Estimating Taiwan's QALY league table for catastrophic illnesses: Providing real-world evidence to integrate prevention with treatment for resources allocation.

BACKGROUND/PURPOSE: Curative technologies improve patient's survival and/or quality of life but increase financial burdens. Effective prevention benefits all three. We summarize estimation methods and provide examples of how much money is spent per quality-adjusted life year (QALY) or life year (LY) on treating a catastrophic illness under a lifetime horizon and how many QALYs/LYs and lifetime medical costs (LMC) could be potentially saved by prevention. METHODS: We established cohorts by interlinkages of Taiwan's nation-wide databases including National Health Insurance. We developed methods to estimate lifetime survival functions, which were multiplied with the medical costs and/or quality of life and summed up to estimate LMC, quality-adjusted life expectancy (QALE) and lifetime average cost per QALY/LY for catastrophic illnesses. By comparing with the age-, sex-, and calendar year-matched referents simulated from vital statistics, we obtained the loss-of-QALE and loss-of-life expectancy (LE). RESULTS: The lifetime cost-effectiveness ratios of ventilator-dependent comatose patients, dialysis, spinal cord injury, major trauma, and cancers were US$ 96,800, 16,200-20,000, 5500-5,900, 3400-3,600, and 2900-11,900 per QALY or LY, respectively. The successful prevention of lung, liver, oral, esophagus, stomach, nasopharynx, or ovary cancer would potentially save US$ 28,000-97,000 and > 10 QALYs; whereas those for end-stage kidney disease, stroke, spinal injury, or major trauma would be US$ 55,000-300,000 and 10-14 QALYs. Loss-of-QALE and loss-of-LE were less confounded indicators for comparing the lifetime health benefits of different technologies estimated from real-world data. CONCLUSIONS: Integration of prevention with treatment for resources allocation seems feasible and would improve equity and efficiency.

Urban climate and cardiovascular health: Focused on seasonal variation of urban temperature, relative humidity, and PM2.5 air pollution.

Seasonal effects on subclinical cardiovascular functions (CVFs) are an important emerging health issue for people living in urban environment. The objectives of this study were to demonstrate the effects of seasonal variations of temperature, relative humidity, and PM2.5 air pollution on CVFs. A total of 86 office workers in Taipei City were recruited, their arterial pressure waveform was recorded by cuff sphygmomanometer using an oscillometric blood pressure (BP) device for CVFs assessment. Results of paried t-test with Bonferroni correction showed significantly increased systolic and diastolic BP (SBP, DBP), central end-systolic and diastolic BP (cSBP, cDBP) and systemic vascular resistance, but decreased heart rate (HR), stroke volume (SV), cardio output (CO), and cardiac index in winter compared with other seasons. After controlling for related confounding factors, SBP, DBP, cSBP, cDBP, LV dp/dt max, and brachial-ankle pulse wave velocity (baPWV) were negatively associated with, and SV was positively associated with seasonal temperature changes. Seasonal changes of air pollution in terms of PM2.5 were significantly positively associated with DBP and cDBP, as well as negatively associated with HR and CO. Seasonal changes of relative humidity were significantly negatively associated with DBP, and cDBP, as well as positively associated with HR, CO, and baPWV. This study provides evidence of greater susceptibility to cardiovascular events in winter compared with other seasons, with ambient temperature, relative humidity, and PM2.5 as the major factors of seasonal variation of CVFs.

Urban Fine Particulate Matter and Elements Associated with Subclinical Atherosclerosis in Adolescents and Young Adults.

