Effectiveness of bosentan in the treatment of systemic sclerosis-related digital ulcers: Systematic review and meta-analysis.

Background: The aim of the present systematic review and meta-analysis was to evaluate the therapeutic efficacy of bosentan, a dual endothelin receptor antagonist, for systemic sclerosis (SSc) patients with digital ulcers (DUs). Materials and Methods: A systematic search of MEDLINE, Embase, Web of Science, and Scopus was done using appropriate keywords till September 2021. Weighted mean difference (WMD) as the effect of therapeutic efficacy of bosentan on continuous outcomes was an estimate. Furthermore, the pooled prevalence of diffuse SSc and limited SSc was computed. Fixed or random effects models when appropriate were used for data synthesis. Results: Totally, 469 patients, with a mean age ranging from 48.1 to 63.7 years, from 8 studies were included in the systematic review and meta-analysis. The pooled frequency of diffuse SSc and limited SSc was 56% (95% confidence interval [CI]: 39%, 73%) and 44% (95% CI: 27%, 61%). The pooled prevalence of new DUs following bosentan treatment was 21% (95% CI: 10%, 33%). The results of the meta-analysis showed a pooled mean decrease of WMD: -0.09 (95% CI: -0.020, 0.02, P = 0.10), WMD: -2.82 (95% CI: -5.91, 0.27, P = 0.07), and WMD: -6.65 (95% CI: -9.49, -3.82, P < 0.001) in mean SSc-Health Assessment Questionnaire, pain, and Rodnan score, respectively. Our meta-analysis also indicated a significant pooled decrease in the number of new DUs in SSc patients compared to placebo subjects (WMD: -0.89 [95% CI: -1.40, -0.37; P = 0.001]) and baseline values (WMD: -1.34 (95% CI: -1.95, -0.73; P < 0.001). Conclusion: Bosentan possibly is an efficacious treatment option for SSc-related DUs. Although further large-scale randomized clinical trials are required to confirm the preliminary finding and underlying mechanisms of action.

Evaluation of Diagnostic Accuracy of Alpha-Fodrin Antibody in Iranian Patients with Sjogren's Disease.

Background: Sjogren's syndrome, as a chronic autoimmune disease, involves in lymphocytic infiltration in the exocrine glands. As the result of exocrine glands disruption, the clinical hallmark of this disease including dryness of mouth and eyes along with fatigue and joint pain occur. However, heterogeneity of clinical presentations among newly diagnosed adult patients with Sjogren's syndrome leads to difficulty in its diagnosis. One of the diagnostic criteria for Sjogren's syndrome is the presence of autoantibodies in patient serum. One of the novel biomarkers suggested for diagnosis of Sjogren is alpha-fodrin antibody. In this study, we aimed to evaluate the diagnostic power of anti-α-fodrin antibody among the Iranian population for the first time. Materials and Methods: We recruited 82 individuals in this study. Alpha-fodrin were measured in case and control with Elisa kit as 16.71 (9.84) and 18.44 (11.54). Results: There was no any significant difference between two groups regarding alpha-fodrin level (P = 0.35). Then we applied the receiver operating characteristic (ROC) curve analysis to determine the predictive value of alpha-fodrin for diagnosing Sjogren's disease. The area under curve of the ROC curve was calculated as 0.5453. Also, there were significant association between age and alpha-fodrin antibody. Conclusions: Alpha-fodrin test did not have acceptable predictive power for predicting Sjogren's disease; however, it could be associated with disease progression.

Antioxidant and Bone; Protect Your Future: A Brief Review.

The global campaign of osteoporosis has been organized by the International Osteoporosis Foundation (IOF) and them introducing World Osteoporosis Day (WOD) in 1997. The day is celebrated on October 20th each year and aimed to improve the awareness of the population about disease prevention. We present some aspects of bone health and the prevention of osteoporosis related to the use of vitamins. The presenting mini-review covers a variety of sources including PubMed, Embase, Scopus, and directory of open access journals (DOAJ) from 10 years ago (Oct 2009 to Oct 2019) for recent developments in the prevention of bone loss. The search was performed by using combinations of the following keywords and or their equivalents; osteoporosis, bones health, bone loss, and vitamin to find related articles about the prevention of osteoporosis by nutritional factors. The factors affecting bone are various and could begin from fetal periods to the end of life. Some of them are not changeable including age, and genetic; however, it is possible to modify some others such as poor nutrition and vitamin deficiency. Beyond vitamin D deficiency, consumption of other vitamins also is beneficial to maintain bone health. By considering the nutritional factors especially vitamins that affect bones, it is possible to have stronger bones to enjoy life in the elderly and protect your future.

