Analysis of Adverse Reactions Caused by Potentially Inappropriate Prescriptions and Related Medical Costs That Are Avoidable Using the Beers Criteria: The Japanese Version and Guidelines for Medical Treatment and Its Safety in the Elderly 2015.

We conducted a retrospective study to investigate adverse drug reactions and associated medical costs among elderly individuals that could be avoided if pharmacotherapy was performed in accordance with the Beers Criteria: the Japanese Version (BCJV) and Guidelines for Medical Treatment and Its Safety in the Elderly 2015 (GL2015). Patients aged at least 65 years who were either hospitalized at Gifu Municipal Hospital between October 1 and November 30, 2014 (n = 1236) or had outpatient examinations at Gifu Municipal Hospital on October 1-2, 2014 (n = 980) were included in the study. The outcomes measured were usage rates of drugs listed in the BCJV and GL2015, incidence rates of adverse drug reactions, and additional costs incurred per patient due to adverse reactions. Among the inpatients, usage rates of drugs listed in the BCJV and GL2015 were 24.0 and 72.4%, respectively, and adverse reactions to these drugs occurred at rates of 3.0 and 8.2%, respectively. Among the outpatients, while the usage rates were 26.2% (BCJV) and 59.9% (GL2015), the incidence rates of adverse reactions were 4.7% (BCJV) and 3.9% (GL2015). The additional costs incurred due to adverse drug reactions ranged from 12713-163925 yen per patient. Our results demonstrate that appropriate use of drugs based on the BCJV and GL2015 can help prevent adverse reactions; this would reduce the overall medical costs.

The Relationship Between Dialysis Patients' Quality of Life and Caregivers' Quality of Life.

Patients on dialysis require caregiving and assistance in their daily lives from family members and/or others for hospital visitation and supervised administration. This places a considerable burden on caregivers, which can in turn influence caregivers' quality of life (QOL). We recruited dialysis patients and their caregivers to elucidate how the QOL of patients relates to that of their caregivers'. Patients completed the EuroQol 5-Dimension scale (EQ-5D) and Kidney Disease Quality of Life-Short Form. Caregivers completed the EQ-5D and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). We calculated utility index values for the EQ-5D, and physical, mental (MCS), and role-social component summary scores for the SF-36. Compared to national norms, the caregivers of dialysis patients tended to have poor physical health-related QOL but normal mental health-related QOL, as also found with patients. The multivariate analysis revealed that ≥ median dialysis period and ≥ average burden of kidney disease were significantly related to caregiver MCS score (odds ratios; 6.79 and 9.89, respectively). Caregivers tended to have lower physical health-related QOL if their patients had high social QOL, and lower mental health-related QOL during the early stage of the patient's dialysis treatment, and when patients experienced low disease-targeted QOL.

The Effect of Quality of Life on Medication Compliance Among Dialysis Patients.

Dialysis treatment is known to lead to reduced quality of life (QOL) among patients. This decreased QOL is believed to influence medication compliance, although this effect has not yet been clarified. In this study, we investigated whether decreased QOL due to dialysis treatment does in fact influence medication compliance. Participants were 92 patients who self-managed their medication and were receiving dialysis treatment at Secomedic Hospital or Chiba Central Medical Center. We surveyed their age, sex, dialysis period, and medication management situation, and administered the EQ-5D and Kidney Disease Quality of Life Instrument-Short Form. A multiple logistic regression analysis with medication compliance as the dependent variable and QOL as the independent variable was conducted. The recovery rate and effective response rate were both 100%. The results indicated that patients with good sleep QOL (mean or above) had higher odds of medication compliance (odds ratio, 3.36; 95% confidence interval, 1.26-8.96; P = 0.016). Therefore, improving the quality of sleep of dialysis patients might help to improve their medication compliance.

Signals of gastroesophageal reflux disease caused by incretin-based drugs: a disproportionality analysis using the Japanese adverse drug event report database.

