Clinical characteristics, management and 1-year outcomes of patients with acute coronary syndrome in Iran: The Iranian Project for Assessment of Coronary Events 2 (IPACE2)

Objectives: To assess contemporary data on characteristics, management and 1-year postdischarge outcomes in Iranian patients hospitalised with acute coronary syndrome (ACS). Setting: 11 tertiary care hospitals in 5 major cities in the Islamic Republic of Iran. Participants: Patients aged �20 and �80 years discharged alive with confirmed diagnosis of ACS including ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) and high-risk unstable angina (HR-UA). Primary and secondary outcome measures: Patients were followed up regarding the use of medications and the end points of the study at 1 month and 1 year after discharge. The primary end point of the study was 1-year postdischarge major adverse cardiac and cerebrovascular events (MACCEs), defined as mortality (cardiac and non-cardiac), ACS and cerebrovascular attack (stroke and/or transient ischaemic attack). The secondary end points were hospital admission because of congestive heart failure, revascularisation by coronary artery bypass grafting surgery or percutaneous coronary intervention (PCI), and major and minor bleeds. Results: A total of 1799 patients (25.7 STEMI and 74.3 HR-UA/NSTEMI) discharged alive with confirmed diagnosis of ACS were included in the final analysis. During hospitalisation, the majority of the patients received aspirin (98.6), clopidogrel (91.8), anticoagulants (93.4), statins (94.3) and β-blockers (89.3). Reperfusion therapy was performed in 62.6 of patients with STEMI (46.3 thrombolytic therapy and 17.3 primary PCI). The mean door-to-balloon and door-to-needle times were 82.9 and 45.6 min, respectively. In our study, 64.7 and 79.5 of the patients in HR-UA/NSTEMI and STEMI groups, respectively, underwent coronary angiography. During the 12 months after discharge, MACCEs occurred in 15.0 of all patients. Conclusions: Our study showed that the composition of Iranian patients with ACS regarding the type of ACS is similar to that in developed European countries and is unlike that in developing countries of the Middle East and Africa. We found that our patients with ACS are treated with high levels of adherence to guideline-recommended in-hospital medications

Vitamin D supplementation and serum heat shock protein 60 levels in patients with coronary heart disease: A randomized clinical trial

Background: The aim in this study was to investigate the effect of vitamin D (25(OH)D3) supplementation on heat shock protein 60 (HSP 60) and other inflammatory markers (IL-17, TNF-α, PAB) in patients with coronary heart disease (CHD). Methods: In this double-blind, randomized clinical trial, we recruited 80 male and female patients aged 30-60 with CHD and 25(OH)D3 serum levels < 30 ng/ml from Rasool-e-Akram Hospital in Tehran, Iran. Serum levels of HSP 60 as primary outcome, and 25(OH)D3, IL-17, TNF-α, PAB, lipid profiles and parathyroid hormone (PTH) as secondary outcomes were measured at baseline and post-intervention. We randomly assigned eligible participants to a placebo group (N = 40) or an intervention group (N = 40) (50,000 IU/wk. vitamin D supplement) for eight weeks. Results: The results demonstrated that vitamin D supplementation resulted in a significant increase in 25(OH) D3 serum levels in the intervention group compared to the placebo group (46.86 vs. 7.28 ng/ml). PTH levels decreased in the intervention group compared to the placebo group (- 19.81 vs. 2.92 pg/ml) after eight weeks of supplementation. Furthermore, we observed a significant change in waist circumference (- 0.97 vs. -0.26 cm), fat percentage (-.13 vs. 0.1), systolic blood pressure (- 3.85 vs. -2.11 mmHg) and diastolic blood presure (- 4 vs. -1.86 mmHg) in the vitamin D group compared to the placebo group (all P values < 0.05). Other variables did not significantly change after the intervention. Conclusion: Based on our findings, weekly vitamin D supplementation of 50,000 IU for eight weeks in patients with CHD resulted in decreased systolic and diastolic blood pressure, waist circumference and fat percentage. No significant effect on HSP 60, inflammatory markers or lipid profiles was observed. Trial registration: IRCT, IRCT201612122365N14. Registered 12 December 2016. © 2018 The Author(s)

Intermediate versus standard-dose prophylactic anticoagulation and statin therapy versus placebo in critically-ill patients with COVID-19: Rationale and design of the INSPIRATION/INSPIRATION-S studies