A Phase IV Study of the Safety and Efficacy of CinnoPar® in Iranian Patients with Osteoporosis.

The safety of teriparatide has been studied in various phase III and phase IV trials. However, a postmarketing study of the biosimilar of teriparatide, CinnoPar®, has not been conducted on Iranian patients. This was a phase IV study conducted on osteoporotic patients who received an Iranian teriparatide biosimilar with a dose of 20 µg daily. The primary outcome of this study was to monitor for adverse events (AEs). Effectiveness as the secondary outcome was measured using the EQ-5D quality-of-life questionnaire and back pain Visual Analogue Scale (VAS) score. Among 193 analyzed patients between September 2015 and March 2019, the most common AEs were hypercalcemia (4%), nausea, and pain (3%). No deaths, serious AEs, or other significant AEs occurred in this study. The mean EQ-5D scores decreased after the course of the treatment from 2.3 ± 0.66 at the baseline to 2 ± 0.66. The mean back pain VAS scores also decreased from 4.9 ± 3.6 at baseline to 1.8 ± 2.1 at the end of the study. Both changes were statistically significant (p < 0.001). Consistent with the findings of previous studies and the drug monograph, no new safety concern was observed with this biosimilar teriparatide, and the drug was effective based on the VAS score and EQ-5D in osteoporotic patients.

Assessment of Treatment Safety and Quality of Life in Patients Receiving Etanercept Biosimilar for Autoimmune Arthritis (ASQA): A Multicenter Post-marketing Surveillance Study.

INTRODUCTION: Phase IV post-marketing surveillance studies are needed to evaluate the real-world safety and effectiveness of drug products. This study aimed to evaluate the safety and effectiveness of biosimilar etanercept (Altebrel, AryoGen Co., Iran) in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA). METHODS: In this open-label, multicenter, prospective, observational, post-marketing surveillance study, 583 patients received biosimilar etanercept 25 mg twice weekly or 50 mg once weekly and were followed up to 12 months. The primary objective was to evaluate the safety of biosimilar etanercept by documenting all the adverse events in the case report forms throughout the study period. The secondary objective was to evaluate the effectiveness of biosimilar etanercept in study patients, where longitudinal changes in health assessment questionnaire (HAQ), pain, and disease activity scores were assessed. RESULTS: A total of 583 patients (44.80 ± 13.09 years of age) were included and followed for an average of 8.12 ± 3.96 months. Among all patients, 172 (29.50%) experienced at least one adverse event, and injection site reaction, abdominal pain, and upper respiratory tract infection were the most common. HAQ scores decreased from 1.32 ± 0.77 at baseline to 0.81 ± 0.61 at 12 months in patients with RA/PsA (p < 0.01) and from 0.82 ± 0.58 at baseline to 0.66 ± 0.63 at 12 months in patients with AS (p = 0.18). Pain scores decreased from 6.49 ± 2.41 at baseline to 3.51 ± 2.39 at 12 months (p < 0.01). CONCLUSION: The results demonstrated the real-world safety and effectiveness of biosimilar etanercept in patients with RA, PsA, and AS. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04582084.

The effects of conventional drugs in the treatment of rheumatoid arthritis on the serum lipids.

