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Background The biological mechanisms of how prenatal smoke exposure leading to atopic disorders remain to be addressed. Whether prenatal smoke exposure affects DNA methylation leading to atopic disorders is not clear. Objective As most children suffering from atopic dermatitis ( AD) continue to develop asthma later in life, we explored whether prenatal smoke exposure induces cord blood DNA methylation. Methods Methylation differences associated with smoke exposure were screened by Illumina Infinium 27K methylation arrays for 14 children from the Taiwan birth panel study cohort initially. Information about development of atopic dermatitis ( AD) and risk factors was collected. Cord blood cotinine levels were measured to represent prenatal smoke exposure. CpG loci that demonstrated a statistically significant difference in methylation were validated by methylation-dependent fragment separation ( MDFS). Differential methylation in three genes ( TSLP, GSTT1, and CYB5R3) was identified through the screen. Results Among these, only thymic stromal lymphopoietin ( TSLP) gene displayed significant difference in promoter methylation percentage after being validated by MDFS ( p = 0.018). TSLP gene was further investigated in a larger sample of 150 children from the cohort who completed the follow-up study. Methylation status of the TSLP 5′-CpG island ( CGI) was found to be significantly associated with prenatal smoke exposure ( OR=3.17, 95% CI=1.63-6.19) and with AD ( OR=2.32, 95% CI=1.06-5.11). The degree of TSLP 5′ CGI methylation inversely correlated with TSLP protein expression levels ( r = −0.45, P = 0.001). Conclusions & Clinical Relevance The effect of prenatal tobacco smoke exposure on the risk for AD may be mediated through DNA methylation. [ABSTRACT FROM AUTHOR]

Hematopoietic SCT (HSCT) is one treatment modality for hematological malignancies. It is increasingly common but remains centralized in certain hospitals wherein procedures and protocols can vary. This study examined 100-day readmission for patients with hematological malignancies undergoing HSCT in Taiwan from the years 2001 to 2006. Of particular interest was an examination of how HSCT program characteristics might influence outcomes. This population-based retrospective cohort study with longitudinal follow-up used Taiwan's National Health Insurance Research Database. A generalized linear model with a logistic-dependent variable representing being admitted or not admitted was used to model 100-day readmission, adjusting for the nested design. There were 718 HSCT recipients for hematological malignancies in the 5-year study period from 10 HSCT programs. In spite of the average length of stay of 43.71 days (s.d.=25.75) days, 52% of recipients were readmitted within 100 days of discharge. Ownership status, the number of HSCT hematologists, and the ratio of HSCT procedures to HSCT hematologists independently predicted 100-day readmission after adjusting for clustered data and controlling for recipient characteristics. [ABSTRACT FROM AUTHOR]

Background: The proportion of injury deaths with unspecified external cause codes has been used as an indicator of the level of comprehensiveness and specificity of information on death certificates provided by certifiers. Objective: To compare the proportion of unspecified external cause codes across countries. Methods: Multiple-cause-of-death mortality data for people who died in 2001 due to external causes in Australia, Sweden, Taiwan and the USA were used for this international comparison study. The proportion of injury deaths coded as due to an unspecified external cause (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, ICD-10, chapter XX) to all injury deaths in each block was calculated. Results: Sweden (33%) had the highest proportion of use of the least specific code (lCD-10 code X59 exposure to unspecified factor), followed by Australia (17%), Taiwan (13%) and the USA (7%). More than two-thirds of the deceased for whom an lCD-10 code X59 was assigned in Sweden and Australia were those aged ⩾65 years, and more than half of them had femoral fractures. The percentage of use of the unspecified codes within specific groups of external causes was relatively high for falls and unintentional drowning. Conclusions: Caution should be used in examining the compensatory effects of the unspecified external event code (lCD-10 code X59) on specific external causes (especially falls) when making international comparisons. Efforts are needed to educate certifiers to report sufficient information for specific coding so as to provide more useful information for injury prevention. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess differences in the certification practices of physicians in Sweden, Taiwan and the USA with regard to diabetes-related cause-of-death (COD) statements. Multiple-cause-of-death data from Sweden (2000), Taiwan (2001) and the USA (2001) were used for this study. All deaths with mention of diabetes anywhere on the death certificate were extracted for analysis. Two types of inappropriate COD statements were: (1) reporting two or more diagnoses per line; and (2) entering an incorrect causal sequence among reported diagnoses. Of those deaths in which diabetes was reported in Part I of the death certificate, American physicians (19%) were less likely to report two or more diagnoses per line than physicians in Sweden (46%) and Taiwan (56%). On the other hand, Swedish physicians (5%) were less likely to report incorrect causal sequences than were their counterparts in Taiwan (21%) and the USA (28%). These findings reveal substantial differences in diabetes-related COD statements among physicians in Sweden, Taiwan and the USA, implying that caution should be used when interpreting differences in mortality statistics between these countries. [ABSTRACT FROM AUTHOR]

