Development of a Remote Health Support Program by Pharmacists and Elucidation of Its Effectiveness: A Randomized Controlled Study.

No progress has been made in using remote communication tools for less urgent but equally important health support services, such as preventive medicine and health education. In this study, we developed a remote health support program by pharmacists for community residents and conducted a randomized controlled study on its effectiveness in proper self-medication through pharmacists. People over the age of 20 years who lived in the vicinity of Gifu City, Japan were eligible to participate in this study. Participants were recruited using posters and brochures. This program comprised a lecture, based on the health belief model and behavioral economics, and access to remote health support. The participants were randomly assigned to two groups: the medicine/health class only (control) and the medicine/health class along with the program (intervention) groups. The participants were administered questionnaire surveys immediately before (the first survey) and 2 months after (the second survey) the medicine/health class, which allowed us to compare the changes in the two groups' behavior regarding performing proper self-medication through pharmacists. The percentage of individuals who started consulting pharmacists about self-medication in the intervention group (63.9%, 23/36) was significantly higher than that in the control group (15.2%, 5/33; p < 0.001). The percentage of individuals who started recording information about their self-medication in their medication notebooks in the intervention group (16.7%, 6/36) was significantly higher than that in the control group (0%, 0/33; p = 0.026). We clarified the effectiveness of this program for behavioral changes toward proper self-medication using support from pharmacists.

Impact of Polypharmacy and Risk Factors for Exacerbation of Lower Urinary Tract Symptoms in Patients with Urological Conditions: A Retrospective Study in a Japanese Municipal Hospital.

Polypharmacy exacerbates lower urinary tract symptoms (LUTS). Japan exhibits a higher prevalence of concomitant medication use in drug therapy than other countries. Previous age- and sex-specific reports exist; however, none include patients of all ages. Therefore, this retrospective study determined the impact of polypharmacy and its associated risk factors on LUTS exacerbation in outpatients with urological conditions. We included patients receiving medication who visited the Department of Urology at the Gifu Municipal Hospital (Gifu, Japan) between January, 2018 and December, 2018. The association between LUTS and polypharmacy and the risk factors for LUTS exacerbation were investigated. Patients were categorized into two groups according to their polypharmacy status. We performed propensity score matching and compared the International Prostate Symptom Score (IPSS) between the groups using the unpaired t-test. Multiple logistic regression analysis was performed to examine the risk factors, including "polypharmacy" and "taking multiple anticholinergic medications" for LUTS exacerbation. When comparing the IPSS between the groups, the polypharmacy group was found to have significantly higher scores than the non-polypharmacy group in six items, including "total score" and "storage score." Multiple logistic regression analysis results showed high significance in three items, including "polypharmacy" (odds ratio (OR) = 1.67, 95% confidence interval (CI): 1.03-2.71) and "taking multiple anticholinergic medications" (OR = 8.68, 95% CI: 1.05-71.7). In conclusion, this study revealed that "polypharmacy" and "taking multiple anticholinergic medications" were risk factors for LUTS. Particularly, "polypharmacy" is associated with storage symptom exacerbation. Therefore, eliminating "polypharmacy" and "taking multiple anticholinergic medications" is expected to improve LUTS.

Probable effects of polypharmacy and equivalent doses of psychotropic drugs on prevalence of adverse drug events among psychiatric inpatients in a general hospital in Japan.