BACKGROUND: Rheumatoid arthritis (RA) is a common chronic autoimmune disorder that leads to damage of human joints. There are various treatment approaches in which different drugs are prescribed which have several alterations in serum lipids. This research aimed to study the effect of RA treatments on the serum lipids. MATERIALS AND METHODS: Two hundred randomly selected patients with RA were randomly assigned to three different groups. The first group of patients was treated with a combination of prednisolone (PRD) and hydroxychloroquine (HCQ). The second group was treated with three drugs including PRD, HCQ, and methotrexate (MTX). The third group was treated with four medications including PRD, HCQ, MTX, and sulfasalazine. Within each group, the lipid factors such as triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), erythrocyte sedimentation rate, and visual analog scale were measured at the beginning of the experiment and 6 months after exposing the treatments. For each group, we also calculated the Disease Activity Score-28 (DAS-28). The analysis of variance revealed that the overall DAS-28 was significantly different among the three groups. RESULTS: In the first group, the level of TG and TC significantly decreased (P = 0.015 and P ≤ 0.001, respectively). In the second group, the level of TG and LDL significantly decreased (P = 0.009). In the third group, the LDL level increased considerably (P < 0.001). The HDL level significantly increased in all three groups (P = 0.012, P = 0.014, and P = 0.028, respectively). CONCLUSION: The treatment PRD + HCQ + MTX was more effective in reducing the LDL level and increasing the HDL level. To reduce the risk of cardiovascular diseases in patients with RA, it is important to prescribe the combination of drugs which leads and normalizes the lipid profile levels.

Prevalence of Chondrocalcinosis in Patients above 50 Years and the Relationship with Osteoarthritis.

BACKGROUND: Some studies showed a relation between chondrocalcinosis and osteoarthritis (OA). Hence, considering the importance of chondrocalcinosis diagnosis andnecessity for its integration with OA, the current study aims at investigating prevalence of chondrocalcinosis in patients above 50 years admitted to Isfahan Al-Zahra Medical Center and its relationship with OA. MATERIALS AND METHODS: In a cross-sectional study, 600 patients who referred to the radiology units of Al-Zahra Hospital for radiography of different joints were studied during 2013-2014. The patients images were studied for chondrocalcinosis and OA by a radiologist and also examined clinically and results of imaging by an expert rheumatologist. The prevalence of chondrocalcinosis and it relation with OA was determined by Statistical Package for Social Sciences software and using of Chi-square and t-test. RESULTS: 23 patients under study had chondrocalcinosis (3.83%). patients with chondrocalcinosis had higher age average, and they were in age group of 70 years and older, but no significant difference was observed regarding the prevalence of the disease in both genders. Chondrocalcinosis prevalence in terms of body mass index showed significant differences (P = 0.001). All patients with chondrocalcinosis had a history of joint disease and prevalence of chondrocalcinosis in terms of joint disease history showed a significant difference (P < 0.001). CONCLUSION: Prevalence of chondrocalcinosis is relatively high in the Iranian population of 70 years and older. Hence, more investigation considering to the diagnosis of chondrocalcinosis among patients with OA is very important.

Venous insufficiency after prolonged standing: Is joint hypermobility an important risk factor?

BACKGROUND: Varicose veins are extremely common disease which is due to elevated superficial venous pressures. We aimed to know that if joint hypermobility causes the venous insufficiency following the prolonged standing. MATERIALS AND METHODS: This prospective cohort study conducted on the soldiers of training periods in a military base of Iran Army in Isfahan in 2013. The active-duty soldiers were first examined by a physician and their Beighton scores (BSs) were obtained. At the onset of the training period, the presence of chronic venous insufficiency was clinically evaluated according to the C class of clinical, etiological, anatomical, and pathological classification. After 3 months, soldiers with and without joint hypermobility were reexamined for manifestations of venous insufficiency based on clinical examination. RESULTS: Of 718 soldiers, 211 subjects were diagnosed for joint hypermobility syndrome (29.3%). The mean BS was significantly higher in hypermobility soldiers (5.5 ± 1.5) than the healthy ones (1.2 ± 1.1). Before the training period, the prevalence of spider and varicose veins in soldiers with joint hypermobility was significantly higher than healthy subjects (P > 0.001). After the training period, the prevalence of venous insufficiency significantly increased in soldiers with joint hypermobility (P > 0.001) while there was no significant difference in healthy group before and after the period of training (P = 0.25). CONCLUSION: Hypermobility could be considered as a risk factor for the development of venous insufficiency, so it seems necessary to evaluate the population who need to be standing for a long time for evidence of joint hypermobility.

Benign joint hypermobility syndrome in soldiers; what is the effect of military training courses on associated joint instabilities?

