Universal health coverage in the context of population ageing: catastrophic health expenditure and unmet need for healthcare.

BACKGROUND: Universal health coverage means that all people can access essential health services without incurring financial hardship. Even in countries with good service coverage and financial protection, the progress towards universal health coverage may decelerate or be limited with respect to the growing older population. This study investigates the incidence/prevalence, determinants, and consequences of catastrophic health expenditure (CHE) and unmet need for healthcare and assesses the potential heterogeneity between younger (≤ 64 years) and older people (65 years≤). METHODS: Utilising an annual nationally representative survey of Japanese aged 20 years and over, we estimated the incidence of CHE and unmet need for healthcare using disaggregated estimates by household members' age (i.e. ≤64 years vs. 65 years≤) between 2004 and 2020. Using a fixed-effects model, we assessed the determinants of CHE and unmet need along with the consequences of CHE. We also assessed the heterogeneity by age. RESULTS: Households with older members were more likely to have their healthcare needs met but experienced CHE more so than households without older members. The financial consequences of CHE were heterogeneous by age, suggesting that households with older members responded to CHE by reducing food and social expenditures more so than households without older members reducing expenditure on education. Households without older members experienced an income decline in the year following the occurrence of CHE, while this was not found among households with older members. A U-shaped relationship was observed between age and the probability of experiencing unmet healthcare need. CONCLUSIONS: Households with older members are more likely to experience CHE with different financial consequences compared to those with younger members. Unmet need for healthcare is more common among younger and older members than among their middle-aged counterparts. Different types and levels of health and financial support need to be incorporated into national health systems and social protection policies to meet the unique needs of individuals and households.

An overview of systems for providing integrated and comprehensive care for older people in Japan.

As longevity occurs, people encounter various risks associated with ageing, including economic uncertainty and health issues. Therefore, in addition to extending healthy life expectancy, it is crucial to create an environment where older people can live better even when their intrinsic capacity declines. Additionally, integrated and comprehensive care for older adults is needed to maintain their functional ability and well-being at higher levels. This review provides an overview of the systems and initiatives in Japan, a forerunner of population ageing that supports the quality of life of older people and summarises their remaining challenges. In Japan, with support for access to necessary care available from social welfare councils and community comprehensive support centres, various health and welfare services are provided to respond to the needs of people with different levels of intrinsic capacity, including medical care, preventive care, long-term care, adult guardianship systems, pensions, and social assistance. Nevertheless, there are challenges for the systems, including the gap between life and healthy life expectancy, moderate accumulation and decumulation of retirement assets, lack of human and financial resources for care, and user-unfriendliness and non-covered needs of the current system. Therefore, integrated and comprehensive care beyond health and long-term care is needed to maintain the well-being of older adults, even with their intrinsic capacity declining.

Binding affinities of paclitaxel and docetaxel for generic and nanoparticle albumin-bound paclitaxel-derived albumin from human serum.

Nanoparticle albumin-bound (nab)-paclitaxel is a 130-nm formulation containing human serum albumin (HSA). The clinical efficacy of this formulation is considered to depend on its affinity for HSA. The high pressure employed during the manufacture of nab-paclitaxel HSA (nab HSA) may influence its conformation and/or oligomerization, and ultimately its affinity for HSA. Therefore, studies are required to evaluate whether the affinity of paclitaxel for nab HSA is similar to that of generic HSA (control HSA). In the present study, nab HSA was isolated from nab-paclitaxel by gel filtration, and the binding affinities (KDs) were determined by surface plasmon resonance. Furthermore, the affinity of docetaxel for nab HSA and control HSA was measured, as their binding sites are similar. Paclitaxel showed KDs of 8.93±8.60 and 7.39±5.81 µM for nab HSA and control HSA, respectively, whereas the corresponding KDs for docetaxel were 44.3±9.50 and 55.9±2.28 µM, respectively. This suggests that the paclitaxel binding site was not modified during the nab-paclitaxel manufacturing process. Additionally, nab HSA likely does not affect paclitaxel and blood HSA binding, as evidenced by the similar affinities of paclitaxel and docetaxel for nab HSA and control HSA. In conclusion, the binding affinities of paclitaxel and docetaxel for nab HSA and control HSA were found to be comparable. Additionally, the manufacturing process did not influence the paclitaxel binding affinity for nab HSA. These results also suggest that nab HSA may not affect the clinical effectiveness of nab-paclitaxel.

