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author:("Chou, pests")
1.  The Protective Effect of Adenoidectomy on Pediatric Tympanostomy Tube Re-Insertions: A Population-Based Birth Cohort Study 
PLoS ONE  2014;9(7):e101175.
Objectives
Adenoidectomy in conjunction with tympanostomy tube insertion for treating pediatric otitis media with effusion and recurrent acute otitis media has been debated for decades. Practice differed surgeon from surgeon. This study used population-based data to determine the protective effect of adenoidectomy in preventing tympanostomy tube re-insertion and tried to provide more evidence based information for surgeons when they do decision making.
Study Design
Retrospective birth cohort study.
Methods
This study used the National Health Insurance Research Database for the period 2000–2009 in Taiwan. The tube reinsertion rate and time to tube re-insertion among children who received tympanostomy tubes with or without adenoidectomy were compared. Age stratification analysis was also done to explore the effects of age.
Results
Adenoidectomy showed protective effects on preventing tube re-insertion compared to tympanostomy tubes alone in children who needed tubes for the first time (tube re-insertion rate 9% versus 5.1%, p = 0.002 and longer time to re-insertions, p = 0.01), especially those aged over 4 years when they had their first tube surgery. After controlling the effect of age, adenoidectomy reduced the rate of re-insertion by 40% compared to tympanostomy tubes alone (aHR: 0.60; 95% CI: 0.41–0.89). However, the protective effect of conjunction adenoidectomy was not obvious among children with a second tympanostomy tube insertion. Children who needed their first tube surgery at the age 2–4 years were most prone to have tube re-insertions, followed by the age group of 4–6 years.
Conclusions
Adenoidectomy has protective effect in preventing tympanostomy tube re-insertions compared to tympanostomy tubes alone, especially for children older than 4 years old and who needed tubes for the first time. Nonetheless, clinicians should still weigh the pros and cons of the procedure for their pediatric patients.
doi:10.1371/journal.pone.0101175
PMCID: PMC4077749  PMID: 24983459
2.  Increased Risk of Ischemic Stroke after Hyperosmolar Hyperglycemic State: A Population-Based Follow-Up Study 
PLoS ONE  2014;9(4):e94155.
Background
Although much attention has been focused on the association between chronic hyperglycemia and cerebrovascular diseases in type 2 diabetes mellitus (DM) patients, there is no data regarding the risk of ischemic stroke after a hyperosmolar hyperglycemic state (HHS) attack. The objective of this study was to investigate the risk of ischemic stroke in type 2 DM patients after an HHS attack.
Methods
From 2004 to 2008, this retrospective observational study was conducted on a large cohort of Taiwanese using Taiwan’s National Health Insurance Research Database (NHIRD). We identified 19,031 type 2 DM patients who were discharged with a diagnosis of HHS and 521,229 type 2 DM patients without an HHS diagnosis. Using the propensity score generated from logistic regression models, conditional on baseline covariates, we matched 19,031 type 2 DM patients with an HHS diagnosis with the same number from the comparison cohort. The one-year cumulative rate for ischemic stroke was estimated using the Kaplan-Meier method. After adjusting covariates, Cox proportional hazard regression was used to compute the adjusted one-year rate of ischemic stroke.
Results
Of the patients sampled, 1,810 (9.5%) of the type 2 DM patients with HHS and 996 (5.2%) of the comparison cohort developed ischemic stroke during the one-year follow-up period. After adjusting for covariates, the adjusted HR for developing ischemic stroke during the one-year follow-up period was 1.8 (95% C.I., 1.67 to 1.95, P<0.001) for type 2 DM patients with HHS compared with those without HHS.
Conclusion
Although DM is a well-recognized risk factor for atherosclerosis, type 2 DM patients that have suffered a HHS attacks are at an increased risk of developing ischemic stroke compared with those without HHS.
doi:10.1371/journal.pone.0094155
PMCID: PMC3979762  PMID: 24714221
3.  Association of Clinical Symptomatic Hypoglycemia With Cardiovascular Events and Total Mortality in Type 2 Diabetes 
Diabetes Care  2013;36(4):894-900.
OBJECTIVE
Hypoglycemia is associated with serious health outcomes for patients treated for diabetes. However, the outcome of outpatients with type 2 diabetes who have experienced hypoglycemia episodes is largely unknown.
RESEARCH DESIGN AND METHODS
The study population, derived from the National Health Insurance Research Database released by the Taiwan National Health Research Institutes during 1998–2009, comprised 77,611 patients with newly diagnosed type 2 diabetes. We designed a prospective study consisting of randomly selected hypoglycemic type 2 diabetic patients and matched type 2 diabetic patients without hypoglycemia. We investigated the relationships of hypoglycemia with total mortality and cardiovascular events, including stroke, coronary heart disease, cardiovascular diseases, and all-cause hospitalization.
RESULTS
There were 1,844 hypoglycemic events (500 inpatients and 1,344 outpatients) among the 77,611 patients. Both mild (outpatient) and severe (inpatient) hypoglycemia cases had a higher percentage of comorbidities, including hypertension, renal diseases, cancer, stroke, and heart disease. In multivariate Cox regression models, including diabetes treatment adjustment, diabetic patients with hypoglycemia had a significantly higher risk of cardiovascular events during clinical treatment periods. After constructing a model adjusted with propensity scores, mild and severe hypoglycemia still demonstrated higher hazard ratios (HRs) for cardiovascular diseases (HR 2.09 [95% CI 1.63–2.67]), all-cause hospitalization (2.51 [2.00–3.16]), and total mortality (2.48 [1.41–4.38]).
