Factors Affecting Patients' Acceptance of Switching to Biosimilars Are Disease-Dependent: A Cross-Sectional Study.

Biosimilars (BS) are promoted worldwide because of the high cost of biologics. However, patients are apprehensive about switching to BS. For some diseases, several factors, which may be disease-dependent, influence patients' acceptance of switching to BS. Herein, we evaluated whether factors influencing acceptance for switching were disease-dependent among Japanese patients with different diseases. This cross-sectional study involved pharmacists' interviews with patients who used or planned to use biologics. Demographic and clinical characteristics were retrospectively investigated using the patients' medical records. Multivariate logistic regression showed that switch refusal was associated with a history of adverse reactions to biologics (odds ratio [95% confidence interval (CI)] = 3.38 [1.35-8.44]), history of complaints related to disease activity (3.57 [1.53-8.32]), and unacceptability of generic drugs (7.62 [2.70-21.60]). Subgroup analyses suggested that the unacceptability of generic drugs was a common factor, regardless of the disease. Concomitantly, histories of adverse reactions to biologics and complaints related to disease activity were disease-dependent factors. Healthcare professionals should help patients in selecting BS, considering these factors according to the disease.

Investigation of Prescription Status and Exploration of Risk Factors Related to Denosumab-Induced Hypocalcemia in Combination Therapy with 1α,25-Dihydroxy-vitamin D3.

To prevent denosumab-induced hypocalcemia in patients with renal dysfunction, combination therapy with 1α,25-dihydroxy-vitamin D3 (active vitamin D) is recommended. We previously developed a risk prediction model for hypocalcemia in patients with cholecalciferol/calcium (natural vitamin D). However, the prescription status and the risk factors of patients with active vitamin D have not been identified, so we designed this retrospective observational study using a large practice database covering June 2013 to May 2020 to analyze prescription status and risk factors. Patients were classified according to vitamin D type. After that, factors associated with development of hypocalcemia in patients with active vitamin D were explored. Univariate analysis was conducted to compare patient backgrounds between the hypocalcemia and non-hypocalcemia groups. Receiver operating characteristic analysis was conducted to evaluate the predictive potential of the extracted factors. Of the 33442 patients who received denosumab, 22347 and 3560 patients were co-administered natural and active vitamin D, respectively. Patients with active vitamin D had significantly lower renal function (estimated glomerular filtration rate (eGFR) median: 74.0 vs. 69.7 mL/min/1.73 m2), but some patients (23.6%) with sufficient renal function (eGFR ≥90) were also receiving active vitamin D. Of the 3560 patients with active vitamin D, non-hypocalcemia (n = 166) and hypocalcemia (n = 17) groups who met the study criteria were analyzed. Renal function was lower in the hypocalcemia group, and alkaline phosphatase gave the best discrimination. High aspartate aminotransferase (AST), renal dysfunction, high alkaline phosphatase (ALP), and low hemoglobin may be significant factors in risk prediction for hypocalcemia in patients with active vitamin D.

Shared decision-making practices and patient values in pharmacist outpatient care for rheumatic disease: A multiple correspondence analysis.

Purpose: To investigate the value-to-value relationships, relationship between values and patient background, continuation rate of treatment after shared decision-making (SDM), and disease status in order to clarify the values involved in drug therapy decisions for patients with rheumatic disease. Methods: We investigated patient values (efficacy of drug therapy [effectiveness], safety, economics, daily life, and other) and the continuance rate and disease status of treatment after 6 months in 94 patients with rheumatic disease aged ≥18 years who made decisions with pharmacists and physicians in the pharmacy outpatient clinic between September 2019 and April 2021. Multiple correspondence and K-means cluster analyses were performed to show the relationship between values and basic patient information. Results: Among the selected patients, 87% and 47% selected effectiveness for multiple selections and single selection, respectively. Effectiveness was at the center of the graph; three clusters containing other values were placed around it. History of allergy or side effects caused by biologics or Janus kinase inhibitors were in the safety cluster. The non-usage history of biologics or Janus kinase inhibitors was in the economic cluster. Conclusion: Effectiveness was the most important factor for patients with rheumatic disease; the values that patients consider important may shift from effectiveness to other values based on each patient's subjective experience with the treatment and/or the stage of life in which they were treated. It is important to positively link patient values and information about the treatment plan in shared decision-making while establishing rapport with the patient.

Characteristics of hospitals that report adverse drug reactions: Results of a nationwide survey in Japan.