Relationship between epicardial adipose tissue thickness and early impairment of left ventricular systolic function in patients with preserved ejection fraction.

Epicardial adipose tissue (EAT) is metabolically bioactive fat. The present study aimed to clarify the relationship between EAT amount and early impairment of left ventricular (LV) systolic function in patients with preserved ejection fraction (EF), all evaluated echocardiographically. Participants comprised 62 elderly women (mean age ± standard deviation, 68 ± 11 years) with lifestyle-related diseases and EF ≥ 60 %. EAT amount was evaluated as thickness. Parameters suggesting early impairment of systolic function such as decreases in systolic mitral annular velocity (S') and tissue mitral annular displacement percentage (TMAD %) were evaluated along with EF. Correlations between EAT thickness and these LV systolic functions were assessed. Influences of various factors on the resultant significant relationships were also assessed. EAT thickness correlated inversely with S' and TMAD % (r = -0.402, p = 0.001 and r = -0.585, p < 0.001, respectively), but did not correlate with EF (r = 0.054, not significant). These significant relationships were maintained after considering factors such as body mass index, age, presence of lifestyle-related diseases and blood test results. A significant relationship existed between EAT amount and early impairment of LV systolic function in patients with preserved EF. Accumulation of EAT might contribute to the initial development of LV systolic dysfunction.

[Investigation of the procalcitonin and microbiology test and antibiotics situation from our hospital].

Procalcitonin (PCT) was first described as a sepsis-associated protein in 1993. PCT is increased in the blood at the time of infection by bacteria. Therefore, it is used as an auxiliary indicator of sepsis diagnosis. In addition, PCT is reduced quickly by antibiotics. And use as a stop or change marker is also expected. We have investigated the antimicrobial use and microbial testing of measurement patient and PCT running performance. Number of requests was 3,387 cases (inpatient 2,649 and outpatient 742 cases) for one year. It was subject to the 820 cases that had inspection request to July to October 2012. In 820 cases, 57 cases had exhibited a PCT >0.5 ng/ml and diagnosed with infectious diseases. In 57 cases, 44 cases (77%) were performed microbiology and blood culture. And only blood culture performed in 8 (14%), blood culture and microbiology is not performed for 5 cases (9%), In 21 (40%) cases of 52 cases performed the blood culture shown positive. Detecting bacteria accounted for more than half in 17 cases of Gram-negative bacilli. Also, it had exhibited a systemic inflammatory response syndrome (SIRS) in 18 cases. Antibiotics have been used in all cases regardless of implementation of the microbiology test. If sepsis is suspected, it is necessary for diagnosis is done correctly and quickly. Therefore, PCT has been suggested high usefulness by examining in the hospital. It is required that the reference identification and drug susceptibility results of the pathogenic bacterium combination of microbiology test and the PCT. We considered useful to PCT monitoring that as an indicator of antimicrobial agents change or shorten of antibiotic use period. Future, proactive use of clinical practice is expected.

Effect of carryover of clot activators on coagulation tests during phlebotomy.

We investigated the effect of clot activators carried over from the serum tube on major coagulation tests during phlebotomy. First, blood specimens from 30 normal subjects were mixed with small amounts of fluid containing clot activators, and their effects on various coagulation tests were determined. Only the value of fibrin monomer complex displayed a remarkable change when thrombin-containing fluid was added to the blood specimens. Subsequently, 100 paired blood specimens (taken from 75 healthy volunteers and 25 patients taking warfarin) were collected in coagulation tubes before and after the serum tube using standard phlebotomy procedures. Various coagulation tests were performed to determine the effect of contamination of thrombin-containing blood on coagulation parameters. Differences between the 2 tubes were minimal but significant for some of the coagulation tests. Therefore, we conclude that the effect of clot activators in the serum tube on coagulation tests is minimal when standard phlebotomy procedures are used.