The relationships between the elemental constituents of PM2.5 and atherosclerosis remain limited, especially in young populations. This study included 755 subjects aged 12-30 years in the Taipei metropolis. A land use regression model was used to estimate residential annual mean concentrations of PM2.5 and eight elemental constituents. We evaluated the percent differences in carotid intima-media thickness (CIMT) with PM2.5 and elemental constituent exposures by linear regressions. Interquartile range increments for PM2.5 (4.5 µg/m3), sulfur (108.6 ng/m3), manganese (2.0 ng/m3), iron (34.5 ng/m3), copper (3.6 ng/m3), and zinc (20.7 ng/m3) were found to associate with 0.92% (95% confidence interval (CI): 0.17-1.66), 0.51% (0.02-1.00), 0.36% (0.05-0.67), 0.98% (0.15-1.82), 0.74% (0.01-1.48), and 1.20% (0.33-2.08) higher CIMTs, respectively. Factor analysis identified four air pollution source-related factors, and the factors interpreted as traffic and industry sources were associated with higher CIMTs. Stratified analyses showed the estimates were more evident in subjects who were ≥18 years old, females, or who had lower household income. Our study results provide new insight into the impacts of source-specific air pollution, and future research on source-specific air pollution effects in young populations, especially in vulnerable subpopulations, is warranted.

Quality of Life and Multilevel Contact Network Structures Among Healthy Adults in Taiwan: Online Participatory Cohort Study.

BACKGROUND: People's quality of life diverges on their demographics, socioeconomic status, and social connections. OBJECTIVE: By taking both demographic and socioeconomic features into account, we investigated how quality of life varied on social networks using data from both longitudinal surveys and contact diaries in a year-long (2015-2016) study. METHODS: Our 4-wave, repeated measures of quality of life followed the brief version of the World Health Organization Quality of Life scale (WHOQOL-BREF). In our regression analysis, we integrated these survey measures with key time-varying and multilevel network indices based on contact diaries. RESULTS: People's quality of life may decrease if their daily contacts contain high proportions of weak ties. In addition, people tend to perceive a better quality of life when their daily contacts are face-to-face or initiated by others or when they contact someone who is in a good mood or someone with whom they can discuss important life issues. CONCLUSIONS: Our findings imply that both functional and structural aspects of the social network play important but different roles in shaping people's quality of life.

Association between urinary manganese and pulmonary function in young adults: A cross-sectional design with a longitudinal cohort validation.

BACKGROUND: The impact of heavy metals on pulmonary function among young adults has been scarcely studied, especially by a longitudinal cohort study. METHODS: We prospectively enrolled 974 young adults (aged 20-45 years) during 2017-2019 and measured pulmonary function and urinary heavy metals, including manganese, copper, chromium, iron, nickel, zinc, cadmium, and lead. Among them, 461 participants had examination of the same urinary heavy metals during 2006-2008, which could be used as a cohort for long-term effect of urinary metals on pulmonary function. RESULTS: In the 974 enrolled participants, urinary heavy metals were within normal range. The urinary manganese level was the only significant factor for the observed/predicted ratios of forced vital capacity (FVC %)(ß coefficient: -1.217, p = 0.030), forced expiratory volume in one second (FEV1%)(ß: -1.664, p < 0.001), and FEV1/FVC% of predicted (ß: -0.598, p = 0.047) in multivariable linear regression under cross sectional design. In cohort analysis, the urinary manganese level was also negatively associated with the FEV1% (ß: -1.920, p = 0.021). There was no significance between other urinary heavy metals and pulmonary function for all participants. The urinary manganese significantly negatively correlated with FVC%, FEV1% and FEV1/FVC% in female subgroup whereas copper and iron were significantly negatively correlated with FVC% in male subgroup. CONCLUSIONS: Among urinary heavy metals, urinary manganese level was associated with pulmonary function negatively, even the level was within normal range. In addition, women might be more susceptible to manganese. There is emergent need to conduct further investigation to confirm the respiratory hazardous effects of manganese.

QALYs and medical costs saved from prevention of a cancer: Analysis of nation-wide real-world data of Taiwan with lifetime horizon.

