Antidiabetic Drugs for the Risk of Alzheimer Disease in Patients With Type 2 DM Using FAERS.

Alzheimer disease (AD) may develop after the onset of type 2 diabetes mellitus (T2DM), and the risk of AD may depend on the antidiabetic drug administered. We compared the risk of AD among 66 085 patients (≥ 65 years) with T2DM (1250 having concomitant AD) who had been administered antidiabetic drug monotherapy for T2DM who had voluntarily reported themselves in the Food and Drug Administration Adverse Event Reporting System. The risk of AD from the use of different antidiabetic drug monotherapies compared to that of metformin monotherapy was assessed by logistic regression. Rosiglitazone (adjusted reporting odds ratio [aROR] = 0.11; 95% confidence interval [CI]: 0.07-0.17; P < .001), exenatide (aROR = 0.22; 95% CI: 0.11-0.37; P < .001), liraglutide (aROR = 0.36; 95% CI: 0.19-0.62; P < .001), dulaglutide (aROR = 0.39; 95% CI: 0.17-0.77; P = .014), and sitagliptin (aROR = 0.75; 95% CI: 0.60-0.93; P = .011) were found to have a significantly lower associated risk of AD than that of metformin. Therefore, the administration of glucagon-like peptide 1 receptor agonists and rosiglitazone may reduce the risk of AD in patients with T2DM.

Discrepancies between patients' and pharmacists' perceptions of the role of community pharmacists as advisors on the use of pharmaceuticals in Japan: A comparison prior to and following revision of the Pharmacists' Act.

OBJECTIVES: In 2014, immediately prior to the revision of Article 25-2 of the Pharmacists' Act, we conducted a survey on pharmacists' and patients' perceptions of pharmacists' roles. A role discrepancy between the two was identified. The objective was to examine changes in role perceptions and awareness of pharmacists as medication specialists following revision to the Pharmacists' Act. METHODS: The survey was conducted using an Internet-based questionnaire. A total of 469 patients and 354 pharmacists responded to 12 questions about the perceived roles of pharmacists. RESULTS: Analysis revealed that the only evaluation that changed as a result of revisions was pharmacists' role as "family or regular pharmacist," with scores dropping by about half. As in 2014, the high rating rate for pharmacists surpassed the high rating of patients for all other items. The greatest discrepancy in role perception was observed for the same three items ("Understanding the effects of the drugs the patients are taking," "Understanding the health changes caused by the drugs dispensed to the patients," and "Consciously protecting patients from the adverse effects of drugs") as 2014. CONCLUSION: A major role discrepancy continues to exist between patients and pharmacists, and it is necessary for pharmacists to take on a more advanced role in patient care. Results suggest that pharmacists must monitor changes in patients' lifestyles and provide clear explanations for patients to rate them highly as medication specialists.

Onset timing of statin-induced musculoskeletal adverse events and concomitant drug-associated shift in onset timing of MAEs.

To evaluate the onset timing of musculoskeletal adverse events (MAEs) that develop during statin monotherapy and to determine whether concomitant drugs used concurrently with statin therapy shifts the onset timing of MAEs. Cases in which statins (atorvastatin, rosuvastatin, simvastatin, lovastatin, fluvastatin, pitavastatin, and pravastatin) were prescribed were extracted from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) Data Files. The onset timing of MAEs during statin monotherapy was evaluated by determining the difference between statin start date and MAE onset date. The use of concomitant drugs with statin therapy was included in the analysis. Statins used in combination with concomitant drugs were compared with statin monotherapy to determine if the use of concomitant drugs shifted the onset timing of MAEs. The onset of MAEs was significantly faster with atorvastatin and rosuvastatin than with simvastatin. A difference in onset timing was not detected with other statins because the number of cases was too small for analysis. When evaluating concomitant drug use, the concomitant drugs that shifted the onset timing of MAEs could not be detected. Statins with strong low-density lipoprotein cholesterol-lowering effects (atorvastatin and rosuvastatin) contributed not only to a high risk of MAE onset, but also to a shorter time-to-onset. No concomitant drug significantly shifted the onset timing of MAEs when used concurrently with statins.