The anti-ischemic mechanism of action of ranolazine in stable ischemic heart disease.

OBJECTIVES: The purpose of this explanatory analysis was to investigate the relationship between ST-segment depression and the rate-pressure product (RPP) during exercise to determine whether ranolazine's mechanism of action was related to a reduction in myocardial oxygen demand or preservation of myocardial oxygen supply. BACKGROUND: In patients with stable ischemic heart disease, ranolazine increases exercise duration and reduces maximal ST-segment depression while exerting minimal effects on heart rate and blood pressure, although its mechanism of action during exercise has not been investigated. METHODS: Patients with stable ischemic heart disease (n = 191) were randomly allocated to a 4-period, double-blind, balanced Latin square crossover study to receive placebo, and ranolazine 500, 1,000, and 1,500 mg twice daily (bid) for 1 week each. Exercise treadmill tests were performed at baseline and at the end of each treatment period. The RPP and ST-segment depression were assessed before starting exercise, at each stage of exercise, and at maximal exercise. RESULTS: Compared with placebo, ranolazine produced a dose-dependent reduction in ST-segment depression that became more marked as exercise-induced ischemia became more pronounced, associated with clinically minor decreases in heart rate and blood pressure. At 12-min exercise, the amount of ST-segment depression compared with placebo and controlled for RPP was reduced by 22.3% on ranolazine 500 mg bid (p = 0.137), by 35.4% on 1,000 mg bid (p = 0.005), and by 45.8% on 1,500 mg bid (p < 0.001). CONCLUSIONS: The progressive magnitude of ischemia reduction on ranolazine was proportionally more substantial than the minor reductions in heart rate or RPP, suggesting that ranolazine's beneficial mechanism of action is most likely primarily due to an improvement in regional coronary blood flow in areas of myocardial ischemia.

Electrocardiography screening for cardiotoxicity after modified Vaccinia Ankara vaccination.

BACKGROUND: Symptomatic myopericarditis has been described after smallpox vaccination using replication-competent vaccinia strains. METHODS: We examined the incidence of new electrocardiogram (ECG) abnormalities and evaluated the safety and immunogenicity related to vaccination. Volunteer subjects (n=90) aged 18 to 32 years were enrolled in a National Institutes of Health-sponsored phase I smallpox vaccination trial (Division of Microbiology and Infectious Diseases 02-017) and observed over a 26-week period after 2 injections of IMVAMUNE, Modified Vaccinia Ankara vaccine (Bavarian Nordic A/S, Copenhagen, DK), followed by scarification with Dryvax (Wyeth Laboratories, Marietta, Penn). Diagnostic computer-derived ECG statements were available to the clinical study team and compared with those of a board-certified cardiologist who independently read the ECG tracings. RESULTS: Serial ECG tracings available for 89 of the subjects revealed new ST-segment abnormalities in 2.2% and new T-wave abnormalities in 15.7%; the majority (71.4%) resolved on subsequent tracings. Cardiologist over-read of computer statements resulted in frequent changes in readings, particularly negation of cardiac arrhythmias. A cardiology consultation was requested in 17 subjects for nonspecific cardiac symptoms or new abnormal ECG findings. Echocardiograms were performed in 12 of the 17 subjects and were normal except for 1 subject with possible myopericarditis after receiving Dryvax. CONCLUSION: New minor ECG abnormalities are common in apparently young healthy volunteers considered for smallpox vaccination trials. Cardiologist over-read of computer-generated ECG statements in vaccine trials using ECG as a screening tool for safety can reduce false-positive computer-determined ECG diagnoses and the need for inappropriate cardiology referral and additional noninvasive testing.

Multiple yellow plaques assessed by angioscopy with quantitative colorimetry in patients with myocardial infarction.

