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Objectives: This interim report presents the 12-week results of a post-marketing surveillance evaluating the safety of desmopressin orally disintegrating tablets 25 and 50 μg in Japanese men with nocturia due to nocturnal polyuria., Methods: Of the planned study population of 1000 Japanese men receiving desmopressin for the first time for nocturia due to nocturnal polyuria, 971 cases were enrolled. In this interim analysis, 9 cases, including 6 registry violations and 3 cases of unconfirmed desmopressin dosing, were excluded from the 354 case report forms collected and fixed by the end of December 2021, and data up to 12 weeks after administration in 345 cases were defined as the safety analysis set., Results: The mean age was 74.5 ± 9.9 years and 88.7% of the survey participants were aged ≥65 years. Desmopressin was started at a dose of 25 μg in 153 cases (44.3%). There were 102 adverse drug reactions (ADRs) reported in 71 cases, including 6 serious ADRs in 3 cases (0.9%). The most common ADR was hyponatremia occurring in 29 cases (8.4%). Eight of the hyponatremic cases were asymptomatic. Symptoms were resolved or slightly improved within 4 weeks of onset in 13 of 29 cases of hyponatremia. In addition, hyponatremia occurred in 11 of 217 cases (5.1%), with a serum sodium level before the administration of desmopressin of ≥140 mmol/L, and in 13 of 87 cases (14.9%), with a level of 135-139 mmol/L, and was not measured in 5 hyponatremia cases. Patient characteristics that showed significant differences in the occurrence of hyponatremia included body weight, body mass index, renal function, and pretreatment serum sodium level. Regular monitoring of serum sodium is necessary for early detection of hyponatremia., Conclusions: Hyponatremia was the most common ADR when desmopressin orally disintegrating tablets were used to treat nocturia due to nocturnal polyuria over a 12-week period., (© 2024 The Authors. LUTS: Lower Urinary Tract Symptoms published by John Wiley & Sons Australia, Ltd.)

Objective: Acute myeloid leukemia (AML) is the most common form of leukemia among adults in Japan. This study aimed to understand the treatment patterns, health care resource utilization, and costs of FMS-like tyrosine kinase 3 mutation-positive (FLT3m+) AML patients in Japan., Methods: A retrospective cohort study of Japanese FLT3m + AML patients was conducted using data extracted from a national hospital-based claims database provided by Medical Data Vision Co. Ltd. (MDV; Tokyo, Japan). Patients were identified from the MDV database between April 2008 and April 2021 inclusive., Results: A total of 360 patients were included in this study. The study results suggest that cytarabine + anthracyclines was the most common first-line (1 L) treatment, accounting for 41.3% of the patients. FLT3 inhibitors (FLT3i) was the most common treatment across the study period (95.7%). The mean age of patients was 62.4 years, and most were 65 years or older. The median overall survival (OS) after initiating FLT3i treatment was 394 days. The median treatment duration of FLT3i was 88.5 days, while it was 66.0 days for patients treated with FLT3i within 60 days after hematopoietic stem cell transplantation (HSCT). The overall mean monthly total treatment cost was JPY 2,009,531.7/per patient per month (PPPM) (USD 17,967.9/PPPM)., Conclusions: The study found specific treatment patterns, trends and features in patients with FLT3m + AML. FLT3i was the most prescribed treatment across the study period and the overall median OS after initiating FLT3i treatment was over 1 year. The findings of this study could be helpful for clinicians to optimize treatment strategies for FLT3m + AML in Japan.

Objectives: Our objective was to investigate the effectiveness and safety of silodosin in patients with benign prostatic hyperplasia (BPH) who switched to silodosin from another α 1 blocker because of inadequate response., Methods: This was a prospective observational study conducted at 715 medical facilities in Japan in patients with BPH who received an α 1 blocker other than silodosin for at least 3 months but had experienced unsatisfactory treatment outcomes. Patients completed questionnaires, including the International Prostate Symptom Score (IPSS), quality of life (QOL) score and Overactive Bladder Symptom Score (OABSS) at baseline (time of switching) and after 3 months of treatment with silodosin., Results: Overall, 3355 patients were assessed for safety and 3144 patients for effectiveness. Mean ± standard deviation age was 73.1 ± 8.2 years, and most patients had been receiving tamsulosin (53.6%) or naftopidil (45.5%) before silodosin. Silodosin was well tolerated, with an overall incidence of adverse drug reactions of 8.1% and no unexpected safety signals. Significant improvements were observed after switching to silodosin in all effectiveness outcome measures, including total IPSS, all IPSS subscale scores, QOL score, total OABSS, all OABSS subscale scores and residual urine volume. Significant improvements in total IPSS were seen in patients who had been receiving tamsulosin or naftopidil before switching and in almost all other patient subgroups, with the exception of patients with mild symptoms (total IPSS ≤ 7) at baseline., Conclusions: This post-marketing analysis indicates that switching to silodosin from tamsulosin or naftopidil significantly improved symptoms associated with BPH, and silodosin was well tolerated in Japanese patients.

