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author:("Chou, pests")
1.  The Low Proportion and Associated Factors of Involuntary Admission in the Psychiatric Emergency Service in Taiwan 
PLoS ONE  2015;10(6):e0129204.
The involuntary admission regulated under the Mental Health Act has become an increasingly important issue in the developed countries in recent years. Most studies about the distribution and associated factors of involuntary admission were carried out in the western countries; however, the results may vary in different areas with different legal and socio-cultural backgrounds.
The aim of this study was to investigate the proportion and associated factors of involuntary admission in a psychiatric emergency service in Taiwan.
The study cohort included patients admitted from a psychiatric emergency service over a two-year period. Demographic, psychiatric emergency service utilization, and clinical variables were compared between those who were voluntarily and involuntarily admitted to explore the associated factors of involuntary admission.
Among 2,777 admitted patients, 110 (4.0%) were involuntarily admitted. Police referrals and presenting problems as violence assessed by psychiatric nurses were found to be associated with involuntary admission. These patients were more likely to be involuntarily admitted during the night shift and stayed longer in the psychiatric emergency service.
The proportion of involuntary admissions in Taiwan was in the lower range when compared to Western countries. Dangerous conditions evaluated by the psychiatric nurses and police rather than diagnosis made by the psychiatrists were related factors of involuntary admission. As it spent more time to admit involuntary patients, it was suggested that multidisciplinary professionals should be included in and educated for during the process of involuntary admission.
PMCID: PMC4457903  PMID: 26046529
2.  Thyroid Fine-Needle Aspiration Biopsy and Thyroid Cancer Diagnosis: A Nationwide Population-Based Study 
PLoS ONE  2015;10(5):e0127354.
Thyroid cancer is the most common endocrine gland malignancy and fine-needle aspiration biopsy is widely used for thyroid nodule evaluation. Repeated aspiration biopsies are needed due to plausible false-negative results. This study aimed to investigate the overall relationship between aspiration biopsy and thyroid cancer diagnosis, and to explore factors related to shorter diagnostic time.
This nationwide retrospective cohort study retrieved data from the Longitudinal Health Insurance Database in Taiwan. Subjects without known thyroid malignancies and who received the first thyroid aspiration biopsy after 2004 were followed-up from 2004 to 2009 (n = 7700). Chi-square test, Kaplan-Meier survival analysis, and Cox proportional hazards model were used for data analysis.
Of 7700 newly-aspirated patients, 276 eventually developed thyroid cancer (malignancy rate 3.6%). Among the 276 patients with thyroid cancer, 61.6% underwent only one aspiration biopsy and 81.2% were found within the first year after the initial aspiration. Cox proportional hazards model revealed that aspiration frequency (HR 1.07, 95% CI 1.06–1.08), ultrasound frequency (HR 1.02, 95% CI 1.01–1.03), older age, male sex, and aspiration biopsies arranged by surgery, endocrinology or otolaryngology subspecialties were all associated with shorter time to thyroid cancer diagnosis.
About 17.4% of thyroid cancer cases received more than two aspiration biopsies and 18.8% were diagnosed one year after the first biopsy. Regular follow-up with repeated aspiration or ultrasound may be required for patients with clinically significant thyroid nodules.
PMCID: PMC4447367  PMID: 26020790
3.  Tonsillectomy and the Risk for Deep Neck Infection—A Nationwide Cohort Study 
PLoS ONE  2015;10(4):e0117535.
Although the tonsils contribute to first line immunity against foreign pathogens in the upper aero-digestive tract, the association of tonsillectomy with the risk of deep neck infection remains unclear. The aim of this study was to assess the incidence rate and risk of deep neck infection among patients who had undergone a tonsillectomy.
This retrospective cohort study evaluated all patients who had undergone tonsillectomy between 2001 and 2009 as identified from the Taiwan National Health Insurance Research Database. For each post-tonsillectomy patient, 10 age-, sex-, and index date-matched controls without a history of tonsillectomy were randomly selected. Cox Proportional hazard model and propensity score model were performed to evaluate the association between tonsillectomy and deep neck infection after adjusting for demographic and clinical data.