BACKGROUND: Multiple angioscopic yellow plaques are associated with diffuse atherosclerotic plaque, and may be prevalent in patients with myocardial infarction (MI), so in the present study the yellow plaques in the coronary arteries of patients with MI was evaluated using quantitative colorimetry, and compared with those of patients with stable angina (SA). METHODS AND RESULTS: In the recorded angioscopic images of 3 coronary vessels in 29 patients (15 patients with MI, 14 with SA), yellow plaques were determined as visually yellow regions with b* value >0 (yellow color intensity) measured by the quantitative colorimetric method. A total of 90 yellow plaques were identified (b* =19.35+/-8.3, 3.05-45.35). Yellow plaques were significantly more prevalent in 14 (93%) of 15 culprit lesions of MI as compared with 8 (57%) of 14 of SA (p=0.03). In non-culprit segments, yellow plaques were similarly prevalent in 13 (87%) patients with MI and 11 (79%) with SA (p=0.65). Overall, multiple (> or =2) yellow plaques were prevalent in 13 (87%) patients with MI, similar to the 10 (71%) with SA (p=0.38). The number of yellow plaques was significantly higher in patients with MI (3.8+/-1.9) than in those with SA (2.4+/-1.6, p=0.03). CONCLUSION: The present study suggests that patients with MI tend to have diffuse atherosclerotic plaque in their coronary arteries.

Phytosterols dissolved in diacylglycerol oil reinforce the cholesterol-lowering effect of low-dose pravastatin treatment.

BACKGROUND AND AIMS: Dietary therapy using phytosterols can reinforce statin treatment; however the value of a low-dose combination of those agents remains to be investigated. Plant sterols (PS), dissolved in diacylglycerol (DAG) oil, (PS/DAG) can be effective at a relatively low dose. The objective of the present study was to examine the effect of PS/DAG oil on blood cholesterol concentrations in hypercholesterolemic outpatients on low-dose pravastatin (10 mg/day). METHODS AND RESULTS: The patients (n=61) were randomly assigned to one of three groups, who consumed TAG (control), DAG or PS/DAG oil. The average intake of PS from the PS/DAG oil during the test period was significantly higher than that for TAG and DAG oils (502 vs. 49 and 38 mg/day, P<0.05). Significant cholesterol-lowering effects from the baseline were observed in the case of the PS/DAG oil treatment alone. Changes in low-density lipoprotein (LDL) cholesterol were inversely correlated with baseline serum campesterol concentrations (r=-0.560, P<0.05), but not baseline LDL cholesterol concentrations. In addition, serum apolipoprotein B concentrations were reduced to a greater extent in subjects with high versus low levels of baseline campesterol (-13.2 mg/dL vs. -3.1 mg/dL, P<0.05). Furthermore, there was a mild, but significant reduction in serum lipoprotein (a) concentration from the baseline (-5.9 mg/dL), which was correlated with the reduction in serum apolipoprotein B concentration (r=0.596, P<0.05). CONCLUSION: A low-dose combination of PS/DAG oil and pravastatin may be a useful strategy for further ameliorating blood cholesterol and lipoprotein (a) concentrations for hypercholesterolemic patients with a low response to pravastatin.

Tea catechin consumption reduces circulating oxidized low-density lipoprotein.

It has been reported that green tea consumption reduces the risk of coronary artery disease and cardiac events. Catechin is a major constituent of Japanese green tea and an antioxidant. Lipids and oxidization of low-density lipoprotein cholesterol (LDL-C) play important roles in atherosclerosis. Therefore, we evaluated the effect of catechin intake on the lipid profile and plasma oxidized LDL. The study population consisted of 40 healthy adult volunteers (10 men, 30 women). Catechin was extracted from green tea leaves. The subjects were randomly divided into two groups, a catechin group (n = 29) and a control group (n = 11). In the catechin group, catechin (500 mg: equivalent to 6 or 7 cups of green tea) was administered orally. Venous blood samples were obtained before eating a meal at the start and after 4 weeks without any lifestyle modification. Plasma oxidized LDL assay was performed with a sandwich-type enzyme immunoassay using anti-oxidized phosphatidylcholine monoclonal antibody. The baseline lipid profiles and tea consumptions were similar between the two groups. Plasma oxidized LDL was significantly decreased after catechin administration (from 9.56 +/- 9.2 to 7.76 +/- 7.7 U/mL, P = 0.005), while plasma LDL-C, triglyceride, and HDL-C concentrations did not change. Catechin decreased the plasma oxidized LDL concentration without significant change in plasma LDL concentration. The mechanism of the beneficial effects of green tea on coronary artery disease might result from a decrease in plasma oxidized LDL.