OBJECTIVE: In psychiatry, polypharmacy or high psychotropic drug doses increase adverse drug event (ADE) prevalence. However, the full relationship between polypharmacy and ADEs is unclear, and few studies have evaluated dose equivalents for psychotropic drugs for ADEs. Thus, we conducted a retrospective analysis to clarify the effects of polypharmacy and chlorpromazine (CP)-, diazepam (DAP)-, and imipramine- equivalent doses on all ADEs in inpatients. METHODS: Psychiatric inpatients in a Japanese hospital from April 1, 2016 to March 31, 2018, were enrolled. ADE severity and causality were assessed. Multiple logistic regression analyses were performed to evaluate ADE risk factors. RESULTS: Among 462 patients analyzed, out of 471 patients enrolled, 145 (31.4%) experienced ADEs. The causality assessment determined that "possible" was 96.5%. The most common ADEs were nervous system disorders (35%). Multiple logistic regression analyses indicated an increase in ADE prevalence with the number of drugs used (≥5; p = 0.026); CP-equivalent dose (p = 0.048); and endocrine, nutritional, and metabolic disorders (p = 0.045). DAP-equivalent dose; infectious and parasitic diseases; and injury, poisoning, and consequences of other external causes decreased ADE prevalence (p = 0.047, 0.022, and 0.021, respectively). CONCLUSIONS: Avoiding polypharmacy in psychiatric inpatients and adjusting drug regimens to safe equivalent doses could reduce ADEs during hospitalization.

[Effectiveness of Pharmaceutical Intervention While Administering 5-Aminolevulinic Acid Hydrochloride through a Collaboration of Physicians and Pharmacists].

5-aminolevulinic acid hydrochloride is a highly effective drug in reducing tumor residuals in transurethral resection of the bladder tumors; however, hypotension is a serious side effect that causes clinical problems. To avoid serious side effects, a pharmacist, in consultation with a physician, decided to discontinue the antihypertensive medication, and the effect of this pharmaceutical intervention was examined retrospectively. This study included patients who received 5-aminolevulinic acid hydrochloride at Gifu Municipal Hospital and were instructed to continue receiving their usual antihypertensive medication on the day of surgery. The control group comprised 17 patients before the pharmaceutical intervention, and the intervention group comprised 18 patients after the pharmaceutical intervention. The difference in systolic blood pressure before and after 5-aminolevulinic acid hydrochloride administration was -19.4±22.5 mmHg in the control group and -2.8±16.0 mmHg in the intervention group. The intervention group showed a significantly lower decrease in blood pressure(p=0.019). Intervention to avoid hypotension through the collaboration between physicians and pharmacists may be effective in improving the safety of 5-aminolevulinic acid hydrochloride.

Melphalan Febrile Neutropenia Risk Factors.

This study aimed to identify the risk factors of febrile neutropenia(FN)onset associated with melphalan(L-PAM)therapy. Thirty-nine patients(21 men, 18 women)were administered L-PAM intravenously for multiple myeloma(MM)from April 2011 to February 2022 at the Department of Hematology of Gifu Municipal Hospital. Patients were classified into those with and without FN(Grade 3 or higher), complete blood count and liver function tests were performed immediately before starting therapy. Univariate analysis with Fisher's exact probability test was performed. Factors with p<0.2 were considered as independent variables for multivariate analysis in the multiple logistic regression analysis. A multivariate analysis with 2 independent variables, lactate dehydrogenase(LD)level>222 U/L(upper limit of the facility reference value)and white <3.3×103/µL(lower limit of the facility reference value)from the univariate analysis, and FN onset(Grade 3 or higher)as the dependent variable showed that LD level>222 U/L(odds ratio: 6.33, 95% confidence interval: 1.12-35.8, p=0.037)was a significant factor. In conclusion, patients with LD levels >222 U/L immediately before starting therapy require adequate monitoring for FN onset following L-PAM administration.

Effectiveness of distributing pocket cards in improving the behavior, attitude, and knowledge regarding proper medication use among junior high school students in Japan.

Objective: This study aimed to explore the effectiveness of distributing pocket cards with summaries of key information on appropriate medication usage after the implementation of a structured school-based medication education program for junior high school students in Japan. Methods: A total of 227 3rd-grade high school students participated in the intervention. Students who received the program without the provision of pocket cards in 2022 were included in the comparison group, and students who took the program with the provision of pocket cards in 2023 were included in the intervention group. After propensity score matching, the final sample of N = 116 comprised n = 58 comparison group participants and n = 58 intervention group participants. Questionnaires were administered at baseline, end-of-class, and 3-month follow-up to assess the changes in behavior, attitude, and knowledge scores. Results: The matched intervention group showed significantly lower scores at the 3-month follow-up than the matched comparison group. The results of the multiple linear regression analysis showed that for both groups, only the attitude scores were significantly correlated with the behavior scores. In addition, regardless of the baseline scores, the matched intervention group demonstrated smaller or negative changes in scores at the 3-month follow-up. Conclusion: Overall, the results of this study did not support the effectiveness of distributing pocket cards after in-class intervention. However, the usefulness of medication education intervention was confirmed. These results emphasize the need to explore other supplemental teaching tools to further enhance the impact of structured medication education programs.

