The Association between Molecular Initiating Events and Drug-Induced Hiccups.

Hiccups can significantly reduce the quality of life of patients and can occur as a drug side effect. Previous reports have revealed sex-specific differences in the incidence of drug-induced hiccups. However, the pathogenesis of drug-induced hiccups remains unknown, and there is limited evidence on its treatment or prevention. This study examined molecular initiating events (MIEs), which are the starting point of adverse events, to investigate the drug-induced pathways of hiccups. We extracted drugs suspected to cause hiccups using the FDA Adverse Event Reporting System, a large database on adverse drug reactions. Information on drugs suspected to be associated with hiccups was extracted from the overall population and sex-specific subgroups were divided. In each data table, the predicted activity values of nuclear receptors and stress response pathways for each drug were calculated using the Toxicity Predictor, a machine-learning model. Transforming growth factor-beta and antioxidant response elements were considered an independent factor for hiccups in the male and female subgroups, respectively. This report first examined one of the mechanisms of drug-induced hiccups and identified MIEs associated with drug-induced hiccups. The use of an adverse event database and the machine-learning model, Toxicity Predictor, may be useful for generating hypotheses for other adverse effects with unknown mechanisms.

Analysis of Factors Associated with Hiccups Using the FAERS Database.

In this study, we used the large number of cases in the FDA adverse-event reporting system (FAERS) database to investigate risk factors for drug-induced hiccups and to explore the relationship between hiccups and gender. From 11,810,863 adverse drug reactions reported between the first quarter of 2004 and the first quarter of 2020, we extracted only those in which side effects occurred between the beginning and end of drug administration. Our sample included 1454 adverse reactions for hiccups, with 1159 involving males and 257 involving females (the gender in 38 reports was unknown). We performed univariate analyses of the presence or absence of hiccups for each drug and performed multivariate analysis by adding patient information. The multivariate analysis showed nicotine products to be key suspect drugs for both men and women. For males, the risk factors for hiccups included older age, lower body weight, nicotine, and 14 other drugs. For females, only nicotine and three other drugs were extracted as independent risk factors. Using FAERS, we were thus able to extract new suspect drugs for drug-induced hiccups. Furthermore, this is the first report of a gender-specific analysis of risk factors for hiccups that provides novel insights into drug-induced hiccups, and it suggests that the mechanism responsible is strongly related to gender. Thus, this study can contribute to elucidating the mechanism underlying this phenomenon.

[Investigation into the Effect of Shitei Extract, a Traditional Chinese Medicine Formulation, on Hiccups].

Hiccups are occasionally experienced by most individuals, and although not life-threatening, they may leadto a decline in quality of life. Shitei extract(shitei, persimmon calyx)may be usedfor the treatment of hiccups. The effects of shitei extract were investigatedin patients admittedto the Japanese RedCross Musashino Hospital between October 2011 andM ay 2016. Numerous prescriptions for shitei extract were reportedin the Department of Respiratory Organs andNeurosurgery. The primary causes of hiccups were chemotherapy andbrain disease. Of 149 patients, 107(71.8%)sufferedfrom hiccups. None of the patients reported adverse events related to the administration of shitei extract. The incidence of hiccups was significantly higher in patients with brain disease(p=0.0075), treatedwith chemotherapy for cancer(p=0.0402), or requiring the insertion of a gastric tube(p=0.0065). Among those treatedwith chemotherapy for cancer, shitei extract was effective against hiccups in 82.0% patients(45 of 55). Furthermore, four patients receivedprophylaxis with shitei extract for the prevention of hiccups after chemotherapy. In conclusion, these results indicate that shitei extract is an effective and safe therapeutic drug for the treatment of hiccups. In particular, shitei extract was effective in the prevention of hiccups after chemotherapy.

Association between Delirium and Prehospitalization Medication in Poststroke Patients.

PURPOSE: Medication is an important risk factor for delirium; however, the association between delirium and prehospitalization medication is unclear. We investigated the association between prestroke medication and poststroke delirium. MATERIALS AND METHODS: All patients hospitalized in the stroke care unit from September 2011 to September 2012 were selected, and their delirium symptoms, patient information, and pre- and poststroke medications were analyzed. Delirium was defined as a score of 4 or higher on the Intensive Care Delirium Screening Checklist. Factors that were related to delirium were extracted using univariate analysis, and the independent risk factors were determined using multivariate analysis. RESULTS: Of the 269 patients analyzed, 97 (36%) experienced delirium. Univariate analysis revealed significant differences between the delirium and nondelirium groups in age, dementia, previous cerebrovascular disease, craniotomy, all insertion-tube types, and 6 categories of prestroke medication. Prestroke polypharmacy was associated with poststroke delirium (P = .002). Multivariate analysis showed that taking antianxiety agents or sleep aids was an independent risk factor for delirium (odds ratio: 3.17, 95% confidence interval: 1.16-8.82). CONCLUSIONS: The present study suggests that prestroke medication affects the onset of poststroke delirium. These findings can contribute to the prediction and prevention of this condition.

Analysis of factors associated with hiccups based on the Japanese Adverse Drug Event Report database.

Hiccups are occasionally experienced by most individuals. Although hiccups are not life-threatening, they may lead to a decline in quality of life. Previous studies showed that hiccups may occur as an adverse effect of certain medicines during chemotherapy. Furthermore, a male dominance in hiccups has been reported. However, due to the limited number of studies conducted on this phenomenon, debate still surrounds the few factors influencing hiccups. The present study aimed to investigate the influence of medicines and patient characteristics on hiccups using a large-sized adverse drug event report database and, specifically, the Japanese Adverse Drug Event Report (JADER) database. Cases of adverse effects associated with medications were extracted from JADER, and Fisher's exact test was performed to assess the presence or absence of hiccups for each medication. In a multivariate analysis, we conducted a multiple logistic regression analysis using medication and patient characteristic variables exhibiting significance. We also examined the role of dexamethasone in inducing hiccups during chemotherapy. Medicines associated with hiccups included dexamethasone, levofolinate, fluorouracil, oxaliplatin, carboplatin, and irinotecan. Patient characteristics associated with hiccups included a male gender and greater height. The combination of anti-cancer agent and dexamethasone use was noted in more than 95% of patients in the dexamethasone-use group. Hiccups also occurred in patients in the anti-cancer agent-use group who did not use dexamethasone. Most of the medications that induce hiccups are used in chemotherapy. The results of the present study suggest that it is possible to predict a high risk of hiccups using patient characteristics. We confirmed that dexamethasone was the drug that has the strongest influence on the induction of hiccups. However, the influence of anti-cancer agents on the induction of hiccups cannot be denied. We consider the results of the present study to be helpful for the prevention and treatment of hiccups.