There were 34 (71.6 cases per 100,000 person-years) and 174 (36.6 cases per 100,000 person-years) patients that developed deep neck infection in the tonsillectomized and comparison cohorts, respectively. After adjusting for covariates, patients who had undergone a tonsillectomy had a 1.71-fold greater risk of deep neck infection by both Cox proportional hazard model (95% confidence interval, 1.13-2.59) and propensity score model (95% confidence interval, 1.10-2.66). This association was not altered regardless of the indication for tonsillectomy (i.e. chronic/recurrent tonsillitis or sleep apnea/hypertrophy of tonsil) (p = 0.9797).
Based on our review of a nationwide cohort study we identified that the risk of deep neck infection is significantly increased among patients who have undergone a tonsillectomy. Additional research is needed to explore the possible mechanisms behind these findings.
PMCID: PMC4388732  PMID: 25849535
4.  Impact of Pneumococcal Conjugate Vaccine on Pediatric Tympanostomy Tube Insertion in Partial Immunized Population 
The Scientific World Journal  2015;2015:248678.
Objective. To investigate the impact of seven-valent pneumococcal conjugate vaccine on tube insertions in a partial immunized pediatric population. Study Design. Retrospective ecological study. Methods. This study used Taiwan National Health Insurance Research Database for the period 2000–2009. Every child under 17 years old who received tubes during this 10-year period was identified and analyzed. The tube insertion rates in different age groups and the risk to receive tubes in different birth cohorts before and after the release of the vaccine in 2005 were compared. Results. The tube insertion rates for children under 17 years of age ranged from 21.6 to 31.9 for 100,000 persons/year. The tube insertion rate of children under 2 years old decreased significantly after 2005 in period effect analysis (β = −0.074, P < 0.05, and the negative β value means a downward trend) and increased in children 2 to 9 years old throughout the study period (positive β values which mean upward trends, P < 0.05). The rate of tube insertion was lower in 2004-2005 and 2006-2007 birth cohorts than that of 2002-2003 birth cohort (RR = 0.90 and 0.21, 95% CI 0.83–0.97 and 0.19–0.23, resp.). Conclusion. The seven-valent pneumococcal conjugate vaccine may reduce the risk of tube insertion for children of later birth cohorts. The vaccine may have the protective effect on tube insertions in a partial immunized pediatric population.
PMCID: PMC4370197  PMID: 25839052
5.  Comparing the Factors Correlated with Tuberculosis-Specific and Non-Tuberculosis-Specific Deaths in Different Age Groups among Tuberculosis-Related Deaths in Taiwan 
PLoS ONE  2015;10(3):e0118929.
Nearly 20% of tuberculosis (TB) patients die within one year, and TB-related mortality rates remain high in Taiwan. The study aimed to identify factors correlated with TB-specific deaths versus non-TB-specific deaths in different age groups among TB-related mortalities.
A retrospective cohort study was conducted from 2006-2008 with newly registered TB patients receiving follow-up for 1 year. The national TB database from the Taiwan-CDC was linked with the National Vital Registry System and the National Health Insurance database. A chi-squared test and logistic regression were used to analyse the correlated factors related to TB-specific and non-TB-specific deaths in different age groups.
Elderly age (odds ratio [OR] 2.68-8.09), Eastern residence (OR 2.01), positive sputum bacteriology (OR 2.54), abnormal chest X-ray (OR 2.28), and comorbidity with chronic kidney disease (OR 2.35), stroke (OR 1.74) or chronic liver disease (OR 1.29) were most likely to be the cause of TB-specific deaths, whereas cancer (OR 0.79) was less likely to be implicated. For non-TB-specific deaths in patients younger than 65 years of age, male sex (OR 2.04) and comorbidity with HIV (OR 5.92), chronic kidney disease (OR 8.02), stroke (OR 3.75), cancer (OR 9.79), chronic liver disease (OR 2.71) or diabetes mellitus (OR 1.38) were risk factors.