Novel therapeutic approaches to treating chronic angina in the setting of chronic ischemic heart disease.

Pharmacologic therapy to alleviate symptoms in chronic angina has been enhanced by the recent approval of several novel compounds that complement the traditional approach using beta-adrenergic blocking drugs, calcium antagonists, and long-acting nitrates. In the United States, ranolazine, a drug that inhibits late I(Na), was approved for patients with chronic angina that remain symptomatic on beta-blockers, calcium antagonists, or long-acting nitrates, on the basis of an acceptable safety profile and efficacy in several randomized placebo controlled studies. A slight increase in the QT interval is observed (<10 ms on average) at the maximum approved dose of 1,000 mg twice daily. Therefore, an ECG should be acquired at baseline and during follow-up, and the drug should not be used in patients with QT prolongation or those who are on QT prolonging drugs unless longer term randomized outcome data demonstrates no excess risk. The MERLIN trial of non-ST-elevation acute coronary syndrome (NSTE ACS) randomized 6,560 patients to assess the potential benefit of ranolazine in reducing the composite endpoint of cardiovascular death, myocardial infarction, and recurrent ischemia, with results expected in 2007. In Europe, ivabradine, a drug that inhibits the hyperpolarization-activated mixed sodium/potassium inward I(f) current, which slows the rest and exercise heart rate, was approved in 2005. Ivabradine at a dose of 10 mg twice daily has been shown to have similar efficacy to amlodipine 10 mg once daily or atenolol 100 mg once daily in alleviating chronic angina symptoms. In this review, several other novel investigational approaches are presented and patient selection considerations for the most recent approved drugs for chronic angina are discussed.

Assessment of contractile response to dobutamine stress by means of ECG-gated myocardial SPECT: comparison with myocardial perfusion and fatty acid metabolism.

UNLABELLED: The present study assessed left ventricular performance during dobutamine stress measured using gated SPECT, and compared the results to myocardial perfusion and fatty acid metabolism. METHODS: Thirty-six patients with myocardial infarction given (99m)Tc-sestamibi or (99m)Tc-tetrofosmin were examined by gated SPECT at rest and during dobutamine stress (4-20 microg x kg(-1) x min(-1)). After acquiring data at the highest dose, 201TlCl was injected and dual-isotope SPECT was performed to assess myocardial ischemia. Thirty of 36 patients also underwent myocardial SPECT with 123I-BMIPP. Regional wall motion changes during dobutamine infusion were determined from the gated SPECT data and classified as: (1) Improvement, (2) Worsening, (3) No change, and (4) Biphasic response. For myocardial segments of each infarct area, stress 201Tl, rest (99m)Tc and (123)I-BMIPP uptakes were graded on a five-point scoring system of defects from 0 (normal) to 4 (grossly defective). RESULTS: Rest 99mTc defect score index (DSI) in No change area was significantly higher than that in Biphasic area. The ADSI (stress 201Tl - rest (99m)Tc) in Biphasic area was significantly higher than those in Improvement and No change areas. The deltaDSI (BMIPP - (99m)Tc) in Worsening area tended to be higher than that in No Change area. CONCLUSIONS: Regional contractile response to dobutamine stress analyzed by gated SPECT showed that the response in-myocardial infarct areas could be classified by rest and stress myocardial perfusion and BMIPP accumulation.

Effects of green tea intake on the development of coronary artery disease.

