Cost-effectiveness of primary prophylaxis of febrile neutropenia with pegfilgrastim in docetaxel, cisplatin and 5-fluorouracil therapy for esophageal cancer.

Objective: The efficacy of docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy in treating esophageal cancer has been reported. However, febrile neutropenia (FN) is a potentially serious adverse event of DCF therapy with an incidence of 10 to 40%. Pegfilgrastim, a granulocyte colony-stimulating factor (G-CSF), has been shown to have a primary prophylactic role in FN. However, it has been suggested that excessive use of expensive G-CSF should be avoided. Therefore, we performed a cost-utility analysis of primary prophylaxis with pegfilgrastim. Design: Cost-effectiveness analysis using decision tree modelling. Methods: We used a decision tree analysis model based on the report of primary prophylaxis with pegfilgrastim. Based on a previous study, the FN incidence rate was set at 40.0% (95% confidence interval (CI): 11.9-68.1) for the pegfilgrastim group and 43.5% (95%CI: 21.6-65.4) for the no pegfilgrastim group. The FN treatment cost was US$726.63, and the duration of FN was 3.65±1.20 days. The utility value of patients who received DCF therapy was 0.643, and the change in utility value at FN onset was -0.15. Expected cost, quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER) were calculated, and cost-utility analysis was performed. Results: The ICER of pegfilgrastim was 184,976.75 USD/QALY. As a result of sensitivity analysis, the utility of FN had the greatest impact on the cost-effectiveness analysis, followed by the drug cost of pegfilgrastim. Conclusion: Primary prophylaxis of FN with pegfilgrastim might not be cost-effectiveness. In determining whether to administer pegfilgrastim it is necessary to consider patient factors, not just the incidence of FN.

Development of quality of life questionnaire in Japan: quality of life assessment of cancer patients receiving chemotherapy.

The Japanese Quality of Life Research Group has developed a general questionnaire suitable for assessing the Quality of Life (QOL) in patients undergoing chemotherapy. The questionnaire covers four major categories: (1) daily activities, (2) physical condition, (3) social activities, and (4) mental and psychological status. The State-Trait Anxiety Inventory (STAI), Self-Rating Depression Scale (SDS), and Performance Status (PS) were used as external measures of quality of life and for the validation of our tool. On the basis of two basic surveys and two studies we selected 22 questions from a larger set of items. Validity and reliability were verified for the final 22-question form. This questionnaire, named the QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs (QOL-ACD), can be used to detect changes in QOL over time. Its use as an additional outcome measure in Phase III chemotherapy trials should be encouraged.

[Assessment method for supporting programs for social activities of the elderly by city, town and village governments in Japan].

OBJECTIVES: The authors developed a questionnaire to assess the activities of supporting programs for social activities for the elderly conducted by city, town and village governments, based on the number of such programs. This study aims to examine the validity of the questionnaire. METHODS: We conducted a study of 145 cities, towns and villages from two prefectures in Japan using the questionnaire. The questionnaire asks government officers whether they had each of 32 programs, and the number of programs in total, as well as each of four domains of social activities (i.e., employment, social participation/volunteering, education/training, individual activities) were calculated. They were also asked to classify each of the programs into one of four domains of social activity to which the programs were most related; they were asked to rate how active the programs were for each domain in their community. To examine the validity of the questionnaire, the following indicators were assessed: (1) proportion of reported programs which were not covered by the questionnaire; (2) concordance of classification of programs into four domains of social activity with those judged by government officers; (3) correlations between number of programs and self-rated activity levels by government officers; and (4) correlations of number programs with characteristics of cities, towns or villages. RESULTS: The results indicated that the list of programs covered most of the programs. Proposed classification of programs into four domains of social activities which they are most related to agreed with judgments by officials. The number of programs positively correlated with self-rated activity levels by officers for employment and education/training domains in both prefectures; and for social participation/volunteering and individual activities in one of the prefecture. The numbers of programs for employment of the elderly positively correlated with the total population of the community, number of staffs, proportion of people employed in the tertiary industries and total budget for social welfare of the elderly; it negatively correlated with proportion of people employed in the primary industries. CONCLUSION: It is suggested that the list of programs in the questionnaire is applicable and assessment based on the number of programs by four social activity domains is valid to some extent in either prefecture. The questionnaire can be improved further, e.g., by adding other programs to the list.

Reliability and validity of a questionnaire for assessment of energy expenditure and physical activity in epidemiological studies.