Different factors correlated with TB-specific deaths compared with non-TB-specific deaths, and the impact of comorbidities gradually decreased as age increased. To reduce TB-specific mortality, special consideration for TB patients with old age, Eastern residence, positive sputum bacteriology and comorbidity with chronic kidney disease or stroke is crucial. In particular, Eastern residence increased the risk of TB-specific death in all age groups. In terms of TB deaths among patients younger than 65 years of age, patients with HIV, chronic kidney disease or cancer had a 6-10 times increased risk of non-TB-specific deaths.
PMCID: PMC4348515  PMID: 25734444
6.  The Risk of Cancer in Patients with Congenital Heart Disease: A Nationwide Population-Based Cohort Study in Taiwan 
PLoS ONE  2015;10(2):e0116844.
The relationship between congenital heart disease (CHD) and malignancies has not been determined. This study aimed to explore the association of CHD with malignancies and examine the risk factors for the development of cancer after a diagnosis of CHD.
Patients and Methods
This nationwide, population-based cohort study on cancer risk evaluated 31,961 patients with newly diagnosed CHD using the Taiwan National Health Insurance Research Database (NHIRD) between 1998 and 2006. The standardized incidence ratios (SIRs) for all and specific cancer types were analyzed, while the Cox proportional hazard model was used to evaluate risk factors of cancer occurrence.
Among patients with newly diagnosed CHD regardless of ages, 187 (0.6%) subsequently developed cancers after a diagnosis of CHD. Patients with CHD had increased risk of cancer (SIR, 1.45; 95% CI, 1.25–1.67), as well as significantly elevated risks of hematologic (SIR, 4.04; 95% CI, 2.76–5.70), central nervous system (CNS) (SIR, 3.51; 95% CI, 1.92–5.89), and head and neck (SIR, 1.81; 95% CI, 1.03–2.94) malignancies. Age (HR, 1.06; 95% CI, 1.05–1.06) and co-morbid chronic liver disease (HR, 1.91; 95% CI, 1.27–2.87) were independent risk factors for cancer occurrence among CHD patients.
Patients with CHD have significantly increased cancer risk, particularly hematologic, CNS, and head and neck malignancies. Physicians who care for patients with CHD should be aware of their predisposition to malignancy after the diagnosis of CHD. Further studies are warranted to clarify the association between CHD and malignancies.
PMCID: PMC4338195  PMID: 25706872
7.  Enhancing the Early Differential Diagnosis of Plateau Iris and Pupillary Block Using A-Scan Ultrasonography 
PLoS ONE  2015;10(2):e0118811.
To distinguish the frequently misdiagnosed plateau iris eyes from pupillary block group and normal group, we compared the ocular biometrical parameters of them by A-scan ultrasongraphy.
In total, we retrospectively reviewed general characteristics and ocular findings including ocular biometric measurements of 71 normal, 39 plateau iris, and 83 pupillary block eyes.
The normal controls, plateau iris group and pupillary block group were significantly different in age, but not in gender. The anterior chamber depth tended to decrease and the lens thickness tended to increase from normal to plateau iris to pupillary block eyes. Compared to those of plateau iris group, the pupillary block group had significantly shallower anterior chamber depth (2.90mm vs. 2.33mm; p<0.001), thicker lens (4.77mm vs. 5.11mm; p<0.001), shorter axial length (23.16mm vs. 22.63mm; p<0.001), smaller relative lens position (2.28 vs. 2.16; p<0.001) and larger lens/axial length factor (2.06 vs. 2.26; p<0.001). However, when comparing plateau iris and normal eyes, only axial length and lens/axial length factor were significantly different (23.16 vs. 23.54; p<0.05 and 2.06 vs. 1.96; p<0.05).
