±12.04 vs. 12.81±9.04, P<0.05 for all comparisons), while people above the age of 55 reported better self-management and patient-physician relationship. HRQoL was lower in women compared to men (0.77±0.23 vs. 0.81±0.18, P=0.02). The final SEM suggested that the effect (standardized ß coefficient) of gender and age on affective variables was 0.25 and -0.19 (P<0.05), respectively, though psychosocial factors did not directly influence HbA1c. CONCLUSIONS: This study shows that psychosocial factors are associated with age and gender in patients with T2D; with younger women demonstrating higher level of depressive symptoms, anxiety, and diabetes-related distress independent of status of glycemic control.

Biphasic insulin Aspart 30 vs. NPH plus regular human insulin in type 2 diabetes patients; a cost-effectiveness study.

BACKGROUND: The aim of this study was to compare the efficacy, safety, costs, and cost-effectiveness of biphasic insulin aspart 30 (BIAsp 30) with NPH plus regular human insulin (NPH/Reg) in patients with type 2 diabetes mellitus (T2DM). METHODS: It was a Single-center, parallel-group, randomized, clinical trial (Trial Registration: NCT01889095). One hundred and seventy four T2DM patients with poorly controlled diabetes (HbA1c ≥ 8 % (63.9 mmol/mol)) were randomly assigned to trial arms (BIAsp 30 and NPH/Reg) and were followed up for 48 weeks. BIAsp 30 was started at an initial dose of 0.2-0.6 IU/Kg in two divided doses and was titrated according to the glycemic status of the patient. Similarly, NPH/Reg insulin was initiated at a dose of 0.2-0.6 IU/Kg with a 2:1 ratio and was subsequently titrated. Level of glycemic control, hypoglycemic events, direct and indirect costs, quality adjusted life year (QALY) and incremental cost-effectiveness ratio have been assessed. RESULTS: HbA1c, Fasting plasma glucose (FPG), and two-hour post-prandial glucose (PPG) were improved in both groups during the study (P < 0.05 for all analyses). Lower frequencies of minor, major, and nocturnal hypoglycemic episodes were observed with BIAsp 30 (P < 0.05). Additionally, BIAsp 30 was associated with less weight gain and also higher QALYs (P < 0.05). Total medical and non-medical costs were significantly lower with BIAsp 30 as compared with NPH/Reg (930.55 ± 81.43 USD vs. 1101.24 ± 165.49 USD, P = 0.004). Moreover, BIAsp 30 showed lower ICER as a dominant alternative. CONCLUSIONS: Despite being more expensive, BIAsp 30 offers the same glycemic control as to NPH/Reg dose-dependently and also appears to cause fewer hypoglycemic events and to be more cost-effective in Iranian patients with type 2 diabetes.

The Association Between Subclinical Hypothyroidism and Metabolic Syndrome as Defined by the ATP III Criteria.

The association between subclinical hypothyroidism (SCH) and metabolic syndrome (MetS) is a matter of debate. In this study, we aimed to examine the risk of MetS in SCH through a systematic review and meta-analysis. A systematic search of published literature up to September 2015 was conducted. General population studies were included if they had considered SCH as the independent variable. After data extraction, a meta-analysis was run to assess the odds ratio (OR) of MetS and its components between subclinical hypothyroid and euthyroid groups. Only studies employing Adult Treatment Panel III (ATP III) criteria for MetS were included in the meta-analysis. In the SCH group, female gender was more prevalent [OR = 1.65, 95% confidence interval (95% CI) 1.29-2.13]. Meta-analysis showed no significant difference in MetS prevalence between SCH and euthyroid individuals (OR = 1.13, 95% CI 0.95-1.34). However, the prevalence of central obesity (OR = 1.43, 95% CI 1.04-1.96) was significantly higher in the SCH group. On the other hand, hypertriglyceridemia was more prevalent in the female-only SCH subgroup. In conclusion, although we found some MetS components to be more prevalent in SCH, the prevalence of MetS as defined by ATP III criteria was not increased in SCH. Considerable heterogeneity observed may have influenced the results on MetS components.

The cost of diabetes chronic complications among Iranian people with type 2 diabetes mellitus.