WHAT IS KNOWN AND OBJECTIVE: Adverse drug reactions (ADRs) are one of the primary reasons for hospitalization. The spontaneous reporting of ADRs by healthcare professionals is important for issuing post-marketing drug safety measures. The Japanese Society of Hospital Pharmacists (JSHP) conducts a nationwide survey annually. Using data from this large-scale survey, we identified the characteristics of hospitals that reported ADRs to regulatory authorities and pharmaceutical companies. METHODS: Data were obtained from annual surveys conducted by JSHP from 2015 to 2020. All variables were expressed as categorical variables and tabulated. The Chi-square test was used to compare the categorical variables. The Cochran-Armitage trend test was used to identify significant trends in the proportion of hospitals reporting ADRs. RESULTS AND DISCUSSION: From 2015 to 2020, 22,362 responses were recorded. There was a significant increase in the proportion of hospitals that reported ADRs with an increase in number of beds and pharmacists (p < 0.0001). The proportion of hospitals reporting ADRs to regulatory authorities was also significantly higher in those charging an additional fee for pharmacist-performed ward operations and in those with an ADR data management section than in hospitals without these attributes (p < 0.0001). WHAT IS NEW AND CONCLUSION: Hospitals that submitted ADR reports to the regulatory authorities and pharmaceutical companies charged an additional fee for pharmacist-performed ward operations, had a central ADR data management section, and had fewer beds per pharmacist. This trend was similar, regardless of the size of the hospital.

Viability of a Serum Infliximab Concentration-Detecting Reagent as a Qualitative Assay for an Infliximab Biosimilar.

The efficacy of infliximab in treating rheumatoid arthritis depends on its serum trough concentration, which must be maintained at a minimum of 1 µg/mL to achieve the desired effects. However, Japan's National Health Insurance system does not cover tests for rheumatoid arthritis patients undergoing treatment with biosimilar infliximab because its performance as a biosimilar remains unclear. This study aimed to investigate whether the Remi-check Q qualitative assay yields comparable results for biosimilar infliximab and the originator product. Infliximab BS 100 "NK" and Remicade 100® were separately diluted in pooled human serum to yield test samples at the following concentrations: 0.30, 0.70, 1.20, and 3.00 µg/mL. Prepared samples were quantitatively assessed using an enzyme-linked immunosorbent assay (ELISA) and qualitatively using Remi-check Q, and the results obtained for the originator and biosimilar product were compared. For both originator and biosimilar infliximab, Remi-check Q yielded a negative result for all 0.30 and 0.70 µg/mL samples and a positive result for all 3.00 µg/mL samples. However, negative results were obtained with a fraction of the 1.20 µg/mL samples (biosimilar, 4/15; originator, 3/15). Concurrence rates between the results of quantitative ELISA and qualitative Remi-check Q analyses were comparable between originator and biosimilar infliximab at all tested concentrations. These results indicate that Remi-check Q yields comparable results for biosimilar infliximab and the originator product on being used as a qualitative assay for trough serum levels.

Droperidol Reduces Postoperative Nausea and Vomiting and Supports the Continuation of Intravenous Patient-Controlled Analgesia with Fentanyl.

PURPOSE: To examine the impact of adding droperidol to fentanyl-based intravenous patient- controlled analgesia (IVPCA) on the discontinuation of IVPCA use due to postoperative nausea and vomiting (PONV). METHODS: Patients who underwent surgeries other than abdominal surgeries and used IVPCA between April 2014 and March 2018 were selected. Patients using IVPCA with fentanyl alone were compared to patients using droperidol added to IVPCA. Patients were allocated to one of two groups depending on the drug used for IVPCA: 1) control group, fentanyl alone; 2) droperidol group, droperidol with fentanyl. The primary endpoint was the discontinuation of IVPCA due to PONV. Secondary endpoints included PONV within 48 hours after surgery, the number of antiemetics used, pain score, and adverse effects. Propensity score matching was used to control the differences in clinical features among patients. RESULTS: Among the 793 patients initially enrolled in this study, 145 were excluded via propensity score matching; 364 of the remaining patients received IVPCA supplemented with droperidol. Propensity score matching showed that discontinuation of IVPCA due to PONV was significantly decreased in the droperidol group compared to the control group (P = 0.01). Further, compared with the control group, the droperidol group had reduced nausea up to 24 hours after surgery (P < 0.01), and the number of vomiting episodes and use of antiemetics decreased within 12 hours after surgery (P < 0.01). CONCLUSIONS: The addition of droperidol to IVPCA is associated with a decrease in PONV, as well as the improved continuation of pain treatment with fentanyl-based IVPCA, similar to IVPCA with morphine. However, it is necessary to monitor the side effects of this treatment.