Measured by A-scan ultrasonography, the ocular biometrics of plateau iris were significantly different from those of pupillary block eyes. However, our A-scan ultrasongraphy generally found no significant biometric differences between plateau iris and normal eyes. These findings suggest that while A-scan ultrasonography might be used as a practical tool for differentiating plateau iris and papillary block eyes, a more meticulous gonioscopy and other assessments may be necessary to distinguish plateau iris from normal eyes.
PMCID: PMC4331545  PMID: 25689856
8.  The safety and immunogenicity of a MF59-adjuvanted H5N1 prepandemic influenza vaccine in healthy adults primed with homologous or heterologous H5N1 vaccines: an observational study 
BMC Infectious Diseases  2014;14:587.
World Health Organization (WHO) has recommended individuals with increased risk of contracting influenza A H5N1 infection to be immunized against the virus during the inter-pandemic period. Safety and immunogenicity of H5N1 vaccine among participants primed with homologous or heterologous H5N1 vaccines produced by diverse manufactures have not been reported.
Healthy individuals aged 20 to 60 years old were recruited and stratified into three groups: participants without priming (control group), participants primed with A/Indonesia/05/2005 vaccine, participants primed with A/Vietnam/1194/2004 vaccine and A/Indonesia/05/2005 vaccine. Enrolled participants received two doses of MF59-adjuvanted A/Vietnam/1194/2004 vaccine (study vaccine). Solicited reactions were recorded by vaccine recipients. Blood samples were obtained for hemagglutination inhibition test.
A total of 131 participants were enrolled. No significant adverse events were recorded. Tenderness, fatigue and general muscle ache were the most common solicited reactions which alleviated within one week of immunization. Three weeks after two doses of the study vaccine, 63%, 68% and 88% were in seroprotective status in the control group, A/Indonesia/05/2005 primed group and A/Vietnam/1194/2004 and A/Indonesia/05/2005 primed group, respectively. Participants primed with A/Vietnam/1194/2004 and A/Indonesia/05/2005 showed high immune response after booster with one dose of the study vaccine.
The study vaccine did not cause severe adverse events. It elicited mostly mild to moderate reactions among participants. Participants primed with A/Vietnam/1194/2004 and A/Indonesia/05/2005 vaccine showed higher immune response than those without priming or primed with A/Indonesia/05/2005 vaccine. The report suggested those with an increased risk of influenza A H5N1 virus exposure may benefit from receiving influenza A H5N1 priming during the inter-pandemic period if the antigenicity of the pandemic influenza strain is similar to that of the priming strain.
PMCID: PMC4236496  PMID: 25394941
A/Vietnam/1194/2004; A/Indonesia/05/2005; H5N1 vaccine; Priming
9.  Nosocomial Neonatal Legionellosis Associated with Water in Infant Formula, Taiwan 
Emerging Infectious Diseases  2014;20(11):1921-1924.
We report 2 cases of neonatal Legionella infection associated with aspiration of contaminated water used in hospitals to make infant formula. The molecular profiles of Legionella strains isolated from samples from the infants and from water dispensers were indistinguishable. Our report highlights the need to consider nosocomial legionellosis among neonates who have respiratory symptoms.
PMCID: PMC4214307  PMID: 25340315
water; infant formula; Legionella; neonatal legionellosis; neonate; nosocomial infection; Taiwan; bacteria
10.  The Impact of Prior Tonsillitis and Treatment Modality on the Recurrence of Peritonsillar Abscess: A Nationwide Cohort Study 
PLoS ONE  2014;9(10):e109887.
Studies suggest an increased risk of peritonsillar abscess (PTA) recurrence in patients with prior tonsillitis. However, this association is inconsistent and could be confounded by different treatment modalities. This study aimed to assess the risk of recurrence among PTA patients with different degrees of prior tonsillitis and treatment modalities, and the role of tonsillectomy in current practice.
