[Factors Affecting Development of Cholinergic Symptoms after Irinotecan Administration].

Upon administration of irinotecan(CPT-11), cholinergic symptoms, such as perspiration and abdominal pain, may develop. These symptoms are reported to increase with higher doses of CPT-11. However, to date, in Japan, factors influencing cholinergic symptoms, such as dosage of CPT-11, regular medications, and laboratory values indicating liver function, have not been studied. Therefore, to assess such factors, we conducted a retrospective investigation. Cholinergic symptoms occurred in 74(40.4%)of 183 patients. Moreover, of these 74 patients, cholinergic symptoms occurred in 45 patients(60.8%)in the first course, and sweating was the most common symptom in these patients. According to binomial logistic regression analysis, the most significant factor affecting cholinergic symptom expression was a single dose(per body surface area)(odds ratio: 1.03, 95% confidence interval: 1.02-1.05, p<0.01), and the cut-off value in the receiver operating characteristic curve was 137mg/m2. By detecting cholinergic symptoms at an early stage after the administration of a single dose of CPT-11, the discontinuation of therapy administration can be avoided, and cholinergic symptoms can be alleviated.

Home blood pressure level and decline in renal function among treated hypertensive patients: the J-HOME-Morning Study.

We examined the association between home and office blood pressure (BP) levels and further decline in renal function among treated hypertensive patients with and without renal dysfunction. We calculated annual decline in estimated glomerular filtration rate (ΔeGFR) in 1535 treated hypertensive patients with home and office BP measurements. We defined ΔeGFR <0 as decline in renal function, and ΔeGFR ⩾0 as non-decline in renal function based on 1.5 years of follow-up. For 520 patients with low eGFR at baseline, morning home, evening home and office systolic BP (SBP) levels and morning home diastolic BP (DBP) levels were positively associated with the risk of decline in renal function (trend P=0.003, 0.002, 0.003 and 0.004). Compared to patients with home SBP <125 mm Hg, the risk of decline in renal function was higher in those with home SBPs ⩾135 mm Hg and between 130-135 mm Hg, while the risk was similar in those with home SBP of 125-130 mm Hg. For 1015 patients with normal eGFR at baseline, only morning home SBP level was positively associated with the risk of decline in renal function (trend P=0.004). Morning home BP might be useful for risk evaluation of decline in renal function even among treated hypertensive patients with normal renal function. Target levels of home BP control among treated hypertensive patients need to be further investigated.

The velocity of home blood pressure reduction in response to low-dose eplerenone combined with other antihypertensive drugs determined by exponential decay function analysis.

BACKGROUND/OBJECTIVE: Eplerenone is a highly selective aldosterone blocker, which has the potential to lower blood pressure (BP) in patients with hypertension. The objective of this study was to assess the hypotensive effects of low-dose eplerenone (25 mg) using home BP measurements. We also assessed the time required to reach 95% of the maximum antihypertensive effect (stabilization time) by analyzing exponential decay functions using home BP measurements. METHODS: We reviewed the medical records of 83 hypertensive patients who were taking eplerenone 25 mg (age, 68.6±11.8 years; men, 36.1%) in addition to other antihypertensive agents. Home BPs were averaged in each patient for the last 5 days of each observation period. The morning versus evening effect (M/E ratio) and the evening versus morning effect (E/M ratio) were calculated to assess the duration of action of eplerenone. RESULTS: The mean home systolic/diastolic BPs at baseline were 136.8±8.8/77.2±9.3 mmHg, respectively. After 8 weeks of treatment with eplerenone, home systolic/diastolic BP significantly decreased by -7.1±10.1/-2.6±5.0 mmHg (p<0.0001). The time for stabilization of home systolic and diastolic BPs was 13.7 days (p=0.006) and 16.5 days (p=0.001), respectively. When eplerenone was administered in the morning, the M/E ratio was 1.1±0.3. The corresponding E/M ratio for evening administration was 0.9±0.6. Although no nocturia was observed, there was a slight but significant increase in serum potassium levels (p=0.03). CONCLUSIONS: Our data suggest that the combination of eplerenone with other antihypertensive drugs may be a promising therapeutic strategy for the treatment of essential hypertension.

Associations between visit-to-visit variability in blood pressure measured in the office and antihypertensive drugs: the J-HOME-Morning study.

The factors associated with visit-to-visit variability in blood pressure (BP) measured in the office between the two visits were identified in 1379 treated hypertensive patients (mean age, 66.1 ± 11.0 y; women, 53.8%). Multivariate regression analysis showed that office BP and visit-to-visit heart rate variability were positively associated with visit-to-visit BP variability, whereas body mass index, duration of antihypertensive medication, and taking amlodipine were negatively associated with visit-to-visit BP variability. Further prospective studies are required to clarify the causal relationships between these factors and visit-to-visit BP variability among treated hypertensive patients.

Change of the management of treated hypertensive patients with or without diabetes in Japan.