Chorea-like symptoms and high blood concentration of ceftriaxone in a patient undergoing hemodialysis: A case report.

Ceftriaxone (CTRX) is a third-generation cephalosporin commonly used to treat infections such as community-acquired pneumonia and urinary tract infections caused by mainly Gram-negative bacteria and some Gram-positive bacteria. Here, we report a case of a patient on hemodialysis who had chorea-like symptoms with high blood concentration of CTRX. A 74-year-old Japanese woman receiving hemodialysis was admitted with obstructive cholangitis and was started on CTRX therapy at a dose of 2 g every 24 hours. On the 6th day after starting administration of CTRX, chorea-like symptoms appeared. We suspected that her symptoms were caused by a high blood concentration of CTRX. We performed a series of blood sampling to determine the concentration of CTRX at different time points before and after discontinuing CTRX administration. CTRX concentrations were higher than those expected in healthy adults, and her chorea-like symptoms had disappeared from the second day of discontinuation of CTRX. The association between CTRX blood concentration and chorea-like symptoms is unclear. However, measuring a series of plasma or serum concentrations from symptom onset to disappearance suggested that chorea-like symptoms appeared when the concentration exceeded approximately 450 µg/mL. Care should be taken when administering CTRX to patients with cholestasis undergoing hemodialysis, as blood CTRX levels may rise unexpectedly and result in complications.

Effects of proton pump inhibitors, esomeprazole and vonoprazan, on the disposition of proguanil, a CYP2C19 substrate, in healthy volunteers.

AIMS: Vonoprazan, a new class of potassium-competitive proton pump inhibitors has been found to attenuate the antiplatelet function of clopidogrel in a recent clinical study, despite weak in vitro activity against CYP2C19. To elucidate the mechanism of this interaction, the present study investigated the effects of esomeprazole and vonoprazan on the pharmacokinetics of proguanil, a CYP2C19 substrate. METHODS: Seven healthy male volunteers (CYP2C19 extensive metabolizers) received a single oral administration of 100 mg proguanil/250 mg atovaquone (control phase), oral esomeprazole (20 mg) for 5 days followed by proguanil/atovaquone (esomeprazole phase) and oral vonoprazan (20 mg) for 5 days followed by proguanil/atovaquone (vonoprazan phase). Concentrations of proguanil and its metabolite, cycloguanil, in plasma and urine in each phase were determined using liquid chromatography-tandem mass spectrometry. RESULTS: Coadministration with proton pump inhibitors resulted in increase and decrease in the area under the plasma concentration-time curve (AUC) of proguanil and cycloguanil, respectively, significantly reducing their AUC ratio (cycloguanil/proguanil) to 0.317-fold (95% confidence interval [CI] 0.256-0.379) and 0.507-fold (95% CI 0.409-0.605) in esomeprazole phase and vonoprazan phase, respectively. Esomeprazole and vonoprazan also significantly reduced the apparent formation clearance (cumulative amount of cycloguanil in urine divided by AUC of proguanil) to 0.324-fold (95% CI 0.212-0.436) and 0.433-fold (95% CI 0.355-0.511), respectively, without significant changes in renal clearance of proguanil and cycloguanil. CONCLUSIONS: Although further studies are needed, both esomeprazole and vonoprazan potentially inhibit CYP2C19 at clinical doses, suggesting caution in the coadministration of these drugs with CYP2C19 substrates.

Pharmacist-led intervention in the multidisciplinary team approach optimizes heart failure medication.

We evaluated the impact of pharmacist-led heart failure (HF) drug recommendations during hospitalization for hospitalized patients with HF. Hospitalized patients with HF were retrospectively reviewed. Patients were hospitalized before (n = 208, non-intervention group) or after (n = 170, intervention group) the launch of the HF multidisciplinary team (HFMDT) approach with pharmacist-led HF medication optimization. There were no significant group differences in patient background characteristics at admission. Patients with HF with reduced ejection fraction who were not on beta blockers or angiotensin-converting enzyme inhibitor/angiotensin receptor blockers (ACE-I/ARB) at admission were significantly more likely to be on beta blockers at the time of discharge in the intervention group (73.3 vs 96.3%, P = 0.027) compared to those in non-intervention group; however, the change in ACE-I/ARB prescriptions was not significant (53.3 vs 63.3%, P = 0.601). The proportion of patients on any drug with recommendations against its use in patients with HF did not change from admission to discharge in the non-intervention group (21.2 vs. 20.2%, P = 0.855), but was significantly reduced in the intervention group (22.9 vs. 12.9%, P = 0.005). There were no group differences in the in-hospital all-cause mortality (non-intervention, 3.4%; intervention, 2.4%; P = 0.761) or length of hospital stay (median: non-intervention, 13 days; intervention, 14 days; P = 0.508). Pharmacist-led HF drug recommendations during hospitalization as part of a HFMDT approach for hospitalized patients with HF can increase beta blocker prescriptions and decrease non-preferred drug prescriptions.

