Efficacy and Safety Considerations With Dose-Reduced Direct Oral Anticoagulants: A Review.

Importance: Dose-reduced regimens of direct oral anticoagulants (DOACs) may be used for 2 main purposes: dose-adjusted treatment intended as full-intensity anticoagulation (eg, for stroke prevention in atrial fibrillation [AF] in patients requiring dose reduction) or low-intensity treatment (eg, extended-duration treatment of venous thromboembolism [VTE]). We reviewed randomized clinical trials (RCTs) to understand the scenarios in which dose-adjusted or low-intensity DOACs were tested and reviewed the labeled indications by regulatory authorities, using data from large registries to assess whether the use of dose-reduced DOACs in routine practice aligned with the findings of RCTs. Observations: Among 4191 screened publications, 35 RCTs that used dose-adjusted DOACs were identified for dabigatran, apixaban, rivaroxaban, and edoxaban. Of these 35 RCTs, 29 were related to stroke prevention in AF. Efficacy and safety results for dose-adjusted DOACs in large RCTs of AF were similar to those found for full-dose DOACs. To our knowledge, dabigatran, apixaban, and rivaroxaban have not been studied as dose-adjusted therapy for acute VTE treatment. Low-intensity DOACs were identified in 37 RCTs. Low-intensity DOACs may be used for extended-duration treatment of VTE (apixaban and rivaroxaban), primary prevention in orthopedic surgeries (dabigatran, apixaban, and rivaroxaban), primary prevention in ambulatory high-risk cancer patients (apixaban and rivaroxaban) or (postdischarge) high-risk medical patients (rivaroxaban), in stable atherosclerotic vascular disease, or after a recent revascularization for peripheral artery disease in conjunction with aspirin (rivaroxaban). Minor variations exist between regulatory authorities in different regions regarding criteria for dose adjustment of DOACs. Data from large registries indicated that dose-reduced DOACs were used occasionally with doses or for clinical scenarios different from those studied in RCTs or recommended by regulatory authorities. Conclusions and Relevance: Dose adjustment and low-intensity treatment are 2 different forms of dose-reduced DOACs. Dose adjustment is mostly relevant for AF and should be done based on the approved criteria. Dose adjustment of DOACs should not be used for acute VTE treatment in most cases. In contrast, low-intensity DOACs may be used for primary or secondary VTE prevention for studied and approved indications. Attention should be given to routine practice patterns to align the daily clinical practice with existing evidence of safety and efficacy.

Effects of methylphenidate on blood pressure, QT-interval, and cardiac output in ADHD diagnosed children: A three months' follow-up study.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders of childhood. It's been suggested that both the condition and the medications used to treat it can affect the cardiovascular system. This study aims to determine whether methylphenidate has the significant effects in cardiac indices. METHODS: In this prospective study, 100 newly ADHD-diagnosed children aged 6 to 11 whom all on methylphenidate were included. The demographic, clinical data including the blood pressure and heart rate (HR), echocardiographic, and QT-interval were recorded at baseline and after three months of follow-up. RESULTS: After the follow-up period, we observed no abnormal systolic, diastolic, or mean arterial pressure in any of the participants based on their age, height, and gender (p < 0.001). However, the mean of all these variables was significantly increased (p ã€ˆ0 0 1). Mean pulse pressure was also higher than baseline but it wasn't statistically significant (p = 0.059). No significant change was observed in echocardiographic parameters and QT. CONCLUSION: Short-term treatment of ADHD in children with methylphenidate does not have a meaningful relationship with hypertension and increased corrected QT interval. However, an increase in blood pressure and corrected QT interval within a non-pathological range suggests that longer follow-ups may reveal an association.

Echocardiographic and electrocardiographic assessments in patients with psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory disease affecting many organs. Recent studies have demonstrated that psoriasis is associated with cardiovascular disorders. We investigated the echocardiographic and conduction system changes in psoriasis patients. METHODS: In this case-control study, 36 psoriatic patients and 36 healthy controls were enrolled. Demographic and clinical data, echocardiographic and P wave dispersion (PWD) in 12-lead electrocardiogram were evaluated in both groups. We recruited patients with confirmed diagnosis via biopsy and have not been under recent systemic treatment. Patients with underlying cardiovascular disease were excluded from the study. RESULTS: Mean age was 41.56±16.20 and 39.67±13.85 year in case and control groups, respectively. There was no significant difference in the baseline characteristics of the two groups. PWD was significantly higher in the case group (p<0.05). High pulmonary artery pressure was observed in 14 psoriatic patients and 1 individual in the control group (p<0.001). Left ventricular diastolic dysfunction was significantly higher among individuals who were above 60 years of age (p<0.01) but not significantly different between the two groups. CONCLUSION: Psoriatic patients are more susceptible to future development of atrial fibrillation because of higher PWD. There is no significant difference between the diastolic function in these patients.