Identification and Characteristics of Time-Related Shifts in Suicide-Related Event Frequency During Smoking Cessation Treatment with Varenicline.

Objectives: To survey time-related shifts in number of suicide-related events (SRE) during smoking cessation treatment with varenicline (VAR) in cases from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), as well as the characteristics of these shifts. Methods: We isolated cases from the FAERS database involving VAR usage where SRE was reported as an adverse event (SRE+/VAR+ case) and established a histogram of SRE+/VAR+ case numbers per week. Furthermore, we focused on "cases reporting specific adverse events prior to drug usage start" using X-bar and R chart concepts. We also attempted to exclude the influence of smoking history from the created histogram. Moreover, we constructed a histogram on central nervous system adverse events, which were frequently seen during VAR usage. Results: By removing the effects of smoking history, SRE onset signals were detected over a long period from the start of VAR use. However, expression signals for nausea and abnormal dreams were detected only in the early VAR administration period. Discussion: These results suggest that VAR use-induced SRE is expressed over a long timeframe from the start of treatment. Additionally, the period of SRE expression signal detection was longer than that of the other central nervous system adverse events (nausea and abnormal dreams). Therefore, SRE onset must be carefully monitored during smoking cessation treatment with VAR over the entire treatment period.

Comparison of the Benefit Feeling Rate Based on the Sho of OTC Kakkonto, Cold Remedy and Cold Remedy with Kakkonto Combination Product.

Kakkonto (KK), a traditional Japanese Kampo formulation for cold and flu, is generally sold as an OTC pharmaceuticals used for self-medication. Kampo formulations should be used according to the Sho-symptoms of Kampo medicine. These symptoms refer to the subjective symptoms themselves. Although with OTC pharmaceuticals, this is often not the case. We surveyed the relationship of agreement of Sho with the benefit feeling rate (BFR) of patients who took KK (n=555), cold remedies with KK (CK, n=315), and general cold remedies (GC, n=539) using internet research. BFR of a faster recovery was greater in participants who took the medication early and who had confidence in their physical strength in all treatment groups. BFR was significantly higher in the GC group than in the KK group for patients with headache, runny nose, blocked nose, sneezing, and cough. BFR was also significantly higher in the GC group than in the CK group for headache (males) and cough (females). BFR was the highest in the KK group for stiff shoulders. All cold remedies were more effective when taken early, and the larger the number of Sho that a patient had, the greater the BFR increased. Therefore, a cold remedy is expected to be most effective when there are many cold symptoms and when it is taken at an early stage of the common cold.

Study on the Increased Probability of Detecting Adverse Drug Reactions Based on Bayes' Theorem: Evaluation of the Usefulness of Information on the Onset Timing of Adverse Drug Reactions.

In order to avoid adverse drug reactions (ADRs), pharmacists are reconstructing ADR-related information based on various types of data gathered from patients, and then providing this information to patients. Among the data provided to patients is the time-to-onset of ADRs after starting the medication (i.e., ADR onset timing information). However, a quantitative evaluation of the effect of onset timing information offered by pharmacists on the probability of ADRs occurring in patients receiving this information has not been reported to date. In this study, we extracted 40 ADR-drug combinations from the data in the Japanese Adverse Drug Event Report database. By applying Bayes' theorem to these combinations, we quantitatively evaluated the usefulness of onset timing information as an ADR detection predictor. As a result, when information on days after taking medication was added, 54 ADR-drug combinations showed a likelihood ratio (LR) in excess of 2. In particular, when considering the ADR-drug combination of anaphylactic shock with levofloxacin or loxoprofen, the number of days elapsed between start of medication and the onset of the ADR was 0, which corresponded to increased likelihood ratios (LRs) of 138.7301 or 58.4516, respectively. When information from 1-7 d after starting medication was added to the combination of liver disorder and acetaminophen, the LR was 11.1775. The results of this study indicate the clinical usefulness of offering information on ADR onset timing.

