Israel Medical Association Journal

Background: Direct oral anticoagulants (DOACs) have significantly transformed anticoagulant therapy, improving effectiveness, safety, and convenience in managing thromboembolic conditions. However, concerns persist regarding drug-related problems (DRPs) associated with DOACs, necessitating the establishment of multidisciplinary antithrombotic stewardship programs to optimize the selection, dosing, and monitoring of DOACs.

Objectives: To evaluate the incidence and types of DRPs associated with DOACs, the frequency of clinical pharmacist consultations, the acceptance rates of the clinical pharmacist recommendations, and physicians' adherence to appropriate DOACs prescribing practices.

Methods: A retrospective cohort study was conducted over 4 months in the internal medicine departments at Shamir Medical Center (Assaf Harofeh), Israel. The study included patients aged 18 years and older who were prescribed DOACs (apixaban, rivaroxaban, and dabigatran). Data on patient characteristics and clinical outcomes were collected from electronic medical records. A clinical pharmacist reviewed and reassessed the appropriateness of DOAC prescribing.

Results: During the study period, 415 patients receiving DOACs were identified. Among them, 28.4% had inappropriate DOAC prescriptions leading to 128 recommended interventions. The most common DRP was underdosing (29.7%) followed by unjustified antiplatelet use (26.6%). Clinical pharmacists performed 85.9% of the interventions, with a physician acceptance rate of 72.7%. Patients with inappropriate DOAC prescriptions exhibited increased trends in thromboembolic events and in-hospital mortality.

Conclusions: Despite over a decade of clinical experience with DOACs, DRPs remain a significant challenge. Implementing antithrombotic stewardship programs is critical for optimizing DOACs use, reducing DRPs, and enhancing patient safety.

Background: Patients with juvenile myoclonic epilepsy (JME) are especially prone to having antiseizure medications (ASMs) withdrawal seizures (WS).

Objectives: To clarify whether WS in JME patients are caused by a high tendency of non-adherence from seizure-free patients or by a constitutive increased sensitivity to drug withdrawal.

Methods: Epilepsy patients followed in a tertiary epilepsy clinic between 2010 and 2013 were included in the study. WS prevalence was compared between drug-responsive and drug-resistant JME patients and patients with other types of epilepsy.

Results: The study included 23 JME patients (16 drug-responsive and 7 drug-resistant) and 138 patients with other epilepsies (74 drug-responsive and 64 drug-resistant). JME patients were younger and included more women than non-JME patients. Significantly more WS were seen in JME than in non-JME patients (P = 0.01) and in the drug-resistant fraction of JME patients in comparison to drug-resistant non-JME patients (P = 0.02). On logistic regression, the type of epilepsy, but not the patient’s sex, was found to significantly predict WS. No significant difference was found in the prevalence of WS between drug-responsive and drug-resistant JME patients. The main ASM discontinued in JME was valproic acid (VPA), especially in women.

Conclusion: Our findings suggest a higher sensitivity of JME patients to withdrawal of medications. It is important to educate JME patients about treatment adherence and to explain to their physicians how to carefully reduce or replace ASMs to mitigate the morbidity and mortality related to ASM withdrawal

Extremely preterm infants are at high risk for mortality and morbidity including neurodevelopmental impairment from invasive Candida infections. Prophylactic antifungal therapy has been shown to reduce both colonization and invasive candidemia in high-risk preterm infants. Prophylactic treatment should be started in the first 48 to 72 hours after birth to extremely low birth weight (ELBW) infants (weighing ≤ 1000 grams at birth) or below 27 weeks gestation age with risk factors, or in any NICU with moderate (5–10%) or high (≥ 10%) rates of invasive candidiasis. Studies demonstrated the benefits of fluconazole prophylaxis regarding its safety of the short-term and long-term without the development of fungal resistance. Empiric antifungal therapy may lower mortality and improve outcomes

Background: Bisphosphonates are effective in the prevention and treatment of osteoporosis, yet their use is suboptimal.

Objectives: To measure bisphosphonate compliance among first-time users and identify factors associated with compliance.

Methods: We conducted a prospective follow-up of all women aged 45+ in the second largest health management organization in Israel who were prescribed bisphosphonates for the first time. The 4448 women were classified by drug dosage. Persistence and adherence measures of compliance were calculated for each woman over a 1 year period.

Results: Mean bisphosphonate persistence over a year was 216 days, with a mean medication possession ratio of 66%. Women whose medication was changed, whether from weekly to daily or daily to weekly, always had better persistence rates than those who consistently took the original dose. Persistence rates were as follows: 264 days for women who switched back and forth between daily and weekly doses, 229 days for those who switched from daily to weekly, 222 days for those who took the dosage weekly only, 191 days for those who switched to daily dosage, and 167 days for those who took the dosage daily only (P < 0.001). Switchers were also more likely to have adequate adherence rates (MPR[1] ≥ 80%): 81.3%, 76.6%, 67.5%, 61.3% and 52.2% respectively (P < 0.001). More than 20% of women stopped taking their medication within the first month. Women with higher supplemental insurance (offering significant discounts for weekly dose medications) had better persistence rates: 221 vs. 208 days (P = 0.03). Younger women and women on national pension insurance had the lowest persistence rates: 204 and 209 days respectively.

Conclusions: While weekly bisphosphonate takers had better compliance rates, persistence and adherence rates were inadequate for all groups. Changing medication to meet the needs of the patient, discounting weekly medications, and providing follow-up within the first months of prescription may promote compliance.