A self-administered physical activity questionnaire (PA-questionnaire) was developed to assess daily energy expenditure and weekly physical activity in epidemiological studies. The Calorie Counter method (CC-method) was administered to 49 male and 32 female volunteers aged 18-64 years, on 7 consecutive days; after the measurement, the subjects were asked to complete the PA-questionnaire (validation study). The PA-questionnaire was completed by 95 males and 119 females (aged 35-73 years) twice with one-year interval (reliability study). The validation study showed that the mean daily energy expenditure estimated by the PA-questionnaire was slightly and significantly (4.5%) lower than that determined by the CC-method for males (p < 0.05); while no significant difference was observed for females (p > 0.05), mean weekly physical activities were similar between the PA-questionnaire and CC-method in males and females. Daily energy expenditures by the two methods strongly correlated with each other: r = 0.56 (p < 0.001) in males and r = 0.67 (p < 0.001) in females. Weekly physical activities by the two methods also strongly correlated with each other: r = 0.68 (p < 0.001) in males and r = 0.69 (p < 0.001) in females. The reliability study indicated that the Pearson's correlation coefficients between two assessments of daily energy expenditure and weekly physical activity over one-year ranged from 0.37 to 0.62 (p < 0.001). These data indicate that the PA-questionnaire has adequate levels of validity and test-retest reliability in assessment of daily energy expenditure and weekly physical activity in epidemiological studies.

Association of diet and other lifestyle with onset of menopause in Japanese women.

OBJECTIVES: To evaluate the cross-sectional relationships of dietary and other lifestyle variables to menopause. METHODS: A total of 4186 female residents aged 45-55 in Takayama City, Japan, responded to a self-administered questionnaire (the response rate was 89.3%). Diet in the past year was assessed by semiquantitative food frequency questionnaire. Using the logistic regression model, associations between study variables and menopausal status were estimated in terms of odds ratio (OR). RESULTS: Nulliparity and lower relative weight were significantly associated with menopause after controlling for age (P < 0.05). The association of smoking with menopause was marginally significant after controlling for age (P = 0.06). Higher intakes of fat, cholesterol, and coffee were inversely and significantly associated with later menopause after controlling for age, total energy, parity, menarche age, and relative weight (ORs for the highest tertiles of fat, cholesterol and coffee intakes were 0.78, 0.79, and 0.70, respectively, P < 0.05). The highest tertiles of calcium and soy product intakes were significantly associated with menopause after controlling for the covariates (ORs = 1.25 and 1.42, respectively, P < 0.05), but postmenopausal women who had menopause at later age showed higher calcium intake than those who had menopause at early age. CONCLUSION: Dietary factors appear to be associated with onset of menopause.

Accuracy of Calorie Counter method to assess daily energy expenditure and physical activities in athletes and nonathletes.

OBJECTIVE: The aim of this study was to examine the accuracy of the Calorie Counter personal activity computer (CC method) for athletic activity. DESIGN: An observational study for a week or on a day. SETTING: Healthy Japanese volunteers. PARTICIPANTS: Nonathletes (54 males and 53 females) and 38 male athletes, with ages between 13 and 73 years old. MEASURES: Daily energy expenditure and weekly physical activity were simultaneously assessed using the CC method and a daily record on physical activity (daily record method) for a week for the nonathletes and one day for the athletes. RESULTS: Mean daily energy expenditures were 9630 (standard deviation, SD, 1250) kJ.d-1 by the CC method, compared with 9530 (SD, 1120) kJ.d-1 by the daily record method for male nonathletes; 7822 (SD, 768) kJ.d-1 and 7790 (SD, 810) kJ.d-1, respectively, for female nonathletes; and 1120 (SD, 1520) kJ.d-1 and 11580 (SD, 1580) kJ.d-1, respectively, for athletes. The correlation coefficients between daily energy expenditures by these two methods ranged from 0.72 to 0.90. Mean daily physical activities were 1520 (SD, 637) kJ.d-1 by the CC method, compared with 1580 (SD, 691) kJ.d-1 by the daily record method for male nonathletes; 1033 (SD, 318) kJ.d-1 and 1080 (SD, 346) kJ.d-1, respectively, for female nonathletes; and 2770 (SD, 914) kJ.d-1 and 3250 (SD, 1090) kJ.d-1, respectively, for athletes. The correlation coefficients between daily physical activities by these two methods ranged from 0.56 to 0.96. CONCLUSIONS: Our results suggest that the CC method may be reliable enough for assessing the energy expenditure in athletes as well as in nonathletes during free-living activities.

Choice of response scale for health measurement: comparison of 4, 5, and 7-point scales and visual analog scale.