BACKGROUND: Hypermobile joints are joints with beyond normal range of motion and may be associated with joint derangements. This study aimed to evaluate the prevalence of benign joint hypermobility syndrome (BJHS) among soldiers and effect of training courses on related joint instabilities. MATERIALS AND METHODS: In a prospective cohort study on 721 soldiers of Iran Army in Isfahan in 2013 the prevalence of joint hypermobility was obtained by using Beighton criteria. Soldiers divided in two groups of healthy and suffered based on their scores. The prevalence of ankle sprain, shoulder and temporomandibular joint (TMJ) dislocations identified before beginning service by history-taking and reviewing paraclinical documents. After 3 months of military training, a recent occurrence of mentioned diseases was revaluated in two groups. The collected data were analyzed using SPSS-20 software using Independent-T and Chi-square tests. RESULTS: The frequency of BJHS before military training was 29.4%. After passing military training period, the incidence of ankle sprain was significantly higher in suffered group achieving the minimum Beighton score (BS) of 4 (4.3%, P = 0.03), 5 (5.5%, P = 0.005) and also 6 out of 9 (6.5%, P = 0.01). The incidence of TMJ dislocation was not significantly different based on a minimum score of 4, while it was higher in suffered group when considering the score of 5 (2.1%) and 6 (2.6%) for discrimination of two groups (P = 0.03). There was no significant difference between two groups in case of shoulder dislocation anyway. CONCLUSION: Military training can increase the incidence of ankle sprains and TMJ dislocations in hypermobility persons with higher BS in comparison with healthy people. Therefore, screening of joint hypermobility may be useful in identifying individuals at increased risk for joint instabilities.

Serum cryoglobulins and disease activity in systematic lupus erythematosus.

BACKGROUND: To determine the prevalence of cryoglobulins in Iranian patients with systemic lupus erythematosus (SLE) and evaluate the correlation of cryoglobulins with disease activity in these patients. MATERIALS AND METHODS: In a cross-sectional study, we investigated 80 consecutive women who fulfilled the 1982 revised criteria of the American College of Rheumatology for the classification of SLE. All the patients had undergone a medical interview and general physical examination by a rheumatologist for clinical and serologic characteristics of SLE. For the determination of cryoglobulins, sera were collected by a standard protocol at 37°C, and after incubation at 4°C for seven days, the level of cryoglobulins was estimated for each patient. RESULTS: Cryoglobulins were detected in the sera of 39 (48.8%) patients. All of these patients had cryocrit over 5%. Disease was active in 30 patients [SLEDAI ≥6 (DAI: disease activity index)] and inactive in 50 (SLEDAI <6). There was no significant difference between active and inactive patients for the presence of serum cryoglobulins (r = 0.086, P = 0.56). A significant positive correlation was observed between antinuclear antibody (ANA), anti-dsDNA (dsDNA: Double-stranded deoxyribonucleic acid), CH50 (CH50: total hemolytic complement assay), and C-reactive protein (CRP) (r = 0.21, P = 0.004, r = 0.65, P = 0.001, r = 0.45, P = 0.023, r = 0.38, P = 0.036, respectively). Hepatitis C virus (HCV) infection was not detected in any of the SLE patients. CONCLUSION: Although the presence of cryoglobulins in the SLE patients correlated with positive anti-ds DNA and low CH50, it could not be predict activity of the disease.

Benign joint hypermobility syndrome among children with inguinal hernia.

BACKGROUND: Benign joint hypermobility syndrome (BJHS) is a disorder due to laxity of supporting connective tissue of joints. Inguinal hernia is also proposed due to weak supporting tissue that may be a clinical presentation of a more widespread problem of connective tissue. MATERIALS AND METHODS: In a cross-sectional study, prevalence of benign hypermobility joint syndrome (BHJS) was assessed among 100 children aged 2-12 year admitted with inguinal hernia during 2010-2011. RESULTS: BJHS (Beighton score ≥ 4) were detected in most of children (92%) with inguinal hernias. CONCLUSION: BHJS amongst this population was substantially greater than reported prevalence in healthy children and due to subsequent clinical significances; it is worthy to screen such patient s for BHJS.