Evaluation of hospital pharmacists' activities using additional reimbursement for infection prevention as an indicator in small and medium-sized hospitals.

BACKGROUND: Hospitals in Japan established the healthcare delivery system from FY 2018 to 2021 by acquiring an additional reimbursement for infection prevention (ARIP) of category 1 or 2. However, research on outcomes of ARIP applications related to the practice of hospital pharmacists is scarce. METHODS: This study assessed the activities performed by hospital pharmacists in hospitals with 100 to 299 beds, using ARIP acquirement as an indicator, using data from an annual questionnaire survey conducted in 2020 by the Japanese Society of Hospital Pharmacists on the status of hospital pharmacy departments. Out of the survey items, this study used those related to hospital functions, number of beds, number of pharmacists, whether the hospital is included in the diagnosis procedure combination (DPC) system, average length of stay, and nature of work being performed in the analysis. The relationship between the number of beds per pharmacist and state of implementation of pharmacist services or the average length of hospital stay was considered uncorrelated when the absolute value of the correlation coefficient was within 0-0.2, whereas the relationship was considered to have a weak, moderate, or strong correlation when the absolute value ranged at 0.2-0.4, 0.4-0.7, or 0.7-1, respectively. RESULTS: Responses were received from 3612 (recovery rate: 43.6%) hospitals. Of these, 210 hospitals meeting the criteria for ARIP 1 with 100-299 beds, and 245 hospitals meeting the criteria for ARIP 2 with 100-299 beds, were included in our analysis. There was a significant difference in the number of pharmacists, with a larger number in ARIP 1 hospitals. For the pharmacist services, significant differences were observed, with a more frequency in ARIP 1 hospitals in pharmaceutical management and guidance to pre-hospitalization patients, sterile drug processing of injection drugs and therapeutic drug monitoring. In DPC hospitals with ARIP 1 (173 hospitals) and 2 (105 hospitals), the average number of beds per pharmacist was 21.7 and 24.7, respectively, while the average length of stay was 14.3 and 15.4 d, respectively. Additionally, a weak negative correlation was observed between the number of pharmacist services with "Fairly well" or "Often" and the number of beds per pharmacist for both ARIP 1 (R = -0.207) and ARIP 2 (R = -0.279) DPC hospitals. Furthermore, a weak correlation (R = 0.322) between the average number of beds per pharmacist and the average length of hospital stay was observed for ARIP 2 hospitals. CONCLUSIONS: Our results suggest that lower beds per pharmacist might lead to improved pharmacist services in 100-299 beds DPC hospitals with ARIP 1 or 2. The promotion of proactive efforts in hospital pharmacist services and fewer beds per pharmacist may relate to shorter hospital stays especially in small and medium-sized hospitals with ARIP 2 when ARIP acquisition was used as an indicator. These findings may help to accelerate the involvement of hospital pharmacists in infection control in the future.

[Usefulness of Pharmacist Outpatient Services for Inflammatory Bowel Disease].

Inflammatory bowel disease (IBD) is an autoimmune disease that inflames the intestinal tract and reduces patient quality of life. In recent years, prescriptions of biologics and Janus kinase inhibitors have made outpatient pharmacists indispensable to clinics and hospitals. Therefore, we retrospectively investigated the effectiveness of immunopharmacist outpatient services in treating IBD. The survey spanned between January 2019 and December 2020 and included patients who had visited an IBD-specialized outpatient clinic. The endpoints were the number of pharmaceutical and accepted interventions, improvement rates, and cost-effectiveness of the pharmacist outpatient services. The definition of pharmaceutical intervention involves the pharmacist outpatient clinic, which refers to the number of prescription proposals made to doctors, and the dispensing room, which refers to the number of inquiries made to doctors. The survey included 139 patients, and 579 assessments were performed in the pharmacist outpatient clinic. Out of 352 pharmaceutical interventions by the outpatient pharmacist group, 341 (96.9%) were accepted by physicians. Similarly, out of 74 pharmaceutical interventions by the dispensing group, 54 (73.0%) were accepted by physicians (p<0.0001). The overall improvement rate of pharmaceutical interventions was 93.5%. The immunopharmacist outpatient clinic was found to be cost-effective, with an estimated value of 44068000 yen. In IBD outpatient services, clinical pharmacists and physicians are integral members of the medical care team and have a positive impact on drug treatment outcomes.