CONCLUSIONS
Symptomatic hypoglycemia, whether clinically mild or severe, is associated with an increased risk of cardiovascular events, all-cause hospitalization, and all-cause mortality. More attention may be needed for diabetic patients with hypoglycemic episodes.
doi:10.2337/dc12-0916
PMCID: PMC3609481  PMID: 23223349
4.  The Association of Socioeconomic Status and Access to Low-Volume Service Providers in Breast Cancer 
PLoS ONE  2013;8(12):e81801.
Background
No large-scale study has explored the combined effect of patients’ individual and neighborhood socioeconomic status (SES) on their access to a low-volume provider for breast cancer surgery. The purpose of this study was to explore under a nationwide universal health insurance system whether breast cancer patients from a lower individual and neighborhood SES are disproportionately receiving breast cancer surgery from low-volume providers.
Methods
5,750 patients who underwent breast cancer surgery in 2006 were identified from the Taiwan National Health Insurance Research Database. The Cox proportional hazards model was used to compare the access to a low-volume provider between the different individual and neighborhood SES groups after adjusting for possible confounding and risk factors. Hosmer-Lemeshow goodness-of-fit statistic was used to determine how well the model fit the data.
Results
Univariate analysis data shows that patients in disadvantaged neighborhood were more likely to receive breast cancer surgery at low-volume hospitals; and lower-SES patients were more likely to receive surgery from low-volume surgeons. In multivariate analysis, after adjusting for patient characteristics, the odds ratios of moderate- and low-SES patients in disadvantaged neighborhood receiving surgery at low-volume hospitals was 1.47 (95% confidence interval=1.19-1.81) and 1.31 (95% confidence interval=1.05-1.64) respectively compared with high-SES patients in advantaged neighborhood. Moderate- and low-SES patients from either advantaged or disadvantaged neighborhood had an odds ratios ranging from 1.51 to 1.80 (p<0.001) to receiving surgery from low-volume surgeons. In Hosmer-Lemeshow goodness-of-fit test, p>0.05 that shows the model has a good fit.
Conclusions
In this population-based cross-sectional study, even under a nationwide universal health insurance system, disparities in access to healthcare existed. Breast cancer patients from a lower individual and neighborhood SES are more likely to receive breast cancer surgery from low-volume providers. The authorities and public health policies should keep focusing on these vulnerable groups.
doi:10.1371/journal.pone.0081801
PMCID: PMC3846901  PMID: 24312589
5.  Directly Observed Therapy Reduces Tuberculosis-Specific Mortality: A Population-Based Follow-Up Study in Taipei, Taiwan 
PLoS ONE  2013;8(11):e79644.
Objectives
To determine the effect of directly observed therapy (DOT) on tuberculosis-specific mortality and non-TB-specific mortality and identify prognostic factors associated with mortality among adults with culture-positive pulmonary TB (PTB).
Methods
All adult Taiwanese with PTB in Taipei, Taiwan were included in a retrospective cohort study in 2006–2010. Backward stepwise multinomial logistic regression was used to identify risk factors associated with each mortality outcome.
Results
Mean age of the 3,487 patients was 64.2 years and 70.4% were male. Among 2471 patients on DOT, 4.2% (105) died of TB-specific causes and 15.4% (381) died of non-TB-specific causes. Among 1016 patients on SAT, 4.4% (45) died of TB-specific causes and 11.8% (120) died of non-TB-specific causes. , After adjustment for potential confounders, the odds ratio for TB-specific mortality was 0.45 (95% CI: 0.30–0.69) among patients treated with DOT as compared with those on self-administered treatment. Independent predictors of TB-specific and non-TB-specific mortality included older age (ie, 65–79 and ≥80 years vs. 18–49 years), being unemployed, a positive sputum smear for acid-fast bacilli, and TB notification from a general ward or intensive care unit (reference: outpatient services). Male sex, end-stage renal disease requiring dialysis, malignancy, and pleural effusion on chest radiography were associated with increased risk of non-TB-specific mortality, while presence of lung cavities on chest radiography was associated with lower risk.
Conclusions
DOT reduced TB-specific mortality by 55% among patients with PTB, after controlling for confounders. DOT should be given to all TB patients to further reduce TB-specific mortality.
doi:10.1371/journal.pone.0079644
PMCID: PMC3838349  PMID: 24278152
6.  Impact of Young Age on the Prognosis for Oral Cancer: A Population-Based Study in Taiwan 
PLoS ONE  2013;8(9):e75855.
Background
Oral cancer leads to a considerable use of health care resources. Wide resection of the tumor and reconstruction with a pedicle flap/ free flap is widely used. This study was conducted to investigate if young age at the time of diagnosis of oral cancer requiring this treatment confers a worse prognosis.
Methods
A total of 2339 patients who underwent resections for oral cancer from 2004 to 2005 were identified from The Taiwan National Health Insurance Research Database. Survival analysis, Cox proportional regression model, propensity scores, and sensitivity test were used to evaluate the association between 5-year survival rates and age.
Results
In the Cox proportional regression model, the older age group (>65 years) had the worst survival rate (hazard ratio [HR], 1.80; 95% confidence interval [CI], 1.45-2.22; P<0.001). When analyzed using the propensity scores, the adjusted 5-year survival rates were also poorer for oral cancer patients with older age (>65 years), compared to those with younger age (<45 years) (P<0.001). In sensitivity test, the adjusted hazard ratio remained no statistically elevated in the younger age group (<45 years).
Conclusions
For those oral cancer patients who underwent wide excision and reconstruction, young age did not confer a worse prognosis using a Cox proportional regression model, propensity scores or sensitivity test. Young oral cancer patients may be treated using general guidelines and do not require more aggressive treatment.
doi:10.1371/journal.pone.0075855
PMCID: PMC3784390  PMID: 24086646
7.  Differential Impact of Statin on New-Onset Diabetes in Different Age Groups: A Population-Based Case-Control Study in Women from an Asian Country 
PLoS ONE  2013;8(8):e71817.