Objective: The association between depression and benign paroxysmal positional vertigo (BPPV) remains debated. This study aimed to investigate the risk of BPPV in patients with depressive disorders., Design: Longitudinal nationwide cohort study., Setting: National health insurance research database in Taiwan., Participants: We enrolled 10 297 patients diagnosed with depressive disorders between 2000 and 2009 and compared them to 41 188 selected control patients who had never been diagnosed with depressive disorders (at a 1:4 ratio matched by age, sex and index date) in relation to the risk of developing BPPV., Methods: The follow-up period was defined as the time from the initial diagnosis of depressive disorders to the date of BPPV, censoring or 31 December 2009. Cox proportional hazard regression analysis was used to investigate the risk of BPPV by sex, age and comorbidities, with HRs and 95% CIs., Results: During the 9-year follow-up period, 44 (0.59 per 1000 person-years) patients with depressive disorders and 99 (0.33 per 1000 person-years) control patients were diagnosed with BPPV. The incidence rate ratio of BPPV among both cohorts calculating from events of BPPV per 1000 person-years of observation time was 1.79 (95% CI 1.23 to 2.58, p=0.002). Following adjustments for age, sex and comorbidities, patients with depressive disorders were 1.55 times more likely to develop BPPV (95% CI 1.08 to 2.23, p=0.019) as compared with control patients. In addition, hyperthyroidism (HR=3.75, 95% CI 1.67-8.42, p=0.001) and systemic lupus erythematosus (SLE) (HR=3.47, 95% CI 1.07 to 11.22, p=0.038) were potential risk factors for developing BPPV in patients with depressive disorders., Conclusions: Patients with depressive disorders may have an increased risk of developing BPPV, especially those who have hyperthyroidism and SLE., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: There are limited studies describing the association between ankylosing spondylitis (AS) and osteoporosis. We conducted a nationwide retrospective cohort study to investigate this epidemiologic evidence., Methods: Data were obtained from the Taiwan National Health Insurance Research Database (NHIRD). Of 10,290 participants, 2,058 patients with AS and 8,232 patients without AS were enrolled from the NHIRD between 2000 to 2013. Cumulative incidences of osteoporosis were compared between 2 groups. Cox regression model was used to estimate the hazard ratio (HR) of developing osteoporosis after controlling for demographic and other co-morbidities, and subgroup analyses were conducted to examine the risk factors for osteoporosis in AS patients., Results: The incidence rate ratio (IRR) of osteoporosis in AS patients was 2.17 times higher than that non-AS group (95% confidence interval [CI], 1.83-2.57). The adjusted HRs of osteoporosis for AS patients after controlling for demographic characteristics and comorbid medical disorders was 1.99 (95% CI 1.68-2.36). Among AS group, after adjustment for major comorbidities, old age (≥65 years, HR 4.32, 95% CI 3.01-6.18), female sex (HR 2.48, 95% CI 1.87-3.28), dyslipidemia (HR 1.44, 95% CI 1.01-2.06) were risk factors associated with osteoporosis., Conclusions: This cohort study demonstrated that patients with AS had a higher risk of developing osteoporosis, especially in those aged over 65, female sex and with dyslipidemia in this patient group., Competing Interests: The authors have declared that no competing interests exist.

Background: In cancer patients, depressive disorder comorbidity is associated with greater suicide risk and poorer treatment outcomes, quality of life, and adherence to treatment. The aim of the study was to evaluate the incidence of newly-diagnosed depressive disorders after a gastric cancer diagnosis compared with a matched cohort using the National Health Insurance Research Database in Taiwan., Methods: We conducted a retrospective cohort study of 57,506 patients (28,753 patients with gastric cancer and 28,753 matched patients) selected from the National Health Insurance Research Database. Patients were observed for a maximum of 12 years to determine the incidence of newly-diagnosed depressive disorders. Also, a Cox regression analysis which included death as an independent censor was performed to identify the potentially predictive variables for developing subsequent depressive disorders following a cancer diagnosis among the patients suffering from gastric cancer., Results: The cumulative incidence of depressive disorders in the gastric cancer patients was significantly higher compared to those in the matched cohort (p < .001). The adjusted hazard ratio was 1.54 (95% confidence interval, CI = 1.39-1.70, P < .001) in the gastric cancer cohort compared with the matched cohort. Independent predictive variables for developing subsequent depressive disorders among the patients with gastric cancer included female sex and hypertension., Conclusions: In the study, higher incidence of new-onset depression, being defined by the records of the diagnostic codes combining antidepressants use in a nationwide database, was noted in the gastric cancer patients compared with the matched cohort. In addition, female sex and comorbid hypertension may be predictive variables for the subsequent depression among the patients with gastric cancer. Further clinical prospective studies were necessary to confirm these findings.

Nonapnea sleep disorders (NASDs) and associated problems, which are highly prevalent in patients with kidney diseases, are associated with unfavorable medical sequelae. Nonetheless, whether NASDs are associated with acute kidney injury (AKI) development has not been thoroughly analyzed. We examined the association between NASD and AKI. We conducted a population-based study by using 1,000,000 representative data from the Taiwan National Health Insurance Research Database for the period from January 1, 2000, to December 31, 2010. We studied the incidence and risk of AKI in 9178 newly diagnosed NASD patients compared with 27,534 people without NASD matched according to age, sex, index year, urbanization level, region of residence, and monthly income at a 1:3 ratio. The NASD cohort had an adjusted hazard ratio (hazard ratio [HR]; 95% confidence interval [CI] = 1.15-2.63) of subsequent AKI 1.74-fold higher than that of the control cohort. Older age and type 2 diabetes mellitus were significantly associated with an increased risk of AKI (P < 0.05). Among different types of NASDs, patients with insomnia had a 120% increased risk of developing AKI (95% CI = 1.38-3.51; P = 0.001), whereas patients with other sleep disorders had a 127% increased risk of subsequent AKI (95% CI = 1.07-4.80; P = 0.033). Men with NASDs were at a high risk of AKI (P < 0.05). This nationwide population-based cohort study provides evidence that patients with NASDs are at higher risk of developing AKI than people without NASDs.

Menopausal transition is highly symptomatic in at least 20% of women. A higher prevalence of psychiatric symptoms, including depression, anxiety, and sleep disturbance, has been shown in women with symptomatic menopausal transition. However, a clear correlation between symptomatic menopausal transition and psychiatric disorders has not been established.We explored the association between symptomatic menopausal transition and subsequent newly diagnosed psychiatric disorders, including schizophrenia as well as bipolar, depressive, anxiety, and sleep disorders.We investigated women who were diagnosed with symptomatic menopausal transition by an obstetrician-gynecologist according to the data in the Taiwan National Health Insurance Research Database. A comparison cohort comprised age-matched women without symptomatic menopausal transition. The incidence rate and the hazard ratios of subsequent newly diagnosed psychiatric disorders were evaluated in both cohorts, based on the diagnoses of psychiatrists.The symptomatic menopausal transition and control cohorts each consisted of 19,028 women. The incidences of bipolar disorders (hazard ratio [HR] = 1.69, 95% confidence interval [CI] = 1.01-2.80), depressive disorders (HR = 2.17, 95% CI = 1.93-2.45), anxiety disorders (HR = 2.11, 95% CI = 1.84-2.41), and sleep disorders (HR = 2.01, 95% CI = 1.73-2.34) were higher among the symptomatic menopausal transition women than in the comparison cohort. After stratifying for follow-up duration, the incidence of newly diagnosed bipolar disorders, depressive disorders, anxiety disorders, and sleep disorders following a diagnosis of symptomatic menopausal transition remained significantly increased in the longer follow-up groups (1-5 and ≥ 5 years).Symptomatic menopausal transition might increase the risk of subsequent newly onset bipolar disorders, depressive disorders, anxiety disorders, and sleep disorders. A prospective study is necessary to confirm these findings.