We investigate the change of the management of treated hypertensive patients with or without diabetes in Japan using the data in 2003 and the data in 2005-2006. Physicians treated hypertensive patients more aggressively and evaluated their patients' blood pressure (BP) control more strictly in 2005-2006 than in 2003. However, physicians' assessment of BP control might be still insufficient and the BP control status of patients with diabetes was still poorer than that of non-diabetes patients even in 2005-2006. Further investigation for the change of the management of treated hypertensive patients in Japan is needed.

Associations between day-by-day variability in blood pressure measured at home and antihypertensive drugs: the J-HOME-Morning study.

We identified the factors associated with home blood pressure (BP) variability in 1933 patients treated with hypertensive drugs (mean age, 67 years; women, 55%). Multivariate regression analysis showed that female gender, advanced age, home BP value, and home heart rate variability were positively associated with home BP variability, whereas home heart rate, body mass index, and duration of antihypertensive treatment were negatively associated with home BP variability. Moreover, not being medicated with amlodipine and being medicated with angiotensin II receptor blockers were associated with increased home systolic BP variability only among patients who were treated for less than 12 months.

Pharmacists' awareness and attitude toward blood pressure measurement at home and in the pharmacy in Japan.

The aim of this study is to investigate the status of Japanese pharmacists' awareness and attitude toward blood pressure (BP) measurement at home (HBP) and in the pharmacy. Of the 708 community pharmacists and the 117 hospital pharmacists, more than 90% of pharmacists answered that HBP was equally important to or more important than clinic BP, 71.9% (community) and 48.7% (hospital) recommended HBP measurement to the hypertensive patients, and about 15% correctly recognized the reference values of HBP hypertension. Among community pharmacists, 54.0% answered that BP-measuring devices were available in their pharmacy. More aggressive promotion of HBP measurement among pharmacists is warranted.

Association of arterial stiffness with silent cerebrovascular lesions: the Ohasama study.

BACKGROUND: Arterial stiffness is a risk factor for symptomatic stroke, and is associated with symptomatic cerebral infarction and cognitive impairment. Hence, we hypothesized that arterial stiffness would be a significant determinant of silent cerebrovascular lesions. METHODS: The subjects were 363 individuals without symptomatic cerebrovascular lesions who had their arterial stiffness assessed by brachial-ankle pulse wave velocity (baPWV) measurement. The subjects were classified into two groups by the presence or absence of lacunar infarcts, as well as into three groups by grade of white matter hyperintensity (WMH). baPWV was compared among these groups. RESULTS: Eighty-six subjects had lacunar infarcts. Of 138 subjects with WMHs, 102 were classified as having grade 1 and 36 as having grade 2 or 3 WMHs. baPWV was significantly higher in subjects with lacunar infarcts than in those without (17.3 ± 0.3 vs. 16.4 ± 0.2 m/s). baPWV tended to increase with higher WMH grade (16.2 ± 0.2, 16.9 ± 0.3, and 17.8 ± 0.5 m/s in grade 0, 1, and 2 or 3, respectively) after adjustments for confounding factors. The adjusted odds ratio (OR) for lacunar infarcts in subjects with middle-tertile baPWV was significantly higher (OR, 2.37; 95% confidence interval, CI, 1.10-5.11) and the OR in subjects with the highest-tertile baPWV tended to be higher (OR 2.26; 95% CI 0.99-5.45) compared with the lowest-tertile baPWV. The adjusted OR for WMH tended to increase with increased baPWV. CONCLUSIONS: Arterial stiffness appeared to be associated with the presence of a lacunar infarct and WMH, independently of the risks for other cerebrovascular diseases.

Electrocardiographic abnormalities and home blood pressure in treated elderly hypertensive patients: Japan home versus office blood pressure measurement evaluation in the elderly (J-HOME-Elderly) study.

This study compares relationships between each of morning home blood pressure (BP), evening home BP and office BP with electrocardiographic (ECG) abnormalities among treated hypertensive Japanese patients. We defined ECG left ventricular hypertrophy (LVH) as Sokolow-Lyon voltage and/or Cornell voltage duration product. Abnormal T waves and ST segment depression were categorized based on the Minnesota code. Office BP was calculated as the mean of four readings taken during two visits. Morning and evening home BP were calculated as the mean of five readings measured once each morning and evening for 5 days, respectively. Multivariate analysis showed that ECG-LVH in 747 hypertensives (mean age: 72 years; women: 63%) was more closely associated with morning home BP than with either office or evening home BP. Even the first reading of morning home BP on day 1 was significantly associated with ECG-LVH independently of office BP. The association between home BP and ECG-LVH increased with the cumulative number of home BP measurements. The results for abnormal T waves were similar. Home and office BP did not significantly differ between patients with and without ST segment depression. Morning home BP was more closely associated with ECG-LVH and abnormal T waves than either office or evening home BP among treated hypertensive Japanese patients.