To compare the feasibility of response scales with different numbers of steps for measuring health status, we assessed the ease of completing 4, 5, and 7-point scales and a visual analog scale. Four forms of the questionnaire, each of which consisted of the same ten questions about health status, but with a different type of scale among the four above mentioned, were given to 48 patients with a variety of conditions and diagnoses. The forms were attached together and the order in which they were presented was systematically varied considering permutations of forms. Respondents were asked to complete the forms following the order of the sheets. The 5-point scale form was most commonly chosen as the easiest to complete, and item omission was least frequent with this form. Similar high- reliability results in terms of Cronbach's alpha were achieved for each of the four forms. An additional survey among 153 patients confirmed the results of the first survey. The selection of the easiest scale to complete varied by sex (men preferred the 7-point scale), but was not affected by the conditions or diagnoses of the patients. The study suggests that the 5-point scale is most useful for measuring health status.

Serum hyaluronate in the assessment of liver endothelial cell function after orthotopic liver transplantation in the rat.

This study was designed to evaluate the use of serum hyaluronate as a marker of liver endothelial cell function after liver transplantation. We performed orthotopic liver transplantation in both isogeneic and allogeneic rejector models. After transplantation, hepatocyte function was assessed on the basis of serum ALT and total bilirubin levels, and liver endothelial cell function was judged on the basis of serum hyaluronate levels. Significant increase of hyaluronate in the rejector model, compared with the isogeneic model, was seen before any significant results could be obtained from conventional liver function tests. The impaired metabolism of hyaluronate in the rejector model was observed after intravenous injection of trace amounts of radioactive material. Serial studies demonstrate that the endothelial cell is a more susceptible target for the immune response than the hepatocyte. Serum hyaluronate concentration may be a better indicator in the early assessment of graft function. We also examined serum hyaluronate levels to evaluate cold ischemia-reperfusion injury to the liver endothelial cells in the isogeneic model. At 2 hr after reperfusion, hyaluronate levels in the 6-hr cold ischemia (nonviable allograft) group were significantly higher than in the 1-hr and 3-hr cold ischemia (viable allograft) groups. However, there was little difference between the viable allograft groups. After an intravenous injection of 1 mg/kg hyaluronate, the hyaluronate elimination rate in the 3-hr group was distinctly slower than that in the 1-hr group. These data indicate that the hyaluronate elimination rate may be a more sensitive marker of liver endothelial cell function in viable liver after a short period of ischemia.

[Factors related to demand for cancer mass screening].

The demand for cancer mass screening was studied by a survey conducted in a city of Gifu Prefecture using a mailed self-administered questionnaire. Subjects (n = 300) were randomly selected by age groups from among residents aged 40 years or over, and the response rate was 65.1% (n = 192). Eight subjects were excluded from analysis because of missing data. The demand for mass screening was much lower in both sexes in the age groups 70 years old or over (stomach: 51.6%, lung: 45.2%, colon: 41.9%) than in younger age groups (stomach: 85.8%, lung: 77.8%, colon: 80.8%). Demand level of housewives and persons without regular occupation were lower than those in other occupational groups. Persons with prior experience of receiving screening at their work-site had higher demand for screening than others. A multivariate analysis of screening for stomach cancer showed that prior experience of screening is the most important factor predicting demand for the next screening.

Assessment of testicular biopsy after cessation of maintenance chemotherapy in childhood acute lymphoblastic leukemia: a report from the Children's Cancer and Leukemia Study Group.

Among 484 male patients with acute lymphoblastic leukemia (ALL) registered into the protocols CCLSG 811, 841 and 874, from 1981 through 1990, 246 patients completed their protocols and were in continuous complete remission (CCR) for more than 3 years. One hundred and seven patients received bilateral testicular biopsies at the time of cessation of maintenance chemotherapy. Eight patients (7.5%) were found to have occult testicular leukemia (TL). Three of them did not receive any additional therapy and all suffered subsequent relapses; one bone marrow relapse and two testicular relapses. The other 3 patients received testicular radiation combined with an additional 2 years of chemotherapy, resulting in CCR for more than 6 years 10 months, 7 years 6 months, and 8 years 6 months. One with chemotherapy alone and another with radiation alone showed subsequent relapse. Overt TL after negative initial biopsy was developed in 3 (3.0%) of the 99 patients. All of them received testicular radiation with chemotherapy, resulting again in CCR for more than 1 year 0 months and 5 years 3 months; one patient showed relapse in testes and bone marrow after 3 years 8 months of CCR. These studies suggested that occult TL has an adverse prognostic significance unless retrieval chemotherapy is given and that performance of testicular biopsy at completion of maintenance chemotherapy is not contributory to prolongation of disease-free survival for males with ALL because the treatment employing testicular radiation plus retrieval chemotherapy for both occult TL and isolated overt TL after off-therapy is similarly very effective.