BACKGROUND: Green tea, a popular beverage in Japan, contains many polyphenolic antioxidants, which might prevent atherosclerosis. This study was designed to determine whether the consumption of green tea is proportionately associated with a decreased incidence of coronary artery disease (CAD) and the cardiovascular and cerebrovascular prognosis. METHODS AND RESULTS: The study group comprised 203 patients who underwent coronary angiography (109 patients with significant coronary stenosis and 94 patients without). Predictors for CAD were analyzed and the patients' cardiovascular and cerebrovascular events were followed. Green tea consumption was significantly higher in patients without CAD than in those with CAD (5.9+/-0.5 vs 3.5+/-0.3 cups/day; p<0.001). An inverse relationship between the intake of green tea and the incidence of CAD was observed (p<0.001). The green tea intake per day was an independent predictor for CAD based on a multivariate logistic regression analysis (odds ratio: 0.84 and 95% confidence interval: 0.76-0.91). In contrast, the green tea intake was not a predictor of cardiovascular and cerebrovascular events based on the Cox proportional hazard model. CONCLUSIONS: Green tea consumption was associated with a lower incidence of CAD in the present study population in Japan. Therefore, the more green tea patients consume, the less likely they are to have CAD.

Effects of statins on circulating oxidized low-density lipoprotein in patients with hypercholesterolemia.

UNLABELLED: Recently, it has been reported that circulating oxidized low-density lipoprotein (Ox-LDL) might be a pivotal indicator for coronary artery disease and the severity of acute coronary syndromes. The purpose of this study was to investigate the effects of statins on Ox-LDL in patients with hypercholesterolemia. Sixteen patients with hypercholesterolemia were randomly assigned to 2 groups, one received 10 mg of pravastatin (n = 8) and the other received 20 mg of fluvastatin (n = 8). The plasma level of Ox-LDL was measured using a newly developed sandwich enzyme-linked immunosorbent assay (ELISA) method. There were no differences between the two groups in Ox-LDL, total cholesterol (TC), or LDL cholesterol (LDL-C) at the baseline. The reduction in Ox-LDL in the fluvastatin group was significantly higher than that in the pravastatin group (47.5% versus 25.2%, P = 0.033). The reductions in TC and LDL-C did not differ between the two groups. CONCLUSION: The present study has shown for the first time that the level of circulating Ox-LDL was significantly decreased by treatment with statins. In addition, the lowering effect of statins on the circulating Ox-LDL was independent of their lipid-lowering effect. Fluvastatin was more effective than pravastatin with regard to decreasing the circulating Ox-LDL.

Serial assessment of left ventricular performance at rest and during bicycle exercise by ECG-gated myocardial perfusion SPECT.

UNLABELLED: The present study evaluates left ventricular performance during exercise by ECG-gated myocardial perfusion SPECT with short-time data collection. METHODS: The study population consisted of 10 healthy volunteers (Group N) and 9 patients with ischemic heart disease (Group I). Seven patients in Group I had a history of prior myocardial infarction. Rest ECG-gated SPECT was performed 40 min after an injection of Tc-99m-tetrofosmin (555-740 MBq). After resting data acquisition, Group N underwent up to two 5-min stages of exercise (75 and 125 watts) on a detachable bicycle ergometer. The Group I patients all underwent symptom-limited, maximal testing on the ergometer. ECG-gated SPECT data were acquired from both groups for 3 min at rest and during the last 3 min of each exercise stage. RESULTS: Significant increases occurred in LVEF from rest to peak stress in both groups (from 55.4 +/- 5.8 to 66.6 +/- 4.1% in group N, p < 0.0001; from 49.0 +/- 12.8 to 56.7 +/- 13.8% in Group I, p < 0.001). The LVESV values significantly decreased to peak stress in Group N (from 49.9 +/- 13.1 to 37.8 +/- 10.0 ml, p < 0.0001), whereas LVEDV did not change (from 110.6 +/- 18.9 to 112.0 +/- 19.0 ml). In contrast, the LVESV values at rest and under peak stress were similar in Group I (from 52.6 +/- 23.9 to 51.7 +/- 31.4 ml) and LVEDV in Group I at peak exercise tended to increase (from 102.8 +/- 36.7 to 111.3 +/- 39.0 ml). The changes in LVESV from rest to peak stress were significantly different between Groups N and I (-12.1 +/- 6.3 vs. -0.9 +/- 11.6 ml, p < 0.02). CONCLUSION: ECG-gated SPECT with short-time data collection can assess left ventricular function during exercise and may offer useful information for evaluating patients with ischemic heart disease.