Intravenous pamidronate for refractory rheumatoid arthritis.

BACKGROUND: Patients with rheumatoid arthritis may be resistant to conventional treatment with disease-modifying antirheumatic drugs (DMARDs). On the other hand, biologic therapy is costly and may be inconvenient for many patients. Pamidronate is a potent bisphosphonate with the capacity of modifying the biological activity of the immune system cells. It may thus be used as an anti-inflammatory agent in patients with inflammatory joint diseases. MATERIALS AND METHODS: To assess the effectiveness of pamidronate in the management of rheumatoid arthritis, we selected 38 patients with rheumatoid arthritis to enroll in a pilot study to receive pamidronate and conventional treatment with prednisolone and DMARDs in combination. These patients received 60 mg of pamidronate for 3 consecutive months and were followed for 6 months since the first infusion. RESULTS: The mean visual analogue score (VAS) and disease activity score (DAS28) fell steadily until one month after the third infusion. However, no improvements were observed during the 3 months after the last infusion of the drug. All patients, except one, reported decreased pain in response to 3 consecutive pulses of pamidronate and most had improvements in the assessed laboratory and clinical indices. The drug was tolerated well in our patients. CONCLUSION: Pamidronate infusions had beneficial effects on various clinical and laboratory parameters of patients, but alleviation of symptoms were temporary and did not last for more than 6 months. This treatment option can be a choice for difficult cases of rheumatoid arthritis with severe pain and osteoporosis.

Pamidronate infusion improved two cases of intractable seronegative rheumatoid arthritise.

Pamidronate is a bisphosphonate derivative that can inhibit bone resorption by actions on osteoclasts and increase bone density in spite of treatment with steroids. This drug has the anti-inflammatory effect by increase apoptosis of monocytes. 5-10 percent of rheumatoid arthritis patients is seronegative and may be resistant to conventional disease modifying anti rheumatic drugs (DMARDs). Intravenous (IV) pamidronate can be effective in disease control in seronegative rheumatoid arthritis. We report two cases of seronegative and drug resistant rheumatoid arthritis that favorably responds to pamidronate.

A case of SLE with bilateral osteonecrosis of femoral heads and bone infarct in distal of femur.

Osteonecrosis of bone is a major cause of morbidity in lupus patients, and is most common in the femoral head. It has been reported in wide range of patients (2-30%). In different studies presence of arthritis, Raynaud phenomenon, vasculitis, pleuritis, antiphospholipid and other factors were associated with this occurrence. Bone infarcts were also associated with these factors. We report a 21-year-old patient who was diagnosed as SLE about 3 years ago. When the patient was stable with hydroxychloroquine and prednisolone referred to rheumatologic clinic for mechanical knee pain, in evaluation she had bone infarct in distal femur. Two months later she came back with bilateral hip pain, and in evaluation she had bilateral osteonecrosis of femoral heads. There are many reports of femoral head osteonecrosis in lupus patients, and also one report of multiple bone infarct and pain in SLE, but we did not find any report of these two phenomena together in a patient whose disease was controlled and she took minimum of steroid and DMARD in the about 2-month follow-up, and this was very interesting for us.

Intravenous bisphosphonates for postmenopausal osteoporosis.

Numerous clinical studies have shown bisphoshonates (BPs) to be useful and cost-effective options for the fractures prevention and postmenopausal bone loss. The use of oral bisphoshonates is an established option for managment of osteoporosis in postmenopausal women, but many of them complaint from gastrointestinal side effect or frequently dosed oral regimens. To improve upon the suboptimal therapeutic compliance in postmenopausal women, newer, longer-acting intravenous formulations of BPs has been approved for intermittent administration in postmenopausal women. These preparations would become an option for patients who can not tolerate oral BPs or it was ineffective in increasing their bone density.This article proposed to review effectiveness and tolerability of intravenous BPs in postmenopausal women with osteoporosis.

Devic's syndrome concomitant with nephritis in a young woman.

We presented a 34-year-old woman with blurred vision and inability to walk due to acute optic neuritis and transverse myelitis, neuromyelitis optica (Devic's syndrome), for an interesting presentation of this syndrome with proteinuria as the first manifestation of systemic lupus erythematosus.