Assessment of flow profile of left anterior descending coronary artery in hypertrophic cardiomyopathy by transesophageal pulsed Doppler echocardiography.

This study assessed the flow velocity profiles of the left anterior descending coronary artery (LAD) in 7 patients with nonobstructive hypertrophic cardiomyopathy (HC) and in 6 normal subjects by transesophageal pulsed Doppler echocardiography, and evaluated their characteristics and the hemodynamic determinants. Systolic peak flow velocity of the LAD (7 +/- 30 cm/sec) was significantly lower in patients with HC than in normal subjects (34 +/- 11 cm/s, p < 0.05), and there was a significant inverse correlation between systolic peak flow velocity and the thickness of the ventricular septum (r = 0.81, p < 0.01). In 2 cases of HC with ventricular septal thickness of > 20 mm, a remarkable systolic reverse flow was observed in the LAD. However, there was no significant difference in diastolic peak flow velocity between HC and normal subjects. During early diastole, the acceleration time of LAD flow velocity was significantly prolonged (210 +/- 67 vs 95 +/- 15 ms, p < 0.01) and the acceleration rate was significantly decreased (3.6 +/- 2.0 vs 6.6 +/- 1.8 m/s2, p < 0.02) in patients with HC. The time constant of the left ventricular pressure decay was significantly prolonged in patients with HC (55 +/- 6 ms) compared with normal subjects (39 +/- 2 ms, p < 0.001). In HC, increased intramural perivascular pressure of the thickened ventricular septum during systole may be attributed to systolic LAD flow pattern. However, the early and mid-diastolic LAD flow pattern may be affected by impaired left ventricular relaxation.

[Relationship of in- and outpatient medical expenditure for the elderly to socioeconomics, medical services, and health and welfare projects].

In order to clarify what factors are associated with per capita medical care expenditure for those aged 65 years and over, for inpatients and outpatients respectively, correlation analyses were performed using several indices of medical services, socioeconomics, medical supply, health and welfare projects for fiscal 1989 among 99 administrative areas in Gifu Prefecture. The expense for inpatients was correlated with the service-acceptance rate, while on the other hand the expense for outpatients was correlated with average cost of medical receipts. Two major factors were number of physicians per person aged 65 years and over and per capita income. For outpatients, population density and per capita amount of subsidy for "elderly welfare projects" were significantly correlated with medical expenditure, with the latter showing a negative correlation. Multiple regression analyses indicated that these factors were independently correlated with the expenses. These findings indicate that expenses for inpatients and outpatients have different construction, with each being associated with different factors.

Cancers of the prostate and breast among Japanese and white immigrants in Los Angeles County.

Using age-adjusted incidence rates and proportional incidence ratios, the risks of prostate cancer and breast cancer in three racial/ethnic groups - Spanish-surnamed whites, other whites and Japanese - were studied in Los Angeles County native residents and compared with those in immigrants and representative 'homeland' populations. An algorithm based on social security numbers was developed and utilised to estimate age at immigration for non-US-born Los Angeles County cancer patients. For prostate cancer, the incidence rates in Los Angeles County were much higher than those in the homelands for each racial/ethnic group. However, prostate cancer rates of immigrants were similar to those of US-born patients in the Spanish-surnamed white and Japanese populations, regardless of age at immigration. For breast cancer, the incidence rates in Los Angeles County were also high compared with those in the homelands. However, the timing of immigration to the US was important in determining breast cancer risk. When social security numbers indicated that migration occurred later in life, rates for breast cancer were substantially lower than when migration occurred early, although they were still much higher than in the homeland populations. These findings suggest that environmental factors in early life rather than in later life are important in the etiology of breast cancer and that later life events can substantially impact the likelihood of developing clinically detectable prostate cancer.

Different rates of acceptance of health examination among the people under 2 separate health insurance programs in Japan.