Effect of Dipeptidyl Peptidase-4 Inhibitors vs. Metformin on Major Cardiovascular Events Using Spontaneous Reporting System and Real-World Database Study.

BACKGROUND: Metformin had been recommended as the first-line treatment for type 2 diabetes since 2006 because of its low cost, high efficacy, and potential to reduce cardiovascular events, and thus death. However, dipeptidyl peptidase-4 (DPP-4) inhibitors are the most commonly prescribed first-line agents for patients with type 2 diabetes in Japan. Therefore, it is necessary to clarify the effect of DPP-4 inhibitors on preventing cardiovascular events, taking into consideration the actual prescription of antidiabetic drugs in Japan. METHODS: This study examined the effect of DPP-4 inhibitors on preventing cardiovascular events. The Japanese Adverse Drug Event Report (JADER) database, a spontaneous reporting system in Japan, and the Japanese Medical Data Center (JMDC) Claims Database, a Japanese health insurance claims and medical checkup database, were used for the analysis. Metformin was used as the DPP-4 inhibitor comparator. Major cardiovascular events were set as the primary endpoint. RESULTS: In the analysis using the JADER database, a signal of major cardiovascular events was detected with DPP-4 inhibitors (IC: 0.22, 95% confidence interval: 0.03-0.40) but not with metformin. In the analysis using the JMDC Claims Database, the hazard ratio of major cardiovascular events for DPP-4 inhibitors versus metformin was 1.01 (95% CI: 0.84-1.20). CONCLUSIONS: A comprehensive analysis using two different databases in Japan, the JADER and the JMDC Claims Database, showed that DPP-4 inhibitors, which are widely used in Japan, have a non-inferior risk of cardiovascular events compared to metformin, which is used as the first-line drug in the United States and Europe.

Cost-effectiveness analysis of olanzapine in four-drug antiemetic therapy in Japanese patients treated with highly emetogenic cisplatin-containing chemotherapy.

BACKGROUND: Olanzapine has been shown to have an additive effect on the three-drug antiemetic therapy consisting of aprepitant, palonosetron, and dexamethasone, in a highly emetogenic cisplatin-containing chemotherapy. Although olanzapine may be more economical than aprepitant or palonosetron, an adequate cost-efficacy analysis has not been conducted. METHODS: We conducted a cost-utility analysis to evaluate the cost-effectiveness of olanzapine use in four-drug antiemetic therapy among Japanese patients. We simulated model patients treated with highly emetogenic cisplatin-containing chemotherapy and developed a decision-analytical model of patients receiving triple antiemetic therapy with or without olanzapine in an inpatient setting. The cost and probabilities of each treatment were calculated from the perspective of the Japanese healthcare payer. The probabilities, utility value, and other costs were obtained from published sources. One-way and probabilistic sensitivity analyses were conducted to examine the influence of each parameter on the model and the robustness of a base-case analysis. Threshold analysis was conducted to determine the cost of olanzapine that would make the incremental cost-effectiveness ratio (ICER) equivalent to the threshold ICER). The threshold incremental cost-effectiveness ratio was set at 5 million Japanese Yen (JPY) per quality-adjusted life-year (QALY) gained. RESULTS: The cost was 10,238 JPY in the olanzapine regimen and 9719 JPY in the non-olanzapine regimen. The QALY gained were 0.01065 QALYs and 0.01029 QALYs in the olanzapine and non-olanzapine regimen, respectively. The incremental cost of the olanzapine regimen relative to the non-olanzapine regimen was 519 JPY, and the incremental QALYs were 0.00036 QALY, resulting in an ICER of 1,428,675 JPY per QALY gained. In the one-way sensitivity analysis, the results were most sensitive to the utility value of incomplete control. The probabilistic sensitivity analysis revealed the probability that the ICER was below the willingness-to-pay, and the incremental QALYs was positive was 96.2%. The calculated cost of olanzapine per 5 mg that would make the incremental cost-effectiveness ratio equivalent to the threshold incremental cost-effectiveness ratio was calculated to be 475 JPY. CONCLUSIONS: Olanzapine was cost-effective in the four-drug antiemetic therapy for Japanese patients treated with highly emetogenic cisplatin-containing chemotherapy.