BACKGROUND/PURPOSE: To quantify savings of loss-of-QALE (quality-adjusted life expectancy) and lifetime medical costs from prevention of different cancers. METHODS: We collected nation-wide data on 808,700 new cancer cases of 14 different organ systems and followed them from 1998 to 2014 in Taiwan. We also collected 13,005 cancer patients from a medical center and 47,320 repeated measurements of quality of life (QoL) of EQ-5D to obtain utility values and multiplied them with the corresponding survival rates to calculate QALE. With Kaplan-Meier estimation to survival function to the end of follow-up, we extrapolated to lifetime through a rolling over algorithm on the logit transform of the survival ratio between the index cohort and age-, sex, and calendar year matched referents simulated from vital statistics. Lifetime costs for each cancer were estimated by multiplying survival with average monthly costs after adjustment with annual discount rate. The loss-of-QALE was estimated by the difference in QALE between the index cancer cohort and corresponding referents. RESULTS: The dynamic changes and weighted averages of the QoL utility values of 14 different cancers ranged from 0.82 to 0.95. Successful prevention of liver, lung, esophagus, or nasopharynx cancer would save more than 10 quality-adjusted life years and more than 21,000 USD per case for both genders. Since the saving of loss-of-QALE was adjusted for different age, sex, and calendar-year distributions, it could be used in cost effectiveness evaluation. CONCLUSION: Savings of loss-of-QALE and lifetime costs could be used for comparison of prevention, diagnosis, treatment and rehabilitation from a lifetime horizon.

New approach to identifying proper thresholds for a heat warning system using health risk increments.

BACKGROUND: A critical adaptation strategy for reducing heat-related health risk under climate change is to establish a heat warning system with a proper threshold that requires evaluation of heat-health relationships using empirical data. OBJECTIVES: This work presents a new approach to selecting proper health-based thresholds for a heat warning system which are different from thresholds of heat-health relationship. METHODS: The proposed approach examined heat-health relationships through analyzing 15 years of health records with a modified generalized additive model (GAM), compared risk ratio increments (RRIs) of threshold candidates against a reference, assessed frequency of days above these candidates, and presented results graphically for easy communication. The candidate with the maximum RRI and proper occurring frequency is potentially the best threshold. Three heat indicators, including wet-bulb globe temperature (WBGT), temperature (T), and apparent temperature (AT), as well as three health outcomes, including all-cause mortality, heat-related hospital admissions, and heat-related emergency visits were evaluated. RESULTS: Risk ratios for all three health outcomes showed a consistent rising trend with increasing threshold candidates for all three heat indicators among different age and gender groups. WBGT had the most obvious increasing trend of RRIs with the three health outcomes. The maximum RRI was observed in heat-related emergency visits (242%), followed by heat-related hospital admissions (73%), and all-cause mortality (9%). The RRIs assessed for the three health outcomes pointed to the same thresholds, 33.0 °C, 34.0 °C, and 37.5 °C for WBGT, T, and AT, respectively. The number of days above these thresholds and for warning to be issued ranged between 0 and 7 days during 2000-2014. DISCUSSION: This study demonstrated a new approach to determining heat-warning thresholds with different heat indicators and health outcomes. The proposed approach provides a straightforward, feasible, and flexible scientific tool that assists the authorities around the world in selecting a proper threshold for a heat warning system.

Assessing effects of personal behaviors and environmental exposure on asthma episodes: a diary-based approach.

BACKGROUND: Quantifying the effects of personal health behaviors and environmental exposure on asthma flare-ups is a challenge. Most studies have focused on monitoring the symptoms and drug usage for relieving symptoms. In this study, we emphasize the need to understand how personal and environmental conditions are related to the occurrence of asthma symptoms. METHODS: We designed an online health diary platform to collect personal health behaviors from children, their parents and other adults with any allergic diseases including asthma, allergic rhinitis, atopic dermatitis and allergic conjunctivitis. The participants used mobile devices or computers to record their daily health-related activities such as sleep, exercise, diet, perception of air quality and temperature, and asthma symptoms. The participants also recorded secondhand smoke exposure and the time of activities, which were combined with ambient air quality measurements for calculating personal air pollution exposure. A generalized linear mixed model was used to estimate the effects of the factors. RESULTS: During the study period (January 2017-June 2017, and October 2017-September 2018), 132 participants provided 25,016 diary entries, and 84 participants had experienced asthma symptoms in 1458 diary entries. The results showed some different risk factors for the minors and adults. For minors, high-intensity exercise, contact with persons with influenza-like illness (ILI) and the perception of hot temperature and bad indoor air quality were associated with the occurrence of asthma episodes. The identified risk factors for the adult participants included having dehumidifiers at home, exposure to secondhand smoke, having bad sleep quality, contact with persons with ILI, not eating fruit and seafood, perceiving cold temperature, bad quality of indoor and outdoor air, and exposure to high concentration of ozone. CONCLUSIONS: The revealed personal risk factors and perceptions of air quality and temperature may provide guidance on behavioral change for people susceptible to asthma to help control acute onset and severe exacerbation of asthma flare-ups.

