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Purpose: The dose-limiting factor of ramucirumab plus docetaxel (RAM + DTX) in patients with non-small cell lung cancer (NSCLC) is febrile neutropenia (FN), which has a high incidence in Asians. This study aimed to evaluate the cost-effectiveness of pegfilgrastim (Peg-G) in patients with NSCLC receiving RAM + DTX in Japan. Methods: We simulated model patients treated with RAM + DTX in Japan and developed a decision-analytical model for patients receiving Peg-G prophylaxis or no primary prophylaxis. The expected cost, quality-adjusted life-year (QALY), and incremental cost-effectiveness ratio (ICER) of each treatment were calculated from the perspective of a Japanese healthcare payer. The willingness-to-pay (WTP) threshold was set at 45,867 United States dollars (USD) (5 million Japanese yen) per QALY gained. The probabilities, utility values, and other costs were obtained from published sources. Deterministic sensitivity analysis (DSA) and probabilistic analysis were conducted to evaluate the effect of each parameter and robustness of the base-case results. Results: The expected cost and QALYs were 20,275 USD and 0.701 for Peg-G prophylaxis and 17,493 USD and 0.672 for no primary prophylaxis, respectively. The ICER was calculated to be 97,519 USD per QALY gained. The results were most sensitive to FN risk with Peg-G. When FN risk with no primary prophylaxis exceeded 51% or the cost of Peg-G was less than 649 USD per injection, the ICER was below the WTP threshold. The probabilistic analysis revealed a 9.1% probability that the ICER was below the WTP threshold. Conclusion: Peg-G is not cost-effective in patients with NSCLC receiving RAM + DTX in Japan. [ABSTRACT FROM AUTHOR]

Background: The Functional Independence Measure (FIM) evaluates the activities of daily living (ADL), and FIM efficiency represents daily improvement in FIM. Polypharmacy affects both ADL and FIM; however, few studies have evaluated its relationship with FIM efficiency. Aim: This retrospective study investigated the effect of polypharmacy on FIM efficiency in patients undergoing rehabilitation at our acute care hospital in 2014. Methods: We collected data on the patients' age, sex, diagnosis, length of hospital stay, type and duration of rehabilitation, indications for rehabilitation, FIM score before and after rehabilitation, and number of pharmaceuticals being used. Polypharmacy was defined as the administration of five or more pharmaceuticals. Using propensity score matching, we compared the FIM efficiency between the polypharmacy and non-polypharmacy groups (sub-scales and totals). Results: A total of 2455 patients were included. The analytical population included 2168 patients. The analytical population used for propensity score matching included 727 patients in each group (total: 1454 patients). The following FIM sub-scale items were found to be associated with significantly low FIM efficiency in the polypharmacy group: self-care (polypharmacy group FIM efficiency: 0.43 points/day, non-polypharmacy group FIM efficiency: 0.54 points/day) and sphincter control (0.11 points/day and 0.18 points/day, respectively). No significant differences in the FIM efficiency were observed either for any other sub-scales or for totals. Discussion: In the polypharmacy group, self-care and sphincter control, in particular, were associated with inhibited improvement in ADL and FIM. Conclusions: Reducing polypharmacy among acute-phase patients would allow an earlier return to their normal daily lives. [ABSTRACT FROM AUTHOR]

In pediatric individuals, polypharmacy would increase the prevalence of adverse drug reactions (ADRs). However, there is no report on the ADR increase adjusted for the influence of concomitant disease types. We conducted a retrospective study in pediatric patients to determine whether polypharmacy is a risk factor for ADR development, after the adjustment. Patients aged 1–14 years on medication who visited Gifu Municipal Hospital (Gifu, Japan) were included. We evaluated patient characteristics, ADR causality, ADR classification and severity, and ADR-causing drugs. We examined the association between ADR prevalence and number of drugs used. We performed multiple logistic regression analyses to investigate risk factors for ADR development. Of 1330 patients, 3.5% sought medical attention for ADRs. ADR causality was most often assessed as "possible," with gastrointestinal ADRs being the most common. Grade 1 ADRs were the most and antibiotics were the most common suspected ADR-inducing drug. The multiple logistic regression analysis showed that ≥ 2 or ≥ 4 drug use, neoplasms, mental and behavioral disorders, and circulatory system diseases significantly increased ADR prevalence. Polypharmacy increased the prevalence of ADR resulting in hospital visits in children, after adjusting for the influence of disease types. Therefore, proactive polypharmacy control measures are necessary for children. [ABSTRACT FROM AUTHOR]

Purpose: Cetuximab and panitumumab are monoclonal antibodies that target the epidermal growth factor receptor (EGFR). Treatment with cetuximab and panitumumab commonly causes hypomagnesemia, and optimal management of this adverse effect remains unclear. Here, we evaluated the optimal magnesium replacement points based on the risk of severe hypomagnesemia in colorectal cancer patients who received cetuximab or panitumumab. Methods: We retrospectively evaluated 184 patients who received cetuximab or panitumumab for colorectal cancer at Ogaki Municipal Hospital (Ogaki, Japan) between January 2010 and December 2019. Univariate analyses were conducted to evaluate the relationship between patient baseline characteristics and development of hypomagnesemia following cetuximab or panitumumab treatment. Variables that were significantly associated with hypomagnesemia in the univariate analyses as well as previously reported risk factors were entered into a multivariate logistic regression model. Results: The incidence of hypomagnesemia was associated with panitumumab treatment, pre-replenishment serum magnesium concentration, treatment duration, and treatment line. Severe hypomagnesemia post-cetuximab or panitumumab treatment was significantly associated with low baseline magnesium concentrations (< 1.8 mg/dL; odds ratio 18.100, 95% confidence interval 1.570–210.000; p = 0.020) and low serum magnesium concentrations during treatment (< 1.1 mg/dL; odds ratio 93.800, 95% confidence interval 3.510–2510.000; p = 0.007). Conclusion: To minimize the risk of severe hypomagnesemia during anti-EGFR treatment, magnesium replenishment should be initiated in patients with pre-replenishment concentrations of < 1.8 mg/dL, preferably before reaching intra-treatment concentrations of < 1.1 mg/dL. [ABSTRACT FROM AUTHOR]