Background
Statins reduce cardiovascular risks but increase the risk of new-onset diabetes (NOD). The aim of this study is to determine what effect, if any, statins have on the risk of NOD events in a population-based case-control study. An evaluation of the relationship between age and statin-exposure on NOD risks was further examined in a female Asian population.
Method
In a nationwide case-controlled study, the authors assessed 1065 female NOD patients and 10650 controls with matching ages, genders and physician visit dates. The impact of statin-exposure on NOD was examined through multiple logistic regression models. Subgroup analysis for exploring the risk of NOD and statin-exposure in different age groups was performed.
Results
Statin-exposure was statistically significantly associated with increased new-onset diabetes risks using multivariate analysis. Interaction effect between age and statin-exposure on NOD risk was noted. For atorvastatin, the risk of cDDDs>60 was highest among the 55–64 year-olds (adjusted odds ratio [OR], 8.0; 95% confidence interval [CI], 2.57–24.90). For rosuvastatin, the risk of cDDDs>60 was highest among the 40–54 year-olds (adjusted OR, 14.8; 95% CI, 2.27–96.15). For simvastatin, the risk of cDDDs>60 was highest among the 55–64 year-olds (adjusted OR, 15.8; 95% CI, 5.77–43.26). For pravastatin, the risk of cDDDs>60 was highest among the 55–64 year-olds (adjusted OR, 14.0; 95% CI, 1.56–125.18).
Conclusions
This population-based study found that statin use is associated with an increased risk of NOD in women. The risk of statin-related NOD was more evident for women aged 40–64 years compared to women aged 65 or more, and was cumulative-dose dependent. The use of statins should always be determined by weighing the clinical benefits and potential risks for NOD, and the patients should be continuously monitored for adverse effects.
doi:10.1371/journal.pone.0071817
PMCID: PMC3741277  PMID: 23951249
8.  Disparities in Oral Cancer Survival among Mentally Ill Patients 
PLoS ONE  2013;8(8):e70883.
Background
Many studies have reported excess cancer mortality in patients with mental illness. However, scant studies evaluated the differences in cancer treatment and its impact on survival rates among mentally ill patients. Oral cancer is one of the ten most common cancers in the world. We investigated differences in treatment type and survival rates between oral cancer patients with mental illness and without mental illness.
Methods
Using the National Health Insurance (NHI) database, we compared the type of treatment and survival rates in 16687 oral cancer patients from 2002 to 2006. The utilization rate of surgery for oral cancer was compared between patients with mental illness and without mental illness using logistic regression. The Cox proportional hazards model was used for survival analysis.
Results
Oral cancer patients with mental disorder conferred a grave prognosis, compared with patients without mental illness (hazard ratios [HR] = 1.58; 95% confidence interval [CI] = 1.30–1.93; P<0.001). After adjusting for patients’ characteristics and hospital characteristics, patients with mental illness were less likely to receive surgery with or without adjuvant therapy (odds ratio [OR] = 0.47; 95% CI = 0.34–0.65; P<0.001). In multivariate analysis, oral cancer patients with mental illness carried a 1.58-times risk of death (95% CI = 1.30–1.93; P<0.001).
Conclusions
Oral cancer patients with mental illness were less likely to undergo surgery with or without adjuvant therapy than those without mental illness. Patients with mental illness have a poor prognosis compared to those without mental illness. To reduce disparities in physical health, public health strategies and welfare policies must continue to focus on this vulnerable group.
doi:10.1371/journal.pone.0070883
PMCID: PMC3737269  PMID: 23951029
9.  Epidemiology of Idiopathic Central Serous Chorioretinopathy in Taiwan, 2001–2006: A Population-based Study 
PLoS ONE  2013;8(6):e66858.
Objectives
The epidemiology of idiopathic central serous chorioretinopathy (CSCR) is not well understood in an Asian population. The present study aimed to investigate the incidence and risk factors for corticosteroid-unrelated CSCR using Taiwan’s National Health Insurance Research Database.
Methods and Results
From 2001 to 2006, a total of 786 patients (500 [63.6%] males) who were newly diagnosed with CSCR, aged from 20 to 64 years and had no history of corticosteroid prescription were identified as incident cases of idiopathic CSCR. 3606 age-, gender-, and enrollment time-matched subjects were randomly selected as the control group. The mean annual incidence was 0.21‰ (0.27‰ for males, and 0.15‰ for females; P<0.001), with a male/female ratio of 1.74. The peak incidence was in the 35- to 39-year-old age group (0.30‰), followed by the 40- to 44-year-old age group (0.26‰). Males had a significantly higher mean annual incidence than female only in the middle age groups. Conditional logistic regression was used to estimate the odds ratios (ORs) for potential risk factors of idiopathic CSCR. Only exposure to anti-anxiety drugs (OR, 1.63; 95% confidence interval, 1.09–2.44) was found to be independently associated with idiopathic CSCR among males. No risk factors of idiopathic CSCR were found for females.
Conclusions
This study provides the nationwide, population-based data on the incidence of idiopathic CSCR in adult Asians, and suggests that exposure to anti-anxiety drugs is an independent risk factor for idiopathic CSCR among males.
doi:10.1371/journal.pone.0066858
PMCID: PMC3691239  PMID: 23826160
10.  Association between Provider Volume and Healthcare Expenditures of Patients with Oral Cancer in Taiwan: A Population-Based Study 
PLoS ONE  2013;8(6):e65077.
Background
Oral cancer requires considerable utilization of healthcare services. Wide resection of the tumor and reconstruction with free flap are widely used. Due to high recurrence rate, close follow-up is mandatory. This study was conducted to explore the relationship between the healthcare expenditure of oncological surgery and one-year follow up and provider volume.