Aim: Coronary artery disease is the main cause of mortality and morbidity in dialysis-dependent renal failure patients. Both the prevalence and incidence of renal failure are high in Taiwan. However, there were few reports exploring the outcome of coronary aortic bypass grafting (CABG) in these patients. The aim of this study was to determine the survival outcome and risk factors for mortality from CABG in this population., Methods: The operative, early postoperative and late results of 170 dialysis patients undergoing isolated coronary artery bypass grafting from January, 2000 to January, 2012 were retrospectively reviewed. Operative mortality, long-term survival, and risk factors were analyzed., Results: One hundred and seventeen patients (68.8%) were male, and the mean age was 61.5±10.3 years (range, 34-86 years). Follow-up was 40.3±32.1 months. Operative mortality was 8.2%. Actuarial survival, including operative mortality, was 81±3% at 1 year, 68±4% at 3 years, 58±5% at 5 years and 49±6% at 10 years, better than the natural course of dialysis-dependent renal failure patients. Age, emergent operation, postoperative ventricular tachycardia or fibrillation, postoperative intra-aortic balloon pump insertion, gastrointestinal bleeding, and left internal mammary artery graft were significant predictors of operative or long term mortality. Most causes of late death were due to infection or cardiac events., Conclusion: CABG in dialysis patients is associated with a higher incidence of complications, but has acceptable mortality. CABG is beneficial in this population. Internal mammary artery grafting may provide more favorable long term outcomes.

Background: Recent studies have shown that the peripheral inflammation may cause the up-regulation of central nervous system inflammation and therefore possibly plays a vital role in the pathophysiology of subsequent psychiatric disorders., Objective: We explored the relationship between gastroesophageal reflux disease (GERD) and the subsequent development of psychiatric disorders including schizophrenia as well as bipolar, depressive, anxiety, and sleep disorders., Methods: We investigated patients who were diagnosed with GERD according to the data in the Taiwan National Health Insurance Research Database. A comparison cohort comprised patients without GERD who were matched according to age and sex. The incidence rate and the hazard ratios (HRs) of subsequent new-onset psychiatric disorders were calculated for both cohorts, based on the diagnoses of psychiatrists., Results: The GERD cohort consisted of 3813 patients, and the comparison cohort comprised 15,252 matched control patients without GERD. The risks of depressive disorder (HR=3.37, 95% confidence interval [CI]=2.49-4.57), anxiety disorder (HR=2.99, 95% CI=2.12-4.22), and sleep disorder (HR=2.69, 95% CI=1.83-3.94), were higher in the GERD cohort than in the comparison cohort. In addition, the incidence of newly diagnosed depressive, anxiety, and sleep disorders remained significantly increased in all of the stratified follow-up durations (0-1, ≥1year)., Conclusions: GERD may increase the risks of subsequent depressive, anxiety, and sleep disorders. These psychiatric disorders have a negative effect on people's quality of life. Clinicians should pay a particular attention to psychiatric comorbidities in GERD patients., (Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

This study aimed to develop a prediction model for post-operative delirium among older patients receiving elective orthopedic surgery and to evaluate its effectiveness in predicting long-term health outcomes. This prospective cohort study screened all subjects aged over 60 years who were admitted for elective orthopedic surgery in a tertiary medical center in Taiwan from April, 2011, to December, 2013. Demographic characteristics, surgery-related factors, and results of comprehensive geriatric assessment (CGA) were all used to develop the prediction model. Long-term health outcomes, including mortality, nursing home admission, and functional status in the first year after surgery, were used to further evaluate the effectiveness of the prediction model. Overall, 461 patients (median age, 73 years; interquartile range [IQR], 67-80 years; 42.3% males) were enrolled, and 37 patients (8.0%) developed post-operative delirium. Prediction models were developed on the basis of demographic characteristics and surgery-related factors (model 1) and of demographic characteristics, surgery-related factors, and geriatric assessment variables (model 2). Although both models effectively predicted the occurrence of post-operative delirium, duration of post-operative delirium, total hospital days, nursing home admission, and mortality, model 2 was more likely to differentiate cases with functional decline during the first year after surgery. In conclusion, a prediction model developed by using demographic characteristics, surgery-related factors, and results of CGA was highly predictive for post-operative delirium, as well as long-term health and functional outcomes.

Objective: We explored the association between IBS and the development of bipolar disorder, and the risk factors for bipolar disorders in patients with IBS., Methods: We identified patients who were newly diagnosed with IBS between 2000 and 2010 in the Taiwan National Health Insurance Research Database. We also identified a comparison matched cohort without IBS. The occurrence of new-onset bipolar disorder was evaluated in both cohorts., Results: The IBS cohort consisted of 30,796 patients and the comparison cohort consisted of 30,796 matched patients without IBS. The incidence of bipolar disorder (incidence rate ratio, 2.63, 95% confidence interval (CI) 2.10-3.31, P < .001) was higher in the IBS patients than in the matched cohort. Multivariate matched regression models indicated that autoimmune diseases (HR 1.52, 95% CI 1.07-2.17, P = .020), and asthma (HR 1.45, 95% CI 1.08-1.95, P = .013) were independent risk factors for the development of bipolar disorder in the IBS patients., Conclusion: IBS may increase the risk of developing subsequent bipolar disorder. Additional prospective studies are required to confirm these findings.

Background: This study identified possible risk factors for newly diagnosed mood disorders, including depressive and bipolar disorders, in prostate cancer patients., Methods: From 2000 to 2006, two cohorts were evaluated on the occurrence of mood disorder diagnosis and treatment. For the first cohort, data of patients diagnosed with prostate cancer was obtained from the Taiwan National Health Insurance (NHI) Research Database. As the second cohort, a cancer-free comparison group was matched for age, comorbidities, geographic region, and socioeconomic status., Results: Final analyses involved 12,872 men with prostate cancer and 12,872 matched patients. Increased incidence of both depressive (IRR 1.52, 95% CI 1.30-1.79, P <0.001) and bipolar disorder (IRR 1.84, 95% CI 1.25-2.74, P = 0.001) was observed among patients diagnosed with prostate cancer. Multivariate matched regression models show that cerebrovascular disease (CVD) and radiotherapy treatment could be independent risk factors for developing subsequent depressive and bipolar disorders., Conclusion: We observed that the risk of developing newly diagnosed depressive and bipolar disorders is higher among Taiwanese prostate cancer patients. Clinicians should be aware of the possibility of increased depressive and bipolar disorders among prostate cancer patients in Taiwan. A prospective study is necessary to confirm these findings.

