Severe Neutropenia and Hepatotoxicity After Carbimazole Drug Therapy for Hyperthyroidism in a Pediatric Patient: A Case Report.

BACKGROUND Hyperthyroidism is an overproduction of thyroid hormones. Carbimazole is an anti-thyroid medication used to treat hyperthyroidism in adults and children. It is a thionamide associated with rare adverse effects such as neutropenia, leukopenia, agranulocytosis, and hepatotoxicity. Severe neutropenia is a life-threatening event characterized by a sharp drop in absolute neutrophil count. Severe neutropenia can be treated by discontinuation of the precipitating medication. Administration of granulocyte colony-stimulating factor provides longer protection against neutropenia. Elevated liver enzymes indicate hepatotoxicity, which usually normalize after discontinuation of the offending medication. CASE REPORT A 17-year-old girl was treated with carbimazole since the age of 15 for hyperthyroidism secondary to Graves' disease. She initially received 10 mg of carbimazole orally twice daily. After 3 months, the patient's thyroid function reflected residual hyperthyroidism and was then up-titrated to 15 mg orally in the morning and 10 mg orally in the evening. She presented to the emergency department reporting fever, body aches, headache, nausea, and abdominal pain for 3 days. She was diagnosed with severe neutropenia and hepatotoxicity induced by carbimazole after 18 months of dose modification. CONCLUSIONS In hyperthyroidism, it is important to maintain patients in a euthyroid state for a long period to minimize the autoimmunity and hyperthyroid relapse, which often requires long-term use of carbimazole. However, severe neutropenia and hepatotoxicity are rare and serious adverse effects of carbimazole. Clinicians should be aware of the importance to discontinuation of carbimazole, administration of granulocyte colony-stimulating factors, and supportive treatment to reverse the consequences.

Real-World Evaluation of the Safety and Effectiveness of Apixaban & Rivaroxaban Lead-in Dosing Compared to Parenteral Lead-in Dosing in the Treatment of Venous Thromboembolism: A Multi-Center Retrospective Cohort Study.

Background: Although parenteral anticoagulation lead-in is not recommended with apixaban and rivaroxaban, parenteral anticoagulation is often used to replace apixaban or rivaroxaban lead-in doses for the initial phase treatment of VTE. Thus, our study compares the safety and effectiveness of lead-in parenteral anticoagulation to lead-in apixaban or rivaroxaban in patients who received apixaban or rivaroxaban for VTE treatment. Methods: A multi-center retrospective cohort study included adult patients (aged ≥ 18 years) admitted to the hospital with acute VTE and treated with either apixaban or rivaroxaban. Patients were grouped depending on the lead-in anticoagulation received for initial VTE treatment into the "Direct oral anticoagulation (DOAC) lead-in" group if patients received an appropriate lead-in dose of apixaban and rivaroxaban and patients who received parenteral lead-in the "parenteral lead-in" group. Results: A total of 389 patients were included; the DOAC lead-in group included 296 patients, whereas 93 patients were in the parenteral lead-in group. VTE recurrence (rVTE) during hospitalization and within 30 days was numerically higher in the parenteral lead-in group compared to the DOAC lead-in group (3.3% vs 0.6%; p=0.09 and 1.1% vs 0.7%; p=0.560), with a significantly higher number of patients with rVTE at 90 days (5.4% vs 1.4%; p=0.039). However, none of the patient's characteristics were significantly associated with the incidence of rVTE. In addition, the major bleeding rate during hospitalization was significantly higher among the parenteral lead-in group than in the DOAC lead-in group (14.0% vs 3.7%; p<0.001). Conclusion: Parenteral anticoagulation lead-in before starting maintenance of apixaban and rivaroxaban showed a significantly higher risk of bleeding and a trend toward higher VTE recurrence than the DOAC lead-in. This study adds to the evidence supporting the utilization of the DOAC lead-in regimen in treating patients with VTE. Still, larger studies with robust designs are needed to confirm these findings.

The prescribing pattern of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in patient with type two diabetes mellitus: A two-center retrospective cross-sectional study.

Background: The use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) in patients with type 2 diabetes mellitus (T2DM) remains limited, especially in those with other compelling indications. Thus, this study aimed to describe the prescribing patterns of GLP-1-RA and SGLT2i in patients with T2DM and to determine the factors that affect the prescribing of these medications. Methods: This multicenter retrospective cross-sectional study reviewed the electronic health records of adult patients diagnosed with T2DM who received care between January and December 2020. The patients were classified according to their compelling indications into "patients who are more likely" to benefit from SGLT2i or GLP-1 RA and "patients who are less likely" to benefit from them. They were then further categorized depending on whether these medications were prescribed. Results: A total of 1,220 patients were included; most were female (56.9%). SGLT2i or GLP-1 RA were preferably prescribed in only 19% of the patients for reasons including BMI ≥ 27 kg/m2 (85.6%), uncontrolled T2DM (68.5%), high risk for ASCVD (23.9%), or established ASCVD (14%). The remaining 81.0% were underprescribed these agents. Patients at an older age or with a history of stroke or transient ischemic attack had higher odds of being underprescribed (OR 1.02; 95% CI: 1.01-1.03 and OR 2.86; 95% CI: 1.33-6.15), respectively. Conclusion: The results concur with those of previous studies highlighting the underutilization of GLP-1 RA and SGLT2i in patients with T2DM but also with compelling indications. To optimize the use of GLP-1 RA and SGLT2i for their additional benefits, prescribers need to assess the benefits of using these agents in patients who would likely benefit from them, regardless of DM control.

Patients, Prescribers, and Institutional Factors Associated with Inappropriate Use of Acid Suppressive Therapy in Medical Wards: An Experience of a Single-Center in Saudi Arabia.

PURPOSE: To identify factors associated with inappropriate acid-suppressive therapy (AST) use in hospitalized medical ward patients. PATIENTS AND METHODS: This was a combined retrospective cohort study reviewing the electronic medical records of medical ward in a secondary university hospital between January 2018 and July 2019, in addition to prescriber surveys about AST knowledge. We included adult patients (≥18 years old) admitted to the medical ward who received at least one dose of AST during their hospitalization. Statistical analyses included descriptive statistics and logistic regression. RESULTS: A total of 335 patients were included. Most of the patients were female (66.6%), with a mean age of 42.37 ± 17.72 years; 76% (n=256) of the study subjects were prescribed AST for an inappropriate indication. Patients who were not receiving any home medications associated with high bleeding risk had higher odds of being prescribed AST inappropriately (OR, 4.06; 95% CI, 1.09-13.8). A total of 27 physicians completed the prescriber survey, and the average prescriber's knowledge score was 46.8 ± 15.6%. This score did not differ by the prescriber's position. CONCLUSION: This study demonstrated the overuse of AST in the medical ward. Therefore, improving providers' awareness about AST and implementing an AST stewardship program in institutions is necessary to limit this long-lasting issue.