The Role of Interleukin-27 in Atherosclerosis: A Contemporary Review.

Atherosclerosis is a chronic inflammation characterized by an imbalance between inhibitors and stimulators of the inflammatory system that leads to the formation of atherosclerotic plaques in the vessel walls. Interleukin (IL)-27 is one of the recently discovered cytokines that have an immunomodulatory role in autoimmune and inflammatory diseases. However, the definite role of IL-27 in the pathogenesis of atherosclerosis remains unclear. Recent studies on cardiomyocytes and vascular endothelium have demonstrated mechanisms through which IL-27 could potentially modulate atherosclerosis. Upregulation of the IL-27 receptor was also observed in the atherosclerotic plaques. In addition, circulatory IL-27 levels were increased in patients with acute coronary syndrome and myocardial infarction. A regenerative, neovascularization, and cardioprotective role of IL-27 has also been implicated. Future studies are warranted to elucidate the biologic function and clinical significance of IL-27 in atherosclerosis.

Prognostic Value of Biomarkers in Cardiac Allograft Vasculopathy following Heart Transplantation: A Literature Review.

Cardiac allograft vasculopathy (CAV), also known as cardiac transplant vasculopathy, is a major determinant of long-term survival among cardiac transplantation recipients. Histologically, CAV is featured by diffuse, concentric thickening of the vascular wall, and primarily affects large and small epicardial coronary arteries, intramyocardial arteries, and veins. Owing to graft denervation, CAV typically follows an insidious course, and patients may not experience classic angina symptoms but instead present with progressive heart failure or ventricular arrhythmias. Recent studies on biomarkers have furthered the knowledge concerning the prediction and prognosis of CAV. Given its association with metabolic, thrombotic, inflammatory, and immunologic markers, CAV is likely to represent a complex multifactorial process that involves both immune-mediated and non-immune-mediated pathways. In order to identify the high-risk patients that would benefit from early intervention, future research is warranted to examine the usefulness of a biomarker panel in CAV risk stratification.

Recurrence of fatty liver disease following liver transplantation for NAFLD-related cirrhosis: Current status and challenges.

Non-alcoholic fatty liver disease (NAFLD) is emerging as a major health problem worldwide. NAFLD is a continuum of disease ranging from mild liver steatosis to severe steatohepatitis, which will ultimately lead to end-stage liver disease with high morbidity and mortality rates. This disorder is considered as a silent liver disease. The metabolic syndrome and its components are accounted as the major risk factors for the progression of NAFLD to NASH and cirrhosis. Liver transplantation is considered as an appropriate treatment for the end-stage disease. For the last two decades, NASH has been the most common reason for liver transplantation, especially in the developed countries; however, the outcome of post-transplantation in these patients is of a great concern. The recurrent NASH and NAFLD seem to be the usual issues in LT. Steatosis appears in more than 80% of LTs; however, re-transplantation caused by steatohepatitis is rare. Recently, several risk factors of the recurrent NAFLD, including age, donor steatosis, metabolic syndrome, and immunosuppressant agents, have been introduced. Among the metabolic syndrome components, obesity seriously has negative effects on the outcomes of post-liver transplantation in patients. Unfortunately, there is no standard medicine to prevent or treat the recurrent NAFLD; however, it seems that weight loss and lifestyle modification play critical roles in controlling or inhibiting the recurrent NAFLD or NASH.

Prevalence of Osteosarcopenia and Its Association with Cardiovascular Risk Factors in Iranian Older People: Bushehr Elderly Health (BEH) Program.

Osteosarcopenia is an increasingly recognized geriatric syndrome with a considerable prevalence which increases morbidity and mortality. Although osteosarcopenia is a result of age-related deterioration in muscle and bone, there are many risk factors that provoking osteosarcopenia. These risk factors should be considered by the clinicians to treat osteosarcopenia. We assessed the link between osteosarcopenia and conventional risk factors of cardiovascular diseases. This study was a cross-sectional study that has been conducted within the framework of Bushehr Elderly Health (BEH) program stage II in which participants aged ≥ 60 years were included. Osteopenia/osteoporosis was defined as a t-score ≤ - 1.0 standard deviation below the mean values of a young healthy adult. We defined sarcopenia as reduced skeletal muscle mass plus low muscle strength and/or low physical performance. Osteosarcopenia was considered as the presence of both osteopenia/osteoporosis and sarcopenia. We estimated the age-standardized prevalence of osteosarcopenia for men and women, separately. Using modified Poisson regression analysis, adjusted prevalence ratio (PR) with 95% CI was used to show the measure of associations in the final model. Among 2353 participants, 1205 (51.2%) were women. Age-standardized prevalence of osteosarcopenia was 33.8 (95% CI 31.0-36.5) in men and 33.9 (30.9-36.8) in women. In both sexes, the inverse association was detected with body mass index and having osteosarcopenia (PR 0.84, 95% CI 0.81-0.88 in men and 0.77, 95% CI 0.74-0.80 in women). In both sexes, high-fat mass was positively associated with osteosarcopenia [PR 1.46 (95% CI 1.11-1.92) in men, and 2.25 (95% CI 1.71-2.95) in women]. Physical activity had a significant inverse association in men (PR = 0.64, 95% CI 0.46, 0.88), but not in women. Diabetes was also showed a direct association with osteosarcopenia in men (PR 1.33, 95% CI 1.04-1.69). No associations were detected between the lipid profiles and osteosarcopenia. Results demonstrated a high prevalence of osteosarcopenia in both sexes suggesting a high disease burden in a rapidly aging country. Lifestyle and socioeconomic factors, as well as chronic diseases, were significantly associated with osteosarcopenia.