Methods
From the National Health Insurance Research Database published by the Taiwanese National Health Research Institute, the authors selected a total of 1300 oral cancer patients who underwent tumor resection and free flap reconstruction in 2008. Hierarchical linear regression analysis was subsequently performed to explore the relationship between provider volume and expenditures of oncological surgery and one-year follow-up period. Emergency department (ED) visits and 30-day readmission rates were also analyzed.
Results
The mean expenditure for oncological surgery was $11080±4645 (all costs are given in U.S. dollars) and $10129±9248 for one-year follow up. For oncological surgery expenditure, oral cancer patients treated by low-volume surgeons had an additional $845 than those in high-volume surgeons in mixed model. For one-year follow-up expenditure, patients in low-volume hospitals had an additional $3439 than those in high-volume hospitals; patient in low-volume surgeons and medium-volume surgeons incurred an additional expenditure of $2065 and $1811 than those in high-volume surgeons. Oral cancer patients treated in low-volume hospitals incurred higher risk of 30-day readmission rate (odds ratio, 6.6; 95% confidence interval, 1.6–27).
Conclusions
After adjusting for physician, hospital, and patient characteristics, low-volume provider performing wide excision with reconstructive surgery in oral cancer patients incurred significantly higher expenditure for oncological surgery and one-year healthcare per patient than did others with higher volumes. Treatment strategies adapted by high-volume providers should be further analyzed.
doi:10.1371/journal.pone.0065077
PMCID: PMC3672134  PMID: 23750234
11.  The Role of Secondary Cytoreductive Surgery in Patients with Recurrent Epithelial Ovarian, Tubal, and Peritoneal Cancers: A Comparative Effectiveness Analysis 
The Oncologist  2012;17(6):847-855.
This study aims to provide supportive evidence for previous reports that secondary cytoreductive surgery may increase overall survival for patients with recurrent epithelial, tubal, and peritoneal cancers by using comparative effectiveness methods to adjust for confounding.
Background.
All published reports concerning secondary cytoreductive surgery for relapsed ovarian cancer have essentially been observational studies. However, the validity of observational studies is usually threatened from confounding by indication. We sought to address this issue by using comparative effectiveness methods to adjust for confounding.
Methods.
Using a prospectively collected administrative health care database in a single institution, we identified 1,124 patients diagnosed with recurrent epithelial, tubal, and peritoneal cancers between 1990 and 2009. Effectiveness of secondary cytoreductive surgery using the conventional Cox proportional hazard model, propensity score, and instrumental variable were compared. Sensitivity analyses for residual confounding were explored using an array approach.
Results.
Secondary cytoreductive surgery prolonged overall survival with a hazard ratio (95% confidence interval) of 0.76 (range 0.66–0.87), using the Cox proportional hazard model. Propensity score methods produced comparable results: 0.75 (range 0.64–0.86) by nearest matching, 0.73 (0.65–0.82) by quintile stratification, 0.71 (0.65–0.77) by weighting, and 0.72 (0.63–0.83) by covariate adjustment. The instrumental variable method also produced a comparable estimate: 0.75 (range 0.65–0.86). Sensitivity analyses revealed that the true treatment effects may approach the null hypothesis if the association between unmeasured confounders and disease outcome is high.
Conclusions.
This comparative effectiveness study provides supportive evidence for previous reports that secondary cytoreductive surgery may increase overall survival for patients with recurrent epithelial, tubal, and peritoneal cancers.
doi:10.1634/theoncologist.2011-0373
PMCID: PMC3380884  PMID: 22591974
Instrumental variable; Ovarian cancer; Propensity score; Secondary cytoreductive surgery
12.  Dental prosthetic treatment needs of inpatients with schizophrenia in Taiwan: a cross-sectional study 
BMC Oral Health  2013;13:8.
Background
The need to obtain information on the dental prosthetic treatment needs (DPTNs) of inpatients with schizophrenia is unrecognized. This study aims to assess the DPTNs of this population and investigate the association between these needs and related factors.
Methods
The results of an oral health survey involving 1,103 schizophrenic adult inpatients in a long-term care institution in Taiwan were used. Chi-square tests and multiple logistic analyses were used to measure the independent effects of the characteristics of each subject on their DPTNs.
Results
Of the subjects, 805 (73.0%) were men and 298 (27.0%) were women. The mean age was 50.8 years. A total of 414 (37.5%) required fixed prosthesis, whereas 700 (63.5%) needed removable prosthesis. Multivariate analyses show that fixed prosthesis is associated with age only after adjusting for other potential independent variables. Older subjects who had a lower educational attainment or a longer length of stay required removable prosthesis.
Conclusions
The findings of this study show that the DPTNs of schizophrenic inpatients are not being met. Therefore, a special approach to the dental prosthetic treatment of these patients should be developed.
doi:10.1186/1472-6831-13-8
PMCID: PMC3554600  PMID: 23331491
Fixed prosthesis; Removable prosthesis; Treatment needs; Schizophrenia
13.  Pneumococcal Pneumonia and the Risk of Stroke: A Population-Based Follow-Up Study 
PLoS ONE  2012;7(12):e51452.
Background
To investigate the risk of developing stroke in patients hospitalized following a diagnosis of pneumococcal pneumonia.
Methods
The study cohorts comprised of patients hospitalized with a principal diagnosis of pneumococcal pneumonia (n  = 745), with a random sampling of control individuals in 2004 (n  = 1490). The Cox proportional hazard model was used to compare the stroke-free survival rate between the cohorts after adjusting for possible confounding and risk factors for a two-year follow up. Instrumental variable analysis (IVA) was used to address potential biases associated with measured and unmeasured confounding variables.