Background: The impact of postoperative delirium on post-discharge functional status of older patients remains unclear, and little is known regarding the interrelationship between cognitive impairment and post-operative delirium. Therefore, the main purpose was to evaluate the post-discharge functional status of patients who experience delirium after undergoing orthopaedic surgery and the interrelationship of postoperative delirium with underlying cognitive impairment., Method: This prospective cohort study, conducted at a tertiary care medical center from April 2011 to March 2012, enrolled all subjects aged over 60 years who were admitted for orthopaedic surgery. The baseline characteristics (age, gender, BMI, and living arrangement), surgery-related factors (ASA class, admission type, type of surgery, and length of hospital stay), results of geriatric assessment (postoperative delirium, cognition, depressive mood, comorbidity, pain, malnutrition, polypharmacy, ADL, and instrumental [I]ADL) and 1-12-month postoperative ADL and IADL functional status were collected for analysis., Results: Overall, 9.1% of 232 patients (mean age: 74.7 ± 7.8 years) experienced postoperative delirium, which was significantly associated with IADL decline at only 6 and 12 months postoperatively (RR: 6.22, 95% CI: 1.08-35.70 and RR: 12.54, 95% CI: 1.88-83.71, respectively). Delirium superimposed on cognitive impairment was a significant predictor for poor functional status at 6 and 12 months postoperatively (RR: 12.80, 95% CI: 1.65-99.40 for ADL at the 6th month, and RR: 7.96, 95% CI: 1.35-46.99 at the 12th month; RR: 13.68, 95% CI: 1.94-96.55 for IADL at the 6th month, and RR: 30.61, 95% CI: 2.94-318.54 at the 12th month, respectively)., Conclusion: Postoperative delirium is predictive of IADL decline in older patients undergoing orthopaedic surgery, and delirium superimposed on cognitive impairment is an independent risk factor for deterioration of ADL and IADL functional status. Early identification of cognitive function and to prevent delirium are needed to improve functional status following orthopaedic surgery.

Background: Studies have shown that chronic inflammation may play a vital role in the pathophysiology of both gastroesophageal reflux disease (GERD) and bipolar disorder. Among patients with GERD, the risk of bipolar disorder has not been well characterized., Objective: We explored the relationship between GERD and the subsequent development of bipolar disorder, and examined the risk factors for bipolar disorder in patients with GERD., Methods: We identified patients who were diagnosed with GERD in the Taiwan National Health Insurance Research Database. A comparison cohort without GERD was matched according to age, sex, and comorbidities. The occurrence of bipolar disorder was evaluated in both cohorts based on diagnosis and the prescription of medications., Results: The GERD cohort consisted of 21,674 patients, and the comparison cohort consisted of 21,674 matched control patients without GERD. The incidence of bipolar disorder (incidence rate ratio [IRR] 2.29, 95% confidence interval [CI] 1.58-3.36, P<.001) was higher among GERD patients than among comparison cohort. Multivariate, matched regression models showed that the female sex (hazard ratio [HR] 1.78, 95% CI 1.76-2.74, P = .008), being younger than 60 years old (HR 2.35, 95% CI 1.33-4.16, P = .003), and alcohol use disorder (HR 4.89, 95% CI 3.06-7.84, P = .004) were independent risk factors for the development of bipolar disorder among GERD patients., Conclusions: GERD may increase the risk of developing bipolar disorder. Based on our data, we suggest that attention should be focused on female patients younger than 60 years, and patients with alcohol use disorder, following a GERD diagnosis.

Background: Studies have suggested that chronic inflammation plays an essential role in the pathophysiology of both rheumatoid arthritis (RA) and bipolar disorder. The most common clinical features associated with RA are anxiety and depression. The risk of bipolar disorder among patients with RA has not been characterized adequately., Objective: To determine the association between RA and the subsequent development of bipolar disorder and examine the risk factors for bipolar disorder among patients with RA., Methods: We identified patients who were diagnosed with RA in the Taiwan National Health Insurance Research Database. A comparison cohort was created by matching patients without RA with those with RA according to age, sex, and comorbidities. The occurrence of bipolar disorder was evaluated in both cohorts., Results: The RA cohort consisted of 2,570 patients, and the comparison cohort consisted of 2,570 matched control patients without RA. The incidence of bipolar disorder (incidence rate ratio  = 2.13, 95% confidence interval [CI]  = 1.12-4.24, P =  .013) was higher among patients with RA than among control patients. Multivariate, matched regression models revealed that asthma (hazard ratio [HR]  = 2.76, 95% CI 1.27-5.96, P =  .010), liver cirrhosis (HR  = 3.81, 95% CI  = 1.04-14.02, P =  .044), and alcohol use disorders (HR  = 5.29, 95% CI  = 1.71-16.37, P =  .004) were independent risk factors for the development of bipolar disorder among patients with RA., Conclusion: RA might increase the incidence of bipolar disorder development. Based on our data, we suggest that, following RA diagnosis, greater attention be focused on women with asthma, liver cirrhosis, and alcohol use disorder. Prospective clinical studies of the relationship between RA and bipolar disorder are warranted.

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. A higher prevalence of psychiatric comorbidities, including depressive disorder, anxiety disorder, and bipolar disorder has been proved in patients with PCOS. However, a clear temporal causal relationship between PCOS and psychiatric disorders has not been well established., Objective: We explored the relationship between PCOS and the subsequent development of psychiatric disorders including schizophrenia, bipolar disorder, depressive disorder, anxiety disorder, and sleep disorder., Methods: We identified patients who were diagnosed with PCOS by an obstetrician-gynecologist in the Taiwan National Health Insurance Research Database. A comparison cohort was constructed of patients without PCOS who were matched according to age and sex. The occurrence of subsequent new-onset psychiatric disorders was evaluated in both cohorts based on diagnoses made by psychiatrists., Results: The PCOS cohort consisted of 5431 patients, and the comparison cohort consisted of 21,724 matched control patients without PCOS. The incidence of depressive disorder (hazard ratio [HR] 1.296, 95% confidence interval [CI] 1.084-.550), anxiety disorder (HR 1.392, 95% CI 1.121-1.729), and sleep disorder (HR 1.495, 95% CI 1.176-1.899) were higher among the PCOS patients than among the patients in the comparison cohort. In addition, a higher incidence of newly diagnosed depressive disorder, anxiety disorder, and sleep disorder remained significantly increased in all of the stratified follow-up durations (0-1, 1-5, ≥5 y)., Conclusions: PCOS might increase the risk of subsequent newly diagnosed depressive disorder, anxiety disorder, and sleep disorder. The risk of newly diagnosed bipolar disorder, which has often been reported in the literature to be comorbid with PCOS, was not significantly elevated.