Purpose: Adverse events (AEs) caused by polypharmacy have recently become a clinical problem, and it is important to monitor the safety profile of drug-drug interactions (DDIs). Mining signals using the spontaneous reporting systems is a very effective method for single drug-induced AE monitoring as well as early detection of DDIs. The objective of this study was to compare signal detection algorithms for DDIs based on frequency statistical models. Methods: Five frequency statistical models: the Ω shrinkage measure, additive (risk difference), multiplicative (risk ratio), combination risk ratio, and chi-square statistics models were compared using the Japanese Adverse Drug Event Report (JADER) database as the spontaneous reporting system in Japan. The drugs targeted for the survey are all registered and classified as "suspect drugs" in JADER, and the AEs targeted for this study were the same as those in a previous study on Stevens-Johnson syndrome (SJS). Results: Of 3924 pairs that reported SJS, the number of signals detected by the Ω shrinkage measure, additive, multiplicative, combination risk ratio, and chi-square statistics models was 712, 3298, 2252, 739, and 1289 pairs, respectively. Among the five models, the Ω shrinkage measure model showed the most conservative signal detection tendency. Conclusion: Specifically, caution should be exercised when the number of reports is low because results differ depending on the statistical models. This study will contribute to the selection of appropriate statistical models to detect signals of potential DDIs. [ABSTRACT FROM AUTHOR]

Purpose: Dipeptidyl peptidase-4 inhibitor (DPP-4-Is), a kind of drug used for the treatment of diabetes, is considered to prevent the degradation of substance P that suppresses the occurrence of dysphagia. On the other hand, DPP-4 inhibitors are also known to act on the immune system. In this study, we used a spontaneous reporting system to evaluate the signals for dysphagia and aspiration pneumonia with DPP-4-Is. Methods: We calculated reporting odds ratio (ROR) and information coefficients (IC) as disproportionality analysis to evaluate DPP-4-Is induced dysphagia and aspiration pneumonia using the Japanese Adverse Drug Event Report (JADER) database. Results: For DPP-4-Is as a class, no signals were detected for dysphagia, but the signal for aspiration pneumonia was detected at ROR 1.67 (95% confidence interval [95% CI]: 1.20 to 2.34) and IC 0.70 (95% CI: 0.21 to 1.19). For aspiration pneumonia, trelagliptin was the only drug among the DPP-4-Is for which both ROR and IC signals were detected (ROR 9.99, 95% CI: 4.10 to 24.36; IC: 1.98, 95% CI: 0.78 to 3.18). ROR signals, but not IC signals, were detected for linagliptin (ROR 2.66, 95% CI: 1.19 to 5.94; IC: 1.09, 95% CI: − 0.004 to 2.19) and sitagliptin (ROR 1.84, 95% CI: 1.04 to 3.25; IC: 0.78, 95% CI: − 0.03 to 1.58). Conclusion: Since DPP-4 inhibitors prevent the degradation of substance P involved in swallowing reflex, DPP-4 inhibitors were expected to prevent dysphagia and aspiration pneumonia. However, this study revealed that DPP-4 inhibitors strongly were associated with onset rather than preventing aspiration pneumonia. This result suggests that DPP-4 inhibitors may affect the immune function associated with the development of aspiration pneumonia. Furthermore, there is a possibility that the amount of DPP-4-Is used clinically cannot increase the amount of substance P in sufficient quantity to prevent aspiration pneumonia. [ABSTRACT FROM AUTHOR]

Background: Accurate glomerular filtration rate (GFR) evaluation is significant for drug dosing of carboplatin, anticancer drug excreted mainly from kidney. Serum cystatin-C (sCys-C) is a GFR marker with little affected by body muscle mass volume. And GFR equations based on serum creatinine (eGFRcreat) and sCys-C (eGFRcys) were developed; however, accuracy of eGFRcys has not been elucidated fully among patients with cancer. Therefore, we analyzed the performance of GFR equations among patients with cancer whose GFR values were measured by inulin clearance (Cin). Methods: Study design was a cross-sectional study. Subjects were 41 patients with cancer whose GFR values were measured by Cin for drug dosing studies of carboplatin or S-1 in Nagoya University Hospital from 2007 to 2010 and 29 non-cancer patients. Correlation with Cin and slope of regression line were evaluated in eGFRcreat and eGFRcys. Single and multiple regression analyses were analyzed to identify associating factors with eGFRcreat/Cin or eGFRcys/Cin. Results: Age, body weight, body mass index (BMI) and sCr were different between cancer patients and non-cancer patients, but sCys-C and Cin were consistent in 2 groups. The slope of the regression line for Cin vs. eGFRcys with zero intercept in cancer patients was 1.10 (95 % CI: 1.02-1.17), which was significantly different from 1.0. In multiple regression analysis revealed that BMI and urinary creatinine excretion were significantly associated with eGFRcreat/Cin, and cancer was only associating factor with eGFRcys/Cin. Conclusion: eGFRcys should not be used for evaluation of renal function in patients with cancer because it underestimates GFR. [ABSTRACT FROM AUTHOR]