Psychometric evaluation of the WHOQOL-BREF, Taiwan version, across five kinds of Taiwanese cancer survivors: Rasch analysis and confirmatory factor analysis.

BACKGROUND: Quality of life (QoL) is important for clinicians to evaluate how cancer survivors judge their sense of well-being, and WHOQOL-BREF may be a good tool for clinical use. However, at least three issues remain unresolved: (1) the psychometric properties of the WHOQOL-BREF for cancer patients are insufficient; (2) the scoring method used for WHOQOL-BREF needs to be clarify; (3) whether different types of cancer patients interpret the WHOQOL-BREF similarly. METHODS: We recruited 1000 outpatients with head/neck cancer, 1000 with colorectal cancer, 965 with liver cancer, 1438 with lung cancer and 1299 with gynecologic cancers in a medical center. Data analyses included Rasch models, confirmatory factor analysis (CFA), and Pearson correlations. RESULTS: The mean WHOQOL-BREF domain scores were between 13.34 and 14.77 among all participants. CFA supported construct validity; Rasch models revealed that almost all items were embedded in their expected domains and were interpreted similarly across five types of cancer patients; all correlation coefficients between Rasch scores and original domain scores were above 0.9. CONCLUSION: The linear relationship between Rasch scores and domain scores suggested that the current calculations for domain scores were applicable and without serious bias. Clinical practitioners may regularly collect and record the WHOQOL-BREF domain scores into electronic health records.

Comparative cardiovascular safety of nonsteroidal anti-inflammatory drugs in patients with hypertension: a population-based cohort study.

AIMS: Previous studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with higher cardiovascular risks. However, few have been active comparison studies that directly assessed the potential differential cardiovascular risk between NSAID classes or across individual NSAIDs. We compared the risk of major cardiovascular events between cyclooxygenase 2 (COX-2)-selective and nonselective NSAIDs in patients with hypertension. METHODS: We conducted a cohort study of patients with hypertension who initiated COX-2-selective or nonselective NSAIDs in a population-based Taiwanese database. The outcomes included hospitalization for the following major cardiovascular events: ischaemic stroke, acute myocardial infarction, congestive heart failure, transient ischaemic attack, unstable angina or coronary revascularization. We followed patients for up to 4 weeks, based on the as-treated principle. We used inverse probability weighting to control for baseline and time-varying covariates, and estimated the on-treatment hazard ratios (HRs) and 95% conservative confidence interval (CIs). RESULTS: We identified 2749 eligible COX-2-selective NSAID users and 52 880 eligible nonselective NSAID users. The HR of major cardiovascular events comparing COX-2-selective with nonselective NSAIDs after adjusting for baseline and time-varying covariates was 1.07 (95% CI 0.65, 1.74). We did not observe a differential risk when comparing celecoxib to diclofenac (HR 1.17; 95% CI 0.61, 2.25), ibuprofen (HR 1.36; 95% CI 0.58, 3.18) or naproxen (HR 0.75; 95% CI 0.23, 2.44). There was an increased risk with COX-2-selective NSAIDs, however, when comparing COX-2-selective NSAIDs with mefenamic acid (HR 2.11; 95% CI 1.09, 4.09). CONCLUSIONS: Our results provide important information about the comparative cardiovascular safety of NSAIDs in patients with hypertension.