Results
Of the 153 patients with stroke, 80 (10.7%) were from the pneumococcal pneumonia cohort, and 73 (4.9%) were from the control group. The risk of stroke was 3.65 times higher (95% confidence interval, 2.25–5.90; P<0.001) in patients with pneumococcal pneumonia after adjusting for patient characteristics, co-morbidities, geographic region, urbanization level of residence, and socioeconomic status during the first year. IVA showed an additional 14% risk of stroke for pneumococcal pneumonia patients (odds ratio = 1.14; 95% CI, 1.02–1.26, P = 0.032).
Conclusions
Patients with pneumococcal pneumonia carry an increased risk for stroke than the general population. Further studies are warranted for developing better diagnostic and follow-up strategies for patients with increased risk.
doi:10.1371/journal.pone.0051452
PMCID: PMC3520842  PMID: 23251538
14.  The Impact of Influenza Vaccinations on the Adverse Effects and Hospitalization Rate in the Elderly: A National Based Study in an Asian Country 
PLoS ONE  2012;7(11):e50337.
Objectives
To examine the risk of adverse effects of special interest in persons vaccinated against seasonal influenza compared with unvaccinated persons aged 65 and above.
Methods
We retrospectively observed 41,986 vaccinated elderly persons and 50,973 unvaccinated elderly persons in Taiwan from October 1, 2008, through September 30, 2009, using the National Health Insurance database. Neurological and autoimmune disorders and one-year hospitalization rates and in-hospital mortality rates were analyzed according to the vaccination status. Propensity score analysis was used to assess the relationship between adverse outcomes, hospitalization rates, and vaccination status.
Results
45% of the elderly received influenza vaccination. Multiple logistic regression showed that the probability of being vaccinated was related to more patients visiting for URI symptoms (odds ratio (OR), 1.03; 95% CI, 1.02–1.03), men (OR, 1.15; 95% CI, 1.12–1.17), increased age (OR, 1.02; 95% CI, 1.02–1.03), and more comorbidities (OR, 1.2; 95% CI, 1.17–1.23). There were no statistical differences in neurological and autoimmune diseases between the vaccinated and unvaccinated individuals using propensity score analysis, but vaccinated persons had a reduced hospitalization rate of 19% (odds ratio [OR], 0.81; 95% CI, 0.77–0.84) for the first six-months and 13% for one-year of follow-up (OR, 0.87; 95% CI, 0.85–0.9).
Conclusions
Based on data from the one-year follow-ups among 93,049 elderly persons in Taiwan, reassuring results for selected neurological and autoimmune diseases were found among the vaccinated individuals after adjusting other factors. Influenza vaccination decreased the risk for hospitalization. Public health strategies must continue to improve the influenza vaccination rate among the elderly with information based upon tangible evidence.
doi:10.1371/journal.pone.0050337
PMCID: PMC3508921  PMID: 23209714
15.  Infectious Complications in Head and Neck Cancer Patients Treated with Cetuximab: Propensity Score and Instrumental Variable Analysis 
PLoS ONE  2012;7(11):e50163.
Background
To compare the infection rates between cetuximab-treated patients with head and neck cancers (HNC) and untreated patients.
Methodology
A national cohort of 1083 HNC patients identified in 2010 from the Taiwan National Health Insurance Research Database was established. After patients were followed for one year, propensity score analysis and instrumental variable analysis were performed to assess the association between cetuximab therapy and the infection rates.
Results
HNC patients receiving cetuximab (n = 158) were older, had lower SES, and resided more frequently in rural areas as compared to those without cetuximab therapy. 125 patients, 32 (20.3%) in the group using cetuximab and 93 (10.1%) in the group not using it presented infections. The propensity score analysis revealed a 2.3-fold (adjusted odds ratio [OR] = 2.27; 95% CI, 1.46–3.54; P = 0.001) increased risk for infection in HNC patients treated with cetuximab. However, using IVA, the average treatment effect of cetuximab was not statistically associated with increased risk of infection (OR, 0.87; 95% CI, 0.61–1.14).
Conclusions
Cetuximab therapy was not statistically associated with infection rate in HNC patients. However, older HNC patients using cetuximab may incur up to 33% infection rate during one year. Particular attention should be given to older HNC patients treated with cetuximab.
doi:10.1371/journal.pone.0050163
PMCID: PMC3509146  PMID: 23209663
16.  Surveillance on secular trends of incidence and mortality for device–associated infection in the intensive care unit setting at a tertiary medical center in Taiwan, 2000–2008: A retrospective observational study 
BMC Infectious Diseases  2012;12:209.
Background
Device–associated infection (DAI) plays an important part in nosocomial infection. Active surveillance and infection control are needed to disclose the specific situation in each hospital and to cope with this problem effectively. We examined the rates of DAI by antimicrobial-resistant pathogens, and 30–day and in–hospital mortality in the intensive care unit (ICU).
Methods
Prospective surveillance was conducted in a mixed medical and surgical ICU at a major teaching hospital from 2000 through 2008. Trend analysis was performed and logistic regression was used to assess prognostic factors of mortality.
Results
The overall rate of DAIs was 3.03 episodes per 1000 device–days. The most common DAI type was catheter–associated urinary tract infection (3.76 per 1000 urinary catheter–days). There was a decrease in DAI rates in 2005 and rates of ventilator–associated pneumonia (VAP, 3.18 per 1000 ventilator–days) have remained low since then (p < 0.001). The crude rates of 30–day (33.6%) and in–hospital (52.3%) mortality, as well as infection by antibiotic-resistant VAP pathogens also decreased. The most common antimicrobial-resistant pathogens were methicillin–resistant Staphylococcus aureus (94.9%) and imipenem–resistant Acinetobacter baumannii (p < 0.001), which also increased at the most rapid rate. The rate of antimicrobial resistance among Enterobacteriaceae also increased significantly (p < 0.05). After controlling for potentially confounding factors, the DAI was an independent prognostic factor for both 30–day mortality (OR 2.51, 95% confidence interval [CI] 1.99–3.17, p = 0.001) and in–hospital mortality (OR 3.61, 95% CI 2.10–3.25, p < 0.001).
