Development of Risk Prediction Model for Grade 2 or Higher Hypocalcemia in Patients With Bone Metastasis Treated With Denosumab Plus Cholecalciferol (Vitamin D3 )/Calcium Supplement.

Denosumab-induced hypocalcemia is sometimes severe, and although a natural vitamin D/calcium combination is used to prevent hypocalcemia, some patients rapidly develop severe hypocalcemia even under supplementation. It is clinically important to predict this risk. This study aimed to develop a risk prediction model for grade ≥2 hypocalcemia within 28 days after the first denosumab dose under natural vitamin D/calcium supplementation. Using a large database containing multicenter practice data, 2399 patients with bone metastasis who were treated with denosumab between June 2013 and May 2020 were retrospectively analyzed. Background factors in patients who developed grade ≥2 hypocalcemia within 28 days after the first denosumab dose and those who did not were compared by univariate analysis. Multivariate analysis was conducted to develop a risk prediction model. The model was evaluated for discriminant performance (receiver operating characteristic-area under the curve, sensitivity, specificity) and predictive performance (calibration slope). A total of 124 patients in the hypocalcemia group and 1191 patients in the nonhypocalcemia group were extracted. A risk prediction model consisting of sex, calcium, albumin, alkaline phosphatase, osteoporosis, breast cancer, gastric cancer, proton pump inhibitor combination, and pretreatment with zoledronic acid was developed. The receiver operating characteristic-area under the curve was 0.87. Sensitivity and specificity were 83% and 81%, respectively, and the calibration slope indicated acceptable agreement between observed and predicted risk. This model appears to be useful to predict the risk of denosumab-induced hypocalcemia and thus should be helpful for risk management of denosumab treatment in patients with bone metastases.

Meta-Analysis: Effects of Probiotic Supplementation on Lipid Profiles in Normal to Mildly Hypercholesterolemic Individuals.

INTRODUCTION: Recent experimental and clinical studies have suggested that probiotic supplementation has beneficial effects on serum lipid profiles. However, there are conflicting results on the efficacy of probiotic preparations in reducing serum cholesterol. OBJECTIVE: To evaluate the effects of probiotics on human serum lipid levels, we conducted a meta-analysis of interventional studies. METHODS: Eligible reports were obtained by searches of electronic databases. We included randomized, controlled clinical trials comparing probiotic supplementation with placebo or no treatment (control). Statistical analysis was performed with Review Manager 5.3.3. Subanalyses were also performed. RESULTS: Eleven of 33 randomized clinical trials retrieved were eligible for inclusion in the meta-analysis. No participant had received any cholesterol-lowering agent. Probiotic interventions (including fermented milk products and probiotics) produced changes in total cholesterol (TC) (mean difference -0.17 mmol/L, 95% CI: -0.27 to -0.07 mmol/L) and low-density lipoprotein cholesterol (LDL-C) (mean difference -0.22 mmol/L, 95% CI: -0.30 to -0.13 mmol/L). High-density lipoprotein cholesterol and triglyceride levels did not differ significantly between probiotic and control groups. In subanalysis, long-term (> 4-week) probiotic intervention was statistically more effective in decreasing TC and LDL-C than short-term (≤ 4-week) intervention. The decreases in TC and LDL-C levels with probiotic intervention were greater in mildly hypercholesterolemic than in normocholesterolemic individuals. Both fermented milk product and probiotic preparations decreased TC and LDL-C levels. Gaio and the Lactobacillus acidophilus strain reduced TC and LDL-C levels to a greater extent than other bacterial strains. CONCLUSIONS: In conclusion, this meta-analysis showed that probiotic supplementation could be useful in the primary prevention of hypercholesterolemia and may lead to reductions in risk factors for cardiovascular disease.

[Effect on duration of antibiotic therapy and drug cost by introducing critical pathway for patients with CAP in Japan].

The aim of this study was to assess whether Marrie's critical pathway is an effective approach to reduce the duration of antibiotic intravenous therapy and drug cost in patients with community-acquired pneumonia (CAP) in Japan. We conducted a retrospective cohort study in patients with CAP who were admitted to a community hospital or a university hospital. We collected clinical and economic data from medical records and medical fee receipts and estimated drug cost for switching the dosage form using Marrie's critical pathway. Outcomes of this study were change in duration of intravenous therapy and drug cost. Fifty patients with CAP were selected from two hospitals. Actual days of antibiotic intravenous therapy were 9.5+/-4.2 days; in contrast, estimated days were 1.2+/-3.0 days (p<0.001). Actual drug cost was 37148+/-28791 yen; in contrast, estimated drug cost was 8364+/-18356 yen (p<0.001). Average reduction of days of therapy and drug cost were 8.3 days and 28704 yen, respectively. This study suggests that the implementation of Marrie's critical pathway may be an effective approach to reduce medical resources used for CAP treatment in Japan.