Background: Bupropion, which is widely used in patients with depressive disorder, may cause allergic reactions. However, the real prevalence of these side effects may be overlooked and underreported due to the delayed onset phenomenon., Objective: This study aimed to estimate the real incidence of bupropion-induced urticaria and clarify the delayed onset phenomenon., Methods: We conducted a nationwide cohort study between 2000 and 2009 using Taiwan's National Health Insurance Dataset. Among 65,988 patients with depressive disorders, we identified new users of bupropion with depressive disorders (bupropion cohort, n = 2,839) and matched them at a ratio of 1:4 regarding age and sex (non-bupropion matched cohort, n = 11,356). The risk of urticaria was compared between the two cohorts., Results: The risk of urticaria occurrence was higher in bupropion users than in matched controls within 4 weeks of starting the medication (risk ratio 1.81; 95% confidence interval 1.28-2.54; p = 0.001). The occurrence of urticaria in the bupropion cohort were more frequent on Days 15-28 than Day 1-14 (p = 0.002). Cox proportional hazards model showed that a history of urticaria was an independent risk factor for developing bupropion-induced urticaria., Conclusions: Of the antidepressants, bupropion may pose a higher risk of drug-induced urticaria, and this condition might be ignored due to the delayed onset phenomenon. Depressive patients with a history of urticaria are at higher risk of the adverse drug reaction. This study emphasizes the need for increased clinical awareness of this adverse outcome to bupropion use.

Background: This study estimates the risk of stroke within 5 years of newly diagnosed dementia among elderly persons aged 65 and above. We examined the relationship between antipsychotic usage and development of stroke in patients with dementia., Methods: We conducted a nationwide 5-year population-based study using data retrieved from the Longitudinal Health Insurance Database 2005 (LHID2005) in Taiwan. The study cohort comprised 2243 patients with dementia aged ≥65 years who had at least one inpatient service claim or at least 2 ambulatory care claims, whereas the comparison cohort consisted of 6714 randomly selected subjects (3 for every dementia patient) and were matched with the study group according to sex, age, and index year. We further classified dementia patients into 2 groups based on their history of antipsychotic usage. A total of 1450 patients were classified into the antipsychotic usage group and the remaining 793 patients were classified into the non-antipsychotic usage group. Cox proportional-hazards regressions were performed to compute the 5-year stroke-free survival rates after adjusting for potentially confounding factors., Results: The dementia patients have a 2-fold greater risk of developing stroke within 5 years of diagnosis compared to non-dementia age- and sex-matched subjects, after adjusting for other risk factors (95% confidence interval (CI) = 2.58-3.08; P<.001). Antipsychotic usage among patients with dementia increases risk of stroke 1.17-fold compared to patients without antipsychotic treatment (95% CI = 1.01-1.40; P<.05)., Conclusions: Dementia may be an independent risk factor for stroke, and the use of antipsychotics may further increase the risk of stroke in dementia patients.

Objectives: To compare the differences in plasma brain-derived neurotrophic factor (BDNF) levels among institutionalized ethnic Chinese elderly participants with major depression, those with subclinical depression, and a nondepressed control group., Design: A cross-sectional study., Setting: The veterans' home in southern Taiwan., Participants: One hundred sixty-seven residents., Measurements: Questionnaires including the Minimum Data Set Nursing Home 2.1, Chinese-language version, and the short-form Geriatric Depression Scale, Chinese-language version. Depressive disorder was diagnosed by a well-trained psychiatrist using DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision) criteria. We measured plasma BDNF levels in the following 3 groups: nondepressive subjects (n = 122), subclinically depressive subjects (n = 33), and subjects with major depression (n = 12). Plasma BDNF was assayed using the sandwich ELISA method., Results: We noted a significantly negative association between age and plasma BDNF in the regression model. There was no significant correlation between BDNF plasma levels and body weight or platelet counts. We found that plasma BDNF was significantly lower in the major depressive group (mean, 115.1 pg/mL; SD, 57.2) than in the nondepressive group (mean, 548.8 pg/mL; SD, 370.6; P < .001). The BDNF plasma concentrations in the subclinically depressive group (mean, 231.8 pg/mL; SD, 92.4; P < .001) and control group were also significantly different., Conclusions: Our findings revealed that plasma BDNF levels were reduced not only in ethnic Chinese elderly patients with major depressive disorder but also in those with subclinical depression. This makes the plasma BDNF level a potential biological marker for clinical or subclinical depression., (Copyright © 2012 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Pre-incisional infiltration of anaesthetic is proven to reduce postoperative pain in breast cancer surgery. However, studies of post-incisional infiltration for modified radical mastectomy are rare. The purpose of this study was to investigate whether post-incisional infiltration with bupivacaine provides improved postoperative pain relief and a cost-effective benefit., Methods: This is a retrospective study. Between January 2006 and May 2008, 139 patients who received modified radical mastectomy were recruited to participate in the study. Patients receiving local infiltration received bupivacaine (0.5% bupivacaine, 5 ml diluted to 10 ml with distilled water) injected into the dermis surrounding the incision after wound suture. Pain intensity was evaluated using a Visual Analogue Scale (VAS) score and measurement of the required doses of meperidine and acetaminophen. The pain score was recorded every eight hours for three days., Results: All patients were female. Seventy-two patients received local infiltration with bupivacaine after wound suture and 67 patients did not. There were no significant differences between the two patient groups in age, body weight and height, length of general anaesthesia and operative time. Hospital stay was significantly shorter for patients receiving local infiltration of bupivacaine. The VAS score was higher up to 16 hours post-surgery for patients who did not receive local infiltration. Meperidine and acetaminophen consumption was less for patients who received local infiltration (P = 0.010)., Conclusion: Post-incisional wound infiltration with bupivacaine can relieve pain during the first 16 hours after surgery and shorten hospital stay, and it provides a cost-effective benefit.