Conclusions
The decrease in the rate of DAI and infection by resistant bacteria on the impact of severe acute respiratory syndrome can be attributed to active infection control and improved adherence after 2003.
doi:10.1186/1471-2334-12-209
PMCID: PMC3458996  PMID: 22963041
Surveillance; Secular trend; Device–associated infection; Intensive care unit; Infection control
17.  Cardiac vagal control and theoretical models of co-occurring depression and anxiety: A cross-sectional psychophysiological study of community elderly 
BMC Psychiatry  2012;12:93.
Background
In order to elucidate the complex relationship between co-occurring depression and anxiety with cardiac autonomic function in the elderly, this study examined the correlation between cardiac vagal control (CVC) and pre-defined, theoretical factors from the Hospital Anxiety and Depression Scale (HADS).
Methods
Three hundred fifty-four randomly selected Chinese male subjects aged ≥65 years and living in the community were enrolled. CVC was measured using a frequency-domain index of heart rate variability.
Results
Confirmatory factor analysis showed that the flat tripartite model of HADS provided a modest advantage in model fit when compared with other theoretical factor solutions. In the flat tripartite model, there was a significant negative association between anhedonic depression and CVC. In contrast, autonomic anxiety showed a significant positive correlation with CVC. In the hierarchical tripartite model, negative affectivity was not directly associated with CVC; instead, it had positive and negative indirect effects on CVC via autonomic anxiety and anhedonic depression, respectively. As scores for negative affectivity increased, these specific indirect effects diminished.
Conclusions
Among competing models of co-occurring depression and anxiety, constructs from tripartite models demonstrate fair conformity with the data but unique and distinct correlations with CVC. Negative affectivity may determine the relationship of anhedonic depression and autonomic anxiety with CVC. Separating affective symptoms under the constructs of the tripartite models helps disentangle complex associations between co-occurring depression and anxiety with CVC.
doi:10.1186/1471-244X-12-93
PMCID: PMC3499166  PMID: 22846457
Cardiac vagal control; Co-occurring depression and anxiety; Heart rate variability; The Hospital Anxiety and Depression Scale; Tripartite model
18.  Multivariate Analyses to Assess the Effects of Surgeon and Hospital Volume on Cancer Survival Rates: A Nationwide Population-Based Study in Taiwan 
PLoS ONE  2012;7(7):e40590.
Background
Positive results between caseloads and outcomes have been validated in several procedures and cancer treatments. However, there is limited information available on the combined effects of surgeon and hospital caseloads. We used nationwide population-based data to explore the association between surgeon and hospital caseloads and survival rates for major cancers.
Methodology
A total of 11677 patients with incident cancer diagnosed in 2002 were identified from the Taiwan National Health Insurance Research Database. Survival analysis, the Cox proportional hazards model, and propensity scores were used to assess the relationship between 5-year survival rates and different caseload combinations.
Results
Based on the Cox proportional hazard model, cancer patients treated by low-volume surgeons in low-volume hospitals had poorer survival rates, and hazard ratios ranged from 1.3 in head and neck cancer to 1.8 in lung cancer after adjusting for patients’ demographic variables, co-morbidities, and treatment modality. When analyzed using the propensity scores, the adjusted 5-year survival rates were poorer for patients treated by low-volume surgeons in low-volume hospitals, compared to those treated by high-volume surgeons in high-volume hospitals (P<0.005).
Conclusions
After adjusting for differences in the case mix, cancer patients treated by low-volume surgeons in low-volume hospitals had poorer 5-year survival rates. Payers may implement quality care improvement in low-volume surgeons.
doi:10.1371/journal.pone.0040590
PMCID: PMC3398946  PMID: 22815771
19.  Increased Risk of Vascular Events in Emergency Room Patients Discharged Home with Diagnosis of Dizziness or Vertigo: A 3-Year Follow-Up Study 
PLoS ONE  2012;7(4):e35923.
Background
Dizziness and vertigo symptoms are commonly seen in emergency room (ER). However, these patients are often discharged without a definite diagnosis. Conflicting data regarding the vascular event risk among the dizziness or vertigo patients have been reported. This study aims to determine the risk of developing stroke or cardiovascular events in ER patients discharged home with a diagnosis of dizziness or vertigo.
Methodology
A total of 25,757 subjects with at least one ER visit in 2004 were identified. Of those, 1,118 patients were discharged home with a diagnosis of vertigo or dizziness. A Cox proportional hazard model was performed to compare the three-year vascular event-free survival rates between the dizziness/vertigo patients and those without dizziness/vertigo after adjusting for confounding and risk factors.
Results
We identified 52 (4.7%) vascular events in patients with dizziness/vertigo and 454 (1.8%) vascular events in patients without dizziness/vertigo. ER patients discharged home with a diagnosis of vertigo or dizziness had 2-fold (95% confidence interval [CI], 1.35–2.96; p<0.001) higher risk of stroke or cardiovascular events after adjusting for patient characteristics, co-morbidities, urbanization level of residence, individual socio-economic status, and initially taking medications after the onset of dizziness or vertigo during the first year.
Conclusions
ER patients discharged home with a diagnosis of dizziness or vertigo were at a increased risk of developing subsequent vascular events than those without dizziness/vertigo after the onset of dizziness or vertigo. Further studies are warranted for developing better diagnostic and follow-up strategies in increased risk patients.
doi:10.1371/journal.pone.0035923
PMCID: PMC3338765  PMID: 22558272
20.  CENTRAL VERSUS AMBULATORY BLOOD PRESSURE IN THE PREDICTION OF ALL-CAUSE AND CARDIOVASCULAR MORTALITIES 
Journal of hypertension  2011;29(3):454-459.