Background: Microvascular and macrovascular thrombotic events are among the hallmarks of coronavirus disease 2019 (COVID-19). Furthermore, the exuberant immune response is considered an important driver of pulmonary and extrapulmonary manifestations of COVID-19. The optimal management strategy to prevent thrombosis in critically-ill patients with COVID-19 remains unknown. Methods: The Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) and INSPIRATION-statin (INSPIRATION-S) studies test two independent hypotheses within a randomized controlled trial with 2 � 2 factorial design. Hospitalized critically-ill patients with reverse transcription polymerase chain reaction confirmed COVID-19 will be randomized to intermediate-dose versus standard dose prophylactic anticoagulation. The 600 patients undergoing this randomization will be screened and if meeting the eligibility criteria, will undergo an additional double-blind stratified randomization to atorvastatin 20 mg daily versus matching placebo. The primary endpoint, for both hypotheses will be tested for superiority and includes a composite of adjudicated acute arterial thrombosis, venous thromboembolism (VTE), use of extracorporeal membrane oxygenation, or all-cause death within 30 days from enrollment. Key secondary endpoints include all-cause mortality, adjudicated VTE, and ventilator-free days. Key safety endpoints include major bleeding according to the Bleeding Academic Research Consortium definition and severe thrombocytopenia (platelet count 3 times upper normal limit and clinically-diagnosed myopathy. The primary analyses will be performed in the modified intention-to-treat population. Results will be tested in exploratory analyses across key subgroups and in the intention-to-treat and per-protocol cohorts. Conclusions: INSPIRATION and INSPIRATON-S studies will help address clinically-relevant questions for antithrombotic therapy and thromboinflammatory therapy in critically-ill patients with COVID-19. © 2020 Elsevier Lt

Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality among Patients with COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial

Importance: Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis. Objective: To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized trial with a 2 � 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020. Interventions: Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. Main Outcomes and Measures: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 �103/µL). All outcomes were blindly adjudicated. Results: Among 600 randomized patients, 562 (93.7) were included in the primary analysis (median interquartile range age, 62 50-71 years; 237 42.2% women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% 95% CI,-6.6% to 9.8%; odds ratio, 1.06 95% CI, 0.76-1.48; P =.70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% 1-sided 97.5% CI,-� to 3.4%; odds ratio, 1.83 1-sided 97.5% CI, 0.00-5.93), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% 95% CI, 0.4%-3.8%; P =.01). Conclusions and Relevance: Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04486508. © 2021 American Medical Association. All rights reserved

High Dose Oral Calcium Treatment in Patients with Vitamin D-dependent Rickets Type II

BACKGROUND AND OBJECTIVE: Vitamin D-dependent rickets type II (VDDR2) is a rare genetic disorder caused by mutations in vitamin D receptor (VDR) and leads to resistance to biological effects of calcitriol. Based on the type of mutation, this disease is resistant to calcitriol even at high doses of calcitriol and successful treatment of these patients requires hypocalcemic modification through administration of high doses of calcium and bypassing the intestinal defect in VDR signaling. In addition to the need for frequent hospitalization and high costs, intravenous administration of calcium is associated with complications and problems such as arrhythmia and sepsis, venous catheter infection and hypercalciuria. This study aims to report the positive treatment effects of high doses of oral calcium in 4 patients with vitamin D-dependent rickets type II. CASE REPORT: In this study, 4 patients with vitamin D-dependent rickets type II, diagnosed based on clinical and biochemical symptoms of rickets with alopecia, underwent therapy using high doses of oral calcium (300 mg/kg/day) in pediatric endocrinology and metabolism center of Imam Reza hospital. After a short period, increased growth rate in height, strength and elasticity of muscles was observed in addition to biochemical improvements without serious side effects and even one patient started walking independently within the first week of therapy for the first time. Patients were regularly followed up in terms of height and weight, growth rate and biochemical factors including calcium, phosphorus and alkaline phosphatase every 3 months for one year. CONCLUSION: Regardless of the type of mutation in vitamin D receptor, it is suggested that a 3-6 months trial of high dose oral calcium be started in each patient with vitamin D-dependent rickets type II, particularly for patients whose disease was diagnosed at lower ages

Anthropometric and Biochemical Measures in Bariatric Surgery Candidates: What Is the Role of Inflammatory Potential of Diet?

Background: The present study aimed to assess dietary total antioxidant capacity (TAC), dietary phytochemical intake (PI), and dietary inflammatory index (DII) in patients with morbid obesity who are candidates of bariatric surgery and their association with anthropometric and biochemical parameters. Methods and Materials: One hundred seventy patients with morbid obesity who were referred to surgery clinic of Firoozgar Hospital were enrolled in the study. Ideal body weight and adjusted ideal body weight were calculated. The dietary data were collected using a food frequency questionnaire. Anthropometrics and biochemical parameters were assessed. A p-value of <0.05 was considered significant. Results: The strongest correlations of DII with dietary intakes and anthropometric and biochemical biomarkers were found for iron (p<0.0001). Significant association was also observed for ferritin (p=0.02) and transferrin (p=0.02). In terms of PI, The strongest associations were also found for iron (p<0.0001). Additionally, the value of body mass index (BMI) showed significant correlation with PI (p=0.04). The correlations of dietary total antioxidant indices with dietary intakes and anthropometric and biochemical biomarkers were assessed. Non-significant correlation was found between fasting blood sugar (FBS), hemoglobin A1C (HbA1C), vitamin B12, and vitamin D3 with ORAC index. Significant strong correlation showed for the value of iron in both ferric reducing ability of plasma (FRAP) and Oxygen Radical Absorbance Capacity (ORAC) indices (p<0.0001). Conclusion: We find statistical significance correlation for dietary PI and BMI. The inflammatory and antioxidant properties of diet were not related to biochemical markers associated with obesity. Figure not available: see fulltext. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature

Whether vitamin a supplementation is effective in T-bet and IFN-γ gene expression reduction?