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.

Actual status of patient information sharing among healthcare delivery facilities: a survey by the third subcommittee, committee on academic research, the Japanese society of hospital pharmacists.

BACKGROUND: Information sharing among medical professionals is important for providing quality medical care. The purpose of the present study was to elucidate the actual status of information sharing between hospitals and other healthcare delivery facilities by surveying information sharing among the pharmaceutical departments of Japanese hospitals in 2020 conducted by the Japanese Society of Hospital Pharmacists. METHODS: Responses were received from 3612 (43.6%) of the 8278 target medical institutions between May 2020 and August 2020. RESULTS: The proportions of hospitals that shared information with community pharmacies, other hospitals, and long-term nursing homes were 40.6%, 36.4%, and 27.3%, respectively. While tracing reports were the most common tool used by hospitals for information sharing with community pharmacies (54.3%), drug summaries were used for sharing information with other hospitals and long-term nursing homes (77.4% and 78.0%, respectively). The proportion of hospitals sharing information with community pharmacies and other hospitals showed a tendency to increase as the number of hospital beds increased. No relationship could be established between the number of hospital beds and the proportion of hospitals sharing information with long-term nursing homes. CONCLUSION: Information between hospitals and community pharmacies was shared primarily using tracing reports, whereas information between hospitals and other hospitals and long-term nursing homes was primarily shared via drug summaries.

A laboratory data-based evaluation of the efficacy and safety of generic pravastatin sodium for long-term use.

BACKGROUND: Increasing the use of generic drugs may reduce the growing healthcare spending. Nevertheless, in Japan, the generic drug market share remains low compared to that of European countries and the United States, mainly because of the general distrust of generic drugs. To address this problem, we retrospectively evaluated the efficacy and safety of the long-term use of generic pravastatin sodium in a study from January 2008 to December 2011. METHODS: Patients receiving generic pravastatin sodium for ≥15 months were defined as long-term users and were included in the study, totaling 595 out of 1337 patients. Efficacy assessment was based on the total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) plasma levels. Safety assessment was based on the aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase (CPK), gamma-glutamyl transferase (γ-GTP), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total-bilirubin (T-Bil), blood urea nitrogen (BUN), serum creatinine (Scr), and hemoglobin A1c (HbA1c) plasma levels. The patients' reasons for discontinuing generic pravastatin sodium were obtained from the electronic medical records. RESULTS & DISCUSSION: No significant difference in the laboratory data was observed between short-term and long-term users, except for significantly lower ALT levels in the long-term users than in the short-term users. No liver dysfunction was observed. Although 37 patients discontinued the study possibly owing to drug-related adverse events, we considered these events unrelated to generic pravastatin sodium. CONCLUSIONS: This study shows that the long-term use of generic pravastatin sodium is effective and safe, and may help dispel the concerns about generic drugs.

[Effect of pharmaceutical care in the diagnosis of Helicobacter pylori infection using 13C-urea breath test].

The urea breath test (UBT) is used widely for assessment of Helicobacter pylori (H. pylori) eradication after treatment. A false-negative UBT is common during administration of anti-ulcer drugs and immediately after their discontinuation. It was thought that the pharmaceutical care by the pharmacists was necessary for the diagnostic accuracy of UBT after H. pylori eradication therapy. Therefore, we investigated the effect of pharmaceutical care on diagnosis based on assessment of UBT. The patients who performed UBT were classified into two groups according to the pharmacists' intervention. From 2008 April to 2009 September, the number of the patients taken pharmaceutical care was 57 (intervention group) and that of the patients taken no pharmaceutical care was 62 (control group). When drugs for H. pylori infection and anamnestic therapy were same, the percentage that avoided administration of double drugs was significantly increased by the pharmaceutical care (93.3% in intervention group versus 21.4% in control group, p<0.05). Therefore, the percentage of noncompliance that performed UBT 4 weeks after treatment onward was significantly decreased by the pharmaceutical care (1.6% in intervention group versus 17.5% in control group, p<0.05). Moreover, the percentage of recurrence after treatment was significantly decreased, there were 3.3% in the intervention group and 14.0% in the control group. In conclusion, it was very important that the pharmacists take care in the management of treatment and UBT for H. pylori eradication therapy.