Estimating lifetime medical costs from censored claims data.

Claims databases consisting of routinely collected longitudinal records of medical expenditures are increasingly utilized for estimating expected medical costs of patients with a specific condition. Survival data of the patients of interest are usually highly censored, and observed expenditures are incomplete. In this study, we propose a survival-adjusted estimator for estimating mean lifetime costs, which integrates the product of the survival function and the mean cost function over the lifetime horizon. The survival function is estimated by a new algorithm of rolling extrapolation, aided by external information of age- and sex-matched referents simulated from national vital statistics. The mean cost function is estimated by a weighted average of mean expenditures of patients in a number of months prior to their death, of which the number could be determined by observed costs in their final months, and the weights depend on extrapolated hazards. We evaluate the performance of the proposed approach in comparison with that of a popular method using simulated data under various scenarios and 2 cohorts of intracerebral hemorrhage and ischemic stroke patients with a maximum follow-up of 13 years and conclude that our new method estimates the mean lifetime costs more accurately.

Life Expectancy and Lifetime Health Care Expenditures for Type 1 Diabetes: A Nationwide Longitudinal Cohort of Incident Cases Followed for 14 Years.

OBJECTIVES: To assess additional life expectancy (LE), expected years of life lost , and lifetime health care expenditures after type 1 diabetes diagnosis, stratified by sex and age of first diagnosis (early: 0-12 years; late: 13-40 years). METHODS: A longitudinal cohort of patients with diabetes was constructed from Taiwan's National Health Insurance Research Database of 1999 to 2012. The survival functions for diabetic patients and age- and sex-matched general population were estimated by using a semiparametric extrapolation method with annual life tables. The average monthly health care expenditures were multiplied by the corresponding monthly survival rates and summed to calculate the lifetime health care expenditures. Cox proportional hazard models were constructed to corroborate the effects of sex and age, after being adjusted for comorbidities, complications, and calendar years. RESULTS: A total of 2386 cases (45% early diagnosis, 49% males) were identified. An additional LE after diabetes diagnosis was 45.12 years, with an estimated 17.63 years of life lost. The predicted total and diabetes-related lifetime costs were $56,939 and $102,140, respectively. Early diagnosed patients had a longer LE and lower health care spending compared with those of late-diagnosed patients. Male patients had a shorter LE and a higher expected years of life lost than the female patients, which corresponded to lower lifetime costs for the former. The Cox model results for overall mortality corroborated these trends. CONCLUSIONS: Early detection of type 1 diabetes and sex-specific strategies would probably improve long-term health outcomes and save on the cost of diabetes care.

Health-related quality of life after first-line anti-cancer treatments for advanced non-small cell lung cancer in clinical practice.

PURPOSE: This study attempted to compare changes in the Quality-of-Life (QoL) scores after three different first-line anti-cancer treatments for advanced non-small cell lung cancer (NSCLC) in a real-world clinical setting. PATIENTS AND METHODS: From May 2011 to December 2013, we prospectively measured the QoL scores of patients with locally advanced or metastatic NSCLC using the World Health Organization Quality-of-Life-Brief (WHOQOL-BREF) questionnaire. Each QoL measurement was matched by age and sex with one healthy referent from the National Health Interview Survey. Dynamic changes in patients' QoL scores and major determinants were repeatedly assessed by construction of a mixed-effects model to adjust for possible confounders. RESULTS: A total of 336 patients with 577 QoL measurements related to first-line anti-cancer treatments were enrolled. Performance status was the most important predictor of QoL scores in all domains after controlling for potential confounders. With age- and sex-matched healthy subjects as the reference, patients treated with gemcitabine + platinum showed significantly lower scores in multiple physical and psychological domain items in the WHOQOL-BREF. However, pemetrexed + platinum and gefitinib/erlotinib affected patients' QoL scores in 'energy/fatigue' and 'daily activities' with smaller magnitudes, and the scores appeared to improve after 3-4 months of treatment. CONCLUSIONS: Patients receiving gemcitabine + platinum as first-line anti-cancer treatment for advanced NSCLC experienced relatively poor QoL scores throughout treatment course. Studies to develop a real-time computerized system automatically updating the mixed-effects model for QoL to facilitate participatory clinical decision making by physicians, patients, and their families merit further research.