Deprescribing Using the Guidelines for Medical Treatment and Its Safety in the Elderly and Changes in Patient QOL and Activities of Daily Living.

Pharmacists applied deprescribing, which is a process for the rational use of drugs, for 13 at-home patients. The standard used for the rational use of drugs was the "Guidelines for Medical Treatment and Its Safety in the Elderly" (the Guidelines). The results of the deprescribing were discussed with physicians to determine prescriptions. After the prescription change, activities of daily living (ADL) and QOL were assessed using the Barthel Index and SF-36v2, respectively. Potentially inappropriate medications (PIMs) were detected in 10 of the 13 patients (76.9%). This detection rate is higher than previous PIM detection rates of 48.4% and 40.4% reported in prescriptions for home-care patients in Japan under the Beers and STOPP/START criteria. The Guidelines appeared useful as a decision support tool for deprescribing. The patients continuing the changed prescriptions showed no decrease in ADL or QOL after deprescribing, suggesting its rationality. The 10 measurement items of the Barthel Index were all suitable for evaluating the physical conditions of the patients. Meanwhile, SF-36v2 includes many items, but few indexes were directly applicable.

A survey of subcutaneous blood flow in patients with SMID and subcutaneous ceftazidime administration using mentholated warm compresses in healthy subjects.

OBJECTIVES: To investigate subcutaneous blood flow rate (SBFR) in healthy volunteers and patients with severe motor and intellectual disabilities (SMID), and evaluate the effect of mentholated warm compresses (MWCs) on SBFR and subcutaneous ceftazidime absorption in healthy volunteers. METHODS: SBFR at the forearm, chest and abdomen were evaluated in Japanese healthy volunteers and in adults with SMID. The effects of MWCs on blood flow rate and ceftazidime pharmacokinetics were evaluated in healthy volunteers. RESULTS: SBFR was significantly lower in the forearms of female patients with SMID (n = 11) than in the forearms of healthy females (n = 6); it was not significantly lower in the abdomen or chest. There were no significant differences between male patients (n = 18) or controls (n = 12) in SBFR at any site. MWC application increased SBFR 1.3- to 2.0-fold compared with baseline in healthy controls (n = 6). MWC application increased ceftazidime maximum blood concentration, SBFR and time above mutant prevention concentration in a single healthy subject. CONCLUSIONS: Abdominal SBFR in patients with SMID did not differ from that of healthy subjects. MWC application increases SBFR and subcutaneous drug absorption rate in healthy humans.

Absorption Kinetics of Subcutaneously Administered Ceftazidime in Hypoperfused Guinea Pigs.

BACKGROUND: Pneumonia is the most common cause of death in patients with severe motor and intellectual disabilities (SMID), and intravenous ceftazidime (CAZ) is a widely used treatment for such infections. However, intravenous administration in patients with SMID may be difficult because of insufficient vascular development. OBJECTIVES: The aim of our study was to determine the feasibility of subcutaneous drug administration by mentholated warm compresses (WMCs) as an alternative delivery method for ceftazidime in patients with SMID. METHODS: CAZ was subcutaneously administered to the abdominal region of naphazoline-treated hypoperfused guinea pigs, which were used as a hemodynamic model of patients with SMID. MWCs or warm compresses (WCs) were applied to the injection site to increase blood flow. We calculated the cumulative CAZ absorption over time by using the deconvolution method. RESULTS: Application of MWCs or WCs increased blood flow at the administration site and increased CAZ plasma levels. Application of MWCs or WCs after subcutaneous CAZ injection led to higher CAZ plasma levels than the mutant prevention concentration for a longer period than was observed for CAZ administration without the application of MWCs or WCs. CONCLUSIONS: The application of MWCs or WCs enhanced subcutaneous CAZ absorption by increasing blood flow. MWCs and WCs are considered to be safe and routine methods to induce defecation after surgery on the digestive system; thus, the combination of these methods and subcutaneous CAZ administration is a potential method for treating pneumonia in patients with SMID.