Fear of falling (FF) can have multiple adverse consequences in the elderly. Although there are various fall prevention programs, little is known of FF and its associated characteristics. This study examined FF-associated physical and psychosocial factors in older Chinese men living in a veterans home in southern Taiwan. Subjects with a recent episode of delirium, of bed-ridden or wheelchair-bound status, severe hearing impairment or impaired cognition were excluded. Overall, 371 residents (mean age 82.1 ± 5.11 years, all males) participated. The prevalence of FF was 25.3%. Univariate analysis revealed that subjects in the FF group were older age, having lower education level, poorer sitting and standing balance, poorer activities of daily living (ADL), more depressive symptoms, higher chances of using walking aids, neurologic diseases, and a history of fall within the past 6 months. Logistic regression showed that depressive symptoms (odds ratio = OR = 6.73, 95%CI: 3.03-14.93, p < 0.001), activities of daily living (OR = 2.48, 95%CI: 1.08-5.71, p = 0.033), history of fall in the past 6 months (OR = 2.47, 95%CI: 1.04-5.9, p = 0.041), and neurological diseases (OR = 2.75, 95%CI: 1.15-6.56, p = 0.023) were all independent risk factors for FF., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: This study was conducted to evaluate the risks of adverse birth outcomes including low birthweight, preterm and small-for-gestational age among teen mothers., Methods: Data were collected from the Taiwan Birth Registry between 1985 and 1997. Among a total of 1,185,597 live births born to mothers aged 24 years or less, 151,259 (12.8%) were born to teen mothers aged 19 years or less. Crude odds ratios (ORs), adjusted ORs (AORs), their 95% confidence intervals and test for linear trend of maternal age-specific AOR were estimated using logistic regression analysis., Results: After controlling for certain birth characteristics and socio-economic factors, the age-specific analysis showed significantly gradient variations in increased risks of adverse birth outcomes among births of teen mothers, where the elevated risk was lessened in older teen mothers. Teen mothers aged 16 years or less were observed to experience particularly high AORs for all adverse birth outcomes of interest., Conclusions: Not all teen mothers experienced the same magnitude of increased risk of adverse birth outcomes in Taiwan. Considering all teen mothers as the same group may have overlooked the particularly high risks of adverse birth outcomes among very young teen mothers (16 years or less), who are especially vulnerable to such elevated risks.

Objective: To identify locations to target for suicide preventive measures to reduce suicide by jumping in Taipei city, Taiwan., Method: A descriptive study of suicide by jumping from a height was conducted in Taipei, 2002-2005. Information on sites from which suicide jumps occurred was obtained from death certificates as well as ambulance, medical and newspaper records., Results: Of the 210 jumping suicide deaths with sufficient information on the site of the jump, private residential buildings comprised the highest proportion (67%) of all jumping sites, followed by business office buildings (13%), hospitals (8%) and shopping malls (5%). However, the number of jumping suicides per 1000 sites was highest for hospitals (307 per 1000 hospitals) and shopping malls (275 per 1000 shopping malls) compared with 2 per 1000 for residential buildings. Women and older people who died by jumping were more likely to have jumped from buildings where they lived, compared with men and other age groups., Conclusion: Although two-thirds of suicides occurred from residential buildings, the sites with the greatest number of jumps per location were hospitals and shopping malls, making them the most cost-effective focus for preventive efforts.

Background: There is limited data about how appropriate medical care is in the emergency department (ED)., Objectives: To investigate the rate and types of preventable deaths among patients with early mortality after emergency admission from the ED., Methods: We retrospectively reviewed charts of early mortality (defined as mortality which occurred within 24 hours after admission from the ED) over a 3 year period. Those patients with terminal cancer or out of hospital cardiac arrest (OHCA) at presentation were excluded. Two independent assessors reviewed each eligible chart and determined whether early mortality was preventable. Any disagreements were resolved through discussion between the investigators. A mortality event was considered preventable if actions or missed actions were identified that would have prevented the death. The types of preventability were categorised as misdiagnosis, delayed diagnosis, and inappropriate medical management. Interrater reliability in the initial determination was assessed using Cohen kappa statistic., Results: Over a 3 year period, 210 early mortality cases were identified. Excluding patients with terminal cancer or OHCA, the rate of preventable deaths was 25.8% (32/124). The types of preventability were inappropriate medical management (17 patients), delayed diagnosis (eight), and misdiagnosis (seven). There was good agreement between assessors with a Cohen kappa statistic of 0.81., Conclusions: Preventable deaths in emergency admitted patients with early mortality are not uncommon. Analysis and identification of preventability early mortality by using a chart based method may be used as a quality assurance index in emergency medical care.

Between July 2002 and July 2004, all male patients (n=307) presenting to a sexually transmitted disease (STD) clinic who reported unprotected sex were enrolled in the study. Of these, 63 (20.5%), 19 (6.2%) and one (0.3%) were infected with one, two and three pathogens, respectively. The prevalences of chlamydial infection, gonorrhoea, syphilis, human immunodeficiency virus infection and trichomoniasis were 14.3%, 10.1%, 6.8%, 2.2% and 0%, respectively. The sensitivities of urethral discharge syndrome for detection of chlamydial, gonococcal, and combined forms of infection were 31.8%, 58.5% and 70.0%, respectively, with specificities of 93.5%, 97.1% and 93.9%, respectively. Positive predictive values (PPVs) were 56.0%, 68.0% and 28.0% for chlamydial and gonococcal infections and combinations of the two forms, respectively. In contrast, the sensitivity of genital ulceration syndrome for syphilis detection was only 38.0%, although the specificity was 82.5%, and the PPV was 32.0%. To reduce the number of false-positive results for STD patients who practise unprotected sex, incorporation of risk assessment and rapid diagnostic tests are recommended.

Setting: Population-based study in Taiwan., Objective: To determine the tuberculosis (TB) mortality trends in Taiwan by site and age., Design: Mortality data for the years 1972 to 2001 were used to calculate the age/site-specific mortality rate (deaths per 100000 population). The year of change in the slope of mortality trends was estimated by iterative piecewise regression analysis., Results: A levelling off in mortality trends was noted in the late 1980s for all age groups except those aged 75 and above. Except in the age group 25-44 years, the trends in respiratory TB mortality showed a smooth decline. However, for non-respiratory TB mortality, a reversal of the decline was noted for all age groups since 1994-1995. A twofold increase in the number of deaths from central nervous system (CNS) and 'other' TB was noted. A marked increase in the number of deaths from old TB was noted since 1992-1996., Conclusion: TB mortality trends in Taiwan have not declined as expected over the past decade. The slowing down of the decline in TB mortality was mainly attributable to a levelling off of respiratory TB mortality in the age group 25-44 and a reversal of non-respiratory TB mortality trends, especially in the 25-44 and > or =65 years age groups.