Daily forecast of dengue fever incidents for urban villages in a city.

BACKGROUND: Instead of traditional statistical models for large spatial areas and weekly or monthly temporal units, what public health workers urgently need is a timely risk prediction method for small areas. This risk prediction would provide information for early warning, target surveillance and intervention. METHODS: Daily dengue cases in the 457 urban villages of Kaohsiung City, Taiwan from 2009 to 2012 were used for model development and evaluation. There were in total 2,997 confirmed dengue cases during this period. A logistic regression model was fitted to the daily incidents occurring in the villages for the past 30 days. The fitted model was then used to predict the incidence probabilities of dengue outbreak for the villages the next day. A percentile of the 457*30 fitted incidence probabilities was chosen to determine a cut-point for issuing the alerts. The covariates included three different levels of spatial effect, and with four lag time periods. The population density and the meteorological conditions were also included for the prediction. RESULTS: The performance of the prediction models was evaluated on 122 consecutive days from September 1 to December 31, 2012. With the 80th percentile threshold, the median sensitivity was 83% and the median false positive rate was 23%. We found that most of the coefficients of the predictors of having cases at the same village in the previous 14 days were positive and significant for the 122 daily updated models. The estimated coefficients of population density were significant during the peak of the epidemic in 2012. CONCLUSIONS: The proposed method can provide near real-time dengue risk prediction for a small area. This can serve as a useful decision making tool for front-line public health workers to control dengue epidemics. The precision of the spatial and temporal units can be easily adjusted to different settings for different cities.

Detection of influenza-like illness aberrations by directly monitoring Pearson residuals of fitted negative binomial regression models.

BACKGROUND: Emerging novel influenza outbreaks have increasingly been a threat to the public and a major concern of public health departments. Real-time data in seamless surveillance systems such as health insurance claims data for influenza-like illnesses (ILI) are ready for analysis, making it highly desirable to develop practical techniques to analyze such readymade data for outbreak detection so that the public can receive timely influenza epidemic warnings. This study proposes a simple and effective approach to analyze area-based health insurance claims data including outpatient and emergency department (ED) visits for early detection of any aberrations of ILI. METHODS: The health insurance claims data during 2004-2009 from a national health insurance research database were used for developing early detection methods. The proposed approach fitted the daily new ILI visits and monitored the Pearson residuals directly for aberration detection. First, negative binomial regression was used for both outpatient and ED visits to adjust for potentially influential factors such as holidays, weekends, seasons, temporal dependence and temperature. Second, if the Pearson residuals exceeded 1.96, aberration signals were issued. The empirical validation of the model was done in 2008 and 2009. In addition, we designed a simulation study to compare the time of outbreak detection, non-detection probability and false alarm rate between the proposed method and modified CUSUM. RESULTS: The model successfully detected the aberrations of 2009 pandemic (H1N1) influenza virus in northern, central and southern Taiwan. The proposed approach was more sensitive in identifying aberrations in ED visits than those in outpatient visits. Simulation studies demonstrated that the proposed approach could detect the aberrations earlier, and with lower non-detection probability and mean false alarm rate in detecting aberrations compared to modified CUSUM methods. CONCLUSIONS: The proposed simple approach was able to filter out temporal trends, adjust for temperature, and issue warning signals for the first wave of the influenza epidemic in a timely and accurate manner.

ClickDiary: Online Tracking of Health Behaviors and Mood.