BACKGROUND: To evaluate the cost of diabetes related micro- and macrovascular complications in Iranian people with type 2 diabetes mellitus. METHODS: In routine clinical practice, people with type 2 diabetes mellitus were assessed for 10 years at a diabetes care center. The type of medications and clinical data were extracted from patients' documents. Mortality rate and the incidence of micro- and macrovascular complications recorded in patients' documents were analyzed. Cost analysis was comprised of 1) para clinic costs as well as laboratory, medications, clinical visits and nonmedical costs 2) inpatient costs as well as hospital admission costs, disability, and mortality costs. RESULTS: From 1562 people with type 2 diabetes mellitus, a total of 1000 patients with mean duration disease of 11.2 years, who had completed information in their documents, were studied. All people were free from complications at baseline. Mean cumulative incidence of diabetes-related complications over 10 years were 10.9 ± 3.5%, 8.0 ± 3.1%, 4.6 ± 1.7%, 9.1 ± 3.6% and 2.3 ± 0.9% for peripheral neuropathy and diabetic foot ulcer, nephropathy, ophthalmic complications, cardiovascular disease and death, respectively. People with better glycemic control had less complication and also related expenditures. Average para clinic cost per patient was 393.6 ± 47.8 and average inpatient cost per patient was 1520.7 ± 104.5 USD. CONCLUSIONS: Our findings demonstrate considerable incidence of diabetes chronic complications and also high health care expenditure for related complications among our patients. As the number of people with diabetes continues to rise, early detection of the disease and implementation of timely and appropriate therapeutic strategies could decrease the burden of diabetes chronic complications and also huge related expenditures.

Effects of morning report case presentation on length of stay and hospitalisation costs.

CONTEXT: The primary goal of discussing patient cases during the morning report is to teach appropriate clinical decision making. In addition, the selection of the best diagnostic strategy and application of evidence-based patient care are important. Reducing hospital costs is fundamental to controlling inflation in health care costs, especially in university hospitals that are subject to budget constraints in developing countries. The goal of this study was to explore the effect of morning report case presentation on length of stay (LoS) and hospitalisation costs in a university teaching hospital. METHODS: A total of 54 patients whose cases had been presented at morning report sessions in the department of internal medicine during a 3-month period (presented group) were selected and their medical records reviewed for data on final diagnosis, hospital LoS and detailed hospital costs. A control group of 104 patients, whose cases had not been presented, were selected on the basis that their final diagnoses matched with those of the presented group. In addition, the groups were matched for age, sex, occupation, comorbidities and insurance coverage. Final diagnoses were based on International Classification of Disease 10 (ICD-10) diagnostic code criteria. RESULTS: The mean ± standard deviation (SD) hospital LoS was 8.32 ± 4.11 days in the presented group and 10.46 ± 4.92 days in the control group (p = 0.045). Mean ± SD hospitalisation costs per patient were significantly lower in the presented group (US$553.43 ± 92.16) than the control group (US$1621.93 ± 353.14) (p = 0.004). Although costs for paraclinical services were similar, there were very significant reductions in costs for medications used during hospitalisation and bed-days (p = 0.002). CONCLUSIONS: Discussing clinical aspects of patient cases in morning report sessions facilitates the management process and has a significant effect on LoS and hospitalisation costs in patients admitted to hospital.

Effect of chromium on glucose and lipid profiles in patients with type 2 diabetes; a meta-analysis review of randomized trials.

PURPOSE: Chromium (Cr) as an essential trace element in metabolism of carbohydrate, lipid and protein is currently prescribed to control diabetes mellitus (DM). The objective of this meta-analysis was to compare the effect of Cr versus placebo (Pl) on glucose and lipid profiles in patients with type 2 DM. METHODS: Literature searches in PubMed, Scopus, Scirus, Google Scholar and IranMedex was made by use of related terms during the period of 2000-2012. Eligible studies were randomized clinical trials (RCTs) with intake of Cr higher than 250 µg at least for three months in type 2 DM. Glycated hemoglobin (HbA1c), fasting blood sugar (FBS), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglyceride (TG), and body mass index (BMI) were the main outcomes. RESULTS: Seven out of 13 relevant studies met the criteria and were included in the meta-analysis. HbA1c change in diabetic patients in Cr supplement therapy comparing to Pl was -0.33 with 95%CI= -0.72 to 0.06 (P= 0.1). Change of FBG in Cr therapy vs. Pl was -0.95 with 95%CI= -1.42 to -0.49 (P< 0.0001). TC change in Cr therapy vs. Pl was 0.07 with 95%CI= -0.16 to 0.31 (P= 0.54). TG change in diabetic patients in Cr supplement therapy comparing to Pl was -0.15 with 95%CI= -0.36 to 0.07 (P= 0.18). CONCLUSIONS: Cr lowers FBS but does not affect HbA1c, lipids and BMI.

Impact of clinical pharmacy services on stress ulcer prophylaxis prescribing and related cost in patients with renal insufficiency.