All in-patients with peritonsillar abscess between January 2001 and December 2009 were identified in a nationwide, retrospective cohort study. Recurrence was defined as the first occurrence of PTA ≧30 days from the initial PTA. Factors independently associated with recurrence were analyzed using Cox proportional hazard model after adjusting for demographic and clinical data.
There were 28,837 patients, with a 5.15% recurrence rate and 4.74 years of follow-up. The recurrence rates were significantly higher among subjects with more than five prior tonsillitis or 1–4 prior tonsillitis compared to those without prior tonsillitis (adjusted hazard ratio, 2.82 [95% confidence interval, 2.39–3.33] and 1.59 [95% CI: 1.38–1.82]). The adjusted HR in patients treated with needle aspiration was 1.08 compared to those treated with incision & drainage (95% CI: 0.85–1.38). After age stratification, the adjusted HRs of more than five prior tonsillitis increased to 2.92 and 3.50 in patients aged ≦18 and 19–29 years respectively. The adjusted HR ofneedle aspiration only increased in patients ≦18 years old (aHR: 1.98 [95% CI: 0.99–3.97]). The overall tonsillectomy rate was 1.48% during our study period.
The risk of PTA recurrence increases with higher degrees of prior tonsillitis in all age groups and management by needle aspiration only in the pediatric population. Patients younger than 30 years old with PTA and more than five prior tonsillitis have the greatest risk of recurrence.
PMCID: PMC4188615  PMID: 25291179
11.  Dental Prophylaxis Decreases the Risk of Esophageal Cancer in Males; A Nationwide Population-Based Study in Taiwan 
PLoS ONE  2014;9(10):e109444.
Periodontal disease (PD) is one of the most common chronic inflammatory diseases. Esophageal cancer (EC) is also a common cause of death due to cancer among males. Systemic inflammatory processes have been shown to increase the risk of cancer. We conducted a retrospective cohort study to investigate the association between PD and EC.
A total of 718,409 subjects were recruited from the Taiwan National Health Insurance Research Database (NHIRD) and followed from January 1, 2000 to December 31, 2010. Of these, 519,831 subjects were diagnosed with PD and were grouped according to the most advanced treatment they received: dental prophylaxis, intensive treatment, or no treatment. The IRs of EC were compared among groups.
A total of 682 patients developed EC, resulting in an overall IR of 0.11 case-number per 1000 person-years (‰/y). The dental prophylaxis group had a significantly lower IR of EC (0.06‰/y) than other groups (p<0.001). Multivariable Cox regression analysis further revealed that male subjects [hazard ratio (HR) = 10.04, 95% confidence interval (CI)  = 7.58–13.30], as well as a history of esophageal ulcers (HR = 7.10, 95% CI = 5.03–10.01), alcohol abuse (HR = 5.46, 95% CI = 2.26–13.18), or esophageal reflux (HR = 1.86, 95% CI = 1.02–3.52), were factors associated with a higher risk of EC. And the dental prophylaxis group showed a significantly lower risk for EC (HR = 0.53, 95% CI = 0.44–0.65). Further subgroup analysis showed that the dental prophylaxis group among males had a significant lower risk (HR = 0.54, 95% CI = 0.44–0.66) for EC, while that of the females did not has statistically significant difference.
For this cohort, subjects received dental prophylaxis reduced the risk of EC compared to all PD and no PD groups among males.
PMCID: PMC4184879  PMID: 25279666
12.  Anxiety and Depression Mediate the Health-Related Quality of Life Differently in Patients with Cardiovascular Disease and Stroke–Preliminary Report of the Yilan Study: A Population-Based Community Health Survey 
PLoS ONE  2014;9(9):e107609.
Cardiovascular disease and stroke have emerged as substantial and growing health challenges to populations around the world. Besides for the survival and medical prognosis, how to improve the health-related quality of life (HRQoL) might also become one of the goals of treatment programs. There are multiple factors that influence HRQol, including comorbidity, mental function and lifestyle. However, substantial research and investigation have still not clarified these underlying pathways, which merit further attention. The purpose of this study was to determine how psychological factors affect the link between cardiovascular disease and stroke with HRQoL.