BACKGROUND: Traditional studies of health behaviors are typically conducted using one-shot, cross-sectional surveys. Thus, participants' recall bias may undermine the reliability and validity of the data. To capture mood changes and health behaviors in everyday life, we designed an online survey platform, ClickDiary, which helped collect more complete information for comprehensive data analyses. OBJECTIVE: We aim to understand whether daily mood changes are related to one's personal characteristics, demographic factors, and daily health behaviors. METHODS: The ClickDiary program uses a Web-based platform to collect data on participants' health behaviors and their social-contact networks. The name ClickDiary comes from the platform's interface, which is designed to allow the users to respond to most of the survey questions simply by clicking on the options provided. Participants were recruited from the general population and came from various backgrounds. To keep the participants motivated and interested, the ClickDiary program included a random drawing for rewards. We used descriptive statistics and the multilevel proportional-odds mixed model for our analysis. RESULTS: We selected 130 participants who had completed at least 30 days of ClickDiary entries from May 1 to October 31, 2014 as our sample for the study. According to the results of the multilevel proportional-odds mixed model, a person tended to be in a better mood on a given day if he or she ate more fruits and vegetables, took in more sugary drinks, ate more fried foods, showed no cold symptoms, slept better, exercised longer, and traveled farther away from home. In addition, participants were generally in a better mood during the weekend than on weekdays. CONCLUSIONS: Sleeping well, eating more fruits and vegetables, and exercising longer each day all appear to put one in a better mood. With the online ClickDiary survey, which reduces the recall biases that are common in traditional one-shot surveys, we were able to collect and analyze the daily variations of each subject's health behaviors and mood status.

Latitude-based approach for detecting aberrations of hand, foot, and mouth disease epidemics.

BACKGROUND: Epidemics of hand, foot and mouth disease (HFMD) among children in East Asia have been a serious annual public health problem. Previous studies in China and island-type territories in East Asia showed that the onset of HFMD epidemics evolved with increased latitude. Based on the natural characteristics of the epidemics, we developed regression models for issuing aberration alerts and predictions. METHODS: HFMD sentinel surveillance data from 2008 to 2014 in Japan are used in this study, covering 365 weeks and 47 prefectures between 24 and 46° of north latitude. Average HFMD cases per sentinel are standardized as Z rates. We fit weekly Z rate differences between prefectures located in the south and north of a designated prefecture with linear regression models to detect the surging trend of the epidemic for the prefecture. We propose a rule for issuing an aberration alert determined by the strength of the upward trend of south-north Z rate differences in the previous few weeks. In addition to the warning, we predict a Z rate for the next week with a 95% confidence interval. RESULTS: We selected Tokyo and Kyoto for evaluating the proposed approach to aberration detection. Overall, the peaks of epidemics in Tokyo mostly occurred in weeks 28-31, later than in Kyoto, where the disease peaked in weeks 26-31. Positive south-north Z rate differences in both prefectures were clearly observed ahead of the HFMD epidemic cycles. Aberrations in the major epidemics of 2011 and 2013 were successfully detected weeks earlier. The prediction also provided accurate estimates of the epidemic's trends. CONCLUSIONS: We have used only the latitude, one geographical feature affecting the spatiotemporal distribution of HFMD, to develop rules for early aberration detection and prediction. We have also demonstrated that the proposed rules performed well using real data in terms of accuracy and timeliness. Although our approach may provide helpful information for controlling epidemics and minimizing the impact of diseases, the performance could be further improved by including other influential meteorological factors in the proposed latitude-based approach, which is worth further investigation.

Estimation of physical functional disabilities and long-term care needs for patients under maintenance hemodialysis.