OBJECTIVES: Compared to the general population, chronic kidney disease patients are more vulnerable to gastrointestinal haemorrhage and its morbidity and mortality. Due to the fear of gastrointestinal bleeding consequences in these patients on the one hand, and the perception of general safety of acid suppressive medications on the other hand, inappropriate stress ulcer prophylaxis (SUP) seems to be encountered in nephrology wards. The objectives of this study were to evaluate appropriateness of acid suppression therapy in kidney disease patients and to assess the role of clinical pharmacists to decrease inappropriate SUP prescribing and related costs for these patients. METHODS: All inpatients at nephrology wards of a teaching hospital were assessed regarding appropriate SUP prescribing during a 6-month pre-intervention phase of the study without any clinical pharmacists' involvement in patients' management. Thereafter, during a 6-month post-intervention phase clinical pharmacists provided local SUP protocol and educational classes for physicians regarding appropriate SUP prescribing and participated actively in the patient-care team. MAIN FINDINGS: The results showed significant relative reduction in inappropriate SUP prescribing and related cost in patients with renal insufficiency by about 44% and 67% respectively. CONCLUSION: This study showed that implementing institutional guidelines, and active involvement of clinical pharmacists in the nephrology healthcare team, could reduce inappropriate SUP prescribing and related costs for these patients.

A misdiagnosis led to an extensive skull base surgery: infratemporal tuberculosis mimicking giant cell tumor.

Tuberculosis is a major health problem in developing countries. Tuberculosis of the infratemporal region is not common and the diagnosis could be complicated because of the similarity of the presentation to neoplasm. In our paper, we report a 49 year old male presented with a preauricular mass with extension to parotid in right side of the face. The primary histologic diagnosis was giant cell tumor with bony involvement and radical surgery was taken. After 16 months the patient was developed recurrence of the primary lesion in association with post auricular fistula. Ultimately, infratemporal tuberculosis was diagnosed according to result of the drained discharge by AFB microscopy. Therefore, tuberculosis should be considered as an important differential diagnosis of mass lesions in head and neck area, even when there is no history of significant exposure and no systemic signs or symptoms of tuberculosis.

Structured self monitoring of blood glucose in Iranian people with type 2 diabetes; A cost consequence analysis.

BACKGROUND: Self-Monitoring of Blood Glucose (SMBG) is considered as a key factor in management of people with diabetes which is a growing and cost demanding health problem. The purpose of this study was to investigate the effect of comprehensive patient management using structured SMBG on metabolic control as well as its cost consequence analysis. METHODS: Sixty subjects were recruited in an observational study for a period of 6 months. They were provided with the ACCU-CHEK 360° View tool to fill in the values of the 7-point blood glucose profiles in three consecutive days during the study on a monthly basis. Changes in metabolic control were assessed by HbA1c and lipid profile measurement at the beginning and at the end of the study. In addition, cost consequence analysis was done considering different level of health care professionals with or without insurance coverage. The Average Cost Effectiveness Ratio (ACER) as well as Cost saving analysis were calculated and compared. RESULTS: The analysis showed significant reduction in HbA1c during the 6-month period in all subjects (P = 0.000). Furthermore, a positive effect was observed on lipid profile. The cost of endocrinologist's visit in private sector was estimated to be 265.76 USD while this figure was149.15 USD for general practitioner in public sector with insurance coverage. Total complications and mortality cost saving was 154.8 USD. The lowest ACER was calculated for intervention with general practitioner in public sector with insurance coverage. CONCLUSION: Structured SMBG results in significant improvement of glycemic status. Moreover, it is more cost saving in public sector with insurance coverage. It seems that general practitioner visits with insurance coverage is the most affordable option for people with type 2 diabetes.

Comparison the analgesic effects of single dose administration of tramadol or piroxicam on postoperative pain after cesarean delivery.

A multimodal approach to postcesarean pain management may enhance analgesia and reduce side effects after surgery. We investigated postoperative pain in a double-blinded, randomized, single-dose comparison of the monoaminergic and mu-opioid agonist tramadol, 100 mg (Group T) and piroxicam 20 mg (Group P) given IM alone--single dose in 150 patients who had elective cesarean delivery. All patients were assessed at 0, 6, 12 and 24 hours post operation for pain degree (by Visual Analogue Score: VAS 1-10), nausea and vomiting. Pain degree was classified as: Painless: 0, Mild: 1-4, Moderate: 5-8, Severe: 9-10. There was no significant difference between the efficacy of tramadol and piroxicam injections (P > 0.05). Pain intensity decreased markedly over time in both groups. Mean +/- SEM pain degrees were as follows: P = 7.7 +/- 0.5, T = 8.2 +/- 0.8 after 0 hours; P=5.4 +/- 0.6, T = 6.1 +/- 0.5 after 6 hours; P=3.3 +/- 0.4, T = 3.4 +/- 0.7 after 12 hours; P = 1.1 +/- 0.4, T = 1.3 +/- 0.5 after 24 hours of surgery. Side effects were similarly minimal with all treatments. It might be concluded that i.m. injections of 20 mg piroxicam (single dose therapy) could relieve postoperative pain after cesarean section as well as tramadol and it could reduce opioid analgesic requirements with less adverse side effects during the first postoperative 24 h.