for the GENCAT Study Group IMPORTANCE Carbamazepine, a commonly used antiepileptic drug, is one of the most common causes of cutaneous adverse drug reactions (cADRs) worldwide. The allele HLA-A*31:01 is reportedly associated with carbamazepine-induced cADRs in Japanese and European populations; however, the clinical utility of HLA-A*31:01 has not been evaluated.OBJECTIVE To assess the use of HLA-A*31:01 genetic screening to identify Japanese individuals at risk of carbamazepine-induced cADRs.DESIGN, SETTING, AND PARTICIPANTS This cohort study was conducted across 36 hospitals in Japan from January 2012 to November 2014 among 1202 patients who had been deemed suitable to start treatment with carbamazepine. Preemptive HLA-A*31:01 genetic screening was performed for 1187 participants. Patients who did not start treatment with carbamazepine or alternative drugs were excluded. Participants were interviewed once weekly for 8 weeks to monitor the development of cADRs. Data analysis was performed from June 8, 2015, to December 27, 2016.EXPOSURES Neuropsychiatrists were asked to prescribe carbamazepine for patients who tested negative for HLA-A*31:01 and alternative drugs for those who tested positive for HLA-A*31:01. MAIN OUTCOMES AND MEASURES Incidence of carbamazepine-induced cADRs.RESULTS Of the 1130 included patients who were prescribed carbamazepine or alternative drugs, the mean (range) age was 37.4 (0-95) years, 614 (54.3%) were men, and 198 (17.5%) were positive for HLA-A*31:01. Expert dermatologists identified 23 patients (2.0%) who had carbamazepine-induced cADRs, of which 4 patients required hospitalization. Drug-induced hypersensitivity syndrome was observed for 3 patients, maculopapular eruption for 9 patients, erythema multiforme for 5 patients, and an undetermined type of cADR for 6 patients. No patient developed Stevens-Johnson syndrome or toxic epidermal necrolysis. Compared with historical controls, the incidence of carbamazepine-induced cADRs was significantly decreased (for BioBank Japan data: incidence, 3.4%; odds ratio, 0.60; 95% CI, 0.36-1.00; P = .048; for the Japan Medical Data Centre claims database: incidence, 5.1%; odds ratio, 0.39; 95% CI, 0.26-0.59; P < .001).CONCLUSIONS AND RELEVANCE Preemptive HLA-A*31:01 genetic screening significantly decreased the incidence of carbamazepine-induced cADRs among Japanese patients, which suggests that it may be warranted in routine clinical practice.
Background: With the ageing of the general population, demand has grown for measures to prevent hospitalization for dementia, which can exacerbate problems associated with activities of daily living in elderly individuals. Anticholinergic medication has been shown to cause falls, delirium, and cognitive impairment in aged patients. However, the risk of hospitalization associated with the administration of anticholinergics is unclear. Methods: We analyzed the records of 61 outpatients (26 men, 35 women; mean age: 78 AE 7 years; mean follow-up period: 420 days) diagnosed with dementia (Alzheimer's disease: n = 45; dementia with Lewy bodies: n = 3; undifferentiated n = 13) and prescribed anti-dementia drugs between May 2013 and December 2014. Medication history was noted, and the patients were divided into two groups according to the Anticholinergic Risk Scale: with risk (n = 13) and without risk (n = 48). Outcome was judged based on an end-point of hospitalization or death. Kaplan-Meier survival and Cox proportional hazard analyses were performed. Results: Eight patients with anticholinergic risk and 12 without anticholinergic risk reached the end-point (P < 0.005). Analysis with a proportional hazard model showed that anticholinergic medication administration was related to a higher risk for reaching the end-point (crude hazard ratio: 3.62, 95% confidence interval: 1.45-9.04, P < 0.01; adjusted hazard ratio: 4.54, 95% confidence interval: 1.03-20.0, P < 0.05). In contrast, Mini-Mental State Examination score, Charlson Comorbidity Index, and the number of drugs were not major risk factors for hospitalization in patients with dementia. Conclusion: The Anticholinergic Risk Scale findings were shown to be a strong predictor of hospitalization for patients with dementia. We should evaluate the anticholinergic burden before initiating anti-dementia therapy.
Three cases involving a previously unreported association of acute pancreatic damage following convulsive status epilepticus (SE) are presented. A review of literature failed to reveal a similar association between SE and acute pancreatic damage. As possible pathophysiological mechanisms of this so far unknown sequel of SE, increased intraduodenal pressure during SE leading to the reflux of the duodenal contents into the pancreatic duct, along with altered metabolism of oxygen-derived free radicals during a prolonged seizure with hypoxia and ischemia resulting in acinar cell injury are suggested. We believe that SE should be considered as an additional risk factor of acute pancreatitis and that pancreatic enzymes should be monitored in patients who have prolonged seizures.
Purpose The aim of this study was to examine the efficacy and safety of electroconvulsive therapy (ECT) for psychotic symptoms of dementia with Lewy bodies (DLB), and also to determine its use as an adaptive criterion. Methods Eight patients aged 66–83 years old (mean 75.4 ± 5.9 years) diagnosed with probable DLB based on the criteria for DLB and who received ECT between September 2013 and December 2019 at Aichi Medical University were enrolled. The efficacy and safety of ECT were retrospectively examined. Psychotic symptoms were evaluated using the Brief Psychiatric Rating Scale (BPRS), while parkinsonism was evaluated based on Hoehn‐Yahr (HY) stage, with both scores analyzed and compared statistically between before and after ECT. Additionally, a follow‐up survey after undergoing ECT was performed. Results Two incidents occurred during ECT sessions, arrhythmia in one patient and respiratory arrest in another, both of whom quickly recovered. Following ECT, a significant improvement in BPRS score was noted (p < 0.018, Wilcoxon signed rank test), whereas no significant difference was seen in regard to HY stage (p = 0.059). Follow‐up survey findings obtained after ECT (mean observation period 15.9 ± 16.7 months), showed that all eight patients were alive and none had a relapse of psychotic symptoms. Conclusion The present results suggest that ECT for patients with mild to moderate DLB and drug therapy‐resistant psychotic symptoms is safe, well tolerated and effective. We consider it worth considering as a DLB therapeutic option.
Background Phantom boarder symptom (PBS) is classified as a delusional misidentification syndrome, and is often encountered in elderly individuals who have mild or major neurocognitive disorders. With the ageing of society, patients presenting with PBS are increasing in Japan. This retrospective study was conducted to examine the aetiology and identify significant predictors of PBS. Methods The records of 511 consecutive patients who visited our hospital with suspicion of dementia between September 2013 and September 2019 were retrospectively examined. From those, 16 patients who presented with PBS (1 male, 15 females; mean age 79.9 ± 4 years) were selected and case features were investigated in detail. Clinical symptoms, background factors, and final diagnoses were noted. PBS was most common in patients affected by dementia with Lewy bodies (DLB). Predictive factors were evaluated using multiple logistic regression analysis. Results The final diagnosis of the 16 subjects was DLB in 7, Alzheimer's disease in 3, delusional disorder in 3, unspecified dementia in 2, and vascular dementia in 1. Analysis limited to DLB cases showed that a low Mini‐Mental State Examination (MMSE) score and living alone were related to higher risk for PBS. Conclusion Various types of dementia, especially DLB, as well as cognitive impairment and living alone were found to be strong predictors of PBS.
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