BACKGROUND: Incretin-based drugs are important in the treatment of type 2 diabetes. However, among the incretin-based drugs, glucagon-like peptide-1 receptor agonists (GLP-1-RAs) have been reported to cause gastroesophageal reflux disease (GERD)-like symptoms making it difficult to continue treatment. Therefore, with the aim of clarifying the relationship between incretin-based drugs and GERD-like symptoms, we conducted a pharmacoepidemiological study using the Japanese adverse drug event report database (JADER). METHODS: Dipeptidyl peptidase-4 inhibitors (DPP-4-Is) and GLP-1-RAs were set as the incretin-based target drugs. The reporting odds ratio (ROR) and the information component (IC) was used for the detection of quantitative signals. Furthermore, we also compared the time to onset of GERD-like symptoms by log-rank test. RESULTS: GERD-like symptoms were reported in 36 GLP-1-RAs cases (ROR: 5.61, 95% confidence interval (95% CI): 3.95-7.96 and IC: 2.17, 95% CI: 1.66-2.67) and GLP-1-RAs were detected in the signal. In contrast, DPP-4-Is were not detected in the signal.There was no sex difference with regard to the expression time of GERD-like symptoms by GLP-1-RAs (log-rank test, p = 0.5381). However, the expression time of GERD-like symptoms from GLP-1-RAs was shorter in patients older than 70 years of age than that in those younger than 70 years of age (log-rank test, p < 0.0001). CONCLUSIONS: The administration of GLP-1-RA had a higher incidence of GERD-like symptoms earlier than the administration of DPP-4-Is. In this study, although we think that further investigation is necessary, and suggest that patients older than 70 years of age who have been administered GLP-1-RAs need earlier attention to address GERD-like symptoms than younger patients.

Analyses of non-benzodiazepine-induced adverse events and prognosis in elderly patients based on the Japanese adverse drug event report database.

BACKGROUND: The contents of the guidelines for the use of non-benzodiazepines (Z-drugs) differ slightly between THE JAPANESE SOCIETY OF SLEEP RESEARCH and THE JAPAN GERIATRIC SOCIETY, and the recommended directions are conflicting. Therefore, we analyzed the use of the Japanese Adverse Drug Event Report database (JADER) for identifying adverse events (AEs) caused by Z-drugs and clarifying their occurrence trend and prognosis. METHODS: The signal value for comparison was calculated by using the proportional reporting ratio (PRR) and chi-squared test (χ2) results of data of elderly and non-elderly patients. Among AEs for which signals were detected in the elderly, we determined that those with lower signal values for non-elderly patients that were half the signal value of the elderly should be used with particular caution in the elderly. We also compared the prognoses. RESULTS: The AEs with > 1 risk ratio (RR) in elderly and non-elderly patients were regarded as those that should be noted in the prognosis of AEs in elderly patients. Furthermore, 28 AEs were detected in elderly patients' signals. In this study, in addition to movement disorders such as "falls" and "bone fractures," identified by two academic societies, signal characteristics of the elderly were obtained for psychiatric disorders and eye disorders. CONCLUSIONS: There was no difference in prognosis, but these disorders could reduce the quality of life of patients. Therefore, we consider that in prescribing appropriate drug therapy for insomnia, attention should be paid to the occurrence of the AEs caused by the Z-drugs revealed by this study and the guidelines.

A simple method for exploring adverse drug events in patients with different primary diseases using spontaneous reporting system.