Methods and Result
A total of 1,285 elder subjects at least 65 years of age (47.2% male) were enrolled. The mental function and HRQol of each patient was then measured using the Hospital Anxiety and Depression Scale and Short Form-12. After multiple regression analysis, anxiety, depression, cardiovascular disease, stroke, education level and age were shown to be associated with both mental component score (MCS) and physical component score (PCS). In the mediation analysis using the SPSS macro provided by Preacher and Hayes, cardiovascular disease and stroke affected HRQoL via anxiety and depression, respectively.
These results suggest that cardiovascular disease and stroke have negative impacts on patient MCS and PCS through different underlying pathways. Cardiovascular disease influences the HRQoL both directly and indirectly with the mediation of anxiety, and stroke influences the HRQoL by way of depression. These findings support the proposition that different combinations of both physical and psychological support are necessary to best manage these diseases.
PMCID: PMC4166664  PMID: 25226168
13.  The Incidence of Japanese Encephalitis in Taiwan—A Population-Based Study 
A mass Japanese encephalitis (JE) vaccination program targeting children was launched in Taiwan in 1968, and the number of pediatric JE cases substantially decreased thereafter. The aim of this study was to elucidate the long-term trend of JE incidence, and to investigate the age-specific seroprevalence of JE-neutralizing antibodies.
Methodology/Principal Findings
A total of 2,948 laboratory-confirmed JE cases that occurred between 1966 and 2012 were analyzed using a mandatory notification system managed by the Centers for Disease Control, Taiwan. A total of 6,594 randomly-sampled serum specimens obtained in a nationwide population-based survey in 2002 were analyzed to estimate the seroprevalence of JE-neutralizing antibodies in the general population. The average annual JE incidence rate of the group aged 30 years and older was 0.167 cases per 100,000 people between 2001 and 2012, which was higher than the 0.052 cases per 100,000 people among those aged under 30 years. These seroepidemiological findings indicate that the cohort born between 1963 and 1975, who generally received two or three doses of the vaccine and were administered the last booster dose more than 20 years ago, exhibited the lowest positive rate of JE-neutralizing antibodies (54%). The highest and second highest antibody rates were observed, respectively, in the oldest unvaccinated cohort (86%) and in the youngest cohort born between 1981 and 1986, who received four doses 10–15 years ago (74%).
Over the past decade, the main age group of the confirmed JE cases in Taiwan shifted from young children to adults over 30 years of age. People who were born between 1963 and 1975 exhibited the lowest seroprevalence of JE-neutralizing antibodies. Thus, the key issue for JE control in Taiwan is to reduce adult JE cases through a cost-effective analysis of various immunization strategies.
Author Summary
JE is one of the major public health problems in Asian and the Western Pacific regions, and most cases occur in children under the age of 14 years. A JE virus infection can cause severe sequelae such as an impairment of language ability, cognitive ability, or movement. Because humans are a dead-end host of the JE virus, the disease cannot be transmitted among people. Vaccination is currently the most effective method for preventing JE, and children in most endemic areas are vaccinated. After decades of mass vaccination, the number of confirmed JE cases has considerably declined in Taiwan, Japan, and South Korea. Most JE cases have occurred in adults rather than children in these countries, thus, the disease must be controlled by reducing the number of adult JE cases. Therefore, a prevention policy for the adult and elderly population should be implemented in the near future.
PMCID: PMC4109885  PMID: 25058573
14.  Prevalence and factors associated with HIV infection among injection drug users at methadone clinics in Taipei, Taiwan 
BMC Public Health  2014;14:682.
Methadone treatment was introduced in Taiwan in 2006 as a harm-reduction program for injection drug users (IDUs), among whom HIV was endemic. We examined the association of HIV serostatus with demographic characteristics, substance use, and sexual behaviors among IDUs at methadone clinics in Taipei, Taiwan.
