Delirium risk of histamine-2 receptor antagonists and proton pump inhibitors: A study based on the adverse drug event reporting database in Japan.

OBJECTIVE: Although histamine-2 receptor antagonists (H2RAs) have been shown to be more likely to cause delirium than proton pump inhibitors (PPIs), these results were not adjusted for potential confounding factors. Accordingly, we investigated whether H2RAs and PPIs are risk factors for delirium, even when adjusting for other risk factors by analyzing adverse drug event reports compiled in the post-marketing stages of drugs provided by the Japanese regulatory authorities. METHOD: We analyzed 577,431 reports in the Japanese Adverse Drug Event Report database from April 2004 to July 2020. RESULTS: Of all reports analyzed, 2532 described delirium, and 574,899 described other adverse events. Delirium was associated with H2RAs (crude reporting odds ratio, ROR, 4.17; 95% CI, 3.34-5.22) but not PPIs (crude ROR 0.62; 95% CI 0.43-0.90). Even with adjustment for age, sex, history of dementia or depression, and concomitant drugs reported as risk factors for delirium, the use of H2RAs showed a significantly higher adjusted ROR than that of PPIs (H2RAs: adjusted ROR 3.99; 95% CI 3.18-5.01 and PPIs: adjusted ROR 0.58; 95%CI 0.40-0.84). CONCLUSIONS: These results suggest that, from a cognitive perspective, PPIs may be preferable to H2RAs for patients with or at risk for delirium.

Failure mode and effects analysis of medication adherence in patients with chronic myeloid leukemia.

BACKGROUND: Poor adherence to ABL tyrosine kinase inhibitors (ABL TKIs) is associated with reduced treatment efficacy and increased healthcare costs. To examine the hazards associated with poor adherence, we implemented failure mode and effects analysis (FMEA). METHODS: We surveyed 54 chronic myeloid leukemia (CML) patients treated at Saga University Hospital from October 2012 to May 2014. The survey consisted of items regarding the type of ABL TKI used, adherence to ABL TKIs, the appearance of adverse effects, utilisation of the high cost medical care benefit system, and factors affecting adherence. Four factors that likely affected adherence were identified, including the level of understanding of ABL TKIs treatment outcomes, adverse effects, the high cost of medications, and careless slips in the taking of medicine. Results of the survey were analysed by FMEA. RESULTS: The risk priority number was highest for careless slips in the taking of medicine at 7.0 ± 1.0 (mean ± SEM), followed in descending order by the inadequate understanding of treatment outcomes (4.9 ± 0.6), adverse effects (3.8 ± 0.8), and high medication cost (2.2 ± 0.5). Thus, the prevention of careless slips was the most important factor affecting adherence to ABL TKIs. Contrary to our preoccupation, FMEA revealed that high medication cost was the lowest risk factor for poor adherence. This finding may be attributed to the high utilisation (96.3 %) of the high cost medical care benefit system. CONCLUSION: These findings suggest that an inadequate medication-taking habit such as careless slips may represent a potential target to improve and maximize adherence in CML patients.

Association between cytochrome P450 3A5 polymorphism and the lung function in Saskatchewan grain workers.

OBJECTIVE: The activity of the enzymes that metabolize tobacco smoke may affect the susceptibility to chronic obstructive pulmonary disease (COPD). Cytochrome P450 (CYP) 3A5 is expressed selectively over CYP3A4 in human lung, but the association between the CYP3A5 polymorphisms and the airway injury is unknown. METHODS: Two hundred and six male Saskatchewan grain workers participated in this longitudinal study, and their lung function values of forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC), respiratory symptoms, smoking status, and the occupational history were analyzed. RESULTS: A significant interactive effect was observed between the CYP3A5 genotype and current smoking status on FEV1, and the annual decline rates of FEV1 and FVC in current smokers were greater among CYP3A5*1/*3 carriers than CYP3A5*3/*3 carriers (-48.7+/-16.4 vs. -31.5+/-4.7 ml/years, P=0.02; -27.4+/-18.9 vs. -5.8+/-6.5 ml/years, P=0.04). The incidences of chronic cough and COPD were also higher in current smokers with CYP3A5*1/*3 than in nonsmokers and current smokers with CYP3A5*3/*3. The adjusted odds ratios for chronic cough and COPD current smokers with CYP3A5*1/*3 versus nonsmokers with the CYP3A5*3/*3 genotype were 11.4 (P=0.009) and 4.3 (P=0.13), respectively. CONCLUSION: The results suggest that CYP3A5*1 may be a novel genetic risk factor for airway injury in smokers, and that CYP3A5 may play a role in airway injury owing to the bioactivation of chemicals in tobacco smoke.

Quantification of cibenzoline by enzyme-linked immunosorbent assay.

We have developed an enzyme-linked immunosorbent assay (ELISA) suitable for routine monitoring of serum levels of cibenzoline. Anti-cibenzoline antibody was obtained by immunizing rabbits with cibenzoline conjugated with bovine serum albumin using N-(4-maleimidobutyryloxy)succinimide as a heterobifunctional coupling agent. An enzyme marker was prepared by coupling 2,2-diphenylethylamine with beta-D-galactosidase using glutaraldehyde. The detection limit of cibenzoline by ELISA was approximately 640 pg/ml with 50-microl samples. Cross-reactivity data showed that the antibody well recognizes both the diphenyl and cyclopropyl moieties, and is thus specific enough to the structure of cibenzoline. The values for the cibenzoline concentrations detected using this assay were comparable with those detected using HPLC. There was a good correlation between the values determined by the two methods. Moreover, ELISA was about 15-fold more sensitive in detecting cibenzoline at lower concentrations. Using this assay, drug levels were easily measured in the serum of rabbits after oral administration of cibenzoline at a single dose of 3 mg/kg.