BACKGROUND: Patient background (e.g. age, sex, and primary disease) is an important factor to consider when monitoring adverse drug events (ADEs) for the purpose of pharmacovigilance. However, in disproportionality methods, when additional factors are considered, the number of combinations that have to be computed increases, and it becomes very difficult to explore the whole spontaneous reporting system (SRS). Since the signals need to be detected quickly in pharmacovigilance, a simple exploration method is required. Although association rule mining (AR) is commonly used for the analysis of large data, its application to pharmacovigilance is rare and there are almost no studies comparing AR with conventional signal detection methods. METHODS: In this study, in order to establish a simple method to explore ADEs in patients with kidney or liver injury as a background disease, the AR and proportional reporting ratio (PRR) signal detection methods were compared. We used oral medicine SRS data from the Japanese Adverse Drug Event Report database (JADER), and used AR as the proposed search method and PRR as the conventional method for comparison. "Rule count ≥ 3", "min lift value > 1", and "min conviction value > 1" were used as the AR detection criteria, and the PRR detection criteria were "Rule count ≥3", "PRR ≥ 2", and "χ2 ≥ 4". RESULTS: In patients with kidney injury, the AR method had a sensitivity of 99.58%, specificity of 94.99%, and Youden's index of 0.946, while in patients with liver injury, the sensitivity, specificity, and Youden's index were 99.57%, 94.87%, and 0.944, respectively. Additionally, the lift value and the strength of the signal were positively correlated. CONCLUSIONS: It was suggested that computation using AR might be simple with the detection power equivalent to that of the conventional signal detection method as PRR. In addition, AR can theoretically be applicable to SRS other than JADER. Therefore, complicated conditions (patient's background etc.) that must take factors other than the ADE into consideration can be easily explored by selecting the AR as the first screening for ADE exploration in pharmacovigilance using SRS.

The adoption of generic drugs by a hospital: effects on drug dispensation among community pharmacies.

BACKGROUND: The objective of the current study is to elucidate the effect that the adoption of generic drugs by a large hospital has on the dispensation of generic drugs by community pharmacies. We evaluated the percentage of generic drugs dispensed by pharmacies and the cost of drugs dispensed before and after the adoption of generic drugs by a large hospital. METHODS: Participants comprised patients who were admitted to Gifu Municipal Hospital prior to its adoption of generic drugs (November 1, 2013 to November 14, 2013) and after its adoption (November 1, 2014 to November 14, 2014) and who utilized generic drugs dispensed by pharmacies. RESULTS: Results indicated that the pre-adoption dispensation rate of generic drugs by pharmacies was 48.3% (477/926 drugs), while the post-adoption rate was 57.7% (604/1046 drugs), indicating an increase of 9.4 points (P < 0.001). Furthermore, an investigation into the price paid for generic drugs as a percentage of the total price paid for all drugs indicated the following: the pre-adoption percentage was 23.5% (9756/41,461 yen), and the post-adoption percentage was 34.1% (19,221/56,438 yen), indicating an increase of 10.6 points (P < 0.001). CONCLUSIONS: The results of this study revealed that the adoption of generic drugs by a hospital may promote the use of generic drugs by pharmacies and lead to reduced medical costs as well.

A New Search Method Using Association Rule Mining for Drug-Drug Interaction Based on Spontaneous Report System.

Background: Adverse events (AEs) can be caused not only by one drug but also by the interaction between two or more drugs. Therefore, clarifying whether an AE is due to a specific suspect drug or drug-drug interaction (DDI) is useful information for proper use of drugs. Whereas previous reports on the search for drug-induced AEs with signal detection using spontaneous reporting systems (SRSs) are numerous, reports on drug interactions are limited. This is because in methods that use "a safety signal indicator" (signal), which is frequently used in pharmacovigilance, a huge number of combinations must be prepared when signal detection is performed, and each risk index must be calculated, which makes interaction search appear unrealistic. Objective: In this paper, we propose association rule mining (AR) using large dataset analysis as an alternative to the conventional methods (additive interaction model (AI) and multiplicative interaction model (MI)). Methods: The data source used was the Japanese Adverse Drug Event Report database. The combination of drugs for which the risk index is detected by the "combination risk ratio (CR)" as the target was assumed to be true data, and the accuracy of signal detection using the AR methods was evaluated in terms of sensitivity, specificity, Youden's index, F-score. Results: Our experimental results targeting Stevens-Johnson syndrome indicate that AR has a sensitivity of 99.05%, specificity of 92.60%, Youden's index of 0.917, F-score of 0.876, AI has a sensitivity of 95.62%, specificity of 96.92%, Youden's index of 0.925, and F-score of 0.924, and MI has a sensitivity of 65.46%, specificity of 98.78%, Youden's index of 0.642, and F-score of 0.771. This result was about the same level as or higher than the conventional method. Conclusions: If you use similar calculation methods to create combinations from the database, not only for SJS, but for all AEs, the number of combinations would be so enormous that it would be difficult to perform the calculations. However, in the AR method, the "Apriori algorithm" is used to reduce the number of calculations. Thus, the proposed method has the same detection power as the conventional methods, with the significant advantage that its calculation process is simple.