Background: The aim of present study is evaluation of vitamin A supplementation efficacy on IFN-γ and T-bet gene expression in atherosclerotic patients. Methods: Thirty-one patients and 15 healthy controls participated in this study. Healthy control and patients in Vitamin A group received 25 000 IU retinyl palmitate daily for 4 months. Control patients also received 1 pearl of placebo per day up to 4 months. Gene expression levels were assessed by real-time PCR using SYBR green detection method. Results: IFN-γ gene expression in fresh cells of patients taking vitamin A declined slightly (0.85-fold, p = 0.068), whereas the expression of this gene was increased in patients taking placebo, and in healthy control subjects 1.2-fold (p = 0.267) and 1.7-fold (p = 0.580), respectively. There were no significant difference (p = 0.159) between 3 groups in terms of IFN-γ gene expression in cells stimulated with PHA. In order to determine whether PHA stimulation of PBMCs in vitro had an effect on T-bet expression, we measured the difference between the 3 groups of studied. The results showed significant differences between the groups (p = 0.046). IFN-γ gene expression in cells activated with ox-LDL in healthy control subjects and patients taking vitamin A, was reduced 0.43 (p = 0.0001) and 0.41 (p = 0.001) respectively, but in placebo patients was increased 2.2-fold (p = 0.959). Conclusion: Considering role of vitamin A on suppression of Th1 cells in atherosclerotic patients, it can be concluded that vitamin A supplementation may be advantageous for these patients. © Informa Healthcare USA, Inc

Low-dose oral contraceptive to re-induce menstrual bleeding in amenorrheic women on DMPA treatment: A randomized clinical trial

Background: Depot medroxyprogesterone acetate (DMPA), a long-acting contraceptive, has many advantages over other hormonal contraceptives. However, its major discontinuance reason is bleeding disorders. Our aim was to study bleeding complications of DMPA when used as a contraceptive in the Ardabil district and a clinical trial of low-dose oral contraceptive (LD-OC) pills in controlling these complications. Material/Methods: All 917 women referred to Ardabil's health centers to have a DMPA injection for the first time were entered into a longitudinal study. Those complaining of menstrual cessation were entered into a double-blinded randomized clinical trial. Data were collected by means of nine questionnaires, seven of which were used for descriptive purposes and two for clinical trial study. The data were analyzed with the SPSS statistical package. Results: Those DMPA users with a cesarean section history had a higher chance of bleeding complications. Four hundred forty-four of the 917 women receiving the injection discontinued using it before the end of the study period. The main reason for discontinuation (in 70) was irregular menstrual bleedings and menstrual cessation. In the clinical trial of women with bleeding cessation, 70 of those receiving the LD-OC pill experienced menstrual bleedings again, compared with only 22.7 in the placebo group. The discontinuation rate in the drug group was lower than in the placebo group as well (p<0.05). Conclusions: Treating the menstrual cessation caused by DMPA with LD-OC improves the bleeding pattern and decreases the discontinuation rate. © Med Sci Monit, 2006

Metabolic syndrome and the iodine-dose/creatinine clearance ratio as determinants of contrast-induced acute kidney injury

Background: Finding patients at risk of developing contrast-induced acute kidney injury (CI-AKI) is important because of its associated complications. In the present study, the contribution of different variables, such as the presence of metabolic syndrome (MetS), the volume creatinine clearance (V/CrCl) ratio, the iodine-dose (I-dose)/CrCl ratio, or hypertension, to CI-AKI was evaluated. Methods: A total of 255 patients undergoing elective coronary angiography with or without intervention were enrolled and divided into a MetS and a control group. All patients were assessed for the development of CI-AKI after the procedures. Results: CI-AKI occurred in 39.23 (51 of 130) of the MetS patients and 14.4 (18 of 125) of the control group (p 0.52, MetS, CrCl �60 mL/min, and age �70 years increased the risk of CI-AKI, independent of confounding factors. The difference in the mean V/CrCl ratio was statistically significant between patients who developed CI-AKI and those who did not show renal impairment (2.36 ± 1.35 vs. 1.43 ± 0.89, respectively; p < 0.001). The ROC curve analysis of I-dose/CrCl determined the best cutoff value for patients with and those without MetS as 0.51 and 0.63, with a sensitivity value of 68 and 72 and a specificity value of 73 and 74, respectively. Conclusions: We showed that MetS is a strong risk factor for CI-AKI in nondiabetic patients undergoing elective coronary interventions; and the I-dose/CrCl ratio is a strong predictor of CI-AKI in these patients. We suggest that clinicians identify MetS patients and calculate their I-dose/CrCl ratio before coronary interventions. © 2018 S. Karger AG, Basel. Copyright: All rights reserved