Cost-effectiveness analysis of pegfilgrastim in patients with non-small cell lung cancer receiving ramucirumab plus docetaxel in Japan.

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.

Evaluation of the Direct Costs of Managing Adverse Drug Events in all Ages and of Avoidable Adverse Drug Events in Older Adults in Japan.

In Japan, medical costs are increasing annually, and the increase in national medical costs, particularly in the direct cost of managing adverse drug events, is high. An in-depth understanding of these costs is important for their reduction. This study aimed to calculate the direct cost of managing adverse drug events in all ages, including older adults, and that of avoidable adverse drug events in older adults. We conducted a retrospective survey on patients aged 1 year or older who visited Gifu Municipal Hospital in Japan. We investigated and calculated the direct cost of managing adverse drug events and that of avoidable adverse drug events based on the Beers Criteria Japanese version (BCJ) and "Guidelines for medical treatment and its safety in the elderly 2015" (GMTSE-2015) in inpatients and outpatients. Among 6,504 patients, 11.1% visited the hospital or were hospitalized due to adverse drug events. The direct costs per patient with adverse drug events were 21,281 and 22,590 yen (166 and 176 euros as on September 13, 2021) for outpatients, and 853,175 and 874,582 yen (6,648 and 6,815 euros) for inpatients of all ages and older adults, respectively. The direct costs of avoidable adverse drug events per patient using drugs listed in the BCJ and GMTSE-2015 for older adults were 3,212 and 3,341 yen (25 and 26 euros) for outpatients, and 55,548 and 80,246 yen (433 and 625 euros) for inpatients, respectively. In sum, considering both inpatients and outpatients in the whole country, the direct costs of managing adverse drug events were 804.53 billion and 597.19 billion yen (6,269 million and 4,653 million euros) per year for all ages and older ages, respectively. The direct cost of avoidable adverse drug events in older adults was 83.43-258.44 billion yen (650-2,013 million euros) per year. We found that, in Japan, high medical costs are often caused by managing adverse drug events, and that the costs of avoidable adverse drug events in older adults based on the BCJ and GMTSE-2015 account for a substantial proportion of the medical cost. Therefore, by using the BCJ and GMTSE-2015, avoiding adverse drug events and reducing medical costs may be possible.

Angioedema Caused by Drugs That Prevent the Degradation of Vasoactive Peptides: A Pharmacovigilance Database Study.

Angioedema results from the decreased degradation of vasoactive peptides such as substance P and bradykinin. In this study, we sought to clarify whether dipeptidyl peptidase-4 (DPP-4) and angiotensin-converting enzyme (ACE) inhibitors that suppress the degradation of substance P and bradykinin are involved in angioedema onset. We calculated information coefficients (ICs) by performing a disproportionality analysis to evaluate DPP-4/ACE inhibitor-induced angioedema using the Japanese Adverse Drug Event Report (JADER) database. No angioedema signals were detected for DPP-4 inhibitors; however, a signal was detected for ACE inhibitors (IC: 2.42, 95% confidence interval (CI): 2.19 to 2.65). Of the patients treated with DPP-4 inhibitors, four developed drug-induced angioedema in combination with ACE inhibitors, and all were taking vildagliptin. Signals were detected for enalapril (IC: 2.39, 95% CI: 2.06 to 2.71), imidapril (IC: 2.83, 95% CI: 2.38 to 3.27), lisinopril (IC: 2.28, 95% CI: 1.55 to 3.00), temocapril (IC: 1.35, 95% CI: 0.29 to 2.40), and trandolapril (IC: 1.57, 95% CI: 0.19 to 2.95). Both inhibitors inhibited the degradation of substance P and bradykinin and were thus expected to cause angioedema. However, no signal of angioedema was detected with the DPP-4 inhibitors, in contrast to some ACE inhibitors. This study found that ACE inhibitors and DPP-4 inhibitors, which inhibit the degradation of substance P and bradykinin, tended to have different effects on the onset of angioedema in clinical practice.