Medical and economic factors influencing generic drug use in the Japanese public health system: Influencing factors in different populations.

Factors influencing generic drug use must be considered when new drug policies are established and initiatives are implemented to promote generic drug use. This study was conducted to elucidate medical and economic factors that influence generic drug use in the Japanese public health system by evaluating the degree of generic drug use via a multivariate analysis. We conducted a retrospective study of medications administered to inpatients at Gifu Municipal Hospital (Japan) from November 1 to 14, 2014. Details of inpatients (age, sex, and type of medical insurance) and the drugs administered (prescribing institution, dispensing pharmacy, price, and class) were assessed. A total of 1409 drugs (original, 639; generic, 770) were analyzed. Multivariate analysis showed significant differences in out-of-pocket medical fees [odds ratio (OR), 0.595], drugs prescribed at Gifu Municipal Hospital (OR, 1.811), drugs prepared at a health insurance pharmacy (OR, 1.541), drugs containing the same active substances as in the generic drugs used at Gifu Municipal Hospital (OR, 3.712), and drugs costing ≥30 yen and containing the same active substance/having the same specifications (OR, 0.516). Drugs prescribed at a large key hospital in the community with high adoption rates of generic drugs, drugs containing the same active substances as the generic drugs adopted by the hospital, and drugs prepared at health insurance pharmacies contributed to a more frequent use of generic drugs. By contrast, out-of-pocket medical fees and being prescribed expensive drugs contributed to the less frequent use of generic drugs.

Renoprotective Effect of Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes Mellitus.

Diabetic nephropathy is one of three major complications of diabetes mellitus, often leading to chronic renal failure requiring dialysis. Recently developed dipeptidyl peptidase-4 (DPP-4) inhibitors may exhibit renoprotective effects in addition to antihyperglycemic effects. In this study, we retrospectively investigated temporal changes in the renal function index of patients with type 2 diabetes mellitus (DM) and examined the influence of DPP-4 inhibitors on renal function. Patients with type 2 DM (>18 years old) prescribed hypoglycemic agents at Gifu Municipal Hospital for ≥3 months between March 2010 and April 2014 were included in the study. Renal function was evaluated as estimated the decline in 12-month glomerular filtration rate from the baseline in patients receiving and not receiving DPP-4 inhibitors. Patient data from the DPP-4 inhibitor-treated (501 patients, 58.6%) and untreated (354, 41.4%) groups were analyzed using multiple logistic regression analysis, as well as Cox proportional-hazards regression analysis (616, 55.6% and 491, 44.4%, for DPP-4 inhibitors-treated and untreated groups). Multiple logistic regression analysis indicated that DPP-4 inhibitors significantly lowered the estimated glomerular filtration rate (eGFR) decline [20% over 12 months; odds ratio (OR), 0.626; 95% confidence interval [CI], 0.409-0.958; P = 0.031]. Similar results were obtained using Cox proportional-hazards regression analysis (hazard ratio [HR], 0.707; 95% CI, 0.572-0.874; P = 0.001). These findings suggest that DPP-4 inhibitors suppress the decrease of estimated glomerular filtration rate in patients with type 2 DM and show a renoprotective effect.