OBJECTIVES
Central systolic (SBP-C) and/or pulse pressure (PP-C) better predicts cardiovascular events than does peripheral blood pressure. The present study compared the prognostic significance of office central blood pressure with multiple measurements of out-of-office ambulatory peripheral blood pressure, with reference to office peripheral systolic (SBP-B) or pulse pressure (PP-B).
METHODS
In a community-based population of 1014 healthy participants, SBP-C and PP-C were estimated using carotid tonometry, and 24-hour systolic (SBP-24h) and pulse pressure (PP-24h) were obtained from 24-hour ambulatory blood pressure monitoring. Associations of SBP-B, PP-B, SBP-C, PP-C, SBP-24h, and PP-24 with all-cause and cardiovascular mortalities over a median follow-up of 15-years were examined by Cox regression analysis.
RESULTS
In multivariate analyses accounting for age, sex, body mass index, smoking, fasting plasma glucose, and total cholesterol/high-density lipoprotein cholesterol, only PP-C [hazard ratio 1.16, 95% confidence interval 1.01–1.32, per 1 standard deviation increment] was significantly predictive of all-cause mortality, while all but PP-B were significantly predictive of cardiovascular mortality. When SBP-B was simultaneously included in the models, SBP-24h [2.01, 1.42–2.85] and SBP-C [1.71, 1.21–2.40] remained significantly predictive of cardiovascular mortality. When SBP-C was simultaneously included in the models, SBP-24h [1.71, 1.16–2.52] remained significantly predictive of cardiovascular mortality.
CONCLUSION
Office central blood pressure is more valuable than office peripheral blood pressure in the prediction of all-cause and cardiovascular mortalities. Out-of-office ambulatory peripheral blood pressure (SBP-24h) may be superior to central blood pressure in the prediction of cardiovascular mortality, but PP-C may better predict all-cause mortality than SBP-24h or PP-24h.
doi:10.1097/HJH.0b013e3283424b4d
PMCID: PMC3086730  PMID: 21252703
Ambulatory blood pressure; Central blood pressure; Pulse pressure; Target organ damage; Mortality
21.  Completeness and timeliness of tuberculosis notification in Taiwan 
BMC Public Health  2011;11:915.
Tuberculosis (TB) is a notifiable disease by the Communicable Disease Control Law in Taiwan. Several measures have been undertaken to improve reporting of TB but the completeness and timeliness of TB notification in Taiwan has not yet been systemically evaluated.
Methods
To assess completeness and timeliness of TB notification, potential TB cases diagnosed by health care facilities in the year 2005-2007 were identified using the reimbursement database of national health insurance (NHI), which has 99% population coverage in Taiwan. Potential TB patients required notification were defined as those who have TB-related ICD-9 codes (010-018) in the NHI reimbursement database in 2005-2007, who were not diagnosed with TB in previous year, and who have been prescribed with 2 or more types of anti-TB drugs. Each potential TB case was matched to the national TB registry maintained at Taiwan Centers for Disease Control (CDC) by using national identity number or, if non-citizen, passport number to determine whether the patients had been notified to local public health authorities and Taiwan CDC. The difference in the number of days between date of anti-tuberculosis treatment and date of notification was calculated to determine the timeliness of TB reporting.
Results
Of the 57,405 TB patients who were prescribed with 2 or more anti-tuberculosis drugs, 55,291 (96.3%) were notified to National TB Registry and 2,114 (3.7%) were not. Of the 55,291 notified cases, 45,250 (81.8%) were notified within 7 days of anti-tuberculosis treatment (timely reporting) and 10,041(18.2%) after 7 days (delayed reporting). Factors significantly associated with failure of notification are younger age, previously notified cases, foreigner, those who visited clinics and those who visited health care facilities only once or twice in 6 months.
Conclusion
A small proportion of TB cases were not notified and a substantial proportion of notified TB cases had delayed reporting, findings with implication for strengthening surveillance of tuberculosis in Taiwan. Countries where the completeness and timeliness of TB notification has not yet been evaluated should take similar action to strengthen surveillance of TB.
doi:10.1186/1471-2458-11-915
PMCID: PMC3260335  PMID: 22151346
Completeness; Notification; Reporting; Tuberculosis
22.  Epidemiological survey of orthopedic joint dislocations based on nationwide insurance data in Taiwan, 2000-2005 
Background
The epidemiology of acute orthopedic dislocations is poorly understood. A nationwide database provides a valuable resource for examining this issue in the Taiwanese population.
Methods
A 6-year retrospective cohort study of 1,000,000 randomly-sampled beneficiaries from the year 2005 was used as the original population. Based on the hospitalized and ambulatory data, the concomitant ICD9-CM diagnosis codes and treatment codes were evaluated and classified into 8 and 3 major categories, respectively. The cases matching both inclusive criteria of dislocation-related diagnosis codes and treatment codes were defined as incident cases.
Results
During 2000-2005, the estimated annual incidence (per 100,000 population) of total orthopedic dislocations in Taiwan was 42.1 (95%CI: 38.1-46.1). The major cause of these orthopedic dislocations was traffic accidents (57.4%), followed by accident falls (27.5%). The annual incidence dislocation by location was shoulder, 15.3; elbow, 7.7; wrist, 3.5; finger, 4.6; hip, 5.2; knee, 1.4; ankle, 2.0; and foot, 2.4. Approximately 16% of shoulder dislocations occurred with other concomitant fractures, compared with 17%, 53%, 16%, 76% and 52%, respectively, of dislocated elbow, wrist, hip, knee, and ankle cases. Including both simple and complex dislocated cases, the mean medical cost was US$612 for treatment of a shoulder dislocation, $504 for the elbow, $1,232 for the wrist, $1,103 for the hip, $1,888 for the knee, and $1,248 for the ankle.