During 2012–2013, IDUs at methadone clinics in Taipei were recruited to complete a risk assessment interview and undergo serologic testing for HIV infection. Correlates of HIV infection were identified by multivariate logistic regression.
Of the 827 eligible participants, 85.9% were male, median age was 45 years, and mean years of injecting was 18.0 (range 1–56). The prevalence of HIV infection was 17.7%. In multivariate analysis, HIV infection was significantly associated with age ≤45 years (adjusted odds ratio [AOR] = 1.62, 95% confidence interval [CI] 1.01–2.62), being divorced (AOR = 1.67, 95% CI 1.06–2.62), deriving the majority of income during the previous 6 months from temporary jobs or other noncriminal sources (AOR = 1.53, 95% CI 1.02–2.30), unstable housing during the previous 6 months (AOR = 1.47, 95% CI 1.003–2.15), higher number of incarcerations (AOR = 1.14, 95% CI 1.03–1.26), and a history of overdose (AOR = 1.51, 95% CI 1.01–2.28).
Taiwanese IDUs at methadone clinics have a relatively high HIV prevalence, which was associated with younger age and history of overdose. It is imperative to educate IDUs’ about HIV transmission, particularly for the younger and overdosed IDUs.
PMCID: PMC4098925  PMID: 24996558
HIV; Taiwan; Injection drug use; Methadone
15.  The Protective Effect of Adenoidectomy on Pediatric Tympanostomy Tube Re-Insertions: A Population-Based Birth Cohort Study 
PLoS ONE  2014;9(7):e101175.
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.
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.
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.
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.
PMCID: PMC4077749  PMID: 24983459
16.  Increased Risk of Ischemic Stroke after Hyperosmolar Hyperglycemic State: A Population-Based Follow-Up Study 
PLoS ONE  2014;9(4):e94155.
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.
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.
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.
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.
PMCID: PMC3979762  PMID: 24714221
17.  Association of Clinical Symptomatic Hypoglycemia With Cardiovascular Events and Total Mortality in Type 2 Diabetes 
Diabetes Care  2013;36(4):894-900.
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.
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.
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]).
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.
PMCID: PMC3609481  PMID: 23223349
18.  The Association of Socioeconomic Status and Access to Low-Volume Service Providers in Breast Cancer 
PLoS ONE  2013;8(12):e81801.
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.
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.
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.
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.
PMCID: PMC3846901  PMID: 24312589
19.  Directly Observed Therapy Reduces Tuberculosis-Specific Mortality: A Population-Based Follow-Up Study in Taipei, Taiwan 
PLoS ONE  2013;8(11):e79644.
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).
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.
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.
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.
PMCID: PMC3838349  PMID: 24278152
20.  Impact of Young Age on the Prognosis for Oral Cancer: A Population-Based Study in Taiwan 
PLoS ONE  2013;8(9):e75855.
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.
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.
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).
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.
PMCID: PMC3784390  PMID: 24086646
21.  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.
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.
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.
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).
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.
PMCID: PMC3741277  PMID: 23951249
22.  Disparities in Oral Cancer Survival among Mentally Ill Patients 
PLoS ONE  2013;8(8):e70883.
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.
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.
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).
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.
PMCID: PMC3737269  PMID: 23951029
23.  Epidemiology of Idiopathic Central Serous Chorioretinopathy in Taiwan, 2001–2006: A Population-based Study 
PLoS ONE  2013;8(6):e66858.
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.
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.
PMCID: PMC3691239  PMID: 23826160
24.  Association between Provider Volume and Healthcare Expenditures of Patients with Oral Cancer in Taiwan: A Population-Based Study 
PLoS ONE  2013;8(6):e65077.
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.
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.
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).
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.
PMCID: PMC3672134  PMID: 23750234
25.  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.
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.
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.
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.
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.
PMCID: PMC3380884  PMID: 22591974
Instrumental variable; Ovarian cancer; Propensity score; Secondary cytoreductive surgery

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