Verification of the "Upward Variation in the Reporting Odds Ratio Scores" to Detect the Signals of Drug-Drug Interactions.

The reporting odds ratio (ROR) is easy to calculate, and there have been several examples of its use because of its potential to speed up the detection of drug-drug interaction signals by using the "upward variation of ROR score". However, since the validity of the detection method is unknown, this study followed previous studies to investigate the detection trend. The statistics models (the Ω shrinkage measure and the "upward variation of ROR score") were compared using the verification dataset created from the Japanese Adverse Drug Event Report database (JADER). The drugs registered as "suspect drugs" in the verification dataset were considered as the drugs to be investigated, and the target adverse event in this study was Stevens-Johnson syndrome (SJS), as in previous studies. Of 3924 pairs that reported SJS, the number of positive signals detected by the Ω shrinkage measure and the "upward variation of ROR score" (Model 1, the Susuta Model, and Model 2) was 712, 2112, 1758, and 637, respectively. Furthermore, 1239 positive signals were detected when the Haldane-Anscombe 1/2 correction was applied to Model 2, the statistical model that showed the most conservative detection trend. This result indicated the instability of the positive signal detected in Model 2. The ROR scores based on the frequency-based statistics are easily inflated; thus, the use of the "upward variation of ROR scores" to search for drug-drug interaction signals increases the likelihood of false-positive signal detection. Consequently, the active use of the "upward variation of ROR scores" is not recommended, despite the existence of the Ω shrinkage measure, which shows a conservative detection trend.

Detection algorithms and attentive points of safety signal using spontaneous reporting systems as a clinical data source.

Continuous evaluation of drug safety is needed following approval to determine adverse events (AEs) in patient populations with diverse backgrounds. Spontaneous reporting systems are an important source of information for the detection of AEs not identified in clinical trials and for safety assessments that reflect the real-world use of drugs in specific populations and clinical settings. The use of spontaneous reporting systems is expected to detect drug-related AEs early after the launch of a new drug. Spontaneous reporting systems do not contain data on the total number of patients that use a drug; therefore, signal detection by disproportionality analysis, focusing on differences in the ratio of AE reports, is frequently used. In recent years, new analyses have been devised, including signal detection methods focused on the difference in the time to onset of an AE, methods that consider the patient background and those that identify drug-drug interactions. However, unlike commonly used statistics, the results of these analyses are open to misinterpretation if the method and the characteristics of the spontaneous reporting system cannot be evaluated properly. Therefore, this review describes signal detection using data mining, considering traditional methods and the latest knowledge, and their limitations.

What activities of daily living at discharge affect the discharge destination of patients in an acute-care hospital in Japan: A retrospective factor analysis.