Conclusions
In Taiwan, three-quarters of all orthopedic dislocations were of the upper limbs. The most common complex fracture-dislocation was of the knee, followed by the wrist and the ankle. Those usually needed a treatment combined with open reduction of fractures and resulted in a higher direct medical expenditure.
doi:10.1186/1471-2474-12-253
PMCID: PMC3228707  PMID: 22053727
incidence; orthopedic dislocation
23.  CENTRAL OR PERIPHERAL SYSTOLIC OR PULSE PRESSURE: WHICH BEST RELATES TO TARGET-ORGANS AND FUTURE MORTALITY? 
Journal of hypertension  2009;27(3):461-467.
OBJECTIVE
We examined the relationship between brachial and central carotid pressures and target organ indices at baseline, and their association with future mortality.
METHODS
We examined cross-sectionally and longitudinally the relations of baseline systolic and pulse pressures in central (calibrated tonometric carotid pulse) and peripheral (brachial, mercury sphygmomanometer) arteries to baseline left ventricular mass, carotid intima-media thickness, estimated glomerular filtration rate, and 10-year all-cause and cardiovascular mortality in 1272 participants (47% women, aged 30–79 years) from a community of homogeneous Chinese.
RESULTS
Left ventricular mass was more strongly related to central and peripheral systolic pressures than pulse pressures. Intima-media thickness and glomerular filtration rate were more strongly related to central pressures than peripheral pressures. A total of 130 participants died, 37 from cardiovascular causes. In univariate analysis, all four blood pressure variables significantly predicted all-cause and cardiovascular mortality. Each blood pressure variable was entered into the multivariate models, both individually and jointly with another blood pressure variable. With adjustment for age, sex, heart rate, body mass index, current smoking, glucose, total cholesterol/high-density-lipoprotein-cholesterol ratio, carotid-femoral pulse wave velocity, left ventricular mass, intima-media thickness, and glomerular filtration rate, only central systolic pressure consistently independently predicted cardiovascular mortality (Hazards ratio=1.30 per 10 mmHg). No significant sex interactions were observed in all analyses.
CONCLUSION
Systolic and pulse pressures relate differently to different target organs. Central systolic pressure is more valuable than other blood pressure variables in predicting cardiovascular mortality.
PMCID: PMC3178100  PMID: 19330899
Pulse pressure; Central blood pressure; Glomerular filtration rate; Mortality
24.  Treatment incidence of and medical utilization for hospitalized subjects with pathologic fractures in Taiwan-Survey of the 2008 National Health Insurance data 
Background
Almost all studies of pathologic fractures have been conducted based on patients with tumours and hospital-based data; however, in the present study, a nationwide epidemiological survey of pathologic fractures in Taiwan was performed and the medical utilization was calculated.
Methods
All claimants of Taiwan's National Health Insurance (NHI) Program in 2008 were included in the target population of this descriptive cross-sectional study. The registration and inpatient expenditure claims data by admission of all hospitalized subjects of the target population were examined and the concomitant International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes were evaluated and classified into seven major categories of fracture.
Results
A total of 5,244 incident cases of pathologic fracture were identified from the 2008 hospitalized patient claims data. The incidence of pathologic fracture of the humerus, distal radius/ulna, vertebrae, femoral neck, other part of the femur, and tibia/fibula was 0.67, 0.08, 10.58, 1.11, 0.56, and 0.11 per 100,000 people, respectively, and patients with those fractures were hospitalized for 43.9 ± 42.9, 31.1 ± 32.9, 29. 4 ± 34.4, 43.3 ± 41.2, 42.4 ± 38.1, and 42.0 ± 32.8 days, respectively, incurring an average medical cost of US$11,049 ± 12,730, US$9,181 ± 12,115, US$6,250 ± 8,021, US$9,619 ± 8,906, US$10,646 ± 11,024, and US$9,403 ± 9,882, respectively. The percentage of patients undergoing bone surgery for pathologic fracture of the humerus, radius/ulna, vertebrae, femoral neck, other part of the femur, and tibia/fibula was 31.2%, 44.4%, 11.3%, 46.5%, 48.4%, and 52.5% respectively.
Conclusions
Comparing Taiwan to other countries, this study observed for Taiwan higher medical utilization and less-aggressive surgical intervention for patients hospitalized with pathologic fractures.
doi:10.1186/1472-6963-11-230
PMCID: PMC3196905  PMID: 21939550
Incidence; utilization; pathologic fracture
25.  Survival rate in nasopharyngeal carcinoma improved by high caseload volume: a nationwide population-based study in Taiwan 
Background
Positive correlation between caseload and outcome has previously been validated for several procedures and cancer treatments. However, there is no information linking caseload and outcome of nasopharyngeal carcinoma (NPC) treatment. We used nationwide population-based data to examine the association between physician case volume and survival rates of patients with NPC.
Methods
Between 1998 and 2000, a total of 1225 patients were identified from the Taiwan National Health Insurance Research Database. Survival analysis, the Cox proportional hazards model, and propensity score were used to assess the relationship between 10-year survival rates and physician caseloads.
Results
As the caseload of individual physicians increased, unadjusted 10-year survival rates increased (p < 0.001). Using a Cox proportional hazard model, patients with NPC treated by high-volume physicians (caseload ≥ 35) had better survival rates (p = 0.001) after adjusting for comorbidities, hospital, and treatment modality. When analyzed by propensity score, the adjusted 10-year survival rate differed significantly between patients treated by high-volume physicians and patients treated by low/medium-volume physicians (75% vs. 61%; p < 0.001).
Conclusions
Our data confirm a positive volume-outcome relationship for NPC. After adjusting for differences in the case mix, our analysis found treatment of NPC by high-volume physicians improved 10-year survival rate.
doi:10.1186/1748-717X-6-92
PMCID: PMC3170221  PMID: 21835030

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