The entire population in Japan is covered by either workplace-based health insurance program or region-based health insurance program. While both programs were originally for curative medical care, only the former program has recently extended its financial support to preventive health examination. The attitude of the people toward health examination was studied in Miyagi prefecture in north-east Japan by questionnaires with more than 32,000 respondents to examine whether the difference in health insurance reflect on the rates of acceptance of 4 health examination items (i.e., blood pressure measurement, chest x-ray taking, and 2 screening tests for stomach and cervical cancer). Throughout the 4 items, the rate of acceptance was higher among those who were covered by workplace-based health insurance than among those covered by regional health insurance. The difference is large for the insured and less so for the family dependents of the insured. Further analysis for the preferred opportunities for health examination such as personal examination at clinics in contrast to region-based mass examination showed that the weight of clinics was quite large for the insured of national health insurance and their family dependents (i.e., 50% or even larger) but it was less so for the people covered by workplace-based insurance.

Urban-rural difference in the acceptance of mass health examination in north-eastern Japan.

Over 40,000 residents (less than or equal to 40 years of age) in a city (Sendai; the city group), a town (Shiroishi; the town group) and two villages (Wakuya and Tajiri; the village group) in Miyagi prefecture in north-eastern Japan responded in a questionnaire survey on their attitude towards mass health examinations (i.e., whether they underwent in the previous year and if so where) on 4 items of blood pressure measurement, chest x-ray examination and screening tests for stomach and cervical cancer. The coverage rates were about 70% on an average both for blood pressure measurement and for chest x-ray examination, whereas the rates for cancer screening were between 30-40%. As for the opportunity of the former two examinations, the workplace mass examination played a large role in the case of the city and town groups (especially among men but not women) in addition to visit to clinics, in contrast to the case of the village group in which people depended much on regional mass examination service. The trend was essentially reproducible in stomach cancer screening although the over-all coverage rate was low, whereas women in the three groups almost exclusively utilized clinics for cervical cancer screening with one exception that the mobile unit service appeared to be equally accepted in the village group.

Medical costs of nonsmoking women and children in a town of Miyagi.

To know the differences in utilization of medical care and medical costs among children and nonsmoking women depending on the states of smoking of other household members, the records of a health survey conducted in a town of Miyagi in 1987 were linked to the medical insurance records. The rates of medical care use and medical costs among nonsmoking women in nonsmoking households were almost the same as those in smoking households. Children in smoking households had medical care more often than those in nonsmoking households (74.1% vs. 56.4%) and the difference in the medical costs was also observed (Y33,713 vs. Y26,558). The costs were almost correlated with the number of cigarettes smoked in the home.

A model of flagellar movement based on cooperative dynamics of dynein-tubulin cross-bridges.

A theoretical model based on molecular mechanisms of both dynein cross-bridges and radial spokes is used to study bend propagation by eukaryotic flagella. Though nine outer doublets are arranged within an axoneme, a simplified model with four doublets is constructed on the assumption that cross-bridges between two of the four doublets are opposed to those between the other two, corresponding to the geometric array of cross-bridges on the 6-9 and the 1-4 doublets in the axoneme. We also assume that external viscosity is zero, whereas internal viscosity is non-zero in order to reduce numerical complexity. For demonstrating flagellar movement, computer simulations are available by dividing a long flagellum into many straight segments. Considering the fact that dynein cross-bridge spacing is almost equal to attachment site spacing, we may use a localized cross-bridge distribution along attachment sites in each straight segment. Dynamics of cross-bridges are determined by a three-state model, and effects of radial spokes are represented by a periodic mechanical potential whose periodicity is considered to be a stroke distance of the radial spoke. First of all, we examine the model of a short segment to know basic properties of the system. Changing parameters relating to "activation" of cross-bridges, our model demonstrates various phenomena; for example "excitable properties with threshold phenomena" and "limit cycle oscillation". Here, "activation" and "inactivation" (i.e. switching mechanisms) between a pair of oppositely-directed cross-bridges are essential for generation of excitable or oscillatory properties. Next, the model for a flagellar segment is incorporated into a flagellum with a whole length to show bending movement. When excitable properties of cross-bridges, not oscillatory properties, are provided along the length of the flagellum and elastic links between filaments are presented at the base, then our model can demonstrate self-organization of bending waves as well as wave propagation without special feedback control by the curvature of the flagellum. Here, "cooperative interaction" between adjacent short segments, based on "cooperative dynamics" of cross-bridges, is important for wave propagation.

[Regional differences in family patterns in an aging society].

PIP: Questions related to demographic aging are considered, with particular reference to the situation in Japan. The focus of the study is on the support that families provide to the elderly, including emotional and financial support and assistance in everyday activities. Differences in family patterns in the various regions are reviewed, with reference to the present and future extent of the stem family system and the conjugal family system. The author concludes that differences in family patterns will mean that different support mechanisms will be needed by the elderly in the various regions.^ieng