BACKGROUND AND OBJECTIVES: Physical functional disabilities in hemodialysis (HD) patients may increase their mortality and long-term care needs. The aim of this study was to estimate the changes of proportion for different physical functional disabilities along time after beginning HD and the lifelong care needs. METHODS: We used a population-based cohort consisting of 84,657 incident HD patients in Taiwan between 1998 and 2009 to estimate the survival function and extrapolate to lifetime through a semiparametric method. The Barthel Index (BI) was used to measure the functional disability levels cross-sectionally in 1334 HD patients recruited from 9 HD centers. A BI score <50 was considered as severe disability. Lifetime care needs were obtained by extrapolating the age-stratified survival functions to lifetime and then multiplying them with proportions of different kinds of functional disabilities over time. RESULTS: On average, HD patients had at least 6.4, 2.0, and 1.3 years without disability, with moderate disability, and severe disability, respectively. The most common care needs were stair-climbing and bathing, which were 3.0 and 1.7 years, respectively. HD patients were expected to have about 3 years living with disabilities for those beginning HD at an age above 35 years; however, the older the patient, the higher the proportion of functional disabilities and care needs. CONCLUSIONS: HD patients are in need of long-term care and require early intervention and resource planning. The method developed in this study can also be applied to other chronic illnesses with various functional disabilities.

Estimation of potential gain in quality of life from early detection of cervical cancer.

OBJECTIVE: To estimate the lifetime gain in the health-related quality of life (HRQOL) from early detection of cervical cancer. METHODS: A consecutive, cross-sectional sample of 421 patients with cervical cancer was administered the World Health Organization Quality of Life-brief version questionnaires. A nationwide sample of 22,543 patients with invasive cervical cancer (ICC) was collected from the national cancer registry for estimation of lifetime survival function from 1998 to 2007, which was further multiplied by the ratio of HRQOL score functions for patients with ICC and patients with carcinoma in situ (CIS), and summed up over lifetime to obtain expected relative-quality-adjusted survival. The difference between lifetime survival and the expected relative-quality-adjusted survival gives the expected total dissatisfied time during the life course. RESULTS: In comparison with patients with CIS postconization, patients with ICC showed consistently lower scores in the physical and psychological domains and that of sexual life after adjustment for other risk factors. The expected years of life lost for an invasive cancer was 6.48 years using the general population as the reference cohort, while the durations of equivalent to living with a very dissatisfied HRQOL were 1.71 and 0.25 for the physical and psychological domains, respectively, and 1.47 years for sexual life. Validation of the extrapolation method based on a subcohort followed from the 6th to the 13th year shows a relative bias of 0.4%. Sensitivity analysis with 37,000 CIS cases as the reference cohort yields a similar result. CONCLUSIONS: Early detection of cervical cancer not only avoids premature mortality but also prevents long-term living under lower HRQOL scores, including sexual life.

Fine particulate matter results in hemodynamic changes in subjects with blunted nocturnal blood pressure dipping.

Particulate matter with aerodynamic diameter of <2.5 µm (PM2.5) is associated with blood pressure and hemodynamic changes. Blunted nocturnal blood pressure dipping is a major risk factor for cardiovascular events; limited information is available on whether PM2.5 exposure-related hemodynamic changes vary with day-night blood pressure circadian rhythms. In this study, we enrolled 161 subjects and monitored the changes in ambulatory blood pressure and hemodynamics for 24h. The day-night blood pressure and cardiovascular metrics were calculated according to the sleep-wake cycles logged in the subject׳s diary. The effects of PM2.5 exposure on blood pressure and hemodynamic changes were analyzed using generalized linear mixed-effect model. After adjusting for potential confounders, a 10-µg/m(3) increase in PM2.5 was associated with 1.0 mmHg [95% confidence interval (CI): 0.2-1.8 mmHg] narrowing in the pulse pressure, 3.1% (95% CI: 1.4-4.8%) decrease in the maximum rate of left ventricular pressure rise, and 3.6% (95% CI: 1.6-5.7%) increase in systemic vascular resistance among 79 subjects with nocturnal blood pressure dip of <10%. In contrast, PM2.5 was not associated with any changes in cardiovascular metrics among 82 subjects with nocturnal blood pressure dip of ≥10%. Our findings demonstrate that short-term exposure to PM2.5 contributes to pulse pressure narrowing along with cardiac and vasomotor dysfunctions in subjects with nocturnal blood pressure dip of <10%.