Frequency and determinants of serum calcium monitoring during eldecalcitol therapy in patients with osteoporosis.

INTRODUCTION: Eldecalcitol (ELD) is an active vitamin D3 analog (AVD) commonly used to treat osteoporosis in Japan. Although routine monitoring of serum calcium levels during ELD therapy is recommended, little is known about the actual frequency and determinants of monitoring. MATERIALS AND METHODS: This was a descriptive cohort study using a Japanese electronic medical records database. We identified osteoporosis patients who initiated treatment with ELD or other AVDs (alfacalcidol and calcitriol) between April 1, 2011 and September 10, 2021. The index date for cohort entry was the first prescription date of ELD or other AVDs. The frequency of serum calcium monitoring was evaluated every 6 months. Determinants of serum calcium monitoring were identified using multivariable logistic regression models. We also calculated the incidence of hypercalcemia and the frequency of serum calcium monitoring within 6 months before hypercalcemia. RESULTS: We identified 12,671 ELD users and 7867 other AVD users. Within 6 months after cohort entry, 45.9% of ELD users and 58.7% of other AVD users underwent serum calcium monitoring. Female sex, no use of systemic corticosteroids, moderate-to-good renal function, treatment in smaller hospitals, and treatment in orthopedic surgery departments were associated with a lower likelihood of receiving serum calcium monitoring during ELD therapy. The incidence of hypercalcemia among ELD users was 6.36 per 100 person-years, with 20.6% of cases not receiving serum calcium monitoring before hypercalcemia. CONCLUSION: Our findings suggest that serum calcium monitoring is not given adequate attention during ELD therapy in routine clinical practice.

Carrier-Mediated Process of Putrescine Elimination at the Rat Blood-Retinal Barrier.

Putrescine is a bioactive polyamine. Its retinal concentration is strictly controlled to maintain a healthy sense of vision. The present study investigated putrescine transport at the blood-retinal barrier (BRB) to gain a better understanding of the mechanisms of putrescine regulation in the retina. Our microdialysis study showed that the elimination rate constant during the terminal phase was significantly greater (1.90-fold) than that of [14C]D-mannitol, which is a bulk flow marker. The difference in the apparent elimination rate constants of [3H]putrescine and [14C]D-mannitol was significantly decreased by unlabeled putrescine and spermine, suggesting active putrescine transport from the retina to the blood across the BRB. Our study using model cell lines of the inner and outer BRB showed that [3H]putrescine transport was time-, temperature-, and concentration-dependent, suggesting the involvement of carrier-mediated processes in putrescine transport at the inner and outer BRB. [3H]Putrescine transport was significantly reduced under Na+-free, Cl--free, and K+-replacement conditions, and attenuated by polyamines or organic cations such as choline, a choline transporter-like protein (CTL) substrate. Rat CTL1 cRNA-injected oocytes exhibited marked alterations in [3H]putrescine uptake, and CTL1 knockdown significantly reduced [3H]putrescine uptake in model cell lines, suggesting the possible participation of CTL1 in putrescine transport at the BRB.

Risk of parkinsonism and related movement disorders with gabapentinoids or tramadol: A case-crossover study.

INTRODUCTION: A safety signal concerning parkinsonism and related movement disorders with gabapentinoids (gabapentin and pregabalin) or tramadol was detected by reviewing individual case reports and data mining in spontaneous report databases. Well-designed pharmacoepidemiological studies are needed to assess the signal. OBJECTIVE: This study aimed to investigate the association of exposure to gabapentinoids or tramadol with the risk of parkinsonism and related movement disorders. METHODS: We conducted a case-crossover study using a Japanese electronic medical records database. Patients with newly diagnosed parkinsonism or related movement disorders between January 1, 2007, and April 14, 2019, were identified. The diagnosis date of outcomes was defined as the index date. We assessed the exposure of each patient to gabapentinoids or tramadol during a 90-day hazard period ending 1 day before the index date and in three 90-day reference periods. Multivariable conditional logistic regression models were employed to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). To confirm the robustness of the primary findings, we also performed sensitivity analyses using a case-case-time-control design, a different time window for hazard and reference periods, a different definition of outcome, and different number of reference periods. RESULTS: A total of 28,972 eligible cases were included in the primary analysis. Exposure to gabapentinoids (aOR, 2.12; 95% CI, 1.73-2.61) and tramadol (aOR, 2.04; 95% CI, 1.57-2.64) was associated with increased risk. Results were consistent across sensitivity analyses. CONCLUSION: Our findings serve as a caution to physicians who prescribe gabapentinoids or tramadol in routine clinical practice.