Effect of Dosage Reduction of Hypoglycemic Multidrug Regimens on the Incidences of Acute Glycemic Complications in People With Type 2 Diabetes Who Fast During Ramadan: A Randomized Controlled Trial.

Objective: We aimed to investigate the effect of dosage reduction of four hypoglycemic multidrug regimens on the incidences of acute glycemic complications in people with type 2 diabetes who fast during Ramadan. Methods: We conducted an open-label, parallel-group, randomized controlled trial at a tertiary care center in Amman, Jordan. We recruited adults with type 2 diabetes who expressed an intention to fast during Ramadan and were adherent to one of four regimens-namely: metformin and glimepiride; metformin and vildagliptin; metformin and insulin glargine U100; or, metformin, insulin glargine U100, and human regular insulin. We randomly assigned participants in a 2:1 ratio to low- or regular-dosage therapy. The primary outcomes were the incidences of hypoglycemia and hyperglycemia during the 29 days of Ramadan 2017, and the secondary outcomes were the incidences of diabetic ketoacidosis and hyperosmolar hyperglycemic state during the same period. Results: We randomly assigned 687 participants to low-dosage therapy (n = 458) or regular-dosage therapy (n = 229) and included 678 (452 and 226, respectively) in the final analysis. The incidence of hypoglycemia was lower in the low-dosage group compared with the regular-dosage group (19 [4.2%] vs. 52 [23.0%], respectively; OR, 0.15 [95% CI, 0.08-0.26]; P < 0.001). The incidence of hyperglycemia did not differ between the low- and regular-dosage groups (319 [70.6%] vs. 154 [68.1%], respectively; OR, 1.12 [95% CI, 0.79-1.58]; P = 0.5). No participants experienced diabetic ketoacidosis or hyperosmolar hyperglycemic state. Each 1% decrease in the baseline HbA1c concentration was associated with a 19.9-fold (95% CI, 9.6-41.5; P < 0.001) increase in the odds of hypoglycemia, and each 1% increase in the baseline HbA1c concentration was associated with a 15.7-fold (95% CI, 10.0-24.6; P < 0.001) increase in the odds of hyperglycemia. Conclusion: Dosage reduction decreases the incidence of hypoglycemia without a concomitant increase in the incidences of hyperglycemia, diabetic ketoacidosis, and hyperosmolar hyperglycemic state in people with type 2 diabetes who fast during Ramadan. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT04237493.

Heart Failure in Relation to Anthracyclines and Other Chemotherapies.

Anthracyclines are the cornerstone of therapy for a wide range of solid and hematologic malignancies; however, their use is limited by the risk of chemotherapy-induced cardiotoxicity leading to cardiomyopathy and heart failure. The incidence of cardiotoxicity in the literature depends on the definition being used, anthracycline dose, duration of follow-up, and surveillance methods used to identify cardiac injury. The reported risk of clinical heart failure has been around 2% to 4% with low-dose anthracycline regimens, whereas the incidence of cardiac injury defined by an abnormal increase in cardiac biomarkers has been reported as high as 35%. Multiple mechanisms have been proposed for anthracycline cardiotoxicity, including the deleterious effects of oxidative stress and reactive oxygen species and the inhibition of topoisomerase II beta, which leads to cardiomyocyte death. In addition, genetic susceptibility is an emerging field that is currently generating active research. The risk factors associated with anthracycline cardiotoxicity include lifetime cumulative dose, age, prior cardiac dysfunction, and the presence of cardiovascular risk factors, in particular hypertension. In this review, we summarize the incidence, mechanisms, and risk factors for anthracycline-mediated left ventricular dysfunction and discuss the role of risk stratification and early detection in patient management.

Heart Failure in Relation to Tumor-Targeted Therapies and Immunotherapies.

Tumor-targeted therapies such as trastuzumab have led to significant improvements in survival of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, these therapies have also been associated with significant left ventricular dysfunction. The incidence of trastuzumab-induced heart failure has decreased significantly since the initial reports, in large part due to improved screening, closer monitoring for early changes in left ventricular function, and a significant decrease in the concurrent administration of anthracyclines. The mechanism of trastuzumab cardiotoxicity is still not well understood, but current knowledge suggests that ErbB2 inhibition in cardiac myocytes plays a key role. In addition to trastuzumab and other HER2-targeted agents, vascular endothelial growth factor inhibitors, proteasome inhibitors, and immune checkpoint inhibitors are all additional classes of drugs used with great success in the treatment of solid tumors and hematologic malignancies. Yet these, too, have been associated with cardiac toxicity that ranges from a mild asymptomatic decrease in ejection fraction to fulminant myocarditis. In this review, we summarize the cardiotoxic effects of tumor-targeted and immunotherapies with a focus on HER2 antagonists.

Consanguinity and the Risk of Hashimoto's Thyroiditis.

BACKGROUND: Hashimoto's thyroiditis (HT) is the most common autoimmune thyroid disease that may lead to hypothyroidism due to progressive destruction of the thyroid. The etiology of HT is unclear. However, it is associated with multiple genetic predispositions. Consanguinity has been associated with an increased susceptibility to different inherited conditions. This study investigated the association between consanguinity and risk of HT for the first time. METHODS: Using a case-control study design, 298 HT patients were compared with two subject groups: (i) 299 participants with non-HT hypothyroidism, and (ii) 298 healthy control participants. The three groups were age and sex matched. Presence of consanguinity among the parents was compared in these groups, and odds ratios (OR) were calculated to establish a correlation. RESULTS: Consanguinity significantly increased the risk of HT (compared with healthy subjects; OR = 3.3; p < 0.0001). In addition, consanguinity was a significant risk factor for HT compared with non-HT hypothyroidism patients (OR = 2.8; p < 0.0001). However, the prevalence of consanguinity was not significantly different in non-HT hypothyroidism patients and healthy subjects. CONCLUSIONS: The results suggest that the risk for HT is increased in consanguineous unions, but no significant increase in the risk of non-HT hypothyroidism was observed. However, for more precise risk estimates, larger studies that include different populations may be helpful. These findings highlight the health impact of consanguinity and have applications in empiric risk estimations in genetic counseling, particularly in countries with high rates of consanguineous marriages.