Background and Purpose: In outcome analyses of clinical trials and mortality follow-up studies, the underlying cause of death (UCOD) is commonly assigned either by official coders or by a panel of physicians. We evaluated the validity of UCOD assigned by official coders by comparison with the assignments of a panel of physicians who reviewed the available medical records of the deceased., Methods: The comparisons focused on deaths occurring from October 1995 through June 1998 in a series of residents in a veterans home. Because of limited resources, only the first 104 deaths that occurred during the study period were included. Agreement rate, sensitivity, specificity, and kappa statistics were calculated to assess the consistency of coder versus physician panel assignment of UCOD by selected main causes of death. For 32 of the 104 deaths, the panel concluded that the information obtained from medical records was insufficient to determine the UCOD, and the following analyses were confined to the other 72 deaths., Results: For the 72 deaths considered by the panel to have sufficient information to determine UCOD, all four physicians agreed on a single UCOD in 50 (69%) cases, while three or four agreed in 66 (92%) cases. A consensus was reached in cases with disagreement. The two procedures completely agreed in 40 (56%) of the deaths. For general category UCOD, the kappa value was high for cancer (0.83) and cardiovascular disease (CVD, 0.73) but only moderate for pulmonary disease (PD, 0.60). When the UCOD assigned by the panel was used as the gold standard, official coders showed relatively low sensitivity for correct determination of UCOD in cases of CVD (0.76) compared with cancer (0.86) and PD (0.80)., Conclusions: Given the high inter-physician consistency and the relatively low sensitivity of official coders in assigning CVD as the UCOD, we conclude that the use of clinical review panels would provide more accurate UCOD assignments for use in outcome analyses in mortality follow-up studies and clinical trials in Taiwan.

To identify characteristics of certifying physicians and the deceased that are associated with errors in death certificate completion in Taiwan, we retrospectively reviewed 4123 systematically sampled death certificates issued in 1994. Multivariate analyses were used to assess the associations of various characteristics of the certifying physicians and the deceased with four types of error. Of the 4123 death certificates reviewed, 2525 (61%) were completed correctly. In 289 (7%), only the mechanism(s) of death was given (Major Error 1); in 146 (4%), multiple causal sequences were given in part I (Major Error 2); in 800 (19%), a single causal sequence was given but was not specific enough (Minor Error 1); and in 363 (9%), a single causal sequence was given but the order was incorrect (Minor Error 2). Multiple logistic regression analyses revealed that the probability of error in death certification increased as the age of the deceased increased, the age of the certifier decreased, and the level of the hospital decreased. These findings suggest that training in death certificate completion should focus on younger certifiers and those working at lower level teaching hospitals and nonteaching hospitals. Given the high rate of Minor Error 1, physicians should be reminded to state information as specifically as possible to render cause-of-death statistics more informative.

Background: The objectives of this study were to assess the accuracy of cause-of-death coding, determine the extent to which coders follow the selection rules of coding set out in the International Classification of Diseases, 9th Revision (ICD-9), and the effects of miscoding on mortality statistics in Taiwan., Method: A systematic sample of 5621 death certificates was reviewed. The underlying cause of death (UCD) selected by the reviewer for each death certificate was compared with that selected by the original coder. The UCD was selected according to ACME (Automated Classification of Medical Entities) Decision Tables., Results: The overall agreement rates between the reviewer and coders according to the three-digit and two-digit categories of ICD-9 were 80.9% and 83.9%, respectively. Good agreement was found for malignant neoplasms (kappa = 0.94) and injuries and poisoning (kappa = 0.97), but there was poor agreement for nephrotic diseases (kappa = 0.74), hypertension-related diseases (kappa = 0.74), and cerebral infarction (kappa = 0.77). Reasons for disagreements included disagreement in nomenclature (42.8%), inappropriate judgement of causal relationships (41.5%), and incorrect interpretation of Selection Rule 3 and Modification Rules (15.7%)., Conclusion: This study showed various levels of agreement for different diseases between the reviewer and the original coders in selection of the UCD. Owing to the 'compensatory effect of errors', the national mortality statistics were not affected significantly. The national administration should undertake routine internal studies to control the quality of UCD coding practices.

Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder with expansion of trinucleotide CAG repeats in the coding region of the gene. Expansion of the repeat tract beyond the normal range produces gene products with extended polyglutamine tracts. In this study, we analyzed the distribution of the CAG repeats in the DRPLA alleles in a normal Taiwanese population. We observed 15 different alleles and found that the range of the CAG repeat number was from 7-21. The most frequent allele contained 15 CAG repeats that represented 20% of the total analyzed alleles, followed by the 17 repeats (15.8%). The heterozygosity rate of this locus was 88%. Twelve parents-to-children transmissions of the DRPLA alleles in a Machado-Joseph disease family appeared to be normal without any alteration of the CAG repeat numbers. Phenotypes of DRPLA overlapped those of autosomal dominant cerebellar ataxia (ADCA). In order to identify DRPLA patients in Taiwan, we screened six autosomal dominant cerebellar ataxia patients without expansion in known spinocerebellar ataxia genes. All six patients had the repeat numbers within the normal range; thus, the possibility of DRPLA could be excluded.

Regional mortality data, which are compiled according to place-of-residence of the decedent, are an important reference for regional health planning and resource allocation. However, it would be inappropriate to apply these data to studies of environmental risk factors if a large proportion of fatal motor vehicle traffic injuries (MVTI) in fact occur outside the resident county. The aim of this study was to determine the proportion and characteristics of residents of a rural area of Taiwan who died from MVTIs that occurred outside the county of residence. We also explored the relationships among the place-of-occurrence, place-of-death, and place-of-residence of these decedents. The families or neighbors of residents of Huatung Area (eastern Taiwan) who died from MVTIs in 1994 or 1995 were interviewed to identify the place-of-occurrence of the MVTI. Of the 882 Huatung Area residents who died as a result of an MVTI during the study period and for whom relevant data were available, the MVTI occurred outside the resident county in 207 (23%) cases. Residents whose MVTI occurred outside the county of residence were more likely to be youths (aged 15-24) or young adults (aged 25-44) and driving automobiles or trucks. Of the 866 cases in which the exact place was known, the place-of-occurrence and the place-of-death (recorded on the death certificate) were in the same county in 849 (98%). Because a high proportion of fatal MVTIs occurred outside the resident county, the mortality rate calculated according to place-of-residence does not accurately reflect the environmental risk factors in this area. The finding that the characteristics of those whose MVTI occurred outside the county differed from those decedents whose MVTI occurred within the county indicates that there are two target groups for prevention programs. In addition, at least in Huatung Area, the place-of-death recorded on the death certificate could serve as a surrogate for the place-of-occurrence in epidemiologic studies.