PREVALENCE OF HYPERTENSION IN ELDERLY JAPANESE PATIENTS: Data collected from post-mortem information at the Tokyo Metropolitan Geriatric Hospital showed that the overall prevalence of hypertension in Japanese patients aged over 60 years was 53%; one-third of these elderly hypertensives had isolated systolic hypertension. Isolated systolic and systolodiastolic hypertension were each associated with a similar degree of increased atherosclerosis and cardiovascular complications. In a placebo-controlled study antihypertensive treatment produced a reduction in withdrawal from treatment in elderly patients with mild hypertension. INTERIM TRIAL RESULTS: Some interim results have been obtained from a new trial which is currently under way in Japan, the National Intervention Cooperative Study for the Treatment of Elderly Hypertensives, a long-term study comparing the effects of a calcium antagonist (nicardipine) and a thiazide diuretic (trichlormethiazide) on cardiovascular complications in elderly patients with mild to moderate hypertension.

We applied the Weibull distribution to the life-table and age-patterns of diseases in Japan. The life-table follows a composite Weibull distribution composed of initial failure and two stage wear-out failure periods. The extension of lifespan during the past century is manifested as increases in the scale parameters in all three periods and the shape parameters in the wear-out periods with female predominancy. The shape parameters of diseases show time-independent sex-dependent specific values. When consistent changes are observed, such as increases in the shape parameters of tuberculosis and pneumonia, legitimate causes such as prevention and repair at the societal and medical level are present. Cancer and arteriosclerosis share a common range of shape parameters suggesting analogous underlying biological processes. An analysis of the epidemiology of human aging and disease by the Weibull distribution discloses intrinsic properties of man as a biological organization as well as a societal presence.

Of 1721 consecutive autopsies performed on patients over 60 years of age in Tokyo Metropolitan Geriatric Hospital, 550 (32% of all autopsied cases) revealed symptomatic cerebrovascular lesions. Among the 550 patients, intracranial hemorrhage was found in 19%, cerebral infarction in 75%, and coexisting cerebral hemorrhage and cerebral infarction in 6%. Twenty-eight percent of the cerebral infarctions were embolic infarctions of cardiac origin, half of which were caused by nonvalvular atrial fibrillation, and 69% were non-embolic infarctions of cardiac origin. Progressive subcortical vascular encephalopathy accounted for 15% of the cerebral infarctions. Two-thirds of all lobar cerebral hemorrhages were amyloid angiopathy-related. Nonvalvular atrial fibrillation is the most important cardiac source of embolic stroke. Progressive subcortical vascular encephalopathy is one of the characteristic features of ischemic lesions, and cerebral amyloid angiopathy is an important cause of lobar cerebral hemorrhage in the aged.