It is important to clarify the influence of activities of daily living (ADL) at discharge on the discharge destination of hospitalised patients. The Functional Independence Measure (FIM) is a widely used ADL assessment scale. In this retrospective study, we aimed to identify what ADL based on FIM at discharge affect the discharge destination of hospitalised patients in an acute-care hospital, in addition to how nutritional status and the number of drugs used, as well as types of disease, affect discharge-to-home. We surveyed age, sex, disease type, length of hospital stay, discharge destination, FIM score at discharge, serum albumin level, and the number of continued drugs in hospitalised patients who underwent rehabilitation in Gifu Municipal Hospital (Gifu, Japan) between January 2014 and December 2014. Multiple logistic regression analysis was performed with discharge to home as a dependent variable and age, sex, disease, FIM score and polypharmacy as independent variables. Multiple logistic regression analysis indicated that a significantly high percentage of discharged-to-home patients were associated with 'self-care' (≥33 points; OR: 2.03), 'sphincter control' (≥14 points; OR: 1.49), 'transfers' (≥13 points; OR: 1.94), and 'locomotion' (≥7 points; OR: 3.55), among others. High FIM sub-scale scores at discharge for self-care, sphincter control, transfers, and locomotion were clarified as factors associated with discharge-to-home. These findings of the association of ADL based on FIM and discharge destination would be useful in deciding discharge destinations for patients in an acute-phase hospital.

Differences in detected safety signals between benzodiazepines and non-benzodiazepine hypnotics: pharmacovigilance study using a spontaneous reporting system.

Introduction: In recent years, there has been an increasing number of people who feel sleep-deprived owing to sudden changes in the social environment. Patients prescribed benzodiazepine-based hypnotics (BZ drugs) also develop movement disorder action and memory disorders as adverse events (AEs), and they have further problems such as dependency and tolerance because of long-term use. Therefore, the use of non-benzodiazepine-based hypnotics (Z-drugs) is recommended for patients with insomnia. However, as AEs have also been reported for Z-drugs, it is important to identify these when switching hypnotics. Methods: To understand AEs to be noted when switching from BZ drugs to Z-drugs, we evaluated the differences in AEs developed by both these drugs using volcano plots and safety signals. For this, data registered in the Japanese Adverse Drug Event Report database were used. Results: The volcano plot and safety signals revealed six characteristic Z-drug-induced AEs. Parasomnias (ln odds ratio [OR]: 3.28, -log P: 4.34, proportional reporting ratio [PRR]: 23.47, χ 2: 309.27), Cortical dysfunction NEC (ln OR: 2.76, -log P: 4.34, PRR: 3.62, χ 2: 16.14), and Psychiatric symptoms NEC (ln OR: 2.66, -log P: 2.18, PRR: 2.51, χ 2: 6.63) were detected only in Z-drugs, and safety signals of Suicidal and self-injurious behaviour, Deliria, and Overdoses NEC were also detected with BZ drugs. However, the strength of safety signals was much higher with the Z-drugs. Conclusion: AEs related to falls and bone fractures are expected to be more strongly onset in BZ drugs than in Z-drugs, which are said to have less muscle relaxant action. However, there was no particularly significant difference in this parameter between the two drug classes. Understanding the difference between these AEs of Z-drugs and BZ drugs is important for the proper use of hypnotics.

The association between polypharmacy and the efficiency of the functional independence measure in an acute-stage hospital: a retrospective cohort study.

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.

Improved Detection Criteria for Detecting Drug-Drug Interaction Signals Using the Proportional Reporting Ratio.

There is a current demand for "safety signal" screening, not only for single drugs but also for drug-drug interactions. The detection of drug-drug interaction signals using the proportional reporting ratio (PRR) has been reported, such as through using the combination risk ratio (CRR). However, the CRR does not consider the overlap between the lower limit of the 95% confidence interval of the PRR of concomitant-use drugs and the upper limit of the 95% confidence interval of the PRR of single drugs. In this study, we proposed the concomitant signal score (CSS), with the improved detection criteria, to overcome the issues associated with the CRR. "Hypothetical" true data were generated through a combination of signals detected using three detection algorithms. The signal detection accuracy of the analytical model under investigation was verified using machine learning indicators. The CSS presented improved signal detection when the number of reports was ≥3, with respect to the following metrics: accuracy (CRR: 0.752 → CSS: 0.817), Youden's index (CRR: 0.555 → CSS: 0.661), and F-measure (CRR: 0.780 → CSS: 0.820). The proposed model significantly improved the accuracy of signal detection for drug-drug interactions using the PRR.