The Association Between Low Levels of Vitamin D and Clinical Outcomes in Critically-Ill Children: A Systematic Review and Meta-Analysis.

Background: We conducted a meta-analysis to investigate the possible effects of vitamin D deficiency on clinical outcomes of critically-ill children.Methods: We searched Scopus-Embase and PubMed-Medline databases to find eligible observational articles. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations.Results: Seventeen articles (eighteen studies) involving 2987 critically ill patients met our inclusion criteria. Vitamin D deficiency was not associated with increased mortality. A significant association was only observed in very high developed countries between vitamin D deficiency and risk of sepsis [OR (95%CIs): 2.65 (1.30, 5.41)] and ventilation support requirement [OR (95%CIs): 1.35 (1.03, 1.77)].Conclusion: Our findings suggest that vitamin D deficiency is not associated with higher mortality among critically ill children but increases susceptibility to sepsis and the need for ventilator support in critical care settings.

Association of vitamin D deficiency and premature coronary artery disease.

BACKGROUND: Evidence suggests hypovitaminosis D is associated with increased risk of coronary artery disease (CAD) and its extent and related risk factors. However, some investigations have produced contrary results. Therefore, we aimed to evaluate the association between serum vitamin D levels and the severity of premature coronary artery involvement. METHODS: This randomized prospective, case-control study was conducted in Babol from April 2013 to June 2017. We collected the demographic data and measured serum 25-OH-D levels of 294 patients (age≤50 years) diagnosed with CAD with coronary angiography as case group as well as 438 age and sex-matched controls. CAD severity was assessed using the Gensini score. Statistical analyses were used to assess the associations and p<0.05 was considered as significant. RESULTS: The mean serum level of 25-OH-D was 13.12±11.13 and 18.28±8.34 in case and control groups, respectively (P=0.036). In the case group, mean serum vitamin D levels were significantly lower among hypertensives (P=0.018), those with a family history of CVD (P=0.016) and those who used aspirin (P=0.036). The mean Gensini score of patients in the case group was 45.02±23.62 and was higher among men (P=0.022). There was a weak significant correlation between the serum vitamin D levels and the Gensini score (P=0.001 & R=-0.543). The mean Gensini score was not significantly different between patients with deficient (47.02±22.78), insufficient (26.0±21.72) and sufficient (39.0±43.84) vitamin D levels (P>0.05). CONCLUSION: The results showed that the lower levels of vitamin D is associated with increased risk and extent of coronary artery involvement as well as some of the risk factors of CAD, including male gender, hypertension and positive family history for CVD.

Relationship of Serum Uric Acid Level with Demographic Features, Risk Factors, Severity, Prognosis, Serum Levels of Vitamin D, Calcium, and Magnesium in Stroke.

INTRODUCTION: Stroke is one of the most common neurological disorders with high mortality rates. A large financial burden is imposed on the families and health systems of countries in addition to the problems related to the disabilities caused by the disease for the patients. Extensive research is being conducted on the disease, including studies seeking possible relationships between some biomarkers such as uric acid and stroke. METHODS: This descriptive-analytic cross-sectional study was conducted on 170 stroke patients at Babol Ayatollah Rohani Hospital during 2015-2016. Serum uric acid (SUA) levels were measured and recorded at admission time. Patients' demographic data as well as the stroke type and some of their risk factors were entered in a checklist. The data were analyzed by SPSS.v.23 using chi-square and logistic regression tests. P < 0.05 was considered as significant in all analyses. RESULTS: Of the total 170 included patients, 57% had normal, 25% had low, and the remaining patients (18%) had high SUA levels. There was no significant difference in SUA levels in different types of stroke in both genders. Diabetic ischemic embolic patients had higher levels of SUA than diabetic ischemic thrombotic cases. Patients with low magnesium levels had higher rate of low levels of SUA in ischemic stroke. CONCLUSION: Serum uric acid levels are not associated with stroke types and gender. Diabetic embolic ischemic stroke cases had high SUA levels than thrombotic types and in ischemic stroke patients with low serum levels of magnesium, SUA levels were also lower.