Clinicopathologic correlations of nonbacterial thrombotic endocarditis (NBTE) were studied with special reference to their pathogenetic role in cerebral and myocardial infarction. In 2340 cases of consecutive autopsies of the aged, NBTE was observed in 217 cases or 9.3%. The age distribution of NBTE revealed a gradual increase with advancing age. The underlying diseases of NBTE were malignant neoplasm (51.6%), infection (28.3%) and other diseases (20.1%). The incidence of NBTE in each cancer was high in cancers of the colon (16.2%), pancreas (15.2%), gall bladder or bile duct (14.1%) and lung (13.0%). The vegetations of NBTE were found on the aortic valve in 46.1%, on the mitral valve in 40.6% and on the both valves in 8.3%. The incidence of myocardial infarction and scar was 51.2% in the NBTE group, while it was 38.6% in the non-NBTE control group (p less than 0.02). This difference was marked in patients with a small infarction (10.6% vs. 5.3%) and a myocardial scar (30.4% vs. 19.0%). The grade of coronary stenosis was less in the NBTE group than in the control group (p less than 0.001), suggesting that the origin of the myocardial ischemic lesion was embolism from NBTE. The incidence of large cerebral infarction was 14.7% in NBTE and 9.2% in the control group, and that of medium sized cerebral infarction was 35.0% and 23.6% respectively. In this latter group, cortical infarction comprised 57.9% in the NBTE group and 26.6% in the control group. In large cerebral infarction, cerebral atherosclerosis was less severe in NBTE than in the control group (p less than 0.001), also suggesting an embolic mechanism. Disseminated intravascular coagulation was found in 41.9% of NBTE.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathogenetic role of atrial fibrillation (AF) on myocardial and cerebral infarctions was studied in 2340 consecutive autopsies of the aged. AF was found in 405 cases or 17.3%, and the incidence of AF increased with age. Myocardial infarction and scar were found in 56.8% in AF, but in 36.4% in non-AF (p less than 0.001). Small myocardial infarction was 2.9 times (12.6% vs. 4.3%), and the scar was 1.5 times (27.2% vs. 18.7%) as prevalent in AF as in non-AF. Intracardiac mural thrombus was found in 14.8% in AF and in 4.8% in non-AF, 8 to 10 times as prevalent in small myocardial infarction (29.4% vs. 3.7%) and scar (17.4% vs. 1.7%) in AF as in non-AF. Coronary stenotic index revealed no difference between AF and non-AF. Large cerebral infarction was observed in 21.9% in AF and 7.3% in non-AF, and this difference was prominent in cases with myocardial infarction or myocardial scar indicating the common pathogenetic role of AF. In cases with large cerebral infarction severe cerebral atherosclerosis was less frequent in AF than in non-AF. Medium sized cortical infarction was also prevalent in AF. The prevalences of myocardial and cerebral infarctions were not different in AF complicated with valvular heart disease from those without it, but increased in the permanent AF in comparison to the transient AF. AF induced small myocardial infarction and large or medium sized cerebral infarctions by embolism from mural thrombus. The mechanism for the difference in size is discussed.

As an overview of cardiovascular disease in the aged, 3657 autopsy cases were analyzed for the frequency and age-wise incidence of cardiovascular disease. The three major categories, ischemic heart disease, valvular heart disease, and aortic aneurysm and dissection were described. 1. The incidence of overall cardiovascular disease increases sharply between the ages of 60 and 75. Prevention and treatment could be effectively directed at this age group. 2. The incidence of organic cardiovascular disease was: myocardial infarction 19.8 percent; valvular disease 10.0 percent; arteriosclerosis obliterans 3.5 percent; aortic aneurysm and dissection 3.3 percent; pericarditis 2.1 percent; cardiomyopathy 1.6 percent; cor pulmonale 1.4 percent; congenital heart disease 0.7 percent; and others 0.8 percent. 3. As coronary sclerosis progresses, death from ischemic heart disease increases; however, 7 out of 10 patients with 3 vessel disease still die of causes other than ischemic heart disease (pneumonia, malignancy etc.). The general management of infection and malignant neoplasms is important in addition to treatment of cardiovascular disease. 4. Except for mitral stenosis, valvular heart disease, the etiology of which is mostly non-rheumatic, increases with advancing age. 5. In aortic aneurysm, the rupture rate is relatively high in the thoracic aorta; however, this may be caused by the successful surgical repair of abdominal aneurysms. An aneurysm below 6 cm in diameter is not absolutely safe from rupture. 6. In aortic dissection, the interval from onset to the death of the patient is often too short to consider surgery.

Japanese studies of six calcium antagonists are reviewed, and the antihypertensive response to these drugs is analyzed in groups of young, middle-aged, and old subjects. The phase III clinical trials were performed in double-blind group studies that compared the calcium antagonist with a standard drug. In accordance with the guidelines for the clinical evaluation of antihypertensive agents, patients with a blood pressure level greater than or equal to 160/95 mm Hg after receiving a placebo for 4 weeks were enrolled in the study. The test drug was then administered for 12 weeks. A decrease in blood pressure by 20/10 mm Hg from the pretreatment level or a blood pressure level below 149/89 mm Hg was considered to indicate a response. The response rates for nicardipine, diltiazem, nifedipine tablets, long-acting nicardipine, nilvadipine, and nitrendipine were 64.6, 67.4, 68.6, 69.7, 70.7, and 65.9%, respectively. The average pretreatment blood pressure level was 170-175/100 mm Hg, and the average decrease in blood pressure was about 25/14 mm Hg. The reproducibility of the response rate of nicardipine used as a standard drug was shown in four different double-blind studies, where the response rate ranged from 65 to 72%. Side effects were observed in 8-18% of subjects, and the rate of side effects was also found to be reproducible in nicardipine studies. In severe hypertension unresponsive to diuretics and beta-blockers, response rates ranged from 79 to 93%. The antihypertensive response to calcium antagonists was not related to age, but correlated with the pretreatment blood pressure level. Therefore, calcium antagonists are effective and useful in treating mild, moderate, and severe hypertension in patients of all ages.