It has been well accepted that effective programs for prevention of adolescent pregnancy should involve adolescent women and their partners. Using data from certificates of live births in Taichung County, Taiwan, in 1994, the demographic characteristics of fathers whose infants were born to adolescent women were compared with a matched group fathers whose infants were born to women aged > or =20 years. Most of the fathers of infants born to adolescent women were adults: 57% of the fathers of infants born to women aged < or =15 years were > or =30 years of age. Fathers of infants born to adolescent women had a lower educational level than that of matched fathers. These demographic characteristics of fathers should be carefully interpreted and taken into consideration in developing intervention programs.

Background: It is well-known that pregnancy in adolescence has an increased risk of adverse reproductive outcomes. It remains unclear whether this association is due mainly to the unfavourable sociodemographic status or due solely to biological immaturity of pregnant adolescents., Objective: The purpose of this study was to determine the association of parental sociodemographic characteristics with the adverse outcomes of adolescent pregnancy., Method: Data from certificates of live births in Taichung County, Taiwan in 1994 of 7994 singleton, first-born babies whose mothers were 15-34 years of age were analysed. The relative risk of having adverse pregnancy outcomes for adolescent subgroups was obtained as compared with that among mothers 20-34 years of age with the same characteristics. The adjusted relative risk of having adverse pregnancy outcomes for each covariate was calculated by a multiple logistic regression analysis., Results: Of 7994 babies born to mothers of 15-34 years of age, 8.3% were born to adolescent mothers. In all age groups, the younger adolescent mothers (15-17 years of age) had the highest percentage of both infants with low birth weight (10.6%) and preterm births (7.1 %). Younger adolescent mothers in almost all sociodemographic categories had higher risks of having both low-birth-weight and preterm births than those of older adolescent mothers. Multiple logistic regression analysis showed that a younger maternal age is the only significant risk factor for having infants with low birth weight (adjusted RR = 2.5, 95% Cl 1.8-4.5 and adjusted RR = 1.7, 95% Cl 1.2-2.6 for younger and older adolescent mothers, respectively) or preterm birth (adjusted RR = 1.9, 95% Cl 1.1-3.4 and adjusted RR = 1.5, 95% Cl 1.0-2.3 for younger and older adolescent mothers, respectively)., Conclusions: Adolescent pregnancy carries an increased risk of having low-birth-weight and preterm births, and a younger maternal age is causally implicated.

Objectives: To describe trends in injury mortality among adolescents in Taiwan for prioritising preventive interventions., Methods: Adolescent injury mortality data for Taiwan were derived from official publications of vital statistics from 1965 to 1994 to determine trends by sex and cause of death. Simple linear regression was used to test the trends., Results: The number of deaths due to injury among adolescents aged 10-19 years in Taiwan increased from 983 in 1965 to 1783 in 1994, an 81% increase. The injury mortality rate increased 42%, from 32.2 per 100,000 in 1965 to 45.6 per 100,000 in 1994. The proportion of injury deaths also increased, from 45.3% in 1965 to 72.8% in 1994. The trends in mortality from motor vehicle injury (MVI) among four demographic groups were all significantly positive (p < 0.001). The proportion of deaths due to MVI among injury was 14% in 1965 and increased to 63% in 1994., Conclusions: The increase in injury mortality rates among adolescents over the past three decades appears to be due largely to the increase in MVI mortality rates with males aged 15-19 years accounting for most of this increase. Priorities for adolescents in Taiwan are MVI (especially motorcyclists) and drownings.

To determine factors related to adolescents' perceived treatment outcomes of their health problems in an adolescent health clinic located at a college hospital, 246 adolescent patients between the ages of 11 and 21 who visited the clinic twice or more during the period January 1994 to December 1995 were included in this study. Information concerning adolescents' sociodemographic characteristics, family function, office visits and health problems of first visits was collected by reviewing subjects' medical and other clinic-related records. In addition, a structured questionnaire was mailed to assess subjects' satisfaction with physicians and the environment and services provided by the clinic as well as their perceived treatment outcomes. 148 patients completed the questionnaire, a response rate of 60.2%. Most of the respondents were in late-stage adolescence (71.0%) and were in school (71.0%). About half of respondents had normal family function, while the other half had moderate or severe family dysfunction. Most of the health problems of respondents were acute (64.2%) and were biological (76.4%) conditions. Most of the respondents were satisfied with the various characteristics of physicians except confidentiality emphasized by the physicians, while many fewer respondents were satisfied with the environment and services provided by the clinic. Family function, physicians' respect toward the adolescents, and the adolescents' satisfaction with the services provided in general were the factors significantly related to adolescents' perceived treatment outcomes based on a stepwise, multiple logistic regression analysis. We conclude that efforts to provided could result in better adolescent perceived treatment outcomes.

Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar degeneration characterized by cerebellar ataxia and pyramidal signs associated in varying degrees with a dystonic-rigid extrapyramidal syndrome or peripheral amyotrophy. Unstable CAG trinucleotide repeat expansion in the MJD gene on the long arm of chromosome 14 has been identified as the pathological mutation for MJD. While investigating the distribution of CAG repeat lengths of the MJD gene in Taiwan's population, we have identified 18 MJD-affected patients and 12 at-risk individuals in seven families. In addition, we have analyzed the range of CAG repeat lengths in 96 control individuals. The CAG repeat number ranged from 13 to 44 in the controls and 72-85 in the affected and at-risk individuals. Our results indicated that the CAG repeat number was inversely correlated with the age of onset. The differences in CAG repeat length between parent and child and between siblings are greater with paternal transmission than maternal transmission. Our data show a tendency towards the phenomenon of anticipation in the MJD families but do not support unidirectional expansion of CAG repeats during transmission. We also demonstrated that PCR amplification of the CAG repeats in the MJD gene from villous DNA was possible and might prove useful as a diagnostic tool for affected families in the future.